Science.gov

Sample records for 2-year carcinogenicity studies

  1. Low-Dose Carcinogenicity Studies

    EPA Science Inventory

    One of the major deficiencies of cancer risk assessments is the lack of low-dose carcinogenicity data. Most assessments require extrapolation from high to low doses, which is subject to various uncertainties. Only 4 low-dose carcinogenicity studies and 5 low-dose biomarker/pre-n...

  2. Re-evaluation of the kidney tumors and renal histopathology occurring in a 2-year rat carcinogenicity bioassay of quercetin.

    PubMed

    Hard, Gordon C; Seely, John Curtis; Betz, Laura J; Hayashi, Shim-Mo

    2007-04-01

    Renal histopathology in the most recent 2-year carcinogenicity bioassay of quercetin, in Fischer 344 rats, was re-evaluated in an attempt to determine a mode of action underlying a small increase in renal tubule tumors reported in the males (). The re-evaluation confirmed the reported increase in renal tumors in mid- and high-dose males, including a single carcinoma in a high-dose male, as well as an exacerbation of spontaneous, chronic progressive nephropathy (CPN) in male rats only. The re-evaluation also showed that there were no cellular alterations in the kidney indicative of chemical toxicity at 6 months, 15 months, or 2 years. The evidence linked the occurrence of the predominant basophilic adenomas and foci of atypical tubule hyperplasia (ATH) with the exacerbation of CPN to advanced grades of severity, supporting a mode of action involving quercetin interaction with CPN. This mode of action represents a secondary mechanism for renal tumor development, with no relevance for extrapolation to humans. In addition, the single carcinoma present in the high-dose males, along with 4 other lesions ranging from ATH to adenoma in male and female groups, were considered to have a unique phenotype associated previously with neoplasms of spontaneous and familial origin.

  3. Design of carcinogenicity studies: a backward glance.

    PubMed

    Diener, R

    1983-01-01

    Despite extensive research carried out over many years, a completely satisfactory method of testing drugs and chemicals for carcinogenicity continues to elude toxicologists. In the past, numerous scientific groups, regulatory agencies, and regional bodies have discussed and published specific recommendations and guidelines regarding the testing requirements for carcinogenicity studies. The Food, Drug and Cosmetic Act became law in 1938, but it was not until after the Second World War that serious concerns regarding chemicals became prevalent. Testing guidelines were nonexistent until 1949 when the FDA published "Procedures for the Appraisal of the Toxicity of Chemicals in Foods." This key publication was the forerunner of the famous "Gray Book" (1959) in which were outlined many of the specific carcinogenicity testing procedures still used today. Guidelines and regulations became the watchwords during the 60's and 1970's. Formation of the EPA, more stringent testing requirements, Toxic Substances legislation, and Environmental Control Acts followed one another in short order. NCl's Technical Report #1 (1976) entitled, "Guidelines for Carcinogen Bioassay in Small Rodents" probably had the greatest impact of any publication on carcinogenicity testing. Many later guidelines and recommendations were based on this publication. PMID:6681394

  4. Study of Chemical Carcinogens by Positron Annihilation Lifetime Spectroscopy

    NASA Astrophysics Data System (ADS)

    Pivtsaev, A. A.; Razov, V. I.; Karasev, A. O.

    2013-11-01

    We have used positron annihilation lifetime spectroscopy to study the carcinogens C21H20BrN3, C4H7Cl2O4P, CCl4, CHCl3, AlF3, C8H12N4O, C6H4Cl2 and the non-carcinogens H2O, AlCl3, CH2Cl2, C2H6OS. We have established a correlation between the annihilation characteristics of the studied compounds and their degree of carcinogenicity.

  5. Best practices for clinical pathology testing in carcinogenicity studies.

    PubMed

    Young, Jamie K; Hall, Robert L; O'Brien, Peter; Strauss, Volker; Vahle, John L

    2011-02-01

    The Society of Toxicologic Pathology (STP) and American Society for Veterinary Clinical Pathology (ASCVP) convened a Clinical Pathology in Carcinogenicity Studies Working Group to recommend best practices for inclusion of clinical pathology testing in carcinogenicity studies. Regulatory guidance documents and literature were reviewed, and veterinary pathologists from North America, Japan, and Europe were surveyed regarding current practices, perceived value, and recommendations for clinical pathology testing in carcinogenicity studies. For two-year rodent carcinogenicity studies, the Working Group recommends that clinical pathology testing be limited to collection of blood smears at scheduled and unscheduled sacrifices to be examined only if indicated to aid in the diagnosis of possible hematopoietic neoplasia following histopathologic evaluation. Additional clinical pathology testing is most appropriately used to address specific issues from prior toxicity studies or known test article-related class effects. Inadequate data were available to make a recommendation concerning clinical pathology testing for alternative six-month carcinogenicity assays using genetically modified mice, although the Working Group suggests that it may be appropriate to use the same approach as for two-year carcinogenicity studies since the study goal is the same.

  6. Carcinogenic and co-carcinogenic studies of thiram on mouse skin.

    PubMed

    Shukla, Y; Baqar, S M; Mehrotra, N K

    1996-03-01

    Thiram (tetramethyl thiuram disulfide), a carbamate fungicide, is used in the rubber processing industry as an accelerator and vulcanizing agent. Previous studies evaluated the tumorigenic potential of thiram in rodents, but failed to provide conclusive results. In the present study the tumorigenic potential of thiram was evaluated in Swiss albino mice by a two-stage initiation-promotion protocol and a long-term in vivo bioassay for carcinogenicity. Results revealed that following tumour initiation with thiram and promotion with 12-O-tetradecanoyl phorbol 13-acetate, skin tumours developed, mostly at the site of treatment (dorsal skin) in single and multiple dose-initiated animals. Similarly, papillomatous growths were observed on the dorsal skin of the mice initiated with a single subcarcinogenic dose of dimethylbenzanthracene and promoted with thiram. Thiram failed to provoke tumorigenesis when tested as a complete carcinogen for up to 52 wk and thereafter the study was terminated due to increased mortality. It is concluded that thiram has both tumour initiating and tumour-promoting potential in both sexes of Swiss albino mice following topical exposure at the tested dose level.

  7. Issues in the Design and Interpretation of Chronic Toxicity and Carcinogenicity Studies in Rodents: Approaches to Dose Selection

    EPA Science Inventory

    For more than three decades chronic studies in rodents have been the benchmark for assessing the potential long-term toxicity, and particularly the carcinogenicity, of chemicals. With doses typically administered for about 2 years (18 months to lifetime), the rodent bioassay has ...

  8. Tamoxifen experimental carcinogenicity studies: Implications for human effects

    SciTech Connect

    Williams, G.M.

    1995-02-01

    Tamoxifen is an effective antiestrogen in the treatment of breast cancer and is considered highly safe. In recent years, several trials have been initiated in women to evaluate its potential for the prevention of breast cancer. Such long-term administration of a medication to healthy people requires a substantial degree of safety. This review examines experimental carcinogenicity and mechanistic studies on tamoxifen and the implications for human effects. 25 refs.

  9. Studies in vitro to discern the structural requirements for carcinogenicity in analogues of the carcinogen 4-dimethylaminoazobenzene (butter yellow).

    PubMed

    Ashby, J; Styles, J A; Paton, D

    1980-01-01

    4-Dimethylaminoazobenzene (butter yellow, DAB), is the parent member of a large family of 'azo-carcinogens'. Experiments have been conducted in vitro to determine the key structural requirements for carcinogenic activity in this chemical class, and it is suggested, based on the activity observed for 4-cyano-N,N-dimethylaniline, that the 4-phenylazo group of DAB is not an essential structural feature per se. The N-oxide derivative of DAB has been evaluated in vitro and the positive response observed related to its metabolic activation. It is concluded that cyclic amines, such as pyrrolidine, can replace the N-dimethyl group of DAB with a retention of biological activity. The confusion that exists in the literature concerning the chemical identity and carcinogenic status of 2-dimethylaminobenzo[c]cinnoline has been investigated, and it is concluded that it is a potential animal carcinogen. This observation also indicates that the phenylazo group of DAB can be incorporated within an aromatic ring system with a retention of biological activity. As observed earlier with a mixture of azobenzene and DAB, azobenzene also potentiates the cell transforming properties of the above cinnoline derivative in vitro. Two charts are presented. The first attempts to integrate DAB within a much larger family of carcinogens, and the second illustrates the usefulness of structure-activity studies in general.

  10. Oral carcinogenicity study with nickel sulfate hexahydrate in Fischer 344 rats

    SciTech Connect

    Heim, Katherine E.; Bates, Hudson K.; Rush, Rusty E.; Oller, Adriana R.

    2007-10-15

    Until now, existing data on the oral carcinogenicity of nickel substances have been inconclusive. Yet, the assessment of oral carcinogenicity of nickel has serious scientific and regulatory implications. In the present study, nickel sulfate hexahydrate was administered daily to Fischer 344 rats by oral gavage for 2 years (104 weeks) at exposure levels of 10, 30 and 50 mg NiSO{sub 4}{center_dot}6H{sub 2}O/kg. This treatment produced a statistically significant reduction in body weight of male and female rats, compared to controls, in an exposure-related fashion at 30 and 50 mg/kg/day. An exposure-dependent increase in mortality was observed in female rats. However, the overall study survival rate (males and females) was at least 25 animals per group (compliant with OECD guidelines) in the treated animals. Daily oral administration of nickel sulfate hexahydrate did not produce an exposure-related increase in any common tumor type or an increase in any rare tumors. One tumor type was statistically increased in a nickel sulfate-treated group compared to the study controls (keratoacanthoma in the 10 mg NiSO{sub 4}{center_dot}6H{sub 2}O/kg/day males), but there was no exposure-response relationship for this common tumor type. This study achieved sufficient toxicity to reach the Maximum Tolerated Dose (MTD) while maintaining a sufficiently high survival rate to allow evaluation for carcinogenicity. The present study indicated that nickel sulfate hexahydrate does not have the potential to cause carcinogenicity by the oral route of exposure in the Fischer 344 rat. Data from this and other studies demonstrate that inhalation is the only route of exposure that might cause concern for cancer in association with nickel exposures.

  11. Evaluation of carcinogenic potential of the herbicide glyphosate, drawing on tumor incidence data from fourteen chronic/carcinogenicity rodent studies.

    PubMed

    Greim, Helmut; Saltmiras, David; Mostert, Volker; Strupp, Christian

    2015-03-01

    Abstract Glyphosate, an herbicidal derivative of the amino acid glycine, was introduced to agriculture in the 1970s. Glyphosate targets and blocks a plant metabolic pathway not found in animals, the shikimate pathway, required for the synthesis of aromatic amino acids in plants. After almost forty years of commercial use, and multiple regulatory approvals including toxicology evaluations, literature reviews, and numerous human health risk assessments, the clear and consistent conclusions are that glyphosate is of low toxicological concern, and no concerns exist with respect to glyphosate use and cancer in humans. This manuscript discusses the basis for these conclusions. Most toxicological studies informing regulatory evaluations are of commercial interest and are proprietary in nature. Given the widespread attention to this molecule, the authors gained access to carcinogenicity data submitted to regulatory agencies and present overviews of each study, followed by a weight of evidence evaluation of tumor incidence data. Fourteen carcinogenicity studies (nine rat and five mouse) are evaluated for their individual reliability, and select neoplasms are identified for further evaluation across the data base. The original tumor incidence data from study reports are presented in the online data supplement. There was no evidence of a carcinogenic effect related to glyphosate treatment. The lack of a plausible mechanism, along with published epidemiology studies, which fail to demonstrate clear, statistically significant, unbiased and non-confounded associations between glyphosate and cancer of any single etiology, and a compelling weight of evidence, support the conclusion that glyphosate does not present concern with respect to carcinogenic potential in humans.

  12. Carcinogenic mixtures.

    PubMed

    Krewski, D; Thomas, R D

    1992-03-01

    Human populations are generally exposed simultaneously to a number of toxicants present in the environment, including complex mixtures of unknown and variable origin. While scientific methods for evaluating the potential carcinogenic risks of pure compounds are relatively well established, methods for assessing the risks of complex mixtures are somewhat less developed. This article provides a report of a recent workshop on carcinogenic mixtures sponsored by the Committee on Toxicology of the U.S. National Research Council, in which toxicological, epidemiological, and statistical approaches to carcinogenic risk assessment for mixtures were discussed. Complex mixtures, such as diesel emissions and tobacco smoke, have been shown to have carcinogenic potential. Bioassay-directed fractionation based on short-term screening test for genotoxicity has also been used in identifying carcinogenic components of mixtures. Both toxicological and epidemiological studies have identified clear interactions between chemical carcinogens, including synergistic effects at moderate to high doses. To date, laboratory studies have demonstrated over 900 interactions involving nearly 200 chemical carcinogens. At lower doses, theoretical arguments suggest that risks may be near additive. Thus, additivity at low doses has been invoked as as a working hypothesis by regulatory authorities in the absence of evidence to the contrary. Future studies of the joint effects of carcinogenic agents may serve to elucidate the mechanisms by which interactions occur at higher doses.

  13. Carcinogenicity and co-carcinogenicity studies on propoxur in mouse skin.

    PubMed

    Shukla, Y; Baqar, S M; Mehrotra, N K

    1998-12-01

    Propoxur (2-isopropoxyphenyl methylcarbamate) is a widely used broad spectrum carbamate insecticide mainly used to control household pests. Propoxur exposure is reported to inhibit cholinesterase activity in rodents. Apart from other toxic effects, propoxur was found to possess tumorigenic activity in rats after oral administration. Propoxur does not produce tumours in mice or hamsters, or bladder hyperplasia in dogs and monkeys following oral feeding. In this set of investigations the complete carcinogenic, tumour initiating and promoting potential of propoxur was evaluated in male and female Swiss albino mice, since no information was available following dermal exposure of propoxur. The animals were exposed to propoxur through topical painting on the interscapular region at a dose of 100 mg/kg body weight. The results revealed that propoxur has tumour promoting potential on mouse skin following a two-stage initiation-promotion protocol, but it failed to induce the tumour(s) at a significant level, when tested for tumour initiating and complete carcinogenic property.

  14. Evaluation of carcinogenic potential of the herbicide glyphosate, drawing on tumor incidence data from fourteen chronic/carcinogenicity rodent studies

    PubMed Central

    Greim, Helmut; Saltmiras, David; Mostert, Volker; Strupp, Christian

    2015-01-01

    Abstract Glyphosate, an herbicidal derivative of the amino acid glycine, was introduced to agriculture in the 1970s. Glyphosate targets and blocks a plant metabolic pathway not found in animals, the shikimate pathway, required for the synthesis of aromatic amino acids in plants. After almost forty years of commercial use, and multiple regulatory approvals including toxicology evaluations, literature reviews, and numerous human health risk assessments, the clear and consistent conclusions are that glyphosate is of low toxicological concern, and no concerns exist with respect to glyphosate use and cancer in humans. This manuscript discusses the basis for these conclusions. Most toxicological studies informing regulatory evaluations are of commercial interest and are proprietary in nature. Given the widespread attention to this molecule, the authors gained access to carcinogenicity data submitted to regulatory agencies and present overviews of each study, followed by a weight of evidence evaluation of tumor incidence data. Fourteen carcinogenicity studies (nine rat and five mouse) are evaluated for their individual reliability, and select neoplasms are identified for further evaluation across the data base. The original tumor incidence data from study reports are presented in the online data supplement. There was no evidence of a carcinogenic effect related to glyphosate treatment. The lack of a plausible mechanism, along with published epidemiology studies, which fail to demonstrate clear, statistically significant, unbiased and non-confounded associations between glyphosate and cancer of any single etiology, and a compelling weight of evidence, support the conclusion that glyphosate does not present concern with respect to carcinogenic potential in humans. PMID:25716480

  15. Evaluation of carcinogenic potential of the herbicide glyphosate, drawing on tumor incidence data from fourteen chronic/carcinogenicity rodent studies.

    PubMed

    Greim, Helmut; Saltmiras, David; Mostert, Volker; Strupp, Christian

    2015-03-01

    Abstract Glyphosate, an herbicidal derivative of the amino acid glycine, was introduced to agriculture in the 1970s. Glyphosate targets and blocks a plant metabolic pathway not found in animals, the shikimate pathway, required for the synthesis of aromatic amino acids in plants. After almost forty years of commercial use, and multiple regulatory approvals including toxicology evaluations, literature reviews, and numerous human health risk assessments, the clear and consistent conclusions are that glyphosate is of low toxicological concern, and no concerns exist with respect to glyphosate use and cancer in humans. This manuscript discusses the basis for these conclusions. Most toxicological studies informing regulatory evaluations are of commercial interest and are proprietary in nature. Given the widespread attention to this molecule, the authors gained access to carcinogenicity data submitted to regulatory agencies and present overviews of each study, followed by a weight of evidence evaluation of tumor incidence data. Fourteen carcinogenicity studies (nine rat and five mouse) are evaluated for their individual reliability, and select neoplasms are identified for further evaluation across the data base. The original tumor incidence data from study reports are presented in the online data supplement. There was no evidence of a carcinogenic effect related to glyphosate treatment. The lack of a plausible mechanism, along with published epidemiology studies, which fail to demonstrate clear, statistically significant, unbiased and non-confounded associations between glyphosate and cancer of any single etiology, and a compelling weight of evidence, support the conclusion that glyphosate does not present concern with respect to carcinogenic potential in humans. PMID:25716480

  16. Perinatal Toxicity and Carcinogenicity Studies of Styrene –Acrylonitrile Trimer, A Ground Water Contaminant

    PubMed Central

    Behl, Mamta; Elmore, Susan A.; Malarkey, David E.; Hejtmancik, Milton R.; Gerken, Diane K.; Chhabra, Rajendra S.

    2015-01-01

    Styrene Acrylonitrile (SAN) Trimer is a by-product in the production of acrylonitrile styrene plastics. Following a report of a childhood cancer cluster in the Toms River section of Dover Township, New Jersey, SAN Trimer was identified as one of the groundwater contaminants at Reich Farm Superfund site in the township. The contaminants from the Reich Farm site’s ground water plume impacted two wells at the Parkway well field. The National Toxicology Program (NTP) studied the toxicity and carcinogenicity of SAN Trimer in rats exposed during their perinatal developmental period and adulthood. The chronic toxicity and carcinogenicity studies in F344/N rats were preceded by 7- and 18-week perinatal toxicity studies to determine the exposure concentrations for the 2-year studies. Subsequently, Fisher 344 pregnant dams were exposed to SAN Trimer containing diet at 400, 800, or 1600 ppm concentrations during gestation, nursing and weaning periods of offspring followed by two year of adult exposures to both male and female pups. There was no statistically significant evidence of carcinogenic activity following SAN-Trimer exposure; however, rare neoplasms in the brain and spinal cord were observed in males and to lesser extent in female rats. These incidences were considered within the range of historical background in the animal model used in the current studies. Therefore, the presence of a few rarely occurring CNS tumors in the treated groups were not judged to be associated with the SAN Trimer exposure. The major finding was a dose-related peripheral neuropathy associated with the sciatic nerves in females and spinal nerve roots in males and females thereby suggesting that SAN trimer is potentially a nervous system toxicant. PMID:24060431

  17. Use of historical control data in carcinogenicity studies in rodents.

    PubMed

    Haseman, J K; Huff, J; Boorman, G A

    1984-01-01

    This paper considers the use of historical control data in the evaluation of tumor incidences from carcinogenicity studies in rodents. Although the most appropriate control group for interpretative purposes is always the concurrent control, there are instances in which the use of historical control information can aid an investigator in the overall evaluation of tumor incidence data. One example is rare tumors; another is a tumor that shows a marginally significant result relative to concurrent controls. However, before historical control data can be used in a formal testing framework, a number of important issues must first be considered. The nomenclature conventions and diagnostic criteria for each study should be identical to insure unambiguous identification of all relevant tumors in the historical control database. Criteria should be established that will aid in determining whether a particular study should be included in the database. This will assure a homogeneous set of studies upon which to base statistical comparisons. Since study-to-study variability in tumor rates may exceed what would be expected by chance alone, these sources of variability should be identified and controlled. Finally, statistical procedures should be employed that adjust for extra-binomial variability. This paper also summarizes tumor incidence data from untreated Fischer 344 rats and B6C3F1 mice in the National Toxicology Program (NTP) historical control database. All studies in the database are of two years duration, and all neoplasms occurring with a frequency of 0.5% or more are reported. PMID:11478313

  18. LARGE SCALE CARCINOGEN DOSE RESPONSE STUDIES WITH JAPANESE MEDAKA (ORYZIAS LATIPES)

    EPA Science Inventory

    To investigate the responses to low carcinogen doses in animal models, large sample sizes are needed and it is an advantage if the model has a low spontaneous tumor rate. Three large scale dose response studies were conducted using Japanese medaka and the carcinogen diethylnitros...

  19. A study of the carcinogenicity of glycidol in Syrian hamsters.

    PubMed

    Lijinsky, W; Kovatch, R M

    1992-01-01

    The industrial chemical glycidol is a directly acting mutagen and a broadly acting carcinogen in rats. It was administered to Syrian golden hamsters (20 male and 20 female) by gavage of 12 mg twice a week for 60 weeks. The total dose per animal was 1.45 g or 20 mmol. Survival was not different from control hamsters treated with corn oil/ethyl acetate. Of the treated males, 9 had tumors and 13 of the treated females had tumors, some of which were adrenal cortex tumors seen in controls. More tumors were seen in the glycidol-treated hamsters than in controls, but the spleen was the only notable target organ and the number of animals with spleen hemangiosarcomas was small. Glycidol appeared to be less carcinogenic in hamsters than in rats or mice.

  20. Inhalation toxicity and carcinogenicity studies of cobalt sulfate.

    PubMed

    Bucher, J R; Hailey, J R; Roycroft, J R; Haseman, J K; Sills, R C; Grumbein, S L; Mellick, P W; Chou, B J

    1999-05-01

    Cobalt sulfate is a water-soluble cobalt salt with a variety of industrial and agricultural uses. Several cobalt compounds have induced sarcomas at injection sites in animals, and reports have suggested that exposure to cobalt-containing materials may cause lung cancer in humans. The present studies were done because no adequate rodent carcinogenicity studies had been performed with a soluble cobalt salt using a route relevant to occupational exposures. Groups of 50 male and 50 female F344/N rats and B6C3F1 mice were exposed to aerosols containing 0, 0.3, 1.0, or 3.0 mg/m3 cobalt sulfate hexahydrate, 6 h/day, 5 days/week, for 104 weeks. Survival and body weights of exposed rats and mice were generally unaffected by the exposures. In rats, proteinosis, alveolar epithelial metaplasia, granulomatous alveolar inflammation, and interstitial fibrosis were observed in the lung in all exposed groups. Nonneoplastic lesions of the nose and larynx were also attributed to exposure to all concentrations of cobalt sulfate. In 3.0 mg/m3 male rats and in female rats exposed to 1.0 or 3.0 mg/m3, the incidences of alveolar/bronchiolar neoplasms were increased over those in the control groups. Lung tumors occurred with significant positive trends in both sexes. The incidences of adrenal pheochromocytoma in 1.0 mg/m3 male rats and in 3.0 mg/m3 female rats were increased. Nonneoplastic lesions of the respiratory tract were less severe in mice than in rats. In mice, alveolar/bronchiolar neoplasms in 3.0 mg/m3 males and females were greater than those in the controls, and lung tumors occurred with significantly positive trends. Male mice had liver lesions consistent with a Helicobacter hepaticus infection. Incidences of liver hemangiosarcomas were increased in exposed groups of male mice; however, because of the infection, no conclusion could be reached concerning an association between liver hemangiosarcomas and cobalt sulfate. In summary, exposure to cobalt sulfate by inhalation

  1. Motor recovery after stroke depends on intact sustained attention: a 2-year follow-up study.

    PubMed

    Robertson, I H; Ridgeway, V; Greenfield, E; Parr, A

    1997-04-01

    The functional recovery of 47 right-brain-damaged stroke patients was studied over a 2-year period. The researchers hypothesized that sustained attention capacity should predict the degree of motor and functional recovery over this period because of a proposed privileged role of sustained attention in learning-based recovery of function. As predicted, significant correlations were found between sustained attention capacity at 2 months and functional status (including the Barthel Index) at 2 years. This relationship was shown to exist independently of 2-month functional status. Furthermore, compared with a left-brain-damaged group of cerebrovascular accident (CVA) patients, the right-brain CVA group did not recover functional ability as well over the 2-year period. This increasing difference in functional status over a 2-year period was mirrored by an emerging difference in sustained attention capacity, in favor of the left-brain CVA group.

  2. Improving Social Competence through Emotion Knowledge in 2-Year-Old Children: A Pilot Study

    ERIC Educational Resources Information Center

    Giménez-Dasí, Marta; Fernández-Sánchez, Marta; Quintanilla, Laura

    2015-01-01

    Research Findings: The goal of this study was to determine the efficacy of an educational intervention program to improve emotion knowledge, emotion regulation, and social competence in 2-year-old Spanish children. This study makes two original contributions because there are no validated education programs for such young children and because it…

  3. Sexual abstinence in patients with HIV infection: a 2-year follow-up study.

    PubMed

    Jordan, W C

    1991-12-01

    Thirty-five human immunodeficiency virus (HIV)-positive patients were followed over a 2-year period. All agreed to abstain from sexual intercourse. This group had a low level of recurring infections. A comparison study of sexually active HIV males is underway.

  4. Genetic, kinetic, and mechanistic studies on the inhibition of interferon production by polycyclic aromatic hydrocarbon carcinogens

    SciTech Connect

    Golemboski, K.A.L.

    1984-01-01

    Interferon (IFN) production is inhibited by treatment with chemical carcinogens. The significance of this inhibition is not clear. The interaction of IFN with cytochrome P-450 and associated enzymes, which are responsible for the metabolism and/or activation of many carcinogens, and with the immune system suggests that the developement of a cancer could be influenced by this inhibition. The effect of 7,12-dimethylbenz(a)anthracene (DMBA) on IFN-..gamma.. production in murine spleen cell cultures was inhibited when DMBA was given 24 hours before or 4-5 hours after IFN-..gamma.. was induced with phytohemagglutinin-p (PHA-P). The influence of genetic controls of IFN inhibition was examined using DBA/2, C57B1/6, ICR, and SENCAR mouse strains. Kinetic studies examined parameters of IFN inhibition by benzo(a)pyrene (BP). IFN production in treated cells equaled that of untreated cells, but was delayed by six to twelve hours, suggesting a reversible inhibition. The approximate decrease in cell number which would be required to decrease IFN significantly was determined to be 50%. These results indicated that production of all types of IFN is inhibited by carcinogen treatment and that the inhibition may be genetically controlled. The inhibition of IFN production is actually a rapidly reversible delay. Exposure to the carcinogen is required only for uptake, and extended exposure, or another carcinogen, can interfere with the inhibition of IFN production by subsequent doses.

  5. A feasibility study: Can information collected to classify for mutagenicity be informative in predicting carcinogenicity?

    PubMed

    Petkov, Petko I; Patlewicz, Grace; Schultz, Terry W; Honma, Masamitsu; Todorov, Milen; Kotov, Stefan; Dimitrov, Sabcho D; Donner, E Maria; Mekenyan, Ovanes G

    2015-06-01

    Carcinogenicity is a complex endpoint of high concern yet the rodent bioassay still used is costly to run in terms of time, money and animals. Therefore carcinogenicity has been the subject of many different efforts to both develop short-term tests and non-testing approaches capable of predicting genotoxic carcinogenic potential. In our previous publication (Mekenyan et al., 2012) we presented an in vitro-in vivo extrapolation workflow to help investigate the differences between in vitro and in vivo genotoxicity tests. The outcomes facilitated the development of new (Q)SAR models and for directing testing. Here we have refined this workflow by grouping specific tests together on the basis of their ability to detect DNA and/or protein damage at different levels of biological organization. This revised workflow, akin to an Integrated Approach to Testing and Assessment (IATA) informed by mechanistic understanding was helpful in rationalizing inconsistent study outcomes and categorizing a test set of carcinogens with mutagenicity data on the basis of regulatory mutagenicity classifications. Rodent genotoxic carcinogens were found to be correctly predicted with a high sensitivity (90-100%) and a low rate of false positives (3-10%). The insights derived are useful to consider when developing future (non-)testing approaches to address regulatory purposes.

  6. Toxicity and carcinogenicity studies of boric acid in male and female B6C3F1 mice.

    PubMed Central

    Dieter, M P

    1994-01-01

    Toxicity and potential carcinogenicity studies of boric acid were investigated in mice to verify in a second rodent species that this was a noncarcinogenic chemical. Earlier chronic studies in rats indicated boric acid was not a carcinogen. The chemical is nominated for testing because over 200 tons are produced annually, there are multiple uses for the product, and there is potential for widespread human exposure, both orally and dermally. Both sexes of B6C3F1 mice were offered diets mixed with boric acid for 14 days, 13 weeks, or 2 years. Dietary doses used in the acute, 14-day study were 0, 0.62, 1.25, 2.5, 5, and 10%; those in the subchronic, 13-week study were 0, 0.12, 0.25, 0.50, 1, and 2%; and doses in the 2-year, chronic study were 0, 0.25, and 0.50% in the diet. Mortality, clinical signs of toxicity, estimates of food consumption, body weight gain, and histopathologic examination of selected tissues constituted the variables measured. In the 14-day study mortality was proportional to dose and time of exposure in both sexes, occurring in dose groups as low as 2.5% and as early as 7 days of exposure. Body weights were depressed more than 10% below controls in the higher dose groups of both sexes. Mortality in the 13-week study was confined to the two highest dose groups in male mice and to the 2%-dose group in females. Body weight depression from 8 to 23% below those of controls occurred in the 0.50% and higher dose groups of both sexes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7889889

  7. Auditory sensory memory in 2-year-old children: an event-related potential study.

    PubMed

    Glass, Elisabeth; Sachse, Steffi; von Suchodoletz, Waldemar

    2008-03-26

    Auditory sensory memory is assumed to play an important role in cognitive development, but little is known about it in young children. The aim of this study was to estimate the duration of auditory sensory memory in 2-year-old children. We recorded the mismatch negativity in response to tone stimuli presented with different interstimulus intervals. Our findings suggest that in 2-year-old children the memory representation of the standard tone remains in the sensory memory store for at least 1 s but for less than 2 s. Recording the mismatch negativity with stimuli presented at various interstimulus intervals seems to be a useful method for studying the relationship between auditory sensory memory and normal and disturbed cognitive development.

  8. Natrelle 410 Extra-Full Projection Silicone Breast Implants: 2-Year Results from Two Prospective Studies

    PubMed Central

    McGuire, Patricia; Murphy, Diane K.

    2015-01-01

    Background: The safety and effectiveness of the Natrelle Style 410 highly cohesive silicone gel breast implant (Allergan, Inc., Irvine, Calif.) in full or moderate height and projection have been shown in a 10-year study. Extra-full projection implants may be an appropriate option for some women undergoing breast reconstruction. Methods: A total of 2795 women received at least one Natrelle 410 extra-full projection implant (X-style) for breast reconstruction in two similarly designed, prospective, multicenter studies. Data collected for 2 years after implantation in these studies were pooled to evaluate complication rates and subject and physician satisfaction. Results: Most subjects (76.0 percent) underwent bilateral reconstruction; a total of 4912 devices were implanted. Complication rates at 2 years were low. The most common complications were asymmetry (4.8 percent) and capsular contracture (3.3 percent). The cumulative risk of reoperation was 21.6 percent by subject and 16.6 percent by device; the most common reasons for reoperation were scarring (n = 97), asymmetry (n = 89), implant malposition (n = 78), and infection (n = 71). Subject and physician satisfaction rates exceeded 90 percent. At 2 years, 97 percent of physicians reported that the shape of the breast reflected the shape of the implant, and that the breast implant had maintained its original position. Conclusions: The safety profile of the Natrelle 410 extra-full projection implant mirrors that of its moderate projection and full projection counterparts. Both physicians and subjects were highly satisfied with the implants 2 years after surgery. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV. PMID:26090764

  9. Uric acid in relapsing-remitting multiple sclerosis: a 2-year longitudinal study.

    PubMed

    Moccia, Marcello; Lanzillo, Roberta; Costabile, Teresa; Russo, Cinzia; Carotenuto, Antonio; Sasso, Gabriella; Postiglione, Emanuela; De Luca Picione, Carla; Vastola, Michele; Maniscalco, Giorgia Teresa; Palladino, Raffaele; Brescia Morra, Vincenzo

    2015-01-01

    Uric acid (UA) is reduced in multiple sclerosis (MS), and possibly relates to MS outcomes, with lower UA levels in subjects experiencing a relapse or presenting higher disability scores. The present retrospective longitudinal study evaluated UA variations in MS, in relation to clinical relapses, disability progression, and cognitive functions. We included 141 subjects with relapsing-remitting MS (RRMS) and performed expanded disability status scale (EDSS), symbol digit modalities test (SDMT) and UA evaluation at baseline visit and after 2-year follow-up. Paired t test showed significantly lower UA levels after 2-year follow-up than at baseline (3.987 ± 1.135 and 4.167 ± 1.207 mg/dL, respectively) (p = 0.001). The difference in UA levels between 2-year follow-up and baseline related to EDSS sustained progression (p < 0.001; OR = 0.099), and presented a trend for clinical relapses at logistic regression (p = 0.211; OR = 0.711) and for the time to relapse at Cox regression (p = 0.236; HR = 0.792). Analysis of variance showed reduced baseline UA levels in subjects with impaired SDMT at baseline (p = 0.045; adjusted R(2) = 0.473) and after 2-year follow-up (p = 0.034; adjusted R(2) = 0.470). This is the first study showing a progressive reduction of UA levels during the course of RRMS, suggesting a progressive decrease of antioxidant reserves, in relation to relapse risk, disability progression and cognitive function. PMID:25673130

  10. Comprehensive review of epidemiological and animal studies on the potential carcinogenic effects of nicotine per se

    PubMed Central

    Haussmann, Hans-Juergen; Fariss, Marc W.

    2016-01-01

    Abstract The effects of long-term use of nicotine per se on cancer risk, in the absence of tobacco extract or smoke, are not clearly understood. This review evaluates the strength of published scientific evidence, in both epidemiological and animal studies, for the potential carcinogenic effects of nicotine per se; that is to act as a complete carcinogen or as a modulator of carcinogenesis. For human studies, there appears to be inadequate evidence for an association between nicotine exposure and the presence of or lack of a carcinogenic effect due to the limited information available. In animal studies, limited evidence suggests an association between long-term nicotine exposure and a lack of a complete carcinogenic effect. Conclusive studies using current bioassay guidelines, however, are missing. In studies using chemical/physical carcinogens or transgenic models, there appears to be inadequate evidence for an association between nicotine exposure and the presence of or lack of a modulating (stimulating) effect on carcinogenesis. This is primarily due to the large number of conflicting studies. In contrast, a majority of studies provides sufficient evidence for an association between nicotine exposure and enhanced carcinogenesis of cancer cells inoculated in mice. This modulating effect was especially prominent in immunocompromized mice. Overall, taking the human and animal studies into consideration, there appears to be inadequate evidence to conclude that nicotine per se does or does not cause or modulate carcinogenesis in humans. This conclusion is in agreement with the recent US Surgeon General’s 2014 report on the health consequences of nicotine exposure. PMID:27278157

  11. P-Nitrobenzoic acid alpha2u nephropathy in 13-week studies is not associated with renal carcinogenesis in 2-year feed studies.

    PubMed

    Williams, K D; Dunnick, J; Horton, J; Greenwell, A; Eldridge, S R; Elwell, M; Sills, R C

    2001-01-01

    The objective of this study was to characterize the renal toxicity and carcinogenicity of p-nitrobenzoic acid in F344 rats. Dose levels in 13-week and 2-year studies ranged from 630-10,000 ppm and 1,250-5,000 ppm, respectively. At 13 weeks, renal lesions included minimal to mild hyaline droplet accumulation in male rats and karyomegaly in male and female rats. At 2 years, renal lesions included proximal tubule epithelial cell hyperplasia in male rats and oncocytic hyperplasia in high-dose male and female rats, and a decreased severity of nephropathy in males and females. The hvaline droplets in renal tubular epithelial cells of male rats at 13 weeks were morphologically similar to those described in alpha2u-globulin nephropathy. Using immunohistochemical methods, alpha2u-globulin accumulation was associated with the hyaline droplets. In addition, at 13 weeks, cell proliferation as detected by PCNA immunohistochemistry was significantly increased in males exposed to 5,000 and 10,000 ppm when compared to controls. Cytotoxicity associated with alpha2U-globulin nephropathy such as single-cell necrosis of the P2 segment epithelium or accumulation of granular casts in the outer medulla did not occur in the 13-week study. In addition, chronic treatment related nephrotoxic lesions attributed to accumulation of alpha2u-globulin such as linear foci of mineralization within the renal papilla, hyperplasia of the renal pelvis urothelium and kidney tumors were not observed. Although there was histologic evidence of alpha2u-globulin accumulation in male rats at 13 weeks, the minimal severity of nephropathy suggests that the degree of cytotoxicity was below the threshold, which would contribute to the development of renal tumors at 2 years.

  12. Inhalation carcinogenicity study with nickel metal powder in Wistar rats.

    PubMed

    Oller, Adriana R; Kirkpatrick, Daniel T; Radovsky, Ann; Bates, Hudson K

    2008-12-01

    Epidemiological studies of nickel refinery workers have demonstrated an association between increased respiratory cancer risk and exposure to certain nickel compounds (later confirmed in animal studies). However, the lack of an association found in epidemiological analyses for nickel metal remained unconfirmed for lack of robust animal inhalation studies. In the present study, Wistar rats were exposed by whole-body inhalation to 0, 0.1, 0.4, and 1.0 mg Ni/m(3) nickel metal powder (MMAD=1.8 microm, GSD=2.4 microm) for 6 h/day, 5 days/week for up to 24 months. A subsequent six-month period without exposures preceded the final euthanasia. High mortality among rats exposed to 1.0 mg Ni/m(3) nickel metal resulted in the earlier termination of exposures in this group. The exposure level of 0.4 mg Ni/m(3) was established as the MTD for the study. Lung alterations associated with nickel metal exposure included alveolar proteinosis, alveolar histiocytosis, chronic inflammation, and bronchiolar-alveolar hyperplasia. No increased incidence of neoplasm of the respiratory tract was observed. Adrenal gland pheochromocytomas (benign and malignant) in males and combined cortical adenomas/carcinomas in females were induced in a dose-dependent manner by the nickel metal exposure. The incidence of pheochromocytomas was statistically increased in the 0.4 mg Ni/m(3) male group. Pheochromocytomas appear to be secondary to the lung toxicity associated with the exposure rather than being related to a direct nickel effect on the adrenal glands. The incidence of cortical tumors among 0.4 mg Ni/m(3) females, although statistically higher compared to the concurrent controls, falls within the historical control range; therefore, in the present study, this tumor is of uncertain relationship to nickel metal exposure. The lack of respiratory tumors in the present animal study is consistent with the findings of the epidemiological studies. PMID:18822311

  13. Inhalation carcinogenicity study with nickel metal powder in Wistar rats

    SciTech Connect

    Oller, Adriana R. Kirkpatrick, Daniel T.; Radovsky, Ann; Bates, Hudson K.

    2008-12-01

    Epidemiological studies of nickel refinery workers have demonstrated an association between increased respiratory cancer risk and exposure to certain nickel compounds (later confirmed in animal studies). However, the lack of an association found in epidemiological analyses for nickel metal remained unconfirmed for lack of robust animal inhalation studies. In the present study, Wistar rats were exposed by whole-body inhalation to 0, 0.1, 0.4, and 1.0 mg Ni/m{sup 3} nickel metal powder (MMAD = 1.8 {mu}m, GSD = 2.4 {mu}m) for 6 h/day, 5 days/week for up to 24 months. A subsequent six-month period without exposures preceded the final euthanasia. High mortality among rats exposed to 1.0 mg Ni/m{sup 3} nickel metal resulted in the earlier termination of exposures in this group. The exposure level of 0.4 mg Ni/m{sup 3} was established as the MTD for the study. Lung alterations associated with nickel metal exposure included alveolar proteinosis, alveolar histiocytosis, chronic inflammation, and bronchiolar-alveolar hyperplasia. No increased incidence of neoplasm of the respiratory tract was observed. Adrenal gland pheochromocytomas (benign and malignant) in males and combined cortical adenomas/carcinomas in females were induced in a dose-dependent manner by the nickel metal exposure. The incidence of pheochromocytomas was statistically increased in the 0.4 mg Ni/m{sup 3} male group. Pheochromocytomas appear to be secondary to the lung toxicity associated with the exposure rather than being related to a direct nickel effect on the adrenal glands. The incidence of cortical tumors among 0.4 mg Ni/m{sup 3} females, although statistically higher compared to the concurrent controls, falls within the historical control range; therefore, in the present study, this tumor is of uncertain relationship to nickel metal exposure. The lack of respiratory tumors in the present animal study is consistent with the findings of the epidemiological studies.

  14. The retrospective study of the carcinogenic hydrocarbon benz[a]pyrene in the biosphere.

    PubMed

    Ilnitsky, A P; Vinogradov, V N; Riabchun, V K; Mischenko, V S; Gvildis, V Y; Belitsky, G A; Shabad, L M

    1979-11-01

    The major aim of this study was to determine taking, as an example, the carcinogenic polycyclic aromatic hydrocarbon benz[a]pyrene (BaP), the present biologically active compounds in the early historical and geological epochs with the following assessment of the degree of danger of such compounds in the modern times. In the first section of work, study results of soil samples in the areas of eternal frost confirmed the presence of BaP in the frozen layers of soil aged 10 years, 100 years, 3000--4000 and 10,000 years of age. In the second part of the work, results are furnished on the BaP content in the ice of modern glaciers and their moraines, located in Kamchatka. BaP was found in 11 samples in the concentration of 0.001--0.003 microgram/l. These data represent the first results in the retrospective study of carcinogenic substances in the biosphere.

  15. Methylated arsenicals: the implications of metabolism and carcinogenicity studies in rodents to human risk assessment.

    PubMed

    Cohen, Samuel M; Arnold, Lora L; Eldan, Michal; Lewis, Ari S; Beck, Barbara D

    2006-02-01

    Monomethylarsonic acid (MMA(V)) and dimethylarsinic acid (DMA(V)) are active ingredients in pesticidal products used mainly for weed control. MMA(V) and DMA(V) are also metabolites of inorganic arsenic, formed intracellularly, primarily in liver cells in a metabolic process of repeated reductions and oxidative methylations. Inorganic arsenic is a known human carcinogen, inducing tumors of the skin, urinary bladder, and lung. However, a good animal model has not yet been found. Although the metabolic process of inorganic arsenic appears to enhance the excretion of arsenic from the body, it also involves formation of methylated compounds of trivalent arsenic as intermediates. Trivalent arsenicals (whether inorganic or organic) are highly reactive compounds that can cause cytotoxicity and indirect genotoxicity in vitro. DMA(V) was found to be a bladder carcinogen only in rats and only when administered in the diet or drinking water at high doses. It was negative in a two-year bioassay in mice. MMA(V) was negative in 2-year bioassays in rats and mice. The mode of action for DMA(V)-induced bladder cancer in rats appears to not involve DNA reactivity, but rather involves cytotoxicity with consequent regenerative proliferation, ultimately leading to the formation of carcinoma. This critical review responds to the question of whether DMA(V)-induced bladder cancer in rats can be extrapolated to humans, based on detailed comparisons between inorganic and organic arsenicals, including their metabolism and disposition in various animal species. The further metabolism and disposition of MMA(V) and DMA(V) formed endogenously during the metabolism of inorganic arsenic is different from the metabolism and disposition of MMA(V) and DMA(V) from exogenous exposure. The trivalent arsenicals that are cytotoxic and indirectly genotoxic in vitro are hardly formed in an organism exposed to MMA(V) or DMA(V) because of poor cellular uptake and limited metabolism of the ingested compounds

  16. Learning, Memory, and Executive Function in New MDMA Users: A 2-Year Follow-Up Study

    PubMed Central

    Wagner, Daniel; Tkotz, Simon; Koester, Philip; Becker, Benjamin; Gouzoulis-Mayfrank, Euphrosyne; Daumann, Joerg

    2015-01-01

    3,4-Methylenedioxymethamphetamine (MDMA) is associated with changes in neurocognitive performance. Recent studies in laboratory animals have provided additional support for the neurodegeneration hypothesis. However, results from animal research need to be applied to humans with caution. Moreover, several of the studies that examine MDMA users suffer from methodological shortcomings. Therefore, a prospective cohort study was designed in order to overcome these previous methodological shortcomings and to assess the relationship between the continuing use of MDMA and cognitive performance in incipient MDMA users. It was hypothesized that, depending on the amount of MDMA taken, the continued use of MDMA over a 2-year period would lead to further decreases in cognitive performance, especially in visual paired association learning tasks. Ninety-six subjects were assessed, at the second follow-up assessment: 31 of these were non-users, 55 moderate-users, and 10 heavy-users. Separate repeated measures analyses of variance were conducted for each cognitive domain, including attention and information processing speed, episodic memory, and executive functioning. Furthermore, possible confounders including age, general intelligence, cannabis use, alcohol use, use of other concomitant substances, recent medical treatment, participation in sports, level of nutrition, sleep patterns, and subjective well-being were assessed. The Repeated measures analysis of variance (rANOVA) revealed that a marginally significant change in immediate and delayed recall test performances of visual paired associates learning had taken place within the follow-up period of 2 years. No further deterioration in continuing MDMA-users was observed in the second follow-up period. No significant differences with the other neuropsychological tests were noted. It seems that MDMA use can impair visual paired associates learning in new users. However, the groups differed in their use of concomitant use of

  17. Methylene chloride: a 2-year inhalation toxicity and oncogenicity study in rats

    SciTech Connect

    Nitschke, K.D.; Burek, J.D.; Bell, T.J.; Kociba, R.J.; Rampy, L.W.; McKenna, M.J.

    1988-07-01

    Male and female Sprague-Dawley rats were exposed to 0, 50, 200, or 500 ppm methylene chloride for 6 hr/day, 5 days/week for 2 years. Blood carboxyhemoglobin levels were elevated in a dose-dependent (less than linear) manner in rats exposed to 50-500 ppm methylene chloride. Histopathologic lesions related to methylene chloride exposure were confined to the liver and mammary tissue of rats. An increased incidence of hepatocellular vacuolization was observed in male and female rats exposed to 500 ppm methylene chloride. Female rats exposed to 500 ppm methylene chloride also had an increased incidence of multinucleated hepatocytes and number of spontaneous benign mammary tumors/tumor-bearing rat (adenomas, fibromas, and fibroadenomas with no progression toward malignancy); the incidence of benign mammary tumors in female rats exposed to 50 or 200 ppm methylene chloride was comparable to historical control values. No increase in the number of any malignant tumor type was observed in rats exposed to concentrations as high as 500 ppm methylene chloride. Additional groups of female rats were exposed to 500 ppm methylene chloride for the first 12 months or the last 12 months of the 24-month study. The response observed in female rats exposed to 500 ppm for the first 12 months was the same as that observed in female rats exposed to 500 ppm for 2 years. Conversely, the response observed in female rats exposed to 500 ppm during the last 12 months of the study was similar to that observed in control animals. Based upon the results of this study, the no-adverse-effect level for chronic inhalation exposure of Sprague-Dawley rats was judged to be 200 ppm methylene chloride.

  18. Learning, Memory, and Executive Function in New MDMA Users: A 2-Year Follow-Up Study.

    PubMed

    Wagner, Daniel; Tkotz, Simon; Koester, Philip; Becker, Benjamin; Gouzoulis-Mayfrank, Euphrosyne; Daumann, Joerg

    2015-01-01

    3,4-Methylenedioxymethamphetamine (MDMA) is associated with changes in neurocognitive performance. Recent studies in laboratory animals have provided additional support for the neurodegeneration hypothesis. However, results from animal research need to be applied to humans with caution. Moreover, several of the studies that examine MDMA users suffer from methodological shortcomings. Therefore, a prospective cohort study was designed in order to overcome these previous methodological shortcomings and to assess the relationship between the continuing use of MDMA and cognitive performance in incipient MDMA users. It was hypothesized that, depending on the amount of MDMA taken, the continued use of MDMA over a 2-year period would lead to further decreases in cognitive performance, especially in visual paired association learning tasks. Ninety-six subjects were assessed, at the second follow-up assessment: 31 of these were non-users, 55 moderate-users, and 10 heavy-users. Separate repeated measures analyses of variance were conducted for each cognitive domain, including attention and information processing speed, episodic memory, and executive functioning. Furthermore, possible confounders including age, general intelligence, cannabis use, alcohol use, use of other concomitant substances, recent medical treatment, participation in sports, level of nutrition, sleep patterns, and subjective well-being were assessed. The Repeated measures analysis of variance (rANOVA) revealed that a marginally significant change in immediate and delayed recall test performances of visual paired associates learning had taken place within the follow-up period of 2 years. No further deterioration in continuing MDMA-users was observed in the second follow-up period. No significant differences with the other neuropsychological tests were noted. It seems that MDMA use can impair visual paired associates learning in new users. However, the groups differed in their use of concomitant use of

  19. Prophylactic strategies in recurrent vulvovaginal candidiasis: a 2-year study testing a phytonutrient vs itraconazole.

    PubMed

    Chopra, V; Marotta, F; Kumari, A; Bishier, M P; He, F; Zerbinati, N; Agarwal, C; Naito, Y; Tomella, C; Sharma, A; Solimene, U

    2013-01-01

    The aim of the present study was to assess the clinical efficacy of a one week/month treatment with a phytocompound with antimycotic properties (K-712, with following 100 mg composition: 10 mg of oleoresin from Pseudowintera colorata at 30 percent concentration in Polygodial together with trace amounts of Olea europea) in recurrent vulvo-vaginal candidiasis (RVVC), as compared to once a week treatment with an azole drug for 24 months follow up. This prospective randomized study involving 122 women (19 to 63 years old) with a history of proven episodes of RVVC in the prior 12 months. Patients were allocated in two treatment groups of 61 patients each and given A) Itraconazole 200 mg orally once a week or B) 1 tab twice a day of K-712 for one week/month. Each treatment schedule was well tolerated with 19 patients in the azole group complaining of transient mild symptoms (nausea, abdominal discomfort, unpleasant taste), while only 3 patients on K-712 reported slight dyspepsia. The number of relapses was significantly lower in the K-712-treated group as compared to the itraconazole-group (22 vs 39, p less than 0.05). Moreover, the former group showed a significantly decreased number of cases resistant or dose-dependent susceptible as compared to group A (p less than 0.05 vs itraconazole) and the same occurred for the occurrence of non-albicans species (group A 64.1 percent vs group B 31.8 percent, p less than 0.05). The overall mycological cure at the end of the 2-year study showed a comparable benefit between the two groups. From these data it appears that the present antifungal phytonutrient is equally effective as itraconazole in the overall treatment of RVVC over a 2-year follow-up, but yielding a significantly better prophylactic effect and also maintenance benefit with lower relapse rate, antifungal susceptibility and growth of azole-resistant species.

  20. Potential carcinogenicity of foundry fumes: a comparative in vivo-in vitro study.

    PubMed

    Humfrey, C D; Levy, L S; Faux, S P

    1996-01-01

    Epidemiological studies of workers exposed to fumes in the iron and steel foundry industry have consistently demonstrated an increased relative risk of lung cancer of approximately 1.4. Foundry fume is a complex mixture of gases and fine particles generated during the casting process when molten metal is poured into sand moulds bound together with organic binders. The chemical composition of fume varies according to foundry process and, specifically, binder composition. Previous in vitro studies have demonstrated that some fumes have mutagenic activity and that this varies with fume type. The current study has examined the potential carcinogenicity of three fumes in a 2-yr in vivo rodent bioassay using an intrabronchial pellet implantation technique. The toxicity and genotoxicity of the fumes were tested concurrently in a number of in vitro assays including those identifying mutagenicity, unscheduled DNA synthesis, free radical DNA damage and micronucleus induction. The rodent bioassay failed to demonstrate a carcinogenic response, although an increase in preneoplastic lesions was seen in all fume-treated groups relative to controls. When tested in vitro, the fumes were positive in many assays and activity correlated with the polycyclic aromatic hydrocarbon content of the fumes. The employment of a combination of in vitro assays for different genotoxic endpoints, such as those presented in the current study, provides information useful for the overall assessment of carcinogenicity of complex mixtures such as foundry fume. PMID:9119322

  1. Suitability of Chinese oil well loggers for an epidemiologic study of the carcinogenic effects of neutrons.

    PubMed

    Inskip, P D; Wang, Z Y; Fen, Y S

    1991-11-01

    Neutron exposures to 191 well loggers at four oil fields in China were measured over a 3-mo period using CR-39 polycarbonate dosimeters. Doses (96% less than 0.02 mGy) were slightly lower than literature values for well loggers in North America, possibly because of differences in drilling activity. Because doses are so low, an epidemiologic study of cancer among Chinese well loggers is unlikely to be informative about the carcinogenicity of neutrons relative to sparsely ionizing radiation.

  2. [Influence of sport on isoinertial trunk muscle performance development: a 2 years prospective study].

    PubMed

    Rosset, E Bibbo; Mélot, C; Szpalski, M; Keller, T S; Balagué, F

    2013-07-17

    In this study, we investigate the relationship between either regular sports practice or a non sportive way of life, development of trunk muscle performance and occurrence of lower back pain between male schoolchildren. 93 schoolchildren were recruited, then stratified in 4 groups, according to sport practice or sedentary way of life. Participants were evaluated twice at an interval of 2 years with an interview, a physical examination and an evaluation of trunk muscle performance. We identified that basketball players have significantly better results and perfomance concerning isometric and isoinertial tests of trunk muscles than the other groups. Differences in trunk muscle performance exist following the practice of different types of sport. We can deduce that trunk muscle performance has some sport specificity.

  3. Two-year carcinogenicity study of acrylamide in Wistar Han rats with in utero exposure.

    PubMed

    Maronpot, R R; Thoolen, R J M M; Hansen, B

    2015-02-01

    Acrylamide is an important chemical with widespread industrial and other uses in addition to generalized population exposure from certain cooked foods. Previous rat studies to assess the carcinogenic potential of acrylamide have been carried out exclusively in the Fischer 344 rat with identification of a number of tumors amongst which mesotheliomas of the tunica vaginalis is an important tumor endpoint in the classification of acrylamide as a 'probably human carcinogen. In a rat carcinogenicity study to determine the human relevance of mesotheliomas Wistar Han rats were exposed to 0, 0.5, 1.5, or 3.0mg acrylamide/kg body weight/day in drinking water starting at gestation day 6. At the end of two years, mammary gland fibroadenomas in females and thyroid follicular cell tumors in both sexes were the only tumors increased in acrylamide treated rats. These tumor endpoints have rat-specific modes of action suggesting less likelihood of human cancer risk than previously estimated. This study demonstrates that tunica vaginalis mesotheliomas are strain specific and not likely of genotoxic origin.

  4. Carcinogenicity study of cochineal in B6C3F1 mice.

    PubMed

    Mori, H; Iwata, H; Tanaka, T; Morishita, Y; Mori, Y; Kojima, T; Okumura, A

    1991-09-01

    The carcinogenicity of cochineal, a red colouring used in food and other products, was studied in a 2-yr bioassay in B6C3F1 mice. Groups of 50-55 mice of each sex were given 0, 3 or 6% cochineal in the diet for 2 yr. Mice of all groups developed tumours including hepatocellular adenomas or carcinomas, pulmonary adenomas or adenocarcinomas and lymphomas or lymphatic leukaemias, and the incidences of these tumours were not significantly different in treated and control groups. The results indicate that cochineal lacks carcinogenicity in mice and are consistent with those of in vitro short-term assays of cochineal and of carminic acid, an active principle of cochineal. PMID:1937288

  5. Recent progress in studies of metallic nickel and nickel-based nanoparticles' genotoxicity and carcinogenicity.

    PubMed

    Magaye, Ruth; Zhao, Jinshun

    2012-11-01

    Recently, nanoparticles have been the focus of many research and innovation. Metallic nickel and nickel-based nanoparticles are among those being exploited. Nickel fine particles are known to be genotoxic and carcinogenic. It has been discovered that many properties of nano sized elements and materials are not present in their bulk states. The nano size of these particles renders them the ability to be easily transported into biological systems, thus raising the question of their effects on the susceptible system. Therefore scientific research on the effects of nickel nanoparticles is important. This mini-review intends to summarize the current knowledge on the genotoxicity and carcinogenicity potential of metallic nickel and nickel-based nanoparticles implicated in in vitro and in vivo mammalian studies. PMID:23000472

  6. Occurrence of Pineal Gland Tumors in Combined Chronic Toxicity/Carcinogenicity Studies in Wistar Rats.

    PubMed

    Treumann, Silke; Buesen, Roland; Gröters, Sibylle; Eichler, Jens-Olaf; van Ravenzwaay, Bennard

    2015-08-01

    Pineal gland tumors are very rare brain lesions in rats as well as in other species including humans. A total of 8 (out of 1,360 examined) Wistar rats from 3 different combined chronic toxicity/carcinogenicity or mere carcinogenicity studies revealed pineal gland tumors. The tumors were regarded to be spontaneous and unrelated to treatment. The morphology and immunohistochemical evaluation led to the diagnosis malignant pinealoma. The main characteristics that were variably developed within the tumors were the following: cellular atypia, high mitotic index, giant cells, necrosis, Homer Wright rosettes, Flexner-Wintersteiner rosettes and pseudorosettes, positive immunohistochemical reaction for synaptophysin, and neuron-specific enolase. The pineal gland is not a protocol organ for histopathological examination in carcinogenicity studies. Nevertheless, the pineal gland can occasionally be encountered on the routine brain section or if it is the origin of a tumor protruding into the brain, the finding will be recorded. Therefore, although known to be a rare tumor in rats, pineal neoplasms should be included in the list of possible differential diagnoses for brain tumors, especially when the tumor is located in the region of the pineal body.

  7. The Prevalence of Autism Spectrum Disorders in Toddlers: A Population Study of 2-Year-Old Swedish Children

    ERIC Educational Resources Information Center

    Nygren, Gudrun; Cederlund, Mats; Sandberg, Eva; Gillstedt, Fredrik; Arvidsson, Thomas; Gillberg, I. Carina; Andersson, Gunilla Westman; Gillberg, Christopher

    2012-01-01

    Autism Spectrum Disorder (ASD) is more common than previously believed. ASD is increasingly diagnosed at very young ages. We report estimated ASD prevalence rates from a population study of 2-year-old children conducted in 2010 in Gothenburg, Sweden. Screening for ASD had been introduced at all child health centers at child age 21/2 years. All…

  8. A review of some epidemiological studies on cancer risk from low-dose radiation or other carcinogenic agents.

    PubMed

    Ogata, Hiromitsu

    2011-07-01

    It is extremely difficult to assess cancer risks accurately due to health effects of low-dose radiation exposure or other carcinogens based on epidemiological studies. For the detection of minute increases of the risk at low-level exposure, most of epidemiological studies lack statistical power, and they involve various complicated confounding factors. This paper reports on a literature survey of epidemiological studies published since 2000 on cancer risks associated with low-dose radiation and other carcinogens to gather major epidemiological data. Integrated risk indices were derived from those data by using, where possible, statistical models. Regarding risk assessment of low-dose radiation exposure, it is important to lower the degree of uncertainty arising from risk estimation. Risk assessment of low-dose radiation exposure could be scientific evidence when uncertainty is considered in comparing carcinogenic risks of radiation with those of other carcinogens.

  9. A chronic toxicity/carcinogenicity study of FD & C Yellow No. 5 (tartrazine) in mice.

    PubMed

    Borzelleca, J F; Hallagan, J B

    1988-03-01

    Charles River CD-1 mice were fed FD & C Yellow No. 5 in the diet at levels of 0.0, 0.0, 0.5, 1.5 or 5.0% in a long-term toxicity/carcinogenicity study. Each group consisted of 60 males and 60 females. Maximum exposure was 104 wk for both males and females. No consistent, significant compound-related adverse effects were noted. The no-observed-adverse effect level established in this study was 5.0% (8103 mg/kg/day and 9735 mg/kg/day for male and female mice, respectively.)

  10. Residue level and dissipation pattern of spiromesifen in cabbage and soil from 2-year field study.

    PubMed

    Siddamallaiah, Lekha; Mohapatra, Soudamini

    2016-03-01

    Spiromesifen is a new class of insecticide used for the control of whiteflies and mites which have developed resistance to the more commonly used neonicotinoids. Dissipation pattern of spiromesifen on cabbage was evaluated over 2 years by conducting supervised field studies as per good agricultural practices. Cabbage and soil samples were extracted and purified using modified QuEChERS method and analyzed through gas chromatography (GC). Confirmatory studies were carried out by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The recoveries of spiromesifen from cabbage and soil were between 85.44 and 103.37% with the relative standard deviation (RSD) between 3.2 and 9.4% (n = 6). The limit of detection (LOD) and limit of quantification (LOQ) were 0.003 μg mL(-1) and 0.01 mg kg(-1), respectively. The measurement uncertainties (MUs) were within 9.9-14.9%. Initial residues of spiromesifen on cabbage were 0.640 and 1.549 mg kg(-1) during 2013 and 0.723 and 1.438 mg kg(-1) during 2014 from treatments at standard and double doses of 125 and 250 g active ingredient (a.i.) ha(-1), respectively. Spiromesifen residue dissipation followed first-order rate kinetics, and it degraded within the half-lives of 2.9 and 3.9 days during 2013 and 3.2 and 4.5 days during 2014. The residue levels reached below the maximum residue limit (MRL; 0.02 mg kg(-1)) within 15-17 days at the standard dose and 24-27 days at the double dose. The field soil analyzed at harvest (30 days) was free from spiromesifen residues. Metabolite spiromesifen-enol was not detected in any sample which was confirmed through LC-MS/MS analysis.

  11. Residue level and dissipation pattern of spiromesifen in cabbage and soil from 2-year field study.

    PubMed

    Siddamallaiah, Lekha; Mohapatra, Soudamini

    2016-03-01

    Spiromesifen is a new class of insecticide used for the control of whiteflies and mites which have developed resistance to the more commonly used neonicotinoids. Dissipation pattern of spiromesifen on cabbage was evaluated over 2 years by conducting supervised field studies as per good agricultural practices. Cabbage and soil samples were extracted and purified using modified QuEChERS method and analyzed through gas chromatography (GC). Confirmatory studies were carried out by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The recoveries of spiromesifen from cabbage and soil were between 85.44 and 103.37% with the relative standard deviation (RSD) between 3.2 and 9.4% (n = 6). The limit of detection (LOD) and limit of quantification (LOQ) were 0.003 μg mL(-1) and 0.01 mg kg(-1), respectively. The measurement uncertainties (MUs) were within 9.9-14.9%. Initial residues of spiromesifen on cabbage were 0.640 and 1.549 mg kg(-1) during 2013 and 0.723 and 1.438 mg kg(-1) during 2014 from treatments at standard and double doses of 125 and 250 g active ingredient (a.i.) ha(-1), respectively. Spiromesifen residue dissipation followed first-order rate kinetics, and it degraded within the half-lives of 2.9 and 3.9 days during 2013 and 3.2 and 4.5 days during 2014. The residue levels reached below the maximum residue limit (MRL; 0.02 mg kg(-1)) within 15-17 days at the standard dose and 24-27 days at the double dose. The field soil analyzed at harvest (30 days) was free from spiromesifen residues. Metabolite spiromesifen-enol was not detected in any sample which was confirmed through LC-MS/MS analysis. PMID:26869045

  12. Suppression of Alcohol Dependence Using Baclofen: A 2-Year Observational Study of 100 Patients

    PubMed Central

    de Beaurepaire, Renaud

    2012-01-01

    Aims: The purpose of this study was to examine the long-term effects of baclofen in a large cohort of alcohol-dependent patients compliant to baclofen treatment. Methods: A hundred patients with alcohol dependence, resistant to usual treatments, were treated with escalating doses of baclofen (no superior limit). Alcohol consumption (in grams) and craving for alcohol were assessed before treatment and at 3, 6, 12, and 24 months. Assessments were simply based on patients’ statements. The outcome measure was the consumption of alcohol, rated according to the World Health Organization criteria for risk of chronic harm. Results: While all patients were rated “at high risk” at baseline, approximately half of them were rated “at low risk” at 3, 6, 12, and 24 months. The sum of patients who were at “low risk” and at “moderate risk” (improved patients) was 84% at 3 months, 70% at 6 months, 63% at 1 year, and 62% at 2 years. The constancy of improvement over the 2-years was remarkable. The average maximal dose of baclofen taken was 147 mg/day. Ninety-two percentage of patients reported that they experienced the craving-suppressing effect of baclofen. Significant relationships were found between the amount in grams of alcohol taken before treatment and the maximal dose of baclofen required, and between the existence of a mental disorder and a lesser effect of baclofen. Conclusion: Baclofen produces an effortless decrease or suppression of alcohol craving when it is prescribed with no superior limit of dose. Potential limitations in the effectiveness of baclofen include the coexistence of a mental disorder, the concomitant use of other psychotropic drugs, a lack of real motivation in patients to stop drinking, and the impossibility to reach the optimal dose of baclofen because of unbearable side-effects (sometimes possibly related to too sharp a protocol of dose escalation). PMID:23316172

  13. Monitoring Cyp2b10 mRNA expression at cessation of 2-year carcinogenesis bioassay in mouse liver provides evidence for a carcinogenic mechanism devoid of human relevance: The dalcetrapib experience

    SciTech Connect

    Hoflack, J-C.; Mueller, L. Fowler, S.; Braendli-Baiocco, A.; Flint, N.; Kuhlmann, O.; Singer, T.; Roth, A.

    2012-03-15

    Introduction: Dalcetrapib is a cholesteryl ester transfer protein (CETP) modulator in clinical assessment for cardiovascular outcome benefits. In compliance with regulatory requirements, dalcetrapib was evaluated in rodent 2-year carcinogenesis bioassays. In the mouse bioassay, male mice demonstrated increased liver weight and statistically increased incidences of hepatocellular adenoma/carcinoma. Hepatic cytochrome p450 (Cyp) 2b10 mRNA induction and increased Cyp2b10 enzyme activity signify activation of hepatic nuclear receptor constitutive androstane receptor (CAR), a widely established promoter of rodent-specific hepatic tumors. We therefore monitored hepatic Cyp2b10 mRNA and its enzyme activity in a subset of dalcetrapib-treated male mice from the bioassay. Methods: Liver samples were obtained from ∼ 1/3 of male mice from each dose group including vehicle-controls (mean and earliest study day of death 678 and 459 respectively). Quantitative real time PCR (qRT-PCR) was performed to determine Cyp2b10 mRNA expression and Cyp1a-, Cyp2b10- and Cyp3a-selective activities were monitored. Results: Cyp2b10 mRNA was strongly induced by dalcetrapib with an expected wide inter-individual variation (5–1421-fold). Group average fold-induction versus vehicle-controls showed a dose-related increase from 48-fold (250 mg/kg/day) to 160-fold (750 mg/kg/day), which declined slightly at 2000 mg/kg/day (97-fold). Cyp enzyme activities showed approximate doubling of total Cyp P450 content per milligram protein and a 9-fold increase in Cyp2b10-selective pentoxyresorufin O-dealkylase activity (750 mg/kg/day). Discussion: These data from hepatic Cyp2b10 monitoring are strongly suggestive of CAR activation by dalcetrapib, a mechanism devoid of relevance towards hepatocarcinogenesis in humans; results show feasibility of Cyp2b10 as a surrogate marker for this mechanism at cessation of a carcinogenesis bioassay. -- Highlights: ► Liver tumors were induced in male mice by dalcetrapib

  14. Treatment adherence among new triptan users: a 2-year cohort study in Taiwan

    PubMed Central

    2014-01-01

    Background The persistence of triptan use among newly prescribed users is low in the United States and European countries. However, triptan refill patterns in Asian primary care practices have not been well described. Methods Data from the National Health Insurance Research Database in Taiwan were used to conduct a retrospective cohort analysis from 2005 to 2008. All participants were followed for 2 years after receiving a new triptan prescription. Refill and 2-year retention rates of newly prescribed triptans were calculated, and predictors of the first triptan refill and 2-year retention were analyzed. Results Of the 13,951 participants with a new triptan prescription (99.9% sumatriptan), 67.4% were prescribed by a neurologist, 67.4% were prescribed at least one prophylactic agent for migraine. Of them, 34.3% adhered to the newly prescribed triptan at the first refill, 0.01% switched to another triptan, and 40.9% switched to a non-triptan acute migraine medication. The 2-year retention rate was 4.0%. The frequency of headache-related neurologic visits for 1 year before the index date, first prescription of triptan or other acute medications, first triptan prescription by a neurologist, and prophylactic use were associated with higher first refill rates. The frequency of headache-related neurologic visits 1 year before the index date and first triptan prescription by a neurologist were related to higher 2-year retention rates. Diabetes mellitus and first triptan prescription at a local medical clinic were associated with reduced probability of continued triptan use at the first refill and 2 years. Conclusions Similar to Western societies, the refill and 2-year retention rates were low in new users of triptans. Frequency of neurologic visits and triptan prescription by a neurologist were significant predictors of adherence. PMID:25117594

  15. Suitability of Chinese oil well loggers for an epidemiologic study of the carcinogenic effects of neutrons.

    PubMed

    Inskip, P D; Wang, Z Y; Fen, Y S

    1991-11-01

    Neutron exposures to 191 well loggers at four oil fields in China were measured over a 3-mo period using CR-39 polycarbonate dosimeters. Doses (96% less than 0.02 mGy) were slightly lower than literature values for well loggers in North America, possibly because of differences in drilling activity. Because doses are so low, an epidemiologic study of cancer among Chinese well loggers is unlikely to be informative about the carcinogenicity of neutrons relative to sparsely ionizing radiation. PMID:1752747

  16. Clinical and biologic factors related to oral implant failure: a 2-year follow-up study.

    PubMed

    Moheng, Patrick; Feryn, Jean-Marc

    2005-09-01

    The purpose of this study is to evaluate urinary biomarkers of bone formation and resorption as predictive factors for oral implant failure, and to contribute to the knowledge of factors related to oral implant failure. A total of 93 patients between 18 and 85 years old, with an indication of oral implant, were eligible in this 2-year prospective, open, and nonrandomized study. Patients who had bone graft before implantation or presented with prosthetic difficulties (implant-to-crown ratio < 1, and/or unfavorable intermaxillary space) were excluded. All patients received either Frialit-2 (Friadent, Mannheim, Germany), cylinder, or screwed implants or IMZ Twin Plus (Friadent), cylinder implants, with FRIOS (Friadent) titanium coating. Serum osteocalcin, and urinary pyridinoline and deoxypyridinoline were measured, together with bone density at implant location. The primary endpoint (implant failure) was the implant removal (radiographic evidence of peri-implant bone loss and/or pockets). Factors related to implant failure were analyzed using multilevel logistic regression models to consider within-patient effects. Of the 93 patients included, 61% were female, and 16% were current smokers. A total of 266 oral implants were placed and analyzed, with a mean number of 3.1 implants by patient. Eleven and 15% of bone locations scored at D1 and D4, respectively, for the Misch bone density scoring. The majority of implants (72%) were placed more than 3 months after tooth extraction, using a Frialit-2 system in 73% of cases. The mean of osteocalcin was 17.3 (+/-9.4) ng/L; those of pyridinoline and deoxypyridinoline were 33.2 (+/-15.8) and 10.2 (+/-11.9) mmol per creatinine mmol, respectively. At one-year, 95.5% (95% confidence interval 92.5-97.5) of implants have not been removed. One year later, no further implant failed. In both univariate and multivariate analysis, osteocalcin, pyridinoline, and deoxypyridinoline were not significant predictive factors of oral implant

  17. Animal carcinogenicity studies on radiofrequency fields related to mobile phones and base stations

    SciTech Connect

    Dasenbrock, Clemens . E-mail: clemens-dasebrock@bc.boehringer-ingelheim.com

    2005-09-01

    Since a report in 1997 on an increased lymphoma incidence in mice chronically exposed to a mobile phone radiofrequency signal, none of the subsequent long-term studies in rodents have confirmed these results. On the other hand, several of the follow-up co- and carcinogenicity studies are still underway or are presently being initiated. Most of the published long-term studies used 1 exposure level only and suffer from a poor dosimetry which does not consider the animal's growth. Additional points of criticism are a limited, in some cases, questionable histopathology and inadequate group sizes. Overall, if dealing with new chemicals or drugs, these studies would not be acceptable for registration with the responsible authorities. The major critical points are taken into consideration within the European co- and carcinogenicity projects (CEMFEC and PERFORM-A), which are in their final stages and in the US long-term studies in mice and rats which are about to be initiated. Nevertheless, the WHO evaluation for health risk assessment of long-term telephone use and base station exposure will start in late 2005.

  18. Mutagenicity and carcinogenicity studies of homemade "rust-proof cutting fluid".

    PubMed

    Wang, D; Huang, W Q; Wang, H W

    1988-01-01

    A homemade rust-proof cutting fluid (RPCF) used in China was tested for carcinogenicity by an in vivo chronic experiment and for mutagenicity by the Ames Salmonella microsomal assay. Undiluted and threefold water-diluted fluid were given as drinking water to groups of young adult Wistar rats for 2 years. The treatment induced 11/40 malignant tumors with 9/40 acinar adenocarcinomas of the pancreas in the high-dose group. Simultaneous administration of ascorbic acid dissolved in the undiluted fluid at 2 g acid per 1 g sodium nitrite resulted in 1/40 pancreatic carcinoma. The results of the Ames test showed that the technical RPCF was mutagenic to TA100 with or without metabolic activation. It was concluded that the homemade RPCF, which is comprised of sodium nitrite, triethanolamine, and polyethylene glycol, may form direct-acting mutagen(s) upon storage and form, in vivo, e.g., nitrosamines that caused acinar pancreatic carcinoma in Wistar rats. Simultaneous administration of ascorbic acid is suggested for the protection of workers exposed to the rust-proof cutting fluid.

  19. Mutagenicity and carcinogenicity studies of homemade rust-proof cutting fluid

    SciTech Connect

    Wang, D.; Huang, W.Q.; Wang, H.W.

    1988-01-01

    A homemade rust-proof cutting fluid (RPCF) used in China was tested for carcinogenicity by an in vivo chronic experiment and for mutagenicity by the Ames Salmonella microsomal assay. Undiluted and threefold water-diluted fluid were given as drinking water to groups of young adult Wistar rats for 2 years. The treatment induced 11/40 malignant tumors with 9/40 acinar adenocarcinomas of the pancreas in the high-dose group. Simultaneous administration of ascorbic acid dissolved in the undiluted fluid at 2 g acid per 1 g sodium nitrite resulted in 1/40 pancreatic carcinoma. The results of the Ames test showed that the technical RPCF was mutagenic to TA100 with or without metabolic activation. It was concluded that the homemade RPCF, which is comprised of sodium nitrite, triethanolamine, and polyethylene glycol, may form direct-acting mutagen(s) upon storage and form, in vivo, e.g., nitrosamines that caused acinar pancreatic carcinoma in Wistar rats. Simultaneous administration of ascorbic acid is suggested for the protection of workers exposed to the rust-proof cutting fluid.

  20. Lifetime toxicity/carcinogenicity studies of FD & C red no. 40 (allura red) in mice.

    PubMed

    Borzelleca, J F; Olson, J W; Reno, F E

    1991-05-01

    FD & C Red No. 40 (allura red) was fed to Charles River HaM/ICR (CD-1) (study A) and CD-1 outbred (study B) mice as a dietary admixture in two separate lifetime toxicity/carcinogenicity studies. Each study included an in utero exposure phase during which the colouring was fed at dietary concentrations of 0.0, 0.37, 1.39 or 5.19% throughout the mating, gestation and lactation periods. After random selection, the lifetime exposure phase was initiated using the same dietary concentrations with 50 mice/sex/group in study A and 100 mice/sex/group in study B. Exposure was for 104 wk in study A and 109 wk in study B. No compound-related adverse effects were observed. The no-observable-adverse-effect level in these studies was 5.19%; approximately 7300 and 8300 mg/kg body weight/day for male and female mice, respectively.

  1. The retrospective study of the carcinogenic hydrocarbon benz[a]pyrene in the biosphere.

    PubMed

    Ilnitsky, A P; Vinogradov, V N; Riabchun, V K; Mischenko, V S; Gvildis, V Y; Belitsky, G A; Shabad, L M

    1979-11-01

    The major aim of this study was to determine taking, as an example, the carcinogenic polycyclic aromatic hydrocarbon benz[a]pyrene (BaP), the present biologically active compounds in the early historical and geological epochs with the following assessment of the degree of danger of such compounds in the modern times. In the first section of work, study results of soil samples in the areas of eternal frost confirmed the presence of BaP in the frozen layers of soil aged 10 years, 100 years, 3000--4000 and 10,000 years of age. In the second part of the work, results are furnished on the BaP content in the ice of modern glaciers and their moraines, located in Kamchatka. BaP was found in 11 samples in the concentration of 0.001--0.003 microgram/l. These data represent the first results in the retrospective study of carcinogenic substances in the biosphere. PMID:509419

  2. Vanadium carcinogenic, immunotoxic and neurotoxic effects: a review of in vitro studies.

    PubMed

    Zwolak, Iwona

    2014-01-01

    Deleterious health effects induced by inorganic vanadium compounds are linked with carcinogenic, immunotoxic and neurotoxic insults. The goal of this review is to provide a summary of mammalian cell culture studies (from the 1990s to most recent) looking into the mode of the above-mentioned adverse actions of vanadium. Regarding the carcinogenicity potential, the key cell-based studies have evidenced the ability of vanadium to induce genotoxic lesions, cell morphological transformation and anti-apoptotic effects in a certain type of cells. Two contradictory effects of vanadium on the immune functions of cells have been observed in cell culture studies. The first effect involves reduction of cell immune responses such as vanadium-dependent inhibition of cytokine-inducible functions, which may underlie the mechanism of vanadium-induced immunosuppression. The second one involves stimulation of immune activity, for example, a vanadium-mediated increase in cytokine production, which may contribute to vanadium-related inflammation. So far, an in vitro evaluation of vanadium neurotoxicity has only been reported in few articles. These papers indicate probable cytotoxic mechanisms resulting from exposure of neurons and glial cells to vanadium. In summary, this literature review collects in vitro reports on adverse vanadium effects and thus provides vanadium researchers with a single, concise source of data.

  3. Asbestos use and carcinogenicity in Germany and a comparison with animal studies.

    PubMed

    Pott, F

    1994-08-01

    The centralized structure of economic affairs in the former German Democratic Republic (East Germany) and the isolation from the free market led to the situation that imported asbestos was almost exclusively chrysotile. More than 90% came from the Kiembay mining area in the Ural Mountains, and about 7% was long-fibre chrysotile from Canada. Sturm and co-workers detected 1082 mesothelioma cases from 1960 to 1990 in the counties of Magdeburg and Halle. In 843 of these cases an exposure to asbestos was evident. Seventy-two cases were exposed to chrysotile only. Suspected exposure to amphiboles imported before World War II or to fibre contained in talc could not be substantiated. Up to now, there have been no analyses of lung fibre burdens from such cases. Reviewing the carcinogenicity studies in rats performed by inhalation or intra-cavitary injection of chrysotile, amosite and crocidolite fibres, the results give no clear indication of a lower carcinogenic potency per chrysotile fibre than per amphibole fibre if equal fibre numbers and fibre sizes are applied, although the chrysotile content of the lungs is relatively low. Also the mesothelioma rates after inhalation exposure to extremely high concentrations of the different asbestos fibre types are similar for chrysotile and the amphiboles and in the region of 5%. Compared with the asbestos-related cancer rates in chrysotile textile workers, rats have to be exposed to a more than 100-fold higher fibre concentration than humans to induce the same lung tumour incidence.

  4. A carcinogenicity study with mutagenic organic concentrates of drinking-water in the Netherlands.

    PubMed

    Kool, H J; Kuper, F; van Haeringen, H; Koeman, J H

    1985-01-01

    The carcinogenicity in male and female Wistar SSP TOX rats of organic drinking-water concentrates that are positive in the Ames test was studied at three doses. The organic mutagenic concentrates were prepared weekly from drinking-water from one location in The Netherlands by adsorption onto XAD-4/8 resins and elution with dimethylsulphoxide. The organic concentrates in dimethylsulphoxide were mixed with non-mutagenic drinking-water before exposure of the rats. Dose levels were based on multiples of expected human exposure levels. For the calculation the average human daily intake of drinking-water was taken as 2 litres for a body weight of 70 kg. There was no significant increase in tumour induction when male Wistar SSP TOX rats were exposed for 106 wk to 4.5, 14 or 40 times the expected human exposure level and females to 7,22 or 68 times the human level. The development and types of tumours were similar in the treated and control groups. The numbers of animals with tumours and of animals that died as a result of tumours in the exposed groups did not differ significantly from those in the control groups. These results suggest that these organic mutagenic drinking-water concentrates did not contain very potent carcinogens in effective concentrations.

  5. Asbestos use and carcinogenicity in Germany and a comparison with animal studies.

    PubMed

    Pott, F

    1994-08-01

    The centralized structure of economic affairs in the former German Democratic Republic (East Germany) and the isolation from the free market led to the situation that imported asbestos was almost exclusively chrysotile. More than 90% came from the Kiembay mining area in the Ural Mountains, and about 7% was long-fibre chrysotile from Canada. Sturm and co-workers detected 1082 mesothelioma cases from 1960 to 1990 in the counties of Magdeburg and Halle. In 843 of these cases an exposure to asbestos was evident. Seventy-two cases were exposed to chrysotile only. Suspected exposure to amphiboles imported before World War II or to fibre contained in talc could not be substantiated. Up to now, there have been no analyses of lung fibre burdens from such cases. Reviewing the carcinogenicity studies in rats performed by inhalation or intra-cavitary injection of chrysotile, amosite and crocidolite fibres, the results give no clear indication of a lower carcinogenic potency per chrysotile fibre than per amphibole fibre if equal fibre numbers and fibre sizes are applied, although the chrysotile content of the lungs is relatively low. Also the mesothelioma rates after inhalation exposure to extremely high concentrations of the different asbestos fibre types are similar for chrysotile and the amphiboles and in the region of 5%. Compared with the asbestos-related cancer rates in chrysotile textile workers, rats have to be exposed to a more than 100-fold higher fibre concentration than humans to induce the same lung tumour incidence. PMID:7978982

  6. Janus carcinogens and mutagens.

    PubMed

    von Borstel, R C; Higgins, J A

    1998-06-18

    Janus carcinogens are carcinogenic agents that, under differing conditions of cell type or dose, can instead act as anticarcinogens. Studies by Haseman and Johnson [J.K. Haseman, F.M. Johnson, Analysis of rodent NTP bioassay data for anticarcinogenic effects, Mutat. Res. , 350 (1996) 131-142], have demonstrated that many chemicals that are carcinogenic for one tissue type can have anticarcinogenic action on another tissue type. As Magni et al. [G.E. Magni, R.C. von Borstel, S. Sora, Mutagenic action during meiosis and antimutagenic action during mitosis by 5-aminoacridine in yeast, Mutat. Res., 1 (1964) 227-230] have shown in 1964, this principle holds true for chemical mutagens as well, that is 9-aminoacridine is an antimutagen in the vegetative cell and a mutagen in the sporulating cell. The conclusion can be drawn that two established carcinogens, tobacco and ionizing radiation, are indeed Janus carcinogens. In their review of 'ambiguous carcinogens' (their name), Weinberg and Storer [A.M. Weinberg, J.B. Storer, Ambiguous carcinogens and their regulation, Risk Anal., 5 (1985) 151-156], pointed out that tobacco can be classified as an ambiguous carcinogen. The strong carcinogenicity and anticarcinogenicity of tobacco smoke and/or tobacco itself (i.e., chewing tobacco) may be due to components in the mixture, not that of a single carcinogenic chemical that also may be anticarcinogenic. Kondo [S. Kondo, Health Effects of Low-Level Radiation, Kinki Univ. Press, Osaka, Japan and Medical Physics Publishing, Madison, WI, 1995, 213 pp.] has compiled data that demonstrate that human populations who survive exposures to ionizing radiation generally live longer and have less cancer than unirradiated human populations, and this Janus phenomenon goes beyond the more trivial concept of increased sensitivity to radiation of rapidly dividing tumor cells. Thiabendazole is an interesting compound in that it is both aneugenic and antimutagenic, and yet it does not appear to be a

  7. Spontaneous nonneoplastic lesions in control Syrian hamsters in three 24-month long-term carcinogenicity studies.

    PubMed

    McInnes, Elizabeth F; Ernst, Heinrich; Germann, Paul-Georg

    2015-02-01

    Information about the incidence of spontaneously occurring, nonneoplastic background findings in Syrian hamsters is essential if Syrian hamsters are to be used for toxicity studies. Male and female Syrian hamsters of the strain Han:AURA from the Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM) breeding colony were maintained as control animals for carcinogenicity studies and were examined for the presence of nonneoplastic background findings either when they died or when the study was terminated. The nonneoplastic background lesions observed at an incidence of >50% (high), >25% (moderate), and >10% (low) in either male or female animals or in both sexes in one or more long-term studies are detailed. The results are compared to previous published reports of nonneoplastic, spontaneous background lesions in Syrian hamsters. Background information about the incidence of background lesions in Syrian hamsters on short- and long-term studies is useful to both toxicologists and toxicological pathologists.

  8. Carcinogen File.

    ERIC Educational Resources Information Center

    Environment, 1978

    1978-01-01

    First in a series of bulletins designed to provide information about the problem of carcinogens in the environment is on benzo(a)pyrine. Benzo(a)pyrine is a proven cancer-causing substance that has been known for over ten years to occur in broiled sausages, gas-broiled fish and beef steak, and charcoal-broiled meat. (Author/BB)

  9. Chronic toxicity and carcinogenicity studies with the insecticide endosulfan in rats and mice.

    PubMed

    Hack, R; Ebert, E; Leist, K H

    1995-11-01

    The insecticide endosulfan was evaluated for chronic toxicity and carcinogenicity in long-term feeding studies in both Sprague-Dawley rats and NMRI mice. Dietary concentrations of the test substance were administered to rats at 0, 3, 7.5, 15 and 75 ppm and to mice at 0, 2, 6 and 18 ppm for 24 months each. In the rat study, only the treatment with the highest dose caused a significant reduction of body weight gains of the males and females at 75 ppm. The increased incidence of enlarged kidneys seen at autopsy at 75 ppm in females, and the slightly increased incidence of progressive glomerulonephrosis and slightly increased incidence of renal aneurysms seen histopathologically in the 75 ppm males, make the kidney the target organ in rats. On the basis of these findings a dietary concentration of 15 ppm is considered to be the no-observed-effect level (NOEL) in rats, equivalent to a daily test substance intake of 0.6 mg/kg body weight in males and 0.7 mg/kg body weight in females. In the mouse study, the treatment with 18 ppm caused a significant increase of mortality in the females and a slight (in the first third of the study, significant) reduction of body weight gain in males. Since there were no other substance-related findings, the dietary concentration of 6 ppm is considered to be the NOEL in mice, equivalent to a daily test substance intake of 0.84 mg/kg body weight in males and 0.97 mg/kg body weight in females. An evaluation of all relevant tumour data gained in both studies revealed no differences between control and treated groups. It was concluded, therefore, that endosulfan has no carcinogenic potential.

  10. Ovarian toxicity and carcinogenicity in eight recent national toxicology program studies

    SciTech Connect

    Maronpot, R.R.

    1987-08-01

    Ovarian toxicity and/or carcinogenicity has been documented for at least eight chemicals recently tested in National Toxicity Program prechronic and chronic rodent studies. The chemicals that yielded treatment-related ovarian lesions were 1,3-butadiene, 4-vinylcyclohexene, vinylcylohexene deipoxide, nitrofurantoin, nitrofurazone, benzene, ..delta..-9-tetrahydrocannabinol, and tricresylphosphate. Typical nonneoplastic ovarian changes included hypoplasia, atrophy, follicular necrosis, and tubular hyperplasia. The most commonly observed treatment-related neoplasms were granulosa cell tumors and benign mixed tumors. A relationship between antecedent ovarian hypoplasia, atrophy, and hyperplasia and subsequent ovarian neoplasia is supported by some of these National Toxicology Program studies. Pathologic changes in other tissues such as the adrenal glands and uterus were associated with the treatment-related ovarian changes.

  11. Resveratrol modulates drug- and carcinogen-metabolizing enzymes in a healthy volunteer study.

    PubMed

    Chow, H-H Sherry; Garland, Linda L; Hsu, Chiu-Hsieh; Vining, Donna R; Chew, Wade M; Miller, Jessica A; Perloff, Marjorie; Crowell, James A; Alberts, David S

    2010-09-01

    Resveratrol has been shown to exhibit cancer-preventive activities in preclinical studies. We conducted a clinical study to determine the effect of pharmacologic doses of resveratrol on drug- and carcinogen-metabolizing enzymes. Forty-two healthy volunteers underwent baseline assessment of cytochrome P450 (CYP) and phase II detoxification enzymes. CYP1A2, CYP2D6, CYP2C9, and CYP3A4 enzyme activities were measured by the metabolism of caffeine, dextromethorphan, losartan, and buspirone, respectively. Blood lymphocyte glutathione S-transferase (GST) activity and GST-pi level and serum total and direct bilirubin, a surrogate for UDP-glucuronosyl transferase (UGT) 1A1 activity, were measured to assess phase II enzymes. After the baseline evaluation, study participants took 1 g of resveratrol once daily for 4 weeks. Enzyme assessment was repeated upon intervention completion. Resveratrol intervention was found to inhibit the phenotypic indices of CYP3A4, CYP2D6, and CYP2C9 and to induce the phenotypic index of 1A2. Overall, GST and UGT1A1 activities were minimally affected by the intervention, although an induction of GST-pi level and UGT1A1 activity was observed in individuals with low baseline enzyme level/activity. We conclude that resveratrol can modulate enzyme systems involved in carcinogen activation and detoxification, which may be one mechanism by which resveratrol inhibits carcinogenesis. However, pharmacologic doses of resveratrol could potentially lead to increased adverse drug reactions or altered drug efficacy due to inhibition or induction of certain CYPs. Further clinical development of resveratrol for cancer prevention should consider evaluation of lower doses of resveratrol to minimize adverse metabolic drug interactions. PMID:20716633

  12. Equipping public health professionals for youth engagement: lessons learned from a 2-year pilot study.

    PubMed

    Sahay, Tina Binita; Rempel, Benjamin; Lodge, Jennifer

    2014-01-01

    There is strong evidence of the positive role that youth engagement programs and policies play in creating resiliency and producing positive outcomes among youth populations, such as delaying or avoiding the onset of risk-taking behaviors. Research also suggests that achieving positive outcomes ideally includes influence from the individual, the family, the school, the community, and the field of public health (available in A Research Report and Recommendations for Ontario Public Health Association). The authors conducted a comprehensive evaluation of a 2-year pilot project designed to increase the application of engagement and resiliency theory, knowledge, and skills among public health professionals engaging students from Grades 6, 7, and 8 (11- to 14-year-olds). Qualitative methods assessed public health satisfaction with training, resources, and networking activities, whereas quantitative methods assessed changes in capacity with respect to youth engagement knowledge, awareness, confidence, and skills. The findings have helped shed light on public health professional needs concerning capacity and confidence to undertake youth engagement work. Key lessons learned about making youth engagement possible and effective for public health professionals are presented. PMID:23271719

  13. Equipping public health professionals for youth engagement: lessons learned from a 2-year pilot study.

    PubMed

    Sahay, Tina Binita; Rempel, Benjamin; Lodge, Jennifer

    2014-01-01

    There is strong evidence of the positive role that youth engagement programs and policies play in creating resiliency and producing positive outcomes among youth populations, such as delaying or avoiding the onset of risk-taking behaviors. Research also suggests that achieving positive outcomes ideally includes influence from the individual, the family, the school, the community, and the field of public health (available in A Research Report and Recommendations for Ontario Public Health Association). The authors conducted a comprehensive evaluation of a 2-year pilot project designed to increase the application of engagement and resiliency theory, knowledge, and skills among public health professionals engaging students from Grades 6, 7, and 8 (11- to 14-year-olds). Qualitative methods assessed public health satisfaction with training, resources, and networking activities, whereas quantitative methods assessed changes in capacity with respect to youth engagement knowledge, awareness, confidence, and skills. The findings have helped shed light on public health professional needs concerning capacity and confidence to undertake youth engagement work. Key lessons learned about making youth engagement possible and effective for public health professionals are presented.

  14. Human carcinogens: an evaluation study via the COMPACT and HazardExpert procedures.

    PubMed

    Lewi, D F V; Bird, M G; Jacobs, M N

    2002-03-01

    The results of computer-optimized molecular parametric analysis of chemical toxicity (COMPACT) and HazardExpert evaluations on 14 established human carcinogens are reported. The concordances between COMPACT and carcinogenicity (71%) and between HazardExpert and carcinogenicity (57%) are significantly improved when taken in combination, where all 14 carcinogens are correctly identified by the two systems used in conjunction. However, if a negative energy of the highest occupied molecular orbital (E(HOMO)) value is regarded as evidence of electrophilic reactivity likely to give rise to mutagenicity and carcinogenicity, then 13/14 (93%) of the carcinogens are correctly identified by combination with the COMPACT procedure alone. It is possible, therefore, to establish likely carcinogenicity arising from either P450 mediation (CYP1 and CYP2E) or compound electrophilicity via the employment of a straightforward approach to molecular and electronic structure calculation, a process that can be performed in a relatively short time frame (i.e., less than 1 hour per chemical) and at a low cost. PMID:12102536

  15. Significance of durability of mineral fibers for their toxicity and carcinogenic potency in the abdominal cavity of rats in comparison with the low sensitivity of inhalation studies.

    PubMed Central

    Pott, F; Roller, M; Kamino, K; Bellmann, B

    1994-01-01

    At the same time that carcinogenicity of very thin glass fibers after intrapleural and intraperitoneal (ip) administration was demonstrated (1,2) researchers found that gypsum fibers and HCI-leached chrysotile fibers were easily soluble in the peritoneal cavity. This led to the conclusion that the chemical composition of fibers was not responsible for the carcinogenesis but that the degree of carcinogenic potency of a fiber depended on the extent to which it retained its fibrous structure. A thin glass fiber with a low biodurability did not induce tumors after ip injection of a high dose, although the ip test had been criticized for being "overly sensitive." The ip model has been the most successful for determining carcinogenicity of inorganic fibers and establishing dose-response relationships; but to determine the possibilities and limitations of this test model, very high doses of nonfibrous silicon carbide and of a slightly durable glass fiber type were injected ip in Wistar rats. No obviously acute or chronic toxic effect was observed in 90 weeks, but there was a 40% incidence of serosal tumors in the group treated with glass fibers. A pilot study on the persistence of slag fibers in the omentum of rats after ip injection showed a half-time of about 1 year. It was calculated that an ip injection of 10(9) fibers would lead to a concentration of fiber numbers in the ash of the omentum in the same range as the concentration in the lung after 2 years of inhalation exposure. The long-term inhalation study with fibers in rats has been called the "gold standard" for risk characterization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7882919

  16. Evaluation of the carcinogenicity of gallium arsenide.

    PubMed

    Bomhard, Ernst M; Gelbke, Heinz-Peter; Schenk, Hermann; Williams, Gary M; Cohen, Samuel M

    2013-05-01

    Gallium arsenide (GaAs) is an important semiconductor material. In 2-year inhalation studies, GaAs increased the incidence of lung tumors in female rats, but not in male rats or male and female mice. Alveolar proteinosis followed by chronic active inflammation was the predominant non-neoplastic pulmonary findings. IARC classified GaAs as carcinogenic to humans (group 1) based on the assumption that As and Ga ions are bioavailable. The European Chemical Agency Risk Assessment Committee concluded that GaAs should be classified into Carcinogenicity Category 1B (presumed to have carcinogenic potential for humans; ECHA). We evaluate whether these classifications are justified. Physico-chemical properties of GaAs particles and the degree of mechanical treatment are critical in this evaluation. The available data on mode of action (MOA), genotoxicity and bioavailability do not support the contribution of As or Ga ions to the lung tumors in female rats. Most toxicological studies utilized small particles produced by strong mechanical treatment, destroying the crystalline structure. The resulting amorphous GaAs is not relevant to crystalline GaAs at production and processing sites. The likely tumorigenic MOA is lung toxicity related to particulate-induced inflammation and increased proliferation. It is concluded that there is no evidence for a primary carcinogenic effect of GaAs.

  17. EXPOSURE METHODOLOGIES AND SYSTEMS FOR LONG-TERM CHEMICAL CARCINOGENICITY STUDIES WITH SMALL FISH SPECIES

    EPA Science Inventory

    Testing waterborne chemical carcinogens in fish models requires accurate, reliable, and reproducible exposures. Because carcinogenesis is a chronic toxicological process and is often associated with prolonged latency periods, systems must accommodate lengthy in-life test periods ...

  18. Sluggish Cognitive Tempo and ADHD Inattention as Predictors of Externalizing, Internalizing, and Impairment Domains: A 2-Year Longitudinal Study.

    PubMed

    Bernad, Maria del Mar; Servera, Mateu; Becker, Stephen P; Burns, G Leonard

    2016-05-01

    Although sluggish cognitive tempo (SCT) is distinct from attention-deficit/hyperactivity disorder inattention (ADHD-IN), few studies have examined whether SCT longitudinally predicts other symptom or impairment dimensions. This study used 4 sources (mothers, fathers, primary teachers, and secondary teachers) and 3 occasions of measurement (first, second, and third grades) with 758 first grade (55 % boys), 718 second grade (54 % boys), and 585 third grade (53 % boys) children from Spain to determine SCT's and ADHD-IN's unique longitudinal relationships with psychopathology, academic impairment, and social impairment over the 1- and 2-year intervals (i.e., first to third grade, second to third grade). For 1- and 2-year intervals using both mothers' and fathers' ratings, higher levels of SCT uniquely predicted higher levels of anxiety, depression, academic impairment, and social impairment whereas higher levels of ADHD-IN uniquely predicted higher levels of ADHD-HI, ODD, and academic impairment. For 1- and 2-year intervals across different primary and secondary teachers (i.e., first/second and third grade ratings were provided by different teachers), higher scores on ADHD-IN uniquely predicted poorer outcomes across domains whereas higher scores on SCT uniquely predicted lower levels of ADHD-HI and ODD for both intervals in addition to higher levels of depression (for primary teachers only), academic impairment (for 1-year interval only), and peer rejection (2-year interval only for primary teachers). Overall, SCT was significantly associated with important outcomes independent of ADHD-IN over 1- and 2-year intervals and across four different raters. This study provides further evidence for distinguishing between SCT and ADHD-IN in home and school settings.

  19. Safety assessment of dietary administered paprika color in combined chronic toxicity and carcinogenicity studies using F344 rats.

    PubMed

    Inoue, T; Umemura, T; Maeda, M; Ishii, Y; Okamura, T; Tasaki, M; Nishikawa, A

    2008-08-01

    Combined chronic toxicity and carcinogenicity studies of paprika color, used as a food additive in various countries, were performed in male and female F344 rats. Dietary concentrations of 0%, 0.62%, 1.25%, 2.5% and 5% were applied in a 52-week toxicity study and 0%, 2.5% and 5% in a 104-week carcinogenicity study. Treatment with paprika color caused a significant increase in incidence of hepatocellular vacuolation in 5% males, but no toxicological effects were found with reference to survival rates, body weights, hematological or serum biochemical parameters and organ weights at any dose level in either sex in the chronic toxicity study. Also, paprika color did not induce specific tumors nor did it exert significant influence on the development of spontaneous tumors in any of the organs examined in the carcinogenicity study. In conclusion, based on slight histopathological changes observed in 5% male livers, the no-observed-effect level (NOEL) was estimated to be 2.5% in the diet (1,253 mg/kg bw/day) and the no-observed-adverse-effect level (NOAEL) was determined to be 5% in the diet (2,388 mg/kg bw/day) for male rats, and for females, the NOEL was concluded to be 5% in the diet (2,826 mg/kg bw/day). Additionally, paprika color was not carcinogenic to male and female F344 rats under the present experimental conditions.

  20. Chronic toxicity/carcinogenicity studies of FD & C Yellow No. 5 (tartrazine) in rats.

    PubMed

    Borzelleca, J F; Hallagan, J B

    1988-03-01

    FD & C Yellow No. 5 was fed to Charles River CD rats as a dietary admixture in two long-term toxicity/carcinogenicity studies. The studies were conducted with an in utero phase in which the compound was administered to the F0 generation rats (60/sex/group) at levels of 0.0, 0.0, 0.1, 1.0 or 2.0% ('original study') and 0.0 or 5.0% ('high-dose study'). The concurrent control groups received the basal diet. After random selection of the F1 animals, the long-term phase was initiated using the same dietary levels with 70 rats of each sex/group, including the three control groups. The maximum exposure to the colouring was 113 and 114 wk for males and females, respectively, in the 'original' study and 122 and 125 wk for males and females, respectively, in the 'high-dose' study. No compound-related effects were noted. The no-adverse-effect level found in this study was 5.0% in the diet providing an average intake of 2641 and 3348 mg/kg/day for male and female rats, respectively.

  1. Financial Impact of Allogeneic Hematopoietic Cell Transplantation on Patients and Families over 2-years: Results from a Multicenter Pilot Study

    PubMed Central

    Denzen, Ellen M.; Thao, Viengneesee; Hahn, Theresa; Lee, Stephanie J.; McCarthy, Philip L.; Rizzo, J. Douglas; Ammi, Monique; Drexler, Rebecca; Flesch, Susan; James, Heather; Omondi, Nancy; Murphy, Elizabeth; Pederson, Kate; Majhail, Navneet S.

    2016-01-01

    Hematopoietic cell transplantation (HCT) is a procedure that can significantly influence the socioeconomic wellbeing of patients, caregivers and their families. Among 30 allogeneic HCT recipients and their caregivers enrolled on a pilot study evaluating the feasibility of studying financial impact of HCT, 16 agreed to participate in the long-term phase, completed a baseline questionnaire and received phone interviews at 6, 12, 18 and 24 months post-HCT. Analyses showed that by 2-years post-HCT, 54% of patients who previously contributed to household earnings had not returned to work and 80% of patients/caregivers reported transplant as having moderate to great impact on household income. However, patients’ level of confidence in their ability to meet household financial obligations increased from baseline to 2-years. A relatively large proportion of patients reported inability to pay for medical care through this time period. Case studies demonstrated patient individual perception of financial impact of HCT varies considerably, regardless of actual income. We demonstrate the feasibility of conducting a study to evaluate financial impact of allogeneic HCT through 2-years post-transplantation. Some patients/caregivers continue to experience significant long-term financial burden after this procedure. Our study lays the foundation for a larger evaluation of patient/caregiver financial burden associated with HCT. PMID:27088381

  2. Treatment Compliance of Adolescents after Attempted Suicide: A 2-Year Follow-Up Study

    ERIC Educational Resources Information Center

    Burns, Craig D.; Cortell, Ranon; Wagner, Barry M.

    2008-01-01

    The study investigates compliance with mental health treatments among suicidal adolescents. Results show that child psychopathology and parental attitudes toward treatment plays an important part in increasing compliance with mental health treatment for adolescent suicide attempters.

  3. Diagnosis of Autism Spectrum Disorders in 2-Year-Olds: A Study of Community Practice

    ERIC Educational Resources Information Center

    Corsello, Christina M.; Akshoomoff, Natacha; Stahmer, Aubyn C.

    2013-01-01

    Background: Longitudinal research studies have demonstrated that experienced clinicians using standardized assessment measures can make a reliable diagnosis of autism spectrum disorders (ASDs) in children under age 3. Limited data are available regarding the sensitivity and specificity of these measures in community settings. The aims of this…

  4. Pubertal Timing and Substance Use in Middle Adolescence: A 2-Year Follow-Up Study

    ERIC Educational Resources Information Center

    Kaltiala-Heino, Riittakerttu; Koivisto, Anna-Maija; Marttunen, Mauri; Frojd, Sari

    2011-01-01

    Earlier research has associated early puberty with emotional and behavioral symptoms particularly among girls, while among boys, findings have been contradictory as to whether risks are associated with early or late pubertal timing. We studied the association between pubertal timing and substance use behaviors in middle adolescence in a 2-year…

  5. The Development of Falling Intonation in Young Children with Cochlear Implants: A 2-Year Longitudinal Study

    ERIC Educational Resources Information Center

    Snow, David P.; Ertmer, David J.

    2013-01-01

    This article describes the development of intonation in 12 cochlear implant (CI) recipients. In a previously reported study of the first year of CI use, children who were implanted late (after 24 months) acquired intonation more rapidly than the younger participants. The older children's advantage is plausibly owing to their greater maturity.…

  6. Development of Orthographic Knowledge in German-Speaking Children: A 2-Year Longitudinal Study

    ERIC Educational Resources Information Center

    Ise, Elena; Arnoldi, Carolin Judith; Schulte-Körne, Gerd

    2014-01-01

    There is growing evidence that children develop orthographic knowledge from the very beginning of literacy acquisition. This study investigated the development of German-speaking children's orthographic knowledge with a nonword choice task. One nonword in each pair contained a frequent consonant doublet ("zommul") and the other…

  7. Re-defining one's occupational self 2 years after breast cancer: a case study.

    PubMed

    Newman, Robin M

    2013-01-01

    Margaret*, a 56 year-old Caucasian Stage III breast cancer survivor, participated in a 5 week occupational therapy pilot program, called Take Action. This program was designed for breast cancer survivors who self-reported changes in cognitive function following completion of chemotherapy. The goals of the program were to improve participants' knowledge and use of strategies to enhance occupational performance and to improve satisfaction and performance of meaningful daily activities or occupations. Through a client-centered and evidence-based approach, this case study highlights the importance of incorporating the survivors' sense of self into an occupation-based intervention. Occupational therapists play an important role in facilitating exploration of sense of self in the survivorship phase of care to support occupational performance in self care, productivity, work, leisure and social participation. This case study highlights the important work of redefining oneself in the survivorship phase of care. (*denotes name change). PMID:24004739

  8. Involvement in bullying and suicidal ideation in middle adolescence: a 2-year follow-up study.

    PubMed

    Heikkilä, Hanna-Kaisa; Väänänen, Juha; Helminen, Mika; Fröjd, Sari; Marttunen, Mauri; Kaltiala-Heino, Riittakerttu

    2013-02-01

    The objective of the study was to ascertain whether involvement in bullying increases the risk for subsequent suicidal ideation. A total of 2,070 Finnish girls and boys aged 15 were surveyed in the ninth grade (age 15) in schools, and followed up 2 years later in the Adolescent Mental Health Cohort Study. Involvement in bullying was elicited at age 15 by two questions focusing on being a bully and being a victim of bullying. Suicidal ideation was elicited by one item of the short Beck Depression Inventory at age 17. Baseline depressive symptoms and externalizing symptoms, age and sex were controlled for. Statistical analyses were carried out using cross-tabulations with Chi-square/Fisher's exact test and logistic regression. Suicidal ideation at age 17 was 3-4 times more prevalent among those who had been involved in bullying at age 15 than among those not involved. Suicidal ideation at age 17 was most prevalent among former victims of bullying. Being a victim of bullying at age 15 continued to predict subsequent suicidal ideation when depressive and externalizing symptoms were controlled for. Being a bully at age 15 also persisted as borderline significantly predictive of suicidal ideation when baseline symptoms were controlled for. Findings indicate adolescent victims and perpetrators of bullying alike are at long-term risk for suicidal ideation. PMID:23053774

  9. Involvement in bullying and suicidal ideation in middle adolescence: a 2-year follow-up study.

    PubMed

    Heikkilä, Hanna-Kaisa; Väänänen, Juha; Helminen, Mika; Fröjd, Sari; Marttunen, Mauri; Kaltiala-Heino, Riittakerttu

    2013-02-01

    The objective of the study was to ascertain whether involvement in bullying increases the risk for subsequent suicidal ideation. A total of 2,070 Finnish girls and boys aged 15 were surveyed in the ninth grade (age 15) in schools, and followed up 2 years later in the Adolescent Mental Health Cohort Study. Involvement in bullying was elicited at age 15 by two questions focusing on being a bully and being a victim of bullying. Suicidal ideation was elicited by one item of the short Beck Depression Inventory at age 17. Baseline depressive symptoms and externalizing symptoms, age and sex were controlled for. Statistical analyses were carried out using cross-tabulations with Chi-square/Fisher's exact test and logistic regression. Suicidal ideation at age 17 was 3-4 times more prevalent among those who had been involved in bullying at age 15 than among those not involved. Suicidal ideation at age 17 was most prevalent among former victims of bullying. Being a victim of bullying at age 15 continued to predict subsequent suicidal ideation when depressive and externalizing symptoms were controlled for. Being a bully at age 15 also persisted as borderline significantly predictive of suicidal ideation when baseline symptoms were controlled for. Findings indicate adolescent victims and perpetrators of bullying alike are at long-term risk for suicidal ideation.

  10. Acinetobacter Infections among Adult Patients in Qatar: A 2-Year Hospital-Based Study

    PubMed Central

    Al Samawi, Musaed Saad; Khan, Fahmi Yousef; Eldeeb, Yasser; Almaslamani, Muna; Alkhal, Abdullatif; Alsoub, Hussam; Ghadban, Wissam; Howady, Faraj; Hashim, Samar

    2016-01-01

    This retrospective study was conducted at Hamad General Hospital, Qatar, to describe the demographic data, clinical features underlying diseases, antimicrobial susceptibility, and outcome of A. baumannii infection. It involved all adult patients 15 years of age or older who were managed at Hamad General Hospital for A. baumannii infection from January 1, 2012, to December 31, 2013. We identified a total of 239 patients with A. baumannii infection, of which 182 (76.2%) were males. The mean age was 49.10 ± 19.57 years. The majority of the episodes (25.1%) occurred in elderly patients (≥65 years) and the most commonly identified site of A. baumannii infection was the respiratory tract, 117 (48.9%). Most episodes of infection, 231 (96.7%), were hospital-acquired and high rate of nosocomial infections occurred in the medical intensive care unit, 66 (28.6%). All patients had underlying medical conditions. Maximum resistance was seen to cefotaxime, 147 (58.3%), and minimum resistance was seen to colistin, 2 (1.4%). Of the 239 isolates, 102 (42.7%) were susceptible and 137 (57.3%) were multidrug-resistant. The in-hospital mortality in our study was 31%. Male gender, multidrug resistance, and septic shock were found to be independent mortality predictors. PMID:27433169

  11. Anaphylaxis in an emergency department: a 2-year study in a tertiary-care hospital.

    PubMed

    Piromrat, Kanika; Chinratanapisit, Sasawan; Trathong, Sommai

    2008-01-01

    The aim of this study was to estimate the incidence of anaphylaxis in the emergency department of a tertiary-care hospital, describe the clinical features and the management of the patients and determine those with mild manifestations. A retrospective study was conducted from 2005 to 2006 using anaphylaxis-related ICD-10 terms. Two different sets of criteria for the diagnosis of anaphylaxis were applied, first the criteria previously accepted by emergency practice, followed by the recent criteria set forth at the 2005 international meeting. Sixty-four patients fulfilled the previous criteria with an average incidence of 52.5 per 100,000 patients per year with a shift towards females in 2006. The most common presentations were cutaneous, followed by respiratory symptoms. Food allergy was the most common cause, especially prawn. After applying the recent criteria, 13 patients (20.4%) were excluded, which reduced the incidence to 42.2 per 100,000 patients per year. Long term follow up is suggested for the possible or mild cases that were re-categorized.

  12. Carcinogenesis studies in rodents for evaluating risks associated with chemical carcinogens in aquatic food animals.

    PubMed Central

    Huff, J; Bucher, J; Yang, R

    1991-01-01

    Fish and shellfish caught in polluted waters contain potentially dangerous amounts of toxic and carcinogenic chemicals. Public concern was heightened when a large percentage of winter flounder taken from Boston Harbor was found to have visible cancer of the liver; winter flounder outside the estuary area had no liver lesions. Long-term chemical carcinogenesis studies could be easily and feasibly designed using laboratory rodents offered diets containing fish caught in polluted waters. Induced cancers in rodents would corroborate field observations in fish; positive results from these studies would provide further evidence about potential human health hazards from eating substantial amounts of chemically contaminated fish. Nonetheless, fish and aquatic organisms should be viewed as environmental biological monitors of pollution or of potential human health hazards, and authorities responsible for assuring clean and safe rivers, bodies of water, and biota should give more attention to these valid biological indicators or sentinels of environmental pollution. Consequently, fish and other sea creatures alone should serve as alarms regarding whether water areas constitute public health hazards. PMID:2050050

  13. The toxic effects of flame retardants: a gene expression study in elucidating their carcinogenicity

    NASA Astrophysics Data System (ADS)

    Vagula, Mary; Al-Dhumani, Ali; Al-Dhumani, Sajaad; Mastro, Alexandra

    2013-05-01

    Polybrominated Diphenyl Ethers (PBDEs) are flame retardants widely used in many commercial products, including building materials, electronics, furnishings, motor vehicles, airplanes, plastics, polyurethane foams, and textiles. Although the specific toxic action of these chemicals is not clear, it is reported that they can cause serious damage to the nervous, reproductive, and endocrine systems. These chemicals are branded as "probable carcinogens" by Environmental Protection Agency (EPA). Therefore, this study is taken up to investigate the expression of genes namely, TP-53, RAD1, CRADD, and ATM, which are involved in apoptosis, DNA repair and cell cycle regulation. For this study human umbilical vein endothelial cells (HUVEC) are exposed to 5 μM of BDE-85 (a penta-BDE) and BDE-209 (deca-BDE). The results of this report reveal significant alteration in all the genes under investigation in BDE-85 and BDE-209 exposed cells. The BDE-85 induced responses are significantly more than BDE-209. These results emphasize the congener specific action of PBDEs on the expression of genes relevant to DNA repair and cell division of HUVEC cells.

  14. Land management of bracken needs to account for bracken carcinogens--a case study from Britain.

    PubMed

    Rasmussen, Lars Holm; Donnelly, Eric; Strobel, Bjarne W; Holm, Peter E; Hansen, Hans Christian Bruun

    2015-03-15

    Bracken ferns are some of the most widespread ferns in the World causing immense problems for land managers, foresters and rangers. Bracken is suspected of causing cancer in Humans due to its content of the carcinogen ptaquiloside. Ingestion of bracken, or food and drinking water contaminated with ptaquiloside may be the cause. The aim of this study was to monitor the content of ptaquiloside in 20 bracken stands from Britain to obtain a better understanding of the ptaquiloside dynamics and to evaluate the environmental implications of using different cutting regimes in bracken management. The ptaquiloside content in fronds ranged between 50 and 5790 μg/g corresponding to a ptaquiloside load in the standing biomass of up to 590 mg/m(2) in mature fronds. Ptaquiloside was also found in the underground rhizome system (11-657 μg/g) and in decaying litter (0.1-5.8 μg/g). The amount of ptaquiloside present in bracken stands at any given time is difficult to predict and did not show any correlations with edaphic growth factors. The content of ptaquiloside turned out to be higher in fronds emerging after cutting compared to uncut fronds. Environmental risk assessment and bracken management must therefore be based on actual and site specific determinations of the ptaquiloside content. Care must be taken to avoid leaching from cut ferns to aquifers and other recipients and appropriate precautionary measures must be taken to protect staff from exposure to bracken dust.

  15. Molecular epidemiology studies on occupational and environmental exposure to mutagens and carcinogens, 1997-1999.

    PubMed Central

    Srám, R J; Binková, B

    2000-01-01

    Molecular epidemiology is a new and evolving area of research, combining laboratory measurement of internal dose, biologically effective dose, biologic effects, and influence of individual susceptibility with epidemiologic methodologies. Biomarkers evaluated were selected according to basic scheme: biomarkers of exposure--metabolites in urine, DNA adducts, protein adducts, and Comet assay parameters; biomarkers of effect--chromosomal aberrations, sister chromatid exchanges, micronuclei, mutations in the hypoxanthine-guanine phosphoribosyltransferase gene, and the activation of oncogenes coding for p53 or p21 proteins as measured on protein levels; biomarkers of susceptibility--genetic polymorphisms of genes CYP1A1, GSTM1, GSTT1, NAT2. DNA adducts measured by 32P-postlabeling are the biomarker of choice for the evaluation of exposure to polycyclic aromatic hydrocarbons. Protein adducts are useful as a biomarker for exposure to tobacco smoke (4-aminobiphenyl) or to smaller molecules such as acrylonitrile or 1,3-butadiene. Of the biomarkers of effect, the most common are cytogenetic end points. Epidemiologic studies support the use of chromosomal breakage as a relevant biomarker of cancer risk. The use of the Comet assay and methods analyzing oxidative DNA damage needs reliable validation for human biomonitoring. Until now there have not been sufficient data to interpret the relationship between genotypes, biomarkers of exposure, and biomarkers of effect for assessing the risk of human exposure to mutagens and carcinogens. PMID:10698723

  16. Lifetime (149-week) oral carcinogenicity study of vinyl chloride in rats.

    PubMed

    Til, H P; Feron, V J; Immel, H R

    1991-10-01

    A lifetime (149-wk) oral carcinogenicity study of vinyl chloride monomer (VCM) was carried out. Four groups of Wistar rats were used, each consisting of 100 males and 100 females, except for the high-dose group, which comprised 50 males and 50 females. VCM was administered by incorporating polyvinyl chloride powder with a high content of VCM into the diet. The actual exposure levels of VCM were 0 (control), 0.014, 0.13 and 1.3 mg VCM/kg body weight/day. Detailed histopathological examination was restricted to the liver. In the final stage of the study, the mortality in the high-dose group was slightly higher than in controls. A variety of VCM-related liver lesions was found in the high-dose group. The lesions included increased incidences of liver-cell polymorphism, hepatic cysts, foci of cellular alteration, neoplastic nodules, hepatocellular carcinomas and angiosarcomas. Compared with controls, there were increased incidences of hepatic foci of cellular alteration in females of the mid-dose group and of basophilic foci of hepatocellular alteration in females of both the low- and mid-dose groups. There was no evidence that feeding of VCM affected the incidence of tumours in organs other than the liver. Thus, the present study showed that the feeding of VCM at a level of 1.3 mg/kg body weight/day can induce neoplastic and non-neoplastic changes in the livers of male as well as female rats. The feeding of 0.014 or 0.13 mg VCM/kg body weight/day may result in an increased incidence of (basophilic) foci of cellular alteration in the liver of female rats. It was concluded that 0.13 mg VCM/kg body weight/day is the no-observed-adverse-effect level with respect to the induction of tumours in rats.

  17. Sustained efficacy of risedronate in men with primary and secondary osteoporosis: results of a 2-year study.

    PubMed

    Ringe, Johann D; Farahmand, Parvis; Faber, Herbert; Dorst, Alfred

    2009-01-01

    The aim of this study was to assess the effect of treatment with risedronate 5 mg daily relative to control in men with primary or secondary osteoporosis over 2 years. Osteoporosis is a common condition in men that can have serious clinical consequences. In an earlier interim report, we found that 1 year of risedronate therapy resulted in significant increases in bone mineral density (BMD) and a significant reduction in vertebral fractures compared to control in men with osteoporosis. We conducted an open-label, prospective, match-control trial on men with primary or secondary osteoporosis in a single center, outpatient setting. Men with primary or secondary osteoporosis, as defined by a baseline lumbar spine BMD T-score < or = -2.5 and a baseline femoral neck BMD T-score < or = 2.0, were eligible for this study. Patients who had been treated with bisphosphonates or fluoride within the last 12 months were excluded. A total of 316 men were randomized to risedronate (n = 158) or control (n = 158). Patients were stratified by the presence of prevalent vertebral fractures at baseline and case by case allocated to either daily treatment with risedronate 5 mg daily plus calcium (1,000 mg) and vitamin D (800 IU) or to a control group (daily alfacalcidol (1 microg) plus calcium (500 mg) for those with prevalent vertebral fractures; daily vitamin D (800 IU) plus calcium (1,200 mg) for those without previous vertebral fractures). Primary study end points were identified prior to study initiation as the incidence of new vertebral fractures and changes in BMD at the lumbar spine, femoral neck, and total hip. Other end points included incidence of nonvertebral fractures and change in body height and back pain. Compared to control, the incidence of new vertebral fractures was significantly reduced in the risedronate 5 mg daily group at 2 years [14/152 (9.2%) for risedronate vs. 35/148 (23.6%) for control (61% risk reduction; P = 0.0026)]. Treatment with risedronate 5 mg daily

  18. Do cage effects influence tumor incidence? An examination of laboratory animal carcinogenicity studies utilizing Fischer 344 rats.

    PubMed

    Haseman, J K

    1988-08-01

    Approximately 125 carcinogenicity studies in Fischer 344 rats conducted by the National Toxicology Program (NTP) were examined to determine the frequency with which cage effects were associated with observed carcinogenic responses. All studies involving groups of 50 rats housed five per cage and showing evidence of chemically-related carcinogenicity were considered. For each of these experiments, two statistical analyses were carried out for each dosed and control group: (i) a test to determine whether or not the occurrence of tumors clustered within cages; and (ii) an evaluation to determine whether or not tumor incidences differed significantly between differing cage shelf levels. These analyses showed that the numbers of statistically significant (P less than 0.05 or P less than 0.01) effects were consistent with the number expected by chance alone. Thus, cage-related factors appeared to have little or no impact upon tumor incidence in these particular studies. Experimental design protocols now used by the NTP (which include random assignment of animals to cages; random assignment of columns of cages to dosed and control groups; and periodic rotation of cage location) further reduce the likelihood that factors associated with the housing of the animals could influence tumor incidence in current studies. PMID:3183292

  19. A critical assessment of studies on the carcinogenic potential of diesel exhaust.

    PubMed

    Hesterberg, Thomas W; Bunn, William B; Chase, Gerald R; Valberg, Peter A; Slavin, Thomas J; Lapin, Charles A; Hart, Georgia A

    2006-10-01

    After decades of research involving numerous epidemiologic studies and extensive investigations in laboratory animals, a causal relationship between diesel exhaust (DE) exposure and lung cancer has not been conclusively demonstrated. Epidemiologic studies of the transportation industry (trucking, busing, and railroad) show a small elevation in lung cancer incidence (relative risks [RRs] generally below 1.5), but a dose response for DE is lacking. The studies are also limited by a lack of quantitative concurrent exposure data and inadequate or lack of controls for potential confounders, particularly tobacco smoking. Furthermore, prior to dieselization, similar elevations in lung cancer incidence have been reported for truck drivers, and in-cab diesel particulate matter (DPM) exposures of truck drivers were comparable to ambient highway exposures. Taken together, these findings suggest that an unidentified occupational agent or lifestyle factor might be responsible for the low elevations in lung cancer reported in the transportation studies. In contrast, underground miners, many of whom experience the highest occupational DPM exposures, generally do not show elevations in lung cancer. Laboratory studies must be interpreted with caution with respect to predicting the carcinogenic potential of DE in humans. Tumors observed in rats following lifetime chronic inhalation of very high levels of DPM may be attributed to species-specific overload mechanisms that lack relevance to humans. Increased tumor incidence was not observed in other species (hamsters or mice) exposed to DPM at very high levels or in rats exposed at lower levels (studies in which cells were exposed to concentrated extracts of DPM also have limited application to human risk assessment, because such extracts can be obtained from DPM only by using strong organic solvents, agitation, and heat. Most studies have shown that whole DPM itself is not

  20. JaCVAM-organized international validation study of the in vivo rodent alkaline comet assay for detection of genotoxic carcinogens: II. Summary of definitive validation study results.

    PubMed

    Uno, Yoshifumi; Kojima, Hajime; Omori, Takashi; Corvi, Raffaella; Honma, Masamistu; Schechtman, Leonard M; Tice, Raymond R; Beevers, Carol; De Boeck, Marlies; Burlinson, Brian; Hobbs, Cheryl A; Kitamoto, Sachiko; Kraynak, Andrew R; McNamee, James; Nakagawa, Yuzuki; Pant, Kamala; Plappert-Helbig, Ulla; Priestley, Catherine; Takasawa, Hironao; Wada, Kunio; Wirnitzer, Uta; Asano, Norihide; Escobar, Patricia A; Lovell, David; Morita, Takeshi; Nakajima, Madoka; Ohno, Yasuo; Hayashi, Makoto

    2015-07-01

    The in vivo rodent alkaline comet assay (comet assay) is used internationally to investigate the in vivo genotoxic potential of test chemicals. This assay, however, has not previously been formally validated. The Japanese Center for the Validation of Alternative Methods (JaCVAM), with the cooperation of the U.S. NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM)/the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), the European Centre for the Validation of Alternative Methods (ECVAM), and the Japanese Environmental Mutagen Society/Mammalian Mutagenesis Study Group (JEMS/MMS), organized an international validation study to evaluate the reliability and relevance of the assay for identifying genotoxic carcinogens, using liver and stomach as target organs. The ultimate goal of this exercise was to establish an Organisation for Economic Co-operation and Development (OECD) test guideline. The study protocol was optimized in the pre-validation studies, and then the definitive (4th phase) validation study was conducted in two steps. In the 1st step, assay reproducibility was confirmed among laboratories using four coded reference chemicals and the positive control ethyl methanesulfonate. In the 2nd step, the predictive capability was investigated using 40 coded chemicals with known genotoxic and carcinogenic activity (i.e., genotoxic carcinogens, genotoxic non-carcinogens, non-genotoxic carcinogens, and non-genotoxic non-carcinogens). Based on the results obtained, the in vivo comet assay is concluded to be highly capable of identifying genotoxic chemicals and therefore can serve as a reliable predictor of rodent carcinogenicity.

  1. Beryllium: genotoxicity and carcinogenicity.

    PubMed

    Gordon, Terry; Bowser, Darlene

    2003-12-10

    Beryllium (Be) has physical-chemical properties, including low density and high tensile strength, which make it useful in the manufacture of products ranging from space shuttles to golf clubs. Despite its utility, a number of standard setting agencies have determined that beryllium is a carcinogen. Only a limited number of studies, however, have addressed the underlying mechanisms of the carcinogenicity and mutagenicity of beryllium. Importantly, mutation and chromosomal aberration assays have yielded somewhat contradictory results for beryllium compounds and whereas bacterial tests were largely negative, mammalian test systems showed evidence of beryllium-induced mutations, chromosomal aberrations, and cell transformation. Although inter-laboratory differences may play a role in the variability observed in genotoxicity assays, it is more likely that the different chemical forms of beryllium have a significant effect on mutagenicity and carcinogenicity. Because workers are predominantly exposed to airborne particles which are generated during the machining of beryllium metal, ceramics, or alloys, testing of the mechanisms of the mutagenic and carcinogenic activity of beryllium should be performed with relevant chemical forms of beryllium.

  2. Lifetime toxicity/carcinogenicity study of FD & C Red No. 3 (erythrosine) in rats.

    PubMed

    Borzelleca, J F; Capen, C C; Hallagan, J B

    1987-10-01

    FD & C Red No. 3 was fed to Charles River CD rats as a dietary admixture in two long-term toxicity/carcinogenicity studies. The studies consisted of an in utero and an F1 phase. In the former, the compound was administered to five groups of the F0 generation rats (60 of each sex/group) at levels of 0.0, 0.0, 0.1, 0.5 or 1.0% ('original study') and 0.0 or 4.0% ('high-dose study'). The concurrent control groups received the basal diet. After random selection of the F1 animals, the long-term phase was initiated using the same dietary levels and 70 rats of each sex/group, including the three control groups. Rats were exposed for a maximum of 30 months. No compound-related effects were noted in the in utero phase. Mean body weights of the female F1 rats on 4.0% FD & C Red No. 3 (3029 mg/kg/body weight/day) were significantly lower than those of controls (P less than 0.01) throughout the study. Food consumption increased in all treated groups in a dose-related manner. There were no significant effects on the haematology, serum chemistry and urinalysis and no compound-related effects on survival. In male rats receiving 4.0% FD & C Red No. 3 (2464 mg/kg/day) thyroid weights were increased, with a mean weight of 92 mg compared to 44 mg for controls, and statistically significant increases in the incidence of thyroid follicular cell hypertrophy, hyperplasia and adenomas were recorded. A numerically increased incidence of thyroid follicular adenomas in female rats given 0.5, 1.0 or 4.0% FD & C Red No. 3 was not statistically significant. The no-observed-adverse-effect levels established in these studies were 0.5% (251 mg/kg/day) for male rats and 1.0% (641 mg/kg/day) for females.

  3. Progression of fibromyalgia: results from a 2-year observational fibromyalgia and chronic pain study in the US

    PubMed Central

    Adams, Edgar H; McElroy, Heather J; Udall, Margarita; Masters, Elizabeth T; Mann, Rachael M; Schaefer, Caroline P; Cappelleri, Joseph C; Clair, Andrew G; Hopps, Markay; Daniel, Shoshana R; Mease, Philip; Silverman, Stuart L; Staud, Roland

    2016-01-01

    Background A previous fibromyalgia (FM) research reports that 20%–47% of diagnosed patients may not meet the study definition of FM 1–2 years after diagnosis. The aim of this study was to gain a better understanding of the progression of FM in a geographically diverse cohort over a 2-year time period. Methods This cohort study followed 226 subjects recruited online to assess FM and chronic widespread pain (CWP) diagnosis stability over time. At enrollment (baseline), subjects provided informed consent, completed an online questionnaire consisting of the London Fibromyalgia Epidemiology Study Screening Questionnaire to screen for CWP (bilateral pain above/below waist lasting ≥1 week in the past 3 months), visited a site for physician evaluation for FM, and completed a questionnaire with validated patient-reported outcome instruments. Subjects were classified into mutually exclusive groups: FM+CWP+ (screened positive for CWP and received physician diagnosis of FM), FM−CWP+ (screened positive for CWP but did not receive physician diagnosis of FM), and FM−CWP− (screened negative for CWP). Approximately 2 years later (follow-up), subjects were reassessed at the same study site and completed a questionnaire with the same patient-reported outcomes. Results Seventy-six FM+CWP+ subjects completed assessments at both time points; 56 (73.7%) met the FM study definition at follow-up. Twenty subjects no longer met the FM study definition (eleven became FM−CWP− and nine became FM−CWP+). Ten subjects (two from FM−CWP− and eight from FM−CWP+) transitioned into the FM+CWP+ group at follow-up; they reported more tender points and pain interference with sleep and worse physical function at baseline compared with subjects who did not transition to FM+CWP+. Most (76.7%) of the subjects who transitioned into/out of FM+CWP+ experienced changes in CWP, number of positive tender points, or both. Conclusion The results suggest that some FM+CWP+ patients experience

  4. Understanding arsenic carcinogenicity by the use of animal models.

    PubMed

    Wanibuchi, Hideki; Salim, Elsayed I; Kinoshita, Anna; Shen, Jun; Wei, Min; Morimura, Keiichirou; Yoshida, Kaoru; Kuroda, Koichi; Endo, Ginji; Fukushima, Shoji

    2004-08-01

    Although numerous epidemiological studies have indicated that human arsenic exposure is associated with increased incidences of bladder, liver, skin, and lung cancers, limited attempts have been made to understand mechanisms of carcinogenicity using animal models. Dimethylarsinic acid (DMA), an organic arsenic compound, is a major metabolite of ingested inorganic arsenics in mammals. Recent in vitro studies have proven DMA to be a potent clastogenic agent, capable of inducing DNA damage including double strand breaks and cross-link formation. In our attempts to clarify DMA carcinogenicity, we have recently shown carcinogenic effects of DMA and its related metabolites using various experimental protocols in rats and mice: (1) a multi-organ promotion bioassay in rats; (2) a two-stage promotion bioassay by DMA of rat urinary bladder and liver carcinogenesis; (3) a 2-year carcinogenicity test of DMA in rats; (4) studies on the effects of DMA on lung carcinogenesis in rats; (5) promotion of skin carcinogenesis by DMA in keratin (K6)/ornithine decarboxylase (ODC) transgenic mice; (6) carcinogenicity of DMA in p53(+/-) knockout and Mmh/8-OXOG-DNA glycolase (OGG1) mutant mice; (7) promoting effects of DMA and related organic arsenicals in rat liver; (8) promoting effects of DMA and related organic arsenicals in a rat multi-organ carcinogenesis test; and (9) 2-year carcinogenicity tests of monomethylarsonic acid (MMA) and trimethylarsine oxide (TMAO) in rats. The results revealed that the adverse effects of arsenic occurred either by promoting and initiating carcinogenesis. These data, as covered in the present review, suggest that several mechanisms may be involved in arsenic carcinogenesis.

  5. Carcinogenicity of chrysotile asbestos: a case control study of textile workers

    SciTech Connect

    Dement, J.M. )

    1991-01-01

    Chrysotile is the predominant type of asbestos used in the United States and thus represents the most important source of exposure to asbestos already in place. While the steepest exposure-response observed for lung cancer has been in workers exposed to chrysotile in textile operations, some argue that chrysotile is less carcinogenic than amphibole asbestos types. Mineral oil exposures have been hypothesized to be responsible for the highly elevated lung cancer risk seen in textile workers. A lung cancer case-control analysis among a cohort of South Carolina chrysotile asbestos textile workers was conducted. Only a modest reduction in the slope of the lung cancer exposure-response relationship was observed after controlling for mineral oil exposures. These data do not support mineral oil exposure as a plausible explanation for the elevated lung cancer risk seen in chrysotile asbestos textile workers. The possible role of longer, thinner, more carcinogenic fibers in textiles is one plausible hypothesis needing further investigation.

  6. Studies on the potential for genotoxic carcinogenicity of fragrances and other chemicals.

    PubMed

    Rosenkranz, H S; Zhang, Y P; Klopman, G

    1998-08-01

    The potential of fragrances, physiological chemicals, natural products and a group of randomly selected chemicals to induce cancers by a genotoxic mechanism (i.e. "genotoxic" carcinogenesis) was compared using structure-activity relationships (SAR) models. Fragrances are significantly less likely to induce genotoxic carcinogenicity than randomly selected chemicals or natural products. With respect to the latter potential, fragrances were indistinguishable from normal mammalian physiological constituents.

  7. Experimental studies on benzene carcinogenicity at the Bologna Institute of Oncology: current results and ongoing research.

    PubMed

    Maltoni, C; Conti, B; Cotti, G; Belpoggi, F

    1985-01-01

    In 1977 Maltoni and Scarnato were the first to demonstrate that benzene is an experimental carcinogen in rats. With that and other experiments, Maltoni et al have shown that benzene administered by ingestion (stomach tube) or inhalation is a multipotential carcinogen in rats (of two different strains) and mice and produces a variety of tumors, namely: Zymbal gland carcinomas, oral and nasal cavity carcinomas, skin carcinomas, acanthomas, dysplasias and carcinomas of forestomach, mammary malignant tumors, hepatomas, liver angiosarcomas, hemolymphoreticular neoplasias, and pulmonary tumors. The incidence of Zymbal gland carcinomas and carcinomas of the oral and nasal cavities is affected by the length of treatment by inhalation and by the age of animals. However, the available epidemiological and experimental data at present do not provide precise information on the risk of doses around or below 10 ppm. Long-term carcinogenicity bioassays at 50, 25, 10, 5 and 1 ppm may be helpful for scientific risk assessment. In addition, these experiments have shown that toluene, xylene, and ethylbenzene, at high concentrations, cause an increase in the number of total malignant tumors.

  8. Natural carcinogenic fiber and pleural plaques assessment in a general population: A cross-sectional study.

    PubMed

    Ledda, Caterina; Pomara, Cristoforo; Bracci, Massimo; Mangano, Dario; Ricceri, Vincenzo; Musumeci, Andrea; Ferrante, Margherita; Musumeci, Giuseppe; Loreto, Carla; Fenga, Concettina; Santarelli, Lory; Rapisarda, Venerando

    2016-10-01

    Natural carcinogenic fibers are asbestos and asbestiform fibers present as a natural component of soils or rocks. These fibers are released into the environment resulting in exposure of the general population. Environmental contamination by fibers are those cases occurred in: rural regions of Turkey, in Mediterranean countries and in other sites of the world, including northern Europe, USA and China. Fluoro-edenite(FE) is a natural mineral species first isolated in Biancavilla, Sicily. The fibers are similar in size and morphology to some amphibolic asbestos fibers, whose inhalation can cause chronic inflammation and cancer. The aim of the current study is to assess the presence and features of pleural plaques (PPs) in Biancavilla's general population exposed to FE through a retrospective cross-sectional study. All High-Resolution Computed Tomography (HRCT) chest scans carried out between June 2009 and June 2015 in Biancavilla municipality hospital site (exposed subjects) were reviewed. The exposed groups were 1:1 subjects, matched according to age and sex distributions, with unexposed subjects (n.1.240) randomly selected among HRCT chest scans carried out in a Hospital 30km away from Biancavilla. Subjects from Biancavilla with PPs were significantly more numerous than the control group ones (218 vs 38). Average age of either group was >60 years; the age of exposed subjects was significantly (p=0.0312) lesser than the unexposed group. In exposed subjects, in most PPs thickness ranged between 2 and 4.9cm(38%, n=83); while in unexposed ones PPs thickness was less than 2cm (55%, n=21). As to the size of PPs in exposed subjects, in most cases it ranged between 1cm and 24% of chest wall (53%, n=116); while in unexposed ones the size of PPs was lesser than 1cm (23%, n=58). Among exposed subjects, 36 cases (17%) PPs were detected with calcification, whereas in unexposed ones only three (8%) presented calcification. 137 lung parenchymal abnormalities were observed in

  9. Biomonitoring of Carcinogenic Heterocyclic Aromatic Amines in Hair: A Validation Study

    PubMed Central

    Bessette, Erin E.; Yasa, Isil; Dunbar, Deborah; Wilkens, Lynne R.; Marchand, Loic Le; Turesky, Robert J.

    2009-01-01

    A facile method was established to measure heterocyclic aromatic amines (HAAs) accumulated in human hair and rodent fur. The samples were digested by base hydrolysis, and the liberated HAAs were isolated by tandem solvent/solid-phase extraction. Quantification was done by liquid chromatography/tandem mass spectrometry, using a triple stage quadrupole mass spectrometer in the selected reaction monitoring mode. In a pilot study of 12 human volunteers, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) was detected in hair of six meat-eaters at levels ranging from 290 to 890 pg/g hair. 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-9H-pyrido[2,3-b]indole (AαC) were below the limit of quantification (LOQ) (50 pg/g hair) in hair from meat-eaters and six vegetarians. PhIP was detected in the hair from one vegetarian, and at level just above the LOQ (65 pg/g hair), indicating PhIP exposure occurs primarily through meat consumption. The levels of PhIP in hair samples from two meat-eaters varied by less than 24% over a 6-month interval, signifying that the exposure to PhIP and its accumulation in hair are relatively constant over time. In a controlled feeding study, female C57BL/6 mice were given these HAAs in their drinking water for 1 month, at six daily dose concentrations ranging from 0, 0.080 to 800 µg/kg body weight. PhIP was detected in fur of mice at all doses, whereas AαC and MeIQx were detected in fur at dosages ≥0.8 µg AαC/kg body weight and ≥8 µg MeIQx/kg body weight. There was a strong positive relationship between dosage and each of the HAAs accumulated in fur and their DNA adducts formed in liver and colon (p-values <0.0001); however, the levels of HAA in fur did not correlate to the levels of DNA adducts after adjustment of dose. Thus, hair appears to be a promising long-lived biomarker with by which we can assess the exposure to PhIP, a potential human carcinogen. PMID:19588936

  10. Effect of exacerbations on quality of life in patients with chronic obstructive pulmonary disease: a 2 year follow up study

    PubMed Central

    Miravitlles, M; Ferrer, M; Pont, A; Zalacain, R; Alvarez-Sala, J; Masa, F; Verea, H; Murio, C; Ros, F; Vidal, R

    2004-01-01

    Background: A study was undertaken to evaluate exacerbations and their impact on the health related quality of life (HRQL) of patients with chronic obstructive pulmonary disease (COPD). Methods: A 2 year follow up study was performed in 336 patients with COPD of mean (SD) age 66 (8.2) years and mean (SD) forced expiratory volume in 1 second (FEV1) 33 (8)% predicted. Spirometric tests, questions regarding exacerbations of COPD, and HRQL measurements (St George's Respiratory Questionnaire (SGRQ) and SF-12 Health Survey) were conducted at 6 month intervals. Results: A total of 1015 exacerbations were recorded, and 103 (30.7%) patients required at least one hospital admission during the study. After adjustment for baseline characteristics and season of assessment, frequent exacerbations had a negative effect on HRQL in patients with moderate COPD (FEV1 35–50% predicted); the change in SGRQ total score of moderate patients with ⩾3 exacerbations was almost two points per year greater (worse) than those with <3 exacerbations during the follow up (p = 0.042). For patients with severe COPD (FEV1 <35% predicted) exacerbations had no effect on HRQL. The change in SGRQ total score of patients admitted to hospital was almost 2 points per year greater (worse) than patients not admitted, but this effect failed to show statistical significance in any severity group. There was a significant and independent seasonal effect on HRQL since SGRQ total scores were, on average, 3 points better in measurements performed in spring/summer than in those measured in the winter (p<0.001). Conclusions: Frequent exacerbations significantly impair HRQL of patients with moderate COPD. A significant and independent effect of seasonality was also observed. PMID:15115864

  11. Disordered eating behaviors and body image in a longitudinal pilot study of adolescent girls: what happens 2 years later?

    PubMed

    Espinoza, Paola; Penelo, Eva; Raich, Rosa M

    2010-01-01

    We assessed the prospective association of risk factors for eating and body image disturbances after a 2-year follow-up in a community sample of Spanish adolescent girls. The participants included 128 Spanish girls aged 12-14, who took part in a 28-month prospective study. Aspects assessed were eating attitudes (Eating Attitudes Test), influence of the body shape model (questionnaire on influences of the aesthetic body shape model), extreme weight-control behaviors (Eating Disorder Examination-Questionnaire), body image (Body Image Questionnaire) and Body Mass Index (BMI). BMI, extreme weight-control behaviors and body image problems emerged as potential predictors of an increase in eating disturbances. An increased influence of the thinness model was significantly associated with reduced body satisfaction and body image problems. Preventive programs are needed to contribute reducing the impact of sociocultural influences with regard to thinness, the use of extreme weight-control behaviors and overweight in adolescents.

  12. Parental height and child growth from birth to 2 years in the WHO Multicentre Growth Reference Study.

    PubMed

    Garza, Cutberto; Borghi, Elaine; Onyango, Adelheid W; de Onis, Mercedes

    2013-09-01

    Linear growth from birth to 2 years of children enrolled in the World Health Organization Multicentre Growth Reference Study was similar despite substantial parental height differences among the six study sites. Within-site variability in child length attributable to parental height was estimated by repeated measures analysis of variance using generalized linear models. This approach was also used to examine relationships among selected traits (e.g. breastfeeding duration and child morbidity) and linear growth between 6 and 24 months of age. Differences in intergenerational adult heights were evaluated within sites by comparing mid-parental heights (average of the mother's and father's heights) to the children's predicted adult height. Mid-parental height consistently accounted for greater proportions of observed variability in attained child length than did either paternal or maternal height alone. The proportion of variability explained by mid-parental height ranged from 11% in Ghana to 21% in India. The average proportion of between-child variability accounted for by mid-parental height was 16% and the analogous within-child estimate was 6%. In the Norwegian and US samples, no significant differences were observed between mid-parental and children's predicted adult heights. For the other sites, predicted adult heights exceeded mid-parental heights by 6.2-7.8 cm. To the extent that adult height is predicted by height at age 2 years, these results support the expectation that significant community-wide advances in stature are attainable within one generation when care and nutrition approximate international recommendations, notwithstanding adverse conditions likely experienced by the previous generation.

  13. The effects of early headgear treatment on dental arches and craniofacial morphology: a report of a 2 year randomized study.

    PubMed

    Mäntysaari, Raimo; Kantomaa, Tuomo; Pirttiniemi, Pertti; Pykäläinen, Aila

    2004-02-01

    The aim of the present study was to determine the effects of early headgear treatment on dental arches and craniofacial morphology in children in the early mixed dentition. The total study group comprised 68 children of both sexes (40 boys and 28 girls) aged 7.6 years [standard deviation (SD) 0.3]. The children, who had a Class II tendency in occlusion and moderate crowding of the dental arches, were randomly divided into two groups of equal size, matched according to gender. In the headgear (HG) group, treatment was initiated immediately. The mean treatment time was 16 months. In the second group, which served as the control, only interceptive procedures were performed during the follow-up period. The records, which included dental casts and lateral cephalograms, were obtained after follow-up periods of 1 and 2 years. The lengths and the widths of the maxillary and mandibular dental arches were significantly increased in the HG group after the 2 year follow-up period. The mean increase in lower arch length and width was 2.4 mm (SD 1.7) and 2.2 mm (SD 1.2), respectively. On average, the space gain in the lower arch was half that of the upper arch. No significant changes were found in the arch dimensions of the control group. Maxillary growth restraint and labial tilting of the incisors were the most significant cephalometric findings in the HG group when compared with the controls. The use of headgear in the early mixed dentition is effective in the treatment of moderate crowding. It is noteworthy that significant space gain in the dimensions of the lower arch can be achieved by headgear application to the upper first molars.

  14. Prospective study of cognitive function in children receiving whole-brain radiotherapy and chemotherapy: 2-year results

    SciTech Connect

    Packer, R.J.; Sutton, L.N.; Atkins, T.E.; Radcliffe, J.; Bunin, G.R.; D'Angio, G.; Siegel, K.R.; Schut, L. )

    1989-05-01

    As survival rates have risen for children with malignant primary brain tumors, so has the concern that many survivors have significant permanent cognitive deficits. Cranial irradiation (CRT) has been implicated as the major cause for cognitive dysfunction. To clarify the etiology, incidence, and severity of intellectual compromise in children with brain tumors after CRT, a prospective study was undertaken comparing the neuropsychological outcome in 18 consecutive children with malignant brain tumors treated with CRT to outcome in 14 children harboring brain tumors in similar sites in the nervous system who had not received CRT. Children with cortical or subcortical brain tumors were not eligible for study. Neuropsychological testing was performed after surgery prior to radiotherapy, after radiotherapy, and at 1- and 2-year intervals thereafter. Children who had received CRT had a mean full-scale intelligence quotient (FSIQ) of 105 at diagnosis which fell to 91 by Year 2. Similar declines were noted in their performance intelligence quotient (IQ) and verbal IQ. After CRT, patients demonstrated a statistically significant decline from baseline in FSIQ (p less than 0.02) and verbal IQ (p less than 0.04). Children who had not received CRT did not demonstrate a fall in any cognitive parameter over time. The decline between baseline testing and testing performed at Year 2 in patients who had CRT was inversely correlated with age (p less than 0.02), as younger children demonstrated the greatest loss of intelligence. Children less than 7 years of age at diagnosis had a mean decline in FSIQ of 25 points 2 years posttreatment. No other clinical parameter correlated with the overall IQ or decline in IQ. After CRT, children demonstrated a wide range of dysfunction including deficits in fine motor, visual-motor, and visual-spatial skills and memory difficulties.

  15. Carcinogen risk assessment

    SciTech Connect

    Hazelwoold, R.N.

    1987-01-01

    This article describes the methods by which risk factors for carcinogenic hazards are determined and the limitations inherent in the process. From statistical and epidemiological studies, the major identifiable factors related to cancer in the United States were determined to be cigarette smoking, diet, reproductive and sexual behavior, infections, ultraviolet and ionizing radiation, and alcohol consumption. The incidence of lung cancer due to air pollutants was estimated to be less than 2%. Research needs were discussed.

  16. Leisure time activities related to carcinogen exposure and lung cancer risk in never smokers. A case-control study

    SciTech Connect

    Ruano-Ravina, Alberto; García-Lavandeira, José Antonio; Torres-Durán, María; Prini-Guadalupe, Luciana; Parente-Lamelas, Isaura; Leiro-Fernández, Virginia; Montero-Martínez, Carmen; González-Barcala, Francisco Javier; Golpe-Gómez, Antonio; Martínez, Cristina; Castro-Añón, Olalla; Mejuto-Martí, María José; and others

    2014-07-15

    We aim to assess the relationship between leisure time activities related to exposure to carcinogenic substances and lung cancer risk in a hospital-based case-control study performed in never smokers. We included never smoking cases with anatomopathologically confirmed lung cancer and never smoking controls undergoing trivial surgery, at 8 Spanish hospitals. The study was conducted between January 2011 and June 2013. Participants were older than 30 and had no previous neoplasms. All were personally interviewed focusing on lifestyle, environmental tobacco smoke exposure, occupational history and leisure time activities (including duration of such activities). Results were analyzed through logistic regression and adjusted also by residential radon and education level. We included 513 never smokers, 191 cases and 322 controls. The OR for those performing the studied leisure time activities was 1.43 (95%CI 0.78–2.61). When we restricted the analysis to those performing do-it-yourself activities for more than 10 years the OR was 2.21 (95%CI 0.93–5.27). Environmental tobacco smoke exposure did not modify this association. The effect for the different lung cancer histological types was very close to significance for adenocarcinoma but only when these activities were performed for more than 10 years. We encourage health professionals to recommend protective measures for those individuals while performing these hobbies to reduce the risk of lung cancer. - Highlights: • Some leisure time activities are associated with the exposure to carcinogenic substances. • These activities are model-making, painting (artistic or not), furniture refinishing or wood working. • Few studies have assessed lung cancer risk due to these hobbies and none in never-smokers. • Leisure activities related to exposure to carcinogenic substances present higher lung cancer risk. • The risk is higher when these activities are performed for more than 10 years.

  17. Clarifying carcinogenicity of ethylbenzene

    PubMed Central

    Huff, James; Chan, Po; Melnick, Ronald

    2010-01-01

    Ethylbenzene has been evaluated for carcinogenic activity in Fischer rats and B6C3F1 mice exposed by inhalation [Chan et al 1998;Chan & NTP 1999] and in Sprague-Dawley rats after oral exposure [Maltoni et al 1985,1997]. Bioassay findings are summarized below to expand on those not stated clearly or completely in Saghir et al [2010]. Overall in these three studies animals exposed to ethylbenzene had increased tumors in rats for kidneys, testes, head [including rare neuroesthesioepitheliomas], and total malignant tumors, whilst in mice tumors incidences were increased in the lung and liver [Huff,2002]. Thus ethylbenzene was carcinogenic by two exposure routes to both sexes of two species of rodents, two strains of rats, and one strain of mice, causing collectively tumors in five different target organs and a composite of “total malignant”tumors. PMID:20723573

  18. Chronic studies evaluating the carcinogenicity of monomethylarsonic acid in rats and mice.

    PubMed

    Arnold, Lora L; Eldan, Michal; van Gemert, Marcia; Capen, Charles C; Cohen, Samuel M

    2003-08-28

    Monomethylarsonic acid (MMA) was administered in the diet of male and female Fischer F344 rats and B6C3F1 mice in 2-year feeding studies according to US EPA guidelines. Rats were treated with 50, 400, or 1300 ppm MMA and mice were treated with 10, 50, 200, or 400 ppm MMA based on preliminary short-term studies. The highest dose in the male and female rat groups was reduced to 1000 ppm during week 53 and then further reduced to 800 ppm during week 60 due to high mortality in the male rats. There was no treatment-related mortality in the mice. The primary target organ for MMA-induced toxicity in rats and mice was the large intestine. Toxicity was more severe in rats compared to mice and in male rats compared to female rats. The maximum tolerated dose for chronic dietary administration of MMA in rats and mice was assessed as 400 ppm, and the no effect level with regard to intestinal toxicity was assessed as 50 ppm for rats and female mice and 200 ppm for male mice. There were no treatment-related neoplastic effects detected in either the rat or the mouse.

  19. Chronic dietary toxicity and carcinogenicity study with ammonium perfluorooctanoate in Sprague-Dawley rats.

    PubMed

    Butenhoff, John L; Kennedy, Gerald L; Chang, Shu-Ching; Olsen, Geary W

    2012-08-16

    In order to assess the potential chronic toxicity and tumorigenicity of ammonium perfluorooctanoate (APFO), a 2-year dietary study was conducted with male and female rats fed 30 ppm or 300 ppm (approximately 1.5 and 15 mg/kg). In males fed 300 ppm, mean body weights were lower across most of the test period and survival in these rats was greater than that seen either in the 30 ppm or the control group. Non-neoplastic effects were observed in liver in rats fed 300 ppm and included elevated liver weight, an increase in the incidence of diffuse hepatocellular hypertrophy, portal mononuclear cell infiltration, and mild hepatocellular vacuolation without an increase in hepatocellular necrosis. Mean serum activities of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase were elevated up to three times the control means, primarily at the 300 ppm dose. A significant increase in Leydig cell tumors of the testes was seen in the males fed 300 ppm, and tumors of the liver and acinar pancreas, which are often observed in rats from chronic exposure to peroxisome proliferating agents, were not observed in this study. All other tumor types were those seen spontaneously in rats of this stock and age and were not associated with feeding of APFO. PMID:22531602

  20. Chromium carcinogenicity: California strategies.

    PubMed

    Alexeeff, G V; Satin, K; Painter, P; Zeise, L; Popejoy, C; Murchison, G

    1989-10-01

    Hexavalent chromium was identified by California as a toxic air contaminant (TAC) in January 1986. The California Department of Health Services (CDHS) concurred with the findings of the International Agency for Research on Cancer that there is sufficient evidence to demonstrate the carcinogenicity of chromium in both animals and humans. CDHS did not find any compelling evidence demonstrating the existence of a threshold with respect to chromium carcinogenesis. Experimental data was judged inadequate to assess potential human reproductive risks from ambient exposures. Other health effects were not expected to occur at ambient levels. The theoretically increased lifetime carcinogenic risk from a continuous lifetime exposure to hexavalent chromium fell within the range 12-146 cancer cases per nanogram hexavalent chromium per cubic meter of air per million people exposed, depending on the potency estimate used. The primary sources found to contribute significantly to the risk of exposure were chrome platers, chromic acid anodizing facilities and cooling towers utilizing hexavalent chromium as a corrosion inhibitor. Evaluation of genotoxicity data, animal studies and epidemiological studies indicates that further consideration should be given to the potential carcinogenicity of hexavalent chromium via the oral route.

  1. Acute Chikungunya and persistent musculoskeletal pain following the 2006 Indian epidemic: a 2-year prospective rural community study.

    PubMed

    Chopra, A; Anuradha, V; Ghorpade, R; Saluja, M

    2012-05-01

    Chikungunya virus (CHIKV) data from population studies are sparse. During the 2006 epidemic, 509 clinical cases (43% attack rate) were identified in a village survey (West India); laboratory investigations demonstrated normal blood cell counts, elevated acute-phase reactants [erythrocyte sedimentation rate, C-reactive protein and interleukin-6 (IL-6)] and excluded malaria and dengue. Acute CHIKV was characterized by high fever, severe peripheral polyarthralgias, axial myalgias and intense fatigue in over 90% of cases; skin rash (34%) and headache (19%) were uncommon. There were 49% and 62% of survey cases seropositive for IgM (rapid assay) and IgG (immunofluorescence) anti-CHIKV antibodies, respectively. Sixty-five percent of cases recovered within 4 weeks. None of the cases died. Of the population, 4·1% and 1·6% suffered from persistent rheumatic pains, predominantly non-specific, at 1 and 2 years, respectively. Chronic inflammatory arthritis was uncommon (0·3% at 1 year) although serum IL-6 often remained elevated in chronic cases. A larger population study is required to describe post-CHIKV rheumatism and its prognosis.

  2. Studies on the mutagenic mechanisms of the potent environmental carcinogen, benzo[a]pyrene

    SciTech Connect

    Rodriguez, H.

    1993-01-01

    Environmental chemicals that cause cancer have previously been shown to become chemically linked to the genetic substance, DNA, to give DNA adducts. These adducts appear foreign to the cell and mutations occur when the DNA is being duplicated during cell replication. Mutations in proto-oncogenes can change a normal cell into a cancerous cell. Benzo[a]pyrene is one example of a potent mutagen/carcinogen found ubiquitously in the environment: For example, in the soot from internal combustion engines and power plants, in cigarette smoke, and on charred meat. Benzo[a]pyrene is an indirect-acting mutagen/carcinogen, which must be metabolized inside the body to its ultimate mutagen/carcinogen, the corresponding (+)-anti-diol epoxide ((+)-anti-B[a]PDE) which forms many adducts in DNA. By using a newly developed forward mutation assay (ES87/pUB3) mutations induced by (+)-anti-B[a]PDE were isolated and characterized. SOS induction was shown to enhance frameshift and base pairing mutagenesis; G:C->T:A mutations were preferentially enhanced (approximately twelve-fold). Nearest neighbor analysis was performed assuming a guanine (underlined) was being mutated; SOS enhanced (+)-anti-B[a]PDE base pairing mutagenesis in 5[prime]-(A/T)G-3[prime] sequences more than in 5[prime]-G(A/T)-3[prime] sequences, and in 5[prime]-G(C/G)-3[prime] sequences more than in 5[prime]-G(A/T)-3[prime] sequences. Sequence content affected mutagenesis quantitatively where hot-spots for (+)-anti-B[a]PDE was heated prior to transformation into ES87 cells, an approximately two-fold decrease in mutation frequency was observed. In general, heating did not affect mutagenic specificity. Models are proposed to explain these results. Freeze/thawing pUB3 adducted with (+)-anti-B[a]PDE, also caused both an approximately two-fold decrease in mutation frequency and changes similar to those caused by heating.

  3. Differences in predictors of traditional and cyber-bullying: a 2-year longitudinal study in Korean school children.

    PubMed

    Yang, Su-Jin; Stewart, Robert; Kim, Jae-Min; Kim, Sung-Wan; Shin, Il-Seon; Dewey, Michael E; Maskey, Sean; Yoon, Jin-Sang

    2013-05-01

    Traditional bullying has received considerable research but the emerging phenomenon of cyber-bullying much less so. Our study aims to investigate environmental and psychological factors associated with traditional and cyber-bullying. In a school-based 2-year prospective survey, information was collected on 1,344 children aged 10 including bullying behavior/experience, depression, anxiety, coping strategies, self-esteem, and psychopathology. Parents reported demographic data, general health, and attention-deficit hyperactivity disorder (ADHD) symptoms. These were investigated in relation to traditional and cyber-bullying perpetration and victimization at age 12. Male gender and depressive symptoms were associated with all types of bullying behavior and experience. Living with a single parent was associated with perpetration of traditional bullying while higher ADHD symptoms were associated with victimization from this. Lower academic achievement and lower self esteem were associated with cyber-bullying perpetration and victimization, and anxiety symptoms with cyber-bullying perpetration. After adjustment, previous bullying perpetration was associated with victimization from cyber-bullying but not other outcomes. Cyber-bullying has differences in predictors from traditional bullying and intervention programmes need to take these into consideration. PMID:23640732

  4. Differences in predictors of traditional and cyber-bullying: a 2-year longitudinal study in Korean school children.

    PubMed

    Yang, Su-Jin; Stewart, Robert; Kim, Jae-Min; Kim, Sung-Wan; Shin, Il-Seon; Dewey, Michael E; Maskey, Sean; Yoon, Jin-Sang

    2013-05-01

    Traditional bullying has received considerable research but the emerging phenomenon of cyber-bullying much less so. Our study aims to investigate environmental and psychological factors associated with traditional and cyber-bullying. In a school-based 2-year prospective survey, information was collected on 1,344 children aged 10 including bullying behavior/experience, depression, anxiety, coping strategies, self-esteem, and psychopathology. Parents reported demographic data, general health, and attention-deficit hyperactivity disorder (ADHD) symptoms. These were investigated in relation to traditional and cyber-bullying perpetration and victimization at age 12. Male gender and depressive symptoms were associated with all types of bullying behavior and experience. Living with a single parent was associated with perpetration of traditional bullying while higher ADHD symptoms were associated with victimization from this. Lower academic achievement and lower self esteem were associated with cyber-bullying perpetration and victimization, and anxiety symptoms with cyber-bullying perpetration. After adjustment, previous bullying perpetration was associated with victimization from cyber-bullying but not other outcomes. Cyber-bullying has differences in predictors from traditional bullying and intervention programmes need to take these into consideration.

  5. Controlled release study of an anti-carcinogenic agent, gallate from the surface of magnetite nanoparticles

    NASA Astrophysics Data System (ADS)

    Ghotbi, Mohammad Yeganeh; bin Hussein, Mohd Zobir

    2012-07-01

    Immobilization of gallate anion, an anti-carcinogenic, anti-mutagenic, and anti-microbial agent on the surface of magnetite nanoparticles was accomplished by adsorption technique for the formation of a core-shell nanocomposite. A simple co-precipitation technique in the presence of poly vinyl pyrrolidone was successfully applied for the preparation of magnetite nanoparticles as core beads with narrow size distribution. The powders were characterized by X-ray diffraction, particle size analysis, magnetic measurements, atomic force microscope and also infrared spectroscopy. FTIR and CHNS results indicated that the gallate anion was actually adsorbed onto the surface of the magnetite nanoparticles. The release of the anion from the surface of the nanocomposite was found to be controllable by the selection of the release media.

  6. Associations between weather conditions and clinical symptoms in patients with hip osteoarthritis: a 2-year cohort study.

    PubMed

    Dorleijn, Desirée M J; Luijsterburg, Pim A J; Burdorf, Alex; Rozendaal, Rianne M; Verhaar, Jan A N; Bos, Pieter K; Bierma-Zeinstra, Sita M A

    2014-04-01

    The goal of this study was to assess whether there is an association between ambient weather conditions and patients' clinical symptoms in patients with hip osteoarthritis (OA). The design was a cohort study with a 2-year follow-up and 3-monthly measurements and prospectively collected data on weather variables. The study population consisted of 222 primary care patients with hip OA. Weather variables included temperature, wind speed, total amount of sun hours, precipitation, barometric pressure, and relative humidity. The primary outcomes were severity of hip pain and hip disability as measured with the Western Ontario and McMasters University Osteoarthritis Index (WOMAC) pain and function subscales. Associations between hip pain and hip disability and the weather variables were assessed using crude and multivariate adjusted linear mixed-model analysis for repeated measurements. On the day of questionnaire completion, mean relative humidity was associated with WOMAC pain (estimate 0.1; 95% confidence interval=0.0-0.2; P=.02). Relative humidity contributed < or = 1% to the explained within-patient variance and between-patient variance of the WOMAC pain score. Mean barometric pressure was associated with WOMAC function (estimate 0.1; 95% confidence interval=0.0-0.1; P=.02). Barometric pressure contributed < or = 1% to the explained within-patient variance and between-patient variance of the WOMAC function score. The other weather variables were not associated with the WOMAC pain or function score. Our results support the general opinion of OA patients that barometric pressure and relative humidity influence perceived OA symptoms. However, the contribution of these weather variables (< or = 1%) to the severity of OA symptoms is not considered to be clinically relevant.

  7. Oxidative stress in the carcinogenicity of chemical carcinogens.

    PubMed

    Kakehashi, Anna; Wei, Min; Fukushima, Shoji; Wanibuchi, Hideki

    2013-01-01

    This review highlights several in vivo studies utilizing non-genotoxic and genotoxic chemical carcinogens, and the mechanisms of their high and low dose carcinogenicities with respect to formation of oxidative stress. Here, we survey the examples and discuss possible mechanisms of hormetic effects with cytochrome P450 inducers, such as phenobarbital, a-benzene hexachloride and 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane. Epigenetic processes differentially can be affected by agents that impinge on oxidative DNA damage, repair, apoptosis, cell proliferation, intracellular communication and cell signaling. Non-genotoxic carcinogens may target nuclear receptors and induce post-translational modifications at the protein level, thereby impacting on the stability or activity of key regulatory proteins, including oncoproteins and tumor suppressor proteins. We further discuss role of oxidative stress focusing on the low dose carcinogenicities of several genotoxic carcinogens such as a hepatocarcinogen contained in seared fish and meat, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, arsenic and its metabolites, and the kidney carcinogen potassium bromate. PMID:24202448

  8. Breast cancer risk in relation to occupations with exposure to carcinogens and endocrine disruptors: a Canadian case–control study

    PubMed Central

    2012-01-01

    Background Endocrine disrupting chemicals and carcinogens, some of which may not yet have been classified as such, are present in many occupational environments and could increase breast cancer risk. Prior research has identified associations with breast cancer and work in agricultural and industrial settings. The purpose of this study was to further characterize possible links between breast cancer risk and occupation, particularly in farming and manufacturing, as well as to examine the impacts of early agricultural exposures, and exposure effects that are specific to the endocrine receptor status of tumours. Methods 1005 breast cancer cases referred by a regional cancer center and 1146 randomly-selected community controls provided detailed data including occupational and reproductive histories. All reported jobs were industry- and occupation-coded for the construction of cumulative exposure metrics representing likely exposure to carcinogens and endocrine disruptors. In a frequency-matched case–control design, exposure effects were estimated using conditional logistic regression. Results Across all sectors, women in jobs with potentially high exposures to carcinogens and endocrine disruptors had elevated breast cancer risk (OR = 1.42; 95% CI, 1.18-1.73, for 10 years exposure duration). Specific sectors with elevated risk included: agriculture (OR = 1.36; 95% CI, 1.01-1.82); bars-gambling (OR = 2.28; 95% CI, 0.94-5.53); automotive plastics manufacturing (OR = 2.68; 95% CI, 1.47-4.88), food canning (OR = 2.35; 95% CI, 1.00-5.53), and metalworking (OR = 1.73; 95% CI, 1.02-2.92). Estrogen receptor status of tumors with elevated risk differed by occupational grouping. Premenopausal breast cancer risk was highest for automotive plastics (OR = 4.76; 95% CI, 1.58-14.4) and food canning (OR = 5.70; 95% CI, 1.03-31.5). Conclusions These observations support hypotheses linking breast cancer risk and exposures likely to include carcinogens and endocrine disruptors, and

  9. Adrenal Gland Background Findings in CD-1 (Crl:CD-1(ICR)BR) Mice from 104-week Carcinogenicity Studies.

    PubMed

    Petterino, Claudio; Naylor, Stuart; Mukaratirwa, Sydney; Bradley, Alys

    2015-08-01

    The authors performed a retrospective study to determine the incidences of spontaneous findings in the adrenal glands of control CD-1 mice. Data were collected from 2,163 mice from control dose groups in 104-week carcinogenicity studies carried out between 2000 and 2010. Adrenal gland nonproliferative lesions were more common in males than in females. In males, the most common nonproliferative lesions were cortical hypertrophy, cortical atrophy, pigment deposition/pigmentation, cysts, and extramedullary hematopoiesis. In females, the most common nonproliferative lesions were pigment deposition/pigmentation, extramedullary hematopoiesis, and cortical atrophy. Proliferative lesions were more common in females than in males. In both sexes, the most common proliferative lesions were subcapsular cell hyperplasia, focal cortical hyperplasia, and subcapsular cell tumor. Pheochromocytomas were uncommon in both sexes, with a slightly higher incidence in females, and the benign type was more frequent than the malignant type. Lymphoma was the most common metastatic tumor in both males and females, followed by histiocytic sarcoma and erythroid/myeloid leukemia. To the best knowledge of the authors, there are no recent reports on spontaneous pathological findings in the adrenal glands of CD-1 mice, and these results will facilitate the interpretation of background findings in carcinogenicity studies.

  10. Carcinogens in the Schools

    ERIC Educational Resources Information Center

    Block, J. Bradford

    1976-01-01

    Reports the presence and use of known carcinogens in Kentucky colleges, junior colleges, and high schools. Includes a listing of known carcinogens and the synonym names under which each may be labeled. (SL)

  11. Effects of galantamine in a 2-year, randomized, placebo-controlled study in Alzheimer’s disease

    PubMed Central

    Hager, Klaus; Baseman, Alan S; Nye, Jeffrey S; Brashear, H Robert; Han, John; Sano, Mary; Davis, Bonnie; Richards, Henry M

    2014-01-01

    Background Currently available treatments for Alzheimer’s disease (AD) can produce mild improvements in cognitive function, behavior, and activities of daily living in patients, but their influence on long-term survival is not well established. This study was designed to assess patient survival and drug efficacy following a 2-year galantamine treatment in patients with mild to moderately severe AD. Methods In this multicenter, double-blind study, patients were randomized 1:1 to receive galantamine or placebo. One primary end point was safety; mortality was assessed. An independent Data Safety Monitoring Board monitored mortality for the total deaths reaching prespecified numbers, using a time-to-event method and a Cox-regression model. The primary efficacy end point was cognitive change from baseline to month 24, as measured by the Mini-Mental State Examination (MMSE) score, analyzed using intent-to-treat analysis with the ‘last observation carried forward’ approach, in an analysis of covariance model. Results In all, 1,024 galantamine- and 1,021 placebo-treated patients received study drug, with mean age ~73 years, and mean (standard deviation [SD]) baseline MMSE score of 19 (4.08). A total of 32% of patients (661/2,045) completed the study, 27% (554/2,045) withdrew, and 41% (830/2,045) did not complete the study and were discontinued due to a Data Safety Monitoring Board-recommended early study termination. The mortality rate was significantly lower in the galantamine group versus placebo (hazard ratio [HR] =0.58; 95% confidence interval [CI]: 0.37; 0.89) (P=0.011). Cognitive impairment, based on the mean (SD) change in MMSE scores from baseline to month 24, significantly worsened in the placebo (−2.14 [4.34]) compared with the galantamine group (−1.41 [4.05]) (P<0.001). Functional impairment, based on mean (SD) change in the Disability Assessment in Dementia score (secondary end point), at month 24 significantly worsened in the placebo (−10.81 [18

  12. Assessment of carcinogenic risk from personal exposure to benzo(a)pyrene in the Total Human Environmental Exposure Study (THEES).

    PubMed

    Butler, J P; Post, G B; Lioy, P J; Waldman, J M; Greenberg, A

    1993-07-01

    The Total Human Environmental Exposure Study (THEES) was an investigation of multimedia exposure to the ubiquitous environmental carcinogen, benzo(a)pyrene (BaP). The three-phase study was conducted in Phillipsburg, New Jersey and involved the participation of 14-15 individuals (8-10 homes) during each 14-day monitoring period. Microenvironmental sampling of air, food, water and soil indicated that environmental exposure to BaP was primarily through air and food. Exposure and risk estimates were, therefore, based on the results of personal monitoring of breathing zone air and prepared food samples. Based on a comparison of the range and magnitude of inhalation and dietary BaP exposures, food ingestion was clearly the predominant exposure to pathway. The relative contributions of other potential sources of community exposure to BaP (e.g., soil and drinking water ingestion) were also assessed. The excess cancer risk estimates for food ingestion were consistently greater than those for personal air, reflecting both the predominantly higher BaP exposures through the diet and the higher carcinogenic potency value for oral exposure. Overall, the total lifetime risk from personal exposure to BaP for nonsmokers in the community was estimated at 10(-5). In identifying risk reduction options, it is important to account for the observation that personal activities, lifestyle, and diet strongly influenced individual exposures to BaP.

  13. Assessment of carcinogenic risk from personal exposure to benzo(a)pyrene in the Total Human Environmental Exposure Study (THEES)

    SciTech Connect

    Butler, J.P.; Post, G.B.; Lioy, P.J.; Waldman, J.M.; Greenberg, A. )

    1993-07-01

    The Total Human Environmental Exposure Study (THEES) was an investigation of multimedia exposure to the ubiquitous environmental carcinogen, benzo(a)pyrene (BaP). The three-phase study was conducted in Phillipsburg, New Jersey and involved the participation of 14-15 individuals (8-10 homes) during each 14-day monitoring period. Microenvironmental sampling of air, food, water and soil indicated that environmental exposure to BaP was primarily through air and food. Exposure and risk estimates were, therefore, based on the results of personal monitoring of breathing zone air and prepared food samples. Based on a comparison of the range and magnitude of inhalation and dietary BaP exposures, food ingestion was clearly the predominant exposure to pathway. The relative contributions of other potential sources of community exposure to BaP (e.g., soil and drinking water ingestion) were also assessed. The excess cancer risk estimates for food ingestion were consistently greater than those for personal air, reflecting both the predominantly higher BaP exposures through the diet and the higher carcinogenic potency value for oral exposure. Overall, the total lifetime risk from personal exposure to BaP for nonsmokers in the community was estimated at 10(-5). In identifying risk reduction options, it is important to account for the observation that personal activities, lifestyle, and diet strongly influenced individual exposures to BaP.

  14. Regulation of carcinogens

    SciTech Connect

    Crouch, E.; Wilson, R.

    1981-01-01

    A procedure, suitable for regulatory use, is proposed for estimating individual and societal risks of carcinogenic materials by using information on interspecies comparisons of carcinogenic potency. The consistent treatment of uncertainties allows evaluation of confidence limits and hence regulatory measures of risk which incorporate safety factors and incentives for better information. Numerical examples are given, together with discussion of the treatment of undetected carcinogens. Applications of the procedure to setting priorities for carcinogenicity testing and to product substitution are mentioned.

  15. Minimally Invasive Periodontal Treatment Using the Er,Cr: YSGG Laser. A 2-year Retrospective Preliminary Clinical Study

    PubMed Central

    Dyer, Bret; Sung, Eric C.

    2012-01-01

    Minimally invasive surgery (MIS) using the erbium, chromium: yttrium-scandium-gallium-garnet (Er,Cr:YSGG) laser (Waterlase MD, Biolase, Irvine, CA) to treat moderate to advanced periodontal disease is presented as an alternative to conventional therapies. To date, there are few short- or long-term studies to demonstrate the effects of this laser in treating and maintaining periodontal health. Electronic clinical records from 16 patients – total of 126 teeth, with pocket depths ranging from 4 mm to 9 mm – were treated with the same protocol using the Er,Cr:YSGG laser. The mean baseline probing depths (PD) were 5 mm and clinical attachment levels (CAL) were 5 mm in the 4 - 6 mm pretreated laser group. The mean baseline probing depths were 7.5 and 7.6 mm for PD and CAL respectfully in the 7 – 9 mm pretreatment laser group. At the 2 year mark, the average PD was 3.2 ± 1.1 mm for the 4-6 mm pocket group and the 7-9 mm pocket group had a mean PD of 3.7 ± 1.2 mm. mean CAL was 3.1 ± 1.1 mm for the 4-6 mm group and 3.6 ± 1.2 for the 7-9 mm group with an overall reduction of 1.9 mm and 4.0 mm respectively. At one and two years, both groups remained stable with PD comparable to the three-month gains. The CAL measurements at one and two years were also comparable to the three-month gains. PMID:22615717

  16. A computational method for the identification of new candidate carcinogenic and non-carcinogenic chemicals.

    PubMed

    Chen, Lei; Chu, Chen; Lu, Jing; Kong, Xiangyin; Huang, Tao; Cai, Yu-Dong

    2015-09-01

    Cancer is one of the leading causes of human death. Based on current knowledge, one of the causes of cancer is exposure to toxic chemical compounds, including radioactive compounds, dioxin, and arsenic. The identification of new carcinogenic chemicals may warn us of potential danger and help to identify new ways to prevent cancer. In this study, a computational method was proposed to identify potential carcinogenic chemicals, as well as non-carcinogenic chemicals. According to the current validated carcinogenic and non-carcinogenic chemicals from the CPDB (Carcinogenic Potency Database), the candidate chemicals were searched in a weighted chemical network constructed according to chemical-chemical interactions. Then, the obtained candidate chemicals were further selected by a randomization test and information on chemical interactions and structures. The analyses identified several candidate carcinogenic chemicals, while those candidates identified as non-carcinogenic were supported by a literature search. In addition, several candidate carcinogenic/non-carcinogenic chemicals exhibit structural dissimilarity with validated carcinogenic/non-carcinogenic chemicals.

  17. Biologic resurfacing of the ankle and first metatarsophalangeal joint: case studies with a 2-year follow-up.

    PubMed

    Brigido, Stephen A; Troiano, Michael; Schoenhaus, Harold

    2009-10-01

    The goal of biologic resurfacing is to provide a smooth joint surface with a low coefficient of friction, which allows the joint to function with near normal biomechanics, as well as provide intermittent pressure, to the subchondral and cancellous bone. This unique combination often results in the formation of a "neocartilage-like" structure that can reduce pain and restore biomechanics. As well as giving a brief history of cutis arthroplasty, this article describes cases in which the ankle and first metatarsophalangeal joint underwent biologic resurfacing, with a 2-year postoperative follow up.

  18. Listing Occupational Carcinogens

    PubMed Central

    Siemiatycki, Jack; Richardson, Lesley; Straif, Kurt; Latreille, Benoit; Lakhani, Ramzan; Campbell, Sally; Rousseau, Marie-Claude; Boffetta, Paolo

    2004-01-01

    The occupational environment has been a most fruitful one for investigating the etiology of human cancer. Many recognized human carcinogens are occupational carcinogens. There is a large volume of epidemiologic and experimental data concerning cancer risks in different work environments. It is important to synthesize this information for both scientific and public health purposes. Various organizations and individuals have published lists of occupational carcinogens. However, such lists have been limited by unclear criteria for which recognized carcinogens should be considered occupational carcinogens, and by inconsistent and incomplete information on the occupations and industries in which the carcinogenic substances may be found and on their target sites of cancer. Based largely on the evaluations published by the International Agency for Research on Cancer, and augmented with additional information, the present article represents an attempt to summarize, in tabular form, current knowledge on occupational carcinogens, the occupations and industries in which they are found, and their target organs. We have considered 28 agents as definite occupational carcinogens, 27 agents as probable occupational carcinogens, and 113 agents as possible occupational carcinogens. These tables should be useful for regulatory or preventive purposes and for scientific purposes in research priority setting and in understanding carcinogenesis. PMID:15531427

  19. Developmental milestones record - 2 years

    MedlinePlus

    Growth milestones for children - 2 years; Normal childhood growth milestones - 2 years; Childhood growth milestones - 2 years ... cause for concern if not seen by 2 years.) Can run with better coordination . (May still have ...

  20. The carcinogenicity of arsenic.

    PubMed Central

    Pershagen, G

    1981-01-01

    A carcinogenic role of inorganic arsenic has been suspected for nearly a century. Exposure to inorganic arsenic compounds occurs in some occupational groups, e.g., among smelter workers and workers engaged in the production and use of arsenic containing pesticides. Substantial exposure can also result from drinking water in certain areas and the use of some drugs. Tobacco and wine have had high As concentrations due to the use of arsenic containing pesticides. Inorganic arsenic compounds interfere with DNA repair mechanisms and an increased frequency of chromosomal aberrations have been observed among exposed workers and patients. Epidemiological data show that inorganic arsenic exposure can cause cancer of the lung and skin. The evidence of an etiologic role of arsenic for angiosarcoma of the liver is highly suggestive; however, the association between arsenic and cancer of other sites needs further investigation. No epidemiological data are available on exposure to organic arsenic compounds and cancer. Animal carcinogenicity studies involving exposure to various inorganic and organic arsenic compounds by different routes have been negative, with the possible exception of some preliminary data regarding lung cancer and leukemia. Some studies have indicated an increased mortality from lung cancer in populations living near point emission sources of arsenic into the air. The role of arsenic cannot be evaluated due to lack of exposure data. Epidemiological data suggest that the present WHO standard for drinking water (50 micrograms As/l.) provides only a small safety margin with regard to skin cancer. PMID:7023936

  1. Quality of life after laparoscopic gastric banding: Prospective study (152 cases) with a follow-up of 2 years.

    PubMed

    Champault, Axèle; Duwat, Olivier; Polliand, Claude; Rizk, Nabil; Champault, Gérard G

    2006-06-01

    To evaluate influence of laparoscopic gastric banding (LGB) on quality of life (QOL) in patients with morbid obesity. Laparoscopic adjustable gastric banding is a popular bariatric operation in Europe. The objectives of surgical therapy in patients with morbid obesity are reduction of body weight, and a positive influence on the obesity-related comorbidity as well the concomitant psychologic and social restrictions of these patients. In a prospective clinical trial, development of the individual patient QOL was analyzed, after LGB in patients with morbid obesity. From October 1999 to January 2001, 152 patients [119 women, 33 men, mean age 38.4 y (range 24 to 62), mean body mass index 44.3 (range 38 to 63)] underwent evaluation for LGB according the following protocol: history of obesity; concise counseling of patients and relative on nonsurgical treatment alternatives, risk of surgery, psychologic testing, questionnaire for eating habits, necessity of lifestyle change after surgery; medical evaluation including endocrinologic and nutritionist work-up, upper GI endoscopy, evaluation of QOL using the Gastro Intestinal Quality of Life Index (GIQLI). Decision for surgery was a multidisciplinary consensus. This group was follow-up at least 2 years, focusing on weight loss and QOL. Mean operative time was 82 minutes; mean hospital stay was 2.3 days and the mean follow-up period was 34 months. The BMI dropped from 44.3 to 29.6 kg/m and all comorbid conditions improved markedly: diabetes melitus resolved in 71% of the patients, hypertension in 33%, and sleep apnea in 90%. However, 26 patients (17%) had late complications requiring reoperation. Preoperative global GIQLI score was 95 (range 56 to 140), significant different of the healthy volunteers score (120) (70 to 140) P < 0.001. Correlated with weight loss (percentage loss of overweight and BMI), the global score of the group increased to 100 at 3 months, 104 at 6, 111 at 1 year to reach 119 at 2 years which is no

  2. Carcinogenicity of hair dye components.

    PubMed

    Van Duuren, B L

    1980-03-01

    The available animal carcinogenicity data on hair dye components was reviewed. From this review it became clear that certain hair dye components, some of which are still in hair dye formulations now on the market, are animal carcinogens. The compounds of concern that are still in use are: 3-amino-4-methoxyaniline, 2-nitro-4-aminoaniline and 3-nitro-4-hydroxyaniline. Certain azo dyes formerly used, and related compounds still in use, contain the benzidine moiety. Two of these compounds, Direct Blue 6 and Direct Black 38, have been shown to be metabolized in animals to the human carcinogen benzidine. Furthermore, skin absorption studies carried out with radiolabeled hair dye components applied to animal or human skin have conclusively shown that these compounds are systemically absorbed and excreted. Known cocarcinogens such as catechol and pyrogallol, which enhance benzo(a)pyrene carcinogenicity on mouse skin, are used as hair dye components. It is not known whether such compounds will enhance the carcinogenicity of substituted aniline hair dye chemicals. The available epidemiologic data are not sufficient to link hair dye use with an increased incidence in human cancer. PMID:6993608

  3. Carcinogenicity of hair dye components.

    PubMed

    Van Duuren, B L

    1980-03-01

    The available animal carcinogenicity data on hair dye components was reviewed. From this review it became clear that certain hair dye components, some of which are still in hair dye formulations now on the market, are animal carcinogens. The compounds of concern that are still in use are: 3-amino-4-methoxyaniline, 2-nitro-4-aminoaniline and 3-nitro-4-hydroxyaniline. Certain azo dyes formerly used, and related compounds still in use, contain the benzidine moiety. Two of these compounds, Direct Blue 6 and Direct Black 38, have been shown to be metabolized in animals to the human carcinogen benzidine. Furthermore, skin absorption studies carried out with radiolabeled hair dye components applied to animal or human skin have conclusively shown that these compounds are systemically absorbed and excreted. Known cocarcinogens such as catechol and pyrogallol, which enhance benzo(a)pyrene carcinogenicity on mouse skin, are used as hair dye components. It is not known whether such compounds will enhance the carcinogenicity of substituted aniline hair dye chemicals. The available epidemiologic data are not sufficient to link hair dye use with an increased incidence in human cancer.

  4. Longitudinal 2 years field study of conventional vaccination against highly pathogenic avian influenza H5N1 in layer hens.

    PubMed

    Rudolf, Miriam; Pöppel, Manfred; Fröhlich, Andreas; Breithaupt, Angele; Teifke, Jens; Blohm, Ulrike; Mettenleiter, Thomas; Beer, Martin; Harder, Timm

    2010-10-01

    A licensed, inactivated vaccine based on a low pathogenic avian influenza virus strain (H5N2) was evaluated in layer hens kept under field conditions during a 2-year period. Vaccine efficacy was investigated by specific antibodies and by challenge-contact experiments using highly pathogenic avian influenza viruses (HPAIV) H5N1. Basic immunization with two applications induced clinical protection. Virus excretion by vaccinated hens was significantly reduced compared to non-vaccinated controls; transmission to non-vaccinated and vaccinated contact birds was not fully interrupted. Vaccination efficacy is influenced by several factors including antigenic relatedness between vaccine and field strains, but also by species, age and type of commercial uses of the host. Limitations and risks of HPAIV vaccination as silent spread of HPAIV and emergence of escape mutants must be considered a priori and appropriate corrective measures have to be installed. PMID:20727963

  5. International Conference on Harmonisation; proposed change to rodent carcinogenicity testing of pharmaceuticals; request for comments. Notice; request for comments.

    PubMed

    2013-03-18

    The Food and Drug Administration (FDA or the Agency) is considering a proposed change to the International Conference on Harmonisation (ICH) Sl guidance on rodent carcinogenicity testing. The goal of this potential change is to introduce a more comprehensive and integrated approach to address the risk of human carcinogenicity of small molecule pharmaceuticals, and to define conditions under which 2-year rodent carcinogenicity studies add value to that assessment. The basis of this proposed change is the retrospective analyses of several datasets that reflect three decades of experience with such studies. The datasets suggest that knowledge of certain pharmacologic and toxicologic data can sometimes provide sufficient information to anticipate the outcome of 2-year rodent studies and their potential value in predicting the risk of human carcinogenicity of a given pharmaceutical. FDA is requesting public comment regarding a proposed change in approach to carcinogenicity assessment, on the prospective evaluation period intended to test this new approach, and on the proposed weight-of-evidence factors for carcinogenicity assessment. PMID:23530289

  6. Iron-Folic Acid Supplementation During Pregnancy Reduces the Risk of Stunting in Children Less Than 2 Years of Age: A Retrospective Cohort Study from Nepal

    PubMed Central

    Nisar, Yasir Bin; Dibley, Michael J.; Aguayo, Victor M.

    2016-01-01

    The aim of the study was to investigate the effect of antenatal iron-folic acid (IFA) supplementation on child stunting in Nepalese children age <2 years. A retrospective cohort study design was used, in which a pooled cohort of 5235 most recent live births 2 years prior to interview from three Nepal Demographic and Health Surveys (2001, 2006 and 2011) was analysed. The primary outcome was stunting in children age <2 years. The main exposure variable was antenatal IFA supplementation. Multivariate Poisson regression analysis was performed. In our sample, 31% and 10% of Nepalese children age <2 years were stunted and severely stunted, respectively. The adjusted relative risk of being stunted was 14% lower in children whose mothers used IFA supplements compared to those whose mothers did not use (aRR = 0.86, 95% CI = 0.77–0.97). Additionally, the adjusted relative risk of being stunted was significantly reduced by 23% when antenatal IFA supplementation was started ≤6 months with ≥90 IFA supplements used during pregnancy (aRR = 0.77, 95% CI = 0.64–0.92). Antenatal IFA supplementation significantly reduced the risk of stunting in Nepalese children age <2 years. The greatest impact on the risk reduction of child stunting was when IFA supplements were started ≤6 months with ≥90 supplements were used. PMID:26828515

  7. Iron-Folic Acid Supplementation During Pregnancy Reduces the Risk of Stunting in Children Less Than 2 Years of Age: A Retrospective Cohort Study from Nepal.

    PubMed

    Nisar, Yasir Bin; Dibley, Michael J; Aguayo, Victor M

    2016-01-27

    The aim of the study was to investigate the effect of antenatal iron-folic acid (IFA) supplementation on child stunting in Nepalese children age <2 years. A retrospective cohort study design was used, in which a pooled cohort of 5235 most recent live births 2 years prior to interview from three Nepal Demographic and Health Surveys (2001, 2006 and 2011) was analysed. The primary outcome was stunting in children age <2 years. The main exposure variable was antenatal IFA supplementation. Multivariate Poisson regression analysis was performed. In our sample, 31% and 10% of Nepalese children age <2 years were stunted and severely stunted, respectively. The adjusted relative risk of being stunted was 14% lower in children whose mothers used IFA supplements compared to those whose mothers did not use (aRR = 0.86, 95% CI = 0.77-0.97). Additionally, the adjusted relative risk of being stunted was significantly reduced by 23% when antenatal IFA supplementation was started ≤6 months with ≥90 IFA supplements used during pregnancy (aRR = 0.77, 95% CI = 0.64-0.92). Antenatal IFA supplementation significantly reduced the risk of stunting in Nepalese children age <2 years. The greatest impact on the risk reduction of child stunting was when IFA supplements were started ≤6 months with ≥90 supplements were used.

  8. Evaluation of the Xpa-deficient transgenic mouse model for short-term carcinogenicity testing: 9-month studies with haloperidol, reserpine, phenacetin, and D-mannitol.

    PubMed

    Lina, Ben A R; Woutersen, Ruud A; Bruijntjes, Joost P; van Benthem, Jan; van den Berg, Jolanda A H; Monbaliu, Johan; Thoolen, Bob J J M; Beems, Rudolf B; van Kreijl, Coen F

    2004-01-01

    As part of the international evaluation program coordinated by ILSI/HESI, the potential of DNA repair deficient Xpa-/- mice and the double knockout Xpa-/-.p53+/- mice for short term carcinogenicity assays was evaluated. For comparison also wild-type C57BL/6 mice (WT) were included in these studies. Four test compounds were administered to groups of 15 male and 15 female Xpa-/- mice, Xpa-/-.p53+/- mice and WT mice for 39 weeks. The model compounds investigated were haloperidol, reserpine (nongenotoxic rodent carcinogens, putative human noncarcinogens), phenacetin (genotoxic rodent carcinogen, suspected human carcinogen), and D-mannitol (noncarcinogen in rodents and humans). The test compounds were administered as admixture to rodent diet at levels up to 25 mg/kg diet for haloperidol, 7.5 mg/kg diet for reserpine, 0.75% for phenacetin, and 10% for D-mannitol. These levels included the maximum tolerable dose (MTD). Survival was not affected with any of the test compounds. Haloperidol, reserpine and D-mannitol were negative in the carcinogenicity assay with Xpa-/- and Xpa-/-.p53+/- mice, showing low and comparable tumor incidences in controls and high-dose animals. The results obtained with phenacetin may be designated equivocal in Xpa-/-.p53+/- mice, based on the occurrence of a single rare tumor in the target organ (kidney) accompanied by a low incidence of hyperplastic renal lesions and a high incidence of karyomegaly. These results are in agreement with the currently known carcinogenic potential of the 4 test compounds in humans. PMID:15200157

  9. Evaluation of the Xpa-deficient transgenic mouse model for short-term carcinogenicity testing: 9-month studies with haloperidol, reserpine, phenacetin, and D-mannitol.

    PubMed

    Lina, Ben A R; Woutersen, Ruud A; Bruijntjes, Joost P; van Benthem, Jan; van den Berg, Jolanda A H; Monbaliu, Johan; Thoolen, Bob J J M; Beems, Rudolf B; van Kreijl, Coen F

    2004-01-01

    As part of the international evaluation program coordinated by ILSI/HESI, the potential of DNA repair deficient Xpa-/- mice and the double knockout Xpa-/-.p53+/- mice for short term carcinogenicity assays was evaluated. For comparison also wild-type C57BL/6 mice (WT) were included in these studies. Four test compounds were administered to groups of 15 male and 15 female Xpa-/- mice, Xpa-/-.p53+/- mice and WT mice for 39 weeks. The model compounds investigated were haloperidol, reserpine (nongenotoxic rodent carcinogens, putative human noncarcinogens), phenacetin (genotoxic rodent carcinogen, suspected human carcinogen), and D-mannitol (noncarcinogen in rodents and humans). The test compounds were administered as admixture to rodent diet at levels up to 25 mg/kg diet for haloperidol, 7.5 mg/kg diet for reserpine, 0.75% for phenacetin, and 10% for D-mannitol. These levels included the maximum tolerable dose (MTD). Survival was not affected with any of the test compounds. Haloperidol, reserpine and D-mannitol were negative in the carcinogenicity assay with Xpa-/- and Xpa-/-.p53+/- mice, showing low and comparable tumor incidences in controls and high-dose animals. The results obtained with phenacetin may be designated equivocal in Xpa-/-.p53+/- mice, based on the occurrence of a single rare tumor in the target organ (kidney) accompanied by a low incidence of hyperplastic renal lesions and a high incidence of karyomegaly. These results are in agreement with the currently known carcinogenic potential of the 4 test compounds in humans.

  10. Continuity, Comorbidity and Longitudinal Associations between Depression and Antisocial Behaviour in Middle Adolescence: A 2-Year Prospective Follow-Up Study

    ERIC Educational Resources Information Center

    Ritakallio, Minna; Koivisto, Anna-Maija; von der Pahlen, Bettina; Pelkonen, Mirjami; Marttunen, Mauri; Kaltiala-Heino, Riittakerttu

    2008-01-01

    The study investigated continuity, comorbidity and longitudinal associations between depression Beck depression inventory (RBDI) and antisocial behaviour Youth self-report (YSR) in middle adolescence. Data were used from a community sample of 2070 adolescents who participated in a 2-year prospective follow-up study. The results indicate that both…

  11. The impact of cognitive reserve in the outcome of first-episode psychoses: 2-year follow-up study.

    PubMed

    Amoretti, S; Bernardo, M; Bonnin, C M; Bioque, M; Cabrera, B; Mezquida, G; Solé, B; Vieta, E; Torrent, C

    2016-10-01

    The concept of cognitive reserve (CR) suggests that the premorbid intelligence quotient (IQ), years of education and leisure activities provide more efficient cognitive networks and therefore allow a better management of some conditions associated to cognitive impairment. Fifty-two DSM-IV diagnosed FEP subjects were matched with 41 healthy controls by age, gender and parental socio-economic status. All subjects were assessed clinically, neuropsychologically and functionally at baseline and after a two-year follow-up. To assess CR at baseline, three proxies have been integrated: premorbid IQ, years of education-occupation and leisure activities. Higher CR was associated with better cognitive, functional and clinical outcomes at baseline. The CR proxy was able to predict working memory, attention, executive functioning, verbal memory and global composite cognitive score accounting for 48.9%, 19.1%, 16.9%, 10.8% and 14.9% respectively of the variance at two-year follow-up. CR was also significantly predictive of PANSS negative scale score (12.5%), FAST global score (13.4%) and GAF (13%) at two-year follow-up. In addition, CR behaved as a mediator of working memory (B=4.123) and executive function (B=3.298) at baseline and of working memory (B=5.034) at 2-year follow-up. An additional analysis was performed, in order to test whether this mediation could be attributed mainly to the premorbid IQ. We obtained that this measure was not enough by itself to explain this mediation. CR may contribute to neuropsychological and functional outcome. Specific programs addressed to improve cognition and functioning conducted at the early stages of the illness may be helpful in order to prevent cognitive and functional decline.

  12. The impact of cognitive reserve in the outcome of first-episode psychoses: 2-year follow-up study.

    PubMed

    Amoretti, S; Bernardo, M; Bonnin, C M; Bioque, M; Cabrera, B; Mezquida, G; Solé, B; Vieta, E; Torrent, C

    2016-10-01

    The concept of cognitive reserve (CR) suggests that the premorbid intelligence quotient (IQ), years of education and leisure activities provide more efficient cognitive networks and therefore allow a better management of some conditions associated to cognitive impairment. Fifty-two DSM-IV diagnosed FEP subjects were matched with 41 healthy controls by age, gender and parental socio-economic status. All subjects were assessed clinically, neuropsychologically and functionally at baseline and after a two-year follow-up. To assess CR at baseline, three proxies have been integrated: premorbid IQ, years of education-occupation and leisure activities. Higher CR was associated with better cognitive, functional and clinical outcomes at baseline. The CR proxy was able to predict working memory, attention, executive functioning, verbal memory and global composite cognitive score accounting for 48.9%, 19.1%, 16.9%, 10.8% and 14.9% respectively of the variance at two-year follow-up. CR was also significantly predictive of PANSS negative scale score (12.5%), FAST global score (13.4%) and GAF (13%) at two-year follow-up. In addition, CR behaved as a mediator of working memory (B=4.123) and executive function (B=3.298) at baseline and of working memory (B=5.034) at 2-year follow-up. An additional analysis was performed, in order to test whether this mediation could be attributed mainly to the premorbid IQ. We obtained that this measure was not enough by itself to explain this mediation. CR may contribute to neuropsychological and functional outcome. Specific programs addressed to improve cognition and functioning conducted at the early stages of the illness may be helpful in order to prevent cognitive and functional decline. PMID:27511320

  13. The Role of Pictures and Gestures as a Support Mechanism for Novel Word Learning: A Training Study with 2-Year-Old Children

    ERIC Educational Resources Information Center

    Kapalková, Svetlana; Polišenská, Kamila; Süssová, Martina

    2016-01-01

    A training study examined novel word learning in 2-year-old children and assessed two nonverbal mechanisms, pictures and gestures, which are commonly used as communication support. The aim was to (1) compare these two support mechanisms and measure their effects on expressive word learning and (2) to investigate these effects on word production…

  14. Do Deviant Peer Associations Mediate the Contributions of Self-Esteem to Problem Behavior During Early Adolescence? A 2-Year Longitudinal Study

    ERIC Educational Resources Information Center

    DuBois, David L.; Silverthorn, Naida

    2004-01-01

    We investigated deviant peer associations as a mediator of the influences of general and peer-oriented self-esteem on problem behavior using data from a 2-year longitudinal study of 350 young adolescents. Measures of problem behavior included substance use (alcohol use, smoking) and antisocial behavior (fighting, stealing). Using latent growth…

  15. Exploring the Relationship between Autistic-Like Traits and ADHD Behaviors in Early Childhood: Findings from a Community Twin Study of 2-Year-Olds

    ERIC Educational Resources Information Center

    Ronald, Angelica; Edelson, Lisa R.; Asherson, Philip; Saudino, Kimberly J.

    2010-01-01

    Behaviors characteristic of autism and ADHD emerge in early childhood, yet research investigating their comorbidity has focused on older children. This study aimed to explore the nature of the relationship between autistic-like traits and ADHD behaviors in a community sample of 2-year-olds. Twins from the Boston University Twin Project (N = 312…

  16. A facility for studying the carcinogenic and synergistic effects of radon daughters and other agents in rodents

    SciTech Connect

    Strong, J.C.; Walsh, M.

    1992-12-31

    Although there is evidence to link lung cancer with radon exposures in miners, studies have not yet adequately demonstrated a link at domestic levels of exposure. Induction of cancer in animals after acute exposure to high levels of radon and radon daughters has been investigated by several laboratories. It is our intention to study the effects of radon and its daughters on rodents following both acute and chronic exposure. The studies will be extended to investigate the effects of other carcinogens in association with radon daughters. We will describe a facility in which rodents can be exposed continuously to radon and its daughters for periods of up to several months. The facility consists of two exposure chambers with closed air circuits which are operated independently of each other. Aerosol generators provide controlled vector aerosols onto which radon daughters can attach. Particular attention has been paid to accurate measurements of the concentrations of radon gas and of individual radon daughters. Techniques have also been developed for measuring the {open_quotes}unattached{close_quotes} fraction, the activity size distribution of individual daughters, and the potential alpha energy. The environment within the facility will be adjusted to be comparable to that found in dwellings with regard to condensation nucleus concentration, {open_quotes}unattached{close_quotes} fraction, equilibrium factor, and activity size distribution. Other vapors and aerosols, such as tobacco smoke, can be introduced into one of the air circuits to study the combined effects of radiation and toxic chemical agents.

  17. Lifetime toxicity/carcinogenicity study of FD & C Red No. 40 (allura red) in Sprague-Dawley rats.

    PubMed

    Borzelleca, J F; Olson, J W; Reno, F E

    1989-11-01

    FD & C Red No. 40 was fed to Charles River CD (Sprague-Dawley) rats as a dietary admixture in a lifetime toxicity/carcinogenicity study. The study included a phase during which the colouring was administered to parental rats (30 of each sex per group) at concentrations of 0.0, 0.37, 1.39 and 5.19%, throughout the mating, gestation and lactation periods. The concurrent control group received the basal diet. After random selection of the first-generation rats, the lifetime phase was initiated using the same dietary concentrations with 50 rats of each sex per group. The maximum durations of exposure to the colouring were 118 and 121 for males and females, respectively. No compound-related adverse effects were observed, except for a reduction in body weight in high-dose females at the end of the study. The no-adverse-effect levels in this study were 5.19% (2829 mg/kg/day) for male rats, and 1.39% (901 mg/kg/day) for female rats.

  18. TOPICAL REVIEW: MUTAGENICITY AND CARCINOGENICITY OF AIR

    EPA Science Inventory

    Although both outdoor and indoor airs provide exposure to mutagens and carcinogens, this review shows that the level of hazard is highly variable. Outdoor air was first shown to be carcinogenic in 1942 and mutagenic in 1975; and studies examining the genotoxicity of indoor air so...

  19. A retrospective study of radiographic abnormalities in the repositories of 2-year-old Thoroughbred in-training sales in Japan

    PubMed Central

    MIYAKOSHI, Daisuke; SENBA, Hiroyuki; SHIKICHI, Mitsumori; MAEDA, Masaya; SHIBATA, Ryo; MISUMI, Kazuhiro

    2016-01-01

    ABSTRACT This study aimed to evaluate the influence of radiographic abnormalities of 2-year-old Thoroughbred horses that were listed at in-training sales in Japan, on whether they started to race or not at 2–3 years of age. Radiographs of 850 2-year-old Thoroughbreds in the in-training sales repository from 2007 to 2010 were reviewed, and 26 categories of radiographic abnormalities were found. Forty-three horses (5.1%, 43/850) did not start a race at 2–3 years of age. In accordance with the racing results for this age category, as determined by Fisher’s exact test and multiple logistic regression analysis, none of the radiographic abnormalities were significantly related to failure to start a race. At 2 years of age, 198 horses (23.3%, 198/850) did not start a race. Horses with enlargement of the proximal sesamoid bones in the fore (9 of 19 horses) and hind limbs (5 of 9 horses) did not start a race at the age of 2 years, and fewer of these horses (fore, P=0.021; hind, P=0.030) started a race at the age of 2 years compared with the population of horses without these radiographic abnormalities. These results suggest that identification of radiographic enlargement of the proximal sesamoid bones during training sales could derail the racing debut of horses at the age of 2 years. However, this might not necessarily indicate a poor prognosis and resulting in retirement from racing at 2–3 years of age. PMID:27330400

  20. Case study on the utility of hepatic global gene expression profiling in the risk assessment of the carcinogen furan

    SciTech Connect

    Jackson, Anna Francina; Williams, Andrew; Recio, Leslie; Waters, Michael D.; Lambert, Iain B.; Yauk, Carole L.

    2014-01-01

    Furan is a chemical hepatocarcinogen in mice and rats. Its previously postulated cancer mode of action (MOA) is chronic cytotoxicity followed by sustained regenerative proliferation; however, its molecular basis is unknown. To this end, we conducted toxicogenomic analysis of B3C6F1 mouse livers following three week exposures to non-carcinogenic (0, 1, 2 mg/kg bw) or carcinogenic (4 and 8 mg/kg bw) doses of furan. We saw enrichment for pathways responsible for cytotoxicity: stress-activated protein kinase (SAPK) and death receptor (DR5 and TNF-alpha) signaling, and proliferation: extracellular signal-regulated kinases (ERKs) and TNF-alpha. We also noted the involvement of NF-kappaB and c-Jun in response to furan, which are genes that are known to be required for liver regeneration. Furan metabolism by CYP2E1 produces cis-2-butene-1,4-dial (BDA), which is required for ensuing cytotoxicity and oxidative stress. NRF2 is a master regulator of gene expression during oxidative stress and we suggest that chronic NFR2 activity and chronic inflammation may represent critical transition events between the adaptive (regeneration) and adverse (cancer) outcomes. Another objective of this study was to demonstrate the applicability of toxicogenomics data in quantitative risk assessment. We modeled benchmark doses for our transcriptional data and previously published cancer data, and observed consistency between the two. Margin of exposure values for both transcriptional and cancer endpoints were also similar. In conclusion, using furan as a case study we have demonstrated the value of toxicogenomics data in elucidating dose-dependent MOA transitions and in quantitative risk assessment. - Highlights: • Global gene expression changes in furan-exposed mouse livers were analyzed. • A molecular mode of action for furan-induced hepatocarcinogenesis is proposed. • Key pathways include NRF2, SAPK, ERK and death receptor signaling. • Important roles for TNF-alpha, c-Jun, and NF

  1. The Amazon molly, Poecilia formosa, as a test animal in carcinogenicity studies: chronic exposures to physical agents.

    PubMed

    Woodhead, A D; Setlow, R B; Pond, V

    1984-05-01

    The Amazon molly, Poecilia formosa, a small, live-bearing fish native to Texas, has an unusual mode of reproduction that makes it highly suitable for carcinogenicity studies. The species is easy to rear and breed, and withstands handling well. Large broods of young are born, numbering up to 90 when the parent fish are fully grown. The Amazon molly reproduces gynogenetically; eggs are activated after mating with males of closely related species. The male makes no genetic contribution; sperm provides only the stimulus for egg development. The offspring of a female comprise a clone with genotypes identical to that of the mother's so that cell and tissue transplants made between members of the clone are not rejected. We used the Amazon molly as an animal model to show that damage to DNA caused by UV and ionizing radiation and by certain chemicals results in tumor development. Thyroid cells were taken from donor mollies, treated precisely in vitro with the agents, and then injected into homologous recipients. Eight months later, recipient fish had developed large thyroid tumors. The genetic homogeneity of the clone also makes the Amazon molly invaluable in acute or chronic bioassays because variability in the responses of the individual fishes is minimal. Therefore, a limited number will suffice to give statistically significant results. The findings from a study of chronic exposure to asbestos are also described. PMID:6087147

  2. Toxico-Cheminformatics and QSPR Modeling of the Carcinogenic Potency Database

    EPA Science Inventory

    Report on the development of a tiered, confirmatory scheme for prediction of chemical carcinogenicity based on QSAR studies of compounds with available mutagenic and carcinogenic data. For 693 such compounds from the Carcinogenic Potency Database characterized molecular topologic...

  3. Trait and State Attributes of Insight in First Episodes of Early-Onset Schizophrenia and Other Psychoses: A 2-Year Longitudinal Study

    PubMed Central

    Parellada, Mara; Boada, Leticia; Fraguas, David; Reig, Santiago; Castro-Fornieles, Josefina; Moreno, Dolores; Gonzalez-Pinto, Ana; Otero, Soraya; Rapado-Castro, Marta; Graell, Montserrat; Baeza, Inmaculada; Arango, Celso

    2011-01-01

    Background: Increasing evidence supports the important role of illness state and individual characteristics in insight. Methods: Insight, as measured with the Scale to Assess Unawareness of Mental Disorder, over the first 2 years of early-onset first-episode psychosis and its correlations with clinical, socio-demographic, cognitive, and structural brain variables are studied. Results: (1) insight at 2 years is poorer in schizophrenia spectrum disorders (SSDs) than in subjects with other psychoses; (2) the more severe the psychosis, the worse the insight. In SSD, depressive symptoms, poorer baseline executive functioning, lower IQ, longer duration of untreated psychosis (DUP), and poorer premorbid infancy adjustment are associated with poorer insight; frontal and parietal gray matter (GM) reductions at baseline correlate with worse insight into having psychotic symptoms at 2 years; (3) insight into having a mental disorder (Scale to Assess Unawareness of Mental Disorder [SUMD]1) at 1 year, DUP, and baseline IQ are the most consistent variables explaining different aspects of insight at 2 years in SSD patients. IQ and SUMD1 at 1 year, together with left frontal and parietal GM volumes, explain 80% of the variance of insight into having specific psychotic symptoms in SSD patients (adjusted R2 = 0.795, F = 15.576, P < .001). Conclusion: Insight is a complex phenomenon that depends both on severity of psychopathology and also on disease and subject characteristics, such as past adjustment, IQ, DUP, cognitive functioning, frontal and parietal GM volumes, and age, gender, and ethnicity. PMID:20884756

  4. Risk assessment of carcinogens in food

    SciTech Connect

    Barlow, Susan

    2010-03-01

    Approaches for the risk assessment of carcinogens in food have evolved as scientific knowledge has advanced. Early methods allowed little more than hazard identification and an indication of carcinogenic potency. Evaluation of the modes of action of carcinogens and their broad division into genotoxic and epigenetic (non-genotoxic, non-DNA reactive) carcinogens have played an increasing role in determining the approach followed and provide possibilities for more detailed risk characterisation, including provision of quantitative estimates of risk. Reliance on experimental animal data for the majority of risk assessments and the fact that human exposures to dietary carcinogens are often orders of magnitude below doses used in experimental studies has provided a fertile ground for discussion and diverging views on the most appropriate way to offer risk assessment advice. Approaches used by national and international bodies differ, with some offering numerical estimates of potential risks to human health, while others express considerable reservations about the validity of quantitative approaches requiring extrapolation of dose-response data below the observed range and instead offer qualitative advice. Recognising that qualitative advice alone does not provide risk managers with information on which to prioritise the need for risk management actions, a 'margin of exposure' approach for substances that are both genotoxic and carcinogenic has been developed, which is now being used by the World Health Organization and the European Food Safety Authority. This review describes the evolution of risk assessment advice on carcinogens and discusses examples of ways in which carcinogens in food have been assessed in Europe.

  5. Diurnal Cortisol Secretion at Home and in Child Care: A Prospective Study of 2-Year-Old Toddlers

    ERIC Educational Resources Information Center

    Ouellet-Morin, Isabelle; Tremblay, Richard E.; Boivin, Michel; Meaney, Michael; Kramer, Michael; Cote, Sylvana M.

    2010-01-01

    Background: Previous studies indicate that children may experience disrupted cortisol secretion in child care. The extent to which this is a transient or long-term disruption is not known, as most studies have relied on cross-sectional designs, and age-heterogeneous small sample sizes. This study aims to (a) compare cortisol secretion measured at…

  6. Comparison of in vivo genotoxic and carcinogenic potency to augment mode of action analysis: Case study with hexavalent chromium.

    PubMed

    Thompson, Chad M; Bichteler, Anne; Rager, Julia E; Suh, Mina; Proctor, Deborah M; Haws, Laurie C; Harris, Mark A

    2016-04-01

    Recent analyses-highlighted by the International Workshops on Genotoxicity Testing Working Group on Quantitative Approaches to Genetic Toxicology Risk Assessment-have identified a correlation between (log) estimates of a carcinogen's in vivo genotoxic potency and in vivo carcinogenic potency in typical laboratory animal models, even when the underlying data have not been matched for tissue, species, or strain. Such a correlation could have important implications for risk assessment, including informing the mode of action (MOA) of specific carcinogens. When in vivo genotoxic potency is weak relative to carcinogenic potency, MOAs other than genotoxicity (e.g., endocrine disruption or regenerative hyperplasia) may be operational. Herein, we review recent in vivo genotoxicity and carcinogenicity data for hexavalent chromium (Cr(VI)), following oral ingestion, in relevant tissues and species in the context of the aforementioned correlation. Potency estimates were generated using benchmark doses, or no-observable-adverse-effect-levels when data were not amenable to dose-response modeling. While the ratio between log values for carcinogenic and genotoxic potency was ≥1 for many compounds, the ratios for several Cr(VI) datasets (including in target tissue) were less than unity. In fact, the ratios for Cr(VI) clustered closely with ratios for chloroform and diethanolamine, two chemicals posited to have non-genotoxic MOAs. These findings suggest that genotoxicity may not play a major role in the cancers observed in rodents following exposure to high concentrations of Cr(VI) in drinking water-a finding consistent with recent MOA and adverse outcome pathway (AOP) analyses concerning Cr(VI). This semi-quantitative analysis, therefore, may be useful to augment traditional MOA and AOP analyses. More case examples will be needed to further explore the general applicability and validity of this approach for human health risk assessment.

  7. Epidemiologic evidence for chloroprene carcinogenicity: review of study quality and its application to risk assessment.

    PubMed

    Bukowski, John Arthur

    2009-09-01

    This article evaluates the quality and weight of evidence associated with epidemiologic studies of cancer among occupational cohorts exposed to chloroprene. The focus is on liver, lung, and lymphohematopoietic cancers, which had been increased in early studies. Literature searches identified eight morbidity/mortality studies covering seven chloroprene-exposed cohorts from six countries. These studies were summarized and their quality was assessed using the 10 criteria suggested by the U.S. Environmental Protection Agency. The limitations within this literature (primarily the early studies) included crude exposure assessment, incomplete follow-up, uncertain baseline rates, and uncontrolled confounding by factors such as smoking, drinking, and co-exposure to benzene and vinyl chloride. Four cohorts were studied by the same group of investigators, who reported no overall increased associations for any cancers. This four-cohort study was by far the most rigorous, having the most comprehensive exposure assessment and follow-up and the most detailed documentation. This study also contained the two largest cohorts, including an American cohort from Louisville, Kentucky, that ranked at or near the top for each of the 10 quality criteria. There was evidence of a strong healthy worker effect in the four-cohort study, which could have hidden small excess risks. Small increased risks were suggested by internal or company-specific analyses, but these were most likely caused by uncontrolled confounding and low baseline rates. Overall, the weight of evidence does not support any substantial link between chloroprene exposure and cancer, but inconsistencies and a lack of control for major confounders preclude drawing firmer conclusions.

  8. [Endocrine disruptors: are they carcinogens?].

    PubMed

    Rochefort, Henri; Balaguer, Patrick

    2010-06-01

    Concerned with the high incidence of breast and prostate cancers in industrialized countries, including France, we reviewed the literature and national reports on the potential carcinogenic effects of several endocrine disruptors (ED) present in the environment. We examine why it is extremely difficult to obtain clear proof of a carcinogenic effect of ED in humans. Yet the results of several independent studies strongly point to such a carcinogenic effect, particularly in the case of hormone-dependent cancers. Such malignancies have been induced experimentally in rodents and have also been observed in humans. For example, a moderately elevated incidence of prostate cancer has been noted in U.S. farmers and, more recently in the French West Indian population exposed for more than 30 years to the insecticide chlordecone. We discuss the molecular mechanisms involved in this effect in prostate cancer Lessons from the observed trans-generational carcinogenic effect of the synthetic estrogen diethylstilboestrol also strongly suggests that future generations must be protected from widespread distribution of synthetic estrogens in the environment. We argue that a reduction in the use of some EDs in agriculture and the plastics industry would be much more beneficial in France than the prohibition of transgenic plants. PMID:21513143

  9. Predictive testing of environmental carcinogens

    SciTech Connect

    Dickson, J.G.

    1982-01-01

    Two research approaches are presented which address different aspects of predictive testing for environmental carcinogens. In Part I, a well-known microbial assay is used to determine the presence of carcinogens in an environmental sample of suspected hazard. In Part II, a single chemical carcinogen is chosen to demonstrate the utility of three-phase microcosms for prediction of transport and transformations pathways in a reservoir ecosystem. The Ames/Salmonella mutagenicity assay was used to screen processed oil shale extracts for potentially carcinogenic chemicals. Positive mutagenic activity was detected in organic solvent extracts of all four spent shales tested. Problems which might limit application of the Ames assay were explored. The results of assays of one-to-one mixtures of two mutagens which exhibited different dose response curves when assayed separately indicated the response to the mixture was nonadditive. Furthermore, the response to the mixture was determined to be statistically indistinguishable (chi-square analysis) from the dose response curve of one of the mutagens in the majority of cases. This masking effect was found to persist for one strong mutagen (benzo(a)pyrene) even when it composed only 10% of the mixture. The effect of various non-toxic solvents on the mutagenic response of certain mutagens was also determined. Three-phase microcosms were used to study the aquatic fate and effect of a polycyclic aromatic hydrocarbon (PAH), benz(a)antracene.

  10. Genotoxicity studies with the unstable Zeste-White (UZ) system of Drosophila melanogaster: Results with ten carcinogenic compounds

    SciTech Connect

    Batiste-Alentorn, M.; Xamena, N.; Creus, A.; Marcos, R. )

    1991-01-01

    To increase the number of chemicals tested using the Zeste-White (UZ) somatic mutation assay, ten selected carcinogens (acetamide, acrylamide, benzo({alpha})pyrene, cyclophosphamide, diethylstilbestrol, 4-nitroquinoline N-oxide, propyleneimine, safrole, thiourea, and o-toluidine) have been evaluated in this assay. The results show that all the compounds tested produce significant increases in the eye spot frequency at, at least, one of the concentrations assayed, indicating that the Zeste-White assay appears to be highly sensitive to these carcinogenic compounds. That is in agreement with data previously reported by other authors.

  11. The Role of Behavioral Self-Regulation in Learning to Read: A 2-Year Longitudinal Study of Icelandic Preschool Children

    ERIC Educational Resources Information Center

    Birgisdóttir, Freyja; Gestsdóttir, Steinunn; Thorsdóttir, Fanney

    2015-01-01

    Research Findings: Research suggests that behavioral self-regulation skills are critical for early school success, including success in literacy, but few studies have explored the relations that behavioral self-regulation may have with different components of early literacy development. The present study investigated the longitudinal contribution…

  12. Renal histopathology in toxicity and carcinogenicity studies with tert-butyl alcohol administered in drinking water to F344 rats: a pathology working group review and re-evaluation.

    PubMed

    Hard, Gordon C; Bruner, Richard H; Cohen, Samuel M; Pletcher, John M; Regan, Karen S

    2011-04-01

    An independent Pathology Working Group (PWG) re-evaluated the kidney changes in National Toxicology Program (NTP) toxicology/carcinogenicity studies of tert-butyl alcohol (TBA) in F344/N rats to determine possible mode(s) of action underlying renal tubule tumors in male rats at 2-years. In the 13-week study, the PWG confirmed that the normal pattern of round hyaline droplets in proximal convoluted tubules was replaced by angular droplet accumulation, and identified precursors of granular casts in the outer medulla, changes typical of alpha(2u)-globulin (α(2u)-g) nephropathy. In the 2-year study, the PWG confirmed the NTP observation of increased renal tubule tumors in treated male groups. Linear papillary mineralization, another hallmark of the α(2u)-g pathway was present only in treated male rats. Chronic progressive nephropathy (CPN) was exacerbated in high-dose males and females, with a relationship between advanced grades of CPN and renal tumor occurrence. Hyperplasia of the papilla lining was a component of CPN in both sexes, but there was no pelvic urothelial hyperplasia. High-dose females showed no TBA-related nephrotoxicity. The PWG concluded that both α(2u)-g nephropathy and exacerbated CPN modes of action were operative in TBA renal tumorigenicity in male rats, neither of which has relevance for human cancer risk.

  13. Chronic dietary toxicity and carcinogenicity study with potassium perfluorooctanesulfonate in Sprague Dawley rats.

    PubMed

    Butenhoff, John L; Chang, Shu-Ching; Olsen, Geary W; Thomford, Peter J

    2012-03-11

    To investigate toxicity and neoplastic potential from chronic exposure to perfluorooctanesulfonate (PFOS), a two-year toxicity and cancer bioassay was conducted with potassium PFOS (K⁺ PFOS) in male and female Sprague Dawley rats via dietary exposure at nominal K⁺ PFOS concentrations of 0, 0.5, 2, 5, and 20 μg/g (ppm) diet for up to 104 weeks. Additional groups were fed 20 ppm for the first 52 weeks, after which they were fed control diet through study termination (20 ppm Recovery groups). Scheduled interim sacrifices occurred on Weeks 4, 14, and 53, with terminal sacrifice between Weeks 103 and 106. K⁺ PFOS appeared to be well-tolerated, with some reductions in body weight occurring in treated rats relative to controls over certain study periods. Male rats experienced a statistically significant decreased trend in mortality with significantly increased survival to term at the two highest treatment levels. Decreased serum total cholesterol, especially in males, and increased serum urea nitrogen were consistent clinical chemistry observations that were clearly related to treatment. The principal non-neoplastic effect associated with K⁺ PFOS exposure was in livers of males and females and included hepatocellular hypertrophy, with proliferation of endoplasmic reticulum, vacuolation, and increased eosinophilic granulation of the cytoplasm. Statistically significant increases in hepatocellular adenoma were observed in males (p=0.046) and females (p=0.039) of the 20 ppm treatment group, and all of these tumors were observed in rats surviving to terminal sacrifice. The only hepatocellular carcinoma observed was in a 20 ppm dose group female. There were no treatment-related findings for thyroid tissue in rats fed K⁺ PFOS through study termination; however, male rats in the 20 ppm Recovery group had statistically significantly increased thyroid follicular cell adenoma, which was considered spurious. There was no evidence of kidney or bladder effects. In rats, the

  14. The Predictive Relationship between Temperament, School Adjustment, and Academic Achievement: A 2-Year Longitudinal Study of Children At-Risk

    ERIC Educational Resources Information Center

    Al-Hendawi, Maha

    2010-01-01

    Individual differences in temperament can be a risk or a protective factor for a child, especially for children at-risk who possess single or multiple risk factors that may interfere with their educational success and affect their healthy development and their life-long outcomes. This research study examined the concurrent and longitudinal…

  15. Instructional Faculty and Staff in Public 2-year Colleges. Statistical Analysis Report. 1993 National Study of Postsecondary Faculty (NSOPF:93).

    ERIC Educational Resources Information Center

    Palmer, James C.

    Drawing on data from the 1993 National Study of Postsecondary Faculty, this analysis sought to differentiate instructional faculty and staff at public two-year colleges by age (under 35 vs. 55-64) and by years of experience in the current job (under 10 years vs. 20 or more years). The report examines differences by primary teaching field,…

  16. Self-Regulation in Children Born with Extremely Low Birth Weight at 2 Years Old: A Comparison Study

    ERIC Educational Resources Information Center

    Lynn, Lisa N.; Cuskelly, Monica; Gray, Peter H.; O'Callaghan, Michael J.

    2012-01-01

    Survival rates for children born with extremely low birth weight (ELBW) are increasing; however, many of these children experience later problems with learning. This study adopted an integrated approach to these problems, involving the self-regulatory tasks of inhibition and delay of gratification and relevant individual factors including…

  17. Line narrowing spectroscopic studies of DNA-carcinogen adducts and DNA-dye complexes

    SciTech Connect

    Suh, Myungkoo

    1995-12-06

    Laser-induced fluorescence line narrowing and non-line narrowing spectroscopic methods were applied to conformational studies of stable DNA adducts of the 7{beta}, 8{alpha}-dihydoxy-9{alpha}, l0{alpha}-epoxy-7,8,9, 10-tetrahydrobenzo[{alpha}]pyrene (anti-BPDE). Stereochemically distinct (+)-trans-, ({minus})-trans-, (+)-cis- and ({minus})-cis adducts of anti-BPDE bound to exocyclic amino group of the central guanine in an 11-mer oligonucleotide, exist in a mixture of conformations in frozen aqueous buffer matrices. The (+)-trans adduct adopts primarily an external conformation with a smaller fraction ( {approximately} 25 %) exists in a partially base-stacked conformation. Both cis adducts were found to be intercalated with significant {pi}-{pi} stacking interactions between the pyrenyl residues and the bases. Conformations of the trans-adduct of (+)-anti -BPDE in 11-mer oligonucleotides were studied as a function of flanking bases. In single stranded form the adduct at G{sub 2} or G{sub 3} (5 ft-flanking, base guanine) adopts a conformation with strong, interaction with the bases. In contrast, the adduct with a 5ft-flanking, thymine exists in a primarily helixexternal conformation. Similar differences were observed in the double stranded oligonucleotides. The nature of the 3ft-flanking base has little influence on the conformational equilibrium of the (+)-trans-anti BPDE-dG adduct. The formation and repair of BPDE-N{sup 2}-dG in DNA isolated from the skin of mice treated topically with benzo[{alpha}]pyrene (BP) was studied. Low-temperature fluorescence spectroscopy of the intact DNA identified the major adduct as (+)-trans-anti-BPDE-N-dG, and the minor adduct fraction consisted mainly of (+)-cis-anti-BPDE-N{sup 2}-dG.

  18. Prediction of Chemical Carcinogenicity in Rodents from in vitro Genetic Toxicity Assays

    NASA Astrophysics Data System (ADS)

    Tennant, Raymond W.; Margolin, Barry H.; Shelby, Michael D.; Zeiger, Errol; Haseman, Joseph K.; Spalding, Judson; Caspary, William; Resnick, Michael; Stasiewicz, Stanley; Anderson, Beth; Minor, Robert

    1987-05-01

    Four widely used in vitro assays for genetic toxicity were evaluated for their ability to predict the carcinogenicity of selected chemicals in rodents. These assays were mutagenesis in Salmonella and mouse lymphoma cells and chromosome aberrations and sister chromatid exchanges in Chinese hamster ovary cells. Seventy-three chemicals recently tested in 2-year carcinogenicity studies conducted by the National Cancer Institute and the National Toxicology Program were used in this evaluation. Test results from the four in vitro assays did not show significant differences in individual concordance with the rodent carcinogenicity results; the concordance of each assay was approximately 60 percent. Within the limits of this study there was no evidence of complementarity among the four assays, and no battery of tests constructed from these assays improved substantially on the overall performance of the Salmonella assay. The in vitro assays which represented a range of three cell types and four end points did show substantial agreement among themselves, indicating that chemicals positive in one in vitro assay tended to be positive in the other in vitro assays. To help put this project into its proper context, we emphasize certain features of the study: 1) Standard protocols were used to mimic the major use of STTs worldwide--screening for mutagens and carcinogens; no attempt was made to optimize protocols for specific chemicals. 2) The 73 NTP chemicals and their 60% incidence of carcinogenicity are probably not representative of the universe of chemicals but rather reflect the recent chemical selection process for the NTP carcinogenicity assay. 3) The small, diverse group of chemicals precludes a meaningful evaluation of the predictive utility of chemical structure information. 4) The NTP is currently testing these same 73 chemicals in two in vivo STTs for chromosomal effects. 5) Complete data for an additional group of 30 to 40 NTP chemicals will be gathered on

  19. Sensing properties of BN nanotube toward carcinogenic 4-chloroaniline: A computational study

    NASA Astrophysics Data System (ADS)

    Eslami, Majid; Vahabi, Vahid; Ahmadi Peyghan, Ali

    2016-02-01

    The viability of using a BN nanotube for detection of para-chloroaniline molecule was studied by means of density functional theory calculations. The results indicate that the molecule prefers to be adsorbed on the intrinsic BN nanotube from its N atom, releasing energy of 0.65 eV without significant effect on the electrical conductivity of the tube. Thus, para-chloroaniline cannot be detected using this intrinsic nanotube. To overcome this problem, a nitrogen atom of the tube wall was replaced by a Si atom. It was shown that the Si-doped tube not only can adsorb the molecule strongly, but also may detect its presence because of the drastic increase of the electrical conductivity of the tube.

  20. An Evaluation of the Mode of Action Framework for MutagenicCarcinogens Case Study II: Chromium (VI).

    EPA Science Inventory

    In response to the 2005 revised U.S Environmental Protection Agency’s (EPA) Cancer Guidelines, a strategy is being developed to include all mutagenicity and other genotoxicity data with any additional information to determine whether a carcinogen operates through a mutagenic mode...

  1. In silico study of anti-carcinogenic lysyl oxidase-like 2 inhibitors.

    PubMed

    Muhammad, Syed Aun; Ali, Amjad; Ismail, Tariq; Zafar, Rehan; Ilyas, Umair; Ahmad, Jamil

    2014-08-01

    Lysyl oxidase homolog 2 (LOXL2), also known as lysyl oxidase-like protein 2 is recently been explored as regulator of carcinogenesis and has been shown to be involved in tumor progression and metastasis of several carcinomas. Therefore LOXL2 has been considered as potential therapeutic target. Doing so, its inhibitors as new chemotherapeutic lead molecules: 4-amino-5-(2-hydroxyphenyl)-1,2,4-triazol-3-thione (2a) and 4-(2-hydroxybenzalidine) amine-5-(2-hydroxy) phenyl-1,2,4-triazole-3-thiol (2b) are synthesized by fusion method (refluxed at 160 °C). Spectral analysis of these triazole derivatives are characterized by FTIR and NMR. Active binding sites and quality of the LOXL2 model is assessed by Ramachandran plots and finally drug-target analysis is performed by computational virtual screening tools. Compounds 2a and 2b showed optimum target binding affinity with -6.2 kcal/mol and -8.9 kcal/mol binding energies. This insilico study will add to our understanding of the drug designing and development, and to target cancer-causing proteins more precisely and quickly than before. PMID:24703812

  2. In silico study of anti-carcinogenic lysyl oxidase-like 2 inhibitors.

    PubMed

    Muhammad, Syed Aun; Ali, Amjad; Ismail, Tariq; Zafar, Rehan; Ilyas, Umair; Ahmad, Jamil

    2014-08-01

    Lysyl oxidase homolog 2 (LOXL2), also known as lysyl oxidase-like protein 2 is recently been explored as regulator of carcinogenesis and has been shown to be involved in tumor progression and metastasis of several carcinomas. Therefore LOXL2 has been considered as potential therapeutic target. Doing so, its inhibitors as new chemotherapeutic lead molecules: 4-amino-5-(2-hydroxyphenyl)-1,2,4-triazol-3-thione (2a) and 4-(2-hydroxybenzalidine) amine-5-(2-hydroxy) phenyl-1,2,4-triazole-3-thiol (2b) are synthesized by fusion method (refluxed at 160 °C). Spectral analysis of these triazole derivatives are characterized by FTIR and NMR. Active binding sites and quality of the LOXL2 model is assessed by Ramachandran plots and finally drug-target analysis is performed by computational virtual screening tools. Compounds 2a and 2b showed optimum target binding affinity with -6.2 kcal/mol and -8.9 kcal/mol binding energies. This insilico study will add to our understanding of the drug designing and development, and to target cancer-causing proteins more precisely and quickly than before.

  3. Acoustic evidence for the development of gestural coordination in the speech of 2-year-olds: a longitudinal study.

    PubMed

    Goodell, E W; Studdert-Kennedy, M

    1993-08-01

    Studies of child phonology have often assumed that young children first master a repertoire of phonemes and then build their lexicon by forming combinations of these abstract, contrastive units. However, evidence from children's systematic errors suggests that children first build a repertoire of words as integral sequences of gestures and then gradually differentiate these sequences into their gestural and segmental components. Recently, experimental support for this position has been found in the acoustic records of the speech of 3-, 5-, and 7-year-old children, suggesting that even in older children some phonemes have not yet fully segregated as units of gestural organization and control. The present longitudinal study extends this work to younger children (22- and 32-month-olds). Results demonstrate clear differences in the duration and coordination of gestures between children and adults, and a clear shift toward the patterns of adult speakers during roughly the third year of life. Details of the child-adult differences and developmental changes vary from one aspect of an utterance to another. PMID:8377484

  4. Two-year drinking water carcinogenicity study of methyl tertiary-butyl ether (MTBE) in Wistar rats.

    PubMed

    Dodd, Darol; Willson, Gabrielle; Parkinson, Horace; Bermudez, Edilberto

    2013-07-01

    Methyl tertiary-butyl ether (MTBE) has been used as a gasoline additive to reduce tailpipe emissions and its use has been discontinued. There remains a concern that drinking water sources have been contaminated with MTBE. A two-year drinking water carcinogenicity study of MTBE was conducted in Wistar rats (males, 0, 0.5, 3, 7.5 mg ml(-1); and females, 0, 0.5, 3, and 15 mg ml(-1)). Body weights were unaffected and water consumption was reduced in MTBE-exposed males and females. Wet weights of male kidneys were increased at the end of two years of exposure to 7.5 mg ml(-1) MTBE. Chronic progressive nephropathy was observed in males and females, was more severe in males, and was exacerbated in the high MTBE exposure groups. Brain was the only tissue with a statistically significant finding of neoplasms. One astrocytoma (1/50) was found in a female rat (15 mg ml(-1)). The incidence of brain astrocytomas in male rats was 1/50, 1/50, 1/50 and 4/50 for the 0, 0.5, 3 and 7.5 mg ml(-1) exposure groups, respectively. This was a marginally significant statistical trend, but not statistically significant when pairwise comparisons were made or when multiple comparisons were taken into account. The incidence of astrocytoma fell within historical control ranges for Wistar rats, and the brain has not been identified as a target organ following chronic administration of MTBE, ethyl tert-butyl ether, or tertiary butyl alcohol (in drinking water) to mice and rats. We conclude that the astrocytomas observed in this study are not associated with exposure to MTBE.

  5. 2-year study of chemical composition of bulk deposition in a south China coastal city: comparison with east Asian cities.

    PubMed

    Wai, K M; Tanner, P A; Tam, C W F

    2005-09-01

    Using the emission strengths of the precursor gases, the nature of soil in China, the ventilation power and half value rainout region length, the nss-SO42-, NO3-, Ca2+, and NH4+ concentrations, and pH of rainwater at Hong Kong and other cities of China and Japan are compared and rationalized. The chemical composition of Hong Kong bulk deposition from 1998 to 2000 is taken from our collection and analysis of 156 daily samples. The volume-weighted average (VWA) pH is 4.2 over the whole study period. Nonsea salt- (nss-) sulfate is the most abundant species in the samples, and the pH mostly depended upon the concentrations of the major species nss-SO42, NO3-, Ca2+, and NH4+. All species concentrations show higher levels in the cold season (especially NO3- and Ca2+), which indicates the dominant dilution effects in the warm season due to heavy rainfall and the influence of the continental outflow of pollutants during the cold season. For Hong Kong bulk deposition, the VWA pH is slightly lower in the cold season, and there is a slight decrease in VWA pH over the period from 1994 to 2000. The impact of acid rain in Hong Kong is briefly discussed.

  6. 2-year study of chemical composition of bulk deposition in a South China coastal city: comparison with East Asian cities

    SciTech Connect

    K.M. Wai; P.A. Tanner; C.W.F. Tam

    2005-09-01

    Using the emission strengths of the precursor gases, the nature of soil in China, the ventilation power and half value rainout region length, the nss-SO{sub 4}{sup 2-}, NO{sub 3}{sup -}, Ca{sup 2+}, and NH{sub 4}{sup +} concentrations, and pH of rainwater at Hong Kong and other cities of China and Japan are compared and rationalized. The chemical composition of Hong Kong bulk deposition from 1998 to 2000 is taken from the collection and analysis of 156 daily samples. The volume-weighted average (VWA) pH is 4.2 over the whole study period. Nonsea salt- (nss-) sulfate is the most abundant species in the samples, and the pH mostly depended upon the concentrations of the major species nss-SO{sub 4}{sup 2-}, NO{sub 3}{sup -}, Ca{sup 2+}, and NH{sub 4}{sup +}. All species concentrations show higher levels in the cold season (especially NO{sub 3}- and Ca{sup 2+}), which indicates the dominant dilution effects in the warm season due to heavy rainfall and the influence of the continental outflow of pollutants during the cold season. For Hong Kong bulk deposition, the VWA pH is slightly lower in the cold season, and there is a slight decrease in VWA pH over the period from 1994 to 2000. The impact of acid rain in Hong Kong is briefly discussed. 36 refs., 3 figs., 5 tabs.

  7. 2-year study of chemical composition of bulk deposition in a south China coastal city: comparison with east Asian cities.

    PubMed

    Wai, K M; Tanner, P A; Tam, C W F

    2005-09-01

    Using the emission strengths of the precursor gases, the nature of soil in China, the ventilation power and half value rainout region length, the nss-SO42-, NO3-, Ca2+, and NH4+ concentrations, and pH of rainwater at Hong Kong and other cities of China and Japan are compared and rationalized. The chemical composition of Hong Kong bulk deposition from 1998 to 2000 is taken from our collection and analysis of 156 daily samples. The volume-weighted average (VWA) pH is 4.2 over the whole study period. Nonsea salt- (nss-) sulfate is the most abundant species in the samples, and the pH mostly depended upon the concentrations of the major species nss-SO42, NO3-, Ca2+, and NH4+. All species concentrations show higher levels in the cold season (especially NO3- and Ca2+), which indicates the dominant dilution effects in the warm season due to heavy rainfall and the influence of the continental outflow of pollutants during the cold season. For Hong Kong bulk deposition, the VWA pH is slightly lower in the cold season, and there is a slight decrease in VWA pH over the period from 1994 to 2000. The impact of acid rain in Hong Kong is briefly discussed. PMID:16190210

  8. Changes in Intra-pelvic Obliquity Angle 0–2 Years After Total Hip Arthroplasty and Its Effects on Leg Length Discrepancy: A Retrospective Study

    PubMed Central

    Zhang, Yin; Cheng, Tao; Zhang, Xian-Long

    2015-01-01

    Background: Total hip arthroplasty (THA) is one of the most effective treatments for phase III and IV hip arthrosis. Lower limb length balancing is one of the determining factors of a successful surgery, particularly in patients with developmental dysplasia of the hip (DDH). The purpose of this study was to evaluate the postoperative change in intra-pelvic obliquity (intra-PO) angle in the coronal plane and its effects on leg length discrepancy (LLD) within 2 years. Methods: A total of 78 patients (70 females, 8 males) were enrolled in this study. All patients were suffering from DDH with varying degrees of LLD. Pelvic plain radiographs were collected before and after the operation. The intra-PO angles were measured 0, 0.5, 1 and 2 years after THA. At the same time, postoperative LLD was measured with blocking test. Results: PO changed significantly in the first year after THA surgery (0 year vs. 0.5 year, P < 0.01; 0.5 year vs. 1 year, P < 0.01), and the changing value of intra-PO angle (ΔPO) slowed down substantially during the first 2 years after THA (0.5 year vs. 0.5–1 year, P < 0.01; 0.5–1 year vs. 1–2 years, P < 0.01). With the change in intra-PO angle, LLD also got narrow within the 1st year (0 year vs. 0.5 year, P < 0.01; 0.5 year vs. 1 year, P < 0.01). Elderly patients had a smaller intra-PO angle reduction (Group A vs. Group B, P = 0.01; Group B vs. Group C, P < 0.01). Conclusions: Intra-PO angle and LLD gap narrowed with time after THA surgery. In particular, elderly patients had smaller change in intra-PO angle. PMID:25963356

  9. Prospective Study Evaluating Postoperative Radiotherapy Plus 2-Year Androgen Suppression for Post-Radical Prostatectomy Patients With Pathologic T3 Disease and/or Positive Surgical Margins

    SciTech Connect

    Choo, Richard Danjoux, Cyril; Gardner, Sandra; Morton, Gerard; Szumacher, Ewa; Loblaw, D. Andrew; Cheung, Patrick; Pearse, Maria

    2009-10-01

    Purpose: To determine the efficacy of a combined approach of postoperative radiotherapy (RT) plus 2-year androgen suppression (AS) for patients with pathologic T3 disease (pT3) and/or positive surgical margins (PSM) after radical prostatectomy (RP). Methods and Materials: A total of 78 patients with pT3 and/or PSM after RP were treated with RT plus 2-year AS, as per a pilot, prospective study. Androgen suppression started within 1 month after the completion of RT and consisted of nilutamide for 4 weeks and buserelin acetate depot subcutaneously every 2 months for 2 years. Relapse-free rate, including freedom from prostate-specific antigen (PSA) relapse, was estimated using the Kaplan-Meier method. A Cox regression analysis was performed to evaluate prognostic factors for relapse. Prostate-specific antigen relapse was defined as a PSA rise above 0.2 ng/mL, with two consecutive increases over a minimum of 3 months. Results: The median age was 61 years at the time of RP. The median interval between RP and postoperative RT was 4.2 months. Forty-nine patients had undetectable PSA (<0.2 ng/mL), and 29 had persistently detectable postoperative PSA at the time of the protocol treatment. Median follow-up from RT was 6.4 years. Relapse-free rates at 5 and 7 years were 94.4% and 86.3%, respectively. Survival rates were 96% at 5 years and 93.1% at 7 years. On Cox regression analysis, persistently detectable postoperative PSA and pT3b-T4 were significant predictors for relapse. Conclusion: The combined treatment of postoperative RT plus 2-year AS yielded encouraging results for patients with pT3 and/or PSM and warrants a confirmatory study.

  10. Comparison of the expression profiles induced by genotoxic and nongenotoxic carcinogens in rat liver.

    PubMed

    Ellinger-Ziegelbauer, Heidrun; Stuart, Barry; Wahle, Brad; Bomann, Werner; Ahr, Hans Juergen

    2005-08-01

    Application of recently developed gene expression techniques using microarrays in toxicological studies (toxicogenomics) facilitate the interpretation of a toxic compound's mode of action and may also allow the prediction of selected toxic effects based on gene expression changes. In order to test this hypothesis, we investigated whether carcinogens at doses known to induce liver tumors in the 2-year rat bioassay deregulate characteristic sets of genes in a short term in vivo study and whether these deregulated genes represent defined biological pathways. Male Wistar rats were dosed with the four nongenotoxic hepatocarcinogens methapyrilene (MPy, 60 mg/kg/day), diethylstilbestrol (DES, 10 mg/kg/day), Wy-14643 (Wy, 60 mg/kg/day), and piperonylbutoxide (PBO, 1200 mg/kg/day). After 1, 3, 7, and 14 days, the livers were taken for histopathological evaluation and for analysis of the gene expression profiles on Affymetrix RG_U34A arrays. The expression profile of the four nongenotoxic carcinogens were compared to the profiles of the four genotoxic carcinogens 2-nitrofluorene (2-NF), dimethylnitrosamine (DMN), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and aflatoxin B1 (AB1) from a similar study reported previously. By using statistical and clustering tools characteristically deregulated genes were extracted and functionally classified. Distinct cellular pathways were affected by the nongenotoxic carcinogens compared to the genotoxic carcinogens which at least partly correlated with the two-stage model of carcinogenesis. Characteristic to genotoxic carcinogens were a DNA damage response and the activation of proliferative and survival signaling. Nongenotoxic carcinogens showed responses to oxidative DNA or protein damage, as well as cell cycle progression and signs of regeneration. Many of the gene alterations found with the nongenotoxic carcinogens imply compound-specific mechanisms. Although neither a single gene nor a single pathway will be sufficient to

  11. Inter-laboratory study of human in vitro toxicogenomics-based tests as alternative methods for evaluating chemical carcinogenicity: a bioinformatics perspective.

    PubMed

    Herwig, R; Gmuender, H; Corvi, R; Bloch, K M; Brandenburg, A; Castell, J; Ceelen, L; Chesne, C; Doktorova, T Y; Jennen, D; Jennings, P; Limonciel, A; Lock, E A; McMorrow, T; Phrakonkham, P; Radford, R; Slattery, C; Stierum, R; Vilardell, M; Wittenberger, T; Yildirimman, R; Ryan, M; Rogiers, V; Kleinjans, J

    2016-09-01

    The assessment of the carcinogenic potential of chemicals with alternative, human-based in vitro systems has become a major goal of toxicogenomics. The central read-out of these assays is the transcriptome, and while many studies exist that explored the gene expression responses of such systems, reports on robustness and reproducibility, when testing them independently in different laboratories, are still uncommon. Furthermore, there is limited knowledge about variability induced by the data analysis protocols. We have conducted an inter-laboratory study for testing chemical carcinogenicity evaluating two human in vitro assays: hepatoma-derived cells and hTERT-immortalized renal proximal tubule epithelial cells, representing liver and kidney as major target organs. Cellular systems were initially challenged with thirty compounds, genome-wide gene expression was measured with microarrays, and hazard classifiers were built from this training set. Subsequently, each system was independently established in three different laboratories, and gene expression measurements were conducted using anonymized compounds. Data analysis was performed independently by two separate groups applying different protocols for the assessment of inter-laboratory reproducibility and for the prediction of carcinogenic hazard. As a result, both workflows came to very similar conclusions with respect to (1) identification of experimental outliers, (2) overall assessment of robustness and inter-laboratory reproducibility and (3) re-classification of the unknown compounds to the respective toxicity classes. In summary, the developed bioinformatics workflows deliver accurate measures for inter-laboratory comparison studies, and the study can be used as guidance for validation of future carcinogenicity assays in order to implement testing of human in vitro alternatives to animal testing.

  12. Cementless anatomical prosthesis for the treatment of 3-part and 4-part proximal humerus fractures: cadaver study and prospective clinical study with minimum 2 years followup

    PubMed Central

    Obert, Laurent; Saadnia, Rachid; Loisel, François; Uhring, Julien; Adam, Antoine; Rochet, Séverin; Clappaz, Pascal; Lascar, Tristan

    2016-01-01

    Introduction: The purpose of this study was to evaluate the functional and radiological outcomes of a cementless, trauma-specific locked stem for 3- and 4-part proximal humeral fractures. Materials and methods: This study consisted of two parts: a cadaver study with 22 shoulders and a multicenter prospective clinical study of 23 fracture patients evaluated at least 2 years after treatment. In the cadaver study, the locked stem (HumelockTM, FX Solutions) and its instrumentation were evaluated. In the clinical study, five senior surgeons at four different hospitals performed the surgical procedures. An independent surgeon evaluated the patients using clinical (Constant score, QuickDASH) and radiological (X-rays, CT scans) outcome measures. Results: The cadaver study allowed us to validate the height landmarks relative to the pectoralis major tendon. In the clinical study, at the review, abduction was 95° (60–160), forward flexion was 108° (70–160), external rotation (elbow at body) was 34° (0–55), the QuickDASH was 31 (4.5–59), the overall Constant score was 54 (27–75), and the weighted Constant score was 76 (31.5–109). Discussion: This preliminary study of hemiarthroplasty (HA) with a locked stem found results that were at least equivalent to published series. As all patients had at least a 2-year follow-up, integration of the locked stem did not cause any specific complications. These results suggest that it is possible to avoid using cement when hemiarthroplasty is performed for the humeral stem. This implant makes height adjustment and transosseous suturing of the tuberosities more reproducible. PMID:27194107

  13. Joint unloading implant modifies subchondral bone trabecular structure in medial knee osteoarthritis: 2-year outcomes of a pilot study using fractal signature analysis

    PubMed Central

    Miller, Larry E; Sode, Miki; Fuerst, Thomas; Block, Jon E

    2015-01-01

    Background Knee osteoarthritis (OA) is largely attributable to chronic excessive and aberrant joint loading. The purpose of this pilot study was to quantify radiographic changes in subchondral bone after treatment with a minimally invasive joint unloading implant (KineSpring® Knee Implant System). Methods Nine patients with unilateral medial knee OA resistant to nonsurgical therapy were treated with the KineSpring System and followed for 2 years. Main outcomes included Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, function, and stiffness subscores and independent core laboratory determinations of joint space width and fractal signature of the tibial cortex. Results WOMAC scores, on average, improved by 92% for pain, 91% for function, and 79% for stiffness over the 2-year follow-up period. Joint space width in the medial compartment of the treated knee significantly increased from 0.9 mm at baseline to 3.1 mm at 2 years; joint space width in the medial compartment of the untreated knee was unchanged. Fractal signatures of the vertically oriented trabeculae in the medial compartment decreased by 2.8% in the treated knee and increased by 2.1% in the untreated knee over 2 years. No statistically significant fractal signature changes were observed in the horizontally oriented trabeculae in the medial compartment or in the horizontal or vertical trabeculae of the lateral compartment in the treated knee. Conclusion Preliminary evidence suggests that the KineSpring System may modify knee OA disease progression by increasing joint space width and improving subchondral bone trabecular integrity, thereby reducing pain and improving joint function. PMID:25670891

  14. Rodent carcinogens: Setting priorities

    SciTech Connect

    Gold, L.S.; Slone, T.H.; Stern, B.R.; Manley, N.B.; Ames, B.N. )

    1992-10-09

    The human diet contains an enormous background of natural chemicals, such as plant pesticides and the products of cooking, that have not been a focus of carcinogenicity testing. A broadened perspective that includes these natural chemicals is necessary. A comparison of possible hazards for 80 daily exposures to rodent carcinogens from a variety of sources is presented, using an index (HERP) that relates human exposure to carcinogenic potency in rodents. A similar ordering would be expected with the use of standard risk assessment methodology for the same human exposure values. Results indicate that, when viewed against the large background of naturally occurring carcinogens in typical portions of common foods, the residues of synthetic pesticides or environmental pollutants rank low. A similar result is obtained in a separate comparison of 32 average daily exposures to natural pesticides and synthetic pesticides residues in the diet. Although the findings do not indicate that these natural dietary carcinogens are important in human cancer, they cast doubt on the relative importance for human cancer of low-dose exposures to synthetic chemicals.

  15. Experimental studies in rat lungs on the carcinogenicity and dose-response relationships of eight frequently occurring environmental polycyclic aromatic hydrocarbons

    SciTech Connect

    Deutsch-Wenzel, R.P.; Brune, H.; Grimmer, G.; Dettbarn, G.; Misfeld, J.

    1983-09-01

    The biologic activity of eight highly purified polycyclic aromatic hydrocarbons (PAH) widely distributed in the human environment was tested in the respiratory tracts of rats. These studies were performed for the examination of carcinogenic activity of the compounds and determination of a dose-response relationship. The lung implantation method was used in 3-month-old female OM rats. A dose-response relationship was obtained for benzo(a)pyrene (BaP), anthanthrene (ANT), benzo(b)fluoranthene (BbF), indeno(1,2,3-cd)pyrene (IND), benzo(j)fluoranthene (BjF), and benzo(k)fluoranthene (BkF). Benzo(e)pyrene and benzo(ghi)perylene showed no tumor-producing effect in this system when given at doses of 5 mg. The histologic and mathematical evaluations indicated that the investigated compounds had distinct carcinogenic potencies. After probit analysis of the results, the carcinogenic potencies of PAH investigated in the lung implantation model rank as follows: BaP, 1.00; ANT, 0.19; BbF, 0.11; IND, 0.08; BkF, 0.03; and BjF, 0.03.

  16. The carcinogenicity of chromium

    PubMed Central

    Norseth, Tor

    1981-01-01

    The carcinogenicity of chromium compounds is reviewed with specific attention to the gaps in knowledge for risk estimation and research needs. The most important problems at present are whether trivalent chromium compounds cause cancer, and whether there is a difference in cancer causing effects between the soluble and the slightly soluble hexavalent compounds in the practical exposure situation. Dose estimates for risk estimation based on epidemiological investigations are also lacking. Present evidence indicates that the trivalent chromium compounds do not cause cancer although high concentrations in some in vitro systems have shown genetic toxicity. Hexavalent chromium compounds cause cancer in humans, in experimental animals and exert genetic toxicity in bacteria and in mammalian cells in vitro. Epidemiological evidence and animal experiments indicate that the slightly soluble hexavalent salts are the most potent carcinogens, but proper identification and characterization of exposure patterns in epidemiological work are lacking. Workers also tend to have mixed exposures. Soluble and slightly soluble salts are equally potent genotoxic agents in vitro. Further work for establishing dose estimates for risk evaluation in epidemiological work is important. In vitro systems should be applied for further identification of the mechanism of the carcinogenic effects, and animal experiments are urgent for comparison of the carcinogenic potency of the different hexavalent salts. Hexavalent chromium salts must be regarded as established carcinogens, and proper action should be taken in all industries with regard to such exposure. At present the carcinogenic risk to the general population caused by chromium compounds seems to be negligible, chromium in cigarettes, however, is an uncertainty in this respect. The amount of chromium and the type of chromium compounds inhaled from cigarettes is not known. PMID:7023928

  17. Comparative study of the hepatotoxic, genotoxic and carcinogenic effects of praziquantel distocide & the natural myrrh extract Mirazid on adult male albino rats.

    PubMed

    Omar, Ahmed; Elmesallamy, Ghada El-Said; Eassa, Shereen

    2005-04-01

    Praziquantel (PZQ) is widely and effectively used in the control of bilharziasis which constitutes a major endemic health problem in Egypt. However, recent studies recommended that the drug must be re-evaluated because of its potential carcinogenicity and genotoxicity. Mirazid is a new natural anti-schistosomal drug formed of myrrh extract and considered to be a safe drug. This work was conducted to evaluate and compare hepatotoxic, genotoxic and carcinogenic effects of PZQ and Mirazid on adult male albino rats by assessment of serum levels of ALT, AST and bilirubin, histopathological study of the liver and cytogenetic study of bone marrow cells. 100 adult male albino rats were equally divided into 4 groups: (I): negative control, (II): control rats received distilled water, (III): received weekly single oral dose of PZQ (1500 mg/kg) for 6 weeks, (IV): received daily oral dose of Mirazid (500 mg/kg) for 6 weeks. At the end of the study 10 rats of each group were investigated by assessment of the levels of AST, ALT, & Bilirubin. After scarification, liver sections were examined by light microscopy. Another 10 rats of each group were submitted to cytogenetic examination. It was found that praziquantel induced a significant increase in the mean values of AST, ALT and bilirubin with areas of hyaline degeneration, fatty changes, dysplasia and necrosis in the liver sections. It also induced a significant increase in the incidence of chromosomal aberrations as polyploidy, fragment, deletion and ring chromosome as compared with control group. Mirazid induced a non significant increase in the mean values of AST, ALT and bilirubin, with a normal hepatic tissue, and a non significant increase in the incidence of chromosomal aberrations, as compared with the control group. On comparing both drugs, praziquantel induced a significant hepatotoxic, genotoxic and carcinogenic effects. It was concluded that, Praziquantel is considered to be a hepatotoxic, genotoxic and carcinogenic

  18. A randomized study on migration of the Spectron EF and the Charnley flanged 40 cemented femoral components using radiostereometric analysis at 2 years

    PubMed Central

    2011-01-01

    Background and purpose We performed a randomized study to determine the migration patterns of the Spectron EF femoral stem and to compare them with those of the Charnley stem, which is regarded by many as the gold standard for comparison of implants due to its extensive documentation. Patients and methods 150 patients with a mean age of 70 years were randomized, single-blinded, to receive either a cemented Charnley flanged 40 monoblock, stainless steel, vaquasheen surface femoral stem with a 22.2-mm head (n = 30) or a cemented Spectron EF modular, matte, straight, collared, cobalt-chrome femoral stem with a 28-mm femoral head and a roughened proximal third of the stem (n = 120). The patients were followed with repeated radiostereometric analysis for 2 years to assess migration. Results At 2 years, stem retroversion was 2.3° and 0.7° (p < 0.001) and posterior translation was 0.44 mm and 0.17 mm (p = 0.002) for the Charnley group (n = 26) and the Spectron EF group (n = 74), respectively. Subsidence was 0.26 mm for the Charnley and 0.20 mm for the Spectron EF (p = 0.5). Interpretation The Spectron EF femoral stem was more stable than the Charnley flanged 40 stem in our study when evaluated at 2 years. In a report from the Norwegian arthroplasty register, the Spectron EF stem had a higher revision rate due to aseptic loosening beyond 5 years than the Charnley. Initial stability is not invariably related to good long-term results. Our results emphasize the importance of prospective long-term follow-up of prosthetic implants in clinical trials and national registries and a stepwise introduction of implants. PMID:21895504

  19. Effect of Workplace Noise on Hearing Ability in Tile and Ceramic Industry Workers in Iran: A 2-Year Follow-Up Study

    PubMed Central

    Mirmohammadi, Seyyed Jalil; Mehrparvar, Amir Houshang; Mollasadeghi, Abolfazl

    2013-01-01

    Introduction. Noise as a common physical hazard may lead to noise-induced hearing loss, an irreversible but preventable disorder. Annual audiometric evaluations help detect changes in hearing status before clinically significant hearing loss develops. This study was designed to track hearing threshold changes during 2-year follow-up among tile and ceramic workers. Methods. This follow-up study was conducted on 555 workers (totally 1110 ears). Subjects were divided into four groups according to the level of noise exposure. Hearing threshold in conventional audiometric frequencies was measured and standard threshold shift was calculated for each ear. Results. Hearing threshold was increased during 2 years of follow-up. Increased hearing threshold was most frequently observed at 4000, 6000, and 3000 Hz. Standard threshold shift was observed in 13 (2.34%), 49 (8.83%), 22 (3.96%), and 63 (11.35%) subjects in the first and second years of follow-up in the right and left ears, respectively. Conclusions. This study has documented a high incidence of noise-induced hearing loss in tile and ceramic workers that would put stress on the importance of using hearing protection devices. PMID:24453922

  20. Toxicity and Carcinogenicity of Dichlorodiphenyltrichloroethane (DDT)

    PubMed Central

    Harada, Takanori; Takeda, Makio; Kojima, Sayuri; Tomiyama, Naruto

    2016-01-01

    Dichlorodiphenyltrichloroethane (DDT) is still used in certain areas of tropics and subtropics to control malaria and other insect-transmitted diseases. DDT and its metabolites have been extensively studied for their toxicity and carcinogenicity in animals and humans and shown to have an endocrine disrupting potential affecting reproductive system although the effects may vary among animal species in correlation with exposure levels. Epidemiologic studies revealed either positive or negative associations between exposure to DDT and tumor development, but there has been no clear evidence that DDT causes cancer in humans. In experimental animals, tumor induction by DDT has been shown in the liver, lung, and adrenals. The mechanisms of hepatic tumor development by DDT have been studied in rats and mice. DDT is known as a non-genotoxic hepatocarcinogen and has been shown to induce microsomal enzymes through activation of constitutive androstane receptor (CAR) and to inhibit gap junctional intercellular communication (GJIC) in the rodent liver. The results from our previously conducted 4-week and 2-year feeding studies of p,p′-DDT in F344 rats indicate that DDT may induce hepatocellular eosinophilic foci as a result of oxidative DNA damage and leads them to hepatic neoplasia in combination with its mitogenic activity and inhibitory effect on GJIC. Oxidative stress could be a key factor in hepatocarcinogenesis by DDT. PMID:26977256

  1. Dietary Carcinogens and Anticarcinogens.

    ERIC Educational Resources Information Center

    Ames, Bruce N.

    1983-01-01

    Describes 16 mutagens/carcinogens found in plant food and coffee as well as several anticarcinogens also found in such food. Speculates on relevant biochemical mechanisms, particularly the role of oxygen radicals and their inhibitors in the fat/cancer relationship, promotion, anticarcinogenesis, and aging. (JN)

  2. Genomic Models of Short-Term Exposure Accurately Predict Long-Term Chemical Carcinogenicity and Identify Putative Mechanisms of Action

    PubMed Central

    Gusenleitner, Daniel; Auerbach, Scott S.; Melia, Tisha; Gómez, Harold F.; Sherr, David H.; Monti, Stefano

    2014-01-01

    Background Despite an overall decrease in incidence of and mortality from cancer, about 40% of Americans will be diagnosed with the disease in their lifetime, and around 20% will die of it. Current approaches to test carcinogenic chemicals adopt the 2-year rodent bioassay, which is costly and time-consuming. As a result, fewer than 2% of the chemicals on the market have actually been tested. However, evidence accumulated to date suggests that gene expression profiles from model organisms exposed to chemical compounds reflect underlying mechanisms of action, and that these toxicogenomic models could be used in the prediction of chemical carcinogenicity. Results In this study, we used a rat-based microarray dataset from the NTP DrugMatrix Database to test the ability of toxicogenomics to model carcinogenicity. We analyzed 1,221 gene-expression profiles obtained from rats treated with 127 well-characterized compounds, including genotoxic and non-genotoxic carcinogens. We built a classifier that predicts a chemical's carcinogenic potential with an AUC of 0.78, and validated it on an independent dataset from the Japanese Toxicogenomics Project consisting of 2,065 profiles from 72 compounds. Finally, we identified differentially expressed genes associated with chemical carcinogenesis, and developed novel data-driven approaches for the molecular characterization of the response to chemical stressors. Conclusion Here, we validate a toxicogenomic approach to predict carcinogenicity and provide strong evidence that, with a larger set of compounds, we should be able to improve the sensitivity and specificity of the predictions. We found that the prediction of carcinogenicity is tissue-dependent and that the results also confirm and expand upon previous studies implicating DNA damage, the peroxisome proliferator-activated receptor, the aryl hydrocarbon receptor, and regenerative pathology in the response to carcinogen exposure. PMID:25058030

  3. Co-occurrence of and remission from general anxiety, depression, and posttraumatic stress disorder symptoms after acute lung injury: a 2-year longitudinal study

    PubMed Central

    Bienvenu, O. Joseph; Colantuoni, Elizabeth; Mendez-Tellez, Pedro A.; Shanholtz, Carl; Dennison-Himmelfarb, Cheryl R.; Pronovost, Peter J.; Needham, Dale M.

    2014-01-01

    Objective To evaluate the co-occurrence, and predictors of remission, of general anxiety, depression, and posttraumatic stress disorder (PTSD) symptoms during 2-year follow-up in survivors of acute lung injury (ALI) treated in an intensive care unit (ICU). Design, Setting, and Patients This prospective cohort study enrolled 520 patients from 13 medical and surgical ICUs in 4 hospitals, with follow-up at 3, 6, 12, and 24 months post-ALI. Measurements and Main Results The outcomes of interest were measured using the Hospital Anxiety and Depression Scale (HADS) anxiety and depression subscales (scores ≥8 indicating substantial symptoms) and the Impact of Event Scale-Revised (IESR, scores ≥1.6 indicating substantial PTSD symptoms). Of the 520 enrolled patients, 274 died before 3-month follow-up; 186/196 consenting survivors (95%) completed at least one HADS and IESR assessment during 2-year follow-up, and most completed multiple assessments. Across follow-up time points, the prevalence of supra-threshold general anxiety, depression, and PTSD symptoms ranged from 38–44%, 26–33%, and 22–24%, respectively; more than half of the patients had supra-threshold symptoms in at least one domain during 2-year follow-up. The majority (59%) of survivors with any supra-threshold symptoms were above threshold for 2 or more types of symptoms (i.e., of general anxiety, depression, and/or PTSD). In fact, the most common pattern involved simultaneous general anxiety, depression, and PTSD symptoms. Most patients with general anxiety, depression, or PTSD symptoms during 2-year follow-up had supra-threshold symptoms at 24-month (last) follow-up. Higher SF-36 physical functioning domain scores at the prior visit were associated with a greater likelihood of remission from general anxiety and PTSD symptoms during follow-up. Conclusions The majority of ALI survivors had clinically significant general anxiety, depressive, or PTSD symptoms, and these symptoms tended to co-occur across

  4. Examination of low-incidence brain tumor responses in F344 rats following chemical exposures in National Toxicology Program carcinogenicity studies.

    PubMed

    Sills, R C; Hailey, J R; Neal, J; Boorman, G A; Haseman, J K; Melnick, R L

    1999-01-01

    Neoplasms in the brain are uncommon in control Fischer 344 (F344) rats; they occur at a rate of less than 1% in 2-yr toxicity/carcinogenicity studies. Furthermore, only 10 of nearly 500 studies conducted by the National Toxicology Program (NTP) showed any evidence of chemically related neoplastic effects in the brain. Generally, the brain tumor responses were considered equivocal, because the characteristics of potential neurocarcinogenic agents (such as statistically significant increased incidences, decreased latency and/or survival, and demonstration of dose-response relationships) were not observed. A thorough examination, including comparisons with a well-established historical database, is often critical in evaluating rare brain tumors. Chemicals that gave equivocal evidence of brain tumor responses were generally associated with carcinogenicity at other sites, and many chemicals were mutagenic when incubated with metabolic activating enzymes. Other factors that were supportive of the theory that marginal increases in brain tumor incidence were related to chemical exposure were that (a) some of the tumors were malignant, (b) no brain neoplasms were observed in concurrent controls from some studies, and/or (c) brain tumors were also seen following exposure to structurally related chemicals. In 2-yr studies in F344 rats (studies conducted by the NTP), equivocal evidence of carcinogenicity was observed for the following 9 chemicals: isoprene, bromoethane, chloroethane, 3,3'-dimethylbenzidine dihydrochloride, 3,3'-dimethoxybenzidine dihydrochloride, furosemide, C.I. direct blue 15, diphenhydramine hydrochloride, and 1-H-benzotriazole. Glycidol was the only chemical evaluated by the NTP with which there was clear evidence of brain tumor induction in F344 rats. Clarification of the potential neurocarcinogenic risks of chemicals that produce equivocal evidence of a brain tumor response in conventional 2-yr rodent studies may be aided by the use of transgenic mouse

  5. Tobacco smoke carcinogens and lung cancer.

    PubMed

    Hecht, S S

    1999-07-21

    The complexity of tobacco smoke leads to some confusion about the mechanisms by which it causes lung cancer. Among the multiple components of tobacco smoke, 20 carcinogens convincingly cause lung tumors in laboratory animals or humans and are, therefore, likely to be involved in lung cancer induction. Of these, polycyclic aromatic hydrocarbons and the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone are likely to play major roles. This review focuses on carcinogens in tobacco smoke as a means of simplifying and clarifying the relevant information that provides a mechanistic framework linking nicotine addiction with lung cancer through exposure to such compounds. Included is a discussion of the mechanisms by which tobacco smoke carcinogens interact with DNA and cause genetic changes--mechanisms that are reasonably well understood--and the less well defined relationship between exposure to specific tobacco smoke carcinogens and mutations in oncogenes and tumor suppressor genes. Molecular epidemiologic studies of gene-carcinogen interactions and lung cancer--an approach that has not yet reached its full potential--are also discussed, as are inhalation studies of tobacco smoke in laboratory animals and the potential role of free radicals and oxidative damage in tobacco-associated carcinogenesis. By focusing in this review on several important carcinogens in tobacco smoke, the complexities in understanding tobacco-induced cancer can be reduced, and new approaches for lung cancer prevention can be envisioned. PMID:10413421

  6. TOXICITY AND CARCINOGENICITY STUDIES OF 4-METHYLIMIDAZOLE IN F344/N RATS AND B6C3F1 MICE

    PubMed Central

    Chan, P.C.; Hills, G. D; Kissling, G.E.; Nyska, A

    2008-01-01

    4-Methylimidazole (4MI) is used in the manufacture of pharmaceuticals, photographic chemicals, dyes and pigments, cleaning and agricultural chemicals, and rubber. It has been identified as a by-product of fermentation in foods and has been detected in mainstream and side stream tobacco smoke. 4MI was studied because of its high potential for human exposure. Groups of 50 male and 50 female F344/N rats were fed diets containing 0-, 625-, 1,250-, or 2,500-ppm 4MI (males) or 0-, 1,250-, 2,500-, or 5,000-ppm 4MI (females) for 106 weeks. Based on the food consumption the calculated average daily doses were approximately 30, 55, or 115 mg 4MI/kg body weight to males and 60, 120, or 250 mg 4MI/kg to females. Survival of all exposed groups of males and females was similar to that of the control groups. Mean body weights of males in the 1,250- and 2,500-ppm groups and females in the 2,500- and 5,000-ppm groups were less than those of the control groups throughout the study. Feed consumption by 5,000-ppm females was less than that by the controls. Clonic seizures, excitability, hyperactivity, and impaired gait were observed primarily in 2,500- and 5,000-ppm females. The incidence of mononuclear cell leukemia in the 5,000-ppm females was significantly greater than that in the controls. The incidences of hepatic histiocytosis, chronic inflammation, and focal fatty change were significantly increased in all exposed groups of male and female rats. The incidences of hepatocellular eosinophilic and mixed cell foci were significantly increased in 2,500-ppm males and 5,000-ppm females. Groups of 50 male and 50 female B6C3F1 mice were fed diets containing 0-, 312-, 625-, or 1,250-ppm 4MI for 106 weeks. Based on the food consumption the calculated average daily doses were approximately 40, 80, or 170 mg 4MI/kg body weight to males and females. Survival of all exposed groups of males and females was similar to that of the control groups. Mean body weights of males and females in the 1

  7. Evaluation of psychic change through the application of empirical and clinical techniques for a 2-year treatment: a single case study.

    PubMed

    Moreno, Clara M López; Schalayeff, Cristina; Acosta, Silvia R; Vernengo, Pía; Roussos, Andrés J; Lerner, Beatríz Dorfman

    2005-07-01

    Abstract The authors present results obtained by a combination of clinical and empirical methods used in the evaluation of psychic change involving a single case study carried out during 2 years of nonmanualized psychodynamic psychotherapy (Barber & Crits-Christoph, 1993 ; Barber, Foltz, DeRubeis, & Landis, 2002 ). A multidimensional definition of change that includes clinical (psychoanalytic) and empirical perspectives is provided. The authors used material from supervision sessions and clinical meetings to assess the psychodynamic diagnosis and evolution. The following empirical techniques and instruments were used: core conflictual relationship theme (Luborsky & Crits-Christoph, 1990), Symptom Checklist-90-Revised (Derogatis, 1983), and Differential Elements for a Psychodynamic Diagnostic (C. M. López Moreno et al., 1998 ). Several markers of psychic change along the therapeutic process were found. The instruments proved to be sensitive to the changes obtained during the psychotherapy. Used together, the instruments allowed an integrated evaluation of the patient's evolution during the treatment.

  8. Do deviant peer associations mediate the contributions of self-esteem to problem behavior during early adolescence? A 2-year longitudinal study.

    PubMed

    DuBois, David L; Silverthorn, Naida

    2004-06-01

    We investigated deviant peer associations as a mediator of the influences of general and peer-oriented self-esteem on problem behavior using data from a 2-year longitudinal study of 350 young adolescents. Measures of problem behavior included substance use (alcohol use, smoking) and antisocial behavior (fighting, stealing). Using latent growth curve modeling and covariance structure analysis, an extension of a model proposed by DuBois et al. (2002) was evaluated for each type of problem behavior. Findings revealed that lower general self-esteem and greater peer orientation in self-esteem each predicted deviant associations with peers and that deviant peer associations, in turn, were associated with higher levels and rates of change in problem behavior. Deviant peer associations mediated the associations of general and peer-oriented self-esteem with levels and rates of change in problem behavior such that direct paths from self-esteem to problem behavior generally were nonsignificant.

  9. Improvement in hematological, visceral, and skeletal manifestations of Gaucher disease type 1 with oral eliglustat tartrate (Genz-112638) treatment: 2-year results of a phase 2 study

    PubMed Central

    Lukina, Elena; Watman, Nora; Arreguin, Elsa Avila; Dragosky, Marta; Iastrebner, Marcelo; Rosenbaum, Hanna; Phillips, Mici; Pastores, Gregory M.; Kamath, Ravi S.; Rosenthal, Daniel I.; Kaper, Mathilde; Singh, Tejdip; Puga, Ana Cristina

    2010-01-01

    Eliglustat tartrate is an investigational oral substrate reduction therapy for Gaucher disease type 1 that is pharmacologically distinct from intravenous enzyme replacement therapy. Eliglustat tartrate improved clinical manifestations in patients who received 50 or 100 mg twice daily for 1 year during an open-label phase 2 study (Blood. 2010;116(6):893-899). We report further improvements after 2 years of treatment in 20 patients (11 females, 9 males; mean age, 33 years) with baseline splenomegaly and thrombocytopenia and/or anemia. Statistically significant (P < .001) percentage improvements from baseline occurred in platelet count (mean ± SD, 81% ± 56%), hemoglobin level (20% ± 15%), spleen volume (−52% ± 11%), and liver volume (−24% ± 13%). Mean platelet count increased ∼ 50 000/mm3. Mean hemoglobin level increased 2.1 g/dL overall and 3.1 g/dL in 10 patients with baseline anemia. Organ volume reductions were greatest in patients with severe baseline organomegaly. Seventeen (85%) patients met established therapeutic goals for ≥ 3 of the 4 parameters. Lumbar spine bone mineral density increased 7.8% ± 10.6% (P = .01) and T-score 0.6 ± 0.8 (P = .012), with major gains in osteoporotic and osteopenic patients. Magnetic resonance imaging assessment showed that bone marrow infiltration by Gaucher cells was decreased (8/18 patients) or stable (10/18 patients). No safety-related trends emerged during 2 years of treatment. This multisite, open-label, single-arm phase 2 study is registered at www.clinicaltrials.gov as NCT00358150. PMID:20713962

  10. Efficacy, safety and patient-reported outcomes of combination etanercept and sulfasalazine versus etanercept alone in patients with rheumatoid arthritis: a double-blind randomised 2-year study

    PubMed Central

    Combe, B; Codreanu, C; Fiocco, U; Gaubitz, M; Geusens, P P; Kvien, T K; Pavelka, K; Sambrook, P N; Smolen, J S; Khandker, R; Singh, A; Wajdula, J; Fatenejad, S

    2009-01-01

    Objective: To determine the efficacy and safety of etanercept and etanercept plus sulfasalazine versus sulfasalazine in patients with rheumatoid arthritis (RA) despite sulfasalazine therapy. Methods: Patients were randomly assigned to etanercept (25 mg twice weekly; sulfasalazine was discontinued at baseline), etanercept plus sulfasalazine (unchanged regimen of 2–3 g/day) or sulfasalazine in a double-blind, randomised, 2-year study in adult patients with active RA despite sulfasalazine therapy. Efficacy was assessed using the American College of Rheumatology criteria, disease activity scores (DAS) and patient-reported outcomes (PRO). Results: Demographic variables and baseline disease characteristics were comparable among treatment groups; mean DAS 5.1, 5.2 and 5.1 for etanercept (n  =  103), etanercept plus sulfasalazine (n  =  101) and sulfasalazine (n  =  50), respectively. Withdrawal due to lack of efficacy was highest with sulfasalazine (26 (52%) vs 6 (6%) for either etanercept group, p<0.001). Patients receiving etanercept or etanercept plus sulfasalazine had a more rapid initial response, which was sustained at 2 years, than those receiving sulfasalazine: mean DAS 2.8, 2.5 versus 4.5, respectively (p<0.05); ACR 20 response was achieved by 67%, 77% versus 34% of patients, respectively (p<0.01) Overall, PRO followed a similar pattern; a clinically significant improvement in health assessment questionnaire was achieved by 76%, 78% versus 40% of patients, respectively (p<0.01). Commonly reported adverse events occurring in the etanercept groups were injection site reactions and pharyngitis/laryngitis (p<0.01). Conclusion: Etanercept and etanercept plus sulfasalazine are efficacious for the long-term management of patients with RA. The addition of etanercept or substitution with etanercept should be considered as treatment options for patients not adequately responding to sulfasalazine. PMID:18794178

  11. Determinants of “return to work in good health” among workers with back pain who consult in primary care settings: a 2-year prospective study

    PubMed Central

    Bourbonnais, Renée; Frémont, Pierre; Rossignol, Michel; Stock, Susan R.; Nouwen, Arie; Larocque, Isabelle; Demers, Eric

    2006-01-01

    Many factors have been linked to return to work after a back pain episode, but our understanding of this phenomenon is limited and cross-sectional dichotomous indices of return to work are not valid measures of this construct. To describe the course of “return to work in good health” (RWGH—a composite index of back pain outcome) among workers who consulted in primary care settings for back pain and identify its determinants, a 2-year prospective study was conducted. Subjects (n = 1,007, 68.4%) were workers who consulted in primary care settings of the Quebec City area for a nonspecific back pain. They completed five telephone interviews over 2 years (follow-up = 86%). Analyses linking baseline variables with 2-year outcome were conducted with polytomous logistic regression. The proportion of “success” in RWGH increased from 18% at 6 weeks to 57% at 2 years. In women, persistent pain, pain radiating to extremities, increasing job seniority, not having a unionized job, feeling that the physician did listen carefully and increasing fear-avoidance beliefs towards work and activity were determinants of “failure” in RWGH. In men, decreasing age, cigarette smoking, poor self-reported health status, pain in the thoracic area, previous back surgeries, a non-compensated injury, high pain levels, belief that job is below qualifications, likelihood of losing job, job status, satisfaction with health services and fear-avoidance beliefs towards work were all significant. RWGH among workers with back pain receives multiple influences, especially among men. In both genders, however, fear-avoidance beliefs about work are associated with failure and high self-efficacy is associated with success. PMID:16868783

  12. Social Development:: 2 Year Olds

    MedlinePlus

    ... Español Text Size Email Print Share Social Development: 2 Year Olds Page Content Article Body By nature, ... probably are acting the same way. At age two, children view the world almost exclusively through their ...

  13. Language Development: 2 Year Olds

    MedlinePlus

    ... Stages Listen Español Text Size Email Print Share Language Development: 2 Year Olds Page Content Article Body ... Pay attention to how he also is using language to describe ideas and information and to express ...

  14. Issues in carcinogenicity testing: dose selection.

    PubMed

    Haseman, J K

    1985-02-01

    Dose selection in testing chemicals for possible carcinogenicity in rodents continues to be an area of scientific debate. In this paper the definition of "maximum tolerated dose" (MTD) is considered, and the advantages and disadvantages of using MTDs are given. There is no universally accepted definition of an MTD, and as a result, objections to utilizing high doses in carcinogenicity testing may reflect differing definitions of an MTD rather than basic disagreements in dose selection philosophy. Data from 52 National Toxicology Program (NTP) carcinogenicity studies indicate that while dose selection has caused difficulties in certain studies using the gavage route of chemical administration, there is little evidence that this has been a problem in NTP studies using the dietary (feed) route of exposure. These data also indicate that more than two-thirds of the carcinogenic effects detected in feeding studies would have been missed had the high dose been reduced from the estimated MTD to 1/2 MTD. The inherent insensitivity of laboratory animal studies for detecting weak-to-moderate carcinogenic responses also argues against reducing the highest dose level. The addition of a third, lower-dosed group provides for a margin of safety against the possibility of over-estimating the MTD. Primary emphasis should be given to improving procedures for estimating the MTD, particularly for gavage studies. Efforts should also be increased to obtain pharmacokinetic and metabolism data for the test chemical that might be factored into the dose selection and study evaluation processes.

  15. Carcinogenic activity of Symphytum officinale.

    PubMed

    Hirono, I; Mori, H; Haga, M

    1978-09-01

    The carcinogenicity of Symphytum officinale L., Russian comfrey, used as a green vegetable or tonic, was studied in inbred ACI rats. Three groups of 19--28 rats each were fed comfrey leaves for 480--600 days; four additional groups of 15--24 rats were fed comfrey roots for varying lengths of time. A control group was given a normal diet. Hepatocellular adenomas were induced in all experimental groups that received the diets containing comfrey roots and leaves. Hemangioendothelial sarcoma of the liver was infrequently induced. PMID:278864

  16. Impact on malaria morbidity of a programme supplying insecticide treated nets in children aged under 2 years in Tanzania: community cross sectional study

    PubMed Central

    Abdulla, Salim; Schellenberg, Joanna Armstrong; Nathan, Rose; Mukasa, Oscar; Marchant, Tanya; Smith, Tom; Tanner, Marcel; Lengeler, Christian

    2001-01-01

    Objective To assess the impact of a social marketing programme for distributing nets treated with insecticide on malarial parasitaemia and anaemia in very young children in an area of high malaria transmission. Design Community cross sectional study. Annual, cross sectional data were collected at the beginning of the social marketing campaign (1997) and the subsequent two years. Net ownership and other risk and confounding factors were assessed with a questionnaire. Blood samples were taken from the children to assess prevalence of parasitaemia and haemoglobin levels. Setting 18 villages in the Kilombero and Ulanga districts of southwestern Tanzania. Participants A random sample of children aged under 2 years. Main outcome measures The presence of any parasitaemia in the peripheral blood sample and the presence of anaemia (classified as a haemoglobin level of <80 g/l). Results Ownership of nets increased rapidly (treated or not treated nets: from 58% to 83%; treated nets: from 10% to 61%). The mean haemoglobin level rose from 80 g/l to 89 g/l in the study children in the successive surveys. Overall, the prevalence of anaemia in the study population decreased from 49% to 26% in the two years studied. Treated nets had a protective efficacy of 62% (95% confidence interval 38% to 77%) on the prevalence of parasitaemia and of 63% (27% to 82%) on anaemia. Conclusions These results show that nets treated with insecticide have a substantial impact on morbidity when distributed in a public health setting. PMID:11157527

  17. Attitudes to medication after kidney transplantation and their association with medication adherence and graft survival: a 2-year follow-up study.

    PubMed

    Tielen, Mirjam; van Exel, Job; Laging, Mirjam; Beck, Denise K; Khemai, Roshni; van Gelder, Teun; Betjes, Michiel G H; Weimar, Willem; Massey, Emma K

    2014-01-01

    Background. Nonadherence to medication is a common problem after kidney transplantation. The aim of this study was to explore attitudes towards medication, adherence, and the relationship with clinical outcomes. Method. Kidney recipients participated in a Q-methodological study 6 weeks after transplantation. As a measure of medication adherence, respondents completed the Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS(©)-interview). Moreover, the intrapatient variability in the pharmacokinetics of tacrolimus was calculated, which measures stability of drug intake. Data on graft survival was retrieved from patient records up to 2 years after transplantation. Results. 113 renal transplant recipients (19-75 years old) participated in the study. Results revealed three attitudes towards medication adherence-attitude 1: "confident and accurate," attitude 2: "concerned and vigilant," and attitude 3: "appearance oriented and assertive." We found association of attitudes with intrapatient variability in pharmacokinetics of tacrolimus, but not with self-reported nonadherence or graft survival. However, self-reported nonadherence immediately after transplantation was associated with lower two-year graft survival. Conclusion. These preliminary findings suggest that nonadherence shortly after kidney transplantation may be a risk factor for lower graft survival in the years to follow. The attitudes to medication were not a risk factor.

  18. Father's occupational exposure to carcinogenic agents and childhood acute leukemia: a new method to assess exposure (a case-control study)

    PubMed Central

    Perez-Saldivar, Maria Luisa; Ortega-Alvarez, Manuel Carlos; Fajardo-Gutierrez, Arturo; Bernaldez-Rios, Roberto; del Campo-Martinez, Maria de los Angeles; Medina-Sanson, Aurora; Palomo-Colli, Miguel Angel; Paredes-Aguilera, Rogelio; Martínez-Avalos, Armando; Borja-Aburto, Victor Hugo; Rodriguez-Rivera, Maria de Jesus; Vargas-Garcia, Victor Manuel; Zarco-Contreras, Jesus; Flores-Lujano, Janet; Mejia-Arangure, Juan Manuel

    2008-01-01

    Background Medical research has not been able to establish whether a father's occupational exposures are associated with the development of acute leukemia (AL) in their offspring. The studies conducted have weaknesses that have generated a misclassification of such exposure. Occupations and exposures to substances associated with childhood cancer are not very frequently encountered in the general population; thus, the reported risks are both inconsistent and inaccurate. In this study, to assess exposure we used a new method, an exposure index, which took into consideration the industrial branch, specific position, use of protective equipment, substances at work, degree of contact with such substances, and time of exposure. This index allowed us to obtain a grade, which permitted the identification of individuals according to their level of exposure to known or potentially carcinogenic agents that are not necessarily specifically identified as risk factors for leukemia. The aim of this study was to determine the association between a father's occupational exposure to carcinogenic agents and the presence of AL in their offspring. Methods From 1999 to 2000, a case-control study was performed with 193 children who reside in Mexico City and had been diagnosed with AL. The initial sample-size calculation was 150 children per group, assessed with an expected odds ratio (OR) of three and a minimum exposure frequency of 15.8%. These children were matched by age, sex, and institution with 193 pediatric surgical patients at secondary-care hospitals. A questionnaire was used to determine each child's background and the characteristics of the father's occupation(s). In order to determine the level of exposure to carcinogenic agents, a previously validated exposure index (occupational exposure index, OEI) was used. The consistency and validity of the index were assessed by a questionnaire comparison, the sensory recognition of the work area, and an expert's opinion. Results The

  19. Acquired hemophilia A in the United Kingdom: a 2-year national surveillance study by the United Kingdom Haemophilia Centre Doctors' Organisation.

    PubMed

    Collins, Peter W; Hirsch, Sybil; Baglin, Trevor P; Dolan, Gerard; Hanley, John; Makris, Michael; Keeling, David M; Liesner, Ri; Brown, Simon A; Hay, Charles R M

    2007-03-01

    Acquired hemophilia A is a severe bleeding disorder caused by an autoantibody to factor VIII. Previous reports have focused on referral center patients and it is unclear whether these findings are generally applicable. To improve understanding of the disease, a 2-year observational study was established to identify and characterize the presenting features and outcome of all patients with acquired hemophilia A in the United Kingdom. This allowed a consecutive cohort of patients, unbiased by referral or reporting practice, to be studied. A total of 172 patients with a median age of 78 years were identified, an incidence of 1.48/million/y. The cohort was significantly older than previously reported series, but bleeding manifestations and underlying diseases were similar. Bleeding was the cause of death in 9% of the cohort and remained a risk until the inhibitor had been eradicated. There was no difference in inhibitor eradication or mortality between patients treated with steroids alone and a combination of steroids and cytotoxic agents. Relapse of the inhibitor was observed in 20% of the patients who had attained first complete remission. The data provide the most complete description of acquired hemophilia A available and are applicable to patients presenting to all centers.

  20. Bacterial community shift is induced by dynamic environmental parameters in a changing coastal ecosystem (northern Adriatic, northeastern Mediterranean Sea)--a 2-year time-series study.

    PubMed

    Tinta, T; Vojvoda, J; Mozetič, P; Talaber, I; Vodopivec, M; Malfatti, F; Turk, V

    2015-10-01

    The potential link between the microbial dynamics and the environmental parameters was investigated in a semi-enclosed and highly dynamic coastal system (Gulf of Trieste, northern Adriatic Sea, NE Mediterranean Sea). Our comprehensive 2-year time-series study showed that despite the shallowness of this area, there was a significant difference between the surface and the bottom bacterial community structure. The bottom bacterial community was more diverse than the surface one and influenced by sediment re-suspension. The surface seawater temperature had a profound effect on bacterial productivity, while the bacterial community structure was more affected by freshwater-borne nutrients and phytoplankton blooms. Phytoplankton blooms caused an increase of Gammaproteobacteria (Alteromonadaceae, SAR86 and Vibrionaceae) and shift in dominance from SAR11 to Rhodobacteraceae taxon at the surface. Our results propose the importance of the water mass movements as drivers of freshwater-borne nutrients and of allochthonous microbial taxa. This study emphasizes the prediction power based on association networks analyses that are fed with long-term measurements of microbial and environmental parameters. These interaction maps offer valuable insights into the response of marine ecosystem to climate- and anthropogenic-driven stressors.

  1. Influence of Anti-TNF and Disease Modifying Antirheumatic Drugs Therapy on Pulmonary Forced Vital Capacity Associated to Ankylosing Spondylitis: A 2-Year Follow-Up Observational Study

    PubMed Central

    Rocha-Muñoz, Alberto Daniel; Brambila-Tapia, Aniel Jessica Leticia; Zavala-Cerna, María Guadalupe; Vásquez-Jiménez, José Clemente; De la Cerda-Trujillo, Liliana Faviola; Vázquez-Del Mercado, Mónica; Rodriguez-Jimenez, Norma Alejandra; Díaz-Rizo, Valeria; Díaz-González, Viviana; Cardona-Muñoz, Ernesto German; Dávalos-Rodríguez, Ingrid Patricia; Salazar-Paramo, Mario; Gamez-Nava, Jorge Ivan; Nava-Zavala, Arnulfo Hernan; Gonzalez-Lopez, Laura

    2015-01-01

    Objective. To evaluate the effect of anti-TNF agents plus synthetic disease modifying antirheumatic drugs (DMARDs) versus DMARDs alone for ankylosing spondylitis (AS) with reduced pulmonary function vital capacity (FVC%). Methods. In an observational study, we included AS who had FVC% <80% at baseline. Twenty patients were taking DMARDs and 16 received anti-TNF + DMARDs. Outcome measures: changes in FVC%, BASDAI, BASFI, 6-minute walk test (6MWT), Borg scale after 6MWT, and St. George's Respiratory Questionnaire at 24 months. Results. Both DMARDs and anti-TNF + DMARDs groups had similar baseline values in FVC%. Significant improvement was achieved with anti-TNF + DMARDs in FVC%, at 24 months, when compared to DMARDs alone (P = 0.04). Similarly, patients in anti-TNF + DMARDs group had greater improvement in BASDAI, BASFI, Borg scale, and 6MWT when compared to DMARDs alone. After 2 years of follow-up, 14/16 (87.5%) in the anti-TNF + DMARDs group achieved the primary outcome: FVC% ≥80%, compared with 11/20 (55%) in the DMARDs group (P = 0.04). Conclusions. Patients with anti-TNF + DMARDs had a greater improvement in FVC% and cardiopulmonary scales at 24 months compared with DMARDs. This preliminary study supports the fact that anti-TNF agents may offer additional benefits compared to DMARDs in patients with AS who have reduced FVC%. PMID:26078986

  2. Towards a validation of a cellular biomarker suite in native and transplanted zebra mussels: a 2-year integrative field study of seasonal and pollution-induced variations.

    PubMed

    Guerlet, Edwige; Ledy, Karine; Meyer, Antoinette; Giambérini, Laure

    2007-03-30

    Two of the questions raised in the validation process of biomarkers are their relevance in the identification and discrimination of environmental perturbations, and the influence of seasonal factors on these biological endpoints. Determining the advantages and restrictions associated with the use of native or transplanted animals and comparing their responses is also needed. To obtain this information, a 2-year integrative field study was conducted in the vicinity of a nuclear power plant in northeastern France. A station was located in the reservoir receiving the cooling waters of the plant, and two other sites were studied 2 km upstream and 5 km downstream from the reservoir's discharge in the Moselle river. Elevated temperatures, copper contamination and a 1.4-fold-concentration factor of dissolved salts affected water quality of the reservoir. Native and transplanted zebra mussels (Dreissena polymorpha) were collected monthly and their digestive glands were processed for histochemical determinations of the lysosomal and peroxisomal systems and of the lipofuscin and neutral lipid contents. The responses were quantified using automated image analysis and stereology. Apart from neutral lipid contents, there were no systematic seasonal patterns in mussel populations or from 1 year to another. Principal Component Analyses showed a general higher discrimination potential of biological responses in transplanted organisms compared to native ones. They also pointed out the relationships between the cellular and physiological markers and abiotic factors. The present multiple biomarker integrative approach in transplanted D. polymorpha brings promising elements in their validation process as relevant biomonitoring tools.

  3. Evaluation of the potential carcinogenicity of chrysene. Final report

    SciTech Connect

    Not Available

    1988-06-01

    Chrysene is a possible human carcinogen, classified as weight-of-evidence Group C under the EPA Guidelines for Carcinogen Risk Assessment. Evidence on potential carcinogenicity from animal studies is Limited, and the evidence from human studies is No Data. Data available are inadequate for calculating a potency factor (F) and no quantitative inferences can be made. Chrysene is, therefore, assigned to the median potency factor range and placed in potency group 2 according to the CAG's methodology for evaluating potential carcinogens. Combining the weight-of-evidence group and the potency group, chrysene is assigned a LOW hazard ranking.

  4. Evaluation of the potential carcinogenicity of DDD. Final report

    SciTech Connect

    Not Available

    1988-06-01

    The 1,1-Dichloro-2,2-bis(p-chlorophenyl)ethane (DDD) is a probable human carcinogen, classified as weight-of-evidence Group B2 under the EPA Guidelines for Carcinogen Risk Assessment. Evidence on potential carcinogenicity from animal studies is Sufficient, and the evidence from human studies is Inadequate. The potency factor (F) for DDD is estimated to be 1.30 (mg/kg/day)(-1), placing it in potency group 2 according to the CAG's methodology for evaluating potential carcinogens. Combining the weight-of-evidence group and the potency group, DDD is assigned a MEDIUM hazard ranking.

  5. Evaluation of the potential carcinogenicity of DDE. Final report

    SciTech Connect

    Not Available

    1988-06-01

    DDE is a probable human carcinogen, classified as weight-of-evidence Group B2 under the EPA Guidelines for Carcinogen Risk Assessment. Evidence on potential carcinogenicity from animal studies is Sufficient, and the evidence from human studies is Inadequate. The potency factor (F) for DDE is estimated to be 3.82 (mg/kg/day)(-1), placing it in potency group 2 according to the CAG's methodology for evaluating potential carcinogens. Combining the weight-of-evidence group and the potency group, DDE is assigned a MEDIUM hazard ranking.

  6. Comparison of olanzapine long-acting injection and oral olanzapine: a 2-year, randomized, open-label study in outpatients with schizophrenia.

    PubMed

    Detke, Holland C; Weiden, Peter J; Llorca, Pierre-Michel; Choukour, Moutaz; Watson, Susan B; Brunner, Elizabeth; Ascher-Svanum, Haya

    2014-08-01

    We compared long-term treatment effectiveness of monthly olanzapine long-acting injection (LAI) with that of oral olanzapine. Outpatients with 2 or more episodes of psychotic worsening in the past 24 months with Positive and Negative Syndrome Scale total score of lower than 70 were randomized to 405 mg/4 weeks of olanzapine LAI (n = 264) or 10 mg/d of oral olanzapine (n = 260) for 2 years of open-label treatment. Dosing thereafter was flexible (150-405 mg/4 weeks of LAI vs 5-20 mg/d of oral). Primary outcome was time to all-cause discontinuation. At baseline, patients were clinically stable (mean Positive and Negative Syndrome Scale total score of 57). Seventeen percent of patients had been psychiatrically hospitalized in the previous 6 months, and 4.6% were rated nonadherent in the month before study entry. The groups did not differ significantly in median time to all-cause discontinuation (645 days for LAI, 678 days for oral; P = 0.61), discontinuation rate (53.8% for LAI, 51.2% for oral; P = 0.60), or relapse rate (20.1% for LAI, 18.5% for oral; P = 0.66). Postbaseline psychiatric hospitalization rate was low for both groups (7.6% for LAI, 9.2% for oral), but mean hospitalization duration was significantly longer for oral patients (1.80 days [20 for those hospitalized] vs 0.43 days [6 for those hospitalized], P = 0.02). There were no clinically significant group differences in adverse events or safety measures. No post-injection delirium/sedation syndrome events occurred. In conclusion, olanzapine LAI and oral olanzapine were similarly effective and well tolerated for up to 2 years of treatment in patients with schizophrenia. Treatment discontinuation for olanzapine LAI was similar to that of oral olanzapine, despite the 3-hour post-injection observation period and other precautionary procedures related to risk of post-injection delirium/sedation syndrome. PMID:24781441

  7. Statistical analysis of a carcinogen mixture experiment. I. Liver carcinogens.

    PubMed

    Elashoff, R M; Fears, T R; Schneiderman, M A

    1987-09-01

    This paper describes factorial experiments designed to determine whether 2 liver carcinogens act synergistically to produce liver cancers in Fischer 344 rats. Four hepatocarcinogens, cycad flour, lasiocarpine (CAS: 303-34-4), aflatoxin B1 (CAS: 1162-65-8), and dipentylnitrosamine (CAS: 13256-06-9), were studied in pairwise combinations. Each of the 6 possible pairs was studied by means of 4 X 4 factorial experiment, each agent being fed at zero and at 3 non-zero doses. Methods of analysis designed explicitly for this study were derived to study interaction. These methods were supplemented by standard statistical methods appropriate for one-at-a-time studies. Antagonism was not discovered in any chemical mixture. Some chemical mixtures did interact synergistically. Findings for male and female animals were generally, but not always, in agreement.

  8. The Prognosis of Acute Low Back Pain in Primary Care in the U.S. A 2-Year Prospective Cohort Study

    PubMed Central

    Mehling, Wolf E.; Gopisetty, Viranjini; Bartmess-LeVasseur, Elizabeth; Acree, Mike; Pressman, Alice; Goldberg, Harley; Hecht, Frederick M; Carey, Tim; Avins, Andrew L

    2011-01-01

    Study Design Prospective cohort study Objective to assess the prognosis of patients presenting with acute low back pain (LBP) in a primary care setting in the U.S. Summary of Background Data Practice guidelines for acute LBP based on return-to-work outcomes underestimate the development of chronic pain in the primary care setting. Due to differences in inclusion criteria, chronic pain definitions and national health systems, prognostic cohort studies have reported a wide range of results limiting interpretation and generalization. Current data from carefully designed prognostic studies of acute LBP are lacking for the U.S. primary care system. Methods Members of a large health service organization were enrolled after seeking medical care for acute LBP, with or without sciatica, of up to 30 days duration, with no prior episode in the past 12 months and no history of spine surgery. We conducted phone interviews at baseline, six months and two years. Based on receiver operating characteristic analyses, a combination of global perceived recovery with pain intensity was used as primary outcome for chronic pain. Recurrence and multiple secondary outcomes were assessed to allow for comparison with other studies. Results 605 patients had an average pain intensity of 5.6 (numeric rating scale 0–10) and disability of 15.8 (Roland Morris scale 0–24). Eight percent had declared sick leave between pain onset and baseline interview. 13% of 521 patients (86% follow-up) suffered from chronic pain at six months and 19% of 443 patients at 2 years. At six months, 54% had experienced at least one LBP recurrence, and 47% in the subsequent 18 months. Conclusion The prognosis of strictly-defined acute LBP, with or without sciatica, is less favorable than commonly stated in practice guidelines based on failure to return to work. Broad initiatives to develop new means for the primary and secondary prevention of recurrent and chronic LBP are urgently needed. PMID:22504516

  9. Prediction of Chemical Carcinogenicity in Rodents from in vitro Genetic Toxicity Assays

    NASA Astrophysics Data System (ADS)

    Tennant, Raymond W.; Margolin, Barry H.; Shelby, Michael D.; Zeiger, Errol; Haseman, Joseph K.; Spalding, Judson; Caspary, William; Resnick, Michael; Stasiewicz, Stanley; Anderson, Beth; Minor, Robert

    1987-05-01

    Four widely used in vitro assays for genetic toxicity were evaluated for their ability to predict the carcinogenicity of selected chemicals in rodents. These assays were mutagenesis in Salmonella and mouse lymphoma cells and chromosome aberrations and sister chromatid exchanges in Chinese hamster ovary cells. Seventy-three chemicals recently tested in 2-year carcinogenicity studies conducted by the National Cancer Institute and the National Toxicology Program were used in this evaluation. Test results from the four in vitro assays did not show significant differences in individual concordance with the rodent carcinogenicity results; the concordance of each assay was approximately 60 percent. Within the limits of this study there was no evidence of complementarity among the four assays, and no battery of tests constructed from these assays improved substantially on the overall performance of the Salmonella assay. The in vitro assays which represented a range of three cell types and four end points did show substantial agreement among themselves, indicating that chemicals positive in one in vitro assay tended to be positive in the other in vitro assays. To help put this project into its proper context, we emphasize certain features of the study: 1) Standard protocols were used to mimic the major use of STTs worldwide--screening for mutagens and carcinogens; no attempt was made to optimize protocols for specific chemicals. 2) The 73 NTP chemicals and their 60% incidence of carcinogenicity are probably not representative of the universe of chemicals but rather reflect the recent chemical selection process for the NTP carcinogenicity assay. 3) The small, diverse group of chemicals precludes a meaningful evaluation of the predictive utility of chemical structure information. 4) The NTP is currently testing these same 73 chemicals in two in vivo STTs for chromosomal effects. 5) Complete data for an additional group of 30 to 40 NTP chemicals will be gathered on

  10. Carcinogenic, teratogenic, and mutagenic effects of arsenic.

    PubMed Central

    Bencko, V

    1977-01-01

    This review outlines briefly the history and present status of the problem of carcinogenic, teratogenic and mutagenic effects of arsenic. Discrepancies between clinical observations and positive results of epidemiological studies and the experimental induction of cancer by arsenic are discussed. The present knowledge of the mechanism of teratogenic and mutagenic effects of arsenic is analyzed. The growing importance of arsenic as an environmental pollutant is demonstrated. Continuation of throughly organized epidemiological studies in regions with excessive arsenic exposure of the population and standardization of an epidemiological approach to this problem on an international basis are recommended. New approaches in experimental studies of the carcinogenicity of arsenic in combination with other known or suspected carcinogens are recommended as well. PMID:908296

  11. Effects of a 2-year school-based daily physical activity intervention on cardiovascular disease risk factors: the Sogndal school-intervention study.

    PubMed

    Resaland, G K; Anderssen, S A; Holme, I M; Mamen, A; Andersen, L B

    2011-12-01

    The aim of this study was to investigate the effect of a 2-year school-based physical activity (PA) intervention in 9-year-old children on cardiovascular disease (CVD) risk factors. One intervention school (I-school) (n=125) and one control school (C-school) (n=131) were included. The children at the I-school carried out 60 min of PA daily. The PA lessons were planned, organized and led by expert physical education (PE) teachers. In the C-school, children were offered the normal 45 min of PE twice weekly. The intervention resulted in a greater beneficial development in systolic (P=0.003) and diastolic (P=0.002) blood pressure, total cholesterol-to-high-density lipoprotein cholesterol ratio (P=0.011), triglyceride (P=0.030) and peak oxygen uptake (P<0.001) in I-school children than in C-school children. No significant differences were observed in waist circumference, body mass index and the homeostasis model assessment for insulin resistance between the two groups. Furthermore, the intervention, primarily carried out at moderate intensity, had the strongest impact in children with the least favorable starting point. In conclusion, a daily school-based PA intervention can beneficially modify children's CVD risk profile if the intervention has sufficient duration and includes a substantial amount of daily PA, and if the PA is implemented by expert PE teachers.

  12. Serum paraoxonase and arylesterase activities of paraoxonase-1 (PON-1), mild cognitive impairment, and 2-year conversion to dementia: A pilot study.

    PubMed

    Cervellati, Carlo; Trentini, Alessandro; Romani, Arianna; Bellini, Tiziana; Bosi, Cristina; Ortolani, Beatrice; Zurlo, Amedeo; Passaro, Angelina; Seripa, Davide; Zuliani, Giovanni

    2015-10-01

    Converging lines of evidence suggest that paraoxonase-1 (PON-1) may confer protection against inflammatory and oxidative challenge which, in turn, plays a key-role in the onset and progression of dementia. The aim of this study was to evaluate whether serum PON-1 paraoxonase/arylesterase activities might predict the clinical conversion of mild cognitive impairment (MCI) to late-onset Alzheimer's disease (LOAD) or vascular dementia (VAD). Serum paraoxonase and arylesterase activities were measured by spectrophotometric assays at baseline in 141 MCI patients (median age: 77 years; interquartile range 71-81) and in 78 healthy controls (median age: 76 years; interquartile range 73-79). After 2 years of follow-up, 86 MCI remained stable (MCI/MCI), 34 converted to LOAD (MCI/LOAD), whereas 21 converted to VAD (MCI/VAD). Baseline arylesterase activity was lower in all MCI groups compared with controls (all p < 0.01), whereas paraoxonase activity was lower in MCI/VAD group compared to controls (p < 0.05) and MCI/MCI patients (p = 0.009). Low paraoxonase and arylesterase activities (I quartile) were associated to higher risk of conversion to VAD (OR: 3.74, 95% CI: 1.37-10.25 and OR: 3.16, 95% CI: 1.17-8.56, respectively). Our results suggest that in MCI patients low PON-1 activity might contribute to identify individuals susceptible to develop vascular dementia.

  13. Working memory arrest in children with high-functioning autism compared to children with attention-deficit/hyperactivity disorder: results from a 2-year longitudinal study.

    PubMed

    Andersen, Per N; Skogli, Erik W; Hovik, Kjell T; Geurts, Hilde; Egeland, Jens; Øie, Merete

    2015-05-01

    The aim of this study was to analyse the development of verbal working memory in children with high-functioning autism compared to children with attention-deficit/hyperactivity disorder and typically developing children. A total of 34 children with high-functioning autism, 72 children with attention-deficit/hyperactivity disorder and 45 typically developing children (age 9-16 years) were included at baseline and followed up approximately 25 months later. The children were given a letter/number sequencing task to assess verbal working memory. The performance of children with high-functioning autism on verbal working memory did not improve after 2 years, while improvement was observed in children with attention-deficit/hyperactivity disorder and typically developing children. The results indicate a different developmental trajectory for verbal working memory in children with high-functioning autism compared to children with attention-deficit/hyperactivity disorder and typically developing children. More research is needed to construct a developmental framework more suitable for children with autism spectrum disorder.

  14. Corrosion-induced release of Cu and Zn into rainwater from brass, bronze and their pure metals. A 2-year field study.

    PubMed

    Herting, Gunilla; Goidanich, Sara; Odnevall Wallinder, Inger; Leygraf, Christofer

    2008-09-01

    A 2-year field study has been conducted in an urban environment to provide annual release rates of copper and zinc from brass (20 wt% Zn) and copper and tin from bronze (6 wt% Sn) compared to sheets of their pure alloy constituents, copper and zinc. Despite relatively low nominal bulk alloy content, substantially more zinc was released from brass compared to copper. Both metals were released at a significantly slower rate from the brass alloy, compared to the pure metals. The proportion of release rates of copper and zinc from the alloy differed significantly from their proportions in the bulk alloy. Bronze showed relatively constant release rates of copper, being similar to that of pure copper sheet. The release of tin from bronze was negligible. The results clearly show that alloys and the pure metals behave very differently when exposed to rainwater. Accordingly, release rates from pure metals cannot be used to predict release rates of individual constituents from their alloys. Generated data are of importance within REACH, the new chemical policy of the European commission, where metal alloys erroneously are being treated as mixtures of chemical substances.

  15. The performance of moss, grass, and 1- and 2-year old spruce needles as bioindicators of contamination: a comparative study at the scale of the Czech Republic.

    PubMed

    Suchara, Ivan; Sucharova, Julie; Hola, Marie; Reimann, Clemens; Boyd, Rognvald; Filzmoser, Peter; Englmaier, Peter

    2011-05-01

    Moss (Pleurozium schreberi), grass (Avenella flexuosa), and 1- and 2-year old spruce (Picea abies) needles were collected over the territory of the Czech Republic at an average sample density of 1 site per 290km(2). The samples were analysed for 39 elements (Ag, Al, As, Ba, Be, Bi, Ca, Cd, Ce, Co, Cr, Cs, Cu, Fe, Ga, Hg, K, La, Li, Mg, Mn, Mo, Na, Nd, Ni, Pb, Pr, Rb, S, Sb, Se, Sn, Sr, Th, Tl, U, V, Y and Zn) using ICP-MS and ICP-AES techniques (the major nutrients Ca, K, Mg and Na were not analysed in moss). Moss showed by far the highest element concentrations for most elements. Exceptions were Ba (spruce), Mn (spruce), Mo (grass), Ni (spruce), Rb (grass) and S (grass). Regional distribution maps and spatial trend analysis were used to study the suitability of the four materials as bioindicators of anthropogenic contamination. The highly industrialised areas in the north-west and the far east of the country and several more local contamination sources were indicated in the distribution maps of one or several sample materials. At the scale of the whole country moss was the best indicator of known contamination sources. However, on a more local scale, it appeared that spruce needles were especially well suited for detection of urban contamination.

  16. Serum paraoxonase and arylesterase activities of paraoxonase-1 (PON-1), mild cognitive impairment, and 2-year conversion to dementia: A pilot study.

    PubMed

    Cervellati, Carlo; Trentini, Alessandro; Romani, Arianna; Bellini, Tiziana; Bosi, Cristina; Ortolani, Beatrice; Zurlo, Amedeo; Passaro, Angelina; Seripa, Davide; Zuliani, Giovanni

    2015-10-01

    Converging lines of evidence suggest that paraoxonase-1 (PON-1) may confer protection against inflammatory and oxidative challenge which, in turn, plays a key-role in the onset and progression of dementia. The aim of this study was to evaluate whether serum PON-1 paraoxonase/arylesterase activities might predict the clinical conversion of mild cognitive impairment (MCI) to late-onset Alzheimer's disease (LOAD) or vascular dementia (VAD). Serum paraoxonase and arylesterase activities were measured by spectrophotometric assays at baseline in 141 MCI patients (median age: 77 years; interquartile range 71-81) and in 78 healthy controls (median age: 76 years; interquartile range 73-79). After 2 years of follow-up, 86 MCI remained stable (MCI/MCI), 34 converted to LOAD (MCI/LOAD), whereas 21 converted to VAD (MCI/VAD). Baseline arylesterase activity was lower in all MCI groups compared with controls (all p < 0.01), whereas paraoxonase activity was lower in MCI/VAD group compared to controls (p < 0.05) and MCI/MCI patients (p = 0.009). Low paraoxonase and arylesterase activities (I quartile) were associated to higher risk of conversion to VAD (OR: 3.74, 95% CI: 1.37-10.25 and OR: 3.16, 95% CI: 1.17-8.56, respectively). Our results suggest that in MCI patients low PON-1 activity might contribute to identify individuals susceptible to develop vascular dementia. PMID:26178739

  17. A 2-Year Field Study Shows Little Evidence That the Long-Term Planting of Transgenic Insect-Resistant Cotton Affects the Community Structure of Soil Nematodes

    PubMed Central

    Li, Xiaogang; Liu, Biao

    2013-01-01

    Transgenic insect-resistant cotton has been released into the environment for more than a decade in China to effectively control the cotton bollworm (Helicoverpa armigera) and other Lepidoptera. Because of concerns about undesirable ecological side-effects of transgenic crops, it is important to monitor the potential environmental impact of transgenic insect-resistant cotton after commercial release. Our 2-year study included 1 cotton field where non-transgenic cotton had been planted continuously and 2 other cotton fields where transgenic insect-resistant cotton had been planted for different lengths of time since 1997 and since 2002. In 2 consecutive years (2009 and 2010), we took soil samples from 3 cotton fields at 4 different growth stages (seedling, budding, boll-forming and boll-opening stages), collected soil nematodes from soil with the sugar flotation and centrifugation method and identified the soil nematodes to the genus level. The generic composition, individual densities and diversity indices of the soil nematodes did not differ significantly between the 2 transgenic cotton fields and the non-transgenic cotton field, but significant seasonal variation was found in the individual densities of the principal trophic groups and in the diversity indices of the nematodes in all 3 cotton fields. The study used a comparative perspective to monitor the impact of transgenic insect-resistant cotton grown in typical ‘real world’ conditions. The results of the study suggested that more than 10 years of cultivation of transgenic insect-resistant cotton had no significant effects–adverse or otherwise–on soil nematodes. This study provides a theoretical basis for ongoing environmental impact monitoring of transgenic plants. PMID:23613899

  18. Carcinogenic effects of benzene: Cesare Maltoni's contributions.

    PubMed

    Mehlman, Myron A

    2002-12-01

    Cesare Maltoni's contributions to understanding, identifying, and characterizing widely used commercial chemicals in experimental animals are among the most important methods developed in the history of toxicology and serve to protect working men and women, the general population, and our environment from hazardous substances. Maltoni developed experimental methods that have reached the "platinum standard" for protection of public health. Benzene was among the 400 or more chemicals that Maltoni and his associates tested for carcinogenicity. In 1976, Maltoni reported that benzene is a potent experimental carcinogen. Maltoni's experiments clearly demonstrated that benzene is carcinogenic in Sprague-Dawley rats, Wistar rats, Swiss mice, and RF/J mice when administered by inhalation or ingestion. Benzene caused carcinomas of the Zymbal gland, oral cavity, nasal cavities; cancers of the skin, forestomach, mammary glands, and lungs; angiosarcomas and hepatomas of the liver; and hemolymphoreticular cancers. Thus, benzene was shown to be a multipotential carcinogen that produced cancers in several species of animals by various routes of administration. On November 2, 1977, Chemical Week reported that Maltoni provided a "bombshell" when he demonstrated the "first direct link" between benzene and cancer. In this paper, I shall summarize early experiments and human studies and reports; Maltoni's experimental contribution to understanding the carcinogenicity of benzene in humans and animals; earlier knowledge concerning benzene toxicity; and benzene standards and permissible exposure levels.

  19. Emotional Development: 2 Year Olds

    MedlinePlus

    ... Español Text Size Email Print Share Emotional Development: 2 Year Olds Page Content Article Body It’s so ... to follow the ups and downs of a two-year-old. One moment he’s beaming and friendly; ...

  20. Long-term impact of a chef on school lunch consumption: findings from a 2-year pilot study in Boston middle schools.

    PubMed

    Cohen, Juliana F W; Smit, Liesbeth A; Parker, Ellen; Austin, S Bryn; Frazier, A Lindsay; Economos, Christina D; Rimm, Eric B

    2012-06-01

    School cafeterias can play an important role in providing healthy meals. Although schools participating in the National School Lunch Program are required to meet minimum program standards, advocates recommend that innovations be sought to enhance menu dietary quality. This study evaluated the Chef Initiative, a 2-year pilot study in two Boston middle schools, designed to increase the availability and consumption of healthier school foods. Between 2007 and 2009, a professional chef trained cafeteria staff to prepare healthier school lunches (ie, more whole grains, fresh/frozen fruits and vegetables, and less sugar, salt, saturated fats, and trans fats). Meal nutrient compositions were monitored from 2007 to 2009, and a plate waste study conducted in the spring of 2009 compared food selection and consumption patterns among students at Chef Initiative schools, with students receiving standard school lunches at two matched control schools. Paired t tests and descriptive statistics were used to examine differences in menus and mixed-model analysis of variance was used to analyze differences in students' food selection and consumption between Chef Initiative and control schools. Overall, the Chef Initiative schools provided healthier lunches and the percent of foods consumed at Chef Initiative and control schools were similar (61.6% vs 57.3%; P=0.63). Of the areas targeted, there was greater whole-grain selection and vegetable consumption; 51% more students selected whole grains (P=0.02) and students consumed 0.36 more vegetable servings/day (P=0.01) at Chef Initiative schools. The potential of chefs collaborating with cafeteria staff to improve the availability, selection, and consumption of healthier meals is promising. PMID:22504283

  1. Inhalation toxicity studies with 1,3-butadiene 3 two year toxicity/carcinogenicity study in rats

    SciTech Connect

    Owen, P.E.; Glaister, J.R.; Gaunt, I.F.; Pullinger, D.H.

    1987-05-01

    Groups of 110 male and 110 female CD (Sprague-Dawley) rats were exposed to atmospheres containing 0 (control), 1000 or 8000 ppm v/v butadiene for 6 hr/day and 5 days/week. Ten of each sex from each group were killed at 52 weeks. The study was terminated when it was predicted that survival would drop to 20% to 25%. High dose rats had wet, ruffled fur and showed slight incoordination during the first exposure each week. During the second year, mortality in both treated female groups was increased because of humanitarian sacrifice of animals with large subcutaneous masses, while increased mortality in the high dose males was accompanied by an increase of the severity of nephropathy. Body weight was slightly lower than controls in both sexes at the high dose, but statistically significant only over the first 12 weeks. There were no effects in hematological analyses or tests of neuromuscular function that definitely could be associated with treatment. Liver weights at both doses were increased in both sexes with no associated pathological change. Kidney weight was increased in males at the high dose, together with an increase in the severity of nephrosis. There were increases in the incidences of pancreatic exocrine adenoma; uterine sarcoma; Zymbal gland carcinoma; mammary tumors; thyroid follicular cell tumors; and testis Leydig-cell tumors. These data suggest the butadiene is a weak oncogen to the rat under the conditions of exposure used in this study.

  2. Two-year toxicity and carcinogenicity study of methyleugenol in F344/N rats and B6C3F(1) mice.

    PubMed

    Johnson, J D; Ryan, M J; Toft JD, I I; Graves, S W; Hejtmancik, M R; Cunningham, M L; Herbert, R; Abdo, K M

    2000-08-01

    Methyleugenol (MEG) was tested for toxicity/carcinogenicity in a 2-yr carcinogenesis bioassay because of its widespread use in a variety of foods, beverages, and cosmetics as well as its structural resemblance to the known carcinogen safrole. F344/N rats and B6C3F(1) mice (50 animals/sex/dose group) were given MEG suspended in 0.5% methylcellulose by gavage at doses of 37, 75, or 150 mg/kg/day for 2 yr. Control groups (60 rats/sex and 50 mice/sex) received only the vehicle. A stop-exposure group of 60 rats/sex received 300 mg/kg/day by gavage for 53 weeks followed by the vehicle only for the remaining 52 weeks of the study. A special study group (10 animals/sex/species/dose group) were used for toxicokinetic studies. All male rats given 150 and 300 mg/kg/day died before the end of the study; survival of female rats given 150 mg/kg/day and all treated female mice was decreased. Mean body weights of treated male and female rats and mice were decreased when compared to control. Area under the curve results indicated that greater than dose proportional increases in plasma MEG occurred for male 150 and 300 mg/kg/day group rats (6 and 12 month) and male 150 mg/kg/day mice (12 month). Target organs included the liver, glandular stomach, forestomach (female rats) and kidney, mammary gland, and subcutaneous tissue (male rats). Liver neoplasms occurred in all dose groups of rats and mice and included hepatoadenoma, hepatocarcinoma, hepatocholangioma (rats only), hepatocholangiocarcinoma, and hepatoblastoma (mice only). Nonneoplastic liver lesions included eosinophilic and mixed cell foci (rats only), hypertrophy, oval cell hyperplasia, cystic degeneration (rats only), and bile duct hyperplasia. Mice also exhibited necrosis, hematopoietic cell proliferation, and hemosiderin pigmentation. Glandular stomach lesions in rats and mice included benign and malignant neuroendocrine tumors, neuroendocrine cell hyperplasia, and atrophy and in mice included glandular ectasia

  3. Revision Total Hip Arthroplasty Using Tantalum Augment in Patients with Paprosky III or IV Acetabular Bone Defects: A Minimum 2-year Follow Up Study

    PubMed Central

    Jeong, Min; Kim, Hyung-Joo; Lim, Seung-Jae; Moon, Young-Wan

    2016-01-01

    Purpose The purpose of this study is to report the short-term outcomes of revision total hip arthroplasty (THA) using tantalum augments in patients with severe acetabular bone defects. Materials and Methods We retrospectively analyzed 15 revision THAs performed in 15 patients using tantalum augments between June 2010 and December 2013. Acetabular bone defects were Paprosky type IIIA in 7 hips, type IIIB in 7, and type IV in 1. The causes of revision surgery were aseptic loosening in 12 hips and deep infection in 3. Revisions were first in 1 hip, second in 3, and third in 11. Six patients were male and 9 female with a mean age of 59 years (range, 48-75 years). Mean follow-up was 29 months (range, 24-48 months). Results Mean Harris hip score was improved from 34 points (range, 12-54 points) preoperatively to 84 points (range, 38-90 points) at final follow-up. On the final follow-up radiographs, there were 12 hips (80.0%) with stable fixation of the acetabular cup, 2 (13.3%) with secondary stability after mild acetabular protrusion, and 1 (6.7%) with radiolucency around the acetabular cup without mechanical symptoms. Complications included one patient with acute hematogenous infection managed by surgical debridement and long-term antibiotic therapy. There were no cases with nerve palsy or dislocation during the follow-up period. Conclusion The present study showed satisfactory clinical and radiographic outcomes of revision THA using tantalum augments due to severe acetabular bone defects of Paprosky type III or IV at a minimum follow-up of 2 years. PMID:27536651

  4. Scaling up family medicine training in Gezira, Sudan – a 2-year in-service master programme using modern information and communication technology: a survey study

    PubMed Central

    2014-01-01

    Background In 2010 the Gezira Family Medicine Project (GFMP) was initiated in Gezira state, Sudan, designed as an in-service training model. The project is a collaboration project between the University of Gezira, which aims to provide a 2-year master’s programme in family medicine for practicing doctors, and the Ministry of Health, which facilitates service provision and funds the training programme. This paper presents the programme, the teaching environment, and the first batch of candidates enrolled. Methods In this study a self-administered questionnaire was used to collect baseline data at the start of the project from doctors who joined the programme. A checklist was also used to assess the health centres where they work. A total of 188 out of 207 doctors responded (91%), while data were gathered from all 158 health centres (100%) staffed by the programme candidates. Results The Gezira model of in-service family medicine training has succeeded in recruiting 207 candidates in its first batch, providing health services in 158 centres, of which 84 had never been served by a doctor before. The curriculum is community oriented. The mean age of doctors was 32.5 years, 57% were males, and 32% were graduates from the University of Gezira. Respondents stated high confidence in practicing some skills such as asthma management and post-abortion uterine evacuation. They were least confident in other skills such as managing depression or inserting an intrauterine device. The majority of health centres was poorly equipped for management of noncommunicable diseases, as only 10% had an electrocardiography machine (ECG), 5% had spirometer, and 1% had a defibrillator. Conclusions The Gezira model has responded to local health system needs. Use of modern information and communication technology is used to facilitate both health service provision and training. The GFMP represents an example of a large-volume scaling-up programme of family medicine in Africa. PMID:24443978

  5. Respiratory carcinogenicity assessment of soluble nickel compounds.

    PubMed

    Oller, Adriana R

    2002-10-01

    The many chemical forms of nickel differ in physicochemical properties and biological effects. Health assessments for each main category of nickel species are needed. The carcinogenicity assessment of water-soluble nickel compounds has proven particularly difficult. Epidemiologic evidence indicates an association between inhalation exposures to nickel refinery dust containing soluble nickel compounds and increased risk of respiratory cancers. However, the nature of this association is unclear because of limitations of the exposure data, inconsistent results across cohorts, and the presence of mixed exposures to water-insoluble nickel compounds and other confounders that are known or suspected carcinogens. Moreover, well-conducted animal inhalation studies, where exposures were solely to soluble nickel, failed to demonstrate a carcinogenic potential. Similar negative results were seen in animal oral studies. A model exists that relates respiratory carcinogenic potential to the bioavailability of nickel ion at nuclear sites within respiratory target cells. This model helps reconcile human, animal, and mechanistic data for soluble nickel compounds. For inhalation exposures, the predicted lack of bioavailability of nickel ion at target sites suggests that water-soluble nickel compounds, by themselves, will not be complete human carcinogens. However, if inhaled at concentrations high enough to induce chronic lung inflammation, these compounds may enhance carcinogenic risks associated with inhalation exposure to other substances. Overall, the weight of evidence indicates that inhalation exposure to soluble nickel alone will not cause cancer; moreover, if exposures are kept below levels that cause chronic respiratory toxicity, any possible tumor-enhancing effects (particularly in smokers) would be avoided. PMID:12426143

  6. Tobacco smoking, polymorphisms in carcinogen metabolism enzyme genes, and risk of localized and advanced prostate cancer: results from the California Collaborative Prostate Cancer Study

    PubMed Central

    Shahabi, Ahva; Corral, Román; Catsburg, Chelsea; Joshi, Amit D; Kim, Andre; Lewinger, Juan Pablo; Koo, Jocelyn; John, Esther M; Ingles, Sue A; Stern, Mariana C

    2014-01-01

    The relationship between tobacco smoking and prostate cancer (PCa) remains inconclusive. This study examined the association between tobacco smoking and PCa risk taking into account polymorphisms in carcinogen metabolism enzyme genes as possible effect modifiers (9 polymorphisms and 1 predicted phenotype from metabolism enzyme genes). The study included cases (n = 761 localized; n = 1199 advanced) and controls (n = 1139) from the multiethnic California Collaborative Case–Control Study of Prostate Cancer. Multivariable conditional logistic regression was performed to evaluate the association between tobacco smoking variables and risk of localized and advanced PCa risk. Being a former smoker, regardless of time of quit smoking, was associated with an increased risk of localized PCa (odds ratio [OR] = 1.3; 95% confidence interval [CI] = 1.0–1.6). Among non-Hispanic Whites, ever smoking was associated with an increased risk of localized PCa (OR = 1.5; 95% CI = 1.1–2.1), whereas current smoking was associated with risk of advanced PCa (OR = 1.4; 95% CI = 1.0–1.9). However, no associations were observed between smoking intensity, duration or pack-year variables, and advanced PCa. No statistically significant trends were seen among Hispanics or African-Americans. The relationship between smoking status and PCa risk was modified by the CYP1A2 rs7662551 polymorphism (P-interaction = 0.008). In conclusion, tobacco smoking was associated with risk of PCa, primarily localized disease among non-Hispanic Whites. This association was modified by a genetic variant in CYP1A2, thus supporting a role for tobacco carcinogens in PCa risk. PMID:25355624

  7. Tobacco smoking, polymorphisms in carcinogen metabolism enzyme genes, and risk of localized and advanced prostate cancer: results from the California Collaborative Prostate Cancer Study.

    PubMed

    Shahabi, Ahva; Corral, Román; Catsburg, Chelsea; Joshi, Amit D; Kim, Andre; Lewinger, Juan Pablo; Koo, Jocelyn; John, Esther M; Ingles, Sue A; Stern, Mariana C

    2014-12-01

    The relationship between tobacco smoking and prostate cancer (PCa) remains inconclusive. This study examined the association between tobacco smoking and PCa risk taking into account polymorphisms in carcinogen metabolism enzyme genes as possible effect modifiers (9 polymorphisms and 1 predicted phenotype from metabolism enzyme genes). The study included cases (n = 761 localized; n = 1199 advanced) and controls (n = 1139) from the multiethnic California Collaborative Case-Control Study of Prostate Cancer. Multivariable conditional logistic regression was performed to evaluate the association between tobacco smoking variables and risk of localized and advanced PCa risk. Being a former smoker, regardless of time of quit smoking, was associated with an increased risk of localized PCa (odds ratio [OR] = 1.3; 95% confidence interval [CI] = 1.0-1.6). Among non-Hispanic Whites, ever smoking was associated with an increased risk of localized PCa (OR = 1.5; 95% CI = 1.1-2.1), whereas current smoking was associated with risk of advanced PCa (OR = 1.4; 95% CI = 1.0-1.9). However, no associations were observed between smoking intensity, duration or pack-year variables, and advanced PCa. No statistically significant trends were seen among Hispanics or African-Americans. The relationship between smoking status and PCa risk was modified by the CYP1A2 rs7662551 polymorphism (P-interaction = 0.008). In conclusion, tobacco smoking was associated with risk of PCa, primarily localized disease among non-Hispanic Whites. This association was modified by a genetic variant in CYP1A2, thus supporting a role for tobacco carcinogens in PCa risk. PMID:25355624

  8. Arsenic Is A Genotoxic Carcinogen

    EPA Science Inventory

    Arsenic is a recognized human carcinogen; however, there is controversy over whether or not it should be considered a genotoxic carcinogen. Many possible modes of action have been proposed on how arsenic induces cancer, including inhibiting DNA repair, altering methylation patter...

  9. PROPOSED CARCINOGENIC MECHANISMS FOR ARSENIC

    EPA Science Inventory

    PROPOSED CARCINOGENIC MECHANISMS FOR ARSENIC.

    Arsenic is a human carcinogen in skin, lung, liver, urinary bladder and kidney. In contrast,
    there is no accepted experimental animal model of inorganic arsenic carcinogenesis.
    Proposed mechanisms/modes of action for a...

  10. Oxidation of the carcinogenic non-aminoazo dye 1-phenylazo-2-hydroxy-naphthalene (Sudan I) by cytochromes P450 and peroxidases: a comparative study

    PubMed Central

    Stiborová, Marie; Martínek, Václav; Semanská, Marcela; Hodek, Petr; Dračínský, Martin; Cvačka, Josef; Schmeiser, Heinz H.; Frei, Eva

    2009-01-01

    Sudan I [1-(phenylazo)-2-hydroxynaphthalene, C.I. Solvent Yellow 14, CAS No: 842-07-9] is used as the compound employed in chemical industry and to color materials such as hydrocarbon solvents, oils, fats, waxes, plastics, printing inks, shoe and floor polishes and gasoline. Such a wide used could result in a considerable human exposure. Sudan I is known to cause developments of tumors in the liver or urinary bladder in rats, mice, and rabbits, and is considered a possible weak human carcinogen and mutagen. This carcinogen is also a potent contact allergen and sensitizer. Here, we compare the data concerning the Sudan I oxidative metabolism catalyzed by cytochrome P450 (CYP) and peroxidase enzymes, which has been investigated in our laboratory during the last two decades. These two types of enzymes are responsible both for Sudan I detoxication and activation. Among the Sudan I metabolites, C-hydroxylated derivatives and a dimer of Sudan I are suggested to be the detoxication metabolites formed by CYPs and peroxidases, respectively. Metabolic activation of Sudan I by both types of enzymes leads to formation of reactive species (the benzenediazonium ion by CYP and Sudan I radicals by peroxidase) that bind to DNA and RNA, generating covalent adducts in vitro and in vivo. Whereas the structure of the major adduct formed by the benzenediazonium ion in DNA has already been identified to be the 8-(phenylazo)guanine adduct, the structures of adducts formed by peroxidase, have not been characterized as yet. Biological significance of the DNA adducts of Sudan I activated with CYP and peroxidase enzymes and further aims of investigations in this field are discussed in this study. PMID:21217854

  11. Dietary arsenic consumption and urine arsenic in an endemic population: response to improvement of drinking water quality in a 2-year consecutive study.

    PubMed

    Biswas, Anirban; Deb, Debasree; Ghose, Aloke; Du Laing, Gijs; De Neve, Jan; Santra, Subhas Chandra; Guha Mazumder, Debendra Nath

    2014-01-01

    We assessed the association between arsenic intake through water and diet, and arsenic levels in first morning-void urine under variable conditions of water contamination. This was done in a 2-year consecutive study in an endemic population. Exposure of arsenic through water and diet was assessed for participants using arsenic-contaminated water (≥50 μg L(-1)) in a first year (group I) and for participants using water lower in arsenic (<50 μg L(-1)) in the next year (group II). Participants with and without arsenical skin lesions were considered in the statistical analysis. Median dose of arsenic intake through drinking water in groups I and II males was 7.44 and 0.85 μg kg body wt.(-1) day(-1) (p <0.0001). In females, it was 5.3 and 0.63 μg kg body wt.(-1) day(-1) (p <0.0001) for groups I and II, respectively. Arsenic dose through diet was 3.3 and 2.6 μg kg body wt.(-1) day(-1) (p = 0.088) in males and 2.6 and 1.9 μg kg body wt.(-1) day(-1) (p = 0.0081) in females. Median arsenic levels in urine of groups I and II males were 124 and 61 μg L(-1) (p = 0.052) and in females 130 and 52 μg L(-1) (p = 0.0001), respectively. When arsenic levels in the water were reduced to below 50 μg L(-1) (Indian permissible limit), total arsenic intake and arsenic intake through the water significantly decreased, but arsenic uptake through the diet was found to be not significantly affected. Moreover, it was found that drinking water mainly contributed to variations in urine arsenic concentrations. However, differences between male and female participants also indicate that not only arsenic uptake, but also many physiological factors affect arsenic behavior in the body and its excretion. As total median arsenic exposure still often exceeded 3.0 μg kg body wt.(-1) day(-1) (the permissible lower limit established by the Joint Expert Committee on Food Additives) after installation of the drinking water filters, it can be concluded that

  12. Carcinogen Control in the Chemical Laboratory.

    ERIC Educational Resources Information Center

    Johnson, James S.

    1981-01-01

    Presents general and specific guidelines for handling carcinogens. Additional topics include: definition of potential occupational carcinogens; classification of carcinogens; inventory requirements; signs and labels for materials and laboratories; decontamination and disposal procedures; medical surveillance for employees working with controlled…

  13. Consequences of exposure to carcinogens beginning during developmental life.

    PubMed

    Soffritti, Morando; Belpoggi, Fiorella; Esposti, Davide Degli; Falcioni, Laura; Bua, Luciano

    2008-02-01

    The increased incidence of cancer over the last 50-60 years may be largely attributed to two factors: the ageing of the population and the diffusion of agents and situations presenting carcinogenic risks. Today, we have entered into a new era in which populations are ever-increasingly exposed to diffuse carcinogenic risks, present not only in the occupational, but also in the general environment. We must now also consider an additional factor in the carcinogenic process, that is, the age in which exposure to carcinogenic risks begins. Apart from the paradigmatic cases of diethylstilboestrol and ionizing radiation, the available epidemiological data concerning the adult consequences of developmental exposure to carcinogens is very limited. However, important data have been provided by long-term experimental carcinogenicity bioassays conducted using rodents. This paper reports a selection of studies conducted in the laboratories of the Cesare Maltoni Cancer Research Center of the European Ramazzini Foundation in which exposure to the chemical agents vinyl acetate monomer, ethyl alcohol and aspartame was started during developmental life and continued into adulthood. The results of these studies provide supporting evidence that lifespan exposure to carcinogenic agents beginning during developmental life produces an overall increase in the carcinogenic effects observed. Moreover, when comparing prenatal and postnatal exposure, the data demonstrate that the development of cancers may appear earlier in life.

  14. Prediction of the Carcinogenic Potential of Human Pharmaceuticals Using Repeated Dose Toxicity Data and Their Pharmacological Properties

    PubMed Central

    van der Laan, Jan Willem; Buitenhuis, Wenny H. W.; Wagenaar, Laura; Soffers, Ans E. M. F.; van Someren, Eugene P.; Krul, Cyrille A. M.; Woutersen, Ruud A.

    2016-01-01

    relation to potential class effects, both in the negative and positive direction. A high negative and a high positive predictivity will both result in waiving the need for conducting 2-year rat carcinogenicity studies, if this is accepted by Regulatory Authorities, which will save large numbers of animals and reduce drug development costs and time. PMID:27790617

  15. Occupational exposures to carcinogens in developing countries.

    PubMed

    Pearce, N; Matos, E; Boffetta, P; Kogevinas, M; Vainio, H

    1994-09-01

    There have been very few studies of exposure to occupational carcinogens in developing countries, and even fewer studies of the health consequences of such exposures. However, all industrial chemicals, occupations and industrial processes classified by the International Agency for Research on Cancer (IARC) as Group 1 or Group 2A (carcinogenic or possibly carcinogenic to humans) have been described in developing countries, and there is growing concern that the health impact of many chemicals used in the developing world has been underestimated. In all regions a very large workforce is employed in the construction industry, in which substantial exposure to asbestos may occur, and there has been a rapid increase in production in countries such as Brazil and India. There is, for instance, a similar pattern for tyre production with a large increase in production in developing countries in the 1980s. Thus, the number of workers in industries entailing a carcinogenic risk is increasing in developing countries, partly as a result of the transfer of hazardous industry from industrialized countries. There is much that could be achieved in the prevention of occupational cancer in developing countries, and there have been a number of successful initiatives. However, the greatest progress in the prevention of occupational cancer in developing countries is most likely to come from political and economic changes. PMID:7847748

  16. Chemistry of carcinogenic metals.

    PubMed Central

    Martell, A E

    1981-01-01

    The periodic distribution of known and suspected carcinogenic metal ions is described, and the chemical behavior of various types of metal ions is explained in terms of the general theory of hard and soft acids and bases. The chelate effect is elucidated, and the relatively high stability of metal chelates in very dilute solutions is discussed. The concepts employed for the chelate effect are extended to explain the high stabilities of macrocyclic and cryptate complexes. Procedures for the use of equilibrium data to determine the speciation of metal ions and complexes under varying solution conditions are described. Methods for assessing the interferences by hydrogen ion, competing metal ions, hydrolysis, and precipitation are explained, and are applied to systems containing iron(III) chelates of fourteen chelating agents designed for effective binding of the ferric ion. The donor groups available for the building up of multidentate ligands are presented, and the ways in which they may be combined to achieve high affinity and selectivity for certain types of metal ions are explained. PMID:6791915

  17. Multigeneration reproduction and carcinogenicity studies in Sprague-Dawley rats exposed topically to oxidative hair-colouring formulations containing p-phenylenediamine and other aromatic amines.

    PubMed

    Burnett, C M; Goldenthal, E I

    1988-05-01

    Two-generation reproduction and chronic toxicity-carcinogenicity studies were conducted in Sprague-Dawley rats receiving topical applications of six oxidative hair-colouring formulations. These formulations were prepared as prototypes of permanent hair colourings using the base ingredients and primary intermediates and couplers most often used in this kind of product. Among the dyes included in the various formulations were p-phenylenediamine, p-toluenediamine, p-aminophenol, resorcinol, m-aminophenol, 1-naphthol, 2-amino-4-nitrophenol, 4-chlororesorcinol, p-aminodiphenylamine hydrochloride and N-methyl-p-aminophenol sulphate. The dye solutions were mixed with an equal volume of 6% hydrogen peroxide prior to application. In the reproduction study the samples were applied topically twice weekly throughout the growth, mating, gestation and lactation phases of the F0 parents to the weaning of the F1a and F2b litters. Fertility, gestation and foetal viability indices and body weights were evaluated for the six treatment groups and these were compared with the values for the three concurrent control groups. Weanlings selected from the F1a litters were the subjects for the lifetime carcinogenesis study. For 24 months they received twice-weekly topical applications of the same dyes as were administered to their parents. Clinical chemistry, haematological and urinalysis studies were performed at months 3, 12, 18 and 24, and five animals/sex/group were killed at month 12 and autopsied for histological examination of the rat tissues. All animals in the chronic study were evaluated for incidence of neoplastic and non-neoplastic lesions. In the reproduction phase the application of hair dyes had no adverse effect on the fertility of the males or females, or on gestation, lactation and weaning indices. The average number weaned per litter and the mean body weights of the weanlings were comparable among the treated and control groups. No treatment-related gross lesions were

  18. Detection of genotoxic and non-genotoxic carcinogens in Xpc{sup −/−}p53{sup +/−} mice

    SciTech Connect

    Melis, Joost P.M.; Speksnijder, Ewoud N.; Kuiper, Raoul V.; Salvatori, Daniela C.F.; Schaap, Mirjam M.; Maas, Saskia; Robinson, Joke; Verhoef, Aart; Benthem, Jan van; Luijten, Mirjam; Steeg, Harry van

    2013-01-15

    An accurate assessment of the carcinogenic potential of chemicals and pharmaceutical drugs is essential to protect humans and the environment. Therefore, substances are extensively tested before they are marketed to the public. Currently, the rodent two-year bioassay is still routinely used to assess the carcinogenic potential of substances. However, over time it has become clear that this assay yields false positive results and also has several economic and ethical drawbacks including the use of large numbers of animals, the long duration, and the high cost. The need for a suitable alternative assay is therefore high. Previously, we have proposed the Xpa*p53 mouse model as a very suitable alternative to the two-year bioassay. We now show that the Xpc*p53 mouse model preserves all the beneficial traits of the Xpa*p53 model for sub-chronic carcinogen identification and can identify both genotoxic and non-genotoxic carcinogens. Moreover, Xpc*p53 mice appear to be more responsive than Xpa*p53 mice towards several genotoxic and non-genotoxic carcinogens. Furthermore, Xpc*p53 mice are far less sensitive than Xpa*p53 mice for the toxic activity of DNA damaging agents and as such clearly respond in a similar way as wild type mice do. These advantageous traits of the Xpc*p53 model make it a better alternative for in vivo carcinogen testing than Xpa*p53. This pilot study suggests that Xpc*p53 mice are suited for routine sub-chronic testing of both genotoxic and non-genotoxic carcinogens and as such represent a suitable alternative to possibly replace the murine life time cancer bioassay. Highlights: ► The Xpc*p53 mouse model is able to identify genotoxic and non-genotoxic carcinogens. ► Time, animals and cost can be significantly reduced compared to the 2-year bioassay. ► Xpc*p53 mice are more advantageous for carcinogen identification than Xpa*p53 mice. ► Xpc*p53 mice exhibit a wild type response upon exposure to genotoxicants.

  19. Genetic toxicology: current status of methods of carcinogen identification.

    PubMed Central

    Tennant, R W; Zeiger, E

    1993-01-01

    A critical aspect of the efforts to relate the results of short-term genetic toxicity tests with those from long-term rodent tests for carcinogens is the quality and consistency of the studies conducted by the National Toxicology Program. Analysis of the results in relationship to chemical structure has shown that mutagenic potential is a primary risk factor for carcinogen identification. Chemicals positive in the Salmonella assay-generally possess "structural alerts" for electrophilic interactions, are predominantly represented among chemicals producing trans-species carcinogenic effects in rodents, and among those identified as carcinogenic to humans. Current efforts are aimed at defining toxicological, structural, and mechanistic properties of nonmutagens that are carcinogenic in rodents. PMID:8354178

  20. Initiation/promotion versus complete carcinogenicity in the rodent liver

    PubMed Central

    Ashby, John; Elliott, B. M.; Lefevre, P. A.; Styles, Jerry; Longstaff, E.

    1983-01-01

    4-N-Pyrrolidinylazobenzene (4N) is a close structural analog of the rodent liver carcinogen 4-dimethylaminoazobenzene (DAB). This structural similarity led us to evaluate it for genotoxic activity in vitro. We observed activity for 4N and DAB in the BHK cell transformation assay and subsequently in the Salmonella mutation assay of Ames. By a curious chance, Scribner, Miller and Miller, probably prompted by the same structural similarity, had synthesized 4N in the 1960s and found it to be noncarcinogenic to the rodent liver using a bioassay test protocol that detected DAB as carcinogenic. These findings were only described following the publication of our observations made in vitro. The conflict that apparently exists between these data can be interpreted in two separate ways. (a) Scribner et al. have suggested that 4N may be a carcinogenic initiator as opposed to a complete carcinogen like DAB. They also suggested that promotion of 4N-treated rodents with phenobarbitone might lead to the production of liver tumors. (b) We have evaluated the simpler concept that the activities observed for 4N in vitro define a carcinogenic potential that is not realized in vivo due to its rapid detoxification, at least in rodents. The first of these explanations implies that pure carcinogenic initiators may form a separate class of genotoxic agents from complete carcinogens, and perhaps of greater interest, that 4N might provide a valuable model compound for the study of carcinogenic promotion in the rodent liver. The second explanation regards potential carcinogenicity as a single property that can be defined in vitro and which may or may not be expressed in vivo depending on the enzymic environments encountered by the test chemical. It is clearly important to evaluate these different propositions in order to aid progress in the study of carcinogenic promotion, especially in the rodent liver. The presentation will describe our recent studies in vitro and in vivo in this connection

  1. Initiation/promotion versus complete carcinogenicity in the rodent liver.

    PubMed

    Ashby, J; Elliott, B M; Lefevre, P A; Styles, J; Longstaff, E

    1983-04-01

    4-N-Pyrrolidinylazobenzene (4N) is a close structural analog of the rodent liver carcinogen 4-dimethylaminoazobenzene (DAB). This structural similarity led us to evaluate it for genotoxic activity in vitro. We observed activity for 4N and DAB in the BHK cell transformation assay and subsequently in the Salmonella mutation assay of Ames. By a curious chance, Scribner, Miller and Miller, probably prompted by the same structural similarity, had synthesized 4N in the 1960s and found it to be noncarcinogenic to the rodent liver using a bioassay test protocol that detected DAB as carcinogenic. These findings were only described following the publication of our observations made in vitro. The conflict that apparently exists between these data can be interpreted in two separate ways. (a) Scribner et al. have suggested that 4N may be a carcinogenic initiator as opposed to a complete carcinogen like DAB. They also suggested that promotion of 4N-treated rodents with phenobarbitone might lead to the production of liver tumors. (b) We have evaluated the simpler concept that the activities observed for 4N in vitro define a carcinogenic potential that is not realized in vivo due to its rapid detoxification, at least in rodents. The first of these explanations implies that pure carcinogenic initiators may form a separate class of genotoxic agents from complete carcinogens, and perhaps of greater interest, that 4N might provide a valuable model compound for the study of carcinogenic promotion in the rodent liver. The second explanation regards potential carcinogenicity as a single property that can be defined in vitro and which may or may not be expressed in vivo depending on the enzymic environments encountered by the test chemical. It is clearly important to evaluate these different propositions in order to aid progress in the study of carcinogenic promotion, especially in the rodent liver. The presentation will describe our recent studies in vitro and in vivo in this connection.

  2. Carcinogens formed when Meat is Cooked

    SciTech Connect

    Felton, J S; Salmon, C P; Knize, M G

    2003-05-30

    Diet has been associated with varying cancer rates in human populations for many years, yet the causes of the observed variation in cancer patterns have not been adequately explained (Wynder et al. 1977). Along with the effect of diet on human cancer incidence is the strong evidence that mutations are the initiating events in the cancer process (Vogelstein et al. 1992). Foods, when heated, are a good source of genotoxic carcinogens that very likely are a cause for some of these events(Doll et al. 1981). These carcinogens fall into two chemical classes: heterocyclic aromatic amines (HAA) and polycyclic aromatic hydrocarbons (PAH). There is ample evidence that many of these compounds are complete carcinogens in rodents(El-Bayoumy et al. 1995; Ohgaki et al. 1991). Heterocyclic aromatic amines are among the most potent mutagenic substances ever tested in the Ames/Salmonella mutagenicity test (Wakabayashi et al. 1992). Both classes of carcinogen cause tumors in rodents at multiple sites, (El-Bayoumy et al. 1995; Ohgaki et al. 1991) many of which are common tumor sites in people on a Western diet. An HAA, PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine), and a PAH, B[a]P (benzo[a]pyrene), of comparable carcinogenic potency caused mammary gland tumors in a feeding study in female rats (El-Bayoumy et al. 1995). In addition, PhIP has recently been shown to cause carcinomas in the prostate of the male rat (Shirai et al. 1997). Complementing the rodent cancer studies are numerous human case-control and prospective studies suggesting a relationship between overheated beef, chicken, and lamb, and cancer of the colon, breast, prostate, and stomach (Sinha et al. 1999; Ward et al. 1997; Zheng et al. 1998).

  3. An estimation of the carcinogenic risk associated with the intake of multiple relevant carcinogens found in meat and charcuterie products.

    PubMed

    Hernández, Ángel Rodríguez; Boada, Luis D; Almeida-González, Maira; Mendoza, Zenaida; Ruiz-Suárez, Norberto; Valeron, Pilar F; Camacho, María; Zumbado, Manuel; Henríquez-Hernández, Luis A; Luzardo, Octavio P

    2015-05-01

    Numerous epidemiological studies have demonstrated a link between excessive meat consumption and the incidence of various cancers, especially colorectal cancer, and it has been suggested that environmental carcinogens present in meat might be related to the increased risk of cancer associated with this food. However, there are no studies evaluating the carcinogenic potential of meat in relation to its content of carcinogens. Our purpose was to emphasize the relevance of environmental carcinogens existing in meat as a determinant of the association between cancer and meat consumption. Because within Europe, Spain shows high consumption of meat and charcuterie, we performed this study focusing on Spanish population. Based on the preferences of consumers we acquired 100 samples of meat and charcuterie that reflect the variety available in the European market. We quantified in these samples the concentration of 33 chemicals with calculated carcinogenic potential (PAHs, organochlorine pesticides, and dioxin-like PCBs). The carcinogenic risk of these contaminants was assessed for each food using a risk ratio based on the current consumption of meat and charcuterie and the maximum tolerable intake of these foods depending on the level of contamination by the carcinogens they contain. Our results indicate that the current consumption of beef, pork, lamb, chicken, and "chorizo", represents a relevant carcinogenic risk for consumers (carcinogenic risk quotient between 1.33 and 13.98). In order to reduce carcinogenic risk, the study population should halve the monthly consumption of these foods, and also not to surpass the number of 5 servings of beef/pork/chicken (considered together).

  4. Characteristic expression profiles induced by genotoxic carcinogens in rat liver.

    PubMed

    Ellinger-Ziegelbauer, Heidrun; Stuart, Barry; Wahle, Brad; Bomann, Werner; Ahr, Hans-Jurgen

    2004-01-01

    When applied in toxicological studies, the recently developed gene expression profiling techniques using microarrays, which brought forth the new field of toxicogenomics, facilitate the interpretation of a toxic compound's mechanism of action. In this study, we investigated whether genotoxic carcinogens at doses known to induce liver tumors in the 2-year rat bioassay deregulate a common set of genes in a short-term in vivo study and, if so, whether these deregulated genes represent defined biological pathways. Rats were dosed with the four genotoxic hepatocarcinogens dimethylnitrosamine (4 mg/kg/day), 2-nitrofluorene (44 mg/kg/day), aflatoxin B1 (0.24 mg/kg/day), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK, 20 mg/kg/day). After treatment for up to 14 days, the expression profiles of the livers were analyzed on Affymetrix RG_U34A microarrays. Among the significantly upregulated genes were a set of target genes of the tumor suppressor protein p53, indicating a DNA damage response. Such a response was expected and, therefore, confirmed the validity of our approach. In addition, the gene expression changes suggest a specific detoxification response, the activation of proliferative and survival signaling pathways, and some cell structural changes. These responses were strong throughout the 14 day time course for 2-nitrofluorene and aflatoxin B1; in the case of dimethylnitrosamine and NNK, the effects were weakly detectable at day 1 and then increased with time. For dimethylnitrosamine and aflatoxin B1, which caused observable inflammation in vivo, we found a corresponding upregulation of inflammatory genes at the same time points. Thus, by the toxicogenomic analysis of short-term in vivo studies, we identified genes and pathways commonly deregulated by genotoxic carcinogens, which may be indicative for the early events in tumorigenesis and, thus, predictive of later tumor development. PMID:14600272

  5. Age 2: Findings from the 2-Year-Old Follow-Up of the Early Childhood Longitudinal Study, Birth Cohort (ECLS-B). E.D. TAB. NCES 2006-043

    ERIC Educational Resources Information Center

    Mulligan, Gail M.; Flanagan, Kristin Denton

    2006-01-01

    This E.D. TAB is the first report produced using data from the second round of data collection for the Early Childhood Longitudinal Study, Birth Cohort (ECLS-B), a study of a nationally representative sample of children born in the year 2001. The report provides descriptive information about these children when they were about 2 years old. It…

  6. Effects of sediment dredging on nitrogen cycling in Lake Taihu, China: Insight from mass balance based on a 2-year field study.

    PubMed

    Yu, Juhua; Fan, Chengxin; Zhong, Jicheng; Zhang, Lu; Zhang, Lei; Wang, Changhui; Yao, Xiaolong

    2016-02-01

    Sediment dredging can permanently remove pollutants from an aquatic ecosystem, which is considered an effective approach to aquatic ecosystem restoration. In this work, a 2-year field simulation test was carried out to investigate the effect of dredging on nitrogen cycling across the sediment-water interface (SWI) in Lake Taihu, China. The results showed that simulated dredging applied to an area rich in total organic carbon (TOC) and total nitrogen (TN) slightly reduced the NH4(+)-N release from sediments while temporarily enhanced the NH4(+)-N release in an area with lower TOC and/or TN (in the first 180 days), although the application had a limited effect on the fluxes of NO2(-)-N and NO3(-)-N in both areas. Further analysis indicated that dredging induced decreases in nitrification, denitrification, and anaerobic ammonium oxidation (anammox) in sediments, notably by 76.9, 49.0, and 89.9%, respectively, in the TOC and/or TN-rich area. Therefore, dredging slowed down nitrogen cycling rates in sediments but did not increase N loading to overlying water. The main reason for the above phenomenon could be attributed to the removal of the surface sediments enriched with more TOC and/or TN (compared with the bottom sediments). Overall, to minimize internal N pollution, dredging may be more applicable to nutrient-rich sediments.

  7. Mental health service use by patients with dysthymic disorder: treatment use and dropout in a 7 1/2-year naturalistic follow-up study.

    PubMed

    McFarland, Brian R; Klein, Daniel N

    2005-01-01

    Little is known about long-term treatment use among patients with dysthymia. This paper describes patterns of treatment use by 85 outpatients with dysthymic disorder and a comparison group of 36 outpatients with nonchronic (episodic) major depression in a naturalistic follow-up. Patients with dysthymia had higher rates of treatment use across 7 1/2 years compared with patients with episodic major depression. Baseline variables that predicted which patients with dysthymia dropped out of treatment before recovering from dysthymic disorder included age, ethnicity, Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition Axis II pathology as obtained from informant reports, higher self-reported autonomy, and receiving psychotherapy alone as compared to receiving a combination of psychotherapy and medication. Dysthymic disorder places a significant burden on the mental health services system, yet many outpatients with dysthymia may be receiving inadequate treatment. Younger patients, ethnic minority patients, and patients with personality disorders may be at increased risk of dropping out from treatment for depression. Combination treatments may increase treatment retention.

  8. Application of the U.S. EPA Mode of Action Framework for Purposes of Guiding Future Research: A Case Study Involving the Oral Carcinogenicity of Hexavalent Chromium

    PubMed Central

    Thompson, Chad M.; Haws, Laurie C.; Harris, Mark A.; Gatto, Nicole M.; Proctor, Deborah M.

    2011-01-01

    Mode of action (MOA) analysis provides a systematic description of key events leading to adverse health effects in animal bioassays for the purpose of informing human health risk assessment. Uncertainties and data gaps identified in the MOA analysis may also be used to guide future research to improve understanding of the MOAs underlying a specific toxic response and foster development of toxicokinetic and toxicodynamic models. An MOA analysis, consistent with approaches outlined in the MOA Framework as described in the Guidelines for Carcinogen Risk Assessment, was conducted to evaluate small intestinal tumors observed in mice chronically exposed to relatively high concentrations of hexavalent chromium (Cr(VI)) in drinking water. Based on review of the literature, key events in the MOA are hypothesized to include saturation of the reductive capacity of the upper gastrointestinal tract, absorption of Cr(VI) into the intestinal epithelium, oxidative stress and inflammation, cell proliferation, direct and/or indirect DNA modification, and mutagenesis. Although available data generally support the plausibility of these key events, several unresolved questions and data gaps were identified, highlighting the need for obtaining critical toxicokinetic and toxicodynamic data in the target tissue and in the low-dose range. Experimental assays that can address these data gaps are discussed along with strategies for comparisons between responsive and nonresponsive tissues and species. This analysis provides a practical application of MOA Framework guidance and is instructive for the design of studies to improve upon the information available for quantitative risk assessment. PMID:20947717

  9. Micronuclei as biomarkers of carcinogen exposure in populations exposed to arsenic through drinking water in West Bengal, India: a comparative study in three cell types.

    PubMed

    Basu, Anamika; Ghosh, Pritha; Das, Jayanta K; Banerjee, Apurba; Ray, Kunal; Giri, Ashok K

    2004-05-01

    Contamination of groundwater by arsenic, a paradoxical human carcinogen, has become a cause of global public health concern. In West Bengal, India, the groundwater in 9 of 18 districts is heavily contaminated with arsenic. Various adverse health effects including cancer have been reported from these districts and are associated with prolonged arsenic exposure. A cross-sectional biomarker study was conducted to evaluate and compare the frequencies of micronuclei in peripheral blood lymphocytes, oral mucosa cells, and urothelial cells from the inhabitants of North 24 Parganas, one of the arsenic-affected districts. The three cell types were collected from 163 residents exposed to high levels of arsenic in drinking water (214.7213 +/- 9.0273 microg/l) and from 154 unexposed subjects residing in the unaffected East Midnapur district with very little or no exposure to arsenic through drinking water (9.2017 +/- 0.3157 microg/l). Our analysis revealed that micronuclei frequencies in the exposed group were significantly elevated to 5.33-fold over unexposed levels for lymphocytes, 4.63-fold for oral mucosa cells, and 4.71-fold for urothelial cells (increases in micronuclei frequencies significant at P < 0.01). The results indicate that chronic ingestion of arsenic in drinking water by the exposed subjects is linked to the enhanced incidence of micronuclei in all the three cell types, slightly higher level of micronuclei being observed in lymphocytes compared with oral mucosa and urothelial cells.

  10. Historical control background incidence of spontaneous thyroid and parathyroid glands lesions of rats and CD-1 mice used in 104-week carcinogenicity studies.

    PubMed

    Isobe, Kaori; Mukaratirwa, Sydney; Petterino, Claudio; Bradley, Alys

    2016-07-01

    The incidence and range of spontaneous thyroid and parathyroid glands findings were determined in control Han-Wistar and Sprague-Dawley rats, and CD-1 mice from 104-week carcinogenicity studies carried out between 1998 and 2010 at Charles River Edinburgh. In both strains of rats and in CD-1 mice, non-proliferative lesions of the thyroid or parathyroid glands were generally uncommon apart from some findings in CD-1 mice such as ultimobranchial duct/cyst (5.72%), follicular distension/dilatation (3.84%), and cystic follicles (3.53%). In Han-Wistar rats, thyroid proliferative lesions were slightly more frequent in males than in females, but in Sprague-Dawley rats, they were of similar incidence in both sexes. The most common findings overall in Han-Wistar and Sprague-Dawley rats were C-cell hyperplasia (48.11% and 36.56%, respectively) and adenoma (10.87% and 9.52%, respectively), follicular cell hyperplasia (4.21% and 0.91%, respectively) and adenoma (4.32% and 1.36%, respectively). Secondary neoplastic lesions either in thyroid or parathyroid gland were poorly represented. PMID:27559247

  11. State of the science on the carcinogenicity of gasoline with particular reference to cohort mortality study results

    SciTech Connect

    Infante, P.F.

    1993-12-01

    As a result of the content of benzene in various streams of refinery products, including gasoline, it is not surprising that over the years studies and case reports have linked gasoline exposure to lymphopoietic cancers (LPC), particularly leukemia and multiple myeloma (MM). Of three recently conducted studies of gasoline-exposed workers, one shows strong associations with leukemia and MM, a second suggests some association with leukemia and did not analyze data for MM, and the third study is not possible to evaluate because of a major problem with study design. Other diseases of particular interest in relation to gasoline exposure are kidney cancer, malignant melanoma, and heart disease. One study suggests an association with kidney cancer, but the second study did not. There appears to be no association between employment in refineries or gasoline exposure and heart disease. However, evaluation of risk of kidney cancer and heart disease is somewhat difficult because investigators did not control for cigarette smoking, even though it is related to these diseases. This is of particular concern when studying gasoline-exposed workers, who because of the explosive nature of gasoline probably smoke less than the general population used for comparison of mortality. Some studies of refinery workers and gasoline-exposed workers in particular show an excess risk of death from malignant melanoma. Whether this latter association is the result of benzene/gasoline exposure, sunlight exposure, or a combination of the two cannot be determined with the data currently available. The National Toxicology Program benzene cancer bioassay and the Dow Chemical Company epidemiologic study argue in favor of a benzene etiology; the fact that the workers spend a great amount of time outdoors argues in favor of a sunlight etiology. Finally, the American Petroleum Institute is challenged to apply warning labels and filling instructions to gasoline pumps and containers. 32 refs.

  12. Acrylonitrile is a multisite carcinogen in male and female B6C3F1 mice.

    PubMed

    Ghanayem, Burhan I; Nyska, Abraham; Haseman, Joseph K; Bucher, John R

    2002-07-01

    Acrylonitrile is a heavily produced unsaturated nitrile, which is used in the production of synthetic fibers, plastics, resins, and rubber. Acrylonitrile is a multisite carcinogen in rats after exposure via gavage, drinking water, or inhalation. No carcinogenicity studies of acrylonitrile in a second animal species were available. The current studies were designed to assess the carcinogenicity of acrylonitrile in B6C3F1 mice of both sexes. Acrylonitrile was administered by gavage at 0, 2.5, 10, or 20 mg/kg/day, 5 days per week, for 2 years. Urinary thiocyanate and N-acetyl-S-(2-cyanoethyl)-L-cysteine were measured as markers of exposure to acrylonitrile. In general, there were dose-related increases in urinary thiocyanate and N-acetyl-S-(2-cyanoethyl)-L-cysteine concentrations in all dosed groups of mice and at all time points. Survival was significantly (p < 0.001) reduced in the top dose (20 mg/kg) group of male and female mice relative to controls. The incidence of forestomach papillomas and carcinomas was increased in mice of both sexes in association with an increase in forestomach epithelial hyperplasia. The incidence of Harderian gland adenomas and carcinomas was also markedly increased in the acrylonitrile-dosed groups. In female mice, the incidence of benign or malignant granulosa cell tumors (combined) in the ovary in the 10 mg/kg dose group was greater than that in the vehicle control group, but because of a lack of dose response, this was considered an equivocal finding. In addition, the incidences of atrophy and cysts in the ovary of the 10 and 20 mg/kg dose groups were significantly increased. The incidences of alveolar/bronchiolar adenoma or carcinoma (combined) were significantly increased in female mice treated with acrylonitrile at 10 mg/kg/day for 2 years. This was also considered an equivocal result. In conclusion, these studies demonstrated that acrylonitrile causes multiple carcinogenic effects after gavage administration to male and female B6

  13. The Role of Depressive Symptoms, Family Invalidation and Behavioral Impulsivity in the Occurrence and Repetition of Non-Suicidal Self-Injury in Chinese Adolescents: A 2-Year Follow-Up Study

    ERIC Educational Resources Information Center

    You, Jianing; Leung, Freedom

    2012-01-01

    This study used zero-inflated poisson regression analysis to examine the role of depressive symptoms, family invalidation, and behavioral impulsivity in the occurrence and repetition of non-suicidal self-injury among Chinese community adolescents over a 2-year period. Participants, 4782 high school students, were assessed twice during the…

  14. Lymphoblastoid Cell lines: a Continuous in Vitro Source of Cells to Study Carcinogen Sensitivity and DNA Repair.

    PubMed

    Hussain, Tabish; Mulherkar, Rita

    2012-01-01

    Obtaining a continuous source of normal cells or DNA from a single individual has always been a rate limiting step in biomedical research. Availability of Lymphoblastoid cell lines (LCLs) as a surrogate for isolated or cryopreserved peripheral blood lymphocytes has substantially accelerated the process of biological investigations. LCLs can be established by in vitro infection of resting B cells from peripheral blood with Epstein Barr Virus (EBV) resulting in a continuous source, bearing negligible genetic and phenotypic alterations. Being a spontaneous replicating source, LCLs fulfil the requirement of constant supply of starting material for variety of assays, sparing the need of re-sampling. There is a reason to believe that LCLs are in close resemblance with the parent lymphocytes based on the ample supporting observations from a variety of studies showing significant level of correlation at molecular and functional level. LCLs, which carry the complete set of germ line genetic material, have been instrumental in general as a source of biomolecules and a system to carry out various immunological and epidemiological studies. Furthermore, in recent times their utility for analysing the whole human genome has extensively been documented. This proves the usefulness of LCLs in various genetic and functional studies. There are a few contradictory reports that have questioned the employment of LCLs as parent surrogate. Regardless of some inherent limitations LCLs are increasingly being considered as an important resource for genetic and functional research.

  15. A 2-year dose-response study of lesion sequences during hepatocellular carcinogenesis in the male B6C3F(1) mouse given the drinking water chemical dichloroacetic acid.

    PubMed Central

    Carter, Julia H; Carter, Harry W; Deddens, James A; Hurst, Bernadette M; George, Michael H; DeAngelo, Anthony B

    2003-01-01

    Dichloroacetic acid (DCA) is carcinogenic to the B6C3F(1) mouse and the F344 rat. Given the carcinogenic potential of DCA in rodent liver and the known concentrations of this compound in drinking water, reliable biologically based models to reduce the uncertainty of risk assessment for human exposure to DCA are needed. Development of such models requires identification and quantification of premalignant hepatic lesions, identification of the doses at which these lesions occur, and determination of the likelihood that these lesions will progress to cancer. In this study we determined the dose response of histopathologic changes occurring in the livers of mice exposed to DCA (0.05-3.5 g/L) for 26-100 weeks. Lesions were classified as foci of cellular alteration smaller than one liver lobule (altered hepatic foci; AHF), foci of cellular alteration larger than one liver lobule (large foci of cellular alteration; LFCA), adenomas (ADs), or carcinomas (CAs). Histopathologic analysis of 598 premalignant lesions revealed that (a)) each lesion class had a predominant phenotype; (b)) AHF, LFCA, and AD demonstrated neoplastic progression with time; and (c)) independent of DCA dose and length of exposure effects, some toxic/adaptive changes in non-involved liver were related to this neoplastic progression. A lesion sequence for carcinogenesis in male B6C3F(1) mouse liver has been proposed that will enable development of a biologically based mathematical model for DCA. Because all classes of premalignant lesions and CAs were found at both lower and higher doses, these data are consistent with the conclusion that nongenotoxic mechanisms, such as negative selection, are relevant to DCA carcinogenesis at lower doses where DCA genotoxicity has not been observed. PMID:12515679

  16. Towards incorporating epigenetic mechanisms into carcinogen identification and evaluation.

    PubMed

    Herceg, Zdenko; Lambert, Marie-Pierre; van Veldhoven, Karin; Demetriou, Christiana; Vineis, Paolo; Smith, Martyn T; Straif, Kurt; Wild, Christopher P

    2013-09-01

    Remarkable progress in the field of epigenetics has turned academic, medical and public attention to the potential applications of these new advances in medicine and various fields of biomedical research. The result is a broader appreciation of epigenetic phenomena in the a etiology of common human diseases, most notably cancer. These advances also represent an exciting opportunity to incorporate epigenetics and epigenomics into carcinogen identification and safety assessment. Current epigenetic studies, including major international sequencing projects, are expected to generate information for establishing the 'normal' epigenome of tissues and cell types as well as the physiological variability of the epigenome against which carcinogen exposure can be assessed. Recently, epigenetic events have emerged as key mechanisms in cancer development, and while our search of the Monograph Volume 100 revealed that epigenetics have played a modest role in evaluating human carcinogens by the International Agency for Research on Cancer (IARC) Monographs so far, epigenetic data might play a pivotal role in the future. Here, we review (i) the current status of incorporation of epigenetics in carcinogen evaluation in the IARC Monographs Programme, (ii) potential modes of action for epigenetic carcinogens, (iii) current in vivo and in vitro technologies to detect epigenetic carcinogens, (iv) genomic regions and epigenetic modifications and their biological consequences and (v) critical technological and biological issues in assessment of epigenetic carcinogens. We also discuss the issues related to opportunities and challenges in the application of epigenetic testing in carcinogen identification and evaluation. Although the application of epigenetic assays in carcinogen evaluation is still in its infancy, important data are being generated and valuable scientific resources are being established that should catalyse future applications of epigenetic testing.

  17. Improvement of lipid profile by probiotic/protective cultures: study in a non-carcinogenic small intestinal cell model.

    PubMed

    Gorenjak, Mario; Gradišnik, Lidija; Trapečar, Martin; Pistello, Mauro; Kozmus, Carina Pinto; Škorjanc, Dejan; Skok, Pavel; Langerholc, Tomaž; Cencič, Avrelija

    2014-01-01

    Plasma lipid levels are important risk factors for the development of atherosclerosis and coronary heart disease. Previous findings have shown that probiotic bacteria exert positive effects on hypercholesterolemia by lowering serum cholesterol and improving lipid profile that, in turn, leads to a reduced risk of coronary heart disease and atherosclerosis. Most of these studies were carried out with tumoral cell lines that have a metabolism quite different from that of normal cells and may thus respond differently to various stimuli. Here, we demonstrate the beneficial effects of some probiotics on cholesterol levels and pathways in normal small intestinal foetal epithelial tissue cells. The results show that Lactobacillus plantarum strain PCS 26 efficiently removes cholesterol from media, exhibits bile salt hydrolase activity, and up-regulates several genes involved in cholesterol metabolism. This study suggests that Lactobacillus plantarum PCS 26 might act as a liver X receptor agonist and help to improve lipid profiles in hypercholesterolemic patients or even dislipidemias in complex diseases such as the metabolic syndrome.

  18. FBLN-3 as a biomarker of pleural plaques in workers occupationally exposed to carcinogenic fibers: a pilot study.

    PubMed

    Rapisarda, Venerando; Ledda, Caterina; Migliore, Marcello; Salemi, Rossella; Musumeci, Andrea; Bracci, Massimo; Marconi, Andrea; Loreto, Carla; Libra, Massimo

    2015-01-01

    FBLN-3 has recently been proposed as a biomarker for malignant mesothelioma. A significantly increased standardized mortality rate from malignant mesothelioma has been reported in Biancavilla, Italy. Its cause has been identified in environmental exposure to fluoro-edenite. The aim of this study was to seek a correlation between plasma FBLN-3 concentration and pleural plaques in subjects exposed to fluoro-edenite and in a nonexposed control group. Pleural plaques was never detected in the control group, whereas it was found in 52% of exposed subjects. Median FBLN-3 concentrations were 12.96 and 5.29 ng/ml in the exposed and the control group, respectively (p < 0.001). FBLN-3 plasma levels exhibited a high predictive value for the presence of pleural plaques. PMID:26638921

  19. FBLN-3 as a biomarker of pleural plaques in workers occupationally exposed to carcinogenic fibers: a pilot study.

    PubMed

    Rapisarda, Venerando; Ledda, Caterina; Migliore, Marcello; Salemi, Rossella; Musumeci, Andrea; Bracci, Massimo; Marconi, Andrea; Loreto, Carla; Libra, Massimo

    2015-01-01

    FBLN-3 has recently been proposed as a biomarker for malignant mesothelioma. A significantly increased standardized mortality rate from malignant mesothelioma has been reported in Biancavilla, Italy. Its cause has been identified in environmental exposure to fluoro-edenite. The aim of this study was to seek a correlation between plasma FBLN-3 concentration and pleural plaques in subjects exposed to fluoro-edenite and in a nonexposed control group. Pleural plaques was never detected in the control group, whereas it was found in 52% of exposed subjects. Median FBLN-3 concentrations were 12.96 and 5.29 ng/ml in the exposed and the control group, respectively (p < 0.001). FBLN-3 plasma levels exhibited a high predictive value for the presence of pleural plaques.

  20. X-ray structural studies and molecular orbital calculations (CNDO/2) in a series of cyclopenta[a]phenanthrenes: attempts at correlation with carcinogenicity.

    PubMed

    Clayton, A F; Coombs, M M; Henrick, K; McPartlin, M; Trotter, J

    1983-12-01

    Comparative X-ray crystallographic structure analyses have been carried out on seven cyclopenta[a]phenanthrenes, namely 15,16-dihydocyclopenta[a]phenanthren-17-one and its 2-, 6- and 12-methyl homologues (non-carcinogens) and the 7-and 11-methyl and 1,11-methano derivatives (carcinogens). All-valence-electron molecular-orbital calculations by the CNDO/2 method, using the crystallographic parameters, have also been executed. Charge distribution and the energies of the highest occupied molecular orbitals (HOMO) and lowest unoccupied molecular orbitals (LUMO) have been calculated. With one exception all the molecules show only small deviations from planarity, the exception being the strongly carcinogenic 11-methyl-17-ketone in which the bay-region methyl group causes out-of-plane deformation of the benzo rings of 12.5 degrees. Among the other six compounds the two carcinogens are readily differentiated by high angle strain induced by a 7-methyl group or a 1,11-methano bridge. As expected, the HOMO's of these molecules to some extent reflect their ease of chemical oxidation at the 6,7-double bond; biological oxidation is less easy to correlate probably due to spatial restrictions at the active site within the mono-oxygenase.

  1. Is ingested inorganic arsenic a "threshold" carcinogen?

    PubMed

    Abernathy, C O; Chappell, W R; Meek, M E; Gibb, H; Guo, H R

    1996-02-01

    Ingested inorganic arsenic (As) is known to be a human carcinogen. An intriguing question is whether there is a threshold for the carcinogenic effects of As, i.e., is there a level below which it does not induce the development of cancer(s)? This Roundtable will discuss the United States Environmental Protection Agency's As risk assessment using the Taiwan data from different viewpoints. It will also consider the hypothesis that there is a threshold for As and data for or against this hypothesis. For example, some scientists believe that epidemiological data cannot answer this question, while others feel that different study designs and larger sampling will provide adequate data. Reasons for each position are given. This Roundtable discussion demonstrates the controversy surrounding the use of the Taiwan data for risk assessment.

  2. Comparison of rat olfactory mucosal responses to carcinogenic and non-carcinogenic chloracetanilides

    PubMed Central

    Genter, M.B.; Warner, B.M.; Medvedovic, M.; Sartor, M.A.

    2009-01-01

    Alachlor and butachlor are chloracetanilide herbicides that induce olfactory tumors in rats, whereas propachlor does not. The mechanism by which alachlor induces tumors is distinct from many other nasal carcinogens, in that alachlor induces a gradual de-differentiation of the olfactory mucosa (OM) to a more respiratory-like epithelium, in contrast to other agents that induce cytotoxicity, followed by an aberrant regenerative response. We studied biochemical and genomic effects of these compounds to identify processes that occur in common between alachlor- and butachlor-treated rats. Because we have previously shown that matrix metalloproteinase-2 (MMP2) is activated in OM by alachlor, in the present studies we evaluated both MMP2 activation and changes in OM gene expression in response to carcinogenic and non-carcinogenic chloracetanilide treatments. All three chloracetanilides activated MMP2, and > 300 genes were significantly up- or downregulated between control and alachlor-treated rats. The most significantly regulated gene was vomeromodulin, which was dramatically upregulated by alachlor and butachlor treatment (>60-fold), but not by propachlor treatment. Except for similar gene responses in alachlor- and butachlor-treated rats, we did not identify clear-cut differences that would predict OM carcinogenicity in this study. PMID:19425180

  3. Asbestos and metals as carcinogens

    SciTech Connect

    Norseth, T.

    1980-09-01

    Increased incidences of lung carcinoma and pleural mesothelioma in humans exposed to asbestos have been irrefutably established. Different forms of asbestos may have different tumorigenic activities, depending on surface properties, durability, and size of the fibers. A number of metals, such as nickel, chromium and arsenic, are known to be carcinogenic to humans; for beryllium and cadmium the epidemiologic evidence is less extensive. All these metals also induce genetic toxicity in vitro. At present it cannot be concluded that all metals act by the same carcinogenic mechanism, even though direct modification of DNA seems to be the common experimental finding.

  4. Long-term carcinogenicity study in Syrian golden hamster of particulate emissions from coal- and oil-fired power plants

    SciTech Connect

    Persson, S.A.; Ahlberg, M.; Berghem, L.; Koenberg, E.N.; Nordberg, G.F.; Bergman, F.

    1988-04-01

    Male Syrian golden hamsters were given 15 weekly intratracheal instillations with suspensions of coal fly ash or oil fly ash. Controls were instilled with saline containing gelatine (0.5 g/100 mL) or to check particle effects with suspensions of hematite (Fe/sub 2/O/sub 3/). The common weekly dose was 4.5 mg/hamster. In addition, one subgroup of hamsters was treated with oil fly ash at a weekly dose of 3.0 mg/hamster and another with coal fly ash at a weekly dose of 6.0 mg/hamster. Other groups of hamsters were treated with suspensions of benzo(a)pyrene (BaP) or with suspensions on coal fly ash, oil fly ash, or Fe/sub 2/O/sub 3/ coated with BaP. The mass median aerodynamic diameters of the coal and oil fly ashes were 4.4 microns and 28 microns, respectively. Hamsters treated with oil fly ash showed a higher frequency of bronchiolar-alveolar hyperplasia than hamsters in the other treatment groups. Squamous dysplasia and squamous metaplasia were most frequent in animals treated with suspensions of BaP or BaP-coated particles. The earliest appearance of a tumor, the highest incidence of tumors, and the highest incidence of malignant tumors were observed in hamsters treated with oil fly ash coated with BaP. Squamous cell carcinoma and adenosquamous carcinoma were the most frequent malignant tumors. No malignant tumors and only few benign tumors were observed in hamsters instilled with suspensions of fly ash not coated with BaP. The present study gives no indication that coal fly ash could create more serious health problems than oil fly ash.

  5. Fumonisin b1 carcinogenicity in a two-year feeding study using F344 rats and B6C3F1 mice.

    PubMed Central

    Howard, P C; Eppley, R M; Stack, M E; Warbritton, A; Voss, K A; Lorentzen, R J; Kovach, R M; Bucci, T J

    2001-01-01

    Fumonisin B1 (FB1) is a mycotoxin isolated from Fusarium fungi that contaminate crops worldwide. A previous study demonstrated that FB1 promoted preneoplastic foci in initiated rats and induced hepatocellular carcinomas in BD IX rats at 50 parts per million (ppm), but fundamental dose-response data were not available to assist in setting regulatory guidelines for this mycotoxin. To provide this information, female and male F344/N/Nctr BR rats and B6C3F1 Nctr BR mice were fed for two years a powdered NIH-31 diet containing the following concentrations of FB1: female rats, 0, 5, 15, 50, and 100 ppm; male rats, 0, 5, 15, 50, and 150 ppm; female mice, 0, 5, 15, 50, and 80 ppm; male mice, 0, 5, 15, 80, and 150 ppm. FB1 was not tumorigenic in female F344 rats with doses as high as 100 ppm. Including FB1 in the diets of male rats induced renal tubule adenomas and carcinomas in 0/48, 0/40, 9/48, and 15/48 rats at 0, 5, 15, 50, and 150 ppm, respectively. Including up to 150 ppm FB1 in the diet of male mice did not affect tumor incidence. Hepatocellular adenomas and carcinomas were induced by FB1 in the female mice, occurring in 5/47, 3/48, 1/48, 19/47, and 39/45 female mice that consumed diets containing 0, 5, 15, 50, and 80 ppm FB1, respectively. This study demonstrates that FB1 is a rodent carcinogen that induces renal tubule tumors in male F344 rats and hepatic tumors in female B6C3F1 mice. PMID:11359696

  6. Comparative study of comprehensive gas chromatography-nitrogen chemiluminescence detection and gas chromatography-ion trap-tandem mass spectrometry for determining nicotine and carcinogen organic nitrogen compounds in thirdhand tobacco smoke.

    PubMed

    Ramírez, Noelia; Vallecillos, Laura; Lewis, Alastair C; Borrull, Francesc; Marcé, Rosa M; Hamilton, Jacqueline F

    2015-12-24

    Thirdhand tobacco smoke (THS) constitutes a poorly understood pathway of exposure of non-smokers, especially toddlers, to tobacco-related carcinogens. However, to date most of the carcinogens present in tobacco smoke have not been detected in THS and, therefore, the significance of THS health risk is still unknown. In this study, we have compared the performance of two analytical methods - one based on gas chromatography coupled to ion trap mass spectrometry detection (GC-IT-MS) and the other on comprehensive two-dimensional gas chromatography coupled to a nitrogen chemiluminescence detector (GC×GC-NCD) - for simultaneously determining, in settled house dust, the presence of 16 organic nitrogen carcinogens already detected in tobacco smoke. The target compounds included four aromatic amines, two nitrocompounds, eight N-nitrosamines and two tobacco-specific nitrosamines, as well as nicotine as a tobacco marker. Dust samples were extracted using in-cell clean up pressurized liquid extraction with silica as clean up sorbent and ethyl acetate as the organic solvent, with average recovery of 89%. Although GC-IT-MS, using chemical ionization with methanol and tandem MS, performed well, the optimized GC×GC-NCD gave lower limits of detection (from 4 to 22ngg(-1)) and better repeatability and reproducibility a low concentration levels (%RSD<8%) and, therefore, was applicable for determining these different groups of carcinogens without the need for derivatization prior to the GC analysis. The performance of the optimized PLE/GC×GC-NCD method was tested by quantifying the target compounds in house dust samples from smokers' and non-smokers' homes. The median carcinogen compounds detected was 3.8μgg(-1) and 1.1μgg(-1) in smokers' and non-smokers' house dust, respectively. In this study, we have detected highly carcinogenic aromatic amines and nitro compounds for the first time in settled house dust complementing the state of knowledge of THS composition and providing

  7. Comparative study of comprehensive gas chromatography-nitrogen chemiluminescence detection and gas chromatography-ion trap-tandem mass spectrometry for determining nicotine and carcinogen organic nitrogen compounds in thirdhand tobacco smoke.

    PubMed

    Ramírez, Noelia; Vallecillos, Laura; Lewis, Alastair C; Borrull, Francesc; Marcé, Rosa M; Hamilton, Jacqueline F

    2015-12-24

    Thirdhand tobacco smoke (THS) constitutes a poorly understood pathway of exposure of non-smokers, especially toddlers, to tobacco-related carcinogens. However, to date most of the carcinogens present in tobacco smoke have not been detected in THS and, therefore, the significance of THS health risk is still unknown. In this study, we have compared the performance of two analytical methods - one based on gas chromatography coupled to ion trap mass spectrometry detection (GC-IT-MS) and the other on comprehensive two-dimensional gas chromatography coupled to a nitrogen chemiluminescence detector (GC×GC-NCD) - for simultaneously determining, in settled house dust, the presence of 16 organic nitrogen carcinogens already detected in tobacco smoke. The target compounds included four aromatic amines, two nitrocompounds, eight N-nitrosamines and two tobacco-specific nitrosamines, as well as nicotine as a tobacco marker. Dust samples were extracted using in-cell clean up pressurized liquid extraction with silica as clean up sorbent and ethyl acetate as the organic solvent, with average recovery of 89%. Although GC-IT-MS, using chemical ionization with methanol and tandem MS, performed well, the optimized GC×GC-NCD gave lower limits of detection (from 4 to 22ngg(-1)) and better repeatability and reproducibility a low concentration levels (%RSD<8%) and, therefore, was applicable for determining these different groups of carcinogens without the need for derivatization prior to the GC analysis. The performance of the optimized PLE/GC×GC-NCD method was tested by quantifying the target compounds in house dust samples from smokers' and non-smokers' homes. The median carcinogen compounds detected was 3.8μgg(-1) and 1.1μgg(-1) in smokers' and non-smokers' house dust, respectively. In this study, we have detected highly carcinogenic aromatic amines and nitro compounds for the first time in settled house dust complementing the state of knowledge of THS composition and providing

  8. Potential carcinogenic effects of cigarette smoke and Swedish moist snuff on pancreas: a study using a transgenic mouse model of chronic pancreatitis.

    PubMed

    Song, Zhigang; Bhagat, Govind; Quante, Michael; Baik, Gwang Ho; Marrache, Frederic; Tu, Shui Ping; Zhao, Chun-Mei; Chen, Duan; Dannenberg, Andrew J; Wang, Timothy C

    2010-03-01

    The risk of pancreatic cancer is increased in both Snus (the Swedish variant of oral smokeless tobacco) users and, to a greater extent, in cigarette smokers. Concurrent chronic pancreatitis further increases the risk in cigarette smokers. Little is known about the mechanism by which cigarette smoke or Snus increase the risk of pancreatic cancer in individuals with chronic pancreatitis. This study examined the carcinogenic effects of an aqueous extract of cigarette smoke (tobacco smoke, TS) or Snus in an Elastase-IL-1beta transgenic mouse model of chronic pancreatitis. Both transgenic and wild-type (WT) mice were fed diluted TS water or Snus-containing diet for up to 15 months, and monitored for phenotypic and molecular changes in the pancreas. Both TS- and Snus-treated Elastase-IL-1beta mice, but not WT mice, developed significant pancreatic ductal epithelial flattening and severe glandular atrophy compared with untreated transgenic mice. Ductal epithelial cells displayed a high proliferative index, minimal apoptosis, and induction of COX-2 in the setting of chronic inflammation. Up-regulation of TNF-alpha correlated with the onset of severe glandular atrophy. In comparison with Snus-treated mice, TS-Elastase-IL-1beta mice had an earlier onset and a greater extent of phenotypic changes, which were associated with up-regulation of TNF-alpha and increased expression of IL-6, TGF-beta, and SDF-1. Collectively, these findings provide new insights into the mechanism by which tobacco products are likely to promote carcinogenesis in the setting of chronic pancreatitis.

  9. Microspectrofluorometry of carcinogens in living cells.

    PubMed

    Kohen, E; Kohen, C; Hirschberg, J G

    1983-01-01

    A microspectrofluorometric approach has been used to follow the changes undergone by the carcinogen benzo(a)pyrene in malignant L cells, inducible Buffalo rat liver (BRL) cells and oncogenic mouse embryo C3H/10 T 1/2, clone 8 (CCL 226) cells. Since it is known that benzo(a)pyrene (BP) is converted metabolically to at least 40 metabolites, including phenols, epoxides, quinones, dihydrodiols, diol epoxides, and water-soluble conjugates, the interpretation of blue- and red-spectral shifts in fluorescence emission observed in BP-treated cells, compared to the original BP emission, undoubtedly presents considerable difficulties, but a certain number of facts clearly emerge. The sequence of blue-red shifts expressive of intracellular interactions and detoxification of the carcinogen is accelerated in the induced BRL compared to non-induced, and it is also generally accelerated in the malignant and inducible lines compared to the oncogenic line. The detection of highly reactive molecules (? of ultimate carcinogens) representing a small fraction of bulk fluorescence, still remains elusive, but two promising approaches are described: the use of phase-specific fluorescence quenchers which enable us to probe for the presence of metabolites in aqueous, hydrophobic or membrane phases of the cell, and the matrix analysis based on plotting of excitation-emission at different wavelengths for resolution of complex spectra. The former approach has enabled some separation or enhancement of red-blue emissions, and the second has helped to differentiate between emission of BP per se and its intracellular conversion products. Finally, observations at nuclear and cytoplasmic sites open the possibility of studying carcinogen interactions at different target sites.

  10. Selection of an in vitro carcinogenicity test for derivatives of the carcinogen hexamethylphosphoramide.

    PubMed Central

    Ashby, J.; Styles, J. A.; Anderson, D.

    1977-01-01

    The demonstration that hexamethylphosphoramide (HMPA) possesses potent carcinogenic properties has raised doubts about the safety of exposure to other phosphoric amides. In order to define a suitable short-term test with which to evaluate such analogues, the response of the Salmonella typhimurium mutation assay of Ames and cell transformation assay of Styles to HMPA and 3 selected analogues has been studied. These analogues were the related leukaemogen phosphoramide, the putative non-carcinogen, phosphoric trianilide and N.N'N''-trimethylphosphorothioic triamide, a compound of unknown and hitherto unpredictable properties. While both tests found the trianilide negative, the Ames test failed to detect phosphoramide as positive and gave an erratic and predominantly negative response to HMPA. In contrast, the transformation assay found both phosphoramide and HMPA positive. This test response profile indicates that the transformation assay is the preferred test with which to evaluate analogues of HMPA for potential carcinogenicity. Some structural requirements for potential carcinogenicity within this class of compounds are tentatively deduced. PMID:337998

  11. The Regulation of Carcinogenic Hazards.

    ERIC Educational Resources Information Center

    Gori, Gio Batta

    1980-01-01

    It is suggested that a system of relative standards be formulated which would compare utility of substances to their relative risk as carcinogens. This would define a range of use restrictions. Substances intended for specific uses would then be regulated according to these standards. (Author/RE)

  12. Differences in the Rate of in Situ Mammary Gland Development and Other Developmental Endpoints in Three Strains of Female Rat Commonly Used in Mammary Carcinogenesis Studies: Implications for Timing of Carcinogen Exposure.

    PubMed

    Stanko, Jason P; Kissling, Grace E; Chappell, Vesna A; Fenton, Suzanne E

    2016-10-01

    The potential of chemicals to alter susceptibility to mammary tumor formation is often assessed using a carcinogen-induced study design in various rat strains. The rate of mammary gland (MG) development must be considered so that the timing of carcinogen administration is impactful. In this study, in situ MG development was assessed in females of the Harlan Sprague-Dawley (Hsd:SD), Charles River Sprague-Dawley (Crl:SD), and Charles River Long-Evans (Crl:LE) rat strains at postnatal days 25, 33, and 45. Development was evaluated by physical assessment of growth parameters, developmental scoring, and quantitative morphometric analysis. Although body weight (BW) was consistently lower and day of vaginal opening (VO) occurred latest in female Hsd:SD rats, they exhibited accelerated pre- and peripubertal MG development compared to other strains. Glands of Crl:SD and Crl:LE rats exhibited significantly more terminal end buds (TEBs) and TEB/mm than Hsd:SD rats around the time of VO. These data suggest a considerable difference in the rate of MG development across commonly used strains, which is independent of BW and timing of VO. In mammary tumor induction studies employing these strains, administration of the carcinogen should be timed appropriately, based on strain, to specifically target the peak of TEB occurrence. PMID:27613105

  13. Foetal exposure to food and environmental carcinogens in human beings.

    PubMed

    Myöhänen, Kirsi; Vähäkangas, Kirsi

    2012-02-01

    Exposure to many different chemicals during pregnancy through maternal circulation is possible. Transplacental transfer of xenobiotics can be demonstrated using human placental perfusion. Also, placental perfusion can give information about the placental kinetics as well as metabolism and accumulation in the placenta because it retains the tissue structure and function. Although human placental perfusion has been used extensively to study the transplacental transfer of drugs, the information on food and environmental carcinogens is much more limited. This review deals with the foetal exposure to food and environmental carcinogens in human beings. In particular, human transplacental transfer of the food carcinogens such as acrylamide, glycidamide and nitrosodimethylamine are in focus. Because these carcinogens are genotoxic, the functional capacity of human placenta to induce DNA adduct formation or metabolize these above mentioned CYP2E1 substrates is of interest in this context.

  14. Predictors (0-10 Months) of Psychopathology at Age 1 1/2 Years--A General Population Study in the Copenhagen Child Cohort CCC 2000

    ERIC Educational Resources Information Center

    Skovgaard, A. M.; Olsen, E. M.; Christiansen, E.; Houmann, T.; Landorph, S. L.; Jorgensen, T.

    2008-01-01

    Background: Epidemiological studies of mental health problems in the first years of life are few. This study aims to investigate infancy predictors of psychopathology in the second year of life. Methods: A random general population sample of 210 children from the Copenhagen Child Birth Cohort CCC 2000 was investigated by data from National Danish…

  15. Trichloroethylene: Mechanistic, epidemiologic and other supporting evidence of carcinogenic hazard.

    PubMed

    Rusyn, Ivan; Chiu, Weihsueh A; Lash, Lawrence H; Kromhout, Hans; Hansen, Johnni; Guyton, Kathryn Z

    2014-01-01

    The chlorinated solvent trichloroethylene (TCE) is a ubiquitous environmental pollutant. The carcinogenic hazard of TCE was the subject of a 2012 evaluation by a Working Group of the International Agency for Research on Cancer (IARC). Information on exposures, relevant data from epidemiologic studies, bioassays in experimental animals, and toxicity and mechanism of action studies was used to conclude that TCE is carcinogenic to humans (Group 1). This article summarizes the key evidence forming the scientific bases for the IARC classification. Exposure to TCE from environmental sources (including hazardous waste sites and contaminated water) is common throughout the world. While workplace use of TCE has been declining, occupational exposures remain of concern, especially in developing countries. The strongest human evidence is from studies of occupational TCE exposure and kidney cancer. Positive, although less consistent, associations were reported for liver cancer and non-Hodgkin lymphoma. TCE is carcinogenic at multiple sites in multiple species and strains of experimental animals. The mechanistic evidence includes extensive data on the toxicokinetics and genotoxicity of TCE and its metabolites. Together, available evidence provided a cohesive database supporting the human cancer hazard of TCE, particularly in the kidney. For other target sites of carcinogenicity, mechanistic and other data were found to be more limited. Important sources of susceptibility to TCE toxicity and carcinogenicity were also reviewed by the Working Group. In all, consideration of the multiple evidence streams presented herein informed the IARC conclusions regarding the carcinogenicity of TCE.

  16. Trichloroethylene: Mechanistic, Epidemiologic and Other Supporting Evidence of Carcinogenic Hazard

    PubMed Central

    Rusyn, Ivan; Chiu, Weihsueh A.; Lash, Lawrence H.; Kromhout, Hans; Hansen, Johnni; Guyton, Kathryn Z.

    2013-01-01

    The chlorinated solvent trichloroethylene (TCE) is a ubiquitous environmental pollutant. The carcinogenic hazard of TCE was the subject of a 2012 evaluation by a Working Group of the International Agency for Research on Cancer (IARC). Information on exposures, relevant data from epidemiologic studies, bioassays in experimental animals, and toxicity and mechanism of action studies was used to conclude that TCE is carcinogenic to humans (Group 1). This article summarizes the key evidence forming the scientific bases for the IARC classification. Exposure to TCE from environmental sources (including from hazardous waste sites and contaminated water) is common throughout the world. While workplace use of TCE has been declining, occupational exposures remain of concern, especially in developing countries. Strongest human evidence is from studies of occupational TCE exposure and kidney cancer. Positive, although less consistent, associations were reported for liver cancer and non-Hodgkin's lymphoma. TCE is carcinogenic at multiple sites in multiple species and strains of experimental animals. The mechanistic evidence includes extensive data on the toxicokinetics and genotoxicity of TCE and its metabolites. Together, available evidence provided a cohesive database supporting the human cancer hazard of TCE, particularly in the kidney. For other target sites of carcinogenicity, mechanistic and other data were found to be more limited. Important sources of susceptibility to TCE toxicity and carcinogenicity were also reviewed by the Working Group. In all, consideration of the multiple evidence streams presented herein informed the IARC conclusions regarding the carcinogenicity of TCE. PMID:23973663

  17. Carcinogenic potential of gasoline and diesel engine oils.

    PubMed

    McKee, R H; Plutnick, R T

    1989-10-01

    Used gasoline engine oils are carcinogenic in mouse skin and mutagenic in Salmonella. The toxicity of fresh gasoline engine oils and that of fresh and used diesel engine oils are less well defined. The present studies examined the dermal carcinogenic potential of a series of fresh and used oils from both gasoline and diesel engines. The used oils represented a variety of operating conditions. The objective of the study was to assess the potential carcinogenic hazards associated with exposure to these materials. The majority of the used gasoline engine oils tested were carcinogenic although one oil, collected after a relatively short drainage interval, was inactive in the dermal carcinogenesis bioassay. Additionally, polycyclic aromatic hydrocarbon (PAH) concentrations were elevated in the used oils in comparison to the fresh oils. The fresh gasoline engine oils and both the fresh and used diesel engine oil samples were noncarcinogenic, and there was little evidence of elevated PAH levels in the used diesel engine oils. The carcinogenic potency of used oils from gasoline engines was related to drainage interval, but other factors such as contribution of the fuel due to blowby and driving cycle may also have been important. The used diesel engine oils were not carcinogenic even after extended use.

  18. Working Memory Arrest in Children with High-Functioning Autism Compared to Children with Attention-Deficit/Hyperactivity Disorder: Results from a 2-Year Longitudinal Study

    ERIC Educational Resources Information Center

    Andersen, Per N.; Skogli, Erik W.; Hovik, Kjell T.; Geurts, Hilde; Egeland, Jens; Øie, Merete

    2015-01-01

    The aim of this study was to analyse the development of verbal working memory in children with high-functioning autism compared to children with attention-deficit/hyperactivity disorder and typically developing children. A total of 34 children with high-functioning autism, 72 children with attention-deficit/hyperactivity disorder and 45 typically…

  19. Etiological Role and Repeated Infections of Sapovirus among Children Aged Less than 2 Years in a Cohort Study in a Peri-urban Community of Peru.

    PubMed

    Liu, Xiaofang; Jahuira, Helena; Gilman, Robert H; Alva, Alicia; Cabrera, Lilia; Okamoto, Michiko; Xu, Hang; Windle, Henry J; Kelleher, Dermot; Varela, Marco; Verastegui, Manuela; Calderon, Maritza; Sanchez, Gerardo; Sarabia, Vanessa; Ballard, Sarah B; Bern, Caryn; Mayta, Holger; Crabtree, Jean E; Cama, Vitaliano; Saito, Mayuko; Oshitani, Hitoshi

    2016-06-01

    Human sapovirus has been shown to be one of the most important etiologies in pediatric patients with acute diarrhea. However, very limited data are available about the causative roles and epidemiology of sapovirus in community settings. A nested matched case-control study within a birth cohort study of acute diarrhea in a peri-urban community in Peru from 2007 to 2010 was conducted to investigate the attributable fraction (AF) and genetic diversity of sapovirus. By quantitative reverse transcription-real-time PCR (qPCR) sapovirus was detected in 12.4% (37/299) of diarrheal and 5.7% (17/300) of nondiarrheal stools (P = 0.004). The sapovirus AF (7.1%) was higher in the second year (13.2%) than in the first year (1.4%) of life of children. Ten known genotypes and one novel cluster (n = 5) within four genogroups (GI, GII, GIV, and GV) were identified by phylogenetic analysis of a partial VP1 gene. Further sequence analysis of the full VP1 gene revealed a possible novel genotype, tentatively named GII.8. Notably, symptomatic reinfections with different genotypes within the same (n = 3) or different (n = 5) genogroups were observed in eight children. Sapovirus exhibited a high attributable burden for acute gastroenteritis, especially in the second year of life, of children in a Peruvian community. Further large-scale studies are needed to understand better the global burden, genetic diversity, and repeated infections of sapovirus.

  20. Etiological Role and Repeated Infections of Sapovirus among Children Aged Less than 2 Years in a Cohort Study in a Peri-urban Community of Peru.

    PubMed

    Liu, Xiaofang; Jahuira, Helena; Gilman, Robert H; Alva, Alicia; Cabrera, Lilia; Okamoto, Michiko; Xu, Hang; Windle, Henry J; Kelleher, Dermot; Varela, Marco; Verastegui, Manuela; Calderon, Maritza; Sanchez, Gerardo; Sarabia, Vanessa; Ballard, Sarah B; Bern, Caryn; Mayta, Holger; Crabtree, Jean E; Cama, Vitaliano; Saito, Mayuko; Oshitani, Hitoshi

    2016-06-01

    Human sapovirus has been shown to be one of the most important etiologies in pediatric patients with acute diarrhea. However, very limited data are available about the causative roles and epidemiology of sapovirus in community settings. A nested matched case-control study within a birth cohort study of acute diarrhea in a peri-urban community in Peru from 2007 to 2010 was conducted to investigate the attributable fraction (AF) and genetic diversity of sapovirus. By quantitative reverse transcription-real-time PCR (qPCR) sapovirus was detected in 12.4% (37/299) of diarrheal and 5.7% (17/300) of nondiarrheal stools (P = 0.004). The sapovirus AF (7.1%) was higher in the second year (13.2%) than in the first year (1.4%) of life of children. Ten known genotypes and one novel cluster (n = 5) within four genogroups (GI, GII, GIV, and GV) were identified by phylogenetic analysis of a partial VP1 gene. Further sequence analysis of the full VP1 gene revealed a possible novel genotype, tentatively named GII.8. Notably, symptomatic reinfections with different genotypes within the same (n = 3) or different (n = 5) genogroups were observed in eight children. Sapovirus exhibited a high attributable burden for acute gastroenteritis, especially in the second year of life, of children in a Peruvian community. Further large-scale studies are needed to understand better the global burden, genetic diversity, and repeated infections of sapovirus. PMID:27076657

  1. [Growth of breastfed and bottle-fed infants up to 2 years of age: CLACYD (Lactation, Alimentation, Growth and Development) study 1993-1995].

    PubMed

    Agrelo, F; Lobo, B; Chesta, M; Berra, S; Sabulsky, J

    1999-07-01

    Studies done in various countries show important differences in the growth of breastfed and bottle-fed children. In addition, it has been found that breast-fed children grow more slowly beginning at the age of 2 or 3 months in comparison with the reference pattern of the U.S. National Center for Health Statistics (NCHS) and the World Health Organization (WHO). These results cast doubt on whether maximum growth is the same as optimal growth. The objective of this study was to compare the growth in weight and length, from birth to 24 months, for a group of children who were breast-fed with that of a group who were bottle-fed. The study was also intended to describe the growth of the breastfed group in relation to the NCHS/WHO norms and a WHO "12-month breast-fed pooled data set." For this research, data were analyzed from the "Cordoba: lactation, feeding, growth, and development" study (or CLACYD study, for its Spanish-language acronym). That study looked at a representative cohort, stratified by social class, of children born in 1993 in the city of Cordoba, Argentina. The researchers analyzed anthropometric data on 74 children who were breast-fed during the first year of life and on 108 bottle-fed children. The data had been recorded, using standardized techniques, at birth and at 6, 12, and 24 months of age. Both groups were homogenous with respect to the age and schooling of the parents, social stratum, birth order, maternal height, and child's weight and length at birth. The living conditions (housing construction and availability of water and sewer services) were better among the group that was bottle-fed (P = 0.04). The breast-fed children had a lower weight and a shorter length at 6, 12, and 24 months than did the bottle-fed children. The breast-fed children also showed a slowing in growth with respect to the NCHS/WHO guidelines beginning in the second semester. This indicates that the NCHS/WHO norms are not totally adequate for evaluating the growth of breast

  2. Efficacy and safety of finasteride therapy for benign prostatic hyperplasia: results of a 2-year randomized controlled trial (the PROSPECT study). PROscar Safety Plus Efficacy Canadian Two year Study.

    PubMed Central

    Nickel, J C; Fradet, Y; Boake, R C; Pommerville, P J; Perreault, J P; Afridi, S K; Elhilali, M M

    1996-01-01

    OBJECTIVE: To evaluate the efficacy and safety of 2 years' treatment of moderate benign prostatic hyperplasia (BPH) with finasteride. DESIGN: Double-blind, parallel-group, placebo-controlled, multicentre, prospective randomized study. SETTING: Outpatient care in 28 centres across Canada. PARTICIPANTS: Men aged 45 to 80, in good health, with moderate BPH and no evidence of prostate cancer. A total of 613 men were entered into the study; 472 completed the 2 years of treatment. INTERVENTION: After 1 month of receiving a placebo (run-in period), patients were given either finasteride (5 mg/d) or a placebo for 2 years. OUTCOME MEASURES: Efficacy: changes from baseline in BPH symptom scores, maximum urinary flow rates and prostate volume. Safety: onset, course and resolution of all adverse events during the treatment period. RESULTS: In the efficacy analyses the mean BPH symptom scores decreased 2.1 points (from 15.8 to 13.7) in the finasteride group, as compared with a decrease of 0.7 points (from 16.6 to 15.9) in the placebo group (P < or = 0.01). The maximum urinary flow rate increased by a mean of 1.4 mL/s (from 11.1 to 12.5 mL/s) in the finasteride group, as compared with an increase of 0.3 mL/s (from 10.9 to 11.2 mL/s) in the placebo group (p < or = 0.01). The mean prostate volume decreased by 21% (from a mean volume of 44.1 cm3 at baseline) in the treatment group; it increased by 8.4% (from a mean volume of 45.8 cm3 at baseline) in the placebo group (p < or = 0.01). In the safety analysis, the proportion of patients who experienced any adverse event was similar in the two groups (81.0% in the treatment group and 81.2% in the placebo group). However, the incidence of adverse events related to sexual dysfunction were significantly higher in the finasteride group than in the placebo group (ejaculation disorder 7.7% v. 1.7% and impotence 15.8% v. 6.3%; p < or = 0.01 for both parameters). CONCLUSION: Finasteride is a well-tolerated and effective alternative to watchful

  3. Predicting adolescent problematic online game use from teacher autonomy support, basic psychological needs satisfaction, and school engagement: a 2-year longitudinal study.

    PubMed

    Yu, Chengfu; Li, Xian; Zhang, Wei

    2015-04-01

    Problematic online game use (POGU) has become a serious global public health concern among adolescents. However, its influencing factors and mediating mechanisms remain largely unknown. This study provides the first longitudinal design to test stage-environment fit theory empirically in POGU. A total of 356 Chinese students reported on teacher autonomy support, basic psychological needs satisfaction, school engagement, and POGU in the autumn of their 7th-9th grade years. Path analyses supported the proposed pathway: 7th grade teacher autonomy support increased 8th grade basic psychological needs satisfaction, which in turn increased 9th grade school engagement, which ultimately decreased 9th grade POGU. Furthermore, 7th grade teacher autonomy support directly increased 9th grade school engagement, which in turn decreased 9th grade POGU. These findings suggest that teacher autonomy support is an important protective predictor of adolescent POGU, and basic psychological needs satisfaction and school engagement are the primary mediators in this association.

  4. The Role of Human Coronaviruses in Children Hospitalized for Acute Bronchiolitis, Acute Gastroenteritis, and Febrile Seizures: A 2-Year Prospective Study

    PubMed Central

    Jevšnik, Monika; Steyer, Andrej; Pokorn, Marko; Mrvič, Tatjana; Grosek, Štefan; Strle, Franc; Lusa, Lara; Petrovec, Miroslav

    2016-01-01

    Human coronaviruses (HCoVs) are associated with a variety of clinical presentations in children, but their role in disease remains uncertain. The objective of our prospective study was to investigate HCoVs associations with various clinical presentations in hospitalized children up to 6 years of age. Children hospitalized with acute bronchiolitis (AB), acute gastroenteritis (AGE), or febrile seizures (FS), and children admitted for elective surgical procedures (healthy controls) were included in the study. In patients with AB, AGE, and FS, a nasopharyngeal (NP) swab and blood sample were obtained upon admission and the follow-up visit 14 days later, whereas in children with AGE a stool sample was also acquired upon admission; in healthy controls a NP swab and stool sample were taken upon admission. Amplification of polymerase 1b gene was used to detect HCoVs in the specimens. HCoVs-positive specimens were also examined for the presence of several other viruses. HCoVs were most often detected in children with FS (19/192, 9.9%, 95% CI: 6–15%), followed by children with AGE (19/218, 8.7%, 95% CI: 5.3–13.3%) and AB (20/308, 6.5%, 95% CI: 4.0–9.8%). The presence of other viruses was a common finding, most frequent in the group of children with AB (19/20, 95%, 95% CI: 75.1–99.8%), followed by FS (10/19, 52.6%, 95% CI: 28.9–75.6%) and AGE (7/19, 36.8%, 95% CI: 16.3–61.6%). In healthy control children HCoVs were detected in 3/156 (1.9%, 95% CI: 0.4–5.5%) NP swabs and 1/150 (0.7%, 95% CI: 0.02–3.3%) stool samples. It seems that an etiological role of HCoVs is most likely in children with FS, considering that they had a higher proportion of positive HCoVs results than patients with AB and those with AGE, and had the highest viral load; however, the co-detection of other viruses was 52.6%. Trial Registration: ClinicalTrials.gov NCT00987519 PMID:27171141

  5. Decreased use of glucocorticoids in biological-experienced patients with rheumatoid arthritis who initiated intravenous abatacept: results from the 2-year ACTION study

    PubMed Central

    Alten, Rieke; Nüßlein, Hubert; Galeazzi, Mauro; Lorenz, Hanns-Martin; Nurmohamed, Michael T; Bensen, William G; Burmester, Gerd R; Peter, Hans-Hartmut; Pavelka, Karel; Chartier, Mélanie; Poncet, Coralie; Rauch, Christiane; Elbez, Yedid; Le Bars, Manuela

    2016-01-01

    Introduction Prolonged glucocorticoid use may increase the risk of adverse safety outcomes, including cardiovascular events. The European League Against Rheumatism and the Canadian Rheumatology Association advise tapering glucocorticoid dose as rapidly as clinically feasible. There is a paucity of published data on RA that adequately describe concomitant treatment patterns. Methods ACTION (AbataCepT In rOutiNe clinical practice) is a non-interventional cohort study of patients from Europe and Canada that investigated the long-term retention of intravenous abatacept in clinical practice. We assessed concomitant glucocorticoids in patients with established RA who had participated in ACTION and received ≥1 biological agent prior to abatacept initiation. Results The analysis included 1009 patients. Glucocorticoids were prescribed at abatacept initiation in 734 (72.7%) patients at a median 7.5 mg/day dose (n=692). Of the patients who remained on abatacept at 24 months, 40.7% were able to decrease their dose of glucocorticoids, including 26.9% who decreased their dose from >5 mg/day to ≤5 mg/day. Conclusion Reduction and/or cessation of glucocorticoid therapy is possible with intravenous abatacept in clinical practice. PMID:26925253

  6. Risedronate prevents persistent bone loss in prostate cancer patients treated with androgen deprivation therapy: results of a 2-year follow-up study.

    PubMed

    Izumi, K; Mizokami, A; Sugimoto, K; Narimoto, K; Kitagawa, Y; Koh, E; Namiki, M

    2011-09-01

    Androgen deprivation therapy (ADT) for prostate cancer (PCa) causes bone loss. Although we reported previously that risedronate significantly recovers bone mineral density (BMD) for up to 12 months, there have been no reports with longer follow-up periods to date. This study extended our earlier series extending the follow-up period to 24 months. Eligible patients had histologically confirmed PCa without lumbar spine metastasis and underwent ADT. Lumbar spine BMD, urinary deoxypyridinoline (uDPD) and serum bone alkaline phosphatase were measured at 6, 12 and 24 months. Among the total of 96 patients, we analyzed 26 and 18 patients in risedronate administration and control groups, respectively. BMD relative to the young adult mean ratio, uDPD and serum bone alkaline phosphatase of the risedronate administration group recovered significantly after 24 months compared with the control group (P<0.0001, P=0.0001, and P<0.0001, respectively). Transient blurred vision, malaise and vertigo were observed in 1 patient each among the 46 patients treated with risedronate within 28 days after first administration. Oral administration of risedronate is safe and effective for the recovery of ADT-induced bone loss in PCa patients even at 24 months after commencement of treatment.

  7. New clues on carcinogenicity-related substructures derived from mining two large datasets of chemical compounds.

    PubMed

    Golbamaki, Azadi; Benfenati, Emilio; Golbamaki, Nazanin; Manganaro, Alberto; Merdivan, Erinc; Roncaglioni, Alessandra; Gini, Giuseppina

    2016-04-01

    In this study, new molecular fragments associated with genotoxic and nongenotoxic carcinogens are introduced to estimate the carcinogenic potential of compounds. Two rule-based carcinogenesis models were developed with the aid of SARpy: model R (from rodents' experimental data) and model E (from human carcinogenicity data). Structural alert extraction method of SARpy uses a completely automated and unbiased manner with statistical significance. The carcinogenicity models developed in this study are collections of carcinogenic potential fragments that were extracted from two carcinogenicity databases: the ANTARES carcinogenicity dataset with information from bioassay on rats and the combination of ISSCAN and CGX datasets, which take into accounts human-based assessment. The performance of these two models was evaluated in terms of cross-validation and external validation using a 258 compound case study dataset. Combining R and H predictions and scoring a positive or negative result when both models are concordant on a prediction, increased accuracy to 72% and specificity to 79% on the external test set. The carcinogenic fragments present in the two models were compared and analyzed from the point of view of chemical class. The results of this study show that the developed rule sets will be a useful tool to identify some new structural alerts of carcinogenicity and provide effective information on the molecular structures of carcinogenic chemicals.

  8. Clinical instructors' perception of a faculty development programme promoting postgraduate year-1 (PGY1) residents' ACGME six core competencies: a 2-year study.

    PubMed

    Lee, Fa-Yauh; Yang, Ying-Ying; Hsu, Hui-Chi; Chuang, Chiao-Lin; Lee, Wei-Shin; Chang, Ching-Chih; Huang, Chia-Chang; Chen, Jaw-Wen; Cheng, Hao-Min; Jap, Tjin-Shing

    2011-01-01

    Objective The six core competencies designated by Accreditation Council for Graduate Medical Education (ACGME) are essential for establishing a patient centre holistic medical system. The authors developed a faculty programme to promote the postgraduate year 1 (PGY(1)) resident, ACGME six core competencies. The study aims to assess the clinical instructors' perception, attitudes and subjective impression towards the various sessions of the 'faculty development programme for teaching ACGME competencies.' Methods During 2009 and 2010, 134 clinical instructors participated in the programme to establish their ability to teach and assess PGY(1) residents about ACGME competencies. Results The participants in the faculty development programme reported that the skills most often used while teaching were learnt during circuit and itinerant bedside, physical examination teaching, mini-clinical evaluation exercise (mini-CEX) evaluation demonstration, training workshop and videotapes of 'how to teach ACGME competencies.' Participants reported that circuit bedside teaching and mini-CEX evaluation demonstrations helped them in the interpersonal and communication skills domain, and that the itinerant teaching demonstrations helped them in the professionalism domain, while physical examination teaching and mini-CEX evaluation demonstrations helped them in the patients' care domain. Both the training workshop and videotape session increase familiarity with teaching and assessing skills. Participants who applied the skills learnt from the faculty development programme the most in their teaching and assessment came from internal medicine departments, were young attending physician and had experience as PGY(1) clinical instructors. Conclusions According to the clinical instructors' response, our faculty development programme effectively increased their familiarity with various teaching and assessment skills needed to teach PGY(1) residents and ACGME competencies, and these clinical

  9. Vagus nerve stimulation therapy: 2-year prospective open-label study of 40 subjects with refractory epilepsy and low IQ who are living in long-term care facilities.

    PubMed

    Huf, Roger L; Mamelak, Adam; Kneedy-Cayem, Kara

    2005-05-01

    Treating seizures among patients with mental retardation/developmental disabilities (MR/DD) is difficult owing in large part to the presence of additional comorbidities and the resulting need for polytherapy. Therefore, a nonpharmacological treatment option is needed for this population. This prospective, open-label study documented the long-term outcome of 40 low-IQ (<70) patients living in long-term care facilities who received vagus nerve stimulation (VNS) therapy for pharmacoresistant epilepsy. Subjects were seen every 1 to 3 months by their neurologist (R.H.). Seizure frequency, antiepileptic medication, and quality-of-life information were documented preimplantation and quarterly thereafter through 2 years. The surgery and therapy were well tolerated. Seizures were reduced by at least 50% for 11 subjects. Antiepileptic medications were reduced from 3.3 per subject at baseline to an average of 2.3 per subject after 2 years. According to caregiver reports, overall quality of life improved for the majority of subjects; also, using the Client Development Evaluation Report (CDER), statistically significant improvements were reported at both 1 and 2 years in attention span, word usage, clarity of speech, standing balance, washing dishes, and household chores. VNS is a viable treatment option for low-IQ patients with pharmacoresistant epilepsy who are living in long-term care facilities. PMID:15820352

  10. Comparison of 2-year clinical outcomes between diabetic versus nondiabetic patients with acute myocardial infarction after 1-month stabilization: Analysis of the prospective registry of DIAMOND (DIabetic acute myocardial infarctiON Disease) in Korea: an observational registry study.

    PubMed

    Hur, Seung-Ho; Won, Ki-Bum; Kim, In-Cheol; Bae, Jang-Ho; Choi, Dong-Ju; Ahn, Young-Keun; Park, Jong-Seon; Kim, Hyo-Soo; Choi, Rak-Kyeong; Choi, Donghoon; Kim, Joon-Hong; Han, Kyoo-Rok; Park, Hun-Sik; Choi, So-Yeon; Yoon, Jung-Han; Gwon, Hyeon-Cheol; Rha, Seung-Woon; Jang, Wooyeong; Bae, Jang-Whan; Hwang, Kyung-Kuk; Lim, Do-Sun; Jung, Kyung-Tae; Oh, Seok-Kyu; Lee, Jae-Hwan; Shin, Eun-Seok; Kim, Kee-Sik

    2016-06-01

    This study assessed the 2-year clinical outcomes of patients with diabetes mellitus (DM) after acute myocardial infarction (AMI) in a cohort of the DIAMOND (DIabetic Acute Myocardial infarctiON Disease) registry. Clinical outcomes were compared between 1088 diabetic AMI patients in the DIAMOND registry after stabilization of MI and 1088 nondiabetic AMI patients from the KORMI (Korean AMI) registry after 1 : 1 propensity score matching using traditional cardiovascular risk factors. Stabilized patients were defined as patients who did not have any clinical events within 1 month after AMI. Primary outcomes were the 2-year rate of major adverse cardiac events (MACEs), a composite of all-cause death, recurrent MI (re-MI), and target vessel revascularization (TVR). Matched comparisons revealed that diabetic patients exhibited significantly lower left ventricular ejection fraction (LVEF) and estimated glomerular filtration rate and smaller stent size. Diabetic patients exhibited significantly higher 2-year rates of MACE (8.0% vs 3.7%), all-cause death (3.9% vs 1.4%), re-MI (2.8% vs 1.2%), and TVR (3.5% vs 1.3%) than nondiabetic patients (all P < 0.01), and higher cumulative rates in Kaplan-Meier analyses of MACE, all-cause death, and TVR (all P < 0.05). A multivariate Cox regression analysis revealed that chronic kidney disease, LVEF < 35%, and long stent were independent predictors of MACE, and large stent diameter and the use of drug-eluting stents were protective factors against MACE. The 2-year MACE rate beyond 1 month after AMI was significantly higher in DM patients than non-DM patients, and this rate was associated with higher comorbidities, coronary lesions, and procedural characteristics in DM.

  11. Re-evaluation of kidney histopathology from 13-week toxicity and two-year carcinogenicity studies of melamine in the F344 rat: morphologic evidence of retrograde nephropathy.

    PubMed

    Hard, G C; Flake, G P; Sills, R C

    2009-11-01

    The histopathologic changes induced in F344 rat kidney by oral administration of melamine for 13-week and 2-year periods in studies conducted by the National Toxicology Program, NIH,(25) from 1976 to 1983 have been re-evaluated and described in detail. A constellation of tubule changes extending from papilla to cortex consistently included tubule dilatation and tubule basophilia as salient features at the subchronic time point. By 2 years, these lesions had usually resolved into fibrotic scars, in which tubule loss and collagen deposition were prominent, running from superficial cortex into the medulla. These fibrotic lesions required discrimination from chronic scars resulting from infarcts and foci of chronic progressive nephropathy (CPN). A case is presented here for interpreting the constellation of histologic changes induced in rats by melamine as representing an ascending form of nephropathy. The term retrograde nephropathy is considered to be the appropriate nomenclature for both the acute and chronic lesions. The cause for the reflux, emanating from the lower urinary tract, appeared not to be infection as an inflammatory response was not prominent. It can be speculated that melamine precipitation in the lower urinary tract created pressure effects through transient obstruction leading to the renal changes. These changes were different from those involved in a major US outbreak of renal disease and death in cats and dogs associated with triazine-contaminated pet food, in which crystalluria from insoluble melamine/cyanuric acid complexes occurred in the kidney. However, the rat findings may be relevant to melamine-associated kidney disease recently reported in infants in China.

  12. Carcinogenicity of 1,3-butadiene.

    PubMed Central

    Melnick, R L; Shackelford, C C; Huff, J

    1993-01-01

    1,3-Butadiene, a high-production volume chemical used largely in the manufacture of synthetic rubber, is a multiple organ carcinogen in rats and mice. In inhalation studies conducted in mice by the National Toxicology Program, high rates of early lethal lymphomas occurring at exposure levels of 625 ppm or higher reduced the development and expression of later developing tumors at other sites. Use of survival-adjusted tumor rates to account for competing risk factors provided a clearer indication of the dose responses for 1,3-butadiene-induced neoplasms. An increase in lung tumors in female mice was observed at exposure concentrations as low as 6.25 ppm, the lowest concentration ever used in a long-term carcinogenicity study of this gas. Human exposures to 1,3-butadiene by workers employed at facilities that produce this chemical and at facilities that produce styrene-butadiene rubber have been measured at levels higher than those that cause cancer in animals. Furthermore, epidemiology studies have consistently revealed associations between occupational exposure to 1,3-butadiene and excess mortality due to lymphatic and hematopoietic cancers. In response to the carcinogenicity findings for 1,3-butadiene in animals and in humans, the Occupational Safety and Health Administration has proposed lowering the occupational exposure standard for this chemical from 1000 ppm to 2 ppm. Future work is needed to understand the mechanisms of tumor induction by 1,3-butadiene; however, the pursuit of this research should not delay the reduction of human exposure to this chemical. PMID:8354171

  13. Carcinogenic potential of phthalic acid esters and related compounds: structure-activity relationships.

    PubMed Central

    Kluwe, W M

    1986-01-01

    Chronic toxicity and carcinogenicity studies of several phthalic acid esters (PAEs) and compounds containing a 2-ethylhexyl moiety were conducted in Fischer 344 rats and B6C3F1 (hybrid) mice. The compounds studied were phthalic anhydride, di(2-ethylhexyl) phthalate, butyl benzyl phthalate, diallyl phthalate, di(2-ethylhexyl) adipate, tris(2-ethylhexyl) phosphate, and 2-ethylhexyl sulfate (sodium salt). Estimated maximum tolerable doses and fractionally lower doses of each compound were administered to groups of 50 male and 50 female rats and mice for 2 years, followed by sacrifice, necropsy, and histopathological examination of major organs and tissues. The low toxic potencies of most of the compounds allowed for relatively high doses to be given during the chronic studies. In general, the toxic manifestations of the PAEs were closely correlated with their ester substituents. Although many of the PAEs possessed some carcinogenic activity, target sites for such effects were dissimilar, suggesting the absence of a common mode of action. In contrast, all of the 2-ethylhexyl-containing compounds studied possessed some hepatocarcinogenic activity, indicating that this moiety may have a propensity for causing hepatocarcinogenesis in mice, particularly those of the female sex. The 2-ethylhexyl compound that caused the greatest hepatocarcinogenic response in mice, di(2-ethylhexyl) phthalate, was also hepatocarcinogenic in rats. Similarly, those with a relatively greater effect in female mice were also active in male mice. Thus, sex and species differences in 2-ethylhexyl-induced hepatocarcinogenesis in rodents are probably quantitative rather than qualitative in nature. PMID:3709453

  14. In Silico Estimation of Chemical Carcinogenicity with Binary and Ternary Classification Methods.

    PubMed

    Li, Xiao; Du, Zheng; Wang, Jie; Wu, Zengrui; Li, Weihua; Liu, Guixia; Shen, Xu; Tang, Yun

    2015-04-01

    Carcinogenicity is one of the most concerned properties of chemicals to human health, thus it is important to identify chemical carcinogenicity as early as possible. In this study, 829 diverse compounds with rat carcinogenicity were collected from Carcinogenic Potency Database (CPDB). Using six types of fingerprints to represent the molecules, 30 binary and ternary classification models were generated to predict chemical carcinogenicity by five machine learning methods. The models were evaluated by an external validation set containing 87 chemicals from ISSCAN database. The best binary model was developed by MACCS keys and kNN algorithm with predictive accuracy at 83.91 %, while the best ternary model was also generated by MACCS keys and kNN algorithm with overall accuracy at 80.46 %. Furthermore, the best binary and ternary classification models were used to estimate carcinogenicity of tobacco smoke components containing 2251 compounds. 981 ones were predicted as carcinogens by binary classification model, while 110 compounds were predicted as strong carcinogens and 807 ones as weak carcinogens by ternary classification model. The results indicated that our models would be helpful for prediction of chemical carcinogenicity.

  15. Comparative toxicity and carcinogenicity of soluble and insoluble cobalt compounds.

    PubMed

    Behl, Mamta; Stout, Matthew D; Herbert, Ronald A; Dill, Jeffrey A; Baker, Gregory L; Hayden, Barry K; Roycroft, Joseph H; Bucher, John R; Hooth, Michelle J

    2015-07-01

    Occupational exposure to cobalt is of widespread concern due to its use in a variety of industrial processes and the occurrence of occupational disease. Due to the lack of toxicity and carcinogenicity data following exposure to cobalt, and questions regarding bioavailability following exposure to different forms of cobalt, the NTP conducted two chronic inhalation exposure studies in rats and mice, one on soluble cobalt sulfate heptahydrate, and a more recent study on insoluble cobalt metal. Herein, we compare and contrast the toxicity profiles following whole-body inhalation exposures to these two forms of cobalt. In general, both forms were genotoxic in the Salmonella T98 strain in the absence of effects on micronuclei. The major sites of toxicity and carcinogenicity in both chronic inhalation studies were the respiratory tract in rats and mice, and the adrenal gland in rats. In addition, there were distinct sites of toxicity and carcinogenicity noted following exposure to cobalt metal. In rats, carcinogenicity was observed in the blood, and pancreas, and toxicity was observed in the testes of rats and mice. Taken together, these findings suggest that both forms of cobalt, soluble and insoluble, appear to be multi-site rodent carcinogens following inhalation exposure.

  16. Evaluation of the potential carcinogenicity of DDT (50-29-3). Final report

    SciTech Connect

    Not Available

    1988-06-01

    DDT is a probable human carcinogen, classified as weight-of-evidence Group B2 under the EPA Guidelines for Carcinogen Risk Assessment. Evidence on potential carcinogenicity from animal studies is Sufficient. and the evidence from human studies is Inadequate. The potency factor (F) for DDT is estimated to be 5.58 (mg/kg/day)(-1), placing it in potency group 2 according to the CAG's methodology for evaluating potential carcinogens. Combining the weight-of-evidence group and the potency group, DDT is assigned a MEDIUM hazard ranking.

  17. Evaluation of the potential carcinogenicity of aldrin (309-00-2). Final report

    SciTech Connect

    Not Available

    1988-06-01

    Aldrin is a probable human carcinogen, classified as weight-of-evidence Group B2 under the EPA Guidelines for Carcinogen Risk Assessment. Evidence on potential carcinogenicity from animal studies is sufficient, and the evidence from human studies is inadequate. The potency factor (F) for aldrin is estimated to be 239/(mg/kg/day), placing it in potency group 1 according to the CAG's methodology for evaluating potential carcinogens. Combining the weight-of-evidence group and the potency group, aldrin is assigned a HIGH hazard ranking for the purposes of RQ adjustment.

  18. Evaluation of the potential carcinogenicity of benzo(a)pyrene. Final report

    SciTech Connect

    Not Available

    1988-06-01

    Benzo(a)pyrene is a probable human carcinogen, classified as weight-of-evidence Group B2 under the EPA Guidelines for Carcinogen Risk Assessment (US EPA, 1986a). Evidence on potential carcinogenicity from animal studies is Sufficient, and the evidence from human studies is Inadequate. The potency factor (F) for benzo(a)pyrene is estimated to be 248/(mg/kg/day)(-1), placing it in potency group 1 according to the CAG's methodology for evaluating potential carcinogens (US EPA, 1986b). Combining the weight-of-evidence group and the potency group, benzo(a)pyrene is assigned a HIGH hazard ranking for the purposes of RQ adjustment.

  19. Carcinogenicity and toxicity of methoxychlor.

    PubMed Central

    Reuber, M D

    1980-01-01

    Methoxychlor is carcinogenic for the liver of C3H and BALB/c mice and Osborne-Mendel rats, and possibly for the liver of dogs. Methoxychlor is also carcinogenic for the testis of BALB/c male mice, bone of B6C3F1 female mice, and the ovary of Osborne-Mendel female rats. The incidences of carcinomas of the liver were increased in C3H male mice and BALB/c male and female mice fed methoxychlor. There also was an increase in malignant neoplasms at all sites in BALB/c male and female mice. C3H and BALB/c male mice were more susceptible to the carcinogenic effects of methoxychlor than were female mice. BALB/c mice were more susceptible than C3H mice. Osborne-Mendel male and female rats developed significant incidences of carcinomas of the liver. The incidence of sarcomas of the spleen and abdomen, mostly hemangiosarcomas, was increased in male rats. Neoplasms of the pituitary, adrenals, and mammary gland were also increased in methoxychlor-treated female rats. Miniature swine given methoxychlor developed chronic renal disease in relatively short periods of time. There also was hyperplasia of the mammary gland and uterus, suggesting an estrogen-like effect on those organs. Methoxychlor applied to the skin of rabbits caused a dose-related atrophy of the testes, as well as chronic renal disease. Atrophy of the testes and chronic renal disease could not be evaluated in mice and rats because of insufficient data. PMID:7000513

  20. 4,4'-Methylenebis (2-chloroaniline): an unregulated carcinogen

    SciTech Connect

    Ward, E.; Smith, A.B.; Halperin, W.

    1987-01-01

    4,4'-Methylenebis (2-chloroaniline) (MBOCA) is a confirmed animal carcinogen. It is used commercially as a curing agent for polymers containing isocyanate. There are no adequate studies documenting a carcinogenic risk for MBOCA in humans; however, studies in rats and dogs have shown that MBOCA is a carcinogen. Also, MBOCA is structurally similar to aromatic amines, which cause bladder cancer in workers with occupational exposure. Manufacture of MBOCA in the United States ceased in 1979. However, estimates of the number of workers potentially exposed range from 1,400 to 33,000 in the manufacture of MBOCA-cured products. Presently, there are no federal regulations limiting occupational exposure to MBOCA. An occupational standard for MBOCA proposed by the Occupational Safety and Health Administration was remanded by the Third Circuit Court of Appeals on procedural grounds in 1974. NIOSH recommended in 1978 that MBOCA be treated as a potential human carcinogen and that worker exposure be controlled so that it does not exceed 3 micrograms/m3 of air determined as a time-weighted average concentration for up to a 10-hour workshift (the lowest level that can be reliably measured). In this paper, we will review the literature in regard to MBOCA's carcinogenicity, describe industrial use and extent of worker exposure, and review MBOCA's status in relation to occupational regulations in the United States and abroad. 51 references.

  1. Long-term effects of a diet loosely restricting carbohydrates on HbA1c levels, BMI and tapering of sulfonylureas in type 2 diabetes: a 2-year follow-up study.

    PubMed

    Haimoto, Hajime; Iwata, Mitsunaga; Wakai, Kenji; Umegaki, Hiroyuki

    2008-02-01

    The aim was to assess the long-term effect of a loose restriction of carbohydrate intake (carbohydrate-reduced diet: CARD) compared to a conventional diet (CD) in type 2 diabetes. One hundred and thirty-three type 2 diabetic outpatients followed the CD (n=57, 1734+/-410 kcal, carbohydrate:protein:fat ratio=57:16:26) or CARD (n=76, 1773+/-441 kcal, carbohydrate:protein:fat ratio=45:18:33) according to their own will, and were followed up for 2 years. Glycemic control, body mass index (BMI), serum cholesterols and dose of antidiabetic drugs were assessed at baseline and after 1 and 2 years. At baseline, hemoglobin A1c (HbA1c) and BMI levels were 7.1+/-1.0% and 24.2+/-2.9, respectively, in the CD group, and 7.4+/-1.1% and 25.1+/-3.4 in the CARD group, showing no significant differences. During the 2-year follow-up period, HbA1c levels were significantly improved in the CARD group (CD: 7.5+/-1.3%, CARD: 6.7+/-0.6%, P<0.001), and BMI decreased more significantly in the CARD group (CD: 23.8+/-3.0, CARD: 23.8+/-3.5, P<0.001). The doses of sulfonylureas clearly tapered, and serum cholesterol profiles improved significantly with the CARD. Our results warrant a long-term and large-scale randomized study of the diet for type 2 diabetes.

  2. Prediction of rodent carcinogenicity for 30 chemicals

    SciTech Connect

    Ashby, J.

    1996-10-01

    Predictions of carcinogenic activity are made for 30 chemicals currently being assessed for rodent carcinogenicity by the U.S. National Toxicology Program. The predictions are based upon the chemical structure, the anticipated or reported mutagenicity, and the reported sub-chronic toxicity of each chemical. It is predicted that 13 chemicals will be noncarcinogenic to rodents, that 7 will be genotoxic carcinogens, and that 10 may show some evidence of presumed nongenotoxic rodent carcinogenesis. 3 refs., 1 fig.

  3. [Mutagenic Activity of Four Aminoazo Compounds with Different Carcinogenicity for Rat Liver in the Ames Test].

    PubMed

    Frolova, T S; Sinitsyna, O I; Kaledin, V I

    2015-01-01

    In this paper in the bacterial Ames test we compared the mutagenicity of four aminoazo compounds, previously studied by other researchers and used for activation of rat liver enzymes, with the carcinogenicity in the rat liver. It was found that in the Ames test they have mutagenic activity, however, this activity does not correlate quantitatively with rat sensitivity to their hepatocarcinogenic action. Thus, the most active carcinogen 3'-methyl-4-dimethylaminoazobenzene causes mutations almost 2.5 times less than weakly carcinogenic ortho-aminoazotoluene, and exactly the same number of mutations as non-carcinogenic N,N-diethyl-4-aminoazobenzene. PMID:26591610

  4. [Mutagenic Activity of Four Aminoazo Compounds with Different Carcinogenicity for Rat Liver in the Ames Test].

    PubMed

    Frolova, T S; Sinitsyna, O I; Kaledin, V I

    2015-01-01

    In this paper in the bacterial Ames test we compared the mutagenicity of four aminoazo compounds, previously studied by other researchers and used for activation of rat liver enzymes, with the carcinogenicity in the rat liver. It was found that in the Ames test they have mutagenic activity, however, this activity does not correlate quantitatively with rat sensitivity to their hepatocarcinogenic action. Thus, the most active carcinogen 3'-methyl-4-dimethylaminoazobenzene causes mutations almost 2.5 times less than weakly carcinogenic ortho-aminoazotoluene, and exactly the same number of mutations as non-carcinogenic N,N-diethyl-4-aminoazobenzene.

  5. Site-specific cell proliferation in renal tubular cells by the renal tubular carcinogen tris(2,3-dibromopropyl)phosphate.

    PubMed Central

    Cunningham, M L; Elwell, M R; Matthews, H B

    1993-01-01

    Our laboratory has been examining the mechanisms whereby chemicals are mutagenic in short-term in-vitro assays yet are not carcinogenic in 2-year rodent bioassays. Previous studies indicated that mutagenic carcinogens increased the amount of cell turnover in the target organ, but that mutagenic noncarcinogens failed to do so. The present study compares the incidence of cell proliferation in specific regions of the kidney, which is the site of carcinogenicity, with cell proliferation induced in a nontarget tissue, the liver, by the mutagenic renal tubular carcinogen tris(2,3-dibromopropyl)phosphate (TRIS). Renal tubular adenocarcinoma induced by TRIS was the only tumor type identified in male F344 rats, and it was localized in the outer medulla. Male F344 rats were fed a diet containing 0, 50, or 100 ppm TRIS for 14 days. These doses were identical to the doses given in the National Toxicology Program cancer bioassay. Replicating cells were labeled with bromodeoxyuridine administered by an osmotic minipump and identified in tissue sections from liver and kidney using immunohistochemical techniques. Examination of liver sections showed no chemically related increases in cell proliferation above control for either dose group. However, in the kidney, TRIS induced significant cell proliferation that was localized in the renal outer medulla region, the target area for carcinogenesis. The labeling index (number of labeled cells/total number of cells counted) in the kidneys of TRIS-exposed rats was increased approximately 4-fold in the outer medulla and was not increased in the cortex or inner medulla. The results of this study suggest an association between the chemically-induced renal cell proliferation and the renal carcinogenicity of TRIS. Images FIGURE 2. FIGURE 2. PMID:8013416

  6. The role of depressive symptoms, family invalidation and behavioral impulsivity in the occurrence and repetition of non-suicidal self-injury in Chinese adolescents: a 2-year follow-up study.

    PubMed

    You, Jianing; Leung, Freedom

    2012-04-01

    This study used zero-inflated poisson regression analysis to examine the role of depressive symptoms, family invalidation, and behavioral impulsivity in the occurrence and repetition of non-suicidal self-injury among Chinese community adolescents over a 2-year period. Participants, 4782 high school students, were assessed twice during the follow-up period. Results indicate that while Year 1 depressive symptoms and family invalidation were significantly associated with the occurrence of Year 2 NSSI, Year 1 behavioral impulsivity contributed to both the occurrence and repetition of Year 2 NSSI. Findings of this study suggest that adolescents who display multiple impulsive behaviors may be at particular risk for engaging in repetitive NSSI. Clinical implications of these findings and future research directions were discussed.

  7. A review of the carcinogenic potential of bisphenol A.

    PubMed

    Seachrist, Darcie D; Bonk, Kristen W; Ho, Shuk-Mei; Prins, Gail S; Soto, Ana M; Keri, Ruth A

    2016-01-01

    The estrogenic properties of bisphenol A (BPA), a ubiquitous synthetic monomer that can leach into the food and water supply, have prompted considerable research into exposure-associated health risks in humans. Endocrine-disrupting properties of BPA suggest it may impact developmental plasticity during early life, predisposing individuals to disease at doses below the oral reference dose (RfD) established by the Environmental Protection Agency in 1982. Herein, we review the current in vivo literature evaluating the carcinogenic properties of BPA. We conclude that there is substantial evidence from rodent studies indicating that early-life BPA exposures below the RfD lead to increased susceptibility to mammary and prostate cancer. Based on the definitions of "carcinogen" put forth by the International Agency for Research on Cancer and the National Toxicology Program, we propose that BPA may be reasonably anticipated to be a human carcinogen in the breast and prostate due to its tumor promoting properties. PMID:26493093

  8. A call to expand regulation to all carcinogenic fibrous minerals

    NASA Astrophysics Data System (ADS)

    Baumann, F.; Steele, I.; Ambrosi, J.; Carbone, M.

    2013-05-01

    The regulatory term "asbestos" groups only the six fibrous minerals that were commercially used among approximately 400. The carcinogenicity of these six regulated minerals has been largely demonstrated and is related to fiber structure, fiber length/diameter ratio, and bio-persistence. From a public perception, the generic term "asbestos" refers to the fibrous minerals that cause asbestosis, mesothelioma and other cancers. However, other non-regulated fibrous minerals are potentially as dangerous as the regulatory asbestos because they share similar physical and chemical properties, epidemiological studies have demonstrated their relationship with asbestos-related diseases, and both in vitro and in vivo experiments have established the toxicity of these minerals. For example, the non-regulated asbestiform winchite and richterite minerals that contaminated the vermiculite mined from Libby, Montana, (USA) were associated with mesothelioma, lung cancer and asbestosis observed among the area's residents and miners. Many other examples of non-regulated carcinogenic fibrous minerals include, but are not limited to, antigorite, arfvedsonite, balangeroite, carlosturanite, erionite, fluoro-edenite, hornblende, mordenite, palygorskite, and sepiolite. To propose a regulatory definition that would provide protection from all carcinogenic fibers, we have conducted an interdisciplinary literature review to compare the characteristics of "asbestos" and of non-regulated mineral fibers that relate to carcinogenicity. We specifically studied two non-regulated fibrous minerals that are associated with asbestos-related diseases: the serpentine antigorite and the zeolite erionite. Both examples underscore the problem of regulation based on commercial, rather than scientific principles: 1) the occurrence of fibrous antigorite in materials used to pave roads has been correlated with high mesothelioma rates in New Caledonia. Antigorite was also the cause of asbestosis in Poland, and in

  9. Availability of epidemiologic data on humans exposed to animal carcinogens. II. Chemical uses and production volume

    SciTech Connect

    Karstadt, M.; Bobal, R.

    1982-01-01

    We report further findings of a survey of manufacturers, processors, and importers of chemicals determined by the International Agency for Research on Cancer (IARC) to be animal carcinogens, but whose carcinogenicity in humans was considered uncertain because of inadequate epidemiologic data. We requested epidemiologic studies from the companies marketing or using any of the 75 IARC animal carcinogens in commerce in the United States. Eighteen of the 75 IARC animal carcinogens had volumes listed of 10(6) lb/year or greater, with 8 of the 13 chemicals for which studies had been completed or are in progress in this ''high volume'' category. The use category with the largest number of chemicals was drugs--19 of the 75 IARC animal carcinogens were in this category. However, none of the 13 chemicals included in epidemiologic studies was a drug. Seven of the 13 chemicals included in studies were used primarily as pesticides. We received little information on dyes and dye intermediates, experimental carcinogens, and drugs, all of which are produced in relatively low volumes; these categories represent 42 of the 75 IARC animal carcinogens. Low volumes and declining usage/production appear to be barriers to performance of epidemiologic studies. Information we received suggests that sometimes the problem of low production volume may be avoided by studying users rather than production workers. Overall, however, we expect few additional epidemiologic studies of the 75 IARC animal carcinogens.

  10. Carcinogenic effects of polychlorinated biphenyls.

    PubMed

    Faroon, O M; Keith, S; Jones, D; De Rosa, C

    2001-03-01

    As part of its mandate, the Agency for Toxic Substances and Disease Registry (ATSDR) prepares toxicological profiles on hazardous chemicals found at Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) National Priorities List (NPL) sites that have the greatest public health impact. These profiles comprehensively summarize toxicological and environmental information. This article constitutes the release of an important section of the Toxicological profile for polychlorinated biphenyls [ATSDR. 2000: Toxicological profile for polychlorinated biphenyls. Atlanta, GA: US Department of Health and Human Services, Agency for Toxic Substances and Disease Registry.] into the scientific literature. This article focuses on the carcinogenic effects of this group of synthetic organic chemicals (polychlorinated biphenyls) in humans and animals. Information on other health effects, toxicokinetics, mechanisms of toxicity, biomarkers, interactions, chemical and physical properties, potential for human exposure, and regulations and advisories is detailed in the profile. PMID:12117297

  11. [Carcinogenicity of orthoaminoazotoluene for mouse intestines].

    PubMed

    Kaledin, V I; Alekseeva, G V; Volkova, A I

    1978-10-01

    Carcinogenic activity of orthoaminoazotoluene in relation to intestinal tissues of A/He mice was revealed. Intestinal tumours developed in 19 of 60 mice given this carcinogen; the tumours were localized in the cecum and represented adenomas and adenocarcinomas secreting mucus.

  12. Health effects of coal mining and combustion: carcinogens and cofactors.

    PubMed Central

    Falk, H L; Jurgelski, W

    1979-01-01

    Some polynuclear aromatics (PNA) have been found to be potent carcinogens for all tissues and organs of experimental animals that have been exposed to them, but different dose levels are needed for these effects. They have been known for decades to cause cancer at the site of application but also at certain sites distant from the area of contact. Although some hydrocarbons are potent and complete carcinogens, the majority of related hydrocarbons was originally found to be inactive. Since they generally appear together, it was important to know more about their interaction, particularly whether they would synergize, or antagonize. The polycyclic hydrocarbons have been studied by subcutaneous injection, where they prove very potent carcinogens. They are also very active on the skin of mice where they produce cancer on prolonged application. Inhalation studies, require larger doses yielded negative results until particulate matter was introduced which facilitated the development of lung tumors. Although iron oxide dust was used initially, other dusts were also capable of enhancing the response of the tissue to benzo(a)pyrene carcinogenesis. This point is of importance, particularly since the inhalation of PNA in situations of air pollution or coal mining involves particulates, although of a different type. Soot is not a homogenous substance and several factors determine its properties. Soots will lose some of the absorbed chemicals during their residence in air, but they retain their PNAs for long periods of time when they reach the soil. The carcinogenicity of PNAs in the adsorbed state may be completely absent, depending on particle size of the soot and availability of eluting capability of the tissues or cells in contact with the soot. Whenever the carcinogenic polynuclear aromatics can be eluted they will be active in producing cancer if their residence is adequate. There seems to be no reason to assume that a large increase in coal combustion in the future will

  13. Carcinogens as Frameshift Mutagens: Metabolites and Derivatives of 2-Acetylaminofluorene and Other Aromatic Amine Carcinogens

    PubMed Central

    Ames, Bruce N.; Gurney, E. G.; Miller, James A.; Bartsch, H.

    1972-01-01

    Several carcinogenic metabolites of the carcinogen 2-acetyl-aminofluorene, especially 2-nitrosofluorene and N-hydroxy-2-aminofluorene, are potent frameshift mutagens for Salmonella typhimurium. 2-Nitrosonaphthalene, 2-nitrosophenanthrene, 4-nitroso-trans-stilbene, 4-nitrosobiphenyl, and 4-nitrosoazobenzene, all of which are metabolites or likely metabolites of carcinogenic aromatic amines, are also potent frameshift mutagens. These compounds may be frameshift mutagens of the class that intercalates into DNA and then reacts covalently with the DNA; various ultimate carcinogens may be of this type. The utility of a set of bacterial strains for detecting carcinogens as mutagens is shown. PMID:4564203

  14. JaCVAM-organized international validation study of the in vivo rodent alkaline comet assay for the detection of genotoxic carcinogens: I. Summary of pre-validation study results.

    PubMed

    Uno, Yoshifumi; Kojima, Hajime; Omori, Takashi; Corvi, Raffaella; Honma, Masamistu; Schechtman, Leonard M; Tice, Raymond R; Burlinson, Brian; Escobar, Patricia A; Kraynak, Andrew R; Nakagawa, Yuzuki; Nakajima, Madoka; Pant, Kamala; Asano, Norihide; Lovell, David; Morita, Takeshi; Ohno, Yasuo; Hayashi, Makoto

    2015-07-01

    The in vivo rodent alkaline comet assay (comet assay) is used internationally to investigate the in vivo genotoxic potential of test chemicals. This assay, however, has not previously been formally validated. The Japanese Center for the Validation of Alternative Methods (JaCVAM), with the cooperation of the U.S. NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM)/the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), the European Centre for the Validation of Alternative Methods (ECVAM), and the Japanese Environmental Mutagen Society/Mammalian Mutagenesis Study Group (JEMS/MMS), organized an international validation study to evaluate the reliability and relevance of the assay for identifying genotoxic carcinogens, using liver and stomach as target organs. The ultimate goal of this validation effort was to establish an Organisation for Economic Co-operation and Development (OECD) test guideline. The purpose of the pre-validation studies (i.e., Phase 1 through 3), conducted in four or five laboratories with extensive comet assay experience, was to optimize the protocol to be used during the definitive validation study. PMID:26212293

  15. JaCVAM-organized international validation study of the in vivo rodent alkaline comet assay for the detection of genotoxic carcinogens: I. Summary of pre-validation study results.

    PubMed

    Uno, Yoshifumi; Kojima, Hajime; Omori, Takashi; Corvi, Raffaella; Honma, Masamistu; Schechtman, Leonard M; Tice, Raymond R; Burlinson, Brian; Escobar, Patricia A; Kraynak, Andrew R; Nakagawa, Yuzuki; Nakajima, Madoka; Pant, Kamala; Asano, Norihide; Lovell, David; Morita, Takeshi; Ohno, Yasuo; Hayashi, Makoto

    2015-07-01

    The in vivo rodent alkaline comet assay (comet assay) is used internationally to investigate the in vivo genotoxic potential of test chemicals. This assay, however, has not previously been formally validated. The Japanese Center for the Validation of Alternative Methods (JaCVAM), with the cooperation of the U.S. NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM)/the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), the European Centre for the Validation of Alternative Methods (ECVAM), and the Japanese Environmental Mutagen Society/Mammalian Mutagenesis Study Group (JEMS/MMS), organized an international validation study to evaluate the reliability and relevance of the assay for identifying genotoxic carcinogens, using liver and stomach as target organs. The ultimate goal of this validation effort was to establish an Organisation for Economic Co-operation and Development (OECD) test guideline. The purpose of the pre-validation studies (i.e., Phase 1 through 3), conducted in four or five laboratories with extensive comet assay experience, was to optimize the protocol to be used during the definitive validation study.

  16. Mutagenicity, carcinogenicity, and teratogenicity of industrial pollutants

    SciTech Connect

    Kirsch-Volders, M.

    1984-01-01

    This book examines pollutants that present a possible risk to the genetic material of exposed workers. Current data is presented on heavy metals, insecticides, monomers, and halogenated hydrocarbon solvents. An attempt is made to correlate the molecular interaction mechanisms with test results for mutagenicity, carcinogenicity, and teratogenicity. Topics considered include cellular factors which modify the expression of mutagenic action into genetic lesions; the relation between mutation, repair, and chromosome aberration; chromosomal alterations and carcinogenesis; the mutagenicity, carcinogenicity, and teratogenicity of industrially used metals; the mutagenicity, carcinogenicity, and teratogenicity of insecticides; the mutagenicity, carcinogenicity, and teratogenicity of industrially important monomers; and the mutagenicity, carcinogenicity, and teratogenicity of halogenated hydrocarbon solvents. The examined compounds are compared in tables with regard to chemical properties, production, occurrence, accepted standards in the industry, and positive or negative results with different test systems.

  17. FACTORS INFLUENCING AGE AND STRAIN-RELATED SUSCEPTIBILITY TO 3-METHYLCHOLANTHRENE CARCINOGENICITY

    EPA Science Inventory

    Fetal mice are more sensitive to chemical carcinogens than are adults. Further, some strains of mice are more susceptible to chemical carcinogens than others. We have been conducting studies to understand the interactions between age and genetic background underlying these suscep...

  18. [Is talc a carcinogen? Review of current data].

    PubMed

    Pelfrène, A; Shubik, P

    1975-03-15

    The authors review the literature concerned with the carcinogenic hazards of a long term exposure to talc. The epidemiological and experimental data are controversial, but, however, seem to be sufficient to draw attention to, and to introduce special precautions for occupationally exposed individuals. Large experimental and epidemiological studies should be undertaken.

  19. Chemical procedures to detect carcinogenic compound in domestic wastewater

    NASA Astrophysics Data System (ADS)

    S, Abd Manan T.; A, Malakahmad

    2013-06-01

    This review presents chemical methods to detect carcinogenic compound in wastewater. Atomic absorption spectroscopy (AAS), high performance liquid chromatography (HPLC) and gas chromatography mass spectroscopy (GCMS) and their alternative attached equipments were discussed. The application of each method is elaborated using related studies in the field.

  20. The effects of environmental chemical carcinogens on the microRNA machinery.

    PubMed

    Izzotti, A; Pulliero, A

    2014-07-01

    The first evidence that microRNA expression is early altered by exposure to environmental chemical carcinogens in still healthy organisms was obtained for cigarette smoke. To date, the cumulative experimental data indicate that similar effects are caused by a variety of environmental carcinogens, including polycyclic aromatic hydrocarbons, nitropyrenes, endocrine disruptors, airborne mixtures, carcinogens in food and water, and carcinogenic drugs. Accordingly, the alteration of miRNA expression is a general mechanism that plays an important pathogenic role in linking exposure to environmental toxic agents with their pathological consequences, mainly including cancer development. This review summarizes the existing experimental evidence concerning the effects of chemical carcinogens on the microRNA machinery. For each carcinogen, the specific microRNA alteration signature, as detected in experimental studies, is reported. These data are useful for applying microRNA alterations as early biomarkers of biological effects in healthy organisms exposed to environmental carcinogens. However, microRNA alteration results in carcinogenesis only if accompanied by other molecular damages. As an example, microRNAs altered by chemical carcinogens often inhibits the expression of mutated oncogenes. The long-term exposure to chemical carcinogens causes irreversible suppression of microRNA expression thus allowing the transduction into proteins of mutated oncogenes. This review also analyzes the existing knowledge regarding the mechanisms by which environmental carcinogens alter microRNA expression. The underlying molecular mechanism involves p53-microRNA interconnection, microRNA adduct formation, and alterations of Dicer function. On the whole, reported findings provide evidence that microRNA analysis is a molecular toxicology tool that can elucidate the pathogenic mechanisms activated by environmental carcinogens.

  1. The effects of environmental chemical carcinogens on the microRNA machinery.

    PubMed

    Izzotti, A; Pulliero, A

    2014-07-01

    The first evidence that microRNA expression is early altered by exposure to environmental chemical carcinogens in still healthy organisms was obtained for cigarette smoke. To date, the cumulative experimental data indicate that similar effects are caused by a variety of environmental carcinogens, including polycyclic aromatic hydrocarbons, nitropyrenes, endocrine disruptors, airborne mixtures, carcinogens in food and water, and carcinogenic drugs. Accordingly, the alteration of miRNA expression is a general mechanism that plays an important pathogenic role in linking exposure to environmental toxic agents with their pathological consequences, mainly including cancer development. This review summarizes the existing experimental evidence concerning the effects of chemical carcinogens on the microRNA machinery. For each carcinogen, the specific microRNA alteration signature, as detected in experimental studies, is reported. These data are useful for applying microRNA alterations as early biomarkers of biological effects in healthy organisms exposed to environmental carcinogens. However, microRNA alteration results in carcinogenesis only if accompanied by other molecular damages. As an example, microRNAs altered by chemical carcinogens often inhibits the expression of mutated oncogenes. The long-term exposure to chemical carcinogens causes irreversible suppression of microRNA expression thus allowing the transduction into proteins of mutated oncogenes. This review also analyzes the existing knowledge regarding the mechanisms by which environmental carcinogens alter microRNA expression. The underlying molecular mechanism involves p53-microRNA interconnection, microRNA adduct formation, and alterations of Dicer function. On the whole, reported findings provide evidence that microRNA analysis is a molecular toxicology tool that can elucidate the pathogenic mechanisms activated by environmental carcinogens. PMID:24560354

  2. Comparative carcinogenicity of the PAHs as a basis for acceptable exposure levels (AELs) in drinking water

    SciTech Connect

    Rugen, P.J.; Stern, C.D.; Lamm, S.H. )

    1989-06-01

    The carcinogenicity of various polynuclear aromatic hydrocarbons (PAHs) has generally been demonstrated by their ability to act as complete carcinogens in the development of cancers in rodent skin tests. In order to develop proposed acceptable concentration levels for various PAHs in drinking water, we reviewed the studies that formed the basis for determining that these specific PAHs were carcinogenic in animals. We found that the relative potency of these PAHs varied over a range of many orders of magnitude. For example, the carcinogenic strength of benz(a)anthracene (BaA) is found to be about 1/2000th that of benzo(a)pyrene (BaP). We have used the calculated carcinogenic potency of the various PAHs relative to that of BaP as a means for proposing specific acceptable concentration levels in drinking water for each of the specific PAHs. BaP is the only carcinogenic PAH for which EPA has published an acceptable concentration level based on carcinogenicity. Based on the level EPA set for BaP (0.028 micrograms/liter), this methodology has provided for the specific PAHs a determination of proposed acceptable concentration levels quantitatively based on the same data that were used to qualitatively determine them to be animal carcinogens. We have proposed acceptable concentration levels for the carcinogenic PAHs in drinking water that range from 0.03 micrograms/liter for BaP to 6.5 micrograms/liter for BaA. We recommend that acceptable concentration levels for the various PAHs be based on their relative carcinogenic potencies rather than the EPA method of using the potency of only one specific PAH, BaP, to serve as the exposure level determinant for all PAHs. We further suggest that this methodology may be applicable to other classes of carcinogenic compounds.

  3. Dichlorvos carcinogenicity: an assessment of the weight of experimental evidence.

    PubMed

    Mennear, J H

    1994-12-01

    After 30 years of experience with human exposure to dichlorvos (DDVP) in the home, workplace, and sickroom, the U.S. EPA has published its intent to revoke the food additive registration of this cholinesterase-inhibiting insecticide. The basis for the Agency action is the result of the National Toxicology Program (NTP) toxicology and carcinogenesis study of DDVP in rats and mice (NTP Technical Report No. 342, September 1989). In those experiments the NTP considered the result in the female mouse portion of the study to afford unequivocal evidence of carcinogenicity. The NTP considered the interpretations of the male and female rat and the male mouse studies to be less than clear. Despite the NTP interpretation, the EPA considers the male rat data (increased incidence of mononuclear cell leukemia) to be sufficient to warrant the regulatory change. The purpose of this report is to summarize a review of the interpretation of the NTP data and to assess the predictive validity of the results relative to potential human health impact. Critical review of experimental data indicates that the evidence for a carcinogenic effect of DDVP in animals is equivocal. Further, DDVP possess no in vivo mutagenic activity in mammalian assay systems and it bears no significant structural similarity to known carcinogens. Therefore, a weight-of-the-evidence analysis leads to the conclusion that DDVP poses neither mutagenic nor carcinogenic risks to humans exposed under normal conditions of use of foreseeable conditions of misuse. PMID:7724838

  4. Using carcinogenic potency ranking to assign air contaminants to emission classes.

    PubMed

    Schuhmacher-Wolz, Ulrike; Konietzka, Rainer; Schneider, Klaus

    2002-12-01

    Carcinogenic air contaminants are assigned to emission classes with different emission limits on the basis of their inhalation carcinogenic potency within the revised form of the German First General Administrative Regulation Pertaining to the Federal Emission Control Law (Technical Instructions on Air Quality Control-TA Luft). Accordingly, compounds with high carcinogenic potency are regulated more strictly than less potent substances. The data on carcinogenic properties are heterogeneous. Twenty-five substances or substance groups have been scrutinized and a procedure has been developed to rank these chemicals according to their carcinogenic potency. For 14 substances well-founded unit risk estimates were available to allow assignment of these air contaminants to emission classes. Unit risk estimates for bromoethane, 2-butanone oxime, and o-toluidine were derived using the ED(10)/LED(10) method based on animal studies. For several substances no qualified unit risk estimates or carcinogenicity studies were available to estimate carcinogenic potency after inhalation. Carcinogenic potency of these substances was approximated using two simple methods, T25 and CELmin.

  5. Oral exposure to inorganic arsenic: evaluation of its carcinogenic and non-carcinogenic effects.

    PubMed

    Schuhmacher-Wolz, Ulrike; Dieter, Hermann H; Klein, Dominik; Schneider, Klaus

    2009-01-01

    Inorganic arsenic, which is extensively metabolised in humans into even more toxic methylated arsenicals, is a potent carcinogen, causing tumours of the skin, lung, urinary bladder, and other organs. It also induces a number of non-cancer effects. Consumption of drinking water highly contaminated by arsenic causes serious health problems in some countries in southeastern Asia, and arsenic poses problems for drinking-water safety world-wide. Existing risk assessments are based on epidemiological studies from regions with high exposure concentrations (in the mg/L range). It is a matter of debate whether these findings are useful at predicting arsenic-induced effects at low concentrations. In recent years numerous epidemiological studies on cancer and non-cancer effects of inorganic arsenic have been published. This work aims at reviewing recent toxicological and epidemiological data on inorganic arsenic with emphasis on effects at low exposure concentrations. Information obtained from epidemiological studies is supplemented with mechanistic data from in vitro and in vivo studies. Various modes of action for arsenic carcinogenicity are discussed. The information gathered was used to evaluate the reliability of existing cancer-risk assessments and to improve current assessments of non-cancer health effects. A tolerable daily dose, based on epidemiological studies on arsenic-induced skin disorders, is presented.

  6. Computer-Guided Implant Surgery in Fresh Extraction Sockets and Immediate Loading of a Full Arch Restoration: A 2-Year Follow-Up Study of 14 Consecutively Treated Patients.

    PubMed

    Daas, M; Assaf, A; Dada, K; Makzoumé, J

    2015-01-01

    Statement of Problem. Low scientific evidence is identified in the literature for combining implant placement in fresh extraction sockets with immediate function. Moreover, the few studies available on immediate implants in postextraction sites supporting immediate full-arch rehabilitation clearly lack comprehensive protocols. Purpose. The purpose of this study is to report outcomes of a comprehensive protocol using CAD-CAM technology for surgical planning and fabrication of a surgical template and to demonstrate that immediate function can be easily performed with immediate implants in postextraction sites supporting full-arch rehabilitation. Material and Methods. 14 subjects were consecutively rehabilitated (13 maxillae and 1 mandible) with 99 implants supporting full-arch fixed prostheses followed between 6 and 24 months (mean of 16 months). Outcome measures were prosthesis and implant success, biologic and prosthetic complications, pain, oedema evaluation, and radiographic marginal bone levels at surgery and then at 6, 12, 18, and 24 months. Data were analyzed with descriptive statistics. Results. The overall cumulative implant survival rate at mean follow-up time of 16 months was 97.97%. The average marginal bone loss was 0,9 mm. Conclusions. Within the limitations of this study, the results validate this treatment modality for full-arch rehabilitations with predictable outcomes and high survival rate after 2 years. PMID:26064119

  7. Evaluation of the carcinogenicity of inorganic arsenic.

    PubMed

    Cohen, Samuel M; Arnold, Lora L; Beck, Barbara D; Lewis, Ari S; Eldan, Michal

    2013-10-01

    Inorganic arsenic (iAs) at high exposures is a human carcinogen, affecting mainly the urinary bladder, lung and skin. We present an assessment of the mode of action (MOA) of iAs's carcinogenicity based on the United States Environmental Protection Agency/International Programme on Chemical Safety (USEPA/IPCS) framework, focusing primarily on bladder cancer. Evidence is presented for a MOA involving formation of reactive trivalent metabolites interacting with critical cellular sulfhydryl groups, leading to cytotoxicity and regenerative cell proliferation. Metabolism, kinetics, cell transport, and reaction with specific proteins play a critical role in producing the effects at the cellular level, regardless of cell type, whether urothelium, lung epithelium or epidermis. The cytotoxicity induced by iAs results in non-cancer toxicities, and the regenerative cell proliferation enhances development of epithelial cancers. In other tissues, such as vascular endothelium, different toxicities develop, not cancer. Evidence supporting this MOA comes from in vitro investigations on animal and human cells, from animal models, and from epidemiological studies. This MOA implies a non-linear, threshold dose-response relationship for both non-cancer and cancer end points. The no effect levels in animal models (approximately 1 ppm of water or diet) and in vitro (>0.1 µM trivalent arsenicals) are strikingly consistent. Cancer effects of iAs in humans generally are not observed below exposures of 100-150 ppb in drinking water: below these exposures, human urine concentrations of trivalent metabolites are generally below 0.1 µM, a concentration not associated with bladder cell cytotoxicity in in vitro or animal models. Environmental exposures to iAs in most of the United States do not approach this threshold.

  8. Inter-laboratory comparison of turkey in ovo carcinogenicity assessment (IOCA) of hepatocarcinogens.

    PubMed

    Enzmann, H; Brunnemann, K; Iatropoulos, M; Shpyleva, S; Lukyanova, N; Todor, I; Moore, M; Spicher, K; Chekhun, V; Tsuda, H; Williams, G

    2013-09-01

    In three independent laboratories carcinogens (diethylnitrosamine, DEN, 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone, NNK) and non-carcinogens (N-nitrosoproline, nicotine) were evaluated in turkey eggs for in ovo carcinogenicity assessment (IOCA). Compounds were injected into aseptic fertilized eggs. After incubation for 24 days, foci of altered hepatocytes (FAH), some with a pseudoglandular structure and/or signs of compression of the surrounding tissue were observed in the fetal liver. All laboratories were able to distinguish unequivocally the hepatocarcinogen-exposed groups from those exposed to non-carcinogens or the vehicle controls, based on the pre-specified evaluation parameters: tumor-like lesions, pseudoglandular areas and FAH. In addition to focal changes, only the carcinogens induced hepatocellular karyomegaly. Lower doses of the carcinogens, which did not induce FAH, were sufficient to induce hepatocellular karyomegaly. After exposure to 4 mg DEN, gall bladder agenesis was observed in all fetuses. The IOCA may be a valuable tool for early investigative studies on carcinogenicity and since it does not use rodents may complement chronic rat or mouse bioassays. Test substances that are positive in both rodents and fertilized turkey eggs are most probably trans-species carcinogens with particular significance for humans. The good concordance observed among the three laboratories demonstrates that the IOCA is a reliable and robust method.

  9. Results of the International Validation of the in vivo rodent alkaline comet assay for the detection of genotoxic carcinogens: Individual data for 1,2-dibromoethane, p-anisidine, and o-anthranilic acid in the 2nd step of the 4th phase Validation Study under the JaCVAM initiative.

    PubMed

    Takasawa, Hironao; Takashima, Rie; Narumi, Kazunori; Kawasako, Kazufumi; Hattori, Akiko; Kawabata, Masayoshi; Hamada, Shuichi

    2015-07-01

    As part of the Japanese Center for the Validation of Alternative Methods (JaCVAM)-initiative International Validation Study of an in vivo rat alkaline comet assay, we examined 1,2-dibromoethane (DBE), p-anisidine (ASD), and o-anthranilic acid (ANT) to investigate the effectiveness of the comet assay in detecting genotoxic carcinogens. Each of the three test chemicals was administered to 5 male Sprague-Dawley rats per group by oral gavage at 48, 24, and 3h before specimen preparation. Single cells were collected from the liver and glandular stomach at 3h after the final dosing, and the specimens prepared from these two organs were subjected to electrophoresis under alkaline conditions (pH>13). The percentage of DNA intensity in the comet tail was then assessed using an image analysis system. A micronucleus (MN) assay was also conducted using these three test chemicals with the bone marrow (BM) cells collected from the same animals simultaneously used in the comet assay, i.e., combination study of the comet assay and BM MN assay. A genotoxic (Ames positive) rodent carcinogen, DBE gave a positive result in the comet assay in the present study, while a genotoxic (Ames positive) non-carcinogen, ASD and a non-genotoxic (Ames negative) non-carcinogen, ANT showed negative results in the comet assay. All three chemicals produced negative results in the BM MN assay. While the comet assay findings in the present study were consistent with those obtained from the rodent carcinogenicity studies for the three test chemicals, we consider the positive result in the comet assay for DBE to be particularly meaningful, given that this chemical produced a negative result in the BM MN assay. Therefore, the combination study of the comet assay and BM MN assay is a useful method to detect genotoxic carcinogens that are undetectable with the BM MN assay alone.

  10. Human exposure to dioxins through the diet in Catalonia, Spain: carcinogenic and non-carcinogenic risk.

    PubMed

    Llobet, Juan M; Domingo, Jose L; Bocio, Ana; Casas, Conrad; Teixidó, Angel; Müller, Lutz

    2003-03-01

    The main objectives of this study were to estimate the dietary intake of dioxins by the population of Catalonia, Spain, to determine which food groups showed the greatest contribution to this intake, and to assess the health risks potentially associated with the dietary dioxin intake. From June to August 2000, food samples were randomly acquired in seven cities of Catalonia. Dioxin concentrations were determined in 108 samples belonging to the following groups: vegetables, fruits, pulses, cereals, fish and shellfish, meats and meat products, eggs, milk and dairy products, and oils and fats. Estimates of average daily food consumption were obtained from recent studies. Total dietary intake of dioxins for the general population of Catalonia was estimated to be 95.4 pg WHO-TEQ/day (78.4 pg I-TEQ/day), with fish and shellfish (31%), diary products (25%), cereals (14%) and meat (13%) showing the greatest percentages of contribution to dioxin intake. The contribution of all the rest of food groups to the total dietary intake was under 20%. The non-carcinogenic risk index of dioxin intake through the diet was in the range 0.34-1.36, while the carcinogenic risk level was 1,360 excess cancer over a lifetime of 70 years. Our results corroborate the decreasing tendency in dietary intake of dioxins found in recent studies (2000-2001) from various countries.

  11. Comprehensive study of back and leg pain improvements after adult spinal deformity surgery: analysis of 421 patients with 2-year follow-up and of the impact of the surgery on treatment satisfaction.

    PubMed

    Scheer, Justin K; Smith, Justin S; Clark, Aaron J; Lafage, Virginie; Kim, Han Jo; Rolston, John D; Eastlack, Robert; Hart, Robert A; Protopsaltis, Themistocles S; Kelly, Michael P; Kebaish, Khaled; Gupta, Munish; Klineberg, Eric; Hostin, Richard; Shaffrey, Christopher I; Schwab, Frank; Ames, Christopher P

    2015-05-01

    OBJECT Back and leg pain are the primary outcomes of adult spinal deformity (ASD) and predict patients' seeking of surgical management. The authors sought to characterize changes in back and leg pain after operative or nonoperative management of ASD. Outcomes were assessed according to pain severity, type of surgical procedure, Scoliosis Research Society (SRS)-Schwab spine deformity class, and patient satisfaction. METHODS This study retrospectively reviewed data in a prospective multicenter database of ASD patients. Inclusion criteria were the following: age > 18 years and presence of spinal deformity as defined by a scoliosis Cobb angle ≥ 20°, sagittal vertical axis length ≥ 5 cm, pelvic tilt angle ≥ 25°, or thoracic kyphosis angle ≥ 60°. Patients were grouped into nonoperated and operated subcohorts and by the type of surgical procedure, spine SRS-Schwab deformity class, preoperative pain severity, and patient satisfaction. Numerical rating scale (NRS) scores of back and leg pain, Oswestry Disability Index (ODI) scores, physical component summary (PCS) scores of the 36-Item Short Form Health Survey, minimum clinically important differences (MCIDs), and substantial clinical benefits (SCBs) were assessed. RESULTS Patients in whom ASD had been operatively managed were 6 times more likely to have an improvement in back pain and 3 times more likely to have an improvement in leg pain than patients in whom ASD had been nonoperatively managed. Patients whose ASD had been managed nonoperatively were more likely to have their back or leg pain remain the same or worsen. The incidence of postoperative leg pain was 37.0% at 6 weeks postoperatively and 33.3% at the 2-year follow-up (FU). At the 2-year FU, among patients with any preoperative back or leg pain, 24.3% and 37.8% were free of back and leg pain, respectively, and among patients with severe (NRS scores of 7-10) preoperative back or leg pain, 21.0% and 32.8% were free of back and leg pain, respectively

  12. Detection of rare and possibly carcinogenic human papillomavirus genotypes as single infections in invasive cervical cancer.

    PubMed

    Geraets, Daan; Alemany, Laia; Guimera, Nuria; de Sanjose, Silvia; de Koning, Maurits; Molijn, Anco; Jenkins, David; Bosch, Xavier; Quint, Wim

    2012-12-01

    The contribution of carcinogenic human papillomavirus (HPV) types to the burden of cervical cancer has been well established. However, the role and contribution of phylogenetically related HPV genotypes and rare variants remains uncertain. In a recent global study of 8977 HPV-positive invasive cervical carcinomas (ICCs), the genotype remained unidentified in 3.7% by the HPV SPF10 PCR-DEIA-LiPA25 (version 1) algorithm. The 331 ICC specimens with unknown genotype were analysed by a novel sequence methodology, using multiple selected short regions in L1. This demonstrated HPV genotypes that have infrequently or never been detected in ICC, ie HPV26, 30, 61, 67, 68, 69, 73 and 82, and rare variants of HPV16, 18, 26, 30, 34, 39, 56, 67, 68, 69, 82 and 91. These are not identified individually by LiPA25 and only to some extent by other HPV genotyping assays. Most identified genotypes have a close phylogenetic relationship with established carcinogenic HPVs and have been classified as possibly carcinogenic by IARC. Except for HPV85, all genotypes in α-species 5, 6, 7, 9 and 11 were encountered as single infections in ICCs. These species of established and possibly carcinogenic HPV types form an evolutionary clade. We have shown that the possibly carcinogenic types were detected only in squamous cell carcinomas, which were often keratinizing and diagnosed at a relatively higher mean age (55.3 years) than those associated with established carcinogenic types (50.9 years). The individual frequency of the possibly carcinogenic types in ICCs is low, but together they are associated with 2.25% of the 8338 included ICCs with a single HPV type. This fraction is greater than seven of the established carcinogenic types individually. This study provides evidence that possibly carcinogenic HPV types occur as single infections in invasive cervical cancer, strengthening the circumstantial evidence of a carcinogenic role.

  13. Investigating the different mechanisms of genotoxic and non-genotoxic carcinogens by a gene set analysis.

    PubMed

    Lee, Won Jun; Kim, Sang Cheol; Lee, Seul Ji; Lee, Jeongmi; Park, Jeong Hill; Yu, Kyung-Sang; Lim, Johan; Kwon, Sung Won

    2014-01-01

    Based on the process of carcinogenesis, carcinogens are classified as either genotoxic or non-genotoxic. In contrast to non-genotoxic carcinogens, many genotoxic carcinogens have been reported to cause tumor in carcinogenic bioassays in animals. Thus evaluating the genotoxicity potential of chemicals is important to discriminate genotoxic from non-genotoxic carcinogens for health care and pharmaceutical industry safety. Additionally, investigating the difference between the mechanisms of genotoxic and non-genotoxic carcinogens could provide the foundation for a mechanism-based classification for unknown compounds. In this study, we investigated the gene expression of HepG2 cells treated with genotoxic or non-genotoxic carcinogens and compared their mechanisms of action. To enhance our understanding of the differences in the mechanisms of genotoxic and non-genotoxic carcinogens, we implemented a gene set analysis using 12 compounds for the training set (12, 24, 48 h) and validated significant gene sets using 22 compounds for the test set (24, 48 h). For a direct biological translation, we conducted a gene set analysis using Globaltest and selected significant gene sets. To validate the results, training and test compounds were predicted by the significant gene sets using a prediction analysis for microarrays (PAM). Finally, we obtained 6 gene sets, including sets enriched for genes involved in the adherens junction, bladder cancer, p53 signaling pathway, pathways in cancer, peroxisome and RNA degradation. Among the 6 gene sets, the bladder cancer and p53 signaling pathway sets were significant at 12, 24 and 48 h. We also found that the DDB2, RRM2B and GADD45A, genes related to the repair and damage prevention of DNA, were consistently up-regulated for genotoxic carcinogens. Our results suggest that a gene set analysis could provide a robust tool in the investigation of the different mechanisms of genotoxic and non-genotoxic carcinogens and construct a more detailed

  14. Lactoperoxidase-catalyzed activation of carcinogenic aromatic and heterocyclic amines.

    PubMed

    Gorlewska-Roberts, Katarzyna M; Teitel, Candee H; Lay, Jackson O; Roberts, Dean W; Kadlubar, Fred F

    2004-12-01

    Lactoperoxidase, an enzyme secreted from the human mammary gland, plays a host defensive role through antimicrobial activity. It has been implicated in mutagenic and carcinogenic activation in the human mammary gland. The potential role of heterocyclic and aromatic amines in the etiology of breast cancer led us to examination of the lactoperoxidase-catalyzed activation of the most commonly studied arylamine carcinogens: 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP), benzidine, 4-aminobiphenyl (ABP), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx). In vitro activation was performed with lactoperoxidase (partially purified from bovine milk or human milk) in the presence of hydrogen peroxide and calf thymus DNA. Products formed during enzymatic activation were monitored by HPLC with ultraviolet and radiometric detection. Two of these products were characterized as hydrazo and azo derivatives by means of mass spectrometry. The DNA binding level of 3H- and 14C-radiolabeled amines after peroxidase-catalyzed activation was dependent on the hydrogen peroxide concentration, and the highest levels of carcinogen binding to DNA were observed at 100 microM H2O2. Carcinogen activation and the level of binding to DNA were in the order of benzidine > ABP > IQ > MeIQx > PhIP. One of the ABP adducts was identified, and the level at which it is formed was estimated to be six adducts/10(5) nucleotides. The susceptibility of aromatic and heterocyclic amines for lactoperoxidase-catalyzed activation and the binding levels of activated products to DNA suggest a potential role of lactoperoxidase-catalyzed activation of carcinogens in the etiology of breast cancer.

  15. Stability assessment of a moderately conforming all-polyethylene tibial component in total knee arthroplasty: a prospective RSA study with 2 years of follow-up of the Kinemax Plus design.

    PubMed

    Adalberth, G; Nilsson, K G; Byström, S; Kolstad, K; Mallmin, H; Milbrink, J

    1999-01-01

    The magnitude and pattern of the migration of an all-polyethylene tibial component with moderately conforming articular surfaces in total knee arthroplasty was analyzed in 20 patients > or =60 years during a 2-year follow-up using radiostereometry (RSA). Most of the migration occurred during the initial 4 months, whereafter the migration diminished, reaching a mean maximum migration of 0.75 mm at 2 years. Similar patterns were found for rotation of the implant. Maximum subsidence at 2 years was 0.7 mm and was most commonly located at the posteromedial part of the tibial component. These results indicate that an all-polyethylene tibial component with moderately conforming articular geometry and with a thickness of 10-12 mm demonstrated migration patterns compatible with a favorable prognosis in regard to future aseptic loosening.

  16. Decrease in self-esteem mediates the association between symptoms of social phobia and depression in middle adolescence in a sex-specific manner: a 2-year follow-up of a prospective population cohort study

    PubMed Central

    2014-01-01

    Background Social phobia and depression are common, highly comorbid disorders in middle adolescence. The mechanism underlying this comorbidity, however, is unclear. Decrease in self-esteem caused by the initial disorder might play a decisive role in the development of the subsequent disorder. The present study aimed to determine whether the association between symptoms of social phobia and depression is mediated by decrease in self-esteem in mid-adolescent girls and boys. Methods As a part of the prospective Adolescent Mental Health Cohort (AMCH), subjects of this study were 9th grade pupils (mean age, 15.5) responding to a survey conducted in 2002–2003 (T1) and to a 2-year follow-up survey in 2004–2005 (T2) (N = 2070, mean age 17.6 years, 54.5% girls). Results Symptoms of social phobia without symptoms of depression at age 15 and symptoms of depression at age 17 were associated only among boys, and this association was mediated by decrease in self-esteem. Symptoms of depression without symptoms of social phobia at age 15 and symptoms of social phobia at age 17 were associated only among girls, and this association was partially mediated by decrease in self-esteem. Conclusions Decrease in self-esteem plays a decisive role in the association between social phobia and depression. Self-esteem should be a key focus in interventions for adolescents suffering from social phobia or depression. Efficient intervention for the first disorder might help to prevent the decline in self-esteem and thus the incidence of the subsequent disorder. These findings are based on a sample of Finnish adolescents and should be confirmed in other jurisdictions or in more ethnically diverse samples. PMID:24641987

  17. Carcinogen adducts as an indicator for the public health risks of consuming carcinogen-exposed fish and shellfish.

    PubMed Central

    Dunn, B P

    1991-01-01

    A large variety of environmental carcinogens are metabolically activated to electrophilic metabolites that can bind to nucleic acids and protein, forming covalent adducts. The formation of DNA-carcinogen adducts is thought to be a necessary step in the action of most carcinogens. Recently, a variety of new fluorescence, immunochemical, and radioactive-postlabeling procedures have been developed that allow the sensitive measurement of DNA-carcinogen adducts in organisms exposed to environmental carcinogens. In some cases, similar procedures have been developed for protein-carcinogen adducts. In an organism with active metabolic systems for a given carcinogen, adducts are generally much longer lived than the carcinogens that formed them. Thus, the detection of DNA- or protein-carcinogen adducts in aquatic foodstuffs can act as an indicator of prior carcinogen exposure. The presence of DNA adducts would, in addition, suggest a mutagenic/carcinogenic risk to the aquatic organism itself. Vertebrate fish are characterized by high levels of carcinogen metabolism, low body burdens of carcinogen, the formation of carcinogen-macromolecule adducts, and the occurrence of pollution-related tumors. Shellfish, on the other hand, have low levels of carcinogen metabolism, high body burdens of carcinogen, and have little or no evidence of carcinogen-macromolecule adducts or tumors. The consumption of carcinogen adducts in aquatic foodstuffs is unlikely to represent a human health hazard. There are no metabolic pathways by which protein-carcinogen or DNA-carcinogen adducts could reform carcinogens. Incorporation via salvage pathways of preformed nucleoside-carcinogen adducts from foodstuffs into newly synthesized human DNA is theoretically possible.(ABSTRACT TRUNCATED AT 250 WORDS) Images FIGURE 1. FIGURE 1. FIGURE 2. PMID:2050048

  18. Carcinogen adducts as an indicator for the public health risks of consuming carcinogen-exposed fish and shellfish

    SciTech Connect

    Dunn, B.P. )

    1991-01-01

    A large variety of environmental carcinogens are metabolically activated to electrophilic metabolites that can bind to nucleic acids and protein, forming covalent adducts. The formation of DNA-carcinogen adducts is thought to be a necessary step in the action of most carcinogens. Recently, a variety of new fluorescence, immunochemical, and radioactive-postlabeling procedures have been developed that allow the sensitive measurement of DNA-carcinogen adducts in organisms exposed to environmental carcinogens. In some cases, similar procedures have been developed for protein-carcinogen adducts. In an organism with active metabolic systems for a given carcinogen, adducts are generally much longer lived than the carcinogens that formed them. Thus, the detection of DNA- or protein-carcinogen adducts in aquatic foodstuffs can act as an indicator of prior carcinogen exposure. The presence of DNA adducts would, in addition, suggest a mutagenic/carcinogenic risk to the aquatic organism itself. Vertebrate fish are characterized by high levels of carcinogen metabolism, low body burdens of carcinogen, the formation of carcinogen-macromolecule adducts, and the occurrence of pollution-related tumors. Shellfish, on the other hand, have low levels of carcinogen metabolism, high body burdens of carcinogen, and have little or no evidence of carcinogen-macromolecule adducts or tumors. The consumption of carcinogen adducts in aquatic foodstuffs is unlikely to represent a human health hazard. There are no metabolic pathways by which protein-carcinogen or DNA-carcinogen adducts could reform carcinogens. Incorporation via salvage pathways of preformed nucleoside-carcinogen adducts from foodstuffs into newly synthesized human DNA is theoretically possible.

  19. Opportunities for an alternative integrating testing strategy for carcinogen hazard assessment?

    PubMed

    Doktorova, Tatyana Y; Pauwels, Marleen; Vinken, Mathieu; Vanhaecke, Tamara; Rogiers, Vera

    2012-02-01

    The 2-year rodent carcinogenicity bioassay evolved more than 40 years ago, and although it is complex, long lasting, expensive, and animal consuming, it is still the only generally accepted test for assessing the carcinogenicity of chemicals. Over time, different alternative approaches have been developed with the final goal to replace the bioassay. Unfortunately, at present, none of these strategies alone provides sufficient assurance of accurate prediction. In this review paper, we discuss the major advantages and pitfalls of the existing alternative methodologies to the carcinogenicity bioassay. Finally, based on the available scientific data in the public domain, we propose what we would like to call a "feasible integrated testing strategy" which incorporates some promising alternatives, providing at the same time information on the mechanism of action and the toxic nature of the compounds tested. It is, however, clear that the adoption of whatever "new" testing scheme should be considered with caution and its effectiveness should be experimentally demonstrated in advance by addressing a reasonable number of chemical carcinogens and non-carcinogens from a variety of structural and functional classes.

  20. 29 CFR 1990.112 - Classification of potential carcinogens.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 9 2014-07-01 2014-07-01 false Classification of potential carcinogens. 1990.112 Section... CARCINOGENS The Osha Cancer Policy § 1990.112 Classification of potential carcinogens. The following criteria for identification, classification and regulation of potential occupational carcinogens will...

  1. 29 CFR 1990.112 - Classification of potential carcinogens.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 9 2011-07-01 2011-07-01 false Classification of potential carcinogens. 1990.112 Section... CARCINOGENS The Osha Cancer Policy § 1990.112 Classification of potential carcinogens. The following criteria for identification, classification and regulation of potential occupational carcinogens will...

  2. Repetitive Behaviours in Typically Developing 2-Year-Olds

    ERIC Educational Resources Information Center

    Leekam, Susan; Tandos, Jonathan; McConachie, Helen; Meins, Elizabeth; Parkinson, Kathryn; Wright, Charlotte; Turner, Michelle; Arnott, Bronia; Vittorini, Lucia; Le Couteur, Ann

    2007-01-01

    Background: Repetitive behaviours are an essential part of the diagnosis of autism but are also commonly seen in typically developing children. The current study investigated the frequency and factor structure of repetitive behaviours in a large community sample of 2-year-olds. Methods: A new measure, the Repetitive Behaviour Questionnaire (RBQ-2)…

  3. The carcinogenic effects of aspartame: The urgent need for regulatory re-evaluation.

    PubMed

    Soffritti, Morando; Padovani, Michela; Tibaldi, Eva; Falcioni, Laura; Manservisi, Fabiana; Belpoggi, Fiorella

    2014-04-01

    Aspartame (APM) is an artificial sweetener used since the 1980s, now present in >6,000 products, including over 500 pharmaceuticals. Since its discovery in 1965, and its first approval by the US Food and Drugs Administration (FDA) in 1981, the safety of APM, and in particular its carcinogenicity potential, has been controversial. The present commentary reviews the adequacy of the design and conduct of carcinogenicity bioassays on rodents submitted by G.D. Searle, in the 1970s, to the FDA for market approval. We also review how experimental and epidemiological data on the carcinogenic risks of APM, that became available in 2005 motivated the European Commission (EC) to call the European Food and Safety Authority (EFSA) for urgent re-examination of the available scientific documentation (including the Searle studies). The EC has further requested that, if the results of the evaluation should suggest carcinogenicity, major changes must be made to the current APM specific regulations. Taken together, the studies performed by G.D. Searle in the 1970s and other chronic bioassays do not provide adequate scientific support for APM safety. In contrast, recent results of life-span carcinogenicity bioassays on rats and mice published in peer-reviewed journals, and a prospective epidemiological study, provide consistent evidence of APM's carcinogenic potential. On the basis of the evidence of the potential carcinogenic effects of APM herein reported, a re-evaluation of the current position of international regulatory agencies must be considered an urgent matter of public health.

  4. Association between inflammatory cytokines and the risk of post-stroke depression, and the effect of depression on outcomes of patients with ischemic stroke in a 2-year prospective study

    PubMed Central

    Jiao, Jian-Tong; Cheng, Chao; Ma, Ying-Jun; Huang, Jin; Dai, Min-Chao; Jiang, Chen; Wang, Cheng; Shao, Jun-Fei

    2016-01-01

    The association between inflammatory cytokines and the risk of post-stroke depression (PSD) remains unclear. The aim of the present study was to investigate this association and the effect of PSD on the outcomes of ischemic stroke patients. A total of 355 patients who had experienced ischemic stroke participated in inflammatory cytokine detection by ELISA, in addition to depression, quality of life (QOL) and body performance testing. Cox regression was used to evaluate the associations between PSD risk, inflammatory cytokines and the outcomes of patients. Measurement data was evaluated using Student's t test, and counted data was measured by χ2 test. The incidence of PSD during the 2-year follow-up was 23.1%. The risk of PSD elevated with increased interleukin (IL)-6 expression levels [hazard ratio (HR)=3.18; 95% confidence interval (CI), 1.37–7.36] following the adjustment of confounders. However, no significant associations were identified between PSD and other inflammatory cytokines. QOL and body performance in the depressed group were significantly worse compared with those in the non-depressed group. The risk of stroke recurrence in patients with depression increased two-fold compared with patients without depression (HR=2.020; 95% CI, 1.123–3.635; Ptrend=0.019). No significant associations between PSD and the risk of mortality (HR=1.497; 95% CI, 0.547–4.098) were observed. In conclusion, depression is prevalent in patients following ischemic stroke. IL-6 is positively associated with the risk of PSD, and may predict its development in patients following ischemic stroke. PSD correlates with outcomes of patients, and the effective management of PSD may improve the prognosis of patients. PMID:27588080

  5. French multicenter phase III randomized study testing concurrent twice-a-day radiotherapy and cisplatin/5-fluorouracil chemotherapy (BiRCF) in unresectable pharyngeal carcinoma: Results at 2 years (FNCLCC-GORTEC)

    SciTech Connect

    Bensadoun, Rene-Jean . E-mail: rene-jean.bensadoun@nice.fnclcc.fr; Benezery, Karen; Dassonville, Olivier; Magne, Nicolas; Poissonnet, Gilles; Ramaioli, Alain; Lemanski, Claire; Bourdin, Sylvain; Tortochaux, Jacques; Peyrade, Frederic; Marcy, Pierre-Yves; Chamorey, Emmanuel Phar; Vallicioni, Jacques; Seng Hang; Alzieu, Claude; Gery, Bernard; Chauvel, Pierre; Schneider, Maurice; Santini, Jose; Demard, Francois; Calais, Gilles

    2006-03-15

    Background: Unresectable carcinomas of the oropharynx and hypopharynx still have a poor long-term prognosis. Following a previous phase II study, this phase III multicenter trial was conducted between November 1997 and March 2002. Methods: Nontreated, strictly unresectable cases were eligible. Twice-daily radiation: two fractions of 1.2 Gy/day, 5 days per week, with no split (D1{sup {yields}}D46). Total tumor doses: 80.4 Gy/46 day (oropharynx), 75.6 Gy/44 day (hypopharynx). Chemotherapy (arm B): Cisplatin 100 mg/m{sup 2} (D1, D22, D43); 5FU, continuous infusion (D1{sup {yields}}D5), 750 mg/m{sup 2}/day cycle 1; 430 mg/m{sup 2}/day cycles 2 and 3. Results: A total of 163 evaluable patients. Grade 3-4 acute mucositis 82.6% arm B/69.5% arm A (NS); Grade 3-4 neutropenia 33.3% arm B/2.4% arm A (p < 0.05). Enteral nutrition through gastrostomy tube was more frequent in arm B before treatment and at 6 months (p < 0.01). At 24 months, overall survival (OS), disease-free survival (DFS), and specific survival (SS) were significantly better in arm B. OS: 37.8% arm B vs. 20.1% arm A (p = 0.038); DFS: 48.2% vs. 25.2% (p = 0.002); SS: 44.5% vs. 30.2% (p 0.021). No significant difference between the two arms in the amount of side effects at 1 and 2 years. Conclusion: For these unresectable cases, chemoradiation provides better outcome than radiation alone, even with an 'aggressive' dose-intensity radiotherapy schedule.

  6. Searches for ultimate chemical carcinogens and their reactions with cellular macromolecules.

    PubMed

    Miller, E C; Miller, J A

    1981-05-15

    Studies on a variety of chemical carcinogens have demonstrated that their ultimate reactive and carcinogenic forms are strong electrophiles. Some carcinogens, such as alkylating agents, are in their ultimate forms as administered, but most require metabolism to these active derivatives. The ultimate carcinogens react, usually non-enzymatically, with nucleophilic constituents in vivo. Of particular interest in regard to their possible importance in carcinogenesis have been the covalent interactions of these electrophilic reactants with cellular informational macromolecules, the DNAs, RNAs, and proteins. Current data are consistent with the idea that the initiation step of chemical carcinogenesis is a mutagenic event and is caused by alteration of DNA by the ultimate carcinogens. The nature of the carcinogen metabolite(s) involved in the promotion phase has not been determined, but there appears to be no requirement that they be electrophilic. The development of the concept of ultimate chemical carcinogens as strong electrophilic reactants is reviewed, especially with respect to the studies carried in the authors' laboratory.

  7. Results of screening NCI/NTP nongenotoxic carcinogens and genotoxic noncarcinogens with the k sub e test

    SciTech Connect

    Mendelsohn, M.L.; Bakale, G.; McCreary, R.D.

    1989-01-01

    The interdependence of the electrophilic and carcinogenic properties of chemicals that was demonstrated two decades ago rekindled interest in the somatic mutation theory of carcinogenesis. Interest in this theory grew with the development of a reverse-mutation bacterial assay in the laboratory of B.N. Ames that permitted the mutagenic properties of the chemicals to be determined quickly and yielded results which indicated that carcinogens are mutagens.'' Subsequent validation studies of this bioassay, the Salmonella typhimurium/microsome or Ames test,'' by Ames' group and others provided additional support for the correlation between mutagenicity and carcinogenicity which led to the worldwide deployment of the Ames test in thousands of laboratories and to the development of more than 100 other short-term tests that continue to be used to identify potential carcinogens via various end-points of genotoxicity. This document discusses electrophilicity, mutagenicity, and carcinogenicity relationships as well as carcinogen-screening of chemicals. 28 refs., 4 tabs.

  8. A minimum 2-year comparative study of autologous cancellous bone grafting versus beta-tricalcium phosphate in anterior cervical discectomy and fusion using a rectangular titanium stand-alone cage.

    PubMed

    Yamagata, Toru; Naito, Kentaro; Arima, Hironori; Yoshimura, Masaki; Ohata, Kenji; Takami, Toshihiro

    2016-07-01

    Although titanium stand-alone cages are commonly used in anterior cervical discectomy and fusion (ACDF), there are several concerns such as cage subsidence after surgery. The efficacy of β-tricalcium phosphate (β-TCP) granules as a packing material in 1- or 2-level ACDF using a rectangular titanium stand-alone cage is not fully understood. The purpose of this study is to investigate the validity of rectangular titanium stand-alone cages in 1- and 2-level ACDF with β-TCP. This retrospective study included 55 consecutive patients who underwent ACDF with autologous iliac cancellous bone grafting and 45 consecutive patients with β-TCP grafting. All patients completed at least 2-year postoperative follow-up. Univariate and multivariate analyses were performed to examine the associations between study variables and nonunion after surgery. Significant neurological recovery after surgery was obtained in both groups. Cage subsidence was noted in 14 of 72 cages (19.4 %) in the autograft group and 12 of 64 cages (18.8 %) in the β-TCP group. A total of 66 cages (91.7 %) in the autograft group showed osseous or partial union, and 58 cages (90.6 %) in the β-TCP group showed osseous or partial union by 2 years after surgery. There were no significant differences in cage subsidence and the bony fusion rate between the two groups. Multivariate analysis using a logistic regression model showed that fusion level at C6/7, 2-level fusion, and cage subsidence of grades 2-3 were significantly associated with nonunion at 2 years after surgery. Although an acceptable surgical outcome with negligible complication appears to justify the use of rectangular titanium stand-alone cages in 1- and 2-level ACDF with β-TCP, cage subsidence after surgery needs to be avoided to achieve acceptable bony fusion at the fused segments. Fusion level at C6/7 or 2-level fusion may be another risk factor of nonunion. PMID:27098659

  9. A minimum 2-year comparative study of autologous cancellous bone grafting versus beta-tricalcium phosphate in anterior cervical discectomy and fusion using a rectangular titanium stand-alone cage.

    PubMed

    Yamagata, Toru; Naito, Kentaro; Arima, Hironori; Yoshimura, Masaki; Ohata, Kenji; Takami, Toshihiro

    2016-07-01

    Although titanium stand-alone cages are commonly used in anterior cervical discectomy and fusion (ACDF), there are several concerns such as cage subsidence after surgery. The efficacy of β-tricalcium phosphate (β-TCP) granules as a packing material in 1- or 2-level ACDF using a rectangular titanium stand-alone cage is not fully understood. The purpose of this study is to investigate the validity of rectangular titanium stand-alone cages in 1- and 2-level ACDF with β-TCP. This retrospective study included 55 consecutive patients who underwent ACDF with autologous iliac cancellous bone grafting and 45 consecutive patients with β-TCP grafting. All patients completed at least 2-year postoperative follow-up. Univariate and multivariate analyses were performed to examine the associations between study variables and nonunion after surgery. Significant neurological recovery after surgery was obtained in both groups. Cage subsidence was noted in 14 of 72 cages (19.4 %) in the autograft group and 12 of 64 cages (18.8 %) in the β-TCP group. A total of 66 cages (91.7 %) in the autograft group showed osseous or partial union, and 58 cages (90.6 %) in the β-TCP group showed osseous or partial union by 2 years after surgery. There were no significant differences in cage subsidence and the bony fusion rate between the two groups. Multivariate analysis using a logistic regression model showed that fusion level at C6/7, 2-level fusion, and cage subsidence of grades 2-3 were significantly associated with nonunion at 2 years after surgery. Although an acceptable surgical outcome with negligible complication appears to justify the use of rectangular titanium stand-alone cages in 1- and 2-level ACDF with β-TCP, cage subsidence after surgery needs to be avoided to achieve acceptable bony fusion at the fused segments. Fusion level at C6/7 or 2-level fusion may be another risk factor of nonunion.

  10. The multitude and diversity of environmental carcinogens

    SciTech Connect

    Belpomme, D. Irigaray, P.; Hardell, L.; Clapp, R.; Montagnier, L.; Epstein, S.; Sasco, A.J.

    2007-11-15

    We have recently proposed that lifestyle-related factors, screening and aging cannot fully account for the present overall growing incidence of cancer. In order to propose the concept that in addition to lifestyle related factors, exogenous environmental factors may play a more important role in carcinogenesis than it is expected, and may therefore account for the growing incidence of cancer, we overview herein environmental factors, rated as certainly or potentially carcinogenic by the International Agency for Research on Cancer (IARC). We thus analyze the carcinogenic effect of microorganisms (including viruses), radiations (including radioactivity, UV and pulsed electromagnetic fields) and xenochemicals. Chemicals related to environmental pollution appear to be of critical importance, since they can induce occupational cancers as well as other cancers. Of major concerns are: outdoor air pollution by carbon particles associated with polycyclic aromatic hydrocarbons; indoor air pollution by environmental tobacco smoke, formaldehyde and volatile organic compounds such as benzene and 1,3 butadiene, which may particularly affect children, and food pollution by food additives and by carcinogenic contaminants such as nitrates, pesticides, dioxins and other organochlorines. In addition, carcinogenic metals and metalloids, pharmaceutical medicines and cosmetics may be involved. Although the risk fraction attributable to environmental factors is still unknown, this long list of carcinogenic and especially mutagenic factors supports our working hypothesis according to which numerous cancers may in fact be caused by the recent modification of our environment.

  11. Enhanced replication of UV-damaged Simian virus 40 DNA in carcinogen-treated mammalian cells

    SciTech Connect

    Maga, J.A.

    1983-01-01

    The replication of UV-damaged Simian virus 40 (SV40) in carcinogen-treated monkey cells has been studied to elucidate the mechanism of carcinogen-enhanced reactivation. Carcinogen enhanced reactivation is the observed increase in UV-irradiated virus survival in host cells treated with low doses of carcinogen compared to UV-irradiated virus survival in untreated hosts. Carcinogen treatment of monkey kidney cells with either N-acetoxy-2-acetylaminofluorene (AAAF) or UV radiation leads to an enhanced capacity to replicate UV-damaged virus during the first round of infection. To further define the mechanism leading to enhanced replication, a detailed biochemical analysis of replication intermediates in carcinogen-treated cells was performed. Several conclusions can be drawn. First enhanced replication can be observed in the first four rounds of replication after UV irradiation of viral templates. The second major finding is that the relaxed circular intermediate model proposed for the replication of UV-damaged templates in untreated cells appears valid for replication of UV-damaged templates in carcinogen-treated cells. Possible mechanisms and the supporting evidence are discussed and future experiments outlined.

  12. Variation in the effect of five chemical carcinogens on the plaque-forming cell response

    SciTech Connect

    Raikow, R.B.; OKunewick, J.P.; Buffo, M.J.; Jones, D.L.

    1983-03-01

    The effect of five different chemical carcinogens on plaque-forming cell response was measured in order to obtain an index of their effect on humoral antibody formation in vivo. Two alkyl sulfonates: methyl methane sulfonate (MMS) and 1,3-propane sultone (PS); along with three polycyclic aromatic hydrocarbons: benzo(a)pyrene (BP); 7,12-dimethyl benzanthracene (DMBA); and 20-methylcholanthrene (MCA) were chosen for these studies. Each carcinogen was administered as a single intraperitoneal injection to SJL/J mice, and the ability of the animals to generate plaque forming cells to sheep red blood cell antigens was measured as a function of time after exposure to the carcinogen. Some suppression of this humoral immune response was observed with all of the carcinogens tested. The amount and duration of this suppression varied as a function of both the type of carcinogen and the dose. Of the five carcinogens tested only DMBA and MCA produced an immunosuppressive effect that might correlate with their reported carcinogenicity, and PS administration actually resulted in a brief immunostimulatory response during the first four days after administration.

  13. Performance of p16INK4a ELISA as a primary cervical cancer screening test among a large cohort of HIV-infected women in western Kenya: a 2-year cross-sectional study

    PubMed Central

    Wu, Tara J; Smith-McCune, Karen; Reuschenbach, Miriam; von Knebel Doeberitz, Magnus; Maloba, May; Huchko, Megan J

    2016-01-01

    Objective A biomarker with increased specificity for cervical dysplasia compared with human papillomavirus (HPV) testing would be an attractive option for cervical cancer screening among HIV-infected women in resource-limited settings. p16INK4a has been explored as a biomarker for screening in general populations. Design A 2-year cross-sectional study. Setting 2 large HIV primary care clinics in western Kenya. Participants 1054 HIV-infected women in western Kenya undergoing cervical cancer screening as part of routine HIV care from October 2010 to November 2012. Interventions Participants underwent p16INK4a specimen collection and colposcopy. Lesions with unsatisfactory colposcopy or suspicious for cervical intraepithelial neoplasia 2+ (CIN2+; including CIN2/3 or invasive cervical cancer) were biopsied. Following biopsy, disease status was determined by histopathological diagnosis. Primary and secondary outcome measures We measured the sensitivity, specificity and predictive values of p16INK4a ELISA for CIN2+ detection among HIV-infected women and compared them to the test characteristics of current screening methods used in general as well as HIV-infected populations. Results Average p16INK4a concentration in cervical samples was 37.4 U/mL. After colposcopically directed biopsy, 127 (12%) women were determined to have CIN2+. Receiver operating characteristic analysis showed an area under the curve of 0.664 for p16INK4a to detect biopsy-proven CIN2+. At a p16INK4a cut-off level of 9 U/mL, sensitivity, specificity, positive and negative predictive values were 89.0%, 22.9%, 13.6% and 93.8%, respectively. The overall p16INK4a positivity at a cut-off level of 9 U/mL was 828 (78.6%) women. There were 325 (30.8%) cases of correct p16INK4a prediction to detect or rule out CIN2+, and 729 (69.2%) cases of incorrect p16INK4a prediction. Conclusions p16INK4a ELISA did not perform well as a screening test for CIN2+ detection among HIV-infected women due to low

  14. [Carcinogenic N-nitrosamines in the tire industry].

    PubMed

    Sokol?kaia, N N; Krivosheeva, L V; Khesing, A Ia; Piven, V A; Kavun, S M

    1993-01-01

    The level of volatile carcinogenic N-nitrosamines (NA) was studied in the air of various technological sites of tyre production. Reported total levels of NA in air exceeded MACs set in certain countries for the same enterprises. For example, German total MAC for 12 carcinogenic NA is 1 g/m3. N-nitrosomorpholine appeared to have the highest level (91 g/m3), probably, because its derivatives are used as raw material for technological process. Relative rate of volatile NA release from rubber samples containing 4-nitrosodiphenylamine (modifier) was studied. The parameter was reported to have no influence on NA outlet in conditions simulating technological process. NA was detected by means of gas chromatography with thermal energy detector TEA 502A provided by Thermo Electron Corporation, USA. The article necessitates regulation of NA in tyre production and better rubber mixtures to control the pollution of atmosphere. PMID:8069502

  15. [Carcinogenic N-nitrosamines in the tire industry].

    PubMed

    Sokol?kaia, N N; Krivosheeva, L V; Khesing, A Ia; Piven, V A; Kavun, S M

    1993-01-01

    The level of volatile carcinogenic N-nitrosamines (NA) was studied in the air of various technological sites of tyre production. Reported total levels of NA in air exceeded MACs set in certain countries for the same enterprises. For example, German total MAC for 12 carcinogenic NA is 1 g/m3. N-nitrosomorpholine appeared to have the highest level (91 g/m3), probably, because its derivatives are used as raw material for technological process. Relative rate of volatile NA release from rubber samples containing 4-nitrosodiphenylamine (modifier) was studied. The parameter was reported to have no influence on NA outlet in conditions simulating technological process. NA was detected by means of gas chromatography with thermal energy detector TEA 502A provided by Thermo Electron Corporation, USA. The article necessitates regulation of NA in tyre production and better rubber mixtures to control the pollution of atmosphere.

  16. 4-Dimethylaminoazobenzenes: carcinogenicities and reductive cleavage by microsomal azo reductase.

    PubMed

    Lambooy, J P; Koffman, B M

    1985-01-01

    Twenty-four 4-dimethylaminoazobenzenes (DABs) in which systematic structural modifications have been made in the prime ring have been studied for substrate specificity for microsomal azo reductase. The DABs were also evaluated for carcinogenicity and it was found that there was no correlation between carcinogenicity and extent of azo bond cleavage by azo reductase. While any substituent in the prime ring reduces the rate of cleavage of the azo bond relative to the unsubstituted dye, there is a correlation between substituent size and susceptibility to the enzyme. Substituent size was also found to be a significant factor in the induction of hepatomas by the dyes. Preliminary studies have shown that there appears to be a positive correlation between microsomal riboflavin content and the activity of the azo reductase.

  17. Applying Tobacco Carcinogen and Toxicant Biomarkers in Product Regulation and Cancer Prevention

    PubMed Central

    Hecht, Stephen S.; Yuan, Jian-Min; Hatsukami, Dorothy

    2010-01-01

    Tobacco carcinogen and toxicant biomarkers are metabolites or protein or DNA adducts of specific compounds in tobacco products. Highly reliable analytical methods, based mainly on mass spectrometry, have been developed and applied in large studies of many of these biomarkers. A panel of tobacco carcinogen and toxicant biomarkers is suggested here, and typical values for smokers and non-smokers are summarized. This panel of biomarkers has potential applications in the new and challenging area of tobacco product regulation and in development of rational approaches to cancer prevention by establishing carcinogen and toxicant uptake and excretion in people exposed to tobacco products. PMID:20408564

  18. Smoking Patterns, Attitudes and Motives: Unique Characteristics among 2-Year versus 4-Year College Students

    ERIC Educational Resources Information Center

    Berg, C. J.; An, L. C.; Thomas, J. L.; Lust, K. A.; Sanem, J. R.; Swan, D. W.; Ahluwalia, J. S.

    2011-01-01

    Given the previously documented higher rates of smoking among 2-year college students in comparison with 4-year university students, this study compares smoking patterns, attitudes and motives among 2-year and 4-year college students. Two thousand two hundred and sixty-five undergraduate students aged 18-25 years at a 2-year college and a 4-year…

  19. Some carcinogenic polycyclic aromatic hydrocarbons by photoacoustic spectroscopy

    NASA Astrophysics Data System (ADS)

    Garg, R. K.; Kumar, Pardeep; Ram, R. S.; Zaidi, Zahid H.

    1999-12-01

    Polycyclic aromatic hydrocarbons (PAHs) have attracted spectroscopists, astrophysicts and environmentalist because of their importance in our day to day life. It is well known that epoxides are produced during the metabolism of PAHs and have the requisite chemical reactivity to qualify them for the role as an ultimate carcinogenic form of PAHs. Several carcinogenic PAHs such as 3.4-benzopyrene, 1.2,3.4-dibenzopyrene, 3.4,9.10- dibenzopyrene etc. are found to be present in tobacco smoke and among air pollutants. Although PAH molecules are being studied for last several years by using conventional spectroscopy but no systematic attempt has been made to study non-radiative transitions. In our laboratory, we have studied many PAH molecules by a non-destructive technique with unique capability and sensitivity, known as Photoacoustic (PA) spectroscopy. PA spectroscopy is an analytical and research tool to get information about non-radiative transitions and singlet-triplet electronic transitions, where the conventional spectroscopic technique fails. The study of electronic transitions of some carcinogenic molecules are reported using PA and optical absorption spectra in boric acid glass in the region 250 - 400 nm. The electronic transitions of these molecules observed experimentally, have been interpreted using the optimized geometries and CNDO/S-CI method. A good agreement is found between the experimental and calculated results. Assignments of observed electronic transitions are made on the basis of singlet-triplet electronic transitions. Vibrations attached to these electronic transitions are attributed to the ground state vibrational modes.

  20. Application of the improved BALB/c 3T3 cell transformation assay to the examination of the initiating and promoting activities of chemicals: the second interlaboratory collaborative study by the non-genotoxic carcinogen study group of Japan.

    PubMed

    Tsuchiya, Toshiyuki; Umeda, Makoto; Tanaka, Noriho; Sakai, Ayako; Nishiyama, Hiroshi; Yoshimura, Isao; Ajimi, Syozo; Asada, Shin; Asakura, Masumi; Baba, Hiroshi; Dewa, Yasuaki; Ebe, Youji; Fushiwaki, Yuichi; Hagiwara, Yuji; Hamada, Shuichi; Hamamura, Tetsuo; Iwase, Yumiko; Kajiwara, Yoshitsugu; Kasahara, Yasushi; Kato, Yukihiko; Kawabata, Masayoshi; Kitada, Emiko; Kaneko, Kazuko; Kizaki, Yuko; Kubo, Kinya; Miura, Daisaku; Mashiko, Kaori; Mizuhashi, Fukutaro; Muramatsu, Dai; Nakajima, Madoka; Nakamura, Tetsu; Oishi, Hidetoshi; Sasaki, Toshiaki; Shimada, Sawako; Takahashi, Chitose; Takeda, Yuko; Wakuri, Sinobu; Yajima, Nobuhiro; Yajima, Satoshi; Yatsushiro, Tomoko

    2010-03-01

    The Non-genotoxic Carcinogen Study Group in the Environmental Mutagen Society of Japan organised the second step of the inter-laboratory collaborative study on one-stage and two-stage cell transformation assays employing BALB/c 3T3 cells, with the objective of confirming whether the respective laboratories could independently produce results relevant to initiation or promotion. The method was modified to use a medium consisting of DMEM/F12 supplemented with 2% fetal bovine serum and a mixture of insulin, transferrin, ethanolamine and sodium selenite, at the stationary phase of cell growth. Seventeen laboratories collaborated in this study, and each chemical was tested by three to five laboratories. Comparison between the one-stage and two-stage assays revealed that the latter method would be beneficial in the screening of chemicals. In the test for initiating activity with the two-stage assay (post-treated with 0.1microg/ml 12-O-tetradecanoylphorbol-13-acetate), the relevant test laboratories all obtained positive results for benzo[a]pyrene and methylmethane sulphonate, and negative results for phenanthrene. Of those laboratories assigned phenacetin for the initiation phase, two returned positive results and two returned negative results, where the latter laboratories tested up to one dose lower than the maximum dose used by the former laboratories. In the exploration of promoting activity with the twostage assay (pretreated with 0.2microg/ml 3-methylcholanthrene), the relevant test laboratories obtained positive results for mezerein, sodium orthovanadate and TGF-beta1, and negative results for anthralin, phenacetin and phorbol. Two results returned for phorbol 12,13-didecanoate were positive, but one result was negative - again, the maximum dose to achieve the latter result was lower than that which produced the former results. These results suggest that this modified assay method is relevant, reproducible and transferable, provided that dosing issues, such as the

  1. The ISS Carcinogens Data Bank (BDC).

    PubMed

    Binetti, Roberto; Ceccarelli, Federica; Costamagna, Francesca Marina; D'Angiolini, Antonella; Fabri, Alessandra; Ferri, Maurizio; Riva, Giovanni; Roazzi, Paolo; Trucchi, Daniela; Marcello, Ida

    2008-01-01

    The Data Bank on Carcinogens (Banca Dati Cancerogeni, BDC) is a factual data bank, available on the Istituto Superiore di Sanità website, aimed at supporting the risk management decision making of central and local administrators. It can also represent a valuable tool for industry. The available information on carcinogenicity evaluations/classifications produced by European Union and by other institutions (IARC, USEPA, NTP, CCTN) is presented in a concise form accompanied by bibliographic references enabling the users to consult the original sources and, in some cases, to be directly connected to the relevant website. The classifications carried out by each organization in accordance with its own criteria assign the examined agents to specific qualitative categories and do not include quantitative assessment. BDC intends to provide an easy tool for experts, researchers and risk managers dealing with carcinogenic agents. PMID:18469374

  2. Mutagenicity, carcinogenicity and teratogenicity of beryllium.

    PubMed

    Léonard, A; Lauwerys, R

    1987-07-01

    The carcinogenicity of a number of beryllium compounds has been confirmed in experiments on laboratory animals and this metal has to be treated as a possible carcinogenic threat to man. These carcinogenic properties are associated with mutagenic activity as shown by the results of short-term tests performed in vitro with beryllium chloride and beryllium sulfate. These soluble beryllium compounds can produce some infidelity of in vitro synthesis, forward gene mutations in microorganisms and in mammalian cells. They are also able to induce cell transformation. In addition to the positive results obtained in several short-term assays beryllium compounds have been found to bind to nucleoproteins, to inhibit certain enzymes needed for DNA synthesis, to bind nucleic acids to cell membranes and to inhibit microtubule polymerization. The teratogenicity of beryllium salts is relatively unknown and needs additional investigation.

  3. In Silico Methods for Carcinogenicity Assessment.

    PubMed

    Golbamaki, Azadi; Benfenati, Emilio

    2016-01-01

    Screening compounds for potential carcinogenicity is of major importance for prevention of environmentally induced cancers. A large sequence of alternative predictive models, ranging from short-term biological assays (e.g. mutagenicity tests) to theoretical models, have been attempted in this field. Theoretical approaches such as (Q)SAR are highly desirable for identifying carcinogens, since they actively promote the replacement, reduction, and refinement of animal tests. This chapter reports and describes some of the most noted (Q)SAR models based on the human expert knowledge and statistically approach, aiming at predicting the carcinogenicity of chemicals. Additionally, the performance of the selected models has been evaluated and the results are interpreted in details by applying these prediction models to some pharmaceutical molecules.

  4. Contributions of Human Enzymes in Carcinogen Metabolism

    PubMed Central

    Rendic, Slobodan; Guengerich, F. Peter

    2012-01-01

    Considerable support exists for roles of metabolism in modulating the carcinogenic properties of chemicals. In particular, many of these compounds are procarcinogens that require activation to electrophilic forms to exert genotoxic effects. We systematically analyzed the existing literature on metabolism of carcinogens by human enzymes, which has been developed largely in the past 25 years. The metabolism and especially bioactivation of carcinogens are dominated by cytochrome P450 enzymes (66% of bioactivations). Within this group, six P450s—1A1, 1A2, 1B1, 2A6, 2E1, and 3A4—accounted for 77% of the P450 activation reactions. The roles of these P450s can be compared with those estimated for drug metabolism and should be considered in issues involving enzyme induction, chemoprevention, molecular epidemiology, inter-individual variations, and risk assessment. PMID:22531028

  5. [Leather azo dyes: mutagenic and carcinogenic risks].

    PubMed

    Clonfero, E; Venier, P; Granella, M; Levis, A G

    1990-01-01

    The paper reviews the carcinogenicity and mutagenicity data on azo dyes used in the leather industry. Two water soluble benzidine-based dyes were classified as "probably carcinogenic to humans" by the International Agency for Research on Cancer (IARC). No other dyes have been evaluated by the IARC. Of the 48 azo dyes assayed in the Salmonella/microsome test, 20 gave positive results. Attention is drawn to the important role of the in vivo metabolism of azo compounds, which includes a preliminary reduction of the azo bonds and subsequent release of the aromatic amines of the dye. A useful assay (Prival test) for evaluating the mutagenic properties of azo dyes involves a reductive step that permits the release of any genotoxic agents present in the compounds. A list of leather azo dyes is furnished that are considered as potentially harmful due to the presence of a carcinogenic aromatic amine (benzidine, p-aminobenzene and derivatives) in their formulae.

  6. Artificial sweeteners--do they bear a carcinogenic risk?

    PubMed

    Weihrauch, M R; Diehl, V

    2004-10-01

    Artificial sweeteners are added to a wide variety of food, drinks, drugs and hygiene products. Since their introduction, the mass media have reported about potential cancer risks, which has contributed to undermine the public's sense of security. It can be assumed that every citizen of Western countries uses artificial sweeteners, knowingly or not. A cancer-inducing activity of one of these substances would mean a health risk to an entire population. We performed several PubMed searches of the National Library of Medicine for articles in English about artificial sweeteners. These articles included 'first generation' sweeteners such as saccharin, cyclamate and aspartame, as well as 'new generation' sweeteners such as acesulfame-K, sucralose, alitame and neotame. Epidemiological studies in humans did not find the bladder cancer-inducing effects of saccharin and cyclamate that had been reported from animal studies in rats. Despite some rather unscientific assumptions, there is no evidence that aspartame is carcinogenic. Case-control studies showed an elevated relative risk of 1.3 for heavy artificial sweetener use (no specific substances specified) of >1.7 g/day. For new generation sweeteners, it is too early to establish any epidemiological evidence about possible carcinogenic risks. As many artificial sweeteners are combined in today's products, the carcinogenic risk of a single substance is difficult to assess. However, according to the current literature, the possible risk of artificial sweeteners to induce cancer seems to be negligible.

  7. Ames testing of Direct Black 38 parallels carcinogenicity testing.

    PubMed

    Gregory, A R; Elliott, J; Kluge, P

    1981-12-01

    Studies have established that Direct Black 38 and two other benzidine-based dyes are carcinogenic. The carcinogenic effect has been generally considered attributable to the metabolic release of benzidine from Direct Black 38 and similar dyes. However, Ames tests indicated that when Direct Black 38 is reduced with sodium dithionate it is more mutagenic than can be accounted for by complete release of all the benzidine present in the dye molecule. While most dyes are not mutagenic when tested with S-9, a series of benzidine congener dyes were all found to be mutagenic with either TA 98 or TA 100 strains, if the dyes were first reduced with sodium dithionate. Unreduced dyes were not mutagenic. Neither anaerobic conditions nor addition of riboflavin induced mutagenicity of these dyes under the condition of our experiments.

  8. Epigenetic alterations induced by genotoxic occupational and environmental human chemical carcinogens: A systematic literature review.

    PubMed

    Chappell, Grace; Pogribny, Igor P; Guyton, Kathryn Z; Rusyn, Ivan

    2016-01-01

    Accumulating evidence suggests that epigenetic alterations play an important role in chemically-induced carcinogenesis. Although the epigenome and genome may be equally important in carcinogenicity, the genotoxicity of chemical agents and exposure-related transcriptomic responses have been more thoroughly studied and characterized. To better understand the evidence for epigenetic alterations of human carcinogens, and the potential association with genotoxic endpoints, we conducted a systematic review of published studies of genotoxic carcinogens that reported epigenetic endpoints. Specifically, we searched for publications reporting epigenetic effects for the 28 agents and occupations included in Monograph Volume 100F of the International Agency for the Research on Cancer (IARC) that were classified as "carcinogenic to humans" (Group 1) with strong evidence of genotoxic mechanisms of carcinogenesis. We identified a total of 158 studies that evaluated epigenetic alterations for 12 of these 28 carcinogenic agents and occupations (1,3-butadiene, 4-aminobiphenyl, aflatoxins, benzene, benzidine, benzo[a]pyrene, coke production, formaldehyde, occupational exposure as a painter, sulfur mustard, and vinyl chloride). Aberrant DNA methylation was most commonly studied, followed by altered expression of non-coding RNAs and histone changes (totaling 85, 59 and 25 studies, respectively). For 3 carcinogens (aflatoxins, benzene and benzo[a]pyrene), 10 or more studies reported epigenetic effects. However, epigenetic studies were sparse for the remaining 9 carcinogens; for 4 agents, only 1 or 2 published reports were identified. While further research is needed to better identify carcinogenesis-associated epigenetic perturbations for many potential carcinogens, published reports on specific epigenetic endpoints can be systematically identified and increasingly incorporated in cancer hazard assessments. PMID:27234561

  9. Prediction of carcinogenicity for diverse chemicals based on substructure grouping and SVM modeling.

    PubMed

    Tanabe, Kazutoshi; Lučić, Bono; Amić, Dragan; Kurita, Takio; Kaihara, Mikio; Onodera, Natsuo; Suzuki, Takahiro

    2010-11-01

    The Carcinogenicity Reliability Database (CRDB) was constructed by collecting experimental carcinogenicity data on about 1,500 chemicals from six sources, including IARC, and NTP databases, and then by ranking their reliabilities into six unified categories. A wide variety of 911 organic chemicals were selected from the database for QSAR modeling, and 1,504 kinds of different molecular descriptors were calculated, based on their 3D molecular structures as modeled by the Dragon software. Positive (carcinogenic) and negative (non-carcinogenic) chemicals containing various substructures were counted using atom and functional group count descriptors, and the statistical significance of ratios of positives to negatives was tested for those substructures. Very few were judged to be strongly related to carcinogenicity, among substructures known to be responsible for carcinogens as revealed from biomedical studies. In order to develop QSAR models for the prediction of the carcinogenicities of a wide variety of chemicals with a satisfactory performance level, the relationship between the carcinogenicity data with improved reliability and a subset of significant descriptors selected from 1,504 Dragon descriptors was analyzed with a support vector machine (SVM) method: the classification function (SVC) for weighted data in LIBSVM program was used to classify chemicals into two carcinogenic categories (positive or negative), where weights were set depending on the reliabilities of the carcinogenicity data. The quality and stability of the models presented were tested by performing a dual cross-validation procedure. A single SVM model as the first step was developed for all the 911 chemicals using 250 selected descriptors, achieving an overall accuracy level, i.e., positive and negative correct estimate, of about 70%. In order to improve the accuracy of the final model, the 911 chemicals were classified into 20 mutually overlapping subgroups according to contained substructures

  10. Evaluation of the potential carcinogenicity of gamma-hexachlorocyclohexane (lindane). Final report

    SciTech Connect

    Not Available

    1988-06-01

    Gamma-Hexachlorocyclohexane (gamma-BHC or Lindane) is a probable to possible human carcinogen, classified as weight-of-evidence Group B2/C under the EPA Guidelines for Carcinogen Risk Assessment (U.S. EPA, 1986a). Evidence on potential carcinogenicity from animal studies is Sufficient to Limited, and the evidence from human studies is Inadequate. The potency factor (F) for gamma-BHC is estimated to be 7.39/(mg/kg/day), placing it in potency group 2 according to the CAG's methodology for evaluating potential carcinogens (U.S. EPA, 1986b). Combining the weight-of-evidence group and the potency group, gamma-BHC is assigned a MEDIUM hazard ranking for the purposes of RQ adjustment. (When the weight-of-evidence is expressed as a range, the hazard ranking is based on the higher weight-of-evidence group.)

  11. Risk assessment for carcinogens under California's Proposition 65.

    PubMed

    Pease, W S; Zeise, L; Kelter, A

    1990-06-01

    Risk assessments for carcinogens are being developed through an accelerated process in California as a part of the state's implementation of Proposition 65, the Safe Drinking Water and Toxic Enforcement Act. Estimates of carcinogenic potency made by the California Department of Health Services (CDHS) are generally similar to estimates made by the U.S. Environmental Protection Agency (EPA). The largest differences are due to EPA's use of the maximum likelihood estimate instead of CDHS' use of the upper 95% confidence bounds on potencies derived from human data and to procedures used to correct for studies of short duration or with early mortality. Numerical limits derived from these potency estimates constitute "no significant risk" levels, which govern exemption from Proposition 65's discharge prohibition and warning requirements. Under Proposition 65 regulations, lifetime cancer risks less than 10(-5) are not significant and cumulative intake is not considered. Following these regulations, numerical limits for a number of Proposition 65 carcinogens that are applicable to the control of toxic discharges are less stringent than limits under existing federal water pollution control laws. Thus, existing federal limits will become the Proposition 65 levels for discharge. Chemicals currently not covered by federal and state controls will eventually be subject to discharge limitations under Proposition 65. "No significant risk" levels (expressed in terms of daily intake of carcinogens) also trigger warning requirements under Proposition 65 that are more extensive than existing state or federal requirements. A variety of chemical exposures from multiple sources are identified that exceed Proposition 65's "no significant risk" levels. PMID:2367711

  12. Carcinogenicity of azo colorants: influence of solubility and bioavailability.

    PubMed

    Golka, Klaus; Kopps, Silke; Myslak, Zdislaw W

    2004-06-15

    In the past, azo colorants based on benzidine, 3,3'-dichlorobenzidine, 3,3'-dimethylbenzidine (o-tolidine), and 3,3'-dimethoxybenzidine (o-dianisidine) have been synthesized in large amounts and numbers. Studies in exposed workers have demonstrated that the azoreduction of benzidine-based dyes occurs in man. The metabolic conversion of benzidine-, 3,3'-dimethylbenzidine- and 3,3'-dimethoxybenzidine-based dyes to their (carcinogenic) amine precursors in vivo is a general phenomenon that must be considered for each member of this class of chemicals. Several epidemiological studies have demonstrated that the use of the benzidine-based dyes has caused bladder cancer in humans. However, in contrast to water-soluble dyes, the question of biological azoreduction of (practically insoluble) pigments has been a matter of discussion. As a majority of azo pigments are based on 3,3'-dichlorobenzidine, much of the available experimental data are focused on this group. Long-term animal carcinogenicity studies performed with pigments based on 3,3'-dichlorobenzidine did not show a carcinogenic effect. The absence of a genotoxic effect has been supported by mutagenicity studies with the 3,3'-dichlorobenzidine-based Pigment Yellow 12. Studies in which azo pigments based on 3,3'-dichlorobenzidine had been orally administered to rats, hamsters, rabbits and monkeys could generally not detect significant amounts of 3,3'-dichlorobenzidine in the urine. It, therefore, appears well established that the aromatic amine components from azo pigments based on 3,3'-dichlorobenzidine are practically not bioavailable. Hence, it is very unlikely that occupational exposure to insoluble azo pigments would be associated with a substantial risk of (bladder) cancer in man. According to current EU regulations, azo dyes based on benzidine, 3,3'-dimethoxybenzidine and 3,3'-dimethylbenzidine have been classified as carcinogens of category 2 as "substances which should be regarded as if they are carcinogenic

  13. Structural analysis of a carcinogen-induced genomic rearrangement event

    SciTech Connect

    Barr, F.G.; Davis, R.J.; Eichenfield, L.; Emanuel, B.S. Univ. of Pennsylvania, Philadelphia )

    1992-02-01

    The authors have explored the mechanism of genomic rearrangement in a hamster fibroblast cell culture system in which rearrangements are induced 5{prime} to the endogenous thymidine kinase gene by chemical carcinogen treatment. The wild-type region around one rearrangement breakpoint was cloned and sequenced. With this sequence information, the carcinogen-induced rearrangement was cloned from the corresponding rearranged cell line by the inverse polymerase chain reaction. After the breakpoint fragment was sequenced, the wild-type rearrangement partner (RP15) was isolated by a second inverse polymerase chain reaction of unrearranged DNA. Comparison of the sequence of the rearrangement breakpoint with the wild-type RP15 and 5{prime} thymidine kinase gene regions revealed short repeats directly at the breakpoint, as well as nearby A+T-rich regions in rearrangement partner. Therefore, these studies reveal interesting sequence and chromatin features near the rearrangement breakpoints and suggest a role for nuclear organization in the mechanism of carcinogen-induced genomic rearrangement.

  14. Binding of environmental carcinogens to asbestos and mineral fibres.

    PubMed Central

    Harvey, G; Pagé, M; Dumas, L

    1984-01-01

    A rapid method has been developed for measuring the binding capacity of asbestos and other mineral fibres for environmental carcinogens. Benzo(alpha)pyrene (B(alpha)P), nitrosonornicotine (NNN), and N-acetyl-2-aminofluorene (NAAF) were assayed in the presence of Canadian grade 4T30 chrysotile, chrysotile A, amosite, crocidolite, glass microfibres, glasswool, attapulgite, and titanium dioxide. Chrysotile binds significantly more carcinogens than the other mineral fibres. This binding assay is reproducible with coefficients of variation of less than 8% and 6% respectively for inter and intra assay. The influence of pH was also studied, and there is good correlation between the carcinogen binding and the charge of the tested mineral fibres. The in vitro cytotoxicity on macrophage like cell line P388D1 and the haemolytic activity of various mineral fibres were also measured; a good correlation was found between the binding capacity and the cytotoxicity of tested mineral fibres on P388D1 cells. These results give some explanations for the reported synergism between exposure to asbestos and the smoking habits of workers. PMID:6331497

  15. Cosmetic talc should not be listed as a carcinogen: comments on NTP's deliberations to list talc as a carcinogen.

    PubMed

    Wehner, Alfred P

    2002-08-01

    Concerns that cosmetic talc might be carcinogenic are addressed and shown to lack persuasive scientific support. These concerns are based (1). on several, but not all, retrospective epidemiological, statistically barely significant case-control studies of questionable biological import (Their results lack dose-response relationships, are inconsistent and ambiguous, and are therefore inconclusive. Whether inanimate talc particles can translocate from the perineum to the ovaries, a precondition if they were to cause ovarian cancer, remains unresolved.); (2). on one inhalation study in animals whose results, according to a panel of experts, "cannot be considered as relevant predictors of human risk," a position shared by other experts in the field; and (3). on elevated incidence of lung cancer in pottery workers. These workers were occupationally exposed several decades ago to nowadays impermissible concentrations of aerosols comprising a multitude of industrial dusts. To construe a risk for the consumer of pure cosmetic or pharmaceutical-grade talc under consumer conditions, based on these findings, lacks scientific support. Talc is not genotoxic, is not carcinogenic when injected into ovaries of rats, does not cause cancer decades after pleurodesis, and induces apoptosis in vitro in human mesothelioma cells but not in normal mesothelial cells. There is no credible evidence of a cancer risk from inhalation of cosmetic talc by humans. Considering talc a carcinogen lacks convincing scientific documentation.

  16. Carcinogenic compounds in alcoholic beverages: an update.

    PubMed

    Pflaum, Tabea; Hausler, Thomas; Baumung, Claudia; Ackermann, Svenja; Kuballa, Thomas; Rehm, Jürgen; Lachenmeier, Dirk W

    2016-10-01

    The consumption of alcoholic beverages has been classified as carcinogenic to humans by the International Agency for Research on Cancer (IARC) since 1988. More recently, in 2010, ethanol as the major constituent of alcoholic beverages and its metabolite acetaldehyde were also classified as carcinogenic to humans. Alcoholic beverages as multi-component mixtures may additionally contain further known or suspected human carcinogens as constituent or contaminant. This review will discuss the occurrence and toxicology of eighteen carcinogenic compounds (acetaldehyde, acrylamide, aflatoxins, arsenic, benzene, cadmium, ethanol, ethyl carbamate, formaldehyde, furan, glyphosate, lead, 3-MCPD, 4-methylimidazole, N-nitrosodimethylamine, pulegone, ochratoxin A, safrole) occurring in alcoholic beverages as identified based on monograph reviews by the IARC. For most of the compounds of alcoholic beverages, quantitative risk assessment provided evidence for only a very low risk (such as margins of exposure above 10,000). The highest risk was found for ethanol, which may reach exposures in ranges known to increase the cancer risk even at moderate drinking (margin of exposure around 1). Other constituents that could pose a risk to the drinker were inorganic lead, arsenic, acetaldehyde, cadmium and ethyl carbamate, for most of which mitigation by good manufacturing practices is possible. Nevertheless, due to the major effect of ethanol, the cancer burden due to alcohol consumption can only be reduced by reducing alcohol consumption in general or by lowering the alcoholic strength of beverages.

  17. Carcinogenic substances in Soviet tobacco products.

    PubMed

    Zaridze, D G; Safaev, R D; Belitsky, G A; Brunnemann, K D; Hoffmann, D

    1991-01-01

    Chemical carcinogens were determined in mainstream smoke from nonfilter cigarettes produced and consumed in the USSR and in nass, a mixture of tobacco, lime, ash and cotton oil. Cigarettes contained high levels of tar (23-25 mg/cigarette) and nicotine (1.5-1.9 mg/cigarette) and, generally, a high content of polycyclic aromatic hydrocarbons, which are major epithelial carcinogens, N-nitrosamines, which are organ-specific carcinogens, and some carcinogenic metals, such as arsenic and chromium. Nass contained the tobacco-specific N-nitroso compounds, N'-nitrosonornicotine, N'-nitrosoanatabine, N'-nitrosoanabasine and 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone, as well as volatile N-nitrosamines, but at levels lower than in other types of chewing tobacco and snuff. The low levels in nass are due to the short ageing process used, in contrast to commercially produced chewing tobacco and fine-cut snuff, which are highly processed products requiring long ageing and fermentation.

  18. Mycosis fungoides: carcinogens and cerebral involvement.

    PubMed

    Conrad, M E; Omura, G A

    1987-02-01

    Three patients with mycosis fungoides, who were long-term employees of a manufacturer of solid fuel propellants, were seen. Two of these patients had tumorous involvement of the central nervous system, which was successfully treated with radiation therapy. The potential relationship of carcinogens is discussed.

  19. Mutagens and carcinogens in foods. Epidemiologic review.

    PubMed Central

    Hislop, T. G.

    1993-01-01

    Evidence that diet contributes to the development of cancer is strengthening. This paper examines mutagens and carcinogens, such as naturally occurring substances, products of cooking and food processing, intentional and unintentional additives, and contaminants, found in foods. Such substances are present in minute quantities in the diets of average Canadians. Indication of health risk is largely limited to experimental laboratory evidence. PMID:8499796

  20. Carcinogenic compounds in alcoholic beverages: an update.

    PubMed

    Pflaum, Tabea; Hausler, Thomas; Baumung, Claudia; Ackermann, Svenja; Kuballa, Thomas; Rehm, Jürgen; Lachenmeier, Dirk W

    2016-10-01

    The consumption of alcoholic beverages has been classified as carcinogenic to humans by the International Agency for Research on Cancer (IARC) since 1988. More recently, in 2010, ethanol as the major constituent of alcoholic beverages and its metabolite acetaldehyde were also classified as carcinogenic to humans. Alcoholic beverages as multi-component mixtures may additionally contain further known or suspected human carcinogens as constituent or contaminant. This review will discuss the occurrence and toxicology of eighteen carcinogenic compounds (acetaldehyde, acrylamide, aflatoxins, arsenic, benzene, cadmium, ethanol, ethyl carbamate, formaldehyde, furan, glyphosate, lead, 3-MCPD, 4-methylimidazole, N-nitrosodimethylamine, pulegone, ochratoxin A, safrole) occurring in alcoholic beverages as identified based on monograph reviews by the IARC. For most of the compounds of alcoholic beverages, quantitative risk assessment provided evidence for only a very low risk (such as margins of exposure above 10,000). The highest risk was found for ethanol, which may reach exposures in ranges known to increase the cancer risk even at moderate drinking (margin of exposure around 1). Other constituents that could pose a risk to the drinker were inorganic lead, arsenic, acetaldehyde, cadmium and ethyl carbamate, for most of which mitigation by good manufacturing practices is possible. Nevertheless, due to the major effect of ethanol, the cancer burden due to alcohol consumption can only be reduced by reducing alcohol consumption in general or by lowering the alcoholic strength of beverages. PMID:27353523

  1. Iron in asbestos chemistry and carcinogenicity

    SciTech Connect

    Hardy, J.A.; Aust, A.E.

    1995-01-01

    This article reviews the various aspects regarding the carcinogenicity of asbestos and associated reactions catalyzed by iron. Attention is focused on the following: structure of asbestos; physical properties of asbestos involved in carcinogenesis; reactions catalyzed by iron; reactions catalyzed by asbestos; fiber inactivation; physiological effects; and mutations and cancer. 183 refs.

  2. Carcinogenicity evaluation for the application of carbon nanotubes as biomaterials in rasH2 mice

    NASA Astrophysics Data System (ADS)

    Takanashi, Seiji; Hara, Kazuo; Aoki, Kaoru; Usui, Yuki; Shimizu, Masayuki; Haniu, Hisao; Ogihara, Nobuhide; Ishigaki, Norio; Nakamura, Koichi; Okamoto, Masanori; Kobayashi, Shinsuke; Kato, Hiroyuki; Sano, Kenji; Nishimura, Naoyuki; Tsutsumi, Hideki; Machida, Kazuhiko; Saito, Naoto

    2012-07-01

    The application of carbon nanotubes (CNTs) as biomaterials is of wide interest, and studies examining their application in medicine have had considerable significance. Biological safety is the most important factor when considering the clinical application of CNTs as biomaterials, and various toxicity evaluations are required. Among these evaluations, carcinogenicity should be examined with the highest priority; however, no report using transgenic mice to evaluate the carcinogenicity of CNTs has been published to date. Here, we performed a carcinogenicity test by implanting multi-walled CNTs (MWCNTs) into the subcutaneous tissue of rasH2 mice, using the carbon black present in black tattoo ink as a reference material for safety. The rasH2 mice did not develop neoplasms after being injected with MWCNTs; instead, MWCNTs showed lower carcinogenicity than carbon black. Such evaluations should facilitate the clinical application and development of CNTs for use in important medical fields.

  3. Lung tumors in strain A mice as a bioassay for carcinogenicity of environmental chemicals

    SciTech Connect

    Stoner, G.D. )

    1991-03-01

    This report describes the protocol for the strain A mouse lung tumor bioassay and summarizes results on selected chemicals that have been tested for carcinogenicity in the assay. The assay is of 6 months duration and can distinguish 2-fold differences in carcinogenic potential of compounds from several chemical classes. Specifically, the assay is sensitive to polycyclic hydrocarbons, nitrosamines and nitrosoureas, carbamates, aflatoxin, certain metals, hydrazines, and others, but is relatively insensitive to aromatic amines, aliphatic halides, and other compounds that are carcinogenic in the rodent liver and/or bladder. Recommendations are made for future studies on the: (1) distribution and metabolism of chemicals in strain A mouse lung tissue and in specific lung cell types; (2) ability of the lung tumor bioassay to detect inhibitors and promoters of carcinogenesis; and (3) use of the assay for testing mixtures of chemicals for carcinogenic activity.

  4. The impact of low-dose carcinogens and environmental disruptors on tissue invasion and metastasis

    PubMed Central

    Ochieng, Josiah; Nangami, Gladys N.; Ogunkua, Olugbemiga; Miousse, Isabelle R.; Koturbash, Igor; Odero-Marah, Valerie; McCawley, Lisa; Nangia-Makker, Pratima; Ahmed, Nuzhat; Luqmani, Yunus; Chen, Zhenbang; Papagerakis, Silvana; Wolf, Gregory T.; Dong, Chenfang; Zhou, Binhua P.; Brown, Dustin G.; Colacci, Annamaria; Hamid, Roslida A.; Mondello, Chiara; Raju, Jayadev; Ryan, Elizabeth P.; Woodrick, Jordan; Scovassi, Ivana; Singh, Neetu; Vaccari, Monica; Roy, Rabindra; Forte, Stefano; Memeo, Lorenzo; Salem, Hosni K.; Amedei, Amedeo; Al-Temaimi, Rabeah; Al-Mulla, Fahd; Bisson, William H.; Eltom, Sakina E.

    2015-01-01

    The purpose of this review is to stimulate new ideas regarding low-dose environmental mixtures and carcinogens and their potential to promote invasion and metastasis. Whereas a number of chapters in this review are devoted to the role of low-dose environmental mixtures and carcinogens in the promotion of invasion and metastasis in specific tumors such as breast and prostate, the overarching theme is the role of low-dose carcinogens in the progression of cancer stem cells. It is becoming clearer that cancer stem cells in a tumor are the ones that assume invasive properties and colonize distant organs. Therefore, low-dose contaminants that trigger epithelial–mesenchymal transition, for example, in these cells are of particular interest in this review. This we hope will lead to the collaboration between scientists who have dedicated their professional life to the study of carcinogens and those whose interests are exclusively in the arena of tissue invasion and metastasis. PMID:26106135

  5. New public QSAR model for carcinogenicity

    PubMed Central

    2010-01-01

    Background One of the main goals of the new chemical regulation REACH (Registration, Evaluation and Authorization of Chemicals) is to fulfill the gaps in data concerned with properties of chemicals affecting the human health. (Q)SAR models are accepted as a suitable source of information. The EU funded CAESAR project aimed to develop models for prediction of 5 endpoints for regulatory purposes. Carcinogenicity is one of the endpoints under consideration. Results Models for prediction of carcinogenic potency according to specific requirements of Chemical regulation were developed. The dataset of 805 non-congeneric chemicals extracted from Carcinogenic Potency Database (CPDBAS) was used. Counter Propagation Artificial Neural Network (CP ANN) algorithm was implemented. In the article two alternative models for prediction carcinogenicity are described. The first model employed eight MDL descriptors (model A) and the second one twelve Dragon descriptors (model B). CAESAR's models have been assessed according to the OECD principles for the validation of QSAR. For the model validity we used a wide series of statistical checks. Models A and B yielded accuracy of training set (644 compounds) equal to 91% and 89% correspondingly; the accuracy of the test set (161 compounds) was 73% and 69%, while the specificity was 69% and 61%, respectively. Sensitivity in both cases was equal to 75%. The accuracy of the leave 20% out cross validation for the training set of models A and B was equal to 66% and 62% respectively. To verify if the models perform correctly on new compounds the external validation was carried out. The external test set was composed of 738 compounds. We obtained accuracy of external validation equal to 61.4% and 60.0%, sensitivity 64.0% and 61.8% and specificity equal to 58.9% and 58.4% respectively for models A and B. Conclusion Carcinogenicity is a particularly important endpoint and it is expected that QSAR models will not replace the human experts opinions

  6. A comprehensive review of the carcinogenic and anticarcinogenic potential of capsaicin.

    PubMed

    Bley, Keith; Boorman, Gary; Mohammad, Bashir; McKenzie, Donald; Babbar, Sunita

    2012-08-01

    Human exposure to capsaicin, the most abundant pungent chili pepper component, is ubiquitous. Evaluation of capsaicin's carcinogenic potential has produced variable results in in vitro and in vivo genotoxicity and carcinogenicity assays. The capsaicin tested in older studies was often from pepper plant extracts and included other capsaicinoids and diverse impurities. Recent studies utilizing high-purity capsaicin and standardized protocols provide evidence that the genotoxic and carcinogenic potential of capsaicin is quite low and that the purity of capsaicin is important. Several small epidemiological studies suggest a link between capsaicin consumption and stomach or gall bladder cancer, but contamination of capsaicin-containing foods with known carcinogens renders their interpretation problematic. The postulated ability of capsaicin metabolites to damage DNA and promote carcinogenesis remains unsupported. Anticancer activities of capsaicin have been widely reported, as it inhibits the activity of carcinogens and induces apoptosis in numerous cancer cell lines in vitro and explanted into rodents. Diverse mechanisms have been postulated for capsaicin's anticancer properties. One hypothesis is that inhibition of cytochrome P450 enzymes-particularly CYP2E1-retards carcinogen activation but is contradicted by the low potency of capsaicin for CYP inhibition. The potential for dietary capsaicin to act as a chemopreventative is now widely postulated. PMID:22563012

  7. Biomonitoring human exposure to environmental carcinogenic chemicals.

    PubMed

    Farmer, P B; Sepai, O; Lawrence, R; Autrup, H; Sabro Nielsen, P; Vestergård, A B; Waters, R; Leuratti, C; Jones, N J; Stone, J; Baan, R A; van Delft, J H; Steenwinkel, M J; Kyrtopoulos, S A; Souliotis, V L; Theodorakopoulos, N; Bacalis, N C; Natarajan, A T; Tates, A D; Haugen, A; Andreassen, A; Ovrebø, S; Shuker, D E; Amaning, K S; Castelain, P

    1996-07-01

    A coordinated study was carried out on the development, evaluation and application of biomonitoring procedures for populations exposed to environmental genotoxic pollutants. The procedures used involved both direct measurement of DNA or protein damage (adducts) and assessment of second biological effects (mutation and cytogenetic damage). Adduct detection at the level of DNA or protein (haemoglobin) was carried out by 32P-postlabelling, immunochemical, HPLC or mass spectrometric methods. Urinary excretion products resulting from DNA damage were also estimated (immunochemical assay, mass spectrometry). The measurement of adducts was focused on those from genotoxicants that result from petrochemical combustion or processing, e.g. low-molecular-weight alkylating agents, PAHs and compounds that cause oxidative DNA damage. Cytogenetic analysis of lymphocytes was undertaken (micronuclei, chromosome aberrations and sister chromatid exchanges) and mutation frequency was estimated at a number of loci including the hprt gene and genes involving in cancer development. Blood and urine samples from individuals exposed to urban pollution were collected. Populations exposed through occupational or medical sources to larger amounts of some of the genotoxic compounds present in the environmental samples were used as positive controls for the environmentally exposed population. Samples from rural areas were used as negative controls. The project has led to new, more sensitive and more selective approaches for detecting carcinogen-induced damage to DNA and proteins, and subsequent biological effects. These methods were validated with the occupational exposures, which showed evidence of DNA and/or protein and/or chromosome damage in workers in a coke oven plant, garage workers exposed to diesel exhaust and workers exposed to ethylene oxide in a sterilization plant. Dose reponse and adduct repair were studied for methylated adducts in patients treated with methylating cytostatic drugs

  8. Study of the mechanism of carcinogenesis by carcinogens which are negative in the Ames test. Progress report. [ICE; TUMOR PROMOTERS; PROGESTERONE; QUANTITY RATIO; RATS

    SciTech Connect

    Borek, E

    1980-01-01

    Research progress for 1980 is reported. The role of tRNA methyltransferases in two-1 stage carcinogenesis of mice by phorbol esters has been investigated. The mechanisms of elevation of progesterone levels in the rat by ethionine have also beed studied. (ACR)

  9. Prediction of the carcinogenicity of a second group of organic chemicals undergoing carcinogenicity testing

    SciTech Connect

    Zhang, Y.P.; Sussman, N.; Macina, O.T.

    1996-10-01

    Twenty-four organic compounds currently undergoing testing within cancer bioassays under the aegis of the U.S. National Toxicology Program (NTP) were submitted to the computer automated structure evaluation (CASE) and multiple computer automated structure evaluation (MULTICASE) system for predictions of activity. Individual predictions resulting from the NTP combined rodent, NTP mouse, Carcinogenic Potency Database (CPDB) combined rodent, and CPDB mouse databases were combined using Bayes` theorem to yield an overall probability of rodent carcinogenicity. 17 refs., 2 figs., 5 tabs.

  10. Effect of DNA type on response of DNA biosensor for carcinogens

    NASA Astrophysics Data System (ADS)

    Sani, Nor Diyana bt. Md.; Heng, Lee Yook; Surif, Salmijah; Lazim, Azwani Mat

    2013-11-01

    Carcinogens are cancer causing chemicals that can bind to DNA and cause damage to the DNA. These chemicals are available everywhere including in water, air, soil and food. Therefore, a sensor that can detect the presence of these chemicals will be a very useful tool. Since carcinogens bind to DNA, DNA can be used as the biological element in a biosensor. This study has utilized different types of DNA in a biosensor for carcinogen detection. The DNAs include double stranded calf thymus DNA, single stranded calf thymus DNA and guanine rich single stranded DNA. The modified SPE was exposed to a carcinogen followed by interaction with methylene blue which acts as the electroactive indicator. The SPE was then analysed using differential pulse voltammetry (DPV). Optimization studies were conducted for MB concentration and accumulation time, DNA concentration, as well as effect of buffer concentration, buffer pH and ionic strength. The performance of the biosensor was tested on a group 1 carcinogen, formaldehyde. The results indicated that the usage of guanine rich single stranded DNA also gives higher response as carcinogens prefer to bind with guanine compared to other bases.

  11. A study protocol for the evaluation of occupational mutagenic/carcinogenic risks in subjects exposed to antineoplastic drugs: a multicentric project

    PubMed Central

    2011-01-01

    Background Some industrial hygiene studies have assessed occupational exposure to antineoplastic drugs; other epidemiological investigations have detected various toxicological effects in exposure groups labeled with the job title. In no research has the same population been studied both environmentally and epidemiologically. The protocol of the epidemiological study presented here uses an integrated environmental and biological monitoring approach. The aim is to assess in hospital nurses preparing and/or administering therapy to cancer patients the current level of occupational exposure to antineoplastic drugs, DNA and chromosome damage as cancer predictive effects, and the association between the two. Methods/Design About 80 healthy non-smoking female nurses, who job it is to prepare or handle antineoplastic drugs, and a reference group of about 80 healthy non-smoking female nurses not occupationally exposed to chemicals will be examined simultaneously in a cross-sectional study. All the workers will be recruited from five hospitals in northern and central Italy after their informed consent has been obtained. Evaluation of surface contamination and dermal exposure to antineoplastic drugs will be assessed by determining cyclophosphamide on selected surfaces (wipes) and on the exposed nurses' clothes (pads). The concentration of unmetabolized cyclophosphamide as a biomarker of internal dose will be measured in end-shift urine samples from exposed nurses. Biomarkers of effect and susceptibility will be assessed in exposed and unexposed nurses: urinary concentration of 8-hydroxy-2-deoxyguanosine; DNA damage detected using the single-cell microgel electrophoresis (comet) assay in peripheral white blood cells; micronuclei and chromosome aberrations in peripheral blood lymphocytes. Genetic polymorphisms for enzymes involved in metabolic detoxification (i.e. glutathione S-transferases) will also be analysed. Using standardized questionnaires, occupational exposure will

  12. Multiple-site carcinogenicity of benzene in Fischer 344 rats and B6C3F1 mice.

    PubMed Central

    Huff, J E; Haseman, J K; DeMarini, D M; Eustis, S; Maronpot, R R; Peters, A C; Persing, R L; Chrisp, C E; Jacobs, A C

    1989-01-01

    Toxicology and carcinogenesis studies of benzene (CAS No. 71-43-2; greater than 99.7% pure) were conducted in groups of 60 F344/N rats and 60 B6C3F1 mice of each sex for each of three exposure doses and vehicle controls. These composite studies on benzene were designed and conducted because of large production volume and widespread human exposure, because of the epidemiologic association with leukemia, and because previous experiments were considered inadequate or inconclusive for determining carcinogenicity in laboratory animals. Using the results from 17-week studies, doses for the 2-year studies were selected based on clinical observations (tremors in higher dosed mice), on clinical pathologic findings (lymphoid depletion in rats and leukopenia in mice), and on body weight effects. Doses of 0, 50, 100, or 200 mg/kg body weight benzene in corn oil were administered by gavage to male rats, 5 days per week, for 103 weeks. Doses of 0, 25, 50, or 100 mg/kg benzene in corn oil were administered by gavage to female rats and to male and female mice for 103 weeks. Ten animals in each of the 16 groups were killed at 12 months, and necropsies were performed. Hematologic profiles were performed at 3-month intervals. For the 2-year studies, mean body weights of the top dose groups of male rats and of both sexes of mice were lower than those of the controls. Survivals of the top dose group of rats and mice of each sex were reduced; however, at week 92 for rats and week 91 for mice, survival was greater than 60% in all groups; most of the dosed animals that died before week 103 had neoplasia. Compound-related nonneoplastic or neoplastic effects on the hematopoietic system, Zymbal gland, forestomach, and adrenal gland were found both for rats and mice. Further, the oral cavity was affected in rats, and the lung, liver, Harderian gland, preputial gland, ovary, and mammary gland were affected in mice. Under the conditions of these 2-year gavage studies, there was clear evidence

  13. Risk assessment of DNA-reactive carcinogens in food

    SciTech Connect

    Jeffrey, A.M. . E-mail: Alan_Jeffrey@nymc.edu; Williams, G.M.

    2005-09-01

    Risk assessment of DNA-reactive carcinogens in food requires knowledge of the extent of DNA damage in the target organ which results from the competition between DNA adduct formation and repair. Estimates of DNA adduct levels can be made by direct measurement or indirectly as a consequence of their presence, for example, by tumor formation in animal models or exposed populations epidemiologically. Food-borne DNA-reactive carcinogens are present from a variety of sources. They are generally not intrinsically DNA-reactive but require bioactivation to DNA-reactive metabolites a process which may be modulated by the compound itself or the presence of other xenobiotics. A single DNA reactant may form several distinct DNA adducts each undergoing different rates of repair. Some DNA reactants may be photochemically activated or produce reactive oxygen species and thus indirect oxidative DNA damage. The levels of DNA adducts arising from exposures influenced by variations in the doses, the frequency with which an individual is exposed, and rates of DNA repair for specific adducts. Each adduct has a characteristic efficiency with which it induces mutations. Based on experience with the well-studied DNA-reactive food carcinogen aflatoxin B{sub 1} (AFB{sub 1}), a limit of 20 ppb or {approx}30 {mu}g/day has been set and is considered a tolerable daily intake (TDI). Since AFB{sub 1} is considered a potent carcinogen, doses of <1.5 {mu}g of unknown compounds are considered TDIs. Most DNA-reactants, including acrylamide, heterocyclic amines, and {alpha},{beta}-unsaturated carbonyl are below this value. Above that value, measurement of actual DNA adducts levels in either experimental animals with a risk assessment, or, when this occurs, exposed humans are needed. A number of approaches to undertake this are described including immunological, mass spectrometric and {sup 32}P-postlabeling or the use of surrogates such as hemoglobin adducts, together with approaches to evaluate the

  14. Determination of DNA adducts by combining acid-catalyzed hydrolysis and chromatographic analysis of the carcinogen-modified nucleobases.

    PubMed

    Leung, Elvis M K; Deng, Kailin; Wong, Tin-Yan; Chan, Wan

    2016-01-01

    The commonly used method of analyzing carcinogen-induced DNA adducts involves the hydrolysis of carcinogen-modified DNA samples by using a mixture of enzymes, followed by (32)P-postlabeling or liquid chromatography (LC)-based analyses of carcinogen-modified mononucleotides/nucleosides. In the present study, we report the development and application of a new approach to DNA adduct analysis by combining the H(+)/heat-catalyzed release of carcinogen-modified nucleobases and the use of LC-based methods to analyze DNA adducts. Results showed that heating the carcinogen-modified DNA samples at 70 °C for an extended period of 4 to 6 h in the presence of 0.05% HCl can efficiently induce DNA depurination, releasing the intact carcinogen-modified nucleobases for LC analyses. After optimizing the hydrolysis conditions, DNA samples with C8- and N (2) -modified 2'-deoxyguanosine, as well as N (6) -modified 2'-deoxyadenosine, were synthesized by reacting DNA with 1-nitropyrene, acetaldehyde, and aristolochic acids, respectively. These samples were then hydrolyzed, and the released nucleobase adducts were analyzed using LC-based analytical methods. Analysis results demonstrated a dose-dependent release of target DNA adducts from carcinogen-modified DNA samples, indicating that the developed H(+)/heat-catalyzed hydrolysis method was quantitative. Comparative studies with enzymatic digestion method on carcinogen-modified DNA samples revealed that the two hydrolysis methods did not yield systematically different results.

  15. A cross-sectional study on the potential transmission of the carcinogenic liver fluke Opisthorchis viverrini and other fishborne zoonotic trematodes by aquaculture fish.

    PubMed

    Pitaksakulrat, Opal; Sithithaworn, Paiboon; Laoprom, Nonglak; Laha, Thewarach; Petney, Trevor N; Andrews, Ross H

    2013-01-01

    Throughout Southeast Asia and China, eating raw and or partially cooked cyprinid fish causes liver (hepatobiliary) disease and cancer (cholangiocarcinoma) due to fishborne zoonotic trematodes (FZT), in particular Clonorchis sinensis and Opisthorchis viverrini. The primary source of transmission is by native fish, but aquaculture fish are also reported to have high infective potential. Here, a cross-sectional survey of FZT in fish farms was conducted in an endemic area in Khon Kaen Province, Thailand. By using conventional and polymerase chain reaction (PCR) methods, we detected O. viverrini and FZT metacercariae (Centrocestus formosanus and Haplorchis taichui) in two popular fish species, Barbonymus gonionotus (silver barb) and Cirrhinus mrigala (mrigal), from aquaculture farms. Both species were infected in five of six farms examined by PCR but not by conventional methods, yet the prevalence of FZT metacercariae in aquaculture fish was high (46.9%). In addition to O. viverrini (17.1%), the native fish Cyclocheilichthys armatus and Hampala dispar had a prevalence of FZT of 81.4%, which included 5.7% for C. formosanus and 17.1% for H. taichui by conventional method. To our knowledge, this is the first discovery of O. viverrini in aquaculture fish in Thailand. More comprehensive studies are required to determine if human-induced disease transmission coupled with natural transmission cycle occurs throughout the aquaculture industry in the region. This has significant impact on food quality and safety, and provides the basis for the development of an effective strategy for the prevention and control of foodborne diseases.

  16. A comparative study of the structure and vibrational spectra of diphenylmethane, the carcinogen 4,4'-methylenedianiline and 4,4'-methylenebis(N,N-dimethylaniline)

    NASA Astrophysics Data System (ADS)

    Badawi, Hassan M.

    2013-05-01

    The structural stability of 4,4'-methylenedianiline (MDA), 4,4'-methylenebis(N,N-dimethylaniline) (MBDMA) and their parent diphenylmethane (DPM) was investigated by the DFT-B3LYP and ab initio MP2 calculations with the 6-311G** basis set. From the calculations the three diphenylmethanes were predicted to exist predominantly in a non-planar structure with a near C2 molecular symmetry in agreement with X-ray studies. The CCCC angles in DPM and the two dianilines were calculated to be nearly equal of about 60° as compared to X-ray angles of 17° and 67° for MDA. The NH2 inversion barriers in MDA was estimated to be about 1-5 kcal/mol. On comparison of the Raman spectra of the three compounds, the line intensity and position of the characteristic ring breathing mode were shown to be sensitive to the amino substitution. The vibrational wavenumbers of the optimized structures of the two dianilines were computed at the DFT-B3LYP level of theory. Tentative vibrational assignments were made on the basis of combined DFT and experimental FT-IR and FT-Raman data of MDA and MBDMA.

  17. A study on the carcinogenicity of human diets in rats: the influence of heating and the addition of vegetables and fruit.

    PubMed

    Alink, G M; Kuiper, H A; Beems, R B; Koeman, J H

    1989-07-01

    The influence of dietary factors such as total composition, thermal processing, and the addition of vegetables and fruit on the tumour rate in rats was studied in a long-term experiment. Groups of 50 male and 50 female Wistar rats were fed one of the following diets: a semi-synthetic animal diet (A, control); diet A to which vegetables and fruit were added (B); an uncooked human diet (meat, bread and eggs) supplemented with semi-synthetic compounds (C); diet C with fried or baked products (D); a complete human diet consisting of heated products, vegetables and fruit prepared according to mean consumption figures in The Netherlands (E). The animal diets (A and B) contained 26.0 energy (E)% protein, 21.6 E% fat, 52.4 E% carbohydrate and 10.7% (w/w) fibre. The human diets contained 13.2 E% protein, 40.6 E% fat, 46.2 E% carbohydrate and 5% (w/w) fibre. The rats were fed ad lib. for 142 wk. In males and females fed human diets (C, D or E) hepatocellular vacuolization was observed. Male rats (but not female) fed the human diet had a significantly (P less than 0.02) higher incidence of epithelial tumours than those fed the animal diet. This increase was mainly due to tumours of the pituitary and thyroid. Frying and baking of food products (diet D) and the addition of vegetables and fruit (diet E) induced minor differences in tumour rate, but they were not statistically significant. PMID:2777146

  18. A study on the carcinogenicity of human diets in rats: the influence of heating and the addition of vegetables and fruit.

    PubMed

    Alink, G M; Kuiper, H A; Beems, R B; Koeman, J H

    1989-07-01

    The influence of dietary factors such as total composition, thermal processing, and the addition of vegetables and fruit on the tumour rate in rats was studied in a long-term experiment. Groups of 50 male and 50 female Wistar rats were fed one of the following diets: a semi-synthetic animal diet (A, control); diet A to which vegetables and fruit were added (B); an uncooked human diet (meat, bread and eggs) supplemented with semi-synthetic compounds (C); diet C with fried or baked products (D); a complete human diet consisting of heated products, vegetables and fruit prepared according to mean consumption figures in The Netherlands (E). The animal diets (A and B) contained 26.0 energy (E)% protein, 21.6 E% fat, 52.4 E% carbohydrate and 10.7% (w/w) fibre. The human diets contained 13.2 E% protein, 40.6 E% fat, 46.2 E% carbohydrate and 5% (w/w) fibre. The rats were fed ad lib. for 142 wk. In males and females fed human diets (C, D or E) hepatocellular vacuolization was observed. Male rats (but not female) fed the human diet had a significantly (P less than 0.02) higher incidence of epithelial tumours than those fed the animal diet. This increase was mainly due to tumours of the pituitary and thyroid. Frying and baking of food products (diet D) and the addition of vegetables and fruit (diet E) induced minor differences in tumour rate, but they were not statistically significant.

  19. Current and emerging challenges in toxicopathology: Carcinogenic threshold of phenobarbital and proof of arsenic carcinogenicity using rat medium-term bioassays for carcinogens

    SciTech Connect

    Fukushima, Shoji . E-mail: fukuchan@med.osaka-cu.ac.jp; Morimura, Keiichirou; Wanibuchi, Hideki; Kinoshita, Anna; Salim, Elsayed I.

    2005-09-01

    For the last 25 years, Prof. Nobuyuki Ito and his laboratory have focused on the development of liver medium-term bioassay system for detection of carcinogens in F344 rats utilizing glutathione S-transferase placental form (GST-P)-positive foci as an end point marker. In this presentation, the outline and samples of medium-term bioassay systems were described. Furthermore, our data demonstrated the presence of a threshold for the non-genotoxic carcinogen, phenobarbital (PB), and the lack of linearity in the low-dose area of the dose-response curve, providing evidence for hormesis. In addition, the establishment and applications of multiorgan carcinogenicity bioassay (DMBDD model), used for the examination of the carcinogenicity of genotoxic and non-genotoxic chemicals, are discussed. Dimethylarsinic acid, one of organic arsenics, was found to be carcinogenic in rat bladder using DMBDD model and carcinogenicity test.

  20. [Carcinogenic activity of the pesticide propoxur].

    PubMed

    Pylev, L N; Vasil'eva, L A; Smirnova, O V; Khrustalev, S A; Trukhina, G M

    2010-01-01

    Wistar rats were fed propoxur in their diet at 0, 500, 3000, and 8000 ppm during throughout their life. The number of tumors was equal in the control and experimental groups. These were hemoblastoses and breast and uterine tumors. All tumors occurred spontaneously in the rats. A few experimental animals were found to have bladder epithelial hyperplasia that might be pretumorous; however, no bladder tumors were detected. It is concluded that the investigations revealed no carcinogenic activity of propoxur.

  1. Cobalt and antimony: genotoxicity and carcinogenicity.

    PubMed

    De Boeck, Marlies; Kirsch-Volders, Micheline; Lison, Dominique

    2003-12-10

    The purpose of this review is to summarise the data concerning genotoxicity and carcinogenicity of Co and Sb. Both metals have multiple industrial and/or therapeutical applications, depending on the considered species. Cobalt is used for the production of alloys and hard metal (cemented carbide), diamond polishing, drying agents, pigments and catalysts. Occupational exposure to cobalt may result in adverse health effects in different organs or tissues. Antimony trioxide is primarily used as a flame retardant in rubber, plastics, pigments, adhesives, textiles, and paper. Antimony potassium tartrate has been used worldwide as an anti-shistosomal drug. Pentavalent antimony compounds have been used for the treatment of leishmaniasis. Co(II) ions are genotoxic in vitro and in vivo, and carcinogenic in rodents. Co metal is genotoxic in vitro. Hard metal dust, of which occupational exposure is linked to an increased lung cancer risk, is proven to be genotoxic in vitro and in vivo. Possibly, production of active oxygen species and/or DNA repair inhibition are mechanisms involved. Given the recently provided proof for in vitro and in vivo genotoxic potential of hard metal dust, the mechanistic evidence of elevated production of active oxygen species and the epidemiological data on increased cancer risk, it may be advisable to consider the possibility of a new evaluation by IARC. Both trivalent and pentavalent antimony compounds are generally negative in non-mammalian genotoxicity tests, while mammalian test systems usually give positive results for Sb(III) and negative results for Sb(V) compounds. Assessment of the in vivo potential of Sb2O3 to induce chromosome aberrations (CA) gave conflicting results. Animal carcinogenicity data were concluded sufficient for Sb2O3 by IARC. Human carcinogenicity data is difficult to evaluate given the frequent co-exposure to arsenic. Possible mechanisms of action, including potential to produce active oxygen species and to interfere with

  2. Impact and compliance: OSHA Carcinogen Policy

    SciTech Connect

    Meyer, A.F. Jr.; Crowder, C.; Wisniewski, S.; Russell, T.; Senn, K.

    1980-06-26

    This document provides an examination of various aspects of the Occupational Safety and Health Administration (OSHA)Carcinogen Policy. To satisfy the dimensions of the Policy's broad, general nature, a two-fold approach was taken. Throughout, the focus is on the possible effects of the Policy's implementation, but this is first approached as it generally will effect research and compliance activities across broad industry sectors, while specific impacts on DOE are addressed separately. To overview and integrate these approaches, and to provide a quick reference for further information, an outline of information is presented. General or industry-wide applications are addressed both in the Summary and Overview of the Policy (Chapters I and II) and in the discussion of the Model Standard (Chapter V). Also included is a copy of the Policy itself in the General Industry Standards and interpretations Change 10. Sections specifically addressed to the major concerns of DOE and its contractors are a discussion of implications for action regarding the synthetic fuels program, a comparison of the OSHA Model Regulations and the FE OSH Manual Standards for Carcinogens, and finally, a list of known carcinogens in coal gasification/liquefaction. Together, these elements illustrate the broad scope of the policy's impact, which economic and other constraining consequences begin to become visible. Measures to minimize these consequences are a common underlying theme to each of the sections.

  3. Genotoxicity and carcinogenicity risk of carbon nanotubes.

    PubMed

    Toyokuni, Shinya

    2013-12-01

    Novel materials are often commercialized without a complete assessment of the risks they pose to human health because such assessments are costly and time-consuming; additionally, sometimes the methodology needed for such an assessment does not exist. Carbon nanotubes have the potential for widespread application in engineering, materials science and medicine. However, due to the needle-like shape and high durability of multiwalled carbon nanotubes (MWCNTs), concerns have been raised that they may induce asbestos-like pathogenicity when inhaled. Indeed, experiments in rodents supported this hypothesis. Notably, the genetic alterations in MWCNT-induced rat malignant mesothelioma were similar to those induced by asbestos. Single-walled CNTs (SWCNTs) cause mitotic disturbances in cultured cells, but thus far, there has been no report that SWCNTs are carcinogenic. This review summarizes the recent noteworthy publications on the genotoxicity and carcinogenicity of CNTs and explains the possible molecular mechanisms responsible for this carcinogenicity. The nanoscale size and needle-like rigid structure of CNTs appear to be associated with their pathogenicity in mammalian cells, where carbon atoms are major components in the backbone of many biomolecules. Publishing adverse events associated with novel materials is critically important for alerting people exposed to such materials. CNTs still have a bright future with superb economic and medical merits. However, appropriate regulation of the production, distribution and secondary manufacturing processes is required, at least to protect the workers.

  4. Development of quantitative structure-activity relationship (QSAR) models to predict the carcinogenic potency of chemicals

    SciTech Connect

    Venkatapathy, Raghuraman Wang Chingyi; Bruce, Robert Mark; Moudgal, Chandrika

    2009-01-15

    Determining the carcinogenicity and carcinogenic potency of new chemicals is both a labor-intensive and time-consuming process. In order to expedite the screening process, there is a need to identify alternative toxicity measures that may be used as surrogates for carcinogenic potency. Alternative toxicity measures for carcinogenic potency currently being used in the literature include lethal dose (dose that kills 50% of a study population [LD{sub 50}]), lowest-observed-adverse-effect-level (LOAEL) and maximum tolerated dose (MTD). The purpose of this study was to investigate the correlation between tumor dose (TD{sub 50}) and three alternative toxicity measures as an estimator of carcinogenic potency. A second aim of this study was to develop a Classification and Regression Tree (CART) between TD{sub 50} and estimated/experimental predictor variables to predict the carcinogenic potency of new chemicals. Rat TD{sub 50}s of 590 structurally diverse chemicals were obtained from the Cancer Potency Database, and the three alternative toxicity measures considered in this study were estimated using TOPKAT, a toxicity estimation software. Though poor correlations were obtained between carcinogenic potency and the three alternative toxicity (both experimental and TOPKAT) measures for the CPDB chemicals, a CART developed using experimental data with no missing values as predictor variables provided reasonable estimates of TD{sub 50} for nine chemicals that were part of an external validation set. However, if experimental values for the three alternative measures, mutagenicity and logP are not available in the literature, then either the CART developed using missing experimental values or estimated values may be used for making a prediction.

  5. "IARC group 2B Carcinogens" reported in cigarette mainstream smoke.

    PubMed

    Smith, C J; Perfetti, T A; Mullens, M A; Rodgman, A; Doolittle, D J

    2000-09-01

    In the third and final part of a series surveying the international literature on the "IARC carcinogens" in cigarette mainstream smoke, the "IARC Group 2B carcinogens" are reviewed. A search of the published literature shows that of 227 chemical components classified as Group 2B, that is, "possible carcinogens," by the International Agency for Research on Cancer (IARC), 48 have previously been reported in cigarette mainstream smoke. Owing to its highly interactive molecular nature, removal from or inhibition of a given mutagenic or carcinogenic chemical within the complex aerosol mixture cannot reliably be predicted to reduce either the overall mutagenicity or carcinogenicity. However, in the absence of experimental data demonstrating an increase in adverse biological activity resulting from removal or inhibition of a potentially carcinogenic constituent, negation of the activity of the potential carcinogen may be considered as a desirable circumstance.

  6. Hematotoxicity and carcinogenicity of benzene

    SciTech Connect

    Aksoy, M. )

    1989-07-01

    The hematotoxicity of benzene exposure has been well known for a century. Benzene causes leukocytopenia, thrombocytopenia, pancytopenia, etc. The clinical and hematologic picture of aplastic anemia resulting from benzene exposure is not different from classical aplastic anemia; in some cases, mild bilirubinemia, changes in osmotic fragility, increase in lactic dehydrogenase and fecal urobilinogen, and occasionally some neurological abnormalities are found. Electromicroscopic findings in some cases of aplastic anemia with benzene exposure were similar to those observed by light microscopy. Benzene hepatitis-aplastic anemia syndrome was observed in a technician with benzene exposure. Ten months after occurrence of hepatitis B, a severe aplastic anemia developed. The first epidemiologic study proving the leukemogenicity of benzene was performed between 1967 and 1973 to 1974 among shoe workers in Istanbul. The incidence of leukemia was 13.59 per 100,000, which is a significant increase over that of leukemia in the general population. Following the prohibition and discontinuation of the use of benzene in Istanbul, there was a striking decrease in the number of leukemic shoe workers in Istanbul. In 23.7% of the series, consisting of 59 leukemic patients with benzene exposure, there was a preceding pancytopenic period. Furthermore, a familial connection was found in 10.2% of them. The 89.8% of the series showed the findings of acute leukemia. The possible factors that may determine the types of leukemia in benzene toxicity are discussed. The possible role of benzene exposure is presented in the development of malignant lymphoma, multiple myeloma, and lung cancer.

  7. Prevalence and Antifungal Susceptibility of 442 Candida Isolates from Blood and Other Normally Sterile Sites: Results of a 2-Year (1996 to 1998) Multicenter Surveillance Study in Quebec, Canada

    PubMed Central

    St-Germain, G.; Laverdière, M.; Pelletier, R.; Bourgault, A.-M.; Libman, M.; Lemieux, C.; Noël, G.

    2001-01-01

    During a 2-year surveillance program (1996 to 1998) in Quebec, Canada, 442 strains of Candida species were isolated from 415 patients in 51 hospitals. The distribution of species was as follows: Candida albicans, 54%; C. glabrata, 15%; C. parapsilosis, 12%; C. tropicalis, 9%; C. lusitaniae, 3%; C. krusei, 3%; and Candida spp., 3%. These data, compared to those of a 1985 survey, indicate variations in species distribution, with the proportions of C. glabrata and C. parapsilosis increasing by 9 and 4%, respectively, and those of C. albicans and C. tropicalis decreasing by 10 and 7%, respectively. However, these differences are statistically significant for C. glabrata and C. tropicalis only. MICs of amphotericin B were ≥4 μg/ml for 3% of isolates, all of which were non-C. albicans species. Three percent of C. albicans isolates were resistant to flucytosine (≥32 μg/ml). Resistance to itraconazole (≥1 μg/ml) and fluconazole (≥64 μg/ml) was observed, respectively, in 1 and 1% of C. albicans, 14 and 9% of C. glabrata, 5 and 0% of C. tropicalis, and 0% of C. parapsilosis and C. lusitaniae isolates. Clinical data were obtained for 343 patients. The overall crude mortality rate was 38%, reflecting the multiple serious underlying illnesses found in these patients. Bloodstream infections were documented for 249 patients (73%). Overall, systemic triazoles had been administered to 10% of patients before the onset of candidiasis. The frequency of isolation of non-C. albicans species was significantly higher in this group of patients. Overall, only two C. albicans isolates were found to be resistant to fluconazole. These were obtained from an AIDS patient and a leukemia patient, both of whom had a history of previous exposure to fluconazole. At present, it appears that resistance to fluconazole in Quebec is rare and is restricted to patients with prior prolonged azole treatment. PMID:11230409

  8. The association of maternal vitamin D status with infant birth outcomes, postnatal growth and adiposity in the first 2 years of life in a multi-ethnic Asian population: the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort study.

    PubMed

    Ong, Yi Lin; Quah, Phaik Ling; Tint, Mya Thway; Aris, Izzuddin M; Chen, Ling Wei; van Dam, Rob M; Heppe, Denise; Saw, Seang-Mei; Godfrey, Keith M; Gluckman, Peter D; Chong, Yap Seng; Yap, Fabian; Lee, Yung Seng; Foong-Fong Chong, Mary

    2016-08-01

    Maternal vitamin D status during pregnancy has been associated with infant birth and postnatal growth outcomes, but reported findings have been inconsistent, especially in relation to postnatal growth and adiposity outcomes. In a mother-offspring cohort in Singapore, maternal plasma vitamin D was measured between 26 and 28 weeks of gestation, and anthropometric measurements were obtained from singleton offspring during the first 2 years of life with 3-month follow-up intervals to examine birth, growth and adiposity outcomes. Associations were analysed using multivariable linear regression. Of a total of 910 mothers, 13·2 % were vitamin D deficient (<50 nmol/l) and 26·5 % were insufficient (50-75 nmol/l). After adjustment for potential confounders and multiple testing, no statistically significant associations were observed between maternal vitamin D status and any of the birth outcomes - small for gestational age (OR 1·00; 95 % CI 0·56, 1·79) and pre-term birth (OR 1·16; 95 % CI 0·64, 2·11) - growth outcomes - weight-for-age z-scores, length-for-age z-scores, circumferences of the head, abdomen and mid-arm at birth or postnatally - and adiposity outcomes - BMI, and skinfold thickness (triceps, biceps and subscapular) at birth or postnatally. Maternal vitamin D status in pregnancy did not influence infant birth outcomes, postnatal growth and adiposity outcomes in this cohort, perhaps due to the low prevalence (1·6 % of the cohort) of severe maternal vitamin D deficiency (defined as of <30·0 nmol/l) in our population. PMID:27339329

  9. HIV-Exposed Uninfected Infants Show Robust Memory B-Cell Responses in Spite of a Delayed Accumulation of Memory B Cells: an Observational Study in the First 2 Years of Life

    PubMed Central

    Nkumama, Irene N.; Gambo, Faith K.; Muema, Daniel M.; Hassan, Amin S.; Jahangir, Margaret N.; Etyang, Timothy J.; Berkley, James A.; Urban, Britta C.

    2016-01-01

    Improved HIV care has led to an increase in the number of HIV-exposed uninfected (HEU) infants born to HIV-infected women. Although they are uninfected, these infants experience increased morbidity and mortality. One explanation may be that their developing immune system is altered by HIV exposure, predisposing them to increased postnatal infections. We explored the impact of HIV exposure on the B-cell compartment by determining the B-cell subset distribution, the frequency of common vaccine antigen-specific memory B cells (MBCs), and the levels of antibodies to the respective antigens in HEU and HIV-unexposed uninfected (HUU) infants born to uninfected mothers, using flow cytometry, a B-cell enzyme-linked immunosorbent spot assay, and an enzyme-linked immunosorbent assay, respectively, during the first 2 years of life. For the majority of the B-cell subsets, there were no differences between HEU and HUU infants. However, HIV exposure was associated with a lower proportion of B cells in general and MBCs in particular, largely due to a lower proportion of unswitched memory B cells. This reduction was maintained even after correcting for age. These phenotypic differences in the MBC compartment did not affect the ability of HEU infants to generate recall responses to previously encountered antigens or reduce the antigen-specific antibody levels at 18 months of life. Although HIV exposure was associated with a transient reduction in the proportion of MBCs, we found that the ability of HEU infants to mount robust MBC and serological responses was unaffected. PMID:27170641

  10. [Advances in non-carcinogenic toxicity of trichloroethylene].

    PubMed

    Huang, Peiwu; Li, Xuan; Liu, Wei; Liu, Jianjun

    2015-09-01

    Trichloroethylene (TCE) is a widely used organic solvent and an important industrial material. Due to mass production and use, and improper waste disposal, TCE has become a common environmental contaminant, so there is a wide range of occupationally and environmentally exposed population. Occupational and environmental exposure to TCE can produce toxic effects on multiple organs and systems. This paper is a review of the immunotoxicity, reproductive toxicity, neurotoxicity, teratogenic effect and other non-carcinogenic toxic effects of TCE from the aspects of epidemiological study, experimental evidence on animals and toxic mechanisms. PMID:26733146

  11. Clinical outcomes of pars plicata anterior vitrectomy: 2-year results

    PubMed Central

    Narang, Priya; Agarwal, Amar

    2015-01-01

    Purpose: To demonstrate the safety and outcome of a surgical approach that uses pars plicata site for anterior vitrectomy during phacoemulsification procedure complicated by posterior capsule rupture and residual cortical matter. Design: Single center, retrospective, interventional, noncomparative study. Materials and Methods: Medical records of a consecutive series of 35 eyes of 35 patients who underwent pars plicata anterior vitrectomy (PPAV) were reviewed. The main outcome measures were corrected and uncorrected distance visual acuity (CDVA, UDVA), early and late postoperative complications and intraocular pressure (IOP). Ultrasound biomicroscopic (UBM) evaluation of sclerotomy site and spectral domain optical coherence tomography analysis for central macular thickness (CMT) was performed. The final visual outcome at 2 years was evaluated. Results: At 2 years follow-up, the mean postoperative UDVA (logarithm of the minimum angle of resolution [logMAR]) and CDVA (logMAR) was 0.49 ± 0.26 and 0.19 ± 0.14, respectively. There was no significant change in the IOP (P = 0.061) and the mean CMT at 2 years was 192.5 ± 5.54 μm. The postoperative UBM image of the sclerotomy site at 8 weeks demonstrated a clear wound without any vitreous adhesion or incarceration. Intraoperative hyphema was seen in 1 (2.8%) case and postoperative uveitis was seen in 2 (5.7%) cases, which resolved with medications. No case of an iatrogenic retinal break or retinal detachment was reported. Conclusions: PPAV enables a closed chamber approach, allows thorough cleanup of vitreous in the pupillary plane and anterior chamber and affords better access to the subincisional and retropupillary cortical remnant with a significant visual outcome and an acceptable complication rate. PMID:26632124

  12. Differential display in rat livers treated for 13 weeks with phenobarbital implicates a role for metabolic and oxidative stress in nongenotoxic carcinogenicity.

    PubMed

    Elrick, Mollisa M; Kramer, Jeffrey A; Alden, Carl L; Blomme, Eric A G; Bunch, Roderick T; Cabonce, Marc A; Curtiss, Sandra W; Kier, Larry D; Kolaja, Kyle L; Rodi, Charles P; Morris, Dale L

    2005-01-01

    Hepatic enzyme inducers such as phenobarbital are often nongenotoxic rodent hepatocarcinogens. Currently, nongenotoxic hepatocarcinogens can only be definitively identified through costly and extensive long-term, repeat-dose studies (e.g., 2-year rodent carcinogenicity assays). Although liver tumors caused by these compounds are often not found to be relevant to human health, the mechanism(s) by which they cause carcinogenesis are not well understood. Toxicogenomic technologies represent a new approach to understanding the molecular bases of toxicological liabilities such asnongenotoxic carcinogenicity early in the drug discovery/development process. Microarrays have been used to identify mechanistic molecular markers of nongenotoxic rodent hepatocarcinogenesis in short-term, repeat-dose preclinical safety studies. However, the initial "noise" of early adaptive changes may confound mechanistic interpretation of transcription profiling data from short-term studies, and the molecular processes triggered by treatment with a xenobiotic agent are likely to change over the course of long-term treatment. Here, we describe the use of a differential display technology to understand the molecular mechanisms related to 13 weeks of dosing with the prototype rodent nongenotoxic hepatocarcinogen, phenobarbital. These findings implicate a continuing role for oxidative stress in nongenotoxic carcinogenicity.An Excel data file containing raw data is available in full at http://taylorandfrancis.metapress.com/openurl.asp?genre=journal&issn=0192-6233. Click on the issue link for 33(1), then select this article. A download option appears at the bottom of this abstract. The file contains raw data for all gene changes detected by AFLP, including novel genes and genes of unknown function; sequences of detected genes; and animal body and liver weight ratios. In order to access the full article online, you must either have an individual subscription or a member subscription accessed through

  13. B-type natriuretic peptide and high sensitive C-reactive protein predict 2-year all cause mortality in chest pain patients: a prospective observational study from Salta, Argentina

    PubMed Central

    2011-01-01

    Background Several mechanisms are involved in the pathophysiology of the Acute Coronary Syndrome (ACS). We have addressed whether B-type natriuretic peptide (BNP) and high-sensitive C-reactive protein (hsCRP) in admission samples may improve risk stratification in chest pain patients with suspected ACS. Methods We included 982 patients consecutively admitted with chest pain and suspected ACS at nine hospitals in Salta, Northern Argentina. Total and cardiac mortality were recorded during a 2-year follow up period. Patients were divided into quartiles according to BNP and hsCRP levels, respectively, and inter quartile differences in mortality were statistically evaluated applying univariate and multivariate analyses. Results 119 patients died, and the BNP and hsCRP levels were significantly higher among these patients than in survivors. In a multivariable Cox regression model for total death and cardiac death in all patients, the hazard ratio (HR) in the highest quartile (Q4) as compared to the lowest quartile (Q1) of BNP was 2.32 (95% confidence interval (CI), 1.24-4.35), p = 0.009 and 3.34 (95% CI, 1.26-8.85), p = 0.015, respectively. In the TnT positive patients (TnT > 0.01 ng/mL), the HR for total death and cardiac death in Q4 as compared to Q1 was 2.12 (95% CI, 1.07-4.18), p = 0.031 and 3.42 (95% CI, 1.13-10.32), p = 0.029, respectively. The HR for total death for hsCRP in Q4 as compared to Q1 was 1.97 (95% CI, 1.17-3.32), p = 0.011, but this biomarker did not predict cardiac death (p = 0.21). No prognostic impact of these two biomarkers was found in the TnT negative patients. Conclusion BNP and hsCRP may act as clinically useful biomarkers when obtained at admission in a population with suspected ACS. Trial Registration ClinicalTrials.gov Identifier: NCT01377402. PMID:21958326

  14. Infantile Amnesia across the Years: A 2-Year Follow-Up of Children's Earliest Memories

    ERIC Educational Resources Information Center

    Peterson, Carole; Warren, Kelly L.; Short, Megan M.

    2011-01-01

    Although infantile amnesia has been investigated for many years in adults, only recently has it been investigated in children. This study was a 2-year follow-up and extension of an earlier study. Children (4-13 years old) were asked initially and 2 years later for their earliest 3 memories. At follow-up, their age at the time of these memories…

  15. Clinical neuroprediction: Amygdala reactivity predicts depressive symptoms 2 years later.

    PubMed

    Mattson, Whitney I; Hyde, Luke W; Shaw, Daniel S; Forbes, Erika E; Monk, Christopher S

    2016-06-01

    Depression is linked to increased amygdala activation to neutral and negatively valenced facial expressions. Amygdala activation may be predictive of changes in depressive symptoms over time. However, most studies in this area have focused on small, predominantly female and homogenous clinical samples. Studies are needed to examine how amygdala reactivity relates to the course of depressive symptoms dimensionally, prospectively and in populations diverse in gender, race and socioeconomic status. A total of 156 men from predominately low-income backgrounds completed an fMRI task where they viewed emotional facial expressions. Left and right amygdala reactivity to neutral, but not angry or fearful, facial expressions relative to a non-face baseline at age 20 predicted greater depressive symptoms 2 years later, controlling for age 20 depressive symptoms. Heightened bilateral amygdala reactivity to neutral facial expressions predicted increases in depressive symptoms 2 years later in a large community sample. Neutral facial expressions are affectively ambiguous and a tendency to interpret these stimuli negatively may reflect to cognitive biases that lead to increases in depressive symptoms over time. Individual differences in amygdala reactivity to neutral facial expressions appear to identify those at most risk for a more problematic course of depressive symptoms across time. PMID:26865423

  16. Qualitative and quantitative approaches in the dose-response assessment of genotoxic carcinogens.

    PubMed

    Fukushima, Shoji; Gi, Min; Kakehashi, Anna; Wanibuchi, Hideki; Matsumoto, Michiharu

    2016-05-01

    Qualitative and quantitative approaches are important issues in field of carcinogenic risk assessment of the genotoxic carcinogens. Herein, we provide quantitative data on low-dose hepatocarcinogenicity studies for three genotoxic hepatocarcinogens: 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and N-nitrosodiethylamine (DEN). Hepatocarcinogenicity was examined by quantitative analysis of glutathione S-transferase placental form (GST-P) positive foci, which are the preneoplastic lesions in rat hepatocarcinogenesis and the endpoint carcinogenic marker in the rat liver medium-term carcinogenicity bioassay. We also examined DNA damage and gene mutations which occurred through the initiation stage of carcinogenesis. For the establishment of points of departure (PoD) from which the cancer-related risk can be estimated, we analyzed the above events by quantitative no-observed-effect level and benchmark dose approaches. MeIQx at low doses induced formation of DNA-MeIQx adducts; somewhat higher doses caused elevation of 8-hydroxy-2'-deoxyquanosine levels; at still higher doses gene mutations occurred; and the highest dose induced formation of GST-P positive foci. These data indicate that early genotoxic events in the pathway to carcinogenesis showed the expected trend of lower PoDs for earlier events in the carcinogenic process. Similarly, only the highest dose of IQ caused an increase in the number of GST-P positive foci in the liver, while IQ-DNA adduct formation was observed with low doses. Moreover, treatment with DEN at low doses had no effect on development of GST-P positive foci in the liver. These data on PoDs for the markers contribute to understand whether genotoxic carcinogens have a threshold for their carcinogenicity. The most appropriate approach to use in low dose-response assessment must be approved on the basis of scientific judgment.

  17. Role of Cytochrome P450 Monooxygenase in Carcinogen and Chemotherapeutic Drug Metabolism.

    PubMed

    Wahlang, B; Falkner, K Cameron; Cave, Matt C; Prough, Russell A

    2015-01-01

    The purpose of this chapter is to provide insight into which human cytochromes P450 (CYPs) may be involved in metabolism of chemical carcinogens and anticancer drugs. A historical overview of this field and the development of literature using relevant animal models and expressed human CYPs have provided information about which specific CYPs may be involved in carcinogen metabolism. Definition of the biochemical properties of CYP activity came from several groups who studied the reaction stoichiometry of butter yellow and benzo[α]pyrene, including their role in induction of these enzyme systems. This chapter will list as much as is known about the human CYPs involved in carcinogen and anticancer drug metabolism, as well as summarize studies with rodent CYPs. A review of three major classes of anticancer drugs and their metabolism in humans is covered for cyclophosphamide, procarbazine, and anthracycline antibiotics, cancer chemotherapeutic compounds extensively metabolized by CYPs. The emerging information about human CYP gene polymorphisms as well as other enzymes involved in foreign compound metabolism provides considerable information about how these genetic variants affect carcinogen and anticancer drug metabolism. With information available from individual's genomic sequences, consideration of populations who may be at risk due to environmental exposure to carcinogens or how to optimize their cancer therapy regimens to enhance efficacy of the anticancer drugs appears to be an important field of study to benefit individuals in the future. PMID:26233902

  18. Erionite series minerals: mineralogical and carcinogenic properties.

    PubMed

    Dogan, A Umran; Dogan, Meral; Hoskins, John A

    2008-08-01

    Erionite is a human and animal carcinogen and one of the most toxic minerals known. Erionite deposits have been reported in many countries; however, it is only in the area of three villages of Cappadocia, Turkey, that environmental exposure to erionite has been demonstrated to be the cause of an epidemic of the disease mesothelioma. In the USA, no cases of mesothelioma have been reliably proven to be the result of erionite exposure, though the possibility exists. Erionite samples from three villages of the Cappadocia region were characterized mineralogically and compared with three different standards from the USA. Micro morphological details of erionite minerals using a high-resolution field-emission SEM showed that microstructures of "bundles", "fibers", and "fibrils" are important physical properties of fibrous erionite minerals. Typical lung burden of erionite and asbestos fibers were compared in terms of number of fibers. Assuming the lung burden of fibers in a human mesothelioma victim is about 1 mg, and the hazardous fibers are approximately 1 mum in diameter and 10 mum long, that milligram contains approximately 40 million asbestos and 50 million erionite fibers. These microstructures of erionite minerals draw attention to the concepts of surface area or surface-area-to-volume ratio and their relationship to the carcinogenicity of the mineral. The larger surface area creates a wider platform for mineral-cell interaction and thus more possibilities of proliferative transformation of mesothelial cells. Consequently, understanding the exact mineralogical properties will help determination of the true carcinogenic mechanism(s) of the mineral for prevention and possibly treatment of malignant mesothelioma.

  19. Electrochemical methods for monitoring of environmental carcinogens.

    PubMed

    Barek, J; Cvacka, J; Muck, A; Quaiserová, V; Zima, J

    2001-04-01

    The use of modern electroanalytical techniques, namely differential pulse polarography, differential pulse voltammetry on hanging mercury drop electrode or carbon paste electrode, adsorptive stripping voltammetry and high performance liquid chromatography with electrochemical detection for the determination of trace amounts of carcinogenic N-nitroso compounds, azo compounds, heterocyclic compounds, nitrated polycyclic aromatic hydrocarbons and aromatic and heterocyclic amines is discussed. Scope and limitations of these methods are described and some practical applications based on their combination with liquid-liquid or solid phase extraction are given.

  20. Oncozoons and the search for carcinogen-indicator fishes.

    PubMed Central

    Dawe, C J

    1987-01-01

    This essay attempts to bring into perspective the importance of hereditary as well as environmental factors as potential causes of neoplasms in feral fishes. Concepts delineated by Knudson regarding hereditary cancers in man and experimental animals will probably be found operative in certain demographic units (oncozoons) among feral fishes bearing neoplasms. Hereditary factors include: antioncogenes (regulatory genes), which act as suppressors of neoplastic expression in homozygous, heterozygous, or hemizygous states, as well as constitutional (structural) genes that influence carcinogen activation or deactivation through enzyme gene products, genes that influence immunologic responses, and gene abnormalities that favor spontaneous or induced mutations. The two major classes of genes (oncogenes and antioncogenes) that influence the manifestation of cancers appear to operate through different mechanisms, but conceivable interactions have not been widely investigated, especially in tumor enzootics among feral fishes. Some explorations have been undertaken in the laboratory by Anders and collaborators in studies of suppressor genes (antioncogenes) and the cellular sarc gene (an oncogene) in melanophoromas in platyfish-swordtail hybrids and backcrosses. Some feral fish oncozoons that exhibit features of hereditary oncodemes as seen in man have been tentatively identified here as candidate systems to be studied more intensively in laboratories, particularly using cytogenetic analysis and breeding methods. In the search for carcinogen-indicator fish species in feral habitats, the traditional approach has been to survey fish populations with the aim of first finding enzootics of fish neoplasia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3297655

  1. Indoor air-assessment: Indoor concentrations of environmental carcinogens

    SciTech Connect

    Gold, K.W.; Naugle, D.F.; Berry, M.A.

    1991-01-01

    In the report, indoor concentration data are presented for the following general categories of air pollutants: radon-222, environmental tobacco smoke (ETS), asbestos, gas phase organic compounds, formaldehyde, polycyclic aromatic hydrocarbons (PAH), pesticides, and inorganic compounds. These pollutants are either known or suspect carcinogens (i.e., radon-222, asbestos) or more complex mixtures or classes of compounds which contain known or suspect carcinogens. Concentration data for individual carcinogenic compounds in complex mixtures are usually far from complete. The data presented for complex mixtures often include compounds which are not carcinogenic or for which data are insufficient to evaluate carcinogenicity. Their inclusion is justified, however, by the possibility that further work may show them to be carcinogens, cocarcinogens, initiators or promotors, or that they may be employed as markers (e.g., nicotine, acrolein) for the estimation of exposure to complex mixtures.

  2. Toxicity and carcinogenicity of potassium bromate--a new renal carcinogen.

    PubMed

    Kurokawa, Y; Maekawa, A; Takahashi, M; Hayashi, Y

    1990-07-01

    Potassium bromate (KBrO3) is an oxidizing agent that has been used as a food additive, mainly in the bread-making process. Although adverse effects are not evident in animals fed bread-based diets made from flour treated with KBrO3, the agent is carcinogenic in rats and nephrotoxic in both man and experimental animals when given orally. It has been demonstrated that KBrO3 induces renal cell tumors, mesotheliomas of the peritoneum, and follicular cell tumors of the thyroid. In addition, experiments aimed at elucidating the mode of carcinogenic action have revealed that KBrO3 is a complete carcinogen, possessing both initiating and promoting activities for rat renal tumorigenesis. However, the potential seems to be weak in mice and hamsters. In contrast to its weak mutagenic activity in microbial assays, KBrO3 showed relatively strong potential inducing chromosome aberrations both in vitro and in vivo. Glutathione and cysteine degrade KBrO3 in vitro; in turn, the KBrO3 has inhibitory effects on inducing lipid peroxidation in the rat kidney. Active oxygen radicals generated from KBrO3 were implicated in its toxic and carcinogenic effects, especially because KBrO3 produced 8-hydroxydeoxyguanosine in the rat kidney. A wide range of data from applications of various analytical methods are now available for risk assessment purposes.

  3. Partial lipectomy reduces dimethylhydrazine-induced carcinogenic initiation in the colon of rats.

    PubMed

    Kannen, Vinicius; Moreira, Mauro César Silveira; Waaga-Gasser, Ana Maria; Modiano, Patricia; Elias Junior, Jorge; Fernandes, Cleverson R; Garcia, Sérgio B

    2014-02-28

    This study investigated whether visceral adipose tissue directly modulates the development of preneoplastic lesions in the colon of carcinogen-treated rats. Wistar rats (n=64) were randomly assigned to 8 experimental groups in two experiments. In one experiment, 32 rats were exposed or not to either carcinogen treatment (dimethylhydrazine, DMH; 125 mg/kg) or high-fat diet (standard chow enriched with 14% lard) or both for 56 days. In a second experiment, 32 rats were exposed to a carcinogen or they underwent partial lipectomy or both for 30 days (partial lipectomy groups underwent ablation of mesenteric and parametrial fat pads, whereas sham groups did not; all rats were fed with standard chow). Colon was collected for histopathological analysis. After 56 experimental days a high-fat diet increased carcinogenic mutations in the colonic epithelia. Partial lipectomy reduced weight gain in carcinogen-exposed rats and decreased the de novo formation of mesenteric and parametrial fat pads. Partial lipectomy significantly inhibited the mutational process after 30 days: there were fewer colonic preneoplastic lesions and less proliferation, apoptosis, and inflammation. These data suggest that visceral adipose tissue promotes colon carcinogenesis and enhances the establishment and expansion of genetically mutated cells in colonic epithelia.

  4. Quantitative structure carcinogenicity relationship for detecting structural alerts in nitroso-compounds

    SciTech Connect

    Helguera, Aliuska Morales; Gonzalez, Maykel Perez . E-mail: mpgonzalez76@yahoo.es; Cordeiro, Maria Natalia D.S.; Perez, Miguel Angel Cabrera

    2007-06-01

    Prevention of environmentally induced cancers is a major health problem of which solutions depend on the rapid and accurate screening of potential chemical hazards. Lately, theoretical approaches such as the one proposed here - Quantitative Structure-Activity Relationship (QSAR) - are increasingly used for assessing the risks of environmental chemicals, since they can markedly reduce costs, avoid animal testing, and speed up policy decisions. This paper reports a QSAR study based on the Topological Substructural Molecular Design (TOPS-MODE) approach, aiming at predicting the rodent carcinogenicity of a set of nitroso-compounds selected from the Carcinogenic Potency Data Base (CPDB). The set comprises nitrosoureas (14 chemicals), N-nitrosamines (18 chemicals) C-nitroso-compounds (1 chemical), nitrosourethane (1 chemical) and nitrosoguanidine (1 chemical), which have been bioassayed in male rat using gavage as the route of administration. Here we are especially concerned in gathering the role of both parameters on the carcinogenic activity of this family of compounds. First, the regression model was derived, upon removal of one identified nitrosamine outlier, and was able to account for more than 84% of the variance in the experimental activity. Second, the TOPS-MODE approach afforded the bond contributions - expressed as fragment contributions to the carcinogenic activity - that can be interpreted and provide tools for better understanding the mechanisms of carcinogenesis. Finally, and most importantly, we demonstrate the potentialities of this approach towards the recognition of structural alerts for carcinogenicity predictions.

  5. Carcinogenic PAH in waterpipe charcoal products.

    PubMed

    Sepetdjian, Elizabeth; Saliba, Najat; Shihadeh, Alan

    2010-11-01

    Because narghile waterpipe (shisha, hooka) smoking normally involves the use of burning charcoal, smoke inhaled by the user contains constituents originating from the charcoal in addition to those from the tobacco. We have previously found that charcoal accounts for most of the polyaromatic hydrocarbons (PAH) and carbon monoxide in the smoke of the waterpipe, both of which are present in alarming quantities. Because charcoal manufacturing conditions favor formation of PAH, it is reasonable to assume that charcoal sold off the shelf may be contaminated by PAH residues. These residues may constitute a significant fraction of the PAH inhaled by the waterpipe user and those in her/his vicinity. We measured PAH residues on three kinds of raw waterpipe charcoal sampled from Beirut stores and cafés. We found that PAH residues in raw charcoal can account for more than half of the total PAH emitted in the mainstream and sidestream smoke, and about one sixth of the carcinogenic 5- and 6-ring PAH compounds. Total PAH content of the three charcoal types varied systematically by a factor of six from the charcoal with the least to the greatest PAH residue. These findings indicate the possibility of regulating charcoal carcinogen content. PMID:20807559

  6. Carcinogenic PAH in waterpipe charcoal products.

    PubMed

    Sepetdjian, Elizabeth; Saliba, Najat; Shihadeh, Alan

    2010-11-01

    Because narghile waterpipe (shisha, hooka) smoking normally involves the use of burning charcoal, smoke inhaled by the user contains constituents originating from the charcoal in addition to those from the tobacco. We have previously found that charcoal accounts for most of the polyaromatic hydrocarbons (PAH) and carbon monoxide in the smoke of the waterpipe, both of which are present in alarming quantities. Because charcoal manufacturing conditions favor formation of PAH, it is reasonable to assume that charcoal sold off the shelf may be contaminated by PAH residues. These residues may constitute a significant fraction of the PAH inhaled by the waterpipe user and those in her/his vicinity. We measured PAH residues on three kinds of raw waterpipe charcoal sampled from Beirut stores and cafés. We found that PAH residues in raw charcoal can account for more than half of the total PAH emitted in the mainstream and sidestream smoke, and about one sixth of the carcinogenic 5- and 6-ring PAH compounds. Total PAH content of the three charcoal types varied systematically by a factor of six from the charcoal with the least to the greatest PAH residue. These findings indicate the possibility of regulating charcoal carcinogen content.

  7. Occurrence, uses, and carcinogenicity of arylamines.

    PubMed

    Chung, King-Thom

    2015-01-01

    Arylamines are chemically synthesized and contained in oxidants, epoxy polymers, explosives, fungicides, pesticides, colorants, polyurethanes, and used in rubber, pharmacology, cosmetics, and other chemical industries. Many arylamines are ubiquitously present in cigarette smoke, cooking fume hoods, foods, automobile exhaust, industrial sites, etc. Some arylamines can be generated through azo reduction by intestinal, skin, and environmental microorganisms from azo dyes that are widely used. Arylamines can also be generated by reduction of the nitro-group containing polyhydrated hydrocarbons including muntions. Some arylamines are released by burning nitrogen containing organic materials at high temperatures. Some medical drugs are also arylamines. Furthermore, many arylamines are essential constituents of normal metabolism or the result of abnormal metabolism or dietary sources. Some arylamines are mutagenic, carcinogenic or the cause of other kinds of maladies. Some arylamine are considered the major etiological agents of bladder tumors in humans and animals but may also induce other types of cancers in various organs. The organ, tissue, and species specificity of the arylamine-inducing carcinogenesis may be determined by their availability, distribution, and the presence of metabolic activation/detoxicification enzymes of each organ or tissue of different species. The ubiquitous arylamines, therefore, pose serious hazards to human health and environment. This article will address the occurrence, uses, carcinogenicity, and other arylamines-induced diseases.

  8. Risk ranking priority of carcinogenic and/or genotoxic environmental contaminants in food in Belgium.

    PubMed

    Vromman, V; Maghuin-Rogister, G; Vleminckx, C; Saegerman, C; Pussemier, L; Huyghebaert, A

    2014-01-01

    This paper focuses on the risks of environmental carcinogenic and/or genotoxic contaminants in food. It describes, for each contaminant studied, the carcinogenicity and genotoxicity, the toxicological reference values, the exposure and the risk characterisation. The compounds studied were classified into 3 categories based on a risk assessment. Effects others than carcinogenicity and/or genotoxicity (e.g. endocrine disruption activity) were also taken into account for the classification. Given the low margin of exposure values for arsenic and lead, these two compounds are classified as priority 1 (high concern) for food safety and as a first priority to take actions to reduce exposure. Cadmium, methylmercury, dioxins and dioxin-like polychlorinated biphenyls (PCB), non-dioxin-like PCB and toxaphene are classified as priority 2 (medium concern). Polybrominated biphenyls, chlordane, heptachlor, dichlorodiphenyltrichloroethane (DDT) and metabolites, hexachlorobenzene, hexachlorocyclohexane (lindane included), polychlorophenols and their salts are classified as priority 3 (low concern). PMID:24471940

  9. Risk ranking priority of carcinogenic and/or genotoxic environmental contaminants in food in Belgium.

    PubMed

    Vromman, V; Maghuin-Rogister, G; Vleminckx, C; Saegerman, C; Pussemier, L; Huyghebaert, A

    2014-01-01

    This paper focuses on the risks of environmental carcinogenic and/or genotoxic contaminants in food. It describes, for each contaminant studied, the carcinogenicity and genotoxicity, the toxicological reference values, the exposure and the risk characterisation. The compounds studied were classified into 3 categories based on a risk assessment. Effects others than carcinogenicity and/or genotoxicity (e.g. endocrine disruption activity) were also taken into account for the classification. Given the low margin of exposure values for arsenic and lead, these two compounds are classified as priority 1 (high concern) for food safety and as a first priority to take actions to reduce exposure. Cadmium, methylmercury, dioxins and dioxin-like polychlorinated biphenyls (PCB), non-dioxin-like PCB and toxaphene are classified as priority 2 (medium concern). Polybrominated biphenyls, chlordane, heptachlor, dichlorodiphenyltrichloroethane (DDT) and metabolites, hexachlorobenzene, hexachlorocyclohexane (lindane included), polychlorophenols and their salts are classified as priority 3 (low concern).

  10. [Mapping of carcinogens in the chemical production industry in the province of Ferrara].

    PubMed

    Maldotti, M; Spagnolo, M R; Minisci, S; De Rosa, E

    2008-01-01

    This study consists in the reconnaissance of the carcinogenic risk in some processing in Ferrara. The main object is to know, to estimate and to verify the diffusion of the carcinogenic substances and to estimate the number of the exposed or potentially exposed workers. The study has interested the synthesis chemistry and polymer production, woodworking, welding on stainless steel and chromium conversion coating and chrome electroplating. The research has involved 54 factories and 436 workers estimated exposed or potentially exposed to carcinogenic substances. The survey has consisted of inspections in the working places, collection of exposure data, control of the precautionary measures and exposure determination in the case of stainless steel welding. The smallest factories had less knowledge of the risk and for this reason it is necessary to keep constant attention.

  11. Hepatic metabolism of carcinogenic β-asarone.

    PubMed

    Cartus, Alexander T; Stegmüller, Simone; Simson, Nadine; Wahl, Andrea; Neef, Sylvia; Kelm, Harald; Schrenk, Dieter

    2015-09-21

    β-Asarone (1) belongs to the group of naturally occurring phenylpropenes like eugenol or anethole. Compound 1 is found in several plants, e.g., Acorus calamus or Asarum europaeum. Compound 1-containing plant materials and essential oils thereof are used to flavor foods and alcoholic beverages and as ingredients of many drugs in traditional phytomedicines. Although 1 has been claimed to have several positive pharmacological effects, it was found to be genotoxic and carcinogenic in rodents (liver and small intestine). The mechanism of action of carcinogenic allylic phenylpropenes consists of the metabolic activation via cytochrome P450 enzymes and sulfotransferases. In vivo experiments suggested that this pathway does not play a major role in the carcinogenicity of the propenylic compound 1 as is the case for other propenylic compounds, e.g., anethole. Since the metabolic pathways of 1 have not been investigated and its carcinogenic mode of action is unknown, we investigated the metabolism of 1 in liver microsomes of rats, bovines, porcines, and humans using (1)H NMR, HPLC-DAD, and LC-ESI-MS/MS techniques. We synthesized the majority of identified metabolites which were used as reference compounds for the quantification and final verification of metabolites. Microsomal epoxidation of the side chain of 1 presumably yielded (Z)-asarone-1',2'-epoxide (8a) which instantly was hydrolyzed to the corresponding erythro- and threo-configurated diols (9b, 9a) and the ketone 2,4,5-trimethoxyphenylacetone (13). This was the main metabolic pathway in the metabolism of 1 in all investigated liver microsomes. Hydroxylation of the side chain of 1 led to the formation of three alcohols at total yields of less than 30%: 1'-hydroxyasarone (2), (E)- and (Z)-3'-hydroxyasarone (4 and 6), with 6 being the mainly formed alcohol and 2 being detectable only in liver microsomes of Aroclor 1254-pretreated rats. Small amounts of 4 and 6 were further oxidized to the corresponding carbonyl

  12. The liver fluke Opisthorchis felineus: biology, epidemiology and carcinogenic potential.

    PubMed

    Pakharukova, Mariya Y; Mordvinov, Viatcheslav A

    2016-01-01

    The liver fluke Opisthorchis felineus is a member of the triad of epidemiologically important liver fluke species belonging to the family Opisthorchiidae and the major agent causing opisthorchiasis over a vast territory, covering Russia, Kazakhstan and several European countries. The similarity between the diseases caused by O. felineus and other liver flukes, O. viverrini and Clonorchis sinensis, in clinical manifestations and course suggests that the scenarios of their development and, possibly, complications have much in common. The International Agency for Research on Cancer classified O. viverrini and C. sinensis as group 1 agents and the major factors inducing cholangiocarcinoma in endemic regions. However, a carcinogenic potential of O. felineus is poorly studied. This review characterizes O. felineus, briefs the epidemiological situation in Western Siberia, the world's largest opisthorchiasis focus, and assesses the carcinogenic potential of this liver fluke. The review is based on a comprehensive analysis of the published medical data on opisthorchiasis and its complications in Western Siberia. Results of performed analysis reflect the actual epidemiological situation in opisthorchiasis focus and suggest an association of this disease with bile duct cancer. PMID:26740360

  13. Evidence supporting product standards for carcinogens in smokeless tobacco products

    PubMed Central

    Hatsukami, Dorothy K.; Stepanov, Irina; Severson, Herb; Jensen, Joni A.; Lindgren, Bruce R.; Horn, Kimberly; Khariwala, Samir S.; Martin, Julia; Carmella, Steven G.; Murphy, Sharon E.; Hecht, Stephen S.

    2014-01-01

    Smokeless tobacco (ST) products sold in the U.S. vary significantly in yields of nicotine and tobacco-specific nitrosamines (TSNA). With the passage of the Family Smoking Prevention and Tobacco Control Act, the Food and Drug Administration now has the authority to establish product standards. However, limited data exist determining the relative roles of pattern of ST use versus constituent levels in the ST product in exposure of users to carcinogens. In this study, ST users of brands varying in nicotine and TSNA content were recruited from three different regions in the U.S. Participants underwent two assessment sessions. During these sessions, demographic and ST use history information along with urine samples to assess biomarkers of exposure and effect were collected. During the time between data collection, ST users recorded the amount and duration of ST use on a daily basis using their diary cards. Results showed that independent of pattern of ST use and nicotine yields, levels of TSNA in ST products played a significant role in carcinogen exposure levels. Product standards for reducing levels of TSNA in ST products are necessary to decrease exposure to these toxicants and potentially to reduce risk for cancer. PMID:25524878

  14. Systems biology perspectives on the carcinogenic potential of radiation

    PubMed Central

    Barcellos-Hoff, Mary Helen; Adams, Cassandra; Balmain, Allan; Costes, Sylvain V.; Demaria, Sandra; Illa-Bochaca, Irineu; Mao, Jian Hua; Ouyang, Haoxu; Sebastiano, Christopher; Tang, Jonathan

    2014-01-01

    This review focuses on recent experimental and modeling studies that attempt to define the physiological context in which high linear energy transfer (LET) radiation increases epithelial cancer risk and the efficiency with which it does so. Radiation carcinogenesis is a two-compartment problem: ionizing radiation can alter genomic sequence as a result of damage due to targeted effects (TE) from the interaction of energy and DNA; it can also alter phenotype and multicellular interactions that contribute to cancer by poorly understood non-targeted effects (NTE). Rather than being secondary to DNA damage and mutations that can initiate cancer, radiation NTE create the critical context in which to promote cancer. Systems biology modeling using comprehensive experimental data that integrates different levels of biological organization and time-scales is a means of identifying the key processes underlying the carcinogenic potential of high-LET radiation. We hypothesize that inflammation is a key process, and thus cancer susceptibility will depend on specific genetic predisposition to the type and duration of this response. Systems genetics using novel mouse models can be used to identify such determinants of susceptibility to cancer in radiation sensitive tissues following high-LET radiation. Improved understanding of radiation carcinogenesis achieved by defining the relative contribution of NTE carcinogenic effects and identifying the genetic determinants of the high-LET cancer susceptibility will help reduce uncertainties in radiation risk assessment.

  15. Predicting carcinogenicity of organic compounds based on CPDB.

    PubMed

    Wu, Xiuchao; Zhang, Qingzhu; Wang, Hui; Hu, Jingtian

    2015-11-01

    Cancer is a major killer of human health and predictions for the carcinogenicity of chemicals are of great importance. In this article, predictive models for the carcinogenicity of organic compounds using QSAR methods for rats and mice were developed based on the data from CPDB. The models was developed based on the data of specific target site liver and classified according to sex of rats and mice. Meanwhile, models were also classified according to whether there is a ring in the molecular structure in order to reduce the diversity of molecular structure. Therefore, eight local models were developed in the final. Taking into account the complexity of carcinogenesis and in order to obtain as much information, DRAGON descriptors were selected as the variables used to develop models. Fitting ability, robustness and predictive power of the models were assessed according to the OECD principles. The external predictive coefficients for validation sets of each model were in the range of 0.711-0.906, and for the whole data in each model were all greater than 0.8, which represents that all models have good predictivity. In order to study the mechanism of carcinogenesis, standardized regression coefficients were calculated for all predictor variables. In addition, the effect of animal sex on carcinogenesis was compared and a trend that female showed stronger tolerance for cancerogen than male in both species was appeared. PMID:26070146

  16. Carcinogenic effects of circadian disruption: an epigenetic viewpoint.

    PubMed

    Salavaty, Abbas

    2015-08-08

    Circadian rhythms refer to the endogenous rhythms that are generated to synchronize physiology and behavior with 24-h environmental cues. These rhythms are regulated by both external cues and molecular clock mechanisms in almost all cells. Disruption of circadian rhythms, which is called circadian disruption, affects many biological processes within the body and results in different long-term diseases, including cancer. Circadian regulatory pathways result in rhythmic epigenetic modifications and the formation of circadian epigenomes. Aberrant epigenetic modifications, such as hypermethylation, due to circadian disruption may be involved in the transformation of normal cells into cancer cells. Several studies have indicated an epigenetic basis for the carcinogenic effects of circadian disruption. In this review, I first discuss some of the circadian genes and regulatory proteins. Then, I summarize the current evidence related to the epigenetic modifications that result in circadian disruption. In addition, I explain the carcinogenic effects of circadian disruption and highlight its potential role in different human cancers using an epigenetic viewpoint. Finally, the importance of chronotherapy in cancer treatment is highlighted.

  17. Evidence supporting product standards for carcinogens in smokeless tobacco products.

    PubMed

    Hatsukami, Dorothy K; Stepanov, Irina; Severson, Herb; Jensen, Joni A; Lindgren, Bruce R; Horn, Kimberly; Khariwala, Samir S; Martin, Julia; Carmella, Steven G; Murphy, Sharon E; Hecht, Stephen S

    2015-01-01

    Smokeless tobacco products sold in the United States vary significantly in yields of nicotine and tobacco-specific nitrosamines (TSNA). With the passage of the Family Smoking Prevention and Tobacco Control Act, the Food and Drug Administration now has the authority to establish product standards. However, limited data exist determining the relative roles of pattern of smokeless tobacco use versus constituent levels in the smokeless tobacco product in exposure of users to carcinogens. In this study, smokeless tobacco users of brands varying in nicotine and TSNA content were recruited from three different regions in the U.S. Participants underwent two assessment sessions. During these sessions, demographic and smokeless tobacco use history information along with urine samples to assess biomarkers of exposure and effect were collected. During the time between data collection, smokeless tobacco users recorded the amount and duration of smokeless tobacco use on a daily basis using their diary cards. Results showed that independent of pattern of smokeless tobacco use and nicotine yields, levels of TSNA in smokeless tobacco products played a significant role in carcinogen exposure levels. Product standards for reducing levels of TSNA in smokeless tobacco products are necessary to decrease exposure to these toxicants and potentially to reduce risk for cancer.

  18. Data quality in predictive toxicology: reproducibility of rodent carcinogenicity experiments.

    PubMed Central

    Gottmann, E; Kramer, S; Pfahringer, B; Helma, C

    2001-01-01

    We compared 121 replicate rodent carcinogenicity assays from the two parts (National Cancer Institute/National Toxicology Program and literature) of the Carcinogenic Potency Database (CPDB) to estimate the reliability of these experiments. We estimated a concordance of 57% between the overall rodent carcinogenicity classifications from both sources. This value did not improve substantially when additional biologic information (species, sex, strain, target organs) was considered. These results indicate that rodent carcinogenicity assays are much less reproducible than previously expected, an effect that should be considered in the development of structure-activity relationship models and the risk assessment process. PMID:11401763

  19. Assessing the potential carcinogenic activity of magnetic fields using animal models.

    PubMed Central

    McCann, J; Kavet, R; Rafferty, C N

    2000-01-01

    We update our 1997 publication by reviewing 29 new reports of tests of magnetic fields (MFs) in six different in vivo animal models of carcinogenesis: 2-year, lifetime, or multigeneration exposure studies in rats or mice; and promotion/progression models (rat mammary carcinoma, rat liver focus, mouse skin, several models of human leukemia/lymphoma in rats and mice, and brain cancer in rats). Individual experiments are evaluated using a set of data quality criteria, and summary judgments are made across multiple experiments by applying a criterion of rough reproducibility. The potential for carcinogenicity of MFs is discussed in light of the significant body of carcinogenesis data from animal bioassays that now exists. Excluding abstracts, approximately 80% of the 41 completed studies identified in this and our previous review roughly satisfy data quality criteria. Among these studies, the criterion for independent reproducibility is not satisfied for any positive results but is satisfied for negative results in chronic bioassays in rats and mice and for negative results in both promotion and co-promotion assays using the SENCAR mouse skin model. Results of independent replication studies using the rat mammary carcinoma model were conflicting. We conclude that long-term exposure to continuous 50- or 60-Hz MFs in the range of 0.002-5 mT is unlikely to result in carcinogenesis in rats or mice. Though results of most promotion/progression assays are negative, a weak promoting effect of MFs under certain exposure conditions cannot be ruled out based on available data. PMID:10698725

  20. Medical Care and Your 1- to 2-Year-Old

    MedlinePlus

    ... Zika & Pregnancy Medical Care and Your 1- to 2-Year-Old KidsHealth > For Parents > Medical Care and Your 1- to 2-Year-Old Print A A A Text Size ... Following simple instructions? Saying a few words? Combining two words by age 2? The doctor may ask ...

  1. Evaluation of human health risks posed by carcinogenic and non-carcinogenic multiple contaminants associated with consumption of fish from Taihu Lake, China.

    PubMed

    Yu, Yingxin; Wang, Xinxin; Yang, Dan; Lei, Bingli; Zhang, Xiaolan; Zhang, Xinyu

    2014-07-01

    The present study estimated the human daily intake and uptake of organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), polycyclic aromatic hydrocarbons (PAHs), and toxic trace elements [mercury (Hg), chromium (Cr), cadmium (Cd), and arsenic (As)] due to consumption of fish from Taihu Lake, China, and the associated potential health risks posed by these contaminants. The health risks posed by the contaminants were assessed using a risk quotient of the fish consumption rate to the maximum allowable fish consumption rate considering the contaminants for carcinogenic and non-carcinogenic effect endpoints. The results showed that fish consumption would not pose non-cancer risks. However, some species would cause a cancer risk. Relative risks of the contaminants were calculated to investigate the contaminant which posed the highest risk to humans. As a result, in view of the contaminants for carcinogenic effects, As was the contaminant which posed the highest risk to humans. However, when non-carcinogenic effects of the contaminants were considered, Hg posed the highest risk. The risk caused by PBDEs was negligible. The results demonstrated that traditional contaminants, such as As, Hg, DDTs (dichlorodiphenyltrichloroethane and its metabolites), and PCBs, require more attention in Taihu Lake than the other target contaminants. PMID:24727049

  2. Evaluation of human health risks posed by carcinogenic and non-carcinogenic multiple contaminants associated with consumption of fish from Taihu Lake, China.

    PubMed

    Yu, Yingxin; Wang, Xinxin; Yang, Dan; Lei, Bingli; Zhang, Xiaolan; Zhang, Xinyu

    2014-07-01

    The present study estimated the human daily intake and uptake of organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), polycyclic aromatic hydrocarbons (PAHs), and toxic trace elements [mercury (Hg), chromium (Cr), cadmium (Cd), and arsenic (As)] due to consumption of fish from Taihu Lake, China, and the associated potential health risks posed by these contaminants. The health risks posed by the contaminants were assessed using a risk quotient of the fish consumption rate to the maximum allowable fish consumption rate considering the contaminants for carcinogenic and non-carcinogenic effect endpoints. The results showed that fish consumption would not pose non-cancer risks. However, some species would cause a cancer risk. Relative risks of the contaminants were calculated to investigate the contaminant which posed the highest risk to humans. As a result, in view of the contaminants for carcinogenic effects, As was the contaminant which posed the highest risk to humans. However, when non-carcinogenic effects of the contaminants were considered, Hg posed the highest risk. The risk caused by PBDEs was negligible. The results demonstrated that traditional contaminants, such as As, Hg, DDTs (dichlorodiphenyltrichloroethane and its metabolites), and PCBs, require more attention in Taihu Lake than the other target contaminants.

  3. Detection of mutagenic/carcinogenic compounds in unused and used motor oils.

    PubMed

    Pasquini, R; Monarca, S

    1983-12-15

    The discharge of used motor oils in the environment poses public health problems because of the mutagenic/carcinogenic compounds in them. Among these hazardous chemicals, polycyclic aromatic hydrocarbons (PAH) are of particular interest since the carcinogenic properties of some of them are known. The authors have applied the Salmonella/microsome test, coupled with two preparation methods of samples, to motor oils of different brands, both before and after use in car petrol engines. A PAH determination method was also studied. The results showed the unused motor oils to be nonmutagenic and to contain traces of PAH, while the used motor oils of the samples taken according to both preparation methods were highly mutagenic and contained a much higher quantity of mutagenic/carcinogenic PAH.

  4. A review of the genotoxic and carcinogenic effects of aspartame: does it safe or not?

    PubMed

    Yılmaz, Serkan; Uçar, Aslı

    2014-12-01

    The objective of this article is to review genotoxicologic and carcinogenic profile of the artificial sweetener aspartame. Aspartame is a synthetic dipeptide, nearly 180-200 times sweeter than sucrose. It is the most widely used artificial sweetener especially in carbonated and powdered soft drinks, beverages, drugs and hygiene products. There is a discussion ongoing for many years whether aspartame posses genotoxic and carcinogenic risk for humans. This question led to many studies to specify the adverse effects of aspartame. Therefore, we aimed to review the oldest to latest works published in major indices to gather information within this article. With respect to published data, genotoxicity and carcinogenicity of aspartame is still confusing. So, consumers should be aware of the potential side effects of aspartame before they consume it.

  5. Genotoxicity and potential carcinogenicity of 2,4,6-TNT trinitrotoluene: structural and toxicological considerations.

    PubMed

    Bolt, Hermann M; Degen, Gisela H; Dorn, Susanne B; Plöttner, Sabine; Harth, Volker

    2006-01-01

    Environmental contamination with 2,4,6-TNT (trinitrotoluene) represents a worldwide problem. Concern for carcinogenicity can be derived from chemically related compounds, especially the dinitrotoluenes. In the metabolism of TNT, the reductive routes are preponderant. The main urinary metabolites of TNT are 4-amino-2,6-dinitrotoluene and 2-amino-4,6-dinitrotoluene. In humans exposed to TNT, the formation of hemoglobin adducts of the amino-dinitrotoluenes is in general concordance with the ratio of urinary excretion. The variations in quantities of excreted metabolites among the different occupational cohorts studied are likely explained by the different routes of exposure to TNT, including dermal uptake. Most studies show that urinary excretion of the amino-dinitrotoluenes (4-amino-dinitrotoluene plus 2-amino-dinitrotoluene) in a range of 1 to 10 mg L(-1) (5-50 microM) are not uncommon--for instance in persons employed with the disposal of military waste. Trinitotoluene is mutagenic in Salmonella typhimurium strains TA98 and TA100, with and without exogenous metabolic activation. Mutagenic activity has been found in urine from workers who were occupationally exposed to TNT. An unpublished 2-year study was reported in 1984 by the IIT Research Institute, Chicago, IL. Fischer 344 rats were fed diets containing 0.4, 2.0, 10, or 50 mg/kg TNT per day. In the urinary bladder, hyperplasia (12 of 47 animals p < .01) and carcinoma (11 of 47 animals, p < .05) were observed at significant levels in high-dose (50 mg kg(-1)) females and in one or two females, respectively, at 10 mg kg(-1). Taking all the available evidence together, the appropriate precautions should be taken.

  6. Immunogenicity, Safety, and Tolerability of 13-Valent Pneumococcal Conjugate Vaccine Followed by 23-Valent Pneumococcal Polysaccharide Vaccine in Recipients of Allogeneic Hematopoietic Stem Cell Transplant Aged ≥2 Years: An Open-Label Study

    PubMed Central

    Cordonnier, Catherine; Ljungman, Per; Juergens, Christine; Maertens, Johan; Selleslag, Dominik; Sundaraiyer, Vani; Giardina, Peter C.; Clarke, Keri; Gruber, William C.; Scott, Daniel A.; Schmoele-Thoma, Beate

    2015-01-01

    Background. Life-threatening Streptococcus pneumoniae infections often occur after hematopoietic stem cell transplant (HSCT); vaccination is important for prevention. Methods. In an open-label study, patients (n = 251) 3–6 months after allogeneic HSCT received 3 doses of 13-valent pneumococcal conjugate vaccine (PCV13) at 1-month intervals, a fourth dose 6 months later, and 1 dose of 23-valent pneumococcal polysaccharide vaccine (PPSV23) 1 month later. Immunogenicity at prespecified time points and vaccine safety were assessed. Results. In the evaluable immunogenicity population (N = 216; mean age, 37.8 years), geometric mean fold rises (GMFRs) of immunoglobulin G geometric mean concentrations from baseline to postdose 3 showed significant increases in antibody levels across all PCV13 serotypes (GMFR range, 2.99–23.85; 95% confidence interval lower limit, >1); there were significant declines over the next 6 months, significant increases from predose 4 to postdose 4 (GMFR range, 3.00–6.97), and little change after PPSV23 (GMFR range, 0.86–1.12). Local and systemic reactions were more frequent after dose 4. Six patients experienced serious adverse events possibly related to PCV13 (facial diplegia, injection-site erythema and pyrexia, autoimmune hemolytic anemia, and suspected lack of vaccine efficacy after dose 3 leading to pneumococcal infection), PCV13 and PPSV23 (Guillain-Barré syndrome), or PPSV23 (cellulitis). There were 14 deaths, none related to study vaccines. Conclusions. A 3-dose PCV13 regimen followed by a booster dose may be required to protect against pneumococcal disease in HSCT recipients. Dose 4 was associated with increased local and systemic reactions, but the overall safety profile of a 4-dose regimen was considered acceptable. Clinical Trials Registration. NCT00980655. PMID:25870329

  7. Carcinogenic and cocarcinogenic effects of inhaled synthetic smog and ferric oxide particles.

    PubMed

    Nettesheim, P; Creasia, D A; Mitchell, T J

    1975-07-01

    The carcinogenic and cocarcinogenic activity of synthetic smog, ferric oxide (Fe2O3) dust, and a mixture of the two air contaminants was determined in a long-term inhalation study with Syrian hamsters. Inhaled Fe2O3 particles definitely enhanced diethylnitrosamine tumorigenicity in the peripheral lung. Synthetic smog did not. When tested at a concentration of 40 ppm methane equivalents or 40 mg/m3, respectively, neither air pollutant by itself appeared carcinogenic. Fe2O3 caused pulmonary fibrosis and synthetic smog caused alveolar bronchiolization in many of the exposed animals.

  8. An evaluation of 6 short-term tests for detecting organic chemical carcinogens.

    PubMed Central

    Purchase, I. F.; Longstaff, E.; Ashby, J.; Styles, J. A.; Anderson, D.; Lefevre, P. A.; Westwood, F. R.

    1978-01-01

    A number of tests have been described which are thought to be capable of identifying carcinogens without using the actual induction of cancer as an endpoint. This study compared the performance of 6 such tests on a selection of 120 organic chemicals. The tests studies were: (1) mutation of Salmonella typhimurium; (2) cell transformation; (3) degranulation of endoplasmic reticulum; (4) sebaceous gland suppression; (5) tetrazolium reduction and (6) subcutaneous implant. A further 4 tests were examined briefly, but were not included in the complete evaluation. The chemicals were classified into carcinogens (58) and non-carcinogens (62) on the basis of published experimental data, and into 1 of 4 broad chemical classes. There was considerable variation between tests in their ability to predict carcinogenicity, with the cell-transformation test and the bacterial-mutation test being the most accurate (94% and 93% accurate respectively). These 2 tests were considered to be of general use in screening, since they were clearly more accurate than the others. Statistical consideration of various combinations of these tests showed that the use of cell transformation and bacterial mutation together, provide an advantage over the use of either test alone. The inclusion of the other 4 tests in a screening battery predictably resulted in a great increase in overall inaccuracy and loss of discrimination, even though the detection of carcinogens is improved. All the tests were shown to generate both false positive and false negative results, a situation which may be controlled by the use, where possible, of appropriate chemical-class controls, to identify the test which is optimal for the class of chemical under test. Structural analogy may have a part to play in the rapid detection of environmental carcinogens, and some general guidelines for its use are given. PMID:354672

  9. Genotoxicity of Swimming Pool Water and Carcinogenicity of Drinking Water

    EPA Science Inventory

    Among the 11 disinfection by-products (DBPs) in drinking water that are regulated by the U.S. EPA, (a) 2 DBPs (chloroaceticacid and chlorite) are not carcinogenic-in either of2 species; (b) chlorite is not carcinogenic in 3 rodent assays and has never been tested for genotoxicity...

  10. Genotoxicity of Swimming Pool Water and Carcinogenicity of Drinking Water**

    EPA Science Inventory

    Among the 11 disinfection by-products (DBPs) in drinking water that are regulated by the U.S. EPA, (a) 2 DBPs (chloroaceticacid and chlorite) are not carcinogenic-in either of2 species; (b) chlorite is not carcinogenic in 3 rodent assays and has never been tested for genotoxicity...

  11. 29 CFR 1915.1003 - 13 carcinogens (4-Nitrobiphenyl, etc.).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 7 2013-07-01 2013-07-01 false 13 carcinogens (4-Nitrobiphenyl, etc.). 1915.1003 Section 1915.1003 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION... Hazardous Substances § 1915.1003 13 carcinogens (4-Nitrobiphenyl, etc.). Note: The requirements...

  12. 29 CFR 1926.1103 - 13 carcinogens (4-Nitrobiphenyl, etc.).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 8 2014-07-01 2014-07-01 false 13 carcinogens (4-Nitrobiphenyl, etc.). 1926.1103 Section 1926.1103 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION... § 1926.1103 13 carcinogens (4-Nitrobiphenyl, etc.). Note: The requirements applicable to...

  13. 29 CFR 1926.1103 - 13 carcinogens (4-Nitrobiphenyl, etc.).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 8 2013-07-01 2013-07-01 false 13 carcinogens (4-Nitrobiphenyl, etc.). 1926.1103 Section 1926.1103 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION... § 1926.1103 13 carcinogens (4-Nitrobiphenyl, etc.). Note: The requirements applicable to...

  14. 29 CFR 1915.1003 - 13 carcinogens (4-Nitrobiphenyl, etc.).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 7 2011-07-01 2011-07-01 false 13 carcinogens (4-Nitrobiphenyl, etc.). 1915.1003 Section 1915.1003 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION... Hazardous Substances § 1915.1003 13 carcinogens (4-Nitrobiphenyl, etc.). Note: The requirements...

  15. 29 CFR 1926.1103 - 13 carcinogens (4-Nitrobiphenyl, etc.).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 8 2012-07-01 2012-07-01 false 13 carcinogens (4-Nitrobiphenyl, etc.). 1926.1103 Section 1926.1103 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION... § 1926.1103 13 carcinogens (4-Nitrobiphenyl, etc.). Note: The requirements applicable to...

  16. 29 CFR 1926.1103 - 13 carcinogens (4-Nitrobiphenyl, etc.).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 8 2010-07-01 2010-07-01 false 13 carcinogens (4-Nitrobiphenyl, etc.). 1926.1103 Section 1926.1103 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION... § 1926.1103 13 carcinogens (4-Nitrobiphenyl, etc.). Note: The requirements applicable to...

  17. 29 CFR 1915.1003 - 13 carcinogens (4-Nitrobiphenyl, etc.).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 7 2010-07-01 2010-07-01 false 13 carcinogens (4-Nitrobiphenyl, etc.). 1915.1003 Section 1915.1003 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION... Hazardous Substances § 1915.1003 13 carcinogens (4-Nitrobiphenyl, etc.). Note: The requirements...

  18. 29 CFR 1915.1003 - 13 carcinogens (4-Nitrobiphenyl, etc.).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 7 2014-07-01 2014-07-01 false 13 carcinogens (4-Nitrobiphenyl, etc.). 1915.1003 Section 1915.1003 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION... Hazardous Substances § 1915.1003 13 carcinogens (4-Nitrobiphenyl, etc.). Note: The requirements...

  19. 29 CFR 1926.1103 - 13 carcinogens (4-Nitrobiphenyl, etc.).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 8 2011-07-01 2011-07-01 false 13 carcinogens (4-Nitrobiphenyl, etc.). 1926.1103 Section 1926.1103 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION... § 1926.1103 13 carcinogens (4-Nitrobiphenyl, etc.). Note: The requirements applicable to...

  20. 29 CFR 1915.1003 - 13 carcinogens (4-Nitrobiphenyl, etc.).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 7 2012-07-01 2012-07-01 false 13 carcinogens (4-Nitrobiphenyl, etc.). 1915.1003 Section 1915.1003 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION... Hazardous Substances § 1915.1003 13 carcinogens (4-Nitrobiphenyl, etc.). Note: The requirements...

  1. Workshop on problem areas associated with developing carcinogen guidelines

    SciTech Connect

    Not Available

    1984-06-01

    A workshop was conducted to discuss problem areas associated with developing carcinogen guidelines. Session topics included (1) definition of a carcinogen for regulatory purposes; (2) potency; (3) risk assessment; (4) uncertainties; (5) de minimis quantity; and (6) legal and regulatory issues. Separate abstracts have been prepared for individual papers. (ACR)

  2. General preventive measures against carcinogenic exposure in the external environment.

    PubMed

    Keiding, L M

    1993-01-01

    Different measures are used to prevent unacceptable carcinogenic exposure from different sources in the external environment, be it accumulated carcinogens from previo