Science.gov

Sample records for 2-year carcinogenicity studies

  1. Historical control data of neoplastic lesions in the Wistar Hannover Rat among eight 2-year carcinogenicity studies.

    PubMed

    Carlus, Marine; Elies, Laëtitia; Fouque, Marie-Claude; Maliver, Pierre; Schorsch, Frédéric

    2013-03-01

    Incidences of neoplastic lesions were evaluated in untreated Hannover Wistar Rats RjHan: WI (470 males and 470 females) used as control animals in eight carcinogenicity studies. All these studies were performed in a similar environment either for the in vivo and the postmortem evaluation. The major neoplastic lesions were found in the endocrine, integumentary and reproductive systems. Pituitary adenoma was the most frequent neoplasm and occurred in 33.9% of the males and 54.6% of the female rats. The other most frequent tumors in males were thyroid C-cell adenoma (8.6%), pancreatic islet cell adenoma (8.1%), subcutaneous fibrosarcoma (6.6%), subcutaneous fibroma (4.7%), benign pheochromocytoma (3.4%), and cutaneous keratoacanthoma (3.4%). In females, the other highest incidences were mammary fibroadenoma (29%), uterine endometrial stromal polyp (18.1%), mammary adenocarcinoma (14.2%), mammary fibroadenoma with atypia (13.7%), thyroid C-cell adenoma (7.5%), benign thymoma (3.7%), and subcutaneous fibrosarcoma (3.6%). All these data were compared to previously published historical control data. This retrospective analysis was undergone in order to illustrate the result of a stable organization which guarantees a robust historical data base for neoplastic and non neoplastic findings.

  2. Techniques for carcinogenicity studies.

    PubMed

    Weisburger, E K

    1981-09-01

    Short-term tests to detect genetic, chromosomal, or DNA damage are now required by regulatory agencies for any new compound proposed for commercial production. Furthermore, full-scale carcinogenicity tests may be required for certain compounds. In this circumstance, the compound-related factors including stability, purity, physical properties, and chemical structure and reactivity must be considered. Animal factors include species and strain of test animal, route of administration, age, sex, diet, and spontaneous tumor incidence. A team of qualified investigators with experience in various disciplines is required to conduct the studies properly. Quality control measures and adherence to the code of good laboratory practice are also necessary during all phases of the study. The investment in a carcinogenicity study therefore becomes fairly substantial in terms of both time and money.

  3. 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...

  4. No carcinogenicity of ethyl tertiary-butyl ether by 2-year oral administration in rats.

    PubMed

    Suzuki, Masaaki; Yamazaki, Kazunori; Kano, Hirokazu; Aiso, Shigetoshi; Nagano, Kasuke; Fukushima, Shoji

    2012-01-01

    The carcinogenicity of ethyl tertiary-butyl ether (ETBE) was examined by oral administration using F344/DuCrlCrlj rats. Groups of 50 male and 50 female rats were given drinking water containing ETBE at doses of 0, 625, 2,500 or 10,000 ppm (w/w) for 104 weeks. No significant increase in the incidence of tumors was detected in any organ of either sex. Rat-specific non-neoplastic lesions were observed in the kidney: An increase in the severity of chronic progressive nephropathy was observed in the male and female 10,000 ppm groups, and increased incidences of urothelial hyperplasia of the pelvis and mineral deposition in the renal papilla were observed in the male 2,500 and 10,000 ppm groups. Besides these lesions, no treatment-related histopathological changes were observed in any organ or tissue in either sex. Thus, the present study demonstrated that a two year administration ETBE in the drinking water did not exert any carcinogenic effects in either male or female rats.

  5. Genotoxicity and carcinogenicity studies of antihistamines.

    PubMed

    Brambilla, Giovanni; Mattioli, Francesca; Robbiano, Luigi; Martelli, Antonietta

    2011-10-01

    This review provides a compendium of the results of genotoxicity and carcinogenicity assays performed on marketed antihistamines. Of the 70 drugs examined, 29 (41.4%) have at least one genotoxicity and/or carcinogenicity test result: 12 tested positive in at least one genotoxicity assay, six in at least one carcinogenicity assay, and four gave a positive response in both at least one genotoxicity assay and at least one carcinogenicity assay. Of 19 drugs with both genotoxicity and carcinogenicity data, eight were neither genotoxic nor carcinogenic, two were carcinogenic in at least one sex of mice or rats but tested negative in genotoxicity assays, five tested positive in at least one genotoxicity assay but were non-carcinogenic, and four gave a positive response in at least one genotoxicity assay and in at least one carcinogenicity assay. Only 12 (17.1%) of the 70 drugs examined have all data required by present guidelines for testing of pharmaceuticals, but it should be considered that a large fraction of them were developed and marketed prior the present regulatory climate.

  6. 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.

  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. Lifetime carcinogenicity study of 1- and 2-naphthylamine in dogs.

    PubMed Central

    Purchase, I. F.; Kalinowski, A. E.; Ishmael, J.; Wilson, J.; Gore, C. W.; Chart, I. S.

    1981-01-01

    Groups of male and female beagle dogs were given daily doses of 400 mg of various mixtures of naphthylamines for up to 109 months. Survivors were killed at 128 months. A variety of pathological conditions was diagnosed, but the only effect related to treatment was the induction of bladder neoplasms. All dogs which received pure 2-naphthylamine developed transitional-cell carcinomas of the bladder within 34 months. Two of 8 dogs receiving 6% 2-naphthylamine in 1-naphthylamine developed early carcinoma and 2/8 dogs receiving 0.5% 2-naphthylamine in 1-naphthylamine developed haemangioma of the bladder. Some of the dogs receiving 1-naphthylamine (total dose 950 g) and the controls had focal cystitis or hyperplasia, but no neoplasia of the bladder. These results confirm the carcinogenicity of 2-naphthylamine to dogs. No carcinogenic effect of 1-naphthylamine was observed, indicating that it is at least 200 times less potent as a carcinogen than 2-naphthylamine. The incidence of bladder cancer in dogs fed mixtures of both naphthylamines explains why previous experimental and epidemiological studies of impure 1-naphthylamine have revealed carcinogenicity. Images Fig. 1 Fig. 2 PMID:7326199

  9. 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.

  10. 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.

  11. Genotoxicity and carcinogenicity studies of bronchodilators and antiasthma drugs.

    PubMed

    Brambilla, Giovanni; Mattioli, Francesca; Robbiano, Luigi; Martelli, Antonietta

    2013-05-01

    This survey is a compendium of genotoxicity and carcinogenicity information of bronchodilators and antiasthma drugs. Data from 46 marketed drugs were collected. Of these 46 drugs, 25 (54.3%) did not have retrievable genotoxicity or carcinogenicity data. The remaining 21 (45.7%) had at least one genotoxicity or carcinogenicity test result. Of these 21 drugs, 10 had at least one positive finding: three tested positive in at least one genotoxicity assay, eight in at least one carcinogenicity assay, and one of them gave positive results in both genotoxicity assay and carcinogenicity assay. Concerning the predictivity of genetic toxicology findings for the result(s) of long-term carcinogenesis assays, 15 drugs had both genotoxicity and carcinogenicity data: seven of them (46.6%) were neither genotoxic nor carcinogenic, 6 (40.0%) were carcinogenic in at least one sex of mice or rats but tested negative in genotoxicity assays, 1 (6.7%) tested positive in genotoxicity assay but was non-carcinogenic, and 1 (6.7%) gave positive responses in both genotoxicity and carcinogenicity assay. Only 11 (23.9%) of the 46 drugs considered had all data required by current guidelines for testing of pharmaceuticals, but a large fraction of them were developed and marketed prior to the present regulatory climate.

  12. Perinatal toxicity and carcinogenicity studies of styrene-acrylonitrile trimer, a ground water contaminant.

    PubMed

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

    2013-12-06

    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 1600ppm 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.

  13. 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

  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. Assessment of the carcinogenic potential of mitemcinal (GM-611): Increased incidence of malignant lymphoma in a rat carcinogenicity study

    SciTech Connect

    Fujii, Etsuko Kimura, Kazuya; Mizoguchi, Keiji; Kato, Atsuhiko; Takanashi, Hisanori; Itoh, Zen; Omura, Satoshi; Suzuki, Masami

    2008-04-01

    Mitemcinal is an erythromycin derivative, which acts as an agonist of the motilin receptor. For assessment of the carcinogenicity of mitemcinal, we conducted a short-term carcinogenicity study in p53 (+/-) C57BL/6 mice and a 104-week carcinogenicity study in CD(SD)IGS rats. There was no evidence of a carcinogenic potential in mouse when administered for 26 consecutive weeks at levels up to 250 mg/kg/day. In the rat study, an increased incidence of lymphoma was noted in 5/60 males and 8/60 females of the high dose group (60 mg/kg/day) compared to 1/60 and 0/60 in control males and females, respectively, with statistical significance in females. Rat lymphomas include different immunomorphologic types (T- or B-cell lineage). Immunohistochemical analysis revealed that lymphomas from mitemcinal-treated rats and spontaneous cases were of T-cell lineage. The overall weight of evidence suggests that the incidence of spontaneous lymphoma was enhanced in the rat study. They also indicate that the increased incidence of lymphomas was based on a non-genotoxic effect with a threshold dose-response and that the tumorigenesis was based on the strain or species specificity of background factors. The high dose in the rat study is approximately 1600-fold higher (AUC) than that of the clinical dose, a sufficient margin of safety for the clinical dose. We conclude that the risk of carcinogenesis due to mitemcinal in humans can be considered to be minimal and is to represent an acceptable risk for the continued administration of mitemcinal to humans.

  16. Studies on genotoxicity and carcinogenicity of antibacterial, antiviral, antimalarial and antifungal drugs.

    PubMed

    Brambilla, Giovanni; Mattioli, Francesca; Robbiano, Luigi; Martelli, Antonietta

    2012-07-01

    This review provides a compendium of retrievable results of genotoxicity and animal carcinogenicity studies performed of antibacterial, antiviral, antimalarial and antifungal drugs of long-term or intermittent frequent use. Of the 48 drugs considered, 9 (18.75%) do not have retrievable data, whereas the other 39 (81.25%) have at least one genotoxicity or carcinogenicity tests result. Of these 39 drugs, 24 tested positive in at least one genotoxicity assay and 19 in at least one carcinogenicity assay; 14 of them gave a positive response in both at least one genotoxicity assay and at least one carcinogenicity assay. Concerning the predictivity of genetic toxicology findings for the results of long-term carcinogenesis assays, of 23 drugs with both genotoxicity and carcinogenicity data: 2 (8.7%) were neither genotoxic nor carcinogenic, 2 (8.7%) tested positive in at least one genotoxicity assay but were non-carcinogenic, 4 (17.4%) tested negative in genotoxicity assays but were carcinogenic, and 15 (65.2%) gave a positive response in at least one genotoxicity assay and in at least one carcinogenicity assay. Only 18 (37.5%) of the 48 drugs examined had all data required by present guidelines for testing of pharmaceuticals, but a fraction of them (49%) were developed and marketed prior to the present regulatory climate. In the absence of compelling indications, the prescription of the 19 drugs that are animal carcinogens should be avoided.

  17. 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...

  18. Carcinogen derived biomarkers: applications in studies of human exposure to secondhand tobacco smoke

    PubMed Central

    Hecht, S

    2004-01-01

    Objective: To review the literature on carcinogen derived biomarkers of exposure to secondhand tobacco smoke (SHS). These biomarkers are specifically related to known carcinogens in tobacco smoke and include urinary metabolites, DNA adducts, and blood protein adducts. Method: Published reviews and the current literature were searched for relevant articles. Results: The most consistently elevated biomarker in people exposed to SHS was 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronides (NNAL-Gluc), urinary metabolites of the tobacco specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). The tobacco specificity of this biomarker as well as its clear relation to an established lung carcinogen are particularly appropriate for its application in studies of SHS exposure. Conclusion: The results of the available carcinogen derived biomarker studies provide biochemical data which support the conclusion, based on epidemiologic investigations, that SHS causes lung cancer in non-smokers. PMID:14985617

  19. Simulation Studies Examining Possible Mechanisms of Trichloroethylene Carcinogenicity.

    DTIC Science & Technology

    1998-03-01

    biologically based dose - response (BBDR) models offer possible means of quantifying these risks. BBDR models have been used to evaluate the effects of...is used to fit parameters to simulated data sets assuming different carcinogenic mechanisms and low- dose response for TCE. Monte Carlo simulations

  20. Toxicity and carcinogenicity studies of Ginkgo biloba extract in rat and mouse: liver, thyroid, and nose are targets.

    PubMed

    Rider, Cynthia V; Nyska, Abraham; Cora, Michelle C; Kissling, Grace E; Smith, Cynthia; Travlos, Gregory S; Hejtmancik, Milton R; Fomby, Laurene M; Colleton, Curtis A; Ryan, Michael J; Kooistra, Linda; Morrison, James P; Chan, Po C

    2014-07-01

    Ginkgo biloba extract (GBE) is a popular herbal supplement that is used to improve circulation and brain function. In spite of widespread human exposure to relatively high doses over potentially long periods of time, there is a paucity of data from animal studies regarding the toxicity and carcinogenicity associated with GBE. In order to fill this knowledge gap, 3-month and 2-year toxicity and carcinogenicity studies with GBE administered by oral gavage to B6C3F1/N mice and F344/N rats were performed as part of the National Toxicology Program's Dietary Supplements and Herbal Medicines Initiative. The targets of GBE treatment were the liver, thyroid, and nose. These targets were consistent across exposure period, sex, and species, albeit with varying degrees of effect observed among studies. Key findings included a notably high incidence of hepatoblastomas in male and female mice and evidence of carcinogenic potential in the thyroid gland of both mice and rats. Various nonneoplastic lesions were observed beyond control levels in the liver, thyroid gland, and nose of rats and mice administered GBE. Although these results cannot be directly extrapolated to humans, the findings fill an important data gap in assessing risk associated with GBE use.

  1. Update of carcinogenicity studies in animals and humans of 535 marketed pharmaceuticals.

    PubMed

    Brambilla, Giovanni; Mattioli, Francesca; Robbiano, Luigi; Martelli, Antonietta

    2012-01-01

    This survey is a compendium of information retrieved on carcinogenicity in animals and humans of 535 marketed pharmaceuticals whose expected clinical use is continuous for at least 6 months or intermittent over an extended period of time. Of the 535 drugs, 530 have the result of at least one carcinogenicity assay in animals, and 279 (52.1%) of them gave a positive response in at least one assay. Only 186 drugs (34.8%) have retrievable information on carcinogenicity in humans, and 104 of them gave to a variable extent evidence of a potential carcinogenic activity. Concerning the correlation between results obtained in animals and epidemiological findings, 58 drugs gave at least one positive result in carcinogenicity assays performed in animals and to a variable extent displayed evidence of carcinogenicity in humans, but 97 drugs tested positive in animals and were noncarcinogenic in humans or vice versa. Our findings, which are in agreement with previous studies, indicate that the evaluation of the benefit/carcinogenic risk ratio should be always made in prescribing a drug.

  2. Comment on the significance of positive carcinogenicity studies using gavage as the route of exposure

    SciTech Connect

    Perera, F.; Brennan, T.; Fouts, J.R. )

    1989-02-01

    There is continuing controversy, extending into regulatory matters, over the significance to human health of positive results in carcinogenicity studies in animals using the gavage technique as the route of exposure. This review of a nonrandom sample of 117 chemicals or chemical processes listed as known or reasonably anticipated to be carcinogenic in the National Toxicology Program's Third Annual Report on Carcinogens provides support for the validity of the gavage route in such studies. Twenty-three chemicals among the 117 substances and processes listed were positive by gavage. Twenty of these 23 chemicals were also appropriately studied by at least one other route of exposure. Nineteen or (95%) of the twenty chemicals were positive for carcinogenicity by at least one other nongavage route in carcinogenicity bioassays. All of the 23 gavage-positive chemicals induced tumors distal to the site of administration in at least one study, as did all 15 chemicals which were also positive by subcutaneous injection. The authors emphasize, however, the limited scope of the survey. Despite this limitation, the review suggests that, although gavage may not be the general method of choice for chemical administration, the results of studies wherein this route was employed are meaningful as a basis for assessing potential carcinogenic hazards.

  3. QSAR Study for Carcinogenic Potency of Aromatic Amines Based on GEP and MLPs

    PubMed Central

    Song, Fucheng; Zhang, Anling; Liang, Hui; Cui, Lianhua; Li, Wenlian; Si, Hongzong; Duan, Yunbo; Zhai, Honglin

    2016-01-01

    A new analysis strategy was used to classify the carcinogenicity of aromatic amines. The physical-chemical parameters are closely related to the carcinogenicity of compounds. Quantitative structure activity relationship (QSAR) is a method of predicting the carcinogenicity of aromatic amine, which can reveal the relationship between carcinogenicity and physical-chemical parameters. This study accessed gene expression programming by APS software, the multilayer perceptrons by Weka software to predict the carcinogenicity of aromatic amines, respectively. All these methods relied on molecular descriptors calculated by CODESSA software and eight molecular descriptors were selected to build function equations. As a remarkable result, the accuracy of gene expression programming in training and test sets are 0.92 and 0.82, the accuracy of multilayer perceptrons in training and test sets are 0.84 and 0.74 respectively. The precision of the gene expression programming is obviously superior to multilayer perceptrons both in training set and test set. The QSAR application in the identification of carcinogenic compounds is a high efficiency method. PMID:27854309

  4. 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…

  5. Saliva in perimenopausal and early postmenopausal women. A 2-year follow-up study.

    PubMed

    Tarkkila, Laura; Furuholm, Jussi; Tiitinen, Aila; Meurman, Jukka H

    2012-06-01

    This study aims to investigate salivary flow and biochemical constituents of menopausal-age women with the hypothesis that women using hormone therapy (HT) might present better saliva values than non-users. Two hundred HT users and 200 non-users were selected at random from a cohort study of 3,173 peri- and postmenopausal women and invited to a 2-year clinical follow-up study. Clinical examination with saliva sampling was made at baseline and 2 years later. Salivary total protein, albumin, and immunoglobulin (Ig) concentrations were analyzed. Final material included 106 consistent HT users and 55 non-users. Backward logistic regression analysis was made to determine the risk factors for higher or lower than medium salivary protein values. No difference was seen in salivary flow rate, total protein, and IgA values between baseline and follow-up measurements or between the groups. Albumin, IgG, and IgM concentrations were significantly lower in the 2-year samples of the HT group when compared with baseline. IgA and IgM values were higher in the non-HT 2-year samples when compared with the corresponding HT samples. The only significant explanatory factor for higher than median salivary albumin concentration was the number of teeth both at baseline and 2 years later. HT possibly improved epithelial integrity since the concentrations of serum components albumin, IgG, and IgM decreased during the follow-up. HT as such does not seem to affect saliva, although it may modify it. The clinical relevance of these results needs to be assessed in future studies.

  6. Experimental studies on betel nut and tobacco carcinogenicity.

    PubMed

    Ranadive, K J; Gothoskar, S V; Rao, A R; Tezabwalla, B U; Ambaye, R Y

    1976-04-15

    Sun-dried Mangalore betel nut extracts in water and in DMSO, and sun-cured Vadakkan tobacco extract in DMSO, were tested for their carcinogenic potency. Inbred Swiss and C17 mice and golden hamsters were used for the experiments. Control animals treated with either DMSO or water did not show any changes at the sites of administration. On subcutaneous administration of betel nut extract, 60% of Swiss mice developed transplantable fibrosarcomas at the site of injection. Skin application of DMSO extracts of tobacco and of betel nut separately did not result in skin lesions in C17 mice; but when a mixed DMSO extract of tobacco and betel nut was used, skin papilloma and epidermoid carcinoma developed in some animals. Similarly, hamster cheek pouches painted with a DMSO extract of tobacco alone did not develop malignant atypia whereas those painted with a DMSO extract of betel nut showed early malignant changes. DMSO extract of a mixture of tobacco and betel nut positively increased the incidence of early malignant changes in the hamster cheek pouch, indicating the enhancing effect of betel nut in carcinogenesis.

  7. 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.

  8. Carcinogens in Israeli milk: a study in regulatory failure.

    PubMed

    Westin, J B

    1993-01-01

    The potential danger to humans of exposure to chemicals shown to be carcinogenic in animals has become increasingly clear in the last 20 years. A gap still exists, however, between the appreciation of the risk by scientists and the willingness of public health authorities to reduce it. Three pesticides, shown repeatedly to produce over a dozen different types of cancer in rats and mice, were discovered in inordinately high concentrations in Israeli milk and dairy products. The three pesticides--alpha-BHC, gamma-BHC (lindane), and DDT--had been shown to be present for ten years or more at mean concentrations up to 100 times those found in U.S. dairy products--with resultant concentrations in breast milk being possibly 800 times greater than those in the United States--yet neither the Ministry of Health nor the Israel Cancer Association made any apparent moves either to warn the public or to rectify the situation. A small consumer organization, Consumer Shield, brought the issue into the open. Through public pressure, court action, and the threat of further legal redress--and despite repeated attacks in the media by the milk producers, the Ministry, and the Cancer Association--Consumer Shield forced the authorities to outlaw the use of alpha-BHC and lindane (DDT no longer being in general use). The ban resulted in a precipitous drop in the concentrations of these substances in Israeli milk. Recent epidemiological and laboratory findings suggest that the dramatic drop in breast cancer mortality rates subsequent to the pesticide ban could be a direct result of that ban.

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

    PubMed

    Dieter, M P

    1994-11-01

    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)

  10. 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

  11. 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.

  12. 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

  13. Comment on the significance of positive carcinogenicity studies using gavage as the route of exposure.

    PubMed Central

    Perera, F; Brennan, T; Fouts, J R

    1989-01-01

    There is continuing controversy, extending into regulatory matters, over the significance to human health of positive results in carcinogenicity studies in animals using the gavage technique as the route of exposure. Our review of a nonrandom sample of 117 chemicals or chemical processes listed as known or reasonably anticipated to be carcinogenic in the National Toxicology Program's Third Annual Report on Carcinogens provides support for the validity of the gavage route in such studies. Twenty-three chemicals among the 117 substances and processes listed were positive by gavage. Twenty of these 23 chemicals were also appropriately studied by at least one other route of exposure. Thus, we were able to evaluate the extent to which positive gavage results were confirmed by another route of exposure in this sample. Nineteen (or 95%) of the twenty chemicals were positive for carcinogenicity by at least one other nongavage route in carcinogenicity bioassays. Moreover, in each of these 19 cases, positive carcinogenesis results were obtained by a nongavage route in the same species of animal where gavage administration led to the induction of cancer. All of the 23 gavage-positive chemicals induced tumors distal to the site of administration in at least one study, as did all 15 chemicals which were also positive by subcutaneous injection. We emphasize, however, the limited scope of our survey. We have not evaluated all chemicals that have tested positive by gavage and by at least one alternative route, nor have we assessed those chemicals found to be negative by the gavage route.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2707209

  14. [Plastic industry and exposure to carcinogenic chemical agents: an Italian Multicentric Study in Lombardy].

    PubMed

    Cirla, P E; Castoldi, M R; Marchese, E; Cavallo, D M; Fustinoni, S; Cattaneo, A; Martinotti, I; Foà, V; Tiso, C

    2007-01-01

    The potential carcinogenic risk at the workplaces is a primary interest of occupational health, but some questions are also controversially discussed. Particularly, in the plastic forming industry a great attention was directed to the hot processing and their possible exposure to monomers, some of which were classified as carcinogen by the International Agency for Research on Cancer (IARC) and/or the European Union (EU). In Lombardy, a study on occupational exposure to chemical carcinogens in the plastic forming industry was planned during last years. The aim was to recognize and promote preventive technical and medical solutions, basing on efficacy. By an investigation at workplace supported with standardized questionnaires, the presence of chemical carcinogens was registered in 59% of a representative sample of firms; but an effective possibility of exposure was found only for 34% of cases. The evaluation of exposure to monomers by air monitoring (acrylonitrile, 1,3-butadiene, styrene, formaldehyde), involving a representative sample of factory with ABS and formaldehydic resins processing, showed low level exposure, because the common hygienic prevention measures were applied; some particular occupation shoved greater exposure to formaldehyde.

  15. 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.

  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. 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.

  18. Can patients with eating disorders learn to eat intuitively? A 2-year pilot study.

    PubMed

    Richards, P Scott; Crowton, Sabree; Berrett, Michael E; Smith, Melissa H; Passmore, Kimberly

    2017-01-01

    The present article reports on a 2-year pilot study that evaluated the effectiveness of an intuitive eating program for patients in an eating disorder treatment center. Standardized measures of intuitive eating and eating disorder and psychological symptoms were administered. Psychotherapists and dietitians rated patients on the healthiness of their eating attitudes and behaviors. Preliminary findings indicated that patients can develop the skills of intuitive eating, and that the ability to eat intuitively is associated with positive treatment outcomes for each diagnostic category (i.e., anorexia nervosa, bulimia nervosa, and eating disorder not otherwise specified). We conclude by offering recommendations about how to implement intuitive eating training safely and effectively in inpatient and residential treatment programs.

  19. A 2-year longitudinal study of prospective predictors of pathological Internet use in adolescents.

    PubMed

    Strittmatter, Esther; Parzer, Peter; Brunner, Romuald; Fischer, Gloria; Durkee, Tony; Carli, Vladimir; Hoven, Christina W; Wasserman, Camilla; Sarchiapone, Marco; Wasserman, Danuta; Resch, Franz; Kaess, Michael

    2016-07-01

    Longitudinal studies of prospective predictors for pathological Internet use (PIU) in adolescents as well as its course are lacking. This three-wave longitudinal study was conducted within the framework of the European Union-funded project "Saving and Empowering Young Lives in Europe" over a 2-year period. The sample consisted of 1444 students at the baseline investigation (T0); 1202 students after 1 year (T1); and 515 students after 2 years (T2). Structured self-report questionnaires were administered at all three time points. PIU was assessed using the Young Diagnostic Questionnaire (YDQ). In addition, demographic (i.e., gender), social (i.e., parental involvement), psychological (i.e., emotional problems), and Internet use-related factors (i.e., online activities) were assessed as prospective predictors. The prevalence of PIU was 4.3 % at T0, 2.7 % at T1 and 3.1 % at T2. However, only 3 students (0.58 %) had persistent categorical PIU (YDQ score of ≥5) over the 2-year period. In univariate models, a variety of variables that have been previously identified in cross-sectional investigations predicted PIU at T2. However, multivariate regression demonstrated that only previous PIU symptoms and emotional problems were significant predictors of PIU 2 years later (adjusted R (2) 0.23). The stability of categorical PIU in adolescents over 2 years was lower than previously reported. However, current PIU symptoms were the best predictor of later PIU; emotional symptoms also predicted PIU over and above the influence of previous problematic Internet use. Both PIU symptoms and emotional problems may contribute to the vicious cycle that supports the perpetuation of PIU.

  20. Consultation training of nurses for cardiovascular prevention - a randomized study of 2 years duration.

    PubMed

    Drevenhorn, Eva; Bengtson, Ann; Nilsson, Peter M; Nyberg, Per; Kjellgren, Karin I

    2012-10-01

    The aim of this study was to increase patients' adherence to the treatment of hypertension through the consultation training of nurses. Thirty-three nurses were included in the study. In the intervention group (IG), 19 nurses took part in a 3-day residential training course on the Stages of Change model, Motivational Interviewing and guidelines for cardiovascular prevention, and recruited 153 patients. Sixteen nurses in the control group (CG) recruited 59 patients. A decrease in systolic and diastolic blood pressure and total cholesterol was noticed in both groups over the 2 years. Heart rate (p = 0.027), body mass index (p = 0.019), weight (p = 0.0001), waist (p = 0.041), low-density lipoprotein-cholesterol (p = 0.0001), the waist-hip ratio (p = 0.024), and perceived stress (p = 0.001) decreased to any great extent only in the IG. After 2 years, 52.6% of the patients in the IG (p = 0.13) reached the target of ≤ 140/90 mmHg in blood pressure compared with 39.2% in the CG. For self-reported physical activity, there was a significant (p = 0.021) difference between the groups. The beneficial effects of the consultation training on patients' weight parameters, physical activity, perceived stress and the proportion of patients who achieved blood pressure control emphasize consultation training and the use of behavioural models in motivating patients to adhere to treatment.

  1. Collagenase injections for Dupuytren's disease: prospective cohort study assessing 2-year treatment effect durability

    PubMed Central

    Lauritzson, Anna; Atroshi, Isam

    2017-01-01

    Objectives To assess 2-year durability of joint contracture correction following collagenase injections for Dupuytren's disease. Design Prospective cohort study. Setting Orthopaedic Department in Sweden. Participants Patients with palpable Dupuytren's cord and active extension deficit (AED) ≥30° in the metacarpophalangeal (MCP) and/or proximal interphalangeal (PIP) joint. A surgeon injected 0.80 mg collagenase into multiple cord parts and performed finger manipulation under local anaesthesia after 24–48 hours. A hand therapist measured joint contracture before and 5 weeks after injection in all treated patients. Of 57 consecutive patients (59 hands), 48 patients (50 hands) were examined by a hand therapist 24–35 months (mean 26) after injection. Five of the patients had received a second injection in the same finger within 6 months of the first injection. Outcome measures Primary outcome was proportion of treated joints with ≥20° worsening in AED from 5 weeks to 2 years. Results Between the 5-week and the 2-year measurements, AED had worsened by ≥20° in seven MCP and seven PIP joints (28% of the treated hands; all had received a single injection). Mean AED for the MCP joints was 54° before injection, 6° at 5 weeks and 9° at 2 years and for the PIP joints 30°, 13° and 16°, respectively. For joints with ≥10° contracture at baseline, mean (95 % CI) baseline to 2 years AED improvement was for MCP 49° (41–54) and for PIP 25° (17–32). No treatment-related adverse events were observed at the 2-year follow-up evaluation. Conclusions Two years after collagenase injections for Dupuytren's disease, improvement was maintained in 72% of the treated hands. Complete contracture correction was seen in more than 80% of the MCP but in less than half of the PIP joints. PMID:28298365

  2. Computer-assisted mechanistic structure-activity studies: application to diverse classes of chemical carcinogens.

    PubMed Central

    Loew, G H; Poulsen, M; Kirkjian, E; Ferrell, J; Sudhindra, B S; Rebagliati, M

    1985-01-01

    In the first part of this paper we have indicated how the techniques and capabilities of theoretical chemistry, together with experimental results, can be used in a mechanistic approach to structure-activity studies of toxicity. In the second part, we have illustrated how this computer-assisted approach has been used to identify and calculate causally related molecular indicators of relative carcinogenic activity in five classes of chemical carcinogens: polycyclic aromatic hydrocarbons and their methyl derivatives, aromatic amines, chloroethanes, chloroalkenes and dialkyl nitrosamines. In each class of chemicals studied, candidate molecular indicators have been identified that could be useful in predictive screening of unknown compounds. In addition, further insights into some mechanistic aspects of chemical carcinogenesis have been obtained. Finally, experiments have been suggested to both verify the usefulness of the indicators and test their mechanistic implications. PMID:3905382

  3. Chemical reactivity as a tool to study carcinogenicity: reaction between estradiol and estrone 3,4-quinones ultimate carcinogens and guanine.

    PubMed

    Huetz, Ph; Kamarulzaman, E E; Wahab, H A; Mavri, J

    2004-01-01

    In this article we study the chemical reactions between guanine and two ultimate carcinogens, the 3,4-quinone forms of the estrogens estrone (E1) and estradiol (E2). DNA was truncated to guanine, i.e. no deoxyribose moiety was included. Due to a complex reaction that involves proton transfer via water molecules we applied linear free energy relationships rather than computation of the transition state and activation energies. The minima corresponding to reactants and products were obtained on the B3LYP/6-31G(d) level. The effects of hydration were considered using the solvent reaction field of Tomasi and co-workers and the Langevin dipoles model of Florian and Warshel. No significant difference in reaction free energy for the reaction involving estrone and estradiol metabolites was found, despite the fact that for the two substances different carcinogenic activities were reported. Differences in carcinogenicity may be therefore attributed to other types of interactions or reactions such as (i) specific interactions of the carbonyl or hydroxyl group with DNA giving rise to different activation free energies for the reactions, (ii) the reaction of depurination and subsequent effects on the DNA, (iii) enzymatic or nonenzymatic oxidation steps (P450, aromatase, peroxidases, O2) and detoxification reactions (catechol-O-methyl transferase, S-transferase), or (iv) binding of the hormone to its nuclear receptors.

  4. 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.

  5. Carcinogenicity study of 3-monochloropropane-1,2-diol in Sprague-Dawley rats.

    PubMed

    Cho, Wan-Seob; Han, Beom Seok; Nam, Ki Taek; Park, Kidae; Choi, Mina; Kim, Seung Hee; Jeong, Jayoung; Jang, Dong Deuk

    2008-09-01

    3-Monochloropropane-1,2-diol (alpha-chlorohydrin, 3-MCPD) is a well-known contaminant, which has been detected in a wide range of foods and ingredients, and is also a suspected cause of cancer. In this study, the carcinogenicity of 3-MCPD in SD rats was investigated. Groups of 50 male and 50 female rats were exposed for two years to drinking water containing 0, 25, 100 or 400ppm 3-MCPD. The body weights and water consumptions of the male and female rats given 400ppm 3-MCPD were significantly lower than those of the controls. The incidences of renal tubule adenomas or carcinomas and Leydig cell tumors occurred with dose-related positive trends in male rats. The incidences of renal tubule carcinomas and Leydig cell tumors were significantly increased in male rats given 400ppm 3-MCPD. The incidence of renal tubule adenomas showed a positive trend in female rats, which was significant in 400ppm 3-MCPD group. In conclusion, there was clear evidence of the carcinogenic activity of 3-MCPD in male SD rats, based on the increased incidences of renal tubule carcinomas and Leydig cell tumors. There was some evidence of the carcinogenic activity of 3-MCPD in female SD rats, based on the increased incidence of renal tubule adenomas.

  6. A 2-Year Psychological Autopsy Study of Completed Suicides in the Athens Greater Area, Greece

    PubMed Central

    Michopoulos, Ioannis; Christodoulou, Christos; Koutsaftis, Filippos; Lykouras, Lefteris; Douzenis, Athanassios

    2015-01-01

    Objective To study the characteristics of a sample of suicide victims from the Athens Greater Area using the psychological autopsy method for the first time in Greece. Methods We studied all recorded cases of completed suicide for the 2-year time period November 2007-October 2009 collecting data from the victims' forensic records as well as from the completion of a psychological autopsy questionnaire. Results 335 persons were recorded as suicide victims. We contacted relatives of 256 victims interviewing those of 248 of them (96.9%). The differences regarding sex, marital and employment status between our sample and the general population were statistically significant (p<0.001). The male/female ratio was 3:1. Comparatively more victims were divorced, separated or single and a greater proportion were pensioners or unemployed. 26.0% of the victims had history of prior attempts (64.4% once, 20.3% twice and 15.3% more times). 42.6% were taking psychiatric medication-significantly more women than men according to blood tests; 14.2% had been hospitalized in a psychiatric clinic the year prior to their death. 84.8% have deceased at the place of suicide and 15.2% died in the hospital; 80.3% died indoors and 19.7% outdoors. Men died primarily by hanging or shooting by a firearm while women preferred jumping from height instead (p<0.001). As many as 48.8% had expressed their intention to die to their relatives; 26.6% left a suicide note. Conclusion Our study has shown that the psychological autopsy method is applicable and widely accepted yielding results comparable to the international literature. Specific parameters associated with suicide have been studied for the first time in Greece. PMID:25866522

  7. 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.

  8. 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

  9. Clinical outcomes and mortality after hip fracture: a 2-year follow-up study.

    PubMed

    Baudoin, C; Fardellone, P; Bean, K; Ostertag-Ezembe, A; Hervy, F

    1996-03-01

    The aim of this study was to evaluate the burden of hip fractures, which occurred in the French region of Picardie, in 1992, among 1103 women and 356 men, whether the fractures occurred at home or in a community (i.e., patients who depended on a collective service). The data are part of the PICAROS study, which was designed to assess prospectively the outcome of patients as judged by clinical, economical, and quality of life factors. Patients and/or proxies were questioned during the 2nd or 3rd week following the fracture, and again at 3, 6, 12, and 24 months after the fracture. The survey was conducted by home interview. Recruitment criteria were: 1) all patients with a hip fracture as defined by the International Classification of Disease (ICD); 2) 20 years of age and over; 3) admitted to one of the 34 surgical units from the region, public and private, and had an operation or not. Patients with metastatic or myelomatous fractures or fractures on prothesis device were not included. For the present analysis, patients under 50 years of age were excluded. Among people aged 50 years and over, 3% of the general population lived in a community; 32% of hip fractures were from a community. Patients in a community, aged 60-69, had 15 times more risk of having a hip fracture than subjects of the same age at home. The excess risk decreased with age and stabilized over 85 years of age at two to threefold. During the 24 month follow-up, 394 women and 173 men died. Among those surviving, 87% were interviewed at 2 years. We analysed seven classes of complications, according to the ICD: (1) pressure sores and blisters; (2) pulmonary infections; (3) urinary infections; (4) surgical complications; (5) orthopedic complications; (6) thrombosis and embolisms; and (7) secondary hip fractures. Patients coming from a community had a higher risk of mortality, pressure sores, surgical complications, and pulmonary and urinary infections. From an economical perspective, the

  10. 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.

  11. 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.

  12. Are genotoxic carcinogens more potent than nongenotoxic carcinogens?

    PubMed Central

    Parodi, S; Malacarne, D; Romano, P; Taningher, M

    1991-01-01

    In this report we have raised the question whether genotoxic carcinogens are more potent than nongenotoxic carcinogens when studied in long-term carcinogenicity assays in rodents. To build a large database of compounds for which both carcinogenicity and genotoxicity had been investigated, we have used a database produced by Gold and co-workers for carcinogenic potency data (975 chemicals) and a database produced by Würgler for genotoxicity data (2834 chemicals). Considering compounds positive or negative in at least three short-term tests and in at least 75% of available tests, we could define 67 genotoxic carcinogens and 46 nongenotoxic carcinogens. Carcinogenic potency of genotoxic carcinogens was about 50 times higher than carcinogenic potency of nongenotoxic carcinogens. Our results are different from the results of Tennant et al.; their database (24 genotoxic carcinogens and 12 nongenotoxic carcinogens compatible with our definition) seems to suggest that there is practically no difference in potency between genotoxic and nongenotoxic carcinogens. The two databases have only four compounds in common and are also different in terms of number of elements for different chemical classes. Nitrosocompounds, nitrogen mustards, hydrazine derivatives, and polycyclic aromatic hydrocarbons are not represented in the database of Tennant. The overall impression from our analysis is that the usefulness of short-term tests of genotoxicity could be significantly better than what has been suggested by the previous work of Tennant et al. because these tests tend to detect, at least for many important chemical classes, the most potent carcinogens. This consideration may not be valid for certain classes of chemicals. PMID:1821372

  13. 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.

  14. 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.

  15. 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.

  16. The limitations of case-control studies in the detection of environmental carcinogens.

    PubMed Central

    Crombie, I K

    1981-01-01

    The ability of the case-control study to detect human carcinogens has been investigated theoretically for varying fractions of the population exposed to hazards carrying different relative risks. The method is shown to be useful for the investigation of factors to which exposure is widespread (for example, common foods or beverages) but it is of limited use for the study of uncommon types of exposure, such as those associated with occupation. The case-control study is unable to detect very small relative risks (less than 1.5) even where exposure is widespread and large numbers of cases of cancer are occurring in the population. The principal limitation of the method is the maximum number of cases which can be recruited and analysed. It will only be through large-scale collaborative multicentre or international studies that important risk factors will be detected. PMID:7338704

  17. Carcinogenicity study of 217 Hz pulsed 900 MHz electromagnetic fields in Pim1 transgenic mice.

    PubMed

    Oberto, Germano; Rolfo, Katia; Yu, Ping; Carbonatto, Michela; Peano, Sergio; Kuster, Niels; Ebert, Sven; Tofani, Santi

    2007-09-01

    In an 18-month carcinogenicity study, Pim1 transgenic mice were exposed to pulsed 900 MHz (pulse width: 0.577 ms; pulse repetition rate: 217 Hz) radiofrequency (RF) radiation at a whole-body specific absorption rate (SAR) of 0.5, 1.4 or 4.0 W/kg [uncertainty (k = 2): 2.6 dB; lifetime variation (k = 1): 1.2 dB]. A total of 500 mice, 50 per sex per group, were exposed, sham-exposed or used as cage controls. The experiment was an extension of a previously published study in female Pim1 transgenic mice conducted by Repacholi et al. (Radiat. Res. 147, 631-640, 1997) that reported a significant increase in lymphomas after exposure to the same 900 MHz RF signal. Animals were exposed for 1 h/day, 7 days/week in plastic tubes similar to those used in inhalation studies to obtain well-defined uniform exposure. The study was conducted blind. The highest exposure level (4 W/kg) used in this study resulted in organ-averaged SARs that are above the peak spatial SAR limits allowed by the ICNIRP (International Commission on Non-ionizing Radiation Protection) standard for environmental exposures. The whole-body average was about three times greater than the highest average SAR reported in the earlier study by Repacholi et al. The results of this study do not suggest any effect of 217 Hz-pulsed RF-radiation exposure (pulse width: 0.577 ms) on the incidence of tumors at any site, and thus the findings of Repacholi et al. were not confirmed. Overall, the study shows no effect of RF radiation under the conditions used on the incidence of any neoplastic or non-neoplastic lesion, and thus the study does not provide evidence that RF radiation possesses carcinogenic potential.

  18. 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)

  19. 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.

  20. Injury risk factors in junior tennis players: a prospective 2-year study.

    PubMed

    Hjelm, N; Werner, S; Renstrom, P

    2012-02-01

    The aim was to investigate injury risk factors in junior tennis players. Fifty-five players, 35 boys and 20 girls, answered a questionnaire about training habits, time of exposure, previous injuries and equipment factors. A battery of clinical tests and functional performance tests were also carried out. All tennis-related injuries that occurred during a 2-year period were identified and recorded. An injury was defined as an injury if it was impossible to participate in regular tennis training or playing matches during at least one occasion, a time loss injury. Potential injury risk factors were tested in a forward stepwise logistic regression model for injury. Thirty-nine players sustained totally 100 new and recurrent injuries. Injuries to the lower extremity were the most common ones (51%) followed by the upper extremity (24%) and the trunk (24%). Injured players performed more singles per week (P<0.0001) and played more tennis hours per year (P=0.016) than the uninjured players. Playing tennis more than 6 h/week was found to be a risk factor for back pain. A previous injury regardless of location was identified as an injury risk factor, and a previous injury to the back was a risk factor for back pain.

  1. Temporal Stability of Obsessive-Compulsive Symptom Dimensions in an Undergraduate Sample: A Prospective 2-Year Follow-Up Study

    ERIC Educational Resources Information Center

    Fullana, Miquel A.; Tortella-Feliu, Miquel; Caseras, Xavier; Taberner, Joan; Torrubia, Rafael; Mataix-Cols, David

    2007-01-01

    The temporal stability of obsessive-compulsive symptom dimensions was studied in a nonclinical student sample. The Obsessive-Compulsive Inventory--Revised was administered twice to 132 undergraduate students during a 2-year period. There were no significant changes in symptom dimension scores between the baseline and follow-up, except for the…

  2. The in vivo rodent test systems for assessment of carcinogenic potential.

    PubMed

    van der Laan, Jan-Willem; Spindler, Per

    2002-02-01

    A Drug Information Association (DIA) workshop was held in May 2001 to discuss the outcome of the International Life Sciences Institute-Health and Environmental Sciences Institute (ILSI-HESI) project on alternative models for carcinogenicity assessment such as the P53(+/-) and XPA(+/-) knockout mouse models, the RasH2 and Tg.AC transgenic mouse models, and the neonatal mouse model. The "ICH Guideline S1B on Testing for Carcinogenicity of Pharmaceuticals" advocates that carcinogenicity testing of pharmaceuticals, when needed, might be carried out choosing one 2-year rodent carcinogenicity study (rat) plus one other study that supplements the 2-year study and providing additional information that is not readily available from the 2-year study: either (1) a short- or medium-term in vivo rodent test system or (2) a 2-year carcinogenicity study in a second rodent species (mouse). Another topic of discussion was pros and cons of the short- and medium-term models being evaluated by the ILSI-HESI project, in particular the usefulness of the models in relation to results of genotoxicity assays. Further discussions were advised following publication of the ILSI-HESI database, which is expected before the end of 2001. The use of the short- and medium-term rodent test systems were not considered appropriate for the assessment of carcinogenic potential of biotechnology-derived medicinal products.

  3. Prediction of mutagenicity and carcinogenicity using in silico modelling: A case study of polychlorinated biphenyls.

    PubMed

    Vračko, M; Bobst, S

    2015-01-01

    In silico modelling is an important alternative method for the evaluation of properties of chemical compounds. Basically, two concepts are used in its applications: QSAR modelling for endpoint predictions, and grouping (categorization) of large groups of chemicals. In the presented report we address both of these concepts. As a case study we present the results on a set of polychlorinated biphenyls (PCBs) and some of their metabolites. Their mutagenicity and carcinogenic potency were evaluated with CAESAR and T.E.S.T. models, which are freely available over the internet. We discuss the value and reliability of the predictions, the applicability domain of models and the ability to create prioritized groupings of PCBs as a category of chemicals.

  4. 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

  5. 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.

  6. The mouse carcinogenicity study is no longer a scientifically justifiable core data requirement for the safety assessment of pesticides.

    PubMed

    Billington, Richard; Lewis, Richard W; Mehta, Jyotigna M; Dewhurst, Ian

    2010-01-01

    Regulatory tests investigating pesticide carcinogenicity potential routinely comprise a battery of in vitro and in vivo genotoxicity studies and two cancer bioassays, one in rats and one in mice. The genotoxicity testing strategy essentially ensures that genotoxic compounds are eliminated, and any carcinogens identified in subsequent lifetime studies are probably nongenotoxic in character. Assessment of 202 pesticide evaluations from the European Union review programme under Directive 91/414/EEC indicated that the mouse carcinogenicity study contributed little or nothing to either derivation of an acceptable daily intake (ADI) for assessment of chronic risk to humans, or hazard classification for labelling purposes. From a pesticide approval perspective, the mouse study did not influence a single outcome. From a risk assessment perspective, the ADI for just one pesticide was based on tumours in mice and this would have barely changed if the mouse data had not been available. In total, only 10 (5%) pesticide ADIs were based solely on the mouse carcinogenicity study and even in these few cases, a similar value would have been identified from other studies if the mouse study had not been available. For pesticides with treatment-related tumours only in mice, just three, or 1.5%, were classified as carcinogens and all were in the lowest category, Category 3 (R40). For pesticides with treatment-related tumours in mice and rats, the mouse data were probably the main, if not the only, cause for another three cases of R40 classification. Absence of the mouse studies would not have influenced assignment of the higher, Category 2 (R45), cancer classification for any substance with treatment-related tumours in both species as all decisions for these substances were limited to Category 3 or 'unclassified' outcomes. Over 100,000 mice were used to test these pesticides. This review shows that the mouse carcinogenicity studies did not provide significant information over and above

  7. 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.

  8. 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 ...

  9. Efficacy and safety of eculizumab in atypical hemolytic uremic syndrome from 2-year extensions of phase 2 studies.

    PubMed

    Licht, Christoph; Greenbaum, Larry A; Muus, Petra; Babu, Sunil; Bedrosian, Camille L; Cohen, David J; Delmas, Yahsou; Douglas, Kenneth; Furman, Richard R; Gaber, Osama A; Goodship, Timothy; Herthelius, Maria; Hourmant, Maryvonne; Legendre, Christophe M; Remuzzi, Giuseppe; Sheerin, Neil; Trivelli, Antonella; Loirat, Chantal

    2015-05-01

    Atypical hemolytic uremic syndrome (aHUS) is a rare, possibly life-threatening disease characterized by platelet activation, hemolysis and thrombotic microangiopathy (TMA) leading to renal and other end-organ damage. We originally conducted two phase 2 studies (26 weeks and 1 year) evaluating eculizumab, a terminal complement inhibitor, in patients with progressing TMA (trial 1) and those with long duration of aHUS and chronic kidney disease (trial 2). The current analysis assessed outcomes after 2 years (median eculizumab exposure 100 and 114 weeks, respectively). At all scheduled time points, eculizumab inhibited terminal complement activity. In trial 1 with 17 patients, the platelet count was significantly improved from baseline, and hematologic normalization was achieved in 13 patients at week 26, and in 15 patients at both 1 and 2 years. The estimated glomerular filtration rate (eGFR) was significantly improved compared with baseline and year 1. In trial 2 with 20 patients, TMA event-free status was achieved by 16 patients at week 26, 17 patients at year 1, and 19 patients at year 2. Criteria for hematologic normalization were met by 18 patients at each time point. Improvement of 15 ml/min per 1.73 m(2) or more in eGFR was achieved by 1 patient at week 26, 3 patients at 1 year, and 8 patients at 2 years. The mean change in eGFR was not significant compared with baseline, week 26, or year 1. Eculizumab was well tolerated, with no new safety concerns or meningococcal infections. Thus, a 2-year analysis found that the earlier clinical benefits achieved by eculizumab treatment of aHUS were maintained at 2 years of follow-up.

  10. Financial impact of allogeneic hematopoietic cell transplantation on patients and families over 2 years: results from a multicenter pilot study.

    PubMed

    Denzen, E M; Thao, V; Hahn, T; Lee, S J; McCarthy, P L; Rizzo, J D; Ammi, M; Drexler, R; Flesch, S; James, H; Omondi, N; Murphy, E; Pederson, K; Majhail, N S

    2016-09-01

    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' levels of confidence in their abilities 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 that patients' individual perceptions of the financial impact of HCT varies considerably, regardless of actual income. We demonstrate the feasibility of conducting a study to evaluate the financial impact of allogeneic HCT through 2 years post transplantation. Some patients/caregivers continue to experience a 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.

  11. 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

  12. Evidence for safety and efficacy of risedronate in men with osteoporosis over 4 years of treatment: Results from the 2-year, open-label, extension study of a 2-year, randomized, double-blind, placebo-controlled study.

    PubMed

    Boonen, Steven; Lorenc, Roman S; Wenderoth, Dietrich; Stoner, Karen J; Eusebio, Rachelle; Orwoll, Eric S

    2012-09-01

    A 2-year, randomized, double-blind, placebo-controlled study in men with osteoporosis demonstrated that treatment with risedronate 35mg once a week significantly decreased bone turnover markers (BTMs) and increased bone mineral density (BMD). This study was extended to include a 2-year, open-label extension to continue to assess the safety and efficacy of risedronate in men with osteoporosis. In the open-label extension, all patients received risedronate 35mg once a week, and 1000mg elemental calcium and 400 to 500IU vitamin D daily for up to 2 years. The safety of risedronate was evaluated based on adverse events, laboratory data, vital signs, and physical examination results. BMD, BTMs, and the incidence of new vertebral fractures were also assessed. A total of 218 (of 284) patients enrolled in the open-label extension. Risedronate continued to produce significant increases in lumbar spine BMD from baseline (7.87%) in the group of patients who took it for 4 years. Risedronate produced significant increases in lumbar spine BMD from baseline (6.27%) in the former placebo group who took it for 2 years during the open-label extension. Few new vertebral and clinical fractures occurred during the study. There were no significant differences in BTMs between the two groups at months 36 and 48. Incidences of any upper GI adverse events during the extension were low and similar in the two groups; however, the percent of moderate to severe events were higher (8% versus 2%) in the group that received placebo prior to the extension. Safety results continued to show that risedronate was well-tolerated in men with osteoporosis. Patients who received risedronate 35mg once a week for 2years in the open-label extension study showed similar safety and efficacy results compared with those who received risedronate treatment in the first 2 double-blind years of the study. Patients who received risedronate for 4 years in total showed similar safety and efficacy to that observed in

  13. 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.

  14. [Epidemiologic studies on carcinogenic risk and occupational activities in tanning, leather and shoe industries].

    PubMed

    Seniori Costantini, A; Merler, E; Saracci, R

    1990-01-01

    A review is made of the epidemiological studies of occupational cancer risks among tannery, leather and shoe industry workers. The risk of nasal cancer associated with exposure to leather dust, which had already been stressed at the beginning of the 1970's, was confirmed in recent studies. However, a decreasing trend of RR was observed among shoe industry workers. The excess of leukemia among shoe workers, which was mainly based on the description of numerous cases of acute myeloblastic leukemia, has also been confirmed by two cohort studies carried out in Italy and the U.K. In addition to the evident increase in these two diseases, there are indications of an excess of cancer of other sites among leather and shoe workers, particularly bladder cancer, both among workers assigned to leather finishing operations and in leather goods and shoe production workers. Another interesting result is the excess of lung cancer among tannery workers. This evidence is unanimous in the studies carried out in Italy but is not supported by the majority of studies performed in other countries. For this reason, we consider it extremely important to carry out a multicentric study in Italy, with particular attention to the definition of occupational exposures to carcinogens. There are also other isolated reports of excesses of other cancers in the shoe and leather industries but in our opinion they are of dubious interpretation.

  15. 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.…

  16. 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…

  17. 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…

  18. 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…

  19. Predicting Expressive Vocabulary Acquisition in Children with Intellectual Disabilities: A 2-Year Longitudinal Study

    ERIC Educational Resources Information Center

    Vandereet, Joke; Maes, Bea; Lembrechts, Dirk; Zink, Inge

    2010-01-01

    Purpose: This study's objectives were to describe expressive vocabulary acquisition in children with intellectual disabilities (ID) and to examine specific pre- and early linguistic behaviors used to request and comment, chronological age, cognitive skills, and vocabulary comprehension as predictors of expressive vocabulary. Method: This study…

  20. Psychological resilience in U.S. military veterans: A 2-year, nationally representative prospective cohort study.

    PubMed

    Isaacs, Kayla; Mota, Natalie P; Tsai, Jack; Harpaz-Rotem, Ilan; Cook, Joan M; Kirwin, Paul D; Krystal, John H; Southwick, Steven M; Pietrzak, Robert H

    2017-01-01

    Although many cross-sectional studies have examined the correlates of psychological resilience in U.S. military veterans, few longitudinal studies have identified long-term predictors of resilience in this population. The current prospective cohort study utilized data from a nationally representative sample of 2157 U.S. military veterans who completed web-based surveys in two waves (2011 and 2013) as part of the National Health and Resilience in Veterans Study (NHRVS). Cluster analysis of cumulative lifetime exposure to potentially traumatic events and Wave 2 measures of current symptoms of posttraumatic stress, major depressive, and generalized anxiety disorders was performed to characterize different profiles of current trauma-related psychological symptoms. Different profiles were compared with respect to sociodemographic, clinical, and psychosocial characteristics. A three-group cluster analysis revealed a Control group with low lifetime trauma exposure and low current psychological distress (59.5%), a Resilient group with high lifetime trauma and low current distress (27.4%), and a Distressed group with both high trauma exposure and current distress symptoms (13.1%). These results suggest that the majority of trauma-exposed veterans (67.7%) are psychologically resilient. Compared with the Distressed group, the Resilient group was younger, more likely to be Caucasian, and scored lower on measures of physical health difficulties, past psychiatric history, and substance abuse. Higher levels of emotional stability, extraversion, dispositional gratitude, purpose in life, and altruism, and lower levels of openness to experiences predicted resilient status. Prevention and treatment efforts designed to enhance modifiable factors such as gratitude, sense of purpose, and altruism may help promote resilience in highly trauma-exposed veterans.

  1. Reduced prepulse inhibition in adolescents at risk for psychosis: a 2-year follow-up study

    PubMed Central

    Ziermans, Tim; Schothorst, Patricia; Magnée, Maurice; van Engeland, Herman; Kemner, Chantal

    2011-01-01

    Background Reduced prepulse inhibition (PPI) of the auditory startle reflex is a hallmark feature of attention-processing deficits in patients with schizophrenia and other psychotic disorders. Recent evidence suggests that these deficits may also be present before the onset of psychosis in individuals at ultra-high risk (UHR) and become progressively worse as psychosis develops. We conducted a longitudinal follow-up study to observe the development of PPI over time in UHR adolescents and healthy controls. Methods Two-year follow-up data of PPI measures were compared between UHR adolescents and a matched control group of typically developing individuals. Results We included 42 UHR adolescents and 32 matched controls in our study. Compared with controls, UHR individuals showed reduced PPI at both assessments. Clinical improvement in UHR individuals was associated with an increase in PPI parameters. Limitations A developmental increase in startle magnitude partially confined the interpretation of the association between clinical status and PPI. Furthermore, post hoc analyses for UHR individuals who became psychotic between assessments had limited power owing to a low transition rate (14%). Conclusion Deficits in PPI are present before the onset of psychosis and represent a stable vulnerability marker over time in UHR individuals. The magnitude of this marker may partially depend on the severity of clinical symptoms. PMID:21266126

  2. Chlorhexidine stabilizes the adhesive interface: a 2 year in vitro study

    PubMed Central

    Breschi, Lorenzo; Mazzoni, Annalisa; Nato, Fernando; Carrilho, Marcela; Visintini, Erika; Tjäderhane, Leo; Ruggeri, Alessandra; Tay, Franklin R; De Stefano Dorigo, Elettra; Pashley, David H

    2013-01-01

    Objectives This study evaluated the role of endogenous dentin MMPs in auto-degradation of collagen fibrils within adhesive-bonded interfaces. The null hypotheses tested were that adhesive blends or chlorhexidine digluconate (CHX) application does not modify dentin MMPs activity and that CHX used as therapeutic primer does not improve the stability of adhesive interfaces over time. Methods Zymograms of protein extracts from human dentin powder incubated with Adper Scotchbond 1XT (SB1XT) on untreated or 0.2–2% CHX treated dentin were obtained to assay dentin MMPs activity. Microtensile bond strength and interfacial nanoleakage expression of SB1XT bonded interfaces (with or without CHX pre-treatment for 30s on the etched surface) were analyzed immediately and after 2 yr of storage in artificial saliva at 37°C. Results Zymograms showed that application of SB1XT to human dentin powder increases MMP-2 activity, while CHX pre-treatment inhibited all dentin gelatinolytic activity, irrespective from the tested concentration. CHX significantly lowered the loss of bond strength and nanoleakage seen in acid-etched resin-bonded dentin artificially aged for 2 yr. Significance The study demonstrates the active role of SB1XT in dentin MMP-2 activation and the efficacy of CHX inhibition of MMPs even if used at low concentration (0.2%). PMID:20045177

  3. 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.

  4. 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.

  5. Mineral trioxide aggregate as pulp capping agent for primary teeth pulpotomy: 2 year follow up study.

    PubMed

    Subramaniam, Priya; Konde, Sapna; Mathew, Somy; Sugnani, Sony

    2009-01-01

    The aim of the present study was to clinically and radiographically evaluate Mineral Trioxide Aggregate (MTA) as an agent for pulpotomy in primary teeth and to compare it with that of formocresol (FC) pulpotomy. Nineteen children between the ages of 6 to 8 years with 40 carious primary molars were treated with pulpotomy using either FC or MTA. All the molars were evaluated clinically and radiographically at regular intervals over a twenty four month period. The observations were tabulated and statistically analyzed. Eighty five percent success was observed with FC pulpotomy whereas MTA showed 95% success. MTA showed a higher clinical and radiographic success rate than FC. MTA may be a favorable material for pulpotomy in primary teeth whose pulps have been compromised by a carious or mechanical pulp exposure.

  6. A longitudinal study of cryptosporidiosis in dairy cattle from birth to 2 years of age.

    PubMed

    Santín, Mónica; Trout, James M; Fayer, Ronald

    2008-08-01

    Fecal specimens were collected from 30 calves from birth to 24 months of age at a dairy farm in Maryland to determine the prevalence and age distribution of Cryptosporidium species/genotypes. After centrifugation to remove debris and concentrate oocysts, specimens were examined by immunofluorescence microscopy and polymerase chain reaction (PCR). Fragments of the SSU-rDNA gene amplified by PCR were purified and PCR products were sequenced. All 30 calves shed Cryptosporidium oocysts at some time during the 24 months of the study. Of 990 specimens, 190 were Cryptosporidium-positive (19.2%). The highest prevalence of infection was at 2 weeks of age when 29 of the 30 calves were excreting oocysts. Prevalence was higher in pre-weaned calves (1-8 weeks of age) (45.8%) than in post-weaned calves (3-12 months of age) (18.5%) and heifers (12-24 months of age) (2.2%). Sequence data for 190 PCR-positive specimens identified: C. parvum, C. bovis, the Cryptosporidium deer-like genotype and C. andersoni, with cumulative prevalences of 100, 80, 60, and 3.3%, respectively. C. parvum constituted 97% of infections in pre-weaned calves but only 4% and 0% of infections in post-weaned calves and heifers, respectively. All C. parvum GP60 nucleotide sequences were subtype IIaA15G2R1.

  7. Psychiatric disorders in children with Prader-Willi syndrome-Results of a 2-year longitudinal study.

    PubMed

    Lo, S T; Collin, P J L; Hokken-Koelega, A C S

    2015-05-01

    Psychiatric disorders such as psychosis are highly prevalent in adults with Prader-Willi syndrome (PWS). However, knowledge about the presence and progression of psychiatric disorders in children with PWS is very limited. Sixty-one children with PWS aged 7-17 years were tested using the Diagnostic Interview Schedule for Children (DISC) and Compulsive Behaviour Checklist (CBC), and 38/61 were retested after 2 years. Prevalence of psychiatric disorders and the association with age, gender, genetic subtype, and total IQ were assessed. In addition, occurrence and characteristics of compulsions were determined. Prior to the study, two boys were known with psychotic symptoms and treated with antipsychotics. At baseline, none scored positive for psychotic disorder. During the follow-up, only one boy with known psychotic symptoms required a dose adjustment of his antipsychotic medication. After 2 years, none of the children had a psychotic disorder according to the DISC. Oppositional defiant disorder (ODD) was the most common diagnosis and present in 20% of children with PWS, and this was not associated with age (β = -0.081, P = 0.546), gender (β = 0.013, P = 0.923), genetic subtype (β = -0.073, P = 0.584), or total IQ (β = -0.150, P = 0.267). The most common compulsions were hoarding and fixed hygiene sequences. In our large group of 61 children with PWS, the majority had no psychotic disorder and no progression was found during 2-year follow-up. ODD was present in 20% of children. No changes in the prevalence of psychiatric disorders were found during the 2-year follow-up study and genetic subtype was not related to psychosis, depression, or ODD.

  8. Clinical and biochemical studies support smokeless tobacco’s carcinogenic potential in the human oral cavity

    PubMed Central

    Mallery, Susan R.; Tong, Meng; Michaels, Gregory C.; Kiyani, Amber R.; Hecht, Stephen S.

    2014-01-01

    In 2007, International Agency for Cancer Research presented compelling evidence that linked smokeless tobacco use to the development of human oral cancer. While these findings imply vigorous local carcinogen metabolism, little is known regarding levels and distribution of Phase I, II and drug egress enzymes in human oral mucosa. In the study presented here, we integrated clinical data, imaging and histopathologic analyses of an oral squamous cell carcinoma that arose at the site of smokeless tobacco quid placement in a patient. Immunoblot and immunohistochemical (IHC) analyses were employed to identify tumor and normal human oral mucosal smokeless tobacco-associated metabolic activation and detoxification enzymes. Human oral epithelium contains every known Phase I enzyme associated with nitrosamine oxidative bioactivation with ~2 fold inter-donor differences in protein levels. Previous studies have confirmed ~3.5 fold inter-donor variations in intraepithelial Phase II enzymes. Unlike the superficially located enzymes in non-replicating esophageal surface epithelium, IHC studies confirmed oral mucosal nitrosamine metabolizing enzymes reside in the basilar and suprabasilar region which notably is the site of ongoing keratinocyte DNA replication. Clearly, variations in product composition, nitrosamine metabolism and exposure duration will modulate clinical outcomes. The data presented here form a coherent picture consistent with the abundant experimental data that links tobacco-specific nitrosamines to human oral cancer. PMID:24265177

  9. 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.

  10. 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

  11. Carcinogenicity study of 3-monochloropropane-1, 2-diol (3-MCPD) administered by drinking water to B6C3F1 mice showed no carcinogenic potential.

    PubMed

    Jeong, Jayoung; Han, Beom Seok; Cho, Wan-Seob; Choi, Mina; Ha, Chang-Su; Lee, Byoung-Seok; Kim, Yong-Bum; Son, Woo-Chan; Kim, Choong-Yong

    2010-09-01

    3-Monochloropropane-1, 2-diol (or 3-chloro-1,2-propanediol, 3-MCPD) is a well-known food processing contaminant found in a wide range of foods and ingredients. It has been classified as non-genotoxic carcinogen but its carcinogenic potential in the rodents has been controversial. The carcinogenicity to B6C3F1 mice by drinking water administration was assessed over a period of 104 weeks. Three groups, each comprising 50 male and 50 female mice received 3-MCPD at dosages of 30, 100 or 300 ppm up to Day 100 and 200 ppm onward (4.2, 14.3 and 33.0 mg/kg for males; 3.7, 12.2, and 31.0 mg/kg for females), were allocated. Survival was good, with at least 80% of males and 72% of females in each group surviving 104 weeks. Body weights and body weight gain were decreased in males and females receiving 200 ppm. Water and food consumptions of both sexes at 300/200 ppm were lowered. Emaciated or crouching position was observed for animals of both sexes exposed to 200 ppm. There were some differences in hematology and serum biochemistry compared with controls, although there was no histopathological evidence to support those changes. Histopathological examination did not reveal any neoplastic or non-neoplastic findings attributable to treatment with 3-MCPD. It is concluded that drinking water administration of 3-MCPD for 104 weeks revealed no evidence of carcinogenic potential.

  12. 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

  13. Carcinogenicity studies on fibres, metal compounds, and some other dusts in rats.

    PubMed

    Pott, F; Ziem, U; Reiffer, F J; Huth, F; Ernst, H; Mohr, U

    1987-01-01

    About 50 dusts were examined on their carcinogenicity in rats mainly after intraperitoneal injection and some after intratracheal instillation. In the i.p. test, very low doses between 0.05 and 0.5 mg asbestos led to tumour incidences of about 20 to 80%. Polyvinyl-pyridine-N-oxide prolonged the tumour latency after injection of actinolite. 60 mg attapulgite from three sources with short fibre lengths were not shown to be carcinogenic but an attapulgite sample with longer fibres had a moderate effect. Relatively thick rock and ceramic fibres (median greater than 1 micron) induced tumours, but slag and wollastonite fibres did not, probably because of their better solubility. Intratracheal instillations of glass microfibres (20 X 0.5 mg) led to lung tumours in 5 of 34 rats (0 in control). The carcinogenic potency of an inorganic fibre depends on its size and persistency, and possibly also on other properties, especially on the surface. Nickel powder, nickel oxide, nickel subsulfide and cadmium sulfide were all found to be carcinogenic in the two tests. Cadmium chloride and cadmium oxide could only be administered in very low doses because of their high acute toxicity. A high amount of magnetite (15 X 15 mg i.tr.) led to an unexpected lung tumour incidence of 69%. The i.p. test in rats proved to be very sensitive for detecting the carcinogenic potency of non-acute toxic natural and man-made mineral dusts as well as metal compounds. This means that, if a high dose of one of these dusts does not induce tumours in this test, no suspicion of carcinogenic potency can be substantiated.

  14. Association between the high-dose use of benzodiazepines and rehospitalization in patients with schizophrenia: a 2-year naturalistic study

    PubMed Central

    Takita, Yukika; Takaesu, Yoshikazu; Ono, Kotaro; Futenma, Kunihiro; Shimura, Akiyoshi; Murakoshi, Akiko; Komada, Yoko; Inoue, Yuichi; Inoue, Takeshi

    2016-01-01

    Background High-dose use of benzodiazepines (BZPs) reportedly causes adverse effects on cognitive function and quality of life in patients with schizophrenia. However, effects of BZPs on the clinical course of schizophrenia have not been clarified. This study was set out to investigate the association between BZPs and rehospitalization of patients with schizophrenia. Methods In this retrospective study, patients with schizophrenia who were discharged from Tokyo Medical University Hospital between January 2009 and February 2012 were eligible as subjects. One hundred and eight patients who continued treatment for >2 years after hospital discharge were included in this study. Clinical characteristics, doses of prescribed medication such as BZPs and antipsychotics, and Global Assessment of Functioning scores at discharge were investigated. The primary outcome was rehospitalization of patients for any reason. Results In a total of 108 subjects with schizophrenia, 44 subjects (40.7%) experienced rehospitalization during the 2-year study period. A multivariate analysis by the Cox proportional hazards model revealed that low educational history (hazard ratio =2.43, P=0.032), younger onset age of schizophrenia (hazard ratio =2.10, P=0.021), and higher diazepam-equivalent dose (hazard ratio =6.53, P=0.011) were significantly associated with the time to rehospitalization after hospital discharge. Conclusion The results of this study suggest that high-dose use of BZPs at discharge in patients with schizophrenia might be associated with a shorter time to rehospitalization. PMID:28008260

  15. 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

  16. Novel Transgenic Mouse Model for Studying Human Serum Albumin as a Biomarker of Carcinogenic Exposure.

    PubMed

    Sheng, Jonathan; Wang, Yi; Turesky, Robert J; Kluetzman, Kerri; Zhang, Qing-Yu; Ding, Xinxin

    2016-05-16

    Albumin is a commonly used serum protein for studying human exposure to xenobiotic compounds, including therapeutics and environmental pollutants. Often, the reactivity of albumin with xenobiotic compounds is studied ex vivo with human albumin or plasma/serum samples. Some studies have characterized the reactivity of albumin with chemicals in rodent models; however, differences between the orthologous peptide sequences of human and rodent albumins can result in the formation of different types of chemical-protein adducts with different interaction sites or peptide sequences. Our goal is to generate a human albumin transgenic mouse model that can be used to establish human protein biomarkers of exposure to hazardous xenobiotics for human risk assessment via animal studies. We have developed a human albumin transgenic mouse model and characterized the genotype and phenotype of the transgenic mice. The presence of the human albumin gene in the genome of the model mouse was confirmed by genomic PCR analysis, whereas liver-specific expression of the transgenic human albumin mRNA was validated by RT-PCR analysis. Further immunoblot and mass spectrometry analyses indicated that the transgenic human albumin protein is a full-length, mature protein, which is less abundant than the endogenous mouse albumin that coexists in the serum of the transgenic mouse. The transgenic protein was able to form ex vivo adducts with a genotoxic metabolite of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, a procarcinogenic heterocyclic aromatic amine formed in cooked meat. This novel human albumin transgenic mouse model will facilitate the development and validation of albumin-carcinogen adducts as biomarkers of xenobiotic exposure and/or toxicity in humans.

  17. The Auckland Cataract Study: 2 year postoperative assessment of aspects of clinical, visual, corneal topographic and satisfaction outcomes

    PubMed Central

    Thompson, A M; Sachdev, N; Wong, T; Riley, A F; Grupcheva, C N; McGhee, C N

    2004-01-01

    Aim: To assess clinical, visual, computerised corneal topographic, and subjective satisfaction with visual acuity, in a cohort of subjects 2 years after phacoemulsification surgery in a public hospital in New Zealand. Methods: Prospective study of a representative sample of 97 subjects (20%) randomly selected from 480 subjects in the original Auckland Cataract Study (ACS) cohort. The clinical assessment protocol was identical to the ACS and included an extensive questionnaire to enable direct comparisons to be made between the two groups. Results: The study population was predominantly female (66%) with a mean age of 76.3 (SD 9.9) years. New systemic and ocular disease affected 18.4% and 10.3% of subjects respectively, and 10.3% required referral to either a general practitioner (2.1%) or ophthalmologist (8.2%). Mean best spectacle corrected visual acuity (BSCVA) was 0.2 (0.2) logMAR units (6/9 Snellen equivalent), with mean spherical equivalent −0.37 (1.01) dioptres (D) and astigmatism −1.07 (0.70) D 2 years postoperatively, compared to mean BSCVA 0.1 (0.2) logMAR units (6/7.5 Snellen equivalent), spherical equivalent −0.59 (1.07) D, and astigmatism −1.14 (0.77) D 4 weeks after surgery. 94.9% of subjects retained a BSCVA of 6/12 or better, irrespective of pre-existing ocular disease. The overall posterior capsule opacification (PCO) rate was 20.4% and this was visually insignificant in all but 3.1% of eyes that had already undergone Nd:YAG posterior capsulotomy. Orbscan II elevation technology demonstrated corneal stability 2 years after uncomplicated phacoemulsification. Although corneal astigmatism was eliminated in approximately half of the subjects 1 month postoperatively, astigmatism showed a tendency to regress towards the preoperative level with local corneal thickening at the site of incision 2 years after cataract surgery. Of fellow eyes, 61.2% had undergone cataract surgery. Overall, 75.3% of subjects were moderately to very satisfied with their

  18. 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.

  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. 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.

  1. Iron intakes and status of 2-year-old children in the Cork BASELINE Birth Cohort Study.

    PubMed

    McCarthy, Elaine K; Ní Chaoimh, Carol; O'B Hourihane, Jonathan; Kenny, Louise C; Irvine, Alan D; Murray, Deirdre M; Kiely, Mairead

    2016-08-09

    Young children are at risk of iron deficiency and subsequent anaemia, resulting in long-term consequences for cognitive, motor and behavioural development. This study aimed to describe the iron intakes, status and determinants of status in 2-year-old children. Data were collected prospectively in the mother-child Cork BASELINE Birth Cohort Study from 15 weeks' gestation throughout early childhood. At the 24-month assessment, serum ferritin, haemoglobin and mean corpuscular volume were measured, and food/nutrient intake data were collected using a 2-day weighed food diary. Iron status was assessed in 729 children (median [IQR] age: 2.1 [2.1, 2.2] years) and 468 completed a food diary. From the food diary, mean (SD) iron intakes were 6.8 (2.6) mg/day and 30% had intakes < UK Estimated Average Requirement (5.3 mg/day). Using WHO definitions, iron deficiency was observed in 4.6% (n = 31) and iron deficiency anaemia in five children (1.0%). Following an iron series workup, five more children were diagnosed with iron deficiency anaemia. Twenty-one per cent had ferritin concentrations <15 µg/L. Inadequate iron intakes (OR [95% CI]: 1.94 [1.09, 3.48]) and unmodified cows' milk intakes ≥ 400 mL/day (1.95 [1.07, 3.56]) increased the risk of low iron status. Iron-fortified formula consumption was associated with decreased risk (0.21 [0.11, 0.41] P < 0.05). In this, the largest study in toddlers in Europe, a lower prevalence of low iron status was observed than in previous reports. Compliance with dietary recommendations to limit cows' milk intakes in young children and consumption of iron-fortified products appears to have contributed to improved iron status at two years.

  2. 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

  3. Quantitative sensory tests before and 1(1/2) years after orthognathic surgery: a cross-sectional study.

    PubMed

    Baad-Hansen, L; Arima, T; Arendt-Nielsen, L; Neumann-Jensen, B; Svensson, P

    2010-05-01

    Quality control is very important in relation to invasive and lengthy treatments, such as integrated orthodontic and surgical correction of dentofacial deformities. The aim of this cross-sectional study was to compare self-reported somatosensory disturbances and quantitative sensory testing (QST) findings between two groups of patients and a healthy control group (n = 24); one group (n = 21) scheduled for bimaxillary orthognathic surgery (BOS) (pre-op) and one group (n = 24) examined 1(1/2) years after BOS (post-op). Self-reported data on pain and somatosensory disturbances were collected, and QST was performed at six trigeminal and one extratrigeminal site. Sensitivity to brush stroke, tactile stimuli, pinprick, two-point-discrimination threshold (2P-DT), pinch pain threshold (PiPT) and pressure pain threshold (PPT) was evaluated. Results were analysed with anovas, Spearman's Correlation, and chi square tests. Eight per cent of post-op patients reported intra-oral, 46% extra-oral, and 46% no somatosensory disturbances. Sensitivity to brush stroke, pinprick and 2P-DT was significantly increased at all examination sites in the post-op patients compared with healthy controls (P < 0.002). Tactile thresholds and PPT did not differ between groups (P > 0.071). Pinch pain threshold were decreased in pre-op patients compared with controls (P < 0.040). Self-reported somatosensory disturbances were not correlated with QST findings. In conclusion; 1(1/2) years after BOS, a large proportion of patients reported somatosensory disturbances and was hypersensitive to mechanical stimuli when compared with pre-op patients and healthy controls. Pre-op patients showed minor somatosensory changes. In addition to patients serving as their own control in prospective studies, a healthy control group and extratrigeminal control sites should be included in future studies.

  4. 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.

  5. 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.

  6. Executive functioning correctly classified diagnoses in patients with first-episode psychosis: evidence from a 2-year longitudinal study.

    PubMed

    Peña, Javier; Ojeda, Natalia; Segarra, Rafael; Eguiluz, Jose Ignacio; García, Jon; Gutiérrez, Miguel

    2011-03-01

    Few studies have analysed factors that predict the ultimate clinical diagnosis in first-episode psychosis (FEP), and none has included cognitive factors. Eighty-six FEP patients and 34 healthy controls were recruited and followed up for two years. Positive and negative symptoms, depression, mania, duration of untreated psychosis (DUP), premorbid functioning, functional outcome and neurocognition were assessed over 2 years. Logistic regression models revealed that Wisconsin Card Sorting Test correctly distinguished the patients ultimately diagnosed with schizophrenia (87%) from those with bipolar disorder (80%) and those with other psychoses (85%), for an overall correct-diagnosis rate of 84.4%. The prediction was stable despite the inclusion of clinical and affective symptoms, DUP, clinical impression, and functional outcome scores. Results highlight the importance of reconsidering neurocognition as a diagnostic criterion for psychosis and schizophrenia.

  7. Carcinogenicity studies on natural and man-made fibres with the intraperitoneal test in rats.

    PubMed

    Pott, F; Roller, M; Ziem, U; Reiffer, F J; Bellmann, B; Rosenbruch, M; Huth, F

    1989-01-01

    Female Wistar rats were injected intraperitoneally (i.p.) with a suspension of 11 fibrous and 3 granular dusts. A dose of 0.25 mg actinolite or UICC chrysotile induced tumours of the peritoneum in more than 50% of the animals. Even 0.05 and 0.01 mg proved to be carcinogenic, although no adhesions of the abdominal organs could be observed. The findings are in conflict with the hypothesis that a scar is always the morphological precondition for the development of an asbestos-induced tumour. Actinolite injected i.p. in a solution of polyvinylpyridine-N-oxide gave a lower tumour incidence than when suspended only in saline, possibly due to inactivation of the fibre surface. Persistent glass fibres were less effective than actinolite having a similar fibre size distribution. On the other hand, relatively thick basalt fibres and ceramic fibres gave higher tumour incidences than expected. Wollastonite fibres were not carcinogenic, probably because of their low durability. Large amounts of polyvinylchloride, alpha-ferric oxide hydrate and wood dust also led only to adhesions of the abdominal organs and fibrosis; a definite carcinogenic effect was not detected.

  8. 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.

  9. 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.

  10. 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.

  11. Carcinogenic human papillomavirus infection.

    PubMed

    Schiffman, Mark; Doorbar, John; Wentzensen, Nicolas; de Sanjosé, Silvia; Fakhry, Carole; Monk, Bradley J; Stanley, Margaret A; Franceschi, Silvia

    2016-12-01

    Infections with human papillomavirus (HPV) are common and transmitted by direct contact. Although the great majority of infections resolve within 2 years, 13 phylogenetically related, sexually transmitted HPV genotypes, notably HPV16, cause - if not controlled immunologically or by screening - virtually all cervical cancers worldwide, a large fraction of other anogenital cancers and an increasing proportion of oropharyngeal cancers. The carcinogenicity of these HPV types results primarily from the activity of the oncoproteins E6 and E7, which impair growth regulatory pathways. Persistent high-risk HPVs can transition from a productive (virion-producing) to an abortive or transforming infection, after which cancer can result after typically slow accumulation of host genetic mutations. However, which precancerous lesions progress and which do not is unclear; the majority of screening-detected precancers are treated, leading to overtreatment. The discovery of HPV as a carcinogen led to the development of effective preventive vaccines and sensitive HPV DNA and RNA tests. Together, vaccination programmes (the ultimate long-term preventive strategy) and screening using HPV tests could dramatically alter the landscape of HPV-related cancers. HPV testing will probably replace cytology-based cervical screening owing to greater reassurance when the test is negative. However, the effective implementation of HPV vaccination and screening globally remains a challenge.

  12. Use of Ergonomic Measures Related to Musculoskeletal Complaints among Construction Workers: A 2-year Follow-up Study

    PubMed Central

    Boschman, Julitta S.; Frings-Dresen, Monique H.W.; van der Molen, Henk F.

    2015-01-01

    Background The physical work demands of construction work can be reduced using ergonomic measures. The aim of this study was to evaluate the use of ergonomic measures related to musculoskeletal disorders (MSDs) among construction workers. Methods A questionnaire was sent at baseline and 2 years later to 1,130 construction workers. We established (1) the proportion of workers reporting an increase in their use of ergonomic measures, (2) the proportion of workers reporting a decrease in MSDs, (3) the relative risk for an increase in the use of ergonomic measures and a decrease in MSDs, and (4) workers' knowledge and opinions about the use of ergonomic measures. Results At follow-up, response rate was 63% (713/1,130). The proportion of workers using ergonomic measures for vertical transport increased (34%, 144/419, p < 0.01); for measures regarding horizontal transport and the positioning of materials, no change was reported. The proportion of workers reporting shoulder complaints decreased (28%, 176/638, p = 0.02). A relationship between the use of ergonomic measures and MSDs was not found; 83% (581/704) of the workers indicated having sufficient knowledge about ergonomic measures. Lightening the physical load was reported to be the main reason for using them. Conclusion Only the use of ergonomic measures for vertical transport increased over a 2-year period. No relationship between the use of ergonomic measures and MSDs was found. Strategies aimed at improving the availability of ergonomic equipment complemented with individualized advice and training in using them might be the required next steps to increase the use of ergonomic measures. PMID:26106507

  13. Acrylonitrile: a suspected human carcinogen.

    PubMed

    Koerselman, W; van der Graaf, M

    1984-01-01

    The literature on carcinogenicity of acrylonitrile (an important intermediate in the chemical industry) is reviewed. The three main conclusions are: (1) Acrylonitrile has genotoxic effects in various tests in microorganisms and in mammal cells. (2) Chronic exposure to acrylonitrile causes tumours in rats. (3) Results of epidemiological studies indicate that acrylonitrile may be a human carcinogen. From this it is clear that acrylonitrile is very probably carcinogenic to humans. Therefore the authors plead for a reduction of acrylonitrile standards to the lowest practicable limit.

  14. Carcinogen testing. Fact and fallacy.

    PubMed

    Moore, J A

    1988-10-15

    In the absence of human information on the carcinogenicity of chemical substances, one must rely primarily on information from long-term animal testing. Although far from perfect, animal studies seem to be reasonable predictors of the human experience, both qualitatively and quantitatively. Short-term tests for genotoxicity may be helpful for establishing priorities for chemical testing, but they are not as strong indicators of potential carcinogenicity as had been previously thought. New directions in toxicologic research hold the promise for scientists being able to perform more reasoned assessments of carcinogenic risk.

  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. A 2-year follow-up study on muscle size and dynamic strength in teenage tennis players.

    PubMed

    Kanehisa, H; Kuno, S; Katsuta, S; Fukunaga, T

    2006-04-01

    Growth trends in the cross-sectional area of the quadriceps femoris (CSA(QF)) and its dynamic strength in 12 teenage tennis players (six boys and six girls), aged from 10.7 to 13.2 years at the onset of the study, were investigated through a 2-year follow-up survey. CSA(QF) values at the three levels (proximal, mid, and distal to the knee joint) and dynamic torques during knee extensions at three pre-set velocities (1.05, 3.14, and 5.24 rad/s) were determined year by year, i.e., three times (T1, T2, and T3), using magnetic resonance imaging and an isokinetic dynamometer, respectively. In both genders, the CSA(QF) values at the three levels tended to increase across the measurement times, with greater gains in the boys than in the girls at the levels mid and distal to the knee joint. Among these changes, only the CSA(QF) at the level proximal to the knee joint significantly increased regardless of changes in both skeletal age and body height. The ratios of torque to the sum of CSA(QF) at the three levels (T/CSA) at 3.14 and 5.24 rad/s for the boys and at 5.24 rad/s for the girls were significantly higher in T2 and T3 than T1. Further, the relative increases in torque and T/CSA values at 3.14 and 5.24 rad/s were greater in the boys than the girls. The findings presented here indicate that young tennis players who are in the earlier stage of adolescence increase the CSA of the QF muscle beyond normally expected growth change at the level proximal to the knee joint and show a predominant development in torque generation capability during high-velocity knee extensions, with a greater gain in boys compared with girls.

  18. A 2-year longitudinal study of eating attitudes, BMI, perfectionism, asceticism and family climate in adolescent girls and their parents.

    PubMed

    Westerberg, J; Edlund, B; Ghaderi, A

    2008-06-01

    The aim of this longitudinal study of 383 Swedish adolescent girls (11 and 13 years old at year 1) and their parents was to examine changes in eating attitudes over a two-year period, and to investigate the predictive value of eating attitudes, perfectionism, asceticism, family climate and body mass index (BMI) for the development of disturbed eating attitudes. The following self-report questionnaires were used: Children's Eating Attitudes test, Eating Attitudes Test, Eating Disorder Inventory for Children, Eating Disorder Inventory 2, I Think I Am and The Family Climate. The frequency of disturbed eating attitudes increased with increased age in the girls. Children's eating attitudes, higher BMI than peers, the girls rating of a less healthy relation to family and their fathers' eating attitudes at year 1 contributed most to the prediction of disturbed eating attitudes for the girls 2 years later. The results suggest that early signs of disturbed eating attitudes and higher BMI than peers may be important predictors for the development of more serious eating disturbances among adolescent girls.

  19. 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.

  20. The micronucleus test and NTP rodent carcinogens: not so many false negatives.

    PubMed

    Galloway, S M

    1996-06-10

    In the study by Shelby et al. (1993) on 49 chemicals, the results of the micronucleus (MN) test in mouse bone marrow were compared with the results of the 2 year rodent carcinogenicity assays. Seven of the 25 rodent carcinogens were considered positive in the MN test, 5 following a protocol in which chemicals were given in three daily doses, and a further 2 when the chemical was administered only once. This low rate of positive results has led to disappointment in the MN test as a screen for carcinogens, but a careful examination of the data and of its analysis by Shelby et al. (1993) shows that many of the negative results are appropriate because: of the 18 carcinogens that were negative in the MN test, 1 has been retested and found to be non-carcinogenic, 9 were non-genotoxic and at least 2 were site-of-contact carcinogens not expected to be detected in the bone marrow. Two others were clearly positive in the MN test in other labs. Thus, the MN test 'missed' not 18 carcinogens, but 4 genotoxic carcinogens. The significance of these 4 needs further assessment, since three were liver specific carcinogens and the fourth was a very weak inducer of hemangiosarcomas in female mice only. Overall, the results of Shelby et al. (1993) do not cast such a shadow on the micronucleus test as many feared, and must be examined in the context of all the information available on each chemical. As Ashby and Tinwell emphasize in the accompanying article and in Tinwell and Ashby (1994), the data show that the MN test is capable of identifying human carcinogens and rodent germ cell mutagens, and remains a useful part of genotoxicity evaluation of chemicals.

  1. 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.

  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. 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

  4. 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

  5. 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

  6. 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)

  7. Trajectories of CKD-MBD biochemical parameters over a 2-year period following diagnosis of secondary hyperparathyroidism: a pharmacoepidemiological study

    PubMed Central

    Filipozzi, Pierre; Ayav, Carole; Ngueyon Sime, Willy; Laurain, Emmanuelle; Kessler, Michèle; Brunaud, Laurent; Frimat, Luc

    2017-01-01

    Objectives To define groups of patients according to the changes of biochemical parameters, that is, serum calcium, phosphate and parathyroid hormone (PTH), over a 2-year follow-up period using group-based multi-trajectory modeling (GBMM) among a cohort of dialysis patients with newly diagnosed secondary hyperparathyroidism (SHPT) (ie, PTH≥500 ng/L for the first time) and to compare their patient characteristics and treatments. Design Pharmacoepidemiological study. Setting In the 12 dialysis units located in the French region of Lorraine. Participants A total of 269 dialysis patients with newly diagnosed SHPT were prospectively included from December 2009 to May 2012 and followed-up for 2 years. Results We identified four distinct trajectory groups: ‘rapid PTH drop’ experiencing a rapid and sharp decrease (over weeks) in PTH level associated with decreasing phosphate level within normal range (n=34; 12.7%), ‘gradual PTH decrease’ experiencing a gradual and continuous decrease (over months) in PTH level and maintaining phosphate at a middle level throughout the study (n=98; 36.4%), ‘slow PTH decrease with high phosphate’ experiencing a slow decrease in PTH level associated with a relatively high phosphate level (n=105; 39.0%) and ‘uncontrolled SHPT’ with high levels of PTH and phosphate throughout the study (n=32; 11.9%). Patients in the ‘uncontrolled SHPT’ group were significantly (p<0.00001) younger than patients in other groups. Kidney Disease Improving Global Outcomes (KDIGO) targets for PTH, phosphate and calcium were reached simultaneously for 14.9% of patients at baseline and 16.7% at the end of the study. Patients were given cinacalcet more frequently at months 3 and 6 in the ‘rapid PTH drop’ and at month 24 in the ‘uncontrolled SHPT’ groups. Conclusions Over 2 years following a new SHPT diagnosis, a younger age and a higher rate of alkaline phosphatase were associated to a continuous uncontrolled SHPT. Patients with the

  8. 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.

  9. Results of long-term experimental studies on the carcinogenicity of ethylene-bis-dithiocarbamate (Mancozeb) in rats.

    PubMed

    Belpoggi, Fiorella; Soffritti, Morando; Guarino, Marina; Lambertini, Luca; Cevolani, Daniela; Maltoni, Cesare

    2002-12-01

    Mancozeb, an ethylene-bis-dithiocarbamate (EBDC), has been one of the most commonly used fungicides in commercial use for several decades. Nevertheless, up to now, no adequate published experimental studies on the carcinogenicity of Mancozeb have been published. Because of the importance of the compound and of the number of people potentially exposed (workers engaged in the production and use of the fungicide, people living in agricultural areas where the compound is sprayed, and people consuming polluted products), a long-term experimental study of Mancozeb was begun at the Cancer Research Center of the Ramazzini Foundation. Groups of 150 male and female Sprague-Dawley rats, 8 weeks old at the start of the treatment, were administered Mancozeb at the concentration of 1000, 500, 100, 10, and 0 ppm in feed supplied ad libitum for 104 weeks. At the end of the treatment, animals were kept under controlled conditions until spontaneous death. Mancozeb caused an increase in (1) total malignant tumors, (2) malignant mammary tumors, (3) Zymbal gland and ear duct carcinomas, (4) hepatocarcinomas, (5) malignant tumors of the pancreas, (6) malignant tumors of the thyroid gland, (7) osteosarcomas of the bones of the head, and (8) hemolymphoreticular neoplasias. On the basis of these data, Mancozeb must be considered a multipotent carcinogenic agent.

  10. 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.

  11. Radiation- and Depleted Uranium-Induced Carcinogenesis Studies: Characterization of the Carcinogenic Process and Development of Medical Countermeasures

    DTIC Science & Technology

    2005-01-01

    osteoblast cells, HOS) to evaluate the carcinogenic potential of DU in vitro by assessing morphological transformation, genotoxicity ( chromosomal aberrations...hypoxanthine reductase transferase (HPRT) assay, and chromosomal ab- erration assays, i.e., micronuclei, we have examined the carcinogenic, mutagenic, and...or chromosomal aberrations (i.e., micronuclei) [Miller 1998a, Miller 2001]. These in vitro results continue to suggest that DU has carcinogenic

  12. Cutting fluids and their effects on the skin of mice. An experimental study with special reference to carcinogenicity.

    PubMed

    Jepsen, J R; Stoyanov, S; Unger, M; Clausen, J; Christensen, H E

    1977-09-01

    Reports of skin malignancies due to occupational exposure have decreased since the introduction of solvent-refining of mineral oil fraction in the manufacture of oil based cutting fluids. Commercial mineral oil based cutting fluids caused local and general pathological changes after repeated application to the skin of mice in the present study. Forty-eight per cent of the mice exposed to oils showed severe dysplasia or malignancy of the skin on histological examination. The corresponding figure for the control group, where various additives were used was 8 per cent. The frequency of papillomas was also increased in the mice exposed to oils. The systemic lesions included focal necrosis of the liver, associated with amyloid deposition, as well as amyloidosis of the skin, spleen and kidneys. The substances responsible for these apparent carcinogenic properties of the complex mixtures may be polycyclic hydrocarbons; the latter are still present in the commercial products despite solvent refining; on the other hand the carcinogens may be additives to the cutting oils the composition of which is generally a trade secret.

  13. 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.

  14. Toxicity and carcinogenicity studies of Caramel Colour IV in F344 rats and B6C3F1 mice.

    PubMed

    MacKenzie, K M; Boysen, B G; Field, W E; Petsel, S R; Chappel, C I; Emerson, J L; Stanley, J

    1992-05-01

    Caramel Colour IV, a type of caramel colour used in the manufacture of cola soft drinks, was evaluated for subchronic and chronic toxicity in rats, and carcinogenicity in Fischer-344 (F344) rats and B6C3F1 mice. In each of the studies, Caramel Colour IV was mixed with demineralized water and the solutions given to the animals ad lib. in the drinking fluid. The concentrations of Caramel Colour IV in the drinking fluid were adjusted periodically to achieve the desired caramel colour intake per kg body weight. In the range-finding studies, groups of 30 rats/sex were given Caramel Colour IV at levels of 0, 15, 20, 25 or 30 g/kg for 13 wk, and groups of 10 male rats were given levels of 0, 2.5, 5, 10 or 15 g/kg for 6 wk followed, for some dose groups, by a 2-wk withdrawal period, and then re-initiation of dosing for another 2 wk. In the rat chronic toxicity study, levels of Caramel Colour IV of 0, 2.5, 5, 7.5 or 10 g/kg were given to groups of 25 rats/sex for 12 months. The test groups in the rat and mouse carcinogenicity studies were composed of 50 animals/sex and each species was given the caramel colour at levels of 0, 0, 2.5, 5 or 10 g/kg for 24 months. In each of the studies, treated animals tended to have dose-related lower water consumption than controls. This was attributed to poor palatability of the drinking fluid, and was generally associated with decreased food consumption and body weights. Rats given caramel colour often had soft or liquid malodorous faeces although there were no treatment-related ante-mortem observations in mice. Blood biochemical changes in the rat (i.e. reduced blood urea nitrogen, alkaline phosphatase and total serum protein) appeared to be related to dietary influences and were not considered toxicologically significant. There were no treatment-related alterations in haematological variables or treatment-related differences in survival or in the incidence of benign or malignant tumours among treated and control groups and no

  15. Progress report on the guidance for industry for statistical aspects of the design, analysis, and interpretation of chronic rodent carcinogenicity studies of pharmaceuticals.

    PubMed

    Lin, K K

    2000-11-01

    The U.S. Food and Drug Administration (FDA) is in the process of preparing a draft Guidance for Industry document on the statistical aspects of carcinogenicity studies of pharmaceuticals for public comment. The purpose of the document is to provide statistical guidance for the design of carcinogenicity experiments, methods of statistical analysis of study data, interpretation of study results, presentation of data and results in reports, and submission of electronic study data. This article covers the genesis of the guidance document and some statistical methods in study design, data analysis, and interpretation of results included in the draft FDA guidance document.

  16. Developmental milestones record - 2 years

    MedlinePlus

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

  17. Inter-species comparisons of carcinogenicity.

    PubMed Central

    Purchase, I. F.

    1980-01-01

    The carcinogenicity of 250 chemicals in 2 species, usually the rat and the mouse, was obtained from the published literature through 3 independent sources. Of the 250 compounds listed, 38% were non-carcinogenic in both rats and mice, and 44% were carcinogenic in both species. A total of 43 compounds had different results in the two species, 21 (8%) being carcinogenic in mice only, 17 (7%) in rats only and 5 (2%) having differing results from other species. A comparison of the major target organs affected by chemicals carcinogenic in both species revealed that 64% of the chemicals studied produced cancer at the same site. This comparison of carcinogenic activity in 2 species suggests that extrapolation from results in a single-animal study to man may be subject to substantial errors. PMID:7387835

  18. Use of IC tags in short-term carcinogenicity study on CB6F1 TGrasH2 mice.

    PubMed

    Urano, Koji; Suzuki, Syuzo; Machida, Kazuhiko; Sawa, Nobuko; Eguchi, Natsuko; Kikuchi, Koji; Fukasawa, Kazumasa; Taguchi, Fukushi; Usui, Toshimi

    2006-12-01

    We studied the effect of IC tags, subcutaneously implanted animal identification tools, on rasH2 mice. A 26-week short-term carcinogenicity study was performed on a total of 299 mice including 75 male and female rasH2 mice each, and 74 male and 75 female non-Tg mice from the same litter as the rasH2 mice divided into a non-IC tag group, the IC-tag group, acetone group, TPA group and MNU group (all of the animals except for those in the non-IC tag group) had IC tags implanted subcutaneously in their backs. The administration methods of the positive control drugs TPA (2.5 micro g/kg, 3 times/week, percutaneously) and MNU (75 mg/kg, single intraperitoneal injection) were based on the protocol of the ILSI/HESI international collaborative study. The results showed no differences in the tumorigenic incidence and organs developing tumors between the IC tag and non-IC tag groups in both rasH2 and non-Tg mice. In the positive control MNU group, the tumorigenic incidence and organs developing tumors were the same as the background data and no promotion of carcinogenesis was observed. In all IC tag groups including the TPA group and MNU group, a fibrous capsule was formed around the IC tags subcutaneously, but no inflammatory changes or neoplastic changes were observed. From these findings, it was concluded that the IC tag has no effect on a 26-week carcinogenicity test of rasH2 mice under the conditions of the present study.

  19. 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

  20. 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

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

    PubMed

    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, 2mg/kgbw) or carcinogenic (4 and 8mg/kgbw) 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.

  2. 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.

  3. 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

  4. 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.

  5. Genetic profiles of Shiga toxin and intimin genes found in stool broth cultures: a 2-year reference laboratory study.

    PubMed

    Michel, Pierre A; Kase, Julie A

    2009-10-01

    Shiga toxin (Stx)-producing Escherichia coli (STEC) are associated with potentially serious illness in humans. STEC detection is often based on the presence of Stxs, Stx(1) and/or Stx(2), and intimin, encoded by the eae gene. A 2-year collection of stool broth cultures was tested for variants of stx(1), stx(2), and eae. Approximately 80% (138 of 174) were positive for stx(1) and/or stx(2), with stx(1) as the most prevalent (66%). Of the stx(1) variants, stx(1) was the most common (76%) followed by stx(1c) (22%). Analysis of stx(2)-positive isolates found 20 (53%) stx(2), 13 (34%) stx(2)/stx(2v-ha), 3 (8%) stx(2v-ha), 1 (3%) stx(2v-hb), and 1 (3%) stx(2d-activatable). Findings of stx(2)/stx(2v-ha) and stx(2d-activatable) are noteworthy given associations with hemolytic uremic syndrome and increased cytotoxicity, respectively. Of the Stx positive, 94 (68%) were eae positive with 31 (33%) eae(varepsilon1), 19 (20%) eae(gamma1), and 18 (19%) eae(beta1). A predominance of eae(varepsilon1) may suggest a new pathogenic significance because, reportedly, eae(beta1) is one of the most widespread variants.

  6. 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…

  7. 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…

  8. 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…

  9. 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

  10. 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...

  11. Carcinogenicity of chloroform.

    PubMed Central

    Reuber, M D

    1979-01-01

    Chloroform is carcinogenic in rats, mice, and probably in dogs. Chloroform induced carcinomas of the liver and kidney and malignant tumors in other organs in rats and mice. Liver neoplasms have been described in three strains of mice. Carcinomas of the kidney were found in a first study in mice and in the repeat of that study. Dogs given chloroform developed neoplasms of the liver as well as in other organs. Rats given chloroform also developed toxic changes, particularly male rats, as a result of treatment. These lesions included interstitial fibrosis of the kidney; polyarteritis of the mesenteric, pancreatic, and other arterioles and arteries; and atrophy of the testes. These toxic changes may have interfered with the development of neoplasms in male rats. PMID:227668

  12. 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

  13. Spontaneous occurrence of a distinctive renal tubule tumor phenotype in rat carcinogenicity studies conducted by the national toxicology program.

    PubMed

    Hard, Gordon C; Seely, John Curtis; Kissling, Grace E; Betz, Laura J

    2008-04-01

    The Toxicology Data Management System (TDMS) of the National Toxicology Program, National Institutes of Environmental Health Sciences, National Institutes of Health, was surveyed for occurrence and distribution of a distinctive renal tubule tumor type in rats. The hallmark features of this tumor included eosinophilic/amphophilic staining, large finely granular cells, and numerous vacuoles and/or minilumens. It is referred to here as the amphophilic-vacuolar (AV) variant of renal tubule tumor. Of 154 studies in which renal tubule tumors had been recorded in the standard single sections of kidney in the TDMS, there were collectively 1012 rats with renal adenomas, carcinomas, or adenocarcinomas, and of these, 100 displayed the distinctive AV morphology, representing 74 studies involving mostly the F344 rat, but also the Sprague-Dawley and Wistar strains. The AV tumors (mainly adenomas but also some carcinomas) occurred usually as solitary lesions in the affected animals. However, they were multiple and bilateral in a few cases. They were equally distributed between the sexes, did not metastasize (at least to the lung), and were not associated with chronic progressive nephropathy. The distribution of this renal tumor type was random across studies and dose groups, underscoring the likelihood that it was of spontaneous origin and not chemically induced. Accordingly, it is suggested that this distinctive renal tumor phenotype be recorded as a separate category from conventional RTT when assessing the carcinogenic potential of a test compound.

  14. Twenty-six-week oral carcinogenicity study of 3-monochloropropane-1,2-diol in CB6F1-rasH2 transgenic mice.

    PubMed

    Lee, Byoung-Seok; Park, Sang-Jin; Kim, Yong-Bum; Han, Ji-Seok; Jeong, Eun Ju; Son, Hwa-Young; Moon, Kyoung-Sik

    2017-01-01

    The carcinogenic potential of 3-monochloro-1,2-propanediol (3-MCPD) was evaluated in a short-term carcinogenicity testing study using CB6F1 rasH2-Tg (rasH2-Tg) mice. 3-MCPD is found in many foods and food ingredients as a result of storage or processing and is regarded as a carcinogen since it is known to induce Leydig cell and kidney tumors in rats. Male and female rasH2-Tg mice were administered 3-MCPD once daily by oral gavage at doses of 0, 10, 20, and 40 mg/kg body weight (bw) per day for 26 weeks. As a positive control, N-methyl-N-nitrosourea (MNU) was administered as a single intraperitoneal injection (75 mg/kg). In 3-MCPD-treated mice, there was no increase in the incidence of neoplastic lesions compared to the incidence in vehicle control mice. However, 3-MCPD treatment resulted in an increased incidence of tubular basophilia in the kidneys and germ cell degeneration in the testes, with degenerative germ cell debris in the epididymides of males at 20 and 40 mg/kg bw per day. In 3-MCPD-treated females, vacuolation of the brain and spinal cord was observed at 40 mg/kg bw per day; however, only one incidence of vacuolation was observed in males. Forestomach and cutaneous papilloma and/or carcinoma and lymphoma were observed in most rasH2 mice receiving MNU treatment. We concluded that 3-MCPD did not show carcinogenic potential in the present study using rasH2-Tg mice. The findings of this study suggest that the carcinogenic potential of 3-MCPD is species specific.

  15. Transformation assay in Bhas 42 cells: a model using initiated cells to study mechanisms of carcinogenesis and predict carcinogenic potential of chemicals.

    PubMed

    Sasaki, Kiyoshi; Umeda, Makoto; Sakai, Ayako; Yamazaki, Shojiro; Tanaka, Noriho

    2015-01-01

    Transformation assays using cultured cells have been applied to the study of carcinogenesis. Although various cell systems exist, few cell types such as BALB/c 3T3 subclones and Syrian hamster embryo cells have been used to study chemically induced two-stage carcinogenesis. Bhas 42 cells were established as a clone by the transfection with the v-Ha-ras gene into mouse BALB/c 3T3 A31-1-1 cells and their subsequent selection based on their sensitivity to 12-O-tetradecanoylphorbol-13-acetate. Using Bhas 42 cells, transformed foci were induced by the treatment with nongenotoxic carcinogens, most of which act as tumor promoters. Therefore, Bhas 42 cells were considered to be a model of initiated cells. Subsequently, not only nongenotoxic carcinogens but also genotoxic carcinogens, most of which act as tumor initiators, were found to induce transformed foci by the modification of the protocol. Furthermore, transformation of Bhas 42 cells was induced by the transfection with genes of oncogenic potential. We interpret this high sensitivity of Bhas 42 cells to various types of carcinogenic stimuli to be related to the multistage model of carcinogenesis, as the transfection of v-Ha-ras gene further advances the parental BALB/c 3T3 A31-1-1 cells toward higher transforming potential. Thus, we propose that Bhas 42 cells are a novel and sensitive cell line for the analysis of carcinogenesis and can be used for the detection of not only carcinogenic substances but also gene alterations related to oncogenesis. This review will address characteristics of Bhas 42 cells, the transformation assay protocol, validation studies, and the various chemicals tested in this assay.

  16. 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

  17. 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…

  18. 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.

  19. 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…

  20. How well can in vitro data predict in vivo effects of chemicals? Rodent carcinogenicity as a case study.

    PubMed

    Anthony Tony Cox, Louis; Popken, Douglas A; Kaplan, A Michael; Plunkett, Laura M; Becker, Richard A

    2016-06-01

    A recent research article by the National Center for Computational Toxicology (NCCT) (Kleinstreuer et al., 2013), indicated that high throughput screening (HTS) data from assays linked to hallmarks and presumed pathways of carcinogenesis could be used to predict classification of pesticides as either (a) possible, probable or likely rodent carcinogens; or (b) not likely carcinogens or evidence of non-carcinogenicity. Using independently developed software to validate the computational results, we replicated the majority of the results reported. We also found that the prediction model correlating cancer pathway bioactivity scores with in vivo carcinogenic effects in rodents was not robust. A change of classification of a single chemical in the test set was capable of changing the overall study conclusion about the statistical significance of the correlation. Furthermore, in the subset of pesticide compounds used in model validation, the accuracy of prediction was no better than chance for about three quarters of the chemicals (those with fewer than 7 positive outcomes in HTS assays representing the 11 histopathological endpoints used in model development), suggesting that the prediction model was not adequate to predict cancer hazard for most of these chemicals. Although the utility of the model for humans is also unclear because a number of the rodent responses modeled (e.g., mouse liver tumors, rat thyroid tumors, rat testicular tumors, etc.) are not considered biologically relevant to human responses, the data examined imply the need for further research with HTS assays and improved models, which might help to predict classifications of in vivo carcinogenic responses in rodents for the pesticide considered, and thus reduce the need for testing in laboratory animals.

  1. 2-Year Natural Decline of Cardiac Sympathetic Innervation in Idiopathic Parkinson Disease Studied with 11C-Hydroxyephedrine PET.

    PubMed

    Wong, Ka Kit; Raffel, David M; Bohnen, Nicolaas I; Altinok, Gulcin; Gilman, Sid; Frey, Kirk A

    2017-02-01

    The objective of this study was to detect regional patterns of cardiac sympathetic denervation in idiopathic Parkinson disease (IPD) using (11)C-hydroxyephedrine ((11)C-HED) PET and determine the denervation rate over 2 y.

  2. Alcoholics anonymous involvement and positive alcohol-related outcomes: cause, consequence, or just a correlate? A prospective 2-year study of 2,319 alcohol-dependent men.

    PubMed

    McKellar, John; Stewart, Eric; Humphreys, Keith

    2003-04-01

    A positive corelation between Alcoholics Anonymous (AA) involvement and better alcohol-related outcomes has been identified in research studies, but whether this correlation reflects a causal relationship remains a subject of meaningful debate. The present study evaluated the question of whether AA affiliation appears causally related to positive alcohol-related outcomes in a sample of 2,319 male alcohol-dependent patients. An initial structural equation model indicated that 1-year posttreatment levels of AA affiliation predicted lower alcohol-related problems at 2-year follow-up, whereas level of alcohol-related problems at 1-year did not predict AA affiliation at 2-year follow-up. Additional models found that these effects were not attributable to motivation or psychopathology. The findings are consistent with the hypothesis that AA participation has a positive effect on alcohol-related outcomes.

  3. 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.

  4. 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…

  5. 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,…

  6. 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…

  7. 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.

  8. Educational system for transplant coordinators in Poland: postgraduate studies at Warsaw Medical University; 2 years of experience.

    PubMed

    Czerwiński, J; Jakubowska-Winecka, A; Becler, R; Kubik, T; Milecka, A; Sekta, S; Pabisiak, K; Malanowski, P; Rowinński, W

    2009-10-01

    Donor hospital transplant coordinators play crucial roles in the donation process. There are only a few coordinators in Poland, while there are about 400 hospitals with intensive care units (ICU). Coordinators must be professionals in medical sciences, clinical psychology, law, organization, management, and statistics. Coordinators acquire these skills during the Transplant Coordinators Postgraduate Studies at Warsaw Medical University which began in 2007. Lectures, seminars and exercises (99 hours, 6 weekends) are run by experts. The studies end with an examination and a diploma. The main criterion for acceptance of a candidate is employment in a key department in the donation process. The aim of studies is to educate coordinators for each hospital in the country. Until now 4 editions of the course have been completed. Among 123 graduates, 71 (60%) are employed in strategic departments of 48 hospitals. Preliminary results of graduates' activities in donor detection were compared in the periods before (2005-2006) and after the course (2007-2008). The background was the overall activity in Poland, where in 2007-2008 the activity fell to 79% of 2005-2006. This fall for hospitals with the graduates of this program was 82% versus hospitals without them (76%). Of the 48 hospitals that employed the graduates: 14 improved donation 5 were the same, in 12 in both periods showed no donations; whereas in 11 it was much lower (>20%), and in 6 lower but consistent with the national trend.

  9. Evolution of Charcot-Marie-Tooth disease type 1A duplication: a 2-year clinico-electrophysiological and lower-limb muscle MRI longitudinal study.

    PubMed

    Pelayo-Negro, Ana L; Gallardo, Elena; García, Antonio; Sánchez-Juan, Pascual; Infante, Jon; Berciano, José

    2014-04-01

    The objective of this study was to analyze Charcot-Marie-Tooth disease type 1A (CMT1A) evolution. We conducted a 2-year longitudinal study in 14 CMT1A patients and 14 age- and sex-matched controls. In the patients, we performed neurological examination with hand-held dynamometry, electrophysiology, and lower-limb muscle MRI, both at baseline and 2 years later, while controls were examined at baseline only. Patients' ages ranged from 12 to 51 years. Outstanding manifestations on initial evaluation included pes cavus, areflexia, lower-limb weakness, and foot hypopallesthesia. In evaluating muscle power, good correlation was observed between manual testing and dynamometry. Compared to controls, Lunge, 10-Meter-Walking, and 9-Hole-Peg tests were impaired. Their CMT neuropathy score and functional disability scale showed that patients exhibited mild phenotype and at most slight walking difficulty. Electrophysiology revealed marked nerve conduction slowing and variable compound muscle action potential amplitude reduction. On lower-limb muscle MRI, there was distally accentuated fatty infiltration accompanied by edema in calf muscles. All these clinico-electrophysiological and imaging findings remained almost unaltered during monitoring. Using multivariate analysis, no significant predictors of progression associated to the disease were obtained. We conclude that in the 2-year period of study, CMT1A patients showed mild progression with good concordance between clinico-electrophysiological and imaging findings.

  10. 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.

  11. Effects of chemical carcinogens on bacteria and yeast: a review

    SciTech Connect

    Hancock, R.L.; Gerritsen, N.; Meadows, H.

    1981-03-01

    Early studies and reviews of the effects of carcinogens on bacteria and yeast are noted, after which a brief discussion deals specifically with chemical carcinogens and their relations with mutagenesis, deficiencies in DNA repair, RNA synthesis and function, and respiration-deficient mutants. Specific chemical carcinogens are then reviewed as to their mode of action, mutagenic and carcinogenic potency, and biochemical effects, including induced biological alterations such as cytogenetic variants. Structure-function relations are discussed for some types of compounds.

  12. Cardiovascular effects of dietary salt intake in aged healthy cats: a 2-year prospective randomized, blinded, and controlled study.

    PubMed

    Chetboul, Valérie; Reynolds, Brice Stéphane; Trehiou-Sechi, Emilie; Nguyen, Patrick; Concordet, Didier; Sampedrano, Carolina Carlos; Testault, Isabelle; Elliott, Jonathan; Abadie, Jérôme; Biourge, Vincent; Lefebvre, Hervé Pierre

    2014-01-01

    High salt dry expanded diets are commercially available for cats to increase water intake and urine volume, as part of the prevention or treatment of naturally occurring urinary stone formation (calcium oxalates and struvites). However, chronic high salt intake may have potential cardiovascular adverse effects in both humans, especially in aging individuals, and several animal models. The objective of this prospective, randomized, blinded, and controlled study was to assess the long-term cardiovascular effects of high salt intake in healthy aged cats. Twenty healthy neutered cats (10.1 ± 2.4 years) were randomly allocated into 2 matched groups. One group was fed a high salt diet (3.1 g/Mcal sodium, 5.5 g/Mcal chloride) and the other group a control diet of same composition except for salt content (1.0 g/Mcal sodium, 2.2 g/Mcal chloride). Clinical examination, systolic and diastolic arterial blood pressure measurements, standard transthoracic echocardiography and conventional Doppler examinations were repeatedly performed on non-sedated cats by trained observers before and over 24 months after diet implementation. Radial and longitudinal velocities of the left ventricular free wall and the interventricular septum were also assessed in systole and diastole using 2-dimensional color tissue Doppler imaging. Statistics were performed using a general linear model. No significant effect of dietary salt intake was observed on systolic and diastolic arterial blood pressure values. Out of the 33 tested imaging variables, the only one affected by dietary salt intake was the radial early on late diastolic velocity ratio assessed in the endocardium of the left ventricular free wall, statistically lower in the high salt diet group at 12 months only (P = 0.044). In conclusion, in this study involving healthy aged cats, chronic high dietary salt intake was not associated with an increased risk of systemic arterial hypertension and myocardial dysfunction, as observed in some

  13. Degrees of Antioxidant Protection: A 2-Year Study of the Bioactive Properties of Organic Milk in Poland.

    PubMed

    Puppel, Kamila; Sakowski, Tomasz; Kuczyńska, Beata; Grodkowski, Grzegorz; Gołębiewski, Marcin; Barszczewski, Jerzy; Wróbel, Barbara; Budziński, Arkadiusz; Kapusta, Aleksandra; Balcerak, Marek

    2017-02-01

    The aim of this study was to determine the nutritional value of organic milk in Poland, investigate the influence of diet on antioxidant capacity and degree of antioxidant protection (DAP), and to examine the effect of season on the bioactive properties of milk from organic farms. From 2014 to 2015, 820 milk samples were collected from 6 organic farms during indoor feeding season (IDS) and pasture feeding season (PS). Pasture feeding season + corn grain (PSCG) cows' daily ration during pasture feeding season was enriched with 4 kg a day of corn to improve dietary energy balance. Milk obtained during PS was found to have a higher fat content, slight but significantly lower protein content compared with milk from IDS. The study showed that the content of monounsaturated fatty acids (MUFA) in milk fat was strongly linked to the concentration of polyunsaturated fatty acids (PUFA) and, to a lesser extent, on the supply of MUFA. The IDS data (concentration of vitamin E, A, and β-carotene) showed the lowest values compared with the PS and PSCG groups. Total antioxidant status (TAS) and DAP showed an increasing trend in organic milk. PSCG was associated with highest level of DAP (9% higher than PS and 79% higher than IDS) and TAS (37% higher than PS and 79% higher than IDS). The results obtained show that supplementation of the basic ration with corn grain improved both TAS and DAP. The higher DAP and TAS value is responsible for product stability, considering the risk factor related to levels of cholesterol-oxide intake in humans.

  14. Use of iron supplements in children aged 1-2 years with iron deficiency anemia: A cross-sectional study

    PubMed Central

    Sezik, Handan Atsiz; Can, Huseyin; Kurnaz, Mehmet Ali; Tuna, Mine; Ay, Zeynep

    2015-01-01

    Objectives: Iron deficiency (ID) is the most common nutritional problem in the world and is the most common cause of childhood anemia. In this study, our aim was to find out about the state of usage of iron preparation, which is distributed free of charge by the Ministry of Health, for the infants between 4-12 months in our country, as well as detecting the awareness degree of families those who are informed about iron-deficiency anemia (IDA), prophylaxis of the drug and to determine the drug’s effectiveness. Methods: It was a cross-sectional survey. The laboratory values from the files of the children aged 1-2 those who visited our hospital’s department of pediatrics, between January 2010 to August 2013, were collected. The survey included families who have children diagnosed with IDA. Questions included about families’ sociodemographic characteristics, the state of the usage of the iron drug, how much information received in terms of the side effects- consumption period and dosage. Results: A total of 139 children were enrolled in our study. While 77.7% of the families who participated stated that (n = 108) iron medicine was prescribed other 43.2% of families stated (n = 60) was prescribed and they were informed about iron pills and IDA. 25.9% of families had received information about drug’s side effects, 74.8% of them had information about period of consumption and 77.7% said they were given information about the drug dose. The average duration of use of iron medicine was 6.98±4.52 (min: 1, max: 24) months. It has been noted that; parent’s education level, mother’s occupation, child’s gender, how the child was born and receiving information about how to use the medicine had no effects on usage of the drug in children. Nevertheless, it has been noticed that, when the families were given proper information the drug use increased and the patients compliance with medications also increased. Conclusion: We believe that, due to frequent diagnosis of

  15. Cardiovascular Effects of Dietary Salt Intake in Aged Healthy Cats: A 2-Year Prospective Randomized, Blinded, and Controlled Study

    PubMed Central

    Chetboul, Valérie; Reynolds, Brice Stéphane; Trehiou-Sechi, Emilie; Nguyen, Patrick; Concordet, Didier; Sampedrano, Carolina Carlos; Testault, Isabelle; Elliott, Jonathan; Abadie, Jérôme; Biourge, Vincent; Lefebvre, Hervé Pierre

    2014-01-01

    High salt dry expanded diets are commercially available for cats to increase water intake and urine volume, as part of the prevention or treatment of naturally occurring urinary stone formation (calcium oxalates and struvites). However, chronic high salt intake may have potential cardiovascular adverse effects in both humans, especially in aging individuals, and several animal models. The objective of this prospective, randomized, blinded, and controlled study was to assess the long-term cardiovascular effects of high salt intake in healthy aged cats. Twenty healthy neutered cats (10.1±2.4 years) were randomly allocated into 2 matched groups. One group was fed a high salt diet (3.1 g/Mcal sodium, 5.5 g/Mcal chloride) and the other group a control diet of same composition except for salt content (1.0 g/Mcal sodium, 2.2 g/Mcal chloride). Clinical examination, systolic and diastolic arterial blood pressure measurements, standard transthoracic echocardiography and conventional Doppler examinations were repeatedly performed on non-sedated cats by trained observers before and over 24 months after diet implementation. Radial and longitudinal velocities of the left ventricular free wall and the interventricular septum were also assessed in systole and diastole using 2-dimensional color tissue Doppler imaging. Statistics were performed using a general linear model. No significant effect of dietary salt intake was observed on systolic and diastolic arterial blood pressure values. Out of the 33 tested imaging variables, the only one affected by dietary salt intake was the radial early on late diastolic velocity ratio assessed in the endocardium of the left ventricular free wall, statistically lower in the high salt diet group at 12 months only (P = 0.044). In conclusion, in this study involving healthy aged cats, chronic high dietary salt intake was not associated with an increased risk of systemic arterial hypertension and myocardial dysfunction, as observed in some

  16. 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.

  17. A longitudinal study of Giardia duodenalis genotypes in dairy cows from birth to 2 years of age.

    PubMed

    Santín, Mónica; Trout, James M; Fayer, Ronald

    2009-05-26

    Fecal specimens were collected from 30 calves from birth to 24 months of age at a dairy farm in Maryland to determine the prevalence of Giardia duodenalis genotypes in cattle of different ages. Fecal samples were subjected to density gradient centrifugation to remove debris and concentrate cysts. Specimens were analyzed by immunofluorescence microscopy and polymerase chain reaction (PCR). All PCR positive specimens were sequenced using the SSU-rRNA gene of Giardia. All 30 calves shed G. duodenalis cysts at some time during the study. Of 990 specimens, 312 were positive for G. duodenalis (31.5%). The highest prevalence of infection occurred at weeks 4 and 5 of age with 25 out of 30 calves shedding cysts at those sampling times. Overall, pre-weaned calves (<8 weeks of age) exhibited the highest prevalence (60.8%), followed by post-weaned calves (3-12 months of age) (32.1%) and heifers (12-24 months of age) (11.4%). Sequence analysis of the 312 PCR-positive samples revealed the presence of both Assemblages A and E, G. duodenalis, with cumulative prevalences of 70% and 100%, respectively. Assemblage A was not detected in pre-weaned calves, but was detected in 6.9% and 4.7% of post-weaned calves and heifers, respectively. These data indicate not only that calves are infected with both Assemblages A and E simultaneously, but also that infections with zoonotic Assemblage A, G. duodenalis are more common than previously reported. Thus, calves appear to be a more significant reservoir of human infectious G. duodenalis than previous data have suggested.

  18. Identification of chemicals carcinogenic to man

    SciTech Connect

    Wilbourn, J.D.; Haroun, L.; Vainio, H.; Montesano, R.

    1984-01-01

    Although both the epidemiologic and experimental studies have led to the identification of chemical carcinogens, the limitations in epidemiologic approaches and the need for primary prevention of cancer require a greater reliance on experimental studies. Long-term carcinogenicity studies in experimental animals have been instrumental in identifying chemicals with carcinogenic activity, and, in some cases, the experimental evidence has preceded the epidemiologic evidence (for 4-aminobiphenyl, aflatoxin B1, diethylstilbestrol, melphalan, mustard gas, and vinyl chloride). A better understanding of the multistage process of carcinogenesis and the findings from various short-term tests available more recently may provide a more solid basis for extrapolating experimental findings to man.

  19. 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

  20. 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 7β, 8α-dihydoxy-9α, l0α-epoxy-7,8,9, 10-tetrahydrobenzo[α]pyrene (anti-BPDE). Stereochemically distinct (+)-trans-, (-)-trans-, (+)-cis- and (-)-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 ( ~25 %) exists in a partially base-stacked conformation. Both cis adducts were found to be intercalated with significant π-π 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 G2 or G3 (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-N2-dG in DNA isolated from the skin of mice treated topically with benzo[α]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-N2-dG.

  1. 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...

  2. Results of long-term carcinogenicity studies of chlorine in rats.

    PubMed

    Soffritti, M; Belpoggi, F; Lenzi, A; Maltoni, C

    1997-12-26

    Four groups, each of 50 male and 50 female Sprague-Dawley rats, of the colony used in the Cancer Research Center of Bentivoglio of the Ramazzini Foundation, 12 weeks old at the start of the study, received drinking water containing sodium hypochlorite, resulting in concentrations of active chlorine of 750, 500, and 100 mg/l (treated groups), and tap water (active chlorine < 0.2 mg/l) (control group), respectively, for 104 weeks. Among the female rats of the treated groups, an increased incidence of lymphomas and leukemias has been observed, although this is not clearly dose related. Moreover, sporadic cases of some tumors, the occurrence of which is extremely unusual among the untreated rats of the colony used (historical controls), were detected in chlorine-exposed animals. The results of this study confirm the results of the experiment of the United States National Toxicology Program (1991), which showed an increase of leukemia among female Fischer 344/N rats following the administration of chlorine (in the form of sodium hypochlorite and chloramine) in their drinking water. The data here presented call for further research aimed at quantifying the oncogenic risks related to the chlorination of drinking water, to be used as a basis for consequent public health measures.

  3. 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

  4. 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

  5. Development of hibernomas in rats dosed with phentolamine mesylate during the 24-month carcinogenicity study.

    PubMed

    Poulet, Frederique M; Berardi, Mark R; Halliwell, William; Hartman, Barbara; Auletta, Carol; Bolte, Henry

    2004-01-01

    Phentolamine is a reversible competitive alpha-adrenergic antagonist with similar affinities for alphal and alpha2 receptors. It has a long history of safe clinical use, and was developed as a potential therapy for male erectile dysfunction because of its capacity to increase the arteriolar blood flow to the corpora cavernosa. Phentolamine mesylate was administered to rats by oral gavage at daily doses of 10, 50, and 150 mg/kg for 24 months. A dose-related increase in mortality, ascribed to an exaggerated pharmacologic effect, was seen at high doses. Systemic exposure as measured by plasma drug concentration increased with dose and duration of dosing and slight drug accumulation occurred, particularly in high-dose males. In the treated groups, 10 males and 1 female were diagnosed with hibernomas, neoplasms of brown adipose tissue, which appeared in the thoracic cavity or retroperitoneal area as circumscribed, tan to reddish-brown lobulated masses. Histologically, the masses were well circumscribed with variably sized lobules defined by a rich capillary network and consisted of closely apposed oval to polygonal cells with large amounts of cytoplasm and a centrally located nucleus. The cytoplasm's appearance varied from multivacuolated to univacuolated to granular eosinophilic. In a few cases, neoplastic emboli were observed in capsular vessels. Ultrastructurally, the neoplastic cells contained numerous mitochondria with transverse parallel cristae that occupied over 60% of the cytoplasm and lipid droplets. This study documents the previously unreported development of hibernomas in rats treated with phentolamine mesylate.

  6. Rat liver foci study on coexposure with 50 Hz magnetic fields and known carcinogens

    SciTech Connect

    Rannug, A.; Holmberg, B.; Ekstroem, T. ); Mild, K.H. )

    1993-01-01

    A study was performed to investigate possible interactions by magnetic fields (MF) with the processes of initiation and promotion of chemically induced preneoplastic lesions in rat liver. Male Sprague-Dawley rats were subjected to a 70% partial hepatectomy followed after 24 h by i.p. injection of diethylnitrosamine (DENA) as a tumor initiator. Starting one week after the DENA-treatment phenobarbital (PB) was given to promote growth of enzymatically altered foci of liver cells. MF was applied immediately after the partial hepatectomy and continued until sacrifice after 12 weeks of PB exposure. Homogeneous horizontal AC magnetic fields with a frequency of 50Hz and flux densities of 0.5 [mu]T or 0.5 mT were used. The rats coexposed with MF and DENA plus PB did not gain weight as much as the rats exposed to the chemical agents only. The MF-exposure also resulted in a slight reduction in size and numbers of the focal lesions. The results suggest an interaction of MF with the processes of chemical carcinogenesis either as a result of stress or depending on effects on the proliferation of preneoplastic cells.

  7. Chronic Carcinogenicity Study of Gasoline Vapor Condensate (GVC) and GVC Containing Methyl Tertiary-Butyl Ether in F344 Rats

    PubMed Central

    Benson, Janet M.; Gigliotti, Andrew P.; March, Thomas H.; Barr, Edward B.; Tibbetts, Brad M.; Skipper, Betty J.; Clark, Charles R.; Twerdok, Lorraine

    2011-01-01

    Chronic inhalation studies were conducted to compare the toxicity and potential carcinogenicity of evaporative emissions from unleaded gasoline (GVC) and gasoline containing the oxygenate methyl tertiary-butyl ether (MTBE; GMVC). The test materials were manufactured to mimic vapors people would be exposed to during refueling at gas stations. Fifty F344 rats per gender per exposure level per test article were exposed 6 h/d, 5 d/wk for 104 wk in whole body chambers. Target total vapor concentrations were 0, 2, 10, or 20 g/m3 for the control, low-, mid-, and high-level exposures, respectively. Endpoints included survival, body weights, clinical observations, organs weights, and histopathology. GVC and GMVC exerted no marked effects on survival or clinical observations and few effects on organ weights. Terminal body weights were reduced in all mid- and high-level GVC groups and high-level GMVC groups. The major proliferative lesions attributable to gasoline exposure with or without MTBE were renal tubule adenomas and carcinomas in male rats. GMV exposure led to elevated testicular mesothelioma incidence and an increased trend for thyroid carcinomas in males. GVMC inhalation caused an increased trend for testicular tumors with exposure concentration. Mid- and high-level exposures of GVC and GMVC led to elevated incidences of nasal respiratory epithelial degeneration. Overall, in these chronic studies conducted under identical conditions, the health effects in F344 rats following 2 yr of GVC or GMVC exposure were comparable in the production of renal adenomas and carcinomas in male rats and similar in other endpoints. PMID:21432714

  8. Chronic carcinogenicity study of gasoline vapor condensate (GVC) and GVC containing methyl tertiary-butyl ether in F344 rats.

    PubMed

    Benson, Janet M; Gigliotti, Andrew P; March, Thomas H; Barr, Edward B; Tibbetts, Brad M; Skipper, Betty J; Clark, Charles R; Twerdok, Lorraine

    2011-01-01

    Chronic inhalation studies were conducted to compare the toxicity and potential carcinogenicity of evaporative emissions from unleaded gasoline (GVC) and gasoline containing the oxygenate methyl tertiary-butyl ether (MTBE; GMVC). The test materials were manufactured to mimic vapors people would be exposed to during refueling at gas stations. Fifty F344 rats per gender per exposure level per test article were exposed 6 h/d, 5 d/wk for 104 wk in whole body chambers. Target total vapor concentrations were 0, 2, 10, or 20 g/m³ for the control, low-, mid-, and high-level exposures, respectively. Endpoints included survival, body weights, clinical observations, organs weights, and histopathology. GVC and GMVC exerted no marked effects on survival or clinical observations and few effects on organ weights. Terminal body weights were reduced in all mid- and high-level GVC groups and high-level GMVC groups. The major proliferative lesions attributable to gasoline exposure with or without MTBE were renal tubule adenomas and carcinomas in male rats. GMV exposure led to elevated testicular mesothelioma incidence and an increased trend for thyroid carcinomas in males. GVMC inhalation caused an increased trend for testicular tumors with exposure concentration. Mid- and high-level exposures of GVC and GMVC led to elevated incidences of nasal respiratory epithelial degeneration. Overall, in these chronic studies conducted under identical conditions, the health effects in F344 rats following 2 yr of GVC or GMVC exposure were comparable in the production of renal adenomas and carcinomas in male rats and similar in other endpoints.

  9. 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.

  10. Carcinogenic effects of oil dispersants: A KEGG pathway-based RNA-seq study of human airway epithelial cells.

    PubMed

    Liu, Yao-Zhong; Zhang, Lei; Roy-Engel, Astrid M; Saito, Shigeki; Lasky, Joseph A; Wang, Guangdi; Wang, He

    2017-02-20

    The health impacts of the BP oil spill are yet to be further revealed as the toxicological effects of oil products and dispersants on human respiratory system may be latent and complex, and hence difficult to study and follow up. Here we performed RNA-seq analyses of a system of human airway epithelial cells treated with the BP crude oil and/or dispersants Corexit 9500 and Corexit 9527 that were used to help break up the oil spill. Based on the RNA-seq data, we then systemically analyzed the transcriptomic perturbations of the cells at the KEGG pathway level using two pathway-based analysis tools, GAGE (generally applicable gene set enrichment) and GSNCA (Gene Sets Net Correlations Analysis). Our results suggested a pattern of change towards carcinogenesis for the treated cells marked by upregulation of ribosomal biosynthesis (hsa03008) (p=1.97E-13), protein processing (hsa04141) (p=4.09E-7), Wnt signaling (hsa04310) (p=6.76E-3), neurotrophin signaling (hsa04722) (p=7.73E-3) and insulin signaling (hsa04910) (p=1.16E-2) pathways under the dispersant Corexit 9527 treatment, as identified by GAGE analysis. Furthermore, through GSNCA analysis, we identified gene co-expression changes for several KEGG cancer pathways, including small cell lung cancer pathway (hsa05222, p=9.99E-5), under various treatments of oil/dispersant, especially the mixture of oil and Corexit 9527. Overall, our results suggested carcinogenic effects of dispersants (in particular Corexit 9527) and their mixtures with the BP crude oil, and provided further support for more stringent safety precautions and regulations for operations involving long-term respiratory exposure to oil and dispersants.

  11. Chemically exacerbated chronic progressive nephropathy not associated with renal tubular tumor induction in rats: an evaluation based on 60 carcinogenicity studies by the national toxicology program.

    PubMed

    Melnick, Ronald L; Burns, Kathleen M; Ward, Jerrold M; Huff, James

    2012-08-01

    Chronic progressive nephropathy (CPN) is a common age-related degenerative-regenerative disease of the kidney that occurs in both sexes of most strains of rats. Recently, claims have been made that enhanced CPN is a mode of action for chemically induced kidney tumors in male rats and that renal tubular tumors (RTTs) induced by chemicals that concomitantly exacerbate CPN are not relevant for human cancer risk assessments. Although CPN is an observable histopathological lesion that may be modified by diet, the etiology of this disease and the mechanisms for its exacerbation by chemicals are unknown, and it fails to meet fundamental principles for defining carcinogenic modes of action and human relevance. Our comprehensive evaluation of possible relationships between exacerbated CPN and induction of RTTs in 58 carcinogenicity studies, conducted by the National Toxicology Program, in male and 11 studies in female F344 rats using 60 chemicals revealed widespread inconsistency in the claimed association. Because the proposed hypothesis lacks evidence of biological plausibility, and due to inconsistent relationships between exacerbated CPN and kidney tumor incidence in carcinogenicity studies in rats, dismissing the human relevance of kidney tumors induced by chemicals that also exacerbate CPN in rats would be wrong.

  12. Prevalidation study of the Syrian hamster embryo (SHE) cell transformation assay at pH 7.0 for assessment of carcinogenic potential of chemicals.

    PubMed

    Maire, Marie-Aline; Pant, Kamala; Poth, Albrecht; Schwind, Karl-Rainer; Rast, Claudine; Bruce, Shannon W; Sly, Jamie E; Kunz-Bohnenberger, Susanne; Kunkelmann, Thorsten; Engelhardt, Günter; Schulz, Markus; Vasseur, Paule

    2012-04-11

    The European Centre for the Validation of Alternative Methods (ECVAM) has organised an interlaboratory prevalidation study on the Syrian hamster embryo (SHE) cell transformation assay (CTA) at pH 7.0 for the detection of rodent carcinogens. The SHE CTA at pH 7.0 has been evaluated for its within-laboratory reproducibility, transferability and between-laboratory reproducibility. Four laboratories using the same basic protocol with minor modifications participated in this study and tested a series of six coded-chemicals: four rodent carcinogens (benzo(a)pyrene, 3-methylcholanthrene, 2,4-diaminotoluene and o-toluidine HCl) and two non-carcinogens (anthracene and phthalic anhydride). All the laboratories found the expected results with coded chemicals except for phthalic anhydride which resulted in a different call in only one laboratory. Based on the outcome of this study, it can be concluded that a standardised protocol is available that should be the basis for future use. This protocol and the assay system itself are transferable between laboratories and the SHE CTA at pH 7.0 is reproducible within- and between-laboratories.

  13. Toxicology and carcinogenicity studies of diuretics in F344 rats and B6C3F1 mice. 1. Hydrochlorothiazide.

    PubMed

    Bucher, J R; Huff, J; Haseman, J K; Eustis, S L; Elwell, M R; Davis, W E; Meierhenry, E F

    1990-10-01

    Toxicology and carcinogenesis studies of hydrochlorothiazide, a benzothiadiazide diuretic, were conducted by administering diets containing the drug to both sexes of F344 rats and B6C3F1 mice in 15-day, 13-week and 2-year studies. No rats died during the 15-day or 13-week studies at dietary concentrations of up to 50,000 ppm. Deaths of male mice in the top dose group in the 13-week study were likely to be related to chemical administration. In the prechronic studies, increased nephrosis and mineralization at the kidney corticomedullary junction were the primary toxic effects of hydrochlorothiazide observed in rats. In mice, chemical-related effects included nephrosis and calculi, inflammation and epithelial hyperplasia in the urinary bladder. In 2-year studies using dietary concentrations of 0, 250, 500 and 2000 ppm in rats and 0, 2500 and 5000 ppm in mice, survival of dosed and control groups of rats and mice was similar, as were body weights of mice. Dosed groups of male and female rats were uniformly lighter than controls (up to 25%) throughout the studies. Severe chronic renal disease with secondary parathyroid hyperplasia and fibrous osteodystrophy of the bone were attributed to chemical administration in rats. No neoplasms in rats or female mice or non-neoplastic lesions in mice were associated with hydrochlorothiazide. In high-dose male mice, liver neoplasms were increased but were not considered to be related to hydrochlorothiazide administration because of an unusually low incidence in the control group relative to historical controls.

  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. 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

  16. Discriminating between adaptive and carcinogenic liver hypertrophy in rat studies using logistic ridge regression analysis of toxicogenomic data: The mode of action and predictive models.

    PubMed

    Liu, Shujie; Kawamoto, Taisuke; Morita, Osamu; Yoshinari, Kouichi; Honda, Hiroshi

    2017-03-01

    Chemical exposure often results in liver hypertrophy in animal tests, characterized by increased liver weight, hepatocellular hypertrophy, and/or cell proliferation. While most of these changes are considered adaptive responses, there is concern that they may be associated with carcinogenesis. In this study, we have employed a toxicogenomic approach using a logistic ridge regression model to identify genes responsible for liver hypertrophy and hypertrophic hepatocarcinogenesis and to develop a predictive model for assessing hypertrophy-inducing compounds. Logistic regression models have previously been used in the quantification of epidemiological risk factors. DNA microarray data from the Toxicogenomics Project-Genomics Assisted Toxicity Evaluation System were used to identify hypertrophy-related genes that are expressed differently in hypertrophy induced by carcinogens and non-carcinogens. Data were collected for 134 chemicals (72 non-hypertrophy-inducing chemicals, 27 hypertrophy-inducing non-carcinogenic chemicals, and 15 hypertrophy-inducing carcinogenic compounds). After applying logistic ridge regression analysis, 35 genes for liver hypertrophy (e.g., Acot1 and Abcc3) and 13 genes for hypertrophic hepatocarcinogenesis (e.g., Asns and Gpx2) were selected. The predictive models built using these genes were 94.8% and 82.7% accurate, respectively. Pathway analysis of the genes indicates that, aside from a xenobiotic metabolism-related pathway as an adaptive response for liver hypertrophy, amino acid biosynthesis and oxidative responses appear to be involved in hypertrophic hepatocarcinogenesis. Early detection and toxicogenomic characterization of liver hypertrophy using our models may be useful for predicting carcinogenesis. In addition, the identified genes provide novel insight into discrimination between adverse hypertrophy associated with carcinogenesis and adaptive hypertrophy in risk assessment.

  17. 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

  18. 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

  19. 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

  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. The importance of carcinogen dose in chemoprevention studies: quantitative interrelationships between, dibenzo[a,l]pyrene dose, chlorophyllin dose, target organ DNA adduct biomarkers and final tumor outcome.

    PubMed

    Pratt, M Margaret; Reddy, Ashok P; Hendricks, Jerry D; Pereira, Cliff; Kensler, Thomas W; Bailey, George S

    2007-03-01

    Chlorophyllin (CHL) is a potent antimutagen in vitro, an effective anti-carcinogen in several animal models, and significantly reduced urinary biomarkers of aflatoxin B(1) (AFB(1)) exposure in a human population. Here we report an expanded analysis of CHL chemoprevention using the potent environmental hydrocarbon dibenzo[a,l]pyrene (DBP). A dose-dose matrix design employed over 12 000 rainbow trout to evaluate the interrelationships among dietary carcinogen dose, anti-carcinogen dose, carcinogen-DNA adduct levels at exposure and eventual tumor outcome in two target organs. Included was an evaluation of the pharmaceutical CHL preparation (Derifil), used previously in a study of individuals chronically exposed to AFB(1). CHL was pre-, co- and post-fed at doses of 0-6000 p.p.m. and co-fed with DBP at doses of 0-371.5 p.p.m. for 4 weeks. This protocol generated a total of 21 dose-dose treatment groups, each evaluated with three or more replicates of 100 animals. The DBP-only treatment produced dose-responsive increases in liver and stomach DBP-DNA adducts, whereas increasing CHL co-treatment doses produced successive inhibition in liver (49-83%) and stomach (47-75%) adduct levels at each DBP dose examined. The remaining 8711 trout were necropsied, 10 months later. DBP treatment alone produced a logit incidence versus log [DBP] dose-response curve in stomach that was linear; CHL co-treatment provided dose-dependent tumor inhibition which ranged from 30 to 68% and was predictable from the adduct response. The Derifil CHL preparation was also found to effectively reduce DNA adduction and final tumor incidence in stomach (as well as liver), with a potency compatible with its total chlorin content. Liver tumor incidence in the DBP-only groups appeared to plateau near 60%. At DBP doses of

  2. Respiratory symptoms and ventilatory function among health-care workers exposed to cleaning and disinfectant chemicals, a 2-year follow-up study.

    PubMed

    El-Helaly, Mohamed; Balkhy, Hanan H; Waseem, Khan; Khawaja, Sahdia

    2016-12-01

    Previous cross-sectional studies have shown that exposure to cleaning chemicals among health-care workers (HCWs) is associated with respiratory disorders and ventilatory function changes. This study aimed to further explore this association using a longitudinal approach. A prospective 2-year follow-up study was carried out at a tertiary care hospital in Saudi Arabia from June 2012 to June 2014 among 56 nurses who were responsible for disinfection and sterilization of medical instruments and equipment. The workplaces of the participants were assessed for engineering, environmental, and safety control measures. Self-administered questionnaires were distributed to all participants to assess their exposure to cleaning chemicals and their medical history. Spirometric parameters were measured for all nurses in 2012 (baseline) and again in 2014 (follow-up). The prevalence of work-related respiratory symptoms did not increase significantly over this time. Among all the spirometric parameters, only forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio decreased significantly, and only 10.7% of participants who were exposed to cleaning chemicals for more than 10 years had FEV1 and FVC less than their longitudinal normal limits at the end of the study. Smoking and gender were associated with statistically significant decreases in some of the spirometric parameters. Our 2-year follow-up study did not demonstrate significant association between exposure to cleaning chemicals among HCWs and changes in the prevalence of work-related respiratory symptoms, but indicated early effects on ventilatory function among them. The study highlights the importance of periodic spirometry, proper work practices, and effective control measures to protect HCWs against potentially harmful workplace chemicals for disinfection and sterilization.

  3. Quantifying the carcinogenicity of antineoplastic drugs.

    PubMed

    Kaldor, J M; Day, N E; Hemminki, K

    1988-04-01

    It has been well established that many of the drugs used in cancer therapy are themselves potentially carcinogenic. It is therefore important to quantify the carcinogenic risk associated with specific agents, and to investigate ways of predicting their risk from animal and in vitro studies. In this paper, an index of carcinogenic potency is defined, and applied to published data on acute non-lymphocytic leukemia following therapy with cytotoxic drugs used as single agents. Carcinogenic potency estimates for rats and mice are also obtained for 15 antineoplastic drugs, and the potency correlation between humans and rodents is examined for the five agents for which there are data in common. The broader implications for quantitative cancer risk prediction are discussed.

  4. 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)

  5. Amplitude of Low-frequency Oscillations in Parkinson's Disease: A 2-year Longitudinal Resting-state Functional Magnetic Resonance Imaging Study

    PubMed Central

    Hu, Xiao-Fei; Zhang, Jiu-Quan; Jiang, Xiao-Mei; Zhou, Chao-Yang; Wei, Lu-Qing; Yin, Xun-Tao; Li, Jing; Zhang, Yan-Ling; Wang, Jian

    2015-01-01

    Background: Neuroimaging studies have found that functional changes exist in patients with Parkinson's disease (PD). However, the majority of functional magnetic resonance imaging (fMRI) studies in patients with PD are task-related and cross-sectional. This study investigated the functional changes observed in patients with PD, at both baseline and after 2 years, using resting-state fMRI. It further investigated the relationship between whole-brain spontaneous neural activity of patients with PD and their clinical characteristics. Methods: Seventeen patients with PD underwent an MRI procedure at both baseline and after 2 years using resting-state fMRI that was derived from the same 3T MRI. In addition, 20 age- and sex-matched, healthy controls were examined using resting-state fMRI. The fractional amplitude of low-frequency fluctuation (fALFF) approach was used to analyze the fMRI data. Nonlinear registration was used to model within-subject changes over the scanning interval, as well as changes between the patients with PD and the healthy controls. A correlative analysis between the fALFF values and clinical characteristics was performed in the regions showing fALFF differences. Results: Compared to the control subjects, the patients with PD showed increased fALFF values in the left inferior temporal gyrus, right inferior parietal lobule (IPL) and right middle frontal gyrus. Compared to the baseline in the 2 years follow-up, the patients with PD presented with increased fALFF values in the right middle temporal gyrus and right middle occipital gyrus while also having decreased fALFF values in the right cerebellum, right thalamus, right striatum, left superior parietal lobule, left IPL, left precentral gyrus, and left postcentral gyrus (P < 0.01, after correction with AlphaSim). In addition, the fALFF values in the right cerebellum were positively correlated with the Unified PD Rating Scale (UPDRS) motor scores (r = 0.51, P < 0.05, uncorrected) and the change in

  6. Lack of effects of vagus nerve stimulation on drug-resistant epilepsy in eight pediatric patients with autism spectrum disorders: a prospective 2-year follow-up study.

    PubMed

    Danielsson, Susanna; Viggedal, Gerd; Gillberg, Christopher; Olsson, Ingrid

    2008-02-01

    Vagus nerve stimulation (VNS) therapy has been reported to reduce seizure frequency in some children with drug-resistant epilepsy who are not suitable candidates for epilepsy surgery. It has been suggested that there may be positive cognitive and/or behavioral effects independent of seizure control. We describe the effects of VNS with respect to seizure frequency, cognition, and autistic symptoms and behavior in eight children and adolescents with medically intractable epilepsy and autism. In comparison to baseline, seizure frequency had not decreased in anyone in our series at the 2-year follow-up. In three cases, minor improvements in general functioning were noted, but there were no positive cognitive effects. This open prospective pilot study highlights the need for more prospective studies to prevent false expectations of improvement in this severely disabled group.

  7. Anterior cervical fusion with interbody cage containing beta-tricalcium phosphate augmented with plate fixation: a prospective randomized study with 2-year follow-up.

    PubMed

    Dai, Li-Yang; Jiang, Lei-Sheng

    2008-05-01

    A variety of bone graft substitutes, interbody cages, and anterior plates have been used in cervical interbody fusion, but no controlled study was conducted on the clinical performance of beta-tricalcium phosphate (beta-TCP) and the effect of supplemented anterior plate fixation. The objective of this prospective, randomized clinical study was to evaluate the effectiveness of implanting interbody fusion cage containing beta-TCP for the treatment of cervical radiculopathy and/or myelopathy, and the fusion rates and outcomes in patients with or without randomly assigned plate fixation. Sixty-two patients with cervical radiculopathy and/or myelopathy due to soft disc herniation or spondylosis were treated with one- or two-level discectomy and fusion with interbody cages containing beta-TCP. They were randomly assigned to receive supplemented anterior plate (n = 33) or not (n = 29). The patients were followed up for 2 years postoperatively. The radiological and clinical outcomes were assessed during a 2-year follow-up. The results showed that the fusion rate (75.0%) 3 months after surgery in patients treated without anterior cervical plating was significantly lower than that (97.9%) with plate fixation (P < 0.05), but successful bone fusion was achieved in all patients of both groups at 6-month follow-up assessment. Patients treated without anterior plate fixation had 11 of 52 (19.2%) cage subsidence at last follow-up. No difference (P > 0.05) was found regarding improvement in spinal curvature as well as neck and arm pain, and recovery rate of JOA score at all time intervals between the two groups. Based on the findings of this study, interbody fusion cage containing beta-TCP following one- or two-level discectomy proved to be an effective treatment for cervical spondylotic radiculopathy and/or myelopathy. Supplemented anterior plate fixation can promote interbody fusion and prevent cage subsidence but do not improve the 2-year outcome when compared with those treated

  8. Evaluating Pesticides for Carcinogenic Potential

    EPA Pesticide Factsheets

    EPA reviews pesticides for potential carcinogenicity. Learn about EPA's guidelines for evaluating a chemical's potential carcinogenicity and updates to EPA's guidelines to reflect increased understanding of ways chemicals may cause cancer.

  9. Effects of enzyme replacement therapy on five patients with advanced late-onset glycogen storage disease type II: a 2-year follow-up study.

    PubMed

    Furusawa, Yoshihiko; Mori-Yoshimura, Madoka; Yamamoto, Toshiyuki; Sakamoto, Chikako; Wakita, Mizuki; Kobayashi, Yoko; Fukumoto, Yutaka; Oya, Yasushi; Fukuda, Tokiko; Sugie, Hideo; Hayashi, Yukiko K; Nishino, Ichizo; Nonaka, Ikuya; Murata, Miho

    2012-03-01

    We examined the efficacy of 2-year enzyme replacement therapy (ERT) using recombinant human α-glucosidase (GAA; Myozyme®) in five long-term ventilator-dependent adults and aged patients with advanced, late-onset glycogen storage disease type II (GSDII, also known as Pompe disease). Although all patients had advanced respiratory failure and were ventilator-dependent for more than 6 years, four showed obvious improvements in muscle strength, pulmonary function, and activities of daily living after ERT. Improvement in each parameter was more prominent in the first year than in the second year. Values in the second year were still significantly better than those at study entry and indicate stabilization in the clinical status of all patients. These results suggest that ERT continues to be effective in the second year of treatment even in patients suffering from advanced late-onset GSDII disease with severe respiratory failure.

  10. 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.

  11. Associations Among Symptoms of Autism, Symptoms of Depression and Executive Functions in Children with High-Functioning Autism: A 2 Year Follow-Up Study.

    PubMed

    Andersen, Per Normann; Skogli, Erik Winther; Hovik, Kjell Tore; Egeland, Jens; Øie, Merete

    2015-08-01

    This study investigated the course of and association among changes in autism symptoms, depression symptoms and executive functions (EF) in children with high-functioning autism (HFA). Thirty-four children with HFA and 45 typically developing children (age 9-16) were assessed at baseline and after 2 years. Children with HFA had impaired scores on all measures at both time points. According to parent reports, depressive symptoms decreased over time, while EF improved and autism symptoms were stable. Children's reports did not reveal less depressive symptoms over time. A positive association was found only between changes in autism symptoms and changes in symptoms of depression. A possible implication is that interventions aimed at either autism symptoms or symptoms of depression may improve the other.

  12. Real-Life ILUVIEN (Fluocinolone Acetonide) Case Study: Rapid Drying of the Macula and Improved Vision within 2 Years after Therapy Initiation

    PubMed Central

    Quhill, Hibba; Quhill, Fahd

    2016-01-01

    Importance A case showing sustained structural and functional responses 2 years after a single treatment with ILUVIEN (0.2 µg/day fluocinolone acetonide, FAc) despite suboptimal responses to ranibizumab. Observations A 68-year-old female patient with diabetic macular oedema (DME) from type 2 diabetes mellitus was first diagnosed in October 2010 and had a baseline visual acuity (VA) of 46 Early Treatment Diabetic Retinopathy Study (ETDRS) letters in the left eye. Central foveal thickness (CFT) was 712 microns. The patient was treated with 11 intravitreal injections of ranibizumab (5 in combination with a small-interfering RNA agent), and by March 2014, VA and CFT were largely unchanged (55 ETDRS letters and 774 microns). The patient was treated with ILUVIEN as she had a pseudophakic lens and a clearly suboptimal response to the prior therapy with ranibizumab. An implant releasing FAc at a dosage of 0.2 µg/day was administered in March 2014, and the optical coherence tomography indicated that the macula was dry after 7 days (CFT was below 300 microns). This was sustained at 6, 12, and 24 months after the treatment. VA improved by 5 letters within 7 days and by 15 letters within 14 days, and this was maintained after 24 months. Throughout the duration of this study, the intraocular pressure was ≤22 mm Hg, and no glaucoma medication was administered. Conclusions and Relevance In real-life UK practice, this DME patient showed a suboptimal response to multiple intravitreal injections of ranibizumab. When subsequently treated with a single injection of ILUVIEN, there were large and rapid improvements in VA and CFT that were maintained for the following 2 years. PMID:28203186

  13. 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 ...

  14. Baseline increased 18F-fluoride uptake lesions at vertebral corners on positron emission tomography predict new syndesmophyte development in ankylosing spondylitis: a 2-year longitudinal study.

    PubMed

    Park, Eun-Kyoung; Pak, Kyoungjune; Park, Ji-Heh; Kim, Keunyoung; Kim, Seong-Jang; Kim, In-Joo; Kim, Geun-Tae; Lee, Seung-Geun

    2017-02-02

    The goal of this study was to demonstrate whether increased 18F-fluoride uptake lesions on positron emission tomography (PET) scan can predict new syndesmophyte development in patients with ankylosing spondylitis (AS). In 12 AS patients, 18F-fluoride PET and magnetic resonance imaging (MRI) was performed at baseline, and radiography was performed at baseline and the 2-year follow-up. The following data were recorded: the presence of increased 18F-fluoride uptake lesions on PET defined as an uptake greater than the uptake in the adjacent normal vertebral body; acute (type A) and advanced (type B) corner inflammatory lesions (CILs) and fat lesions on MRI; and syndesmophytes on radiography. Of 231 anterior vertebral corners without syndesmophyte at baseline, 13 type A CILs (5.5%), 2 type B CILs (0.9%), and 20 fat lesions (8.7%) on MRI and six increased fluoride uptake lesions (2.6%) on PET were observed. At the 2-year follow-up, 16 new syndesmophytes (6.9%) in eight AS patients (66.7%) occurred. New syndesmophytes developed significantly more frequently in anterior vertebral corners with increased 18F-fluoride uptake lesions (50%) or fat lesions (25%) at baseline than in those without such lesions (5.8 and 5.2%; p = 0.005 and p = 0.007, respectively). After adjusting confounding factors, baseline increased 18F-fluoride uptake lesions was independently associated with new syndesmophytes development (OR 13.8, 95% CI 1.5-124.3, p = 0.019). Fat lesions were also associated with new syndesmophytes formation. Our data suggest that 18F-fluoride PET may be applied to identify AS patients with high risk of future syndesmophyte formation.

  15. CCL2, CCL18 and sIL-4R in renal, meningeal and pulmonary TB; a 2 year study of patients and contacts.

    PubMed

    Mendez, Armando; Hernandez-Pando, Rogelio; Contreras, Salvador; Aguilar, Diana; Rook, Graham A W

    2011-03-01

    The role of Th2 cytokines and Th2-associated chemokines in tuberculosis (TB) remains controversial, though in Mexico a polymorphism causing increased production of CCL2 is a risk factor. We studied levels of the Th2-associated chemokines CCL2 and CCL18, circulating soluble IL-4 receptors (sIL-4R), IL-4 and the inhibitory splice variant of IL-4 (IL-4δ2) in a cohort of patients with pulmonary TB and their healthy contacts. These were followed for 2 years during which time 10 contacts developed pulmonary TB. Results were compared with measurements made in renal and meningeal TB, and in disease controls with bacterial pneumonias or Dengue fever that have large Th2 components. In these disease controls both chemokines were significantly raised. They were also very significantly raised in all forms of TB, irrespective of age or disease site. Levels of CCL18 were raised least in meningeal TB, and most in pulmonary patients with long histories, when levels were similar to those in disease controls. Levels of CCL2, although also raised in all three forms of TB, were negatively correlated with CCL18. We found that levels of sIL-4R were strikingly reduced in all forms of TB, particularly meningeal. Contacts who progressed could not be distinguished from contacts who remained healthy at 2 years in terms of IL-4, sIL-4R, CCL2 or CCL18. However contacts had raised expression of IL-4δ2 as previously found. These results indicate vigorous and previously unrecorded activity within the Th2 axis, and further investigation is warranted.

  16. 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

  17. Time to remission for eating disorder patients: a 2(1/2)-year follow-up study of outcome and predictors.

    PubMed

    Clausen, Loa

    2008-01-01

    The aim of the present study was to analyse outcome, time to remission, and predictors of time to remission in a cohort of Danish eating disorder patients. Seventy-eight patients (35 anorexic, 30 bulimic and 13 unspecified eating disorder patients) were interviewed 2(1/2) years after initial assessment. Method of assessment was Eating Disorder Examination (EDE), Longitudinal Interval Follow-up Evaluation of Eating Disorders (LIFE-EAT-II), Eating Disorder Inventory (EDI), Symptom Check List (SCL-90R), Present State Examination (PSE) and the Structured Clinical Interview for DSM-III-R Axis-II (SCID-II). Method of analysis was Kaplan-Meier estimate of survival, Log Rank test and Cox regression analysis. In total 48.7% reached remission with mean time to remission at 27 months. A trend difference between the diagnostic groups when measuring time to remission was found, i.e. patients with unspecified eating disorders remitted faster than bulimic (BN) patients who in turn remitted faster than anorexic (AN) patients. Body mass index (BMI) at baseline was the best predictor of time to remission for the total sample. Predictors differed when looking at diagnostic groups separately. Final outcome was comparable with earlier studies while relapse frequency was low. Patients with AN remitted faster than found in earlier survival analysis studies, while the remission rate for BN patients was comparable with earlier studies. Despite the prognostic value of BMI for the total sample, predictor analysis implied more disorder diversity than homogeneity.

  18. Plantar Pressure Changes and Correlating Risk Factors in Chinese Patients with Type 2 Diabetes: Preliminary 2-year Results of a Prospective Study

    PubMed Central

    Qiu, Xuan; Tian, De-Hu; Han, Chang-Ling; Chen, Wei; Wang, Zhan-Jian; Mu, Zhen-Yun; Liu, Kuan-Zhi

    2015-01-01

    Background: Plantar pressure serves as a key factor for predicting ulceration in the feet of diabetes patients. We designed this study to analyze plantar pressure changes and correlating risk factors in Chinese patients with type 2 diabetes. Methods: We recruited 65 patients with type 2 diabetes. They were invited to participate in the second wave 2 years later. The patients completed identical examinations at the baseline point and 2 years later. We obtained maximum force, maximum pressure, impulse, pressure-time integral, and loading rate values from 10 foot regions. We collected data on six history-based variables, six anthropometric variables, and four metabolic variables of the patients. Results: Over the course of the study, significant plantar pressure increases in some forefoot portions were identified (P < 0.05), especially in the second to forth metatarsal heads. Decreases in heel impulse and pressure-time integral levels were also found (P < 0.05). Plantar pressure parameters increased with body mass index (BMI) levels. Hemoglobin A1c (HbA1c) changes were positively correlated with maximum force (β = 0.364, P = 0.001) and maximum pressure (β = 0.366, P = 0.002) changes in the first metatarsal head. Cholesterol changes were positively correlated with impulse changes in the lateral portion of the heel (β = 0.179, P = 0.072) and pressure-time integral changes in the second metatarsal head (β = 0.236, P = 0.020). Ankle-brachial index (ABI) changes were positively correlated with maximum force changes in the first metatarsal head (β = 0.137, P = 0.048). Neuropathy symptom score (NSS) and common peroneal nerve sensory nerve conduction velocity (SCV) changes were positively correlated with some plantar pressure changes. In addition, plantar pressure changes had a correlation with the appearance of infections, blisters (β = 0.244, P = 0.014), and calluses over the course of the study. Conclusions: We should pay attention to the BMI, HbA1c, cholesterol, ABI

  19. Cancer mortality and exposure to chemical carcinogens in the work place: an ecological study in the Valencian Community, Spain (1981-1995).

    PubMed

    Corella, D; Herranz, C; Calatayud, A; Font, G; Celma, C; Laborda, R

    2000-05-01

    To evaluate the geographical distribution of the mortality from malignant tumours in relationship with exposure to chemical carcinogens in the work place, and to asses the possible association between these questions and the percentage of population employed in certain high-risk sectors, an ecological study in the Valencian Community (VC), Spain was carried out. Age-adjusted mortality rates for the total number of malignant tumours, lung, bladder, lymphomas and leukaemia during the periods 1981-1985 and 1991-1995 were calculated for the 34 geographical areas. The percentage of population in each area working in sectors in which they may be exposed to chemical carcinogens was obtained. The relationship between mortality on-the-job exposure was studied using linear regression methods. Large differences in cancer mortality were seen. In men, the geographical pattern was very stable and reveals a significant association with the distribution of certain high-risk jobs. Statistically significant positive correlations (p < 0.001) were found between cancer mortality and the percentage of the population working in metal, wood and furniture sectors. In contrast, a negative and statistically significant (p < 0.001) correlation was observed between cancer mortality and the percentage of the population working in agriculture. In conclusion, although the variability in cancer mortality in men was significantly associated with some occupational sectors in the VC, caution is needed when drawing conclusions about causation from ecological studies.

  20. [Estimated number of workers exposed to carcinogens in Italy, within the context of the European study CAREX].

    PubMed

    Mirabelli, D

    1999-01-01

    CAREX is an international information system on occupational exposure to known or suspected carcinogens, built within the framework of the Europe Against Cancer Programme of the European Union. It provides estimates of the number of exposed workers by country, industry, and agent, including data about 139 agents evaluated by the International Agency for Research on Cancer (group 1 and 2A agents, plus selected group 2B ones), across 55 industries classified according to UN-ISIC revision 2. The 1990-3 occupational exposures to these agents were estimated for the fifteen countries of the European Union in two steps. At first, estimates were generated on the basis of the national workforce data, and of the exposure prevalence estimates from two reference countries: Finland and the USA. These estimates are adjusted by economic structure, but they do not take into account country specific patterns of exposure to carcinogens. For selected countries, among which Italy, it was possible to correct these estimates by national experts, who were invited to allow for the exposure patterns that they considered specific to their countries. According to the estimates for Italy, there were about 4.2 million workers, i.e. 24% of the work force, exposed to the agents included in CAREX, with some 5.5 million exposures. The most common exposures were: environmental tobacco smoke (770,000 exposed workers), solar radiation (550,000), diesel engine exhaust (550,000), asbestos (350,000), wood dust (300,000), crystalline silica (260,000), lead and inorganic lead compounds (220,000), benzene (180,000), hexavalent chromium and compounds (130,000) and PAHs (130,000).

  1. The carcinogenicity of chrysotile asbestos

    SciTech Connect

    Harington, J.S. )

    1991-12-31

    In in vitro test systems, chrysotile is markedly toxic, causes chromosomal aberrations, and is capable of inducing morphological and preneoplastic transformation. In carefully designed animal experiments, chrysotile produces lung cancer and mesothelioma as effectively as do the amphiboles tested. Human population studies do not refute these experimental results. Chrysotile asbestos is carcinogenic to humans, especially for the induction of lung cancer and mesothelioma in exposed populations. For cancers of other sites, with the exception of laryngeal and possibly gastrointestinal cancer, the evidence for association with exposure to all forms of asbestos, including chrysotile, is not yet adequate for evaluation.48 references.

  2. 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.

  3. 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.

  4. Twenty-four mini-pool HCV RNA screening outside a blood transfusion setting: results of a 2-year prospective study.

    PubMed

    Seme, Katja; Mocilnik, Tina; Fujs, Kristina; Babic, Dunja Z; Todorović, Aleksandra; Fras-Stefan, Tamara; Poljak, Mario

    2007-03-01

    The usefulness of 24 mini-pool hepatitis C virus (HCV) RNA screening was evaluated in a 2-year prospective study carried out on a total of 6432 consecutive anti-HCV negative specimens in a routine diagnostic laboratory setting. A total of 268 mini-pools were tested using an automated commercial PCR assay for qualitative detection of HCV RNA, with a lower limit of detection of 50 IU/ml. Eighteen (0.28%) anti-HCV negative/HCV RNA positive serum samples obtained from 12 patients (all intravenous drug users), were detected. Ten patients responded to an invitation for follow-up testing. Five, three and one patient seroconverted in the first, second and third follow-up sample, respectively. One patient had not seroconverted by the end of the study period. The interval between the first HCV RNA positive sample and the first anti-HCV positive samples was 24-192 days. The costs of detecting a single anti-HCV negative/HCV RNA positive sample and a single anti-HCV negative/HCV RNA positive patient using the 24 mini-pool HCV RNA screening strategy were estimated to be around euro 643 and 965, respectively. It was shown that screening for HCV infection using the 24 mini-pool HCV RNA screening strategy can also be both useful and cost effective outside a blood transfusion setting.

  5. 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

  6. 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.

  7. A phase 1 study of obinutuzumab induction followed by 2 years of maintenance in patients with relapsed CD20-positive B-cell malignancies.

    PubMed

    Sehn, Laurie H; Assouline, Sarit E; Stewart, Douglas A; Mangel, Joy; Gascoyne, Randy D; Fine, Gregg; Frances-Lasserre, Susan; Carlile, David J; Crump, Michael

    2012-05-31

    This phase 1 study evaluated the safety, tolerability, pharmacokinetics, and antitumor activity of obinutuzumab (GA101), a glycoengineered type II anti-CD20 monoclonal antibody administered as induction followed by 2 years of maintenance. Cohorts of 3 to 6 patients received obinutuzumab (200-2000 mg) intravenously weekly for 4 weeks. Patients with a complete or partial response (or stable disease and clinical benefit) continued to receive obinutuzumab every 3 months, for a maximum of 8 doses. Twenty-two patients with relapsed CD20-positive non-Hodgkin lymphoma or chronic lymphocytic leukemia with an indication for treatment and no therapy of higher priority were enrolled. Patients received a median of 4 prior regimens; 86% had received at least 1 rituximab-containing regimen. No dose-limiting or unexpected AEs were observed. Infusion-related reactions were most common (all grades, 73%; grade 3/4, 18%), followed by infection (32%), pyrexia (23%), neutropenia (23%), headache (18%), and nausea (18%). At end of induction, 5 (23%) patients achieved partial responses and 12 (54%) had stable disease. Eight patients received maintenance; best overall response was 32% (6 partial responses/1 complete response). Obinutuzumab induction and maintenance therapy was well tolerated with promising efficacy in this heterogeneous, highly pretreated population and warrants further investigation. This study was registered at www.clinicaltrials.gov (identifier NCT00576758).

  8. 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

  9. 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

  10. 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

  11. Observation on therapeutic efficacy of ursodeoxycholic acid in Chinese patients with primary biliary cirrhosis: a 2-year follow-up study.

    PubMed

    Zhu, Jiangyi; Shi, Yongquan; Zhou, Xinmin; Li, Zengshan; Huang, Xiaofeng; Han, Zheyi; Wang, Jianhong; Wang, Ruian; Ding, Jie; Wu, Kaichun; Han, Ying; Fan, Daiming

    2013-06-01

    The efficacy of ursodeoxycholic acid (UDCA) on long-term outcome of primary biliary cirrhosis (PBC) has been less documented in Chinese cohort. We aimed to assess the therapeutic effect of UDCA on Chinese patients with PBC. In the present study, 67 patients with PBC were treated with UDCA (13-15 mg·kg(-1)·day(-1)) and followed up for 2 years to evaluate the changes of symptoms, laboratory values and histological features. As the results indicated, fatigue and pruritus were obviously improved by UDCA, particularly in patients with mild or moderate symptoms. The alkaline phosphatase and γ-glutamyl transpetidase levels significantly declined at year 2 comparing to baseline values, with the most profound effects achieved in patients at stage 2. The levels of alanine aminotransferase and aspartate aminotransferase significantly decreased whereas serum bilirubin and immunoglobulin M levels exhibited no significant change. Histological feature was stable in patients at stages 1-2 but still progressed in patients at stages 3-4. The biochemical response of patients at stage 2 was much better than that of patients at stages 3-4. These data suggest that, when treated in earlier stage, patients in long-term administration of UDCA can gain favorable results not only on symptoms and biochemical responses but also on histology. It is also indicated that later histological stage, bad biochemical response and severe symptom may be indicators of poor prognosis for UDCA therapy.

  12. Violence and Abuse Against Women Who Have Attempted Suicide by Deliberate Self-Poisoning: A 2-Year Follow-Up Study in Iran.

    PubMed

    Hassanian-Moghaddam, Hossein; Zamani, Nasim; Sarjami, Saeedeh

    2016-04-01

    Sources of data about the occurrence of domestic violence are scarce in Iran. The aim of this study was to evaluate the behavioral effects of different types of domestic violence on women who had attempted suicide by deliberate self-poisoning (DSP). A total of 195 women who had attempted suicide by DSP in response to "violence and abuse" were followed up for 2 years. The most common type of violence, as mentioned by the women themselves as the motive of self-poisoning, was physical abuse (92%) followed by verbal abuse (2.1%), multi-abuses (2.1%), emotional abuse (1.6%), and sexual abuse (1.1%). Suicidal ideation and attempt were more common in those who were consulted sometime after they had initially presented to the hospital with DSP or those who had suffered repeated domestic abuse. It was concluded that invention of methods other than the current consultation system is necessary to prevent repeated suicide attempts among abused women in Iran.

  13. 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.

  14. 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.

  15. 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

  16. 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; ...

  17. Increased Regulatory T-Cell Percentage Contributes to Poor CD4(+) Lymphocytes Recovery: A 2-Year Prospective Study After Introduction of Antiretroviral Therapy.

    PubMed

    Saison, Julien; Maucort Boulch, Delphine; Chidiac, Christian; Demaret, Julie; Malcus, Christophe; Cotte, Laurent; Poitevin-Later, Francoise; Miailhes, Patrick; Venet, Fabienne; Trabaud, Mary Anne; Monneret, Guillaume; Ferry, Tristan

    2015-04-01

    Background.  The primary aim of this study was to determine the impact of regulatory T cells (Tregs) percentage on immune recovery in human immunodeficiency virus (HIV)-infected patients after antiretroviral therapy introduction. Methods.  A 2-year prospective study was conducted in HIV-1 chronically infected naive patients with CD4 count <500 cells/mm(3). Regulatory T cells were identified as CD4(+)CD25(high)CD127(low) cells among CD4(+) lymphocytes. Effect of Treg percentage at inclusion on CD4 evolution overtime was analyzed using a mixed-effect Poisson regression for count data. Results.  Fifty-eight patients were included (median CD4 = 293/mm(3), median Treg percentage = 6.1%). Percentage of Treg at baseline and CD4 nadir were independently related to the evolution of CD4 absolute value according to time: (1) at any given nadir CD4 count, 1% increase of initial Treg was associated with a 1.9% lower CD4 absolute value at month 24; (2) at any given Treg percentage at baseline, 10 cell/mm(3) increase of CD4 nadir was associated with a 2.4% increase of CD4 at month 24; and (3) both effects did not attenuate with time. The effect of Treg at baseline on CD4 evolution was as low as the CD4 nadir was high. Conclusions.  Regulatory T-cell percentage at baseline is a strong independent prognostic factor of immune recovery, particularly among patients with low CD4 nadir.

  18. Effect of ONO-5334 on bone mineral density and biochemical markers of bone turnover in postmenopausal osteoporosis: 2-year results from the OCEAN study.

    PubMed

    Eastell, Richard; Nagase, Shinichi; Small, Maria; Boonen, Steven; Spector, Tim; Ohyama, Michiyo; Kuwayama, Tomohiro; Deacon, Steve

    2014-02-01

    Cathepsin K inhibitors, such as ONO-5334, are being developed for the treatment of postmenopausal osteoporosis. However, their relative effects on bone resorption and formation, and how quickly the effects resolve after treatment cessation, are uncertain. The aim of this study was to examine the efficacy and safety of 24-month treatment with ONO-5334 and to assess the effect of treatment cessation over 2 months. We studied 197 postmenopausal women with osteoporosis or osteopenia with one fragility fracture. Patients were randomized to ONO-5334 50 mg twice daily, 100 mg or 300 mg once daily, alendronate 70 mg once weekly (positive control), or placebo for 24 months. After 24 months, all ONO-5334 doses were associated with increased bone mineral density (BMD) for lumbar spine, total hip, and femoral neck (p < 0.001). ONO-5334 300 mg significantly suppressed the bone-resorption markers urinary (u) NTX and serum and uCTX-I throughout 24 months of treatment and to a similar extent as alendronate; other resorption marker levels remained similar to placebo (fDPD for ONO-5334 300 mg qd) or were increased (ICTP, TRAP5b, all ONO-5334 doses). Levels of B-ALP and PINP were suppressed in all groups (including placebo) for approximately 6 months but then increased for ONO-5334 to close to baseline levels by 12 to 24 months. On treatment cessation, there were increases above baseline in uCTX-I, uNTX, and TRAP5b, and decreases in ICTP and fDPD. There were no clinically relevant safety concerns. Cathepsin K inhibition with ONO-5334 resulted in decreases in most resorption markers over 2 years but did not decrease most bone formation markers. This was associated with an increase in BMD; the effect on biochemical markers was rapidly reversible on treatment cessation.

  19. Ethylene dibromide and disulfiram: studies in vivo and in vitro on the mechanism of the observed synergistic carcinogenic response.

    PubMed

    Elliott, B M; Ashby, J

    1980-01-01

    Two possible mechanisms for the reported carcinogenic synergism between ethylene dibromide (EDB) and disulfiram have been investigated in vivo and in vitro, the first involving increased production of an EDB-derived glutathione mustard and the second increased production of bromoacetaldehyde. Consistent with both of these suggested mechanisms, repeated administrations of disulfiram to rats inreased liver glutathione-S-transferase activity and decreased liver low Km aldehyde dehydrogenase activity. However, when added to a rat liver S-9 fraction in vitro, disulfiram decreased transferase activity and only depressed the dehydrogenase activity after a period of preincubation. Although the mutagenic potency of EDB to Salmonella typhimurium was slightly enhanced in vitro by the addition of a rat liver S-9 fraction, the further addition of disulfiram to the assay medium produced no additional change. Similarly, the addition of a range of S-9 and S-0.5 liver fractions derived from disulfiram-treated rats also failed to enhance significantly its mutagenic potency over the normal S-9 fraction. The general implications of these findings are discussed.

  20. Evaluation of the national toxicology program report on carcinogens.

    PubMed

    Rodu, Brad; Cole, Philip; Mandel, Jack S

    2012-10-01

    This study evaluates the National Toxicology Program's Report on Carcinogens program (RoCP) and compares it with the International Agency for Research on Cancer Monographs Program (IMP). We tracked agents classified in the RoCP since 1983 as known human carcinogens (A-List), or as reasonably anticipated to be human carcinogens (B-List). The first A-list included 24 agents, and twenty-four unique agents were added in the following 28years; twenty were listed by IMP as Group 1 (carcinogenic to humans) 7years before their A-list appearance. Group 1 also includes 30 or more agents eligible for, but not on, the A-list. The first B-list included 98 agents, and this increased to 185. Of these, 39 are in Group 2A (probably carcinogenic), and 122 are in Group 2B (possibly carcinogenic). Only 5% of the 204 agents ever on the B-list have been upgraded to the A-list. The RoCP is severely limited because it evaluates few agents and because its B-list does not distinguish between probable and possible human carcinogens. Further, it mislabels likely non-carcinogens as reasonably anticipated to be carcinogens. If the RoCP were terminated there would be no loss or delay of information available to scientific, public health and regulatory communities.

  1. Oral health-related quality of life in partially edentulous patients before and after implant therapy: a 2-year longitudinal study

    PubMed Central

    BRAMANTI, E.; MATACENA, G.; CECCHETTI, F.; ARCURI, C.; CICCIÙ, M.

    2013-01-01

    SUMMARY Objectives. The aim of this study was to measure the Oral Health-Related Quality of Life (OHRQoL) before and after a prosthodontic implant therapy so to determine the physical and psychological impact of implant-supported fixed partial dentures (IFPD) rehabilitation among edentulous patients. Methods. 50 partially edentulous patients aged 40–70 years, treated with IFPD, completed the OHRQoL questionnaire before the implant surgery (Time 0) and 2 years after their whole implant-prosthetic rehabilitation (Time 1). The questionnaire was proposed in a short version of Oral Health Impact Profile (OHIP-14, range 0–56) and analyzed through the ‘additive method’. We evaluated statistical mean, standard deviation, median, variance and mode of all OHIP-14 domains and the statistical significance about oral changes at Time 0 and Time 1 using the Chi-square test (p-values < 0.05). Results. Patients reported significant changes in mean OHIP scores (Time 0: 2.15; Time 1: 0.65; p < 0.01). The most prevalently affected domain was “functional limitation”, followed by “psychological discomfort” and “physical pain”. There were no significant differences dependent on age, gender and antagonistic teeth (p > 0.05). Patients with I and IV Kennedy’s class edentulism showed better improvement (p < 0.05). Conclusions. Preoperative and post-treatment assessments of OHRQoL exhibited significant differences. The IFPD treatment had a positive effect on the OHRQoL, which improved better in patients with I and IV Kennedy’s edentulous class. PMID:24175052

  2. 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

  3. 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.

  4. Anemia on Admission Is an Independent Predictor of Long-Term Mortality in Hip Fracture Population: A Prospective Study With 2-Year Follow-Up.

    PubMed

    Zhang, Licheng; Yin, Pengbin; Lv, Houchen; Long, Anhua; Gao, Yuan; Zhang, Lihai; Tang, Peifu

    2016-02-01

    Anemia is a disputable factor for long-term mortality in hip fracture population in previous studies. Previous studies indicated that the level of hemoglobin (Hb) might fluctuate due to various factors, such as comorbidities and in-hospital interventions, and the changing level of Hb, may lead to discordance diagnosis of anemia and thus to the conflicting conclusions on prognostic value of anemia. So in this study, we aim to compare factors affecting the diagnosis of anemia at different time-points, admission, postoperation, and discharge, and to determine which the time point is most suitable for mortality prediction.This prospective cohort study included 1330 hip fracture patients from 1 January 2000 to 18 November 2012. Hb levels at 3 different time points, such as admission, postoperation, and discharge, were collected and used to stratify the cohort into anemia and nonanemia groups. Candidate factors including commodities, perioperative factors, blood transfusion, and other in-hospital interventions were collected before discharge. Logistic regression analyses were performed to detect risk factors for anemia for the 3 time points separately. Kaplan-Meier and multivariate Cox regression analyses were used to evaluate the association between anemia and 2-year mortality.Factors affecting the diagnosis of anemia were different for the 3 time points. Age, female sex, American Society of Anesthesiologists score (ASA), and intertrochanteric fracture were associated with admission anemia, while surgical procedure, surgical duration, blood transfusion, blood loss during the operation, and drainage volume were major risk factors for postoperation anemia. Cox proportional-hazards regression analysis suggested that the risk of all-cause mortality was higher in the anemia group on admission (1.680, 95%CI: 1.201-2.350, P < 0.01), but not postoperation or on discharge, after adjustment for confounding factors.Our study showed that risk factors for anemia varied at

  5. Known occupational carcinogens and their significance.

    PubMed Central

    Ernst, P.; Thériault, G.

    1984-01-01

    Although rates of occupational cancer can be excessive in certain industries, less than 5% of all cancers seem attributable to exposure to carcinogens in the workplace. For example, workers in hard-rock mining and the woodworking industries are at increased risk; cigarette smoking has a synergistic effect. There is conclusive evidence of carcinogenicity for fewer than 20 substances, including asbestos, arsenic, chromium, nickel, cadmium, radon, several aromatic hydrocarbons and certain herbicides. Most of the hundreds of organic compounds known to be mutagenic in in-vitro tests have not been shown to be carcinogenic in epidemiologic studies. Both laboratory and epidemiologic approaches, however, can identify probable causes of cancer and permit the application of effective preventive measures. In addition, it is still possible for the alert individual clinician to make the initial discovery of an occupational hazard. PMID:6367918

  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

    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.

  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 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

  8. Quantitation of pyridyloxobutyl-DNA adducts in tissues of rats treated chronically with (R)- or (S)-N’-nitrosonornicotine (NNN) in a carcinogenicity study

    PubMed Central

    Zhao, Lijiao; Balbo, Silvia; Wang, Mingyao; Upadhyaya, Pramod; Khariwala, Samir S.; Villalta, Peter W.; Hecht, Stephen S.

    2013-01-01

    We quantified DNA adducts resulting from 2’-hydroxylation of enantiomers of the tobacco-specific nitrosamine N’-nitrosonornicotine (NNN) in tissues of male F-344 rats after 10, 30, 50, and 70 weeks of treatment with 14 ppm in the drinking water. These rats were in subgroups of a carcinogenicity study in which (S)-NNN was highly tumorigenic in the oral cavity and esophagus while (R)-NNN was relatively weakly active. DNA adducts were quantified by liquid chromatography-electrospray ionization-tandem mass spectrometry in six tissues – oral mucosa, esophageal mucosa, nasal respiratory mucosa, nasal olfactory mucosa, liver, and lung. O2-[4-(3-Pyridyl)-4-oxobut-1-yl]thymidine (O2-POB-dThd, 7) and 7-[4-(3-pyridyl)-4-oxobut-1-yl]-2′-deoxyguanosine (7-POB-dGuo, 8), the latter as 7-[4-(3-pyridyl)-4-oxobut-1-yl]guanine (7-POB-Gua, 11), were detected at each time point in each tissue. In the target tissues for carcinogenicity, oral mucosa and esophageal mucosa, levels of 7-POB-Gua (11) and O2-POB-dThd (7) were similar, or 11 predominated, while in all other tissues at all time points for both enantiomers, 7 was clearly present in greater amounts than 11. Total measured DNA adduct levels in esophageal mucosa and oral mucosa were higher in rats treated with (S)-NNN than (R)-NNN. The highest adduct levels were found in the nasal respiratory mucosa. DNA adducts generally persisted in all tissues without any sign of substantial decreases throughout the 70 week time course. The results of this study suggest that inefficient repair of 7-POB-dGuo (8) in the rat oral cavity and esophagus may be important in carcinogenesis by NNN and support the development of these DNA adducts as potential biomarkers of NNN metabolic activation in people who use tobacco products. PMID:24001146

  9. 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...

  10. 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...

  11. Carcinogenicity and drinking water.

    PubMed

    Dayan, A D

    1993-01-01

    Water is a powerful solvent that readily dissolves many natural and synthetic substances from the environment (e.g. inorganic salts, humic acids and pesticide residues). The processes of purification, disinfection and preparation and storage necessary to provide and distribute drinking water may introduce further chemicals, including some used for these purposes and others derived by interaction between them and the compounds of natural origin. The composition of drinking water, therefore, is complex and varies between sites and with the seasons. Modern technology is employed to minimise the amounts of many of these substances, but some may persist, including derivatives generated by halogenation and ozonation for disinfection. Some of the substances are genotoxic in the laboratory and a few are proven experimental carcinogens--all at much higher concentrations than those normally found in a drinking water supply. Many ecological and epidemiological surveys have been done to compare the occurrence of various types of tumour in man with exposure to different types of drinking, but no consistent or reliable association has been found. There are serious and probably irremediable methodological weaknesses in these attempts, because of the difficulty of defining the nature of the waters consumed over a major part of life, and the variable composition of waters. The surveys do not permit even a realistic assessment of the upper confidence limit of the exclusion of the risk. Thus, although there is some experimental indication of the possible presence of carcinogenic substances in most or all drinking waters, and of how they are formed, the concentrations are very low and there is no realistic evidence that they have caused harm to man.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. 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

  13. The Limits of Two-Year Bioassay Exposure Regimens for Identifying Chemical Carcinogens

    PubMed Central

    Huff, James; Jacobson, Michael F.; Davis, Devra Lee

    2008-01-01

    Background Chemical carcinogenesis bioassays in animals have long been recognized and accepted as valid predictors of potential cancer hazards to humans. Most rodent bioassays begin several weeks after birth and expose animals to chemicals or other substances, including workplace and environmental pollutants, for 2 years. New findings indicate the need to extend the timing and duration of exposures used in the rodent bioassay. Objectives In this Commentary, we propose that the sensitivity of chemical carcinogenesis bio-assays would be enhanced by exposing rodents beginning in utero and continuing for 30 months (130 weeks) or until their natural deaths at up to about 3 years. Discussion Studies of three chemicals of different structures and uses—aspartame, cadmium, and toluene—suggest that exposing experimental animals in utero and continuing exposure for 30 months or until their natural deaths increase the sensitivity of bioassays, avoid false-negative results, and strengthen the value and validity of results for regulatory agencies. Conclusions Government agencies, drug companies, and the chemical industry should conduct and compare the results of 2-year bioassays of known carcinogens or chemicals for which there is equivocal evidence of carcinogenicity with longer-term studies, with and without in utero exposure. If studies longer than 2 years and/or with in utero exposure are found to better identify potential human carcinogens, then regulatory agencies should promptly revise their testing guidelines, which were established in the 1960s and early 1970s. Changing the timing and dosing of the animal bioassay would enhance protection of workers and consumers who are exposed to potentially dangerous workplace or home contaminants, pollutants, drugs, food additives, and other chemicals throughout their lives. PMID:19057693

  14. 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…

  15. 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

  16. 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.

  17. Immunologic methods for monitoring carcinogen exposure

    NASA Astrophysics Data System (ADS)

    Santella, Regina M.; Perera, Frederica P.; Zhang, Yu J.; Chen, Chen J.; Young, Tie L.

    1993-03-01

    Immunologic methods have been developed for monitoring human exposure to environmental and occupational carcinogens. These methods involve the development of monoclonal and polyclonal antisera which specifically recognize the carcinogens themselves or their DNA or protein adducts. Antisera recognizing the DNA adducts of several polycyclic aromatic hydrocarbon diol epoxides have been used in competitive enzyme-linked immunosorbent assays to monitor adducts in tissue or blood samples. Elevated levels of DNA adducts have been seen in mononuclear cells of smokers and in total white blood cells of foundry and coke oven workers. Environmental exposure to PAH has been measured in individuals living in a highly polluted region of Poland. Antisera recognizing PAH-DNA adducts have also been used in immunohistochemical studies to monitor adducts in specific cells of biopsy samples. The DNA adducts of aflatoxin B1 have been monitored in liver tissue of hepatocellular carcinoma patients in Taiwan. Detectable adducts were seen in 50 - 70% of the patients suggesting that dietary exposure to this carcinogen may be a risk factor for cancer induction. Thus, immunoassays for monitoring exposure to carcinogens are an important tool in epidemiologic studies.

  18. Markers of exposure to carcinogens

    SciTech Connect

    Wogan, G.N. )

    1989-05-01

    Methods have been developed for the detection of exposure to carcinogens and other DNA damaging agents in experimental animals and man through the detection of carcinogens or their metabolic derivatives in body fluids, or through adducts bound covalently to DNA or hemoglobin. The successful use of urinary markers of genotoxic exposures has been reported with respect to nitrosoproline as an indicator of exposure to N-nitroso compounds. The same approach has been used to detect AFB1 and AFB1-N7-Gua as markers of exposure to aflatoxin B1; of 3-methyladenine produced as a result of exposure to methylating agents; and thymine glycol as an indicator of exposure to agents causing oxidative damage to DNA. Detection of adducts formed between genotoxic agents and hemoglobin has been reported in studies of populations occupationally exposed to ethylene oxide, in which 3-hydroxyhistidine and 3-hydroxyvaline have been measured, and in smokers, whose hemoglobin has been found to contain levels of 4-aminobiphenyl and 3-hydroxyvaline that were correlated with the frequency of cigarette smoking. Detection of DNA adducts of genotoxic agents in the cells and tissues of exposed individuals has also been accomplished through the use of several types of analytical methods. Immunoassays and physicochemical methods have been applied to detect adducts formed through the major intermediate in the activation of benzo(a)pyrene, the 7,8-diol-9,10-epoxide (BPDE). This adduct has been found in the DNA of peripheral leukocytes of workers in foundries, aluminum manufacturing plants, roofers, and coke oven plants, and also in cigarette smokers. 36 references.

  19. A 2-Year, Phase IV, Multicentre, Observational Study of Ranibizumab 0.5 mg in Patients with Neovascular Age-Related Macular Degeneration in Routine Clinical Practice: The EPICOHORT Study.

    PubMed

    Pagliarini, Sergio; Beatty, Stephen; Lipkova, Blandina; Perez-Salvador Garcia, Eduardo; Reynders, Stefaan; Gekkieva, Margarita; Si Bouazza, Abdelkader; Pilz, Stefan

    2014-01-01

    Purpose. To assess the safety profile of ranibizumab 0.5 mg in patients with neovascular age-related macular degeneration (nAMD) in routine clinical practice. Methods. This 2-year, multicentre, observational study was conducted to capture real-world early practice and outcomes across Europe, shortly after European licensing of ranibizumab for nAMD. Being observational in nature, the study did not impose diagnostic/therapeutic interventions/visit schedule. Patients were to be treated as per the EU summary of product characteristics (SmPC) in effect during the study. Key outcome measures were incidence of selected adverse events (AEs), treatment exposure, bilateral treatment, compliance to the EU SmPC, and best-corrected visual acuity (BCVA) over 2 years. Results. 755 of 770 patients received treatment. Ranibizumab was generally well tolerated with low incidence of selected AEs (0%-1.9%). Patients received 6.2 (mean) injections and 133 patients received bilateral treatment over 2 years. Protocol deviation to treatment compliance was reported in majority of patients. The observed decline in mean BCVA (Month 12, +1.5; Month 24, -1.3 letters) may be associated with undertreatment as suggested by BCVA subgroup analysis. Conclusion. The EPICOHORT study conducted in routine clinical practice reinforces the well-established safety profile of ranibizumab in nAMD. In early European practice it appeared that the nAMD patients were undertreated.

  20. Prediction of thyroid C-cell carcinogenicity after chronic administration of GLP1-R agonists in rodents.

    PubMed

    van den Brink, Willem; Emerenciana, Annette; Bellanti, Francesco; Della Pasqua, Oscar; van der Laan, Jan Willem

    2017-04-01

    Increased incidence of C-cell carcinogenicity has been observed for glucagon-like-protein-1 receptor (GLP-1r) agonists in rodents. It is suggested that the duration of exposure is an indicator of carcinogenic potential in rodents of the different products on the market. Furthermore, the role of GLP-1-related mechanisms in the induction of C-cell carcinogenicity has gained increased attention by regulatory agencies. This study proposes an integrative pharmacokinetic/pharmacodynamic (PKPD) framework to identify explanatory factors and characterize differences in carcinogenic potential of the GLP-1r agonist products. PK models for four products (exenatide QW (once weekly), exenatide BID (twice daily), liraglutide and lixisenatide) were developed using nonlinear mixed effects modelling. Predicted exposure was subsequently linked to GLP-1r stimulation using in vitro GLP-1r potency data. A logistic regression model was then applied to exenatide QW and liraglutide data to assess the relationship between GLP-1r stimulation and thyroid C-cell hyperplasia incidence as pre-neoplastic predictor of a carcinogenic response. The model showed a significant association between predicted GLP-1r stimulation and C-cell hyperplasia after 2years of treatment. The predictive performance of the model was evaluated using lixisenatide, for which hyperplasia data were accurately described during the validation step. The use of a model-based approach provided insight into the relationship between C-cell hyperplasia and GLP-1r stimulation for all four products, which is not possible with traditional data analysis methods. It can be concluded that both pharmacokinetics (exposure) and pharmacodynamics (potency for GLP-1r) factors determine C-cell hyperplasia incidence in rodents. Our work highlights the pharmacological basis for GLP-1r agonist-induced C-cell carcinogenicity. The concept is promising for application to other drug classes.

  1. 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).

  2. 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).

  3. Preoperative screening/decolonization for Staphylococcus aureus to prevent orthopedic surgical site infection: prospective cohort study with 2-year follow-up.

    PubMed

    Rao, Nalini; Cannella, Barbara A; Crossett, Lawrence S; Yates, Adolph J; McGough, Richard L; Hamilton, Cindy W

    2011-12-01

    We quantified surgical site infections (SSIs) after preoperative screening/selective decolonization before elective total joint arthroplasty (TJA) with 2-year follow-up and 2 controls. Concurrent controls (n = 2284) were patients of surgeons not participating in screening/decolonization. Preintervention controls (n = 741) were patients of participating surgeons who underwent TJA the previous year. Staphylococcus aureus nasal carriers (321/1285 [25%]) used intranasal mupirocin and chlorhexidine baths as outpatients. Staphylococcal SSIs occurred in no intervention patients (0/321) and 19 concurrent controls. If all SSIs occurred in carriers and 25% of controls were carriers, staphylococcal SSI rate would have been 3.3% in controls (19/571; P = .001). Overall SSI rate decreased from 2.7% (20/741) in preintervention controls to 1.2% (17/1440) in intervention patients (P = .009). Preoperative screening/selective decolonization was associated with fewer SSIs after elective TJA.

  4. Relationship of carcinogenicity and cellular proliferation induced by mutagenic noncarcinogens vs carcinogens. III. Organophosphate pesticides vs tris(2,3-dibromopropyl)phosphate.

    PubMed

    Cunningham, M L; Elwell, M R; Matthews, H B

    1994-10-01

    Our laboratory has been examining the mechanisms whereby chemicals produce mutagenicity in short-term in vitro assays yet fail to produce carcinogenesis in 2-year rodent bioassays. Previous studies indicated that some mutagenic hepatocarcinogens increased cell proliferation in the target organ, the liver, while other structurally related mutagens that were noncarcinogenic failed to do so. We demonstrate in this report that another mutagenic carcinogen, tris(2,3-dibromopropyl phosphate), increased cell proliferation that was localized in the outer medulla of the kidney. This was also the target site for carcinogenesis in a 2-year bioassay and is another example of the association between chemically induced cell proliferation and carcinogenesis. This study also reports the absence of increased cell proliferation in the liver or kidney after exposure in the diet to the mutagenic organophosphate insecticides dimethoate, dioxathion, and dichlorvos following dietary exposure for 2 weeks at the same dose levels and routes of exposure that did not increase the tumor incidence in either organ in 2-year carcinogenesis assays. The present studies support the tenet that chemically induced cell proliferation may be a necessary prerequisite for chemical carcinogenesis, since in rat liver and kidney there was neither cell proliferation after 2 weeks nor tumor development after 2 years dietary exposure to the mutagenic organophosphate insecticides dimethoate, dioxathion, and dichlorvos.

  5. Guidelines for Carcinogen Risk Assessment

    EPA Pesticide Factsheets

    The Guidelines for Carcinogen Risk Assessment provide EPA staff with guidance for developing and using risk assessments. They also provide basic information to the public about the Agency's risk assessment methods.

  6. 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…

  7. Metabolic activation and inactivation of chemical carcinogens

    SciTech Connect

    Pelkonen, O.; Vaehaekangas, K.

    1980-09-01

    Chemical carcinogens are metabolized by numerous pathways catalyzed by enzymes in endoplasmic reticulum and other parts of the cell. Reactions in which functional groups are created are especially important in the activation of polycyclic hydrocarbon carcinogens to ultimate carcinogenic forms, although other enzymes may also participate in the activation of other chemical carcinogens. The reasons why carcinogens act on specific target tissues are incompletely understood, although differences in enzyme profiles between tissues certainly contribute to the target tissue variability. The concept of metabolic activation of carcinogens by body's own enzymes has led to the development of short-term assay systems, which essentially measure the production of biologically active metabolites from potential carcinogens.

  8. Serum levels of osteoprotegerin and receptor activator of nuclear factor -κB ligand in children with early juvenile idiopathic arthritis: a 2-year prospective controlled study

    PubMed Central

    2010-01-01

    Background The clinical relevance of observations of serum levels of osteoprotegerin (OPG) and receptor activator of nuclear factor -κB ligand (RANKL) in juvenile idiopathic arthritis (JIA) is not clear. To elucidate the potential role of OPG and RANKL in JIA we determined serum levels of OPG and RANKL in patients with early JIA compared to healthy children, and prospectively explored changes in relation to radiographic score, bone and lean mass, severity of the disease, and treatment. Methods Ninety children with early oligoarticular or polyarticular JIA (ages 6-18 years; mean disease duration 19.4 months) and 90 healthy children individually matched for age, sex, race, and county of residence, were examined at baseline and 2-year follow-up. OPG and RANKL were quantified by enzyme-immunoassay. Data were analyzed with the use of t-tests, ANOVA, and multiple regression analyses. Results Serum OPG was significantly lower in patients than controls at baseline, and there was a trend towards higher RANKL and a lower OPG/RANKL ratio. Patients with polyarthritis had significantly higher increments in RANKL from baseline to follow-up, compared to patients with oligoarthritis. RANKL was a significant negative predictor for increments in total body lean mass. Patients who were receiving corticosteroids (CS) or disease-modifying antirheumatic drugs (DMARDs) at follow-up had higher OPG/RANKL ratio compared with patients who did not receive this medication. Conclusions The data supports that levels of OPG are lower in patients with JIA compared to healthy children, and higher levels of RANKL is associated with more serious disease. RANKL was a significant negative predictor of lean mass in patients with JIA. The OPG/RANKL ratio was higher in patients on DMARDs or CS treatment. PMID:21134287

  9. 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…

  10. 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

  11. 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.

  12. Use of shuttle vectors to study the molecular processing of defined carcinogen-induced DNA damage: mutagenicity of single O4-ethylthymine adducts in HeLa cells.

    PubMed Central

    Klein, J C; Bleeker, M J; Lutgerink, J T; van Dijk, W J; Brugghe, H F; van den Elst, H; van der Marel, G A; van Boom, J H; Westra, J G; Berns, A J

    1990-01-01

    We developed a simian virus 40 based shuttle vector system to study the molecular consequences of distinct carcinogen-induced DNA lesions in human cells. To establish the mutagenicity of O4-ethylthymine adducts, oligonucleotides carrying a single O4-ethylthymine adduct at a unique position were ligated into the vector molecules. Following replication in HeLa cells on average 23% of the progeny molecules carried a mutation in the region of modification. The vast majority of these mutations represented single T----C transitions at the position of the modified base, most probably as a consequence of mispairing of the O4-ethylthymine residues during replication. To a minor extent the O4-ethylthymine adduct may also induce T----A transversions or double point mutations. The in vivo mutation frequency of the adduct was found to be comparable to that of a C-A mismatch at the same position, but was lower than that expected from in vitro experiments with adducted DNA templates and purified DNA polymerases. Images PMID:2377457

  13. 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

  14. Occupational exposure to carcinogens: Benzene, pesticides and fibers

    PubMed Central

    Falzone, Luca; Marconi, Andrea; Loreto, Carla; Franco, Sabrina; Spandidos, Demetrios A.; Libra, Massimo

    2016-01-01

    It is well known that the occupational exposure to contaminants and carcinogens leads to the development of cancer in exposed workers. In the 18th century, Percivall Pott was the first to hypothesize that chronic exposure to dust in the London chimney sweeps was associated with an increased risk of developing cancer. Subsequently a growing body of evidence indicated that other physical factors were also responsible for oncogenic mutations. Over the past decades, many carcinogens have been found in the occupational environment and their presence is often associated with an increased incidence of cancer. Occupational exposure involves several factors and the association between carcinogens, occupational exposure and cancer is still unclear. Only a fraction of factors is recognized as occupational carcinogens and for each factor, there is an increased risk of cancer development associated with a specific work activity. According to the International Agency for Research on Cancer (IARC), the majority of carcinogens are classified as ‘probable’ and ‘possible’ human carcinogens, while, direct evidence of carcinogenicity is provided in epidemiological and experimental studies. In the present review, exposures to benzene, pesticides and mineral fibers are discussed as the most important cancer risk factors during work activities. PMID:27748850

  15. Carcinogenic potency of alkylating agents in rodents and humans.

    PubMed

    Dedrick, R L; Morrison, P F

    1992-05-01

    Alkylating agents are known to produce second tumors in cancer patients treated for their primary cancer. Since therapeutic doses are high and the pharmacokinetics of the drugs are thoroughly studied, these agents provide a unique opportunity to compare intrinsic carcinogenic potency between experimental animals and humans. We have examined the carcinogenicity of melphalan, chlorambucil, and cyclophosphamide in causing leukemia in patients treated for cancer or polycythemia vera and lymphosarcoma in rats and mice. A good correlation among species is observed when the carcinogenic potency is based on the total lifetime exposure to active species derived from these drugs.

  16. Report on carcinogens monograph on 1-bromopropane.

    PubMed

    2013-09-01

    The National Toxicology Program conducted a cancer evaluation on 1 bromopropane for possible listing in the Report on Carcinogens (RoC). The cancer evaluation is captured in the RoC monograph, which was peer reviewed in a public forum. The monograph consists of two components: (Part 1) the cancer evaluation, which reviews the relevant scientific information, assesses its quality, applies the RoC listing criteria to the scientific information, and provides the NTP recommendation for listing status for 1 bromopropane in the RoC, and (Part 2) the substance profile proposed for the RoC, containing the NTP's listing status recommendation, a summary of the scientific evidence considered key to reaching that decision, and data on properties, use, production, exposure, and Federal regulations and guidelines to reduce exposure to 1-bromopropane. This monograph provides an assessment of the available scientific information on 1 bromopropane, including human exposure and properties, disposition and toxicokinetics, cancer studies in experimental animals, and studies of mechanisms and other related effects, including relevant toxicological effects, genetic toxicology, and mechanisms of carcinogenicity. From this assessment, the NTP recommended that 1 bromopropane be listed as reasonably anticipated to be a human carcinogen in the RoC based on sufficient evidence from studies in experimental animals, which found inhalation exposure to 1-bromopropane caused skin tumors in male rats, large intestine tumors in female and male rats, and lung tumors in female mice. Also noted was that 1 bromopropane, either directly or via reactive metabolites, caused molecular alterations that typically are associated with carcinogenesis, including genotoxicity, oxidative stress, and glutathione depletion. These alterations, observed in mainly in vitro and toxicity studies in rodents, are relevant to possible mechanisms of human carcinogenicity and support the relevance of the cancer studies in

  17. Towards incorporating epigenetic mechanisms into carcinogen identification and evaluation

    PubMed Central

    Herceg, Zdenko

    2013-01-01

    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. PMID:23749751

  18. 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.

  19. Assessment and 2-Year Institutions.

    ERIC Educational Resources Information Center

    Bradley, Jama L.; And Others

    1994-01-01

    Describes a national study of the current availability and use of commercially and institutionally developed educational assessment instruments. Indicates that two-year institutions reported less activity than four-year institutions in assessing the major fields of study but that 77% of all two-year institutions assessed basic skills. (MAB)

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

    PubMed Central

    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. PMID:24551762

  1. Interactions of carcinogens with DNA (deoxyribonucleic acid)

    SciTech Connect

    Broyde, S.; Shapiro, R.

    1989-10-01

    The principal goal of this research has been the determination of the conformational changes produced in DNA by the covalent binding of a carcinogenic aromatic amine, and the correlation of these changes with the mutations and carcinogenic effects initiated by the same substances. To this end, we have devised new synthetic methods for the preparation of oligonucleotides modified by derivatives af 4-aminobiphenyl and aniline. We have also performed potential energy minimization studies on the above substances and on single and double stranded DNA fragments bearing the above amines as well as acetylaminofluorene, aminofluorene, aminopyrene and the antibiotic mitomycin. Our computations have been carried out on DOE supercomputers using our program, DUPLEX. We have defined a number of novel structures for these modified DNAs, including Hoogsteen, wedge'' (see below) denatured, cross-linked and intercalated forms. Some suggestions have been made about the relation of these forms to mutagenesis. 7 refs.

  2. Statistical analysis of results of carcinogenicity studies of synthetic vitreous fibres at Research and Consulting Company, Geneva.

    PubMed

    Rossiter, C E; Chase, J R

    1995-10-01

    Five inhalation studies of synthetic vitreous fibres have recently investigated experimental tumorigenic responses to four different refractory ceramic fibres (RCF), two fibre glasses, one stone (rock) wool and one slag wool. Except for one RCF, the source materials were typical commercial products. Three studies included positive control groups exposed to chrysotile or crocidolite asbestos. The studies were conducted using state-of-the-art technologies for fibre size separation, fibre lofting and nose-only inhalation exposure. The target average fibre size was 20 microns long by 1 micron diameter. Hamsters exposed to a kaolin RCF yielded a mesothelioma rate of 38%, but no lung cancers. There were no tumours among the chrysotile-exposed hamsters. At the highest dose of 30 mg m-3 in rat studies, the commercial RCF all produced significant numbers of lung tumours, and some mesotheliomas. The fourth RCF, which had been heat-treated to simulate an after-service fibre, did not produce a significant excess of lung cancers, but did produce one mesothelioma. A rat multi-dose experiment with three lower doses of the kaolin RCF yielded one mesothelioma among 379 rats, but no excess of lung tumours. The overall dose-response relation for lung cancer did not appear to be linear, consistent with the possibility of a threshold close to the Maximum Tolerated Dose. No insulation wool (glass, stone or slag) exposure group had a lung tumour rate that differed statistically significantly from the tumour rate for the respective concurrent control groups, sham-exposed to filtered air. There was no significant difference in the total tumour rates between the four insulation wool groups and the control animals, and no significant dose-response relation above the respective sham-exposed control tumour rates. The total lung tumour rates for rats in both chrysotile and crocidolite exposure groups were significantly raised. One animal in each asbestos-exposed group developed a mesothelioma

  3. 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.

  4. 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

  5. Effects of SO2 or NOx on toxic and genotoxic properties of chemical carcinogens. II. Short term in vivo studies.

    PubMed

    Pool, B L; Brendler, S; Klein, R G; Monarca, S; Pasquini, R; Schmezer, P; Zeller, W J

    1988-07-01

    Short term in vivo studies were performed to study biological effects of the common air pollutants SO2 or NOx and their influence on the genotoxic activities of nitrosamines. Hepatocytes and lung cells were isolated from Sprague-Dawley rats which had inhaled 50 p.p.m. of SO2 or NOx for 2 weeks. After incubating the cells for 1 h, genotoxicity was determined in hepatocytes by measuring DNA single-strand breaks induced by N-nitroso-acetoxymethylmethylamine, N-nitrosodimethylamine and N-nitrosomethylbenzylamine. Parameters of toxicity (trypan blue exclusion and leakage of serum enzymes) were determined in both liver and lung cells also following 1 h incubation. The activities of aryl hydrocarbon hydroxylase (AHH), nitrosodimethylamine demethylase (NDMA-D) and glutathione-S-transferase (GST) were determined in subcellular microsomal fractions isolated from lung and liver tissues. Finally, as a measure of overall toxicity, the activities of various serum enzymes were determined in the blood serum of the rats. It was found that the induction of DNA single-strand breaks by three nitrosamines was decreased in hepatocytes from SO2-treated animals. The viability of rat hepatocytes and of rat lung cells, as determined by trypan blue exclusion, was similar in all three treatment groups immediately after isolation, as well as after 1 h incubation with DMSO or with the nitrosamines. In contrast, the leakage of enzymes was different in hepatocytes of SO2-treated rats, since lactate dehydrogenase activity was decreased. Leakage of enzymes from the lung cells did not differ from group to group, but was lower than from hepatocytes. Foreign compound metabolizing enzymes were mainly decreased in NOx-treated animals, namely AHH, NDMA-D and GST in liver and GST in the lung. For SO2-treated animals NDMA-D was increased in liver and GST was decreased in lung. Blood serum enzyme levels were not greatly different from each other, except for lactate dehydrogenase which was elevated in SO2

  6. Studies on the mechanism of the acute and carcinogenic effects of N-nitrosodimethylamine on mink liver

    SciTech Connect

    Martino, P.E.; Diaz Gomez, M.I.; Tamayo, D.; Lopez, A.J.; Castro, J.A.

    1988-01-01

    Outbreaks of liver necrosis and liver hemangiosarcoma were detected in a mink breeding colony in Argentina. Analysis of the Minks' food revealed the presence of 2.6 ppm dimethylnitrosamine (NDMA) in it, apparently as a result of the addition of nitrite as preservative. Previous studies gave evidence of the particular susceptibility of minks to NDMA and other hepatic insults. The authors have determined several biochemical parameters known to correlate with NDMA hepatotoxic effects and compared with them those in rat liver. NDMA administration to both species resulted in the formation of reactive metabolites able to interact with liver DNA to give N/sup 7/-methylguanine and O/sup 6/-methylguanine adducts. Biotransformation of NDMA by liver slices to CO/sub 2/ was significantly lower in the mink than in the rat, whereas the covalent binding (CB) to nucleic acids was slightly lower than in the rat. Aminopyrine N-demethylase activity was also significantly less in mink than in rat liver. The CB of NDMA reactive metabolites to microsomal proteins was not significantly lower in mink as compared to the rat, and the same holds true for the biotransformation of NDMA to formaldehyde by microsomal preparations. Results suggest that the high susceptibility of minks to NDMA might be partially due to a decreased ability to detoxicate NDMA but also a higher intrinsic susceptibility of their liver cells to a given chemical insult.

  7. Studies on the mechanism of the acute and carcinogenic effects of N-nitrosodimethylamine on mink liver.

    PubMed

    Martino, P E; Diaz Gomez, M I; Tamayo, D; Lopez, A J; Castro, J A

    1988-01-01

    Outbreaks of liver necrosis and liver hemangiosarcoma were detected in a mink breeding colony in Argentina. Analysis of the Minks' food revealed the presence of 2.6 ppm dimethylnitrosamine (NDMA) in it, apparently as a result of the addition of nitrite as preservative. Previous studies gave evidence of the particular susceptibility of minks to NDMA and other hepatic insults. We have determined several biochemical parameters known to correlate with NDMA hepatotoxic effects and compared them with those in rat liver. NDMA administration to both species resulted in the formation of reactive metabolites able to interact with liver DNA to give N7-methylguanine and O6-methylguanine adducts. Biotransformation of NDMA by liver slices to CO2 was significantly lower in the mink than in the rat, whereas the covalent binding (CB) to nucleic acids was slightly lower than in in the rat. Aminopyrine N-demethylase activity was also significantly less in mink than in rat liver. The CB of NDMA reactive metabolites to microsomal proteins was not significantly lower in mink as compared to the rat, and the same holds true for the biotransformation of NDMA to formaldehyde by microsomal preparations. Results suggest that the high susceptibility of minks to NDMA might be partially due to a decreased ability to detoxicate NDMA but also to a higher intrinsic susceptibility of their liver cells to a given chemical insult.

  8. Your Child's Development: 2 Years (24 Months)

    MedlinePlus

    ... 1- to 2-Year-Old Your Child’s Development: 2 Years (24 Months) KidsHealth > For Parents > Your Child’s Development: 2 Years (24 Months) Print A A A en español El desarrollo de su hijo: 2 años (24 meses) Tired of changing diapers? When ...

  9. 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.

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

    PubMed Central

    Persson, S A; Ahlberg, M; Berghem, L; Könberg, E; Nordberg, G F; Bergman, F

    1988-01-01

    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 (Fe2O3). 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 Fe2O3 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. Images FIGURE 3. FIGURE 4. PMID:3383816

  11. 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…

  12. Summary of carcinogenic potency and positivity for 492 rodent carcinogens in the carcinogenic potency database.

    PubMed Central

    Gold, L S; Slone, T H; Bernstein, L

    1989-01-01

    A tabulation of carcinogenic potency (TD50) by species for 492 chemicals that induce tumors in rats or mice is presented. With the use of the Carcinogenic Potency Database, experimental results are summarized by indicating in which sex-species groups the chemical was tested and the respective evaluations of carcinogenicity. A comparison of three summary measures of TD50 for chemicals with more than one positive experiment per species shows that the most potent TD50 value is similar to measures that average values or functions of values. This tabulation can be used to investigate associations between rodent potency and other factors such as mutagenicity, teratogenicity, chemical structure, and human exposure. PMID:2707207

  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. 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

  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. 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)

  17. 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…

  18. 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 Central

    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; Oshitani, Hitoshi

    2016-01-01

    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

  19. Update on the genotoxicity and carcinogenicity of cobalt compounds

    PubMed Central

    Lison, D; De Boeck, M; Verougstraete, V; Kirsch-Volders, M

    2001-01-01

    OBJECTIVE—To integrate recent understandings of the mechanisms of genotoxicity and carcinogenicity of the different cobalt compounds.
METHOD—A narrative review of the studies published since the last IARC assessment in 1991 (genotoxicity, experimental carcinogenesis, and epidemiology).
RESULTS—Two different mechanisms of genotoxicity, DNA breakage induced by cobalt metal and especially hard metal particles, and inhibition of DNA repair by cobalt (II) ions contribute to the carcinogenic potential of cobalt compounds. There is evidence that soluble cobalt (II) cations exert a genotoxic and carcinogenic activity in vitro and in vivo in experimental systems but evidence in humans is lacking. Experimental data indicate some evidence of a genotoxic potential for cobalt metal in vitro in human lymphocytes but there is no evidence available of a carcinogenic potential. There is evidence that hard metal particles exert a genotoxic and carcinogenic activity in vitro and in human studies, respectively. There is insufficient information for cobalt oxides and other compounds.
CONCLUSION—Although many areas of uncertainty remain, an assessment of the carcinogenicity of cobalt and its compounds requires a clear distinction between the different compounds of the element and needs to take into account the different mechanisms involved.


Keywords: cobalt; DNA breakage; inhibition of DNA repair PMID:11555681

  20. [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

  1. Variability of NT-proBNP and Its Relationship with Inflammatory Status in Patients with Stable Essential Hypertension: A 2-Year Follow-Up Study

    PubMed Central

    Roselló-Lletí, Esther; Calabuig, Jose R.; Morillas, Pedro; Cortés, Raquel; Martínez-Dolz, Luis; Almenar, Luis; González-Juanatey, Jose R.; Lauwers, Catheline; Salvador, Antonio; Portolés, Manuel; Bertomeu, Vicente; Rivera, Miguel

    2012-01-01

    Background The variability of NT-proBNP levels has been studied in heart failure, yet no data exist on these changes over time in hypertensive patients. Furthermore, studies on the relationship between natriuretic peptides and inflammatory status are limited. Methodology/Principal Findings 220 clinically and functionally asymptomatic stable patients (age 59±13, 120 male) out of 252 patients with essential hypertension were followed up, and NT-proBNP was measured at baseline, 12 and 24 months. No differences in NT-proBNP were found with respect to the basal stage in the hypertrophic group, but significant changes were found in non-hypertrophic subjects. The reproducibility of NT-proBNP measurements was better in patients with hypertrophy than in the non-hypertrophic group for the three intervals (stage I-basal; stage II-stage I; stage II-basal) with a reference change value of 34%, 35% and 41%, respectively, in the hypertrophic group. A more elevated coefficient of correlation was obtained in the hypertrophic group than in patients without hypertrophy: basal versus stage I (r = 0.79, p<0.0001 and r = 0.59, p<0.0001) and stage I versus stage II (r = 0.86, p<0.0001 and r = 0.56, p<0.0001). Finally, levels of NT-proBNP significantly correlated with sTNF-R1 (p<0.0001) and IL-6 (p<0.01) during follow-up. A multivariate linear regression analysis showed that sTNF-R1 is an independent factor of NT-proBNP. Conclusions/Significance This work shows that there is good stability in NT-proBNP levels in a follow-up study of asymptomatic patients with stable hypertension and left ventricular hypertrophy. As a consequence, assessment of NT-proBNP concentrations may be a useful tool for monitoring the follow-up of hypertensive patients with hypertrophy. Measured variations in peptide levels, exceeding 35% in a 12-month follow-up and 41% in a 24-month follow-up, may indicate an increase in cardiovascular risk, and therefore implies adjustment in the medical treatment

  2. Mutagenicity, carcinogenicity, and teratogenicity of acrylonitrile.

    PubMed

    Léonard, A; Gerber, G B; Stecca, C; Rueff, J; Borba, H; Farmer, P B; Sram, R J; Czeizel, A E; Kalina, I

    1999-05-01

    Acrylonitrile (AN) is an important intermediary for the synthesis of a variety of organic products, such as artificial fibres, household articles and resins. Although acute effects are the primary concern for an exposure to AN, potential genotoxic, carcinogenic and teratogenic risks of AN have to be taken seriously in view of the large number of workers employed in such industries and the world-wide population using products containing and possibly liberating AN. An understanding of the effect of acrylonitrile must be based on a characterization of its metabolism as well as of the resulting products and their genotoxic properties. Tests for mutagenicity in bacteria have in general been positive, those in plants and on unscheduled DNA synthesis doubtful, and those on chromosome aberrations in vivo negative. Wherever positive results had been obtained, metabolic activation of AN appeared to be a prerequisite. The extent to which such mutagenic effects are significant in man depends, however, also on the conditions of exposure. It appears from the limited data that the ultimate mutagenic factor(s), such as 2-cyanoethylene oxide, may have little opportunity to act under conditions where people are exposed because it is formed only in small amounts and is rapidly degraded. The carcinogenic action of AN has been evaluated by various agencies and ranged from 'reasonably be anticipated to be a human carcinogen' to 'cannot be excluded', the most recent evaluation being 'possibly carcinogenic to humans'. Animal data that confirm the carcinogenic potential of AN have certain limitations with respect to the choice of species, type of tumors and length of follow up. Epidemiological studies which sometimes, but not always, yielded positive results, encounter the usual difficulties of confounding factors in chemical industries. Exposure of workers to AN should continue to be carefully monitored, but AN would not have to be considered a cancer risk to the population provided

  3. Antimicrobial susceptibility profile, treatment outcome and serotype distribution of clinical isolates of Salmonella enterica subspecies enterica: a 2-year study from Kerala, South India

    PubMed Central

    Harichandran, Deepa; Dinesh, Kavitha Radhakrishnan

    2017-01-01

    Background/purpose Typhoid and paratyphoid fever continue to be important causes of illness and death in parts of Asia, being associated with poor sanitation and consumption of unsafe food and water. Antimicrobial resistance has emerged to traditional first-line drugs, namely, the fluoroquinolones, as well as to third-generation cephalosporins, posing challenges to treatment. Azithromycin has proven to be an effective alternative for treatment of uncomplicated typhoid fever. The purpose of this study was to determine the antimicrobial susceptibility, clinical outcome and serotype distribution pattern of clinical isolates belonging to Salmonella enterica subspecies enterica. Methodology All clinical isolates of S. enterica obtained from blood, sterile body fluids, as well as stool and urine samples at Amrita Institute of Medical Sciences and Research Centre, Kerala, India, between August 2011 and July 2013 were included in the study and processed based on standard microbiology protocols. Results A total of 118 isolates of Salmonella were obtained during the study period. Out of these, 79 were of S. Typhi (66.95%), followed by isolates of S. Paratyphi A (22; 18.64%) and S. Typhimurium 12 (10.17%). Five isolates could not be identified further. There was 100% susceptibility to ceftriaxone in all S. enterica subspecies. Ciprofloxacin susceptibility was 32.91% for S. Typhi and 40.90% for S. Paratyphi A as determined by the disk diffusion method. The susceptibility profile of S. Typhi isolates to different antimicrobials was as follows: chloramphenicol (94.93%), ampicillin (77.21%), cotrimoxazole (75.94%) and azithromycin (78.48%). For S. Typhi, the minimum inhibitory concentration (MIC) of ciprofloxacin required to inhibit the growth of 50% of organisms was 0.5 μg/mL (intermediate) and MIC required to inhibit the growth of 90% of organisms was 1 μg/mL (resistant). S. Typhimurium was 100% susceptible to cotrimoxazole, ampicillin, ceftriaxone, chloramphenicol, ofloxacin

  4. Detection of viruses in weekly stool specimens collected during the first 2 years of life: A pilot study of five healthy Australian infants in the rotavirus vaccine era.

    PubMed

    Ye, Suifang; Whiley, David M; Ware, Robert S; Sloots, Theo P; Kirkwood, Carl D; Grimwood, Keith; Lambert, Stephen B

    2017-05-01

    Several viruses are associated with gastroenteritis in infants. This pilot study, nested within a larger community-based project of early childhood infections, collected daily symptom data and 511 weekly stool samples from five healthy, fully vaccinated, term infants from birth until their second birthday. Real-time PCR assays were used to detect six enteric viruses. Frequent, silent shedding of one or more of the six viruses was observed, particularly involving adenovirus where shedding could be for up to 3 months without gastrointestinal symptoms. These pilot data demonstrate that a positive PCR result for enteric viruses may not always indicate the cause of childhood gastroenteritis. J. Med. Virol. 89:917-921, 2017. © 2016 Wiley Periodicals, Inc.

  5. 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

  6. 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

  7. The MCT-ketogenic diet as a treatment option in refractory childhood epilepsy: A prospective study with 2-year follow-up.

    PubMed

    Lambrechts, Danielle A J E; de Kinderen, Reina J A; Vles, Hans S H; de Louw, Anton J; Aldenkamp, Albert P; Majoie, Marian J M

    2015-10-01

    The present study assessed the long-term (i.e., 24months) efficacy of the ketogenic diet (KD) as an add-on therapy in children with refractory epilepsy, with focus on seizure frequency, seizure severity, and tolerability. Most patients were treated with the MCT-diet. At one and two years, 33% and 23%, respectively, of the 48 included patients were still on the KD. After three months, one year, and two years of treatment, 16.7% of the patients were responders. The highest responder rate (i.e., 22.9%) was seen at six and nine months of treatment. Of the fifteen patients with seizure clusters during baseline, 60% were responders after three months when looking at cluster reduction and most of them were not responders for the total seizure frequency. From three months of treatment onwards, most of the patients had a relevant decrease in seizure severity which was mainly related to the most severe seizure type. Gastrointestinal dysfunction was often reported, especially in the first six weeks of treatment. Growth deceleration was present in 30% of the patients, and weight reduction in 15%. Improved arousal was mentioned in 30% of patients. No patients developed ECG abnormalities or kidney stones. Increase in lipid profile was rare. The KD is an effective therapy for children with therapy-resistant epilepsy. Effectiveness is reflected in the reduction of seizure frequency as well as in the reduction of seizure severity. After 6months of treatment, it is obvious which patients are responders and tolerate the treatment well. Most of these patients will continue to benefit from the KD for a longer time. Long-term use of the diet was well tolerated.

  8. Change in Care Dependency and Nursing Care Problems in Nursing Home Residents with and without Dementia: A 2-Year Panel Study.

    PubMed

    Schüssler, Sandra; Lohrmann, Christa

    2015-01-01

    Over time, chronic conditions like dementia can lead to care dependency and nursing care problems, often necessitating nursing home admission. This panel study (2012-2014) aims to explore changes in care dependency and nursing care problems (incontinence, malnutrition, decubitus, falls and restraints) in residents with and without dementia over time. In total, nine Austrian nursing homes participated, including 258 residents (178 with, 80 without dementia) who completed all five measurements. Data were collected with the International Prevalence Measurement of Care Problems questionnaire, the Care Dependency Scale and the Mini-Mental State Examination-2. Repeated measures ANOVA and crosstabs were used to analyse changes. The results showed that care dependency in dementia residents increased significantly for all 15 items of the Care Dependency Scale, with the highest increase being residents' day-/night pattern, contact with others, sense of rules/values and communication. In contrast, care dependency in residents without dementia increased for four of the 15 items, with the highest increase being for continence, followed by getting (un)dressed. With respect to the assessed nursing care problems, residents with dementia and those without only differed significantly in terms of an increase in urinary- (12.3% vs. 14.2%), fecal- (17.4% vs. 10%), and double incontinence (16.7% vs. 11.9%). The results indicated that residents with dementia experienced increased care dependency in different areas than residents without dementia. Furthermore, residents with dementia experienced a lower increase in urinary incontinence but a higher increase in fecal- and double incontinence. These results help professionals to identify areas for improvement in dementia care.

  9. The relationships of change in work climate with changes in burnout and depression: a 2-year longitudinal study of Chinese mental health care workers.

    PubMed

    Fong, Ted C T; Ho, Rainbow T H; Au-Yeung, Friendly S W; Sing, C Y; Law, K Y; Lee, L F; Ng, S M

    2015-09-01

    Mental health care workers face heavy emotional demand and are prone to work burnout. Work burnout has been associated with poor mental health and work climate, which refers to individual perceptions about work setting. The purpose of this study was to examine whether intra-individual changes in work climate were associated with intra-individual changes in burnout and depression over two years. The present sample included Chinese mental health care workers (N = 312; mean age = 38.6, SD = 9.9) working in a psychosocial rehabilitation institution. The participants completed questionnaires on work climate, work burnout and depression at seven time points across two years. Parallel process latent growth modeling was used to analyze the associations of change between work climate and burnout and depression. Work climate displayed a logarithmic decreasing trend while burnout and depression displayed logarithmic increasing trends over two years. Baseline levels of work climate were negatively and moderately associated with baseline levels of burnout and depression (r = -.44 to -.60, p < .01). Changes in work climate were negatively and moderately associated with change in burnout (r = -.43, p < .01) and change in depression (r = -.31, p < .05). Change in burnout was positively and strongly associated (r = .58, p < .01) with change in depression. The current results support temporal relationships among changes in work climate, burnout and depression across time. Practical implications for future preventive work in burnout interventions were discussed within this population.

  10. 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

  11. 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

    2016-04-02

    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.

  12. Interactions of chemical carcinogens and genetic variation in hepatocellular carcinoma

    PubMed Central

    Zhang, Yu-Jing

    2010-01-01

    In the etiology of hepatocellular carcinoma (HCC), in addition to hepatitis B virus and hepatitis C virus infections, chemical carcinogens also play important roles. For example, aflatoxin B1 (AFB1) epoxide reacts with guanine in DNA and can lead to genetic changes. In HCC, the tumor suppressor gene p53 codon 249 mutation is associated with AFB1 exposure and mutations in the K-ras oncogene are related to vinyl chloride exposure. Numerous genetic alterations accumulate during the process of hepatocarcinogenesis. Chemical carcinogen DNA-adduct formation is the basis for these genetic changes and also a molecular marker which reflects exposure level and biological effects. Metabolism of chemical carcinogens, including their activation and detoxification, also plays a key role in chemical hepatocarcinogenesis. Cytochrome p450 enzymes, N-acetyltransferases and glutathione S-transferases are involved in activating and detoxifying chemical carcinogens. These enzymes are polymorphic and genetic variation influences biological response to chemical carcinogens. This genetic variation has been postulated to influence the variability in risk for HCC observed both within and across populations. Ongoing studies seek to fully understand the mechanisms by which genetic variation in response to chemical carcinogens impacts on HCC risk. PMID:21160980

  13. Glyphosate rodent carcinogenicity bioassay expert panel review.

    PubMed

    Williams, Gary M; Berry, Colin; Burns, Michele; de Camargo, Joao Lauro Viana; Greim, Helmut

    2016-09-01

    Glyphosate has been rigorously and extensively tested for carcinogenicity by administration to mice (five studies) and to rats (nine studies). Most authorities have concluded that the evidence does not indicate a cancer risk to humans. The International Agency for Research on Cancer (IARC), however, evaluated some of the available data and concluded that glyphosate probably is carcinogenic to humans. The expert panel convened by Intertek assessed the findings used by IARC, as well as the full body of evidence and found the following: (1) the renal neoplastic effects in males of one mouse study are not associated with glyphosate exposure, because they lack statistical significance, strength, consistency, specificity, lack a dose-response pattern, plausibility, and coherence; (2) the strength of association of liver hemangiosarcomas in a different mouse study is absent, lacking consistency, and a dose-response effect and having in high dose males only a significant incidence increase which is within the historical control range; (3) pancreatic islet-cell adenomas (non-significant incidence increase), in two studies of male SD rats did not progress to carcinomas and lacked a dose-response pattern (the highest incidence is in the low dose followed by the high dose); (4) in one of two studies, a non-significant positive trend in the incidence of hepatocellular adenomas in male rats did not lead to progression to carcinomas; (5) in one of two studies, the non-significant positive trend in the incidence of thyroid C-cell adenomas in female rats was not present and there was no progression of adenomas to carcinomas at the end of the study. Application of criteria for causality considerations to the above mentioned tumor types and given the overall weight-of-evidence (WoE), the expert panel concluded that glyphosate is not a carcinogen in laboratory animals.

  14. Dietary Carcinogens and Breast Cancer.

    DTIC Science & Technology

    1997-07-01

    bile acid sulfotransferase also referred to as dehydroepiandrosterone (DHEA) sulfotransferase (70). The two phenol sulfotransferase (PST) can be...distinguished from each other on the basis of thermal sensitivity and resistance to 2.6- dichloro-4- nitrophenol (DCNP) (70). Carcinogenic arylamines and...arachidonic acid -dependent peroxidase, is known to be present in the microsomal fraction of several tissues. PHS is a bifunctional enzyme that initiates

  15. Reassessing the two-year rodent carcinogenicity bioassay: a review of the applicability to human risk and current perspectives.

    PubMed

    Marone, Palma Ann; Hall, William C; Hayes, A Wallace

    2014-02-01

    The 2-year rodent carcinogenicity test has been the regulatory standard for the prediction of human outcomes for exposure to industrial and agro-chemicals, food additives, pharmaceuticals and environmental pollutants for over 50 years. The extensive experience and data accumulated over that time has spurred a vigorous debate and assessment, particularly over the last 10 years, of the usefulness of this test in terms of cost and time for the information obtained. With renewed interest in the United States and globally, plus new regulations in the European Union, to reduce, refine and replace sentinel animals, this review offers the recommendation that reliance on information obtained from detailed shorter-term, 6 months rodent studies, combined with genotoxicity and chemical mode of action can realize effective prediction of human carcinogenicity instead of the classical two year rodent bioassay. The aim of carcinogenicity studies should not be on the length of time, and by obligation, number of animals expended but on the combined systemic pathophysiologic influence of a suspected chemical in determining disease. This perspective is in coordination with progressive regulatory standards and goals globally to utilize effectively resources of animal usage, time and cost for the goal of human disease predictability.

  16. The sensitivity of rainbow trout and other fish to carcinogens.

    PubMed

    Bailey, G S; Hendricks, J D; Nixon, J E; Pawlowski, N E

    1984-01-01

    Systematic design of replacement chemicals with reduced toxicities will require knowledge of mechanisms of action of parent compounds, especially in species which occupy the environment of most likely exposure. For aquatic systems, the rainbow trout has proven a valuable model for studying mechanisms of carcinogenicity. By comparison, small aquarium species show great potential as in situ field monitors of aquatic contamination by toxic chemicals but are less developed for mechanism studies. Fish species, especially rainbow trout, have also proven useful alternatives to traditional rodent models for comparative studies on mechanisms of action of nonaquatic carcinogens. These kinds of comparative studies form an essential basis for extrapolation of animal studies to man. Carcinogenicity testing of individual compounds and their replacements can provide only limited information on the expected impact of such chemicals on natural populations, since these populations are unavoidably exposed to potent modulators of the carcinogenic response. Hence any program which aims at redesign of commercial chemicals with reduced toxicities must have as a prior aim the full understanding of the mechanisms of joint carcinogen-inhibitor-promotor interactions. Because of their high sensitivity, low cost per individual, and low background tumor incidences, fish models such as the rainbow trout may be the only vertebrate models in which it is economically practical to initiate such complex studies.

  17. Carcinogenicity of methyl-tertiary butyl ether in gasoline.

    PubMed

    Mehlman, Myron A

    2002-12-01

    Methyl tertiary butyl ether (MTBE) was added to gasoline on a nationwide scale in 1992 without prior testing of adverse, toxic, or carcinogenic effects. Since that time, numerous reports have appeared describing adverse health effects of individuals exposed to MTBE, both from inhalation of fumes in the workplace and while pumping gasoline. Leakage of MTBE, a highly water-soluble compound, from underground storage tanks has led to contamination of the water supply in many areas of the United States. Legislation has been passed by many states to prohibit the addition of MTBE to gasoline. The addition of MTBE to gasoline has not accomplished its stated goal of decreasing air pollution, and it has posed serious health risks to a large portion of the population, particularly the elderly and those with respiratory problems, asthma, and skin sensitivity. Reports of animal studies of carcinogenicity of MTBE began to appear in the 1990s, prior to the widespread introduction of MTBE into gasoline. These reports were largely ignored. In ensuing years, further studies have shown that MTBE causes various types of malignant tumors in mice and rats. The National Toxicology Program (NTP) Board of Scientific Counselors' Report on Carcinogens Subcommittee met in December 1998 to consider listing MTBE as "reasonably anticipated to be a human carcinogen." In spite of recommendations from Dr. Bailer, the primary reviewer, and other scientists on the committee, the motion to list MTBE in the report was defeated by a six to five vote, with one abstention. On the basis of animal studies, it is widely accepted that if a chemical is carcinogenic in appropriate laboratory animal test systems, it must be treated as though it were carcinogenic in humans. In the face of compelling evidence, NTP Committee members who voted not to list MTBE as "reasonably anticipated to be a human carcinogen" did a disservice to the general public; this action may cause needless exposure of many to health risks

  18. 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

  19. Report on carcinogens monograph on cumene.

    PubMed

    2013-09-01

    The National Toxicology Program conducted a cancer evaluation on cumene for possible listing in the Report on Carcinogens (RoC). The cancer evaluation is captured in the RoC monograph, which was peer reviewed in a public forum. The monograph consists of two components: (Part 1) the cancer evaluation, which reviews the relevant scientific information, assesses its quality, applies the RoC listing criteria to the scientific information, and provides the NTP recommendation for listing status for cumene in the RoC, and (Part 2) the substance profile proposed for the RoC, containing the NTP's listing status recommendation, a summary of the scientific evidence considered key to reaching that decision, and data on properties, use, production, exposure, and Federal regulations and guidelines to reduce exposure to cumene. This monograph provides an assessment of the available scientific information on cumene, including human exposure and properties, disposition and toxicokinetics, cancer studies in experimental animals, and studies of mechanisms and other related effects, including relevant toxicological effects, genetic toxicology, and mechanisms of carcinogenicity. From this assessment, the NTP recommended that cumene be listed as reasonably anticipated to be a human carcinogen in the RoC based on sufficient evidence from studies in experimental animals, which found that cumene exposure caused lung tumors in male and female mice and liver tumors in female mice. Several proposed mechanisms of carcinogenesis support the relevance to humans of the lung and liver tumors observed in experimental animals. Specifically, there is evidence that humans and experimental animals metabolize cumene through similar metabolic pathways. In addition, mutations of the K-ras oncogene and p53 tumor-suppressor gene observed in cumene-induced lung tumors in mice, along with altered expression of many other genes, resemble molecular alterations found in human lung and other cancers.

  20. Asbestos and carcinogenicity

    SciTech Connect

    McDonald, J.C.; McDonald, A.D. )

    1990-08-24

    It is alleged that there have been 67 or more cases of mesothelioma among Quebec chrysotile miners and millers. Of the many thousand individuals employed by the Quebec chrysotile mining and milling industry since its inception, no one known how many have died or of these how many from mesothelioma. At a 1989 meeting in Ottawa, Ontario, Canada, it was stated that a cohort of 11,379 persons born between 1891 and 1920 and employed for 1 month or more, there had been 11 cases of mesothelioma among 4,547 deaths to the end of 1975; by 1978 there were 18 cases, and a follow-up to 1990 will soon be completed. More than 70% of the cohort have now died, and a study of a subsample indicates that the eventual number of cases of mesotheliomas may be about 30. A disproportionate number of these (at least seven) were exposed to crocidolite in a small local factory, and one had substantial exposure to amosite. Could the remaining cases be attributed to fibrous tremolite contamination Whether or not chrysotile per se is capable of inducing mesothelioma, it is clear that workers whose exposure has been only to commercial chrysotile have suffered much less from mesothelioma than, for example, those exposed for even a few months to crocidolite in gas mask filter manufacture or cigarette filter manufacture, in whom 16 to 19% of all deaths were attributable to this cause. In the general population of the Quebec chrysotile mining towns, exposed over generations to chrysotile concentrations far greater than anything encountered in public buildings, there have been few if any cases of mesothelioma attributable to nonoccupational exposure.

  1. 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.

  2. Evaluation of the potential carcinogenicity of epichlorohydrin (106-89-8). Final report

    SciTech Connect

    Not Available

    1988-06-01

    Epichlorohydrin 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 epichlorohydrin is estimated to be 0.37 (mg/kg/day)-1, placing it in potency group 3 according to the CAG's methodology for evaluating potential carcinogens. Combining the weight-of-evidence group and the potency group, epichlorohydrin is assigned a LOW hazard ranking.

  3. 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.

  4. 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

    2015-07-03

    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.

  5. The application of hepatic P450 reductase null gpt delta mice in studying the role of hepatic P450 in genotoxic carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced mutagenesis.

    PubMed

    Luan, Yang; Xing, Guozhen; Qi, Xinming; Wu, Mengjun; Li, Chenggang; Yao, Jun; Gong, Likun; Nohmi, Takehiko; Gu, Jun; Zhou, Wanhong; Zheng, Saijing; Ren, Jin

    2012-11-01

    The cytochrome P450 (P450 or CYP) is involved in both detoxification and metabolic activation of many carcinogens. In order to identify the role of hepatic P450 in the mutagenesis of genotoxic carcinogens, we generated a novel hepatic P450 reductase null (HRN) gpt delta mouse model, which lacks functional hepatic P450 on a gpt delta mouse background. In this study, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was used to treat HRN gpt delta mice and control littermates. Gene mutations in the liver and lungs were detected, and mutation spectra were analyzed. Pharmacokinetic analyses were performed, and tissue levels of NNK and metabolite were determined. NNK-induced mutant frequencies (MFs) were equivalent to spontaneous MFs in the liver, but increased more than 3 times in the lungs of HRN gpt delta mice compared to control mice. NNK-induced mutation spectra showed no difference between HRN gpt delta mice and control littermates. Toxicokinetic studies revealed reduced clearance of NNK with elevated tissue concentrations in HRN gpt delta mice. To our knowledge, these are the first data demonstrating that NNK cannot induce mutagenesis in the liver without P450 metabolic activation, but can induce mutagenesis in lungs by a hepatic P450-independent mechanism. Moreover, our data show that hepatic P450 plays a major role in the systemic clearance of NNK, thereby protecting the lungs against NNK-induced mutagenesis. Our model will be useful in establishing the role of hepatic versus extrahepatic P450-mediated mutagenesis, and the relative contributions of P450 compared to other biotransformation enzymes in the genotoxic carcinogens' activation.

  6. Critical review on the carcinogenic potential of pesticides used in Korea.

    PubMed

    Choi, Sangjun

    2014-01-01

    Pesticides used in Korea are grouped by four classes of hazard (extremely, highly, moderately and slightly hazardous) based on acute oral and dermal toxicity in the rat. However, there is little information of carcinogenic effects. The aim of this study was to evaluate potential carcinogenicity for active ingredients of pesticides used in Korea. A total of 1,283 pesticide items were registered under the Pesticide Control Act of which 987 were commercially available. Of these 987 items, 360 active ingredients not duplicated were evaluated for carcinogenicity using the carcinogen list established by the US Environmental Protection Agency (EPA). Some 25 out of 360 ingredients were classified as likely to be carcinogenic (probable) to humans and 52 had suggestive evidence of carcinogenic potential (suspected) based on the US EPA classification. Some 31% of 987 items contained probable or suspected human carcinogenic ingredients. Carcinogenic pesticides accounted for 24% (5,856/24,795 tons) of the total volume of consumption in Korea. Interestingly, pesticides with lower acute toxicity were found to have higher carcinogenic potential. Based on these findings, the study suggests that it is important to provide information on long-term toxicity to farmers, in addition to acute toxicity data.

  7. Carcinogenicity prediction of noncongeneric chemicals by a support vector machine.

    PubMed

    Zhong, Min; Nie, Xianglei; Yan, Aixia; Yuan, Qipeng

    2013-05-20

    The ability to identify carcinogenic compounds is of fundamental importance to the safe application of chemicals. In this study, we generated an array of in silico models allowing the classification of compounds into carcinogenic and noncarcinogenic agents based on a data set of 852 noncongeneric chemicals collected from the Carcinogenic Potency Database (CPDBAS). Twenty-four molecular descriptors were selected by Pearson correlation, F-score, and stepwise regression analysis. These descriptors cover a range of physicochemical properties, including electrophilicity, geometry, molecular weight, size, and solubility. The descriptor mutagenic showed the highest correlation coefficient with carcinogenicity. On the basis of these descriptors, a support vector machine-based (SVM) classification model was developed and fine-tuned by a 10-fold cross-validation approach. Both the SVM model (Model A1) and the best model from the 10-fold cross-validation (Model B3) runs gave good results on the test set with prediction accuracy over 80%, sensitivity over 76%, and specificity over 82%. In addition, extended connectivity fingerprints (ECFPs) and the Toxtree software were used to analyze the functional groups and substructures linked to carcinogenicity. It was found that the results of both methods are in good agreement.

  8. Medium-term bioassays as alternative carcinogenicity test.

    PubMed

    Ito, N; Imaida, K; Tamano, S; Hagiwara, A; Shirai, T

    1998-07-01

    A medium-term liver bioassay system for rapid detection of carcinogenic agents using male F344 rats has been developed, in order to bridge the gap between long-term carcinogenicity tests and short-term screening assays. The system is fundamentally based on the two-stage hypothesis of carcinogenesis: initiation with diethylnitrosamine (200 mg/kg bw, i.p.) is followed by test chemical administration during the second, in combination with 2/3 partial hepatectomy. It requires only 8 weeks for animal experimental treatment and a further few weeks for quantitative analysis of immunohistochemically-demonstrated glutathione S-transferase placental form positive hepatic foci. A total of 291 chemicals/substances have already been analyzed in this laboratory and the efficacy of the system for hepatocarcinogens has thereby been well established. This bioassay is particularly useful for dose-response and chemical mixture studies, usually requiring large-scale experiments and also for evaluation of chemopreventive agents. Another bioassay, a medium-term multiorgan bioassay system, using 5 different chemical carcinogens, diethylnitrosamine (DEN), N-methylnitrosourea (MNU), N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), 1,2-dimethylhydrazine (DMH) and 2,2'-dihydroxy-di-n-propylnitrosamine (DHPN), has also been established for rapid detection of not only hepatocarcinogens, but also other organ-target carcinogens. Rats were initially treated with a single i.p. administration of 100 mg/kg DEN, 4 i.p. administrations of 20 mg/kg MNU, 4 s.c. doses of 40 mg/kg DMH for 2 weeks and then 0.1% DHPN for 2 weeks. Test chemicals are administered after the carcinogens exposure. Animals were sacrificed at the end of week 36, and major organs were examined histologically. Carcinogenic activities of test chemicals were compared between the test chemical treated group and carcinogen exposures group (control group). It is increasingly becoming regarded that these bioassays are useful methods and are

  9. 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.

  10. 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.

  11. Carcinogen metabolism in human lung tissues and the effect of tobacco smoking: results from a case--control multicenter study on lung cancer patients.

    PubMed Central

    Bartsch, H; Petruzzelli, S; De Flora, S; Hietanen, E; Camus, A M; Castegnaro, M; Alexandrov, K; Rojas, M; Saracci, R; Giuntini, C

    1992-01-01

    Cigarette smoking is the strongest risk factor for lung cancer, but genetically determined variations in the activities of pulmonary enzyme that metabolize tobacco-derived carcinogens may affect individual risk. To investigate whether these enzymes (e.g., CYP1A-related) can serve as markers for carcinogen-DNA damage, lung tissue specimens were taken during surgery from middle-aged men with either lung cancer or non-neoplastic lung disease. Phase I [aryl hydrocarbon hydroxylase (AHH), ethoxycoumarin O-deethylase (ECOD)] and phase II (epoxide hydrolase, UDP-glucuronosyltransferase, glutathione S-transferase) enzyme activities, glutathione and malondialdehyde contents were determined in lung parenchyma and/or bronchial tissues; some samples were also analyzed for DNA adducts, using 32P-postlabeling. The data were then analyzed for the following: a) differences in metabolic profiles between bronchial and parenchymal lung tissue; b) the effect of recent exposure to tobacco smoke on enzyme inducibility and benzo[a]pyrene metabolism; c) differences in enzyme inducibility between lung cancer and non-lung cancer patients; d) the effect of smoking on metabolism of mutagens in vitro; e) pulmonary DNA adduct levels and AHH activity in lung parenchyma of smokers and ex-smokers; f) lipid peroxidation products in lung tissue from lung cancer and non-lung cancer patients, as related to smoking habits and degree of airway obstruction; and g) prognostic value of AHH pulmonary activity in lung cancer patients. The results demonstrate a pronounced effect of tobacco smoke on pulmonary metabolism of xenobiotics and prooxidant state and suggest the existence of a metabolic phenotype at higher risk for tobacco-associated lung cancer. PMID:1336722

  12. An Evaluation of the Human Carcinogenic Potential of ...

    EPA Pesticide Factsheets

    This position paper, An Evaluation of the Human Carcinogenic Potential of Ethylene Glycol Butyl Ether, was developed in support of the EPA's evaluation of a petition from the American Chemistry Council requesting to delist EGBE per the Clean Air Act Amendments (CAAA), Title III, section 112(b)(1). The position paper was a key component of the Agency's recent determination to grant this petition. It will also be used in the Agency's IRIS assessment of ethylene glycol butyl ether (EGBE). An NTP (1998; 2000) study has reported some evidence of carcinogenic activity in male B6C3F1 mice based on increased incidence of hemangiosarcomas of the liver, and some evidence of carcinogenic activity in female B6C3F1 mice based on increased incidence of forestomach squamous cell papillomas or carcinomas.

  13. Formaldehyde generators: relationship between stability, lipophilicity and carcinogenic potency.

    PubMed

    Ashby, J; Lefevre, P A

    1982-01-01

    The rate of hydrolysis to formaldehyde of methylenedimorpholine (MDM), hexamethylenetetramine (HMT) and dinitrosopentamethylenetetramine (DNPT) have been compared with the enzyme-mediated formation of formaldehyde from hexamethylphosphoramide (HMPA). The bio-distribution of [14C]HMPA following nasal instillation in rats has also been studied and compared with that of [14C]methyl methanesulphonate (MMS). These data are used to relate the several carcinogenic/genotoxic properties of the chemicals named above. It is concluded from these data and related considerations that three classes of formaldehyde-generators should be recognized (a) labile agents such as MDM (and formaldehyde) which are likely to be locally active as carcinogens, (b) lipophilic and relatively stable agents such as HMPA which may be both locally active (if bio-accumulated) and systemically active as carcinogens, and (c) agents such as HMT and DNPT, of intermediate stability, which are unlikely to be systemically active and to be of low or zero activity locally.

  14. Hepatotumorigenicity of ethyl tertiary-butyl ether with 2-year inhalation exposure in F344 rats.

    PubMed

    Saito, Arata; Sasaki, Toshiaki; Kasai, Tatuya; Katagiri, Taku; Nishizawa, Tomoshi; Noguchi, Tadashi; Aiso, Shigetoshi; Nagano, Kasuke; Fukushima, Shoji

    2013-05-01

    Carcinogenicity of ethyl tertiary-butyl ether (ETBE) was examined with inhalation exposure using F344/DuCrlCrlj rats. Groups of 50 male and 50 female rats, 6 week old at commencement, were exposed to ETBE at 0, 500, 1,500 or 5,000 ppm (v/v) in whole-body inhalation chambers for 6 h/day, 5 days/week for 104 weeks. A significant increase in the incidence of hepatocellular adenomas was indicated in males exposed at 5,000 ppm, but not in females at any concentration. In addition, significantly increased incidences of eosinophilic and basophilic cell foci were observed in male rats at 5,000 ppm. Regarding non-neoplastic lesions, rat-specific changes were observed in kidney, with an increase in the severity of chronic progressive nephropathy in both sexes at 5,000 ppm. Increased incidences of urothelial hyperplasia of the pelvis were observed at 1,500 ppm and above, and mineral deposition was apparent in the renal papilla at 5,000 ppm in males. There were no treatment-related histopathological changes observed in any other organs or tissues in either sex. The present 2-year inhalation study demonstrated hepatotumorigenicity of ETBE in male, but not in female rats.

  15. 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

  16. Induction of hepatocellular carcinoma in nonhuman primates by chemical carcinogens

    SciTech Connect

    Adamson, R.H. )

    1989-01-01

    Several compounds were evaluated in nonhuman primates for their potential to induce neoplasms, especially hepatocellular carcinoma (HCC). The compounds can be classified into three groups: food contaminants, model rodent carcinogens, and nitrosamines. All three compounds in the food contaminants group, namely, aflatoxin B1, sterigmatocystin, and methylazoxymethanol acetate, induced HCC. None of the model rodent carcinogens tested consistently induced HCC in rhesus and cynomolgus monkeys. Three of four nitrosamines evaluated induced HCC in rhesus and cynomolgus monkeys. One nitrosamine, diethylnitrosamine, is a predictable and potent inducer of HCC and is useful for establishment of a nonhuman primate model for numerous oncologic studies.

  17. 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.

  18. Health effects of coal mining and combustion: carcinogens and cofactors.

    PubMed

    Falk, H L; Jurgelski, W

    1979-12-01

    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

  19. 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...

  20. 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.

  1. Carcinogenicity and other health effects of acrylonitrile with reference to occupational exposure limit.

    PubMed

    Sakurai, H

    2000-04-01

    The occupational exposure limit for acrylonitrile (AN) has been set by many organizations on the basis of its carcinogenicity. However, recent epidemiological studies do not afford evidence supporting the hypothesis that AN is carcinogenic to humans. Review of the 18 published cohort studies revealed that, although there is not adequate evidence in humans for carcinogenicity of AN, the possibility of a causal association between high exposure to AN and lung cancer in humans cannot be excluded. It was pointed out that carcinogenic potential of AN may be weak, if any, to humans, and the current occupational exposure limit (OEL) for AN of 2 ppm was evaluated as appropriate in view of AN exposure levels reported by epidemiological studies. Based also on review of the literature on health effects other than carcinogenicity, it was concluded that the current OEL for AN is a reasonable value and there is no need for a revision at present.

  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. 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 Central

    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

  4. Clinical and radiological evaluation of Trabecular Metal and the Smith-Robinson technique in anterior cervical fusion for degenerative disease: a prospective, randomized, controlled study with 2-year follow-up.

    PubMed

    Löfgren, Håkan; Engquist, M; Hoffmann, P; Sigstedt, B; Vavruch, L

    2010-03-01

    A prospective, randomized, controlled study was carried out to compare the radiological and clinical outcomes after anterior cervical decompression and fusion (ACDF) with Trabecular Metal (TM) to the traditional Smith-Robinson (SR) procedure with autograft. The clinical results of cervical fusion with autograft from the iliac crest are typically satisfactory, but implications from the donor site are frequently reported. Alternative materials for cervical body interfusion have shown lower fusion rates. Trabecular Metal is a porous tantalum biomaterial with structure and mechanical properties similar to that of trabecular bone and with proven osteoconductivity. As much as 80 consecutive patients planned for ACDF were randomized for fusion with either TM or tricortical autograft from the iliac crest (SR) after discectomy and decompression. Digitized plain radiographic images of 78 (98%) patients were obtained preoperatively and at 2-year follow-up and were subsequently evaluated by two senior radiologists. Fusion/non-fusion was classified by visual evaluation of the A-P and lateral views in forced flexion/extension of the cervical spine and by measuring the mobility between the fused vertebrae. MRI of 20 TM cases at 2 years was successfully used to assess the decompression of the neural structures, but was not helpful in determining fusion/non-fusion. Pain intensity in the neck, arms and pelvis/hip were rated by patients on a visual analog scale (VAS) and neck function was rated using the Neck Disability Index (NDI) the day before surgery and 4, 12 and 24 months postoperatively. Follow-ups at 12 and 24 months were performed by an unbiased observer, when patients also assessed their global outcome. Fusion rate in the SR group was 92%, and in the TM group 69% (P < 0.05). The accuracy of the measurements was calculated to be 2.4 degrees . Operating time was shorter for fusion with TM compared with autograft; mean times were 100 min (SD 18) and 123 min (SD 23

  5. Carcinogenicity of antineoplastic agents in man.

    PubMed

    Rieche, K

    1984-03-01

    Review of the literature shows that: Anticancer drugs are in all probability mostly also carcinogenic. Alkylating agents such as melphalan, chlorambucil and cyclophosphamide seem to lead to the highest rate of second malignancies. Second malignancies after antitumour drugs are mostly acute leukaemias. Conditions which could influence the carcinogenicity of an antitumour drug are (a) its carcinogenic potency; (b) long-term administration; (c) the total dose used and (d) long-term survival of the patient. Irradiation and chemotherapy seem to have the greatest carcinogenic potential, e.g. in malignant lymphomas. The role of immunosuppression as a co-carcinogenic factor is difficult to estimate. Although transplant patients on anticancer drugs for immunosuppression have a higher risk of reticulosarcomas, but not of solid tumours, there is no evidence to suppose that in general immunosuppression and carcinogenicity are directly related. There is no reason to abandon intensive chemotherapy regimes if they lead to significant therapeutic results on the grounds of possible carcinogenicity of these drugs.

  6. Survey of animal drugs with carcinogenic properties.

    PubMed

    Somogyi, A

    1984-01-01

    Residues of animal drugs with carcinogenic potential cannot always be avoided in food. The risk/benefit evaluation of carcinogenic drugs used in food-producing animals is a scientifically unresolved problem. Nonetheless, a pragmatic solution taking into account such drugs' putative mechanisms of action, their relative potency, and their significance in the prevention and therapy of disease must and can be achieved. While it is unlikely that a new animal drug possessing overt carcinogenic properties would pass the approval process practiced in most countries today, a number of carcinogenic drugs for use in food-producing animals are currently on the market. Their re-evaluation from the viewpoint of human food safety is necessary, particularly if they are genotoxic (for example nitrofurans, nitroimidazoles, quinoxaline-di-N-oxides). The carcinogenicity of hormonally active animal drugs, none of which has genotoxic potential, is believed to be related to their hormonal action. Thus, the establishment of a threshold level for these drugs and their residues appears possible. It is difficult to evaluate certain other nongenotoxic animal drugs which are carcinogenic at very high dose levels and in one species only. No carcinogenic substance, regardless of its hypothetical mechanism of action, should be used in food-producing animals for which a very significant therapeutic benefit has not been demonstrated.

  7. Lack of carcinogenicity of lyophilized Agaricus blazei Murill in a F344 rat two year bioassay.

    PubMed

    Lee, I P; Kang, B H; Roh, J K; Kim, J R

    2008-01-01

    The Brazilian mushroom Agaricus blazei Murill has antimutagenic, antioxidant, immunostimulatory and antitumorigenic activities, and is increasingly consumed as a health food worldwide. We undertook the present study to evaluate the chronic toxicity and oncogenicity of A. blazei Murill in F344 rats. To establish a no-observed-adverse-effect level (NOAEL), four treatment groups of 100 rats each (50 males and 50 females) were fed a powder diet containing lyophilized A. blazei aqueous extract at 0, 6250, 12,500, and 25,000 ppm for up to 2 years. During this period, there was no remarkable change in mean body weight, body weight gain, hematologic or serum chemistry parameters, or absolute or relative organ weights in control or treatment groups. Mortality in male treatment groups (26%, 16%, and 30%), however, was significantly lower than in controls (48%). Histopathological studies showed no increased incidence of tumors in any treatment group, and total tumor incidence across all groups was comparable to historical data. In conclusion, an A. blazei Murill lyophilized powder diet even at 25,000 ppm (1176 mg/kgb x w x /day for male rats and 1518 mg/kgb.w./day for female rats) resulted in no remarkable carcinogenic effects in F344 rats over a 2-year period. Therefore, the dietary NOAEL is 25,000 ppm.

  8. 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.

  9. 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

  10. Exploring Faculty Retirement Issues in Public 2-Year Institutions

    ERIC Educational Resources Information Center

    Conley, Valerie Martin

    2005-01-01

    Much of the research on faculty retirement focuses exclusively on 4-year institutions. This study fills a gap by describing the age distribution of faculty in public 2-year institutions, the retirement plans of these faculty, and factors related to the retirement decision-making process using data from the 1999 National Study of Postsecondary…

  11. Triadic Interaction among Newly Acquainted 2-Year-Olds

    ERIC Educational Resources Information Center

    Ishikawa, Fumiko; Hay, Dale F.

    2006-01-01

    Are children as young as 2 years old able to interact in groups of three? The study applied the family triad model first introduced by Parke, Power, and Gottman (1979) to the case of peer interaction. In Experiment 1, the model was refined for use in studies of peer interaction and applied to an existing dataset of 16 triads of newly acquainted…

  12. Carcinogenicity of the insulation wools: reassessment of the IARC evaluation.

    PubMed

    Brown, R C; Davis, J M; Douglas, D; Gruber, U F; Hoskins, J A; Ilgren, E B; Johnson, N F; Rossiter, C E; Wagner, J C

    1991-08-01

    In assessing the health evidence concerning man-made mineral fibers, the chemical composition, surface activity, durability, and size of fibers have to be taken into account. Special-purpose fine glass fibers need to be separated from the insulation wools (glass, rock, and slag wool). The epidemiological evidence is sufficient to conclude that there has been no mesothelioma risk to workers producing or using glass wool, rock wool, or slag wool. The epidemiological studies have been large and powerful, and they show no evidence of a cause-effect relationship between lung cancer and exposure to glass wool, rock wool, or slag wool fibers. There is some evidence of a small cancer hazard attached to the manufacturing process in slag wool plants 20 to 50 years ago, when asbestos was used in some products and other carcinogenic substances were present. However, this hazard is not associated with any index of exposure to slag wool itself. Animal inhalation studies of ordinary insulation wools also show that there is no evidence of hazard associated with exposure to these relatively coarse, soluble fibers. The evidence of carcinogenicity is limited to experiments with special-purpose fine durable glass fibers or experimental fibers, and only when these fibers are injected directly into the pleural or peritoneal cavity. Multiple chronic inhalation studies of these same special-purpose fine glass fibers have not produced evidence of carcinogenicity. It is suggested that the present IARC evaluation of the carcinogenic risk of insulation wools should be revised to Category 3: not classifiable as to carcinogenicity to humans.

  13. Asphalt fume dermal carcinogenicity potential: I. dermal carcinogenicity evaluation of asphalt (bitumen) fume condensates.

    PubMed

    Clark, Charles R; Burnett, Donald M; Parker, Craig M; Arp, Earl W; Swanson, Mark S; Minsavage, Gary D; Kriech, Anthony J; Osborn, Linda V; Freeman, James J; Barter, Robert A; Newton, Paul E; Beazley, Shelley L; Stewart, Christopher W

    2011-10-01

    Asphalt (bitumen) fume condensates collected from the headspace above paving and Type III built up roofing asphalt (BURA) tanks were evaluated in two-year dermal carcinogenicity assays in male C3H/HeNCrl mice. A third sample was generated from the BURA using a NIOSH laboratory generation method. Similar to earlier NIOSH studies, the BURA fume condensates were applied dermally in mineral oil twice per week; the paving sample was applied 7 days/week for a total weekly dose of 50 mg/wk in both studies. A single benign papilloma was observed in a group of 80 mice exposed to paving fume condensate at the end of the two-year study and only mild skin irritation was observed. The lab generated BURA fume condensate resulted in statistically significant (P<0.0001) increases in squamous cell carcinomas (35 animals or 55% of animals at risk). The field-matched BURA condensate showed a weaker but significant (P=0.0063) increase (8 carcinomas or 13% of animals) and a longer average latency (90 weeks vs. 76 for the lab fume). Significant irritation was observed in both BURA condensates. It is concluded that the paving fume condensate was not carcinogenic under the test conditions and that the field-matched BURA fume condensate produced a weak tumor response compared to the lab generated sample.

  14. 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.

  15. 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.

  16. Contributions of human enzymes in carcinogen metabolism.

    PubMed

    Rendic, Slobodan; Guengerich, F Peter

    2012-07-16

    Considerable support exists for the roles of metabolism in modulating the carcinogenic properties of chemicals. In particular, many of these compounds are pro-carcinogens that require activation to electrophilic forms to exert genotoxic effects. We systematically analyzed the existing literature on the 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, interindividual variations, and risk assessment.

  17. Hemimicelles of alkyl carboxylates chemisorbed onto magnetic nanoparticles: study and application to the extraction of carcinogenic polycyclic aromatic hydrocarbons in environmental water samples.

    PubMed

    Ballesteros-Gómez, Ana; Rubio, Soledad

    2009-11-01

    In this work, magnetic nanoparticles (MNPs) coated with hemimicelles of alkyl (C(10)-C(18)) carboxylates, which have traditionally been used to prepare ferrofluids for technological applications, were used for the first time to extract organic contaminants from environmental water samples. The nanoparticles were coated by following a simple, rapid procedure (30 min at 85 degrees C) that uses commercially available magnetite of 20-30 nm mean particle diameter. The strong chemical bonding between the surfactant and magnetite relative to the electrostatic forces involved in conventional hemimicelle-based sorbents precludes leaching of the surfactant and facilitates its reuse and the obtainment of surfactant-free extracts. Tetradecanoate hemimicelles were used here to extract carcinogenic polycyclic aromatic hydrocarbons (CPAHs) prior to analysis by liquid chromatography (using a C(18) Supelcosil LC-PAH column and a gradient elution program with water and acetonitrile) and fluorescence detection. The procedure involved stirring filtered aqueous samples (350 mL) with 200 mg of tetradecanoate-coated MNPs for 15 min, isolating the sorbent with a Nd-Fe-B magnet and eluting the CPAHs with a mixture of acetonitrile and tetrahydrofuran. The extraction efficiency was not influenced by salt concentrations up to 1 M and pH values over the range 2.5-9. The preconcentration factor was 116. No cleanup of the extracts was needed, and the method proved matrix-independent. The limits of quantitation thus obtained, 0.2-0.5 ng L(-1), meet the stringent water quality requirements established by the recently amended European Water Framework Directive 2000/60/EC and also the U.S. EPA for the determination of CPAHs in surface and ground waters. The proposed method was successfully applied to the determination of these pollutants in surface and ground environmental water samples collected from various places in southern Spain. Recoveries from samples spiked with CPAHs at concentrations of 1

  18. 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.

  19. 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)…

  20. Predictive Models for Carcinogenicity and Mutagenicity ...

    EPA Pesticide Factsheets

    Mutagenicity and carcinogenicity are endpoints of major environmental and regulatory concern. These endpoints are also important targets for development of alternative methods for screening and prediction due to the large number of chemicals of potential concern and the tremendous cost (in time, money, animals) of rodent carcinogenicity bioassays. Both mutagenicity and carcinogenicity involve complex, cellular processes that are only partially understood. Advances in technologies and generation of new data will permit a much deeper understanding. In silico methods for predicting mutagenicity and rodent carcinogenicity based on chemical structural features, along with current mutagenicity and carcinogenicity data sets, have performed well for local prediction (i.e., within specific chemical classes), but are less successful for global prediction (i.e., for a broad range of chemicals). The predictivity of in silico methods can be improved by improving the quality of the data base and endpoints used for modelling. In particular, in vitro assays for clastogenicity need to be improved to reduce false positives (relative to rodent carcinogenicity) and to detect compounds that do not interact directly with DNA or have epigenetic activities. New assays emerging to complement or replace some of the standard assays include VitotoxTM, GreenScreenGC, and RadarScreen. The needs of industry and regulators to assess thousands of compounds necessitate the development of high-t

  1. 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

  2. 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.

  3. 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.

  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. 29 CFR 1990.112 - Classification of potential carcinogens.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 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...

  6. 29 CFR 1990.112 - Classification of potential carcinogens.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 9 2012-07-01 2012-07-01 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...

  7. 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...

  8. 29 CFR 1990.112 - Classification of potential carcinogens.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 9 2013-07-01 2013-07-01 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...

  9. 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...

  10. 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.

  11. The Weight of Evidence Does Not Support the Listing of Styrene as "Reasonably Anticipated to be a Human Carcinogen" in NTP's Twelfth Report on Carcinogens.

    PubMed

    Rhomberg, Lorenz R; Goodman, Julie E; Prueitt, Robyn L

    2013-01-01

    Styrene was listed as "reasonably anticipated to be a human carcinogen" in the twelfth edition of the National Toxicology Program's Report on Carcinogens based on what we contend are erroneous findings of limited evidence of carcinogenicity in humans, sufficient evidence of carcinogenicity in experimental animals, and supporting mechanistic data. The epidemiology studies show no consistent increased incidence of, or mortality from, any type of cancer. In animal studies, increased incidence rates of mostly benign tumors have been observed only in certain strains of one species (mice) and at one tissue site (lung). The lack of concordance of tumor incidence and tumor type among animals (even within the same species) and humans indicates that there has been no particular cancer consistently observed among all available studies. The only plausible mechanism for styrene-induced carcinogenesis-a non-genotoxic mode of action that is specific to the mouse lung-is not relevant to humans. As a whole, the evidence does not support the characterization of styrene as "reasonably anticipated to be a human carcinogen," and styrene should not be listed in the Report on Carcinogens.

  12. 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.

  13. 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.

  14. 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

  15. 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…

  16. 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.

  17. Applying tobacco carcinogen and toxicant biomarkers in product regulation and cancer prevention.

    PubMed

    Hecht, Stephen S; Yuan, Jian-Min; Hatsukami, Dorothy

    2010-06-21

    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 nonsmokers are summarized. This panel of biomarkers has potential applications in the new and challenging area of tobacco product regulation and in the development of rational approaches to cancer prevention by establishing carcinogen and toxicant uptake and excretion in people exposed to tobacco products.

  18. 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

  19. 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.

  20. Model carcinogen adsorption dynamics of DNA gel.

    PubMed

    Tomita, Naoko; Naito, Daisuke; Rokugawa, Isamu; Yamamoto, Takao; Dobashi, Toshiaki

    2014-09-01

    We have derived theoretical equations describing the adsorption of carcinogen to gels in an immersion medium containing carcinogens. The theory was developed for a cylindrical boundary condition under the assumption of a carcinogen diffusion-limited process combined with the "moving boundary picture (Furusawa et al., 2007)". The time course of the adsorbed carcinogen layer thickness and that of the carcinogen concentration in an immersion medium were expressed by a set of scaled variables, and the asymptotic behavior in the initial stage was derived. Experiments based on the theory were performed using a DNA gel sandwiched between a set of coverglasses in a medium containing acridine orange (AO). The boundary between the AO-adsorbed gel layer and AO-nonadsorbed gel layer was traced during the immersion. The time courses of the AO-adsorbed gel layer thickness and the AO concentration in the immersion medium were well explained by the theory, and the number ratio of the total AO molecules to the adsorption sites in the DNA gel was determined.

  1. Carcinogenicity bioassays of vinyl chloride monomer: a model of risk assessment on an experimental basis.

    PubMed Central

    Maltoni, C; Lefemine, G; Ciliberti, A; Cotti, G; Carretti, D

    1981-01-01

    Data are presented regarding the final results of the Bentivoglio (Bologna) project on long-term carcinogenicity bioassays of vinyl chloride (VC). The experimental project studied the effects of the monomer, administered by different routes, concentrations and schedules of treatment, to animals (near 7000) of different species, strains, sex and age. To our knowledge this is the largest experimental carcinogenicity study performed on a single compound by a single institution. The results indicate that VC is a multipotential carcinogen, affecting a variety of organs and tissues. In the experimental conditions studied, the neoplastic effects of the monomer were also detected at low doses. The experimental and biological factors greatly affect the neoplastic response to VC. Long-term carcinogenicity bioassays are, at present, a unique tool for the identification and quantification of environmental and occupational risks. Precise and highly standardized experimental procedures are needed to obtain data for risk assessment. PMID:6800782

  2. The dermal carcinogenic potential of unrefined and hydrotreated lubricating oils.

    PubMed

    McKee, R H; Daughtrey, W C; Freeman, J J; Federici, T M; Phillips, R D; Plutnick, R T

    1989-08-01

    Unrefined lubricating oils contain relatively high levels of polycyclic aromatic hydrocarbons (PAH) and have been shown to induce tumors in mouse skin. Exxon has developed a new method of refining these materials, a severe hydrotreatment process that is optimized for PAH removal. The specific objectives of the current study were to assess PAH reduction and then to evaluate directly the dermal carcinogenic potential of the materials that spanned the range of products produced by this method. The test samples included unrefined light and heavy vacuum distillates from a naphthenic crude oil, as well as the corresponding severely hydrotreated products. Two sets of samples were prepared to assess the effects of various operating parameters in the reactor. Additionally, positive (benzo[a]pyrene), negative (white mineral oil) and vehicle (toluene) control groups were included to assess the sensitivity and specificity of the bioassay. Each sample was applied in twice-weekly aliquots to the backs of 40 male C3H mice. In the analytical studies, significant reductions in the levels of several specific PAH were demonstrated. In the dermal carcinogenesis studies, the unrefined oils and the positive control induced tumors and also significantly reduced survival. None of the mice treated with severely hydrotreated oils or with the negative or vehicle controls developed skin tumors, and survival of these mice was not significantly different from the control. Thus, the data demonstrated that this new, severe hydrotreatment process was an effective means of converting carcinogenic feedstocks to non-carcinogenic products.

  3. 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.

  4. Capsaicin in hot chili pepper: carcinogen, co-carcinogen or anticarcinogen?

    PubMed

    Surh, Y J; Lee, S S

    1996-03-01

    Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is a major pungent ingredient of the Capsicum fruits such as hot green and red peppers. Besides its use as a food additive in various spicy cuisines, capsaicin is currently utilized for therapeutic purposes to treat various peripheral painful conditions such as rheumatoid arthritis and diabetic neuropathy. Considering consumption of capsaicin as a food additive and its current medicinal application in humans, correct evaluation and precise assessment of any harmful effects of this compound are essential from the public health standpoint. Numerous investigations have been conducted to determine the potential mutagenic and carcinogenic activity of capsaicin and chili pepper, but results are discordant. This review briefly examines findings in the literature of studies testing mutagenicity and tumorigenicity of capsaicin and presents a possible mechanistic basis for the dual effects exerted by the compound.

  5. 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.

  6. 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

  7. Epigenetic alterations induced by genotoxic occupational and environmental human chemical carcinogens: A systematic literature review

    PubMed Central

    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

  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.

  9. A Review of the Carcinogenic Potential of Bisphenol A

    PubMed Central

    Seachrist, Darcie D; Bonk, Kristen W.; Ho, Shuk-Mei; Prins, Gail S.; Soto, Ana M.; Keri, Ruth A.

    2015-01-01

    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

  10. [Assessment of a carcinogenic risk to the population of Bratsk].

    PubMed

    Efimova, N V; Iushkov, I N; Bodienkova, G M

    2008-01-01

    The paper provides data on the assessment of a carcinogenic risk to the population of Bratsk, a large industrial center. Long-term ambient air pollution with 3,4-benz(a)pyrene, formaldehyde, chromium, and other impurities causes the inadmissible level of a risk that has some differences for dwellers in some districts of the town. Clinical and immunological studies of an apparently healthy population revealed the tension of defensive immune mechanisms in the residents who were more exposed to pollution. Comparison of the level of breast cancer oncomarkers, neurospecific enolase in the sera of populations in the differently carcinogenic areas enables the level of man-made exposure to be considered as a significant risk factor.

  11. Comparison between carcinogenicity and mutagenicity based on chemicals evaluated in the IARC monographs.

    PubMed Central

    Bartsch, H; Tomatis, L

    1983-01-01

    The qualitative relationship between carcinogenicity and mutagenicity (DNA-damaging activity), based on chemicals which are known to be or suspected of being carcinogenic to man and/or to experimental animals, is analyzed using 532 chemicals evaluated in Volumes 1-25 of the IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. About 40 compounds (industrial processes) were found to be either definitely or probably carcinogenic to man, and 130 chemicals have been adequately tested in rodents and most of them also in various short-term assays. For a comparison between the carcinogenicity of a chemical and its behavior in short-term tests, systems were selected that have a value for predicting carcinogenicity. These were divided into mutagenicity in (A) the S. typhimurium/microsome assay, (B) other submammalian systems and (C) cultured mammalian cells; (D) chromosomal abnormalities in mammalian cells; (E) DNA damage and repair; (F) cell transformation (or altered growth properties) in vitro. The following conclusions can be drawn. In the absence of studies in man, long-term animal tests are still today the only ones capable of providing evidence of the carcinogenic effect of a chemical. The development and application of an appropriate combination of short-term tests (despite current limitations) can significantly contribute to the prediction/confirmation of the carcinogenic effects of chemicals in animals/man. Confidence in positive tests results is increased when they are confirmed in multiple short-term tests using nonrepetitive end points and different activation systems. Assays to detect carcinogens which do not act via electrophiles (promoters) need to be developed. The results of a given short-term test should be interpreted in the context of other toxicological data. Increasing demand for quantitative carcinogenicity data requires further examination of whether or not there is a quantitative relationship between the potency of a

  12. Sucralose Non-Carcinogenicity: A Review of the Scientific and Regulatory Rationale.

    PubMed

    Berry, Colin; Brusick, David; Cohen, Samuel M; Hardisty, Jerry F; Grotz, V Lee; Williams, Gary M

    2016-01-01

    Regulatory authorities worldwide have found the nonnutritive sweetener, sucralose, to be noncarcinogenic, based on a range of studies. A review of these and other studies found through a comprehensive search of electronic databases, using appropriate key terms, was conducted and results of that review are reported here. An overview of the types of studies relied upon by regulatory agencies to assess carcinogenicity potential is also provided as context. Physiochemical and pharmacokinetic/toxicokinetic studies confirm stability under conditions of use and reveal no metabolites of carcinogenic potential. In vitro and in vivo assays reveal no confirmed genotoxic activity. Long-term carcinogenicity studies in animal models provide no evidence of carcinogenic potential for sucralose. In studies in healthy adults, sucralose was well-tolerated and without evidence of toxicity or other changes that might suggest a potential for carcinogenic effects. In summary, sucralose does not demonstrate carcinogenic activity even when exposure levels are several orders of magnitude greater than the range of anticipated daily ingestion levels.

  13. Sucralose Non-Carcinogenicity: A Review of the Scientific and Regulatory Rationale

    PubMed Central

    Berry, Colin; Brusick, David; Cohen, Samuel M.; Hardisty, Jerry F.; Grotz, V. Lee; Williams, Gary M.

    2016-01-01

    ABSTRACT Regulatory authorities worldwide have found the nonnutritive sweetener, sucralose, to be noncarcinogenic, based on a range of studies. A review of these and other studies found through a comprehensive search of electronic databases, using appropriate key terms, was conducted and results of that review are reported here. An overview of the types of studies relied upon by regulatory agencies to assess carcinogenicity potential is also provided as context. Physiochemical and pharmacokinetic/toxicokinetic studies confirm stability under conditions of use and reveal no metabolites of carcinogenic potential. In vitro and in vivo assays reveal no confirmed genotoxic activity. Long-term carcinogenicity studies in animal models provide no evidence of carcinogenic potential for sucralose. In studies in healthy adults, sucralose was well-tolerated and without evidence of toxicity or other changes that might suggest a potential for carcinogenic effects. In summary, sucralose does not demonstrate carcinogenic activity even when exposure levels are several orders of magnitude greater than the range of anticipated daily ingestion levels. PMID:27652616

  14. Evaluation of the potential carcinogenicity of 1,1 dimethylhydrazine. Final report

    SciTech Connect

    Not Available

    1988-06-01

    1,1-Dimethylhydrazine is a probable human carcinogen, classified as weight-of-evidence Group B2 under the EPA Guidelines for Carcinogen Risk Assessment (U.S. EPA, 1986a). Evidence on potential carcinogenicity from animal studies is Sufficient, and the evidence from human studies is No Data. The potency factor (F) for 1,1-dimethylhydrazine is estimated to be 82.5/(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, 1,1-dimethylhydrazine is assigned a MEDIUM hazard ranking for the purposes of RQ adjustment.

  15. NTP Comparative Toxicity and Carcinogenicity Studies of o-Nitrotoluene and o-Toluidine Hydrochloride (CAS Nos. 88-72-2 and 636-21-5) Administered in Feed to Male F344/N Rats.

    PubMed

    Elwell, M

    1996-03-01

    o-Nitrotoluene and o-toluidine hydrochloride are structurally related chemicals that are suspected and demonstrated animal carcinogens, respectively. The metabolic potential of the gastrointestinal flora is considered an important factor in o-nitrotoluene-induced toxicity and involves the reduction of the nitro group to the corresponding amine (forming o-toluidine). These studies were designed to 1) compare the target organ toxicities of o-nitrotoluene and o-toluidine hydrochloride administered in feed at approximately equimolar doses (5,000 ppm) to male F344/N rats for 13 or 26 weeks, 2) determine the potential progression or reversibility of toxic or proliferative lesions following chemical withdrawal (stop-exposure) for 13 weeks after 13 weeks of exposure, and 3) examine the effect of antibiotic-altered gastrointestinal flora on the toxicity and/or carcinogenicity of o-nitrotoluene. o-Nitrotoluene and o-toluidine hydrochloride caused mesothelial hyperplasia and mesothelioma in male rats after 13 or 26 weeks of dietary exposure. The incidence of mesothelioma was greater and the latency was less in rats administered o-nitrotoluene than in rats administered o-toluidine hydrochloride. Additionally, o-nitrotoluene caused testicular degeneration in rats. Effects of o-nitrotoluene administration in the liver included progressive, irreversible increases in liver weight and irreversible increases in the incidences of cytoplasmic vacuolization and oval-cell hyperplasia. Placental glutathione S-transferase (PGST)-positive foci of cellular alteration occurred in the liver after 13 weeks of o-nitrotoluene exposure, and the number and size (as reflected by the volume fraction) of foci were increased after 26 weeks of continuous exposure. During the recovery period, the number of PGST-positive foci in rats in the stop-exposure group decreased slightly, but the size of the foci continued to increase. After 26 weeks, cholangiocarcinoma occurred in 2 of 20 rats in the stop

  16. Critical factors in assessing risk from exposure to nasal carcinogens.

    PubMed

    Bogdanffy, M S; Mathison, B H; Kuykendall, J R; Harman, A E

    1997-10-31

    Anatomical, physiological, biochemical and molecular factors that contribute to chemical-induced nasal carcinogenesis are either largely divergent between test species and humans, or we know very little of them. These factors, let alone the uncertainty associated with our knowledge gap, present a risk assessor with the formidable task of making judgments about risks to human health from exposure to chemicals that have been identified in rodent studies to be nasal carcinogens. This paper summarizes some of the critical attributes of the hazard identification and dose-response aspects of risk assessments for nasal carcinogens that must be accounted for by risk assessors in order to make informed decisions. Data on two example compounds, dimethyl sulfate and hexamethylphosphoramide, are discussed to illustrate the diversity of information that can be used to develop informed hypotheses about mode of action and decisions on appropriate dosimeters for interspecies extrapolation. Default approaches to interspecies dosimetry extrapolation are described briefly and are followed by a discussion of a generalized physiologically based pharmacokinetic model that, unlike default approaches, is flexible and capable of incorporating many of the critical species-specific factors. Recent advancements in interspecies nasal dosimetry modeling are remarkable. However, it is concluded that without the development of research programs aimed at understanding carcinogenic susceptibility factors in human and rodent nasal tissues, development of plausible modes of action will lag behind the advancements made in dosimetry modeling.

  17. 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.

  18. 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

  19. Polycyclic Aromatic Hydrocarbons In Edible Mushrooms from Niger Delta, Nigeria: Carcinogenic and Non-Carcinogenic Health Risk Assessment

    PubMed

    Igbiri, Sorbari; Udowelle, Nnaemeka Arinze; Ekhator, Osazuwa Clinton; Asomugha, Rose Ngozi; Igweze, Zelinjo Nkeiruka; Orisakwe, Orish Ebere

    2017-02-01

    In the oil-rich Niger Delta, hydrocarbon pollution and oil spillages, gas flaring and sundry anthropogenic activities constitute sources of polycyclic aromatic hydrocarbons (PAHs), with food contamination playing a major role in human exposure. In this study we assessed PAH levels in wild and cultivated edible mushroom species consumed by the general population from the oil producing Niger Delta, Nigeria. The concentrations of USEPA-16 PAHs were determined by gas chromatography and carcinogenic and non-carcinogenic health risks were calculated. The concentrations of USEPA-16 PAHs ranged from 0.02 mg/kg – 3.37 mg/kg. The dietary intake of carcinogenic and non-carcinogenic USEPA-16 PAHs (Naphthalene, Acenaphthylene, Acenaphthene, Anthracene, Phenanthrene, Flourene, Flouranthene, Pyrene, Benzo[a]Anthracene, Chrysene, Benzo[a]Pyrene, Benzo[b]Flouranthene, Benzo[K]Flouranthene, Benzo[g,h,i] Perylene, Dibenz[a,h]Anthracene and Ideno[1,2,3-cd]Pyrene) for adults, adolescents and seniors ranged from 0.00 – 0.05 mg/kg/day, 0.00 – 0.06 mg/kg/day and 0.00 – 0.07 mg/kg/day. The BaPeq ranged from 0.02 – 2.76 with margin of exposure MOE values of BaP ranging from 3,500,000 to 700,000, 3,500,000 and 3,500,000 to 7,000,000 for adults, adolescents and seniors indicating very insignificant health risk. The incremental lifetime cancer risk was within the safe range of 1.56x10-8 – 1.73x10-6 with the highest calculated risk found for wild Pleurotus ostreatus mushroom species from the study area.

  20. 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.

  1. 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

  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. Carcinogenicity evaluation for the application of carbon nanotubes as biomaterials in rasH2 mice

    PubMed Central

    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

    2012-01-01

    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. PMID:22787556

  4. 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.

  5. 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.

  6. 1,2,3-Trichloropropane: a multisite carcinogen in rats and mice.

    PubMed

    Irwin, R D; Haseman, J K; Eustis, S L

    1995-05-01

    1,2,3-Trichloropropane was evaluated in 2-year toxicology and carcinogenesis studies by the National Toxicology Program. The selection of this chemical for study was based on the potential for human exposure, its positive in vitro genotoxicity, and the carcinogenicity of structurally related chemicals. During the 2-year study 1,2,3-trichloropropane was administered in corn oil by gavage 5 days per week; groups of 60 F344/N rats received 0, 3, 10, or 30 mg/kg, while groups of 60 B6C3F1 mice received 0,6,20, or 60 mg/kg. Because of reduced survival associated with the development of chemical-related neoplasms, rats that received 30 mg/kg were terminated at 65 weeks (females) or 76 weeks (males). Similarly, mice that received 60 mg/kg were terminated at 73 weeks (females) or 79 weeks (males), while groups of mice that received 20 mg/kg were terminated at 88 weeks. 1,2,3-Trichloropropane induced benign and/or malignant neoplasms at multiple sites in both rats and mice; this included increased incidences of benign and malignant neoplasms of the squamous epithelium of the oral mucosa and forestomach of male and female rats, benign neoplasms of the kidney and pancreas and benign or malignant neoplasms of the preputial gland in male rats, malignant neoplasms of the mammary gland, and benign or malignant neoplasms of the clitoral gland in female rats. In mice, 1,2,3-trichloropropane induced a low incidence of malignant neoplasms of the oral mucosa in females, high incidences of benign and malignant neoplasms of the forestomach in males and females, benign neoplasms of the liver and harderian gland of males and females, and uterine neoplasms in females.

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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)

  13. Multiple-site carcinogenicity of benzene in Fischer 344 rats and B6C3F sub 1 mice

    SciTech Connect

    Huff, J.E.; Haseman, J.K.; Eustis, S.; Maronpot, R.R. ); DeMarini, D.M. ); Peters, A.C.; Persing, R.L. ); Chrisp, C.E. ); Jacobs, A.C. )

    1989-07-01

    Toxicology and carcinogenesis studies of benzene were conducted in groups of 60 F344/N rats and 60 B6C3F{sub 1} mice of each sex for each of three exposure doses and vehicle controls. Using the results from 17-week studies, doses for the 2-year studies were selected based on clinical observations, on clinical pathologic findings 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 of carcinogenicity of benzene in male F344/N rats, female F344/N rats, male B6C3F{sub 1} mice, and female B6C3F{sub 1} mice. Dose-related lymphocytopenia was observed for male and female F344/N rats and male and female B6C3F{sub 1} mice. These unequivocal observations show clearly that benzene is a trans-species, trans-sex, multisite potent carcinogen.

  14. Risk assessment of DNA-reactive carcinogens in food.

    PubMed

    Jeffrey, A M; 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(1) (AFB(1)), a limit of 20 ppb or approximately 30 microg/day has been set and is considered a tolerable daily intake (TDI). Since AFB(1) is considered a potent carcinogen, doses of <1.5 microg 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 (32)P-postlabeling or the use of surrogates such as hemoglobin adducts, together with approaches to evaluate the results. A

  15. 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

  16. Toxicity and carcinogenicity of 2,3-dibromo-1-propanol in F344/N rats and B6C3F1 mice.

    PubMed

    Eustis, S L; Haseman, J K; Mackenzie, W F; Abdo, K M

    1995-06-01

    2,3-Dibromo-1-propanol is a metabolite of the flame retardant tris(2,3-dibromopropyl) phosphate, previously shown to be a mutagen and carcinogen in experimental animals. Toxicology and carcinogenesis studies of 2,3-dibromo-1-propanol were conducted by applying the chemical in 95% ethanol to the interscapular skin of male and female F344/N rats and B6C3F1 mice 5 days a week for 13 weeks in the prechronic study and 48-55 weeks (rats) or 36-42 weeks (mice) in the carcinogenicity study. In the 13-week study, 10 rats and 10 mice of each sex received doses of 0, 44, 88, 177, 375, or 750 mg/kg. Deaths associated with chemical application occurred only in the high-dose (750 mg/kg) male mice. Chemical-related lesions were seen in the kidney of male rats, liver of female rats, and liver and lung of both sexes of mice. Based on the toxicity observed in the 13-week study, 50 rats of each sex received doses of 0, 188, or 375 mg/kg and 50 mice of each sex received 0, 88, or 177 mg/kg in the carcinogenicity study. The planned 2-year study was terminated early because of reduced survival of rats related to chemical-induced neoplasia and because of the appearance of antibodies to lymphocytic choriomeningitis virus in sentinel mice. Nearly all dosed rats had malignant neoplasms at one or more sites, while only one control male and one control female had malignant neoplasms. In rats, neoplasms induced by 2,3-dibromo-1-propanol occurred in the skin, nasal mucosa, Zymbal's gland, oral mucosa, esophagus, forestomach, intestines, liver, kidney, mammary gland (females), clitoral gland (females), spleen (males), and mesothelium (males). In mice, chemical-induced neoplasms occurred in the skin, forestomach, liver (males), and lung (males).

  17. 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

  18. Evaluation of the Inhalation Carcinogenicity of Ethylene Oxide (Final Report)

    EPA Science Inventory

    EPA has finalized its Evaluation of the Inhalation Carcinogenicity of Ethylene Oxide. This assessment addresses the potential carcinogenicity from long-term inhalation exposure to ethylene oxide. Now final, this assessment updates the carcinogenicity information in EPA’s 1985 Hea...

  19. Assessment of the carcinogenicity of the nonnutritive sweetener cyclamate.

    PubMed

    Ahmed, F E; Thomas, D B

    1992-01-01

    The weight of the evidence from metabolic studies, short-term tests, animal bioassays, and epidemiological studies indicates that cyclamate (CHS) is not carcinogenic by itself; however, there is evidence from in vitro and in vivo studies in animals that implies it may have cancer-promoting or cocarcinogenic activity. Epidemiological studies indicate that the use of nonnutritive sweeteners (CHS and saccharin) has not resulted in a measurable overall increase in the risk of bladder cancer in individuals who have ever used these products. No epidemiological information exists on the possible associations of these sweeteners and cancers other than those of the urinary tract. It is recommended that (1) no further studies on the metabolism of CHS to evaluate its carcinogenicity are required since no potentially hazardous metabolites have been appreciably detected in humans; (2) no further animal bioassays to test for the carcinogenicity of CHS by itself are necessary; (3) the studies in rodents that suggest a promotional or cocarcinogenic effect of CHS should be repeated because they cannot be ruled out; (4) because the significance to human health of a positive outcome of such studies is uncertain, additional research aimed at understanding the predictive value for human health of such results and more generic studies to develop well-validated systems that can be relied on in the assessment of cancer-promoting agents are recommended; (5) in populations where CHS continues to be used, epidemiological monitoring should be continued to determine whether there is an increased risk of cancer in humans who are heavy or long-term users or for those observed long after first exposure. In such monitoring, other cancer sites--in addition to the bladder--should be considered.

  20. 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.

  1. 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.

  2. Feeding Your 1- to 2-Year-Old

    MedlinePlus

    ... to 2-Year-Old Feeding Your 1- to 2-Year-Old KidsHealth > For Parents > Feeding Your 1- to 2-Year-Old Print A A A What's in ... español Alimentar a su hijo de 1 a 2 años de edad Toddlers this age are moving ...

  3. Growth and Your 1- to 2-Year-Old

    MedlinePlus

    ... 2-Year-Old Growth and Your 1- to 2-Year-Old KidsHealth > For Parents > Growth and Your 1- to 2-Year-Old Print A A A You're ... down. Your toddler may gain about 5 pounds (2.27 kg) and grow about 4 or 5 ...

  4. Social competence at 2 years following child traumatic brain injury.

    PubMed

    Anderson, Vicki; Beauchamp, Miriam Helen; Yeates, Keith Owen; Crossley, Louise; Ryan, Nicholas Peter; Hearps, Stephen J C; Catroppa, Cathy

    2017-02-08

    Children with traumatic brain injury (TBI) are at risk of social impairment, but research is yet to document the trajectory of these skills post-injury and factors that may predict social problems. The study addressed these gaps in knowledge, reporting on findings from a prospective, longitudinal follow-up study which investigated social outcomes post injury and explored factors contributing to these outcomes at 2 years post-injury. The sample included 113 children, 74 with TBI and 39 typically developing (TD) controls. TBI participants were recruited on presentation to hospital. Parents rated pre-injury function at that time and all children underwent magnetic resonance imaging (MRI) scan. Participants were followed up at 2 years post-injury. Outcomes were social adjustment, social participation, social relationships, and social cognition. Predictors of social outcomes examined included brain lesion characteristics, child cognition (6 months post-TBI) and behavior and environmental factors (pre-injury and 2 years). Reduced social adjustment (p=.011) and social participation (p<.001) were evident in children with TBI compared to TD controls. Poor social adjustment was predicted by externalizing behaviour problems and younger age at injury. Reduced social participation was linked to internalizing behavior problems. Greater lesion volume, lower socioeconomic status and family burden contributed to poorer social relationships, while age at injury predicted social cognition. Within the TBI group, 23% of children exhibited social impairment: younger age at injury, greater pre-injury and current behavior problems and family dysfunction, poorer IQ, processing speed, and empathy were linked to impairment. Further follow-up is required to track social recovery and the influences of cognition, brain, and environment over time.

  5. Characterization of the toxicity, mutagenicity, and carcinogenicity of methacrylonitrile in F344 Rats and B6C3F1 mice.

    PubMed

    Nyska, Abraham; Ghanayem, Burhan I

    2003-04-01

    Methacrylonitrile is an unsaturated aliphatic nitrile. It is widely used in the preparation of homopolymers and copolymers, elastomers, and plastics, and as a chemical intermediate in the preparation of acids, amides, amines, esters, and other nitriles. Methacrylonitrile was nominated for study by the National Cancer Institute (USA) because of the potential for human exposure, structural similarity to the known carcinogen acrylonitrile, and a lack of toxicity and carcinogenicity data. Doses selected for the 2-year study were based on the results of the 13-week gavage studies. Groups of 50 male and 50 female animals were exposed by gavage to 0, 3, 10, or 30 mg/kg in F344 rats, and 0, 1.5, 3 or 6 mg/kg in B6C3F1 mice, 5 days per week for 2 years. Urinary excretion of N-acetyl- S-(2-cyanopropyl)- l-cysteine (NACPC) and N-acetyl- S-(2-hydroxypropyl)- l-cysteine (NAHPC) were measured as markers of exposure at various time points after methacrylonitrile administration, and demonstrated that exposure of animals to methacrylonitrile occurred as intended. Urinary excretion of NACPC and NAHPC increased in rats and mice in a dose-dependent manner. In contrast to observations in rats, the ratios of NACPC/creatinine were generally higher in female than in male mice. Further, the ratios of NAHPC/creatinine in rats were significantly greater at all time points and all doses than the corresponding ratios of NACPC/creatinine in male and female mice. In both rats and mice, survival was not affected by treatment. In rats, mean body weights of the 30 mg/kg groups were less than those of the vehicle controls after weeks 21 and 37 for males and females, respectively. No treatment-related effect on body weight was seen in mice. There were no neoplasms (in either species) or non-neoplastic lesions (mice only) that were attributed to methacrylonitrile administration. In rats, the incidences of olfactory epithelial atrophy and metaplasia of the nose were significantly greater in 30 mg

  6. 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.

  7. 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

  8. Carcinogenicity of Embedded Tungsten Alloys in Mice

    DTIC Science & Technology

    2007-03-01

    out a two-year protocol in mice based upon NTP guidelines. The uses the B6C3F1 hybrid mouse , a strain commonly used in carcinogenicity and toxicity...the same percentages present in the alloys). Aim 2: Sacrifice mice at various times after alloy implantation to detect early signs of tumor...Alloys in Mice PRINCIPAL INVESTIGATOR: David E. McClain, Ph.D. CONTRACTING ORGANIZATION: Henry M. Jackson Foundation for the

  9. 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.

  10. 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.

  11. Industry viewpoint on thresholds for genotoxic carcinogens.

    PubMed

    Morelli, M A

    2000-01-01

    Modern chemical control of pests has contributed to a dramatic improvement in public welfare since its introduction 50 years ago. Millions of lives have been saved through the control of disease vectors, and millions more have been improved by the use of chemicals to produce an inexpensive and abundant food supply. Hundreds of pesticidally active ingredients are in commercial use today, and among these are found genotoxic and nongenotoxic carcinogens. In the United States, the Environmental Protection Agency regulates carcinogens using threshold and nonthreshold approaches depending upon the outcome of a weight-of-evidence determination. More than one-half of all pesticides with some evidence of carcinogenic potential are regulated by the nonthreshold approach. The limitations on product use imposed by this approach have restricted the number of products available to growers and to the public. This restriction has had a direct impact on industry with respect to commercial success and financial returns on investment as well as an indirect impact on the industry's ability to fund the discovery and development of new compounds. This paper explores the question of how well regulation by the nonthreshold approach has achieved the goal of protecting public health, whether it does this better than the alternative use of the threshold approach, and whether the incremental protection it affords is a meaningful public benefit that justifies the aforementioned impacts on industry.

  12. Chief Student Affairs Officers in 2-Year Colleges: Their Demographics and Educational Backgrounds

    ERIC Educational Resources Information Center

    Keim, Marybelle C.

    2008-01-01

    The purpose of this study was to determine demographics and educational backgrounds of chief student affairs officers (CSAOs) in public 2-year colleges. Using systematic sampling techniques, 300 2-year colleges were selected from the AACC Membership Directory for inclusion in the study. Each college's website was visited to determine the name of…

  13. 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…

  14. 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

  15. Reevaluating the carcinogenicity of ortho-toluidine: a new conclusion and its implications.

    PubMed

    Sellers, C; Markowitz, S

    1992-12-01

    The aromatic amine ortho-toluidine has been recognized by IARC as an animal carcinogen for the past decade. Three recent epidemiological studies of worker populations have now implicated this chemical as a human bladder carcinogen. In a study by E. Ward, A. Carpenter, S. Markowitz, D. Roberts, and W. Halperin ((1991), J. Natl. Cancer Inst. 83, 501-506), workers definitely exposed to ortho-toluidine for at least 10 years experienced a Standardized Incidence Ratio (SIR) of 27.2 (90% CI = 11.8-53.7). The other major exposure was to aniline, which significant epidemiological studies have failed to confirm as a human carcinogen. In retrospect, studies by G. F. Rubino, G. Scansetti, G. Piolatto ((1982) Environ. Res. 27, 241-254) and M. J. Stasik ((1988) Int. Arch. Occup. Environ. Health 60, 21-24) also support the hypothesis that ortho-toluidine is a human bladder carcinogen. Animal studies of both ortho-toluidine and its possible confounders in these epidemiological investigations further confirm this hypothesis. When evaluated in a suitably comprehensive way, according to the traditional standards for assessing causality outlined by A. B. Hill ((1977) A Short Textbook of Medical Statistics, pp. 288-294, Lippincott, Philadelphia) the evidence that ortho-toluidine causes human bladder cancer has become much more conclusive. In this case, animal tests have proven a good predictor of human carcinogenicity.

  16. [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.

  17. 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.

  18. Complementarity of genotoxic and nongenotoxic predictors of rodent carcinogenicity.

    PubMed

    Kitchin, K T; Brown, J L; Kulkarni, A P

    1994-01-01

    Twenty-one chemicals carcinogenic in rodent bioassays were selected for study. The chemicals were administered by gavage in two dose levels to female Sprague-Dawley rats. The effects of these 21 chemicals on four biochemical assays [hepatic DNA damage by alkaline elution (DD), hepatic ornithine decarboxylase activity (ODC), serum alanine aminotransferase activity (ALT), and hepatic cytochrome P-450 content (P450)] were determined. Available data from seven cancer predictors published by others [the Ames test (AMES), mutation in Salmonella typhimurium TA 1537 (TA 1537), structural alerts (SA), mutation in mouse lymphoma cells (MOLY), chromosomal aberrations in Chinese hamster ovary cells (ABS), sister chromatid exchange in hamster ovary cells (SCE), and the ke test (ke)] were also compiled for these 21 chemical carcinogens plus 28 carcinogens and 62 noncarcinogens already published by our laboratory. From the resulting 111 (chemicals) by 11 (individual cancer predictors) data matrix, the five operational characteristics (sensitivity, specificity, positive predictivity, negative predictivity, and concordance) of each of the 11 individual cancer predictors (four biochemical parameters of this study and seven cancer predictors of others) are presented. Two examples of complementarity or synergy of composite cancer predictors were found. To obtain maximum concordance it was necessary to combine both genotoxic and nongenotoxic cancer predictors. The composite cancer predictor (DD or [ODC and P450] or [ODC and ALT]) had higher concordance than did any of the four individual cancer predictors from which it was constructed. Similarly, the composite cancer predictor (TA 1537 or DD or [ODC and P450] or [ODC and ALT]) had higher concordance than any of its five individual constituent cancer predictors. Complementarity or synergy has been demonstrated both 1) among genotoxic cancer predictors (DD and TA 1537) and 2) between nongenotoxic (ODC, P450, and ALT) and genotoxic cancer

  19. 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.

  20. Predictive models for carcinogenicity and mutagenicity: frameworks, state-of-the-art, and perspectives.

    PubMed

    Benfenati, E; Benigni, R; Demarini, D M; Helma, C; Kirkland, D; Martin, T M; Mazzatorta, P; Ouédraogo-Arras, G; Richard, A M; Schilter, B; Schoonen, W G E J; Snyder, R D; Yang, C

    2009-04-01

    Mutagenicity and carcinogenicity are endpoints of major environmental and regulatory concern. These endpoints are also important targets for development of alternative methods for screening and prediction due to the large number of chemicals of potential concern and the tremendous cost (in time, money, animals) of rodent carcinogenicity bioassays. Both mutagenicity and carcinogenicity involve complex, cellular processes that are only partially understood. Advances in technologies and generation of new data will permit a much deeper understanding. In silico methods for predicting mutagenicity and rodent carcinogenicity based on chemical structural features, along with current mutagenicity and carcinogenicity data sets, have performed well for local prediction (i.e., within specific chemical classes), but are less successful for global prediction (i.e., for a broad range of chemicals). The predictivity of in silico methods can be improved by improving the quality of the data base and endpoints used for modelling. In particular, in vitro assays for clastogenicity need to be improved to reduce false positives (relative to rodent carcinogenicity) and to detect compounds that do not interact directly with DNA or have epigenetic activities. New assays emerging to complement or replace some of the standard assays include Vitotox, GreenScreenGC, and RadarScreen. The needs of industry and regulators to assess thousands of compounds necessitate the development of high-throughput assays combined with innovative data-mining and in silico methods. Various initiatives in this regard have begun, including CAESAR, OSIRIS, CHEMOMENTUM, CHEMPREDICT, OpenTox, EPAA, and ToxCast. In silico methods can be used for priority setting, mechanistic studies, and to estimate potency. Ultimately, such efforts should lead to improvements in application of in silico methods for predicting carcinogenicity to assist industry and regulators and to enhance protection of public health.

  1. Development and validation of a robust QSAR model for prediction of carcinogenicity of drugs.

    PubMed

    Kar, Supratik; Roy, Kunal

    2011-04-01

    Carcinogenicity is one of the toxicological endpoints causing the highest concern. Also, the standard bioassays in rodents used to assess the carcinogenic potential of chemicals and drugs are extremely long, costly and require the sacrifice of large numbers of animals. For these reasons, we have attempted development of a global quantitative structure-activity relationship (QSAR) model using a data set of 1464 compounds (the Galvez data set available from http://www.uv.es/-galvez/tablevi.pdf), including many marketed drugs for their carcinogenesis potential. Though experimental toxicity testing using animal models is unavoidable for new drug candidates at an advanced stage of drug development, yet the developed global QSAR model can in silico predict the carcinogenicity of new drug compounds to provide a tool for initial screening of new drug candidate molecules with reduced number of animal testing, money and time. Considering large number of data points with diverse structural features used for model development (n(training) = 732) and model validation (n(test) = 732), the model developed in this study has an encouraging statistical quality (leave-one-out Q2 = 0.731, R2pred = 0.716). Our developed model suggests that higher lipophilicity values and conjugated ring systems, thioketo and nitro groups contribute positively towards drug carcinogenicity. On the contrary, tertiary and secondary nitrogens, phenolic, enolic and carboxylic OH fragments and presence of three-membered rings reduce the carcinogenicity. Branching, size and shape are found to be crucial factors for drug-induced carcinogenicity. One may consider all these points to reduce carcinogenic potential of the molecules.

  2. Carcinogenic HPV infection in the cervical squamo-columnar junction.

    PubMed

    Mirkovic, Jelena; Howitt, Brooke E; Roncarati, Patrick; Demoulin, Stephanie; Suarez-Carmona, Meggy; Hubert, Pascale; McKeon, Frank D; Xian, Wa; Li, Anita; Delvenne, Philippe; Crum, Christopher P; Herfs, Michael

    2015-07-01

    Recent studies have suggested the involvement of a unique population of cells at the cervical squamo-columnar junction (SCJ) in the pathogenesis of early (squamous intraepithelial lesion or SIL) and advanced (squamous cell and adeno-carcinomas) cervical neoplasia. However, there is little evidence to date showing that SCJ cells harbour carcinogenic HPV or are instrumental in the initial phases of neoplasia. This study was designed to (1) determine if normal-appearing SCJ cells contained evidence of carcinogenic HPV infection and (2) trace their transition to early SIL. Sections of cervix from high-risk reproductive age women were selected and SCJ cells were analysed by using several techniques which increasingly implicated HPV infection: HPV DNA (genotyping and in situ hybridization)/RNA (PCR), immunostaining for HPV16 E2 (an early marker of HPV infection), p16(ink4), Ki67, and HPV L1 protein. In 22 cases with a history of SIL and no evidence of preneoplastic lesion in the excision specimen, HPV DNA was isolated from eight of ten with visible SCJ cells, six of which were HPV16/18 DNA-positive. In five of these latter cases, the SCJ cells were positive for p16(ink4) and/or HPV E2. Transcriptionally active HPV infection (E6/E7 mRNAs) was also detected in microdissected SCJ cells. Early squamous atypia associated with the SCJ cells demonstrated in addition diffuse p16(ink4) immunoreactivity, elevated proliferative index, and rare L1 antigen positivity. We present for the first time direct evidence that normal-appearing SCJ cells can be infected by carcinogenic HPV. They initially express HPV E2 and their progression to SIL is heralded by an expanding metaplastic progeny with increased proliferation and p16(ink4) expression. Whether certain SCJs are more vulnerable than others to carcinogenic HPV genotypes and what variables determine transition to high-grade SIL remain unresolved, but the common event appears to be a vulnerable cell at the SCJ.

  3. 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.

  4. Voltammetric studies on the potent carcinogen, 7,12-dimethylbenz[a]anthracene: Adsorptive stripping voltammetric determination in bulk aqueous forms and human urine samples and detection of DNA interaction on pencil graphite electrode.

    PubMed

    Yardim, Y; Keskin, E; Levent, A; Ozsöz, M; Sentürk, Z

    2010-01-15

    7,12-Dimethylbenz[a]anthracene (DMBA), is a widely studied polycyclic aromatic hydrocarbon that has long been recognized as a very potent carcinogen. Initially, the electrochemical oxidation of DMBA at the glassy carbon and pencil graphite electrodes in non-aqueous media (dimethylsulphoxide with lithium perchlorate) was studied by cyclic voltammetry. DMBA was irreversibly oxidized in two steps at high positive potentials, resulting in the ill-resolved formation of a couple with a reduction and re-oxidation wave at much lower potentials. Special attention was given to the use of adsorptive stripping voltammetry together with a medium exchange procedure on disposable pencil graphite electrode in aqueous solutions over the pH range of 3.0-9.0. The response was characterized with respect to pH of the supporting electrolyte, pre-concentration time and accumulation potential. Using square-wave stripping mode, the compound yielded a well-defined voltammetric response in acetate buffer, pH 4.8 at +1.15V (vs. Ag/AgCl) (a pre-concentration step being carried out at a fixed potential of +0.60V for 360s). The process could be used to determine DMBA concentrations in the range 2-10nM, with an extremely low detection limit of 0.194nM (49.7ngL(-1)). The applicability to assay of spiked human urine samples was also illustrated. Finally, the interaction of DMBA with fish sperm double-stranded DNA based on decreasing of the oxidation signal of adenine base was studied electrochemically by using differential pulse voltammetry with a pencil graphite electrode at the surface and also in solution. The favorable signal-to-noise characteristics of biosensor resulted in low detection limit (ca. 46nM) following a 300-s interaction. These results displayed that the electrochemical DNA-based biosensor could be used for the sensitive, rapid, simple and cost effective detection of DMBA-DNA interaction.

  5. Reduced T cell response in carcinogen-sensitive Donryu rats compared with carcinogen-resistant DRH rats.

    PubMed

    Mise-Omata, S; Sugiura, T; Higashi, K; Yamashita, U

    1999-12-01

    Carcinogen-resistant DRH rats were developed from carcinogen-sensitive Donryu rats, which showed a high incidence of hepatic tumors when they were exposed to 3'-methyl-4-dimethyl-amino-azobenzene (3'-MeDAB4) or other aminoazo hepatocarcinogens. In order to study the mechanism of the difference of carcinogenesis, we studied the immunological competence of Donryu rats compared with that of DRH rats. Anti-keyhole limpet hemocyanin (KLH) antibody and KLH-specific delayed hypersensitivity (DTH) responses after immunization with KLH were reduced in Donryu rats compared with DRH rats. Proliferative responses of spleen cells to KLH and nonspecific mitogens such as conconavalin A (Con A) and phytohemagglutinin (PHA) were significantly lower in Donryu rats than in DRH rats. Upon the cross-linking of T cell receptor (TCR) complex using anti-CD3 monoclonal antibody (Mab), spleen cells from Donryu rats proliferated poorly. Two other strains of rats, SD and Wistar, exhibited high responsiveness, comparable to that of DRH rats, indicating that the responsiveness of Donryu rats was impaired. The production of interleukin-2 (IL-2) upon stimulation with Con A and the responsiveness of Con A blasts to exogenous IL-2 were also attenuated in Donryu rats. In contrast to T cell responsiveness, natural killer (NK) cell activity of spleen was increased in Donryu rats. Flow cytometric analysis revealed that the expression of CD4 and CD8 on T cells was decreased in Donryu rats, though the expression of other T cell markers such as CD2, CD3 and CD5 was not different. These results indicate that Donryu rats, which have been used in many years for cancer research in Japan, have impaired immunological surveillance mechanisms. This is likely to be one of the factors accounting for the high sensitivity to chemical carcinogens and the high susceptibility to transplanted tumor cells of Donryu rats.

  6. Langerhans cell histiocytosis in children under 2 years of age.

    PubMed

    Rivera-Luna, R; Alter-Molchadsky, N; Cardenas-Cardos, R; Martínez-Guerra, G

    1996-05-01

    This is a retrospective study of 55 children under the age of 2 years diagnosed with Langerhans cell histiocytosis (LCH). They were classified according to age and organ function and dysfunction following Lahey's criteria. The studied population was divided into four groups by age of diagnosis (0-6, 7-12, 13-18, and 19-24 months). Statistical analysis showed no significant difference in outcome between age groups, although the population under 6 months had a 81.3% fatality rate. The presence of organ dysfunction was a major cause of death in all age groups, being statistically significant in outcome (P > 0.005) compared with patients without organ dysfunction. The presence of thrombocytopenia and/or respiratory dysfunction was also highly associated with a fatal outcome. In the surviving population, no second malignancies have been reported. The late secondary effects of therapy include endocrine, orofacial, and osseous pathologies.

  7. A review of evidence leading to the prediction that 1,4-butanediol is not a carcinogen.

    PubMed

    Irwin, Richard D

    2006-01-01

    of pheochromocytomas of the adrenal medulla. Because the absence of chronic toxicity and significant carcinogenicity of gamma-hydroxybutyric acid were established in NTP prechronic and chronic studies with gamma-butyrolactone, it is concluded that similar results would be obtained in a 2-year study with 1,4-butanediol, and that 1,4-butanediol is not a carcinogen.

  8. The carcinogenicity of the biocide ortho-phenylphenol.

    PubMed

    Appel, K E

    2000-04-01

    The biocides ortho-phenylphenol and its sodium salt (OPP and SOPP) are widely used as fungicides and antibacterial agents for commercial and consumer purposes. The carcinogenicity of OPP/SOPP toward the urinary bladder was demonstrated when rats were chronically fed concentrations of 0.5%-4% in their diet. Other species tested so far did not develop tumours. Understanding the mechanisms underlying OPP/SOPP-induced bladder carcinogenesis is critical to determine whether risks observed at high doses in rats are of relevance to humans exposed at much lower levels. This overview details experimental studies of carcinogenicity, genotoxicity as well as metabolism/toxicokinetics and other mechanistic studies which bear on cancer hazard and risk evaluation of exposure to humans. Based on the presently available knowledge, it is concluded that reactive quinoid metabolites exhibiting redox cycling activities are the crucial factors. At certain concentration levels, these metabolites are able to produce cytotoxic events with concomitant enhanced cell proliferation of the target tissue. Further important risk factors are probably promutagenic lesions induced by oxidative stress and a higher urinary pH. Supposed that these mechanisms are the basis for the tumourigenicity observed, then suitable low doses of OPP/SOPP will practically pose no cancer risk.

  9. Important aspects of the evidence for TCDD carcinogenicity in man.

    PubMed Central

    Johnson, E S

    1993-01-01

    Most of the evidence for the carcinogenicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in humans has centered on whether TCDD causes soft-tissue sarcomas (STS) and malignant lymphomas (ML). Recently, reports from two of the largest occupational cohort studies have become available. A critical reappraisal of these and other recent reports indicates that it is unlikely that TCDD causes malignant lymphomas in humans. For STS, the evidence for an etiologic role for TCDD is not convincing. However, more data and further clarification are needed before a clear and objective evaluation can be made. Factors such as level of exposure, sex, and host susceptibility may be critical determinants of whether cancer occurs; there is evidence from both humans and animals that these factors play a role, and therefore these factors should be considered in future evaluations. There is a serious need to rule out the possibility that observed effects are due to other concomitant exposures. Consideration of the carcinogenic effects of TCDD in animals reveals consistency with the human data and points to other cancers such as those of the thyroid gland and lung, for example, which are more likely candidates for investigating the role of TCDD in their occurrence, while at the same time providing a basis for a better understanding and interpretation of the human data. There are now sufficient epidemiologic studies in place that will provide a better climate for a definitive evaluation in the near future. PMID:8319655

  10. Comparative pulmonary carcinogenicity of inhaled beryllium A/J and C3H/HeJ mice

    SciTech Connect

    Nikula, K.J.; Belinsky, S.A.; Hoover, M.D.; Finch, G.L.

    1994-11-01

    The purpose of these investigations was to compare the pulomonary carcinogenicity of beryllium (Be) metal in A/J and C3H/HeJ mice, strains which are sensitive and resistant, respectively, to pulmonary neoplasia. Lesions in these mice will be used to study the molecular mechanisms of Be-induced carcinogenesis. Be, a metal that is generally negative in short-term genotoxicity assays, is a potent pulmonary carcinogen in F344/N rats. Although the epidemiological evidence is weak, Be is classified as a suspect human carcinogen.

  11. Small difference in carcinogenic potency between GBP nanomaterials and GBP micromaterials.

    PubMed

    Gebel, Thomas

    2012-07-01

    Materials that can be described as respirable granular biodurable particles without known significant specific toxicity (GBP) show a common mode of toxicological action that is characterized by inflammation and carcinogenicity in chronic inhalation studies in the rat. This study was carried out to compare the carcinogenic potency of GBP nanomaterials (primary particle diameter 1-100 nm) to GBP micromaterials (primary particle diameter >100 nm) in a pooled approach. For this purpose, the positive GBP rat inhalation carcinogenicity studies have been evaluated. Inhalation studies on diesel engine emissions have also been included due to the fact that the mode of carcinogenic action is assumed to be the same. As it is currently not clear which dose metrics may best explain carcinogenic potency, different metrics have been considered. Cumulative exposure concentrations related to mass, surface area, and primary particle volume have been included as well as cumulative lung burden metrics related to mass, surface area, and primary particle volume. In total, 36 comparisons have been conducted. Including all dose metrics, GBP nanomaterials were 1.33- to 1.69-fold (mean values) and 1.88- to 3.54-fold (median values) more potent with respect to carcinogenicity than GBP micromaterials, respectively. Nine of these 36 comparisons showed statistical significance (p < 0.05, U test), all of which related to dose metrics based on particle mass. The maximum comparative potency factor obtained for one of these 9 dose metric comparisons based on particle mass was 4.71. The studies with diesel engine emissions did not have a major impact on the potency comparison. The average duration of the carcinogenicity studies with GBP nanomaterials was 4 months longer (median values 30 vs. 26 months) than the studies with GBP micromaterials, respectively. Tumor rates increase with age and lung tumors in the rat induced by GBP materials are known to appear late, that is, mainly after study

  12. 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.

  13. No-observed effect levels for carcinogenicity and for in vivo mutagenicity of a genotoxic carcinogen.

    PubMed

    Hoshi, Manabu; Morimura, Keiichirou; Wanibuchi, Hideki; Wei, Min; Okochi, Eriko; Ushijima, Toshikazu; Takaoka, Kunio; Fukushima, Shoji

    2004-10-01

    To elucidate the relationship between in vivo carcinogenic and mutagenic potentials of genotoxic carcinogens, low doses were tested in the livers of Big Blue transgenic rats with 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx). Male Big Blue rats were fed a diet containing 0.001, 0.01, 0.1, 1, 10, or 100 ppm of MeIQx for 16 weeks, and the frequencies of lacI mutants and glutathione S-transferase placental form (GST-P) positive foci in the liver were determined. The mutation frequencies significantly increased at doses of 10 and 100 ppm, and GST-P positive foci significantly increased at a dose of 100 ppm. However, no statistical increases in both frequencies were observed at lower doses. MeIQx most frequently induced G frameshifts, followed by G to T transversions. Thus, no observed effect level (NOEL) was demonstrated for both carcinogenicity in terms of preneoplastic lesion induction and in vivo mutagenicity of MeIQx, and the NOEL for in vivo mutagenicity was lower than that for carcinogenicity.

  14. Toxicity and carcinogenicity of potassium bromate--a new renal carcinogen

    SciTech Connect

    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.111 references.

  15. Medical Care and Your 1- to 2-Year-Old

    MedlinePlus

    ... Year-Old Medical Care and Your 1- to 2-Year-Old KidsHealth > For Parents > Medical Care and Your 1- to 2-Year-Old A A A The toddler months ... Following simple instructions? Saying a few words? Combining two words by age 2? The doctor may ask ...

  16. Neonates with extra-renal pelvis: the first 2 years.

    PubMed

    Katzir, Ze'ev; Witzling, Michaela; Nikolov, Gallina; Gvirtz, Gabriela; Arbel, Eliana; Kohelet, David; Boaz, Mona; Smetana, Shmuel; Lorberboym, Mordechai

    2005-06-01

    Extra-renal pelvis (ERpel) is a common ultrasonographic finding among neonates who have undergone recurrent ultrasound examinations for a better definition of prenatal renal pelvic dilatation. This study tries to determine whether or not ERpel has important prognostic implications. Seventy-nine neonates (17 female) were examined. All had a diagnosis of prenatal renal pelvis dilatation, which was shown by postnatal ultrasound to be ERpel. Sixty ERpel neonates were examined 1.5 months to 2.5 months after the ultrasound (US) diagnosis by both Tc-99m diethylene triamine penta-acetic acid (DPTA) dynamic renal scanning and (99m)Tc-pertechnetate direct cystography. Clinical assessment, urine cultures and renal ultrasound follow-up were maintained for 2 years. The proportion of urinary tract infections (UTIs) in patients with ERpel was compared with that of the total neonatal and infantile population with normal US scans in the region of our hospital. Associated minor congenital malformations were found in 12 of 79 neonates (15.2%). Four had a family history of ERpel. Among 60 neonates who underwent renal scanning, 36 (60%) were found to have urinary retention in the collecting system. Another nine (15%) had vesico-ureteral (VU) reflux, of which seven had urinary retention. Fifteen (25%) showed normal isotope imaging. Urinary tract infection was diagnosed in 16 ERpel neonates in whom only one exhibited VU reflux (grade 2). The incidence of neonatal UTI in the ERpel group was more than that of either neonatal or infantile UTI in those with normal US scans in the local population (20.2% vs 1.2% and 4.3%, respectively). Fifty-three infants completed a 2-year follow-up. Repeat renal ultrasonography indicated that one infant (1.8%) had developed bilateral hydronephrosis, 12 (22.6%) had unchanged findings, 18 (40%) showed an improvement (decrease of ERpel width or resolution in one side) and, in 22 (41.5%) infants, the condition had resolved. No clinical or kidney function

  17. Multiple organ carcinogenicity of inhaled chloroprene (2-chloro-1,3-butadiene) in F344/N rats and B6C3F1 mice and comparison of dose-response with 1,3-butadiene in mice.

    PubMed

    Melnick, R L; Sills, R C; Portier, C J; Roycroft, J H; Chou, B J; Grumbein, S L; Miller, R A

    1999-05-01

    Chloroprene (2-chloro-1,3-butadiene) is a high production chemical used almost exclusively in the production of polychloroprene (neoprene) elastomer. Because of its structural similarity to 1,3-butadiene, a trans-species carcinogen, inhalation studies were performed with chloroprene to evaluate its carcinogenic potential in rats and mice. Groups of 50 male and female F344/N rats and 50 male and female B6C3F1 mice were exposed to 0, 12.8, 32 or 80 p.p.m. chloroprene (6 h/day, 5 days/week) for 2 years. Under these conditions, chloroprene was carcinogenic to the oral cavity, thyroid gland, lung, kidney and mammary gland of rats, and to the lung, circulatory system (hemangiomas and hemangiosarcomas), Harderian gland, kidney, forestomach, liver, mammary gland, skin, mesentery and Zymbal's gland of mice. Survival adjusted tumor rates in mice were fit to a Weibull model for estimation of the shape of the dose-response curves, estimation of ED10 values (the estimated exposure concentration associated with an increased cancer risk of 10%) and comparison of these parameters with those for 1,3-butadiene. Butadiene has been identified as a potent carcinogen in mice and has been associated with increased risk of lymphatic and hematopoietic cancer in exposed workers. Shape parameter values for most of the neoplastic effects of chloroprene and 1,3-butadiene were consistent with linear or supralinear responses in the area near the lowest tested exposures. The most potent carcinogenic effect of 1,3-butadiene was the induction of lung neoplasms in female mice, which had an ED10 value of 0.3 p.p.m. Since the ED10 value for that same response in chloroprene exposed mice was also 0.3 p.p.m., we conclude that the carcinogenic potency of chloroprene in mice is similar to that of 1,3-butadiene. Cancer potency of chloroprene is greater in the mouse lung than in the rat lung, but greater in the rat kidney than in the mouse kidney and nearly equivalent in the mammary gland of each species.