Science.gov

Sample records for 90-day subchronic toxicity

  1. SUBCHRONIC 90-DAY TOXICITY OF DICHLOROACETIC AND TRICHLORACETIC ACID IN RATS

    EPA Science Inventory

    Male Sprague-Dawley rats were treated with either dichloroacetic acid (DCA) or trichloroacetic acid (TCA) in the drinking water at levels of 0, 50, 500 and 5000 ppm for a period of 90 days to determine the toxicities associated with subchronic exposure. ll animals were sacrificed...

  2. A 90-day subchronic toxicity study of neem oil, a Azadirachta indica oil, in mice.

    PubMed

    Wang, C; Cao, M; Shi, D-X; Yin, Z-Q; Jia, R-Y; Wang, K-Y; Geng, Y; Wang, Y; Yao, X-P; Yang, Z-R; Zhao, J

    2013-09-01

    To determine the no-observed-adverse-effect level (NOAEL) of exposure and target organs of neem oil for establishing safety criteria for human exposure, the subchronic toxicity study with neem oil in mice was evaluated. The mice (10 per sex for each dose) was orally administered with neem oil with the doses of 0 (to serve as a control), 177, 533 and 1600 mg/kg/day for 90 days. After the treatment period, observation of reversibility or persistence of any toxic effects, mice were continuously fed without treatment for the following 30 days. During the two test periods, the serum biochemistry, organ weight and histopathology were examined. The results showed that the serum biochemistry and organ coefficient in experimental groups had no statistical difference compared with those of the control group. At the 90th day, the histopathological examinations showed that the 1600 mg/kg/day dose of neem oil had varying degrees of damage on each organ except heart, uterus and ovarian. After 30-day recovery, the degree of lesions to the tissues was lessened or even restored. The NOAEL of neem oil was 177 mg/kg/day for mice and the target organs of neem oil were determined to be testicle, liver and kidneys. PMID:23444337

  3. 90-Day subchronic toxicity study of sodium molybdate dihydrate in rats.

    PubMed

    Murray, F Jay; Sullivan, Frank M; Tiwary, Asheesh K; Carey, Sandra

    2014-12-01

    This study investigated the subchronic toxicity of molybdenum (Mo) in Sprague-Dawley rats given sodium molybdate dihydrate in the diet for 90days at dose levels of 0, 5, 17 or 60mgMo/kgbw/day. The study complied with OECD Test Guideline (TG) 408, with additional examination of estrus cycles and sperm count, motility, and morphology from OECD TG 416. The overall no-observed-adverse-effect level was 17mgMo/kgbw/day, based on effects on body weight, body weight gain, food conversion efficiency and renal histopathology (females only) at 60mgMo/kgbw/day. No treatment-related adverse effects on reproductive organ weights or histopathology, estrus cycles or sperm parameters were observed at any dose level. No adverse effects were observed in the high dose animals after the 60-day recovery period, with the exception that male rats did not fully recover from reduced body weight. Serum blood, liver and kidney samples were analyzed for molybdenum, copper, zinc, manganese, iron, cobalt and selenium; high levels of molybdenum and copper were found in the serum, blood, liver and kidneys of rats treated with 60mgMo/kgbw/day. In conclusion, the LOAEL and NOAEL for molybdenum were determined to be 60 and 17mgMo/kgbw/day, respectively. PMID:24041747

  4. A 90-day subchronic toxicity study and reproductive toxicity studies on ACE-inhibiting lactotripeptide.

    PubMed

    Dent, M P; O'Hagan, S; Braun, W H; Schaetti, P; Marburger, A; Vogel, O

    2007-08-01

    In recent years there has been an increasing body of literature describing the antihypertensive effects of peptides produced from milk protein. The tripeptides isoleucine-proline-proline (IPP) and valine-proline-proline (VPP), isolated from hydrolysed casein have been shown to lower blood pressure by inhibiting angiotensin I-converting enzyme (ACE). This has led to the use of these tripeptides, collectively referred to as lactotripeptide (LTP) as ingredients of functional foods intended to help control blood pressure. A programme of studies including a 90-day repeat-dose oral gavage toxicity study in the rat and an embryo-fetal (pre-natal) development study in the rabbit was conducted to ensure the safety of this ACE-inhibiting ingredient. In addition, a non-standard pre- and post-natal development study in the rat was performed. This study included direct dosing of the neonates, and was designed specifically to investigate renal development and to ensure that the bioactive peptides were not associated with the same type of fetopathy exhibited by ACE inhibiting drugs. These studies showed that there were no adverse effects of treatment at the highest doses tested. PMID:17383063

  5. A 90-Day Subchronic Toxicity Study of Submerged Mycelial Culture of Cordyceps cicadae (Ascomycetes) in Rats.

    PubMed

    Chen, Yen-Lien; Yeh, Shu-Hsing; Lin, Ting-Wei; Chen, Chin-Chu; Chen, Chin-Shuh; Kuo, Chia-Feng

    2015-01-01

    Cordyceps cicadae is a parasitic fungus that hibernates inside a host (Cicada flammata Dist.) and then grows its fruiting body on the surface of the insect. The complete insect/fungus combination of C. cicadae has been widely applied in Chinese traditional medicine. Recent studies have demonstrated that the medicinal benefits of cultured mycelia are as effective as those found in the wild. However, toxicological information regarding the chronic consumption of C. cicadae mycelia culture is not available. This study was conducted to evaluate the possible toxicity arising from repeated exposure to freeze-dried submerged mycelial culture of C. cicadae for 90 days. A total of eighty 8-week-old Sprague-Dawley rats were divided into 4 groups (10 males and 10 females in each group). C. cicadae was administered daily to animals by gavage at doses of 0, 500, 1000, and 2000 mg/kg body weight for 90 days. No animal deaths occurred and no treatment-related clinical signs were observed during the study period. No statistical differences in body weight gain, relative organ weight, hematology, serum chemistry, and urinalysis were observed. Gross necropsy and histopathological findings indicated that there was no treatment-related abnormality. Based on the results, the no observed adverse effect level of C. cicadae whole broth is determined to be > 2000 mg/kg for male and female Sprague-Dawley rats. The results of this study provides support for the use of C. cicadae fermentation product as a safe agent in functional food. PMID:26559863

  6. Safety assessment of essential oil from Minthostachys verticillata (Griseb.) Epling (peperina): 90-days oral subchronic toxicity study in rats.

    PubMed

    Escobar, Franco Matías; Sabini, María Carola; Cariddi, Laura Noelia; Sabini, Liliana Inés; Mañas, Fernando; Cristofolini, Andrea; Bagnis, Guillermo; Gallucci, Mauro Nicolas; Cavaglieri, Lilia Renée

    2015-02-01

    Minthostachys verticillata (Lamiaceae), popularly known as peperina is largely used in popular medicine for its digestive, carminative, antispasmodic and antirheumatic properties. There are no reports of repeated exposure toxicity to guarantee their safety. The present study investigated the chemical composition, analyzed by GC-FID, and the 90-day toxicity and genotoxicity effect of M. verticillata essential oil (Mv-EO), using Wistar rats as test animals. The rats were divided into four groups (5 rats/sex/group) and Mv-EO was administered on diet at doses of 0, 1, 4 and 7 g/kg feed. The main components of Mv-EO were pulegone (64.65%) and menthone (23.92%). There was no mortality, adverse effects on general conditions or changes in body weight, food consumption and feed conversion efficiency throughout the study in male and female rats. Subchronic administration of Mv-EO did not alter the weights, morphological and histopathological analyses of liver, kidney and intestine. Genotoxicity was tested by micronucleus and comet assays. Mv-EO up to a concentration of 7 g/kg feed for 90 days did not exert a cyto-genotoxic effect on the bone marrow and cells blood of Wistar rats. These results suggest that Mv-EO appears to be safe and could be devoid of any toxic risk. PMID:25445298

  7. ACUTE, 14-DAY REPEATED DOSING, AND 90-DAY SUBCHRONIC TOXICITY STUDIES OF POTASSIUM PICLORAM (JOURNAL VERSION)

    EPA Science Inventory

    Potassium picloram was administered either by gavage (acute studies) or in drinking water to male and female Sprague-Dawley derived rats (14-day and 90-day studies). The acute oral LD50 was 950 mg/kg (812-1120) for males and 686 mg/kg (599-786) for females. Depression, prostratio...

  8. Subchronic 90-day oral (Gavage) toxicity study of a Luo Han Guo mogroside extract in dogs.

    PubMed

    Qin, X; Xiaojian, S; Ronggan, L; Yuxian, W; Zhunian, T; Shouji, G; Heimbach, J

    2006-12-01

    A combined 28-day and 90-day oral (Gavage) study was conducted in male and female dogs to investigate the safety of PureLo, a non-caloric sweetener derived from the Chinese fruit Luo Han Guo, which achieves its sweetness from the presence of triterpene glycosides known as mogrosides. Three dogs of each sex were administered 10 mL/kg bw/day of either an aqueous solution providing 3000 mg/kg bw/day of PureLo or distilled water for either 28 days or 90 days. Measurements included clinical observations, body weight, food consumption, hematology, blood chemistry, urinalysis, gross necropsy, organ weight, and histopathology. There were no significant adverse effects on any of these measures. Based on the lack of toxicological effects in the study, the NOAEL for PureLo is 3000 mg/kg bw/day when administered to dogs by Gavage for 90 consecutive days. PMID:17011100

  9. A 90-day study of subchronic oral toxicity of 20 nm, negatively charged zinc oxide nanoparticles in Sprague Dawley rats

    PubMed Central

    Park, Hark-Soo; Shin, Sung-Sup; Meang, Eun Ho; Hong, Jeong-sup; Park, Jong-Il; Kim, Su-Hyon; Koh, Sang-Bum; Lee, Seung-Young; Jang, Dong-Hyouk; Lee, Jong-Yun; Sun, Yle-Shik; Kang, Jin Seok; Kim, Yu-Ri; Kim, Meyoung-Kon; Jeong, Jayoung; Lee, Jong-Kwon; Son, Woo-Chan; Park, Jae-Hak

    2014-01-01

    Purpose The widespread use of nanoparticles (NPs) in industrial and biomedical applications has prompted growing concern regarding their potential toxicity and impact on human health. This study therefore investigated the subchronic, systemic oral toxicity and no-observed-adverse-effect level (NOAEL) of 20 nm, negatively charged zinc oxide (ZnOSM20(−)) NPs in Sprague Dawley rats for 90 days. Methods The high-dose NP level was set at 500 mg/kg of bodyweight, and the mid- and low-dose levels were set at 250 and 125 mg/kg, respectively. The rats were observed during a 14-day recovery period after the last NP administration for the persistence or reduction of any adverse effects. Toxicokinetic and distribution studies were also conducted to determine the systemic distribution of the NPs. Results No rats died during the test period. However, ZnOSM20(−) NPs (500 mg/kg) induced changes in the levels of anemia-related factors, prompted acinar cell apoptosis and ductular hyperplasia, stimulated periductular lymphoid cell infiltration and excessive salivation, and increased the numbers of regenerative acinar cells in the pancreas. In addition, stomach lesions were seen at 125, 250, and 500 mg/kg, and retinal atrophy was observed at 250 and 500 mg/kg. The Zn concentration was dose-dependently increased in the liver, kidney, intestines, and plasma, but not in other organs investigated. Conclusion A ZnOSM20(−) NP NOAEL could not be established from the current results, but the lowest-observed-adverse-effect level was 125 mg/kg. Furthermore, the NPs were associated with a number of undesirable systemic actions. Thus, their use in humans must be approached with caution. PMID:25565828

  10. A 90-day subchronic toxicity study with sodium formononetin-3'-sulphonate (Sul-F) delivered to dogs via intravenous administration.

    PubMed

    Li, Chunmei; Li, Guisheng; Gao, Yonglin; Sun, Chengfeng; Wang, Xiaoyan

    2016-06-01

    Sodium formononetin-3'-sulphonate (Sul-F) is a water-soluble derivate of formononetin, and an increasing number of studies have shown that Sul-F not only possesses favorable water solubility but also exhibits good lipid-lowering and bioactivities. In the current study, the toxicity of Sul-F was evaluated in dogs after 90-day intravenous infusion. Dogs were treated with Sul-F at dose of 0, 33.3, 100, and 300 mg/kg, and observed for 90-day followed by 28-day recovery period. Weekly measurement of body weight, temperature and food consumption were conducted. Ophthalmoscopy, ECG examination, urinalysis, serum biochemistry and hematology examination were performed at pre-test, on days 45 and 90, and following by 28-day recovery period. Histological examination was performed on day 90 and 28-day recovery period. No mortality, ophthalmic abnormalities or treatment-related findings in body weight, clinical chemistry, hematology, and histopathological examination were detected. However, a white crystal (non-metabolic Sul-F), transient vomiting and recoverable vascular stimulation were observed in 300 mg/kg/day Sul-F treated dogs. Under the conditions, the no-observed-adverse-effect-level (NOAEL) for Sul-F was 100 mg/kg in dogs. PMID:26924788

  11. Toxicity studies on agent GA (Phase 2): 90 day subchronic study of GA (Tabun) in cd rats. Appendices. Final report, July 1985-August 1991

    SciTech Connect

    Not Available

    1992-03-01

    The purpose of the report is to provide essential toxicologic information on Tabun administration over a 90 day period. This toxicologic information may be used to adjust the maximum-tolerated dose for subsequent dominant-lethal and two-generation reproduction studies. The objectives were to determine the toxic effects of nerve agent exposure (e.g., target organs); and to determine the effects of nerve agent GA on sperm morphology and motility and vaginal cytology.

  12. A 90-day study of sub-chronic oral toxicity of 20 nm positively charged zinc oxide nanoparticles in Sprague Dawley rats

    PubMed Central

    Park, Hark-Soo; Kim, Seon-Ju; Lee, Taek-Jin; Kim, Geon-Yong; Meang, EunHo; Hong, Jeong-Sup; Kim, Su-Hyon; Koh, Sang-Bum; Hong, Seung-Guk; Sun, Yle-Shik; Kang, Jin Seok; Kim, Yu-Ri; Kim, Meyoung-Kon; Jeong, Jayoung; Lee, Jong-Kwon; Son, Woo-Chan; Park, Jae-Hak

    2014-01-01

    Purpose The study reported here was conducted to determine the systemic oral toxicity and to find the no-observed-adverse-effect level of 20 nm positively charged zinc oxide (ZnOSM20(+)) nanoparticles in Sprague Dawley rats for 90 days. Methods For the 90-day toxicity study, the high dose was set as 500 mg per kg of body weight (mg/kg) and the middle and low dose were set to 250 mg/kg and 125 mg/kg, respectively. The rats were held for a 14-day recovery period after the last administration, to observe for the persistence or reduction of any toxic effects. A distributional study was also carried out for the systemic distribution of ZnOSM20(+) NPs. Results No rats died during the test period. There were no significant clinical changes due to the test article during the experimental period in functional assessment, body weight, food and water consumption, ophthalmological testing, urine analysis, necropsy findings, or organ weights, but salivation was observed immediately after administration in both sexes. The total red blood cell count was increased, and hematocrit, albumin, mean cell volume, mean cell hemoglobin, and mean cell hemoglobin concentration were decreased significantly compared with control in both 500 mg/kg groups. Total protein and albumin levels were decreased significantly in both sexes in the 250 and 500 mg/kg groups. Histopathological studies revealed acinar cell apoptosis in the pancreas, inflammation and edema in stomach mucosa, and retinal atrophy of the eye in the 500 mg/kg group. Conclusion There were significant parameter changes in terms of anemia in the hematological and blood chemical analyses in the 250 and 500 mg/kg groups. The significant toxic change was observed to be below 125 mg/kg, so the no-observed-adverse-effect level was not determined, but the lowest-observed-adverse-effect level was considered to be 125 mg/kg in both sexes and the target organs were found to be the pancreas, eye, and stomach. PMID:25565829

  13. 40 CFR 799.9346 - TSCA 90-day inhalation toxicity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 33 2013-07-01 2013-07-01 false TSCA 90-day inhalation toxicity. 799.9346 Section 799.9346 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) IDENTIFICATION OF SPECIFIC CHEMICAL SUBSTANCE AND MIXTURE TESTING REQUIREMENTS Health Effects Test Guidelines...

  14. The 90-day oral toxicity of d-psicose in male Wistar rats

    PubMed Central

    Matsuo, Tatsuhiro; Ishii, Reika; Shirai, Yoko

    2012-01-01

    d-Psicose is a rare sugar present in small quantities in natural products. In a previous study, we showed that d-psicose suppresses increase in plasma glucose and reduces body fat accumulation in rats. Based on acute toxicity testing in rats, d-psicose is classified as an ordinary substance (LD50 = 16 g/kg). Elucidating the effects of sub-chronic feeding of d-psicose in rats is essential before it can be utilized as a physiologically functional food. In this study, male Wistar rats (3 weeks old) were fed diets containing 3% d-psicose or sucrose for 90 days. The body weight gain and intra-abdominal adipose tissue weight did not differ between the sucrose and the d-psicose groups. The weights of the liver and kidneys were significantly higher in the d-psicose group than in the sucrose group. However, no gross pathological findings were evident at dietary doses of 3% d-psicose or were correlated with hypertrophy of the liver and kidney. In a clinical chemistry analysis, the erythrocyte and leukocyte courts were significantly higher in the d-psicose group, but that was not considered to be toxicologically significant. Therefore, the present study found no adverse effects of d-psicose in rats fed a diet containing 3% d-psicosefor 90 days. PMID:22448098

  15. 90-Day toxicity study of dichloroacetate in dogs.

    PubMed

    Cicmanec, J L; Condie, L W; Olson, G R; Wang, S R

    1991-08-01

    Male and female juvenile beagle dogs were dosed daily for 90 days with dichloroacetate (DCA). The compound was administered orally via gelatin capsules at doses of 0, 12.5, 39.5, and 72 mg/kg/day. Each dose group consisted of five males and five females. The dogs were observed clinically and blood samples were taken at 15-day intervals for hematologic and serum chemistry values. Decreased total erythrocyte count and hemoglobin levels were observed in mid- and high-dose dogs beginning at Day 30. Serum concentrations of LDH were elevated at Days 30 and 45 in females and at Day 75 in males treated with DCA at 72 mg/kg/day. One female of the high-dose group died at Day 50 and two high-dose males died at Days 51 and 74. Hindlimb partial paralysis was observed in many high-dose dogs. Vacuolization of myelinated white tracts of cerebrum, cerebellum, and/or spinal cord was observed in many high-dose dogs as well as some mid- and low-dose subjects. Degeneration of testicular germinal epithelium and syncytial giant cell formation was noted in males of all dose groups. Hepatic vacuolar change and chronic hepatitis appeared only in DCA-treated dogs. In addition, suppurative bronchopneumonia and chronic pancreatitis were noted in many high-dose and some middose subjects. A "no-adverse-effect level" was not determined in this study. PMID:1765225

  16. Zinc oxide nanoparticles: a 90-day repeated-dose dermal toxicity study in rats

    PubMed Central

    Ryu, Hwa Jung; Seo, Mu Yeb; Jung, Sung Kyu; Maeng, Eun Ho; Lee, Seung-Young; Jang, Dong-Hyouk; Lee, Taek-Jin; Jo, Ki-Yeon; Kim, Yu-Ri; Cho, Kyu-Bong; Kim, Meyoung-Kon; Lee, Beom Jun; Son, Sang Wook

    2014-01-01

    Zinc oxide (ZnO) works as a long-lasting, broad-spectrum physical sunblock, and can prevent skin cancer, sunburn, and photoaging. Nanosized ZnO particles are used often in sunscreens due to consumer preference over larger sizes, which appear opaque when dermally applied. Although the US Food and Drug Administration approved the use of nanoparticles (NPs) in sunscreens in 1999, there are ongoing safety concerns. The aim of this study was to evaluate the subchronic toxicity of ZnO NPs after dermal application according to the Organization for Economic Cooperation and Development Test Guidelines 411 using Good Laboratory Practice. Sprague Dawley rats were randomly divided into eight (one control, one vehicle control, three experimental, and three recovery) groups. Different concentrations of ZnO NPs were dermally applied to the rats in the experimental groups for 90 days. Clinical observations as well as weight and food consumption were measured and recorded daily. Hematology and biochemistry parameters were determined. Gross pathologic and histopathologic examinations were performed on selected tissues from all animals. Analyses of tissue were undertaken to determine target organ tissue distribution. There was no increased mortality in the experimental group. Although there was dose-dependent irritation at the site of application, there were no abnormal findings related to ZnO NPs in other organs. Increased concentrations of ZnO in the liver, small intestine, large intestine, and feces were thought to result from oral ingestion of ZnO NPs via licking. Penetration of ZnO NPs through the skin seemed to be limited via the dermal route. This study demonstrates that there was no observed adverse effect of ZnO NPs up to 1,000 mg/kg body weight when they are applied dermally. PMID:25565832

  17. Zinc oxide nanoparticles: a 90-day repeated-dose dermal toxicity study in rats.

    PubMed

    Ryu, Hwa Jung; Seo, Mu Yeb; Jung, Sung Kyu; Maeng, Eun Ho; Lee, Seung-Young; Jang, Dong-Hyouk; Lee, Taek-Jin; Jo, Ki-Yeon; Kim, Yu-Ri; Cho, Kyu-Bong; Kim, Meyoung-Kon; Lee, Beom Jun; Son, Sang Wook

    2014-01-01

    Zinc oxide (ZnO) works as a long-lasting, broad-spectrum physical sunblock, and can prevent skin cancer, sunburn, and photoaging. Nanosized ZnO particles are used often in sunscreens due to consumer preference over larger sizes, which appear opaque when dermally applied. Although the US Food and Drug Administration approved the use of nanoparticles (NPs) in sunscreens in 1999, there are ongoing safety concerns. The aim of this study was to evaluate the subchronic toxicity of ZnO NPs after dermal application according to the Organization for Economic Cooperation and Development Test Guidelines 411 using Good Laboratory Practice. Sprague Dawley rats were randomly divided into eight (one control, one vehicle control, three experimental, and three recovery) groups. Different concentrations of ZnO NPs were dermally applied to the rats in the experimental groups for 90 days. Clinical observations as well as weight and food consumption were measured and recorded daily. Hematology and biochemistry parameters were determined. Gross pathologic and histopathologic examinations were performed on selected tissues from all animals. Analyses of tissue were undertaken to determine target organ tissue distribution. There was no increased mortality in the experimental group. Although there was dose-dependent irritation at the site of application, there were no abnormal findings related to ZnO NPs in other organs. Increased concentrations of ZnO in the liver, small intestine, large intestine, and feces were thought to result from oral ingestion of ZnO NPs via licking. Penetration of ZnO NPs through the skin seemed to be limited via the dermal route. This study demonstrates that there was no observed adverse effect of ZnO NPs up to 1,000 mg/kg body weight when they are applied dermally. PMID:25565832

  18. A 90-day subchronic feeding study of genetically modified rice expressing Cry1Ab protein in Sprague-Dawley rats.

    PubMed

    Song, Huan; He, Xiaoyun; Zou, Shiying; Zhang, Teng; Luo, Yunbo; Huang, Kunlun; Zhu, Zhen; Xu, Wentao

    2015-04-01

    Bacillus thuringiensis (Bt) transgenic rice line (mfb-MH86) expressing a synthetic cry1Ab gene can be protected against feeding damage from Lepidopteran insects, including Sesamia inferens, Chilo suppressalis, Tryporyza incertulas and Cnaphalocrocis medinalis. Rice flour from mfb-MH86 and its near-isogenic control MH86 was separately formulated into rodent diets at concentrations of 17.5, 35 and 70 % (w/w) for a 90-day feeding test with rats, and all of the diets were nutritionally balanced. In this study, the responses of rats fed diets containing mfb-MH86 were compared to those of rats fed flour from MH86. Overall health, body weight and food consumption were comparable between groups fed diets containing mfb-MH86 and MH86. Blood samples were collected prior to sacrifice and a few significant differences (p < 0.05) were observed in haematological and biochemical parameters between rats fed genetically modified (GM) and non-GM diets. However, the values of these parameters were within the normal ranges of values for rats of this age and sex, thus not considered treatment related. In addition, upon sacrifice a large number of organs were weighed, macroscopic and histopathological examinations were performed with only minor changes to report. In conclusion, these results demonstrated that no toxic effect was observed in the conditions of the experiment, based on the different parameters assessed. GM rice mfb-MH86 is as safe and nutritious as non-GM rice. PMID:25367203

  19. Evaluation of silica nanoparticle toxicity after topical exposure for 90 days

    PubMed Central

    Ryu, Hwa Jung; Seong, Nak-won; So, Byoung Joon; Seo, Heung-sik; Kim, Jun-ho; Hong, Jeong-Sup; Park, Myeong-kyu; Kim, Min-Seok; Kim, Yu-Ri; Cho, Kyu-Bong; Seo, Mu Yeb; Kim, Meyoung-Kon; Maeng, Eun Ho; Son, Sang Wook

    2014-01-01

    Silica is a very common material that can be found in both crystalline and amorphous forms. Well-known toxicities of the lung can occur after exposure to the crystalline form of silica. However, the toxicities of the amorphous form of silica have not been thoroughly studied. The majority of in vivo studies of amorphous silica nanoparticles (NPs) were performed using an inhalation exposure method. Since silica NPs can be commonly administered through the skin, a study of dermal silica toxicity was necessary to determine any harmful effects from dermal exposures. The present study focused on the results of systemic toxicity after applying 20 nm colloidal silica NPs on rat skin for 90 days, in accordance with the Organization for Economic Cooperation and Development test guideline 411 with a good laboratory practice system. Unlike the inhalation route or gastrointestinal route, the contact of silica NPs through skin did not result in any toxicity or any change in internal organs up to a dose of 2,000 mg/kg in rats. PMID:25565831

  20. Evaluation of silica nanoparticle toxicity after topical exposure for 90 days.

    PubMed

    Ryu, Hwa Jung; Seong, Nak-won; So, Byoung Joon; Seo, Heung-sik; Kim, Jun-ho; Hong, Jeong-Sup; Park, Myeong-kyu; Kim, Min-Seok; Kim, Yu-Ri; Cho, Kyu-Bong; Seo, Mu Yeb; Kim, Meyoung-Kon; Maeng, Eun Ho; Son, Sang Wook

    2014-01-01

    Silica is a very common material that can be found in both crystalline and amorphous forms. Well-known toxicities of the lung can occur after exposure to the crystalline form of silica. However, the toxicities of the amorphous form of silica have not been thoroughly studied. The majority of in vivo studies of amorphous silica nanoparticles (NPs) were performed using an inhalation exposure method. Since silica NPs can be commonly administered through the skin, a study of dermal silica toxicity was necessary to determine any harmful effects from dermal exposures. The present study focused on the results of systemic toxicity after applying 20 nm colloidal silica NPs on rat skin for 90 days, in accordance with the Organization for Economic Cooperation and Development test guideline 411 with a good laboratory practice system. Unlike the inhalation route or gastrointestinal route, the contact of silica NPs through skin did not result in any toxicity or any change in internal organs up to a dose of 2,000 mg/kg in rats. PMID:25565831

  1. Toxicity of colloidal silica nanoparticles administered orally for 90 days in rats

    PubMed Central

    Kim, Yu-Ri; Lee, Seung-Young; Lee, Eun Jeong; Park, Sung Ha; Seong, Nak-won; Seo, Heung-Sik; Shin, Sung-Sup; Kim, Seon-Ju; Meang, Eun-Ho; Park, Myeong-Kyu; Kim, Min-Seok; Kim, Cheol-Su; Kim, Soo-Ki; Son, Sang Wook; Seo, Young Rok; Kang, Boo Hyon; Han, Beom Seok; An, Seong Soo A; Lee, Beom-Jun; Kim, Meyoung-Kon

    2014-01-01

    This study was undertaken to investigate the potential toxicity and establish the no observed adverse effect level (NOAEL) and target organ(s) of negatively charged colloidal silica particles of different sizes, ie, SiO2EN20(−) (20 nm) or SiO2EN100(−) 2(100 nm), administered by gavage in Sprague-Dawley rats. After verification of the physicochemical properties of the SiO2 particles to be tested, a preliminary dose range-finding study and 90-day repeated dose study were conducted according to the Organisation for Economic Cooperation and Development test guideline. Based on the results of the 14-day dose range-finding study, a high dose was determined to be 2,000 mg/kg, and middle and low doses were set at 1,000 and 500 mg/kg, respectively. In the 90-day toxicity study, there were no animal deaths in relation to administration of SiO2 particles of either size. In addition, no treatment-related clinical changes or histopathological findings were observed in any of the experimental groups. Moreover, no difference in toxic effects from chronic exposure to SiO2EN20(−)(20 nm) or SiO2EN100(−) (100 nm) was observed. The results of this study indicate that the NOAEL for SiO2EN20(−) and SiO2 EN100(−) would most likely be 2,000 mg/kg, and no target organ was identified in rats of either sex. PMID:25565827

  2. SUBACUTE AND SUBCHRONIC TOXICITY OF ETHYLENE GLYCOL ADMINISTERED IN DRINKING WATER TO SPRAGUE-DAWLEY RATS

    EPA Science Inventory

    Subacute (10-day) and subchronic (90-day) toxicity studies of ethylene glycol (EG) were conducted in male and female sprague-Dawley rats to provide the U.S. Environmental Protection Agency's (EPA) Office of Drinking Water with toxicity data for final preparation of a Health Advis...

  3. A 90 day chronic toxicity study of Nigerian herbal preparation DAS-77 in rats

    PubMed Central

    2012-01-01

    Background The herbal preparation DAS-77, used for the treatment of various ailments in Nigeria, contains the milled bark of Mangifera indica L. and root of Carica papaya L. Toxicological assessment of the preparation was carried out in this study. Methods In the acute toxicity study, DAS-77 was administered to mice p.o. up to 20 g/kg in divided doses and i.p. at 250–3000 mg/kg. Mortality within 24 h was recorded. In the chronic toxicity study, rats were treated p.o. for 90 days at doses of 80, 400 (therapeutic dose, TD) and 2000 mg/kg. By 90 days, animals were sacrificed and blood samples collected for hematological and biochemical analysis. Organs were harvested for weight determination, antioxidants and histopathological assessments. Results DAS-77 did not produce any lethality administered p.o. up to 20 g/kg in divided doses but the i.p. LD50 was 1122.0 mg/kg. At TD, DAS-77 produced significant (p < 0.05) reductions in body weight, food intake and K+, and increases in ovary weight, neutrophils and HDL, which were reversible. Histopathological presentations were generally normal. Effects at the other doses were comparable to those at TD except for reversible increases in antioxidants in the liver, kidney and testes, and sperm abnormality, and reductions in liver enzymes, sperm motility and count. Conclusions Findings in this study revealed that DAS-77 is relatively safe with the potential for enhancing in vivo antioxidant activity. However, possibly reversible side-effects include electrolyte imbalance and sterility in males. PMID:22892317

  4. Bioaccumulation and locomotor effects of manganese sulfate in Sprague-Dawley rats following subchronic (90 days) inhalation exposure

    SciTech Connect

    Tapin, Danielle; Kennedy, Greg; Lambert, Jean; Zayed, Joseph . E-mail: joseph.zayed@umontreal.ca

    2006-03-01

    Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic compound that was introduced as an antiknock additive to replace lead in unleaded fuel. The combustion of MMT results in the emission of fine Mn particulates mainly in the form of manganese sulfate and manganese phosphate. The objective of this study is to determine the effects of subchronic exposure to Mn sulfate in different tissues, on locomotor activity, on neuropathology, and on blood serum biochemical parameters. A control group and three groups of 30 male Sprague-Dawley rats were exposed 6-h/day, 5 days/week for 13 consecutive weeks at 30, 300, or 3000 {mu}g/m{sup 3} Mn sulfate. Locomotor activity was measured during 36 h using an Auto-Track System. Blood and the following tissues were collected and analyzed for manganese content by neutron activation analysis: olfactory bulb, globus pallidus, caudate/putamen, cerebellum, frontal cortex, liver, lung, testis, and kidney. Neuronal cell counts were obtained for the caudate/putamen and the globus pallidus and clinical biochemistry was assessed. Manganese concentrations were increased in blood, kidney, lung, and testis and in all brain regions in the 3000 {mu}g/m{sup 3} exposure group. Significant differences were also noted in the 300 {mu}g/m{sup 3} exposure group. Neuronal cell counts for the globus pallidus were significantly different between the two highest exposed groups and the controls. Locomotor activity for all exposure concentrations and resting time for the middle and highest concentrations for the two night resting periods were significantly increased. Total ambulatory count was decreased significantly for all exposure concentrations. Biochemical profiles also presented significant differences. No body weight loss was observed between all groups. These results suggest that neurotoxicity could occur at low exposure levels of Mn sulfate, one of the main combustion products of MMT.

  5. A 90-day oral (dietary) toxicity study of rebaudioside A in Sprague-Dawley rats.

    PubMed

    Nikiforov, Andrey I; Eapen, Alex K

    2008-01-01

    Rebaudioside A is one of several glycosides found in the leaves of Stevia rebaudiana (Bertoni) Bertoni (Compositae) stevia that has been identified as a potential sweetener. The present study (initiated in April 2006 and completed in October 2006) evaluated the safety of this sweetener when administered as a dietary admix at target exposure levels of 500, 1000, and 2000 mg/kg/day to Sprague-Dawley rats for 90 days. There were no treatment-related effects on the general condition and behavior of the animals as determined by clinical observations, functional observational battery, and locomotor activity assessments. Evaluation of clinical pathology parameters revealed no toxicologically relevant, treatment-related effects on hematology, serum chemistry, or urinalysis. Macroscopic and microscopic findings revealed no treatment-related effects on any organ evaluated. Lower mean body weight gains were noted in males in the 2000 mg/kg/day group throughout the study, which was considered to be test article related; however, given the small magnitude of the difference as compared to controls, this effect was not considered to be adverse. Results of this study clearly demonstrate that dietary administration of high concentrations of rebaudioside A for 90 consecutive days to Sprague-Dawley rats was not associated with any signs of toxicity. PMID:18293214

  6. SUBCHRONIC TOXICITY OF 1,3,5-TRINITROBENZENE IN FISCHER 344 RATS

    EPA Science Inventory

    The subchronic toxicity of 1,3,5-trinitrobenzene (TNB) in male and female Fischer 344 rats was evaluated by feeding a powdered certified laboratory diet containing 0, 66.7, 400 and 800 mg TNB/kg diet for 90 days. The calculated average TNB intake was 4.29, 24.70, and 49.28 mg/kg...

  7. Acute and subchronic toxicity of danshensu in mice and rats.

    PubMed

    Gao, Yonglin; Liu, Zhifeng; Li, Guisheng; Li, Chunmei; Li, Min; Li, Bafang

    2009-06-01

    Danshensu (3-(3,4-dihydroxyphenyl) lactic acid), a natural phenolic acid, is isolated from Salvia miltiorrhiza root, and is the most widely used traditional Chinese medicine for the treatment of various cardiovascular diseases. It has been reported to have potential protective effects from oxidative injury. However, there is a little information about its possible toxicity. In this study, acute and subchronic toxicity of danshensu in mice and rats have been evaluated. In the acute study, danshensu intraveniouslly administered to rats failed to induce any signs of toxicity or mortality up to a maximum practical dosage of 1500 mg/kg body weight. Test substance administered acutely to mice caused dose-dependent general behavior adverse effects and mortality with the medial lethal dose of 2356.33 mg/kg. The no observed adverse effect level and the lowest observed adverse effect level were 1835 mg/kg and 2000 mg/kg, respectively. In the subchronic study, rats were tested by daily intraperitoneal injection of danshensu at the doses of 50, 150, and 450 mg/kg for 90 days, resulting in no mortality, no changes in body weight, food consumption, hematological and serum chemistry parameters, organ weights, or gross pathology or histopathology. The only treatment-related finding was transient writhing response observed in the 450 mg/kg group after administration. PMID:19778213

  8. A 90-day subchronic study of rats fed lean pork from genetically modified pigs with muscle-specific expression of recombinant follistatin.

    PubMed

    Zou, Shiying; Tang, Min; He, Xiaoyun; Cao, Yuan; Zhao, Jie; Xu, Wentao; Liang, Zhihong; Huang, Kunlun

    2015-11-01

    Because cardiovascular disease incidence has rapidly increased in recent years, people are choosing relatively healthier diets with low animal fat. A transgenic pig with low fat and a high percentage of lean meat was created in 2011; this pig overexpresses the follistatin (FST) gene. To evaluate the safety of lean pork derived from genetically modified (GM) pigs, a subchronic oral toxicity study was conducted using Sprague-Dawley rats. GM pork and non-GM pork were incorporated into the diet at levels of 3.75%, 7.5%, and 15% (w/w), and the main nutrients of the various diets were subsequently balanced. The safety of GM pork was assessed by comparison of the toxicology response variables in Sprague-Dawley rats consuming diets containing GM pork with those consuming non-GM pork. No treatment-related adverse or toxic effects were observed based on an examination of the daily clinical signs, body weight, food consumption, hematology, serum biochemistry, and organ weight or based on gross and histopathological examination. The results demonstrate that GM pork is as safe for consumption as conventional pork. PMID:26363208

  9. Safety assessment of aditoprim acute, subchronic toxicity and mutagenicity studies.

    PubMed

    Wang, Xu; Tan, Ziqiang; Pan, Yuanhu; Ihsan, Awais; Liu, Qianying; Huang, Lingli; Cheng, Guyue; Chen, Dongmei; Tao, Yanfei; Liu, Zhenli; Yuan, Zonghui

    2015-11-01

    Aditoprim (ADP), a new developed dihydrofolate reductase (DHFR) inhibitor, has great potential in clinical veterinary medicine because of its greater pharmacokinetic properties than structural analogs. Preclinical toxicology studies were performed to assess the safety of ADP including an acute oral toxicity test, a subchronic toxicity test and five mutagenicity tests. In the acute oral toxicity test, ADP was administered singly by oral gavage to Wistar rats and Kunming mice. The LD50 calculated was 1400 mg kg(-1) body weight (BW) day(-1) in rats and 1130 mg kg(-1) BW day(-1) in mice. In a subchronic study, Wistar rats were administered ADP at dose levels of 0, 20, 100 and 1000 mg kg(-1) diet for 90 days. Significant decreases were observed on body weight and food efficiency in the high-dose group. Treatment-related changes in clinical serum biochemistry were found in the medium- and high-dose groups. Significant increases in the relative weights of livers and kidneys in females and testis in males in the 1000 mg kg(-1) diet, and significant decrease in relative weights of livers in males in the 100 mg kg(-1) diet were noted. Histopathological observations revealed that the 1000 mg kg(-1) ADP diet could induce lymphocytic infiltration and hepatocytic necrosis near the hepatic portal area. The genotoxicity of ADP was negative in tests, such as the bacterial reverse mutation assay, mice bone marrow erythrocyte micronucleus assay, in vitro chromosomal aberration test, in vitro cho/hgprt mammalian cell mutagenesis assay and mice testicle cells chromosome aberration. Based on the subchronic study, the no-observed-adverse-effect level for ADP was a 20 mg kg(-1) diet, which is about 1.44-1.53 mg kg(-1) BW day(-1) in rats. PMID:25663419

  10. Azadirachtin, a neem biopesticide: subchronic toxicity assessment in rats.

    PubMed

    Raizada, R B; Srivastava, M K; Kaushal, R A; Singh, R P

    2001-05-01

    Azadirachtin, a biopesticide obtained from neem, was subjected to subchronic toxicological testing to document its safety for use as a pesticide. Azadirachtin technical 12% orally administered to male and female rats at doses of 500, 1000 and 1500 mg/kg/day for 90 days did not produce any signs of toxicity, mortality, changes in tissue weight, pathology and serum and blood parameters. It can be suggested that azadirachtin at the highest dose tested is well tolerated by rats of both sexes. The highest dose, 1500 mg/kg, can be used as a basal dose for the determination of the no-observed-effect level (NOEL) of azadirachtin to calculate its safety margin. PMID:11313114

  11. Toxicity of Carbon Nanotubes in the Lungs of Mice 7 and 90 Days After Intratracheal Instillation

    NASA Technical Reports Server (NTRS)

    Lam, Chiu-Wing; James, John T.; McCluskey, Richard; Hunter, Robert L.

    2002-01-01

    Single-walled carbon nanotubes have many potential applications in the electronic, computer, and aerospace industries. Because unprocessed nanotubes could become airborne and potentially reach the lungs, their pulmonary toxicity was investigated. The three products studied were made by different methods, and contained different types and amounts of residual catalytic metals. Mice were each intratracheally instilled once with 0,0.1 or 0.5 mg of nanotubes, a carbon black negative control, or a quartz positive control, and killed for histopathological study 7 d or 90 d after the treatment. All nanotube products induced epithelioid granulomas and, in some cases, interstitial inflammation in the animals of the 7 -d groups. These lesions persisted and were worse in the 90-d groups. We found that, if nanotubes reach the lung, they can be more toxic than quartz, which is considered a serious occupational health hazard in chronic inhalation exposures.

  12. Evaluation of the 90-day inhalation toxicity of petroleum and oil shale JP-5 jet fuel. Technical report, July 1977-July 1983

    SciTech Connect

    Gaworski, C.L.; MacEwen, J.D.; Vernot, E.H.; Haun, C.C.; Leahy, H.F.

    1985-04-01

    Subchronic 90-day inhalation studies were conducted to compare the toxicity of Petroleum and Oil Shale derived JP-5 jet fuel. Beagle dogs, Fischer 344 rats, and C57BL/6 mice were continuously exposed to JP-5 at concentrations of 150 mg/m cum and 750 mg/cum 3. Unexposed control groups were also maintained. All dogs and a portion of each rodent group were sacrificed and examined at exposure termination. Remaining rodents were held for observation up to 21 months postexposure. The most significant exposure related effect occurred in male rats, where JP-5 produced nephropathy characterized by hyaline droplets, necrosis, and intratubular casts. Accentuated tubular degeneration and medullary mineralization were noted in exposed rats held for long-term postexposure observation. Female rats were free of significant JP-5 related renal damage. Consistent with the pathologic changes in male rats exposed to 750 mg/cu m 3 were increased kidney weight and increased serum creatinine and BUN levels. Reduced body weight gains also occurred in male rats exposed to JP-5. No pathologic lesions were observed in dogs exposed to JP-5. Hepatocellular vacuolization and fatty change occurred in mice exposed to JP-5 from either source and in rats exposed to Shale JP-5. The results of this study suggest that there are no substantial differences between Petroleum and Shale JP-5.

  13. Safety assessment of freeze-dried powdered Tenebrio molitor larvae (yellow mealworm) as novel food source: Evaluation of 90-day toxicity in Sprague-Dawley rats.

    PubMed

    Han, So-Ri; Lee, Byoung-Seok; Jung, Kyung-Jin; Yu, Hee-Jin; Yun, Eun-Young; Hwang, Jae Sam; Moon, Kyoung-Sik

    2016-06-01

    Worldwide demand for novel food source has grown and edible insects are a promising food sources for humans. Tenebrio molitor, as known as yellow mealworm, has advantages of being rich in protein, and easy to raise as a novel food source. The objective of this study was to evaluate subchronic toxicity, including potential hypersensitivity, of freeze-dried powdered T. molitor larvae (fdTML) in male and female Sprague-Dawley rats. The fdTML was administered orally once daily at dose levels of 0, 300, 1000 and 3000 mg/kg/day for 90 days. A toxicological assessment was performed, which included mortality, clinical signs, body and organ weights, food consumption, ophthalmology, urinalysis, hematology, serum chemistry, gross findings, histopathologic examination and allergic reaction. There were no fdTML- related findings in clinical signs, urinalysis, hematology and serum chemistry, gross examination, histopathologic examination or allergic reaction. In conclusion, the No Observed Adverse Effect Level (NOAEL) for fdTML was determined to be in excess of 3000 mg/kg/day in both sexes of rats under the experimental conditions of this study. PMID:26993751

  14. Toxicity of 100 nm zinc oxide nanoparticles: a report of 90-day repeated oral administration in Sprague Dawley rats

    PubMed Central

    Kim, Yu-Ri; Park, Jong-Il; Lee, Eun Jeong; Park, Sung Ha; Seong, Nak-won; Kim, Jun-Ho; Kim, Geon-Yong; Meang, Eun-Ho; Hong, Jeong-Sup; Kim, Su-Hyon; Koh, Sang-Bum; Kim, Min-Seok; Kim, Cheol-Su; Kim, Soo-Ki; Son, Sang Wook; Seo, Young Rok; Kang, Boo Hyon; Han, Beom Seok; An, Seong Soo A; Yun, Hyo-In; Kim, Meyoung-Kon

    2014-01-01

    Nanoparticles (NPs) are used commercially in health and fitness fields, but information about the toxicity and mechanisms underlying the toxic effects of NPs is still very limited. The aim of this study is to investigate the toxic effect(s) of 100 nm negatively (ZnOAE100[−]) or positively (ZnOAE100[+]) charged zinc oxide (ZnO) NPs administered by gavage in Sprague Dawley rats, to establish a no observed adverse effect level, and to identify target organ(s). After verification of the primary particle size, morphology, hydrodynamic size, and zeta potential of each test article, we performed a 90-day study according to Organisation for Economic Co-operation and Development test guideline 408. For the 90-day study, the high dose was set at 500 mg/kg and the middle and low doses were set at 125 mg/kg and 31.25 mg/kg, respectively. Both ZnO NPs had significant changes in hematological and blood biochemical analysis, which could correlate with anemia-related parameters, in the 500 mg/kg groups of both sexes. Histopathological examination showed significant adverse effects (by both test articles) in the stomach, pancreas, eye, and prostate gland tissues, but the particle charge did not affect the tendency or the degree of the lesions. We speculate that this inflammatory damage might result from continuous irritation caused by both test articles. Therefore, the target organs for both ZnOAE100(−) and ZnOAE100(+) are considered to be the stomach, pancreas, eye, and prostate gland. Also, the no observed adverse effect level for both test articles was identified as 31.25 mg/kg for both sexes, because the adverse effects were observed at all doses greater than 125 mg/kg. PMID:25565830

  15. Toxicity of 100 nm zinc oxide nanoparticles: a report of 90-day repeated oral administration in Sprague Dawley rats.

    PubMed

    Kim, Yu-Ri; Park, Jong-Il; Lee, Eun Jeong; Park, Sung Ha; Seong, Nak-won; Kim, Jun-Ho; Kim, Geon-Yong; Meang, Eun-Ho; Hong, Jeong-Sup; Kim, Su-Hyon; Koh, Sang-Bum; Kim, Min-Seok; Kim, Cheol-Su; Kim, Soo-Ki; Son, Sang Wook; Seo, Young Rok; Kang, Boo Hyon; Han, Beom Seok; An, Seong Soo A; Yun, Hyo-In; Kim, Meyoung-Kon

    2014-01-01

    Nanoparticles (NPs) are used commercially in health and fitness fields, but information about the toxicity and mechanisms underlying the toxic effects of NPs is still very limited. The aim of this study is to investigate the toxic effect(s) of 100 nm negatively (ZnO(AE100[-])) or positively (ZnO(AE100[+])) charged zinc oxide (ZnO) NPs administered by gavage in Sprague Dawley rats, to establish a no observed adverse effect level, and to identify target organ(s). After verification of the primary particle size, morphology, hydrodynamic size, and zeta potential of each test article, we performed a 90-day study according to Organisation for Economic Co-operation and Development test guideline 408. For the 90-day study, the high dose was set at 500 mg/kg and the middle and low doses were set at 125 mg/kg and 31.25 mg/kg, respectively. Both ZnO NPs had significant changes in hematological and blood biochemical analysis, which could correlate with anemia-related parameters, in the 500 mg/kg groups of both sexes. Histopathological examination showed significant adverse effects (by both test articles) in the stomach, pancreas, eye, and prostate gland tissues, but the particle charge did not affect the tendency or the degree of the lesions. We speculate that this inflammatory damage might result from continuous irritation caused by both test articles. Therefore, the target organs for both ZnO(AE100(-)) and ZnO(AE100(+)) are considered to be the stomach, pancreas, eye, and prostate gland. Also, the no observed adverse effect level for both test articles was identified as 31.25 mg/kg for both sexes, because the adverse effects were observed at all doses greater than 125 mg/kg. PMID:25565830

  16. The added value of the 90-day repeated dose oral toxicity test for industrial chemicals with a low (sub)acute toxicity profile in a high quality dataset.

    PubMed

    Taylor, Katy; Andrew, David J; Rego, Laura

    2014-08-01

    A survey conducted on the EU Notification of New Substances (NONS) database suggested that for industrial chemicals with a profile of low toxicity in (sub)acute toxicity tests there is little added value to the conduct of the 90-day repeated dose study. Avoiding unnecessary animal testing is a central aim of the EU REACH chemicals legislation; therefore we sought to verify the profile using additional data. The OECD's eChemPortal was searched for substances that had both a 28-day and a 90-day study and their robust study summaries were then examined from the ECHA CHEM database. Out of 182 substances with high quality 28-day and 90-day study results, only 18 reported no toxicity of any kind in the (sub)acute tests. However, for 16 of these there were also no reported signs of toxicity at or close to the limit dose (1000mg/kgbw/d) in the 90-day study. Restricting the 'low (sub)acute toxicity in a high quality dataset' profile to general industrial chemicals of no known biological activity, whilst allowing irritant substances, increases the data set and improves the prediction to 95% (20 substances out of 21 substances). The low toxicity profile appears to be of low prevalence within industrial chemicals (10-15%), nevertheless, avoidance of the conduct of a redundant 90-day study for this proportion of the remaining REACH phase-in substances would avoid the use of nearly 50,000 animals and save industry 50million Euros, with no impact on the assessment of human health. PMID:24768988

  17. Acute and subchronic toxicity of sucralose.

    PubMed

    Goldsmith, L A

    2000-01-01

    The toxicity of sucralose has been evaluated in acute and subchronic toxicity studies. Acute oral toxicity studies in male and female mice and male rats documented no deaths or treatment-related signs at doses of 16g/kg for mice and 10g/kg for rats. Sucralose was administered to male and female rats for 4 and 8 weeks at dietary concentrations of 1.0, 2.5 or 5.0%. Achieved dose ranges (mg/kg/day) for the respective dietary levels were 737-1287, 1865-3218 and 2794-6406. There were no toxicologically significant effects observed at the 1.0% or 2.5% dietary levels. However, decreases in food consumption, body weight gain and selected organ weights and ratios as well as splenic and thymic histopathologic changes occurred in rats administered 5.0% for 4 or 8 weeks. A gavage study wherein doses of 0, 750, 1500 or 3000mg/kg/day were administered to male and female rats for 26 weeks investigated further the observations from the dietary study as well as general subchronic toxicity. The gavage study documented no sucralose-related toxicity. These results implicate the reduced palatability and digestibility of diets containing high concentrations of sucralose seen in the diet study as the cause for the decreased food consumption and other accompanying alterations. Dose selection for chronic toxicity studies in rats took into consideration the effect of high concentrations of sucralose on digestion and food consumption and the limitations that would be imposed on subsequent studies. In male and female dogs, no sucralose-related adverse effects were observed following the dietary administration of 0.3, 1.0 or 3.0% for 12 months achieving doses of approximately 90, 300 and 900mg/kg/day respectively. These studies establish that sucralose is non-toxic in rodents following acute oral administration. The rat no-observed-adverse-effect level ranged between 2.5 and 5.0% following subchronic dietary administration. A 3.0% dietary concentration equivalent to a dose of 900mg

  18. Pulmonary toxicity of simulated lunar and Martian dusts in mice: I. Histopathology 7 and 90 days after intratracheal instillation

    NASA Technical Reports Server (NTRS)

    Lam, Chiu-Wing; James, John T.; McCluskey, Richard; Cowper, Shawn; Balis, John; Muro-Cacho, Carlos

    2002-01-01

    O(3) and MSS coexposure appeared to be more than additive. Results for the TiO(2) and quartz controls were consistent with the known pulmonary toxicity of these compounds. The overall severity of lung injury was TiO(2) < LSS < MSS < O(3) + MSS < quartz. Except for TiO(2), the increased duration of dust presence in the lung from 7 to 90 days transformed the acute inflammatory response to a chronic inflammatory lesion. This study showed that LSS and MSS are more hazardous in the lungs than nuisance dusts.

  19. A Study on Subchronic Inhalation Toxicity of 1-Chloropropane

    PubMed Central

    Chung, Yong Hyun; Han, Jeong Hee

    2015-01-01

    This study was conducted to measure toxicity of 1-chloropropane (CAS No. : 540-54-5). According to the OECD Test Guideline 413 (Subchronic inhalation toxicity: 90-day study), SD rats were exposed to 0, 310, 1,250, and 5,000 ppm of 1-chloropropane for 6 h/day, 5 day/week for 13 weeks via whole-body inhalation. Mortality, clinical signs, body weights, food consumption, motor activity, ophthalmoscopy, hematology, serum chemistry, urinalysis, organ weights, gross and histopathological findings were compared between control and all tested groups. No mortality or remarkable clinical signs were examined during the study. No gross lesions or adverse effects on body weight, food consumption, motor activity, ophthalmoscopy, urinalysis, hematology, organ weights were observed in any of male or female rats in all tested groups. In serum biochemistry, glucose was significantly decreased in males of 1,250 and 5,000 ppm groups compared to control group in dose-dependent relationship. In histopathological examination, vacuolation of acinar cells was observed in pancreas of all male and female groups exposed to 1-chloropropane. In conclusion, no observable adverse effect level (NOAEL) was considered to be below 310 ppm/6 h/day, 5 day/week for rats. PMID:26877841

  20. Subchronic Inhalation Toxicity Study of n-pentane in Rats

    PubMed Central

    Cho, Hae-Won; Han, Jeong-Hee; Lee, Sung-Bae; Chung, Yong-Hyun; Rim, Kyung-Taek; Yang, Jeong-Sun

    2012-01-01

    Objectives This study was conducted in order to obtain information concerning the health hazards that may result from a 13 week inhalation exposure of n-pentane in Sprague-Dawley rats. Methods This study was conducted in accordance with the Organization for Economic Co-operation and Development (OECD) guidelines for the testing of chemicals No. 413 'Subchronic inhalation toxicity: 90-day study (as revised in 2009)'. The rats were divided into 4 groups (10 male and 10 female rats in each group), and were exposed to 0, 340, 1,530, and 6,885 ppm n-pentane in each exposure chamber for 6 hour/day, 5 days/week, for 13 weeks. All of the rats were sacrificed at the end of the treatment period. During the test period, clinical signs, mortality, body weights, food consumption, ophthalmoscopy, locomotion activity, urinalysis, hematology, serum biochemistry, gross findings, organ weights, and histopathology were assessed. Results During the period of testing, there were no treatment related effects on the clinical findings, body weight, food consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, relative organ weight, and histopathological findings. Conclusion The no-observable-adverse-effect level (NOAEL) of n-pentane is evaluated as being more than 6,885 ppm (20.3 mg/L) in both male and female rats. n-pentane was not a classified specific target organ toxicity in the globally harmonized classification system (GHS). PMID:23019535

  1. Repeated exposure toxicity of 2-ethyl-1,3-hexanediol by cutaneous applications to the rat for 9 and 90 days.

    PubMed

    Van Miller, J P; Losco, P E; Neptun, D A; Ballantyne, B

    1995-02-01

    2-Ethyl-1,3-hexanediol (EHD; CASRN 94-96-2), an industrial chemical and insect repellent, has a high potential for recurrent skin contact. Short-term (9 d) and subchronic (13 w) repeated epicutaneous contact studies were conducted to determine the potential for cumulative local skin irritation and systemic toxicity in Fischer 344 rats. Doses were 0.5, 2.0 or 4.0 ml/kg/d of undiluted EHD. There were no clinical signs and no treatment-related effects on hematology, clinical chemistry or histology of a large number of organs and tissues including the treated skin. The only effects where slight decreases in body weight gain for the high-dose males in the 9-d study and males and females of the high-dose group in the subchronic study; slight decreases in food consumption for females of all treatment groups in the subchronic study; and slight increases in relative liver weight for high-dose females in the 9-d study and high-dose males in the subchronic study, which is probably a compensatory hypertrophy for the metabolism of EHD. Thus, recurrent epicutaneous applications of undiluted EHD to the rat did not cause any local skin irritation or cumulative or organ-specific toxicity. PMID:7709587

  2. Acute and Subchronic Oral Toxicity Evaluation of Aqueous Root Extract of Dicoma anomala Sond. in Wistar Rats

    PubMed Central

    Balogun, Fatai Oladunni; Tom Ashafa, Anofi Omotayo

    2016-01-01

    The present study evaluated the safety of aqueous root extract of Dicoma anomala (AQRED) through acute and subchronic toxicity studies. Single oral dose of AQRED at the concentration of 0, 5, 300, and 2000 mg/kg as well as 125, 250, and 500 mg/kg/day was administered to rats for 14-day acute and 90-day subchronic oral toxicity studies. The results revealed no mortalities or observed clinical signs of toxicity in all the rats during both investigation periods. In subchronic toxicity testing, administration of AQRED also did not cause any changes in body weight as well as food and water consumption patterns. The haematological parameters and blood chemistry revealed no significant difference (p > 0.05) between the treatment and the control except in platelet count, alkaline phosphatase, and sodium levels where there was a significant increase (p < 0.05), although there was also a significant reduction (p < 0.05) in alanine transaminase, aspartate transaminase, and creatinine when compared to control. However, these changes were not reflecting the results from histology. Conclusively, the obtained results suggested that the LD50 of AQRED is in excess of 2000 mg/kg and its oral administration for 90 days revealed that it is unlikely to be toxic, hence, safe. PMID:27200099

  3. Subchronic inhalation toxicity of gold nanoparticles

    PubMed Central

    2011-01-01

    Background Gold nanoparticles are widely used in consumer products, including cosmetics, food packaging, beverages, toothpaste, automobiles, and lubricants. With this increase in consumer products containing gold nanoparticles, the potential for worker exposure to gold nanoparticles will also increase. Only a few studies have produced data on the in vivo toxicology of gold nanoparticles, meaning that the absorption, distribution, metabolism, and excretion (ADME) of gold nanoparticles remain unclear. Results The toxicity of gold nanoparticles was studied in Sprague Dawley rats by inhalation. Seven-week-old rats, weighing approximately 200 g (males) and 145 g (females), were divided into 4 groups (10 rats in each group): fresh-air control, low-dose (2.36 × 104 particle/cm3, 0.04 μg/m3), middle-dose (2.36 × 105 particle/cm3, 0.38 μg/m3), and high-dose (1.85 × 106 particle/cm3, 20.02 μg/m3). The animals were exposed to gold nanoparticles (average diameter 4-5 nm) for 6 hours/day, 5 days/week, for 90-days in a whole-body inhalation chamber. In addition to mortality and clinical observations, body weight, food consumption, and lung function were recorded weekly. At the end of the study, the rats were subjected to a full necropsy, blood samples were collected for hematology and clinical chemistry tests, and organ weights were measured. Cellular differential counts and cytotoxicity measurements, such as albumin, lactate dehydrogenase (LDH), and total protein were also monitored in a cellular bronchoalveolar lavage (BAL) fluid. Among lung function test measurements, tidal volume and minute volume showed a tendency to decrease comparing control and dose groups during the 90-days of exposure. Although no statistically significant differences were found in cellular differential counts, histopathologic examination showed minimal alveoli, an inflammatory infiltrate with a mixed cell type, and increased macrophages in the high-dose rats. Tissue distribution of gold

  4. Acute, mutagenicity, teratogenicity and subchronic oral toxicity studies of diaveridine in rodents.

    PubMed

    Wang, Jianzhong; Sun, Feifei; Tang, Shusheng; Zhang, Suxia; Cao, Xingyuan

    2015-09-01

    Diaveridine (DVD) is a member of the 2,4-pyrimidinediamine class of dihydrofolate reductase inhibitors. It is used in combination with sulfaquinoxaline as an antiprotozoal agent in animals for the prophylaxis and treatment of coccidiosis and leucocytozoonosis. Herein, we report a complete toxicological safety assessment of DVD for clinical use. The study of toxicity, genetic toxicity (mammalian erythrocyte micronucleus assay, mice sperm abnormality test and in vivo chromosome aberration test of mammalian bone marrow), 90-day sub-chronic toxicity and teratogenicity test were performed. In the acute oral toxicity tests, median lethal dose, LD50, was more than 2378mg/kg body weight in Sprague Dawley rats (1025mg/kg body weight in ICR mice). The testing results for three terms of mutagenicity toxicity (mouse chromosome aberration, erythrocyte micronucleus and sperm abnormality) were all negative at 128-512mg/kg body weight. For 90-day feeding of DVD at the dosage of 10mg/kg body weight in both male and female SD rats, no signs of toxicological effects were detected. Meanwhile, for teratogenicity test in female SD rats at the dosage of 37mg/kg body weight, there were no toxicological signs observed. Thus, our results suggested that the DVD is safe when administered orally in rats at 10mg/kg body weight per day. PMID:26397222

  5. 90-Day Cycle Handbook

    ERIC Educational Resources Information Center

    Park, Sandra; Takahashi, Sola

    2013-01-01

    90-Day Cycles are a disciplined and structured form of inquiry designed to produce and test knowledge syntheses, prototyped processes, or products in support of improvement work. With any type of activity, organizations inevitably encounter roadblocks to improving performance and outcomes. These barriers might include intractable problems at…

  6. Pulmonary toxicity of single-wall carbon nanotubes in mice 7 and 90 days after intratracheal instillation

    NASA Technical Reports Server (NTRS)

    Lam, Chiu-Wing; James, John T.; McCluskey, Richard; Hunter, Robert L.

    2004-01-01

    Nanomaterials are part of an industrial revolution to develop lightweight but strong materials for a variety of purposes. Single-wall carbon nanotubes are an important member of this class of materials. They structurally resemble rolled-up graphite sheets, usually with one end capped; individually they are about 1 nm in diameter and several microns long, but they often pack tightly together to form rods or ropes of microscopic sizes. Carbon nanotubes possess unique electrical, mechanical, and thermal properties and have many potential applications in the electronics, computer, and aerospace industries. Unprocessed nanotubes are very light and could become airborne and potentially reach the lungs. Because the toxicity of nanotubes in the lung is not known, their pulmonary toxicity was investigated. The three products studied were made by different methods and contained different types and amounts of residual catalytic metals. Mice were intratracheally instilled with 0, 0.1, or 0.5 mg of carbon nanotubes, a carbon black negative control, or a quartz positive control and euthanized 7 d or 90 d after the single treatment for histopathological study of the lungs. All nanotube products induced dose-dependent epithelioid granulomas and, in some cases, interstitial inflammation in the animals of the 7-d groups. These lesions persisted and were more pronounced in the 90-d groups; the lungs of some animals also revealed peribronchial inflammation and necrosis that had extended into the alveolar septa. The lungs of mice treated with carbon black were normal, whereas those treated with high-dose quartz revealed mild to moderate inflammation. These results show that, for the test conditions described here and on an equal-weight basis, if carbon nanotubes reach the lungs, they are much more toxic than carbon black and can be more toxic than quartz, which is considered a serious occupational health hazard in chronic inhalation exposures.

  7. Subacute and subchronic toxicity of Avalon(®) mixture (bentazone+dicamba) to rats.

    PubMed

    Brkić, Dragica; Szakonyne-Pasics, Ilona; Gašić, Slavica; Teodorović, Ivana; Rašković, Božidar; Brkić, Nenad; Nešković, Neško

    2015-05-01

    Subacute and subchronic toxicity of the herbicide Avalon(®), a mixture of bentazone and dicamba, were tested on rats. Avalon(®) was administered at dose levels of 250, 500 and 1000mg/kg body weight/day for 28 and 90 days. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) activities were monitored together with biochemistry parameters. The results showed that the mixture caused increases in the activities of ALT, AST and ALP, elevated concentrations of sodium, albumin and albumin/globulin ratio in males. In females, ALT activity, cholesterol and phosphate levels were increased. The changes generally were dose related and, in most cases, females exhibited lower susceptibility than males. The effects of a mixture are, in the most cases, different from the effects of the individual substances. The effects of bentazone were not prevalent which would be expected taking the composition of the mixture into account. PMID:25863332

  8. Subchronic Toxicity Study in Rats of Two New Ethyl-Carbamates with Ixodicidal Activity

    PubMed Central

    Prado-Ochoa, María Guadalupe; Abrego-Reyes, Víctor Hugo; Velázquez-Sánchez, Ana María; Muñoz-Guzmán, Marco Antonio; Ramírez-Noguera, Patricia; Angeles, Enrique; Alba-Hurtado, Fernando

    2014-01-01

    Female and male Wistar rats were used to determine the subchronic oral toxicities of two new ethyl-carbamates with ixodicidal activities (ethyl-4-bromphenyl-carbamate and ethyl-4-chlorphenyl-carbamate). The evaluated carbamates were administered in the drinking water (12.5, 25 and 50 mg/kg/day) for 90 days. Exposure to the evaluated carbamates did not cause mortality or clinical signs and did not affect food consumption or weight gain. However, exposure to these carbamates produced alterations in water consumption, hematocrit, percentages of reticulocytes, plasma proteins, some biochemical parameters (aspartate aminotransferase, gamma-glutamyl transpeptidase, cholinesterase, and creatinine activities), thiobarbituric acid reactive substances, and the relative weight of the spleen. Histologically, slight pathological alterations were found in the liver that were consistent with the observed biochemical alterations. The nonobserved adverse effect levels (NOAELs) of the evaluated carbamates were 12.5 mg/kg/day for both the female and male rats. The low severity and reversibility of the majority of the observed alterations suggest that the evaluated carbamates have low subchronic toxicity. PMID:24818142

  9. Acute and subchronic toxicity of metal complex azo acid dye and anionic surfactant oil on fish Oreochromis niloticus.

    PubMed

    Amwele, Hilma Rantilla; Papirom, Pittaya; Chukanhom, Kanit; Beamish, Fredrick Henry William; Petkam, Rakpong

    2015-01-01

    The acute toxicity study of metal complex dark green azo acid dye, anionic surfactant oil and their mixture determined the 96 hr LC50, and fish behaviours. Subchronic toxicity determined haematology parameters and concentrations of copper and chromium in blood. The 96 hr LC50 was determined by probit analysis and subchronic toxicity was conducted in 90 days. No mortalities were observed in control and anionic surfactant oil treatments. The 96 hr LC50 value of mixture was 26.7 mg I(-1) (95% CL = 20.7 - 46.8) and that of metal complex dark green azo acid dye was not met as the percentage of dead was below 50% of tested organisms. In a treatment of anionic surfactant oil and that of mixture observed behaviours were respiration response, uncoordinated movement, loss of equilibrium, erratic posture and loss of responsiveness. Subchronic toxicity indicated fluctuations in number of erythrocytes, leukocytes and thrombocytes in all chemical treatments. Erythrocyte morphology such as anisocytosis, erythrocytes hypertrophy, karyolysis, cytoplasm vacuolation, ghost cell were observed in fish blood in all chemical treatments. An inverse relation was observed between total copper and chromium concentration in blood. However, the toxicity effect was chemical dose dependent and length of exposure. PMID:26536793

  10. A 90-day toxicity study of the effects of petroleum middle distillates on the skin of C3H mice.

    PubMed

    Freeman, J J; McKee, R H; Phillips, R D; Plutnick, R T; Scala, R A; Ackerman, L J

    1990-01-01

    Petroleum middle distillates (PMDs) elicit skin tumors in mouse epidermal carcinogenesis studies. The response is characterized by a long latency with only a small percentage of animals developing tumors. Although the carcinogenic activity of certain other petroleum hydrocarbons largely depends upon the presence of polycyclic aromatic hydrocarbons (PAHs), many PMDs contain relatively low concentrations of PAHs. PMDs are also irritating to mouse skin, and chronic irritation may be involved in the development of skin tumors. This study was conducted to investigate the patterns of cutaneous irritation elicited by topical application of PMDs having compositional differences. The three PMDs selected for study were a steam cracked gas oil (SCGO), a lightly refined paraffinic oil (LRPO), and a jet fuel (JF). Male C3H/HeNCr1BR mice (25/group) were treated topically (37.5 microliters 2x/week for 13 weeks) with 10%, 50% or 100% (undiluted) concentrations of each PMD. Catalytically cracked clarified oil (CCCO, 10%), a potent carcinogen to mouse skin, was also tested. The vehicle was a noncarcinogenic mineral oil with a viscosity of 90 SUS. Cutaneous changes were evaluated by gross observations and light microscopy. Cutaneous irritation was the only significant toxic response in this study. Neither the vehicle nor any of the 10% PMD concentrations produced significant cutaneous irritation. The 10% CCCO and 50% PMD treatments all elicited slight to moderate proliferative and inflammatory changes in mouse skin. Ulcers were also observed microscopically in mice treated with 10% CCCO and 50% SCGO. The 100% SCGO treatment produced evidence of necrosis on Days 1-7 but not later in the study despite continued treatment. In contrast, the irritating effects of 100% LRPO were not evident until 2-3 weeks of study, and at study completion were characterized by moderately severe inflammatory and proliferative changes. The effects of 100% JF were qualitatively similar to 100% LRPO but less

  11. A 90-Day Dietary Toxicity Study of Genetically Modified Rice T1C-1 Expressing Cry1C Protein in Sprague Dawley Rats

    PubMed Central

    Tang, Xueming; Han, Fangting; Zhao, Kai; Xu, Yan; Wu, Xiao; Wang, Jinbin; Jiang, Lingxi; Shi, Wei

    2012-01-01

    In a 90-day study, Sprague Dawley rats were fed transgenic T1C-1 rice expressing Cry1C protein and were compared with rats fed non-transgenic parental rice Minghui 63 and rats fed a basal diet. No adverse effects on animal behavior or weight gain were observed during the study. Blood samples were collected and analyzed, and standard hematological and biochemical parameters were compared. A few of these parameters were found to be significantly different, but were within the normal reference intervals for rats of this breed and age, and were thus not considered to be treatment-related. Following sacrifice, a large number of organs were weighed, and macroscopic and histopathological examinations were performed with no changes reported. The aim of this study was to use a known animal model to determine the safety of the genetically modified (GM) rice T1C-1. The results showed no adverse or toxic effects due to T1C-1 rice when tested in this 90-day study. PMID:23300690

  12. Acute and subchronic toxicity of aflatoxin B1 to rohu, Labeo rohita (Hamilton).

    PubMed

    Sahoo, P K; Mukherjee, S C; Nayak, S K; Dey, S

    2001-05-01

    Pathological alterations in various organs of rohu (L. rohita) fingerlings following acute (0, 7.50, 11.25 and 13.75 mg/kg body weight) and subchronic (0, 1.25 and 2.50 mg/kg body weight) single i.p. aflatoxin B1 exposure for 10 and 90 days, respectively, were investigated. Mortality (dose-dependent) was marked only during acute toxicosis. The changes observed in various organs were dose and time dependent. The acute dose groups revealed toxic changes viz., necrotic and vascular changes in liver and gill lamellae; meningitis, congestion in brain, degeneration and inflammatory reaction in heart along with degenerative to necrotic changes in kidney tubules and sloughing of the intestinal mucosa. During subchronic exposure to this toxin, preneoplastic lesions in liver along with changes in spleen, intestine, gill and pancreas were recorded. With low doses of aflatoxin, the fish did not reveal any mortality or external signs other than catchexia and increased pigmentation on scales. In composite culture practice of Indian major carps, this could be of economic significance. PMID:11510129

  13. Acute and subchronic dermal toxicity of nanosilver in guinea pig

    PubMed Central

    Korani, M; Rezayat, SM; Gilani, K; Bidgoli, S Arbabi; Adeli, S

    2011-01-01

    Silver has been used as an antimicrobial agent for a long time in different forms, but silver nanoparticles (nanosilver) have recently been recognized as potent antimicrobial agents. Although nanosilver is finding diverse medical applications such as silver-based dressings and silver-coated medical devices, its dermal and systemic toxicity via dermal use has not yet been identified. In this study, we analyzed the potential toxicity of colloidal nanosilver in acute and subchronic guinea pigs. Before toxicity assessments, the size of colloidal nanosilver was recorded in sizes <100 nm by X-ray diffraction and transmission electron microscopy. For toxicological assessments, male guinea pigs weighing 350 to 400 g were exposed to two different concentrations of nanosilver (1000 and 10,000 μg/mL) in an acute study and three concentrations of nanosilver (100, 1000, and 10,000 μg/mL) in a subchronic study. Toxic responses were assessed by clinical and histopathologic parameters. In all experimental animals the sites of exposure were scored for any type of dermal toxicity and compared with negative control and positive control groups. In autopsy studies during the acute test, no significant changes in organ weight or major macroscopic changes were detected, but dose-dependent histopathologic abnormalities were seen in skin, liver, and spleen of all test groups. In addition, experimental animals subjected to subchronic tests showed greater tissue abnormalities than the subjects of acute tests. It seems that colloidal nanosilver has the potential to provide target organ toxicities in a dose- and time-dependent manner. PMID:21720498

  14. Subchronic oral toxicity of zinc in rats

    SciTech Connect

    Llobet, J.M.; Domingo, J.L.; Colomina, M.T.; Mayayo, E.; Corbella, J.

    1988-07-01

    It is well known that zinc has important biological functions. Clinical manifestations in zinc-deficient animals include growth retardation, testicular atrophy, skin changes, and poor appetite. On the other hand, high levels of dietary zinc have been shown to induce copper deficiency in rats and to interfere with the metabolism of calcium and iron. Little is known on the oral toxicity of zinc in mammals. However, some toxic effects in human subjects, rodents, and sheep have been reported. In order to extend the information about the oral toxicity of zinc, a semichronic toxicity study of zinc acetate in rats has been carried out in this paper.

  15. Genotoxicity and subchronic toxicity studies of DHA-rich oil in rats.

    PubMed

    Blum, René; Kiy, Thomas; Tanaka, Satohiro; Wong, Andrea W; Roberts, Ashley

    2007-12-01

    Polyunsaturated fatty acids, including docosahexaenoic acid (DHA), are natural constituents of the human diet. DHA-algal oil is produced through the use of the non-toxigenic and non-pathogenic marine protist, Ulkenia sp. The safety of DHA-algal oil was assessed in a subchronic toxicity study and in genotoxicity studies. In a 90-day study, rats were orally administered water or DHA-algal oil at concentrations of 0, 500, 1000, and 2000 mg/kg in combination with 2000, 1500, 1000 or 0 mg/kg DHA-containing fish oil, respectively. Additional animals were administered water, 2000 mg/kg DHA-algal oil, or 2000 mg/kg fish oil for 90 days, followed by a 4-week recovery phase. No treatment-related effects were observed in clinical observations, food and water consumption, mortality, gross pathology, and histopathology. Increased body weights and liver weights in oil-treated groups were attributed to the large lipid load and were not regarded as toxicologically significant. Furthermore, no treatment-related differences in the measured parameters between the DHA-algal oil and fish oil groups were detected. In genotoxicity experiments, DHA-algal oil exerted no mutagenic activity in various bacterial strains, nor did it induce chromosomal aberrations in Chinese hamster fibroblast cells. These results support the safety of DHA-algal oil as a dietary source of DHA. PMID:17933446

  16. Evaluation of 90-day Repeated Dose Oral Toxicity, Glycometabolism, Learning and Memory Ability, and Related Enzyme of Chromium Malate Supplementation in Sprague-Dawley Rats.

    PubMed

    Feng, Weiwei; Wu, Huiyu; Li, Qian; Zhou, Zhaoxiang; Chen, Yao; Zhao, Ting; Feng, Yun; Mao, Guanghua; Li, Fang; Yang, Liuqing; Wu, Xiangyang

    2015-11-01

    Our previous study showed that chromium malate improved the regulation of blood glucose in mice with alloxan-induced diabetes. The present study was designed to evaluate the 90-day oral toxicity of chromium malate in Sprague-Dawley rats. The present study inspected the effect of chromium malate on glycometabolism, glycometabolism-related enzymes, lipid metabolism, and learning and memory ability in metabolically healthy Sprague-Dawley rats. The results showed that all rats survived and pathological, toxic, feces, and urine changes were not observed. Chromium malate did not cause measurable damage on liver, brain, and kidney. The fasting blood glucose, serum insulin, insulin resistance index, C-peptide, hepatic glycogen, glucose-6-phosphate dehydrogenase, glucokinase, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride levels of normal rats in chromium malate groups had no significant change when compared with control group and chromium picolinate group under physiologically relevant conditions. The serum and organ content of Cr in chromium malate groups had no significant change compared with control group. No significant changes were found in morris water maze test and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and true choline esterase (TChE) activity. The results indicated that supplementation with chromium malate did not cause measurable toxicity and has no obvious effect on glycometabolism and related enzymes, learning and memory ability, and related enzymes and lipid metabolism of female and male rats. The results of this study suggest that chromium malate is safe for human consumption. PMID:25900579

  17. Acute and subchronic oral toxicity studies in rats with nanoscale and pigment grade titanium dioxide particles.

    PubMed

    Warheit, D B; Brown, S C; Donner, E M

    2015-10-01

    Data generated using standardized testing protocols for toxicity studies generally provide reproducible and reliable results for establishing safe levels and formulating risk assessments. The findings of three OECD guideline-type oral toxicity studies of different duration in rats are summarized in this publication; each study evaluated different titanium dioxide (TiO2) particles of varying sizes and surface coatings. Moreover, each study finding demonstrated an absence of any TiO2 -related hazards. To briefly summarize the findings: 1) In a subchronic 90-day study (OECD TG 408), groups of young adult male and female rats were dosed with rutile-type, surface-coated pigment-grade TiO2 test particles (d50 = 145 nm - 21% nanoparticles by particle number criteria) by oral gavage for 90 days. The no-adverse-effect level (NOAEL) for both male and female rats in this study was 1000 mg/kg bw/day, the highest dose tested. The NOAEL was determined based on a lack of TiO2 particle-related adverse effects on any in-life, clinical pathology, or anatomic/microscopic pathology parameters; 2) In a 28-day repeated-dose oral toxicity study (OECD TG 407), groups of young adult male rats were administered daily doses of two rutile-type, uncoated, pigment-grade TiO2 test particles (d50 = 173 nm by number) by daily oral gavage at a dose of 24,000 mg/kg bw/day. There were no adverse effects measured during or following the end of the exposure period; and the NOAEL was determined to be 24,000 mg/kg bw/day; 3) In an acute oral toxicity study (OECD TG 425), female rats were administered a single oral exposure of surface-treated rutile/anatase nanoscale TiO2 particles (d50 = 73 nm by number) with doses up to 5000 mg/kg and evaluated over a 14-day post-exposure period. Under the conditions of this study, the oral LD50 for the test substance was >5000 mg/kg bw. In summary, the results from these three toxicity studies - each with different TiO2 particulate-types, demonstrated an absence of

  18. Induction of multiple granulomas in the liver with severe hepatocyte damage by montan wax, a natural food additive, in a 90-day toxicity study in F344 rats.

    PubMed

    Ikeda, Mico; Yamakawa, Keiko; Saoo, Kousuke; Matsuda, Yoko; Hosokawa, Kyoko; Takeuchi, Hijiri; Li, Jia-Qing; Zeng, Yu; Yokohira, Masanao; Imaida, Katsumi

    2008-02-01

    Montan wax is a mineral wax extracted from lignite type coal. It has been registered as a food additive in Japan though there have been no reports of toxicological evaluation, mainly due to the fact that it is considered a natural product. As part of a general safety assessment of montan wax, we have performed a 90-day toxicity study in Fisher 344 (F344) rats. Groups of 10 males and 10 females were given the material at dose levels of 0 (Group 1), 0.56 (Group 2), 1.67 (Group 3), or 5% (Group 4) in the diet for 90 days. During the experiment, there were no remarkable changes in general conditions and no deaths occurred in any group. On hematological examination, Hb, Ht, MCV and MCH were significantly decreased and WBC was significantly increased in all treated rats. On serum biochemical examination, AST and ALT were found to be elevated more than four fold in all treated groups as compared to the respective control group values in both sexes. Furthermore, relative organ weights for the liver, spleen, lung and kidneys were increased in all treated groups of both sexes. Histopathological examination revealed diffuse multiple granulomas in the livers with severe hepatocyte damage and lymphocytic infiltration. Granulomatous lesions were also apparent in the mesenteric lymph nodes in all treated males and females. These findings clearly demonstrate that montan wax, at doses of more than 0.56% in the diet, induces multiple granulomas with severe inflammation in the liver. Because pathological, hematological and serum biochemical changes were observed in the lowest dose group, a no-observed-adverse-effect level (NOAEL) could not be determined in the present study. PMID:17950973

  19. ORAL TOXICITY OF CARBON TETRACHLORIDE: ACUTE, SUBACUTE, AND SUBCHRONIC STUDIES IN RATS

    EPA Science Inventory

    The investigation was conducted to characterize the acute, subacute and subchronic toxic potency of ingested carbon tetrachloride (CCl4). In the first acute and subchronic toxicity study, male Sprague-Dawley rats of 300-350 g were gavaged with 0, 20, 40 or 80 mg CCl4/kg once dail...

  20. 40 CFR 798.6560 - Subchronic delayed neuro-toxicity of organophosphorus substances.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 33 2013-07-01 2013-07-01 false Subchronic delayed neuro-toxicity of organophosphorus substances. 798.6560 Section 798.6560 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Neurotoxicity § 798.6560 Subchronic...

  1. 40 CFR 798.6560 - Subchronic delayed neuro-toxicity of organophosphorus substances.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 32 2014-07-01 2014-07-01 false Subchronic delayed neuro-toxicity of organophosphorus substances. 798.6560 Section 798.6560 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Neurotoxicity § 798.6560 Subchronic...

  2. Modifications of azoxymethane-induced carcinogenesis and 90-day oral toxicities of 2-tetradecylcyclobutanone as a radiolytic product of stearic acid in F344 rats

    PubMed Central

    Sato, Makoto; Todoriki, Setsuko; Takahashi, Tetsuyuki; Hafez, Ezar; Takasu, Chie; Uehara, Hisanori; Yamakage, Kohji; Kondo, Takashi; Matsumoto, Kozo; Furuta, Masakazu; Izumi, Keisuke

    2015-01-01

    A 90-day oral toxicity test in rats was performed to evaluate the toxicity of 2-tetradecylcyclobutanone (2-tDCB), a unique radiolytic product of stearic acid. Six-week-old male and female F344 rats (n=15/group) were given 2-tDCB at concentrations of 0, 12, 60 and 300 ppm in a powder diet for 13 weeks. Slight dose-dependent increases in serum total protein and albumin in male rats were found, but these changes were not considered to be a toxic effect. The fasting, but not non-fasting, blood glucose levels of the male rats in the 300 ppm group and female rats in the 60 and 300 ppm groups were lower than those of the controls. Gas chromatography-mass spectrometry analysis showed dose-dependent accumulation of 2-tDCB in adipose tissue, notably in males. Next, we performed an azoxymethane (AOM)-induced two-stage carcinogenesis study. After injection of 6-week-old male F344 rats (n=30/group) once a week for 3 weeks, the animals received 2-tDCB at concentrations of 0, 10, 50 and 250 ppm in a powder diet for 25 weeks. The incidences of colon tumors for the 2-tDCB dosages were 34%, 45%, 40% and 37%, respectively, and were not statistically significant. These data suggest that 2-tDCB shows no toxic or tumor-modifying effects under the present conditions, and that the no-observed-adverse-effect level for 2-tDCB is 300 ppm in both sexes, equivalent to 15.5 mg/kg b.w./day in males and 16.5 mg/kg b.w./day in females. PMID:26028819

  3. Modifications of azoxymethane-induced carcinogenesis and 90-day oral toxicities of 2-tetradecylcyclobutanone as a radiolytic product of stearic acid in F344 rats.

    PubMed

    Sato, Makoto; Todoriki, Setsuko; Takahashi, Tetsuyuki; Hafez, Ezar; Takasu, Chie; Uehara, Hisanori; Yamakage, Kohji; Kondo, Takashi; Matsumoto, Kozo; Furuta, Masakazu; Izumi, Keisuke

    2015-04-01

    A 90-day oral toxicity test in rats was performed to evaluate the toxicity of 2-tetradecylcyclobutanone (2-tDCB), a unique radiolytic product of stearic acid. Six-week-old male and female F344 rats (n=15/group) were given 2-tDCB at concentrations of 0, 12, 60 and 300 ppm in a powder diet for 13 weeks. Slight dose-dependent increases in serum total protein and albumin in male rats were found, but these changes were not considered to be a toxic effect. The fasting, but not non-fasting, blood glucose levels of the male rats in the 300 ppm group and female rats in the 60 and 300 ppm groups were lower than those of the controls. Gas chromatography-mass spectrometry analysis showed dose-dependent accumulation of 2-tDCB in adipose tissue, notably in males. Next, we performed an azoxymethane (AOM)-induced two-stage carcinogenesis study. After injection of 6-week-old male F344 rats (n=30/group) once a week for 3 weeks, the animals received 2-tDCB at concentrations of 0, 10, 50 and 250 ppm in a powder diet for 25 weeks. The incidences of colon tumors for the 2-tDCB dosages were 34%, 45%, 40% and 37%, respectively, and were not statistically significant. These data suggest that 2-tDCB shows no toxic or tumor-modifying effects under the present conditions, and that the no-observed-adverse-effect level for 2-tDCB is 300 ppm in both sexes, equivalent to 15.5 mg/kg b.w./day in males and 16.5 mg/kg b.w./day in females. PMID:26028819

  4. Subchronic toxicity and genotoxicity of diiodomethyl-p-tolylsulfone (DIMPTS) in laboratory animals.

    PubMed

    Berdasco, Nancy Anne M; Pitt, Jeffrey A; Saghir, Shakil A; Spencer, Pamela J

    2012-04-01

    These studies were conducted to determine subchronic toxicity and genotoxicity of the biocide diiodomethyl-p-tolysulfone (DIMPTS) in rats and dogs. Male and female Sprague-Dawley rats and Beagle dogs were administered DIMPTS for 90-days via the diet at 0, 5, 20, and 80 mg/kg/day to rats and via capsules at 0, 2, 10, and 60 mg/kg/day to dogs. In rats, the only treatment-related finding was squamous metaplasia of the salivary gland duct in the 80 mg/kg/day group. In dogs, female body weights in the high-dose group were significantly lower than controls. Altered clinical pathology parameters were considered secondary to inflammatory changes observed in some of the dogs. Treatment-related alterations were found in the thyroid glands, salivary glands, GI-tract in the mid- and/or high-dose groups. DIMPTS was negative in the four in vitro and one in vivo genotoxicity assays. The toxicological effects noted in the two mammalian species are consistent with the principal toxic effects of iodine, and are proposed to arise from release of iodide from the DIMPTS molecule with toxic sequelae. PMID:22210449

  5. Subchronic oral toxicity in guinea pigs of soot from a polychlorinated biphenyl-containing transformer fire

    SciTech Connect

    DeCaprio, A.P.; McMartin, D.N.; Silkworth, J.B.; Rej, R.; Pause, R.; Kaminsky, L.S.

    1983-04-01

    The soot was determined to contain polychlorinated biphenyls, biphenylenes, dibenzodioxins, and dibenzofurans. The present study evaluates soot toxicity in guinea pigs receiving 0, 0.2, 1.9, 9.3, or 46.3 ppm soot in the feed for 90 days or 231.5 ppm for 32 days. At 231.5 ppm, body weight loss, thymic atrophy, bone marrow depletion, skeletal muscle and gastrointestinal tract epithelial degeneration, and fatty infiltration of hepatocytes were observed. Mortality had reached 35% by Day 32 (when survivors were killed), with total soot consumption of approximately 400 mg/kg. At 46.3 or 9.3 ppm soot, a reduced rate of body weight gain was observed, and at 46.3 ppm, the mortality by Day 90 was 30%. Relative (to body) thymus weights were decreased in both groups, while relative spleen weights were increased at 46.3 ppm soot only. Salivary gland interlobular duct squamous metaplasia and focal lacrimal gland adenitis were detected histopathologically, while bone marrow depletion was noted only in females at the higher dose. Diminished serum alanine aminotransferase (ALT) activity in both sexes and decreased serum sodium levels in male and potassium levels in female animals were detected at both dose levels. No effectse were noted in animals receiving 0.2 ppm soot for 90 days. Salivary gland duct metaplasia has not been previously reported. Toxic effects of this subchronic exposure were observed at lower total doses than with acute exposure, although variations in absorption due to the effects of different vehicles (aqueous in the acute study versus the feed in this study) could account for some or all of this difference.

  6. [Subchronic toxicity testing of mold-ripened cheese].

    PubMed

    Schoch, U; Lüthy, J; Schlatter, C

    1984-08-01

    The biological effects of known mycotoxins of Penicillium roqueforti or P. camemberti and other still unknown, but potentially toxic metabolites in mould ripened cheese (commercial samples of Blue- and Camembert cheese) were investigated. High amounts of mycelium (equivalents of 100 kg cheese/man and day) were fed to mice in a subchronic feeding trial. The following parameters were determined: development of body weight, organ weights, hematology, blood plasma enzymes. No signs of adverse effects produced by cheese mycotoxins could be detected after 28 days. No still unknown toxic metabolites could be demonstrated. From these results no health hazard from the consumption of mould ripened cheese, even in high amounts, appears to exist. PMID:6485557

  7. 40 CFR 79.62 - Subchronic toxicity study with specific health effect assessments.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 16 2011-07-01 2011-07-01 false Subchronic toxicity study with specific health effect assessments. 79.62 Section 79.62 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) REGISTRATION OF FUELS AND FUEL ADDITIVES Testing Requirements for Registration § 79.62 Subchronic...

  8. Acute and subchronic toxicity of ethylene glycol monobutyl ether.

    PubMed Central

    Tyler, T R

    1984-01-01

    The available information on the acute and subchronic toxicity of ethylene glycol monobutyl ether is reviewed. Data from animal studies have been examined from the standpoint of dose-response relationships and the sensitivity of various animal species, including man, to the effects of this chemical. In view of recent findings with other chemically related glycol ethers, particular attention has been given to possible adverse effects on blood and testicular tissue. In evaluating the hazard that this chemical may pose to man, consideration has been given to likely routes of exposure and its irritant properties. It is concluded that the available information continues to support the current ACGIH TWA8-TLV of 25 ppm with a STEL of 75 ppm. PMID:6499803

  9. Toxicologic evaluation of DHA-rich algal oil: Genotoxicity, acute and subchronic toxicity in rats.

    PubMed

    Schmitt, D; Tran, N; Peach, J; Bauter, M; Marone, P

    2012-10-01

    DHA-rich algal oil ONC-T18, tested in a battery of in vitro and in vivo genotoxicity tests, did not show mutagenic or genotoxic potential. The acute oral LD50 in rats has been estimated to be greater than 5000 mg/kg of body weight. In a 90-day subchronic dietary study, administration of DHA-rich algal oil at concentrations of 0, 10,000, 25,000, and 50,000 ppm in the diet for 13 weeks did not produce any significant toxicologic manifestations. The algal oil test article was well tolerated as evidenced by the absence of major treatment-related changes in the general condition and appearance of the rats, neurobehavioral endpoints, growth, feed and water intake, ophthalmoscopic examinations, routine hematology and clinical chemistry parameters, urinalysis, or necropsy findings. The no observed adverse effect level (NOAEL) was the highest level fed of 50,000 ppm which is equivalent to 3,305 and 3,679 mg/kg bw/day, for male and female rats, respectively. The studies were conducted as part of an investigation to examine the safety of DHA-rich algal oil. The results confirm that it possesses a toxicity profile similar to other currently marketed algal oils and support the safety of DHA-rich algal oil for its proposed use in food. PMID:22898615

  10. Genotoxicity and subchronic oral toxicity of L-ornithine monohydrochloride.

    PubMed

    Ishida, Shigeru; Sarada, Miko; Seki, Hiroshi; McGirr, Larry; Lau, Annette; Morishita, Koji

    2013-12-01

    L-Ornithine monohydrochloride was evaluated in two in vitro genotoxicity assays and a rat 90-day oral toxicity study. No evidence of genotoxicity was observed in the reverse bacterial mutation assay or the chromosome aberration test at doses of up to 5000 μg/plate or 1686 μg/mL, respectively, both in the presence and absence of metabolic activation. Rats were administered L-ornithine monohydrochloride at dietary concentrations of 0 (basal diet), 1.25%, 2.5%, or 5.0% for 90 days. No changes in body weight, food consumption, ophthalmoscopy, or hematology were observed. Transient increases in water intake and urinary volume, and a decrease in specific gravity were observed in males receiving 5.0% L-ornithine monohydrochloride; however, these were likely attributable to the central role of ornithine in the urea cycle and the consequent increase in urea production. A decrease in serum chloride concentration and an increase in urinary chloride excretion were observed; however, these were likely attributable to administration of the hydrochloride salt of ornithine and were not considered to be of any toxicological significance. No remarkable findings were noted at necropsy. Based on the results of the study, a no-observed-adverse effect level (NOAEL) of 3445 and 3986 mg/kg body weight/day was established for male and female rats. PMID:23994624

  11. Safety assessment of meat from transgenic cattle by 90-day feeding study in rats.

    PubMed

    Liu, Shan; Li, Chen-Xi; Feng, Xiao-Lian; Wang, Hui-Ling; Liu, Hai-Bo; Zhi, Yuan; Geng, Gui-Ying; Zhao, Jie; Xu, Hai-Bin

    2013-07-01

    The study was carried out to evaluate the subchronic toxicity of meat derived from human lactoferrin gene-modified cattle in male and female Wistar rats. Rats were fed 5% or 10% transgenic meat diet, 5% or 10% conventional meat diet, or AIN93G diet for 90 days. During the study, body weight and food consumption were weighed weekly and clinical observations were conducted daily. At the end of the study, urinary examination, hematology and blood biochemistry examination, macroscopic and microscopic examinations were performed. There were no biologically significant differences in these factors between the rat groups fed transgenic meat diet and conventional meat diet. Therefore, the present 90-day rodent feeding study suggests that meat derived from the transgenic cattle is equivalent to meat from conventional cattle in use as dietary supplements. PMID:23583492

  12. Toxicological assessment of enzyme-treated asparagus extract in rat acute and subchronic oral toxicity studies and genotoxicity tests.

    PubMed

    Ito, Tomohiro; Ono, Tomoko; Sato, Atsuya; Goto, Kazunori; Miura, Takehito; Wakame, Koji; Nishioka, Hiroshi; Maeda, Takahiro

    2014-03-01

    The safety of enzyme-treated asparagus extract (ETAS) developed as a novel anti-stress functional material was assessed in acute and subchronic studies and genotoxicity assays. In the acute oral dose toxicity study, all rats survived during the test period and ETAS did not influence clinical appearance, body weight gain and necropsy findings at a dosage of 2000mg/kg body weight. Thus, the 50% lethal dose (LD50) of ETAS was determined to be greater than 2000mg/kg. The 90-day subchronic study (500, 1000 and 2000mg/kg body weight, delivered by gavage) in rats reported no significant adverse effects in food consumption, body weight, mortality, urinalysis, hematology, biochemistry, necropsy, organ weight and histopathology. In the micronucleus test of mice, the incidence of micronuclei in ETAS-administered groups (500, 1000 and 2000mg/kg/day, injected twice) was equivalent to that of the negative control group, while the positive control group receiving mitomycin C showed a high incidence. The potential of ETAS to induce gene mutation was tested using four Salmonella typhimurium strains and Escherichia coli WP2uvrA. The test sample was not mutagenic to the test strains. These results support the safety of ETAS as food and dietary supplement. PMID:24389363

  13. Proteomic analysis of rat cerebral cortex following subchronic acrolein toxicity

    SciTech Connect

    Rashedinia, Marzieh; Lari, Parisa; Abnous, Khalil; Hosseinzadeh, Hossein

    2013-10-01

    Acrolein, a member of reactive α,β-unsaturated aldehydes, is a major environmental pollutant. Acrolein is also produced endogenously as a toxic by-product of lipid peroxidation. Because of high reactivity, acrolein may mediate oxidative damages to cells and tissues. It has been shown to be involved in a wide variety of pathological states including pulmonary, atherosclerosis and neurodegenerative diseases. In this study we employed proteomics approach to investigate the effects of subchronic oral exposures to 3 mg/kg of acrolein on protein expression profile in the brain of rats. Moreover effects of acrolein on malondialdehyde (MDA) levels and reduced glutathione (GSH) content were investigated. Our results revealed that treatment with acrolein changed levels of several proteins in diverse physiological process including energy metabolism, cell communication and transport, response to stimulus and metabolic process. Interestingly, several differentially over-expressed proteins, including β-synuclein, enolase and calcineurin, are known to be associated with human neurodegenerative diseases. Changes in the levels of some proteins were confirmed by Western blot. Moreover, acrolein increases the level of MDA, as a lipid peroxidation biomarker and decreased GSH concentrations, as a non-enzyme antioxidant in the brain of acrolein treated rats. These findings suggested that acrolein induces the oxidative stress and lipid peroxidation in the brain, and so that may contribute to the pathophysiology of neurological disorders. - Highlights: • Acrolein intoxication increased lipid peroxidation and deplete GSH in rat brain. • Effect of acrolein on protein levels of cerebral cortex was analyzed by 2DE-PAGE. • Levels of a number of proteins with different biological functions were increased.

  14. Subchronic inhalation toxicity of benzene in rats and mice

    SciTech Connect

    Ward, C.O.; Kuna, R.A.; Snyder, N.K.; Alsaker, R.D.; Coate, W.B.; Craig, P.H.

    1985-01-01

    A subchronic inhalation toxicity study of benzene was conducted in CD-1 mice and Sprague-Dawley rats. Four groups of animals consisting of 150 mice and 50 rats/sex each were exposed to concentrations of 1, 10, 30, and 300 ppm benzene vapor, 6 hours/day, 5 days/week, for 13 weeks. Additional groups of mice and rats, of equal size, were exposed under similar conditions to filtered air and served as control groups. Thirty mice and 10 rats/sex in each group were sacrificed after 7, 14, 28, 56, and 91 days of treatment. Criteria used to evaluate exposure-related effects included behavior, body weights, organ weights, clinical pathology, gross pathology, and histopathology. Fifty animals per sex of each species were exposed concurrently for cytogenetic studies. In addition, blood serum was obtained for immunological assays. The results of these two studies will be reported separately. No consistent exposure-related trends were seen in the clinical observations and body weight data. Exposure-related clinical pathology changes were seen in the high-level (300 ppm) animals of both species. In the mice, these changes included decreases in hematocrit, total hemoglobin, erythrocyte count, leukocyte count, platelet count, myeloid/erythroid ratios, and percentage of lymphocytes. Mean cell volume, mean cell hemoglobin, glycerol lysis time, and the incidence and severity of red cell morphologic changes were increased in the mice. In the rats, decreased lymphocyte counts and a relative increase in neutrophil percentages were the only exposure-related clinical pathology alterations. Histopathologic changes were present in the thymus, bone marrow, lymph nodes, spleen, ovaries, and testes of mice exposed to 300 ppm and in most cases the incidence and severity of the lesions were greater in the males.

  15. A 90-day study of three bruchid-resistant mung bean cultivars in Sprague-Dawley rats.

    PubMed

    Yao, Yang; Cheng, Xuzhen; Ren, Guixing

    2015-02-01

    Mung bean has been traditionally and widely used as an edible and medicinal plant in the South and Southeast Asia. Bruchid resistance mung bean has more potential in commercial use, but scarcely been evaluated for safety through standard in vivo toxicological studies. In the present study, subchronic oral toxicity studies of bruchid-resistant mung bean were designed and conducted in Sprague-Dawley (SD) rats for 90 days. During the subchronic oral toxicity study, no mortality and toxicologically significant changes in clinical signs, food consumption, opthalmoscopic examination, hematology, clinical biochemistry, macroscopic findings, organ weights and histopathological examination were noted in animal administered diet containing bruchid-resistant mung bean. These results demonstrated that bruchid resistant mung bean is as safe as conventional mung bean. PMID:25533792

  16. Safety assessment of methanol extract of red dragon fruit (Hylocereus polyrhizus): acute and subchronic toxicity studies.

    PubMed

    Hor, Sook Yee; Ahmad, Mariam; Farsi, Elham; Yam, Mun Fei; Hashim, Mohd Akmal; Lim, Chung Pin; Sadikun, Amirin; Asmawi, Mohd Zaini

    2012-06-01

    Recently, the fruits of Hylocereus polyrhizus, known as red dragon fruit, have received much attention from growers worldwide. However, there is little toxicological information regarding the safety of repeated exposure to these fruits. The present study evaluated the potential toxicity of a methanol extract of H. polyrhizus fruit after acute and subchronic administration in rats. In the acute toxicity study, single doses of fruit extract (1250, 2500 and 5000 mg/kg) were administered to rats by oral gavage, and the rats were then monitored for 14 days. In the subchronic toxicity study, the fruit extract was administered orally to rats at doses of 1250, 2500 and 5000 mg/kg/day for 28 days. There was no mortality or signs of acute or subchronic toxicity. There was no significant difference in body weight, relative organ weight or hematological parameters in the subchronic toxicity study. Biochemical analysis showed some significant changes, including creatinine, globulin, total protein and urea levels. No abnormality of internal organs was observed between treatment and control groups. The lethal oral dose of the fruit extract is more than 5000 mg/kg and the no-observed-adverse-effect level (NOAEL) of the extract for both male and female rats is considered to be 5000 mg/kg per day for 28 days. PMID:22440551

  17. Subchronic toxicity study of standardized methanolic extract of Mitragyna speciosa Korth in Sprague-Dawley Rats.

    PubMed

    Ilmie, Mohd U; Jaafar, Hasnan; Mansor, Sharif M; Abdullah, Jafri M

    2015-01-01

    Mitragyna speciosa Korth, or better known as ketum, has long been used by traditional folk around Southeast Asia to prevent fatigue from working under hot tropical weather and as a replacement of opium, which can then cause addiction. To date, no findings have been reported of the toxic effect of ketum subchronically (28 days). Hence, the aim of this study was to investigate the toxicity of subchronic effect of standardized methanolic extract of ketum (SMEMS) in Sprague-Dawley rats. Rats were orally administered with 100, 200, and 500 mg/kg of SMEMS for 28 days. Body weights were recorded daily. They were terminated at day 28 to obtain data for hematology, biochemistry, and histopathology of the brain, liver, kidney, lung, heart, sciatic nerve, and spinal cord. The SMEMS affected body weight compared to control group. Biochemistry findings showed that liver and kidney were affected with the abnormal values in AST, creatinine, globulin, glucose, total protein, and urea. However, SMEMS produced toxic effect more to liver, kidney, and lung than other organs as observed histopathologically. The results suggested subchronic exposure of ketum is toxic to the physiology of the animals. PMID:26136645

  18. Subchronic toxicity study of standardized methanolic extract of Mitragyna speciosa Korth in Sprague-Dawley Rats

    PubMed Central

    Ilmie, Mohd U.; Jaafar, Hasnan; Mansor, Sharif M.; Abdullah, Jafri M.

    2015-01-01

    Mitragyna speciosa Korth, or better known as ketum, has long been used by traditional folk around Southeast Asia to prevent fatigue from working under hot tropical weather and as a replacement of opium, which can then cause addiction. To date, no findings have been reported of the toxic effect of ketum subchronically (28 days). Hence, the aim of this study was to investigate the toxicity of subchronic effect of standardized methanolic extract of ketum (SMEMS) in Sprague-Dawley rats. Rats were orally administered with 100, 200, and 500 mg/kg of SMEMS for 28 days. Body weights were recorded daily. They were terminated at day 28 to obtain data for hematology, biochemistry, and histopathology of the brain, liver, kidney, lung, heart, sciatic nerve, and spinal cord. The SMEMS affected body weight compared to control group. Biochemistry findings showed that liver and kidney were affected with the abnormal values in AST, creatinine, globulin, glucose, total protein, and urea. However, SMEMS produced toxic effect more to liver, kidney, and lung than other organs as observed histopathologically. The results suggested subchronic exposure of ketum is toxic to the physiology of the animals. PMID:26136645

  19. Applicability of subchronic toxicity test with Hyalella azteca for toxicity identification evaluation programs

    SciTech Connect

    Putt, A.E.; Jop, K.M.

    1995-12-31

    A series of screening tests including the short-term chronic exposure of Ceriodaphnia dubia to sediment pore waters, 10-day exposures of Chironomus tentans and Hyalella azteca to bulk sediments and a bioaccumulation study with Lumbriculus variegatus were performed as part of an ecological risk assessment of Plow Shop Pond, Fort Devens, Massachusetts. Chronic endpoints such as reproduction and growth indicated sediment toxicity, however, a toxicity identification evaluation program was initiated to further define the source and extent of the toxicity. A short-term chronic exposure with C. dubia was a logical choice for the TIE, however, since amphipods are epibenthic organisms, they are a better surrogate of sediment dwelling organisms than a water column species such as C. dubia. Observations performed during H. azteca culture suggested that this species of amphipod could thrive in the water column for up to three weeks. Therefore, 7-day old H. azteca were exposed to pore water samples under static-renewal conditions for 10 days. Survival and growth (i.e., dry weight) were determined at the termination of each exposure. Laboratory control group performance consistently averaged a {>=}90% survival and {>=}43 {micro}g of dry weight per amphipod. Growth of amphipods used in each exposure generally exceeded two times the initial body weight after 10 days of exposure. Previous studies have indicated that the growth and reproductive response of H. azteca are positively correlated for a given set of exposure conditions. The results of these 10-day subchronic exposures with H. azteca provide a consistent and reliable measure of the chronic sediment toxicity with a benthic invertebrate for toxicity identification evaluation programs.

  20. Subchronic toxicity study in vivo and allergenicity study in vitro for genetically modified rice that expresses pharmaceutical protein (human serum albumin).

    PubMed

    Sheng, Yao; Qi, Xiaozhe; Liu, Yifei; Guo, Mingzhang; Chen, Siyuan; He, Xiaoyun; Huang, Kunlun; Xu, Wentao

    2014-10-01

    Genetically modified (GM) crops that express pharmaceutical proteins have become an important focus of recent genetic engineering research. Food safety assessment is necessary for the commercial development of these crops. Subchronic toxicity study in vivo and allergenicity study in vitro were designed to evaluate the food safety of the rice variety expressing human serum albumin (HSA). Animals were fed rodent diets containing 12.5%, 25.0% and 50.0% GM or non-GM rice for 90 days. The composition analysis of the GM rice demonstrated several significant differences. However, most of the differences remained within the ranges reported in the literature. In the animal study, a range of indexes including clinical observation, feed efficiency, hematology, serum chemistry, organ weights and histopathology were examined. Random changes unrelated to the GM rice exposure, within the range of historical control values and not associated with any signs of illness were observed. The results of heat stability and in vitro digestion of HSA indicated no evidence of potential allergenicity of the protein. Overall, the results of these studies suggest that the GM rice appears to be safe as a dietary ingredient when it is used at up to 50% in the diet on a subchronic basis. PMID:25086369

  1. Anti-atherogenic and anti-ischemic potentials of Croton membranaceus observed during sub-chronic toxicity studies

    PubMed Central

    Afriyie, Dan K.; Asare, George A.; Bugyei, Kwasi; Asiedu-Gyekye, Isaac; Gyan, Ben A.; Adjei, Samuel; Addo, Phyllis; Sittie, Archibald; Nyarko, Alexander K.

    2013-01-01

    Background: Croton membranaceus (CM) is used for benign prostate hyperplasia treatment. Objective: Sub-chronic toxicity studies are non-existent and provided the basis for this study. Materials and Methods: 90 days oral administration of a low dose (LD) (30 mg/kg b. wt.), medium dose (MD) (150 mg/kg b. wt.), and high dose (HD) (300 mg/kg b. wt.) CM aqueous root extract to 3 groups (n=6 each) of male Sprague-Dawley rats, alongside a control group, was undertaken. Urinalysis, hepato-renal function tests, lipid profile, cardiac enzymes, and routine hematology tests were performed. Results: Triglyceride levels (C=1.05±0.19, LD=0.64±0.08, MD=0.55±0.04, HD=0.50±0.02 mmol/L) were significantly reduced (P<0.05). Very low density lipoprotein (C=0.48±0.09, LD=0.29±0.04, MD=0.25±0.02, HD=0.23±0.01 mmol/L) decreased significantly (P<0.05). Cardiac enzymes-creatinine kinase (C=568±172, LD=315±79, MD=441±209, HD=286±81 IU/L) decreased markedly (P<0.05) alongside lactate dehydrogenase (C=2675±875, LD=1667±1229, MD=1186±442, HD=855±239 IU/L) (P<0.05). Conclusion: C. membranaceus aqueous root extract is non-toxic but demonstrates anti-atherogenic and anti-ischemic potentials. PMID:23598919

  2. Subchronic and chronic toxicity of ingested 1,3-dichloropropene in dogs.

    PubMed

    Stebbins, K E; Quast, J F; Haut, K T; Stott, W T

    1999-12-01

    The potential toxicologic effects to dogs of 1,3-dichloropropene (1, 3-D), a soil fumigant used for the control of nematodes, were investigated. The 13-week subchronic toxicity study consisted of male and female beagle dogs (4/sex/dose group) given approximately 0, 5, 15, or 41 mg 1,3-D/kg body wt/day (approximately equivalent amounts of cis and trans isomers) via their diets. The 1-year chronic toxicity study consisted of male and female beagle dogs (4/sex/dose group) provided diets delivering approximately 0, 0.5, 2. 5, or 15 mg/kg body wt/day. The test material was stabilized in the feed by microencapsulation in a starch/sucrose matrix (80/20). In both the 13-week and the 1-year studies, the primary effect of 1,3-D in male and female dogs ingesting a dosage of >/=15 mg/kg/day was hypochromic, microcytic anemia. The anemia was regenerative, with increased erythropoietic activity characterized by polychromasia of erythrocytes and increased numbers of reticulocytes in peripheral blood. In the 13-week study, the anemia in dogs given 41 mg/kg/day progressively worsened over time, while the anemia in dogs given 15 mg/kg/day remained relatively constant between 42 and 90 days of dosing. Partial reversal of the anemia of high-dose animals occurred during a 5-week recovery period following the 13-week dosing regimen. In the 13-week study, terminal fasted body weights of males given 15 or 41 mg/kg/day were decreased 3 and 28%, respectively, and body weights of females given 5, 15, or 41 mg/kg/day were decreased 4.5, 12, and 24%, respectively, relative to controls. Males given 5 mg/kg/day for 13 weeks had no change in body weights relative to controls. In the 1-year study, the hypochromic microcytic anemia in dogs given 15 mg/kg/day remained relatively constant in severity between 3 and 12 months of treatment. Histopathologic alterations associated with anemia in the 1-year study consisted of increased hematopoiesis of the bone marrow and increased extramedullary

  3. Nephroprotective effect of bee honey and royal jelly against subchronic cisplatin toxicity in rats.

    PubMed

    Ibrahim, Abdelazim; Eldaim, Mabrouk A Abd; Abdel-Daim, Mohamed M

    2016-08-01

    Cisplatin is one of the most potent and effective chemotherapeutic agents. However, its antineoplastic use is limited due to its cumulative nephrotoxic side effects. Therefore, the present study was undertaken to examine the nephroprotective potential of dietary bee honey and royal jelly against subchronic cisplatin toxicity in rats. Male Wistar rats were randomly divided into controls, cisplatin-treated, bee honey-pretreated cisplatin-treated and royal jelly-pretreated cisplatin-treated groups. Bee honey and royal jelly were given orally at doses of 20 and 100 mg/kg, respectively. Subchronic toxicity was induced by cisplatin (1 mg/kg bw, ip), twice weekly for 10 weeks. Cisplatin treated animals revealed a significant increase in serum level of renal injury products (urea, creatinine and uric acid). Histopathologically, cisplatin produced pronounced tubulointerstitial injuries, upregulated the fibrogenic factors, α-smooth muscle actin (α-SMA) and transforming growth factor β1(TGF-β1), and downregulated the cell proliferation marker, bromodeoxyuridine (Brdu). Dietary bee honey and royal jelly normalized the elevated serum renal injury product biomarkers, improved the histopathologic changes, reduced the expression of α-SMA and TGF-β1 and increased the expression of Brdu. Therefore, it could be concluded that bee honey, and royal jelly could be used as dietary preventive natural products against subchronic cisplatin-induced renal injury. PMID:25720368

  4. Sub-chronic toxicity of low concentrations of industrial volatile organic pollutants in vitro

    SciTech Connect

    McDermott, Catherine; Allshire, Ashley; Pelt, Frank N.A.M. van; Heffron, James J.A. . E-mail: j.heffron@ucc.ie

    2007-02-15

    Organic solvents form an important class of pollutants in the ambient air and have been associated with neurotoxicity and immunotoxicity in humans. Here we investigated the biological effects of sub-chronic exposure to industrially important volatile organic solvents in vitro. Jurkat T cells were exposed to toluene, n-hexane and methyl ethyl ketone (MEK) individually for 5 days and solvent exposure levels were confirmed by headspace gas chromatography. A neuroblastoma cell line (SH-SY5Y) was exposed to toluene for the same period. Following exposure, cells were harvested and toxicity measured in terms of the following endpoints: membrane damage (LDH leakage), perturbations in intracellular free Ca{sup 2+}, changes in glutathione redox status and dual-phosphorylation of MAP kinases ERK1/2, JNK and p38. The results show that sub-chronic exposure to the volatile organic solvents causes membrane damage, increased intracellular free calcium and altered glutathione redox status in both cell lines. However, acute and sub-chronic solvent exposure did not result in MAP kinase phosphorylation. Toxicity of the solvents tested increased with hydrophobicity. The lowest-observed-adverse-effect-levels (LOAELs) measured in vitro were close to blood solvent concentrations reported for individuals exposed to the agents at levels at or below their individual threshold limit values (TLVs)

  5. Safety Evaluation of Yukmijihwang-tang: Assessment of Acute and Subchronic Toxicity in Rats

    PubMed Central

    Ha, Hyekyung; Lee, Jun Kyoung; Lee, Ho Young; Koh, Woo Suk; Seo, Chang Seob; Lee, Mi-Young; Huang, Dae Sun; Shin, Hyeunkyoo

    2011-01-01

    Yukmijihwang-tang (YMJ; Liu wei di huang tang (China), Rokumigan (Japan)) has been used in the treatment of diseases including renal disorder, cognitive vitality, and diabetes mellitus. However, there is very little information regarding the toxicity of YMJ to give an assurance of safety for clinical treatment. To provide safety information for YMJ, we evaluated its acute and sub-chronic toxicity in rats. The single-dose toxicity of YMJ was examined using Sprague-Dawley rats. Rats were treated with YMJ extract orally at 0, 500, 1000, or 2000 mg/kg body weight. After a single administration, clinical signs were observed every day for two weeks, and body weights were measured five times, including an initial measurement on day 1 (the day of administration). In the sub-chronic oral toxicity study, YMJ was administered to rats at 0, 500, 1000, or 2000 mg/kg/day for 13 weeks. Mortalities, clinical signs, body weight changes, food and water consumption, ophthalmologic findings, urinalysis, hematological and biochemical parameters, gross findings, organ weights, and histological examination were monitored during the study period. We found no mortality and no abnormalities in clinical signs, body weights, and necropsy findings for any of the animals in the acute and sub-chronic studies following oral administration in the rat at up to 2000 mg/kg/day YMJ. YMJ may not have any single-dose toxicity; the LD50 of YMJ was over 2000 mg/kg, and it is safe for rats. The no-observed-adverse-effect-level (NOAEL) was considered to be 2000 mg/kg/day. PMID:21234385

  6. Subchronic oral toxicity study of diisopropyl methylphosphonate in mink.

    PubMed

    Bucci, T J; Wustenberg, W; Perman, V; Weiss, D J; Dacre, J C; Baumel, I P; Parker, R M

    1994-02-01

    Diisopropyl methylphosphonate (DIMP), produced during manufacture of the chemical agent GB (Sarin), is a groundwater contaminant at Rocky Mountain Arsenal, Colorado. DIMP was fed for 90 days to dark brown "Ranch Wild" mink housed under controlled indoor conditions. One-year-old mink, 10 of each sex, were fed 0, 50, 450, 2700, 5400, or 8000 ppm in standard ranch diet. Actual DIMP consumption was 0, 8, 73, 400, 827, and 1136 mg/kg body wt/day, respectively. Two additional groups of 10 served as "pair-fed" controls. Body weight and food intake were recorded weekly. Complete blood count and 15 chemical analytes were measured at Weeks 0, 3, 7, and 13. Necropsy and microscopic examination were performed on all mink. No clinical morbidity or deaths occurred. Both sexes fed 8000 ppm ate approximately 20% less and weighed approximately 20% less than the controls; 5400 ppm females had a 10% weight decrement. Plasma cholinesterase (ChE) decreased in the top three dose groups starting at Week 3. At 13 weeks, decrements were approximately 50% but returned to normal after 1 week without DIMP. Erythrocyte ChE was not reduced. Heinz bodies occurred in 10-15% of RBCs in 50% of 8000 ppm mink at 13 weeks, and 0.1-2.0% of RBCs in 25% at 2700 ppm. There were mild decreases in RBC count, hematocrit, and hemoglobin, and increases in reticulocyte count, at the 5400 and 8000 ppm doses. All recovered within 3 weeks after DIMP was withdrawn. The 8000 ppm group had marginal splenic hematopoiesis, histologically. No other treatment-related changes were noted. The 450 ppm dose was a clear no-effect level (approximately 73 mg DIMP/kg body wt/day). Compared to reports of similar studies of DIMP in rats and dogs, these mink displayed no unique species susceptibility. PMID:8005374

  7. Acute and Subchronic Toxic Effects of the Fruits of Physalis peruviana L.

    PubMed

    Perk, Basak Ozlem; Ilgin, Sinem; Atli, Ozlem; Duymus, Hale Gamze; Sirmagul, Basar

    2013-01-01

    The fruit of Physalis peruviana L. (PPL) has been traditionally used as antispasmodic, diuretic, antiseptic, sedative, and analgesic all over the world. We aimed to perform qualitative content analysis of the fruits of PPL and to clarify the in vitro genotoxicity and in vivo acute and subchronic toxicity of the fruit. Lyophilized fruit juice does not induce genetic damage. In the acute toxicity studies, LD50 value of the fruit was found to be more than 5000 mg kg(-1) for both sexes. According to the subchronic toxicity studies, hepatic, renal, and hematological toxic effects were not induced in both sexes. Plasma troponin I (only in the group treated with 5000 mg kg(-1) of lyophilized fruit juice) and troponin T levels were significantly increased in male groups treated with lyophilized fruit juice compared to the control group. Furthermore, potassium level was significantly increased in the male group treated with 5000 mg kg(-1) of lyophilized fruit juice. These findings were considered to indicate the myocardial damage particularly in the male group treated with 5000 mg kg(-1) of lyophilized fruit juice. In conclusion, lyophilized fruit juice of PPL is shown to induce cardiac toxicity only at high doses and in male gender. PMID:24369482

  8. Acute and Subchronic Toxic Effects of the Fruits of Physalis peruviana L.

    PubMed Central

    Perk, Basak Ozlem; Ilgin, Sinem; Atli, Ozlem; Duymus, Hale Gamze; Sirmagul, Basar

    2013-01-01

    The fruit of Physalis peruviana L. (PPL) has been traditionally used as antispasmodic, diuretic, antiseptic, sedative, and analgesic all over the world. We aimed to perform qualitative content analysis of the fruits of PPL and to clarify the in vitro genotoxicity and in vivo acute and subchronic toxicity of the fruit. Lyophilized fruit juice does not induce genetic damage. In the acute toxicity studies, LD50 value of the fruit was found to be more than 5000 mg kg−1 for both sexes. According to the subchronic toxicity studies, hepatic, renal, and hematological toxic effects were not induced in both sexes. Plasma troponin I (only in the group treated with 5000 mg kg−1 of lyophilized fruit juice) and troponin T levels were significantly increased in male groups treated with lyophilized fruit juice compared to the control group. Furthermore, potassium level was significantly increased in the male group treated with 5000 mg kg−1 of lyophilized fruit juice. These findings were considered to indicate the myocardial damage particularly in the male group treated with 5000 mg kg−1 of lyophilized fruit juice. In conclusion, lyophilized fruit juice of PPL is shown to induce cardiac toxicity only at high doses and in male gender. PMID:24369482

  9. Study of Subchronic Toxicity of Relatox on Sexually Immature Animals.

    PubMed

    Churin, A A; Fomina, T I; Ermolaeva, L A; Vetoshkina, T V; Dubskaya, T Yu; Lamzina, T Yu; Fedorova, E P; Neupokoeva, O V; Nikiforova, A N

    2015-11-01

    Intramuscular injections of Relatox in therapeutic and toxic doses to young outbred laboratory rats for 14 days caused no changes in the peripheral blood and bone marrow parameters, serum biochemical parameters, and morphology of the major viscera. In the toxic dose, the drug caused local irritation (inflammation, atrophy, and sclerosis in muscle tissue). Regeneration processes started in muscle tissue 7 days after Relatox withdrawal. PMID:26593416

  10. Pentachlorotoluene and pentabromotoluene: results of a subacute and a subchronic toxicity study in the rat

    SciTech Connect

    Chu, I.; Villeneuve, D.C.; McDonald, B.; Secours, V.E.; Valli, V.E.

    1987-06-01

    Pentachlorotoluene (PCT) and pentabromotoluene (PBT) are environmental contaminants detected in the Great Lakes ecosystem. In view of the paucity of toxicity data and the potential for human exposure, a subacute (28 day) and a subchronic (91 day) study were conducted in the rat. In the subacute study, groups of 10 male and 10 female rats were fed the diet containing PCT or PBT at 0, 0.5, 5.0, 50 or 500 ppm for 28-days. In the subchronic study, the group size was increased to 15, the dose levels were 0, 0.05, 0.5, 5.0, 50 and 500 ppm in the diet and the exposure period was 91 days. Growth rate and food consumption were not affected by exposure to either chemical in the subacute and subchronic study. Clinical observations revealed no abnormalities. Decreased hemoglobin was observed in female rats fed 5.0 ppm PCT and higher levels in the subacute (28 day) study. In the same study the hematocrit value and erythrocyte numbers of females fed 5.0 or 500 ppm PCT diets were significantly lower than the control. In both subacute and subchronic studies mild dose-dependent histopathological changes were observed in the thyroid, liver and kidney of rats fed PCT and PBT diets. In general male rats were more susceptible than females to the treatment of PCT and PBT. Based on these data, it was concluded that the no observable adverse effect level for PCT was 50 ppm in the diet (3.5 mg/kg b.w./day) and that of PBT was 5.0 ppm (0.35 mg/kg b.w./day).

  11. Assessment of sub-chronic, hematological and histopathological toxicities of a herbal combination.

    PubMed

    Ahmed, Shadab; Khan, Rafeeq Alam; Feroz, Zeeshan

    2015-11-01

    The herbal combination under study consists of Withania somnifera, Tribulus terrestris, Mucuna pruriens and Argyria speciosa. Present study is mainly designed to investigate the gross physical, sub-chronic, hematological and histopathological effects of the combination widely used for its stimulating, revitalizing and fertility boosting effects in Pakistan. Sub-chronic, hematological and histopathological outcomes of herbal combination were assessed on 27 albino rabbits weighing from 1000 gm-1500 gm after giving herbal combination for 60 days in two doses 27 and 81 mg/kg against control. No significant toxicity was revealed during the entire period of study, however some biochemical changes were observed in kidney and liver but these changes did not coincide with histopathological findings. There was no mortality and evidence of systemic toxicity including hematological toxicity following 60 days administration of herbal combination. Results of present study suggest that further studies are required on large number of animals before reaching to a definite conclusion, more over clinical studies should also be conducted to confirm the possible toxic effects of the herbal combination. PMID:26639483

  12. Acute and sub-chronic toxicity of aqueous extracts of Chenopodium ambrosioides leaves in rats.

    PubMed

    da Silva, Marcel Gianni C; Amorim, Raimundo Neilson L; Câmara, Carlos C; Fontenele Neto, José Domingues; Soto-Blanco, Benito

    2014-09-01

    The present study aimed to evaluate the toxicity of aqueous extract of Chenopodium ambrosioides leaves. To measure acute toxicity, rats were administered 0, 0.3, 1.0, or 3.0 g/kg of aqueous extract from C. ambrosioides leaves by gavage. To analyze sub-chronic toxicity, rats were treated by oral gavage for 15 consecutive days with 0, 0.3, or 1.0 g/kg of extract of C. ambrosioides leaves. No animals from either trial exhibited any signs of toxicity. In the acute study, the highest dose of the extract led to an increase in the serum activities of alanine transaminase (ALT) and aspartate transaminase (AST) and a decrease in the serum levels of urea. In the sub-chronic test, rats treated with 1.0 g/kg for 15 days exhibited increased serum ALT activity and creatinine levels and mild cytoplasmic vacuolation of hepatocytes. The results indicate that aqueous extract from C. ambrosioides leaves produce slight hepatotoxic lesions in rats. PMID:24892475

  13. Aqueous extract of Senecio candicans DC induce liver and kidney damage in a sub-chronic oral toxicity study in Wistar rats.

    PubMed

    Lakshmanan, Hariprasath; Raman, Jegadeesh; Pandian, Arjun; Kuppamuthu, Kumaresan; Nanjian, Raaman; Sabaratam, Vikineswary; Naidu, Murali

    2016-08-01

    Senecio candicans DC. (Asteraceae) is used as a remedy for gastric ulcer and stomach pain in the Nilgiris, district, Tamil Nadu. The present investigation was carried out to evaluate the sub-chronic toxicity of an aqueous extract of Senecio candicans (AESC) plant in Wistar albino rats. The study was conducted in consideration of the OECD 408 study design (Repeated Dose 90-Day Oral Toxicity Study in Rodents) and the extract was administered via gavage at doses of 250, 500 or 750 mg/kg body weight per day for 90-days. Hematological, biochemical parameters were determined on days 0, 30, 60 and 90 of administration. Animals were euthanized after 90 d treatment and its liver and kidney sections were taken for histological study. The results of sub-chronic study showed significant increase (P < 0.05) in serum uric acid, creatinine, aspartate transaminase (AST) and alanine transaminase (ALP) levels. Histological examination of liver showed mild mononuclear infiltration in the portal trait, enlarged nucleus around the central vein and mild loss of hepatocyte architecture in rats treated with 750 mg/kg of AESC. Histological examination of kidney showed focal interstitial fibrosis, crowding of glomeruli and mild hydropic change with hypercellular glomeruli in rats treated with 750 mg/kg of AESC. However, no remarkable histoarchitectural change in hepatocytes and glomeruli were observed in rats treated with lower concentrations (250 and 500 mg/kg b.w.) of AESC compared to control group animals. The no-observed adverse effect level (NOAEL) of AESC in the present study was 500 mg/kg b.w. Signs of toxic effects are evident from the current study. Although AESC contains low concentrations of PA, findings from this study suggest that regular consumers of herbal remedies derived from this plant may develop kidney and liver toxicity. Further studies on the isolation and characterization of PAs are necessary to determine the safe dose level of the extract for therapeutic use

  14. Acute and subchronic toxicity assessment model of Ferula assa-foetida gum in rodents

    PubMed Central

    Goudah, Ayman; Abdo-El-Sooud, Khaled; Yousef, Manal A.

    2015-01-01

    Aim: The present study was performed to investigate acute and subchronic oral toxicity of Ferula assa-foetida gum (28 days) in Sprague Dawley rats. Materials and Methods: Acute oral administration of F. assa-foetida was done as a single bolus dose up to 5 g/kg in mice and subchronic toxicity study for 28 days was done by oral administration at doses of 0 (control) and 250 mg/kg in Sprague Dawley rats. Results: The obtained data revealed that oral administration of F. assa-foetida extract in rats for 28 successive days had no significant changes on body weight, body weight gain, the hematological parameters in rats all over the period of the experiment, and there are no significant increases in the activity of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine and urea. Liver of treated rats showed mild changes as thrombosis and sinusoidal leukocytosis. It also showed portal infiltration with inflammatory cells, while kidney of treated rat showed an atrophy of glomerular tuft, thickening of parietal layer of Bowman capsule, and focal tubular necrosis. It also showed dilatation and congestion of renal blood vessels. Conclusion: We concluded that F. assa-foetida gum had broad safety and little toxicity for short term use in dose of 250 mg/kg. PMID:27047139

  15. Subchronic Inhalation Toxicity of Trichloroacetonitrile on the Sprague Dawley Rats

    PubMed Central

    Han, Jeong-Hee; Chung, Yong-Hyun

    2015-01-01

    Trichloroacetonitrile is used as an intermediate in insecticides, pesticides, and dyes. In Korea alone, over 10 tons are used annually. Its oral and dermal toxicity is classified as category 3 according to the globally harmonized system of classification and labelling of chemicals, and it is designated a toxic substance by the Ministry of Environment in Korea. There are no available inhalation toxicity data on trichloroacetonitrile. Thus, the present study performed inhalation tests to provide data for hazard and risk assessments. Sprague-Dawley rats were exposed to trichloroacetonitrile at concentrations of 4, 16, or 64 ppm for 6 hour per day 5 days per week for 13 weeks in a repeated study. As a result, salivation, shortness of breath, and wheezing were observed, and their body weights decreased significantly (p < 0.05) in the 16 and 64 ppm groups. All the rats in 64 ppm group were dead or moribund within 4 weeks of the exposure. Some significant changes were observed in blood hematology and serum biochemistry (e.g., prothrombin time, ratio of albumin and globulin, blood urea nitrogen, and triglycerides), but the values were within normal physiological ranges. The major target organs of trichloroacetonitrile were the nasal cavity, trachea, and lungs. The rats exposed to 16 ppm showed moderate histopathological changes in the transitional epithelium and olfactory epithelium of the nasal cavity. Nasal-associated lymphoid tissue (NALT) and respiratory epithelium were also changed. Respiratory lesions were common in the dead rats that had been exposed to the 64 ppm concentration. The dead animals also showed loss of cilia in the trachea, pneumonitis in the lung, and epithelial hyperplasia in the bronchi and bronchioles. In conclusion, the no-observed-adverse-effect level (NOAEL) was estimated to be 4 ppm. The main target organs of trichloroacetonitrile were the nasal cavity, trachea, and lungs. PMID:26191387

  16. Broccoli seed extract: Genotoxicity and subchronic toxicity studies.

    PubMed

    Zhou, Yu; Yang, Hui; Li, Yongning; Lynch, B; Jia, Xudong

    2015-10-01

    Potential health benefits have been attributed to broccoli consumption. Hence, there is potential for use of broccoli seed extract (BSE) in food or for use as a dietary supplement. To assess the potential safety of a BSE product, three genotoxicity experiments, including an Ames, in vivo mouse micronucleus, and in vivo mouse sperm abnormality assay, were carried out. BSE was subject to an acute oral toxicity test and was evaluated in a 30-day feeding study in rats. BSE showed no mutagenic activity in the Ames assay and no evidence of genotoxic potential in the in vivo assays at doses up to 10 g/kg body weight (bw). The LD50 of BSE in rats was >10 g/kg bw/d. In the 30-day feeding study, in which BSE was administered in the diet to provide doses of 0, 0.3, 1.0, or 3.0 g/kg bw/d, no toxicological significant effects were noted on body weight, body weight gain, organ weights, or on the results of hematological, clinical chemistry and histopathological evaluations. The no-observed-adverse-effect level was considered to be 3.0 g/kg bw/d, the highest dose tested. Collectively, these results support the safe use of BSE as a food ingredient or product. PMID:26271574

  17. Acute and subchronic toxic effects of atrazine and chlorpyrifos on common carp (Cyprinus carpio L.): Immunotoxicity assessments.

    PubMed

    Xing, Houjuan; Liu, Tao; Zhang, Ziwei; Wang, Xiaolong; Xu, Shiwen

    2015-08-01

    Atrazine (ATR) and chlorpyrifos (CPF) are widely used pesticides in agricultural practices throughout world. It has resulted in a series of toxicological and environmental problems, such as impacts on many non-target aquatic species, including fish. The spleen and head kidney in the bony fish are the major hematopoietic organs, and play a crucial part in immune responses. This study evaluated the subchronic effects of ATR and CPF on the mRNA and protein levels of HSP60, HSP70 and HSP90 in the immune organs of common carp and compared the acute and subchronic effects of ATR and CPF on the swimming speed (SS) of common carp. The results of acute toxicity tests showed that the 96 h-LC50 of ATR and CPF for common carp was determined to be 2.142 and 0.582 mg/L, respectively. Meanwhile, acute and subacute toxicity of ATR and CPF in common carp resulted in hypoactivity. We also found that the mRNA and protein levels of HSP60, HSP70 and HSP90 genes were induced in the spleen and head kidney of common carp exposed to ATR and CPF in the subchronic toxicity test. Our results indicate that ATR and CPF are highly toxic to common carp, and hypoactivity in common carp by acute and subchronic toxicity of ATR and CPF may provide a useful tool for assessing the toxicity of triazine herbicide and organophosphorous pesticides to aquatic organisms. In addition, the results from the subchronic toxicity test exhibited that increasing concentration of ATR and CPF in the environment causes considerable stress for common carp, suggesting that ATR and CPF exposure cause immunotoxicity to common carp. PMID:25917970

  18. Acute and subchronic toxicity of naturally weathered Exxon Valdez crude oil in mallards and ferrets

    SciTech Connect

    Stubblefield, W.A.; Hancock, G.A.; Ford, W.H.; Ringer, R.K.

    1995-11-01

    The toxic properties of naturally weathered Exxon Valdez crude oil (WEVC) were assessed in a battery of acute and subchronic toxicity tests using mallards, Anas platyrhynchos, and European ferrets, Mustela putorius. Adult mallard acute oral toxicity study results indicated no mortalities or signs o toxicity, i.e., no-observed-adverse-effect level (NOAEL) and median lethal dose (LD50) > 5,000 mg/kg. Acute oral feeding and food avoidance tests with ducklings also indicated no toxicity (NOAEL and LC50 > 50,000 mg/kg diet) with no evidence of food avoidance (FAC50 > 20,000 mg/kg diet). No mortalities or toxic signs were noted in a 14-d feeding study with adult birds at dietary concentrations up to 100,000 mg WEVC/kg diet. Among clinical and physiological end points evaluated, the only significant difference noted was an increase in liver: body weight ratios in the 100,000-mg WEVC/kg diet dose group. No differences in clinical chemistry or hematological parameters were noted, and there were no consistent differences in histological evaluations of organ tissues. Daily oral doses of up to 5,000 mg/kg of WEVC over 5 d resulted in minimal effects on ferrets. Increased serum albumin concentrations were observed in the 5,000-mg/kg dose group females and decreased spleen weights were noted in females of all WEVC treatment groups. No other significant observations were noted.

  19. Testicular toxicity of para-phenylenediamine after subchronic topical application in rat.

    PubMed

    Bharali, Manuj Kr; Dutta, Karabi

    2012-01-01

    Para-phenylenediamine (PPD) is a most widely used chemical in almost all hair dye formulations. The present experiment was conducted in order to assess the reproductive toxicity of PPD in male rats. After sub-chronic topical application of different doses (0, 1, 2 and 3 mg/kg/day) of PPD, the male albino rats exhibited significant decrease in the total sperm count (p<0.05, 0.01) with consistent decrease in the testicular weight (p<0.05), increase in the germ cell apoptosis indicated by cellular morphology as well as loss of germinal layer, sloughing of testicular cellular layers. Elevation of lipid peroxidation product in the testicular tissue indicated the potential oxidative stress that may be crucial in the induction of the apoptosis and further tissue injury in the PPD-treated rats. The study was designed to examine the testicular effect of 1% to 3% PPD which mimic the actual dosage available in most of the hair dying formulation. The possibilities of impaired testicular function after sub-chronic topical exposure to PPD on male rats have demonstrated. PMID:22149045

  20. Acute and sub-chronic toxicity of four cytostatic drugs in zebrafish.

    PubMed

    Kovács, Róbert; Bakos, Katalin; Urbányi, Béla; Kövesi, Judit; Gazsi, Gyöngyi; Csepeli, Andrea; Appl, Ádám János; Bencsik, Dóra; Csenki, Zsolt; Horváth, Ákos

    2016-08-01

    The acute and sub-chronic effects of four cytostatic drugs-5-fluorouracil (5-FU), cisplatin (CisPt), etoposide (ET) and imatinib mesylate (IM)-on zebrafish (Danio rerio) were investigated. Acute tests were carried out in a static system in accordance with the OECD guideline 203 for adult fish and the draft guideline for fish embryos (FET test) in order to find the LC50 values of the four cytostatic drugs. Early-life stage toxicity test on zebrafish was conducted according the OECD guideline 210 using the cytostatic drugs 5-FU and IM in a semistatic system with the objective of investigating the sub-chronic effects of the cytostatic drugs on fish. In adult fish, the cytostatic drugs 5-FU and ET did not pass the limit test, thus, are considered non-toxic. In case of cisplatin, LC50 was calculated at 64.5 mg L(-1), whereas in case of IM, LC50 was at 70.8 mg L(-1). In the FET test, LC50 of 5-FU at 72-h post fertilization (hpf) was 2441.6 mg L(-1). In case of CisPt, LC50 was 349.9 mg L(-1) at 48 hpf and it progressively decreased to 81.3 mg L(-1) at 120 hpf. In addition, CisPt caused a significant delay in the hatch of larvae. In case of ET, LC50 values were not calculable as they were higher than 300 mg L(-1) at which concentration the substance crystallized in the solution. LC50 values of IM were 48 hpf; 158.3 mg L(-1) , 72 hpf; 141.6 mg L(-1), 96 hpf; 118.0 mg L(-1), and 120 hpf; 65.9 mg L(-1). In the Early-life Stage Test with 5-FU, embryonic deformities were not detected during the tests. Regarding mortalities, the 10 mg L(-1) concentration can be considered as LOEC, as statistically significant difference in mortalities was detected in this group alone. Concerning dry body weight and standard length, 1 mg L(-1) is the LOEC. In case of IM, the highest tested concentration (10 mg L(-1)) can be considered LOEC for mortalities, however, the treatment did not have an effect on the other investigated parameters (dry and wet weight, standard length). All four cytostatic

  1. Acute and subchronic (13-week) toxicity of fermented Acanthopanax koreanum extracts in Sprague Dawley rats.

    PubMed

    Cho, MyoungLae; Shin, Gi-Hae; Kim, Jae-Min; Lee, Jin-Ha; Park, Sun-Ok; Lee, Sang-Jong; Shin, HyunMu; Lee, Boo-Yong; Kang, Il-Jun; Lee, Ok-Hwan

    2016-06-01

    The biological fermentation of plants is usually used to improve their product properties, including their biological activity. Acanthopanax koreanum is a plant indigenous to Jeju, Korea; however, fermented A. koreanum (FAK) has not been guaranteed to be safe. Therefore, in this study, a safety evaluation of aqueous extracts of FAK was performed using Sprague Dawley rats. The acute toxicity of FAK did not influence animal mortality, body weight changes or the animals' clinical appearance at a concentration of 5000 mg/kg body weight. Using doses of 500, 1000 and 2000 mg/kg/day in a subchronic (13-week) toxicity study, the administration of FAK in male rats increased their body weight, food consumption, absolute liver weight, liver-associated enzymes and total cholesterol content. However, these effects of FAK were not considered toxic because the changes were not accompanied by any evidence of clinical signs or any change in the histopathological examination. On the other hand, the FAK-treated female rats did not exhibit significant changes in their body weight, food consumption, absolute and relative organ weights or liver enzymes. These results suggest that the acute oral administration of FAK is non-toxic to rats, and 13 weeks of repeated dosing demonstrated no FAK-related toxicity at a concentration of 2000 mg/kg. Therefore, the no-observed-adverse-effect level (NOAEL) of FAK was determined to be 2000 mg/kg/day for both male and female rats. PMID:26925497

  2. Acute and subchronic toxicity analysis of surface modified paclitaxel attached hydroxyapatite and titanium dioxide nanoparticles

    PubMed Central

    Venkatasubbu, Gopinath Devanand; Ramasamy, S; Gaddam, Pramod Reddy; Kumar, J

    2015-01-01

    Nanoparticles are widely used for targeted drug delivery applications. Surface modification with appropriate polymer and ligands is carried out to target the drug to the affected area. Toxicity analysis is carried out to evaluate the safety of the surface modified nanoparticles. In this study, paclitaxel attached, folic acid functionalized, polyethylene glycol modified hydroxyapatite and titanium dioxide nanoparticles were used for targeted drug delivery system. The toxicological behavior of the system was studied in vivo in rats and mice. Acute and subchronic studies were carried out. Biochemical, hematological, and histopathological analysis was also done. There were no significant alterations in the biochemical parameters at a low dosage. There was a small change in alkaline phosphatase (ALP) level at a high dosage. The results indicate a safe toxicological profile. PMID:26491315

  3. Acute and subchronic toxicity as well as evaluation of safety pharmacology of eucalyptus oil-water emulsions.

    PubMed

    Hu, Zhiqiang; Feng, Ruizhang; Xiang, Fa; Song, Xu; Yin, Zhongqiong; Zhang, Chao; Zhao, Xinghong; Jia, Renyong; Chen, Zhenzhen; Li, Li; Yin, Lizi; Liang, Xiaoxia; He, Changliang; Shu, Gang; Lv, Cheng; Zhao, Ling; Ye, Gang; Shi, Fei

    2014-01-01

    Essential oil has performed a variety of indirect services used as insect/pest repellent. The present study investigated the acute and subchronic toxicity of eucalyptus oil emulsion in water (EOE). In addition, we conduct safety pharmacology evaluation of EOE to supplement the toxicity tests and provide a basis for a comprehensive understanding of the toxicity of EOE. Acute administration of EOE was done as single dose from 2772 mg to 5742 mg of EOE per kg/bodyweight (b.wt.) and subchronic toxicity study for thirty days was done by daily oral administration of EOE at doses of 396, 792 and 1188 mg/kg b.wt. In SPF SD rats. The acute toxicity study showed the LD50 of EOE was 3811.5 mg/kg. The subchronic toxicity study suggested the high-dose and middle-dose EOE slowed down the growth of male rats. The clinical pathology showed the high-dose and middle-dose EOE could cause damage to liver and kidney. The safety pharmacology indicated that EOE had no side effects on rats. These results suggest that EOE is a safe veterinary medicine for external use. PMID:25663980

  4. Acute and subchronic toxicity as well as evaluation of safety pharmacology of eucalyptus oil-water emulsions

    PubMed Central

    Hu, Zhiqiang; Feng, Ruizhang; Xiang, Fa; Song, Xu; Yin, Zhongqiong; Zhang, Chao; Zhao, Xinghong; Jia, Renyong; Chen, Zhenzhen; Li, Li; Yin, Lizi; Liang, Xiaoxia; He, Changliang; Shu, Gang; Lv, Cheng; Zhao, Ling; Ye, Gang; Shi, Fei

    2014-01-01

    Essential oil has performed a variety of indirect services used as insect/pest repellent. The present study investigated the acute and subchronic toxicity of eucalyptus oil emulsion in water (EOE). In addition, we conduct safety pharmacology evaluation of EOE to supplement the toxicity tests and provide a basis for a comprehensive understanding of the toxicity of EOE. Acute administration of EOE was done as single dose from 2772 mg to 5742 mg of EOE per kg/bodyweight (b.wt.) and subchronic toxicity study for thirty days was done by daily oral administration of EOE at doses of 396, 792 and 1188 mg/kg b.wt. In SPF SD rats. The acute toxicity study showed the LD50 of EOE was 3811.5 mg/kg. The subchronic toxicity study suggested the high-dose and middle-dose EOE slowed down the growth of male rats. The clinical pathology showed the high-dose and middle-dose EOE could cause damage to liver and kidney. The safety pharmacology indicated that EOE had no side effects on rats. These results suggest that EOE is a safe veterinary medicine for external use. PMID:25663980

  5. Toxicological evaluation of L-proline in a 90-day feeding study with Fischer 344 rats.

    PubMed

    Tada, Y; Yano, N; Takahashi, H; Yuzawa, K; Ando, H; Kubo, Y; Nagasawa, A; Ohashi, N; Ogata, A; Nakae, D

    2010-10-01

    L-proline (L-Pro) is a non-essential amino acid, and has become widely used as supplements and health foods, recently. A subchronic oral toxicity study of L-Pro was conducted with groups of 10 male and 10 female Fischer 344 rats fed a powder diet containing 0%, 0.625%, 1.25%, 2.5% and 5.0% of L-Pro for 90 days. No treatment-related clinical signs and mortality were noted. We observed no clear treatment-related effects with regard to body weight, food intake or urinalysis data. The average daily water intakes of the treated female groups were significantly increased compared to the controls. The hematology (red blood cell parameter) and serum biochemistry (glucose, blood urea nitrogen, creatinine or uric acid) of the treated male and/or female groups were lower than those of the control groups. However, these changes were lacked dose-dependence, and no abnormalities were found in corresponding pathological findings. In conclusion, the no-observed-adverse-effect-level (NOAEL) for L-Pro was determined to be a dietary dose of 5.0% (2772.9 mg/kg body weight/day for males and 3009.3mg/kg body weight/day for females) under the present experimental conditions. PMID:20447433

  6. Ninety-Day Subchronic Oral Toxicity Study of Senecio scandens Extract in Rats.

    PubMed

    Wang, Xiu-Kun; Zhao, Yong; Liu, Ting; Yi, Yan; Li, Chun-Ying; Wang, Hong-Jie; Wang, Chang-Hong; Wang, Zheng-Tao; Ye, Zu-Guang; Liang, Ai-Hua

    2015-01-01

    The present study assessed the safety/toxicity of Senecio scandens, a well-known Chinese herb that is used as an anti-inflammatory, antibiosis, and antipyretic drug. A 90-d subchronic oral toxicity study of S. scandens was performed in Wistar rats. The extract of S. scandens was administered orally to male and female rats at a single dose of 225, 450, and 900 mg/kg/d. There was no obvious toxicity. Certain changes in hematology and coagulation parameters (red cell distribution width (RDW), platelet count (PLT), monocyte percentage (Mo%), activated partial thromboplastin time (APTT), prothrombin time (PT)) were observed in some administration groups. In regards to the blood biochemical parameters, the levels of creatinine (CRN), potassium, and chloride were increased in a number of the treated rats. There were no significant changes in other hematology, coagulation, or biochemical parameters in rats orally administered S. scandens. S. scandens has a slight effect on rat coagulation and metabolism systems. The herb was safe at all doses tested, but caution should be taken when administering S. scandens at higher doses. PMID:26195160

  7. A k-NN algorithm for predicting the oral sub-chronic toxicity in the rat.

    PubMed

    Gadaleta, Domenico; Pizzo, Fabiola; Lombardo, Anna; Carotti, Angelo; Escher, Sylvia E; Nicolotti, Orazio; Benfenati, Emilio

    2014-01-01

    Repeated dose toxicity is of the utmost importance to characterize the toxicological profile of a chemical after repeated administration. Its evaluation refers to the Lowest-Observed-(Adverse)-Effect-Level (LO(A)EL) explicitly requested in several regulatory contexts, such as REACH and EC Regulation 1223/2009 on cosmetic products. So far in vivo tests have been the sole viable option to assess repeated dose toxicity. We report a customized k-Nearest Neighbors approach for predicting sub-chronic oral toxicity in rats. A training set of 254 chemicals was used to derive models whose robustness was challenged through leave-one-out cross-validation. Their predictive power was evaluated on an external dataset comprising 179 chemicals. Despite the intrinsically heterogeneous nature of the data, our models give promising results, with q²≥0.632 and external r²≥0.543. The confidence in prediction was ensured by implementing restrictive user-adjustable rules excluding suspicious chemicals irrespective of the goodness in their prediction. Comparison with the very few LO(A)EL predictive models in the literature indicates that the results of the present analysis can be valuable in prioritizing the safety assessment of chemicals and thus making safe decisions and justifying waiving animal tests according to current regulations concerning chemical safety. PMID:25048736

  8. Bioaccumulation and Subchronic Toxicity of 14 nm Gold Nanoparticles in Rats.

    PubMed

    Rambanapasi, Clinton; Zeevaart, Jan Rijn; Buntting, Hylton; Bester, Cornelius; Kotze, Deon; Hayeshi, Rose; Grobler, Anne

    2016-01-01

    Colloidal suspensions of 14 nm gold nanoparticles (AuNPs) were repeatedly administered intravenously at three dose levels (0.9, 9 and 90 µg) to male Sprague Dawley rats weekly for 7 weeks, followed by a 14-day washout period. After sacrificing, the amount of gold was quantified in the liver, lungs, spleen, skeleton and carcass using neutron activation analysis (NAA). During the study, pre- and post (24 h) administration blood samples were collected from both the test and control groups, the latter which received an equal injection volume of normal saline. General health indicators were monitored together with markers of kidney and liver damage for acute and subchronic toxicity assessment. Histopathological assessments were done on the heart, kidneys, liver, lungs and spleen to assess any morphological changes as a result of the exposure to AuNPs. The mass measurements of all the groups showed a steady increase with no signs of overt toxicity. The liver had the highest amount of gold (µg) per gram of tissue after 56 days followed by the spleen, lungs, skeleton and carcass. Markers of kidney and liver damage showed similar trends between the pre and post samples within each group and across groups. The histopathological examination also showed no hepatotoxicity and nephrotoxicity. There was accumulation of Au in tissues after repeated dosing, albeit with no observable overt toxicity, kidney or liver damage. PMID:27294904

  9. Subchronic toxicity studies of the ethanolic root extract of Croton zambesicus.

    PubMed

    Okokon, Jude E; Nwafor, Paul A; Ekpo, Memfin D

    2010-04-01

    Subchronic toxicity study of the crude root extract of Croton zambesicus (27-81 mg/kg), which is used traditionally as malarial remedy, was carried out in rodents to evaluate the safety profile. Effect of the extract on body weights, haematological indices as well as liver and kidney functions and histology of various organs were investigated. Subchronic treatment of rats for 21 days caused comparable increase in body weights of rats in extract treated and control groups. The extract caused a dose-dependent increases in RBC, PCV, Hb, WBC, bleeding time and clotting time. The increases were only significant (P<0.05) at the highest dose of the extract (81 mg/kg) for RBC and WBC when compared to control. There was no significant (P>0.05) differences in the means of other haematological parameters in the extract treated groups compared to control. The extract caused significant (P<0.05-0.01) increases in the level of serum total protein, ALT, ALP, total bilirubin and total cholesterol. The was no significant (P>0.05) changes in the levels of albumin and AST. The extract did not produce any significant (P>0.05) changes in the mean concentrations of urea, creatinine, Na+, K+, and Cl- ions of rats in the extract treated groups compared to that of control. Histopathologic analysis of the vital organs revealed no significant lesions in the brain, liver, kidney, heart, spleen, ovary, and testis. The results suggest the extract to be safe when taken orally though with an insignificant effect on the liver. PMID:20363693

  10. Acute, sub-chronic oral toxicity studies and evaluation of antiulcer activity of Sooktyn in experimental animals

    PubMed Central

    Chandra, Phool; Sachan, Neetu; Kishore, Kamal; Ghosh, Ashoke Kumar

    2012-01-01

    Sooktyn (SKN), mineralo-herbal drug which is being used largely by the patients for its extremely good therapeutic value to treat the gastric ulcers. The present study was undertaken to evaluate the toxicity studies and antiulcer activity of SKN. Acute and sub-chronic toxicities were studied in male and female Wistar rats. A single acute SKN of 2 000 mg/kg was administered by oral gavage for acute toxicity. Sub-chronic doses were 400 and 800 mg/kg/day. The major toxicological end points examined included animal body weight and food intake, selected tissue weights, and detailed gross necropsy. In addition, we examined blood elements: hematocrit, hemoglobin concentration, erythrocyte count, total leukocyte count and MCH, MCHC and platelets as well as biochemical parameters: urea, sugar, alanine transaminase, aspartate transaminase, alkaline phosphatase, total proteins, and creatinine. Also, anti-ulcer activity was carried out by employing indomethacin, ethanol, pylorus ligation, and hypothermic-stress-induced ulcer models. LD50 may be greater than 2 000 mg/kg (orally) for SKN and there were no signs of toxicity on 28 days sub-chronic oral administration of 400 and 800 mg/kg of SKN in rats on the basis of blood elements and biochemical parameters. The ulcer indices decrease in all ulcer models with 66.62%, 61.24%, 80.18%, and 74.76% in indomethacin, ethanol, pylorus ligation, and hypothermic-stress-induced ulcer models, respectively. The results suggest that SKN has no signs of toxicity at 2 000 mg/kg body weight of rats orally; sub-chronically. The drug is safe and has antiulcer activity. PMID:22837960

  11. Scientific evaluation of the subchronic toxicity of Musca domestica larvae extracts in Sprague Dawley rats.

    PubMed

    Li, Yun-Xi; Jin, Xiao-Bao; Chu, Fu-Jiang; Liu, Man-Yu; Shi, Da-Yu; Zhu, Jia-Yong

    2013-09-01

    Musca domestica larvae extracts (MDLE) is a potential drug used to treat lipopolysaccharide-induced atherosclerosis pro-inflammatory responses. The purpose of the study was to evaluate the safety of MDLE via a 13-week repeated dose subchronic toxicity test in rats. Both male and female Sprague Dawley rats were divided into four groups, eight animals each from the control and high-dose group (33.0 g/kg) were allocated into recovery groups. The four groups of rats were administrated with MDLE (0, 13.2, 22.0, 33.0 g/kg) in the diet for 13weeks respectively. During the experimental period, the rats were observed for symptoms and signs of gross toxicity daily, food consumption and body weight were measured weekly. Urinalysis, thrombotest, blood biochemical and hematological analyses were performed regularly; Expression of peroxide dismutase gene in liver was quantified and a histopathological examination was also performed. There were no MDLE-induced abnormalities in any of the groups during or after the 13 weeks except the relative weight of liver of high-dose group and middle-dose group was significantly higher than that of control group in male rats (P<0.05). The results indicate a no observed adverse effect level for MDLE is 13.2 and 33.0 g/kg bw/day in male and female rats, respectively. PMID:23816833

  12. Safety Evaluation of Oral Toxicity of Carica papaya Linn. Leaves: A Subchronic Toxicity Study in Sprague Dawley Rats.

    PubMed

    Ismail, Zakiah; Halim, Siti Zaleha; Abdullah, Noor Rain; Afzan, Adlin; Abdul Rashid, Badrul Amini; Jantan, Ibrahim

    2014-01-01

    The subchronic toxicity effect of the leaf extract of Carica papaya Linn. in Sprague Dawley (SD) rats was investigated in this study. The extract was prepared by dissolving the freeze dried extract of the leaves in distilled water and was administered orally to SD rats (consisted of 10 rats/sex/group) at 0 (control), 0.01, 0.14, and 2 g/kg body weight (BW) for 13 weeks. General observation, mortality, and food and water intake were monitored throughout the experimental period. Hematological and biochemical parameters, relative organ weights, and histopathological changes were evaluated. The study showed that leaf extract when administered for 13 weeks did not cause any mortality and abnormalities of behavior or changes in body weight as well as food and water intake. There were no significant differences observed in hematology parameters between treatment and control groups; however significant differences were seen in biochemistry values, for example, LDH, creatinine, total protein, and albumin. However, these changes were not associated with histopathological changes. In conclusion, the results suggested that daily oral administration of rats with C. papaya leaf extract for 13 weeks at a dose up to fourteen times the levels employed in traditional medicine practice did not cause any significant toxic effect. PMID:25530788

  13. Safety Evaluation of Oral Toxicity of Carica papaya Linn. Leaves: A Subchronic Toxicity Study in Sprague Dawley Rats

    PubMed Central

    Ismail, Zakiah; Abdullah, Noor Rain; Abdul Rashid, Badrul Amini; Jantan, Ibrahim

    2014-01-01

    The subchronic toxicity effect of the leaf extract of Carica papaya Linn. in Sprague Dawley (SD) rats was investigated in this study. The extract was prepared by dissolving the freeze dried extract of the leaves in distilled water and was administered orally to SD rats (consisted of 10 rats/sex/group) at 0 (control), 0.01, 0.14, and 2 g/kg body weight (BW) for 13 weeks. General observation, mortality, and food and water intake were monitored throughout the experimental period. Hematological and biochemical parameters, relative organ weights, and histopathological changes were evaluated. The study showed that leaf extract when administered for 13 weeks did not cause any mortality and abnormalities of behavior or changes in body weight as well as food and water intake. There were no significant differences observed in hematology parameters between treatment and control groups; however significant differences were seen in biochemistry values, for example, LDH, creatinine, total protein, and albumin. However, these changes were not associated with histopathological changes. In conclusion, the results suggested that daily oral administration of rats with C. papaya leaf extract for 13 weeks at a dose up to fourteen times the levels employed in traditional medicine practice did not cause any significant toxic effect. PMID:25530788

  14. Safety assessment of [3S, 3'S]-astaxanthin--Subchronic toxicity study in rats.

    PubMed

    Buesen, R; Schulte, S; Strauss, V; Treumann, S; Becker, M; Gröters, S; Carvalho, S; van Ravenzwaay, B

    2015-07-01

    Astaxanthin, a naturally occurring xanthophyll, is commercially used as a coloring agent in salmon feed, but also marketed as a dietary supplement. The objective of this study was to investigate the subchronic toxicity of synthetic [3S, 3'S]-Astaxanthin in rats. A powder formulation containing approximately 20% [3S, 3'S]-Astaxanthin was administered via the diet to groups of 10 male and 10 female Wistar rats at concentrations of 5000, 15,000 and 50,000 ppm for a period of 13 weeks. A formulation of comparable composition but without [3S, 3'S]-Astaxanthin served as a placebo control. There were no effects observed on survival, clinical examinations, clinical pathology, estrous cycle as well as on sperm parameters. At terminal necropsy, a macroscopically visible brown-blue discoloration of the gastrointestinal contents was noted which was considered to be secondary to the violet-brown color of the test material. No other significant or dose-related abnormalities were found in the tissues collected at termination. Our observations support that ingestion of [3S, 3'S]-Astaxanthin of up to 700-920 mg/kg bw/day in rats in a gelatin/carbohydrate formulation is without adverse effects. PMID:25910834

  15. A subchronic oral toxicity study on pyrroloquinoline quinone (PQQ) disodium salt in rats.

    PubMed

    Liang, Chunlai; Zhang, Xin; Wang, Wei; Song, Yan; Jia, Xudong

    2015-01-01

    A subchronic oral toxicity study on pyrroloquinoline quinone (PQQ) disodium salt was performed in rats. Sprague-Dawley rats were randomly divided into four groups (10 rats/sex/group) and administered with PQQ disodium salt at doses of 0 (control), 100, 200 and 400 mg/kg bw/day by gavage for 13 weeks. Daily clinical observations and weekly measurement of body weights and food consumption were conducted. Blood samples were obtained on day 46 and day 91 for measurement of hematology and serum biochemical parameters. Animals were euthanized for necropsy, selected organs were weighted and recorded. Histological examination was performed on all tissues from animals in the control and PQQ disodium salt treatment groups. No mortality or toxicologically significant changes in clinical signs, body weight, food consumption, necropsy findings or organ weights was observed. Differences between treated and control groups in some hematological and serum biochemical examinations and histopathological examination were not considered treatment-related. The no-observed-adverse-effect-level (NOAEL) of PQQ disodium salt in rats was considered to be 400 mg/kg bw/day for both sexes, the highest dose tested. PMID:25445509

  16. Acute and subchronic toxicity studies of pyrroloquinoline quinone (PQQ) disodium salt (BioPQQ™) in rats.

    PubMed

    Nakano, Masahiko; Takahashi, Hisaaki; Koura, Seiko; Chung, Catherine; Tafazoli, Shahrzad; Roberts, Ashley

    2014-10-01

    The potential use of pyrroloquinoline quinone disodium salt (BioPQQ™), as a supplemental food ingredient, was evaluated in a range of oral toxicity studies in rats including an acute study, a 14-day preliminary and a 28-day repeated-dose study, and a 13-week subchronic study. The median lethal dose of BioPQQ™ was shown to be 1000-2000mg/kg body weight (bw) in male and 500-1000mg/kgbw in female rats. In the 14-day study, high doses of BioPQQ™ resulted in increases in relative kidney weights with associated histopathology in female rats only, while a follow-up 28-day study in female animals resulted in increases in urinary protein and crystals. These findings were reversible, and resolved during the recovery period. In the 13-week study, a number of clinical chemistry findings and histopathological changes were noted, which were deemed to be of no toxicological significance, as the levels were within the historical control range, were not dose-dependent, occurred at a similar frequency in control groups, or only occurred in the control group. Based on these findings, a no-observed-adverse-effect level of 100mg/kgbw/day was determined for BioPQQ™ in rats, the highest dose tested in the 13-week study. PMID:24995591

  17. Subchronic toxicity study of β-hydroxy-β-methylbutyric free acid in Sprague-Dawley rats.

    PubMed

    Fuller, John C; Arp, Lawrence H; Diehl, Lisa M; Landin, Kelly L; Baier, Shawn M; Rathmacher, John A

    2014-05-01

    Calcium β-hydroxy-β-methylbutyrate-monohydrate (CaHMB) is a dietary supplement used as an ergogenic aid and in functional and medical foods. A new delivery form has been developed, β-hydroxy-β-methylbutyric free acid (HMBFA), which has improved bioavailability. While the safety of CaHMB is well documented, there are few published studies demonstrating the safety of HMBFA. Because HMBFA results in greater serum levels of β-hydroxy-β-methylbutyrate (HMB) and greater clearance rates, a 91-day subchronic toxicity study was conducted in male and female Sprague-Dawley Crl:CD rats assigned to HMBFA treatments at either 0%, 0.8%, 1.6%, or 4% of the diet by weight. No deaths or untoward clinical observations, and no negative clinical chemistry or hematology were attributed to the administration of HMBFA. Gross pathology and histopathology results showed no tissue abnormalities due to HMBFA and all measures were within a normal physiological range for the animals or were expected in the population studied. In conclusion, the no-observed-adverse-event-level (NOAEL) for HMBFA was the highest level administered, 4% of the diet, which corresponded to an intake of 2.48 and 2.83 g/kg BW d(-1) in the males and females, respectively. The equivalent human dosage using body surface area conversion would be 402 and 459 mg/kg BW d(-1) for men and women, respectively. PMID:24576552

  18. Subchronic inhalation toxicity of p-nitroaniline and p-nitrochlorobenzene in rats

    SciTech Connect

    Nair, R.S.; Johannsen, F.R.; Levinskas, G.J.; Terrill, J.B.

    1986-05-01

    For evaluation of subchronic toxicity of the two single-ring nitroaromatics, p-nitroaniline (PNA) and p-nitrochlorobenzene (PNCB), groups of 10 male and 10 female Sprague-Dawley rats were exposed to an aerosol/vapor of PNA in isopropanol at target concentrations of 0, 10, 30, or 90 mg/m3 or to PNCB vaporized from a solution in ethylene glycol monoethyl ether at target concentrations of 0, 5, 15, or 45 mg/m3 for 6 hr/day, 5 days/week for 4 weeks. Clinical signs of toxicity, body weights, results of ophthalmoscopic exam, hematology and clinical chemistry tests, organ weights, gross and histopathological changes were recorded. Exposure to PNA or PNCB resulted in a dose-related increase in blood methemoglobin levels. Mean red blood cell counts, hematocrit, and hemoglobin were significantly decreased in mid and high level animals exposed to PNCB. Mean spleen weights (absolute and relative to body weight) were significantly increased at the high dose levels in the two studies. A slight increase in spleen weights was also observed at the low concentration level in the PNA study. Absolute and relative liver weights also were increased among animals exposed to 45 mg/m3 PNCB. Microscopic changes were observed mainly in the spleen and included an increase in intensity of extramedullary hematopoiesis and hemosiderosis with both compounds. Spleens of animals exposed to PNCB also exhibited congestion. Neither PNA nor PNCB exhibited significant toxicological effects other than those of methemoglobinemia, anemia, and splenic changes classically associated with nitroaromatics at levels significantly above presently accepted occupational standard. Our data suggest that the current TLV for PNA which is 3 mg/m3 will provide adequate protection to the workers. OSHA's PEL of 1 mg/m3 for PNCB is to be preferred over the current TLV of 3 mg/m3 to provide a comparable margin of safety.

  19. Toxicity assessment of zinc oxide nanoparticles using sub-acute and sub-chronic murine inhalation models

    PubMed Central

    2014-01-01

    Background Although ZnO nanoparticles (NPs) are used in many commercial products and the potential for human exposure is increasing, few in vivo studies have addressed their possible toxic effects after inhalation. We sought to determine whether ZnO NPs induce pulmonary toxicity in mice following sub-acute or sub-chronic inhalation exposure to realistic exposure doses. Methods Mice (C57Bl/6) were exposed to well-characterized ZnO NPs (3.5 mg/m3, 4 hr/day) for 2 (sub-acute) or 13 (sub-chronic) weeks and necropsied immediately (0 wk) or 3 weeks (3 wks) post exposure. Toxicity was assessed by enumeration of total and differential cells, determination of total protein, lactate dehydrogenase activity and inflammatory cytokines in bronchoalveolar lavage (BAL) fluid as well as measurements of pulmonary mechanics. Generation of reactive oxygen species was assessed in the lungs. Lungs were evaluated for histopathologic changes and Zn content. Zn concentration in blood, liver, kidney, spleen, heart, brain and BAL fluid was measured. Results An elevated concentration of Zn2+ was detected in BAL fluid immediately after exposures, but returned to baseline levels 3 wks post exposure. Dissolution studies showed that ZnO NPs readily dissolved in artificial lysosomal fluid (pH 4.5), but formed aggregates and precipitates in artificial interstitial fluid (pH 7.4). Sub-acute exposure to ZnO NPs caused an increase of macrophages in BAL fluid and a moderate increase in IL-12(p40) and MIP-1α, but no other inflammatory or toxic responses were observed. Following both sub-acute and sub-chronic exposures, pulmonary mechanics were no different than sham-exposed animals. Conclusions Our ZnO NP inhalation studies showed minimal pulmonary inflammation, cytotoxicity or lung histopathologic changes. An elevated concentration of Zn in the lung and BAL fluid indicates dissolution of ZnO NPs in the respiratory system after inhalation. Exposure concentration, exposure mode and time post

  20. Sub-chronic Dermal Toxicity of Silver Nanoparticles in Guinea Pig: Special Emphasis to Heart, Bone and Kidney Toxicities

    PubMed Central

    Korani, Mitra; Rezayat, Seyed Mahdi; Arbabi Bidgoli, Sepideh

    2013-01-01

    Silver nanoparticles (Ag NPs) have been widely used as new potent antimicrobial agents in cosmetic and hygienic products. Present study compares the tissue levels of Ag NPs in different organs of Guiana Pigs quantitatively after dermal application and analysis the morphological changes and pathological abnormalities on the basis of the Ag NPs tissue levels. Before toxicological assessments,the size of colloidal nanosilver was recorded by X-Ray Diffraction and Transmission Electron Microscope tests and the sizes of samples were recorded in sizes less than 100 nm. For toxicological evaluation, male guinea pigs were exposed to three concentrations of Ag NPs (100, 1000 and 10000 ppm) according to acute pretests for further assessments in subchronic model in a period of 13 weeks . A close correlation between dermal exposure and tissue levels of Ag NPs was found (p < 0.05) and tissue uptakes happened in dose dependent manner with the following ranking: ki dney>muscle>bone>skin>liver>heart >spleen. In histopathological studies, severe proximal convoluted tubule degeneration and distal convoluted tubule were seen in the kidneys of the middle and high-dose animals. Separated lines and marrow space narrow were determined as two major signs of bone toxicities which observed in three different dose levels of Ag NPs. Increased dermal dose of Ag NPs caused cardiocyte deformity, congestion and inflammation. The three different Ag NPs concentration gave comparable results for several endpoints measured in heart, bone and kidney, but differed in tissue concentrations and the extent of histopathological changes. It seems that Ag ions could be detected in different organs after dermal exposure ,which has the potential to provide target organ toxicities in a time and dose dependent manner. PMID:24250657

  1. The significance of the subchronic toxicity in the dietary risk assessment of pesticides.

    PubMed

    Zarn, Jürg A; Hänggi, Emanuel; Kuchen, Arnold; Schlatter, Josef R

    2010-10-01

    Based on 289 public pesticide evaluations, geometric means of subchronic/chronic No Observed Adverse Effect Level (NOAEL) ratios of 2.6, 2.5 and 1.6 in mice, rats and dogs were calculated. The 75th percentiles are 5.5, 5.1 and 3.2. Higher ratios correlate with increased dose spacing in chronic studies and may be mainly explained therewith. In rats fed at constant pesticide concentrations in feed, the mean chronic dose decreases by 1.7- and 2.7-fold compared to the subchronic and subacute phase. These dose decreases match the subchronic/chronic NOAEL ratios. The ratio of predicted rat chronic NOAEL (dose decrement adjusted subchronic NOAEL) to experimental chronic NOAEL is 1.5 and the 75th percentile is 3.0. In dietary risk assessment, the Acute Reference Dose and the Acceptable Daily Intake (derived from acute and chronic NOAEL) are compared to acute (IESTI) or mean (TMDI) exposure estimates. Because IESTI and TMDI base on acute or mean food consumption they differ by orders of magnitude for certain commodities. As subchronic and chronic NOAEL are similar, it remains to be shown whether pesticide intake estimates based on mean food consumption are adequate measures to compare against the ADI if repeated daily exposures considerably higher than mean exposures may occur. PMID:20406660

  2. Toxicological evaluation of an Allium-based commercial product in a 90-day feeding study in Sprague-Dawley rats.

    PubMed

    Mellado-García, P; Puerto, M; Pichardo, S; Llana-Ruiz-Cabello, M; Moyano, R; Blanco, A; Jos, A; Cameán, A M

    2016-04-01

    Proallium AP(®) is a commercial Allium extract intended to be used in active food packaging as the antibacterial and antioxidant effects of some organosulfur compounds are well known. However, there is little information on its toxicity and the Scientific Committee on Food (UE) requires the safety assessment of substances used in food contact materials. Thus, the aim of this study was to conduct for the first time a subchronic oral toxicity study of Proallium AP(®) with groups of 10 males and 10 females Sprague-Dawley rats fed a diet containing 0, 25, 100, 400 mg/kg/d for 90 days. No treatment-related clinical signs or mortality were noted. Besides, no treatment-related effects with regard to any of the toxicological biomarkers considered were observed, including biochemical, haematological and histopathology parameters. In conclusion, the non-observed-adverse-effect-level (NOAEL) for Proallium AP(®) in rats was determined to be a dietary dose of 400 mg/kg/d under the present experimental conditions, a value 500-fold higher than the exposure derived from its potential use in active packaging. PMID:26827789

  3. Subchronic toxicity and cardiovascular responses in spontaneously hypertensive rats after exposure to multiwalled carbon nanotubes by intratracheal instillation.

    PubMed

    Chen, Rui; Zhang, Lili; Ge, Cuicui; Tseng, Michael T; Bai, Ru; Qu, Ying; Beer, Christiane; Autrup, Herman; Chen, Chunying

    2015-03-16

    The tremendous demand of the market for carbon nanotubes has led to their massive production that presents an increasing risk through occupational exposure. Lung deposition of carbon nanotubes is known to cause acute localized pulmonary adverse effects. However, systemic cardiovascular damages associated with acute pulmonary lesion have not been thoroughly addressed. Four kinds of multiwalled carbon nanotubes (MWCNTs) with different lengths and/or iron contents were used to explore the potential subchronic toxicological effects in spontaneously hypertensive (SH) rats and normotensive control Wistar-Kyoto (WKY) rats after intratracheal instillation. MWCNTs penetrated the lung blood-gas barrier and accumulated in the liver, kidneys, and spleen but not in the heart and aorta of SH rats. The pulmonary toxicity and cardiovascular effects were assessed at 7 and 30 days postexposure. Compared to the WKY rats, transient influences on blood pressure and up to 30 days persistent decrease in the heart rate of SH rats were found by electrocardiogram monitoring. The subchronic toxicity, especially the sustained inflammation of the pulmonary and cardiovascular system, was revealed at days 7 and 30 in both SH and WKY rat models. Histopathological results showed obvious morphological lesions in abdominal arteries of SH rats 30 days after exposure. Our results suggest that more attention should be paid to the long-term toxic effects of MWCNTs, and particularly, occupationally exposed workers with preexisting cardiovascular diseases should be monitored more thoroughly. PMID:25580880

  4. Toxicity assessment of perfluorooctane sulfonate using acute and subchronic male C57BL/6J mouse models.

    PubMed

    Xing, Jiali; Wang, Gang; Zhao, Jichun; Wang, Eryin; Yin, Boxing; Fang, Dongsheng; Zhao, Jianxin; Zhang, Hao; Chen, Yong Q; Chen, Wei

    2016-03-01

    Perfluorooctane sulfonate (PFOS) is a principal representative and the final degradation product of several commercially produced perfluorinated compounds. However, PFOS has a high bioaccumulation potential and therefore can exert toxicity on aquatic organisms, animals, and cells. Considering the widespread concern this phenomenon has attracted, we examined the acute and subchronic toxic effects of varying doses of PFOS on adult male C57BL/6 mice. The acute oral LD50 value of PFOS in male C57BL/6J mice was 0.579 g/kg body weight (BW). Exposure to the subchronic oral toxicity of PFOS at 2.5, 5, and 10 mg PFOS/kg BW/day for 30 days disrupted the homeostasis of antioxidative systems, induced hepatocellular apoptosis (as revealed by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay), triggered liver injury (as evidenced by the increased serum levels of aspartate aminotransferase, alanine amino transferase, alkaline phosphatase, and gamma-glutamyl transpeptidase and by the altered histology), and ultimately increased the liver size and relative weight of the mice. PFOS treatment caused liver damage but only slightly affected the kidneys and spleen of the mice. This study provided insights into the toxicological effects of PFOS. PMID:26807985

  5. Comparative acute and subchronic toxicity of ethylene glycol monopropyl ether and ethylene glycol monopropyl ether acetate.

    PubMed Central

    Katz, G V; Krasavage, W J; Terhaar, C J

    1984-01-01

    The acute toxicity of ethylene glycol monopropyl ether (EGPE) and ethylene glycol monopropyl ether acetate (EGPEA) was determined in a series of standardized tests. The oral LD50 in rats was 3089 and 9456 mg/kg EGPE and EGPEA, respectively. Skin irritation was slight following an occluded single dose application of either compound to the guinea pig abdomen. The dermal LD50 for guinea pigs was 1 to 5 mL/kg and greater than 20 mL/kg EGPE and EGPEA, respectively. EGPE produced a very weak positive sensitization response in one of five guinea pigs. No positive response was elicited when 10 guinea pigs were similarly challenged with EGPEA. EGPE produced transient moderate to severe eye irritation in rabbits while EGPEA produced slight eye irritation. Subchronic toxicity was determined in a series of oral and inhalation studies. Groups of 10 male rats were dosed with 15, 7.5, 3.75 or 1.88 mmole/kg EGPE and 30, 15 or 7.5 mmole/kg EGPEA by gavage 5 days/week for 6 weeks. Hemoglobinuria was seen at least once at all dose levels of both compounds. EGPE had little effect on feed consumption or body weight gain, while body weight gain was reduced in the two high dose groups exposed to EGPEA and feed consumption was reduced at all dose levels. Hematologic changes were seen at all dose levels of both compounds. Absolute and/or relative spleen weights were increased at all but the lowest EGPE dose level and at all EGPEA dose levels. Gross and histopathologic examinations revealed significant effects on the spleen of animals exposed to EGPE and on the spleen, liver, kidney and testes of animals exposed to EGPEA. The no-observed effect level (NOEL) for splenic changes was 1.88 mmole/kg EGPE. A NOEL for hematology was not established. The NOEL for liver and testicular changes were 15 and 7.5 mmole/kg EGPEA, respectively while a NOEL for hematologic, splenic and renal changes was not established. Groups of 10 rats (5M, 5F) were exposed to 800, 400, 200 or 100 ppm EGPE or EGPEA 6 hr

  6. SUBCHRONIC TOXICITY OF INHALED TOLUENE IN RATS: OXIDATIVE STRESS MARKERS IN BRAIN.

    EPA Science Inventory

    The effects of long-term exposure to volatile organic compounds (VOCs), which is of concern to the EPA, are poorly understood, primarily due to insufficient information about human exposure and unreliable animal models. A sub-chronic inhalation study with multiple endpoints was c...

  7. SUBCHRONIC TOXICITY OF INHALED TOLUENE IN RATS: IMMUNOLOGY, CARDIAC GENE EXPRESSION AND MARKERS OF OXIDATIVE STRESS.

    EPA Science Inventory

    The health effects of long-term exposure to volatile organic compounds (VOCs) are poorly understood, due primarily to insufficient human exposure data and inconsistent animal models. To develop a rodent model of long-term exposure to VOCs, a sub-chronic inhalation study with mult...

  8. SUBACUTE AND SUBCHRONIC ORAL TOXICITY OF P-CHLOROTOLUENE IN THE RAT

    EPA Science Inventory

    P-Chlorotoluene was administered by gavage for 14 and 90 days to male and female Sprague-Dawley-derived rats at dose levels of 200, 600 and 1800 mg/kg/day and 50, 200 and 800 mg/kg/day, respectively. In the 14-day study 8 of 10 animals of each sex in the high-dose group died due ...

  9. NINETY-DAY SUBCHRONIC STUDY OF THE TOXIC EFFECTS OF DICHLOROACETATE IN DOGS

    EPA Science Inventory

    Male and female juvenile Beagle dogs were dosed daily for 90 days with dichloroacetate. he compound was administered orally via gelatin capsule at doses of 0, 12.5, 39.5 and 72 mg/kg/day. ach dose group consisted of 5 males and 5 females. he dogs were observed clinically and bloo...

  10. SUBACUTE AND SUBCHRONIC ORAL TOXICITY OF 1,3-DICHLOROPROPANE IN THE RAT

    EPA Science Inventory

    1,3-Dichloropropane (DCP) was administered by gavage for 14 and 90 days to male and female Sprague-Dawley-derived rats (10/sex/group). valuations included body weight, food consumption, clinical signs, hematology, clinical chemistry, organ weights, and gross and microscopic patho...

  11. 40 CFR 799.9346 - TSCA 90-day inhalation toxicity.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... concentration, white blood cell count, differential leukocyte count, platelet count, and a measure of clotting... requirements specified under 40 CFR part 792, subpart J, the following specific information shall be reported... equipment. The study shall be conducted in compliance with 40 CFR part 792—Good Laboratory...

  12. 40 CFR 799.9346 - TSCA 90-day inhalation toxicity.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... concentration, white blood cell count, differential leukocyte count, platelet count, and a measure of clotting... requirements specified under 40 CFR part 792, subpart J, the following specific information shall be reported... equipment. The study shall be conducted in compliance with 40 CFR part 792—Good Laboratory...

  13. 40 CFR 799.9325 - TSCA 90-day dermal toxicity.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... aminotransferase, alkaline phosphatase, sorbitol dehydrogenase, or gamma glutamyl transpeptidase) should also be... requirements specified under EPA Good Laboratory Practice Standards at 40 CFR part 792, subpart J,...

  14. 40 CFR 799.9346 - TSCA 90-day inhalation toxicity.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... aminotransferase, alkaline phosphatase, sorbitol dehydrogenase, or gamma glutamyl transpeptidase) should also be... requirements specified under 40 CFR part 792, subpart J, the following specific information shall be reported... equipment. The study shall be conducted in compliance with 40 CFR part 792—Good Laboratory...

  15. 40 CFR 799.9325 - TSCA 90-day dermal toxicity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... aminotransferase, alkaline phosphatase, sorbitol dehydrogenase, or gamma glutamyl transpeptidase) should also be... requirements specified under EPA Good Laboratory Practice Standards at 40 CFR part 792, subpart J,...

  16. 40 CFR 799.9346 - TSCA 90-day inhalation toxicity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... aminotransferase, alkaline phosphatase, sorbitol dehydrogenase, or gamma glutamyl transpeptidase) should also be... requirements specified under 40 CFR part 792, subpart J, the following specific information shall be reported... equipment. The study shall be conducted in compliance with 40 CFR part 792—Good Laboratory...

  17. 40 CFR 799.9325 - TSCA 90-day dermal toxicity.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... requirements specified under EPA Good Laboratory Practice Standards at 40 CFR part 792, subpart J, the... to the initiation of the study and periodically during the study. Statistically randomized samples...

  18. 40 CFR 799.9325 - TSCA 90-day dermal toxicity.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... requirements specified under EPA Good Laboratory Practice Standards at 40 CFR part 792, subpart J, the... to the initiation of the study and periodically during the study. Statistically randomized samples...

  19. 40 CFR 799.9325 - TSCA 90-day dermal toxicity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... requirements specified under EPA Good Laboratory Practice Standards at 40 CFR part 792, subpart J, the... to the initiation of the study and periodically during the study. Statistically randomized samples...

  20. Acute and subchronic toxicity as well as evaluation of safety pharmacology of traditional Chinese medicine “Huhezi”

    PubMed Central

    Chen, Yaqin; Chen, Shufan; Song, Chenhui; Yin, Zhongqiong; Chen, Zhenzhen; Jia, Renyong; Liang, Xiaoxia; Li, Lixia; Zou, Yuanfeng; He, Changliang; Ye, Gang; Lv, Cheng

    2015-01-01

    The study was conducted to evaluate the toxicity and safety pharmacology of the traditional Chinese medicine, “Huhezi” granules. The results of acute toxicity test showed that the granules’ LD50 was more than 5000 mg/kg, which indicated that the “Huhezi” belonged to actually non-toxic drug. Subchronic toxicity study showed that non-toxic reaction were detected in high (1000 mg/kg), medium (500 mg/kg) and low dose (250 mg/kg) of “Huhezi” groups by measuring rat body weight, organ coefficient, blood physiological indexes and blood biochemical indexes. Pathological examination showed that no tissue lesions were observed in test organs except liver (mild granular degenerationand reversible vesicular degeneration), spleen (Langerhans cells infiltrating) and kidney (homogeneous red staining of renal tubule). Safety pharmacology study found that “Huhezi” had no effects on the central nervous system, respiratory system and cardiovascular system. These results suggested that the dose of “Huhezi” at or below 1000 mg/kg through oral administration is considered safe. PMID:26550447

  1. Bioassay-guided evaluation of Dioscorea villosa – an acute and subchronic toxicity, antinociceptive and anti-inflammatory approach

    PubMed Central

    2013-01-01

    Background Dioscorea villosa (DV) has been used in Brazil as an alternative medicine to attenuate menopause symptoms, as well as for the treatment of joint pain and rheumatoid arthritis. In spite of the popular use of DV for the treatment of various disorders, there are limited scientific data regarding safety aspects of this herb. In this regard, we carried out to evaluated both antinociceptive and anti-inflammatory activities in experimental models and assess the toxic effects of the acute (single dose) and subchronic (30 days) oral administration of dry extract of Dioscorea villosa in rodents. Methods The LC analyses were performed to assess the presence of the diosgenin in samples of DV. The antinociceptive study of DV was performed using models of acetic acid-induced writhing and formalin-induced pain in mice. The anti-inflammatory study was accomplished by leukocyte migration to the peritoneal cavity. A dry extract of DV was tested at doses of 100, 200 and 400 mg/kg (per os or p.o.). The toxicological properties of the dry extract were evaluated by toxicity assays of acute (5 g/kg, single dose) and subchronic (1 g/kg/day, 30 days) treatment. Haematological, biochemical, and histopathological parameters were studied. The results are expressed as mean ± S.D., and statistical analysis of the data were performed with the Student’s t-test or one-way analysis of variance (ANOVA) followed by Tukey’s test. In all cases differences were considered significant if p < 0.05. Results HPLC-DAD analysis of the extract from DV revealed the presence of diosgenin as the major compound. Doses of 200 and 400 mg⁄kg significantly reduced the amount of acetic acid-induced writhing in relation to the vehicle (p < 0.0001). In the first phase, using the formalin-induced neurogenic pain test, only the 400 mg/kg dose of DV showed significant inhibition of neurogenic pain (p < 0.001). In the second phase, 200 and 400 mg/kg of DV showed significant

  2. A subchronic (180-day) oral toxicity study of ethyl tertiary-butyl ether, a bioethanol, in rats.

    PubMed

    Miyata, Katsumi; Koga, Takayuki; Aso, Sunao; Hoshuyama, Satsuki; Ajimi, Syozo; Furukawa, Kotaro

    2014-07-01

    A subchronic (180-day) toxicity study was conducted to evaluate the effects of ethyl tertiary-butyl ether (ETBE), a biomass fuel, in male and female rats. ETBE was administered at dose levels of 0, 5, 25, 100 and 400 mg/kg/body weight (b.w.)/day by gavage. No treatment-related adverse effects were observed at 5, 25 or 100 mg/kg. Centrilobular hypertrophy of hepatocytes was observed in males and females and their relative liver weights were increased, suggesting enhanced metabolic activity. From these results, we concluded that the no observed adverse effect level of ETBE was 100 mg/kg b.w./day under the conditions tested. PMID:24252074

  3. ACUTE AND SUBCHRONIC TOXICITY OF 2,4-DICHLOROPHENOL IN DC-1 MICE

    EPA Science Inventory

    Male and female CD-1 mice were exposed to 2,4-dichlorophenol (DCP) in drinking water containing 10% emulphor for 90 days at concentrations of 0.2, 0.6, and 2.0 mg/ml. The mean daily consumption values ranged from 46.3 to 542 mg/kg/day for females and 34.9 and 419 mg/kg/day in mal...

  4. The sub-chronic oral toxicity of 1,3,5-trimethylbenzene in Sprague-Dawley rats.

    PubMed

    Adenuga, David; Carrillo, Juan-Carlos; Mckee, Richard H

    2014-07-01

    The systemic toxicity of a trimethylbenzene isomer and constituent of C9 aromatic solvents (1,3,5-trimethylbenzene, 135-TMB) was studied in Sprague-Dawley rats following a 90-day oral gavage exposure to 0, 50, 200 and 600 mg/kg/day. No statistically significant effects on body weight, body weight gain or food consumption were observed at study termination. Treatment-related changes in clinical chemistry parameters at the end of the 90-day dosing period were limited to small, but statistically significant, increases in phosphorus levels in high dose males and females. Liver enlargement in high dose male/female rats was considered an adaptive response as this was reversible and was not associated with histopathological lesions or increased liver enzyme markers indicative of liver damage. Kidney weight changes were limited to a small, but statistically significant, increase in relative weights in high dose males. This was not associated with histopathological lesions and thus not considered toxicologically relevant. Overall, the No-Observed-Adverse-Effect-Level (NOAEL) was the highest concentration tested (600 mg/kg/day). The results of the present study are relevant for assessing the risk of trimethylbenzenes through the oral route of exposure and provide a basis for the development of provisional screening values for trimethylbenzene isomers while avoiding the uncertainty associated with route-to-route extrapolation. PMID:24704044

  5. Evaluation of sub-chronic toxic effects of petroleum ether, a laboratory solvent in Sprague-Dawley rats

    PubMed Central

    Parasuraman, Subramani; Sujithra, Jeyabalan; Syamittra, Balakrishnan; Yeng, Wong Yeng; Ping, Wu Yet; Muralidharan, Selvadurai; Raj, Palanimuthu Vasanth; Dhanaraj, Sokkalingam Arumugam

    2014-01-01

    Background: In general, organic solvents are inhibiting many physiological enzymes and alter the behavioural functions, but the available scientific knowledge on laboratory solvent induced organ specific toxins are very limited. Hence, the present study was planned to determine the sub-chronic toxic effects of petroleum ether (boiling point 40–60°C), a laboratory solvent in Sprague-Dawley (SD) rats. Materials and Methods: The SD rats were divided into three different groups viz., control, low exposure petroleum ether (250 mg/kg; i.p.) and high exposure petroleum ether (500 mg/kg; i.p.) administered group. The animals were exposed with petroleum ether once daily for 2 weeks. Prior to the experiment and end of the experiment animals behaviour, locomotor and memory levels were monitored. Before initiating the study animals were trained for 2 weeks for its learning process and its memory levels were evaluated. Body weight (BW) analysis, locomotor activity, anxiogenic effect (elevated plus maze) and learning and memory (Morris water navigation task) were monitored at regular intervals. On 14th day of the experiment, few ml of blood sample was collected from all the experimental animals for estimation of biochemical parameters. At the end of the experiment, all the animals were sacrificed, and brain, liver, heart, and kidney were collected for biochemical and histopathological analysis. Results: In rats, petroleum ether significantly altered the behavioural functions; reduced the locomotor activity, grip strength, learning and memory process; inhibited the regular body weight growth and caused anxiogenic effects. Dose-dependent organ specific toxicity with petroleum ether treated group was observed in brain, heart, lung, liver, and kidney. Extrapyramidal effects that include piloerection and cannibalism were also observed with petroleum ether administered group. These results suggested that the petroleum ether showed a significant decrease in central nervous system

  6. Subchronic toxicity studies on 1,3,5-trinitrobenzene, 1,3-dinitrobenzene, and tetryl in rats. Subchronic toxicity evaluation of 1,3,5-trinitrobenzene in Fischer 344 rats. Final report

    SciTech Connect

    Reddy, T.V.; Daniel, F.B.; Robinson, M.; Olson, G.R.; Wiechman, B.

    1994-05-01

    Subchronic toxic effects of 1,3,5-trinitrobenzene (TNB) in male and female Fischer 344 rats were evaluated by feeding powdered certified laboratory chow diet supplemented with varied concentrations of TNB (0, 66.67, 400 and 800 mg/kg diet) so as to achieve a final target dose of 0, 5, 30 and 60 mg/kg b.w. for ninety days. Food intake in the 400 and 800 mg TNB dose groups of both sexes was reduced throughout the study and resulted in a significant decrease in absolute body weights. The calculated average TNB dosage was 4, 25 and 49 mg/kg/day for females and 4, 21 and 44 mg/kg/day for males. A decrease in testicular weight in males and increase in relative spleen weight of both sexes in the 400 and 800 mg TNB dose groups were noted. Also, the relative brain weight was increased in the male 400 and 800 mg TNB dose groups while the relative liver weight was increased in 800 mg TNB dose group of both sexes. Histopathological examinations suggested that the susceptible organs for TNB toxicity were kidney (hyaline droplets), spleen (extramedullary hemotopoiesis) and testes (seminiferous tubular degeneration). Hematology and clinical chemistry studies indicated a decrease in red blood cell count and hematocrit, a decrease in alkaline phosphatase, an increase in reticulocytes and increased methemoglobin concentration as compared to controls in both sexes.

  7. Subchronic toxicity and immunotoxicity of MeO-PEG-poly(D,L-lactic-co-glycolic acid)-PEG-OMe triblock copolymer nanoparticles delivered intravenously into rats

    NASA Astrophysics Data System (ADS)

    Liao, Longfei; Zhang, Mengtian; Liu, Huan; Zhang, Xuanmiao; Xie, Zhaolu; Zhang, Zhirong; Gong, Tao; Sun, Xun

    2014-06-01

    Although monomethoxy(polyethyleneglycol)-poly (D,L-lactic-co-glycolic acid)-monomethoxy (PELGE) nanoparticles have been widely studied as a drug delivery system, little is known about their toxicity in vivo. Here we examined the subchronic toxicity and immunotoxicity of different doses of PELGE nanoparticles with diameters of 50 and 200 nm (PELGE50 and PELGE200) in rats. Neither size of PELGE nanoparticles showed obvious subchronic toxic effects during 28 d of continuous intravenous administration based on clinical observation, body weight, hematology parameters and histopathology analysis. PELGE200 nanoparticles showed no overt signs of immunotoxicity based on organ coefficients, histopathology analysis, immunoglobulin levels, blood lymphocyte subpopulations and splenocyte cytokines. Conversely, PELGE50 nanoparticles were associated with an increased organ coefficient and histopathological changes in the spleen, increased serum IgM and IgG levels, alterations in blood lymphocyte subpopulations and enhanced expression of spleen interferon-γ. Taken together, these results suggest that PELGE nanoparticles show low subchronic toxicity but substantial immunotoxicity, which depends strongly on particle size. These findings will be useful for safe application of PELGE nanoparticles in drug delivery systems.

  8. Subacute and subchronic oral toxicity of p-chlorotoluene in the rat

    SciTech Connect

    Terrill, J.B.; Robinson, M.; Wolfe, G.W.; Billups, L.H.

    1990-01-01

    P-Chlorotoluene was administered by gavage for 14 and 90 days to male and female Sprague-Dawley-derived rats at dose levels of 200, 600 and 1800 mg/kg/day and 50, 200 and 800 mg/kg/day, respectively. In the 14-day study 8 of 10 animals of each sex in the high-dose group died due to treatment. Other treatment-related signs for these animals included an adverse effect upon body weight, and clinical signs of salivation, tremors and prostration. In the 200 and 600 mg/kg/day groups there were no apparent treatment-related effects. In the 90-day study, 4 of 10 males and 2 of 10 females in the high-dose group died due to treatment. Other signs for this treatment group included an adverse effect upon body weight, and clinical signs of languid behavior, prostration, tremors, sensitive to touch, epistaxis and respiratory distress. Increases in alkaline phosphatase and creatinine (males only), and increases in adrenal (absolute and relative, females), kidney (relative, both sexes) and liver (relative, both sexes) weights were also noted.

  9. Subchronic 4-month oral toxicity study of dried Smallanthus sonchifolius (yacon) roots as a diet supplement in rats.

    PubMed

    Genta, Susana B; Cabrera, Wilfredo M; Grau, Alfredo; Sánchez, Sara S

    2005-11-01

    Yacon roots are a rich source of fructooligosaccharides (FOS) and have a long use tradition as food in the Andean region. However, there are no published reports regarding their toxicology and use safety. The aim of this study was to analyze the effects of subchronic (4-months) oral consumption of dried yacon root flour as a diet supplement using normal Wistar rats. Two daily intake levels were used, equivalent to 340 mg and 6800 mgFOS/body weight, respectively. Yacon administered as a diet supplement was well tolerated and did not produce any negative response, toxicity or adverse nutritional effect at both intake levels used. Yacon root consumption showed no hypoglycemic activity in normal rats and resulted in significantly reduced post-prandial serum triacylglycerol levels in both doses assayed. Conversely, serum cholesterol reduction was not statistically significant. Cecal hypertrophy was observed in rats fed only the high dose. Our results indicating lack of toxicity and a certain beneficial metabolic activity in normal rats warrant further experiments with normal subjects and patients suffering metabolic disorders. They should also be considered when establishing the regulatory framework of this natural product by national health authorities and international trade agencies. PMID:15979774

  10. Combined subchronic toxicity of dichlorvos with malathion or pirimicarb in mice liver and serum: a metabonomic study.

    PubMed

    Wang, Pan; Wang, Hui-Ping; Xu, Ming-Yuan; Liang, Yu-Jie; Sun, Ying-Jian; Yang, Lin; Li, Li; Li, Wei; Wu, Yi-Jun

    2014-08-01

    Organophosphorus (OP) and carbamate (CM) pesticides are widely used in agriculture. These pesticides are highly toxic to humans and their residues in food pose potential threat to human health. In this study, we investigated the effect of subchronic low-level exposure of OPs (dichlorvos, DDVP; malathion, MAL), CM pirimicarb (PI), or their mixtures (DDVP+MAL, DDVP+PI) on mice liver. Metabonomic analysis based on (1)H nuclear magnetic resonance spectroscopy was carried out in combination with biochemical assays. Serum metabonomic analysis showed that levels of trimethylamine-N-oxide, lactate, acetone, very low- and low-density lipoprotein and 3-hydroxybutyrate changed after exposure to the pesticides. In the liver extracts, lactate, glucose, choline, glutathione, alanine, glutamine and isoleucine levels changed after the treatment by pesticides. Our results indicated that exposure to low dose DDVP, MAL and PI, either alone or in combination lead to alteration of liver glucose, fat and protein metabolism, energy metabolism and oxidative balance. This study also showed that metabonomics is of potential use in food toxicity study. PMID:24907623

  11. Subchronic toxicity of 2,2{prime},3,3{prime},4,4{prime}-hexachlorobiphenyl in rats

    SciTech Connect

    Lecavalier, P.; Chu, I.; Feeley, M.

    1997-06-27

    The subchronic toxicity of 2,2{prime},3,3{prime},4,4{prime}-hexachlorobiphenyl (PCB 128) was investigated in rats following dietary exposure at 0, 0.05, 0.5, 5, or 50 ppm for 13 wk. The growth rate was not affected by treatment and no apparent clinical signs of toxicity were observed. There was a significant increase in liver weight in the 50 ppm females. The liver ethoxy-resorufin deethylase (EROD) activity was increased by five- and fourfold in the highest dose males and females, respectively, while aminopyrine demethylase (ADPM) activity was significantly increased only in the highest dose females. Liver vitamin A was significantly reduced in the highest dose females. No other biochemical or hematological effects were observed. Treatment-related histopathological changes were seen in the thyroid and liver, and to a lesser extent in the bone marrow and thymus. Residue data showed a dose-dependent accumulation of PCB 128 in the following tissues: fat, liver, kidney, brain, spleen, and serum, with the highest concentration being found in fat followed by liver and kidney. Based on these data, the no-observable-adverse-effect level of PCB 128 was judged to be 0.5 ppm in diet or 42 {mu}g/kg body weight. 29 refs., 1 fig., 5 tabs.

  12. A SURROGATE SUBCHRONIC TOXICITY TEST METHOD FOR WATERS WITH HIGH TOTAL DISSOLVED SOLIDS

    EPA Science Inventory

    Total dissolved solids (TDS) are often identified as a toxicant in whole-effluent toxicity (WET) testing. The primary test organism used in WET testing, Ceriodaphnia dubia, is very sensitive to TDS ions, which can be problematic when differentiating the toxicity of TDS from those...

  13. TEN- AND NINETY-DAY TOXICITY STUDIES OF 1,2-DICHLOROBENZENE ADMINISTERED BY ORAL GAVAGE TO SPRAGUE-DAWLEY RATS

    EPA Science Inventory

    Subacute (10-day) and subchronic (90-day) toxicity studies of 1,2-dichlorobenzene (DCB) were conducted in male and female Sprague-Dawley rats. ,2-Dichlorobenzene was administered in corn oil by oral gavage; control animals received corn oil. t time of sacrifice, gross necropsies ...

  14. Subchronic toxicity of ethylene glycol in Wistar and F-344 rats is related to metabolism and clearance of metabolites.

    SciTech Connect

    Cruzan, G; Corley, Rick A.; Hard, G; Mertens, J W.; McMartin, K. E.; Snellings, W; Gingell, Ralph; Deyo, J A.

    2004-10-01

    Ethylene Glycol (CAS RN 107-21-1) can to cause kidney toxicity via the formation of calcium oxalate crystals in a variety of species including humans. Numerous repeated dose studies conducted in rats have indicated that male rats are more susceptible than female rats. Furthermore, subchronic and chronic studies using different dietary exposure regimens have indicated that male Wistar rats may be more sensitive to renal toxicity than male F344 rats. This study was, therefore, conducted to compare the toxicity of ethylene glycol in the two strains of rats under identical exposure conditions and to evaluate the potential contribution of toxicokinetic differences to strain sensitivity. Ethylene glycol was mixed in the diet at concentrations to deliver constant target dosage levels of 0, 50, 150, 500, or 1000 mg/kg/day for 16 weeks to groups of 10 male Wistar and 10 male F-344 rats based upon weekly group mean body weights and feed consumption. Kidneys were examined histologically for calcium oxalate crystals and pathology. Samples of blood, urine and kidneys from satellite animals exposed to 0, 150, 500, or 1000 mg/kg/day for 1 or 16 weeks were analyzed for ethylene glycol, glycolic acid and oxalic acid. Treatment of Wistar rats at 1000 mg/kg/day resulted in the death of 2 rats; in addition, at 500 and 1000 mg/kg/day, group mean body weights were decreased compared to control throughout the 16 weeks. In F-344 rats exposed at 1000 mg/kg/day and in Wistar rats at 500 and 1000 mg/kg/day, there were lower urine specific gravities, higher urine volumes, and increased absolute and relative kidney weights. In both strains of rats treated at 500 and 1000 mg/kg/day, some or all treated animals had increased calcium oxalate crystals in the kidney tubules and crystal nephropathy. The effect was more severe in Wistar rats than in F-344 rats. Accumulation of oxalic acid in the kidneys of both strains of rats were consistent with the dose- and strain-dependent toxicity. As the

  15. Protective effect of edible marine algae, Laminaria japonica and Porphyra haitanensis, on subchronic toxicity in rats induced by inorganic arsenic.

    PubMed

    Jiang, Yanhua; Wang, Lianzhu; Yao, Lin; Liu, Zhantao; Gao, Hua

    2013-09-01

    Arsenic, a potent environmental toxic agent, causes various hazardous effects on human health. This study was performed to evaluate the protective effects of edible marine algae, Laminaria japonica and Porphyra haitanensis, on subchronic stress of rats induced by arsenic trioxide (As2O3). The co-treatment of marine algae could slightly increase the growth rates of body weights compared to the As2O3-treated group. The marine algae application restored liver and renal function by preventing the increment in the activities of alanine transaminase and alkaline phosphatase, and the levels of total protein, blood urea nitrogen, and creatinine. The increase in the contents of total cholesterol, triglyceride, and low density lipoprotein cholesterol, and decrease in the contents of high density lipoprotein cholesterol were observed in algae co-treated groups which indicated that marine algae could reverse the abnormal lipid metabolisms induced by arsenic. Moreover, these algae could protect the rats from lipid peroxidation by restoring the depletion of superoxide dismutase and glutathione peroxidase activities and sulfhydryl group contents, and lowering the enhanced malondialdehyde contents. Therefore, evidences indicate that L. japonica and P. haitanensis can serve as an effective regimen for treating arsenic poisoning. PMID:23842700

  16. 40 CFR 79.62 - Subchronic toxicity study with specific health effect assessments.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... references should be consulted. (1) 40 CFR 798.2450, Inhalation toxicity. (2) 40 CFR 798.2675, Oral Toxicity... chromosome. This assay uses peripheral blood lymphocytes isolated from an exposed rodent test species and... separating blood components, individual lymphocyte cell cultures are set up for SCE analysis. One femur...

  17. 40 CFR 79.62 - Subchronic toxicity study with specific health effect assessments.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... references should be consulted. (1) 40 CFR 798.2450, Inhalation toxicity. (2) 40 CFR 798.2675, Oral Toxicity... chromosome. This assay uses peripheral blood lymphocytes isolated from an exposed rodent test species and... separating blood components, individual lymphocyte cell cultures are set up for SCE analysis. One femur...

  18. 40 CFR 79.62 - Subchronic toxicity study with specific health effect assessments.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... references should be consulted. (1) 40 CFR 798.2450, Inhalation toxicity. (2) 40 CFR 798.2675, Oral Toxicity... chromosome. This assay uses peripheral blood lymphocytes isolated from an exposed rodent test species and... separating blood components, individual lymphocyte cell cultures are set up for SCE analysis. One femur...

  19. 40 CFR 79.62 - Subchronic toxicity study with specific health effect assessments.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... references should be consulted. (1) 40 CFR 798.2450, Inhalation toxicity. (2) 40 CFR 798.2675, Oral Toxicity... chromosome. This assay uses peripheral blood lymphocytes isolated from an exposed rodent test species and... separating blood components, individual lymphocyte cell cultures are set up for SCE analysis. One femur...

  20. Subchronic oral toxicity and metabolite profiling of the p53 stabilizing agent, CP-31398, in rats and dogs.

    PubMed

    Johnson, William D; Muzzio, Miguel; Detrisac, Carol J; Kapetanovic, Izet M; Kopelovich, Levy; McCormick, David L

    2011-11-18

    maximum tolerated dose (MTD) for subchronic oral administration of CP-31398 is 80mg/kg/day (480mg/m(2)/day) in rats and 20mg/kg/day (400mg/m(2)/day) in dogs. Although only modest and apparently reversible toxicities (microscopic changes in rats; reductions in body weight gain and alterations in red cell parameters in dogs) were seen in the low dose groups, no observed adverse effect levels (NOAELs) for CP-31398 could not be established for either species. The toxicity of CP-31398 suggests that this agent may not be suitable for use in cancer prevention. However, should in vivo antitumor efficacy be achievable at doses that do not induce limiting toxicity, CP-31398 may have utility as a cancer therapeutic. Modification of the primary sites of CP-31398 metabolism (N-demethylation of the alkyl side chain; hydroxylation and O-demethylation of the styryl benzene group) may result in the development of CP-31398 analogs with comparable pharmacologic activity and reduced toxicity. PMID:21864638

  1. Subchronic metabolic effects and toxicity of a simulated pulp mill effluent on juvenile lake trout, Salmo trutta m. lacustris.

    PubMed

    Oikari, A; Linström-Seppä, P; Kukkonen, J

    1988-12-01

    Juvenile lake trout (Salmo trutta m. lacustris) were exposed for 7 weeks to 0.05X and 0.2X 96-hr LC50 concentrations of simulated bleached kraft pulp mill effluent (KME - Sa + CP). A sulfate soap preparation, composed mainly of resin and fatty acids, with added chlorophenols (CP, tri-, tetra-, and penta-CP) was used as the toxicant mixture. Concentrations of free CP in plasma and free and conjugated CP in bile were proportional to their concentrations in the water. The greatest total gradient between bile and water CP was 5.2 X 10(4) for pentachlorophenol. The activity of a liver polysubstrate monooxygenase (PSMO) system, assayed with three model substrates, increased 40 to 67% due to KME - Sa + CP. However, the increase was not directly dependent on the exposure concentration. In contrast to PSMO, activities of conjugating enzymes (p-nitrophenol UDP-glucuronosyl and glutathione transferases) were decreased in the liver. Increased concentration of glutathione was noted in the liver and kidney. In addition, a small (9%) but significant decrease in blood hemoglobin concentration was observed at the higher exposure concentration. Although growth rate of lake trout was markedly decreased due to KME - Sa + CP, hydromineral balance and carbohydrate metabolism in fish were unaffected, indicating possible physiological compensation. On the other hand, lethality tests with lake trout preexposed to KME - Sa + CP at 0.2 X LC50 revealed decreased tolerance, whereas at the lower exposure concentration it was unchanged. We therefore conclude that various physiological adjustments in trout during subchronic exposures were not adaptive in terms of short-term tolerance. PMID:3265913

  2. Acute and subchronic toxicity of arsenite and zinc to tadpoles of Rhinella arenarum both alone and in combination.

    PubMed

    Brodeur, Julie Céline; Asorey, Cynthia Melina; Sztrum, Abelardo; Herkovits, Jorge

    2009-01-01

    The current study evaluated acute and subchronic toxicity of arsenite (As(3+)) and zinc (Zn(2+)) to stage 25 tadpoles of Rhinella arenarum in both single and joint laboratory exposures. LC50 values obtained for As(3+) were elevated and remained within the range of 46 to 50 mg/L of As(3+) between 4 and 17 d of exposure. Growth of tadpoles was completely inhibited with 30 mg/L of As(3+), demonstrating the presence of ecologically relevant sublethal effects at concentrations lower than those resulting in lethality. With respect to Zn(2+), a 96-h LC50 value of 2.49 mg/L was calculated in soft water. Contrary to results obtained for As(3+), LC50 values of Zn(2+) gradually decreased with increasing exposure duration, from 2.49 mg/L at 96 h to 1.30 mg/L after 21 d. In joint exposures to both metals, the type of interaction observed between As(3+) and Zn(2+) was concentration dependent. Lethal effects of As(3+) were mitigated, unaffected, or potentiated by 0.01, 0.1, and 1-2 mg/L of Zn(2+), respectively. However, although 0.01 mg/L of Zn(2+) significantly reduced lethality of As(3+)-exposed tadpoles, the same concentration of Zn(2+) did not help to reverse the stunt growth of these animals. Further studies need to examine which are the lowest concentrations As(3+) required to reduce growth and whether Zn(2+) serves to antagonize growth effects in this range of concentrations. PMID:19557616

  3. Subchronic dermal exposure to T-2 toxin produces cardiac toxicity in experimental Wistar rats.

    PubMed

    Chattopadhyay, Pronobesh; Islam, Johirul; Goyary, Danswrang; Agnihotri, Amit; Karmakar, Sanjev; Banerjee, Subham; Singh, Lokendra; Veer, Vijay

    2016-03-01

    Our study aimed to determine the cardiac toxicities of T-2 toxin, a representative mycotoxin that frequently contaminates maize, cereals, and other agricultural products, harvested and stored under damp and cold conditions. Dermal exposure to T-2 toxin caused severe cardiotoxicity in experimental Wistar rats. Electrocardiography studies showed the conduction abnormalities including prolongation of the QT and corrected QT interval, shortening of the PR interval, and tachycardia. Biochemical studies also reported the toxicity of T-2 toxin. T-2 toxin induced acute cardiotoxicity in rats and characterized by significant (p < 0.05) elevation of serum troponin I, creatine kinase (CK) isoenzyme MB, CK isoenzyme NAC, and lactate dehydrogenase as compared to control rats. It is concluded that cardiotoxicity effects of T-2 toxin are thought to be due to direct action on electrocardiac potentials and biochemical changes. PMID:24193048

  4. Protective effects of subchronic caffeine administration on cisplatin induced urogenital toxicity in male mice.

    PubMed

    Khazaei, M; Bayat, P D; Ghanbari, A; Khazaei, S; Feizian, M; Khodaei, A; Alian, H A S

    2012-09-01

    In Cisplatin treated group, the degeneration intensity of the kidneys the diameter of seminiferous tubules as well as the apoptotic index in testes and kidney were increased. In Caffeine+Cisplatin treated groups, the total body weight, the weight of testes and kidneys and also the histopathological data did not show significant differences. The motility of sperm in cisplatin group reduced but in Caffeine+Cisplatin groups this parameter was increased. These data suggest that caffeine recovers toxicity induced by cisplatin in both kidneys and testes of mice. PMID:23140022

  5. Thyroid toxicity due to subchronic exposure to a complex mixture of 16 organochlorines, lead, and cadmium.

    PubMed

    Wade, Michael G; Parent, Sophie; Finnson, Kenneth W; Foster, Warren; Younglai, Edward; McMahon, Avril; Cyr, Daniel G; Hughes, Claude

    2002-06-01

    The human population in the industrialized world is ubiquitously exposed to complex mixtures of persistent pollutants that contaminate food, water, and air. A large number of these contaminants have been shown to cause significant toxicity to the hypothalamic-pituitary-thyroid (HPT) axis in laboratory animal studies, through a variety of mechanisms, although these effects occur at levels of exposure greatly in excess of common human exposure. While many of the mechanisms of thyroid toxicity of these substances are potentially complementary, little is known of the degree of interaction of common persistent contaminants on responses of the HPT axis. To investigate the potential effects of a complex, environmentally relevant mixture on the HPT axis, sexually mature male rats were administered a mixture of 16 common organochlorines (dichlorodiphenoxytrichloroethane [DDT], p,p'-dichlorodiphenoxydichloroethylene [p,p'-DDE], hexachlorobenzene [HCB], tetrachlorodibenzo-p-dioxin [TCDD], polychlorinated biphenyls [PCBs], methoxychlor, endosulfan, heptachlor, hexachlorocyclohexane, dieldrin, aldrin, mirex, and several chlorinated benzenes, and metal contaminants [lead, cadmium]). The doses of the mixture that were administered were related to minimum risk levels or tolerable daily intakes of these substances, as derived by risk assessment with the 1x, 10x, 100x, and 1000x groups receiving mixture components at doses equivalent to 1x, 10x, 100x, or 1000x the minimum risk level (or tolerable daily intake, reference dose), respectively. After 70 daily treatments by gavage, endpoints related to circulating thyroid hormone (serum thyroxine [T(4)], triiodothyronine [T(3)], thyroid stimulating hormone [TSH], and serum T(3) uptake [T(3)-up]), thyroid gland histomorphology (thyroid follicle cross sectional area, epithelial height, follicle roundness or aspect ratio, colloid/epithelial ratio) and hepatic metabolism of thyroid hormone (UDP-glucuronyl transferase [UGT] and outer

  6. Subchronic toxicity study of Caramel Colour II in F344 rats.

    PubMed

    MacKenzie, K M; Carter, J L; Petsel, S R; Chappel, C I; Emerson, J L; Stanley, J

    1992-05-01

    Caramel Colour II is a distinct type of colourant with a pronounced reddish hue. It is made with sulphite reactants but without ammonia. The red colour and a high alcohol solubility provide functional characteristics that are important in foods or beverages containing natural flavour extractives. Caramel Colour II is widely used in ice creams and liqueurs; however, it represents less than 1% of total caramel colour manufacture. The toxicity of Caramel Colour II was evaluated in a 13-wk study in Fischer-344 (F344) rats. The test material was mixed with demineralized water and the solutions were given to the animals ad lib. in the drinking fluid. The concentrations of caramel colour in the drinking fluid were adjusted periodically to achieve the desired caramel colour intake/kg body weight/day. Groups of 20 rats/sex were given Caramel Colour II at levels of 0, 4, 8, 12 or 16 g/kg for at least 13 wk. There were no deaths in any of the groups fed Caramel Colour II. All rats fed caramel colour had soft faeces. All treated groups also had lower fluid consumption that was attributed to poor palatability of the high concentrations of caramel colour that were fed. A number of changes observed (reduced food consumption in all treatment groups except males given 4 g/kg; significantly lower body weights for males given 12 g/kg or more and for females given 8 g/kg or more; lower urine volume and higher specific gravity) were attributed to the reduced water intake and not considered to be toxicologically significant. There were no consistent treatment-related alterations in haematology or blood chemistry variables, and random changes noted were not associated with macroscopic or microscopic pathological alterations. There were no toxicologically important pathological findings. Based on this study, Caramel Colour II was not toxic in F344 rats treated for 13 wk. The highest dose level tested in this study (16 g/kg) was considered to be the no-observed-adverse-effect level. PMID

  7. Subchronic Oral Dose Toxicity of Freeze-dried Powder of Allomyrina dichotoma Larvae

    PubMed Central

    Noh, Jung-Ho; Yun, Eun-Young; Park, Heejin; Jung, Kyung-Jin; Hwang, Jae Sam; Jeong, Eun Ju; Moon, Kyoung-Sik

    2015-01-01

    The objective of this study was to investigate the toxicological information of freeze-dried powder from Allomyrina dichotoma (A. dichotoma) larvae as a food ingredient. The powder, suspended in distilled water, was administered once daily by oral gavage to four groups of Sprague-Dawley (SD) rats at dose levels of 0 (vehicle control), 250, 850, and 2500 mg/kg/day. After 13 wks of repeated administration, the standard toxicological parameters such as mortality, clinical signs, body weight, food consumption, ophthalmologic examination, clinical pathology, organ weights and macro/microscopic examination were applied for assessment of general toxicity. In addition, serum IgE and histamine levels were determined to evaluate allergenicity. The freeze-dried powder from A. dichotoma larvae did not produce treatmentrelated changes or findings in any toxicological parameters in either sex of any dosed groups except for slight increases in serum histamine levels at 2500 mg/kg/day. The changes were considered not to be adverse since the magnitude was minimal. In conclusion, the NOAEL (No Observed Adverse Effect Level) of the freeze-dried powder from A. dichotoma larvae was determined to be 2500 mg/kg/day or more in both sexes of SD rats and it is considered a candidate to be edible material. PMID:25874035

  8. Subchronic Oral Dose Toxicity of Freeze-dried Powder of Allomyrina dichotoma Larvae.

    PubMed

    Noh, Jung-Ho; Yun, Eun-Young; Park, Heejin; Jung, Kyung-Jin; Hwang, Jae Sam; Jeong, Eun Ju; Moon, Kyoung-Sik

    2015-03-01

    The objective of this study was to investigate the toxicological information of freeze-dried powder from Allomyrina dichotoma (A. dichotoma) larvae as a food ingredient. The powder, suspended in distilled water, was administered once daily by oral gavage to four groups of Sprague-Dawley (SD) rats at dose levels of 0 (vehicle control), 250, 850, and 2500 mg/kg/day. After 13 wks of repeated administration, the standard toxicological parameters such as mortality, clinical signs, body weight, food consumption, ophthalmologic examination, clinical pathology, organ weights and macro/microscopic examination were applied for assessment of general toxicity. In addition, serum IgE and histamine levels were determined to evaluate allergenicity. The freeze-dried powder from A. dichotoma larvae did not produce treatmentrelated changes or findings in any toxicological parameters in either sex of any dosed groups except for slight increases in serum histamine levels at 2500 mg/kg/day. The changes were considered not to be adverse since the magnitude was minimal. In conclusion, the NOAEL (No Observed Adverse Effect Level) of the freeze-dried powder from A. dichotoma larvae was determined to be 2500 mg/kg/day or more in both sexes of SD rats and it is considered a candidate to be edible material. PMID:25874035

  9. Health assessment of gasoline and fuel oxygenate vapors: subchronic inhalation toxicity.

    PubMed

    Clark, Charles R; Schreiner, Ceinwen A; Parker, Craig M; Gray, Thomas M; Hoffman, Gary M

    2014-11-01

    Sprague Dawley rats were exposed via inhalation to vapor condensates of either gasoline or gasoline combined with various fuel oxygenates to assess whether their use in gasoline influences the hazard of evaporative emissions. Test substances included vapor condensates prepared from an EPA described "baseline gasoline" (BGVC), or gasoline combined with methyl tertiary butyl ether (G/MTBE), ethyl t-butyl ether (G/ETBE), t-amyl methyl ether (G/TAME), diisopropyl ether (G/DIPE), ethanol (G/EtOH), or t-butyl alcohol (G/TBA). Target concentrations were 0, 2000, 10,000 or 20,000mg/m(3) and exposures were for 6h/day, 5days/week for 13weeks. A portion of the animals were maintained for a four week recovery period to determine the reversibility of potential adverse effects. Increased kidney weight and light hydrocarbon nephropathy (LHN) were observed in treated male rats in all studies which were reversible or nearly reversible after 4weeks recovery. LHN is unique to male rats and is not relevant to human toxicity. The no observed effect level (NOAEL) in all studies was 10,000mg/m(3), except for G/MTBE (<2000) and G/TBA (2000). The results provide evidence that use of the studied oxygenates are unlikely to increase the hazard of evaporative emissions during refueling, compared to those from gasoline alone. PMID:25020274

  10. Subchronic oral toxicity study of furan in B6C3F1 Mice.

    PubMed

    Gill, S; Kavanagh, M; Barker, M; Weld, M; Vavasour, E; Hou, Y; Cooke, G M

    2011-08-01

    Furan is a heterocyclic organic compound formed during heat treatment for processing and preservation of various types of food. Rodent studies have previously shown that furan is a hepatocarcinogen. Those studies were conducted over a high dose range, which induced tumors at nearly 100% incidence at all doses. This ninety-day gavage study in mice was conducted to extend the dose to a lower range (0.0, 0.03, 0.12, 0.5, 2.0, and 8.0 mg/kg body weight [bw] per day) to identify a no-observed adverse effect level for hepatotoxicity and to characterize non-neoplastic effects, including those affecting clinical biochemistry, hematology, tissue morphology, and histopathology. The liver was the primary target organ with dose-dependent toxicity. Liver weights were increased at the 8.0 mg/kg bw dose in females only. Levels of the serum enzyme alanine transaminase, representative of liver damage, were increased three-fold at the highest dose. Histological changes in the liver were observed at 2.0 and 8.0 mg/kg bw in both sexes. Although clinical parameters were also altered for the kidney, these differences were not accompanied by histological changes. Based on these clinical biochemical and histological changes, a no-observed adverse effect level of 0.12 mg/kg bw per day of furan in mice is suggested. PMID:21705744

  11. Sub-chronic toxicity study in rats orally exposed to nanostructured silica

    PubMed Central

    2014-01-01

    Background Synthetic Amorphous Silica (SAS) is commonly used in food and drugs. Recently, a consumer intake of silica from food was estimated at 9.4 mg/kg bw/day, of which 1.8 mg/kg bw/day was estimated to be in the nano-size range. Food products containing SAS have been shown to contain silica in the nanometer size range (i.e. 5 – 200 nm) up to 43% of the total silica content. Concerns have been raised about the possible adverse effects of chronic exposure to nanostructured silica. Methods Rats were orally exposed to 100, 1000 or 2500 mg/kg bw/day of SAS, or to 100, 500 or 1000 mg/kg bw/day of NM-202 (a representative nanostructured silica for OECD testing) for 28 days, or to the highest dose of SAS or NM-202 for 84 days. Results SAS and NM-202 were extensively characterized as pristine materials, but also in the feed matrix and gut content of the animals, and after in vitro digestion. The latter indicated that the intestinal content of the mid/high-dose groups had stronger gel-like properties than the low-dose groups, implying low gelation and high bioaccessibility of silica in the human intestine at realistic consumer exposure levels. Exposure to SAS or NM-202 did not result in clearly elevated tissue silica levels after 28-days of exposure. However, after 84-days of exposure to SAS, but not to NM-202, silica accumulated in the spleen. Biochemical and immunological markers in blood and isolated cells did not indicate toxicity, but histopathological analysis, showed an increased incidence of liver fibrosis after 84-days of exposure, which only reached significance in the NM-202 treated animals. This observation was accompanied by a moderate, but significant increase in the expression of fibrosis-related genes in liver samples. Conclusions Although only few adverse effects were observed, additional studies are warranted to further evaluate the biological relevance of observed fibrosis in liver and possible accumulation of silica in the spleen in the NM-202

  12. Preliminary assessment of the relative toxicity of 1,5-diazido-3-nitrazapentane 90-day dermal application male and female rabbits study number 75-51-y809-90, May 1990 - June 1992. Phase 2. Final report, May 1990-June 1992

    SciTech Connect

    Haight, E.A.; Harvey, J.G.; Beall, P.

    1992-06-01

    A 90-day application of DANPE has the potential to cause testicular hypospermatogenesis in male rabbits and an apparent inhibition of mature ovarian follicles formation in female rabbits. A no-observed-adverse-effect-level was not achieved in the male rabbits but was achieved in female rabbits at 27.3 mg/kg dose level.... 1,5-Diazido-3-Nitrazapentane, Dermal, Approximate Lethal Dose (ALD), Testicular hypospermatogenesis, Ovarian follicle No-observed-adverse-effect-level (NOAEL).

  13. Toxicological evaluation of subchronic use of pioglitazone in mice

    PubMed Central

    Elshama, Said Said; El-Kenawy, Ayman El-Meghawry; Osman, Hosam-Eldin Hussein

    2016-01-01

    Objective(s): Pioglitazone (Actos) is one of the most controversial recent oral antidiabetic drugs. It was originally authorized in the European Union in 2000, and approved as an oral monotherapy for overweight second type of diabetic patients in 2002. It belongs to the thiazolidinedione group which some of its members have been withdrawn from the market due to the hepatotoxicity or cardiotoxicity effects. This study investigates sub-chronic use of pioglitazone induced toxicity in mice by the assessment of renal and liver function tests, cardiac enzymes, and some hematological indices with histological changes of liver, kidney, heart, and bladder. Materials and Methods: 120 albino mice were divided into four groups; 30 in each. The first group (control) received water, second (diabetic) group received alloxan only, while the third and the fourth groups received alloxan with 200 and 400 mg/kg/day of pioglitazone, respectively for 90 days. Results: Prolonged use of pioglitazone induced significant abnormalities of hepatic, renal, and cardiac biomarkers and some hematological indices associated with histopathological changes in the liver, kidney, heart, and bladder that increased based on administered dose. Conclusion: Subchronic use of pioglitazone leads to hepatic, renal, cardiac, hematological, and bladder affection depending on the applied dose.

  14. Baroreflex Sensitivity Decreases During 90-Day Bed Rest

    NASA Technical Reports Server (NTRS)

    Stenger, M. B.; Arzeno, N. M.; Platts, S. H.

    2008-01-01

    Baroreflex sensitivity (BRS) decreases during spaceflight and simulated spaceflight (head down bed rest [BR]). However, previous studies have only examined BRS in response to a limited blood pressure (BP) range or to a single sudden change in BP. PURPOSE: The purpose of this study was to examine BRS during 90 days of 6deg head-down tilt BR over a broad range of BP perturbations. METHODS: Nineteen normal volunteers (12M, 7F) were tested one day before BR, and then near BR days 30, 60 and 90. BP was pharmacologically altered by continuous infusions of phenylephrine (PE) and sodium nitroprusside (SNP). Electrocardiogram and continuous BP were collected during 10 min of normal saline (NS), followed by increasing concentrations of PE (10 min each of 0.4, 0.8 and 1.6 micro-g/kg/min). After a 20 min break, NS was infused again for 10 min, followed by increasing concentrations of SNP (10 min each of 0.4, 0.8, 1.2 micro-g/kg/min). Baroreceptor sensitivity was measured as the slope of a sequence of 3 or more beats in which the systolic BP and following R-R interval (RR) both increased or decreased. Spectral heart rate variability (HRV) and mean RR were analyzed using data from only the NS infusions. Two-way repeated-measures analysis of variance was performed to examine the effects of BR and gender. RESULTS: RR decreased (p<0.001) from pre- BR across BR days. High frequency in normalized units, a measure of parasympathetic activity, decreased with BR (p=0.027) and was lower (p=0.046) in men (0.39+/-0.02, mean+/-SEM) than women (0.48+/-0.02). The spontaneous baroreflex slope, our measure of BRS, increased with PE and decreased with SNP across BR (p<0.001). The percentage decrease in BRS from pre- to post-BR appeared to be larger in women (43.6+/-7.0%) than in men (31.3+/-3.9%, p=0.06). CONCLUSION: Parasympathetic activity and baroreflex sensitivity decrease during 90 days of BR, and BRS tends to diminish more in women than in men.

  15. COMPACT and molecular structure in toxicity assessment: A prospective evaluation of 30 chemicals currently being tested for rodent carcinogenicity by the NCI/NTP

    SciTech Connect

    Lewis, D.F.V.; Ioannides, C.; Parke, D.V.

    1996-10-01

    A new series of 30 miscellaneous National Toxicology Program chemicals has been evaluated prospectively for carcinogenicity and overt toxicity by COMPACT (Computer Optimized Molecular Parametric Analysis for Chemical Toxicity: CYP1A and CYP2E1). Evaluations were also made by Hazard expert, and for metal ion redox potentials; and these, together with COMPACT, were compared with results from the Ames test for mutagenicity in Salmonella, the micronucleus test, and 90-day subchronic rodent pathology. 22 refs., 3 tabs.

  16. Acute and subchronic toxicity of 20  kHz and 60  kHz magnetic fields in rats.

    PubMed

    Nishimura, Izumi; Oshima, Atsushi; Shibuya, Kazumoto; Mitani, Takashi; Negishi, Tadashi

    2016-02-01

    Despite increasing use of intermediate frequency (IF) magnetic fields (MFs) in occupational and domestic settings, scientific evidence necessary for health risk assessments of IF MF is insufficient. Male and female Crl:CD(SD) rats (12 per sex per group) were exposed to 20 kHz, 0.20 mT(root mean square, rms) or 60 kHz, 0.10 mT(rms) sinusoidal MFs for 22 h day(-1) for 14 days (acute) or 13 weeks (subchronic). Experiments were duplicated for each frequency to ensure outcome reproducibility, and examinations were blinded for quality assurance. All rats survived without significant clinical signs until the end of experiments. Some changes in body weight between the MF-exposed and control groups were observed over the course of exposure, although the directions of the changes were inconsistent and not statistically significant after subchronic exposure. There were significant differences between MF-exposed and control groups in some organ weights and parameters in hematology and clinical chemistry, but these were minor in magnitude and not repeated in duplicate experiments. Histopathological findings reflecting toxicity were sporadic. Frequencies of other findings were similar to historic data in this rat strain, and findings had no specific relationship to changes in organ weight or parameters of hematology and clinical chemistry in each animal. The changes observed throughout this study were considered biologically isolated and were attributable to chance associations rather than to MF exposure. The results, in particular the histopathological evidence, indicate an absence of toxicity in IF MF-exposed rats and do not support the hypothesis that IF MF exposure produces significant toxicity. PMID:25982482

  17. SUBCHRONIC TOXICOLOGY OF HUMIC ACID FOLLOWING CHLORINATION IN THE RAT

    EPA Science Inventory

    A subchronic 90-day study was conducted with chlorinated and non-chlorinated humic acids with male Sprague-Dawley rats. Body weight gain, terminal organ and body weights, food and fluid consumption, clinical chemistries, hematological parameters, and urinalyses were determined fo...

  18. Therapeutic effect of Chinese patent medicine "Wuhuanghu" on porcine infectious pleuropneumonia and its acute and subchronic toxicity as well as evaluation of safety pharmacology.

    PubMed

    Wang, Guangxi; Kang, Shuai; Yin, Zhongqiong; Jia, Ren-Yong; Lai, Xin; Zhou, Xun; Liang, Xiao-Xia; Li, Li-Xia; Zou, Yuan-Feng; Lv, Cheng; He, Chang-Liang; Ye, Gang; Yin, Li-Zi; Jing, Bo

    2015-09-01

    Chinese patent medicines play an important role in veterinary clinical use. The aim of this study is to research the anti-infection effect of Chinese patent medicine "Wuhuanghu" for the treatment of porcine infectious pleuropneumonia and to evaluate the safety of "Wuhuanghu" in order to provide a comprehensive understanding of its toxicity. The anti-infection results showed that the treatment with "Wuhuanghu" could significantly inhibit pneumonia and decrement of the pneumonia in high, medium and low doses of "Wuhuanghu" groups were 70.97%, 61.29% and 58.06% respectively. The acute toxicity test showed that rats in the highest group (5000mg/kg) had no death and no abnormal response, suggesting the LD50 of "Wuhuanghu" was more than 5000mg/kg. The subchronic toxicity study showed that hematology indexes in all groups had no obvious differences; blood biochemical index, only albumin and total cholesterol in middle and low doses of "Wuhuanghu" groups were significantly decreased when compared with control group. The clinical pathology showed that the target organ of "Wuhuanghu" was liver. The safety pharmacology study indicated that "Wuhuanghu" had no side effects on rats. In conclusion, "Wuhuanghu" has therapeutic and protective effects to porcine infectious pleuropneumonia in a dose-dependent manner and "Wuhuanghu" is a safe veterinary medicine. PMID:26245812

  19. Dose and time-dependent sub-chronic toxicity study of hydroethanolic leaf extract of Flabellaria paniculata Cav. (Malpighiaceae) in rodents.

    PubMed

    Akindele, Abidemi J; Adeneye, Adejuwon A; Salau, Oluwole S; Sofidiya, Margaret O; Benebo, Adokiye S

    2014-01-01

    Flabellaria paniculata Cav. (Malpighiaceae) is a climbing shrub, the preparations of which are used in the treatment of wounds and ulcers in Nigeria and Ghana. This study investigated the sub-chronic toxicity profile of the hydroethanolic leaf extract of F. paniculata (HLE-FP). HLE-FP was administered p.o. (20, 100, and 500 mg/kg) for 30 and 60 days to different groups of rats. Control animals received 10 ml/kg distilled water. In the group of animals for reversibility study, HLE-FP administration ceased on the 60th day and animals were monitored for a further 15 days. Results showed that oral treatment with HLE-FP for 30 days caused significant (p < 0.05) reductions in weight gain pattern compared to control. These changes were sustained with 60 days treatment. However, no significant (p > 0.05) differences in relative organ weights between control and treatment groups were observed. HLE-FP-treated rats showed significant (p < 0.05) increases in Hb, PCV and RBC on day 30 and significant (p < 0.05) increases in MCV and MCH indices on day 60 compared to control. There were significant (p < 0.05) elevations in serum K(+), urea and creatinine compared to control. The liver function tests showed slight but non-significant alterations in relevant parameters when compared to control. Biochemical findings were supported by histopathological observations of vital organs including the kidney and liver. Toxicities observed in respect of kidney function were irreversible at 15 days of stoppage of treatment. In the acute toxicity study, HLE-FP given p.o. caused no lethality at 5000 mg/kg but behavioral manifestations like restlessness, generalized body tremor, feed, and water refusal were observed. The i.p. LD50 was estimated to be 2951.2 mg/kg. Findings in this study showed that HLE-FP is relatively non-toxic on acute exposure and generally safe on sub-chronic administration, but could be deleterious on the kidneys on prolonged oral exposure at a high dose. Thus, caution

  20. Acute and sub-chronic (28 days) oral toxicity evaluation of tincture Baccharis trimera (Less) Backer in male and female rodent animals.

    PubMed

    da Silva, Andreia R H; Reginato, Fernanda Z; Guex, Camille G; Figueredo, Kássia C; da C Araldi, Isabel C; de Freitas, Robson B; Boligon, Aline A; Athayde, Margareth L; Mazzanti, Cinthia Melazzo de Andrade; Hübscher, Gilberti H; de F Bauermann, Liliane

    2016-02-01

    The infusion of Baccharis trimera (Less) DC, popularly known as "carqueja" (broom), is popularly used in the treatment of hepatic and digestive problems. In this study, we evaluated the acute and sub-chronic oral toxicities of B. trimera tincture on male and female Wistar rats according to Organization for Economic Cooperation and Development (OECD, guidelines 423 e 407, respectively). The B. trimera tincture was administered by oral gavage in a single dose (2000 mg/kg) in doses of 100, 200 and 400 mg/kg daily for 28 days. Blood was collected to analyze hematological and biochemical parameters. Kidneys and liver were homogenized to determine lipid peroxidation and δ-aminolevulinate dehydratase (δ-ALA-D) and catalase (CAT) enzyme activities. In acute treatment, tincture did not induce any signs of toxicity or mortality. Daily oral administration produced no significant changes in the hematological and biochemical parameters, except for the hepatic enzymes alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) that showed a reduction in both sexes. Moreover, the B. trimera tincture did not increase lipid peroxidation or affected ALA-D and CAT activities. In conclusion, the tincture of B. trimera may be considered relatively safe in this protocol. PMID:26522812

  1. Evaluation of Acute 13-Week Subchronic Toxicity and Genotoxicity of the Powdered Root of Tongkat Ali (Eurycoma longifolia Jack)

    PubMed Central

    Liao, Jiunn-Wang; Liao, Po-Lin; Huang, Wei-Kuang; Tse, Ling-Shan; Lin, Cheng-Hui; Kang, Jaw-Jou; Cheng, Yu-Wen

    2013-01-01

    Tongkat Ali (Eurycoma longifolia) is an indigenous traditional herb in Southern Asia. Its powdered root has been processed to produce health supplements, but no detailed toxicology report is available. In this study, neither mutagenicity nor clastogenicity was noted, and acute oral LD50 was more than 6 g/kg b.w. After 4-week subacute and 13-week subchronic exposure paradigms (0, 0.6, 1.2, and 2 g/kg b.w./day), adverse effects attributable to test compound were not observed with respect to body weight, hematology, serum biochemistry, urinalysis, macropathology, or histopathology. However, the treatment significantly reduced prothrombin time, partial thromboplastin time, blood urea nitrogen, creatinine, aspartate aminotransferase, creatine phosphate kinase, lactate dehydrogenase, and cholesterol levels, especially in males (P < 0.05). These changes were judged as pharmacological effects, and they are beneficial to health. The calculated acceptable daily intake (ADI) was up to 1.2 g/adult/day. This information will be useful for product development and safety management. PMID:24062779

  2. Subchronic feeding study of four white mineral oils in dogs and rats.

    PubMed

    Smith, J H; Bird, M G; Lewis, S C; Freeman, J J; Hogan, G K; Scala, R A

    1995-02-01

    Subchronic 90-day feeding studies were conducted on four highly refined white mineral oils to determine any potential for toxicity in Long-Evans rats (20 per sex per dose level) and beagle dogs (4 per sex per dose level). Each oil was fed at dietary dose levels of 300 ppm and 1500 ppm (w/w). No treatment-related effects of toxicological importance were detected in daily observations of general health or in periodic assessments of food consumption and body weight, hematology, serum clinical chemistry, and urinalysis. Observations in dogs suggested that the white oils produced mild laxative effects. Gross and histopathologic examinations, as well as measurements of organ weights, did not reveal any macroscopic or microscopic changes which could be due to treatment. In addition, special staining by Oil Red O of liver, mesenteric lymph nodes, spleen, gastrointestinal tract, stomach, and kidneys indicated no evidence of oil or lipid deposition. A special re-examination of tissues from female and male rats, in response to more recent conflicting data from the Fischer 344 strain, found no histopathologic signs of macrophage accumulation and/or microgranuloma formation in liver, spleen, or mesenteric lymph nodes. These data indicate that repeated exposure to relatively high levels of white mineral oils in the diets does not produce significant subchronic toxicity in Long-Evans rats or beagle dogs. PMID:7768201

  3. Oral subchronic toxicity evaluation of a novel antitumor agent 25-methoxydammarane-3, 12, 20-triol from Panax notoginseng in Sprague-Dawley rats.

    PubMed

    Li, Wei; Zhang, Xiangrong; Xin, Yanfei; Xuan, Yaoxian; Liu, Jinping; Li, Pingya; Zhao, Yuqing

    2016-06-01

    Panax notoginseng and its main active ingredients ginsenosides have long been used as medicines and food additives in China. Comparing with the extensive uses and active researches of P. notoginseng and its products, the side effect and probable toxicity were rare. 25-Methoxydammarane-3,12,20-triol (25-OCH3-PPD), a novel dammarane-type triterpene sapogenin that was first isolated from the extract of P. notoginseng, was proven to have strong antitumor activities against prostate cancer, breast cancer and lung cancer. The aim of the present study was to investigate the potential subchronic toxicity of 25-OCH3-PPD after it was repeatedly orally administered to Sprague-Dawley rats (5/sex/group/each time-point) at dose levels of 0, 150, 300 or 600 mg/kg/day for 13 weeks and 4-week recovery. No mortality and treatment-related toxicity effects were observed as a result of the administration of 25-OCH3-PPD at any dose level (150, 300 and 600 mg/kg) for 92 consecutive days. Although there were some statistical changes, such as increased weights in female rats and decreased organ weights and coefficients of the liver, spleen, kidney, and adrenal gland compared with the control group at the corresponding time, the autopsy and histopathological examination of the target organs did not show any abnormal responses. As a result, 25-OCH3-PPD was well tolerated by SD rat at doses of up to 600 mg/kg and that it is a potential candidate for therapeutic use. PMID:27002186

  4. Toxicology Studies on Lewisite and Sulfur Mustard Agents: Subchronic Toxicity of Sulfur Mustard (HD) In Rats Final Report

    SciTech Connect

    Sasser, L. B.; Miller, R. A.; Kalkwarf, D, R.; Buschbom, R. L.; Cushing, J. A.

    1989-06-30

    Occupational health standards have not been established for sulfur mustard [bis(2- chlorethyl)-sulfide], a strong alkylating agent with known mutagenic properties. Seventytwo Sprague-Dawley rats of each sex, 6-7 weeks old, were divided into six groups (12/group/ sex) and gavaged with either 0, 0.003 , 0.01 , 0.03 , 0.1 or 0.3 mg/kg of sulfur mustard in sesame oil 5 days/week for 13 weeks. No dose-related mortality was observed. A significant decrease (P ( 0.05) in body weight was observed in both sexes of rats only in the 0.3 mg/kg group. Hematological evaluations and clinical chemistry measurements found no consistent treatment-related effects at the doses studied. The only treatment-related lesion associated with gavage exposure upon histopathologic evaluation was epithelial hyperplasia of the forestomach of both sexes at 0.3 mg/kg and males at 0.1 mg/kg. The hyperplastic change was minimal and characterized by cellular disorganization of the basilar layer, an apparent increase in mitotic activity of the basilar epithelial cells, and thickening of the epithelial layer due to the apparent increase in cellularity. The estimated NOEL for HD in this 90-day study is 0.1 mg/kg/day when administered orally.

  5. A comparative study of the sub-chronic toxic effects of three organic arsenical compounds on the urothelium in F344 rats; gender-based differences in response

    SciTech Connect

    Shen, Jun; Wanibuchi, Hideki; Waalkes, Michael P.; Salim, Elsayed I.; Kinoshita, Anna; Yoshida, Kaoru; Endo, Ginji; Fukushima, Shoji . E-mail: fukuchan@med.osaka-cu.ac.jp

    2006-02-01

    Epidemiological studies indicated that human arsenic exposure can induce urinary bladder cancer. Methylation of inorganic arsenic can generate more reactive and toxic organic arsenical species. In this regard, it was recently reported that the methylated arsenical metabolite, dimethylarsinic acid [DMA(V)], induced urinary bladder tumors in rats. However, other methylated metabolites, like monomethylarsonic acid [MMA(V)] and trimethylarsine oxide (TMAO) were not carcinogenic to the urinary bladder. In order to compare the early effects of DMA(V), MMA(V), and TMAO on the urinary bladder transitional cell epithelium at the scanning electron microscope (SEM) level, we investigated the sub-chronic (13 weeks) toxicological effects of MMA(V) (187 ppm), DMA(V) (184 ppm), TMAO (182 ppm) given in the drinking water to male and female F344 rats with a focus on the urinary bladder in this study. Obvious pathological changes, including ropy microridges, pitting, increased separation of epithelial cells, exfoliation, and necrosis, were found in the urinary bladders of both sexes, but particularly in females receiving carcinogenic doses of DMA(V). Urine arsenical metabolic differences were found between males and females, with levels of MMA(III), a potential genotoxic form, higher in females treated with DMA(V) than in males. Thus, this study provides clear evidence that DMA(V) is more toxic to the female urinary bladder, in accord with sensitivity to carcinogenesis. Important gender-related metabolic differences including enhanced presentation of MMA(III) to the urothelial cells might possibly account for heightened sensitivity in females. However, the potential carcinogenic effects of MMA(III) need to be further elucidated.

  6. 49 CFR 24.503 - Replacement housing payment for 90-day mobile home occupants.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 1 2011-10-01 2011-10-01 false Replacement housing payment for 90-day mobile home... ASSISTANCE AND REAL PROPERTY ACQUISITION FOR FEDERAL AND FEDERALLY-ASSISTED PROGRAMS Mobile Homes § 24.503 Replacement housing payment for 90-day mobile home occupants. A displaced tenant or owner-occupant of a...

  7. 49 CFR 24.503 - Replacement housing payment for 90-day mobile home occupants.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Replacement housing payment for 90-day mobile home... ASSISTANCE AND REAL PROPERTY ACQUISITION FOR FEDERAL AND FEDERALLY-ASSISTED PROGRAMS Mobile Homes § 24.503 Replacement housing payment for 90-day mobile home occupants. A displaced tenant or owner-occupant of a...

  8. 19 CFR Annex Viii-A to Part 351 - Schedule for 90-Day Sunset Reviews

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 3 2011-04-01 2011-04-01 false Schedule for 90-Day Sunset Reviews VIII Annex VIII-A to Part 351 Customs Duties INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE ANTIDUMPING AND COUNTERVAILING DUTIES Pt. 351, Annex VIII-A Annex VIII-A to Part 351—Schedule for 90-Day...

  9. 19 CFR Annex Viii-A to Part 351 - Schedule for 90-Day Sunset Reviews

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 3 2010-04-01 2010-04-01 false Schedule for 90-Day Sunset Reviews VIII Annex VIII-A to Part 351 Customs Duties INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE ANTIDUMPING AND COUNTERVAILING DUTIES Pt. 351, Annex VIII-A Annex VIII-A to Part 351—Schedule for 90-Day...

  10. 49 CFR 24.503 - Replacement housing payment for 90-day mobile home occupants.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 1 2012-10-01 2012-10-01 false Replacement housing payment for 90-day mobile home occupants. 24.503 Section 24.503 Transportation Office of the Secretary of Transportation UNIFORM RELOCATION... Replacement housing payment for 90-day mobile home occupants. A displaced tenant or owner-occupant of a...

  11. 49 CFR 24.503 - Replacement housing payment for 90-day mobile home occupants.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 1 2014-10-01 2014-10-01 false Replacement housing payment for 90-day mobile home occupants. 24.503 Section 24.503 Transportation Office of the Secretary of Transportation UNIFORM RELOCATION... Replacement housing payment for 90-day mobile home occupants. A displaced tenant or owner-occupant of a...

  12. 49 CFR 24.503 - Replacement housing payment for 90-day mobile home occupants.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 1 2013-10-01 2013-10-01 false Replacement housing payment for 90-day mobile home occupants. 24.503 Section 24.503 Transportation Office of the Secretary of Transportation UNIFORM RELOCATION... Replacement housing payment for 90-day mobile home occupants. A displaced tenant or owner-occupant of a...

  13. Safety assessment of non-animal chondroitin sulfate sodium: Subchronic study in rats, genotoxicity tests and human bioavailability.

    PubMed

    Miraglia, Niccolò; Bianchi, Davide; Trentin, Antonella; Volpi, Nicola; Soni, Madhu G

    2016-07-01

    Chondroitin sulfate, an amino sugar polymer made of glucuronic acid and N-acetyl-galactosamine, is used in dietary supplements to promote joint health. Commonly used chondroitin sulfate is of animal origin and can pose potential safety problems including bovine spongiform encephalopathy (BSE). The objective of the present study was to investigate potential adverse effects, if any, of microbial derived chondroitin sulfate sodium (CSS) in subchronic toxicity, genotoxicity and bioavailability studies. In the toxicity study, Sprague Dawley rats (10/sex/group) were gavaged with CSS at dose levels of 0, 250, 500 and 1000 mg/kg body weight (bw)/day for 90-days. No mortality or significant changes in clinical signs, body weights, body weight gain or feed consumption were noted. Similarly, no toxicologically relevant treatment-related changes in hematological, clinical chemistry, urinalysis and organ weights were noted. Macroscopic and microscopic examinations did not reveal treatment-related abnormalities. In vitro mutagenic and clastogenic potentials as evaluated by Ames assay, chromosomal aberration test and micronucleus assay did not reveal genotoxicity of CSS. In pharmacokinetic study in human, CSS showed higher absorption as compared to chondroitin sulfate of animal origin. The results of subchronic toxicity study supports the no-observed-adverse-effect level (NOAEL) for CSS as 1000 mg/kg bw/day, the highest dose tested. PMID:27108107

  14. Some considerations concerning the theory of combined toxicity: a case study of subchronic experimental intoxication with cadmium and lead.

    PubMed

    Varaksin, Anatoly N; Katsnelson, Boris A; Panov, Vladimir G; Privalova, Larisa I; Kireyeva, Ekaterina P; Valamina, Irene E; Beresneva, Olga Yu

    2014-02-01

    Rats were exposed intraperitoneally (3 times a week up to 20 injections) to either Cadmium and Lead salts in doses equivalent to their 0.05 LD50 separately or combined in the same or halved doses. Toxic effects were assessed by more than 40 functional, biochemical and morphometric indices. We analysed the results obtained aiming at determination of the type of combined toxicity using either common sense considerations based on descriptive statistics or two mathematical models based (a) on ANOVA and (b) on Mathematical Theory of Experimental Design, which correspond, respectively, to the widely recognised paradigms of effect additivity and dose additivity. Nevertheless, these approaches have led us unanimously to the following conclusions: (1) The above paradigms are virtually interchangeable and should be regarded as different methods of modelling the combined toxicity rather than as reflecting fundamentally differing processes. (2) Within both models there exist not merely three traditionally used types of combined toxicity (additivity, subadditivity and superadditivity) but at least 10 variants of it depending on exactly which effect is considered and on its level, as well as on the dose levels and their ratio. PMID:24291454

  15. Microcystin accumulation and antioxidant responses in the freshwater clam Diplodon chilensis patagonicus upon subchronic exposure to toxic Microcystis aeruginosa.

    PubMed

    Sabatini, Sebastián E; Brena, Beatríz M; Luquet, Carlos M; San Julián, Magdalena; Pirez, Macarena; Carmen Ríos de Molina, María Del

    2011-07-01

    We investigated the accumulation and toxicity of microcystin-LR (MCLR) in the digestive gland of the freshwater clam Diplodon chilensis patagonicus. Treated clams were fed with a toxic strain of Microcystis aeruginosa (NPJB1) during 6 weeks and control clams received the non-toxic strain NPDC1. Filtration rate was estimated for both groups. Toxic effects were evaluated through the hepatosomatic index (HSI) and different oxidative stress biomarkers, lipid peroxidation (content of thiobarbituric reactive substances-TBARS), protein oxidation (carbonyl groups) and reduced glutathione (GSH) levels, and enzymatic activities of superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST). The extractable MCLR measured by ELISA in digestive gland extracts showed little or no change during the first 3 weeks and increased significantly at weeks 5 and 6. HSI was reduced by 30% in treated clams at weeks 5 and 6. No significant oxidative damage to lipids or proteins was. All the antioxidant defense parameters analyzed were significantly increased at week 5 or 6. GSH increased in treated clams at week 5, reaching 62% increase at week 6. SOD, CAT and GST activities were significantly increased in treated clams by 50%, 66% and 60%, respectively, at the end of the experiment. D. chilensis patagonicus can be exposed to prolonged cyanobacterial blooms accumulating significant quantities of MCLR, which could be a risk for mammals and birds, which feed on this species and, in a lesser extent, to humans. PMID:21477863

  16. Subchronic toxicity of copper oxide nanoparticles and its attenuation with the help of a combination of bioprotectors.

    PubMed

    Privalova, Larisa I; Katsnelson, Boris A; Loginova, Nadezhda V; Gurvich, Vladimir B; Shur, Vladimir Y; Valamina, Irene E; Makeyev, Oleg H; Sutunkova, Marina P; Minigalieva, Ilzira A; Kireyeva, Ekaterina P; Rusakov, Vadim O; Tyurnina, Anastasia E; Kozin, Roman V; Meshtcheryakova, Ekaterina Y; Korotkov, Artem V; Shuman, Eugene A; Zvereva, Anastasia E; Kostykova, Svetlana V

    2014-01-01

    In the copper metallurgy workplace air is polluted with condensation aerosols, which a significant fraction of is presented by copper oxide particles<100 nm. In the scientific literature, there is a lack of their in vivo toxicity characterization and virtually no attempts of enhancing organism's resistance to their impact. A stable suspension of copper oxide particles with mean (±SD) diameter 20±10 nm was prepared by laser ablation of pure copper in water. It was being injected intraperitoneally to rats at a dose of 10 mg/kg (0.5 mg per mL of deionized water) three times a week up to 19 injections. In parallel, another group of rats was so injected with the same suspension against the background of oral administration of a "bio-protective complex" (BPC) comprising pectin, a multivitamin-multimineral preparation, some amino acids and fish oil rich in ω-3 PUFA. After the termination of injections, many functional and biochemical indices for the organism's status, as well as pathological changes of liver, spleen, kidneys, and brain microscopic structure were evaluated for signs of toxicity. In the same organs we have measured accumulation of copper while their cells were used for performing the Random Amplification of Polymorphic DNA (RAPD) test for DNA fragmentation. The same features were assessed in control rats infected intraperitoneally with water with or without administration of the BPC. The copper oxide nanoparticles proved adversely bio-active in all respects considered in this study, their active in vivo solubilization in biological fluids playing presumably an important role in both toxicokinetics and toxicodynamics. The BPC proposed and tested by us attenuated systemic and target organs toxicity, as well as genotoxicity of this substance. Judging by experimental data obtained in this investigation, occupational exposures to nano-scale copper oxide particles can present a significant health risk while the further search for its management with the help

  17. Experimental model of microcystin accumulation in the liver of Oreochromis niloticus exposed subchronically to a toxic bloom of Microcystis sp.

    PubMed

    Deblois, Charles P; Giani, Alessandra; Bird, David F

    2011-05-01

    Although accumulation of the liver toxin microcystin in phytoplanktivorous fish has been demonstrated in captive fish and in natural ecosystems, the relation between microcystin in ingested algae and the pattern of buildup of microcystin in fish is poorly known. In this month-long study performed at a Brazilian fish farm, 45 mature Oreochromis niloticus were fed daily with fresh seston periodically dominated by toxic Microcystis sp. Microcystin was measured daily in the food and every 5 days in liver and muscle samples. Control fish received a diet of seston that was low in toxic cyanobacteria. Initially, in treatment ponds, microcystin available for fish increased from 6.5 to 66.9 ng microcystin fish(-1)day(-1), which was accompanied by an increase from 5.5 to 35.4 ng microcysting liver(-1). Microcystin in muscle was below our detection limit of 4 ng g tissue(-1) for the entire study. In the bloom phase, available microcystin reached its highest concentration (4450 ng MC fish(-1)day(-1)) then decreased to 910 ng microcystin fish(-1)day(-1) on day 31. During this period, microcystin reached its highest concentration of 81.6 ng MC g liver(-1) and stayed high until the end of the experiment. A model based on rapid uptake, saturation, and exponential loss was built with these experimental results, and verified with data from the literature. Our model showed that accumulation was up to 50% of ingestion at low doses, but at intermediate doses, the onset of elimination led to a decline of liver burden. Although the accumulation rate confirms the high contamination potential of microcystin, it was balanced by a high depuration rate and this efficient systemic elimination may explain the tolerance of these fish to toxic blooms in the wild. PMID:21392496

  18. Subchronic toxicity studies on 1,3,5-trinitrobenzene, 1,3-dinitrobenzene, and tetryl in rats. Final report

    SciTech Connect

    Reddy, T.V.

    1994-04-20

    Subacute toxic effects of TNB in F344 male and female rats were evaluated by feeding powdered certified laboratory chow diet supplemented with varied concentrations of TNB (0, 50, 200, 400, 800 and 1200 mg/kg diet) so as to achieve a final target dose of (0, 5, 20, 40, 80 and 120 mg TNB/kg body weight) for fourteen days. The calculated average daily TNB doses (50, 200, 400, 800 and 1200 mg/kg) for males was 4, 16, 34, 55 and 94 mg/kg b.w. and for females 4, 17, 34, 58 and 79 mg/kg b.w. Food intake by male and female rats consuming 1200 mg TNB/kg diet was reduced and resulted in a significant decrease in absolute body weights. A decrease in testicular weight in males and an increase in spleen weight of both sexes fed 800 or 1200 mg TNB/kg diet were noted. Histopathological changes for TNB toxicity (200-1200 mg/kg) were evident in the kidneys (hyaline droplets), spleen (extra-medullary hematopoiesis) and testes (seminiferous tubular degeneration). Hematology and clinical chemistry studies indicated a decrease in red blood cell count and hematocrit (400-1200 mg/kg), a decrease in alkaline phosphatase (400-1200 mg/kg) and an increase in Heinz bodies (800-1200 mg/kg) as compared to controls in both sexes. Methemoglobin levels were also significantly increased (400-1200 mg/kg).

  19. Subchronic Toxicity of Copper Oxide Nanoparticles and Its Attenuation with the Help of a Combination of Bioprotectors

    PubMed Central

    Privalova, Larisa I.; Katsnelson, Boris A.; Loginova, Nadezhda V.; Gurvich, Vladimir B.; Shur, Vladimir Y.; Valamina, Irene E.; Makeyev, Oleg H.; Sutunkova, Marina P.; Minigalieva, Ilzira A.; Kireyeva, Ekaterina P.; Rusakov, Vadim O.; Tyurnina, Anastasia E.; Kozin, Roman V.; Meshtcheryakova, Ekaterina Y.; Korotkov, Artem V.; Shuman, Eugene A.; Zvereva, Anastasia E.; Kostykova, Svetlana V.

    2014-01-01

    In the copper metallurgy workplace air is polluted with condensation aerosols, which a significant fraction of is presented by copper oxide particles <100 nm. In the scientific literature, there is a lack of their in vivo toxicity characterization and virtually no attempts of enhancing organism’s resistance to their impact. A stable suspension of copper oxide particles with mean (±SD) diameter 20 ± 10 nm was prepared by laser ablation of pure copper in water. It was being injected intraperitoneally to rats at a dose of 10 mg/kg (0.5 mg per mL of deionized water) three times a week up to 19 injections. In parallel, another group of rats was so injected with the same suspension against the background of oral administration of a “bio-protective complex” (BPC) comprising pectin, a multivitamin-multimineral preparation, some amino acids and fish oil rich in ω-3 PUFA. After the termination of injections, many functional and biochemical indices for the organism’s status, as well as pathological changes of liver, spleen, kidneys, and brain microscopic structure were evaluated for signs of toxicity. In the same organs we have measured accumulation of copper while their cells were used for performing the Random Amplification of Polymorphic DNA (RAPD) test for DNA fragmentation. The same features were assessed in control rats infected intraperitoneally with water with or without administration of the BPC. The copper oxide nanoparticles proved adversely bio-active in all respects considered in this study, their active in vivo solubilization in biological fluids playing presumably an important role in both toxicokinetics and toxicodynamics. The BPC proposed and tested by us attenuated systemic and target organs toxicity, as well as genotoxicity of this substance. Judging by experimental data obtained in this investigation, occupational exposures to nano-scale copper oxide particles can present a significant health risk while the further search for its management with

  20. Sub-chronic Administration of Methanolic Whole Fruit Extract of Lagenaria breviflora (Benth.) Roberty Induces Mild Toxicity in Rats

    PubMed Central

    Olorunnisola, Olubukola Sinbad; Afolayan, Anthony Jide; Adetutu, Adewale

    2015-01-01

    Background: The effect of the methanolic whole fruit extract from Lagenaria breviflora on vital organs and antioxidant enzymes was investigated in this study. Materials and Methods: L. breviflora (250, 500 and 1000 mg/kg/b.w.t./day/rat) was fed orally with the cannula to male albino rats for 28 days. At the end of the treatment, the rats were sacrificed and the effect of the extract on histology of the liver, heart, lipid peroxidation, tissue and serum antioxidant enzymes (superoxide dismutase, catalase, glutathione-s-transferase, glutathione peroxidase) activities, glutathione, myocardial marker enzymes (creatine kinase [CK], lactate dehydrogenase [LDH], alanine transaminase [ALT], and aspartate transaminase [AST]) in serum, and heart homogenate were assessed. Results: The extract demonstrated mild organ doses dependent (500 and 1000 mg/kg) pathological alterations in the architectural section of the liver and heart. At 250 mg/kg/b.w.t., the extract caused a significant (P < 0.05) increase in the level of thiobarbituric reacting acids substance and antioxidant enzyme activities, but causes (P < 0.05) decrease in serum and tissue antioxidant capacity at 500 and 1000 mg/kg/b.w.t., respectively. Also on these two doses, a significant (P < 0.05) increase in serum activity of CK, LDH, ALT, and AST and concomitantly decrease (P < 0.05) in heart homogenate were also observed. Conclusion: The results suggested that the Fruit of L. breviflora may contain phytotoxic Substances(s) which may be hepatotoxic, cardiotoxic or able to induce oxidative stress at high concentration. Hence, the consumption of the plant should be taken with caution. SUMMARY Methanolic whole fruit extract from Lagenaria breviflora demonstrate dose dependent mild toxicity on vital organs (Heart and liver) and anti-oxidant enzymes. The fruit of Lagenaria breviflora may contain Phyto-toxic substance (s) which may be hepatotoxic, Cardio-toxic or able to induce oxidative stress at high concentration. Hence

  1. Subchronic toxicity studies on 1,3,5-trinitrobenzene, 1,3-dinitrobenzene and tetryl in rats. Final report

    SciTech Connect

    Reddy, T.V.; Daniel, F.B.

    1994-09-01

    Toxic effects of 1,3-Dinitrobenzene (1,3-DNB) in male and female F344 rats were evaluated by feeding powdered certified laboratory chow diet supplemented with varied concentrations of 1,3-DNB (0, 2.5, 10, 25, 75 and 150 mg/kg diet) for fourteen days. The average daily 1 ,3-DNB doses consumed were 0.21, 0.87, 2.02, 6.28 and 11.82 mg/kg b.w. for females and 0.21, 0.80, 1.98, 5.77 and 10.56 for males. Food consumption was significantly decreased in high dose animals of both sexes. Final body weights were not altered but relative organ weights were significantly changed in the 150 and 75 mg dose groups involving the spleen (males and females) and testes (males). Hematology and clinical chemistry studies indicated significantly increased values in both sexes relating to reticulocytes and methemoglobin in the 150 and 75 mg/kg dose groups while the red blood cell count, hemoglobin level and % hematocrit were decreased in these same groups. In addition, the levels of bilirubin, protein and albumin were increased in high dose males, Histopathological evaluations suggested that the susceptible organs for 1,3-DNB toxicity were kidneys (hyaline droplets), spleen (erythroid cell hyperplasia), brain (malacia and microgliosis), testes (seminiferous tubular degeneration). These changes were noted mainly in the 150 and 75 mg/kg dose groups except those changes involving the brain (150 mg/kg group only).

  2. 40 CFR 799.9310 - TSCA 90-day oral toxicity in rodents.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, sorbitol dehydrogenase, or... Practice Standards at 40 CFR part 792, subpart J, the following specific information must be reported: (i... performance of laboratory equipment. The study must be conducted in compliance with 40 CFR Part...

  3. 40 CFR 799.9310 - TSCA 90-day oral toxicity in rodents.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, sorbitol dehydrogenase, or... Practice Standards at 40 CFR part 792, subpart J, the following specific information must be reported: (i... performance of laboratory equipment. The study must be conducted in compliance with 40 CFR Part...

  4. 40 CFR 799.9310 - TSCA 90-day oral toxicity in rodents.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Practice Standards at 40 CFR part 792, subpart J, the following specific information must be reported: (i... performance of laboratory equipment. The study must be conducted in compliance with 40 CFR Part 792—Good.... Statistically randomized samples of the mixture should be analyzed to ensure that proper mixing,...

  5. 40 CFR 799.9310 - TSCA 90-day oral toxicity in rodents.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Practice Standards at 40 CFR part 792, subpart J, the following specific information must be reported: (i... performance of laboratory equipment. The study must be conducted in compliance with 40 CFR Part 792—Good.... Statistically randomized samples of the mixture should be analyzed to ensure that proper mixing,...

  6. 40 CFR 799.9310 - TSCA 90-day oral toxicity in rodents.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Practice Standards at 40 CFR part 792, subpart J, the following specific information must be reported: (i... performance of laboratory equipment. The study must be conducted in compliance with 40 CFR Part 792—Good.... Statistically randomized samples of the mixture should be analyzed to ensure that proper mixing,...

  7. Readmission After Robot-assisted Radical Cystectomy: Outcomes and Predictors at 90-Day Follow-up

    PubMed Central

    Al-Daghmin, Ali; Aboumohamed, Ahmed; Din, Rakeeba; Khan, Aabroo; Raza, Syed Johar; Sztorc, Jenna; Mehedint, Diana; Sharif, Mohammad; Shi, Yi; Wilding, Gregory; Guru, Khurshid A.

    2015-01-01

    OBJECTIVE To characterize the outcomes and predictors of readmission after robot-assisted radical cystectomy (RARC) during early (30-day) and late (31–90–day) postoperative periods. METHODS We retrospectively evaluated our prospectively maintained RARC quality assurance database of 272 consecutive patients operated between 2005 and 2012. We evaluated the relationship of readmission with perioperative outcomes and examined possible predictors during the postoperative period. RESULTS Overall 30- and 90-day mortality was 0.7% and 4.8%, respectively, with 25.5% patients readmitted within 90 days after RARC (61% of them were readmitted within 30 days and 39% were readmitted between 31–90 days postoperatively). Infection-related problems were the most common cause of readmission during early and late periods. Overall operative time and obesity were significantly associated with readmission (P = .034 and .033, respectively). Body mass index and female gender were independent predictors of 90-day readmission (P = .004 and .014, respectively). Having any type of complication correlated with 90-day readmission (P = .0045); meanwhile, when complications were graded on the basis of Clavien grading system, only grade 1–2 complications statistically correlated with readmission (P = .046). Four patients needed reoperation (2 patients in early “for appendicitis and adhesive small bowel obstruction” and 2 in late “for ureteroenteric stricture” readmission); meanwhile, 6 patients needed percutaneous procedures (4 patients in early “1 for anastomotic leak and 3 for pelvic collections” and 2 “for pelvic collections and ureterocutaneous fistula” in late readmission). CONCLUSION The rate of readmission within 90 days after RARC is significant. Female gender and body mass index are independent predictors of readmission. Outcomes at 90 days provide more thorough results, essential to proper patient counseling. PMID:24468509

  8. Effects of 90-Day Feeding of Transgenic Maize BT799 on the Reproductive System in Male Wistar Rats

    PubMed Central

    Guo, Qian-ying; He, Li-xia; Zhu, Han; Shang, Jun-li; Zhu, Ling-yan; Wang, Jun-bo; Li, Yong

    2015-01-01

    BT799 is a genetically modified (GM) maize plant that expresses the Cry1Ac gene from Bacillus thuringiensis (Bt). The Cry1Ac gene was introduced into maize line Zhen58 to encode the Bt crystal protein and thus produce insect-resistant maize BT799. Expression of Bt protein in planta confers resistance to Lepidopteran pests and corn rootworms. The present study was designed to investigate any potential effects of BT799 on the reproductive system of male rats and evaluate the nutritional value of diets containing BT799 maize grain in a 90-day subchronic rodent feeding study. Male Wistar rats were fed with diets containing BT799 maize flours or made from its near isogenic control (Zhen58) at a concentration of 84.7%, nutritionally equal to the standard AIN-93G diet. Another blank control group of male rats were treated with commercial AIN-93G diet. No significant differences in body weight, hematology and serum chemistry results were observed between rats fed with the diets containing transgenic BT799, Zhen58 and the control in this 13-week feeding study. Results of serum hormone levels, sperm parameters and relative organ/body weights indicated no treatment-related side effects on the reproductive system of male rats. In addition, no diet-related changes were found in necropsy and histopathology examinations. Based on results of the current study, we did not find any differences in the parameters tested in our study of the reproductive system of male rats between BT799 and Zhen58 or the control. PMID:26633453

  9. Effects of 90-Day Feeding of Transgenic Maize BT799 on the Reproductive System in Male Wistar Rats.

    PubMed

    Guo, Qian-ying; He, Li-xia; Zhu, Han; Shang, Jun-li; Zhu, Ling-yan; Wang, Jun-bo; Li, Yong

    2015-12-01

    BT799 is a genetically modified (GM) maize plant that expresses the Cry1Ac gene from Bacillus thuringiensis (Bt). The Cry1Ac gene was introduced into maize line Zhen58 to encode the Bt crystal protein and thus produce insect-resistant maize BT799. Expression of Bt protein in planta confers resistance to Lepidopteran pests and corn rootworms. The present study was designed to investigate any potential effects of BT799 on the reproductive system of male rats and evaluate the nutritional value of diets containing BT799 maize grain in a 90-day subchronic rodent feeding study. Male Wistar rats were fed with diets containing BT799 maize flours or made from its near isogenic control (Zhen58) at a concentration of 84.7%, nutritionally equal to the standard AIN-93G diet. Another blank control group of male rats were treated with commercial AIN-93G diet. No significant differences in body weight, hematology and serum chemistry results were observed between rats fed with the diets containing transgenic BT799, Zhen58 and the control in this 13-week feeding study. Results of serum hormone levels, sperm parameters and relative organ/body weights indicated no treatment-related side effects on the reproductive system of male rats. In addition, no diet-related changes were found in necropsy and histopathology examinations. Based on results of the current study, we did not find any differences in the parameters tested in our study of the reproductive system of male rats between BT799 and Zhen58 or the control. PMID:26633453

  10. Effects of genetically modified T2A-1 rice on the GI health of rats after 90-day supplement

    PubMed Central

    Yuan, Yanfang; Xu, Wentao; He, Xiaoyun; Liu, Haiyan; Cao, Sishuo; Qi, Xiaozhe; Huang, Kunlun; Luo, Yunbo

    2013-01-01

    Bacillus thuringiensis insecticidal toxin (Bt) rice will be commercialized as a main food source. Traditional safety assessments on genetically modified products pay little attention on gastrointestinal (GI) health. More data about GI health of Bt rice must be provided to dispel public' doubts about the potential effects on human health. We constructed an improved safety assessment animal model using a basic subchronic toxicity experiment, measuring a range of parameters including microflora composition, intestinal permeability, epithelial structure, fecal enzymes, bacterial activity, and intestinal immunity. Significant differences were found between rice-fed groups and AIN93G-fed control groups in several parameters, whereas no differences were observed between genetically modified and non-genetically modified groups. No adverse effects were found on GI health resulting from genetically modified T2A-1 rice. In conclusion, this study may offer a systematic safety assessment model for GM material with respect to the effects on GI health. PMID:23752350

  11. Effects of genetically modified T2A-1 rice on the GI health of rats after 90-day supplement.

    PubMed

    Yuan, Yanfang; Xu, Wentao; He, Xiaoyun; Liu, Haiyan; Cao, Sishuo; Qi, Xiaozhe; Huang, Kunlun; Luo, Yunbo

    2013-01-01

    Bacillus thuringiensis insecticidal toxin (Bt) rice will be commercialized as a main food source. Traditional safety assessments on genetically modified products pay little attention on gastrointestinal (GI) health. More data about GI health of Bt rice must be provided to dispel public' doubts about the potential effects on human health. We constructed an improved safety assessment animal model using a basic subchronic toxicity experiment, measuring a range of parameters including microflora composition, intestinal permeability, epithelial structure, fecal enzymes, bacterial activity, and intestinal immunity. Significant differences were found between rice-fed groups and AIN93G-fed control groups in several parameters, whereas no differences were observed between genetically modified and non-genetically modified groups. No adverse effects were found on GI health resulting from genetically modified T2A-1 rice. In conclusion, this study may offer a systematic safety assessment model for GM material with respect to the effects on GI health. PMID:23752350

  12. Evaluation of the safety of primary metabolites of cyadox: Acute and sub-chronic toxicology studies and genotoxicity assessment.

    PubMed

    Huang, Qin; Ihsan, Awais; Guo, Pu; Luo, Xun; Cheng, Guyue; Hao, Haihong; Chen, Dongmei; Jamil, Farrukh; Tao, Yanfei; Wang, Xu; Yuan, Zonghui

    2016-02-01

    Cyadox (CYA) is a synthetic antimicrobial agent, belonging to quinoxaline (QdNO) family. Cy1 (bidesoxy cyadox), Cy2 (N4-desoxycyadox) and Cy10 (N1-desoxycyadox) are the primary metabolites of CYA. In our present study, an acute toxicity test, a sub-chronic toxicity test, and a battery of three genotoxicity tests were carried out according to standard protocols. The LD50 of the metabolites were above 5000 mg/kg b.w. The maximum tolerated dose (MTD) of Cy1 and Cy-M (mixture of Cy2 and Cy10) in rats, and the MTD of Cy1, Cy2 and Cy10 in mice were above 6000 mg/kg b.w./day. In subchronic study, rats were separately administered Cy1 and Cy-M at the dose levels of 0, 50, 150 and 2500 mg/kg diet for 90 days, with CYA (2500 mg/kg) as a control. Significant decreases in body weight and changes in clinical serum biochemistry were observed in the high-dose group of Cy1 and Cy-M, as well as CYA. Significant changes in relative weights of organs at 150 and 2500 mg/kg diet of Cy1 and CYA were noted. Additionally, the high-dose groups of Cy1, Cy-M and CYA showed pathological changes near the hepatic portal area. There was no evidence for genotoxic activity of any of the three metabolites in the bacterial reverse mutation test, mouse bone marrow micronucleus assay or an in vitro assay for clastogenicity. Based on the subchronic study, the target organ of the primary metabolites was the liver, and the no-observed-adverse-effect level for Cy1 and Cy-M was 150 mg/kg diet. PMID:26617409

  13. Further development of the theory and mathematical description of combined toxicity: An approach to classifying types of action of three-factorial combinations (a case study of manganese-chromium-nickel subchronic intoxication).

    PubMed

    Katsnelson, Boris A; Panov, Vladimir G; Minigaliyeva, Ilzira A; Varaksin, Anatoly N; Privalova, Larisa I; Slyshkina, Tatyana V; Grebenkina, Svetlana V

    2015-08-01

    For characterizing the three-factorial toxicity, we proposed a new health risk-oriented approach, the gist of which is a classification of effects depending on whether a binary combined toxicity's type remains virtually the same or appears to be either more or less adverse when modeled against the background of a third toxic. To explore possibilities of this approach, we used results of an experiment in which rats had been injected ip 3 times a week (up to 20 injections) with a water solution of either one of the toxics (Mn, Ni or Cr-VI salts) in a dose equivalent to 0.05 LD50, or any two of them, or all the three in the same doses, the controls receiving injections of the same volume of distilled water (4mL per rat). Judging by more than 30 indices for the organism's status, all exposures caused subchronic intoxication of mild to moderate strength. For each two-factorial exposure, we found by mathematical modeling based on the isobolograms that the binary combined subchronic toxicity either was of additive type or departed from it (predominantly toward subadditivity) depending on the effect assessed, dose, and effect level. For the three-factorial combination, different classes of effects were observed rather consistently: class A - those regarding which the third toxic's addition made the binary toxicity type more unfavorable for the organism, class B - those regarding which the result was opposite, and class C - those regarding which the type of binary combined toxicity on the background of a third toxic virtually remained the same as in its absence. We found a complicated reciprocal influence of combined metals on their retention in kidneys, liver, spleen and brain which might presumably be one of the possible mechanisms of combined toxicity, but the lack of an explicit correspondence between the above influence and the influence on toxicity effects suggests that this mechanism is not always the most important one. The relevance of the proposed classification

  14. Oral subchronic exposure to silver nanoparticles in rats.

    PubMed

    Garcia, Tania; Lafuente, Daisy; Blanco, Jordi; Sánchez, Domènec J; Sirvent, Juan J; Domingo, José L; Gómez, Mercedes

    2016-06-01

    Because of their extremely small size, silver nanoparticles (AgNPs) show unique physical and chemical properties, with specific biological effects, which make them particularly attractive for being used in a number of consumer applications. However, these properties also influence the potential toxicity of AgNPs. In this study, we assessed the potential toxic effects of an in vivo oral sub-chronic exposure to polyvinyl pyrrolidone coated AgNPs (PVP-AgNPs) in adult male rats. We also assessed if oral PVP-AgNPs exposure could alter the levels of various metals (Fe, Mg, Zn and Cu) in tissues. Rats were orally given 0, 50, 100 and 200 mg/kg/day of PVP-AgNPs. Silver (Ag) accumulation in tissues, Ag excretion, biochemical and hematological parameters, metal levels, as well as histopathological changes and subcellular distribution following PVP-AgNPs exposure, were also investigated. After 90 days of treatment, AgNPs were found within hepatic and ileum cells. The major tissue concentration of Ag was found in ileum of treated animals. However, all tissues of PVP-AgNPs-exposed animals showed increased levels of Ag in comparison with those of rats in the control group. No harmful effects in liver and kidney, as well as in biochemical markers were noted at any treatment dose. In addition, no hematological or histopathological changes were found in treated animals. However, significant differences in Cu and Zn levels were found in thymus and brain of PVP-AgNPs-treated rats. PMID:27090107

  15. SUBCHRONIC TOXICITY STUDY OF OZONATED AND OZONATED/CHLORINATED HUMICS IN SPRAGUE-DAWLEY RATS: A MODEL SYSTEM FOR DRINKING WATER DISINFECTION

    EPA Science Inventory

    Male and female Sprague-Dawley rats were administered drinking water containing humics (1 g/L) alone or after it had been ozonated or ozonated/chlorinated. he rats consumed the treated drinking water ad libitum for a 90-day period. wo levels of humics were studies, 0.25 and 1.0 g...

  16. 49 CFR 24.402 - Replacement housing payment for 90-day occupants.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Replacement housing payment for 90-day occupants. 24.402 Section 24.402 Transportation Office of the Secretary of Transportation UNIFORM RELOCATION... classified as “low income” by the U.S. Department of Housing and Urban Development's Annual Survey of...

  17. 49 CFR 24.402 - Replacement housing payment for 90-day occupants.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 1 2014-10-01 2014-10-01 false Replacement housing payment for 90-day occupants. 24.402 Section 24.402 Transportation Office of the Secretary of Transportation UNIFORM RELOCATION ASSISTANCE AND REAL PROPERTY ACQUISITION FOR FEDERAL AND FEDERALLY-ASSISTED PROGRAMS Replacement...

  18. 49 CFR 24.402 - Replacement housing payment for 90-day occupants.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... occupied the displacement dwelling for at least 90 days immediately prior to the initiation of negotiations... or she moves from the displacement dwelling; or (ii) For an owner-occupant, the later of: (A) The date he or she receives final payment for the displacement dwelling, or in the case of...

  19. 49 CFR 24.402 - Replacement housing payment for 90-day occupants.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... occupied the displacement dwelling for at least 90 days immediately prior to the initiation of negotiations... or she moves from the displacement dwelling; or (ii) For an owner-occupant, the later of: (A) The date he or she receives final payment for the displacement dwelling, or in the case of...

  20. 49 CFR 24.402 - Replacement housing payment for 90-day occupants.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... occupied the displacement dwelling for at least 90 days immediately prior to the initiation of negotiations... or she moves from the displacement dwelling; or (ii) For an owner-occupant, the later of: (A) The date he or she receives final payment for the displacement dwelling, or in the case of...

  1. A 90-Day Tenofovir Reservoir Intravaginal Ring for Mucosal HIV Prophylaxis

    PubMed Central

    Johnson, Todd J.; Clark, Meredith R.; Albright, Theodore H.; Nebeker, Joel S.; Tuitupou, Anthony L.; Clark, Justin T.; Fabian, Judit; McCabe, R. Tyler; Chandra, Neelima; Doncel, Gustavo F.; Friend, David R.

    2012-01-01

    A vaginal gel containing the antiretroviral tenofovir (TFV) recently demonstrated 39% protection against HIV infection in women. We designed and evaluated a novel reservoir TFV intravaginal ring (IVR) to potentially improve product effectiveness by providing a more controlled and sustained vaginal dose to maintain cervicovaginal concentrations. Polyurethane tubing of various hydrophilicities was filled with a high-density TFV/glycerol/water semisolid paste and then end-sealed to create IVRs. In vitro, TFV release increased with polyurethane hydrophilicity, with 35 weight percent water-swelling polyurethane IVRs achieving an approximately 10-mg/day release for 90 days with mechanical stiffness similar to that of the commercially available NuvaRing. This design was evaluated in two 90-day in vivo sheep studies for TFV pharmacokinetics and safety. Overall, TFV vaginal tissue, vaginal fluid, and plasma levels were relatively time independent over the 90-day duration at approximately 104 ng/g, 106 ng/g, and 101 ng/ml, respectively, near or exceeding the highest observed concentrations in a TFV 1% gel control group. TFV vaginal fluid concentrations were approximately 1,000-fold greater than levels shown to provide significant protection in women using the TFV 1% gel. There were no toxicological findings following placebo and TFV IVR treatment for 28 or 90 days, although slight to moderate increases in inflammatory infiltrates in the vaginal epithelia were observed in these animals compared to naïve animals. In summary, the controlled release of TFV from this reservoir IVR provided elevated sheep vaginal concentrations for 90 days to merit its further evaluation as an HIV prophylactic. PMID:23006751

  2. Biochemical effects of vepacide (from Azadirachta indica) on Wistar rats during subchronic exposure.

    PubMed

    Rahman, M F; Siddiqui, M K J

    2004-11-01

    We investigated the effect of Vepacide (from Azadirachta indica), a neem-based pesticide, on acid (AcP) and alkaline (AkP) phosphatase in different tissues of male and female albino Wistar rats. Subchronic doses of Vepacide in coconut oil (80, 160, and 320 mg/kg; maximum volume of 0.2 mL) were administered orally for 45 or 90 days. The administration of Vepacide resulted in a significant increase in AcP and AkP in serum, kidney, lung, and liver tissue (AkP only in liver), whereas a significant decrease of AcP in liver was observed in male and female rats after 45 and 90 days of treatment with moderate and high doses. The alterations in serum, liver, kidney, and lung tissues of both male and female rats caused by this compound were statistically significant, and the changes were also dose and time dependent. The alterations in male rats were not statistically significant when compared with female rats, indicating that there were no sexual differences. The withdrawal study (28 days post-treatment) revealed significant recovery, indicating reversal of the toxic symptoms once the toxicant was removed. There was a high degree of positive correlation between results for serum as compared to those for kidney, lung, and liver (AkP only for liver). However, there was a high negative correlation between AcP results for serum as compared with those for liver. The alterations in these enzymes indicated that lung tissue was the most susceptible, followed by liver and kidney. AcP and AkP are marker enzymes, and their increase in serum, with parallel increases in different tissues, might be due to the increased permeability of plasma membranes. The decrease in liver AcP may be due to the necrosis of cellular tissues. The changes observed in these enzyme activities could be useful as biomarkers of exposure to Vepacide. PMID:15388273

  3. 12 CFR 220.117 - Exception to 90-day rule in special cash account.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... the language and intent of the above-quoted exception in § 220.4(c)(8), until it has been honored by... substantially the same as language found in section 4(f) of Regulation T as originally promulgated in 1934. The language of the subject exception to the 90-day rule of § 220.4(c)(8), i.e., the exception based...

  4. 90-Day feeding and genotoxicity studies on a refined arachidonic acid-rich oil.

    PubMed

    Casterton, P L; Curry, L L; Lina, B A R; Wolterbeek, A P M; Kruger, C L

    2009-10-01

    The safety of a refined arachidonic acid-rich oil (RAO) was evaluated for reverse mutation, chromosome aberration and gene mutation, and in a 90-day Wistar rat feeding study with in utero exposure. The results of the genotoxicity assays were all negative. The in utero phase of the 90-day study involved dietary exposure to 0.5%, 1.5% and 5% RAO and two controls diets, a standard feed low-fat diet and a high-fat diet supplemented with 5% corn oil. This exposure covered four-weeks prior to mating, through mating, gestation and lactation until offspring (F(1)) weaning. A subsequent 90-day feeding study in the F(1) rats evaluated the same test and control diets. Statistically significant effects were seen for selected histopathology, clinical chemistry and organ weight endpoints; however, other than increased absolute and relative monocytes seen in both sexes of high-dose rats, the observations were not attributed to treatment for one or more reasons. Based on these findings, no adverse treatment-related effects for RAO were seen at up to 5% in the diet, equivalent to an overall average RAO intake of 3170 mg/kg bwt/day. These and similar findings for other refined ARA-rich oils establish a strong body of evidence for the safety of this RAO. PMID:19576260

  5. Toxicity Profile of a Nutraceutical Formulation Derived from Green Mussel Perna viridis

    PubMed Central

    Joseph, Deepu; Chakkalakal, Selsa J.

    2014-01-01

    The short-term (acute) and long-term (subchronic) toxicity profile, mean lethal dose 50 (LD50), and no-observed-adverse-effect level (NOAEL) of a nutraceutical formulation developed from green mussel Perna viridis, which showed in vitro and in vivo anti-inflammatory properties, were evaluated in the present study. The formulation was administered to the male and female Wistar rats at graded doses (0.5, 1.0, and 2.5 g/kg body weight) for two weeks of acute toxicity study and 0.5, 1.0, and 2.0 g/kg body weight for 90 days in subchronic toxicity study. The LD50, variations in clinical signs, changes in body weight, body weight, food/water consumption, organ weight (liver, kidney, spleen, and brain), hematology, serum chemistry, and histopathological changes were evaluated. The LD50 of the formulation was 5,000 mg/kg BW. No test article related mortalities as well as change in body weight, and food and water consumption were observed. No toxicity related significant changes were noted in renal/hepatic function, hematological indices, and serum biochemical parameters between the control and treated groups. Histopathological alterations were not observed in the vital organs of rats. The subchronic NOAEL for the formulation in rats is greater than 2000 mg/kg. This study demonstrated that the green mussel formulation is safe to consume without any adverse effects in the body. PMID:24995298

  6. The impact of 90-day prescriptions on adherence at workplace pharmacies compared to traditional mail order.

    PubMed

    Patwardhan, Avinash; Davis, Jeffery; Murphy, Patricia; Khandelwal, Nikhil; Sherman, Bruce; Manfred, James

    2011-12-01

    This study evaluated adherence to medications used to treat chronic conditions for patients with 90-day prescriptions, comparing patients with access to workplace pharmacy services versus patients using mail order services. De-identified pharmacy claims data were used to compute medication possession ratio and gaps in therapy. Results were compared for patients who filled 90-day prescriptions at workplace pharmacies versus patients who filled 90-day prescriptions using mail order pharmacy services in a 1-year period. Statistical tests to assess between group differences were performed controlling for differences because of age, sex, number of select chronic conditions, number of unique medication therapeutic classes, and patient out-of-pocket cost per therapy day. Statistically significant differences were found between patients who filled their maintenance medications at the worksite compared to those who used mail-order pharmacy services. Patients filling prescriptions at a workplace pharmacy were 22% less likely to have a gap in therapy of over 30 days compared to similar patients using mail order services. Workplace pharmacy utilizers also had overall adherence rates 3.68% higher than patients who utilized mail order pharmacy services. Our analysis suggests that it may not be just the quantity of medication dispensed that impacts patients' adherence to their prescription medication, but a variety of other factors including pharmacist-patient interaction. Having a pharmacist on-site and available to patients with chronic considerations could provide added value. These results can aid employers and other stakeholders to decide which prescription benefits to offer their employees and members. PMID:22092153

  7. 76 FR 12683 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the Texas...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-08

    ... Fish and Wildlife Service 50 CFR Part 17 Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the Texas Kangaroo Rat as Endangered or Threatened AGENCY: Fish and Wildlife....S. Fish and Wildlife Service (Service), announce a 90-day finding on a petition to list the...

  8. 75 FR 19925 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition to List a Distinct...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-16

    ... Fish and Wildlife Service 50 CFR Part 17 Endangered and Threatened Wildlife and Plants; 90-Day Finding... 90-day finding (56 FR 1159) indicating that the fisher in the Pacific States is a distinct population... habitat needs, population size and trends, and demographic parameters (56 FR 1159). On December 29,...

  9. 76 FR 23256 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the Arapahoe...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-26

    ... published two 90-day findings, on January 6, 2009 (74 FR 419), and February 5, 2009 (74 FR 6122). The February 5, 2009 (74 FR 6122), 90-day finding concluded that the petition did not present substantial..., as critical habitat for the Preble's meadow jumping mouse (Zapus hudsonius preblei) (68 FR 37275)....

  10. 77 FR 9618 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-17

    ... Fish and Wildlife Service 50 CFR Part 17 Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the Thermophilic Ostracod as Endangered or Threatened AGENCY: Fish and Wildlife Service, Interior. ACTION: Notice of 90-day petition finding. SUMMARY: We, the U.S. Fish and...

  11. 78 FR 72622 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List 11 Tarantula...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-03

    ... Fish and Wildlife Service 50 CFR Part 17 Endangered and Threatened Wildlife and Plants; 90-Day Finding... AGENCY: Fish and Wildlife Service, Interior. ACTION: Notice of petition finding and initiation of status review. SUMMARY: We, the U.S. Fish and Wildlife Service (Service), announce a 90-day finding on...

  12. Effects of Subchronic Exposure to Cadmium and Diazinon on Testis and Epididymis in Rats

    PubMed Central

    Cabaj, Michal; Massanyi, Peter; Martiniakova, Monika; Omelka, Radoslav; Krajcovicova, Vladimira; Duranova, Hana

    2014-01-01

    The present study aimed to elucidate the structural changes in testis and epididymis of adult rats following subchronic peroral administration of cadmium at 30 mg/L, diazinon at 40 mg/L, cadmium at 30 mg/L, and diazinon at 40 mg/L, respectively. At the end of 90-day experiment, the samples of the testes and epididymis were assayed by qualitative and quantitative histological methods. The testis and epididymis weights increased following exposure to cadmium and simultaneous exposure to cadmium and diazinon. Testicular damage following cadmium and diazinon coexposure was significantly less expressive than in groups with individual administration of these compounds. Cadmium caused a significant thickening of seminiferous epithelium, cellular degeneration, and necrosis. Desquamation of immature germ cells resulted in a significant increase of intraepithelial spaces and reduced tubule volume in all experimental groups. Vascular dilation and congestion were detected in the interstitial tissue. The changes in epididymal histology in the group exposed to cadmium and group exposed simultaneously included a reduction of epithelium, necrotic epithelial cells, vasoconstriction, and interstitial edema together with mononuclear cell infiltration. Results did not indicate a synergistic or any additional effect from the simultaneous administration of both toxicants. Further research is needed to determine the significance and the mechanism of the adverse effects. PMID:25548789

  13. Program operational summary: Operational 90 day manned test of a regenerative life support system

    NASA Technical Reports Server (NTRS)

    Jackson, J. K.; Wamsley, J. R.; Bonura, M. S.; Seeman, J. S.

    1972-01-01

    An operational 90-day manned test of a regenerative life support system was successfully completed. This test was performed with a crew of four carefully selected and trained men in a space station simulator (SSS) which had a two gas atmosphere maintained at a total pressure of 68.9, 10 psia, and composed of oxygen at a partial pressure of 3.05 psia with nitrogen as the diluent. The test was planned to provide data on regenerative life support subsystems and on integrated system operations in a closed ecology, similar to that of a space station. All crew equipment and expendables were stored onboard at the start of the mission to eliminate the need for pass-in operations. The significant accomplishments of the test, some of the pertinent test results, some of the problem areas, and conclusions are presented.

  14. Ultrastructural response of rat lung to 90 days' exposure to oxygen at 450 mm Hg

    NASA Technical Reports Server (NTRS)

    Harrison, G. A.

    1974-01-01

    Young Sprague-Dawley rats were exposed to 100% oxygen at 450 mm Hg in constant environment capsules for 90 days. Lung tissue examined by electron microscopy revealed a number of changes, many similar to those observed after exposure to oxygen at 760 mm Hg for shorter periods of time. Alterations in vesicle size and number and in mitochondrial matrix and cristae appear in both the endothelial and epithelial cells. Blebbing and rarefication of cytoplasm occur in both cell layers of the alveolo-capillary wall. Also seen are fluid in the basement membrane, platelets in the capillaries, and alveolar fluid and debris. All of these alterations occur at 1 atm exposure. However, after exposure to 450 mm Hg the changes are not as widespread nor as destructive as they are at the higher pressure.

  15. Training plan for the 1164 {lt}90-day non-radioactive hazardous waste storage building

    SciTech Connect

    Demarest, J.L., Westinghouse Hanford

    1996-07-01

    In accordance with Washington Administrative Code (WAC), Chapter 173- 303, `Dangerous Waste Regulations,` a written training plan is required for a {lt}90-day accumulation area. WAC 173-303-200, `Accumulating Dangerous Waste On-site,` requires compliance with WAC- 173-303-330, Personnel Training. This training plan complies with WAC 173-303-330. This training plan, including the names of personnel in Table 1, may be given to a regulatory agency inspector upon request provided that this plan is cleared for public release. Training records associated with personnel identified in this plan are not be given to an outside regulatory agency inspector unless prior approval by the specific individual is obtained. Training records requests by regulatory agency inspectors without the individual`s approval are to be processed via a Freedom of Information Act request through the U.S. Department of Energy, Richland Operations Office.

  16. Bioregenerative Life Support Experiment for 90-days in a Closed Integrative Experimental Facility LUNAR PALACE 1

    NASA Astrophysics Data System (ADS)

    Liu, Hong

    A 90-day bioregenerative life support experiment with three-member crew was carried out in the closed integrative experimental facility, LUNAR PALACE 1 regenerating basic living necessities and disposing wastes to provide life support for crew. It was composed of higher plant module, animal module, and waste treatment module. The higher plant module included wheat, chufa, pea, carrot and green leafy vegetables, with aim to satisfy requirement of 60% plant food and 100% O2 and water for crew. The yellow mealworm was selected as animal module to provide partial animal protein for crew, and reared on plant inedible biomass. The higher plant and yellow mealworm were both cultivated and harvested in the conveyor-type manner. The partial plant inedible biomass and human feces were mixed and co- fermented in the waste treatment module for preparation of soil-like substrate by bioconversion, maintaining gas balance and increasing closure degree. Meanwhile, in the waste treatment module, the water and partial nitrogen from human urine were recovered by physical-chemical means. Circulation of O2 and water as well as food supply from crops cultivated in the LUNAR PALACE 1 were investigated and calculated, and simultaneously gas exchange, mass flow among different components and system closure degree were also analyzed, respectively. Furthermore, the system robustness with respect to internal variation was tested and evaluated by sensitivity analysis of the aggregative index consisting of key performance indicators like crop yield, gaseous equilibrium concentration, microbial community composition, biogenic elements dynamics, etc., and comprehensively evaluating the operating state, to number change of crew from 2 to 4 during the 90-day closed experiment period.

  17. Co-morbidities and 90-day outcomes in hospitalized COPD exacerbations.

    PubMed

    Roberts, Christopher M; Stone, Robert A; Lowe, Derek; Pursey, Nancy A; Buckingham, Rhona J

    2011-10-01

    COPD exacerbations resulting in hospitalization are accompanied by high mortality and morbidity. The contribution of specific co-morbidities to acute outcomes is not known in detail: existing studies have used either administrative data or small clinical cohorts and have provided conflicting results. Identification of co-existent diseases that affect outcomes provides opportunities to address these conditions proactively and improve overall COPD care. Cases were identified prospectively on admission then underwent retrospective case note audit to collect data including co-morbidities on up to 60 unselected consecutive acute COPD admissions between March and May in each hospital participating in the 2008 UK National COPD audit. Outcomes recorded were death in hospital, length of stay, and death and readmission at 90 days after index admission. 232 hospitals collected data on 9716 patients, mean age 73, 50% male, mean FEV1 42% predicted. Prevalence of co-morbidities were associated with increased age but better FEV1 and ex-smoker status and with worse outcomes for all four measures. Hospital mortality risk was increased with cor pulmonale, left ventricular failure, neurological conditions and non-respiratory malignancies whilst 90 day death was also increased by lung cancer and arrhythmias. Ischaemic and other heart diseases were important factors in readmission. This study demonstrates that co-morbidities adversely affect a range of short-term patient outcomes related to acute admission to hospital with exacerbations of COPD. Recognition of relevant accompanying diseases at admission provides an opportunity for specific interventions that may improve short-term prognosis. PMID:21864116

  18. Effects of furan on male rat reproduction parameters in a 90-day gavage study.

    PubMed

    Cooke, Gerard M; Taylor, Marnie; Bourque, Christine; Curran, Ivan; Gurofsky, Susan; Gill, Santokh

    2014-07-01

    Furan is produced in foods during processing and preservation techniques that involve heat treatment. Previously, we reported that furan-exposed rats exhibited dose-dependent gross and histological changes in liver which correlated with changes in liver serum enzymes ALT, AST and ALP. Here we report the effects of furan on the male reproductive system. There were no histological or weight changes in the reproductive organs. Serum testosterone levels were increased in a dose-dependent manner whereas serum LH was decreased. There were no changes in 17-OHase, 3β-HSD and 17β-HSD activities or serum FSH. Furan did not alter mRNA expression levels for the LH receptor or Tspo but in contrast, mRNA levels of StAR were increased in all doses of furan. The mRNA for the cholesterol side-chain cleavage enzyme (Cyp11a1) was increased by furan at the high dose, as was the level of intratesticular testosterone. We conclude that subchronic furan exposure affects testicular steroidogenesis. PMID:24632374

  19. Evaluation of the oral subchronic toxicity of AHTN (7-Acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene) in the rat.

    PubMed

    Api, Anne Marie; Smith, Robert L; Pipino, Sandra; Marczylo, Timothy; De Matteis, Francesco

    2004-05-01

    7-Acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene (AHTN) is used as a fragrance material in a wide variety of consumer products. Because of its widespread exposure, a 90-day oral feeding study, with 4-week recovery periods for selected rats, was conducted. AHTN was added to the diet of rats at levels calculated to result in mean daily doses of 1.5, 5, 15 or 50 mg AHTN/kg body weight/day. On completion of the treatment period, 3 males and 3 females from each of the high dose groups and controls were maintained for a treatment free period of 4 weeks. There were no adverse effects revealed upon clinical examination or following extensive histopathological examinations. Histopathological examination of the prostate, seminal vesicles, mammary gland and testes of males and ovaries, mammary gland, uterus and vagina of females, undertaken on all animals in all test groups, revealed no evidence of hormonal effects of AHTN. A statistically significant decrease in body weight gain was observed in both sexes in the high dose group only. Statistically significant effects were observed in hematology and blood chemistry, although these effects were all within the range for historical controls and were not proportional to dose. A green to dark brown coloration in the livers and mesenteric lymph nodes was also seen in high dose animals. At the end of the treatment-free period, the color change was almost completely reversed; one high dose male still had green colored lymph nodes, but the liver appeared normal. A green coloration of the lacrimal glands in females, but not males, was also seen in 8/12, 4/15 and in 1 female given 50, 15 and 5 mg/kg body weight/day, respectively. This green color was still present in 2/3 of the high dose females after the treatment-free period. Microscopic examination of unstained sections of frozen livers under UV illumination did not reveal any fluorescence that might have been consistent with porphyrin accumulation. These findings were

  20. 78 FR 10601 - Endangered and Threatened Wildlife; 90-Day Finding on a Petition to List 44 Species of Corals as...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-14

    ... National Oceanic and Atmospheric Administration RIN 0648-XC209 Endangered and Threatened Wildlife; 90-Day... Species Act AGENCY: National Marine Fisheries Service (NMFS), National Oceanic and Atmospheric... temperature, availability of hard substrate, currents and sediment load, and seawater chemistry...

  1. 77 FR 43799 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the Gila...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-26

    ... Regional Office. On December 16, 2009 (74 FR 66866), we published a partial 90-day finding on the petition... and, therefore, less habitat available. Increased siltation may be due to historical overgrazing...

  2. The inhalation toxicity of di- and triethanolamine upon repeated exposure.

    PubMed

    Gamer, A O; Rossbacher, R; Kaufmann, W; van Ravenzwaay, B

    2008-06-01

    Systemic and respiratory tract (RT) toxicity of triethanolamine (TEA) was assessed in a 28-day nose-only inhalation study in Wistar rats (10animals/sex, concentrations: 0, 20, 100, 500mg/m3; 5 days/week, 6h/day). In two nose-only 90-day inhalation studies, with similar exposure design, Wistar rats were exposed to 0, 15, 150, 400mg/m3 diethanolamine (DEA) (DEA Study 1:13animals/sex, general subchronic study) and to 0, 1.5, 3, 8mg/m3 (DEA Study 2:10animals/sex) to specifically investigate respiratory tract toxicity. Only DEA induced systemic toxicity at or above 150mg/m3 (body and organ weight changes, clinical- and histo-pathological changes indicative for mild blood, liver, kidney and testicular effects). Neurotoxicity was not observed for both substances. Exposure to both substances resulted in laryngeal epithelial changes starting from 3mg/m3 for DEA (reversible metaplasia at the base of the epiglottis, inflammation at higher concentrations extending into the trachea) or from 20mg/m3 for TEA (focal inflammation, starting in single male animals). TEA appears to be less potent with respect to systemic toxicity and RT irritancy than DEA. The 90-day no adverse effect concentration" (NOAEC) for changes due to TEA exposure in the respiratory tract was 4.7mg/m3 derived by extrapolation from the NOAEC of the 28day study. PMID:18420328

  3. A 90-Day Oral Toxicological Evaluation of the Methylurate Purine Alkaloid Theacrine

    PubMed Central

    Hirka, Gábor; Glávits, Róbert; Palmer, Philip A.; Endres, John R.; Pasics Szakonyiné, Ilona

    2016-01-01

    A 90-day repeated-dose oral toxicological evaluation was conducted according to GLP and OECD guidelines on the methylurate purine alkaloid theacrine, which is found naturally in certain plants. Four groups of Hsd.Brl.Han Wistar rats (ten/sex/group) were administered theacrine by gavage doses of 0 (vehicle only), 180, 300, and 375 mg/kg bw/day. Two females and one male in the 300 and 375 mg/kg bw/day groups, respectively, died during the study. Histological examination revealed centrilobular hepatocellular necrosis as the probable cause of death. In 375 mg/kg bw/day males, slight reductions in body weight development, food consumption, and feed efficiency, decreased weight of the testes and epididymides and decreased intensity of spermatogenesis in the testes, lack or decreased amount of mature spermatozoa in the epididymides, and decreased amount of prostatic secretions were detected at the end of the three months. At 300 mg/kg bw/day, slight decreases in the weights of the testes and epididymides, along with decreased intensity of spermatogenesis in the testes, and lack or decreased amount of mature spermatozoa in the epididymides were detected in male animals. The NOAEL was considered to be 180 mg/kg bw/day, as at this dose there were no toxicologically relevant treatment-related findings in male or female animals.

  4. Petroleum prices and profits in the 90 days following the invasion of Kuwait

    SciTech Connect

    Not Available

    1990-11-01

    For the third in the past 20 years the world has experienced an interruption in the flow of oil from the Persian Gulf. The Iraqi invasion of Kuwait on August 2, 1990, and shut down of Kuwait oil production capacity followed by the United Nations boycott of Iraqi oil removed 8 percent of the world's oil supply. The result was a sharp increase in the process of crude oil and petroleum products. These events raised numerous questions about the performance of energy markets and energy firms. This report supplies a first answer for some of those questions. At the time this report was prepared the invasion has been in effect for 90 days. Not all the data is available to fully answer every question. Some issues can only be completely resolved after more time has passed in which the invasion and its effects have had an opportunity to be fully assimilated. This report was specifically requested by W. Henson Moore, Deputy Secretary of Energy as a way of supplying the American public with what could be said about the current situation. Rumors abound and mixconceptions have proliferated. This report strives to give a proper perspective on some of the more vexing issues which the invasion produced. The Energy Information Administration (EIA) has addressed many questions in this report. By the way of summary these are the 10 most most frequently asked questions and EIA's quick answers. The page references tell the reader where to look in the report for further explanation. These are not the only issues addressed and EIA hopes that readers will be able to satisfy their curiosity about their own questions within the pages of this report.

  5. Intra- and Inter-Patient Symptom Variability in Fibromyalgia: Results of a 90-Day Assessment.

    PubMed

    Toussaint, Loren; Vincent, Ann; McAllister, Samantha J; Whipple, Mary

    2015-06-01

    Symptoms of fibromyalgia (FM)--chronic widespread pain, fatigue, unrefreshing sleep, dyscognition etcetera--present with varying degrees of severity in different individuals; however, studies reporting daily estimates of variability of symptoms are sparse. Given the limited literature on the stability and variability of FM symptoms, the purpose of the present study was to determine the feasibility of daily visual analogue, self-report measures to assess daily variability and time trends in core FM symptoms. Ten female patients completed daily assessments of common FM symptoms (pain, fatigue, anxiety, depression, stress, cognitive dysfunction, unrefreshing sleep and lightheadedness) for approximately 90 days. The completion rate was excellent (89.6%). The results demonstrated that average symptom intensity differs markedly across the different symptoms that were measured. Unrefreshing sleep, fatigue and pain are clearly higher in intensity than other symptoms and are followed by memory problems, stress, anxiety and depression. There is also notable average intra-individual change across time (10-15 points on a 100-point scale). Average symptom intensity does not appear to be related to the amount of symptom change within individuals. The results of the present study confirm that intensive longitudinal study, using comprehensive symptom assessment in patients with FM, is both possible and informative, in the sense that a rich description of the daily experience of living with FM can be obtained. Future work, utilizing larger samples, will offer the opportunity to investigate better the causes, consequences and correlates of the daily ups and downs of key symptoms that compromise quality of life in patients with FM. PMID:25408116

  6. Recent Trends in the Dispensing of 90-Day-Supply Prescriptions at Retail Pharmacies: Implications for Improved Convenience and Access

    PubMed Central

    Liberman, Joshua N.; Girdish, Charmaine

    2011-01-01

    Background Mail-service pharmacies offer consumers the convenience of prescriptions filled with a 90-day supply of medication. Unlike mail-service pharmacies, retail pharmacies traditionally dispensed maintenance medication prescriptions with a 30-day supply. However, the retail landscape changed in May 2008 with Walmart's announcement of an extension of its $4 Prescription Program to include 90-day-supply prescriptions. Objective To evaluate recent changes in access to and use of 90-day-supply maintenance medications dispensed via retail pharmacy. Summary As of the first quarter of 2007, the proportion of retail-dispensed maintenance medications with a 90-day supply (compared with all maintenance prescriptions dispensed) among Medicare Part D plans, self-insured employers, and private health plans was 5.1%, 5.1%, and 5.0%, respectively. As of December 2009, this ratio had risen to 8.0% for Medicare plans and 8.1% for commercial health plans; the ratio among employers had risen more modestly to 6.1%. Of particular interest and importance, the proportion increased similarly for brand and for generic medications. Conclusion There has been substantial growth in 90-day prescriptions dispensed via retail pharmacy, a trend that is likely to continue as more insurance providers adopt compatible benefit designs. It is important to continue monitoring these trends and to identify opportunities to rigorously evaluate their impact on medication adherence and healthcare costs. PMID:25126341

  7. Effects of 30-, 60-, and 90-Day Bed Rest on Postural Control in Men and Women

    NASA Technical Reports Server (NTRS)

    Esteves, Julie; Taylor, Laura C.; Vanya, Robert D.; Dean, S. Lance; Wood, Scott J.

    2011-01-01

    INTRODUCTION Head-down-tilt bed rest (HDT) has been used as a safe gr ound-based analog to mimic and develop countermeasures for the physiological effects of spaceflight, including decrements in postural stability. The purpose of this investigation was to characterize the effects of 30-, 60-, and 90-day bed rest on postural control in men and women. METHODS Twenty-nine subjects (18M,11F) underwent 13 days of ambula tory acclimatization and were placed in 6? HDT for 30 (n=12), 60 (n=8), or 90 (n=9) days, followed by 14 days of ambulatory recovery. Computerized dynamic posturography (CDP) was used to assess changes in sensory and motor components of postural control, and recovery after HDT. Sensory Organization Tests (SOTs) objectively evaluate one?s ability to effectively use or suppress visual, vestibular, and proprioceptive information for postural control. Stability during the SOTs was assessed using peak-to-peak sway and convergence toward stability limits to derive an equilibrium score. Motor Control Tests (MCTs) evaluate one?s ability to recover from unexpected support surface perturbations, with performance determined by center-of-pressure path length. Whole-body kinematic data were collected to determine body-sway strategy used to maintain stability during each condition. Baselines were determined pre-HDT. Recovery was tracked post-HDT on days 0, 1, 2, and 4. RESULTS Immediately after HDT, subjects showed decreased performance on most SOTs, primarily on sway-referenced support conditions, typically returning to baseline levels within 4 days. MCT performance was not significantly affected. There were no significant gender or duration differences in performance. Kinematic data revealed a tendency to use ankle strategy to maintain an upright stance during most SOT conditions. Interestingly, six subjects (2M,4F) experienced orthostatic intolerance and were unable to complete day 0 testing. CONCLUSION HDT mimics some un loading mechanisms of spaceflight and

  8. Comparative 90-day dietary study of paraffin wax in Fischer-344 and Sprague-Dawley rats.

    PubMed

    Griffis, L C; Twerdok, L E; Francke-Carroll, S; Biles, R W; Schroeder, R E; Bolte, H; Faust, H; Hall, W C; Rojko, J

    2010-01-01

    Highly refined mineral hydrocarbons (MHCs) such as low melting point paraffin wax (LMPW) and low viscosity white oils can cause inflammatory changes in the liver and mesenteric lymph nodes (MLNs) of the Fischer-344 (F-344) rat. In contrast, only minimal MLN changes are seen in the Sprague-Dawley (S-D) rat with no changes in the liver. In this study, the response of female F-344 and S-D rats was compared after 90days dietary treatment with 0%, 0.2% or 2% LMPW. Effects in the F-344 rats were significantly greater than in the S-D rats: increased liver and splenic weights and inflammatory changes (hepatic microgranulomas) in these tissues were observed only in the F-344 rats. Microgranulomas in the MLNs were observed in both strains but the effects were substantially greater in the F-344 rats. Cellular markers of inflammation were examined in a subset of rats from each group using immunohistochemical staining. An increase in staining for CD3 (T-cells), CD8a (suppresser/cytotoxic T-cells) and CD4 (helper T-cells) correlated with an increase in lymphoid cells in the livers of treated F-344 rats. The majority of macrophages in the hepatic microgranulomas of treated F-344 rats were negative for the ED2 marker, indicating a likely origin from non-resident macrophages. Electron microscopy showed Kupffer cell hypertrophy and hyperplasia in treated F-344 rats. However, lysozyme staining (indicating activation of epithelioid macrophages) decreased with increasing granuloma size. Non-ED2 expressing cells may have been recruited but not sufficiently activated to be lysozyme positive. Inflammatory changes in the cardiac mitral valve noted in previous studies of LMPW were also seen in the F-344 rats in this study but not in the S-D rats. Chemical analysis showed that MHC accumulated in livers from treated F-344 but not S-D rats and the concentration was more than 2-fold greater in MLNs from the F-344 than from the S-D rats. The F-344 appears to be more immunologically sensitive to

  9. A 90-day dietary study on kappa carrageenan with emphasis on the gastrointestinal tract.

    PubMed

    Weiner, Myra L; Nuber, David; Blakemore, William R; Harriman, Jay F; Cohen, Samuel M

    2007-01-01

    Groups of Fischer 344 rats (20/sex/group) received control or treated diets at levels of 0, 25,000 or 50,000 ppm kappa carrageenan with a molecular weight range (Mw) of 196,000-257,000 Da for 90 days. The Low Molecular Weight Tail (LMT) ranged between 1.9% and 12.0%<50 kDa (mean 7%) based on the results of a program initiated to develop a validated analytical method to measure the LMT. This is the first GLP dietary study in which carrageenan is characterized by percentage LMT. Clinical examinations were performed daily. Individual food consumption/body weight measurements were made weekly. Ophthalmic exam was conducted prior to and at the end of treatment. Hematology/serum chemistry and urinalysis evaluations were done at necropsy, as were organ weight determinations for adrenals, brain, heart, kidneys, liver, ovaries, spleen, testes and thyroid with parathyroids. Full histopathological evaluation of organs was conducted on the control and 50,000 ppm groups, including hematoxylin-eosin-stained cross sections of paraffin-embedded rolled colon. Clinical signs were limited to soft feces in high dose rats and to a lesser extent in low dose rats. There were no treatment-related effects on body weights, urinalysis, hematology or clinical chemistry parameters, or on organ weights or ophthalmic, macroscopic or microscopic findings. The gastrointestinal tract appeared normal in detailed histopathological evaluation using the Swiss roll technique. The NOAEL is 50,000 ppm in the diet (mean calculated test material consumption of 3394+/-706 mg/kg/day in males, 3867+/-647 mg/kg/day in females). The results of the study provide evidence that it is not necessary to characterize carrageenan by a specification for LMT (less than 5% below 50 kDa) as has been done in Commission Directive 2004/45/EC of 16 April 2004 (Commission Directive, 2004/45/EC of 16 April 2004 amending Directive 96/77/EC laying down specific purity criteria on food additives other than colors and sweeteners

  10. Potential subchronic food safety of the stacked trait transgenic maize GH5112E-117C in Sprague-Dawley rats.

    PubMed

    Han, Shiwen; Zou, Shiying; He, Xiaoyun; Huang, Kunlun; Mei, Xiaohong

    2016-08-01

    The food safety of stacked trait genetically modified (GM) maize GH5112E-117C containing insect-resistance gene Cry1Ah and glyphosate-resistant gene G2-aroA was evaluated in comparison to non-GM Hi-II maize fed to Sprague-Dawley rats during a 90-day subchronic feeding study. Three different dietary concentrations (12.5, 25 and 50 %, w/w) of the GM maize were used or its corresponding non-GM maize. No biologically significant differences in the animals' clinical signs, body weights, food consumption, hematology, clinical chemistry, organ weights and histopathology were found between the stacked trait GM maize groups, and the non-GM maize groups. The results of the 90-day subchronic feeding study demonstrated that the stacked trait GM maize GH5112E-117C is as safe as the conventional non-GM maize Hi-II. PMID:26919987

  11. Ninety-Day Oral Toxicity Assessment of an Alternative Biopolymer for Controlled Release Drug Delivery Systems Obtained from Cassava Starch Acetate

    PubMed Central

    Jesus, Douglas Rossi; Barbosa, Lorena Neris; Prando, Thiago Bruno Lima; Martins, Leonardo Franco; Gasparotto, Francielli; Guedes, Karla Moraes Rocha; Dragunski, Douglas Cardoso; Lourenço, Emerson Luiz Botelho; Dalsenter, Paulo Roberto; Gasparotto Junior, Arquimedes

    2015-01-01

    The large consumption of biodegradable films from cassava starch acetate (FCSA) as ingredients in food and pharmaceutical products requires the assessment of the possible toxicity of these products. The aim of this study was to investigate the toxicity of biodegradable film from cassava starch acetate after oral exposure of Wistar rats for 90 days. The amount of food consumed and the body weight were weekly monitored. Blood and urine samples were obtained for the assessment of serum parameters and renal function. Histopathological analyses in target organs were also performed. No evidence of clinical toxicity in hematological, biochemical, or renal parameters in the FCSA-treated animals was found. In addition, relative organ weight and histopathological evaluations did not differ between groups treated with FCSA and control. Data obtained suggest that the subchronic exposure to FCSA does not cause obvious signs of toxicity in Wistar rats, indicating possible safety of this biofilm. PMID:26451154

  12. Toxic Hazards Research Unit annual report, 1990. Annual report No. 27 (Final), 1 Oct 89-15 Nov 90

    SciTech Connect

    Wall, H.G.; Vinegar, A.; Kinkead, E.R.

    1990-12-01

    This report presents a review of the activities of the Toxic Hazards Research Unit for the period of 1 October 1989 through 15 November 1990. Research activities focused on toxicity evaluations of aerospace and naval chemicals to include aircraft fuels and rocket fuels, hydraulic fluids, ground water contaminants, and chemical defense simulants. There was increased utilization of multidisciplinary efforts for quantitative toxicology studies and the development and validation of physiologically based pharmacokinetic models for predicting toxicity responses. The General Toxicology Laboratory conducted acute studies, toxicokinetic studies, repeated-dose studies, and subchronic inhalation studies to include a 90-day continuous inhalation study using the Thomas Domes. The development and characterization of a unique high pressure aerosol generator was a significant adjunct benefitting the study conducted in the Thomas Domes.

  13. Assessment of anti-depressant effect of nelumbinis semen on rats under chronic mild stress and its subchronic oral toxicity in rats and beagle dogs

    PubMed Central

    2012-01-01

    Background Previously, we examined the antidepressant effects of Nelumbinis Semen (NS). In this study, we assessed the anti-depressant effects of NS in the forced swimming test and chronic mild stress (CMS) models of depression and its oral toxicity in rats and dogs. Methods In the forced swimming test, NS was intraperitoneally injected before 24 h, 5 h and 1 h of forced swimming test. And the rats were forced to swim for 5 min, the duration of immobility was observed. In CMS models, animals were exposed to a variety of CMS for 8 weeks in order to induce depression-like symptoms. They were treated with NS for the last four weeks of the 8-week CMS and then an open field test was conducted. The anti-depression effects were evaluated based on a measured index, which consisted of visiting counts, start latency, rearing number and grooming time. In the toxicological studies, NS was administered to rats by gavages for 13 weeks at doses of 0, 500, 1000, and 2000 mg/kg/day. To assess the toxicity of NS in beagle dogs, NS was administered orally for 28 days at doses of 0, 500, 1000, 2000 and 4000 mg/kg/day. Results 400 mg/kg of NS had the lowest immobility times in forced swimming test. And NS significantly reversed the decreased visiting counts, rearing number and grooming time caused by CMS. In addition, NS treatment significantly decreased the start latency. No treatment-related toxicity was detected during 13 weeks administration in rats and 28 days administration in dogs. Conclusions Based on the results of this study and previous reports that have examined the anti-depressive effects of NS, NS holds great promise for use in the treatment of depression without causing any adverse effects or toxicities. PMID:22640371

  14. A subchronic feeding study of dicamba-tolerant soybean with the dmo gene in Sprague-Dawley rats.

    PubMed

    Wang, Xiaoyun; He, Xiaoyun; Zou, Shiyin; Xu, Wentao; Jia, Xin; Zhao, Bo; Zhao, Changhui; Huang, Kunlun; Liang, Zhihong

    2016-06-01

    The dicamba-tolerant soybean MON87708 expresses the dicamba mono-oxygenase (DMO) enzyme that is encoded by the dmo gene. In order to evaluate the safety of this soybean, a 90-day subchronic feeding toxicity study (13 weeks) was conducted on Sprague-Dawley rats. A total of 140 rats were divided into 7 groups (10/sex/group), including a standard commercial diet control group. The genetically modified (GM) soybean MON87708 and the near isogenic non-GM soybean A3525 were respectively processed to unhulled, full-fat, and heat-treated powder, then mixed into the diet at levels of 7.5%, 15%, and 30% (wt/wt) with the main nutrients of the various diets balanced and then fed to 6 groups. The remaining group of rats fed with a commercial rat diet served as blank control. Some isolated parameters indicated statistically significant differences in body weight, feed consumption/utilization, hematology, serum biochemistry, and relative organ weights. These differences were not consistent across gender or test-diet dose, which were attributed to incidental and biological variability. In conclusion, the results demonstrated that the transgenic soybean MON87708 containing DMO was as safe as non-transgenic isogenic counterpart with historical safe use. PMID:26850684

  15. 76 FR 10299 - Endangered and Threatened Wildlife and Plants: 90-Day Finding on a Petition To List the Wild...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-24

    ... completed a 90-day finding on August 15, 2007 (72 FR 45717). Based upon the information available at that... FR 54707), for the Arctic grayling (Thymallus arcticus) and a 12-month finding published on September 22, 2010, for the plant Agave eggersiana (75 FR 57720), we have focused on wild populations in...

  16. 77 FR 59582 - Endangered and Threatened Wildlife; 90-Day Finding on Petitions To List the Northeastern Pacific...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-28

    ...We, NMFS, announce a 90-day finding on two petitions received to list the northeastern Pacific Ocean population of great white shark (Carcharodon carcharias) as a threatened or endangered distinct population segment (DPS) under the Endangered Species Act (ESA) and to designate critical habitat concurrently with the listing. We find that the petitions and information in our files present......

  17. 78 FR 69376 - Endangered and Threatened Wildlife; 90-Day Finding on a Petition To List 19 Species and 3...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-19

    ...We (NMFS) announce a 90-day finding on a petition to list 19 species and 3 subpopulations of sharks as threatened or endangered under the Endangered Species Act (ESA). We find that the petition presents substantial scientific or commercial information indicating that the petitioned action may be warranted for 9 species: Centrophorus harrissoni, Isogomphodon oxyrhynchus, Mustelus fasciatus,......

  18. 75 FR 18782 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List Thorne's...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-13

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF THE INTERIOR Fish and Wildlife Service 50 CFR Part 17 Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List Thorne's Hairstreak Butterfly as Endangered Correction In Federal...

  19. 78 FR 23533 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To Delist the Wood Bison

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-19

    ... February 8, 2011 (76 FR ] 6734). Please refer to that document for the complete listing history. Here we... Wildlife, which was published in the Federal Register on June 2, 1970 (35 FR 8491). In 1974, the first list... of Wild Fauna and Flora (CITES). In a 90-day finding published on November 25, 1998 (63 FR 65164),...

  20. 77 FR 47583 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List Desert...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-09

    ...We, the U.S. Fish and Wildlife Service (Service), announce a 90-day finding on a petition to list desert massasauga (Sistrurus catenatus edwardsii), a rattlesnake found in the southwestern United States, as endangered or threatened under the Endangered Species Act of 1973, as amended (Act), and to designate critical habitat. Based on our review, we find that the petition presents substantial......

  1. 77 FR 55458 - Endangered and Threatened Species; 90-Day Finding on Petition To Delist the Southern Oregon...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-10

    ... these petitions was published on October 7, 2011 (76 FR 62375) and a second negative 90-day finding for the fourth petition was published on January 11, 2012 (77 FR 1668). The new petition largely..., changes in salmon landings over the past 1-2 decades, and increases in Pacific Ocean water temperature....

  2. 75 FR 42059 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the Giant...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-20

    ... that listing the GPE may be warranted (72 FR 57273). On January 24, 2008, the petitioners filed a... presented a threat (72 FR 57273). The 2009 petition includes a letter of support from Samuel W. James... educational purposes as a potential threat to the GPE. In our October 9, 2007, 90-day finding (72 FR 57273)...

  3. 77 FR 1900 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the Humboldt...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-12

    ...We, the U.S. Fish and Wildlife Service (Service), announce a 90-day finding on a petition to list the Humboldt marten (Martes americana humboldtensis) as endangered or threatened and designate critical habitat under the Endangered Species Act of 1973, as amended (Act). Based on our review, we find that the petition presents substantial scientific or commercial information indicating that......

  4. 78 FR 66675 - Endangered and Threatened Wildlife; 90-Day Finding on a Petition To List Multiple Species of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-06

    ... purposes of listing, delisting, and reclassifying a species under the ESA (``DPS Policy''; 61 FR 4722; February 7, 1996). A species, subspecies, or DPS is ``endangered'' if it is in danger of extinction... extinction risk of concern for the species at issue. To make a 90-day finding on a petition to list a...

  5. 78 FR 57611 - Endangered and Threatened Wildlife; 90-Day Finding on a Petition To List Alabama Shad as...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-19

    ... In 1997, we added Alabama shad to our Candidate Species List (62 FR 37562; July 14, 1997). At that... (49 FR 38900; October 1, 1984). In 2004, we created the Species of Concern list (69 FR 19975; April 15... published a negative 90-day finding in the Federal Register (76 FR 9320) stating that the petition did...

  6. 78 FR 29098 - Endangered and Threatened Wildlife; 90-Day Finding on a Petition To List Iliamna Lake Seals as a...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-17

    ... Vertebrate Population Segments under the ESA (DPS Policy, 61 FR 4722; February 7, 1996). This policy... species under the ESA (61 FR 4722; February 7, 1996). The policy established two criteria that must be met... Threatened Wildlife; 90-Day Finding on a Petition To List Iliamna Lake Seals as a Threatened or...

  7. 75 FR 67341 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the Bay...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-02

    ... on a Petition To List the Bay Springs Salamander as Endangered AGENCY: Fish and Wildlife Service..., announce a 90-day finding on a petition to list the Bay Springs salamander (Plethodon ainsworthi) as... Springs salamander or its habitat at any time. DATES: The finding announced in this document was made...

  8. 77 FR 21920 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the Eastern...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-12

    ... a notice of a 90-day finding for the petition in the Federal Register on July 22, 1994 (59 FR 37439... warranted but precluded by other higher priority actions (60 FR 15281). At that time, a listing priority..., 2005 (70 FR 24870). On October 7, 2002, as part of an agreement regarding multiple species, the...

  9. 75 FR 13068 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition to List the Berry...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-18

    ...We, the U.S. Fish and Wildlife Service, announce a 90-day finding on a petition to list the Berry Cave salamander (Gyrinophilus gulolineatus) as endangered under the Endangered Species Act of 1973, as amended. Based on our review, we find that the petition presents substantial scientific or commercial information indicating that listing this species may be warranted. Therefore, with the......

  10. 77 FR 71757 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List Phoenix...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-04

    ...We, the U.S. Fish and Wildlife Service (Service), announce a 90-day finding on a petition to list Phoenix dactylifera `Sphinx' (sphinx date palm) as endangered or threatened under the Endangered Species Act of 1973, as amended (Act). We find that the petition does not present substantial scientific or commercial information indicating that the petitioned action may be warranted. We find that......

  11. 75 FR 51969 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition to List the Oklahoma...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-24

    ...We, the U.S. Fish and Wildlife Service (Service), announce a 90-day finding on a petition to list Calopogon oklahomensis (Oklahoma grass pink orchid) as endangered or threatened under the Endangered Species Act of 1973, as amended (Act). Based on our review, we find that the petition presents substantial scientific or commercial information indicating that listing the plant species, C.......

  12. 75 FR 13720 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition to List the Striped...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-23

    ...We, the U.S. Fish and Wildlife Service (Service), announce a 90-day finding on a petition to list the striped newt (Notophthalmus perstriatus) as threatened under the Endangered Species Act of 1973, as amended (Act). We find that the petition presents substantial scientific or commercial information indicating that listing the striped newt may be warranted. Therefore, with the publication of......

  13. 77 FR 4973 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition to List the San...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-01

    ...We, the U.S. Fish and Wildlife Service (Service), announce a 90-day finding on a petition to list the San Bernardino flying squirrel (Glaucomys sabrinus californicus) as endangered or threatened and to designate critical habitat under the Endangered Species Act of 1973, as amended (Act). Based on our review, we find that the petition presents substantial scientific or commercial information......

  14. 77 FR 27403 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the Eastern...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-10

    ...We, the U.S. Fish and Wildlife Service (Service), announce a 90-day finding on a petition to list the eastern diamondback rattlesnake (Crotalus adamanteus) as threatened under the Endangered Species Act of 1973, as amended (Act) and to designate critical habitat. Based on our review, we find that the petition presents substantial scientific or commercial information indicating that listing the......

  15. 76 FR 60431 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the American...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-29

    ..., 2005, the Service issued a 90-day finding (70 FR 38849), which found that the petition presented... threatened or ] endangered was not warranted (72 FR 4967). Species Information This section is a summary of the species information presented in the Service's 2007 12-month finding (72 FR 4967),...

  16. Subchronic immunotoxicity and screening of reproductive toxicity and developmental immunotoxicity following single instillation of HIPCO-single-walled carbon nanotubes: purity-based comparison.

    PubMed

    Park, Eun-Jung; Choi, Je; Kim, Jae-Ho; Lee, Byoung-Seok; Yoon, Cheolho; Jeong, Uiseok; Kim, Younghun

    2016-10-01

    Impurity has been suggested as an important factor determining toxicity following exposure to single-walled carbon nanotubes (SWCNTs). In this study, we first compared immunotoxicity based on iron content on day 90 after a single intratracheal instillation of SWCNTs in male and female mice. The inflammatory responses were generally stronger in mice exposed to acid-purified (P)-SWCNTs compared to raw (R)-SWCNTs. In addition, both R- and P-SWCNTs induced Th1-polarized immune responses with apoptotic death of BAL cells and systemically impaired the function of antigen-presenting cells (APC). We also screened reproductive and developmental toxicity by cohabitating male and female mice on day 14 after instillation. Interestingly, the pregnancy rate rapidly decreased following exposure to both types of SWCNTs, especially R-SWCNTs. In addition, we investigated developmental immunotoxicity of the offspring on day 28 after exposure to both types of SWCNTs. Their hematological changes were clearer relative to those of the parents and a significant decrease in the alkaline phosphatase and potassium levels was observed in mice of both sexes exposed to the higher dose of R- and P-SWCNTs. In conclusion, we suggest that SWCNTs may induce Th1-polarized immune responses accompanied by suppression of APC function on day 90 after a single instillation without significant iron content dependance. In addition, the consecutive exposure of SWCNTs to the subsequent generation may exacerbate metabolic and hematological disturbance. Furthermore, our results underscore the need to clarify the reproductive and developmental health effects of SWCNTs. PMID:27310831

  17. Toxic effects of sub-chronic exposure of male albino rats to emamectin benzoate and possible ameliorative role of Foeniculum vulgare essential oil.

    PubMed

    El-Sheikh, El-Sayed A; Galal, Azza A A

    2015-05-01

    Emamectin benzoate (EB) is an avermectin insecticide used extensively in pest control on vegetable and field crops. Few studies have been done for evaluating adverse effects of EB. In the current study, we evaluated the toxic effects of EB on male rats and the possible ameliorative role of fennel essential oil (FEO). Thirty two male rats were randomly divided into 4 equal groups. All groups were treated orally with distilled water (control group), 0.5mlFEOkg(-1) BW (FEO group), 2.5mgEBkg(-1) BW (EB group), and 0.5mlFEOkg(-1) BW+2.5mgEBkg(-1) BW (FEO+EB group) for 28 days. The obtained results showed that EB treatment resulted in a significant decrease in body weight, body weight gain, RBC count, Hb concentration, % PCV, MCV and MCHC. Moreover, EB significantly decreased total leukocyte, lymphocyte, monocyte and platelet count but significantly increased granulocyte count. EB markedly decreased total protein, albumin, globulin, IgG and IgM concentrations with a significant increase in TNF-α secretion. EB had a negative impact on the liver as it significantly increased ALT, ALP, and MDA, while decreasing SOD activity. Regarding to the histopathological examination, EB treatment induced coagulative necrosis and blood vessels congestion of the liver in treated rats. Furthermore, it resulted in depletion and necrosis of the white pulp of the spleen in treated rats. The co-administration of FEO with EB, however, improved the majority of parameters studied, suggesting that FEO is an important substance in decreasing toxic effects of EB. PMID:25935540

  18. Safety evaluation of AB-LIFE(®) (Lactobacillus plantarum CECT 7527, 7528 and 7529): Antibiotic resistance and 90-day repeated-dose study in rats.

    PubMed

    Mukerji, Pushkor; Roper, Jason M; Stahl, Buffy; Smith, Amy B; Burns, Frank; Rae, Jessica Caverly; Yeung, Nicolas; Lyra, Anna; Svärd, Laura; Saarinen, Markku T; Alhoniemi, Esa; Ibarra, Alvin; Ouwehand, Arthur C

    2016-06-01

    AB-LIFE(®) is a probiotic product consisting of equal parts of three strains of Lactobacillus plantarum (CECT 7527, 7528, and 7529) blended with inert excipients. Whole genome sequencing was performed on each of the three strains. Antibiotic resistance was evaluated by genomic mining for resistance genes, and assessment for transferability. No risk of transfer potential was identified for any antibiotic resistance genes in the three strains. AB-LIFE(®) was evaluated for potential subchronic oral toxicity in rats, with dosages of 300 and 1000 mg/kg BW/day (equivalent to 5.55 × 10(10) and 1.85 × 10(11) CFU/kg BW/day). Survival of the three test strains through the gastrointestinal tract was supported by fecal analysis. No adverse effects were identified with respect to in-life parameters, clinical or anatomic pathology, translocation, or fecal chemical analyses. The no-observed-adverse-effect level (NOAEL) for AB-LIFE(®) in male and female rats was 1000 mg/kg BW/day (1.85 × 10(11) CFU of AB-LIFE(®)/kg BW/day), the highest dose level evaluated. These results, in conjunction with a previous acute toxicity study in rats, support the conclusion that AB-LIFE(®) is safe for human consumption. PMID:27016492

  19. Visual-motor response of crewmen during a simulated 90-day space mission as measured by the critical task battery

    NASA Technical Reports Server (NTRS)

    Allen, R. W.; Jex, H. R.

    1973-01-01

    In order to test various components of a regenerative life support system and to obtain data on the physiological and psychological effects of long duration exposure to confinement in a space station atmosphere, four carefully screened young men were sealed in a space station simulator for 90 days and administered a tracking test battery. The battery included a clinical test (Critical Instability Task) designed to measure a subject's dynamic time delay, and a more conventional steady tracking task, during which dynamic response (describing functions) and performance measures were obtained. Good correlation was noted between the clinical critical instability scores and more detailed tracking parameters such as dynamic time delay and gain-crossover frequency. The levels of each parameter span the range observed with professional pilots and astronaut candidates tested previously. The chamber environment caused no significant decrement on the average crewman's dynamic response behavior, and the subjects continued to improve slightly in their tracking skills during the 90-day confinement period.

  20. Subchronic organophosphorus ester-induced delayed neurotoxicity in mallards

    USGS Publications Warehouse

    Hoffman, D.J.; Sileo, L.; Murray, H.C.

    1984-01-01

    Eighteen-week-old mallard hens received 0, 10, 30, 90, or 270 ppm technical grade EPN (phenylphosphonothioic acid O-ethyl-O-4-nitrophenyl ester) in the diet for 90 days. Ataxia was first observed in the 270-ppm group after 16 days, in the 90-ppm group after 20 days, in the 30-ppm group after 38 days; 10 ppm failed to produce ataxia. By the end of 90 days all 6 birds in the 270-ppm group exhibited ataxia or paralysis whereas 5 of 6 birds in the 90-ppm group and 2 of 6 birds in the 30-ppm group were visibly affected. Treatment with 30 ppm or more resulted in a significant reduction in body weight. Brain neurotoxic esterase activity was inhibited by averages of 16, 69, 73, and 74% in the 10-, 30-, 90-, and 270-ppm groups, respectively. Brain acetylcholinesterase, plasma cholinesterase, and plasma alkaline phosphatase were significantly inhibited as well. Distinct histopathological effects were seen in the 30-, 90-, and 270-ppm groups which included demyelination and degeneration of axons of the spinal cord. Additional ducks were exposed in a similar manner to 60-, 270-, or 540-ppm leptophos (phosphonothioic acid O-4-bromo-2,5-dichlorophenyl-O-methylphenyl ester) which resulted in similar behavioral, biochemical, and histopathological alterations. These findings indicate that adult mallards are probably somewhat less sensitive than chickens to subchronic dietary exposure to organophosphorus insecticides that induce delayed neurotoxicity.

  1. 76 FR 9309 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the Sand...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-17

    ...We, the U.S. Fish and Wildlife Service, announce a 90-day finding on a petition to list the sand verbena moth, Copablepharon fuscum, as endangered or threatened under the Endangered Species Act of 1973, as amended. Based on our review, we find the petition presents substantial information indicating that listing the sand verbena moth may be warranted. Therefore, with the publication of this......

  2. 76 FR 36049 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the Utah...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-21

    ...We, the U.S. Fish and Wildlife Service (Service), announce a 90-day finding on a petition to list the Utah population of the Gila monster (Heloderma suspectum) as an endangered or a threatened distinct population segment (DPS) under the Endangered Species Act of 1973, as amended (Act), and to designate critical habitat. Based on our review, we find that the petition does not present......

  3. 77 FR 39666 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List Maytenus cymosa

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-05

    ...We, the U.S. Fish and Wildlife Service (Service), announce a 90-day finding on a petition to list the Maytenus cymosa (Caribbean mayten), a tree, as endangered or threatened under the Endangered Species Act of 1973, as amended (Act), and to designate critical habitat. Based on our review, we find that the petition does not present substantial information indicating that listing M. cymosa may......

  4. Influences of northward propagating 25-90-day and quasi-biweekly oscillations on eastern China summer rainfall

    NASA Astrophysics Data System (ADS)

    Chen, Jiepeng; Wen, Zhiping; Wu, Renguang; Chen, Zesheng; Zhao, Ping

    2015-07-01

    The present study reveals that rainfall anomalies associated with the 25-90-day (quasi-biweekly) tropical convective activity propagates northward (northwestward) into northern China (the Yangtze River). Enhanced rainfall over southern China results directly from enhanced convection propagating northward from the South China Sea (SCS)-western north Pacific (WNP), strengthened northward water vapor transport and intensified upper-level divergence. The anomalous anticyclone over SCS-WNP, which is induced by local lower sea surface temperature, provides a favorable condition for transporting more moisture to southern China. Stronger subtropical westerly jet and South Asia high strengthen upper-level divergence. The northward propagating 25-90-day oscillation over eastern China reaches farther north than the quasi-biweekly oscillation (QBWO). The intensity of QBWO in summer rainfall has significantly strengthened over southern China after 1993 but not for the 25-90-day oscillation. This is mainly contributed by an interdecadal increase in rainfall over southern China and the Yangtze River Basin in the wet phases of QBWO. The interdecadal enhancement of rainfall associated with the QBWO is attributed to three factors. One is lower tropospheric convergence caused by anomalous anticyclone over the WNP and anomalous cyclone over Korean Peninsula and Japan. The second is upper tropospheric divergence resulting from strengthening of subtropical westerly jet and the South Asia high. The last is enhanced ascent over South China through meridional vertical circulation.

  5. Past, present and emerging toxicity issues for jet fuel

    SciTech Connect

    Mattie, David R.

    2011-07-15

    The US Air Force wrote the specification for the first official hydrocarbon-based jet fuel, JP-4, in 1951. This paper will briefly review the toxicity of the current fuel, JP-8, as compared to JP-4. JP-8 has been found to have low acute toxicity with the adverse effects being slight dermal irritation and weak dermal sensitization in animals. JP-4 also has low acute toxicity with slight dermal irritation as the adverse effect. Respiratory tract sensory irritation was greater in JP-8 than in JP-4. Recent data suggest exposure to jet fuel may contribute to hearing loss. Subchronic studies for 90 days with JP-8 and JP-4 showed little toxicity with the primary effect being male rat specific hydrocarbon nephropathy. A 1-year study was conducted for JP-4. The only tumors seen were associated with the male rat specific hydrocarbon nephropathy. A number of immunosuppressive effects have been seen after exposure to JP-8. Limited neurobehavioral effects have been associated with JP-8. JP-8 is not a developmental toxicant and has little reproductive toxicity. JP-4 has not been tested for immune, neurobehavioral or reproductive endpoints. JP-8 and JP-4 were negative in mutagenicity tests but JP-4 showed an increase in unscheduled DNA synthesis. Currently, JP-8 is being used as the standard for comparison of future fuels, including alternative fuels. Emerging issues of concern with jet fuels include naphthalene content, immunotoxicity and inhalation exposure characterization and modeling of complex mixtures such as jet fuels.

  6. Preclinical systemic toxicity evaluation of chitosan-solid lipid nanoparticle-encapsulated aspirin and curcumin in combination with free sulforaphane in BALB/c mice

    PubMed Central

    Thakkar, Arvind; Chenreddy, Sushma; Thio, Astrid; Khamas, Wael; Wang, Jeffrey; Prabhu, Sunil

    2016-01-01

    Our previous studies have established the efficacy of chemopreventive regimens of aspirin and curcumin (CUR) encapsulated within solid lipid nanoparticles (SLNs) in combination with free sulforaphane (ACS combination) to prevent or delay the initiation and progression of pancreatic cancer, classified as one of the deadliest diseases with very low chances of survival upon diagnosis. Although toxicity of individual drugs and SLN has been studied previously, there are no studies in current literature that evaluate the potential toxicity of a combined regimen of ACS, especially when encapsulated within chitosan-SLNs (c-SLNs). Hence, objective of the current study was to investigate the potential toxic effects of ACS c-SLN combined chemopreventive regimens following acute (3 days), subacute (28 days), and subchronic (90 days) administrations by oral gavage in BALB/c mice. Mice were administered the following regimens: saline, blank c-SLN, low-dose ACS c-SLN (2+4.5+0.16 mg/kg), medium-dose ACS c-SLN (20+45+1.6 mg/kg), and high-dose ACS c-SLN (60+135+4.8 mg/kg). The potential toxicity was evaluated based on animal survival, body weight, hematology, blood chemistry, and organ histopathology. During 3-day, 28-day, and 90-day study periods, no animal deaths were observed. Treatment with ACS c-SLNs did not cause alteration in complete blood counts and blood chemistry data. Histopathological examination of various organ sections (pancreas, heart, liver, kidney, and brain) appeared normal. Based on the results of this study, no signs of toxicity in acute, subacute, and subchronic studies following oral administration of ACS c-SLNs were found indicating that the oral dosing regimens were safe at the levels tested for long-term administration to prevent the onset of pancreatic cancer. PMID:27499621

  7. Preclinical systemic toxicity evaluation of chitosan-solid lipid nanoparticle-encapsulated aspirin and curcumin in combination with free sulforaphane in BALB/c mice.

    PubMed

    Thakkar, Arvind; Chenreddy, Sushma; Thio, Astrid; Khamas, Wael; Wang, Jeffrey; Prabhu, Sunil

    2016-01-01

    Our previous studies have established the efficacy of chemopreventive regimens of aspirin and curcumin (CUR) encapsulated within solid lipid nanoparticles (SLNs) in combination with free sulforaphane (ACS combination) to prevent or delay the initiation and progression of pancreatic cancer, classified as one of the deadliest diseases with very low chances of survival upon diagnosis. Although toxicity of individual drugs and SLN has been studied previously, there are no studies in current literature that evaluate the potential toxicity of a combined regimen of ACS, especially when encapsulated within chitosan-SLNs (c-SLNs). Hence, objective of the current study was to investigate the potential toxic effects of ACS c-SLN combined chemopreventive regimens following acute (3 days), subacute (28 days), and subchronic (90 days) administrations by oral gavage in BALB/c mice. Mice were administered the following regimens: saline, blank c-SLN, low-dose ACS c-SLN (2+4.5+0.16 mg/kg), medium-dose ACS c-SLN (20+45+1.6 mg/kg), and high-dose ACS c-SLN (60+135+4.8 mg/kg). The potential toxicity was evaluated based on animal survival, body weight, hematology, blood chemistry, and organ histopathology. During 3-day, 28-day, and 90-day study periods, no animal deaths were observed. Treatment with ACS c-SLNs did not cause alteration in complete blood counts and blood chemistry data. Histopathological examination of various organ sections (pancreas, heart, liver, kidney, and brain) appeared normal. Based on the results of this study, no signs of toxicity in acute, subacute, and subchronic studies following oral administration of ACS c-SLNs were found indicating that the oral dosing regimens were safe at the levels tested for long-term administration to prevent the onset of pancreatic cancer. PMID:27499621

  8. First Report of 90-Day Support of Two Calves with a Continuous-Flow Total Artificial Heart

    PubMed Central

    Karimov, Jamshid H.; Moazami, Nader; Kobayashi, Mariko; Sale, Shiva; Such, Kimberly; Byram, Nicole; Sunagawa, Gengo; Horvath, David; Gao, Shengqiang; Kuban, Barry; Golding, Leonard A.; Fukamachi, Kiyotaka

    2015-01-01

    Objective The Cleveland Clinic continuous-flow total artificial heart (CFTAH) is a compact, single-piece, valveless, pulsatile pump providing self-regulated hemodynamic output to left/right circulation. We evaluated chronic in vivo pump performance, physiologic and hemodynamic parameters, and biocompatibility of the CFTAH in a well-established calf model. Methods CFTAH pumps have been implanted in 17 calves total. Hemodynamics, pump performance, and device-related adverse events were evaluated during studies and at necropsy. Results In vivo experiments demonstrated good hemodynamic performance (pump flow, 7.3 ± 0.7 L/min; left atrial pressure [LAP], 16 ± 3 mm Hg; right atrial pressure [RAP], 17 ± 3 mm Hg; RAP-LAP difference, 1 ± 2 mm Hg; mean arterial pressure, 103 ± 7 mm Hg; arterial pulse pressure, 30 ± 11 mm Hg; pulmonary arterial pressure, 34 ± 5 mm Hg). The CFTAH has operated within design specifications and never failed. With ever-improving pump design, the implants have shown no chronic hemolysis. Three recent animals with the CFTAH recovered well, with no postoperative anticoagulation, during planned in vivo durations of 30, 90, and 90 days (last two were intended to be 90-day studies). All these longest-surviving cases showed good biocompatibility, with no thromboembolism in organs. Conclusions The current CFTAH has demonstrated reliable self-regulation of hemodynamic output and acceptable biocompatibility without anticoagulation throughout 90 days of chronic implantation in calves. Meeting these milestones is in accord with our strategy to achieve transfer of this unique technology to surgical practice, thus filling the urgent need for cardiac replacement devices as destination therapy. PMID:26173607

  9. Toxicological assessment of a prototype e-cigaret device and three flavor formulations: a 90-day inhalation study in rats

    PubMed Central

    Werley, Michael S.; Kirkpatrick, Dan J.; Oldham, Michael J.; Jerome, Ann M.; Langston, Timothy B.; Lilly, Patrick D.; Smith, Donna C.; Mckinney, Willie J.

    2016-01-01

    Abstract A prototype electronic cigaret device and three formulations were evaluated in a 90-day rat inhalation study followed by a 42-day recovery period. Animals were randomly assigned to groups for exposure to low-, mid- and high-dose levels of aerosols composed of vehicle (glycerin and propylene glycol mixture); vehicle and 2.0% nicotine; or vehicle, 2.0% nicotine and flavor mixture. Daily targeted aerosol total particulate matter (TPM) doses of 3.2, 9.6 and 32.0 mg/kg/day were achieved by exposure to 1 mg/L aerosol for 16, 48 and 160 min, respectively. Pre-study evaluations included indirect ophthalmoscopy, virology and bacteriological screening. Body weights, clinical observations and food consumption were monitored weekly. Plasma nicotine and cotinine and carboxyhemoglobin levels were measured at days 28 and 90. After days 28, 56 and 90, lung function measurements were obtained. Biological endpoints after 90-day exposure and 42-day recovery period included clinical pathology, urinalysis, bronchoalveolar fluid (BALF) analysis, necropsy and histopathology. Treatment-related effects following 90 days of exposure included changes in body weight, food consumption and respiratory rate. Dose-related decreases in thymus and spleen weights, and increased BALF lactate dehydrogenase, total protein, alveolar macrophages, neutrophils and lung weights were observed. Histopathology evaluations revealed sporadic increases in nasal section 1–4 epithelial hyperplasia and vacuolization. Following the recovery period, effects in the nose and BALF were persistent while other effects were resolved. The no observed effect level based upon body weight decreases is considered to be the mid-dose level for each formulation, equivalent to a daily TPM exposure dose of approximately 9.6 mg/kg/day. PMID:26787428

  10. Toxicological assessment of a prototype e-cigaret device and three flavor formulations: a 90-day inhalation study in rats.

    PubMed

    Werley, Michael S; Kirkpatrick, Dan J; Oldham, Michael J; Jerome, Ann M; Langston, Timothy B; Lilly, Patrick D; Smith, Donna C; Mckinney, Willie J

    2016-01-01

    A prototype electronic cigaret device and three formulations were evaluated in a 90-day rat inhalation study followed by a 42-day recovery period. Animals were randomly assigned to groups for exposure to low-, mid- and high-dose levels of aerosols composed of vehicle (glycerin and propylene glycol mixture); vehicle and 2.0% nicotine; or vehicle, 2.0% nicotine and flavor mixture. Daily targeted aerosol total particulate matter (TPM) doses of 3.2, 9.6 and 32.0 mg/kg/day were achieved by exposure to 1 mg/L aerosol for 16, 48 and 160 min, respectively. Pre-study evaluations included indirect ophthalmoscopy, virology and bacteriological screening. Body weights, clinical observations and food consumption were monitored weekly. Plasma nicotine and cotinine and carboxyhemoglobin levels were measured at days 28 and 90. After days 28, 56 and 90, lung function measurements were obtained. Biological endpoints after 90-day exposure and 42-day recovery period included clinical pathology, urinalysis, bronchoalveolar fluid (BALF) analysis, necropsy and histopathology. Treatment-related effects following 90 days of exposure included changes in body weight, food consumption and respiratory rate. Dose-related decreases in thymus and spleen weights, and increased BALF lactate dehydrogenase, total protein, alveolar macrophages, neutrophils and lung weights were observed. Histopathology evaluations revealed sporadic increases in nasal section 1-4 epithelial hyperplasia and vacuolization. Following the recovery period, effects in the nose and BALF were persistent while other effects were resolved. The no observed effect level based upon body weight decreases is considered to be the mid-dose level for each formulation, equivalent to a daily TPM exposure dose of approximately 9.6 mg/kg/day. PMID:26787428

  11. The development and succession of microbial communities in 90-day Bioregenerative Life Support Experiment in the Lunar Palace 1

    NASA Astrophysics Data System (ADS)

    Sun, Yi; Liu, Hong; Fu, Yuming; Liu, Bojie; Su, Qiang; Xie, Beizhen; Qin, Youcai; Dong, Chen; Liu, Guanghui

    Lunar Palace 1, as an integrative experiment facility for permanent astrobase life-support artificial closed ecosystem, is an artificial ecosystem which consists of plant cultivation, animal breeding and waste treatment units. It has been used to carry out a 90-day bioregenerative life support experiment with three crew members. Apparently, it’s hard to prevent the growth of microorganisms in such closed ecosystem for their strong adaptive capacity. Original microorganisms in the cabin, microbes in the course of loads delivery and the autologous microorganism by crew members and animals themselves are all the main source of the interior microorganisms, which may grow and regenerate in air, water and plants. Therefore, if these microorganisms could not be effectively monitored and controlled, it may cause microbial contamination and even lead to the unsteadiness of the whole closed ecosystem. In this study, the development and succession of the microbial communities of air, water system, plant system, and key facilities surfaces in Lunar Palace 1 were continuously monitored and analyzed by using plate counting method and molecular biological method during the 90-day experiment. The results were quite useful for the controlling of internal microorganisms and the safe operation of the whole system, and could also reveal the succession rules of microorganisms in an artificial closed ecosystem.

  12. Training and certification program of the operating staff for a 90-day test of a regenerative life support system

    NASA Technical Reports Server (NTRS)

    1972-01-01

    Prior to beginning a 90-day test of a regenerative life support system, a need was identified for a training and certification program to qualify an operating staff for conducting the test. The staff was responsible for operating and maintaining the test facility, monitoring and ensuring crew safety, and implementing procedures to ensure effective mission performance with good data collection and analysis. The training program was designed to ensure that each operating staff member was capable of performing his assigned function and was sufficiently cross-trained to serve at certain other positions on a contingency basis. Complicating the training program were budget and schedule limitations, and the high level of sophistication of test systems.

  13. APPLYING EXPERIENCE SAMPLING METHODS TO PARTNER VIOLENCE RESEARCH: SAFETY AND FEASIBILITY IN A 90-DAY STUDY OF COMMUNITY WOMEN

    PubMed Central

    Sullivan, Tami P.; Khondkaryan, Enna; Dos Santos, Nancy P.; Peters, Erica N.

    2011-01-01

    An experience sampling method (ESM) rarely has been applied in studies of intimate partner violence (IPV) despite the benefits to be gained. Because ESM approaches and women who experience IPV present unique challenges for data collection an empirical question exists: is it safe and feasible to apply ESM to community women who currently are experiencing IPV? A 90-day, design-driven feasibility study examined daily telephone data collection, daily paper diaries, and monthly retrospective semi-structured interview methods among a community sample of 123 women currently experiencing IPV to study within-person relationships between IPV and substance use. Findings suggest that ESM is a promising method for collecting data among this population and can elucidate daily dynamics of victimization as well as associated behaviors and experiences. Lessons learned from the application of ESM to this population are also discussed. PMID:21307033

  14. Dietary and Food Processing for a 90-day Bioregenerative Life Support Experiment in the Lunar Palace 1

    NASA Astrophysics Data System (ADS)

    Zhao, Zhiruo; Fu, Yuming; Dong, Chen; Liu, Guanghui

    A 4-day cycle dietary menu was developed to meet the requirements of balanced diet of the crew within the 90-day closed experiment of bioregenerative life support in the Lunar Palace 1. The menu consisted of items prepared from crops and insect grown inside the system, as well as prestored food. Dairy recipe was composed of breads, vegetables, meats and soups, which provided about 2900 kcal per crew member per day. During food processing, to maximize nutrient recovery and minimize waste production, the whole wheat grains and chufa nuts were milled. Further, the carrot leaves and yellow mealworms were used as salad materials and bread ingredients, respectively. The sensory acceptability of the dishes in the menu was evaluated by flavor, texture, and appearance. Our results show that all dishes in the 4-day cycle menu were highly acceptable, which satisfies nutritional requirement of the crew members in the closed habitation.

  15. Toxicologic evaluations of DHA-rich algal oil in rats: developmental toxicity study and 3-month dietary toxicity study with an in utero exposure phase.

    PubMed

    Schmitt, D; Tran, N; Peach, J; Edwards, T; Greeley, M

    2012-11-01

    DHA-rich algal oil ONC-T18, tested for subchronic, reproductive, and developmental toxicity in the rat, did not produce any significant toxicologic manifestations. Based on the absence of maternal or developmental toxicity at any dosage level, a dosage level of 2000 mg/kg/day was considered to be the no observed adverse-effect level (NOAEL) for maternal toxicity and embryo/fetal development when DHA-rich algal oil was administered orally by gavage to pregnant Crl:CD(SD) rats during gestation days 6-19. In a dietary combined one-generation/90-day reproductive toxicity study in rats, the NOAEL for F0 male and female and F1 male systemic toxicity was considered to be 50,000 ppm (highest concentration administered) and 25,000 ppm for F1 female systemic toxicity (higher mean body weight, body weight gain, and food consumption). F0 reproductive performance values, estrous cycle length, gestation length, or the process of parturition, and the numbers of former implantation sites and unaccounted-for sites were unaffected by algal oil exposure. Postnatal survival and developmental parameters in the F1 generation were unaffected by algal oil exposure at all dietary concentrations. There were no neurotoxic effects noted at any algal oil exposure level. The results support the safety of DHA-rich algal oil for its proposed use in food. PMID:22960629

  16. [Ophthalmoscopic observations of ocular fundus in colony-born cynomolgus monkeys aged from 0 day to 90 days].

    PubMed

    Suzuki, M T; Narita, H; Tanaka, Y; Cho, F; Fukui, M

    1984-04-01

    Apparently healthy 242 colony-born cynomolgus monkeys (Macaca fascicularis) aged from 0 day to 90 days were examined for the findings of ocular fundus by using ophthalmoscope. One drop of mixed solution of 0.5% tropicamide and 0.5% phenylephrine hydrochloride was instilled into each eye of the monkey. Then, those monkeys were anesthetized with ketamine-HC1 at the dose level of 10mg/kg B. W. Regular and fluorescein photographs were taken with Kowa RC-II ophthalmoscope-camera by using daylight typed color film. Following findings were obtained in each age class: Retinal color was salmon pink with 0 to 3-days-old neonates, salmon pink and blue to green with 7 days to 14-days-old animals and blue to green with 60-days to 90-days-old monkeys. As regards optic disc, 0- to 14-days-old animals were observed to be light orange in color, and the infant aged more than 28-days showed orange color. Retinal arteries and veins were lightly reddish in color with every age class. Macular color was salmon pink in 0-day-old cases, slightly dark in 3-days-old neonates and very dark after 14-days of age. Lightly retinal reflex was noted in 0- and 7-days-old animals. The reflex was observable in 14-days-old animals without any case of exception. Retinal hemorrhages were recorded in 22 (67%) of 36 neonates born in natural condition and 10 (33%) of 30 neonates born by cesarean section. These findings will be useful as the criteria for ophthalmoscopic observations of the cynomolgus monkeys as laboratory use. PMID:6468512

  17. A 90-Day Toxicology Study of Meat from Genetically Modified Sheep Overexpressing TLR4 in Sprague-Dawley Rats

    PubMed Central

    Hu, Rui; Kan, Tongtong; Li, Yan; Zhang, Xiaosheng; Zhang, Jinlong; Lian, Ling; Han, Hongbing; Lian, Zhengxing

    2015-01-01

    Genetic modification offers alternative strategies to traditional animal breeding. However, the food safety of genetically modified (GM) animals has attracted increasing levels of concern. In this study, we produced GM sheep overexpressing TLR4, and the transgene-positive offsprings (F1) were confirmed using the polymerase chain reaction (PCR) and Southern blot. The expression of TLR4 was 2.5-fold compared with that of the wild-type (WT) sheep samples. During the 90-day safety study, Sprague-Dawley rats were fed with three different dietary concentrations (3.75%, 7.5%, and 15% wt/wt) of GM sheep meat, WT sheep meat or a commercial diet (CD). Blood samples from the rats were collected and analyzed for hematological and biochemical parameters, and then compared with hematological and biochemical reference ranges. Despite a few significant differences among the three groups in some parameters, all other values remained within the normal reference intervals and thus were not considered to be affected by the treatment. No adverse diet-related differences in body weights or relative organ weights were observed. Furthermore, no differences were observed in the gross necropsy findings or microscopic pathology of the rats whose diets contained the GM sheep meat compared with rats whose diets contained the WT sheep meat. Therefore, the present 90-day rat feeding study suggested that the meat of GM sheep overexpressing TLR4 had no adverse effect on Sprague-Dawley rats in comparison with WT sheep meat. These results provide valuable information regarding the safety assessment of meat derived from GM animals. PMID:25874566

  18. Distribution, elimination, and biopersistence to 90 days of a systemically introduced 30 nm ceria-engineered nanomaterial in rats.

    PubMed

    Yokel, Robert A; Au, Tu C; MacPhail, Robert; Hardas, Sarita S; Butterfield, D Allan; Sultana, Rukhsana; Goodman, Michael; Tseng, Michael T; Dan, Mo; Haghnazar, Hamed; Unrine, Jason M; Graham, Uschi M; Wu, Peng; Grulke, Eric A

    2012-05-01

    Nanoceria is used as a catalyst in diesel fuel, as an abrasive in printed circuit manufacture, and is being pursued as an antioxidant therapeutic. Our objective is to extend previous findings showing that there were no reductions of cerium in organs of the mononuclear phagocyte (reticuloendothelial) system up to 30 days after a single nanoscale ceria administration. An ~5% aqueous dispersion of citrate-stabilized 30 nm ceria, synthesized and characterized in-house, or vehicle, was iv infused into rats terminated 1, 7, 30, or 90 days later. Cageside observations were obtained daily, body weight weekly. Daily urinary and fecal cerium outputs were quantified for 2 weeks. Nine organs were weighed and samples collected from 14 tissues/organs/systems, blood and cerebrospinal fluid for cerium determination. Histology and oxidative stress were assessed. Less than 1% of the nanoceria was excreted in the first 2 weeks, 98% in feces. Body weight gain was initially impaired. Spleen weight was significantly increased in some ceria-treated groups, associated with abnormalities. Ceria was primarily retained in the spleen, liver, and bone marrow. There was little decrease of ceria in any tissue over the 90 days. Granulomas were observed in the liver. Time-dependent oxidative stress changes were seen in the liver and spleen. Nanoscale ceria was persistently retained by organs of the mononuclear phagocyte system, associated with adverse changes. The results support concern about the long-term fate and adverse effects of inert nanoscale metal oxides that distribute throughout the body, are persistently retained, and produce adverse changes. PMID:22367688

  19. EFFECTS OF SUBCHRONIC EXPOSURE TO CONCENTRATED AMBIENT PARTICULATES IN SPONTANEOUSLY HYPERTENSIVE RATS

    EPA Science Inventory


    EFFECTS OF SUBCHRONIC EXPOSURE TO CONCENTRATED AMBIENT PARTICULATES IN SPONTANEOUSLY HYPERTENSIVE RATS. WP Watkinson1, LB Wichers2, JP Nolan1, DW Winsett1, UP Kodavanti1, MCJ Schladweiler1, and DL Costa1 1US EPA, ORD/NHEERL/ETD/PTB, RTP, NC; 2UNC SPH and Curriculum in Toxic...

  20. In vivo genotoxicity evaluation of lung cells from Fischer 344 rats following 28 days of inhalation exposure to MWCNTs, plus 28 days and 90 days post-exposure.

    PubMed

    Kim, Jin Sik; Sung, Jae Hyuck; Choi, Byung Gil; Ryu, Hyeon Yeol; Song, Kyung Seuk; Shin, Jae Hoon; Lee, Jong Seong; Hwang, Joo Hwan; Lee, Ji Hyun; Lee, Gun Ho; Jeon, Kisoo; Ahn, Kang Ho; Yu, Il Je

    2014-03-01

    Despite their useful physico-chemical properties, carbon nanotubes (CNTs) continue to cause concern over occupational and human health due to their structural similarity to asbestos. Thus, to evaluate the toxic and genotoxic effect of multi-wall carbon nanotubes (MWCNTs) on lung cells in vivo, eight-week-old rats were divided into four groups (each group = 25 animals), a fresh air control (0 mg/m(3)), low (0.17 mg/m(3)), middle (0.49 mg/m(3)), and high (0.96 mg/m(3)) dose group, and exposed to MWCNTs via nose-only inhalation 6 h per day, 5 days per week for 28 days. The count median length and geometric standard deviation for the MWCNTs determined by TEM were 330.18 and 1.72 nm, respectively, and the MWCNT diameters ranged from 10 to 15 nm. Lung cells were isolated from five male and five female rats in each group on day 0, day 28 (only from males) and day 90 following the 28-day exposure. The total number of animals used was 15 male and 10 female rats for each concentration group. To determine the genotoxicity of the MWCNTs, a single cell gel electrophoresis assay (Comet assay) was conducted on the rat lung cells. As a result of the exposure, the olive tail moments were found to be significantly higher (p < 0.05) in the male and female rats from all the exposed groups when compared with the fresh air control. In addition, the high-dose exposed male and middle and high-dose exposed female rats retained DNA damage, even 90 days post-exposure (p < 0.05). To investigate the mode of genotoxicity, the intracellular reactive oxygen species (ROS) levels and inflammatory cytokine levels (TNF-α, TGF- β, IL-1, IL-2, IL-4, IL-5, IL-10, IL-12 and IFN-γ) were also measured. For the male rats, the H2O2 levels were significantly higher in the middle (0 days post-exposure) and high- (0 days and 28 days post-exposure) dose groups (p < 0.05). Conversely, the female rats showed no changes in the H2O2 levels. The inflammatory cytokine levels in the

  1. Effect of acute/subchronic samarium exposure on the concentration, motility, and morphology of sperm in male mice.

    PubMed

    Zhang, D Y; Shen, X Y; Xu, X L; Ruan, Q; Hu, S S; Chen, Y Y; Wang, Z M

    2016-01-01

    Male ICR mice were orally administered samarium nitrate [Sm(NO3)3] to investigate its effects on sperm concentration and sperm quality. After acute exposure to ≥2880.00 mg/kg Sm(NO3)3 via intragastric gavage, sperm motility and acrosome integrity were decreased, and the sperm malformation percentage was increased (P < 0.05). After subchronic exposure to ≥500.00 mg/L Sm(NO3)3 administered via drinking water for 90 days, relative gonad weight, sperm concentration, and sperm quality significantly decreased (P < 0.05). Sperm malformation also increased after subchronic exposure to Sm, which was found to be the most sensitive index. Sperm head malformation accounted for the largest proportion of all types of sperm malformations evaluated. Of the six different subtypes of head malformation, irregular shape accounted for the largest proportion. PMID:27420955

  2. Subchronic toxicity studies on 1,3,5-trinitrobenzene, 1,3-dinitrobenzene, and tetryl in rats. 14-day toxicity evaluation of n-methyl-n, 2,4,6-tetranitroaniline in Fischer 344 rats. Final report

    SciTech Connect

    Reddy, T.V.

    1994-05-01

    Subacute toxic effects of Tetryl in male and female rats were evaluated by feeding powdered certified laboratory chow diet supplemented with varied concentrations of Tetryl (0, 500, 1250, 2000, 2500 and 5000 mg/kg diet) for fourteen days. The average daily Tetryl doses consumed were 32, 82, 130, 178 and 374 for females and 31, 80, 121, 170 and 350 for males. Food and water consumption were not significantly altered. Final body weight was reduced in only the high dose males while relative organ weights were significantly changed in this same dose group involving the liver (females), kidneys (males), and spleen (males). Hematology and clinical chemistry studies indicated increased values relating to reticulocytes (females) and methemoglobin (females and males) in high and mid dose groups while total protein and albumin were significantly increased in all groups except the 50 mg/kg female group. Alkaline phosphatase was decreased in these same female groups. The only histopathological change noted which was considered meaningful was a mild increase in hyaline droplet deposition in male kidneys in all dose groups.

  3. Fluid overload is associated with an increased risk for 90-day mortality in critically ill patients with renal replacement therapy: data from the prospective FINNAKI study

    PubMed Central

    2012-01-01

    Introduction Positive fluid balance has been associated with an increased risk for mortality in critically ill patients with acute kidney injury with or without renal replacement therapy (RRT). Data on fluid accumulation prior to RRT initiation and mortality are limited. We aimed to study the association between fluid accumulation at RRT initiation and 90-day mortality. Methods We conducted a prospective, multicenter, observational cohort study in 17 Finnish intensive care units (ICUs) during a five-month period. We collected data on patient characteristics, RRT timing, and parameters at RRT initiation. We studied the association of parameters at RRT initiation, including fluid overload (defined as cumulative fluid accumulation > 10% of baseline weight) with 90-day mortality. Results We included 296 RRT-treated critically ill patients. Of 283 patients with complete data on fluid balance, 76 (26.9%) patients had fluid overload. The median (interquartile range) time from ICU admission to RRT initiation was 14 (3.3 to 41.5) hours. The 90-day mortality rate of the whole cohort was 116 of 296 (39.2%; 95% confidence interval 38.6 to 39.8%). The crude 90-day mortality of patients with or without fluid overload was 45 of 76 (59.2%) vs. 65 of 207 (31.4%), P < 0.001. In logistic regression, fluid overload was associated with an increased risk for 90-day mortality (odds ratio 2.6) after adjusting for disease severity, time of RRT initiation, initial RRT modality, and sepsis. Of the 168 survivors with data on RRT use at 90 days, 34 (18.9%, 95% CI 13.2 to 24.6%) were still dependent on RRT. Conclusions Patients with fluid overload at RRT initiation had twice as high crude 90-day mortality compared to those without. Fluid overload was associated with increased risk for 90-day mortality even after adjustments. PMID:23075459

  4. An estimate of equatorial wave energy flux at 9- to 90-day periods in the Central Pacific

    NASA Technical Reports Server (NTRS)

    Eriksen, Charles C.; Richman, James G.

    1988-01-01

    Deep fluctuations in current along the equator in the Central Pacific are dominated by coherent structures which correspond closely to narrow-band propagating equatorial waves. Currents were measured roughly at 1500 and 3000 m depths at five moorings between 144 and 148 deg W from January 1981 to March 1983, as part of the Pacific Equatorial Ocean Dynamics program. In each frequency band resolved, a single complex empirical orthogonal function accounts for half to three quarters of the observed variance in either zonal or meridional current. Dispersion for equatorial first meridional Rossby and Rossby gravity waves is consistent with the observed vertical-zonal coherence structure. The observations indicate that energy flux is westward and downward in long first meridional mode Rossby waves at periods 45 days and longer, and eastward and downward in short first meridional mode Rossby waves and Rossby-gravity waves at periods 30 days and shorter. A local minimum in energy flux occurs at periods corresponding to a maximum in upper-ocean meridional current energy contributed by tropical instability waves. Total vertical flux across the 9- to 90-day period range is 2.5 kW/m.

  5. Two-hour methyl isocyanate inhalation and 90-day recovery study in B6C3F1 mice

    SciTech Connect

    Boorman, G.A.; Uraih, L.C.; Gupta, B.N.; Bucher, J.R.

    1987-06-01

    B6C3F1 mice were exposed by inhalation to 0, 3, 10, and 30 ppm methyl isocyanate for 2 hr followed by a 90-day recovery period. Sixteen of eight (20%) male mice in the 30 ppm group died following exposure. There were no other unscheduled deaths in the mice. Five mice/sex/group were examined at 2 hr or at 1, 3, 7, 14, 28, 49, or 91 days following exposure. Chemical-related changes were restricted to the respiratory system. At 30 ppm there were extensive necrosis and erosion of the respiratory and olfactory epithelium in the nasal cavity. Severe necrosis and epithelial erosion were also found in the trachea and main bronchi. Regeneration of the mucosal epithelium occurred rapidly in the nasal cavity and airways. In the turbinates, mild incomplete olfactory epithelial regeneration persisted to day 91 in the male mice. Intraluminal fibrotic projections covered by respiratory epithelium and bronchial fibrosis were found in the major airways of the 30 ppm male and female mice by day 7. The intraluminal fibrosis persisted to day 91. In males with severe bronchial fibrosis, chronic alveolitis and atelectasis were found. In mice exposed to 3 or 10 ppm, persistent pulmonary changes were not found. These studies indicate that methyl isocyanate inhalation at or near lethal concentrations can cause persistent fibrosis of the major bronchi in mice.

  6. A 90-day toxicology study of high-amylose transgenic rice grain in Sprague-Dawley rats.

    PubMed

    Zhou, Xing Hua; Dong, Ying; Xiao, Xiang; Wang, Yun; Xu, Yong; Xu, Bin; Shi, Wei Dong; Zhang, Yi; Zhu, Li Jia; Liu, Qiao Quan

    2011-12-01

    A transgenic rice line (TRS) with high amylose level has been developed by antisense RNA inhibition of starch branching enzymes. Compositional analysis of TRS demonstrated that the content of resistant starch (RS) was significantly higher compared to conventional non-transgenic rice. High level of RS is an important raw material in food industry and has various physiological effects for human health. In order to provide the reliable theory basis for field release of TRS rice, we evaluated the potential health effects of long-term consumption of the TRS. The 90-day toxicology feeding experiment was conducted in Sprague-Dawley rats fed with diets containing 70% of either TRS rice flour, its near-isogenic rice flour or the control diet. The clinical performance variables (body weight, body weight gain and food consumption) were measured and pathological responses (hematological parameters and serum chemistry at the midterm and the completion of the experiment, urinalysis profile and serum sex hormone response at the completion of the experiment) were performed. Besides, clinical signs, relative organ weights and microscopic observations were also compared between TRS group and its near-isogenic rice group. The combined data indicates that high-amylose TRS grain is as safe as the conventional non-transgenic rice for rat consumption. PMID:21967780

  7. Oral toxicity evaluation of thiodiglycol in Sprague-Dawley rats.

    PubMed

    Angerhofer, Richard A; Michie, Mark W; Leach, Glenn J; Johnson, Mark S; Reddy, Gunda

    2014-01-01

    Thiodiglycol (TDG) is the main product of sulfur mustard hydrolysis and is an environmental contaminant. Subacute and subchronic oral toxicity studies with TDG were conducted in Sprague-Dawley rats. Neat TDG was administered by gavage at doses of 157, 313, 625, 1250, 2500, 5000, and 9999 mg/kg/d, 5 days per week, for 14 days. In the 14-day study, decreased body weight and food consumption were observed at 5000 mg/kg/d. In the 90-day study, rats received neat TDG at doses of 50, 500, or 5000 mg/kg/d for 5 days per week. A fourth group served as a sham control. Individual body weight and food consumption were measured weekly. At termination of the experiment, urine, blood, and tissue samples were collected. Rats displayed significant decreased body weight with no effect on food consumption following administration of TDG at 5000 mg/kg/d. Both male and female rats showed significant increased kidney weights at 5000 mg/kg/d. The organ to body weight ratios increased significantly for liver, kidneys, testes, and brain in males and adrenals in females for 5000 mg/kg/d. At all doses of TDG, hematological and clinical parameters and tissue histopathology remained unaltered. The no observed adverse effect level (NOAEL) for oral subchronic toxicity was 500 mg/kg/d. Benchmark dose (BMD) was derived from the decreased gain in body weight that was seen in male rats. A BMD based on a 10% decrease in body weight was 1704 mg/kg/d, and the lower confidence limit on the dose BMD, the BMDL, was 372 mg/kg/d. PMID:25163473

  8. Herd-level risk factors for infectious diseases in Swedish dairy calves aged 0-90 days.

    PubMed

    Lundborg, G K; Svensson, E C; Oltenacu, P A

    2005-05-10

    The effect of environmental factors and management routines on the risk of diarrhoea, respiratory disease and other infectious diseases was investigated in 3081 heifer calves 0-90 days old in 122 Swedish dairy herds. The farmers kept records on cases of diseases in their heifer calves and in addition, project veterinarians clinically examined all calves every 2-3 months. At each visit, the veterinarians also measured the ammonia concentration and relative air humidity in the housing facilities for the calves. The cleanliness of the animals and their environment was recorded as a measure of the hygienic status of the farm. The presence or absence of draught (i.e. wind velocity>0.5 m/s) was recorded twice during the study period. The effect of these factors, as well as the placing of the calf pens, the nature of the pen walls, air volume per animal, management factors (such as the status of the caretaker and feeding routines) and presence or absence of a bovine viral diarrhoea virus (BVDV) infection in the herd, was evaluated by means of a two-level variance component logistic model. The placing of calf pens along an outer wall was significantly associated with the risk of diarrhoea (odds ratio (OR): 1.92, P<0.01). The risk for respiratory disease was significantly associated with an ammonia concentration below 6 ppm (OR: 0.42, P<0.05) while the odds ratio for moderately to severely increased respiratory sounds was significantly associated with a BVDV infection in the herd (OR: 2.39, P<0.05) and draught (OR: 3.7, P<0.02). Absence of draught was significantly associated with the risk for infectious diseases other than diarrhoea and respiratory disease (OR: 0.42, P<0.01). PMID:15820112

  9. Sub-chronic Hepatotoxicity of Anacardium occidentale (Anacardiaceae) Inner Stem Bark Extract in Rats

    PubMed Central

    Okonkwo, T. J. N.; Okorie, O.; Okonta, J. M.; Okonkwo, C. J.

    2010-01-01

    The extracts of Anacardium occidentale have been used in the management of different cardiovascular disorders in Nigeria. These have necessitated the assessment of the toxicity of this plant extract in sub-chronic administration. The inner stem bark of Anacardium occidentale was extracted with 80 % methanol and quantitatively analysed for antinutrients and some heavy metals. The phytochemical compositions and acute toxicity of the extract were determined also. Toxicity profiles of the extract on some liver function parameters were evaluated following a sub-chronic oral administration at doses of 1.44 and 2.87 g/kg. The phytochemical screening of extract revealed the presence of high amount of tannins, moderate saponins and trace of free reducing sugars. The antinutrient levels were 5.75 % (tannins), 2.50 % (oxalates), 2.00 % (saponins), 0.25 % (phytate) and 0.03 % (cyanide). The quantity of iron detected from dried crude was 8.92 mg/100 g, while lead and cadmium were non-detectable. The extract had LD50of 2.154g/kg p.o. in mice. Sub-chronic administration of the extract significantly increased the serum levels of alanine aminotransaminase and aspartate aminotransaminase, which are indicative of liver damage. The serum levels of alkaline phosphatase and total protein of the treated animals were not significantly increased. The effects of sub-chronically administered extract on hepatocytes were minimal as the serum alkaline phosphatase; total bilirubin and total protein levels in treated animals were not significant (p< 0.05). Thus, sub-chronic administrations of Anacardium occidentale inner stem bark extract did not significantly (p< 0.05) depress the function of hepatocytes in Wistar rats. PMID:21188045

  10. Past, present and emerging toxicity issues for jet fuel.

    PubMed

    Mattie, David R; Sterner, Teresa R

    2011-07-15

    The US Air Force wrote the specification for the first official hydrocarbon-based jet fuel, JP-4, in 1951. This paper will briefly review the toxicity of the current fuel, JP-8, as compared to JP-4. JP-8 has been found to have low acute toxicity with the adverse effects being slight dermal irritation and weak dermal sensitization in animals. JP-4 also has low acute toxicity with slight dermal irritation as the adverse effect. Respiratory tract sensory irritation was greater in JP-8 than in JP-4. Recent data suggest exposure to jet fuel may contribute to hearing loss. Subchronic studies for 90 days with JP-8 and JP-4 showed little toxicity with the primary effect being male rat specific hydrocarbon nephropathy. A 1-year study was conducted for JP-4. The only tumors seen were associated with the male rat specific hydrocarbon nephropathy. A number of immunosuppressive effects have been seen after exposure to JP-8. Limited neurobehavioral effects have been associated with JP-8. JP-8 is not a developmental toxicant and has little reproductive toxicity. JP-4 has not been tested for immune, neurobehavioral or reproductive endpoints. JP-8 and JP-4 were negative in mutagenicity tests but JP-4 showed an increase in unscheduled DNA synthesis. Currently, JP-8 is being used as the standard for comparison of future fuels, including alternative fuels. Emerging issues of concern with jet fuels include naphthalene content, immunotoxicity and inhalation exposure characterization and modeling of complex mixtures such as jet fuels. PMID:21296101

  11. 7 CFR Appendix B to Subpart C of... - FSA-2510, Notice of Availability of Loan Servicing to Borrowers Who Are 90 Days Past Due

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 7 2011-01-01 2011-01-01 false FSA-2510, Notice of Availability of Loan Servicing to Borrowers Who Are 90 Days Past Due B Appendix B to Subpart C of Part 766 Agriculture Regulations of the... LOAN SERVICING-SPECIAL Loan Servicing Programs Pt. 766, Subpt. C, App. B Appendix B to Subpart C...

  12. 7 CFR Appendix B to Subpart C of... - FSA-2510, Notice of Availability of Loan Servicing to Borrowers Who Are 90 Days Past Due

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 7 2010-01-01 2010-01-01 false FSA-2510, Notice of Availability of Loan Servicing to Borrowers Who Are 90 Days Past Due B Appendix B to Subpart C of Part 766 Agriculture Regulations of the... LOAN SERVICING-SPECIAL Loan Servicing Programs Pt. 766, Subpt. C, App. B Appendix B to Subpart C...

  13. The Model for End-stage Liver Disease accurately predicts 90-day liver transplant wait-list mortality in Atlantic Canada

    PubMed Central

    Renfrew, Paul Douglas; Quan, Hude; Doig, Christopher James; Dixon, Elijah; Molinari, Michele

    2011-01-01

    OBJECTIVE: To determine the generalizability of the predictions for 90-day mortality generated by Model for End-stage Liver Disease (MELD) and the serum sodium augmented MELD (MELDNa) to Atlantic Canadian adults with end-stage liver disease awaiting liver transplantation (LT). METHODS: The predictive accuracy of the MELD and the MELDNa was evaluated by measurement of the discrimination and calibration of the respective models’ estimates for the occurrence of 90-day mortality in a consecutive cohort of LT candidates accrued over a five-year period. Accuracy of discrimination was measured by the area under the ROC curves. Calibration accuracy was evaluated by comparing the observed and model-estimated incidences of 90-day wait-list failure for the total cohort and within quantiles of risk. RESULTS: The area under the ROC curve for the MELD was 0.887 (95% CI 0.705 to 0.978) – consistent with very good accuracy of discrimination. The area under the ROC curve for the MELDNa was 0.848 (95% CI 0.681 to 0.965). The observed incidence of 90-day wait-list mortality in the validation cohort was 7.9%, which was not significantly different from the MELD estimate of 6.6% (95% CI 4.9% to 8.4%; P=0.177) or the MELDNa estimate of 5.8% (95% CI 3.5% to 8.0%; P=0.065). Global goodness-of-fit testing found no evidence of significant lack of fit for either model (Hosmer-Lemeshow χ2 [df=3] for MELD 2.941, P=0.401; for MELDNa 2.895, P=0.414). CONCLUSION: Both the MELD and the MELDNa accurately predicted the occurrence of 90-day wait-list mortality in the study cohort and, therefore, are generalizable to Atlantic Canadians with end-stage liver disease awaiting LT. PMID:21876856

  14. Platelet-to-Lymphocyte Ratio: A Novel Prognostic Factor for Prediction of 90-day Outcomes in Critically Ill Patients With Diabetic Ketoacidosis.

    PubMed

    Liu, Wen-Yue; Lin, Shi-Gang; Wang, Li-Ren; Fang, Chen-Chen; Lin, Yi-Qian; Braddock, Martin; Zhu, Gui-Qi; Zhang, Zhongheng; Zheng, Ming-Hua; Shen, Fei-Xia

    2016-01-01

    Diabetic ketoacidosis (DKA) is a life-threatening acute complication of diabetes mellitus and the novel systemic inflammation marker platelet-to-lymphocyte ratio (PLR) may be associated with clinical outcome in patients with DKA. This study aimed to investigate the utility of PLR in predicting 90-day clinical outcomes in patients with DKA. Patient data exacted from the Multiparameter Intelligent Monitoring in Intensive Care II (MIMIC II) database was analyzed. A cutoff value for PLR of 267.67 was determined using Youden index (P < 0.05) and used to categorize subjects into a high PLR group and a low PLR group. The hazard ratios (HRs) and 95% confidence intervals (CIs) for DKA were calculated across PLR. Clinical outcomes in our study were defined as intensive care unit (ICU) 90-day readmission and all-cause mortality. A total of 278 ICU admissions were enrolled and stratified by cutoff value of PLR. The incidence of readmission and mortality was 17.8% in the high PLR group, significantly higher than 7.4% in the low PLR group. In the multivariable model, after adjusting for known confounding variables including clinical parameters, comorbidities, laboratory parameters, the HRs for DKA were 2.573 (95% CI 1.239-5.345; P = 0.011), 2.648 (95% CI 1.269-5.527; P = 0.009), and 2.650 (95% CI 1.114-6.306; P = 0.028), respectively. The Kaplan-Meier survival curve showed that a high PLR level was associated with a higher risk for 90-day outcomes in patients with DKA. The authors report that higher PLR presents a higher risk for 90-day incidence of readmission and mortality in patients with DKA. It appears to be a novel independent predictor of 90-day outcomes in critically ill DKA patients in ICU units. PMID:26825908

  15. EFFECTS OF CHLOROFORM IN THE DRINKING WATER OF RATS AND MICE: NINETY-DAY SUBACUTE TOXICITY STUDY

    EPA Science Inventory

    This research was initiated to provide toxicologic and range finding data sufficient for setting dose levels for the chronic phase testing of chloroform in drinking water of male Osborne-Mendel rats and female B6C3F1 mice. A 90-day subchronic study was designed to investigate the...

  16. Metabolomics analysis and biomarker identification for brains of rats exposed subchronically to the mixtures of low-dose cadmium and chlorpyrifos.

    PubMed

    Xu, Ming-Yuan; Sun, Ying-Jian; Wang, Pan; Xu, Hai-Yang; Chen, Li-Ping; Zhu, Li; Wu, Yi-Jun

    2015-06-15

    Cadmium (Cd) and chlorpyrifos (CPF) are widespread harmful environmental pollutants with neurotoxicity to mammals. Although the exposure to Cd and CPF at the same time may pose a significant risk to human health, the subchronic combined neurotoxicity of these two chemicals at low levels in the brain is poorly understood. In this study, we treated rats with three doses (low, middle, and high) of Cd, CPF, or their mixture for 90 days. No obvious symptom was observed in the treated animals except those treated with high-dose CPF. Histological results showed that middle and high doses of the chemicals caused neuronal cell damage in brains. GC-MS-based metabonomics analysis revealed that energy and amino acid metabolism were disturbed in the brains of rats exposed to the two chemicals and their combinations even at low doses. We further identified the unique brain metabolite biomarkers for rats treated with Cd, CPF, or both. Two amino acids, tyrosine and l-leucine, were identified as the biomarkers for Cd and CPF treatment, respectively. In addition, a set of five unique biomarkers (1,2-propanediol-1-phosphate, d-gluconic acid, 9H-purine, serine, and 2-ketoisovaleric acid) was identified for the mixtures of Cd and CPF. Therefore, the metabolomics analysis is more sensitive than regular clinical observation and pathological examination for detecting the neurotoxicity of the individual and combined Cd and CPF at low levels. Overall, these results identified the unique biomarkers for Cd and CPF exposure, which provide new insights into the mechanism of their joint toxicity. PMID:25856237

  17. Subchronic Immunotoxicity Assessment of Genetically Modified Virus-Resistant Papaya in Rats.

    PubMed

    Lin, Hsin-Tang; Lee, Wei-Cheng; Tsai, Yi-Ting; Wu, Jhaol-Huei; Yen, Gow-Chin; Yeh, Shyi-Dong; Cheng, Ying-Huey; Chang, Shih-Chieh; Liao, Jiunn-Wang

    2016-07-27

    Papaya is an important fruit that provides a variety of vitamins with nutritional value and also holds some pharmacological properties, including immunomodulation. Genetically modified (GM) papaya plants resistant to Papaya ringspot virus (PRSV) infection have been generated by cloning the coat protein gene of the PRSV which can be used as a valuable strategy to fight PRSV infection and to increase papaya production. In order to assess the safety of GM papaya as a food, this subchronic study was conducted to assess the immunomodulatory responses of the GM papaya line 823-2210, when compared with its parent plant of non-GM papaya, Tainung-2 (TN-2), in Sprague-Dawley (SD) rats. Both non-GM and GM 823-2210 papaya fruits at low (1 g/kg bw) and high (2 g/kg bw) dosages were administered via daily oral gavage to male and female rats consecutively for 90 days. Immunophenotyping, mitogen-induced splenic cell proliferation, antigen-specific antibody response, and histopathology of the spleen and thymus were evaluated at the end of the experiment. Results of immunotoxicity assays revealed no consistent difference between rats fed for 90 days with GM 823-2210 papaya fruits, as opposed to those fed non-GM TN-2 papaya fruits, suggesting that with regard to immunomodulatory responses, GM 823-2210 papaya fruits maintain substantial equivalence to fruits of their non-GM TN-2 parent. PMID:27396727

  18. Vitamin D deficiency at admission is not associated with 90-day mortality in patients with severe sepsis or septic shock: Observational FINNAKI cohort study.

    PubMed

    Ala-Kokko, Tero I; Mutt, Shivaprakash J; Nisula, Sara; Koskenkari, Juha; Liisanantti, Janne; Ohtonen, Pasi; Poukkanen, Meri; Laurila, Jouko J; Pettilä, Ville; Herzig, Karl-Heinz

    2016-01-01

    Introduction Low levels of vitamin D have been associated with increased mortality in patients that are critically ill. This study explored whether vitamin D levels were associated with 90-day mortality in severe sepsis or septic shock. Methods Plasma vitamin D levels were measured on admission to the intensive care unit (ICU) in a prospective multicentre observational study. Results 610 patients with severe sepsis were included; of these, 178 (29%) had septic shock. Vitamin D deficiency (<50 nmol/L) was present in 333 (55%) patients. The 90-day mortality did not differ among patients with or without vitamin D deficiency (28.3% vs. 28.5%, p = 0.789). Diabetes was more common among patients deficient compared to those not deficient in vitamin D (30% vs. 18%, p < 0.001). Hospital-acquired infections at admission were more prevalent in patients with a vitamin D deficiency (31% vs. 16%, p < 0.001). A multivariable adjusted Cox regression model showed that low vitamin D levels could not predict 90-day mortality (<50 nmol/L: hazard ratio (HR) 0.99 (95% CI: 0.72-1.36), p > 0.9; and <25 nmol/L: HR 0.44 (95% CI: 0.22-0.87), p = 0.018). Conclusions Vitamin D deficiency detected upon ICU admission was not associated with 90-day mortality in patients with severe sepsis or septic shock. Key messages In severe sepsis and septic shock, a vitamin D deficiency upon ICU admission was not associated with increased mortality. Compared to patients with sufficient vitamin D, patients with deficient vitamin D more frequently exhibited diabetes, elevated C-reactive protein levels, and hospital-acquired infections upon ICU admission, and they more frequently developed acute kidney injury. PMID:26800186

  19. 29 CFR 37.80 - What happens if a recipient fails to issue a Notice of Final Action within 90 days of the date on...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true What happens if a recipient fails to issue a Notice of Final Action within 90 days of the date on which a complaint was filed? 37.80 Section 37.80 Labor Office of the Secretary of Labor IMPLEMENTATION OF THE NONDISCRIMINATION AND EQUAL OPPORTUNITY PROVISIONS OF THE WORKFORCE INVESTMENT ACT OF 1998...

  20. 29 CFR 37.79 - If, before the 90-day period has expired, a recipient issues a Notice of Final Action with which...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true If, before the 90-day period has expired, a recipient issues a Notice of Final Action with which the complainant is dissatisfied, how long does the complainant have to file a complaint with the Director? 37.79 Section 37.79 Labor Office of the Secretary of Labor IMPLEMENTATION OF THE NONDISCRIMINATION...

  1. IN VIVO EVALUATION OF THE SEALING ABILITY OF TWO ENDODONTIC SEALERS IN ROOT CANALS EXPOSED TO THE ORAL ENVIRONMENT FOR 45 AND 90 DAYS

    PubMed Central

    Kopper, Patrícia Maria Poli; Vanni, José Roberto; Della Bona, Álvaro; de Figueiredo, José Antônio Poli; Porto, Sérgio

    2006-01-01

    This in vivo study evaluated the sealing ability of a resin-based sealer (AH Plus) and a zinc oxide-eugenol sealer (Endofill) in dogs' teeth, exposed to the oral environment for 45 and 90 days. Forty eight lower incisors from 8 dogs were endodonticaly treated. A stratified randomization determined the sealer use in each root canal. All canals were filled using the lateral condensation technique. The excess filling material at the cervical portion of the root canal was sectioned, leaving a 10-mm obturation length inside the canal. Teeth were provisionally sealed with glass ionomer cement for 24 h and the canals were exposed to the oral environment for either 45 or 90 days. Therefore, the experimental groups were as follows: A45- AH Plus for 45 days; A90- AH Plus for 90 days; E45- Endofill for 45 days; and E90- Endofill for 90 days (n=12). After the experimental period, the dogs were killed and the lower jaw was removed. The incisors were extracted and the roots were covered with two coats of nail varnish. The teeth were immersed in India ink for 96 h and submitted to diaphanization. Dye leakage (in mm) was measured using stereomicroscopy (10x magnification). The results were statistically analyzed using two-way ANOVA and Tukey test for multiple comparisons (á = 0.05). Group E90 (2.03±0.94) showed significantly higher mean leakage value than all other groups (p<0.001). None of the sealers, in both study conditions, were able to prevent dye leakage. PMID:19089029

  2. Influence of CO2 change during 90-day experiment on growth characteristics and photosynthetic activity in vegetables grown in Lunar Palace 1

    NASA Astrophysics Data System (ADS)

    Shao, Lingzhi; Liu, Hong; Wang, Minjuan; Fu, Yuming; Dong, Chen; Liu, Guanghui

    To establish bioregenerative life support system (BLSS) on lunar or Mars bases in the future, it is necessary to firstly conduct manned simulation experiments on the ground. For this purpose, Lunar palace 1 as an integrative experimental facility for permanent astrobase life support artificial closed ecosystem was set up, and 90-day experiment was carried out in this system. Vegtables as one of the important plant units, provide various nutrient content for crews in the system, such as vitamin, antioxidants and so on. However, it is not clear yet that how the CO _{2} change during 90-day experiment to affect on growth characteristics and photosynthetic activity in vegtables grown in the system. In this study, red lettuce, red rape, romaine lettuce, and bibb lettuce grown in the system were chosen as the subject investigated. Growth, expressed as dry weight, length of shoot and root, leaf area, was mearsured, and photosynthesis,expressed as net photosynthetic rate, intercellular CO _{2} concentration, chlorophyll contents and fluorescence was analyzed to detemind influence of CO _{2} change during 90-day experiment on growth in vegtables grown in the system.

  3. SUBCHRONIC ENDOTOXIN INHALATION CAUSES PERSISTENT AIRWAY DISEASE

    EPA Science Inventory

    ABSTRACT

    The endotoxin component of organic dusts causes acute reversible airflow obstruction and airway inflammation. To test the hypothesis that endotoxin alone causes airway remodeling, we have compared the response of two inbred mouse strains to subchronic endotoxin ...

  4. 40 CFR 798.2450 - Inhalation toxicity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 33 2013-07-01 2013-07-01 false Inhalation toxicity. 798.2450 Section 798.2450 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Subchronic Exposure § 798.2450 Inhalation toxicity. (a) Purpose. In the assessment...

  5. 40 CFR 798.2650 - Oral toxicity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 33 2013-07-01 2013-07-01 false Oral toxicity. 798.2650 Section 798.2650 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Subchronic Exposure § 798.2650 Oral toxicity. (a) Purpose. In the assessment and evaluation of...

  6. 40 CFR 798.2250 - Dermal toxicity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 33 2013-07-01 2013-07-01 false Dermal toxicity. 798.2250 Section 798.2250 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Subchronic Exposure § 798.2250 Dermal toxicity. (a) Purpose. In the assessment and evaluation of...

  7. Toxicity of vanadium to different freshwater organisms

    SciTech Connect

    Beusen, J.M.; Neven, B.

    1987-08-01

    The aim of this study is to determine the acute and subchronic toxicity of vanadium for various species of freshwater fish. The long-term toxicity and the effect of vanadium on the reproduction of Daphnia magna is also evaluated and compared with the toxicity of other metals.

  8. Subchronic and chronic developmental effects of copper oxide (CuO) nanoparticles on Xenopus laevis.

    PubMed

    Nations, Shawna; Long, Monique; Wages, Mike; Maul, Jonathan D; Theodorakis, Christopher W; Cobb, George P

    2015-09-01

    Metal oxide nanoparticles, such as copper oxide (CuO), are mass produced for use in a variety of products like coatings and ceramics. Acute exposure to CuO nanoparticles has caused toxicity to many aquatic organisms, yet there is no information on the effect of prolonged CuO nanomaterial exposures. This study examined effects of chronic exposure to CuO nanoparticles on Xenopus laevis growth and development. Experiments included a 14 d subchronic exposure and a 47 d chronic exposure throughout metamorphosis. The subchronic exposure caused mortality in all tested CuO concentrations, and significant growth effects occurred after exposure to 2.5 mg L(-1) CuO. Chronic exposure to 0.3 mg L(-1) CuO elicited significant mortality and affected the rate of metamorphosis. Exposure to lower concentrations of CuO stimulated metamorphosis and growth, indicating that low dose exposure can have hormetic effects. PMID:25950410

  9. MELD-Na as a prognostic indicator of 30- and 90-day mortality in patients with end-stage liver disease after creation of transjugular intrahepatic portosystemic shunt.

    PubMed

    Ahmed, Rezwan; Santhanam, Prasanna; Rayyan, Yaser

    2015-10-01

    Previous studies have shown that the Model for End-Stage Liver Disease (MELD) score is superior to other liver disease scoring systems to establish optimal candidates for transjugular intrahepatic portosystemic shunt (TIPS) procedure and liver transplantation. Our aim was to compare MELD-Na score with MELD score as a predictor of 30-day as well as 90-day mortality for individuals with end-stage liver disease (ESLD) after creation of TIPS. We performed a chart review on cirrhotic patients who underwent TIPS procedure and documented presence and severity of ascites and hepatic encephalopathy, patient laboratory values, and results from TIPS procedures. We compared continuous variables by Student's t-test for independent samples and categorical variables by χ-test(s). In non-normal distributions, a nonparametric test was used. We performed a logistic regression to determine the effects of several variables and analyzed variable predictors of likelihood of death within 30 and 90 days of TIPS procedure. Of the six predictor variables, only MELD-Na score was a statistically significant predictor of 30- and 90-day mortality following TIPS procedure for ESLD (P=0.028). For each one point increase in MELD-Na score, the odds of death increased by 1.15 times [95% confidence interval (1.02-1.30), P=0.28]. Since hyponatremia may be associated with poor prognostic features of overall health, its incorporation into the MELD scoring system to predict mortality in ESLD after creation of TIPS serves a useful purpose. Our single-center experience suggests that the MELD-Na score is the most effective predictor of survival after TIPS creation. PMID:26111072

  10. Dam-related effects on heart girth at birth, morbidity and growth rate from birth to 90 days of age in Swedish dairy calves.

    PubMed

    Lundborg, G K; Oltenacu, P A; Maizon, D O; Svensson, E C; Liberg, P G A

    2003-08-01

    We investigated the effects of dam-related factors (such as calving performance, milk leakage, diseases, milk production, and somatic-cell count (SCC)) on heart girth at birth and the incidence risk of diarrhoea and respiratory disease during the first 90 days in Swedish dairy calves. The effects of these dam-related factors and environmental and management-related (but not dietary) factors on the calves' growth rate during the first 90 days of life also were analysed. The study used nearly 3,000 heifer calves born in 1998 on 122 farms in the south-west of Sweden. Individual health records were kept by the farmers and visiting project veterinarians. The calf's heart girth was measured at birth and weaning. We used generalised linear mixed models for the size of the calf at birth and growth rate. Variables associated with the heart girth at birth were breed, calving performance, mastitis in the dam in the last 49 days before calving, milk production and parity. Variables associated with the growth rate were breed, calving performance, disease in the calf during its first 90 days of life, heart girth at birth, and housing of calves. The effect of the dam on the relative risk of diarrhoea and/or respiratory disease in the calf was evaluated by a generalised linear mixed model with a logit link. Morbidity in the dam during late pregnancy, retained placenta and SCC were associated with the relative risk of respiratory disease in the calf. None of the explanatory variables (other then breed) was associated with the relative risk of diarrhoea. PMID:12900157

  11. Predictors of 30-Day Mortality and 90-Day Functional Recovery after Primary Intracerebral Hemorrhage : Hospital Based Multivariate Analysis in 585 Patients

    PubMed Central

    2009-01-01

    Objective The purpose of this study was to identify independent predictors of mortality and functional recovery in patients with primary intracerebral hemorrhage (PICH) and to improve functional outcome in these patients. Methods Data were collected retrospectively on 585 patients with supratentorial PICH admitted to the Stroke Unit at our hospital between 1st January 2004 and the 31st July 2008. Using multivariate logistic regression analysis, the associations between all selected variables and 30-day mortality and 90-day functional recoveries after PICH was evaluated. Results Ninety-day functional recovery was achieved in 29.1% of the 585 patients and 30-day mortality in 15.9%. Age (OR=7.384, p=0.000), limb weakness (OR=6.927, p=0.000), and hematoma volume (OR=5.293, p=0.000) were found to be powerful predictors of 90-day functional recovery. Furthermore, initial consciousness (OR=3.013, p=0.014) hematoma location (lobar, OR=2.653, p=0.003), ventricular extension of blood (OR=2.077, p=0.013), leukocytosis (OR=2.048, p=0.008), alcohol intake (drinker, OR=1.927, p=0.023), and increased serum aminotransferase (OR=1.892, p=0.035) were found to be independent predictors of 90-day functional recovery after PICH. On the other hand, a pupillary abnormality (OR=4.532, p=0.000) and initial unconsciousness (OR=3.362, p=0.000) were found to be independent predictors of 30-day mortality after PICH. Conclusion The predictors of mortality and functional recovery after PICH identified during this analysis may assist during clinical decision-making, when advising patients or family members about the prognosis of PICH and when planning intervention trials. PMID:19609417

  12. STS-90 Day 11 Highlights

    NASA Technical Reports Server (NTRS)

    1998-01-01

    On this eleventh day of the STS-90 mission, the flight crew, Cmdr. Richard A. Searfoss, Pilot Scott D. Altman, and Mission Specialists Richard M. Linnehan, Dafydd Rhys Williams and Kathryn P. Hire, and Payload Specialists Jay C. Buckey and James A. Pawelczyk once again take part in an experiment aimed at exploring the influence of gravity on blood pressure. The lower body negative pressure test places a stress on the cardiovascular system similar to that experienced when standing in Earth's gravity. Pawelczyk also takes part in the Valsalva test, which stimulates the pressure receptors in the neck and chest and measures those responses. Both Buckey and Pawelzyk participate as subjects and as operators in tests of the autonomic nervous system. All four science crew members conduct tests of their pulmonary systems as well as additional runs in a rotating chair to measure the response of their eyes and inner ears in maintaining balance in a weightless environment.

  13. STS-90 Day 06 Highlights

    NASA Technical Reports Server (NTRS)

    1998-01-01

    On this sixth day of the STS-90 mission, the flight crew, Cmdr. Richard A. Searfoss, Pilot Scott D. Altman, and Mission Specialists Richard M. Linnehan, Dafydd Rhys Williams and Kathryn P. Hire, and Payload Specialists Jay C. Buckey and James A. Pawelczyk are back on the job full-time as they begin the day six of on-orbit research on the human nervous system. Additional work with the Pulmonary Function Test (PFT) equipment which is collecting data on the crew's breathing patterns and blood concentrations of oxygen and carbon dioxide also takes place.

  14. STS-90 Day 14 Highlights

    NASA Technical Reports Server (NTRS)

    1998-01-01

    On this fourteenth day of the STS-90 mission, the flight crew, Cmdr. Richard A. Searfoss, Pilot Scott D. Altman, and Mission Specialists Richard M. Linnehan, Dafydd Rhys Williams and Kathryn P. Hire, and Payload Specialists Jay C. Buckey and James A. Pawelczyk focus on the efforts of Neurolab's Neuronal Plasticity Team to better understand how the adult nervous system adapts to the new environment of space. Columbia's science crew -- Mission Specialists Rick Linnehan and Dave Williams and Payload Specialists Jay Buckey and Jim Pawelczyk -- perform the second and final in-flight dissections of the adult male rats on board. The crew euthanizes and dissects nine rats and remove the vestibular or balance organs of the inner ear; the cerebellum, the part of the brain critical for maintaining balance and for processing information from the limbs so they can be moved smoothly; and the cerebrum, one part of which controls automatic functions such as body temperature regulation and the body's internal clock, and the cortical region that controls cognitive functions such as thinking. The first dissection, which was performed on the second day of the flight, went extremely well, according to Neurolab scientists.

  15. STS-90 Day 03 Highlights

    NASA Technical Reports Server (NTRS)

    1998-01-01

    On this third day of the STS-90 mission, the flight crew, Cmdr. Richard A. Searfoss, Pilot Scott D. Altman, and Mission Specialists Richard M. Linnehan, Dafydd Rhys Williams and Kathryn P. Hire, and Payload Specialists Jay C. Buckey and James A. Pawelczyk continue to conduct both human and animal research experiments in the Spacelab module. During the morning, the payload crew members Linnehan, Williams, Buckey and Pawelczyk performs transfer activities with the Animal Enclosure Module, setting up the General Purpose Work Station (GPWS) and operations with the ball catch experiment. In the afternoon, their attention will be on injections and dissections of some of the research animals and an objects recognition test.

  16. Some inferences from in vivo experiments with metal and metal oxide nanoparticles: the pulmonary phagocytosis response, subchronic systemic toxicity and genotoxicity, regulatory proposals, searching for bioprotectors (a self-overview)

    PubMed Central

    Katsnelson, Boris A; Privalova, Larisa I; Sutunkova, Marina P; Gurvich, Vladimir B; Loginova, Nadezhda V; Minigalieva, Ilzira A; Kireyeva, Ekaterina P; Shur, Vladimir Y; Shishkina, Ekaterina V; Beikin, Ya B; Makeyev, Oleg H; Valamina, Irene E

    2015-01-01

    The purpose of this paper is to overview and summarize previously published results of our experiments on white rats exposed to either a single intratracheal instillation or repeated intraperitoneal injections of silver, gold, iron oxide, copper oxide, nickel oxide, and manganese oxide nanoparticles (NPs) in stable water suspensions without any chemical additives. Based on these results and some corroborating data of other researchers we maintain that these NPs are much more noxious on both cellular and systemic levels as compared with their 1 μm or even submicron counterparts. However, within the nanometer range the dependence of systemic toxicity on particle size is intricate and non-unique due to complex and often contra-directional relationships between the intrinsic biological aggressiveness of the specific NPs, on the one hand, and complex mechanisms that control their biokinetics, on the other. Our data testify to the high activity of the pulmonary phagocytosis of NPs deposited in airways. This fact suggests that safe levels of exposure to airborne NPs are possible in principle. However, there are no reliable foundations for establishing different permissible exposure levels for particles of different size within the nanometric range. For workroom air, such permissible exposure levels of metallic NP can be proposed at this stage, even if tentatively, based on a sufficiently conservative approach of decreasing approximately tenfold the exposure limits officially established for respective micro-scale industrial aerosols. It was shown that against the background of adequately composed combinations of some bioactive agents (comprising pectin, multivitamin-multimineral preparations, some amino acids, and omega-3 polyunsaturated fatty acid) the systemic toxicity and even genotoxicity of metallic NPs could be markedly attenuated. Therefore we believe that, along with decreasing NP-exposures, enhancing organisms’ resistance to their adverse action with the help

  17. Applying theoretical premises of binary toxicity mathematical modeling to combined impacts of chemical plus physical agents (A case study of moderate subchronic exposures to fluoride and static magnetic field).

    PubMed

    Katsnelson, B A; Tsepilov, N A; Panov, V G; Sutunkova, M P; Varaksin, A N; Gurvich, V B; Minigalieva, I A; Valamina, I E; Makeyev, O H; Meshtcheryakova, E Y

    2016-09-01

    Sodium fluoride solution was injected i.p. to rats at a dose equivalent to 0.1 LD50 three times a week up to 18 injections. Two thirds of these rats and of the sham-injected ones were exposed to the whole body impact of a 25 mT static magnetic field for 2 or 4 h a day, 5 times a week. For mathematical analysis of the effects they produced in combination, we used a response surface model. This analysis demonstrated that (like in combined toxicity) the combined adverse action of a chemical plus a physical agent was characterized by a diversity of types depending not only on particular effects these types were assessed for but on their level as well. From this point of view, the indices for which at least one statistically significant effect was observed could be classified as identifying (1) single-factor action; (2) additivity; (3) synergism; (4) antagonism (both subadditive unidirectional action and all variants of contradirectional action). Although the classes (2) and (3) taken together encompass a smaller part of the indices, the biological importance of some of them renders the combination of agents studied as posing a higher health risk than that associated with each them acting alone. PMID:27389609

  18. Adaptive tolerance in mice upon subchronic exposure to chloroform: Increased exhalation and target tissue regeneration

    SciTech Connect

    Anand, Sathanandam S. . E-mail: sanand@rx.uga.edu; Philip, Binu K.; Palkar, Prajakta S.; Mumtaz, Moiz M.; Latendresse, John R.; Mehendale, Harihara M. . E-mail: mehendale@ulm.edu

    2006-06-15

    The aims of the present study were to characterize the subchronic toxicity of chloroform by measuring tissue injury, repair, and distribution of chloroform and to assess the reasons for the development of tolerance to subchronic chloroform toxicity. Male Swiss Webster (SW) mice were given three dose levels of chloroform (150, 225, and 300 mg/kg/day) by gavage in aqueous vehicle for 30 days. Liver and kidney injury were measured by plasma ALT and BUN, respectively, and by histopathology. Tissue regeneration was assessed by {sup 3}H-thymidine incorporation into hepato- and nephro-nuclear DNA and by proliferating cell nuclear antigen staining. In addition, GSH and CYP2E1 in liver and kidney were assessed at selected time points. The levels of chloroform were measured in blood, liver, and kidney during the dosing regimen (1, 7, 14, and 30 days). Kidney injury was evident after 1 day with all three doses and sustained until 7 days followed by complete recovery. Mild to moderate liver injury was observed from 1 to 14 days with all three dose levels followed by gradual decrease. Significantly higher regenerative response was evident in liver and kidney at 7 days, but the response was robust in kidney, preventing progression of injury beyond first week of exposure. While the kidney regeneration reached basal levels by 21 days, moderate liver regeneration with two higher doses sustained through the end of the dosing regimen and 3 days after that. Following repeated exposure for 7, 14, and 30 days, the blood and tissue levels of chloroform were substantially lower with all three dose levels compared to the levels observed with single exposure. Increased exhalation of {sup 14}C-chloroform after repeated exposures explains the decreased chloroform levels in circulation and tissues. These results suggest that toxicokinetics and toxicodynamics (tissue regeneration) contribute to the tolerance observed in SW mice to subchronic chloroform toxicity. Neither bioactivation nor

  19. Effect of complications within 90 days on patient-reported outcomes 3 months and 12 months following elective surgery for lumbar degenerative disease.

    PubMed

    Chotai, Silky; Parker, Scott L; Sivaganesan, Ahilan; Sielatycki, J Alex; Asher, Anthony L; McGirt, Matthew J; Devin, Clinton J

    2015-12-01

    OBJECT There is a paradigm shift toward rewarding providers for quality rather than volume. Complications appear to occur at a fairly consistent frequency in large aggregate data sets. Understanding how complications affect long-term patient-reported outcomes (PROs) following degenerative lumbar surgery is vital. The authors hypothesized that 90-day complications would adversely affect long-term PROs. METHODS Nine hundred six consecutive patients undergoing elective surgery for degenerative lumbar disease over a period of 4 years were enrolled into a prospective longitudinal registry. The following PROs were recorded at baseline and 12-month follow-up: Oswestry Disability Index (ODI) score, numeric rating scales for back and leg pain, quality of life (EQ-5D scores), general physical and mental health (SF-12 Physical Component Summary [PCS] and Mental Component Summary [MCS] scores) and responses to the North American Spine Society (NASS) satisfaction questionnaire. Previously published minimum clinically important difference (MCID) threshold were used to define meaningful improvement. Complications were divided into major (surgicalsite infection, hardware failure, new neurological deficit, pulmonary embolism, hematoma and myocardial infarction) and minor (urinary tract infection, pneumonia, and deep venous thrombosis). RESULTS Complications developed within 90 days of surgery in 13% (118) of the patients (major in 12% [108] and minor in 8% [68]). The mean improvement in ODI scores, EQ-5D scores, SF-12 PCS scores, and satisfaction at 3 months after surgery was significantly less in the patients with complications than in those who did not have major complications (ODI: 13.5 ± 21.2 vs 21.7 ± 19, < 0.0001; EQ-5D: 0.17 ± 0.25 vs 0.23 ± 0.23, p = 0.04; SF-12 PCS: 8.6 ± 13.3 vs 13.0 ± 11.9, 0.001; and satisfaction: 76% vs 90%, p = 0.002). At 12 months after surgery, the patients with major complications had higher ODI scores than those without complications (29.1

  20. Collagen content in the vastus lateralis and the soleus muscle following a 90-day bed rest period with or without resistance exercises

    PubMed Central

    Nielsen, Rasmus Oestergaard; Schjerling, Peter; Tesch, Per; Stål, Per; Langberg, Henning

    2015-01-01

    Summary Introduction spaceflight seems associated with deterioration of the function of the skeletal muscles. Since muscle collagen is critical for muscle function, an improved understanding of the content of the muscle collagen during long-term inactivity seems important. Bed-rest with in-bed resistance training serves as a proxy for the conditions in space. Therefore, ground-based studies may improve the understanding of the consequences of long-term inactivity. Purpose the purpose is to compare the change in collagen protein in the vastus lateralis (VL) and the soleus (SOL) muscle amongst persons exposed to a 90-day bed rest with or without resistance exercise. Methods an explorative analysis was completed based on data from a randomized, controlled trial. The intervention group (BRE, SOL n=4, VL n=8) performed supine-based squat exercises, whereas the controls (BE, SOL n=6, VL n=12) remained inactive during follow-up. Muscle biopsies from vastus lateralis and soleus were taken at baseline (pre) and after 90-days’ follow-up (post). Muscle collagen (μg collagen/mg protein) was quantified. Two-way repeated measurements ANOVA was used to compare the interaction between the intervention (BRE/BR) and time (pre/post) for each muscle. Results the collagen content of VL was similar between pre and post in the BRE group (−3.8 μg collagen/mg protein [95% CI: −22.0; 14.4], p=0.68) while it rose amongst individuals in the BR group (14.9 μg collagen/mg protein [95% CI: −0.01; 29.7], p=0.05). The difference of 18.66 [95% CI: −6.5; 43.9] between BRE and BR across time was, however, not significant (p=0.14). No significant reduction in SOL muscle collagen content was observed from pre to post in the BR group (−9.3 μg collagen/mg protein [95% CI: −24.9; 6.4], p=0.25) or in the BRE group (−6.5 μg collagen/mg protein [95% CI: −25.6; 12.6], p=0.50). There was no difference in the effect of BR versus BRE over time (mean difference −2.78 μg collagen

  1. The Effects of Subchronic Exposure to Metribuzin on Danio rerio

    PubMed Central

    Plhalova, Lucie; Stepanova, Stanislava; Praskova, Eva; Chromcova, Lucie; Zelnickova, Lenka; Divisova, Lenka; Skoric, Misa; Pistekova, Vladimira; Bedanova, Iveta; Svobodova, Zdenka

    2012-01-01

    The aim of this study was to assess the impact of metribuzin in surface waters on fish under experimental conditions. The effects of subchronic exposure to metribuzin on fish growth and the development of histopathological changes in selected organs (gill, kidney, liver) and on activity of some biochemical markers (CYP450, EROD) in Danio rerio were investigated during a 28-day toxicity test. Juvenile growth tests were performed on D. rerio according to OECD method number 215. Fish at an initial age of 30 days were exposed to a range of metribuzin concentrations (1.5, 5, 16, 33, and 53 mg L−1). Exposure to metribuzin at 53 mg L−1 was associated with increased mortality. Negative effects with regard to total body weight, length, and the inhibition of specific growth rate were induced at concentrations of 33 and 53 mg L−1. Histopathological examination revealed pathological lesions in the liver in pesticide-exposed fish only at the highest concentration of 53 mg L−1 of metribuzin. Based on the results of growth rate, biochemical markers (CYP450, EROD), and histopathological examination, the lowest observed effect concentration (LOEC) value was 33 mg L−1 and the no observed effect concentration (NOEC) value was 16 mg L−1. PMID:22792050

  2. Sub-chronic toxicity of gold nanoparticles in male mice

    PubMed Central

    Ajdary, Marziyeh; Ghahnavieh, Marziyeh Ziaee; Naghsh, Nooshin

    2015-01-01

    Background: Gold nanoparticles have many industrial applications; moreover, they are photothermic agents for clinical treatment of cancer. This study was provided to investigate the effects associated with different doses of applied gold nanoparticles by injection and contact procedures on the alterations of the serum levels and certain factors in male mice. Materials and Methods: 72 male mice were randomly assigned into two protocols in terms of touching and injection. The injection protocol was included of five groups: Sham, control, 25, 50, and 100 ppm. They received gold nanoparticles at 25, 50, and 100 ppm concentrations administered in form of 0.3 ml/day for the period of 14 days and that of touching protocol were received 0.2 ml/day gold nanoparticles. Blood sample of which was taken to measure the serum level of creatine kinase phosphate, fasting blood, creatinine, albumin, blood urea nitrogen and eventually, the kidney was dissected for the intent of pathological analysis. Results: The serum level of creatine kinase phosphate and fasting blood sugar at middle dose was significantly different (P ≤ 0.05) in touching protocol. In both protocols, the serum level of creatinine in high and medium doses showed a significant difference (P < 0.05) associated with the treated group. In the touching method, in high and medium doses administered to the treated group, the alteration was significant (P ≤ 0.05). In the both protocols, the serum level of albumin in high and medium doses of the treated group showed significant difference (P < 0.05). Thus, the gold nanoparticles could result in undesirable effects upon kidney tissue. Conclusion: The result of this study indicated that the administration of gold nanoparticles by touching method was more effective on the serum levels of these factors than that of injection method. PMID:25878992

  3. Subchronic inhalation toxicity of 1,3,5-trichlorobenzene

    SciTech Connect

    Sasmore, D.P.; Mitoma, C.; Tyson, C.A.; Johnson, J.S.

    1982-10-11

    Male and female rats were exposed to 0, 10, 100 or 1000 ppM of 1,3,5-trichlorobenzene vapors for 6 hours daily, 5 days a week, for up to 13 weeks. After 4 and 13 weeks of exposure, animals were sacrificed and examined for changes in blood, clinical chemistry, internal organs, and tissues resulting from the 1,3,5-trichlorobenzene treatment. No treatment-related effects on the blood and clinical chemistry were evident. The only effects that were considered treatment-related were a squamous metaplasia and hyperplasia in the respiratory epithelium in the nasal passages of high-dose rats and the increased incidence of dried red material on the faces of these rats during exposures compared with other groups.

  4. Safety assessment of SDA soybean oil: results of a 28-day gavage study and a 90-day/one generation reproduction feeding study in rats.

    PubMed

    Hammond, Bruce G; Lemen, Joan K; Ahmed, Gulam; Miller, Kathleen D; Kirkpatrick, Jeannie; Fleeman, Tammye

    2008-12-01

    Long chain polyunsaturated fatty acids (LC-PUFAs) in the diet reduce risk of cardiac mortality. Fish oils are a dietary source of LC-PUFAs (EPA, DHA) but intake is low in Western diets. Adding beneficial amounts of LC-PUFAs to foods is limited by their instability and potential to impart off-flavors. Stearidonic acid (SDA), a precursor of EPA in man, is more stable than EPA/DHA in food matrices. SDA is present in fish oils (0.5-4%) and in nutraceuticals (echium, borage oil). Genes for Delta6, Delta15 desaturases were introduced into soybeans that convert linoleic and alpha-linolenic acid to SDA (15-30% fatty acids). Since addition of SDA soybean oil into human foods increases SDA intake, toxicology studies were undertaken to assess its safety. In a 28-day pilot study, rats were gavaged with SDA soybean oil at dosages up to 3g/kg body weight/day; no treatment-related adverse effects were observed. A 90-day/one generation rat reproduction study was subsequently conducted where SDA soybean oil was added to diets to provide daily doses of 1.5 and 4 g/kg body weight. There were no treatment-related adverse effects on parental animals or on reproductive performance and progeny development. PMID:18804141

  5. Phase II, Randomized, Placebo-controlled, 90-day Study of Emixustat HCL in Geographic Atrophy Associated with Dry Age-Related Macular Degeneration

    PubMed Central

    Dugel, Pravin U.; Novack, Roger L.; Csaky, Karl G.; Richmond, Preston P.; Birch, David G.; Kubota, Ryo

    2015-01-01

    Purpose This study assessed the safety, tolerability, and pharmacodynamics of emixustat hydrochloride (ACU-4429), a novel visual cycle modulator, in subjects with geographic atrophy (GA) associated with dry age-related macular degeneration (AMD). Methods Subjects were randomly assigned to oral emixustat (2, 5, 7, or 10 mg once daily) or placebo (3:1 ratio) for 90 days. Recovery of rod photoreceptor sensitivity following a photobleach was measured by electroretinography. Safety evaluations included analysis of adverse events (AEs) and ophthalmic examinations. Results Seventy-two subjects (54 emixustat, 18 placebo) were evaluated. Emixustat suppressed rod photoreceptor sensitivity in a dose-dependent manner. Suppression plateaued by Day 14, and was reversible within 7-14 days after drug cessation. No systemic AEs of concern were noted. Dose-related ocular AEs (chromatopsia, 57% emixustat vs. 17% placebo; and delayed dark adaptation, 48% emixustat vs. 6% placebo) were mild to moderate, and the majority resolved on study or within 7-14 days after study drug cessation. Conclusions In this phase II study, emixustat produced a dose-dependent, reversible effect on rod function, and an ocular AE profile that is consistent with the proposed mechanism of action. These results support further testing of emixustat for the treatment of GA associated with dry AMD. PMID:25932553

  6. Cariogram outcome after 90 days of oral treatment with Streptococcus salivarius M18 in children at high risk for dental caries: results of a randomized, controlled study.

    PubMed

    Di Pierro, Francesco; Zanvit, Alberto; Nobili, Piero; Risso, Paolo; Fornaini, Carlo

    2015-01-01

    Dental caries is the most common chronic disease of childhood. Cariogram is a well-recognized algorithm-based software program based on different caries-related risk factors and intended to aid clinicians in performing more objective and consistent dental caries risk assessments. This type of approach precedes the diagnosis of caries and allows the dentist to identify at-risk patients and then take appropriate preventive measures before caries develop further. One of the etiological factors favoring the development of dental caries is the mutans streptococci. These acidogenic dental plaque inhabitants can be effectively antagonized by the activity of bacteriocins released by the probiotic Streptococcus salivarius M18 (salivarius M18). Moreover, salivarius M18 after colonizing the human oral mucosa produces the enzymes dextranase and urease that are able to counteract plaque formation and saliva acidity, respectively. Seventy-six subjects at high risk of dental caries were randomized and then either treated or not treated for 90 days with an oral formulation containing the oral probiotic salivarius M18 (Carioblis(®)). The results indicate that the use of salivarius M18 increases the chances of avoiding new dental caries development in children, and its application could be proposed as a new tool in the dentist's armory to be adopted in subjects considered at high risk on the basis of their Cariogram outcome. PMID:26491371

  7. Cariogram outcome after 90 days of oral treatment with Streptococcus salivarius M18 in children at high risk for dental caries: results of a randomized, controlled study

    PubMed Central

    Di Pierro, Francesco; Zanvit, Alberto; Nobili, Piero; Risso, Paolo; Fornaini, Carlo

    2015-01-01

    Dental caries is the most common chronic disease of childhood. Cariogram is a well-recognized algorithm-based software program based on different caries-related risk factors and intended to aid clinicians in performing more objective and consistent dental caries risk assessments. This type of approach precedes the diagnosis of caries and allows the dentist to identify at-risk patients and then take appropriate preventive measures before caries develop further. One of the etiological factors favoring the development of dental caries is the mutans streptococci. These acidogenic dental plaque inhabitants can be effectively antagonized by the activity of bacteriocins released by the probiotic Streptococcus salivarius M18 (salivarius M18). Moreover, salivarius M18 after colonizing the human oral mucosa produces the enzymes dextranase and urease that are able to counteract plaque formation and saliva acidity, respectively. Seventy-six subjects at high risk of dental caries were randomized and then either treated or not treated for 90 days with an oral formulation containing the oral probiotic salivarius M18 (Carioblis®). The results indicate that the use of salivarius M18 increases the chances of avoiding new dental caries development in children, and its application could be proposed as a new tool in the dentist’s armory to be adopted in subjects considered at high risk on the basis of their Cariogram outcome. PMID:26491371

  8. Assessment of the reporting of quality and outcome measures in hepatic resections: a call for 90-day reporting in all hepatectomy series

    PubMed Central

    Egger, Michael E; Ohlendorf, Joanna M; Scoggins, Charles R; McMasters, Kelly M; Martin, Robert C G

    2015-01-01

    Background The aim of this paper is to assess the current state of quality and outcomes measures being reported for hepatic resections in the recent literature. Methods Medline and PubMed databases were searched for English language articles published between 1 January 2002 and 30 April 2013. Two examiners reviewed each article and relevant citations for appropriateness of inclusion, which excluded papers of liver donor hepatic resections, repeat hepatectomies or meta-analyses. Data were extracted and summarized by two examiners for analysis. Results Fifty-five studies were identified with suitable reporting to assess peri-operative mortality in hepatic resections. In only 35% (19/55) of the studies was the follow-up time explicitly stated, and in 47% (26/55) of studies peri-operative mortality was limited to in-hospital or 30 days. The time period in which complications were captured was not explicitly stated in 19 out of 28 studies. The remaining studies only captured complications within 30 days of the index operation (8/28). There was a paucity of quality literature addressing truly patient-centred outcomes. Conclusion Quality outcomes after a hepatic resection are inconsistently reported in the literature. Quality outcome studies for a hepatectomy should report mortality and morbidity at a minimum of 90 days after surgery. PMID:26228262

  9. Sub-chronic inhalation of high concentrations of manganese sulfate induces lower airway pathology in rhesus monkeys

    PubMed Central

    Dorman, David C; Struve, Melanie F; Gross, Elizabeth A; Wong, Brian A; Howroyd, Paul C

    2005-01-01

    Background Neurotoxicity and pulmonary dysfunction are well-recognized problems associated with prolonged human exposure to high concentrations of airborne manganese. Surprisingly, histological characterization of pulmonary responses induced by manganese remains incomplete. The primary objective of this study was to characterize histologic changes in the monkey respiratory tract following manganese inhalation. Methods Subchronic (6 hr/day, 5 days/week) inhalation exposure of young male rhesus monkeys to manganese sulfate was performed. One cohort of monkeys (n = 4–6 animals/exposure concentration) was exposed to air or manganese sulfate at 0.06, 0.3, or 1.5 mg Mn/m3 for 65 exposure days. Another eight monkeys were exposed to manganese sulfate at 1.5 mg Mn/m3 for 65 exposure days and held for 45 or 90 days before evaluation. A second cohort (n = 4 monkeys per time point) was exposed to manganese sulfate at 1.5 mg Mn/m3 and evaluated after 15 or 33 exposure days. Evaluations included measurement of lung manganese concentrations and evaluation of respiratory histologic changes. Tissue manganese concentrations were compared for the exposure and control groups by tests for homogeneity of variance, analysis of variance, followed by Dunnett's multiple comparison. Histopathological findings were evaluated using a Pearson's Chi-Square test. Results Animals exposed to manganese sulfate at ≥0.3 mg Mn/m3 for 65 days had increased lung manganese concentrations. Exposure to manganese sulfate at 1.5 mg Mn/m3 for ≥15 exposure days resulted in increased lung manganese concentrations, mild subacute bronchiolitis, alveolar duct inflammation, and proliferation of bronchus-associated lymphoid tissue. Bronchiolitis and alveolar duct inflammatory changes were absent 45 days post-exposure, suggesting that these lesions are reversible upon cessation of subchronic high-dose manganese exposure. Conclusion High-dose subchronic manganese sulfate inhalation is associated with increased

  10. Cyanobacterium producing cylindrospermopsin cause histopathological changes at environmentally relevant concentrations in subchronically exposed tilapia (Oreochromis niloticus).

    PubMed

    Guzmán-Guillén, Remedios; Prieto, Ana I; Moreno, Isabel; Vasconcelos, Vitor M; Moyano, Rosario; Blanco, Alfonso; Cameán Fernandez, Ana M

    2015-03-01

    The acute toxicity of cylindrospermopsin (CYN) has been established in rodents, based on diverse intraperitoneal an oral exposure studies and more recently in fish. But no data have been reported in fish after subchronic exposure to cyanobacterial cells containing this cyanotoxin, so far. In this work, tilapia (Oreochromis niloticus) were exposed by immersion to lyophilized Aphanizomenon ovalisporum cells added to the aquaria using two concentration levels of CYN (10 or 100 μg CYN L(-1)) and deoxy-cylindrospermopsin (deoxy-CYN) (0.46 or 4.6 μg deoxy-CYN L(-1)), during two different exposure times: 7 or 14 d. This is the first study showing damage in the liver, kidney, hearth, intestines, and gills of tilapia after subchronic exposure to cyanobacterial cells at environmental relevant concentrations. The major histological changes observed were degenerative processes and steatosis in the liver, membranous glomerulopathy in the kidney, myofibrolysis and edema in the heart, necrotic enteritis in the gastrointestinal tract, and hyperemic processes in gill lamellae and microhemorrhages. Moreover, these histopathological findings confirm that the extent of damage is related to the CYN concentration and length of exposure. Results from the morphometric study indicated that the average of nuclear diameter of hepatocytes and cross-sections of proximal and distal convoluted tubules are useful to evaluate the damage induced by CYN in the main targets of toxicity. PMID:24000190

  11. Subchronic Exposure of Mice to Cadmium Perturbs Their Hepatic Energy Metabolism and Gut Microbiome.

    PubMed

    Zhang, Songbin; Jin, Yuanxiang; Zeng, Zhaoyang; Liu, Zhenzhen; Fu, Zhengwei

    2015-10-19

    Cadmium (Cd) is an environmental pollutant known to cause liver damage; however, the mechanisms of its hepatotoxicity remain poorly understood. In this study, the effects of subchronic exposure in mice to low doses of Cd on energy metabolism and the gut microbiome were evaluated. The exposure of mice to 10 mg/L Cd supplied in drinking water for 10 weeks increased hepatic triacylglycerol (TG), serum free fatty acid (FFA), and TG levels. The mRNA levels of several key genes involved in both de novo FFA synthesis and transport pathways and in TG synthesis in the liver also increased significantly in the Cd-treated mice, indicating that alterations of these genes may be a possible mechanism to explain subchronic Cd exposure induced hepatic toxicity at a molecular level. As for the gut microbiome, at the phylum level, the amounts of Firmicutes and γ-proteobacteria decreased significantly in the feces after 4 weeks of Cd exposure, and the quantity of Firmicutes decreased significantly in the cecum contents after 10 weeks of Cd exposure. In addition, 16S rRNA gene sequencing further revealed that Cd exposure significantly perturbed the gut microflora structure and richness at family and genus levels. The alteration of gut microbiome composition might result in an increase in serum lipopolysaccharide (LPS) and induce hepatic inflammation, which may indirectly cause perturbations of energy homeostasis after Cd exposure. Taken together, the present study indicated that subchronic Cd exposure caused the dysregulation of energy metabolism and changed the gut microbiome composition in mice. PMID:26352046

  12. Developmental sub-chronic exposure to chlorpyrifos reduces anxiety-related behavior in zebrafish larvae.

    PubMed

    Richendrfer, Holly; Pelkowski, Sean D; Colwill, Ruth M; Créton, Robbert

    2012-07-01

    Neurobehavioral disorders such as anxiety, autism, and attention deficit hyperactivity disorders are typically influenced by genetic and environmental factors. Although several genetic risk factors have been identified in recent years, little is known about the environmental factors that either cause neurobehavioral disorders or contribute to their progression in genetically predisposed individuals. One environmental factor that has raised concerns is chlorpyrifos, an organophosphate pesticide that is widely used in agriculture and is found ubiquitously in the environment. In the present study, we examined the effects of sub-chronic chlorpyrifos exposure on anxiety-related behavior during development using zebrafish larvae. We found that sub-chronic exposure to 0.01 or 0.1 μM chlorpyrifos during development induces specific behavioral defects in 7-day-old zebrafish larvae. The larvae displayed decreases in swim speed and thigmotaxis, yet no changes in avoidance behavior were seen. Exposure to 0.001 μM chlorpyrifos did not affect swimming, thigmotaxis, or avoidance behavior and exposure to 1 μM chlorpyrifos induced behavioral defects, but also induced defects in larval morphology. Since thigmotaxis, a preference for the edge, is an anxiety-related behavior in zebrafish larvae, we propose that sub-chronic chlorpyrifos exposure interferes with the development of anxiety-related behaviors. The results of this study provide a good starting point for examination of the molecular, cellular, developmental, and neural mechanisms that are affected by environmentally relevant concentrations of organophosphate pesticides. A more detailed understanding of these mechanisms is important for the development of predictive models and refined health policies to prevent toxicant-induced neurobehavioral disorders. PMID:22579535

  13. Morbidity in Swedish dairy calves from birth to 90 days of age and individual calf-level risk factors for infectious diseases.

    PubMed

    Svensson, Catarina; Lundborg, Karin; Emanuelson, Ulf; Olsson, Sven-Ove

    2003-05-15

    The health of 3081 heifer calves born in 122 dairy herds in the south-west of Sweden from 1 January to 31 December, 1998, was monitored from birth until 90 days of age. The calves were kept either in individual pens (n=2167), in group pens, with 3-8 calves to a pen and manual feeding of milk (n=440), in group pens with 6-30 calves per pen and an automatic milk-feeding system (n=431), or with their dams (n=43). Disease incidence was recorded by farmers and project veterinarians, who clinically examined the calves and auscultated their lungs every 2-3 months. A disease was graded as 'severe' if the general loss of condition or of appetite in the calf continued for >2 days or if the animal suffered severe weight loss due to the disease. The effects of season, breed, housing, and type of colostrum feeding, and time, place and supervision of calving on the incidences of diarrhea, severe diarrhea, respiratory disease, other infectious disease and moderately to severely increased respiratory sounds, were analyzed by logistic-regression models (with herd as a random effect). The total morbidity rate was 0.081 cases per calf-month at risk. Incidence rates of arthritis, diarrhea, omphalophlebitis, respiratory disease and ringworm were 0.002, 0.035, 0.005, 0.025 and 0.009 cases per calf-months at risk, respectively. The odds ratios for diarrhea and severe diarrhea were increased in Swedish Red and Whites (OR: 1.6, 2.3) and in calves that received colostrum from first-lactation cows (OR: 1.3-1.8), and for severe diarrhea in calves born in summer or that received colostrum through suckling (OR: 1.7, 1.8). The odds ratios for respiratory disease and increased respiratory sounds were increased in calves housed in large-group pens with an automatic milk-feeding system (OR: 2.2, 2.8). Supervision of calving was associated with a decreased odds ratio for respiratory disease (OR: 0.7) and birth in individual maternity pen or tie stalls with a decreased odds ratio for increased

  14. TOXICITY OF TETRYL (N-METHYL-N,2,4,6-TETRANITROANILINE) IN F344 RATS

    EPA Science Inventory

    The toxicity of tetryl (N-methyl-N,2,4,6-tetranitroaniline) in male and female F344 rats was evaluated after adminstration in the diet for 14 or 90 days. The 14-day study diet concentrations used were 0, 500, 1250, 2000, 2500, and 5000 ppm; the 90-day study diet concentrations we...

  15. Short-term and subchronic repeated exposure studies with 5-ethylidene-2-norbornene vapor in the rat.

    PubMed

    Ballantyne, B; Norris, J C; Dodd, D E; Klonne, D R; Losco, P E; Neptun, D A; Price, S C; Grasso, P

    1997-01-01

    5-Ethylidene-2-norbornene (ENB) is an industrial chemical whose physical properties indicate a likelihood for vapor exposure to humans. The potential for target organ or cumulative toxicity was investigated in rats exposed for 6 h per day for 9 days over an 11-day period, or 66 or 67 days over 14 weeks; 4- week recovery animals were added to the 14-week study. Mean analytically measured ENB vapor concentrations (+/-SD) were 52 +/- 1.5, 148 +/- 2.3 and 359 +/- 4.2 ppm for the 9-day study and 4.9 +/- 0.14, 24.8 +/- 1.23 and 149 +/- 4.40 ppm for the subchronic study. There were no mortalities, and clinical signs were limited to periocular swelling and/or encrustation, and urogenital area wetness. Body weight gain was decreased in the 9-day 359 ppm females and in the subchronic 24.8 and 149 ppm males. A minimal macrocytic anemia was present in subchronically exposed males, which resolved during the recovery period. In the 9-day study increased liver weight was associated with minimal centrilobular hepatocytomegaly and cytoplasmic basophilia with no degenerative or serum biochemical liver function changes, suggesting an adaptive response. Only relative liver weights were increased in the subchronic 149 ppm males, and no histopathological findings were observed. Principal target organ effects were to the thyroid gland, which showed an exposure concentration-related, but not exposure time-related, depletion of follicular colloid that resolved during the recovery period, together with light microscopic evidence for a hypertrophic and hyperplastic response in the follicular epithelium that resolved more slowly. The thyroid colloid depletion was a graded effect without a clear no-effect concentration, but was not accompanied by any clinical or clear biochemical evidence for thyroid dysfunction. A no-effect concentration of 4.9 ppm was established for the follicular cytological effects. PMID:9285532

  16. Effect of subchronic formaldehyde inhalation on minute volume and nasal deposition in Sprague-Dawley rats

    SciTech Connect

    Dallas, C.E.; Theiss, J.C.; Harrist, R.B.; Fairchild, E.J.

    1985-01-01

    Since respiratory depression during formaldehyde (HCHO) inhalation is an important mechanism in reducing the dose received and potentially the toxicity in the nasal passages of exposed animals, this study was conducted to determine if changes in the pattern of minute volume response and nasal deposition occurred in nosepiece challenges to rats after long-term repeated exposures of HCHO. Male Sprague-Dawley rats were exposed to 0, 0.5, 3, or 15 ppm HCHO for 6 h/d, 5 d/wk, for 8 or 16 wk. The preexposed animals and age-specific controls were then submitted to a HCHO nosepiece challenge at the same concentration that was received in the subchronic exposure. Very high nasal deposition was demonstrated in all measurements. There was a diminished maximum minute volume depression in the 16-wk group relative to the 8-wk group. The difference in response was not statistically associated with the sub-chronic preexposure concentration. The substantial recovery of all initially depressed responses that occurred during the challenges probably diminished the impact of the decreased maximum responses on the resulting nasal deposition over the course of the long-term exposures.

  17. Exposure to Pb, Cd, and As mixtures potentiates the production of oxidative stress precursors: 30-day, 90-day, and 180-day drinking water studies in rats

    SciTech Connect

    Whittaker, Margaret H.; Wang, Gensheng; Chen Xueqing; Lipsky, Michael; Smith, Donald; Gwiazda, Roberto; Fowler, Bruce A.

    2011-07-15

    Exposure to chemical mixtures is a common and important determinant of toxicity and is of particular concern due to their appearance in sources of drinking water. Despite this, few in vivo mixture studies have been conducted to date to understand the health impact of chemical mixtures compared to single chemicals. Interactive effects of lead (Pb), cadmium (Cd) and arsenic (As) were evaluated in 30-, 90-, and 180-day factorial design drinking water studies in rats designed to test the hypothesis that ingestion of such mixtures at individual component Lowest-Observed-Effect-Levels (LOELs) results in increased levels of the pro-oxidant delta aminolevulinic acid (ALA), iron, and copper. LOEL levels of Pb, Cd, and As mixtures resulted in the increased presence of mediators of oxidative stress such as ALA, copper, and iron. ALA increases were followed by statistically significant increases in kidney copper in the 90- and 180-day studies. Statistical evidence of interaction was identified for six biologically relevant variables: blood delta aminolevulinic acid dehydratase (ALAD), kidney ALAD, urinary ALA, urinary iron, kidney iron, and kidney copper. The current investigations underscore the importance of considering interactive effects that common toxic agents such as Pb, Cd, and As may have upon one another at low-dose levels. The interactions between known toxic trace elements at biologically relevant concentrations shown here demonstrate a clear need to rigorously review methods by which national/international agencies assess health risks of chemicals, since exposures may commonly occur as complex mixtures.

  18. ADATSA Follow-Up Study of Extended Outpatient Care: A Comparison of 90 Days versus 180 Days of Outpatient Treatment for Clients of Washington State's Alcoholism and Drug Addiction Treatment and Support Act.

    ERIC Educational Resources Information Center

    Van Der Hyde, Vincent A.; And Others

    This study was designed to compare outcomes for two groups of alcohol and substance abuse clients (N=230): a control group assigned to regular 90 days of outpatient treatment, and an experimental group assigned to 180 days of extended outpatient care. Outcomes were compared in the following nine categories: (1) relapse, measured as reported…

  19. How subchronic and chronic health effects can be neglected for GMOs, pesticides or chemicals.

    PubMed

    Séralini, Gilles-Eric; de Vendômois, Joël Spiroux; Cellier, Dominique; Sultan, Charles; Buiatti, Marcello; Gallagher, Lou; Antoniou, Michael; Dronamraju, Krishna R

    2009-01-01

    Chronic health effects are increasing in the world such as cancers, hormonal, reproductive, nervous, or immune diseases, even in young people. During regulatory toxicological subchronic tests to prevent these on mammalian health, prior commercialization of chemicals, including pesticides and drugs, or GMOs, some statistically significant findings may be revealed. This discussion is about the need to investigate the relevant criteria to consider those as biologically significant. The sex differences and the non linear dose or time related effects should be considered in contrast to the claims of a Monsanto-supported expert panel about a GMO, the MON 863 Bt maize, but also for pesticides or drugs, in particular to reveal hormone-dependent diseases and first signs of toxicities. PMID:19584953

  20. Less incidence of coronary artery disease in general anesthesia compared to spinal-epidural anesthesia after total knee replacement: 90-day follow-up period by a population-based dataset.

    PubMed

    Hsieh, Jui-Yang; Lin, Hui-Wen

    2015-07-01

    Total knee replacement (TKR) is an effective and safe procedure. However, large-scale study to compare the incidence of coronary artery disease (CAD) after spinal or epidural anesthesia (SA-EA) or general anesthesia (GA) for TKR has not ever been conducted. To do so, we studied a population-based dataset from the Taiwan National Health Research Institute and hypothesized that the incidence of CAD might be different with regional than with general anesthesia. The risk of CAD-related events during a 90-day follow-up period among patients who received TKR under SA-EA or GA was evaluated in the present study. A total of 1500 patients from the Taiwan National Health Insurance claims database who underwent TKR from January 1, 2004, to December 31, 2006, were allocated into two groups. Group 1 included 1012 patients who received SA-EA during TKR procedure. Group 2 included 488 patients who received GA during this procedure. The number of patients who developed CAD during the 90-day follow-up period was 31 (3.1 %) in group 1 and 6 (1.2 %) in group 2. The Kaplan-Meier survival analysis of IHD-free cumulative survival rate during the 90-day follow-up period for patients who underwent TKR was significantly lower in group 1 than in group 2. The hazard ratio for the occurrence of CAD was 2.80 (95 % CI 1.16-6.78), and the hazard was higher for patients who received SA-EA than for patients who received GA after adjusted potential confounding factors. After the performance of TKR, patients had a potentially increased risk for CAD in SA-EA compared to GA during the 90-day follow-up period. PMID:25761988

  1. Sub-chronic effect of neem based pesticide (Vepacide) on acetylcholinesterase and ATPases in rat.

    PubMed

    Rahman, M F; Siddiqui, M K; Jamil, K

    1999-09-01

    Acetylcholinesterases (AChE), Na(+)-K+, Mg2+ and Ca(2+)-ATPases were monitored in rat brain when treated orally with 80, 160 and 320 mg/kg of Vepacide, an active ingredient from neem seed oil, daily for 90 days. Brain AChE, Na(+)-K+ and Ca(2+)-ATPases were inhibited whereas Mg(2+)-ATPase levels were enhanced in both the sexes after 45 and 90 days of treatment. The relative sensitivities of these ATPases to Vepacide indicated that Ca(2+)-ATPase being more sensitive than Na(+)-K(+)-ATPase in both the sexes. The magnitude of Ca(2+)-ATPase inhibited by this compound was higher than that of brain AChE. It appears to be sexual dimorphism in the alterations of brain AChE, Na(+)-K+ and Mg(2+)-ATPases by Vepacide with females being significant when compared with males. After 28 days of post treatment the alterations observed were approached to those of controls both in male and female rats showing reversal of the toxicity. These results indicated that the ATPases were potently inhibited by Vepacide and seemed to be its precise target among the enzyme studied. This can be used as biochemical marker of exposure to this neem derived product. PMID:10466107

  2. Effect of sub-chronic selenium toxicosis on lipid peroxidation, glutathione redox cycle and antioxidant enzymes in calves.

    PubMed

    Kaur, Rajdeep; Sharma, Sucheta; Rampal, Satyavan

    2003-08-01

    The present investigation reports the effect of sodium selenite-induced sub-chronic toxicity in crossbred cow calves on various antioxidant enzymes. Sodium selenite (0.25 mg/kg for 16 w) resulted in characteristic signs of sub-chronic selenosis, ie alopecia, cracking and enlargement of hooves, interdigital lesions, ring formation on the coronet region, and gangrene at tip of the tail. The sodium selenite resulted in significant rise of blood selenium levels and concurrent increase in erythrocytic glutathione peroxidase (GPx) activity. Blood selenium levels and GPx activity had a high positive correlation (r = 0.97). Blood glutathione levels were lowered from 211.1 +/- 13.4 to 95.56 +/- 11.8 microg/ml. Selenosis caused oxidative stress as evidenced by a 3-fold increase in lipid peroxidation: activities of glutathione-S-transferase, glutathione reductase, superoxide dismutase and catalase were significantly increased. These findings support the hypothesis that the pro-oxidant attributes of selenium play important roles in its toxicity. PMID:12882488

  3. Crocin Restores Hypotensive Effect of Subchronic Administration of Diazinon in Rats

    PubMed Central

    Razavi, Marjan; Hosseinzadeh, Hossein; Abnous, Khalil; Motamedshariaty, Vahideh Sadat; Imenshahidi, Mohsen

    2013-01-01

    Objective(s): In this study, the effects of crocin against subchronic toxicity of diazinon (DZN) on systolic blood pressure (SBP) and heart rate (HR) were evaluated in rats. Materials and Methods: Rats were equally divided into 7 groups; control (corn oil), DZN (15 mg/kg), crocin (each group received 12.5, 25 or 50 mg/kg crocin plus DZN), vitamin E (200 IU/kg plus DZN) and crocin (50 mg/kg) treated groups. Rats were given DZN via gavage once a day for 4 weeks. Vitamin E (three times per week) and crocin (once a day) were intraperitoneally injected to rats for 4 weeks. Plasma cholinesterase activity (Elman method), malondealdehyde (MDA) levels in the aortic tissue (Thiobarbituric acid reactive substances or TBARS method); SBP and HR (tail cuff method) were evaluated at the end of 4th week. Results: A significant decrease in cholinesterase activity was observed in DZN group (P< 0.001). Crocin did not show any effects on cholinesterase activity. DZN increased MDA levels in aortic tissue (P< 0.001) in comparison with control group. Crocin and vitamin E plus DZN decreased MDA elevation induced by DZN in aortic tissue. DZN significantly reduced SBP (P< 0.01) and increased HR (P< 0.001) in comparison with control. Concurrent administration of crocin and DZN, improved the reduction of SBP and the elevation of HR induced by DZN in rat. Crocin alone did not have any effect on SBP and HR. Conclusion: This study showed that concurrent administration of crocin and DZN could restore the effects of subchronic DZN administration on SBP and HR in rats. PMID:23638294

  4. NAPHTHALENE TOXICITY IN CD-1 MICE: GENERAL TOXICOLOGY AND IMMUNOTOXICOLOGY

    EPA Science Inventory

    The purpose of this study was to evaluate the acute and subchronic toxicity, and effects on immune function, of naphthalene (NAP) in random-bred CD-1 mice. The acute oral LD50 of this compound was 533 and 710 mg/kg in male and female mice, respectively. Fourteen- and ninety-day d...

  5. The acute and sub-chronic exposures of goldfish to naphthenic acids induce different host defense responses.

    PubMed

    Hagen, Mariel O; Garcia-Garcia, Erick; Oladiran, Ayoola; Karpman, Matthew; Mitchell, Scott; El-Din, Mohamed Gamal; Martin, Jonathan W; Belosevic, Miodrag

    2012-03-01

    Naphthenic acids (NAs) are believed to be the major toxic component in oil sands process-affected water (OSPW) produced by the oil sands mining industry in Northern Alberta, Canada. We recently reported that oral exposure to NAs alters mammalian immune responses, but the effect of OSPW or NAs on the immune mechanisms of aquatic organisms has not been fully elucidated. We analyzed the effects of acute and sub-chronic NAs exposures on goldfish immune responses by measuring the expression of three pro-inflammatory cytokine genes, antimicrobial functions of macrophages, and host defense after challenge with a protozoan pathogen (Trypanosoma carassii). One week after NAs exposure, fish exhibited increased expression of pro-inflammatory cytokines (IFNγ, IL-1β1, TNF-α2) in the gills, kidney and spleen. Primary macrophages from fish exposed to NAs for one week, exhibited increased production of nitric oxide and reactive oxygen intermediates. Goldfish exposed for one week to 20 mg/L NAs were more resistant to infection by T. carassii. In contrast, sub-chronic exposure of goldfish (12 weeks) to NAs resulted in decreased expression of pro-inflammatory cytokines in the gills, kidney and spleen. The sub-chronic exposure to NAs reduced the ability of goldfish to control the T. carassii infection, exemplified by a drastic increase in fish mortality and increased blood parasite loads. This is the first report analyzing the effects of OSPW contaminants on the immune system of aquatic vertebrates. We believe that the bioassays depicted in this work will be valuable tools for analyzing the efficacy of OSPW remediation techniques and assessment of diverse environmental pollutants. PMID:22227375

  6. Alterations in Hematological Profile of Experimentally Induced Subchronic Thiacloprid Toxicosis in Gallus domesticus

    PubMed Central

    Singla, Saloni; Sandhu, Harpal Singh

    2015-01-01

    Objectives: Thiacloprid, a novel neonicotinoid insecticide is chiefly used as a crop protectant therefore it is likely to cause indirect exposure to poultry through contaminated feed and water because this species is occasionally supplied with feed that is, declared unfit for human consumption. The current study was performed to explore the nonlethal toxic effects of thiacloprid in Gallus domesticus on hematological parameters. Materials and Methods: Fifty-two birds were randomly divided into nine groups. Groups I to IV of four birds each were kept as healthy control. The Groups V, VI, VII, VIII, IX, and X contained six birds each and were administered thiacloprid at 1 mg/kg/day for 15, 30, 45, 60, 75, and 90 days, respectively. Results: Thiacloprid caused variable changes in the hematological parameters. There was a significant decline in the packed cell volume (PCV), hemoglobin (Hb) concentration, and total erythrocyte count (TEC). The PCV declined to the extent of 23.33 ± 0.76% on day 90 from the 0 day value of 29.75 ± 1.26% of experiment. The Hb concentration decreased from 9.93 ± 0.57 g/dl (0 day) to 7.52 ± 0.62 g/dl (90 days). The TEC declined from the 0 day value of 2.41 ± 0.08 × 106/mm3 to 90 days value of 2.08 ± 0.05 × 106/mm3. The total leukocyte count on 0 day was 12.50 ± 0.76 × 103/mm3 and it showed a significant increase from day 45 (17.80 ± 2.67 × 103/mm3) to day 90 (21.33 ± 1.48 × 103/mm3) of thiacloprid treatment. There was a significant rise in value of erythrocyte sedimentation rate to 19.25 ± 1.22 mm/24 h on day 90 of treatment from the 14.42 ± 1.09 mm/24 h on 0 day. The long-term oral administration of thiacloprid produced no significant alterations in the values of erythrocytic indices. Conclusions: The repeated oral toxicity on thiacloprid in present investigation suggested that it has an adverse effect on health of birds and is moderately risk insecticide in G. domesticus. PMID:26862276

  7. The Effects of Subchronic Exposure to Terbuthylazine on Early Developmental Stages of Common Carp

    PubMed Central

    Štěpánová, Stanislava; Plhalová, Lucie; Doleželová, Petra; Prokeš, Miroslav; Maršálek, Petr; Škorič, Miša; Svobodová, Zdeňka

    2012-01-01

    The aim of this study was to assess the impact of terbuthylazine in surface waters on fish under experimental conditions. Subchronic toxic effects on embryos and larvae of common carp (Cyprinus carpio) were investigated during a 30-day toxicity test. The exposure to terbuthylazin showed no effect on mortality, but significant differences (P < 0.0001) were revealed on weight and growth parameters at concentrations of 520 and 820 μg/L. The inhibition of specific growth rate at concentrations of 520 and 820 μg/L was 14% compared to the control group. No significant negative effects on total body length and body weight were observed at lower concentrations (0.9 and 160 μg/L). The concentrations 520 and 820 μg/L were associated with a delay in development compared to other experimental groups and controls. On the basis of weight and growth rate evaluation and determination of developmental stages, the No Observed Effect Concentration (NOEC) of terbuthylazine was estimated at 160 μg/L and the Lowest Observed Effect Concentration (LOEC) was 520 μg/L. According to these results, the reported environmental concentration of terbuthylazine in Czech rivers does not impact growth, development, morphology, or histology of carp embryos and larvae. PMID:22629165

  8. Comparison of growth, serum biochemistries and n-6 fatty acid metabolism in rats fed diets supplemented with high-gamma-linolenic acid safflower oil or borage oil for 90 days.

    PubMed

    Tso, Patrick; Caldwell, Jody; Lee, Dana; Boivin, Gregory P; DeMichele, Stephen J

    2012-06-01

    Recently, steps have been taken to further developments toward increasing gamma-linolenic acid (GLA) concentration and lowering costs in plant seed oils using transgenic technology. Through identification and expression of a fungal delta-6 desaturase gene in the high linoleic acid safflower plant, the seeds from this genetic transformation produce oil with >40% GLA (high GLA safflower oil (HGSO)). The aim of the study was to compare the effects of feeding HGSO to a generally recognized as safe source of GLA, borage oil, in a 90 day safety study in rats. Weanling male and female Sprague-Dawley rats were fed a semi-synthetic, fat free, pelleted diet (AIN93G) supplemented with a 10% (wt/wt) oil blend containing HGSO or borage oil, with equivalent GLA levels. Results demonstrated that feeding diets containing HGSO or borage oil for 90 days had similar biologic effects with regard to growth characteristics, body composition, behavior, organ weight and histology, and parameters of hematology and serum biochemistries in both sexes. Metabolism of the primary n-6 fatty acids in plasma and organ phospholipids was similar, despite minor changes in females. We conclude that HGSO is biologically equivalent to borage oil and provides a safe alternative source of GLA in the diet. PMID:22265940

  9. A subchronic in situ exposure method for evaluating effects in small-bodied fish at contaminated sites.

    PubMed

    Miller, Jason L; Sherry, Jim; Parrott, Joanne; Quinn, James S

    2014-01-01

    In situ fish-caging studies at contaminated sites can provide information that is more realistic compared to traditional laboratory-based studies. However, few methods have been developed for exposing sentinel fish species for subchronic durations, and fewer still are optimized for exposing small-bodied fish while maintaining fish health and growth throughout the caging trial. Those methods typically lack a feeding regimen during the fish caging trial. While that may be acceptable or even appropriate for typical short-term toxicity testing, it does limit the duration of the exposure, and may not be suitable when post-caging trials or observations are necessary. Returning healthy fish to the lab following the in situ exposure would be important, for example, in studies designed to examine long-term or multigenerational effects following an in situ exposure. In this article we describe a subchronic method for caging small fish at contaminated sites while maintaining growth and reproductive development. Fathead minnow (Pimephales promelas) were caged in situ for 6 weeks, after which time they were returned to the lab where they were evaluated for health and reproductive performance. Growth and reproductive endpoints revealed no adverse effect on fish due to fish caging and related handling, demonstrating the suitability of our caging and feeding method for long-term caging studies. PMID:21932263

  10. Subchronic exposure to low-doses of the nerve agent VX: physiological, behavioral, histopathological and neurochemical studies.

    PubMed

    Bloch-Shilderman, Eugenia; Rabinovitz, Ishai; Egoz, Inbal; Raveh, Lily; Allon, Nahum; Grauer, Ettie; Gilat, Eran; Weissman, Ben Avi

    2008-08-15

    The highly toxic organophosphorous compound VX [O-ethyl-S-(isoporopylaminoethyl) methyl phosphonothiolate] undergoes an incomplete decontamination by conventional chemicals and thus evaporates from urban surfaces, e.g., pavement, long after the initial insult. As a consequence to these characteristics of VX, even the expected low levels should be examined for their potential to induce functional impairments including those associated with neuronal changes. In the present study, we developed an animal model for subchronic, low-dose VX exposure and evaluated its effects in rats. Animals were exposed to VX (2.25 microg/kg/day, 0.05 LD(50)) for three months via implanted mini osmotic pumps. The rapidly attained continuous and marked whole-blood cholinesterase inhibition (approximately 60%), fully recovered 96 h post pump removal. Under these conditions, body weight, blood count and chemistry, water maze acquisition task, sensitivity to the muscarinic agonist oxotremorine, peripheral benzodiazepine receptors density and brain morphology as demonstrated by routine histopathology, remained unchanged. However, animals treated with VX showed abnormal initial response in an Open Field test and a reduction (approximately 30%) in the expression of the exocytotic synaptobrevin/vesicle associate membrane protein (VAMP) in hippocampal neurons. These changes could not be detected one month following termination of exposure. Our findings indicate that following a subchronic, low-level exposure to the chemical warfare agent VX some important processes might be considerably impaired. Further research should be addressed towards better understanding of its potential health ramifications and in search of optimal countermeasures. PMID:18485435

  11. Genome-wide gene expression effects in B6C3F1 mouse intestinal epithelia following 7 and 90 days of exposure to hexavalent chromium in drinking water

    SciTech Connect

    Kopec, Anna K.; Kim, Suntae; Forgacs, Agnes L.; Zacharewski, Timothy R.; Proctor, Deborah M.; Harris, Mark A.; Haws, Laurie C.; Thompson, Chad M.

    2012-02-15

    Chronic administration of high doses of hexavalent chromium [Cr(VI)] as sodium dichromate dihydrate (SDD) elicits alimentary cancers in mice. To further elucidate key events underlying tumor formation, a 90-day drinking water study was conducted in B6C3F1 mice. Differential gene expression was examined in duodenal and jejunal epithelial samples following 7 or 90 days of exposure to 0, 0.3, 4, 14, 60, 170 or 520 mg/L SDD in drinking water. Genome-wide microarray analyses identified 6562 duodenal and 4448 jejunal unique differentially expressed genes at day 8, and 4630 and 4845 unique changes, respectively, in the duodenum and jejunum at day 91. Comparative analysis identified significant overlap in duodenal and jejunal differential gene expression. Automated dose–response modeling identified > 80% of the differentially expressed genes exhibited sigmoidal dose–response curves with EC{sub 50} values ranging from 10 to 100 mg/L SDD. Only 16 genes satisfying the dose-dependent differential expression criteria had EC{sub 50} values < 10 mg/L SDD, 3 of which were regulated by Nrf2, suggesting oxidative stress in response to SDD at low concentrations. Analyses of differentially expressed genes identified over-represented functions associated with oxidative stress, cell cycle, lipid metabolism, and immune responses consistent with the reported effects on redox status and histopathology at corresponding SDD drinking water concentrations. Collectively, these data are consistent with a mode of action involving oxidative stress and cytotoxicity as early key events. This suggests that the tumorigenic effects of chronic Cr(VI) oral exposure likely require chronic tissue damage and compensatory epithelial cell proliferation. Highlights: ► Mouse small intestine gene expression is highly responsive to hexavalent chromium [Cr(VI)]. ► Cr(VI) elicits more differential gene expression after 7 days of exposure than 90 days of exposure. ► Oral exposure to Cr(VI) leads to

  12. Subchronic exposure of titanium dioxide nanoparticles to hairless rat skin.

    PubMed

    Adachi, Koji; Yamada, Nanako; Yoshida, Yuichi; Yamamoto, Osamu

    2013-04-01

    The evaluation of the biological effects of industrial nanoparticles on the skin is necessary for their risk assessment. To clarify the influence of TiO2 nanoparticles on the skin, we carried out a subchronic exposure study of TiO2 nanoparticles to hairless rat skin. W/O emulsion containing 10 wt% TiO2 nanoparticles and control emulsion was applied to the dorsal skin of Hairless Wistar Yagi rats once a day for a maximum period of 56 consecutive days. After 2, 4 and 8 weeks, skin samples were taken from the exposed skin area. Histopathologically, the particles were only located in the stratum corneum layer of epidermis and follicular epithelium. Focal parakeratosis and spongiosis were observed in the epidermis. Transmission electron microscopy with energy-dispersive X-ray spectrometry (EDX) analysis failed to show TiO2 nanoparticles in the viable skin areas. There was no evidence of TiO2 penetration in the viable skin areas. In addition, titanium contents in several organs were determined using inductively coupled plasma mass spectroscopy. Increased titanium concentration was detected in lung samples of the TiO2 emulsion-treated groups after 8 weeks. It was most likely that the presence of TiO2 in the lungs was not caused by direct absorption of nanoparticles from the skin but was due to rats inhaling the nanoparticle. We did not find any obvious evidences of nano-TiO2 particle skin penetration using several morphological methods after the subchronic exposure. We believe that the influence of subchronic exposure of TiO2 is not significant based on our study. PMID:23528214

  13. Subchronic and genetic safety evaluation of a calcium fructoborate in rats.

    PubMed

    Marone, Palma Ann; Heimbach, James T; Nemzer, Boris; Hunter, John M

    2016-09-01

    A branded calcium fructoborate product, a nature-identical calcium salt of bis (fructose) ester of boric acid found in plants and a natural source of boron in the human diet and sold under the trade name FruiteX-B(®) Brand Calcium Fructoborate ("FrxB"), was evaluated in a 90-day dietary toxicity study and two genotoxicity studies. In the 90-day study, four groups of 10 male and 10 female Crl:SD CD(®) IGS rats were fed diets with FrxB admixtures of 0.56, 1.12, and 1.68% dietary concentration, providing mean overall daily intakes of FrxB in male rats of 385.8, 774.9, and 1161.3 mg/kg bw/day, and 392.1, 784.4, and 1171.1 mg/kg bw/day in female rats. There were no mortalities, no clinical or ophthalmologic signs, body weight, body weight gain, food consumption, food efficiency, Functional Observational Battery (FOB), or Motor Activity (MA) findings associated with the administration of FrxB. There were no adverse changes in hematology, coagulation, clinical chemistry, or urinalysis parameters in male or female rats considered the result of test substance administration. At necropsy, there were no macroscopic, histopathological findings, or organ weight changes deemed related to administration of the test substance. Under the conditions of this study, based on the toxicological endpoints evaluated, the no-observed-adverse-effect level (NOAEL) for FrxB in the diet was 1161.3 and 1171.1 mg/kg bw/day in male and female rats, respectively. Bacterial mutagenicity studies and a micronucleus test using Chinese hamster V79 cells demonstrated no mutagenic or genotoxic potential of the tested brand of calcium fructoborate. PMID:27350145

  14. Sub-chronic safety evaluation of the ethanol extract of Aralia elata leaves in Beagle dogs.

    PubMed

    Li, Fengjin; He, Xiaoli; Niu, Wenying; Feng, Yuenan; Bian, Jingqi; Kuang, Haixue; Xiao, Hongbin

    2016-08-01

    Aralia elata Seem. (A. elata) is a traditional Chinese medicine to treat some diseases. This investigation aims to evaluate the pharmaceutical safety of the ethanol extract of A. elata leaves, namely ethanol leaves extract (ELE), in Beagle dogs. In sub-chronic oral toxicity study, dogs were treated with the ELE at doses of 50, 100 and 200 mg/kg for 12 weeks and followed by 4 weeks recovery period. During experimental period, clinical signs, mortality, body temperature, food consumption and body weight were recorded. Analysis of electrocardiogram, urinalysis, ophthalmoscopy, hematology, serum biochemistry, organ weights and histopathology were performed. The results showed that both food consumption and body weight significantly decreased in high-dose group. Treatment-related side effects and mortality were observed in high-dose female dogs. Some parameters showed significant alterations in electrocardiogram, urinalysis, serum biochemistry and relative organ weights. These alterations were not related to dose or consistent across gender, which were ascribed to incidental and biological variability. The findings in this study indicated that the no-observed adverse effect level (NOAEL) of the ELE was 100 mg/kg in dogs and provided a vital reference for selecting a safe application dosage for human consumption. PMID:27156779

  15. Irreversible thyroid disruption induced after subchronic exposure to hexachlorobenzene in male rats.

    PubMed

    Chalouati, Hela; Gamet-Payrastre, Laurence; Saad, Moncef Ben

    2016-05-01

    Thyroid hormones play a complex role in the toxicity of hexachlorobenzene (HCB) and related compounds. Time-course and dose-response experiments for free- and total thyroxine (T4) and triiodothyronine (T3) plasma levels for thyroid-stimulating hormone (TSH) and thyroid gland histomorphology were determined in male Wistar rats. Also, we examined the possible reversibility of changes noted after removal of HCB. Rats treated with this organochlorine compound resulted in a hypertrophy of the thyroid gland and altered thyroid function by decreasing significantly the levels of total- and free T4 in a dose-dependent manner (total T4: 28 and 51%; free T4: 21 and 37%), and this decrease was seen as early as 21 days and thereafter. Free T3 was also decreased by 21% with the highest dose starting from day 21. No significant changes were observed in the circulating levels of total T3 In response to the decrease of thyroid hormones, a dose-dependent increase of TSH levels (27 and 31%, respectively, for 4 mg and 16 mg/kg of HCB body weight) was observed after 21 days of HCB treatment. We have observed a hypertrophy and hyperplasia of follicular cells and a decrease in colloid volume in histological picture. When HCB was removed and changed by vehicle, the thyroid relative weight and plasma TSH continued to rise and serum thyroid hormones remained suppressed. These findings suggest that subchronic exposure of rats to HCB induced an irreversible hypothyroidism state. PMID:24311623

  16. Toxicologic studies of emissions from coal gasification process. I. Subchronic feeding studies.

    PubMed

    Kostial, K; Kello, D; Blanusa, M; Maljković, T; Rabar, I; Bunarević, A; Stara, J F

    1980-09-01

    The increasing use of new sources of energy may result in additional contamination of the human environment with inorganic and organic pollutants which are not yet adequately investigated with regard to their potential impact on human health. However, some evidence exists that several trace inorganic and organic contaminants found in coal processing residues may constitute potential health problems. Therefore, the comparative biological hazards of solid wastes and effluents from a Lurgi coal gasification plant were initially evaluated using acute and chronic feeding experiments in male and female rats. In the subchronic experiment, six-week old animals were fed diets wih various levels of ash (slag) additive (0.5%, 1%, and 5%) for period of 16 weeks. Following exposure, blood samples were taken and 22-hour urine samples were collected. Livers and kidneys, and testicles in males, were taken for trace element analysis or histologic examination. The urinary values, erythrocyte and leucocyte count, hemoglobin, packed cell volume, and concentration of trace elements in exposed animals were determined. The addition of ash (slag) to the diet in concentrations much higher than expected in conditions of environmental contamination had no measurable health effects. Although these initial results obtained in relatively short-term experiments cannot be directly extrapolated to human health effects, particularly not for carcinogenic assessment, there is an indication that exposure to solid wastes from the coal gasification plant may not be toxic. PMID:7462912

  17. Serum and testicular testosterone and androgen binding protein profiles following subchronic treatment with carbendazim.

    PubMed

    Rehnberg, G L; Cooper, R L; Goldman, J M; Gray, L E; Hein, J F; McElroy, W K

    1989-10-01

    While the general toxicity of the benzimidazole pesticides for mammals is low, one of these compounds, carbendazim (MBC), causes degeneration of testicular tissue and decreases spermatogenic activity at doses well below the LD50 value. A study conducted by S. D. Carter, R. A. Hess, and J. W. Laskey (1987, Biol. Reprod. 37, 709-717) showed that treatment with 400 mg/kg/day MBC resulted in severe seminiferous tubular atrophy and infertility. Since spermatogenesis is an androgen-dependent process, we characterized the effects of MBC (0-400 mg/kg/day) on the endocrine function of the rat testes. Following subchronic (85 day) exposure, serum hormones (TSH, LH, FSH, and Prl) were measured as were androgen binding protein (ABP) and testosterone in testicular fluids (interstitial fluid and seminiferous tubule fluid). In addition, the functional capacity of the Leydig cell to secrete testosterone was assessed in vitro following an hCG challenge. Subchronic treatment with MBC at doses of 50-100 mg/kg/day had no effect on pituitary or testicular hormone concentrations: 200 mg/kg/day elevated the testosterone concentration in the seminiferous tubule fluid and the ABP concentration in both the interstitial fluid and the seminiferous tubule fluid without affecting serum testosterone or ABP concentrations. The 400 mg/kg/day dose resulted in increased concentration of both testosterone and ABP in the interstitial fluid and seminiferous tubule fluid and elevated serum ABP, with no change in serum testosterone. This endocrine profile is consistent with the testicular atrophy and "Sertoli cell-only" syndrome seen in these animals as reported by Gray et al. (1987, Toxicologist 7, 717). We conclude that seminiferous tubule fluid testosterone may be a result of two factors: (1) increased interstitial fluid testosterone concentrations and (2) decreased testosterone outflow from the testis to the general circulation. Also, increased ABP in the interstitial fluid may reflect a change in

  18. DIETARY SUBACUTE TOXICITY OF ETHYLENEBISISOTHIOCYANATE SULFIDE IN THE LABORATORY RAT

    EPA Science Inventory

    Ethylenebisisothiocyanate sulfide (EBIS) was fed to groups of rats at 0, 1, 10, 100, and 1000 ppm for up to 90 days. Only those rats receiving EBIS at 1000 ppm demonstrated a toxic response to the test chemical reflected as a reversible paralysis of the hind legs noted within 8 t...

  19. A plastic stabilizer dibutyltin dilaurate induces subchronic neurotoxicity in rats☆

    PubMed Central

    Jin, Minghua; Song, Peilin; Li, Na; Li, Xuejun; Chen, Jiajun

    2012-01-01

    Dibutyltin dilaurate functions as a stabilizer for polyvinyl chloride. In this study, experimental rats were intragastrically administered 5, 10, or 20 mg/kg dibutyltin dilaurate to model sub-chronic poisoning. After exposure, our results showed the activities of superoxide dismutase and glutathione peroxidase decreased in rat brain tissue, while the malondialdehyde and nitric oxide content, as well as nitric oxide synthase activity in rat brain tissue increased. The cell cycle in the right parietal cortex was disordered and the rate of apoptosis increased. DNA damage was aggravated in the cerebral cortex, and the ultrastructure of the right parietal cortex tissues was altered. The above changes became more apparent with exposure to increasing doses of dibutyltin dilaurate. Our experimental findings confirmed the neurotoxicity of dibutyltin dilaurate in rat brain tissues, and demonstrated that the poisoning was dose-dependent. PMID:25538742

  20. Evaluation of subchronic genotoxic potential of Swarna Makshika Bhasma

    PubMed Central

    Savalgi, Pavan B.; Patgiri, Biswajyoti; Thakkar, Jalaram H.; Ravishankar, B.; Gupta, Varun B.

    2012-01-01

    Extremely diminutive published information is available on the mutagenic activity of Ayurvedic Bhasmas. Genotoxicity of few Bhasmas were reported on single maximum dose, but no reference is available on the sub-chronic level. Hence the present study was carried to generate and evaluate genotoxic potentials of Swarna Makshika Bhasma (mineral preparation) administered at therapeutic dose for 14 days. Chromosomal aberrations and abnormal sperm assay parameters were taken in this study. Cyclophosphamide (CP) was taken as positive group and results were compared. The results revealed a lack of generation of structural deformity in above parameters by tested drugs compared to CP treated group. Observed data indicate that the Bhasmas tested were non-genotoxic under the experimental conditions. PMID:23723652

  1. Subchronic exposure of mice to Love Canal soil contaminants

    SciTech Connect

    Silkworth, J.B.; McMartin, D.N.; Rej, R.; Narang, R.S.; Stein, V.B.; Briggs, R.G.; Kaminsky, L.S.

    1984-04-01

    The health hazard potential of soil collected from the surface of the Love Canal chemical dump site in Niagara Falls, New York, was assessed in 90-day exposure studies. Female CD-1 mice were exposed to two concentrations of the volatile components of 1 kg of soil with and without direct soil contact. Control mice were identically housed but without soil. The soil was replaced weekly and 87 compounds were detected in the air in the cages above fresh and 7-day-old soil as analyzed by gas chromatography/mass spectrometry. The concentration of many of these compounds decreased during the 7-day exposure cycle. Histopathologic, hematologic, and serum enzyme studies followed necropsy of all mice. There was no mortality of mice exposed for up to 90 days under any condition. Thymus and spleen weights relative to body weight were increased after 4 weeks of exposure by inhalation but not after 8 or 12 weeks of exposure. alpha-, beta-, and delta- Benzenehexachlorides , pentachlorobenzene, and hexachlorobenzene were detected in liver tissue from these animals. Mice exposed to 5- to 10-fold elevated concentration of volatiles had increased body and relative kidney weights. There was no chemically induced lesion in any animal exposed only to the volatile soil contaminants. Mice exposed by direct contact with the soil without elevated volatile exposure had increased body (10%) and relative liver weights (169%). Centrolobular hepatocyte hypertrophy, which involved 40 to 70% of the lobules, was observed in all mice in this group.

  2. Subchronic exposure to low-doses of the nerve agent VX: Physiological, behavioral, histopathological and neurochemical studies

    SciTech Connect

    Bloch-Shilderman, Eugenia Rabinovitz, Ishai; Egoz, Inbal; Raveh, Lily; Allon, Nahum; Grauer, Ettie; Gilat, Eran; Weissman, Ben Avi

    2008-08-15

    The highly toxic organophosphorous compound VX [O-ethyl-S-(isoporopylaminoethyl) methyl phosphonothiolate] undergoes an incomplete decontamination by conventional chemicals and thus evaporates from urban surfaces, e.g., pavement, long after the initial insult. As a consequence to these characteristics of VX, even the expected low levels should be examined for their potential to induce functional impairments including those associated with neuronal changes. In the present study, we developed an animal model for subchronic, low-dose VX exposure and evaluated its effects in rats. Animals were exposed to VX (2.25 {mu}g/kg/day, 0.05 LD{sub 50}) for three months via implanted mini osmotic pumps. The rapidly attained continuous and marked whole-blood cholinesterase inhibition ({approx} 60%), fully recovered 96 h post pump removal. Under these conditions, body weight, blood count and chemistry, water maze acquisition task, sensitivity to the muscarinic agonist oxotremorine, peripheral benzodiazepine receptors density and brain morphology as demonstrated by routine histopathology, remained unchanged. However, animals treated with VX showed abnormal initial response in an Open Field test and a reduction ({approx} 30%) in the expression of the exocytotic synaptobrevin/vesicle associate membrane protein (VAMP) in hippocampal neurons. These changes could not be detected one month following termination of exposure. Our findings indicate that following a subchronic, low-level exposure to the chemical warfare agent VX some important processes might be considerably impaired. Further research should be addressed towards better understanding of its potential health ramifications and in search of optimal countermeasures.

  3. Acute and subchronic toxicological evaluation of the semipurified extract of seeds of guaraná (Paullinia cupana) in rodents.

    PubMed

    Antonelli-Ushirobira, T M; Kaneshima, E N; Gabriel, M; Audi, E A; Marques, L C; Mello, J C P

    2010-07-01

    We evaluated the toxicity of a semipurified extract (EPA fraction, containing caffeine and several flavan-3-ols and proanthocyanidins) of seeds of the native Amazon plant Paullinia cupana (guaraná) in rodents. Acute toxicity was tested in male Swiss mice, which received different doses orally (OR) and intraperitoneally (ip); control groups received water. These tests produced acute mortality, with LD(50) of 1.825 g/kg (OR) and 0.827 g/kg (ip), and a significant weight decrease in lungs of mice receiving a dose of 0.1g/kg. In the repeated-dose toxicity test, the EPA was administered OR daily to male and female Wistar rats at doses of 30, 150, and 300 mg/kg/day/90 days. Their behavior, mortality, weight changes, laboratory tests, and the weights and histopathology of organs were evaluated. No rats died during the tests. Males dosed at 150 or 300 mg/kg gained weight more slowly and lost kidney weight (absolute and relative weights, compared to the control group). Hematological and biochemical tests showed few changes, differing somewhat between males and females; the histopathological evaluation indicated no significant changes. These results indicate that the EPA fraction of guaraná caused no toxicity in rats at the smallest dose evaluated (30 mg/kg). No other species was evaluated. PMID:20398723

  4. Subchronic exposure of mice to Love Canal soil contaminants.

    PubMed

    Silkworth, J B; McMartin, D N; Rej, R; Narang, R S; Stein, V B; Briggs, R G; Kaminsky, L S

    1984-04-01

    The health hazard potential of soil collected from the surface of the Love Canal chemical dump site in Niagara Falls, New York, was assessed in 90-day exposure studies. Female CD-1 mice were exposed to two concentrations of the volatile components of 1 kg of soil with and without direct soil contact. Control mice were identically housed but without soil. The soil was replaced weekly and 87 compounds were detected in the air in the cages above fresh and 7-day-old soil as analyzed by gas chromatography/mass spectrometry. The concentration of many of these compounds decreased during the 7-day exposure cycle. Histopathologic, hematologic, and serum enzyme studies followed necropsy of all mice. There was no mortality of mice exposed for up to 90 days under any condition. Thymus and spleen weights relative to body weight were increased after 4 weeks of exposure by inhalation but not after 8 or 12 weeks of exposure. alpha-, beta-, and delta- Benzenehexachlorides , pentachlorobenzene, and hexachlorobenzene were detected in liver tissue from these animals. Mice exposed to 5- to 10-fold elevated concentration of volatiles had increased body and relative kidney weights. There was no chemically induced lesion in any animal exposed only to the volatile soil contaminants. Mice exposed by direct contact with the soil without elevated volatile exposure had increased body (10%) and relative liver weights (169%). Centrolobular hepatocyte hypertrophy, which involved 40 to 70% of the lobules, was observed in all mice in this group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:6724196

  5. Murine pulmonary responses after sub-chronic exposure to aluminum oxide-based nanowhiskers

    PubMed Central

    2012-01-01

    cytokines levels (IL-6, IFN-γ, MIP-1α, TNF-α, and MIP-2) between shams and exposed mice. Conclusions Sub-chronic inhalation exposures to aluminum-oxide based nanowhiskers induced increased lung macrophages, but no inflammatory or toxic responses were observed. PMID:22713230

  6. Metabolic response to subacute and subchronic iron overload in a rat model.

    PubMed

    Adham, Khadiga G; Farhood, Manal H; Daghestani, Maha H; Aleisa, Nadia A; Alkhalifa, Ahlam A; El Amin, Maha H; Virk, Promy; Al-Obeid, Mai A; Al-Humaidhi, Eman M H

    2015-12-01

    One of the common causes of iron overload is excessive iron intake in cases of iron-poor anemia, where iron saccharate complex (ISC) is routinely used to optimize erythropoiesis. However, non-standardized ISC administration could entail the risk of iron overload. To induce iron overload, Wistar rats were intraperitoneally injected with subacute (0.2 mg kg⁻¹) and subchronic (0.1 mg kg⁻¹) overdoses of ISC for 2 and 4 weeks, respectively. Iron status was displayed by an increase in transferrin saturation (up to 332%) and serum and liver iron burden (up to 19.3 μmol L⁻¹ and 13.2 μmol g⁻¹ wet tissue, respectively) together with a drop in total and unsaturated iron binding capacities "TIBC, UIBC" as surrogate markers of transferrin activity. Iron-induced leukocytosis (up to 140%), along with the decline in serum transferrin markers (up to 43%), respectively, mark positive and negative acute phase reactions. Chemical stress was demonstrated by a significant rise (p > 0.05) in indices of the hemogram (erythrocytes, hemoglobin, hematocrit, leukocytes) and stress metabolites [corticosterone (CORT) and lactate]. Yet, potential causes of the unexpected decline in serum activities of ALT, AST and LDH (p > 0.05) might include decreased hepatocellular enzyme production and/or inhibition or reduction of the enzyme activities. The current findings highlight the toxic role of elevated serum and liver iron in initiating erythropoiesis and acute phase reactions, modifying iron status and animal organ function, changing energy metabolism and bringing about accelerated glycolysis and impaired lactate clearance supposedly by decreasing anaerobic threshold and causing premature entering to the anaerobic system. PMID:26616369

  7. Effect of subchronic exposure to tetradifon on bone remodelling and metabolism in female rat.

    PubMed

    Badraoui, Riadh; Abdelmoula, Nouha Bouayed; Sahnoun, Zouhaier; Fakhfakh, Zouhaier; Rebai, Tarek

    2007-12-01

    This study investigates the effect of subchronic exposure to tetradifon, an organochlorine pesticide with an oestrogen-like structure, in female rat. A single cumulative dose of 2430 mg/kg BW was administrated orally for 12 female rats of 190 g BW. Twelve non-treated additional rats have served as controls. Animals were sacrificed after 6 and 12 weeks of treatment. We studied bone remodelling through histomorphometry and scanning electron microscopy (SEM) analyses. The serum and the right femora were used to determine phosphatase alkaline (AlkP) and/or calcium and phosphorus content. No sign of toxicity was observed until the end of the experiment. The SEM results revealed no structural alteration of the treated animal bone tissue. However, in both treated groups, we have noted an increase in the trabecular distance and a heterogeneous aspect of the endosteum that could be explained by bone-remodelling disturbance, with relative delay of ossification. Following histomorphomotric analysis, these results were coupled with significant increases in Tb.Th and OS/BS. Elsewhere, tetradifon intoxication increased significant serum AlkP level in the group treated for 12 weeks, which could be explained by an osteoblastic hyperactivity. Tetradifon intoxication decreased significantly bone calcium end phosphorus contents. Tetradifon seems not to exert major effects on bone remodelling. However, the osteoblastic hyperactivity could be explained by the oestrogen-like activity of tetradifon and its fatty metabolism. In fact, oestrogen inhibits bone remodelling, and enhances bone formation, which could result in an increase of the osteoid surface and explain the relative delay of ossification. PMID:18068648

  8. Subchronic exposure to ethyl tertiary butyl ether resulting in genetic damage in Aldh2 knockout mice.

    PubMed

    Weng, Zuquan; Suda, Megumi; Ohtani, Katsumi; Mei, Nan; Kawamoto, Toshihiro; Nakajima, Tamie; Wang, Rui-Sheng

    2013-09-15

    Ethyl tertiary butyl ether (ETBE) is biofuel additive recently used in Japan and some other countries. Limited evidence shows that ETBE has low toxicity. Acetaldehyde (AA), however, as one primary metabolite of ETBE, is clearly genotoxic and has been considered to be a potential carcinogen. The aim of this study was to evaluate the effects of ALDH2 gene on ETBE-induced genotoxicity and metabolism of its metabolites after inhalation exposure to ETBE. A group of wild-type (WT) and Aldh2 knockout (KO) C57BL/6 mice were exposed to 500ppm ETBE for 1-6h, and the blood concentrations of ETBE metabolites, including AA, tert-butyl alcohol and 2-methyl-1,2-propanediol, were measured. Another group of mice of WT and KO were exposed to 0, 500, 1750, or 5000ppm ETBE for 6h/day with 5 days per weeks for 13 weeks. Genotoxic effects of ETBE in these mice were measured by the alkaline comet assay, 8-hydroxyguanine DNA-glycosylase modified comet assay and micronucleus test. With short-term exposure to ETBE, the blood concentrations of all the three metabolites in KO mice were significantly higher than the corresponding concentrations of those in WT mice of both sexes. After subchronic exposure to ETBE, there was significant increase in DNA damage in a dose-dependent manner in KO male mice, while only 5000ppm exposure significantly increased DNA damage in male WT mice. Overall, there was a significant sex difference in genetic damage in both genetic types of mice. These results showed that ALDH2 is involved in the detoxification of ETBE and lack of enzyme activity may greatly increase the sensitivity to the genotoxic effects of ETBE, and male mice were more sensitive than females. PMID:23810710

  9. Effects of galanin subchronic treatment on memory and muscarinic receptors.

    PubMed

    Barreda-Gómez, G; Lombardero, L; Giralt, M T; Manuel, I; Rodríguez-Puertas, R

    2015-05-01

    The cholinergic pathways, which originate in the basal forebrain and are responsible for the control of different cognitive processes including learning and memory, are also regulated by some neuropeptides. One of these neuropeptides, galanin (GAL), is involved in both neurotrophic and neuroprotective actions. The present study has evaluated in rats the effects on cognition induced by a subchronic treatment with GAL by analyzing the passive avoidance response, and the modulation of muscarinic cholinergic receptor densities and activities. [(3)H]-N-methyl-scopolamine, [(3)H]-oxotremorine, and [(3)H]-pirenzepine were used to quantify the density of muscarinic receptors (MRs) and the stimulation of the binding of guanosine 5'-(γ-[(35)S]thio)triphosphate by the muscarinic agonist, carbachol, to determine their functionality. Some cognitive deficits that were induced by the administration of artificial cerebrospinal fluid (aCSF) (i.c.v. aCSF 2 μl/min, once a day for 6 days) were not observed in the animals also treated with GAL (i.c.v. 1.5 mmol in aCSF, 2 μl/min, once a day for 6 days). GAL modulates the changes in M1 and M2 MR densities observed in the rats treated with aCSF, and also increased their activity mediated by G(i/o) proteins in specific areas of the dorsal and ventral hippocampus. The subchronic administration of the vehicle was also accompanied by an increased number of positive fibers and cells for GAL around the cortical tract of the cannula used, but that was not the case in GAL-treated rats. In addition, the increase of GAL receptor density in the ventral hippocampus and entorhinal cortex in the aCSF group was avoided when GAL was administered. The number of acetylcholinesterase (AChE)-positive neurons was decreased in the nucleus basalis of Meynert of both GAL- and aCSF-treated animals. In summary, GAL improves memory-related abilities probably through the modulation of MR density and/or efficacy in hippocampal areas. PMID:25732139

  10. Protective effect of crocin against apoptosis induced by subchronic exposure of the rat vascular system to diazinon.

    PubMed

    Razavi, Bibi Marjan; Hosseinzadeh, Hossein; Abnous, Khalil; Khoei, Alireza; Imenshahidi, Mohsen

    2016-07-01

    Research has suggested that natural antioxidant, crocin, an active ingredient of saffron, may protect against diazinon (DZN)-induced toxicity. Although increased production of lipid peroxidation by DZN in rat aorta has been shown previously, the effects of DZN on oxidative stress-induced apoptosis in vascular system have not been evaluated. In this study, the effect of crocin on DZN-induced apoptosis in rat vascular system was investigated. The rats were divided into 7 groups: corn oil (control), DZN (15 mg/kg/day, gavage), crocin (12.5, 25, and 50 mg/kg/day, intraperitoneally (i.p.)) + DZN, vitamin E (200 IU/kg, i.p., 3 days a week) + DZN, and crocin (50 mg/kg/day, i.p.). The treatments were continued for 4 weeks. Levels of apoptotic (Bax, caspase 3, and caspase 9) and antiapoptotic proteins (Bcl2) were analyzed by Western blotting. Transcript levels of Bax and Bcl2 genes were determined using quantitative real-time polymerase chain reaction. Results showed DZN-induced apoptosis by activation of caspase 9 and caspase 3 and by increasing the Bax/Bcl2 ratio (both protein and messenger RNA levels). Crocin and vitamin E inhibited apoptosis induced by DZN. In summary, subchronic exposure to DZN induced caspase-mediated apoptosis, and crocin reduced the toxic effects of DZN by inhibiting apoptosis in aortic tissue. PMID:27353299

  11. A toxicological assessment of Athrixia phylicoides aqueous extract following sub-chronic ingestion in a rat model.

    PubMed

    Chellan, N; De Beer, D; Muller, C; Joubert, E; Louw, J

    2008-11-01

    Athrixia phylicoides is an aromatic, indigenous shrub used to brew "bush tea." Surveys have shown that the consumption of bush tea is widespread and commercialization of the extract holds economic and developmental potential. Aqueous extracts of A. phylicoides are non-toxic to brine shrimp and renal cell lines; however, verification in a mammalian model is needed. In this study, daily ingestion of high doses of aqueous A. phylicoides extract by mature Wistar rats was tested for potential toxicity over a 3-month period. Three-month-old Wistar rats were randomized into a control group (receiving no extract) and three experimental groups receiving 30, 90, or 180 mg dried aqueous A. phylicoides extract/kg body mass/day. After 90 days of daily extract ingestion, blood and tissue were harvested. There was no morbidity or mortality during the study. Food and water intake, as well as body mass and stool production, were unaffected by the consumption of the extract. Urine production was increased in the 90 and 180 mg/kg groups suggesting that A. phylicoides is mildly diuretic. Serum alkaline phosphatase, creatinine, and urea levels were normal for all groups. Histopathology showed no signs of any extract induced toxicity in the liver, kidneys, gastrointestinal tract, and other tissues studied. PMID:19244289

  12. Redox status in liver of rats following subchronic exposure to the combination of low dose dichlorvos and deltamethrin.

    PubMed

    Xu, Ming-Yuan; Wang, Pan; Sun, Ying-Jian; Wang, Hui-Ping; Liang, Yu-Jie; Zhu, Li; Wu, Yi-Jun

    2015-10-01

    Organophosphates and pyrethroids are widely used pesticides with prominent toxicity to humans. However, their joint toxicity has not been thoroughly investigated. In this study, we investigated the oxidative damages induced by low dose dichlorvos (DDVP) and deltamethrin (DM), the representative organophosphate and pyrethroid, respectively, and their mixtures in the liver of rats for 90 consecutive days. Two oxidative stress markers, malondialdehyde (MDA) and protein carbonyl (PCO) levels, were measured to reflect the extent of lipid peroxidation and protein oxidation, respectively. DDVP, DM, and their mixtures induced levels of MDA and PCO dose-dependently, although no toxic signs and pathological changes of liver were found in the rats following 90-day exposure. DDVP and DM induced greater increase of MDA than PCO, which indicated that lipids were particularly sensitive to the oxidative damage. We found that DDVP, DM and their mixtures could inhibit the activity of two antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). The effects of DM on SOD activity, lipid peroxidation and protein oxidation were greater than those of DDVP. The combined effect of DDVP and DM was lower than the sum of their individual effects. Thus the interaction between dichlorvos and deltamethrin may be antagonistic on the induction of oxidative stress in rat liver. PMID:26453231

  13. MODE-OF-ACTION AND CARCINOGENICITY OF CCL CHEMICALS

    EPA Science Inventory

    To establish parameters for 90-day subchronic toxicity studies, a thorough SAR analysis and assessment of the published data on halogenated alkanes and alkanes will be conducted. The toxicity study will be conducted to develop mode-of-action data that can be used for a set of ext...

  14. Antioxidant and Toxicity Studies of 50% Methanolic Extract of Orthosiphon stamineus Benth

    PubMed Central

    Lim, Chung Pin; Fung Ang, Lee; Por, Lip Yee; Wong, Siew Tung; Asmawi, Mohd. Zaini

    2013-01-01

    The present study evaluated the antioxidant activity and potential toxicity of 50% methanolic extract of Orthosiphon stamineus (Lamiaceae) leaves (MEOS) after acute and subchronic administration in rats. Superoxide radical scavenging, hydroxyl radical scavenging, and ferrous ion chelating methods were used to evaluate the antioxidant properties of the extract. In acute toxicity study, single dose of MEOS, 5000 mg/kg, was administered to rats by oral gavage, and the treated rats were monitored for 14 days. While in the subchronic toxicity study, MEOS was administered orally, at doses of 1250, 2500, and 5000 mg/kg/day for 28 days. From the results, MEOS showed good superoxide radical scavenging, hydroxyl radical scavenging, ferrous ion chelating, and antilipid peroxidation activities. There was no mortality detected or any signs of toxicity in acute and subchronic toxicity studies. Furthermore, there was no significant difference in bodyweight, relative organ weight, and haematological and biochemical parameters between both male and female treated rats in any doses tested. No abnormality of internal organs was observed between treatment and control groups. The oral lethal dose determined was more than 5000 mg/kg and the no-observed-adverse-effect level (NOAEL) of MEOS for both male and female rats is considered to be 5000 mg/kg per day. PMID:24490155

  15. Antioxidant status in oral subchronic toxicity of fipronil and fluoride co-exposure in buffalo calves.

    PubMed

    Gill, Kamalpreet Kaur; Dumka, Vinod Kumar

    2016-02-01

    The effects of fipronil and fluoride co-exposure were investigated on antioxidant status of buffalo calves. A total of 24 healthy male buffalo calves divided into 4 groups were treated for 98 consecutive days. Group I, receiving no treatment, served as the control. Animals of groups II and III were orally administered with fipronil at the dosage of 0.5 mg/kg/day and sodium fluoride (NaF) at the dosage of 6.67 mg/kg/day, respectively, for 98 days. Group IV was coadministered with fipronil and NaF at the same dosages as groups II and III. Administration of fipronil alone produced significant elevation in lipid peroxidation (LPO) and decrease in the levels of nonenzymatic antioxidant glutathione (GSH). However, it did not produce any significant effect on the activities of enzymatic antioxidants including glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD). NaF exposure led to enhanced oxidative stress as shown by significant increase in the LPO and SOD activities while GPx and CAT activities and GSH levels were significantly decreased. Co-exposure to fipronil and NaF showed additive effects on LPO, GPx activity, and GSH levels. PMID:24097355

  16. Morphological studies on the subchronic toxicity of a standardized liver- and spleen-extract.

    PubMed

    Leder, G H; Leder, O

    1990-02-01

    A short-term safety study on the liver- and spleen-extract Factor AF2 has been carried out. Daily injections of 4 or 33.3 mg/kg body weight for six weeks were not followed by drug-induced changes. PMID:2334459

  17. 40 CFR 798.6560 - Subchronic delayed neuro-toxicity of organophosphorus substances.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...) Test report. In addition to the reporting requirements specified under 40 CFR part 792, subpart J the... description of clinical manifestations of nervous system damage; where a grading system is used the...

  18. 40 CFR 798.6560 - Subchronic delayed neuro-toxicity of organophosphorus substances.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...) Test report. In addition to the reporting requirements specified under 40 CFR part 792, subpart J the... description of clinical manifestations of nervous system damage; where a grading system is used the...

  19. 40 CFR 798.6560 - Subchronic delayed neuro-toxicity of organophosphorus substances.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...) Test report. In addition to the reporting requirements specified under 40 CFR part 792, subpart J the... description of clinical manifestations of nervous system damage; where a grading system is used the...

  20. Severe Pulmonary Toxicity After Myeloablative Conditioning Using Total Body Irradiation: An Assessment of Risk Factors

    SciTech Connect

    Kelsey, Chris R.; Horwitz, Mitchell E.; Chino, Junzo P.; Craciunescu, Oana; Steffey, Beverly; Folz, Rodney J.; Chao, Nelson J.; Rizzieri, David A.; Marks, Lawrence B.

    2011-11-01

    Purpose: To assess factors associated with severe pulmonary toxicity after myeloablative conditioning using total body irradiation (TBI) followed by allogeneic stem cell transplantation. Methods and Materials: A total of 101 adult patients who underwent TBI-based myeloablative conditioning for hematologic malignancies at Duke University between 1998 and 2008 were reviewed. TBI was combined with high-dose cyclophosphamide, melphalan, fludarabine, or etoposide, depending on the underlying disease. Acute pulmonary toxicity, occurring within 90 days of transplantation, was scored using Common Terminology Criteria for Adverse Events version 3.0. Actuarial overall survival and the cumulative incidence of acute pulmonary toxicity were calculated via the Kaplan-Meier method and compared using a log-rank test. A binary logistic regression analysis was performed to assess factors independently associated with acute severe pulmonary toxicity. Results: The 90-day actuarial risk of developing severe (Grade 3-5) pulmonary toxicity was 33%. Actuarial survival at 90 days was 49% in patients with severe pulmonary toxicity vs. 94% in patients without (p < 0.001). On multivariate analysis, the number of prior chemotherapy regimens was the only factor independently associated with development of severe pulmonary toxicity (odds ratio, 2.7 per regimen). Conclusions: Severe acute pulmonary toxicity is prevalent after TBI-based myeloablative conditioning regimens, occurring in approximately 33% of patients. The number of prior chemotherapy regimens appears to be an important risk factor.

  1. COMPARISON OF SUBCHRONIC NEUROTOXICITY OF 2-HYDROXYETHYL ACRYLATE AND ACRYLAMIDE IN RATS

    EPA Science Inventory

    The comparative neurotoxicity of subchronic exposure to 2 hydroxyethyl acrylate (HEA) and acrylamide (ACR) was evaluated using a functional observational battery (FOB) and neurohistology. hree dose levels of each compound (HEA: 3, 20, 60 mg/kg; ACR: I, 4, 12 mg/kg) were administe...

  2. SUBCHRONIC EFFECTS OF SODIUM SELENITE AND SELENOMETHIONINE ON SEVERAL IMMUNE-FUNCTIONS IN MALLARDS

    EPA Science Inventory

    The subchronic effects of selenomethionine (SeM) and sodium selenite (SeL) on several immunologic, hematologic, and serologic parameters in mallards were measured, using concentrations in drinking water of 0, 0.5, and 3.5 mg/L selenium (Se) as SeL and 2.2 mg/L (Se) as SeM. ycloph...

  3. Adverse Effects of Subchronic Dose of Aspirin on Reproductive Profile of Male Rats

    PubMed Central

    Vyas, Archana; Ram, Heera; Purohit, Ashok; Jatwa, Rameshwar

    2016-01-01

    Aspirin (acetylsalicylic acid) is widely used for cardiovascular prophylaxis and as anti-inflammatory pharmaceutical. An investigation was carried out to evaluate the influence of subchronic dose of aspirin on reproductive profile of male rats, if any. Experimental animals were divided into three groups: control and aspirin subchronic dose of 12.5 mg/kg for 30 days and 60 days, respectively, while alterations in sperm dynamics, testicular histopathological and planimetric investigations, body and organs weights, lipid profiles, and hematology were performed as per aimed objectives. Subchronic dose of aspirin reduced sperm density, count, and mobility in cauda epididymis and testis; histopathology and developing primary spermatogonial cells (primary spermatogonia, secondary spermatogonia, and mature spermatocyte) count were also significantly decreased in rats. Hematological investigations revealed hemopoietic abnormalities in 60-day-treated animals along with dysfunctions in hepatic and renal functions. The findings of the present study revealed that administration with subchronic dose of aspirin to male rats resulted in altered reproductive profiles and serum biochemistry. PMID:27190691

  4. BEHAVIORAL ASSESSMENTS OF LONG EVANS RATS FOLLOWING A 13 WEEK SUBCHRONIC TOLUENE EXPOSURE.

    EPA Science Inventory

    Whereas the acute effects of volatile organic compounds (VOCs) are relatively well understood, there is some controversy regarding the potential for persistent effects following long-term exposure. The current study sought to develop an animal model of subchronic exposure to VOCs...

  5. BEHAVIORAL ASSESSMENTS OF LONG EVANS RATS FOLLOWING A 13-WEEK SUBCHRONIC TOLUENE EXPOSURE.

    EPA Science Inventory

    The current study sought to develop an animal model of the neurotoxicity of long-term exposure to volatile organic compounds (VOCs) which may be used to predict the effects of chronic exposure to VOCs on public health. The effects of Subchronic inhalation exposure to toluene (0,...

  6. CARDIOPATHIC EFFECT OF 1,2,3-TRICHLOROPROPANE AFTER SUBACUTE AND SUBCHRONIC EXPOSURE IN RATS

    EPA Science Inventory

    1,2,3-Trichloropropane (1,2,3-TCP) is an industrial water contaminant with potential for human exposure by the oral route. The systemic toxicology of 1,2,3-TCP was evaluated after subacute or subchronic exposure in male and female Sprague Dawley rate. Animals were treated with 0....

  7. SUBCHRONIC INHALATION EXPOSURE OF RATS TO LIBBY AMPHIBOLE AND AMOSITE ASBESTOS

    EPA Science Inventory

    Exposure to Libby amphibole (LA) is associated with significant increases in asbestosis, lung cancer, and mesothelioma. To support biological potency assessment and dosimetry model development, a subchronic nose-only inhalation exposure study (6 hr/d, 5 d/wk, 13 wk) was conducted...

  8. Subchronic effects of cadmium on the gonads, expressions of steroid hormones and sex-related genes in tilapia Oreochromis niloticus.

    PubMed

    Luo, Yongju; Shan, Dan; Zhong, Huan; Zhou, Yi; Chen, Wenzhi; Cao, Jinling; Guo, Zhongbao; Xiao, Jun; He, Fulin; Huang, Yifan; Li, Jian; Huang, Heming; Xu, Pao

    2015-12-01

    Cadmium (Cd) is one of the most toxic heavy metals in aquatic ecosystem which affects fish health and aquaculture. In the present study, we examined the bioaccumulation of Cd in the gonads of tilapia via dissolved and dietary routes. We evaluated the subchronic effects of Cd on the histology of gonads, steroid hormone levels and sex-related gene expressions in tilapia. In addition, we also studied maternal transfer of Cd. Our results indicated that Cd was accumulated significantly in both ovary and testis from both exposure routes. Histopathological analysis showed that Cd induced ovary and testis injuries. Estradiol levels were significantly increased in dissolved Cd exposed female fish. In addition, the Cd exposure displayed different effects on gene expressions in gonads. In females, the estrogen receptor (ERα) was stimulated in dissolved Cd-exposed fish at 70.32 and 143.78 μg/L for 30 days and in fish at 143.78 μg/L for 60 days. Vitellogenin expression was significantly down-regulated in the ovary of dissolved Cd-exposed fish. In testis, GR expression was elevated after 60 days of dissolved Cd and dietary exposure. Furthermore, Cd level was significantly higher in the eggs than that in the fry. Our results demonstrated that both dissolved and dietary Cd exposures affected gonad development by altering steroid hormone levels and sex-related gene expressions in tilapia. PMID:26471182

  9. Subchronic chloroform priming protects mice from a subsequently administered lethal dose of chloroform

    SciTech Connect

    Philip, Binu K.; Anand, Sathanandam S.; Palkar, Prajakta S.; Mumtaz, Moiz M.; Latendresse, John R.; Mehendale, Harihara M. . E-mail: mehendale@ulm.edu

    2006-10-01

    Protection offered by pre-exposure priming with a small dose of a toxicant against the toxic and lethal effects of a subsequently administered high dose of the same toxicant is autoprotection. Although autoprotection has been extensively studied with diverse toxicants in acute exposure regimen, not much is known about autoprotection after priming with repeated exposure. The objective of this study was to investigate this concept following repeated exposure to a common water contaminant, chloroform. Swiss Webster (SW) mice, exposed continuously to either vehicle (5% Emulphor, unprimed) or chloroform (150 mg/kg/day po, primed) for 30 days, were challenged with a normally lethal dose of chloroform (750 mg chloroform/kg po) 24 h after the last exposure. As expected, 90% of the unprimed mice died between 48 and 96 h after administration of the lethal dose in contrast to 100% survival of mice primed with chloroform. Time course studies indicated lower hepato- and nephrotoxicity in primed mice as compared to unprimed mice. Hepatic CYP2E1, glutathione levels (GSH), and covalent binding of {sup 14}C-chloroform-derived radiolabel did not differ between livers of unprimed and primed mice after lethal dose exposure, indicating that protection in liver is neither due to decreased bioactivation nor increased detoxification. Kidney GSH and glutathione reductase activity were upregulated, with a concomitant reduction in oxidized glutathione in the primed mice following lethal dose challenge, leading to decreased renal covalent binding of {sup 14}C-chloroform-derived radiolabel, in the absence of any change in CYP2E1 levels. Buthionine sulfoximine (BSO) intervention led to 70% mortality in primed mice challenged with lethal dose. These data suggest that higher detoxification may play a role in the lower initiation of kidney injury observed in primed mice. Exposure of primed mice to a lethal dose of chloroform led to 40% lower chloroform levels (AUC{sub 15-360min}) in the systemic

  10. 78 FR 17213 - Agency for Toxic Substances and Disease Registry Availability of Final Toxicological Profile

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-20

    ... of the 275 priority substances was announced in the Federal Register on November 3rd, 2011 (76 FR... published in the Federal Register on April 27, 2011 (76 FR 23600), with notice of a 90-day public comment... HUMAN SERVICES Agency for Toxic Substances and Disease Registry Availability of Final...

  11. Subchronic administration of (R,S)-ketamine induces ketamine ring hydroxylation in Wistar rats.

    PubMed

    Moaddel, R; Sanghvi, M; Ramamoorthy, A; Jozwiak, K; Singh, N; Green, C; O'Loughlin, K; Torjman, M; Wainer, I W

    2016-08-01

    Subchronic administration of (R,S)-ketamine, (R,S)-Ket, is used in the treatment of neuropathic pain, in particular Complex Regional Pain Syndrome, but the effect of this protocol on the metabolism of (R,S)-Ket is unknown. In this study, daily administration of a low dose of (R,S)-Ket for 14-days to Wistar rats was conducted to determine the impact of sub-chronic dosing on the pharmacokinetics of (R,S)-Ket and its major metabolites. The data indicate that, relative to a single administration of (R,S)-Ket, subchronic administration resulted in increased clearance of (R,S)-Ket and the N-demethylated metabolite norketamine measured as elimination half-life (t1/2) and decreased plasma concentrations of these compounds. Subchronic administration produced a slight decrease in t1/2 and an increase in plasma concentration of the major metabolite, (2S,6S;2R,6R)-hydroxynorketamine, and produced significant increases in the plasma concentrations of the (2S,6R;2R,6S)-hydroxynorketamine and (2S,4R;2R,4S)-hydroxynorketamine metabolites. The metabolism of (R,S)-Ket predominately occurs via two microsomal enzyme-mediated pathways: (R,S)-Ket⇒(R,S)-norketamine⇒(2S,6S;2R,6R)-hydroxynorketamine and (2S,4R;2R,4S)-hydroxynorketamine and the (R,S)-Ket⇒(2S,6R;2R,6S)-hydroxyketamine⇒(2S,6R;2R,6S)-hydroxynorketamine and (2S,6S;2R,6R)-hydroxynorketamine. The results indicate that the activity of both metabolic pathways are increased by subchronic administration of (R,S)-Ket producing new metabolite patterns and potential differences in clinical effects. PMID:27017097

  12. Health Effects of Subchronic Inhalation of Simulated Downwind Coal Combustion Emissions

    SciTech Connect

    Joe Mauderly

    2009-01-07

    The purpose of this project was to conduct a comprehensive laboratory-based evaluation of selected respiratory and cardiac health hazards of subchronic (up to 6 months) inhalation of simulated key components of 'downwind plume' emissions of coal combustion. This project was performed as an integral part of a joint government-industry program termed the 'National Environmental Respiratory Center' (NERC), which is aimed at disentangling the roles of different physical-chemical air pollutants and their sources in the health effects associated statistically with air pollution. The characterization of the exposure atmosphere and the health assays were identical to those employed in the NERC protocols used to evaluate other pollution source emissions, such as diesel, gasoline, and wood combustion. The project had two phases, each encompassing multiple tasks. Guidelines for the composition of the exposure atmosphere were set by consensus of an expert workshop. Development of the capability to generate the exposure atmosphere and pilot studies of the comparative exposure composition using two coal types were accomplished in Phase 1. In Phase 2, the toxicological study was conducted using Powder River Basin Sub-bituminous coal. NETL provided 50% support for the work in Phase 1 and had intended to provide 20% support for the work in Phase 2. Phase 1 is completed and Phase 2 is in the final stages. All animal exposures were completed without incident, and the composition of the exposure atmospheres met the targets. All of the health sample collections are completed, but some samples remain to be analyzed. Data summaries and final statistical analysis of results remain to be completed. The goal is to submit all publications before the end of FY-08. Repeated exposure to simulated downwind coal emissions caused some significant health effects, but the number of effects tended to be fewer than those caused by the other NERC exposures (diesel and gasoline emissions and hardwood

  13. Strategies to assess systemic exposure of chemicals in subchronic/chronic diet and drinking water studies

    SciTech Connect

    Saghir, Shakil A. . E-mail: ssaghir@dow.com; Mendrala, Alan L.; Bartels, Michael J.; Day, Sue J.; Hansen, Steve C.; Sushynski, Jacob M.; Bus, James S.

    2006-03-15

    Strategies were developed for the estimation of systemically available daily doses of chemicals, diurnal variations in blood levels, and rough elimination rates in subchronic feeding/drinking water studies, utilizing a minimal number of blood samples. Systemic bioavailability of chemicals was determined by calculating area under the plasma concentration curve over 24 h (AUC-24 h) using complete sets of data ({>=}5 data points) and also three, two, and one selected time points. The best predictions of AUC-24 h were made when three time points were used, corresponding to C {sub max}, a mid-morning sample, and C {sub min}. These values were found to be 103 {+-} 10% of the original AUC-24 h, with 13 out of 17 values ranging between 96 and 105% of the original. Calculation of AUC-24 h from two samples (C {sub max} and C {sub min}) or one mid-morning sample afforded slightly larger variations in the calculated AUC-24 h (69-136% of the actual). Following drinking water exposure, prediction of AUC-24 h using 3 time points (C {sub max}, mid-morning, and C {sub min}) was very close to actual values (80-100%) among mice, while values for rats were only 63% of the original due to less frequent drinking behavior of rats during the light cycle. Collection and analysis of 1-3 blood samples per dose may provide insight into dose-proportional or non-dose-proportional differences in systemic bioavailability, pointing towards saturation of absorption or elimination or some other phenomenon warranting further investigation. In addition, collection of the terminal blood samples from rats, which is usually conducted after 18 h of fasting, will be helpful in rough estimation of blood/plasma half-life of the compound. The amount of chemical(s) and/or metabolite(s) in excreta and their possible use as biomarkers in predicting the daily systemic exposure levels are also discussed. Determining these parameters in the early stages of testing will provide critical information to improve the

  14. Transcriptional responses in the rat nasal epithelium following subchronic inhalation of naphthalene vapor

    SciTech Connect

    Clewell, H.J. Efremenko, A.; Campbell, J.L.; Dodd, D.E.; Thomas, R.S.

    2014-10-01

    Male and female Fischer 344 rats were exposed to naphthalene vapors at 0 (controls), 0.1, 1, 10, and 30 ppm for 6 h/d, 5 d/wk, over a 90-day period. Following exposure, the respiratory epithelium and olfactory epithelium from the nasal cavity were dissected separately, RNA was isolated, and gene expression microarray analysis was conducted. Only a few significant gene expression changes were observed in the olfactory or respiratory epithelium of either gender at the lowest concentration (0.1 ppm). At the 1.0 ppm concentration there was limited evidence of an oxidative stress response in the respiratory epithelium, but not in the olfactory epithelium. In contrast, a large number of significantly enriched cellular pathway responses were observed in both tissues at the two highest concentrations (10 and 30 ppm, which correspond to tumorigenic concentrations in the NTP bioassay). The nature of these responses supports a mode of action involving oxidative stress, inflammation and proliferation. These results are consistent with a dose-dependent transition in the mode of action for naphthalene toxicity/carcinogenicity between 1.0 and 10 ppm in the rat. In the female olfactory epithelium (the gender/site with the highest incidences of neuroblastomas in the NTP bioassay), the lowest concentration at which any signaling pathway was significantly affected, as characterized by the median pathway benchmark dose (BMD) or its 95% lower bound (BMDL) was 6.0 or 3.7 ppm, respectively, while the lowest female olfactory BMD values for pathways related to glutathione homeostasis, inflammation, and proliferation were 16.1, 11.1, and 8.4 ppm, respectively. In the male respiratory epithelium (the gender/site with the highest incidences of adenomas in the NTP bioassay), the lowest pathway BMD and BMDL were 0.4 and 0.3 ppm, respectively, and the lowest male respiratory BMD values for pathways related to glutathione homeostasis, inflammation, and proliferation were 0.5, 0.7, and 0.9 ppm

  15. Hepatotoxicity Induced by Subchronic Exposure of Fluoride and Chlorpyrifos in Wistar Rats: Mitigating Effect of Ascorbic Acid.

    PubMed

    Raina, Rajinder; Baba, Naseer Ahmad; Verma, Pawan K; Sultana, Mudasir; Singh, Maninder

    2015-08-01

    The aim of the study was to investigate the ameliorative properties of ascorbic acid against the subchronic effect of co-exposure of fluoride (F) and chlorpyrifos (CPF) on oxidative damage markers such as lipid peroxidation (MDA) and antioxidant defense system in the liver of adult Wistar rats. The animal groups were provided with either vehicle or ascorbic acid (60 mg/kg, b.w.) or NOAEL dose of fluoride (1 ppm) or CPF (1 mg/kg, b.w.) or ten times of such doses orally alone and in combination or pre-treated with ascorbic acid along with co-exposure of F and CPF every consecutive day for 28 days. Hepatic damage marker analysis in blood revealed that aspartate and alanine aminotransferases, alkaline phosphatase, and lactate dehydrogenase were significantly (P < 0.05) increased with single or combined exposure of F or CPF at either dose levels. Significant increased oxidative damage of hepatocytes as indicated by increased MDA levels with decrease in tissue ascorbate and free radical scavenging enzymes like catalase, superoxide dismutase, and glutathione peroxidase was observed in groups treated with either F or CPF as well as in combinedly treated animals as compared to control animals. Supplementation of ascorbic acid restored the hepatic specific marker enzymes in blood following co-exposure of F and CPF at lower doses which were otherwise increased in the F and CPF co-exposed rats. The results show that ascorbic acid supplementation with F and CPF prevents or diminishes the hepatic damage in rats co-exposed to toxicants and may act as a putative protective agent against toxicant-induced liver tissue injury. PMID:25669166

  16. Norfloxacin—Toxicity for Zebrafish (Danio rerio) Focused on Oxidative Stress Parameters

    PubMed Central

    Bartoskova, Marta; Dobsikova, Radka; Stancova, Vlasta; Pana, Ondrej; Zivna, Dana; Plhalova, Lucie; Blahova, Jana; Marsalek, Petr

    2014-01-01

    The aim of the study was to investigate the effects of subchronic exposure of zebrafish (Danio rerio) to a fluoroquinolone norfloxacin, using selected oxidative stress parameters as a target. Toxicity tests were performed on zebrafish according to the OECD Guidelines number 203 and number 215. In the Subchronic Toxicity Test, a significant (P < 0.01) increase in the activity of glutathione peroxidase, glutathione S-transferase, and catalase was found. In the test, norfloxacin did not affect lipid peroxidation and catalytic activity of glutathione reductase. From the results, we can conclude that norfloxacin has a negative impact on specific biochemical processes connected with the production of reactive oxygen species in fish tested. PMID:24783212

  17. 1H NMR-based metabonomic analysis of the serum and urine of rats following subchronic exposure to dichlorvos, deltamethrin, or a combination of these two pesticides.

    PubMed

    Wang, Hui-Ping; Liang, Yu-Jie; Sun, Ying-Jian; Chen, Jia-Xiang; Hou, Wei-Yuan; Long, Ding-Xin; Wu, Yi-Jun

    2013-05-25

    Metabonomic analysis, clinical chemical analysis and histopathology were used to investigate the toxic effects of subchronic exposure to dichlorvos, deltamethrin, and a combination of these two pesticides, in rats. Weight loss, hind limb weakness and histopathological changes in kidney tissue were only observed in rats exposed to high doses of deltamethrin, or a combination of deltamethrin and dichlorvos. Urinary metabonomic analysis indicated that exposure to a mixture of dichlorvos and deltamethrin was followed by increases in urinary lactate, dimethylamine, N-glycoprotein (NAC) and glycine similar to those observed in rats treated with either dichlorvos or deltamethrin alone. Serum metabonomic analysis suggests that dichlorvos induced an increase in lactate and alanine and a decrease in dimethylglycine (DMG), NAC and very low- and low-density lipoprotein (VLDL/LDL). High levels of lactate and low levels of NAC and VLDL/LDL were observed in the deltamethrin treatment group. Treating rats with a mixture of dichlorvos and deltamethrin caused an increase in serum lactate, trimethylamine-N-oxide (TMAO), choline and alanine, with the highest levels of these metabolites observed in those that received the highest dose. Exposure to a mixture of dichlorvos and deltamethrin also resulted in a decrease in serum acetone, DMG, NAC, and VLDL/LDL. Changes in serum TMAO, alanine, choline and acetone in this treatment group were higher than in rats treated with either dichlorvos or deltamethrin. These results suggest that exposing rats to subchronic doses of dichlorvos, deltamethrin, or a combination of these pesticides, disrupted the energy metabolism of the liver and reduced kidney function. PMID:23566885

  18. Chronic toxicity of environmental contaminants: sentinels and biomarkers.

    PubMed Central

    LeBlanc, G A; Bain, L J

    1997-01-01

    Due to the use of a limited number of species and subchronic exposures, current ecological hazard assessment processes can underestimate the chronic toxicity of environmental contaminants resulting in adverse responses of sentinel species. Several incidences where sentinel species have responded to the effects of chronic exposure to ambient levels of environmental contaminants are discussed, including the development of neoplasia in fish, immunosuppression in marine mammals, pseudohermaphrodism in invertebrates, teratogenicity in amphibians, and aberrations in the sexual development of fish and reptiles. Biomarkers of chronic toxicity, including DNA mutations, alterations in specific protein and mRNA levels, and perturbations in metabolism, are presented. The incorporation of appropriate surrogate species and biomarkers of chronic toxicity into standard toxicity characterizations is proposed as a means of significantly refining the ecological hazard assessment process. PMID:9114278

  19. Damascenine induced hepatotoxicity and nephrotoxicity in mice and in vitro assessed human erythrocyte toxicity

    PubMed Central

    Khettal, Bachra; Tir, Lydia; Boudrioua, Souad

    2015-01-01

    Nigella damascena seed is characterized by the presence of the major alkaloid, damascenine and its related metabolites. To our knowledge, no detailed subchronic toxicological assessment of damascenine (DA) has been reported. The present study evaluated the potential toxicity of DA in vivo after sub-chronic intraperitoneal (i.p) administration in mice and in vitro following human erythrocyte hemolysis. In vivo, a total of 48 adult male and female Swiss albino mice were used in a sub-chronic toxicity study. The mice received intraperitoneally two doses of DA (20 and 100 mg/kg) for 28 days. Food intake, body weight and central body temperature were measured during the experiment. After completion of drug treatment, biochemical and histological analyses were performed. No mortality was observed in any of the treatment groups of mice, showing no toxic effects during the study. Neither were biochemical parameters altered; no significant differences were observed concerning glucose, bilirubin, aspartate transaminase (AST), alanine aminotransferase (ALT), urea, and creatinine parameters. No histopathological alterations were found in kidney and liver structures. In vitro, we focused on the human erythrocyte hemolytic process in the presence of several concentrations of DA. High level concentration of 1 000 μg/ml of DA revealed normal cell shapes and absence of hemolysis and deformation. PMID:27486370

  20. Damascenine induced hepatotoxicity and nephrotoxicity in mice and in vitro assessed human erythrocyte toxicity.

    PubMed

    Bouguezza, Yacine; Khettal, Bachra; Tir, Lydia; Boudrioua, Souad

    2015-09-01

    Nigella damascena seed is characterized by the presence of the major alkaloid, damascenine and its related metabolites. To our knowledge, no detailed subchronic toxicological assessment of damascenine (DA) has been reported. The present study evaluated the potential toxicity of DA in vivo after sub-chronic intraperitoneal (i.p) administration in mice and in vitro following human erythrocyte hemolysis. In vivo, a total of 48 adult male and female Swiss albino mice were used in a sub-chronic toxicity study. The mice received intraperitoneally two doses of DA (20 and 100 mg/kg) for 28 days. Food intake, body weight and central body temperature were measured during the experiment. After completion of drug treatment, biochemical and histological analyses were performed. No mortality was observed in any of the treatment groups of mice, showing no toxic effects during the study. Neither were biochemical parameters altered; no significant differences were observed concerning glucose, bilirubin, aspartate transaminase (AST), alanine aminotransferase (ALT), urea, and creatinine parameters. No histopathological alterations were found in kidney and liver structures. In vitro, we focused on the human erythrocyte hemolytic process in the presence of several concentrations of DA. High level concentration of 1 000 μg/ml of DA revealed normal cell shapes and absence of hemolysis and deformation. PMID:27486370

  1. GLYX-13 (rapastinel) ameliorates subchronic phencyclidine- and ketamine-induced declarative memory deficits in mice

    PubMed Central

    Rajagopal, Lakshmi; Burgdorf, Jeffrey S.; Moskal, Joseph R.; Meltzer, Herbert Y.

    2016-01-01

    GLYX-13 (rapastinel), a tetrapeptide (Thr-Pro-Pro-Thr-amide), has been reported to have fast acting antidepressant properties in man based upon its N-methyl-d-aspartate receptor (NMDAR) glycine site functional partial agonism. Ketamine, a non-competitive NMDAR antagonist, also reported to have fast acting antidepressant properties, produces cognitive impairment in rodents and man, whereas rapastinel has been reported to have cognitive enhancing properties in rodents, without impairing cognition in man, albeit clinical testing has been limited. The goal of this study was to compare the cognitive impairing effects of rapastinel and ketamine in novel object recognition (NOR), a measure of declarative memory, in male C57BL/6J mice treated with phencyclidine (PCP), another NMDAR noncompetitive antagonist known to severely impair cognition, in both rodents and man. C57BL/6J mice given a single dose or subchronic ketamine (30 mg/kg. i.p.) showed acute or persistent deficits in NOR, respectively. Acute i.v. rapastinel (1.0 mg/kg), did not induce NOR deficit. Pre-treatment with rapastinel significantly prevented acute ketamine-induced NOR deficit. Rapastinel (1.0 mg/kg, but not 0.3 mg/kg, iv) significantly reversed both subchronic ketamine- and subchronic PCP-induced NOR deficits. Rapastinel also potentiated the atypical antipsychotic drug with antidepressant properties, lurasidone, to restore NOR in subchronic ketamine-treated mice. These findings indicate that rapastinel, unlike ketamine, does not induce a declarative memory deficit in mice, and can prevent or reverse the ketamine-induced NOR deficit. Further study is required to determine if these differences translate during clinical use of ketamine and rapastinel as fast acting antidepressant drugs and if rapastinel could have non-ionotropic effects as an add-on therapy with antipsychotic/antidepressant medications. PMID:26632337

  2. Evaluation of the toxic properties of naturally weathered Exxon Valdez crude oil to surrogate wildlife species

    SciTech Connect

    Stubblefield, W.A.; Hancock, G.A.; Ford, W.H.; Prince, H.H.; Ringer, R.K.

    1995-12-31

    The toxic properties of naturally weathered Exxon Valdez crude oil (WEVC) to avian and mammalian wildlife species were evaluated using the surrogate species, mallard duck, Anas platyrhynchos, and European ferret, Mustela putorius. This study was conducted to evaluate the potential for toxic (rather than physical) injury to wildlife species that may have been exposed to WEVC, either through external contact or through dietary uptake. Previous studies have assessed the toxicity of unweathered crude oils, including Alaska North Slope Crude, but little information exists regarding the toxicity of a naturally weathered crude oil, typical of that encountered following a spill. A battery of laboratory toxicity tests was conducted, in compliance with standard and published test procedures, to evaluate acute and subchronic toxicity of WEVC. These included tests of food avoidance, reproductive effects, and direct eggshell application toxicity. Naturally weathered EVC, recovered postspill from Prince William Sound, was used as the test material. 36 refs., 7 figs., 4 tabs.

  3. Reversal of social deficits by subchronic oxytocin in two autism mouse models.

    PubMed

    Teng, Brian L; Nikolova, Viktoriya D; Riddick, Natallia V; Agster, Kara L; Crowley, James J; Baker, Lorinda K; Koller, Beverly H; Pedersen, Cort A; Jarstfer, Michael B; Moy, Sheryl S

    2016-06-01

    Social deficits are a hallmark feature of autism spectrum disorder (ASD) and related developmental syndromes. Although there is no standard treatment for social dysfunction, clinical studies have identified oxytocin as a potential therapeutic with prosocial efficacy. We have previously reported that peripheral oxytocin treatment can increase sociability and ameliorate repetitive stereotypy in adolescent mice from the C58/J model of ASD-like behavior. In the present study, we determined that prosocial oxytocin effects were not limited to the adolescent period, since C58/J mice, tested in adulthood, demonstrated significant social preference up to 2 weeks following subchronic oxytocin treatment. Oxytocin was also evaluated in adult mice with underexpression of the N-methyl-d-aspartate receptor NR1 subunit (encoded by Grin1), a genetic model of autism- and schizophrenia-like behavior. Subchronic oxytocin had striking prosocial efficacy in male Grin1 knockdown mice; in contrast, chronic regimens with clozapine (66 mg/kg/day) or risperidone (2 mg/kg/day) failed to reverse deficits in sociability. Neither the subchronic oxytocin regimen, nor chronic treatment with clozapine or risperidone, reversed impaired prepulse inhibition in the Grin1 knockdown mice. Overall, these studies demonstrate oxytocin can enhance sociability in mouse models with divergent genotypes and behavioral profiles, adding to the evidence that this neurohormone could have therapeutic prosocial efficacy across a spectrum of developmental disorders. PMID:26748053

  4. Sub-chronic administration of diphenyl diselenide potentiates cadmium-induced testicular damage in mice.

    PubMed

    Santos, Francielli W; Graça, Dominguita L; Zeni, Gilson; Rocha, João B T; Weis, Simone N; Favero, Alexandre M; Nogueira, Cristina W

    2006-10-01

    Sub-chronic cadmium (Cd) exposure causes testicular damage in mice. The mode of action may involve oxidative stress and especially lipid peroxidation. The present study has monitored the pathogenesis of testicular damage during sub-chronic Cd exposure and has evaluated the potential protective effect of antioxidant therapy with diphenyl diselenide (PhSe)(2). Male mice were dosed with 2.5 mg/kg CdCl(2) (2.5 mg/kg) with or without (PhSe)(2) (5 micromol/kg) at 30 min post-exposure using a model of five weekly subcutaneous injections. Histological evaluation of the testis was performed across a 4 week test period. Animals exposed to CdCl(2) and CdCl(2) plus (PhSe)(2) displayed a reduction in body weight gain and testicular weight. Progressive damage and histolopathological changes in the testis were not remedied with, but rather were potentiated by, (PhSe)(2) therapy. We conclude that (PhSe)(2) enhances testicular injury in an animal model for sub-chronic Cd exposure mice. PMID:16472969

  5. EPA's Reanalysis of Key Issues Related to Dioxin Toxicity and Response to NAS Comments (External Review Draft)

    EPA Science Inventory

  1. Subchronic inhalation exposure of rats to Libby amphibole and amosite asbestos: Effects at 1 and 3 months post exposure#

    EPA Science Inventory

    Increased asbestosis, lung cancer, and mesothelioma rates are evident in humans after exposures to Libby amphibole (LA). To support dosimetry model development and compare potency, a subchronic nose-only inhalation study (6 hr/d, 5 d/wk, 13 wk) was conducted in male F344 rats. Ra...

  2. SUBCHRONIC ENDOTOXIN INHALATION CAUSES CHRONIC AIRWAY DISEASE IN ENDOTOXIN-SENSITIVE BUT NOT ENDOTOXIN-RESISTANT MICE

    EPA Science Inventory

    SUBCHRONIC ENDOTOXIN INHALATION CAUSES CHRONIC AIRWAY DISEASE IN ENDOTOXIN-SENSITIVE BUT NOT ENDOTOXIN-RESISTANT MICE. D. M. Brass, J. D. Savov, *S. H. Gavett, ?C. George, D. A. Schwartz. Duke Univ Medical Center Durham, NC, *U.S. E.P.A. Research Triangle Park, NC, ?Univ of Iowa,...

  3. Subchronic Inhalation Exposure of Rats to Libby Amphibole and Amosite Asbestos: Effects at 18 Months Post Exposure

    EPA Science Inventory

    Increased asbestosis, lung cancer, and mesothelioma rates are evident after exposures to Libby amphibole (LA). To support dosimetry model development and compare potency, a subchronic nose-only inhalation study (6 hr/d, 5 d/wk, 13 wk) was conducted in male F344 rats. Rats were ex...

  4. EFFECTS OF SUBCHRONIC EXPOSURES TO CONCENTRATED AMBIENT PARTICLES: VII. DEGENERATION OF DOPAMINERGIC NEURONS IN APO E-/- MICE.

    EPA Science Inventory

    This research describes the neuropathological consequences of subchronic exposure to particulate matter. A genetically modified animal strain (Apo E-/-) which expresses high levels of oxidative stress was exposed to ambient NYC air for 4-6 months. The brains of these animals were...

  5. Developmental Toxicity

    EPA Science Inventory

    This chapter provides an overview the developmental toxicity resulting from exposure to perfluorinated alkyl acids (PFAAs). The majority of studies of PFAA-induced developmental toxicity have examined effects of perfluorooctane sulfonate (PFOS) or perfluorooctanoic acid (PFOA) a...

  6. Toxicity Studies.

    PubMed

    2016-01-01

    Toxicity studies in the animal models are done to determine the dose level recommended for the treatment of disease as drug. This guideline enables the characterization of adverse effects following repeated daily inhalation exposure to a test. This chapter includes oral and dermal toxicity studies which are discussed as per OECD guidelines. Both acute and subacute toxicity studies are given special emphasis. PMID:26939270

  7. Deposition, clearance, and shortening of Kevlar para-aramid fibrils in acute, subchronic, and chronic inhalation studies in rats.

    PubMed

    Kelly, D P; Merriman, E A; Kennedy, G L; Lee, K P

    1993-10-01

    The deposition and clearance of lung-deposited Kevlar para-aramid fibrils (subfibers) have been investigated as part of a subchronic and chronic inhalation toxicity testing program. Fibrils recovered from lung tissue in para-aramid-exposed Sprague-Dawley rats were microscopically counted and measured after exposures to airborne fibrils which were about 12 microns median length (ML) and < 0.3 micron median diameter. In each of three studies lung-recovered fibrils were progressively shorter with increasing residence time in the lungs. Twenty-eight days after a single 6-hr exposure at 400 respirable fibrils per cubic centimeter (f/cm3) the ML of recovered fibrils decreased to about 5 microns. Twenty-four months after a 3-week exposure to 25 or 400 f/cm3, fibrils reached about 2 microns ML. After 2 years of continuous exposure at 2.5, 25, or 100 f/cm3 or 1 year exposure plus 1 year recovery at 400 f/cm3, fibril ML approached 4 microns. In the 2-year study, the lung-fiber accumulation rate/exposure concentration was similar for the three highest concentrations and was about 3 x greater than that seen at 2.5 f/cm3, indicating that concentrations of about 25 f/cm3 or more may overwhelm clearance mechanisms. Time required for fibrils to be reduced to < 5 microns in the lung was markedly less at lower exposure concentration and shorter exposure time. The primary shortening mechanism is proposed to be long fibril cutting by enzymatic attack at fibril defects. However, length-selective fibril deposition and clearance may contribute to shortening in the first few days after exposure. The enzymatic cutting hypothesis is supported by measured increases in numbers of short fibers following cessation of exposures, continued shortening of the fibril length distribution up to 2 years following exposure, and in vitro fibril shortening after 3 months in a proteolytic enzyme preparation. The conclusion is that para-aramid fibrils are less durable in the lungs of rats than expected from

  8. Absence of adverse effects of sodium metabisulphite in manufactured biscuits: results of subacute (28-days) and subchronic (85-days) feeding studies in rats.

    PubMed

    Ribera, D; Jonker, D; Narbonne, J F; O'Brien, J; Antignac, E

    2001-02-01

    Sulphites are extensively used in the food and drinks industry. Their toxicity has been previously evaluated by addition to the diet or drinking water of laboratory animals. Because interactions between sulphites and food constituents occur, the present work was conducted to determine the subacute and subchronic toxicity of sulphite-bound compounds in a finished product: manufactured biscuits. The studies were performed on Sprague Dawley, rats for 28 and 85 days of dietary exposure. Diets were prepared from sulphited or untreated (controls) biscuits with the addition of sugar, protein, vitamins and minerals according to the nutritional requirements of the animals. Groups of 10 male and 10 female rats were administered diets containing sulphited biscuits at levels of 0, 10, 35 and 75%, corresponding to 10-15, 35-45, 150-170 and 310-340 mg SO2/kg diet. In both studies, no death or clinical abnormalities were reported. Growth rate, food consumption and food conversion efficiency were not affected by treatment. No dose-related changes were observed for haematology, clinical chemistry, ocular examination, renal-function, urinalysis, organ weights or gross and microscopic examinations. The liver concentrations of vitamins A, B1, C and E were not significantly changed except for an increase in vitamin E in high-dose males after 28 days' exposure. Based on these data, the no-observed-adverse-effect level (NOAEL) of sulphites in baked biscuits was judged to be 310 mg SO2/kg diet or 25 mg/kg body weight/day. PMID:11288907

  9. Toxic action/toxicity.

    PubMed

    Hathway, D E

    2000-02-01

    Some six or so physiological systems, essential to normal mammalian life, are involved in poisoning; an intoxication that causes severe injury to any one of them could be life threatening. Reversible chemical reactions showing Scatchard-type binding are exemplified by CO, CN- and cyclodiene neurotoxin insecticide intoxications, and by antigen-antibody complex formation. Haemoglobin (Hb) molecular biology accounts for the allosteric co-operativity and other characteristics of CO poisoning, CN- acts as a powerful cytochrome oxidase inhibitor, and antigen binding in a deep antibody cleft between two domains equipped with epitopes for antigen-binding groups explains hapten-specific immune reactions. Covalent chemical reactions with second-order (SN2) kinetics characterize Hg and Cd poisonings, the reactions of organophosphates and phosphonates with acetylcholinesterase and neurotoxic esterase and the reaction sequence whereby Paraquat accepts electrons and generates superoxide under aerobic conditions. Indirect carcinogens require cytochrome P450 activation to form DNA adducts in target-organ DNA and cause cancer, but a battery of detoxifying enzymes clustered with the P450 system must be overcome. Thus, S-metabolism competes ineffectively with target DNA for reactive vinyl chloride (VC) metabolites, epoxide hydrolase is important to the metabolism and carcinogenicity of alfatoxins and polycyclic aromatic hydrocarbons (benzo[a]pyrene, etc.), and the non-toxic 2-naphthylhydroxylamine N-glucuronide acts as a transport form in 2-naphthylamine bladder cancer. VC liver-cancer pathogenesis is explicable in terms of the presence of the glutathione S-transferase detoxifying system in hepatocytes and its absence from the fibroblastic elements, and of the VC concentrations reaching the liver by different administrative routes. In VC carcinogenicity, chemical reactions give imidazo-cyclization products with nucleoside residues of target DNA, and in benzene leukaemia, Z

  10. Ninety-day oral toxicity studies on two genetically modified maize MON810 varieties in Wistar Han RCC rats (EU 7th Framework Programme project GRACE).

    PubMed

    Zeljenková, Dagmar; Ambrušová, Katarína; Bartušová, Mária; Kebis, Anton; Kovrižnych, Jevgenij; Krivošíková, Zora; Kuricová, Miroslava; Líšková, Aurélia; Rollerová, Eva; Spustová, Viera; Szabová, Elena; Tulinská, Jana; Wimmerová, Soňa; Levkut, Mikuláš; Révajová, Viera; Ševčíková, Zuzana; Schmidt, Kerstin; Schmidtke, Jörg; La Paz, Jose Luis; Corujo, Maria; Pla, Maria; Kleter, Gijs A; Kok, Esther J; Sharbati, Jutta; Hanisch, Carlos; Einspanier, Ralf; Adel-Patient, Karine; Wal, Jean-Michel; Spök, Armin; Pöting, Annette; Kohl, Christian; Wilhelm, Ralf; Schiemann, Joachim; Steinberg, Pablo

    2014-12-01

    The GMO Risk Assessment and Communication of Evidence (GRACE; www.grace-fp7.eu ) project is funded by the European Commission within the 7th Framework Programme. A key objective of GRACE is to conduct 90-day animal feeding trials, animal studies with an extended time frame as well as analytical, in vitro and in silico studies on genetically modified (GM) maize in order to comparatively evaluate their use in GM plant risk assessment. In the present study, the results of two 90-day feeding trials with two different GM maize MON810 varieties, their near-isogenic non-GM varieties and four additional conventional maize varieties are presented. The feeding trials were performed by taking into account the guidance for such studies published by the EFSA Scientific Committee in 2011 and the OECD Test Guideline 408. The results obtained show that the MON810 maize at a level of up to 33 % in the diet did not induce adverse effects in male and female Wistar Han RCC rats after subchronic exposure, independently of the two different genetic backgrounds of the event. PMID:25270621

  11. Anemia and genotoxicity induced by sub-chronic intragastric treatment of rats with titanium dioxide nanoparticles.

    PubMed

    Grissa, Intissar; Elghoul, Jaber; Ezzi, Lobna; Chakroun, Sana; Kerkeni, Emna; Hassine, Mohsen; El Mir, Lassaad; Mehdi, Meriem; Ben Cheikh, Hassen; Haouas, Zohra

    2015-12-01

    Titanium dioxide nanoparticles (TiO2 NPs) are widely used for their whiteness and opacity. We investigated the hematological effects and genotoxicity of anatase TiO2 NPs following sub-chronic oral gavage treatment. TiO2-NPs were characterized by X-ray diffractometry (XRD), X-ray photoelectron spectroscopy (XPS), and transmission electron microscopy (TEM). Wistar rats were treated with anatase TiO2 NPs by intragastric administration for 60 days. Hematological analysis showed a significant decrease in RBC and HCT and a significant increase in MCV, PLT, MPV and WBC at higher doses. Furthermore, abnormally shaped red cells, sometimes containing micronuclei, and hyper-segmented neutrophil nuclei were observed with TiO2 NPs treatment. The micronucleus test revealed damage to chromosomes in rat bone marrow at 100 and 200mg/kg bw; the comet assay showed significant DNA damage at the same doses. PMID:26653980

  12. The relationship between thermodynamics and the toxicity of gadolinium complexes.

    PubMed

    Cacheris, W P; Quay, S C; Rocklage, S M

    1990-01-01

    The suitability of gadolinium complexes as magnetic resonance imaging contrast agents depends on a number of factors. A thermodynamic relationship to toxicity exists if one assumes that the chemotoxicity of the intact complex is minimal but that the toxicity of the components of the complex (free metal and uncomplexed ligands) is substantial. Release of Gd3+ from the complex is responsible for the toxicity associated with gadolinium complexes; this release appears to be a consequence of Zn2+, Cu2+, and Ca2+ transmetallation in vivo. This hypothesis is supported by acute toxicity experiments, which demonstrate that despite a 50-fold range of LD50 values for four Gd complexes, all become lethally toxic when they release precisely the same quantity of Gd3+, and by subchronic rodent toxicity experiments, which demonstrate a set of gross and microscopic findings similar to those known to be caused by Zn2+ deficiency. Finally, this hypothesis predicts that subtle changes in formulation can further enhance the intrinsic safety of these complexes. PMID:2118207

  13. Sub-chronic iron overload triggers oxidative stress development in rat brain: implications for cell protection.

    PubMed

    Piloni, Natacha E; Perazzo, Juan C; Fernandez, Virginia; Videla, Luis A; Puntarulo, Susana

    2016-02-01

    This work was aimed to test the hypothesis that sub-chronic administration of iron-dextran (Fe-dextran) (six doses of 50 mg Fe-dextran/kg) to rats triggers a transient oxidative stress in brain and mechanisms of cellular antioxidant defence. After 2 h of administration of the 6th dose, a significant increase of total Fe, the labile Fe pool (LIP), the lipid radical (LR(•))/α-tocopherol (α-T) content ratio were observed, as compared to values in control brain homogenates. The ascorbyl radical (A(•))/ascorbate (AH(-)) content ratio and the oxidation rate of 2',7'-dichlorodihidrofluorescein (DCFH-DA) were significantly higher in Fe-dextran treated rats, as compared to values in brain from control rats after 4 h treatment. An increase in both catalase (CAT) and superoxide dismutase (SOD) activity was observed at 8 and 1-2 h, respectively. No significant changes were detected in the nuclear factor-κB (NF-κB) levels in nuclear extracts from rat brains after 1-8 h of Fe-dextran administration. After 2 h of Fe administration Fe concentration in cortex, striatum and hippocampus was significantly increased as compared to the same areas from control animals. Both, CAT and SOD activities were significantly increased in cortex after Fe administration over control values, without changes in striatum and hippocampus. Taken as a whole, sub-chronic Fe administration enhances the steady state concentration of Fe in the brain LIP that favors the settlement of an initial oxidative stress condition, both at hydrophilic and lipophilic compartments, resulting in cellular protection evidenced by antioxidant enzyme upregulation. PMID:26677163

  14. Sub-chronic agmatine treatment modulates hippocampal neuroplasticity and cell survival signaling pathways in mice.

    PubMed

    Freitas, Andiara E; Bettio, Luis E B; Neis, Vivian B; Moretti, Morgana; Ribeiro, Camille M; Lopes, Mark W; Leal, Rodrigo B; Rodrigues, Ana Lúcia S

    2014-11-01

    Agmatine is an endogenous neuromodulator which, based on animal and human studies, is a putative novel antidepressant drug. In this study, we investigated the ability of sub-chronic (21 days) p.o. agmatine administration to produce an antidepressant-like effect in the tail suspension test and examined the hippocampal cell signaling pathways implicated in such an effect. Agmatine at doses of 0.01 and 0.1 mg/kg (p.o.) produced a significant antidepressant-like effect in the tail suspension test and no effect in the open-field test. Additionally, agmatine (0.001-0.1 mg/kg, p.o.) increased the phosphorylation of protein kinase A substrates (237-258% of control), protein kinase B/Akt (Ser(473)) (116-127% of control), glycogen synthase kinase-3β (Ser(9)) (110-113% of control), extracellular signal-regulated kinases 1/2 (119-137% and 121-138% of control, respectively) and cAMP response elements (Ser(133)) (127-152% of control), and brain-derived-neurotrophic factor (137-175% of control) immunocontent in a dose-dependent manner in the hippocampus. Agmatine (0.001-0.1 mg/kg, p.o.) also reduced the c-jun N-terminal kinase 1/2 phosphorylation (77-71% and 65-51% of control, respectively). Neither protein kinase C nor p38(MAPK) phosphorylation was altered under any experimental conditions. Taken together, the present study extends the available data on the mechanisms that underlie the antidepressant action of agmatine by showing an antidepressant-like effect following sub-chronic administration. In addition, our results are the first to demonstrate the ability of agmatine to elicit the activation of cellular signaling pathways associated with neuroplasticity/cell survival and the inhibition of signaling pathways associated with cell death in the hippocampus. PMID:25161097

  15. Potential Occupational Risks Associated with Pulmonary Toxicity of Carbon Nanotubes

    PubMed Central

    Manke, Amruta; Luanpitpong, Sudjit; Rojanasakul, Yon

    2014-01-01

    Given their remarkable properties, carbon nanotubes (CNTs) have made their way through various industrial and medicinal applications and the overall production of CNTs is expected to grow rapidly in the next few years, thus requiring an additional recruitment of workers. However, their unique applications and desirable properties are fraught with concerns regarding occupational exposure. The concern about worker exposure to CNTs arises from the results of recent animal studies. Short-term and sub-chronic exposure studies in rodents have shown consistent adverse health effects such as pulmonary inflammation, granulomas, fibrosis, genotoxicity and mesothelioma after inhalation or instillation of several types of CNTs. Furthermore, physicochemical properties of CNTs such as dispersion, functionalization and particle size can significantly affect their pulmonary toxicity. Risk estimates from animal studies necessitate implementation of protective measures to limit worker exposure to CNTs. Information on workplace exposure is very limited, however, studies have reported that CNTs can be aerosolized and attain respirable airborne levels during synthesis and processing activities in the workplace. Quantitative risk assessments from sub-chronic animal studies recommend the health-based need to reduce exposures below the recommended exposure limit of 1 µg/m3. Practice of prevention measures including the use of engineering controls, personal protective equipment, health surveillance program, safe handling and use, as well as worker training can significantly minimize worker exposure and improve worker health and safety. PMID:25621290

  16. Ameliorative Effects of Curcumin on Artesunate-Induced Subchronic Toxicity in Testis of Swiss Albino Male Mice

    PubMed Central

    Rajput, Dhrupadsinh K.; Patel, Pragnesh B.; Highland, Hyacinth N.

    2015-01-01

    India is one of the endemic areas where control of malaria has become a formidable task. Artesunate is the current antimalarial drug used to treat malaria, especially chloroquine resistant. The objective of the present study was to investigate the dose-dependent effect of oral administration of artesunate on the oxidative parameters in testes of adult male Swiss albino mice and ameliorative efficacy of curcumin, a widely used antioxidant. An oral dose of 150 mg/kg body weight (bwt; low dose) and 300 mg/kg bwt (high dose) of artesunate was administered for a period of 45 days to male mice, and ameliorative efficacy of curcumin was also assessed. The results revealed that artesunate caused significant alteration in oxidative parameters in dose-dependent manner. Administration of artesunate brought about significant decrease in activities of superoxide dismutase, glutathione, glutathione peroxidase, and glutathione reductase, whereas lipid peroxidation and glutathione-S-transferase activity were found to be significantly increased. The results obtained show that oxidative insult is incurred upon the intracellular antioxidant system of testis tissue by artesunate treatment. Further, administration of curcumin at the dose level of 80 mg/kg bwt along with both doses of artesunate attenuated adverse effects in male mice. PMID:26673878

  17. Acute and subchronic toxicity studies of rats exposed to vapors of methyl mercaptan and other reduced-sulfur compounds.

    PubMed

    Tansy, M F; Kendall, F M; Fantasia, J; Landin, W E; Oberly, R; Sherman, W

    1981-01-01

    Acute inhalation experiments were conducted to determine 24-h LC50 values for adult Sprague-Dawley rats of both sexes exposed to vapors of methyl mercaptan and other reduced-S compounds for 4 h periods. Using calculated gas concentrations, the following LC50 value for each gas and combination was determined: metyhl mercaptan, 675 ppm; dimethyl sulfide, 40,250 ppm; dimethyl disulfide, 805 ppm; hydrogen sulfide, 444 ppm; and an equimolar mixture of methyl mercaptan, dimethyl sulfide, and dimethyl disulfide, 550 ppm. The effects of body and tissue weights, gross metabolic performance, O2 consumption, systolic blood pressure, various blood parameters, and intestinal transit time associated with 3-mo exposures of young adult male rats to chemically verified concentrations of 2, 17, and 57 ppm methyl mercaptan vapor are summarized in this report. No mortality was experienced by any group. Histopathological findings were essentially nil except for microscopic suggestions of liver damage. The most readily apparent phenomenon was the decrease in body weight. Average values of terminal body weights for all exposed groups were lower than that for the sham control group. This difference was significant in the 57 ppm group and followed a statistically significant dose-related trend. PMID:7328716

  18. SUBCHRONIC SENSITIVITY OF ONE-, FOUR-, AND SEVEN-DAY-OLD FATHEAD MINNOW (PIMEPHALES PROMELAS) LARVAE TO FIVE TOXICANTS

    EPA Science Inventory

    The fathead minnow (pimephales promelas) larval survival and growth test was used to evaluate the relative sensitivity of 1-,4-, and 7-d-old larvae to five contaminants, KC1, NaC1, 1-octanol, carbaryl, and benzaldehyde. The no observable effect concentration (NOEC) for survival o...

  19. Acute and Subchronic Toxicity of Inhaled Toluene in Male Long-Evans Rats: Oxidative Stress Markers in Brain

    EPA Science Inventory

    The effects of exposure to volatile organic compounds (VOCs), which are of concern to the EPA, are poorly understood, in part because of insufficient characterization of how human exposure duration impacts VOC effects. Two inhalation studies with multiple endpoints, one acute an...

  20. Toxic Encephalopathy

    PubMed Central

    Kim, Jae Woo

    2012-01-01

    This article schematically reviews the clinical features, diagnostic approaches to, and toxicological implications of toxic encephalopathy. The review will focus on the most significant occupational causes of toxic encephalopathy. Chronic toxic encephalopathy, cerebellar syndrome, parkinsonism, and vascular encephalopathy are commonly encountered clinical syndromes of toxic encephalopathy. Few neurotoxins cause patients to present with pathognomonic neurological syndromes. The symptoms and signs of toxic encephalopathy may be mimicked by many psychiatric, metabolic, inflammatory, neoplastic, and degenerative diseases of the nervous system. Thus, the importance of good history-taking that considers exposure and a comprehensive neurological examination cannot be overemphasized in the diagnosis of toxic encephalopathy. Neuropsychological testing and neuroimaging typically play ancillary roles. The recognition of toxic encephalopathy is important because the correct diagnosis of occupational disease can prevent others (e.g., workers at the same worksite) from further harm by reducing their exposure to the toxin, and also often provides some indication of prognosis. Physicians must therefore be aware of the typical signs and symptoms of toxic encephalopathy, and close collaborations between neurologists and occupational physicians are needed to determine whether neurological disorders are related to occupational neurotoxin exposure. PMID:23251840

  1. Subchronic haloperidol administration decreases aminopeptidase N activity and [Met5]enkephalin metabolism in rat striatum and cortex.

    PubMed

    Konkoy, C S; Waters, S M; Davis, T P

    1996-02-15

    Previously we have shown that subchronic intraperitoneal (i.p.) administration of haloperidol decreases the degradation of [Met5]enkephalin by regional brain slices (Waters et al., 1995, J. Pharmacol. Exp. Ther. 274, 783). In the present study, subchronic (7-day i.p.) administration of haloperidol (1 mg/kg) decreased the accumulation of aminopeptidase-derived fragments Tyr and Gly-Gly-Phe-Met on cortical and striatal slices. The accumulation of Tyr-Gly-Gly, however, was not altered by haloperidol treatment on slices from either region. Further, aminopeptidase N activity was decreased in P2 membranes isolated from either the cortex or striatum of haloperidol-treated animals. These data suggest that the haloperidol-induced decrease in [Met5]enkephalin metabolism results, at least in part, from a reduction in the activity of aminopeptidase N. PMID:8851165

  2. [Toxic polyneuropathies].

    PubMed

    Neundörfer, B

    1992-08-01

    Toxic factors may have damaging effects on the peripheral nerves at different sites: on the axon, on the myelin sheath, on the cell bodies and on the vasa nervorum. The toxic neuropathies can be divided up into polyneuropathies induced by drugs, by industrial, environmental and stimulant poisons. Mostly symmetrical sensory symptoms and signs are the first disturbances, often followed by symmetrical motor pareses. Some polyneuropathies induced by amiodarone, benzene, lead, cimetidine, chloroquine, dapsone, gentamycin, gold, imipramine, hexacarbons, nialamide, penicillin, triorthocresylphosphate and vincristine are primarily dominated by motory losses. Polyneuropathies induced by amitriptyline, ethylene, oxide, lead, chlorprothixene, heroin, hydralazine, methaqualone, nialamide and penicillin show an asymmetrical distribution pattern of the neural losses. In some types of toxic polyneuropathies the cranial nerves and the autonomic nerves are particularly involved. The clinical symptomatology of the most important types of toxic neuropathies are described shortly. The best therapy is, of course, termination of exposure to the toxic substance concerned. PMID:1509644

  3. Genome wide analysis of DNA methylation and gene expression changes in the mouse lung following subchronic arsenate exposure

    EPA Science Inventory

    Alterations in DNA methylation have been proposed as a mechanism for the complex toxicological effects of arsenic. In this study, whole genome DNA methylation and gene expression changes were evaluated in lungs from female mice exposed for 90 days to 50 ppm arsenate (As) in drink...

  4. New magnetostratigraphy for the Olduvai Subchron in the Koobi Fora Formation, northwest Kenya, with implications for early Homo

    NASA Astrophysics Data System (ADS)

    Lepre, Christopher J.; Kent, Dennis V.

    2010-02-01

    A problematic magnetostratigraphy for the Koobi Fora Formation has contributed to debates on the evolutionary implications for early hominin fossils. To address this, 50 independent samples distributed over a nearly 63-m-thick interval were collected from the lower-middle KBS Member type section in fossil collection Area 102, northeast Turkana Basin. Characteristic directions obtained by thermal demagnetization define a coherent magnetostratigraphy that is supported by alternating-field studies on 28 sister specimens and the prior tephrochronological framework. Two long polarity intervals were recognized, each 30-40 m in thickness, and interpreted as the upper part of the normal polarity Olduvai Subchron and the overlying reverse polarity Matuyama Chron. The end Olduvai consists of a normal-reverse-normal polarity sequence occurring over a thickness of at least 1 m but perhaps up to 5 m, suggesting that this subchron has a short reverse interval in its uppermost part. Such a fine-scale structure also has been reported from several other sites, like the Pliocene-Pleistocene boundary and point stratotype section at Vrica, Italy, which serves as a basis for formally delimiting three temporally discrete polarity subintervals for the Olduvai Subchron. These paleomagnetic results that place the upper boundary of the Olduvai at ˜ 48 m above the base of the KBS Member, coupled with published radioisotopic dates, firmly secure the age of partial cranium KNM-ER 3733 in the interval 1.78-1.48 Ma, with an interpolated age of ˜ 1.7 Ma, giving this fossil the most unambiguous numerical-age constraints, as compared to the oldest Homo cranial remains from Europe and Asia. Nonetheless, assured placement of the top of the Olduvai Subchron in the KBS Member is not sufficient in the face of other uncertainties to influence conventional interpretations of the timing and direction for the global dispersal of early Homo erectus.

  5. Memory and brain-derived neurotrophic factor after subchronic or chronic amphetamine treatment in an animal model of mania.

    PubMed

    Fries, Gabriel R; Valvassori, Samira S; Bock, Hugo; Stertz, Laura; Magalhães, Pedro Vieira da Silva; Mariot, Edimilson; Varela, Roger B; Kauer-Sant'Anna, Marcia; Quevedo, João; Kapczinski, Flávio; Saraiva-Pereira, Maria Luiza

    2015-09-01

    Progression of bipolar disorder (BD) has been associated with cognitive impairment and changes in neuroplasticity, including a decrease in serum brain-derived neurotrophic factor (BDNF). However, no study could examine BDNF levels directly in different brain regions after repeated mood episodes to date. The proposed animal model was designed to mimic several manic episodes and evaluate whether the performance in memory tasks and BDNF levels in hippocampus, prefrontal cortex, and amygdala would change after repeated amphetamine (AMPH) exposure. Adult male Wistar rats were divided into subchronic (AMPH for 7 days) and chronic groups (35 days), mimicking manic episodes at early and late stages of BD, respectively. After open field habituation or inhibitory avoidance test, rats were killed, brain regions were isolated, and BDNF mRNA and protein levels were measured by quantitative real-time PCR and ELISA, respectively. AMPH impaired habituation memory in both subchronic and chronic groups, and the impairment was worse in the chronic group. This was accompanied by increased Bdnf mRNA levels in the prefrontal cortex and amygdala region, as well as reduced BDNF protein in the hippocampus. In the inhibitory avoidance, AMPH significantly decreased the change from training to test when compared to saline. No difference was observed between subchronic and chronic groups, although chronically AMPH-treated rats presented increased Bdnf mRNA levels and decreased protein levels in hippocampus when compared to the subchronic group. Our results suggest that the cognitive impairment related to BD neuroprogression may be associated with BDNF alterations in hippocampus, prefrontal cortex, and amygdala. PMID:26026487

  6. 75 FR 28610 - Draft EPA's Reanalysis of Key Issues Related to Dioxin Toxicity and Response to NAS Comments

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-21

    ...EPA is announcing a 90-day public comment period for the external review draft entitled, ``EPA's Reanalysis of Key Issues Related to Dioxin Toxicity and Response to NAS Comments'' (EPA/600/R- 10/038A). This draft report responds to the key recommendations and comments included in the National Academy of Sciences (NAS) 2006 report. In addition, it includes new analyses on potential human......

  7. Acute and environmental toxicity studies with hexazinone

    SciTech Connect

    Kennedy, G.L. Jr.

    1984-08-01

    The acute toxicity of hexazinone, a herbicide intended for general noncropland areas and selected crop uses (alfalfa and sugarcane), has been evaluated to establish proper handling guidelines and to measure its potential impact on the environment. The material is slightly to moderately toxic when given as a single oral dose; its LD50 in male rats is 1690 mg/kg, in male guinea pigs 860 mg/kg, and in male dogs greater than 3400 mg/kg although in the dog emesis prevented accurate quantitation. When the material is administered intraperitoneally, the LD50 in rats is 530 mg/kg. In both studies, no gross or histologic alterations were apparent. Hexazinone is a moderate to severe eye irritant in the rabbit and produced only mild erythema in rabbit skin at 5278 mg/kg, a dose which did not produce lethality or other clinical signs. Subchronic dermal exposures (10 consecutive doses) to rabbits produced increases in serum alkaline phosphatase and glutamic-pyruvic transaminase at the highest levels tested (680 and 770 mg/kg in two separate experiments) with no effects seen at 150 mg/kg. One-hour inhalation exposure of up to 7.48 mg/liter did not produce mortality in rats.

  8. Safety evaluation of pectin-derived acidic oligosaccharides (pAOS): genotoxicity and sub-chronic studies.

    PubMed

    Garthoff, Jossie A; Heemskerk, Suzanne; Hempenius, Rixta A; Lina, Ben A R; Krul, Cyrille A M; Koeman, Jan H; Speijers, Gerrit J A

    2010-06-01

    Pectin-derived acidic oligosaccharides (pAOS) are non-digestible carbohydrates to be used in infant formulae and medical nutrition. To support its safety, the genotoxic potential of pAOS was evaluated. pAOS was not mutagenic in the Ames test. Positive results were obtained in the chromosome aberration test only at highly cytotoxic concentrations. The effects obtained in the mouse lymphoma test were equivocal; pAOS was not mutagenic in vivo. A sub-chronic dietary study, preceded by 4-week parental and in utero exposure phase, investigated general safety. Administration of pAOS did not affect parental health nor pup characteristics. No effects specific for acidic oligosaccharides were observed in the subsequent sub-chronic study. Slight diffuse hyperplasia of epithelial layer of the urinary bladder was noted to result from concurrently elevated urinary sodium, due to high sodium in pAOS, and elevated urinary pH. This phenomenon was confirmed in a mechanistic (sub-chronic) study. In contrast, in rats fed pAOS in combination with NH(4)Cl, an acidifying agent, the induced low urinary pH completely prevented the development of urothelial hyperplasia. Hyperplasia induced by this mechanism in rats is considered not relevant to man. Based on the current knowledge we consider pAOS safe for human consumption under its intended use. PMID:20026148

  9. Effect of chronic and subchronic organic solvents exposure on balance control of workers in plant manufacturing adhesive materials.

    PubMed

    Herpin, Guillaume; Gargouri, Imed; Gauchard, Gérome C; Nisse, Catherine; Khadhraoui, Moncef; Elleuch, Boubaker; Zmirou-Navier, Denis; Perrin, Philippe P

    2009-02-01

    High-level occupational exposure to volatile organic solvents may elicit neurotoxic effects, especially on central and peripheral structures involved in balance ability. Studies on balance control in relation with exposure levels close to the threshold limit values are scarce. This study aimed to assess the neurotoxic effects of chronic and subchronic exposure to organic solvents among workers in plant manufacturing adhesive materials. Balance control was evaluated in 18 subjects, mainly exposed to n-hexane and toluene, with current median exposure levels of 222 and 102 mg/m(3), respectively, and a median exposure duration of 21 years, and in 32 nonexposed controls, using posturography tests with and without sensory conflicting situations. Tests were undergone at the beginning of the work shift (chronic exposure) following a week end, and after 72 h (subchronic exposure). Balance control performance was lower in chronically exposed workers compared to controls, and got worse after subchronic exposure, particularly during situations, where vestibular information was important. Our study suggests that a low-level and prolonged exposure to volatile organic solvents, mainly n-hexane and toluene, in the workplace is associated with deleterious central effects involved in postural regulation. This neurotoxicity is characterized by difficulties to use the most relevant information to control balance, leading to altered management of sensory conflicting situations. PMID:19384580

  10. Strengths and limitations of using repeat-dose toxicity studies to predict effects on fertility.

    PubMed

    Dent, M P

    2007-08-01

    The upcoming European chemicals legislation REACH (Registration, Evaluation, and Authorisation of Chemicals) will require the risk assessment of many thousands of chemicals. It is therefore necessary to develop intelligent testing strategies to ensure that chemicals of concern are identified whilst minimising the testing of chemicals using animals. Xenobiotics may perturb the reproductive cycle, and for this reason several reproductive studies are recommended under REACH. One of the endpoints assessed in this battery of tests is mating performance and fertility. Animal tests that address this endpoint use a relatively large number of animals and are also costly in terms of resource, time, and money. If it can be shown that data from non-reproductive studies such as in-vitro or repeat-dose toxicity tests are capable of generating reliable alerts for effects on fertility then some animal testing may be avoided. Available rat sub-chronic and fertility data for 44 chemicals that have been classified by the European Union as toxic to fertility were therefore analysed for concordance of effects. Because it was considered appropriate to read across data for some chemicals these data sets were considered relevant for 73 of the 102 chemicals currently classified as toxic to reproduction (fertility) under this system. For all but 5 of these chemicals it was considered that a well-performed sub-chronic toxicity study would have detected pathology in the male, and in some cases, the female reproductive tract. Three showed evidence of direct interaction with oestrogen or androgen receptors (linuron, nonylphenol, and fenarimol). The remaining chemicals (quinomethionate and azafenidin) act by modes of action that do not require direct interaction with steroid receptors. However, both these materials caused in-utero deaths in pre-natal developmental toxicity studies, and the relatively low NOAELs and the nature of the hazard identified in the sub-chronic tests provides an alert

  11. Toxic trauma.

    PubMed

    Moles, T M; Baker, D J

    2001-01-01

    Hazardous materials (HAZMAT) carry many inherent dangers. Such materials are distributed widely in industrial and military sites. Toxic trauma (TT) denotes the complex of systemic and organ injury caused by toxic agents. Often, TT is associated with other injuries that also require the application of life-support techniques. Rapid onset of acute respiratory failure and consequent cardiovascular failure are of primary concern. Management of TT casualties is dependent upon the characteristics of the toxic agents involved and on the demographics surrounding the HAZMAT incident. Agents that can produce TT possess two pairs of salient characteristics: (1) causality (toxicity and latency), and (2) EMS system (persistency and transmissibility). Two characteristics of presentations are important: (1) incident presentation, and (2) casualty presentation. In addition, many of these agents complicate the processes associated with anaesthesia and must be dealt with. Failure of recognition of these factors may result in the development of respiratory distress syndromes and multiorgan system failure, or even death. PMID:11513285

  12. Digitalis toxicity

    MedlinePlus

    These are symptoms of digitalis toxicity: Confusion Irregular pulse Loss of appetite Nausea , vomiting , diarrhea Fast heartbeat Vision changes (unusual), including blind spots, blurred vision, changes in how colors look, or ...

  13. Antimony Toxicity

    PubMed Central

    Sundar, Shyam; Chakravarty, Jaya

    2010-01-01

    Antimony toxicity occurs either due to occupational exposure or during therapy. Occupational exposure may cause respiratory irritation, pneumoconiosis, antimony spots on the skin and gastrointestinal symptoms. In addition antimony trioxide is possibly carcinogenic to humans. Improvements in working conditions have remarkably decreased the incidence of antimony toxicity in the workplace. As a therapeutic, antimony has been mostly used for the treatment of leishmaniasis and schistosomiasis. The major toxic side-effects of antimonials as a result of therapy are cardiotoxicity (~9% of patients) and pancreatitis, which is seen commonly in HIV and visceral leishmaniasis co-infections. Quality control of each batch of drugs produced and regular monitoring for toxicity is required when antimonials are used therapeutically. PMID:21318007

  14. Immunosuppression and oxidative stress induced by subchronic exposure to carbosulfan in rat spleen: immunomodulatory and antioxidant role of N-acetylcysteine.

    PubMed

    Dhouib, Ines Bini; Lasram, Mohamed Montassar; Abdeladhim, Maha; Gharbi, Najoua; Ahmed, Melika Ben; El-Fazaa, Saloua

    2014-09-01

    The present study was designed to determine the immunosuppressive effects of carbosulfan (CB) and their relationship with an increased formation of reactive oxygen species in rat. Further, we aimed to evaluate the protective effects of N-acetyl-cysteine (NAC) against immunopathological changes induced by CB. Carbosulfan (25 mg/kg) and NAC (2 g/l) were given daily to rats during 30 days, via oral gavage and drinking water, respectively. Cell-mediated immune function, cytokines production, biomarkers of cell redox state maintenance, lipid peroxidation and the activities of antioxidant enzymes were measured in the spleen. Our data showed an increase in WBC percent (28.42%), a reduction in spleen CD8 T-lymphocytes (-85.63%) and a decrease in immunosuppressive cytokines production such as INF-gamma and IL-4. There was a switch from Th1-type to Th2-type cytokines with an unbalance toward anti-inflammatory cytokines. Moreover, a significant decrease in reduced glutathione (-71.68%) and total thiols (-39.81%) levels were observed in treated rats. Conversely, malondialdehyde level in spleen was increased (-42.3%), while glutathione-S-transferase, glutathione peroxidase, superoxide dismutase and catalase activities were depleted. Our results suggest that subchronic CB administration affects cellular enzyme and non-enzyme-mediated antioxidant defense systems and promotes immunotoxicity in rat. On the other hand, our data showed protective effects of NAC. Indeed, there was a recovery of oxidative stress markers and cytokines production. The use of NAC, in our study, as a therapeutic agent showed interesting results against CB toxicity. PMID:24916794

  15. Sub-chronic exposure of non-observable adverse effect dose of terbufos sulfone: neuroinflammation in diabetic and non-diabetic rats.

    PubMed

    Nurulain, Syed M; Adeghate, Ernest; Sheikh, Azimullah; Yasin, Javed; Kamal, Mohammad A; Sharma, Charu; Adem, Abdu; Ojha, Shreesh

    2014-01-01

    Neuroinflammation (NI) contributes to the pathogenesis of several neurodegenerative disorders. Epidemiological and a few animal studies have shown that chronic exposure of organophosphorus compounds (OPC) may cause neuronal injury and predispose to neuro- as well as psychotic disorders in conjunction with NI. However, in vivo studies are meager and do not represent the entire toxicologically diversified OPC. The present study aimed to investigate the result of non-observable adverse effect level dose of a highly toxic OPC, terbufos sulfone (TBS), on sub-chronic exposure on the status of proinflammatory cytokines; interleukin-1β, interleukin-6 and tumor necrosis factor-α in rats brain. In addition, lactate dehydrogenase, nitric oxide and reduced glutathione were also determined in brain. Red blood cell acetylcholinesterase was measured weekly. Total of four groups' saline control, diabetes control, non-diabetes TBS and diabetes treated with TBS were employed in the study. Control groups received saline and the experimental groups were injected with TBS intraperitonealy for fifteen days daily. Twenty four hours after the last injection, the animals were euthanized for collection of brain and serum samples. The study showed significant elevation of interleukin-6, tumor necrosis factor-α and lactate dehydrogenase in brain of TBS treated groups, while the presence of interleukin-1β was significantly greater in the non-diabetes TBS treated group when compared with saline control. The increase was observed to be independent of acetylcholinesterase level and diabetes condition. The change in reduced glutathione was modest as compared with control. Based on the findings, the study concludes that the non-observable adverse effect level dose of TBS has potential to cause NI and subsequent neurodegeneration, a remarkable sign of many chronic neuronal and psychotic disorders. Further studies with prolonged exposure and other neurodegenerative parameters are warranted. PMID

  16. In vivo toxicity studies of fusarium mycotoxins in the last decade: a review.

    PubMed

    Escrivá, L; Font, G; Manyes, L

    2015-04-01

    This review summarizes the information regarding the in vivo studies of Fusarium mycotoxins in the last decade. The most common studies are classified as subacute toxicity, subchronic toxicity, acute toxicity, toxicokinetic studies and teratogenicity in order of importance. The most used animals in in vivo studies are pigs, rats, chickens and mice. Fumonisin B1, deoxynivalenol, zearalenone, nivalenol and T-2 toxin are the most studied fusarotoxins. Studies with combinations of mycotoxins are also frequent, deoxynivalenol generally being one of them. The predominant route of administration is oral, administered mostly in the form of naturally contaminated feed. Other administration routes also used are intraperitoneal, intravenous and subcutaneous. In vivo research on Fusarium mycotoxins has increased since 2010 highlighting the need for such studies in the field of food and feed safety. PMID:25680507

  17. Subchronic Arsenic Exposure Induces Anxiety-Like Behaviors in Normal Mice and Enhances Depression-Like Behaviors in the Chemically Induced Mouse Model of Depression

    PubMed Central

    Chang, Chia-Yu; Guo, How-Ran; Tsai, Wan-Chen; Yang, Kai-Lin; Lin, Li-Chuan

    2015-01-01

    Accumulating evidence implicates that subchronic arsenic exposure causes cerebral neurodegeneration leading to behavioral disturbances relevant to psychiatric disorders. However, there is still little information regarding the influence of subchronic exposure to arsenic-contaminated drinking water on mood disorders and its underlying mechanisms in the cerebral prefrontal cortex. The aim of this study is to assess the effects of subchronic arsenic exposure (10 mg/LAs2O3 in drinking water) on the anxiety- and depression-like behaviors in normal mice and in the chemically induced mouse model of depression by reserpine pretreatment. Our findings demonstrated that 4 weeks of arsenic exposure enhance anxiety-like behaviors on elevated plus maze (EPM) and open field test (OFT) in normal mice, and 8 weeks of arsenic exposure augment depression-like behaviors on tail suspension test (TST) and forced swimming test (FST) in the reserpine pretreated mice. In summary, in this present study, we demonstrated that subchronic arsenic exposure induces only the anxiety-like behaviors in normal mice and enhances the depression-like behaviors in the reserpine induced mouse model of depression, in which the cerebral prefrontal cortex BDNF-TrkB signaling pathway is involved. We also found that eight weeks of subchronic arsenic exposure are needed to enhance the depression-like behaviors in the mouse model of depression. These findings imply that arsenic could be an enhancer of depressive symptoms for those patients who already had the attribute of depression. PMID:26114099

  18. Subchronic Arsenic Exposure Induces Anxiety-Like Behaviors in Normal Mice and Enhances Depression-Like Behaviors in the Chemically Induced Mouse Model of Depression.

    PubMed

    Chang, Chia-Yu; Guo, How-Ran; Tsai, Wan-Chen; Yang, Kai-Lin; Lin, Li-Chuan; Cheng, Tain-Junn; Chuu, Jiunn-Jye

    2015-01-01

    Accumulating evidence implicates that subchronic arsenic exposure causes cerebral neurodegeneration leading to behavioral disturbances relevant to psychiatric disorders. However, there is still little information regarding the influence of subchronic exposure to arsenic-contaminated drinking water on mood disorders and its underlying mechanisms in the cerebral prefrontal cortex. The aim of this study is to assess the effects of subchronic arsenic exposure (10 mg/LAs2O3 in drinking water) on the anxiety- and depression-like behaviors in normal mice and in the chemically induced mouse model of depression by reserpine pretreatment. Our findings demonstrated that 4 weeks of arsenic exposure enhance anxiety-like behaviors on elevated plus maze (EPM) and open field test (OFT) in normal mice, and 8 weeks of arsenic exposure augment depression-like behaviors on tail suspension test (TST) and forced swimming test (FST) in the reserpine pretreated mice. In summary, in this present study, we demonstrated that subchronic arsenic exposure induces only the anxiety-like behaviors in normal mice and enhances the depression-like behaviors in the reserpine induced mouse model of depression, in which the cerebral prefrontal cortex BDNF-TrkB signaling pathway is involved. We also found that eight weeks of subchronic arsenic exposure are needed to enhance the depression-like behaviors in the mouse model of depression. These findings imply that arsenic could be an enhancer of depressive symptoms for those patients who already had the attribute of depression. PMID:26114099

  19. Outcomes and toxicities of stereotactic body radiation therapy for non-spine bone oligometastases

    PubMed Central

    Owen, Dawn; Laack, Nadia N.; Mayo, Charles S.; Garces, Yolanda I.; Park, Sean S.; Bauer, Heather J.; Nelson, Kathryn; Miller, Robert W.; Brown, Paul D.; Olivier, Kenneth R.

    2015-01-01

    Purpose Stereotactic body radiation therapy (SBRT) is being applied more widely for oligometastatic disease. This technique is now being used for non-spine bony metastases in addition to liver, spine, and lung. However, there are few studies examining the toxicity and outcomes of SBRT for non-spine bone metastases. Methods and Materials Between 2008 and 2012, 74 subjects with oligometastatic non-spine bony metastases of varying histologies were treated at the Mayo Clinic with SBRT. A total of 85 non-spine bony sites were treated. Median local control, overall survival, and progression-free survival were described. Acute toxicity (defined as toxicity <90 days) and late toxicity (defined as toxicity90 days) were reported and graded as per standardized Common Toxicity Criteria for Adverse Events 4.0 criteria. Results The median age of patients treated was 60 years. The most common histology was prostate cancer (31%) and most patients had fewer than 3 sites of disease at the time of simulation (64%). Most of the non-spine bony sites lay within the pelvis (65%). Dose and fractionation varied but the most common prescription was 24 Gy/1 fraction. Local recurrence occurred in 7 patients with a median time to failure of 2.8 months. Local control was 91.8% at 1 year. With a median follow-up of 7.6 months, median SBRT specific overall survival and progression-free survival were 9.3 months and 9.7 months, respectively. Eighteen patients developed acute toxicity (mostly grade 1 and 2 fatigue and acute pain flare); 9 patients developed grade 1–2 late toxicities. Two patients developed pathologic fractures but both were asymptomatic. There were no late grade 3 or 4 toxicities. Conclusions Stereotactic body radiation therapy is a feasible and tolerable treatment for non-spine bony metastases. Longer follow-up will be needed to accurately determine late effects. PMID:24890360

  20. Studying the General Toxicity and Cumulative Properties of a Radiopharmaceutical Nanocolloid, (99m)Tc-Al2O3.

    PubMed

    Varlamova, N V; Churin, A A; Fomina, T I; Ermolaeva, L A; Vetoshkina, T V; Dubskaya, T Yu; Lamzina, T Yu; Fedorova, E P; Neupokoeva, O V; Skuridin, V S; Nesterov, E A; Larionova, L A; Chernov, V I

    2016-07-01

    We studied toxicity of a new Russian radiopharmaceutical Nanocolloid, (99m)Tc-Al2O3. Tests for acute toxicity showed that this agent belongs to a class of moderate-toxicity substances and does not have cumulative properties. The evaluation of subchronic toxicity after subcutaneous injection of this product to rats (0.04, 0.2, and 0.4 ml/kg) and rabbits (0.02 and 0.2 ml/kg) for 7 days did not reveal changes in the general state, temperature, body weight, indices of the peripheral blood and bone marrow, functions of the heart, liver, kidneys, and nervous system, and morphological characteristics of the internal organs in animals. The drug does not produce a local irritant effect. PMID:27502539

  1. The sediment-contact test using the ostracod Heterocypris incongruens: Effect of fine sediments and determination of toxicity thresholds.

    PubMed

    Casado-Martinez, M Carmen; Burga-Pérez, Karen F; Bebon, Rebecca; Férard, Jean-François; Vermeirssen, Etienne L M; Werner, Inge

    2016-05-01

    The toxicity test using freshwater ostracods of the species Heterocypris incongruens is a sub-chronic static test that exposes individuals to whole sediments over a period of 6 d, the endpoints being mortality and growth. We tested the hypothesis that endpoints of the sediment bioassay using Heterocypris incongruens are affected by the presence of fine sediment particles by testing control sediment supplied with the commercial test kit with increasing proportions of kaolin clay as a proxy for fines. While mortality was not affected, the results showed that increasing the presence of clay reduced ostracod growth. Based on the variability in growth, a sublethal toxicity threshold of 35% is proposed to distinguish effects due to sediment properties from those due to toxicity. The relevance of this threshold was verified using data from toxicity tests of ambient sediment samples with low levels of contamination. PMID:26943743

  2. Subchronic phencyclidine treatment in adult mice increases GABAergic transmission and LTP threshold in the hippocampus.

    PubMed

    Nomura, Toshihiro; Oyamada, Yoshihiro; Fernandes, Herman B; Remmers, Christine L; Xu, Jian; Meltzer, Herbert Y; Contractor, Anis

    2016-01-01

    Repeated administration of non-competitive N-methyl-d-aspartate (NMDA) receptor antagonists such as phencyclidine (PCP) to rodents causes long-lasting deficits in cognition and memory, and has effects on behaviors that have been suggested to be models of the cognitive impairment associated with schizophrenia (CIAS). Despite this being a widely studied animal model, little is known about the long lasting changes in synapses and circuits that underlie the altered behaviors. Here we examined synaptic transmission ex-vivo in the hippocampus of mice after a subchronic PCP (scPCP) administration regime. We found that after at least one week of drug free washout period when mice have impaired cognitive function, the threshold for long-term potentiation (LTP) of CA1 excitatory synapses was elevated. This elevated LTP threshold was directly related to increased inhibitory input to CA1 pyramidal cells through increased activity of GABAergic neurons. These results suggest repeated PCP administration causes a long-lasting metaplastic change in the inhibitory circuits in the hippocampus that results in impaired LTP, and could contribute to the deficits in hippocampal-dependent memory in PCP-treated mice. Changes in GABA signaling have been described in patients with schizophrenia, therefore our results support using scPCP as a model of CIAS. This article is part of the Special Issue entitled 'Synaptopathy--from Biology to Therapy'. PMID:25937215

  3. Subchronic and mild social defeat stress alter mouse nest building behavior.

    PubMed

    Otabi, Hikari; Goto, Tatsuhiko; Okayama, Tsuyoshi; Kohari, Daisuke; Toyoda, Atsushi

    2016-01-01

    Behavioral and physiological evaluations of animal models of depression are essential to thoroughly understand the mechanisms of depression in humans. Various models have been developed and characterized, and the socially defeated mouse has been widely used for studying depression. Here, we developed and characterized a mouse model of social aversion using a subchronic and mild social defeat stress (sCSDS) paradigm. Compared to control mice, sCSDS mice showed significantly increased body weight gain, water intake, and social aversion to dominant mice on the social interaction test. We observed nest building behavior in sCSDS mice using the pressed cotton as a nest material. Although sCSDS mice eventually successfully built nests, the onset of nest building was severely delayed compared to control mice. The underlying mechanism of this significant delay in nest building by sCSDS mice is unclear. However, our results demonstrate that nest building evaluation is a simple and useful assay for understanding behavior in socially defeated mice and screening drugs such as antidepressants. PMID:26524409

  4. Omics Studies of the Murine Intestinal Ecosystem Exposed to Subchronic and Mild Social Defeat Stress.

    PubMed

    Aoki-Yoshida, Ayako; Aoki, Reiji; Moriya, Naoko; Goto, Tatsuhiko; Kubota, Yoshifumi; Toyoda, Atsushi; Takayama, Yoshiharu; Suzuki, Chise

    2016-09-01

    The microbiota-gut-brain axis plays an important role in the development of stress-induced mental disorders. We previously established the subchronic and mild social defeat stress (sCSDS) model, a murine experimental model of depression, and investigated the metabolomic profiles of plasma and liver. Here we used omics approaches to identify stress-induced changes in the gastrointestinal tract. Mice exposed to sCSDS for 10 days showed the following changes: (1) elevation of cholic acid and reduction of 5-aminovaleric acid among cecal metabolites; (2) downregulation of genes involved in the immune response in the terminal ileum; (3) a shift in the diversity of the microbiota in cecal contents and feces; and (4) fluctuations in the concentrations of cecal metabolites produced by gut microbiota reflected in plasma and hepatic metabolites. Operational taxonomic units within the family Lachnospiraceae showed an inverse correlation with certain metabolites. The social interaction score correlated with cecal metabolites, IgA, and cecal and fecal microbiota, suggesting that sCSDS suppressed the ileal immune response, altering the balance of microbiota, which together with host cells and host enzymes resulted in a pattern of accumulated metabolites in the intestinal ecosystem distinct from that of control mice. PMID:27482843

  5. Brain met-enkephalin immunostaining after subacute and subchronic exposure to benzene

    SciTech Connect

    Gandarias, J.M. de; Echevarria, E.; Martinez-Millan, L.; Casis, L.; Martinez-Garcia, F.

    1994-01-01

    Benzene is used in a wide variety of domestic and occupational activities, and due to its lipophilic nature, it accumulates in lipid-rich tissues like the brain. In this sense, neurotoxic action has long been associated with organic solvent exposure and it has been shown that benzene, injected in a single dose or during a prolongued administration, modifies the content of dopamine, noradrenaline, serotonin and its main metabolite 5-hydroxy indolacetic acid, in several brain regions of the rat, then revealing a stimulating action on brain monoamine synthesis and turnover. However, information concerning neurotoxic action of benzene exposure in vivo on peptidergic neuromodulatory systems is still lacking. Nevertheless, it has been recently described that subacute benzene exposure in rats generates regional changes in brain aminopeptidase activity. These proteolytic enzymes have been widely associated with metabolic control of neuropeptides and it has been suggested that they could play a role in benzene neurotoxic mechanism by hypothetically changing regional neuropeptide levels. This being the case, we focused on analyzing met-enkephalin immunostaining in different brain regions of the rat after subacute and subchronic administration of benzene. 12 refs., 3 figs.

  6. Antidepressant treatment decreases daily salt intake and prevents heart dysfunction following subchronic aortic regurgitation in rats.

    PubMed

    De Gobbi, Juliana Irani Fratucci; Omoto, Ana Carolina Mieko; Siqueira, Tamires Ferreira; Matsubara, Luiz Shigueto; Roscani, Meliza Goi; Matsubara, Beatriz Bojikian

    2015-05-15

    Depression is a predictor of poor prognosis in patients with heart failure. Selective serotonin (5-HT) reuptake inhibitors (SSRIs) may improve these outcomes. Left ventricular volume overload induced hypertrophy that is associated with aortic regurgitation (AR) leads to ventricular dysfunction and heart failure. The aim of this study was to verify the effects of the SSRI paroxetine on cardiac function, as well as on fluid intake and excretion, in subchronic AR. Male Wistar rats (260 to 280g) received sham (SH) surgery or AR induced by retrograde puncture of the aortic valve leaflets. The presence of AR was confirmed by echocardiography (ECHO) exams. Four weeks after AR surgery, subcutaneous injections of paroxetine (PAR: 10mg/kg 3 times in a week) or saline were administered. The rats were randomly divided into the following 4 groups and treated for 4 weeks: AR-PAR, ARsaline, SH-PAR and SH-saline. At the end of the treatment period, fractional shortening was preserved in AR-PAR, compared to AR-saline (46.6±2.7% vs 38.3±2.2%, respectively). Daily 0.3 M NaCl intake was reduced in PAR-treated rats. Natriuresis was increased in weeks 2-3 after PAR treatment. Our results suggest that augmentation of central 5-HT neurotransmission has a beneficial effect on cardiovascular remodeling following volume overload. The mechanisms underlying this effect are unknown. PMID:25747768

  7. Subchronic treatment with fluoxetine attenuates the proerectile effect of Aspidosperma ulei Markgr (Apocyanaceae)

    PubMed Central

    Campos, Adriana Rolim; de Andrade Uchôa, Daniel Esdras; Rocha, Edilberto Silveira; Martins da Costa, José Galberto; Rao, Vietla Satyanarayana

    2011-01-01

    Objective: To evaluate the ability of acute or chronic treatment with fluoxetine to alter the proerectile effect of Aspidosperma ulei alkaloid-rich fraction (F3-5). Materials and Methods: In the first series of experiments, three groups of mice received either a single intraperitoneal injection of vehicle, F3-5 (25 mg/kg) or fluoxetine (10 mg/kg) + F3-5. Three behavioral responses were counted over a period of 30 min: erection, erection-like response and genital grooming. In a second series of experiments, animals treated for 13 days with fluoxetine or fluoxetine + F3-5 were assessed. Results: A. ulei has been suggested to have proerectile effect in mice. Subchronic (13-d) treatment with fluoxetine resulted in a reduction in the number erections in F3-5-treated mice. Conclusion: Sexual dysfunction associated with antidepressant treatment continues to be a major compliance issue for antidepressant therapy. Acute administration of fluoxetine resulted in a near total reversal of the proerectile effect of F3-5. PMID:22144779

  8. Toxic Myopathies

    PubMed Central

    Pasnoor, Mamatha; Barohn, Richard J.; Dimachkie, Mazen M.

    2014-01-01

    Muscle tissue is highly sensitive to many substances. Early recognition of toxic myopathies is important, as they potentially are reversible on removal of the offending drug or toxin, with greater likelihood of complete resolution the sooner this is achieved. Clinical features range from mild muscle pain and cramps to severe weakness with rhabdomyolysis, renal failure, and even death. The pathogenic bases can be multifactorial. This article reviews some of the common toxic myopathies and their clinical presentation, histopathologic features and possible underlying cellular mechanisms. PMID:25037083

  9. Short-term toxicity of ammonia, nitrite, and nitrate to early life stages of the rare minnow (Gobiocypris rarus).

    PubMed

    Luo, Si; Wu, Benli; Xiong, Xiaoqin; Wang, Jianwei

    2016-06-01

    Nitrogenous pollutants including ammonia, nitrite, and nitrate are a widespread concern in natural waters and aquaculture. In the present study, the toxicity of ammonia, nitrite, and nitrate to rare minnow (Gobiocypris rarus) in the early life stage were evaluated by 2 short-term toxicity tests. In the short-term toxicity test, conducted on embryo and sac-fry stages, 30 fertilized eggs with 3 replicates were randomly exposed to varying levels of ammonia, nitrite, and nitrate until 3 d posthatch (dph). In the 7-d larval subchronic toxicity test, 30 newly hatched larvae with 3 replicates were randomly exposed to varying levels of ammonia, nitrite, and nitrate until 7 dph. The results showed that the 7-d larval subchronic toxicity test was more sensitive than the short-term toxicity test on embryo and sac-fry stages. Both toxicity tests revealed that ammonia was most toxic to rare minnows, followed by nitrite and nitrate. High levels of ammonia, nitrite, and nitrate decreased growth, retarded development, and increased mortality. The no-observed-effect concentrations of ammonia, nitrite, and nitrate for larval growth were 2.49 mg L(-1) , 13.33 mg L(-1) , and 19.95 mg L(-1) nitrogen, respectively. The present study's results demonstrate that nitrogenous pollutants pose a threat to wild populations of rare minnows and provide useful information for establishing water quality criteria for this laboratory fish. Environ Toxicol Chem 2016;35:1422-1427. © 2015 SETAC. PMID:26472009

  10. Short-Term and Sub-Chronic Dietary Exposure to Aspalathin-Enriched Green Rooibos (Aspalathus linearis) Extract Affects Rat Liver Function and Antioxidant Status.

    PubMed

    van der Merwe, Johanna Debora; de Beer, Dalene; Joubert, Elizabeth; Gelderblom, Wentzel C A

    2015-01-01

    An aspalathin-enriched green rooibos (Aspalathus linearis) extract (GRE) was fed to male Fischer rats in two independent studies for 28 and 90 days. The average dietary total polyphenol (TP) intake was 756 and 627 mg Gallic acid equivalents (GAE)/kg body weight (bw)/day over 28 and 90 days, respectively, equaling human equivalent doses (HEDs) of 123 and 102 GAE mg/kg bw/day. Aspalathin intake of 295 mg/kg bw/day represents a HED of 48 mg/kg bw/day (90 day study). Consumption of GRE increased feed intake significantly (p < 0.05) compared to the control after 90 days, but no effect on body and organ weight parameters was observed. GRE significantly (p < 0.05) reduced serum total cholesterol and iron levels, whilst significantly (p < 0.05) increasing alkaline phosphatase enzyme activity after 90 days. Endogenous antioxidant enzyme activity in the liver, i.e., catalase and superoxide dismutase activity, was not adversely affected. Glutathione reductase activity significantly (p < 0.05) increased after 28 days, while glutathione (GSH) content was decreased after 90 days, suggesting an altered glutathione redox cycle. Quantitative Real Time polymerase chain reaction (PCR) analysis showed altered expression of certain antioxidant defense and oxidative stress related genes, indicative, among others, of an underlying oxidative stress related to changes in the GSH redox pathway and possible biliary dysfunction. PMID:26694346

  11. Sublinear response in lacZ mutant frequency of Muta™ Mouse spermatogonial stem cells after low dose subchronic exposure to N-ethyl-N-nitrosourea.

    PubMed

    O'Brien, Jason M; Walker, Mike; Sivathayalan, Ahalya; Douglas, George R; Yauk, Carole L; Marchetti, Francesco

    2015-05-01

    The transgenic rodent mutation assay was used to compare the dose-response relationship of lacZ mutant frequency (MF) in spermatogonial stem cells exposed acutely or subchronically to N-ethyl-N-nitrosourea (ENU). Muta(™) Mouse males were exposed orally to 0, 25, 50, or 100 mg/kg ENU for acute exposures and 0, 1, 2, or 5 mg/(kg day) for 28-day subchronic exposures. LacZ MF was measured in sperm collected 70 days post-exposure to target spermatogonial stem cells. Dose-response data were fit to linear, quadratic, exponential, or power models. Acute exposure resulted in a dose-dependent increase in MF that was significant (P < 0.05) at all doses tested and was best described by a quadratic dose-response model that was linear in the low dose range. In contrast, similar total doses fragmented over a 28-day subchronic exposure only resulted in a significant increase in lacZ MF at the highest dose tested. Therefore, the subchronic no observable genotoxic effect level (NOGEL) was 2 mg/(kg day) (or 56 mg/kg total dose). The subchronic dose-response was best described by the exponential and power models, which were sublinear in the low dose range. Benchmark dose lower confidence limits (BMDLs) for acute and subchronic exposure were 3.0 and 1.0 mg/(kg day) (or 27.4 mg/kg total dose), respectively. These findings are supportive of a saturable DNA repair mechanism as the mutagenic mode of action for ENU in spermatogonia and imply that sufficiently low exposures would not cause appreciable genotoxic effects over background. This may have important implications for the quantitative risk assessment of germ cell mutagens. PMID:25598316

  12. Interdisciplinary approach to assessing the health risk of air toxic chemicals: An overview

    SciTech Connect

    Grose, E.C.; Selgrade, M.J.K.; Busnell, P.J.; Simmons, J.E.; Allen, J.

    1990-01-01

    To assist the regulatory branch of the Environmental Protection Agency in addressing the risk assessment of air toxics, the Health Effects Research Laboratory initiated a comprehensive inhalation toxicology program to provide key health effects data missing from the current data base. A priority ranking of chemicals based on the potential for substantial human exposure and the need for health effects data was developed to identify candidate chemicals for toxicological research. The major goal of the program is to evaluate the concentration-response from acute, intermittent and subchronic inhalation exposures to developmental, genetic, hepatic, immunologic, neurologic, pulmonary and reproductive toxicity. Although the main emphasis is on inhalation as the primary route of exposure, some of the laboratories will compare inhalation to other routes, such as oral, to better understand the influence of route of exposure and hence the potential applicability of existing health data. Acute and intermittent exposures will be done for all compounds. Upon evaluation of the acute results, a decision will be made as to whether subchronic studies are needed. Endpoints that show unusual sensitivity may be investigated in greater detail. The total length of exposure will vary from 1 to 21 days. The daily length of exposure will range from 1 to 8 hr. If adverse effects are observed at ambient levels, the time to recovery after exposure will be investigated.

  13. Toxic remediation

    DOEpatents

    Matthews, Stephen M.; Schonberg, Russell G.; Fadness, David R.

    1994-01-01

    What is disclosed is a novel toxic waste remediation system designed to provide on-site destruction of a wide variety of hazardous organic volatile hydrocarbons, including but not limited to halogenated and aromatic hydrocarbons in the vapor phase. This invention utilizes a detoxification plenum and radiation treatment which transforms hazardous organic compounds into non-hazardous substances.

  14. The Air Toxics Health Effects Database (ATHED)

    SciTech Connect

    Woodall, George M. Smith, Roy L.

    2008-11-15

    The Air Toxics Health Effects Database (ATHED) is currently used by the EPA's Office of Air Quality Planning and Standards (OAQPS) to support risk assessments for the Residual Risk Program. An assessment of the residual risk is required to be performed at a specified time (typically 8years) following the promulgation of a technology-based Maximum Achievable Control Technologies (MACT) standard. The goal of the Residual Risk Program is to assure that the risk that remains after MACT standards are implemented (i.e., the 'residual risk') is acceptable, and if not, to propose additional regulations to mitigate those risks. ATHED maintains all available reference values for each chemical as separate data records, and includes values for all exposure durations (acute, short-term, subchronic and chronic). These values are used as benchmarks to determine acceptable exposure levels to the hazardous air pollutants (HAPs) listed in Section 112 of the Clean Air Act. ATHED also provides useful background information on the uncertainty and/or modifying factors that were applied in the derivation of each reference value, as well as the point of departure and the critical study/studies. To facilitate comparisons across durations for a specific chemical, ATHED data can be graphically presented.

  15. Tissue Distribution and Associated Toxicological Effects of Decabrominated Diphenyl Ether in Subchronically Exposed Male Rats

    PubMed Central

    Wang, Fuxin; Wang, Jianshe; Hu, Guocheng; Luo, Xiaojun; Mai, Bixian; Dai, Jiayin

    2011-01-01

    Concerns about decabrominated diphenyl ether (BDE-209) have arisen recently due to its increasing concentrations in the environment. We investigated the tissue concentration, distribution, and the debromination of BDE-209 after oral exposure, using rats as a model. Three groups of male rats were administrated by oral gavage with corn oil containing 0, 10, or 50 mg/kg bw/day of BDE-209 over 90 days. After exposure, BDE-209 and its metabolites levels in the liver, kidney, and adipose of the rats were measured. The mRNA expression levels of cytochrome P450 (CYP) enzymes in liver, serum thyroid hormone levels, and open-field tests were also measured. BDE-209 and several octa- and nona-BDE congeners were detected in the tissues of the dosed rats, indicating that BDE-209 was bioavailable and biotransformative in male rats. BDE-209 and its debrominated congeners had no mRNA level effect on selective genes from the CYP family in the liver or on the spontaneous behavior of adult male rats. Conversely, the level of thyroid hormone, total triiodothyronine (T3) in rats from the dosed treatments increased significantly compared to the control group. PMID:23724291

  16. Hematopathology in Sprague-Dawley rats following sub-chronic topical application of para-phenylenediamine.

    PubMed

    Bharali, Manuj Kr; Dutta, Karabi

    2012-10-01

    The aim of the present study was to analyze the hematological profile of male SD rats treated topically with aqueous solution of para-phenylenediamine (PPD), a component of almost all hair dye formulations. The rats were painted with different concentration of PPD (0, 1, 2 and 3 mg Kg(-1) Day(-1)) for 90 days and then sacrificed. The hematological profile indicated severe anemia characterized by significant (p < 0.05, 0.001) reduction of total RBC count (59%), packed cell volume (PCV, 50%) and haemoglobin level (70%) in the peripheral blood of PPD treated animals when compared to control group. The leucocytes profile exhibited an overall elevation of around twofold as compared to the control group with significant lymphocytosis (44.4%) and a higher percentage of blast cells (8.5%) as well as smudge (10.3%) and hairy cells (6.2%) in the peripheral blood of treated animals. Histopathological examination of spleen from treated rat's exhibit red pulp congestion, expansion of the germinal centre, hyperplasia of the membrane capsule and extensive accumulation of hemosidderin pigments in the red pulp of the spleen. Overall this study indicated an abnormal pathophysiological condition indicating adverse effect of PPD in the treated animal groups. The risk assessment of hair dye formulation needs to be reviewed in view of widespread usage of paraphenylenediamine in almost all hair dye formulation. PMID:22886424

  17. Pulmonary and hepatic injury after sub-chronic exposure to sublethal doses of microcystin-LR.

    PubMed

    Carvalho, Giovanna Marcella Cavalcante; Oliveira, Vinícius Rosa; Casquilho, Natália Vasconcelos; Araujo, Andressa Cristine Pereira; Soares, Raquel Moraes; Azevedo, Sandra Maria F O; Pires, Karla Maria Pereira; Valença, Samuel Santos; Zin, Walter Araujo

    2016-03-15

    We had previously shown that microcystin-LR (MCLR) could induce lung and liver inflammation after acute exposure. The biological outcomes following prolonged exposure to MCLR, although more frequent, are still poorly understood. Thus, we aimed to verify whether repeated doses of MCLR could damage lung and liver and evaluate the dose-dependence of the results. Male Swiss mice received 10 intraperitoneal injections (i.p.) of distilled water (60 μL, CTRL) or different doses of MCLR (5 μg/kg, TOX5), 10 μg/kg (TOX10), 15 μg/kg (TOX15) and 20 μg/kg (TOX20) every other day. On the tenth injection respiratory mechanics (lung resistive and viscoelastic/inhomogeneous pressures, static elastance, and viscoelastic component of elastance) was measured. Lungs and liver were prepared for histology (morphometry and cellularity) and inflammatory mediators (KC and MIP-2) determination. All mechanical parameters and alveolar collapse were significantly higher in TOX5, 10, 15 and 20 than CTRL, but did not differ among them. Lung inflammatory cell content increased dose-dependently in all TOX groups in relation to CTRL, being TOX20 the largest. The production of KC was increased in lung and liver homogenates. MIP-2 increased in the liver of all TOX groups, but in lung homogenates it was significantly higher only in TOX20 group. All TOX mice livers showed steatosis, necrosis, inflammatory foci and a high degree of binucleated hepatocytes. In conclusion, sub-chronic exposure to MCLR damaged lung and liver in all doses, with a more important lung inflammation in TOX20 group. PMID:26844922

  18. Decreased hepatic contents of coenzyme A molecular species in mice after subchronic mild social defeat stress.

    PubMed

    Kubota, Yoshifumi; Goto, Tatsuhiko; Hagiya, Yuki; Chohnan, Shigeru; Toyoda, Atsushi

    2016-03-01

    Social stress may precipitate psychiatric disorders such as depression, which is related to the occurrence of the metabolic syndrome, including obesity and type 2 diabetes. We have evaluated the effects of social stress on central and peripheral metabolism using a model of depression in mice. In the present study, we focused on coenzyme A (CoA) molecular species [i.e. non-esterified CoA (CoASH), acetyl-CoA and malonyl-CoA] which play important roles in numerous metabolic pathways, and we analyzed changes in expression of these molecules in the hypothalamus and liver of adult male mice (C57BL/6J) subjected to 10 days of subchronic mild social defeat stress (sCSDS) with ICR mice as aggressors. Mice (n = 12) exposed to showed hyperphagia- and polydipsia-like symptoms and increased body weight gain compared with control mice which were not affected by exposure to ICR mice (n = 12). To elucidate the underlying metabolic features in the sCSDS model, acetyl-CoA, malonyl-CoA and CoASH tissue levels were analyzed using the acyl-CoA cycling method. The levels of hypothalamic malonyl-CoA, which decreases feeding behavior, were not influenced by sCSDS. However, sCSDS reduced levels of acetyl-CoA, malonyl-CoA and total CoA (sum of the three CoA molecular species) in the liver. Hence, hyperphagia-like symptoms in sCSDS mice evidently occurred independently of hypothalamic malonyl-CoA, but might consequently lead to down-regulation of hepatic CoA via altered expression of nudix hydrolase 7. Future studies should investigate the molecular mechanism(s) underlying the down-regulation of liver CoA pools in sCSDS mice. PMID:26864137

  19. Effects of mixed subchronic lead acetate and cadmium chloride on bone metabolism in rats

    PubMed Central

    Yuan, Guiping; Lu, Hongke; Yin, Zhongqiong; Dai, Shujun; Jia, Renyong; Xu, Jiao; Song, Xu; Li, Li

    2014-01-01

    This study aimed to determine the effects of administering a mixture of subchronic lead acetate (Pb (NO3)2) and cadmium chloride (CdCl2·2.5H2O) on the bone metabolism of rats. A control group and three experimental groups consisted of randomly selected rats. Rats in each experimental group were orally administered with a mixture of Pb (NO3)2 and CdCl2·2.5H2O with the following respective doses for 90 consecutive days: 0 mg/kg body weight b.w. (Group I, to serve as a control), 29.96 mg/kg b.w. (Group II, 29.25 + 0.71), 89.88 mg/kg b.w. (Group III, 87.74 + 2.14), and 269.65 mg/kg b.w. (Group IV, 263.23 + 6.42). Serum osteocalcin (OC) and bone-specific alkaline phosphates (BALP) were considered as bone-formation markers, whereas carboxy-terminal cross-linking telopeptides of type I collagen (CTX) in serum acted as bone resorption markers. Calcitonin (CT) and parathormone (PTH) were tested as calciotropic hormones markers. The (Ca) and phosphorus (Pi) concentrations in the serum and urine were determined. These results were indicated by a significant (P < 0.05 - P < 0.01) increase in BALP, CTX, and PTH concentrations and decrease in CT and OC concentrations. Moreover, the concentrations of Ca and Pi in the serum were decreased, whereas those in urine increased. Results indicated that the administration of Pb and Cd induced bone metabolism disorders by decreasing bone formation and increasing bone resorption to destroy the hormonal regulation of mineral metabolism as a result of Ca and Pi imbalance. PMID:24995099

  20. Effect of subchronic administration of antioxidants against cigarette smoke exposure in rats.

    PubMed

    Sohn, H O; Lim, H B; Lee, Y G; Lee, D W; Kim, Y T

    1993-01-01

    Effects of subchronic administration of antioxidants against pulmonary damage mediated by cigarette smoke were investigated in rats. Rats were continuously received ascorbic acid, N-acetylcysteine and ginseng extract together drinking water from day 25 after birth. After 30 days of antioxidant supplementation, rats were exposed to cigarette smoke generated from six cigarettes (11 mg tar) for 20 min per day throughout 30 days, and then several biochemical markers related to the redox status in vivo were analyzed in the respiratory system. The cigarette smoke induced mild histological changes in trachea and lungs. The activity of superoxide dismutase (SOD) in the lung was significantly increased, and catalase and glutathione peroxidase activities were increased less than SOD, but total sulfhydryl compounds (Total-SH) content was decreased by cigarette smoking. In spite of the increase in activities of antioxidant enzymes, the inhibitory capacity of lung preparations on in vitro lipid peroxidation using ox brain homogenates was decreased and the change in the capacity was not related to the changes of these intracellular enzymes activities, but with the content of Total-SH. On the other hand, the content of thiobarbituric acid reactive substances and the ratio of elastase to anti-protease in the lung homogenates were significantly increased. Supplementation of antioxidants, however, effectively attenuated all of such alterations induced by cigarette smoke. These results indicate that although cigarette smoking induces antioxidant enzymes in the lung as a self defense mechanism, it seems to be not sufficient to protect the pulmonary system, and that chronic antioxidant feeding could be effective to reduce pulmonary damage induced by free radicals. PMID:8135656