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Sample records for 90-day subchronic toxicity

  1. Safety assessment of dietary bamboo charcoal powder: a 90-day subchronic oral toxicity and mutagenicity studies.

    PubMed

    Zhenchao, Jia; Yuting, Zhong; Jiuming, Yan; Yedan, Lu; Yang, Song; Jinyao, Chen; Lishi, Zhang

    2015-01-01

    Vegetable carbon has been used as food additive in EU (E153) and China for many years; however, no experimental data have been available on its dietary safety. This study was designed to evaluate the subchronic toxicity and genotoxicity of bamboo charcoal powder (BCP). In the study of subchronic oral toxicity, BCP was administered orally at doses of 2.81, 5.62, and 11.24 g/kg BW for 90 days to SD rats. Additional satellite groups from the control group and high dose group were observed for a 28-day recovery period. At the end of the treatment and recovery periods, animals were sacrificed, and their organs were weighed and blood samples were collected. The toxicological endpoints observed included clinical signs, food consumption, body and organ weights, hematological and biochemical parameters, macroscopic and microscopic examinations. The results showed no significant differences between the BCP treated groups and control group. The genotoxicity of BCP was assessed with the Salmonella typhimurium mutagenicity assay (Ames test) and a combination of comet assay and mammalian erythrocyte micronucleus protocol. The results did not reveal any genotoxicity of BCP. Based on our study, the no-observed-adverse-effect level (NOAEL) for BCP is 11.24 g/kg BW/day.

  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.

  3. 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

  4. 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

  5. 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.

  6. A 90-day subchronic oral toxicity study of triterpene-enriched extract from Alismatis Rhizoma in rats.

    PubMed

    Huang, Ming-Qing; Xu, Wen; Wu, Shui-Shen; Lu, Jin-Jian; Chen, Xiu-Ping

    2013-08-01

    Alismatis Rhizoma has been used in East Asia as a traditional treatment for various illnesses and symptoms, and the presence of protostane-type triterpenes has been claimed to provide health benefits. To investigate the subchronic toxicity of triterpene-enriched extract from Alismatis Rhizoma (TEAR), a 90-day oral toxicity study was conducted in rats. Sprague-Dawley rats were randomly divided into four groups (10 rats/sex/group) and received doses of 0, 360, 720, and 1440 mg/kg/d of TEAR for 90 days. Daily clinical observations as well as weekly measurement of body weight and food consumption were conducted. Blood samples were obtained on day 91 to measure changes in hematology and biochemistry. Urine samples were collected on days 0 and 91 for urinalysis. At necropsy, selected organs were weighed and recorded, and histological examination was performed. No mortality or obvious treatment-related clinical signs, hematology, urinalysis parameters, and macroscopic or microscopic examinations were observed. Differences in weight gain, food consumption, biochemistry, and relative organ weight between the treated group and the control group were not considered treatment-related. On the basis of these findings, the no-observed-adverse-effect level for TEAR was 1440 mg/kg/d in both sexes. PMID:23684999

  7. 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

  8. 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.

  9. Safety assessment of EPA-rich oil produced from yeast: Results of a 90-day subchronic toxicity study.

    PubMed

    MacKenzie, Susan A; Belcher, Leigh A; Sykes, Greg P; Frame, Steven R; Mukerji, Pushkor; Gillies, Peter J

    2010-12-01

    The safety of eicosapentaenoic acid (EPA) oil produced from genetically modified Yarrowia lipolytica yeast was evaluated following 90 days of exposure. Groups of rats received 0 (olive oil), 98, 488, or 976 mg EPA/kg/day, or GRAS fish oil or deionized water by oral gavage. Rats were evaluated for in-life, neurobehavioral, anatomic and clinical pathology parameters. Lower serum cholesterol (total and non-HDL) was observed in Medium and High EPA and fish oil groups. Lower HDL was observed in High EPA and fish oil males, only at early time points. Liver weights were increased in High EPA and Medium EPA (female only) groups with no associated clinical or microscopic pathology findings. Nasal lesions, attributed to oil in the nasal cavity, were observed in High and Medium EPA and fish oil groups. No other effects were attributed to test oil exposure. Exposure to EPA oil for 90 days produced no effects at 98 mg EPA/kg/day and no adverse effects at doses up to 976 mg EPA/kg/day. The safety profile of EPA oil was comparable to that of GRAS fish oil. These results support the use of EPA oil produced from yeast as a safe source for use in dietary supplements.

  10. Assessment of the safety of hydrogenated resistant maltodextrin: reverse mutation assay, acute and 90-day subchronic repeated oral toxicity in rats, and acute no-effect level for diarrhea in humans.

    PubMed

    Yoshikawa, Yuko; Kishimoto, Yuka; Tagami, Hiroyuki; Kanahori, Sumiko

    2013-01-01

    A series of safety assessments were performed on hydrogenated resistant maltodextrin prepared by converting the reducing terminal glucose of resistant maltodextrin into sorbitol. The reverse mutation assay did not show mutagenicity. Acute and 90-day subchronic oral toxicity studies in rats showed no death was observed in any groups, including the group receiving the highest single dose of 10 g/kg body weight or the highest dose of 5 g/kg body weight per day for 90 days. Mucous or watery stools were observed in the hydrogenated resistant maltodextrin treatment group on the acute study, which were transient and were associated with the osmotic pressure caused by intake of the high concentrations. Subchronic study showed dose-dependent increases in the weights of cecum alone, cecal contents alone, and cecum with cecal contents as well as hypertrophy of the cecal mucosal epithelium, which are considered to be common physiological responses after intake of indigestible carbohydrates. These results indicated that the no observed adverse effect level (NOAEL) of hydrogenated resistant maltodextrin was 10 g/kg body weight or more on the acute oral toxicity study and 5.0 g/kg body weight/day or more on the 90-day subchronic repeated oral toxicity study in rats. Further study performed in healthy adult humans showed that the acute no-effect level of hydrogenated resistant maltodextrin for diarrhea was 0.8 g/kg body weight for men and more than 1.0 g/kg body weight for women. The results of the current safety assessment studies suggest that hydrogenated resistant maltodextrin is safe for human consumption.

  11. 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

  12. 90-day dietary toxicity study with esterified propoxylated glycerol (EPG) in rats.

    PubMed

    Christian, Brian J; Bechtel, David H

    2014-12-01

    The subchronic (90-day) toxicity of a "core" version of EPG was assessed in rats. Crl:CD-1®(ICR)BR rats (70/sex) received diets containing a constant level of 5% EPG (w/w) or adjusted to deliver 0 (control), 0.5, 1, or 2g/kg of body weight/day (g/kg bw/day). Subsets of animals from each group (20/sex) were evaluated after 30 days (interim sacrifice); the remainder after 90 days. EPG intake at all dose levels was associated with lower mean liver vitamin E levels; liver vitamin A and serum vitamin D were also lower, but less consistently. Animals given 5% EPG had higher fecal output (males) and cholesterol (males and females) without corresponding changes in serum cholesterol. Urinary pH was also mildly lower in males given 5% EPG. However, detailed evaluation of general health and assessment of blood, organs and tissues showed no evidence that EPG administration compromised the nutritional requirements of the animals, caused a state of fat-soluble vitamin deficiency, or caused' toxicity to any organ system. Based on the results of this study, it was not possible to establish a no-observable-effect level (NOEL). The possible effect of EPG on vitamin levels in the absence of any clinical signs of deficiency was not considered "adverse" per se. As such, the 2g/kg and 5% EPG level were considered to represent a no-observable-adverse-effect levels (NOAELs). PMID:25497991

  13. 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

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

    PubMed

    Matsuo, Tatsuhiro; Ishii, Reika; Shirai, Yoko

    2012-03-01

    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 (LD(50) = 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.

  15. 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

  16. 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

  17. 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.

  18. 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

  19. 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.

  20. Acute and oral subchronic toxicity of D-003 in rats.

    PubMed

    Gámez, R; Mas, R; Noa, M; Menéndez, R; Alemán, C; Acosta, P; García, H; Hernández, C; Amor, A; Pérez, J; Goicochea, E

    2000-12-20

    D-003 is a mixture of higher aliphatic primary acids purified from sugar cane wax (Saccharum officinarum) with cholesterol-lowering and antiplatelet effects experimentally proven. The present work reports the results of two studies investigating the acute and subchronic oral toxicity of D-003 in rats. Oral acute toxicity of D-003 (2000 mg/kg) was investigated according to the Acute Toxic Class (ATC) method (an alternative for the classical LD(50) test), which was performed in Wistar rats. The results obtained in this study defined D-003 oral acute toxicity as unclassified. In the subchronic study, rats of both sexes were orally treated with D-003 at 50, 200 and 1250 mg/kg for 90 days. At this time, animals were sacrificed. No evidence of treatment-related toxicity was detected during the study. Thus, data analysis of body weight gain, food consumption, clinical observations, blood biochemical, haematology, organ weight ratios and histopathological findings did not show significant differences between control and treated groups. It is concluded that D-003 orally administered to rats was safe and that no drug-related toxicity was detected even at the highest doses investigated in both acute (2000 mg/kg) and subchronic (1250 mg/kg) studies.

  1. Safety assessment of the fermented Phylloporia ribis (Lonicera japonica Thunb.) mycelia by oral acute toxicity study in mice and 90-day feeding study in rats.

    PubMed

    Lu, Lianhua; Fan, Yiou; Yao, Wenhuan; Xie, Wei; Guo, Jie; Yan, Yan; Yang, Fei; Xu, Lingchuan

    2014-07-01

    Phylloporia ribis is an edible fungus in China. Its fermented mycelia have been approved by the National Health and Family Planning Commission (NHFPC) of PR China for use as a novel food material, but little information on its safety is available. The present research was the first to evaluate acute and subchronic toxicity in experimental animals of fermented Phylloporia ribis mycelia (FPM) following standard procedures. In acute toxicity study, FPM was orally administered to male and female mice twice a day at single dose of 10 g/kg bw. The Maximum Tolerated Dose (MTD) of FPM for mice of both sexes was over 10 g/kg bw. No death and abnormal behaviors occurred during 14 days study except for an increased locomotor activity in three animals. In 90-day feeding study, male and female Sprague-Dawley rats were fed diets containing 10.0%, 5.0%, 2.5%, 1.25% and 0% (control) FPM for 90 days. The treatment caused no effects on mortality, gross pathology, histology, hematology, and blood chemistry, no dose-dependent changes in food consumption, but caused effect on body weight gain compared with control group. The No Observed Adverse-Effect Level (NOAEL) of FPM was greater than 8.7 g/kg bw/day in both sexes of rats.

  2. 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...

  3. 90-day dermal toxicity study and neurotoxicity evaluation of nitromusks in the albino rat.

    PubMed

    Ford, R A; Api, A M; Newberne, P M

    1990-01-01

    Musk ketone, musk xylene, musk tibetene and moskene, synthetic musks used in fragrances, were applied dermally to rats in daily doses of 240 (musk ketone and musk xylene only), 75, 24 or 7.5 mg/kg body weight for 90 days. The chemically related musk ambrette, a known neurotoxin in rats, was used as a positive control. While musk ambrette was clearly neurotoxic and caused testicular atrophy, as had been previously reported, the other compounds tested caused neither effect. The only effects of application of these materials were some organ weight changes at the higher doses, but these were not associated with histopathological changes in any of the tissues. The no-effect levels were: musk ketone, 75 mg/kg for males and females; musk xylene, 75 mg/kg for males and 24 mg/kg for females; moskene, 24 mg/kg for males and 75 mg/kg (highest dose administered) for females; and musk tibetene, 75 mg/kg (highest dose) for males and females.

  4. 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.

  5. Inhalation toxicity study of disk-shaped potassium octatitanate particles (terracess TF) in rats following 90 days of aerosol exposure.

    PubMed

    Sakai, Seiya; Inada, Kousuke; Tanaka, Akira K; Kelly, David P; Sykes, Greg P; Lee, K P

    2010-01-01

    Since fibrous particles such as asbestos and some man-made fibers (MMF) have been known to produce carcinogenic or fibrogenic effects, disk-shaped potassium octatitanate (POT) particles (trade name: Terracess TF) were manufactured as nonfibrous particles. A 90-day inhalation toxicity study of Terracess TF was performed to evaluate comparative inhalation toxicity of the disk shape with a fibrous shape that was previously evaluated. Four groups of 20 male and 15 female rats each were exposed to Terracess TF aerosols at concentrations of 0, 2, 10, or 50 mg/m(3) for 90 days. Ten male and 10 female rats per group were sacrificed at 90 days of exposure. After 90 days of exposure, 5 male rats per group were sacrificed at 3 wk of recovery period and 4-5 male rats per group or 5 female rats per group were sacrificed at 15 wk of recovery for lung clearance and histopathology. The mass median aerodynamic equivalent diameter (MMAED) of the aerosols of test materials ranged from 2.5 to 2.9 microm. There were no test-substance-related adverse effects on clinical observations. At the end of the 90-day exposure, a slight increase in lung-to-body weight ratios was observed at 50 mg/m(3) in male but not in female rats. However, lung weights were within normal limits after 3- or 15-wk recovery periods. Microscopically, inhaled Terracess TF particles were mostly phagocytized by free alveolar macrophages (AMs) in the alveolar airspaces and alveolar walls maintained normal structure at 2 and 10 mg/m(3). At 50 mg/m(3), some alveoli were distended and filled with aggregates of particle-laden AMs. The alveolar walls showed slight type II pneumocyte hyperplasia, but neither proliferative inflammation nor alveolar fibrosis was present at 50 mg/m(3). The clearance half-times for Terracess TF were estimated to be in the order of 6 to 9 mo for the 50-mg/m(3) group and 2 to 3 mo for the 10- and 2-mg/m(3) groups. The lung responses and lung clearance rate were comparable to those of "nuisance

  6. 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.

  7. Toxicity of 2,4,4{prime}-trichlorobiphenyl in rats following 90-day dietary exposure

    SciTech Connect

    Chu, I.; Villeneuve, D.C.; Yagminas, A.; Lecavalier, P.; Poon, R.

    1996-10-25

    The toxicity of 2,4,4{prime}-trichlorobiphenyl (PCB 28) was investigated in rats after a 90-d dietary exposure. Groups of 10 male and 10 female weanling Sprague-Dawley rats were administered PCB 28 in the diet at 0, 0.05, 0.50, 5.0, or 50.0 ppm for 13 wk. Growth rate and food consumption were not affected by treatment, and no clinical signs of toxicity were observed. Mottled liver was noted in both control and PCB-treated males, but was found with increased incidence in the highest treatment group. Increased urinary ascorbic acid and hepatic microsomal ethoxyresorufin O-deethylase activity were observed in the 50.0 ppm group of both sexes. The vitamin A content in liver, lung, and kidney was not significantly affected by treatment. Analysis of brain biogenic amines showed a decreased dopamine concentration in the substantial nigra region of female rats receiving 0.5 ppm PCB 28 and higher doses. Female rats appeared top be more sensitive than males to the neurochemical effects of PCB 28. Dose-dependent histologic changes were observed in the thyroid and liver, with biologically significant changes occurring at 5.0 ppm and above. Based on these data, the no-observable-adverse-effect level (NOAEL) for this PCB congener was considered to be 0.5 ppm in diet or 36 {mu}g/kg body weight/d. 26 refs., 6 figs., 3 tabs.

  8. A 90 day repeated oral toxicity study on plantamajoside concentrate from Plantago asiatica.

    PubMed

    Park, Byung-Gyu; Lee, Hyun-Sun; Jung, Sung-Hoon; Hong, Chung-Oui; Won, Hye-Jin; Park, Ho-Young; Ryu, Yung-Sun; Lee, Sung-Joon; Kim, Kyoung-Heon; Park, Kuen-Woo; Lee, Kwang-Won

    2007-12-01

    Plantago asiatica is distributed widely in East Asia. Since ancient times it has been used as a diuretic to treat acute urinary infections, and as an antiinflammatory, antiasthmatic, antioxidant, antibacterial, antihyperlipidemic and antihepatitis drug. The major compound, plantamajoside from P. asiatica, which is used as a marker compound in chemotaxonomic studies, was reported to have antibacterial activity, inhibition activity against cAMP phosphodiesterase and 5-lipoxygenase and antioxidant activity. However, there are no reports on the safety of plantamajoside. This study assessed the toxic effects of plantamajoside concentrate (PC), the purity of which was above 80%, in rats following administration at dose levels of 0, 500, 1000 and 2000 mg/kg body weight/day for 13 weeks, as recommended by the OECD guidelines. The results showed that there were no differences in body weight, food intake, water consumption, relative organ weight or the hematological and serum biochemical values among the different dosage groups. No death or abnormal clinical signs were observed during the experimental period. Therefore, the results suggested that no observed adverse effect level (NOAEL) of the PC in rats after oral administration is considered to be greater than 2000 mg/kg in rats under the conditions employed in this study. PMID:17622978

  9. 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

  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 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

  12. 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

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

    PubMed

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

    2002-09-01

    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.

  14. 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.

  15. Subchronic toxicity study of GH transgenic carp.

    PubMed

    Yong, Ling; Liu, Yu-Mei; Jia, Xu-Dong; Li, Ning; Zhang, Wen-Zhong

    2012-11-01

    A subchronic toxicity study of GH (growth hormone) transgenic carp was carried out with 60 SD rats aged 4 weeks, weight 115∼125 g. Ten male and 10 female rats were allotted into each group. Animals of the three groups (transgenic carp group (GH-TC), parental carp group (PC) and control group) were fed soy- and alfalfa-free diet (SAFD) with 10% GH transgenic carp powder, 10% parental carp powder or 10% common carp powder for 90 consecutive days, respectively. In the end of study, animals were killed by exsanguination via the carotid artery under diethyl ether anesthesia, then weights of heart, liver, kidneys, spleen, thymus, brain, ovaries and uterus/testis were measured. Pathological examination of organs was determined. Endocrine hormones of triiodothyronine (T3), thyroid hormone (T4), follicle-stimulating hormone (FSH), 17β-estradiol (E2), progesterone (P) and testosterone (T) levels were detected by specific ELISA kit. Parameters of blood routine and blood biochemical were measured. The weights of the body and organs of the rats, food intake, blood routine, blood biochemical test and serum hormones showed no significant differences among the GH transgenic carp-treated, parental carp-treated and control groups (P>0.05). Thus, it was concluded that at the dose level of this study, GH transgenic carp showed no subchronic toxicity and endocrine disruption to SD rats.

  16. A 90-day subchronic feeding study of genetically modified maize expressing Cry1Ac-M protein in Sprague-Dawley rats.

    PubMed

    Liu, Pengfei; He, Xiaoyun; Chen, Delong; Luo, Yunbo; Cao, Sishuo; Song, Huan; Liu, Ting; Huang, Kunlun; Xu, Wentao

    2012-09-01

    The cry1Ac-M gene, coding one of Bacillus thuringiensis (Bt) crystal proteins, was introduced into maize H99 × Hi IIB genome to produce insect-resistant GM maize BT-38. The food safety assessment of the BT-38 maize was conducted in Sprague-Dawley rats by a 90-days feeding study. We incorporated maize grains from BT-38 and H99 × Hi IIB into rodent diets at three concentrations (12.5%, 25%, 50%) and administered to Sprague-Dawley rats (n=10/sex/group) for 90 days. A commercialized rodent diet was fed to an additional group as control group. Body weight, feed consumption and toxicological response variables were measured, and gross as well as microscopic pathology were examined. Moreover, detection of residual Cry1Ac-M protein in the serum of rats fed with GM maize was conducted. No death or adverse effects were observed in the current feeding study. No adverse differences in the values of the response variables were observed between rats that consumed diets containing GM maize BT-38 and non-GM maize H99 × Hi IIB. No detectable Cry1Ac-M protein was found in the serum of rats after feeding diets containing GM maize for 3 months. The results demonstrated that BT-38 maize is as safe as conventional non-GM maize.

  17. Acute and subchronic oral toxicities of Calendula officinalis extract in Wistar rats.

    PubMed

    Lagarto, Alicia; Bueno, Viviana; Guerra, Isbel; Valdés, Odalys; Vega, Yamile; Torres, Leonid

    2011-05-01

    We have studied the acute and subchronic oral toxicities of Calendula officinalis extract in male and female Wistar rats. A single acute C. officinalis extract dose of 2000 mg/kg dissolved in distilled water was administered by oral gavage for acute toxicity. Subchronic doses of 50, 250 and 1000 mg/kg/day were administered in drinking water. The major toxicological endpoints examined included animal body weight, water and food intake, selected tissue weights, and histopathological examinations. In addition, we examined blood elements: hematocrit, hemoglobin concentration, erythrocyte count, total and differential leukocyte count and blood clotting time and blood chemistry: glucose, total cholesterol, urea, total proteins, alkaline phosphatase, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In the acute study, there were no mortality and signs of toxicity. In the subchronic study, several of the blood elements were significantly affected in males and females after 90 days; hemoglobin, erythrocytes, leukocytes and blood clotting time. For blood chemistry parameters, ALT, AST and alkaline phosphatase were affected. Histopathological examination of tissues showed slight abnormalities in hepatic parenchyma that were consistent with biochemical variations observed. These studies indicate that the acute and subchronic toxicities of C. officinalis extract are low. PMID:20335011

  18. Acute and subchronic oral toxicities of Calendula officinalis extract in Wistar rats.

    PubMed

    Lagarto, Alicia; Bueno, Viviana; Guerra, Isbel; Valdés, Odalys; Vega, Yamile; Torres, Leonid

    2011-05-01

    We have studied the acute and subchronic oral toxicities of Calendula officinalis extract in male and female Wistar rats. A single acute C. officinalis extract dose of 2000 mg/kg dissolved in distilled water was administered by oral gavage for acute toxicity. Subchronic doses of 50, 250 and 1000 mg/kg/day were administered in drinking water. The major toxicological endpoints examined included animal body weight, water and food intake, selected tissue weights, and histopathological examinations. In addition, we examined blood elements: hematocrit, hemoglobin concentration, erythrocyte count, total and differential leukocyte count and blood clotting time and blood chemistry: glucose, total cholesterol, urea, total proteins, alkaline phosphatase, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In the acute study, there were no mortality and signs of toxicity. In the subchronic study, several of the blood elements were significantly affected in males and females after 90 days; hemoglobin, erythrocytes, leukocytes and blood clotting time. For blood chemistry parameters, ALT, AST and alkaline phosphatase were affected. Histopathological examination of tissues showed slight abnormalities in hepatic parenchyma that were consistent with biochemical variations observed. These studies indicate that the acute and subchronic toxicities of C. officinalis extract are low.

  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. Acute and Subchronic Toxicity Study of Euphorbia hirta L. Methanol Extract in Rats

    PubMed Central

    Yuet Ping, Kwan; Darah, Ibrahim; Chen, Yeng; Sreeramanan, Subramaniam

    2013-01-01

    Despite Euphorbia hirta L. ethnomedicinal benefits, very few studies have described the potential toxicity. The aim of the present study was to evaluate the in vivo toxicity of methanolic extracts of E. hirta. The acute and subchronic oral toxicity of E. hirta was evaluated in Sprague Dawley rats. The extract at a single dose of 5000 mg/kg did not produce treatment related signs of toxicity or mortality in any of the animals tested during the 14-day observation period. Therefore, the LD 50 of this plant was estimated to be more than 5000 mg/kg. In the repeated dose 90-day oral toxicity study, the administration of 50 mg/kg, 250 mg/kg, and 1000 mg/kg/day of E. hirta extract per body weight revealed no significant difference (P > 0.05) in food and water consumptions, body weight change, haematological and biochemical parameters, relative organ weights, and gross findings compared to the control group. Macropathology and histopathology examinations of all organs including the liver did not reveal morphological alteration. Analyses of these results with the information of signs, behaviour, and health monitoring could lead to the conclusion that the long-term oral administration of E. hirta extract for 90 days does not cause sub-chronic toxicity. PMID:24386634

  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. Subchronic oral toxicity of silver nanoparticles

    PubMed Central

    2010-01-01

    Background The antibacterial effect of silver nanoparticles has resulted in their extensive application in health, electronic, consumer, medicinal, pesticide, and home products; however, silver nanoparticles remain a controversial area of research with respect to their toxicity in biological and ecological systems. Results This study tested the oral toxicity of silver nanoparticles (56 nm) over a period of 13 weeks (90 days) in F344 rats following Organization for Economic Cooperation and Development (OECD) test guideline 408 and Good Laboratory Practices (GLP). Five-week-old rats, weighing about 99 g for the males and 92 g for the females, were divided into four 4 groups (10 rats in each group): vehicle control, low-dose (30 mg/kg), middle-dose (125 mg/kg), and high-dose (500 mg/kg). After 90 days of exposure, clinical chemistry, hematology, histopathology, and silver distribution were studied. There was a significant decrease (P < 0.05) in the body weight of male rats after 4 weeks of exposure, although there were no significant changes in food or water consumption during the study period. Significant dose-dependent changes were found in alkaline phosphatase and cholesterol for the male and female rats, indicating that exposure to more than 125 mg/kg of silver nanoparticles may result in slight liver damage. Histopathologic examination revealed a higher incidence of bile-duct hyperplasia, with or without necrosis, fibrosis, and/or pigmentation, in treated animals. There was also a dose-dependent accumulation of silver in all tissues examined. A gender-related difference in the accumulation of silver was noted in the kidneys, with a twofold increase in female kidneys compared to male kidneys. Conclusions The target organ for the silver nanoparticles was found to be the liver in both the male and female rats. A NOAEL (no observable adverse effect level) of 30 mg/kg and LOAEL (lowest observable adverse effect level) of 125 mg/kg are suggested from the present study

  3. 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

  4. 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…

  5. Acute and sub-chronic toxicity of glucose-cysteine Maillard reaction products in Sprague-Dawley rats.

    PubMed

    Li, Yixing; Su, Linliang; Li, Fenfang; Wang, Chaozheng; Yuan, Debao; Chen, Jiao; Tan, Lin; Jin, Zhiqiang; Ma, Weihong

    2015-06-01

    Maillard reaction products (MRPs) derived from glucose-cysteine reactions have excellent anti-browning ability. However, there is a lack of information about their acute and sub-chronic toxicities. To our knowledge, the present study is the first to evaluate the acute and sub-chronic toxicities of MRPs in experimental animals. Acute toxicity testing and analysis by Horn's method showed that the median lethal oral dose (LD50) of MRPs in rats was 6.81 g/kg body weight. The sub-chronic toxicity test involved feeding rats with diet containing 0, 0.43, 0.85, or 1.70% (w/w) MRPs for 90 days. These treatments did not affect mortality, gross pathology, histology, hematology, or blood chemistry, and there were no dose-dependent changes in feed consumption. Based on these results, the dietary no-observed-adverse-effect level (NOAEL) for 90-day exposure was 1.29 and 1.51 g MRPs/kg body weight/day for male and female rats, respectively. PMID:25817020

  6. Toxicological assessment of combined lead and cadmium: acute and sub-chronic toxicity study in rats.

    PubMed

    Yuan, Guiping; Dai, Shujun; Yin, Zhongqiong; Lu, Hongke; Jia, Renyong; Xu, Jiao; Song, Xu; Li, Li; Shu, Yang; Zhao, Xinghong

    2014-03-01

    The exposure to chemical mixtures is a common and important determinant of toxicity and receives concern for their introduction by inhalation and ingestion. However, few in vivo mixture studies have been conducted to understand the health effects of chemical mixtures compared with single chemicals. In this study, the acute and 90day sub-chronic toxicity tests of combined Pb and Cd were conducted. In the acute toxicity test, the LD50 value of Pb(NO3)2 and CdCl2 mixture by the oral route was 2696.54mg/kg by Bliss method. The sub-chronic treatment revealed that the low-dose combination of Pb and Cd exposures can significantly change the physiological and biochemical parameters of the blood of Sprague-Dawley (SD) rats with dose-response relationship and causes microcytic hypochromic anemia and the damages of liver and kidney of the SD rats to various degrees. Histopathological exams showed that the target organs of Pb and Cd were testicle, liver, and kidneys. These observations suggest that Pb and Cd are practically additive-toxic for the SD rats in oral acute toxicity studies. The lowest observed adverse-effect level in rats may be lower than a dose of 29.96mg/(kgbwday) when administered orally for 90 consecutive days.

  7. 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.

  8. 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

  9. Acute and subchronic toxicity studies on safety assessment of Paecilomyces tenuipes N45 extracts.

    PubMed

    Du, Linna; Liu, Yan; Liu, Chungang; Meng, Qingfan; Song, Jingjing; Wang, Di; Lu, Jiahui; Teng, Lirong; Zhou, Yulin; Teng, Lesheng

    2015-01-01

    Paecilomyces tenuipes, one of the commonly used Chinese medicinal fungus, has received much attention over the world, which possesses various active compounds and biological activities. However, little toxicological information is available. Therefore, the present study evaluated the potential toxicity of aqueous and ethanol extracts of Paecilomyces tenuipes N45 via acute and subchronic administration in mouse and rat, respectively. For improving the extraction rate of aqueous extract, response surface methodology (RSM) was employed to optimize the extraction condition first in this paper. The obtained optimal extract conditions were temperature 80 °C, liquid-solid ratio 50 mL·g-1 and time 3 h. In the acute toxicity test, aqueous and ethanol extracts caused neither mortality nor toxicological signs, and the maximum tolerance dose was estimated over 15 g/kg. No mortality or adverse effects was observed in subchronic toxicity studies. No significant difference in bodyweight, relative organ weight or hematological parameters was noted during the experiment. Comparing with nontreated rats, ALT, K and BUN levels were changed in experimental group detecting via biochemical analysis. No abnormality of internal organs was noted between treatment and control groups in gross and histopathological examinations. Our present study suggested that the tolerance dose of the Paecilomyces tenuipes N45 extracts were more than 15 g/kg and no-observed-adverse-effect level (NOAEL) of the extracts for both male and female rats after 90-day adminstation. Additionally, the extracts may possess renal-protective and hepato-protective effects.

  10. 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

  11. A 90-day dietary toxicity study of genetically modified rice T1C-1 expressing Cry1C protein in Sprague Dawley rats.

    PubMed

    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.

  12. Safety assessment of lutein and zeaxanthin (Lutemax 2020): subchronic toxicity and mutagenicity studies.

    PubMed

    Ravikrishnan, R; Rusia, Shraddha; Ilamurugan, G; Salunkhe, Ulhas; Deshpande, Jayant; Shankaranarayanan, J; Shankaranarayana, M L; Soni, Madhu G

    2011-11-01

    Lutein and zeaxanthin, naturally occurring carotenoids, have shown to reduce the risk of cataracts and age-related macular degeneration. Lutemax 2020 is a lutein and zeaxanthin (including meso-isomer) enriched product obtained from Marigold flowers (Tagetes erecta L). The objective of the present study was to investigate adverse effects, if any, of Lutemax 2020 in acute and subchronic toxicity, and mutagenicity studies. In acute toxicity study in rats no lethality was noted at 2000 mg Lutemax 2020/kg body weight (bw). In the subchronic study, Wistar rats (10/sex/group) were administered (gavage) lutein/zeaxanthin concentrate at dose levels of 0, 4, 40 and 400mg/kg bw/day for 90-days. Compared with the control group, administration of lutein/zeaxanthin concentrate did not result in any toxicologically significant treatment-related changes in clinical observations, ophthalmic examinations, body weights, body weight gains, feed consumption, and organ weights. No toxicologically relevant findings were noted in urinalysis, hematology or clinical biochemistry parameters at the end of the treatment or recovery period. Terminal necropsy did not reveal any treatment-related gross or histopathology findings. The results of mutagenicity testing in Salmonella typhimurium did not reveal any genotoxicity. The no observed-adverse-effect level (NOAEL) for lutein/zeaxanthin concentrate was determined as 400mg/kg bw/day, the highest dose tested. PMID:21872637

  13. 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

  14. 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.

  15. 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

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

    PubMed

    Korani, M; Rezayat, S M; Gilani, K; Arbabi Bidgoli, S; 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.

  17. A 90-day repeated dose oral (gavage) toxicity study of perfluorohexanoic acid (PFHxA) in rats (with functional observational battery and motor activity determinations).

    PubMed

    Chengelis, Christopher P; Kirkpatrick, Jeannie B; Radovsky, Ann; Shinohara, Motoki

    2009-06-01

    Possible toxic effects of perfluorohexanoic acid (PFHxA) were evaluated when administered orally by gavage to rats at levels up to 200mg/kg/day for 90 days. Lower body weight gains were noted in the 10, 50 and 200mg/kg/day group males (not dose-responsive) throughout dosing. Other changes included lower red blood cell parameters, higher reticulocyte counts and lower globulin in the 200mg/kg/day group males and females, higher liver enzymes in males at 50 and 200mg/kg/day, lower total protein and higher albumin/globulin ratio, and lower cholesterol, calcium in males at 200mg/kg/day. Minimal centrilobular hepatocellular hypertrophy was present in 200mg/kg/day group males and correlated with higher liver weights and slightly higher peroxisome beta oxidation activity at the end of the dosing period. Based on liver histopathology and liver weight changes, the no-observed-adverse-effect level (NOAEL) for oral administration was 50mg/kg/day for males and 200mg/kg/day for females.

  18. 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

  19. 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

  20. Acute and sub-chronic toxicity study of diaveridine in Wistar rats.

    PubMed

    Wang, Xu; Su, Shijia; Ihsan, Awais; Huang, Qin; Chen, Dongmei; Cheng, Guyue; Liu, Zhenli; Wang, Yulian; Yuan, Zonghui

    2015-10-01

    Diaveridine, a developed dihydrofolate reductase inhibitor, has been widely used as anticoccidial drug and antibacterial synergist. However, few studies have been performed to investigate its toxicity. To provide detailed toxicity with a wide spectrum of doses for diaveridine, acute and sub-chronic toxicity studies were conducted. Calculated LD50 was 2330 mg/kg b.w. in females and 3100 mg/kg b.w. in males, and chromodacryorrhea was noted in some females before their death. In the sub-chronic study, diaveridine was fed to Wistar rats during 90 days at dietary levels of 0, 23, 230, 1150 and 2000 mg/kg, which were about 0, 2.0-2.3, 21.0-23.5, 115.2-126.9 and 212.4-217.9 mg/kg b.w., respectively. Significant decrease in body weights in both genders at 1150 and 2000 mg/kg groups and significant increases in relative weights of brain in both genders, liver in females, kidneys and testis in males, alkaline phosphatase and potassium in both genders at 2000 mg/kg diet were noted. Significant decrease in absolute weights of several organs, hemoglobin and red blood cell count in both genders, albumin and total protein in females were observed at 2000 mg/kg diet. Fibroblasts in the kidneys, cell swelling of the glomerular zone in the adrenals and inflammation in the liver were found at 2000 mg/kg group. The no-observed-adverse-effect level of diaveridine was 230 mg/kg diet (21.0-23.5 mg/kg b.w./day). PMID:26209270

  1. Acute and sub-chronic toxicity study of diaveridine in Wistar rats.

    PubMed

    Wang, Xu; Su, Shijia; Ihsan, Awais; Huang, Qin; Chen, Dongmei; Cheng, Guyue; Liu, Zhenli; Wang, Yulian; Yuan, Zonghui

    2015-10-01

    Diaveridine, a developed dihydrofolate reductase inhibitor, has been widely used as anticoccidial drug and antibacterial synergist. However, few studies have been performed to investigate its toxicity. To provide detailed toxicity with a wide spectrum of doses for diaveridine, acute and sub-chronic toxicity studies were conducted. Calculated LD50 was 2330 mg/kg b.w. in females and 3100 mg/kg b.w. in males, and chromodacryorrhea was noted in some females before their death. In the sub-chronic study, diaveridine was fed to Wistar rats during 90 days at dietary levels of 0, 23, 230, 1150 and 2000 mg/kg, which were about 0, 2.0-2.3, 21.0-23.5, 115.2-126.9 and 212.4-217.9 mg/kg b.w., respectively. Significant decrease in body weights in both genders at 1150 and 2000 mg/kg groups and significant increases in relative weights of brain in both genders, liver in females, kidneys and testis in males, alkaline phosphatase and potassium in both genders at 2000 mg/kg diet were noted. Significant decrease in absolute weights of several organs, hemoglobin and red blood cell count in both genders, albumin and total protein in females were observed at 2000 mg/kg diet. Fibroblasts in the kidneys, cell swelling of the glomerular zone in the adrenals and inflammation in the liver were found at 2000 mg/kg group. The no-observed-adverse-effect level of diaveridine was 230 mg/kg diet (21.0-23.5 mg/kg b.w./day).

  2. Subchronic toxicity evaluation of lewisite in rats.

    PubMed

    Sasser, L B; Cushing, J A; Mellick, P W; Kalkwarf, D R; Dacre, J C

    1996-03-01

    Health and exposure criteria have not been established for lewisite [dichloro(2-chlorovinyl)arsine], a potent toxic vesicant that reacts with the sulfhydryl groups of proteins through its arsenic group. Sixty Sprague-Dawley rats of each sex, 6-7 wk old, were divided into 6 groups (10/group/sex) and gavaged with either 0, 0.01, 0.1, 0.5, 1.0, or 2.0 mg/kg of lewisite in sesame oil 5 d/wk for 13 wk. No significant dose-related change in body weight was observed. At the high dose, serum protein, creatinine, SGOT, and SGPT were decreased in males; lymphocytes and platelets were increased in females. A treatment-related lesion was detected in the forestomach of both sexes at 2.0 mg/kg. These lesions were characterized by necrosis of the stratified squamous epithelium accompanied by infiltration of neutrophils and macrophages, proliferation of neocapillaries, hemorrhage, edema, and fibroblast proliferation. Mild acute inflammation of the glandular stomach was also observed in some cases at 1.0 and 2.0 mg/kg. Early deaths were attributed to severe inflammation of the upper and/or lower respiratory tract, possibly from deposition or reflux of test material into the pharynx. Estimated dose range for NOEL appears to be >0.5 and <1.0 mg/kg when administered orally.

  3. 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.

  4. Subchronic percutaneous toxicity testing of two liquid hand dishwashing detergents.

    PubMed

    Petersen, D W

    1988-09-01

    Subchronic percutaneous toxicity studies were conducted on two liquid dishwashing detergents containing anionic surfactants (C12-14 alkylethoxylate sulphate) to assess the safety of these materials for human exposure. The detergents were administered dermally to the shaved backs of rabbits (dose volume of 2 ml/kg body weight) at concentrations of 0, 0.5, 1.0 and 2.5% in distilled water for 91 days. No adverse systemic effects were demonstrated by assessment of haematological parameters or by gross or microscopic tissue examination. Transient slight to moderate dermal irritation at the detergent application site was observed with detergent A. Slight to moderate dermal irritation confined to the detergent application site was noted in the detergent B study.

  5. Impact of aluminum sub-chronic toxicity on body weight and recognition memory of wistar rat.

    PubMed

    Azzaoui, F Z; Ahami, A O T; Khadmaoui, A

    2008-07-15

    The aims of this study was to investigate the impact of aluminum nitrate administered in drinking water during 90 days (sub-chronic toxicity), on body weight gain, motor activity, brain aluminum accumulation and especially in recognition memory of wistar rats. Two groups of young female wistar rats were used. Treated rats received (80 mg L(-1)) of aluminum nitrate diluted in drinking water, while control rats received a drinking water only, for 3 months. An evolution of body weight, a motor activity, object recognition memory (NOR) and brain aluminum concentration has been evaluated. The body weight was taken weekly, whereas the memory abilities and the motor activity are measured once every fortnight alternatively, by submitting rats to the open field test and to the novel object recognizing memory test. The results have showed a significant decrease in rats' body weight (p < 0.05). Though, no significance was registered for motor activity. Nevertheless, a high significance is showed for recognition memory compared to control rats (p < 0.01), especially at the end of testing period, even the difference between control and aluminium treated rats in brain aluminum levels was not significant.

  6. Impact of lead sub-chronic toxicity on recognition memory and motor activity of Wistar rat.

    PubMed

    Azzaoui, F Z; Ahami, A O T; Khadmaoui, A

    2009-01-15

    The aim of this research was to investigate the impact of lead nitrate administered in drinking water during 90 days (sub-chronic toxicity), on body weight gain, motor activity, brain lead accumulation and especially on recognition memory of Wistar rats. Two groups of young female Wistar rats were used. Treated rats received 20 mg L(-1) of lead nitrate diluted in drinking water, while control rats received drinking water only, for 3 months. An evolution of body weight, motor activity, object recognition memory and measure of brain lead levels has been evaluated. The body weight was taken weekly, whereas the memory abilities and the motor activity are measured once every fortnight alternatively, by submitting rats to the Open Field (OF) test and to the Novel Object Recognizing (NOR) memory test. The results have shown a non significant effect in gain of body weight. However, a high significance was shown for horizontal activity (p<0.01), long memory term (p<0.01), at the end of testing period and for brain lead levels (p<0.05) between studied groups.

  7. 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

  8. Evaluation of the safety and nutritional equivalence of a genetically modified cottonseed meal in a 90-day dietary toxicity study in rats.

    PubMed

    Dryzga, M D; Yano, B L; Andrus, A K; Mattsson, J L

    2007-10-01

    Meal prepared from Cry1F/Cry1Ac transgenic/genetically modified cottonseed (WIDESTRIKE Insect Protection, hereafter referred to as WIDESTRIKE) was compared to cottonseed meal prepared from four conventionally bred lines of cotton (three commercial non-transgenic line controls (PHY72, PHY78 and 98M-2983), and a near isoline non-transgenic control (PSC355) in a 90-day dietary study to evaluate safety and nutritional equivalence. Diets were formulated with 10% WIDESTRIKE cottonseed meal equivalent to 7,235 mg/kg/day for males and 7,935 mg/kg/day for females. Animals were evaluated by cage-side and hand-held detailed clinical observations, body weight, and feed consumption. Functional tests, motor activity and ophthalmic examinations were conducted pre-exposure and prior to study termination. Standard hematology, clinical chemistry, prothrombin time and urinalysis parameters were evaluated. All rats had a complete necropsy and selected organs were weighed. Histopathologic examinations were performed on all rats fed the diets containing the near isoline non-transgenic control or WIDESTRIKE. Following 90 days of feeding, no adverse effects were observed during the conduct of clinical observations or in any of the parameters measured in this study. This study demonstrated that rodent diets prepared with 10% cottonseed meal from WIDESTRIKE cottonseeds do not produce any untoward effects and are nutritionally equivalent to cottonseed meals prepared from other, non-transgenic cottonseeds.

  9. 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.

  10. Mice fed on a diet enriched with genetically engineered multivitamin corn show no sub-acute toxic effects and no sub-chronic toxicity.

    PubMed

    Arjó, Gemma; Capell, Teresa; Matias-Guiu, Xavier; Zhu, Changfu; Christou, Paul; Piñol, Carme

    2012-12-01

    Multivitamin corn is a novel genetically engineered variety that simultaneously produces high levels of β-carotene, ascorbate and folate, and therefore has the potential to address simultaneously multiple micronutrient deficiencies caused by the lack of vitamins A, B9 and C in developing country populations. As part of the development process for genetically engineered crops and following European Food Safety Authority (EFSA) recommendations, multivitamin corn must be tested in whole food/feed sub-chronic animal feeding studies to ensure there are no adverse effects, and potential allergens must be identified. We carried out a 28-day toxicity assessment in mice, which showed no short-term sub-acute evidence of diet-related adverse health effects and no difference in clinical markers (food consumption, body weight, organ/tissue weight, haematological and biochemical blood parameters and histopathology) compared to mice fed on a control diet. A subsequent 90-day sub-chronic feeding study again showed no indications of toxicity compared to mice fed on control diets. Our data confirm that diets enriched with multivitamin corn have no adverse effects on mice, do not induce any clinical signs of toxicity and do not contain known allergens.

  11. 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.

  12. Metabonomics study of transgenic Bacillus thuringiensis rice (T2A-1) meal in a 90-day dietary toxicity study in rats.

    PubMed

    Cao, Sishuo; Xu, Wentao; Luo, YunBo; He, Xiaoyun; Yuan, Yanfang; Ran, Wenjun; Liang, Lixing; Huang, Kunlun

    2011-07-01

    Rice is one of the most important staple foods in the world. The Cry2A gene was inserted into the rice genome to help the plant combat insects. As the unintended effects of the genetically modified (GM) organisms are the most important barriers to the promotion of GM organisms, we have carried out a useful exploration to establish a new in vivo evaluation model for genetically modified foods by metabonomics methods. In this study, the rats were fed for 90 days with the GM and NON-GM rice diets. The changes in metabolites of the urine were detected using (1)H-NMR. The metabonomics were analyzed to see whether the GM rice can induce the metabolite changes in the rats' urine when compared with the NON-GM rice group. The multivariate analysis and ANOVA were used to determine the differences and the significance of differences respectively, and eventually we concluded that these differences did not have a biological significance. The conclusion of the metabonomics was comparable with that from the traditional method. As a non-invasive and dynamic monitoring method, metabonomics will be a new way of assessing the food safety of GM foods.

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

    PubMed

    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 3mg/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.

  14. Preliminary acute and subchronic toxicity studies of GLG-V-13, a novel class III antiarrhythmic agent, in mice.

    PubMed

    Chen, C L; Chandra, S A; Kim, S; Sangiah, S; Chen, H; Roder, J D; Qualls, C W; Garrison, G L; Cowell, R L; Berlin, K D; Scherlag, B J; Lazzara, R

    2000-01-01

    The acute and subchronic toxic effects of GLG-V-13 (3-[4-(1H-imidazol-1-yl)benzoyl]-7-isopropyl-3,7-diazabicyclo[3.3.1]nona ne dihydroperchlorate, CAS 155029-33-7), a novel class III with some class Ib antiarrhythmic activity, were investigated in mice. The estimated LD50 for GLG-V-13 given orally were 419 mg/kg for male mice and 383 mg/kg for female mice, respectively. The acute toxic signs appeared to be of the central nervous system in origin. Four groups of mice (15 per sex, group and dose) were fed daily with diets containing GLG-V-13 for 90 consecutive days. The equivalent daily doses were 0, 22, 50 and 121 mg/kg/day and 0, 27, 60 and 136 mg/kg/day for male and female mice, respectively. All of the mice survived. Food consumption was decreased. However, mean body weight and body weight gain were not significantly changed. Gross pathological changes, especially in the lungs and liver, were found in the middle and high dose groups. Consistent increased mean corpuscular hemoglobin concentration and decreased mean corpuscular hemoglobin were observed in all dose groups. Hepatocellular necrosis was found in both male and female mice treated with the drug and was dose-dependent. Marked vacuolation of the X zone in the adrenal gland with mild to moderate deposition of ceroid pigments (brown degeneration) was observed in female mice. Lesions in the kidneys and adrenal glands may be a possible reason for changes in serum sodium and potassium ions concentrations leading to an increase in water intake. A significant reduction in cholesterol in the high dose group may be a favorable pharmacological effect of GLG-V-13. The data from the 90-day subchronic toxicity studies indicate that GLG-V-13 appears to have limited systemic toxicity potential.

  15. Subchronic oral toxicity and cardiovascular safety pharmacology studies of resveratrol, a naturally occurring polyphenol with cancer preventive activity

    PubMed Central

    Johnson, W.D.; Morrissey, R.L.; Usborne, A.L.; Kapetanovic, I.; Crowell, J.A.; Muzzio, M.; McCormick, D.L.

    2011-01-01

    To characterize the subchronic oral toxicity of resveratrol, CD rats received daily gavage doses of 0, 200, 400, or 1000 mg resveratrol/kg/day, and beagle dogs received daily capsule doses of 0, 200, 600, or 1200 mg resveratrol/kg/day for 90 days. Resveratrol induced only minimal toxicity, consisting of dose-related reductions in body weight gain in female rats and both sexes of dogs, and a statistically significant increase in bilirubin levels in rats at the 1000 mg/kg/day dose. Clinical observations, hematology, ophthalmology, neurotoxicity evaluations (functional observational batteries), organ weights, and gross pathology provided no biologically significant evidence of resveratrol toxicity in either species. In rats, the high dose of resveratrol reduced the incidence of cardiomyopathy; no other microscopic changes were seen. Histopathologic changes in dogs were limited to minimal inflammatory infiltrates in the kidney and urinary bladder, which were not considered toxicologically significant. A cardiovascular safety pharmacology (telemetry) study in dogs revealed no evidence of resveratrol toxicity. Based on body weight effects, the No Observed Adverse Effect Level (NOAEL) for resveratrol was 200 mg/kg/day in rats and 600 mg/kg/day in dogs. The apparent cardioprotective activity of resveratrol in rats demonstrates that its potentially beneficial activities may extend beyond efficacy in cancer prevention. PMID:21939727

  16. 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.

  17. 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.

  18. Subchronic inhalation toxicity of benzene in rats and mice.

    PubMed

    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. These changes in the testes and ovaries at 300 ppm were also seen at lower concentrations, but they were of doubtful biological significance. In rats, the only exposure-related lesion

  19. 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

  20. 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.

  1. In vitro penetration and subchronic toxicity of alpha-methyl-1,3-benzodioxole-5-propionaldehyde.

    PubMed

    Api, Anne Marie; Lapczynski, Aurelia; Isola, Daniel A; Glenn Sipes, I

    2007-05-01

    across all dose levels with increased incidence and severity at 300 mg/kg/day. Dermal irritation that initially ranged from slight to marked improved to slight or resolved completely during the recovery phase. Based on the findings in this study, it can be concluded that (1) MMDHCA exhibits moderately high human skin permeation; (2) the NOEL for dermal irritation is below 50mg/kg/day when applied undiluted to 5 cm(2) dorsal skin and (3) the NOEL for systemic toxicity is greater than 300 mg/kg/day. During the 4-week recovery period of the 90-day study, the animals had largely recovered from MMDHCA induced dermal irritation and the associated microscopic findings.

  2. 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

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. Genotoxicity and acute and subchronic toxicity studies of a standardized methanolic extract of Ficus deltoidea leaves

    PubMed Central

    Farsi, Elham; Shafaei, Armaghan; Hor, Sook Yee; Khadeer Ahamed, Mohamed B.; Yam, Mun Fei; Asmawi, Mohd Z.; Ismail, Zhari

    2013-01-01

    OBJECTIVE: Ficus deltoidea leaves have been used in traditional medicine in Southeast Asia to treat diabetes, inflammation, diarrhea, and infections. The present study was conducted to assess the genotoxicity and acute and subchronic toxicity of a standardized methanol extract of F. deltoidea leaves. METHODS: Sprague Dawley rats were orally treated with five different single doses of the extract and screened for signs of toxicity for two weeks after administration. In the subchronic study, three different doses of the extract were administered for 28 days. Mortality, clinical signs, body weight changes, hematological and biochemical parameters, gross findings, organ weights, and histological parameters were monitored during the study. Genotoxicity was assessed using the Ames test with the TA98 and TA100 Salmonella typhimurium strains. Phytochemical standardization was performed using a colorimeter and high-performance liquid chromatography. Heavy metal detection was performed using an atomic absorption spectrometer. RESULTS: The acute toxicity study showed that the LD50 of the extract was greater than 5000 mg/kg. In the subchronic toxicity study, there were no significant adverse effects on food consumption, body weight, organ weights, mortality, clinical chemistry, hematology, gross pathology, or histopathology. However, a dose-dependent increase in the serum urea level was observed. The Ames test revealed that the extract did not have any potential to induce gene mutations in S. typhimurium, either in the presence or absence of S9 activation. Phytochemical analysis of the extract revealed high contents of phenolics, flavonoids, and tannins. High-performance liquid chromatography analysis revealed high levels of vitexin and isovitexin in the extract, and the levels of heavy metals were below the toxic levels. CONCLUSION: The no-observed adverse effect level of F. deltoidea in rats was determined to be 2500 mg/kg. PMID:23778480

  9. 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).

  10. Safety evaluation of Angelica gigas: Genotoxicity and 13-weeks oral subchronic toxicity in rats.

    PubMed

    Yun, Jun-Won; Che, Jeong-Hwan; Kwon, Euna; Kim, Yun-Soon; Kim, Seung-Hyun; You, Ji-Ran; Kim, Woo Ho; Kim, Hyeon Hoe; Kang, Byeong-Cheol

    2015-08-01

    As a well-known traditional medicine, Angelica gigas (AG) and its active constituents, including decursin and decursinol, have been shown to possess several health beneficial properties such as anti-bacterial, immunostimulating, anti-tumor, neuroprotective, anti-nociceptive and anti-amnestic activities. However, there is lack of toxicity studies to assess potential toxicological concerns, especially long-term toxicity and genotoxicity, regarding the AG extract. Therefore, the safety of AG extract was assessed in subchronic toxicity and genotoxicity assays in accordance with the test guidelines published by the Organization for Economic Cooperation and Development. In a subchronic toxicity study for 13 weeks (125, 250, 500, 1000 and 2000 mg/kg body weight, delivered by gavage), data revealed no significant adverse effects of the AG extract in food consumption, body weight, mortality, hematology, biochemistry, necropsy, organ weight and histopathology throughout the study in male and female rats. These results suggest that no observed adverse effect level of the AG extract administered orally was determined to be greater than 2000 mg/kg/day, the highest dose tested. In addition, a battery of tests including Ames test, in vitro chromosome aberration assay and in vivo micronucleus assay suggested that the AG extract was not genotoxic. In conclusion, the AG extract appears to be safe as a traditional medicine for oral consumption.

  11. 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.

  12. 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

  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. Subchronic oral toxicity testing in rats with a liquid hand-dishwashing detergent containing anionic surfactants.

    PubMed

    Scailteur, V; Maurer, J K; Walker, A P; Calvin, G

    1986-02-01

    A subchronic oral toxicity study on a model liquid dishwashing detergent containing anionic surfactants was performed to verify that the formulation, made up of a mixture of various ingredients, did not possess any toxicological properties that would not have been expected from available data for each separate ingredient. The product was administered to rats for 13 wk at dietary levels of 0, 0.025, 0.25 or 2.5% (w/w) in the diet. No adverse effects on gross or microscopic histopathology were apparent at any dose level, although increased relative liver weights at the 2.5% level suggested that this dose caused some adaptive changes.

  15. 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

  16. Leadership Transitions and the First 90 Days.

    PubMed

    Shirey, Maria R

    2016-04-01

    This department highlights change management strategies that may be successful in strategically planning and executing organizational change initiatives. In this article, the author discusses leadership role transitions and provides a framework for successfully navigating the crucial 1st 90 days in an executive leadership role. PMID:27011151

  17. 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

  18. 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.

  19. 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.

  20. Dietary safety of cycloastragenol from Astragalus spp.: subchronic toxicity and genotoxicity studies.

    PubMed

    Szabo, Nancy J

    2014-02-01

    Extracts, teas, and other preparations of Astragalus roots (e.g., Radix Astragali) are historically recognized traditional medicines and foods. Cycloastragenol (CAG), a bioactive triterpene aglycone from Astragalus root extracts, is being developed as a modern dietary ingredient. To this end, studies assessing subchronic toxicity and genotoxic potential were conducted. In the subchronic study with recovery component, rats ingested 0, 40, 80, or 150 mg/kg/d CAG by oral gavage for ⩾91 consecutive days. No treatment-related mortalities occurred and no cardiac effects were identified. Although several endpoints among those monitored (i.e., clinical observations, body weight, food consumption, ophthalmology, urinalysis, hematology, clinical chemistry, gross pathology, organ weights, or histopathology) exhibited statistically significant effects, none was adverse. The oral no-observed-adverse-effect level (NOAEL) for CAG was >150 mg/kg/d in male and female rats. CAG (⩽5000 μg/plate) did not induce mutagenicity in Salmonella typhimurium or Escherichia coli tester strains. Although the in vitro chromosome aberration assay gave a moderately positive response (likely due to poor solubility) for one intermediate concentration (1.50mM) with metabolic activation, responses were negative in all other test groups. Finally, in the in vivo micronucleus assay no clastogenicity was observed in peripheral erythrocytes from mice administered 2000 mg/kg CAG by intraperitoneal injection.

  1. Dietary safety of cycloastragenol from Astragalus spp.: subchronic toxicity and genotoxicity studies.

    PubMed

    Szabo, Nancy J

    2014-02-01

    Extracts, teas, and other preparations of Astragalus roots (e.g., Radix Astragali) are historically recognized traditional medicines and foods. Cycloastragenol (CAG), a bioactive triterpene aglycone from Astragalus root extracts, is being developed as a modern dietary ingredient. To this end, studies assessing subchronic toxicity and genotoxic potential were conducted. In the subchronic study with recovery component, rats ingested 0, 40, 80, or 150 mg/kg/d CAG by oral gavage for ⩾91 consecutive days. No treatment-related mortalities occurred and no cardiac effects were identified. Although several endpoints among those monitored (i.e., clinical observations, body weight, food consumption, ophthalmology, urinalysis, hematology, clinical chemistry, gross pathology, organ weights, or histopathology) exhibited statistically significant effects, none was adverse. The oral no-observed-adverse-effect level (NOAEL) for CAG was >150 mg/kg/d in male and female rats. CAG (⩽5000 μg/plate) did not induce mutagenicity in Salmonella typhimurium or Escherichia coli tester strains. Although the in vitro chromosome aberration assay gave a moderately positive response (likely due to poor solubility) for one intermediate concentration (1.50mM) with metabolic activation, responses were negative in all other test groups. Finally, in the in vivo micronucleus assay no clastogenicity was observed in peripheral erythrocytes from mice administered 2000 mg/kg CAG by intraperitoneal injection. PMID:24316212

  2. Absence of mutagenicity, genotoxicity, and subchronic oral toxicity of Touchi extract.

    PubMed

    Fujita, Hiroyuki; Yamagami, Tomohide

    2007-01-01

    Touchi, a traditional Chinese food used mainly for seasoning is obtained by first steaming soybeans followed by fermentation with Aspergillus oryzae (koji). A series of toxicological studies was conducted to evaluate the mutagenic and genotoxic potential and subchronic toxicity of a water extract of Touchi, a known inhibitor of alpha -glucosidase activity. Touchi extract (TE) did not induce reverse mutations in Salmonella typhimurium strains TA98, TA1537, TA100, TA1535, and Escherichia coli WP2uvrA at concentrations up to 5000 microg/plate, in either the absence or presence of exogenous metabolic activation. No deaths occurred and no abnormal clinical signs were observed in any animal in any group in an in vivo micronucleus test, and TE was devoid of clastogenic activity when administered orally to mice at doses up to 2000 mg/kg/day. Thus, TE was evaluated as negative in the bacterial reverse mutation and mouse bone marrow micronucleus tests under the conditions of these assays. To evaluate its subchronic toxicity, SPF rats were administered TE at doses of 0, 250, 1000, and 2500 mg/kg/day via oral gastric intubation. No treatment-related toxic changes were seen in clinical signs, body weight, food consumption, urinalysis, hematology, blood chemistry, necropsy, organ weight, or histopathology. The no observed adverse effect level for TE was thus considered to be more than 2500 mg/kg/day in both males and females. These results are consistent with Touchi's status as a traditional Chinese food derived from fermented soybeans and its purported long history of use. Specifically, these data are consistent with the expected safety of human consumption of TE up to at least 5 g/day.

  3. Subchronic toxicity study of water pepper extract in F344 rats.

    PubMed

    Kuroiwa, Keiko; Shibutani, Makoto; Inoue, Kaoru; Lee, Kyoung-Youl; Woo, Gye-Hyeong; Hirose, Masao

    2006-08-01

    A subchronic toxicity study of water pepper extract (WPE) from Polygonum hydropiper L. was conducted in groups of 10 male and 10 female F344 rats fed powdered diets containing 0, 62.5, 250, 1000 or 4000 ppm concentrations for 13 weeks. Suppression of body weight gain due to decreased food consumption was observed in both sexes at 4000 ppm, and at autopsy, increase of relative weights was observed for the brain, liver, spleen, kidneys, and testes in these animals, suggestive of the reflection of the reduced body weights. At this dose, slight increases of blood urea nitrogen in both sexes and serum alanine aminotransferase, Na and Cl in females, were observed, suggestive of weak hepatic and renal toxicity, at least in females. The same females also exhibited slight decrease of red blood cells and haematocrit, slight increase of mean corpuscular volume and mean corpuscular haemoglobin, and minimal increase of splenic haemosiderin deposition, providing evidence of slight haemolytic anemia. On the other hand, enhanced accumulation of mast cells was observed in the mesenteric lymph nodes at 4000 ppm in males and 1000 and 4000 ppm in females. Considering the anti-anaphylactic properties of polygodial, a major constituent of WPE, the mast cell accumulation was concluded to be an adaptive change in response to the subchronic oral administration of WPE. Based on the present toxicity data, 1000 ppm was determined to be the no-observed-adverse-effect level, translating into 57.4 and 62.9 mg/kg/day for male and female rats, respectively.

  4. 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.

  5. 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

  6. 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

  7. Subchronic toxicity of chlorine dioxide and related compounds in drinking water in the nonhuman primate.

    PubMed Central

    Bercz, J P; Jones, L; Garner, L; Murray, D; Ludwig, D A; Boston, J

    1982-01-01

    Subchronic toxicities of ClO2, NaClO2, NaClO3 and NH2Cl were studied in the African Green monkeys (Cercopithecus aethiops). The chemicals were administered in drinking water during 30-60 days subchronic rising dose protocols. The only unexpected and significant toxic effect was elicited by ClO2; this chemical inhibited thyroid metabolism in the animals at a dose of ca. 9.0 mg/kg/day. A statistically significant decrease of serum thyroxine occurred after the fourth week of exposure to 100 mg/l.concentration. The extent of thyroid suppression was dose dependent in each individual monkey, and was reversible after cessation of exposure. NaClO2 and NaClO3 failed to elicit similar effects in doses up to ca. 60 mg/kg/day. Also, NaClO4 or NH2Cl did not cause T-4 suppression in doses of 10 mg/kg/day. The selective thyroid effect of ClO2 was unexplained and it appeared to be paradoxical since ClO2 was rapidly reduced by the oral and gastric secretions to nonoxidizing species (presumably Cl-). No evidence of thyroid effects were detected in the serum of human volunteers who ingested approximately 1 mg/l. of ClO2 in drinking water as a result of routine use in the community water treatment process. Sodium chlorite induced dose-dependent oxidative stress on hematopoesis, causing decreased hemoglobin and red cell count and increased methemoglobin content. At the same time, serum transaminase (SGPT) levels showed significant subclinical elevation. The hematologic effects of NaClO2 rebounded during exposure indicating compensatory hemopoietic activity taking effect during oxidative stress. Sodium chlorate and chloramine did not induce detectable hematologic changes in the animals. PMID:7151767

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. Toxicity evaluation of petroleum blending streams: inhalation subchronic toxicity/neurotoxicity study of a light alkylate naphtha distillate in rats.

    PubMed

    Schreiner, C; Lapadula, E; Breglia, R; Bui, Q; Burnett, D; Koschier, F; Podhasky, P; White, R; Mandella, R; Hoffman, G

    1998-10-23

    A 13-wk inhalation study was conducted with Sprague-Dawley CD rats (12/sex/group) were exposed by inhalation for 13 weeks to a light alkylate naphtha distillate (LAND-2, C4-C10; average molecular weight 89.2) at actual average concentrations of 0 (room air), 668, 2220, or 6646 ppm, 6 h/d, 5 d/wk; 12 additional rats/sex in the control and high dose groups were held after final exposure for a 4-wk recovery period. The highest exposure concentration was 75% of the lower explosive limit. Standard parameters of subchronic toxicity were measured throughout the study; at necropsy, organs were weighed and tissues processed for microscopic evaluation. Neurotoxicity evaluations consisted of motor activity (MA) and a functional operational battery (FOB) measured pretest, during 5, 9, and 14 wk of the study, and after the 4-wk recovery period. Whole-body perfusion and microscopic examination of selected organs and nervous tissue from the control and high dose rats were conducted at the end of exposure. No test-related mortality or effects on physical signs, body weight, or food consumption were observed. Statistically significant increases in absolute and relative kidney weights in high-exposure males correlated with microscopically observed hyaline droplet formation and renal nephropathy, effects in male rats that are not toxicologically significant for humans. Increased liver weights in both sexes at the highest dose had no microscopic correlate and appeared reversible after the 4-wk recovery period. Exposure to LAND-2 at any dose did not produce neurotoxicity measured by MA, FOB, or neuropathology. The no-observed-effects level (NOEL) for LAND-2 was 2220 ppm for subchronic toxicity and > or =26646 ppm for neurotoxicity.

  13. 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

  14. Evaluation of the dermal subchronic toxicity of phenoxyethyl isobutyrate in the rat.

    PubMed

    Api, Anne Marie

    2004-02-01

    Phenoxyethyl isobutyrate (PEIB) is a fragrance and food ingredient that has been granted GRAS status and approved by the FDA for food use. The present studies investigated the dermal absorption parameters and subchronic toxicity of PEIB. For the absorption, distribution and elimination study, Sprague-Dawley rats received a dermal application of 2-[ring U 14C]-PEIB under occlusion for 6 h. PEIB was diluted in diethyl phthalate (DEP) to administer, a total application volume of 2 ml/kg, concentrations of 0.5, 5 and 50% ( congruent with 10, 100 and 1000 mg PEIB/kgBW). Approximately 61-69% of the applied dose was recovered from the dressing and skin surface washing procedure performed after 6-h exposure. By 72 h post dose, systemic elimination of radioactivity was congruent with 18 to 19% of the absorbed dose via the urine with small amounts also found in the feces (<1.0%). Terminal (72 h) tissue analysis showed that 0.35-0.72% of the applied dose of radioactivity was retained in the carcass with low levels (subchronic rat toxicity study, daily dermal applications of PEIB were made under occlusion for 6 h. All groups were dosed at a constant 2 ml/kgBW volume of PEIB in the DEP vehicle at concentrations calculated to administer 0, 100, 300 or 1000 mg PEIB/kgBW/day. Clinical observations, assessments of skin irritation, hematology, and blood chemistry, necropsy, and gross and histopathologic evaluation of tissues demonstrated no treatment-related effects. The local skin irritation and systemic toxicity no-observed-effect-levels (NOELs) for PEIB in this study were determined to be >1000 mg/kgBW/day.

  15. Safety Profile of a Polyherbal Formulation (Gynocare capsules) in Female Rats by Subchronic Oral Toxicity Study

    PubMed Central

    Tatke, Pratima A.; Nidhiya, I. S. R.; Deshpande, S. G.

    2012-01-01

    Gynocare capsules, is a polyherbal formulation, are used as uterine tonic and for treating gynaecological ailments like infertility, leucorrhea, and menstrual disorders. The formulation contains ingredients of herbal origin, such as, extracts of Ashoka, Vasaka, Durva, Chandan, Musk, and so on. It was evaluated for its safety at the therapeutic dose level by a repeated dose oral toxicity study in albino Wistar rats. The herbal formulation was administered orally at a therapeutic dose of 100 mg/kg/day, for 90 days. All animals were monitored daily for their health status and signs of abnormalities. The body weight, water consumption, and food intake were measured once weekly. At the end of the experimental period, various hematological and biochemical parameters were estimated and histopathologies of selected organs were conducted. The study resulted from the long-term oral administration of Gynocare capsules (100 mg/kg), did not cause any relevant signs of toxicity nor significant changes in the physical, hematological and biochemical parameters. However, statistically significant differences were seen in the relative organ weights of adrenal gland, ovary, and serum creatinine levels. The reduction in ovary weight revealed the possibility of the drug targeting the ovary. Moreover, no pathological features were identified in the treated group as monitored by the histopathological analysis of the internal organs. The study established that Gynocare capsules at the dose given (100 mg/kg) did not induce any remarkable or significant toxic effects, indicating that it was safe in rats following oral administration for 90 consecutive days. PMID:22778505

  16. Acute and subchronic toxicity as well as mutagenic evaluation of essential oil from turmeric (Curcuma longa L).

    PubMed

    Liju, Vijayasteltar B; Jeena, Kottarapat; Kuttan, Ramadasan

    2013-03-01

    The present study investigated the acute, subchronic and genotoxicity of turmeric essential oil (TEO) from Curcuma longa L. Acute administration of TEO was done as single dose up to 5 g of TEO per kg body weight and subchronic toxicity study for thirteen weeks was done by daily oral administration of TEO at doses 0.1, 0.25 and 0.5 g/kg b.wt. in Wistar rats. There were no mortality, adverse clinical signs or changes in body weight; water and food consumption during acute as well as subchronic toxicity studies. Indicators of hepatic function such as aspartate aminotransferase (AST), alanine amino transferase (ALT) and alkaline phosphatase (ALP) were unchanged in treated animals compared to untreated animals. Oral administration of TEO for 13 weeks did not alter total cholesterol, triglycerides, markers of renal function, serum electrolyte parameters and histopathology of tissues. TEO did not produce any mutagenicity to Salmonella typhimurium TA-98, TA-100, TA-102 and TA-1535 with or without metabolic activation. Administration of TEO to rats (1 g/kg b.wt.) for 14 days did not produce any chromosome aberration or micronuclei in rat bone marrow cells and did not produce any DNA damage as seen by comet assay confirming the non toxicity of TEO.

  17. Evaluation of the dermal subchronic toxicity of diphenyl ether in the rat.

    PubMed

    Api, A M; Ford, R A

    2003-02-01

    Diphenyl ether (DPE) was investigated to determine the dermal absorption parameters and subchronic toxicity of this fragrance ingredient. For the absorption, distribution and elimination study, Sprague-Dawley rats received a dermal application of [14C]DPE under a semi-occlusive dressing for 6 h. DPE was diluted in diethyl phthalate (DEP) to administer a total application volume of 2 ml/kg and concentrations of 0.5, 5 and 50% (approximately equal to 10, 100 and 1000 mg DPE/kg body weight). Approximately 17.7% of the administered dose was eliminated in the urine, with small amounts also found in the feces (1.18-3.79%). At 72 h post-dosing, approximately 0.2% of the applied dose was retained in the body with low levels also measured in the liver, kidney and gastrointestinal tract (approximately equal to 0.04, 0.02 and 0.3%, respectively). The 13-week subchronic toxicity study was performed with groups of 12 Sprague-Dawley rats/sex/dose that received semi-occluded daily dermal applications of DPE for 6 h/day. All groups were dosed at a constant 2 ml/kg body weight volume of DPE in the DEP vehicle at concentrations to administer 0, 100, 300 or 1000 mg DPE/kg body weight/day. At the high dose level, there was a slight reduction in body weight gain in males (13%), increase in albumin (5-6%) and phosphate (10-15%) levels in both sexes, a reduction of cholesterol in females (14%), an increase in kidney (17%) and brain (8%) weights in males, and an increase in liver weight (18-19%) in both sexes. No histopathological lesions were seen in any organ examined. At 300 mg/kg body weight/day, the only notable findings were an increase in liver weight (10%) in both sexes and a slight increase in albumin (5%) in females. In addition, skin irritation reactions at the site of application were observed in all DPE dose groups. The systemic no-observed-effect level (NOEL) in this study is 100 mg/kg body weight/day. Owing to mitigating factors, the systemic findings were judged to lack

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. A 13-week subchronic toxicity study of sodium iron chlorophyllin in F344 rats.

    PubMed

    Toyoda, Takeshi; Cho, Young-Man; Mizuta, Yasuko; Akagi, Jun-ichi; Nishikawa, Akiyoshi; Ogawa, Kumiko

    2014-02-01

    Sodium iron chlorophyllin (SIC), a water-soluble chlorophyll derivative, has been used as a food additive for green coloration. In the present study, a subchronic toxicity study of SIC was performed in male and female F344 rats with oral administration in diet at concentrations of 0%, 0.2%, 1.0%, and 5.0% for 13 weeks. No mortalities, abnormal clinical signs, and hematological changes were observed in any of the groups during the experiment. Significant reduction of body weight gain was noted in 5.0% males. In serum biochemistry, serum transferrin levels were significantly increased in 5.0% males and females. Relative spleen weights of both sexes were markedly reduced with 5.0% SIC as compared to the controls, and absolute weights of spleen were also significantly decreased in males. On histopathological assessment, diffuse hypertrophy of acinar cells in the parotid gland was observed in all examined 5.0% males and females, but not in the other groups. Based on the histopathology of the parotid glands, the no-observed-adverse-effect level (NOAEL) of SIC in the present study was estimated to be 1.0% (609 mg/kg bw/day for males and 678 mg/kg bw/day for females).

  3. Genotoxicity and subchronic toxicity evaluation of dried Euglena gracilis ATCC PTA-123017.

    PubMed

    Simon, Ryan R; Vo, Trung D; Levine, Robert

    2016-10-01

    Euglena gracilis is a microalga capable of synthesizing various nutrients of interest in human and animal nutrition. When cultivated aerobically in the dark, Euglena synthesize paramylon, a storage polysaccharide comprised of high molecular weight beta-1,3-D-glucose polymers organized in cytoplasmic granules. Beta-glucans have been shown to have immune modulation effects, including anti-microbial, anti-tumor, and anti-oxidant properties, and metabolic effects, such as regulation of cholesterol and blood sugar levels. Preparations of E. gracilis and paramylon may therefore have potential utility as functional food ingredients for human and animal nutrition. A battery of toxicological studies was conducted on a dried preparation of E. gracilis and paramylon to support their safe food use. The dried alga was not genotoxic in a bacterial reverse mutation test and mammalian micronucleus test. In the subchronic toxicity study, rats were provided E. gracilis in the diet at levels of 0, 12,500, 25,000 or 50,000 ppm. Paramylon was provided at a concentration of 50,000 ppm. No effects that could be attributable to treatment were observed in clinical observations, body weight, food consumption, ophthalmology, hematology and clinical chemistry, urinalysis, and macroscopic and microscopic findings. A NOAEL of 50,000 ppm in the diet was determined for both ingredients.

  4. Genotoxicity and subchronic toxicity evaluation of dried Euglena gracilis ATCC PTA-123017.

    PubMed

    Simon, Ryan R; Vo, Trung D; Levine, Robert

    2016-10-01

    Euglena gracilis is a microalga capable of synthesizing various nutrients of interest in human and animal nutrition. When cultivated aerobically in the dark, Euglena synthesize paramylon, a storage polysaccharide comprised of high molecular weight beta-1,3-D-glucose polymers organized in cytoplasmic granules. Beta-glucans have been shown to have immune modulation effects, including anti-microbial, anti-tumor, and anti-oxidant properties, and metabolic effects, such as regulation of cholesterol and blood sugar levels. Preparations of E. gracilis and paramylon may therefore have potential utility as functional food ingredients for human and animal nutrition. A battery of toxicological studies was conducted on a dried preparation of E. gracilis and paramylon to support their safe food use. The dried alga was not genotoxic in a bacterial reverse mutation test and mammalian micronucleus test. In the subchronic toxicity study, rats were provided E. gracilis in the diet at levels of 0, 12,500, 25,000 or 50,000 ppm. Paramylon was provided at a concentration of 50,000 ppm. No effects that could be attributable to treatment were observed in clinical observations, body weight, food consumption, ophthalmology, hematology and clinical chemistry, urinalysis, and macroscopic and microscopic findings. A NOAEL of 50,000 ppm in the diet was determined for both ingredients. PMID:27311684

  5. 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

  6. A 13-week subchronic intravaginal toxicity study of pokeweed antiviral protein in mice.

    PubMed

    D'Cruz, O J; Waurzyniakt, B; Uckun, F M

    2004-01-01

    Pokeweed antiviral protein (PAP), a 29-kDa plant-derived protein isolated from Phytolacca americana, is a broad-spectrum antiviral agent. PAP shows unique clinical potential to become the active ingredient of a non-spermicidal microbicide because of its potent in vivo anti-HIV activity, non-interference with in vivo sperm functions, and lack of cytotoxicity to genital tract epithelial cells. Over 13 weeks the subchronic and reproductive toxicity potential of an intravaginally administered gel formulation of PAP was studied in mice to support its further development as a vaginal microbicide. Female B6C3F1 and CD-1 mice in subgroups of 20, were exposed intravaginally to a gel formulation containing 0, 0.025, 0.05, or 0.1% PAP, 5 days/week for 13 consecutive weeks. On a molar basis, these concentrations are 500- to 2000-times higher than the in vitro anti-HIV IC50 value. After 13 weeks of intravaginal treatment, B6C3F1 mice were evaluated for survival, body weight gain, and absolute and relative organ weights. Blood was analyzed for hematology and clinical chemistry profiles. Microscopic examination was performed on hematoxylin and eosin-stained tissue sections from each study animal. Placebo-control and PAP-dosed female CD-1 mice were mated with untreated males in order to evaluate if PAP has any deleterious effects on reproductive performance. There were no treatment-related mortalities. Mean body weight gain was not reduced by PAP treatment during the dosing period. The hemogram and blood chemistry profiles revealed lack of systemic toxicity following daily intravaginal instillation of PAP for 13 weeks. No clinically significant changes in absolute and relative organ weights were noted in the PAP dose groups. Extensive histopathological examination of tissues showed no increase in treatment-related microscopic lesions in any of the three PAP dose groups. Repeated intravaginal exposure of CD-1 mice to increasing concentrations of PAP for 13 weeks showed no adverse

  7. Pathological, immunological and biochemical markers of subchronic arsenic toxicity in rats.

    PubMed

    Nain, Sukhbir; Smits, Judit E G

    2012-03-01

    Subchronic exposure to arsenic in rats was investigated to identify sensitive indicators of subclinical toxicity in rats. Immunological, pathological, and biochemical bioindicators were examined in rats exposed to arsenic in their drinking water. Juvenile male Wistar rats were allocated to four treatment groups receiving 0, 0.4, 4, and 40 ppm of arsenite in drinking water for 18 wks. Besides daily monitoring for clinical signs of adverse health effects, clinical biochemistry, B-cell-mediated and innate immune responses, plus gross, and histopathology were examined. In vitro tests of oxidative damage to basic cellular constituents, lipids, proteins, and nucleic acids, were measured using thiobarbituric acid reacting substances (TBARS) assays, protein carbonyl formation, and 8-hydroxydeoxyguanosine (8-OHdG), respectively. Clinical changes in the rats were limited to decreased feed and water intake in the high- (40 ppm) dose group (P < 0.05), however, growth rate was not affected. Serum biochemical changes occurred in blood urea nitrogen, K(+) , Cl(-) , and alanine aminotransferase (ALT) from arsenic exposure. Immunotoxicity was evident through a dose-dependent suppression of the secondary antibody-mediated response to a T-cell-dependent antigen, keyhole limpet hemocyanin (KLH). Histopathology of the liver revealed marked fatty infiltration and vacuolization particularly evident in periacinar hepatocytes. This pattern of toxicopathology in the high-exposure group may be related to the significantly higher (P < 0.05) oxidative stress, demonstrated through lipid peroxidation (TBARS assay) in the rats exposed to 40 ppm arsenite. The present study revealed that young, growing rats exposed to arsenic for 18 wks tolerated exposures up to 4 ppm. At higher doses, there was evidence of hepatotoxicity, humoral immunity was compromised, and an adverse effect on hepatic organelle and cell membranes was evident through a dose dependent increased in oxidative stress.

  8. Subchronic (13-week) toxicity and prenatal developmental toxicity studies of dietary astaxanthin in rats.

    PubMed

    Vega, Katherine; Edwards, James; Beilstein, Paul

    2015-12-01

    Two studies examined the effects of dietary astaxanthin on Hanlbm Wistar (SPF) rats. Male and female rats receiving astaxanthin concentrations up to 1.52% of the feed for 13 weeks showed no evidence of toxicity; no effects were noted in the offspring of female rats exposed to astaxanthin at up to 1.39% of the feed during the period of organogenesis (GD 7-16). Discoloration of the feces and yellow pigmentation of adipose tissue was seen in the 13-week study, an intrinsic property of the substance, and not a sign of toxicity. Differences between the control and astaxanthin groups, some of which reached statistical significance, were generally sporadic (i.e., transient and/or not related to astaxanthin concentration) and not considered of biological or toxicological significance. Blood cholesterol levels, for example, were greater in animals receiving astaxanthin for 13 weeks, but remained within the normal range. The highest dietary concentration of astaxanthin in each of the studies is proposed as a no-observable-adverse-effect level (NOAEL). Specifically, 1.52% for the 13-week study, corresponding to a mean intake of 1033 mg/kg bw/day (range: 880-1240 mg/kg bw/day), and 1.39% for the developmental toxicity study, corresponding to a mean intake of approximately 830 mg/kg bw/day (range: 457-957 mg/kg bw/day).

  9. Perfluoro-n-butyl iodide: acute toxicity, subchronic toxicity and genotoxicity evaluations.

    PubMed

    Dodd, Darol; Hoffman, Gary; Hardy, Colin

    2004-01-01

    Perfluoro-n-butyl iodide (PFBI) is a promising alternative to chlorofluorocarbon solvents used in aircraft ground maintenance operations and other military and commercial operations, because it cleans well, has zero ozone depletion potential, and has extremely low global warming properties. Toxicity tests were performed with PFBI to determine and evaluate its health hazard. Using standard testing guidelines (e.g., Organization for Economic Cooperation and Development [OECD]), tests included acute (4-h) and 4-week (6 h/day, 5 days/week) inhalation (nose-only) toxicity studies in rats, acute (10-min) inhalation cardiac sensitization study in dogs, in vitro chromosomal aberrations experiments in human lymphocytes, and in vitro mutagenic experiments in Salmonella typhimurium and Escherichia coli. There were no mortalities in rats (n = 10) exposed for 4 h to 10,000 ppm PFBI, but all rats (n = 10) died within 2 h when exposed to 20,000 ppm PFBI. The 4-h LC50 (95% confidence limits) was 14,000 ppm (13,000 ppm to 16,000 ppm). Signs (nasal discharge and labored breathing) observed in the rats exposed to 10,000 ppm returned to normal within 48 h. PFBI has the potential to cause cardiac sensitization in epinephrine-challenged dogs at 6200 ppm. A concentration of 3900 ppm was a no-observed-adverse-effect level (NOAEL) in the cardiac sensitization study. In the 4-week inhalation study (5 rats/sex/group), respiratory mucosal hypertrophy/hyperplasia was observed in rats of the 10,000-ppm group. A NOAEL of 1000 ppm was selected for the 4-week study on the basis that the mild increase in T4 observed at 1000 ppm was considered adaptive, not adverse, because of the absence of frank effects in the thyroid. In the in vitro studies, PFBI showed no evidence of either mutagenic or clastogenic activity. The toxicity profile of PFBI was compared to trifluoroiodomethane. In conclusion, the results of these studies indicate a low order of general toxicity and an absence of genotoxicity

  10. 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.

  11. 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

  12. 40 CFR 799.9325 - TSCA 90-day dermal toxicity.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... possible, throughout the duration of the study, and the research sample should be stored under conditions... clinical chemistry examinations must be made on all animals, including controls, of each sex in each group. The hematology and clinical chemistry parameters should be examined at terminal sacrifice at the...

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

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... and control groups is required. (D) Each animal shall be assigned a unique identification number. Dead... substance shall be measured in the animal's breathing zone. During the exposure period, the actual... provided the mixture at the animal's breathing zone is analogous to the formulation; the grounds for...

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

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... and control groups is required. (D) Each animal shall be assigned a unique identification number. Dead... substance shall be measured in the animal's breathing zone. During the exposure period, the actual... provided the mixture at the animal's breathing zone is analogous to the formulation; the grounds for...

  15. 40 CFR 799.9346 - TSCA 90-day inhalation toxicity.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... and control groups is required. (D) Each animal shall be assigned a unique identification number. Dead... substance shall be measured in the animal's breathing zone. During the exposure period, the actual... provided the mixture at the animal's breathing zone is analogous to the formulation; the grounds for...

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

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... and control groups is required. (D) Each animal shall be assigned a unique identification number. Dead... substance shall be measured in the animal's breathing zone. During the exposure period, the actual... provided the mixture at the animal's breathing zone is analogous to the formulation; the grounds for...

  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... triglycerides, hormones, methemoglobin, and cholinesterases. (iii) Optionally, the following...

  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... triglycerides, hormones, methemoglobin, and cholinesterases. (iii) Optionally, the following...

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

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... of this study to humans is valid only to a limited degree. It can, however, provide useful... human exposure. (b) Source. The source material used in developing this TSCA test guideline is the... substance (grams, milligrams), per unit body weight of test animal (milligrams per kilogram), or as...

  20. 40 CFR 799.9346 - TSCA 90-day inhalation toxicity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...) should be used for each test group. (B) If interim sacrifices are planned, the number of animals shall be increased by the number of animals scheduled to be sacrificed before the completion of the study. (C) To... substance should be used, if possible throughout the duration of the......

  1. 40 CFR 799.9325 - TSCA 90-day dermal toxicity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... level. (B) If interim sacrifices are planned, the number must be increased by the number of animals... solution of oil and then solution of other vehicles. (ii) One lot of the test substance should be used, if... characterization of the test substance, including the purity......

  2. 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...

  3. 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...

  4. [Sub-chronic toxicity and test of eye irritability of leaf aqueous extract from Plantago major (plantaginaceae)].

    PubMed

    García González, Mildred; Coto Morales, Teresita; Soto Rodríguez, Gerardo A; Pazos, Liliana

    2003-01-01

    For the sub-chronic toxicity an aqueous preparation of Plantago major leaves was tested in 20 male NGP mice, with an average weight of 20.15 g and separated in two groups of ten individuals each. The dose used was 2000 mg/kg and the control group received 0.5 ml of distilled water. The extract administration was done daily during five days at week for a total period of 40 days. Signs of sub-chronic toxicity were observed in the days two and 12 of treatment. No significant change in corporal weight was observed. The ocular irritation was tested in five New Zeland male rabbits, with an average weight of 3.640 kg. The dose used was a 200 microliters the preparation (100 mg/ml) of Plantago major leaves, instill into the right eye and the control was used the left eye instill 200 microliters of distilled water. The administration was done daily during five days. The extract shows no significant irritation during the observation period.

  5. [Sub-chronic toxicity and test of eye irritability of leaf aqueous extract from Plantago major (plantaginaceae)].

    PubMed

    García González, Mildred; Coto Morales, Teresita; Soto Rodríguez, Gerardo A; Pazos, Liliana

    2003-01-01

    For the sub-chronic toxicity an aqueous preparation of Plantago major leaves was tested in 20 male NGP mice, with an average weight of 20.15 g and separated in two groups of ten individuals each. The dose used was 2000 mg/kg and the control group received 0.5 ml of distilled water. The extract administration was done daily during five days at week for a total period of 40 days. Signs of sub-chronic toxicity were observed in the days two and 12 of treatment. No significant change in corporal weight was observed. The ocular irritation was tested in five New Zeland male rabbits, with an average weight of 3.640 kg. The dose used was a 200 microliters the preparation (100 mg/ml) of Plantago major leaves, instill into the right eye and the control was used the left eye instill 200 microliters of distilled water. The administration was done daily during five days. The extract shows no significant irritation during the observation period. PMID:15162770

  6. Assessment of the potential reproductive and subchronic toxicity of EDS coal liquids in Sprague-Dawley rats.

    PubMed

    McKee, R H; Plutnick, R T; Traul, K A

    1987-11-01

    The EDS direct coal liquefaction process is one of several methods of producing liquid fuels from coal which have reached the pilot or demonstration stage of development. Relatively high levels of polycyclic aromatic hydrocarbons are present in distillate fractions boiling above approximately 370 degrees C, and unrefined coal-derived liquids which contain substantial amounts of material from this boiling range are relatively potent dermal carcinogens. Because coal-derived liquids containing high boiling (i.e., greater than 370 degrees C) material may pose a variety of toxic hazards, efforts have been made to evaluate the potential effects on biological endpoints other than cancer. The present studies assessed the potential for reproductive and subchronic toxicity following repeated oral administration of 2 coal-derived liquids, recycle solvent and fuel oil, which contained substantial amounts of high boiling material. Few biologically important differences were found in any of the experimental parameters. In the reproductive toxicity study, frequency of fertilization and implantation, mean number of live births, fraction of litter surviving through the lactation period and mean weight gain of the litters during the lactation period were not affected by treatment; in addition, there was no evidence of increased frequency of malformation. In the subchronic toxicity study, weight gain was reduced in animals from the high dose groups, but was not significantly different from controls. Liver weights were significantly elevated, but there was no microscopic evidence of pathologic changes. Erythrocyte counts, hemoglobin levels and hematocrits were significantly reduced suggesting a tendency towards anemia. These findings suggested that repeated exposure to EDS recycle solvent and fuel oil at levels of up to 0.5 g/kg per day had no detectable effect on reproductive capacity or performance and did not induce substantial systemic toxicity.

  7. 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

  8. 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

  9. Subchronic and acute preclinic toxicity and some pharmacological effects of the water extract from leaves of Petiveria alliacea (Phytolaccaceae).

    PubMed

    García-González, Mildred; Morales, Teresita Coto; Ocampo, Rafael; Pazos, Liliana

    2006-12-01

    We tested the effects of the aqueous extract of Petiveria alliacea leaves on acute and sub-chronic toxicity, hematocrit and blood glucose level and intestinal motility of male albino NGP mice of 20 to 25 g mean weight. Treatments were in all cases doses of 1,000 and 2,000 mg/kg animal weight and a control treatment with 0.5 ml distilled water, using 10 animals per treatment and administered orally every day (5 days per week). Experimental periods were 18 and 70 days for acute and sub chronic toxicity, respectively. No mortality nor any toxicity signs could be observed. A slight but significant increase in the glucose levels during the first three weeks was observed with the 1,000 mg/kg dose but not for the higher 2,000 mg/kg dose. After administering the doses once after a starving period of six hours, no significant differences in intestinal motility could be found.

  10. 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.

  11. Nephroprotective effect of jaggery against acute and subchronic toxicity of acetaminophen in Wistar rats.

    PubMed

    Sharma, Chandra Kant; Sharma, Vinay

    2012-01-01

    The present investigation was planned to evaluate the nephroprotective activity of jaggery against acetaminophen (APAP)-induced renal damage in rats. The protective activity of jaggery at different doses (250, 500, and 750 mg/kg, orally) was evaluated against oxidative damage induced by APAP administration (2 g/kg, once orally in acute exposure; 20 mg/kg, orally for 21 days in subchronic exposure) in rats. APAP administration significantly increased the levels of serum urea, creatinine, and renal lipid peroxidation (LPO), whereas substantial decreases were observed in levels of glutathione (GSH), adenosine triphosphatase (ATPase), superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), and glutathione peroxidase (GPx) enzymatic activities after APAP administration. Administration of jaggery significantly moved the studied parameters toward normal levels and also reversed the histopathologic alterations. Thus, jaggery can be used to reduce renal damage and may serve as an alternative medicine in the treatment of renal etiologies.

  12. 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.

  13. 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.

  14. 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.

  15. Subchronic toxicity study in rats and genotoxicity tests with polyvinyl alcohol.

    PubMed

    Kelly, C M; DeMerlis, C C; Schoneker, D R; Borzelleca, J F

    2003-05-01

    The potential systemic and neurotoxicity of polyvinyl alcohol (PVA) was assessed when fed in the diet to male and female Sprague-Dawley rats for 90 days at doses of 2000, 3500 and 5000 mg/kg/day. Control rats received untreated standard laboratory diet. Assessments included clinical observations, ophthalmology, body weight and food consumption, hematology, coagulation, clinical chemistry, urinalyses, motor activity and functional observational battery evaluations and gross and microscopic pathology. The only test-article-related finding observed during the study was unformed stool with brown/black anogenital staining in rats fed 3500 and 5000 mg/kg/day. This finding was attributed to the high levels of test article being consumed and subsequently excreted in the stool. It was not accompanied by macroscopic or microscopic changes in these rats. No test-article-related changes were seen in mortality, ophthalmology, body weight and food consumption data, hematology, clinical chemistry, urinalysis data, functional observational assessments, motor activity, organ weight data and macroscopic and microscopic examinations. Doses of 2000, 3500 and 5000 mg/kg/day of PVA administered as a dietary admixture to male and female Sprague-Dawley rats for up to 90 days did not result in any adverse, toxicological effects. The no-observed-adverse-effect level (NOAEL) was determined to be 5000 mg/kg/day. PVA showed no evidence of mutagenic activity in the Ames test, mouse lymphoma assay and the mouse micronucleus test. (A critical evaluation of the available information on PVA will appear in a review to be published in Food and Chemical Toxicology 2003, 41, 319-326)

  16. 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...

  17. 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

  18. Towards a 90-Day Monthly Storm Outlook for Alaska

    NASA Astrophysics Data System (ADS)

    Partain, J. L.

    2011-12-01

    In all seasons, storms represent high-impact weather events in Alaska. Alaska's extensive coastline makes the region especially vulnerable to coastal flooding and erosion, particularly where a protective sea ice buffer is absent. There exists a major need for an expanded temporal range of storm outlooks to enable proactive responses by coastal communities and the various industries noted above. The expansion envisioned here is to the 90-day range. The NOAA Climate Prediction Center's (CPC) Storm Tracks website presently includes summaries of storm tracks and accumulated precipitation for the past 10-, 30- and 90-day periods, together with Week-1 and Week-2 forecast storm tracks from the Global Forecast System's (GFS) operational run and the GFS ensemble. Given the limits of deterministic predictability, we will extend the window of the storm outlook to 90 days by drawing upon the present and CPC-predicted states of ENSO, the Pacific Decadal Oscillation, and the Arctic Oscillation -- three large-scale modes of variability known to affect Alaska. In order to link the large-scale modes of variability to storm probabilities in various Alaskan sub-regions, we will explore the use of composites and analog years based on the states of the major teleconnection modes. This presentation will include an end-to-end plan for the development and testing of this product.

  19. Subchronic sensitivity of one-, four-, and seven-day-old fathead minnow (Pimephales promelas) larvae to five toxicants

    SciTech Connect

    Pickering, Q.H.; Lazorchak, J.M.; Winks, K.L.

    1996-03-01

    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, KCl, NaCl, 1-octanol, carbaryl, and benzaldehyde. The no observable effect concentration (NOEC) for survival of the two inorganic compounds, KCl and NaCl, was not affected by age of the larvae. The subchronic valve (SCV) for NaCl was always determined by survival. Hypothesis testing of biomass always gave the same NOEC for the three age groups for each of the two inorganic compounds, and a minimum significant difference (MSD) was always calculable. The effect of 1-octanol on growth was more sensitive than the effect on survival in eight of the nine toxicity tests. Within a set of 1-, 4-, and 7-d-old larvae tests the SCV varied only twofold; however, between sets of tests the variation was fourfold. The SCV of carbaryl was determined by the effect on growth in five of six tests. Except for one test the SCV varied only twofold. The 1-d larvae were more sensitive to benzaldehyde than 1- and 7-d larvae in two sets of tests. The SCV was determined on the basis of survival for 1-d-old larvae and on the basis of growth for 4- and 7-d-old larvae.

  20. 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.

  1. 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

  2. Toxicity evaluation of petroleum blending streams: inhalation subchronic toxicity/neurotoxicity study of a light catalytic cracked naphtha distillate in rats.

    PubMed

    Lapin, C; Bui, Q; Breglia, R; Koschier, F; Podhasky, P; Lapadula, E; Roth, R; Schreiner, C; White, R; Clark, C; Mandella, R; Hoffman, G

    2001-01-01

    A 15-week, whole-body inhalation study of the vapors of a distillate (LCCN-D) of light catalytic cracked naphtha (CAS no. 64741-55-5, LCCN) was conducted with Sprague-Dawley rats. Target exposure concentrations were 0, 750, 2500, and 7500 ppm for 6 hours/day, 5 days/week. Over the course of the study, animals received at least 65 exposures. For a portion of the control and 7500-ppm groups, a 4-week postexposure period was included in the study. Subchronic toxicity was evaluated using standard parameters. During life, neurotoxicity was evaluated by motor activity assessment and a functional observational battery. Selected tissues from animals in all exposure groups were examined microscopically. Neuropathologic examination of selected neuronal tissues from animals in the control and high-exposure groups was also conducted. No compound-related effects were seen on survival, clinical chemistry, food consumption, or physical signs. No evidence of neurotoxicity was seen at any exposure level. Slight decreases in hematocrit and hemoglobin concentrations were seen in male rats at the end of exposure to 7500 ppm LCCN-D. However, values were within normal physiological ranges and recovery occurred. Slight decreases in mean body weights and body weight gain were observed in high-exposure females during the first 7 weeks of exposure, but this decrease was not seen during the second half of the study. Male rat nephropathy involving hyaline droplet formation and alpha-2micro-globulin accumulation was seen in mid- and high-exposure males, an effect not relevant to humans. The incidence and severity of goblet cell hypertrophy/hyperplasia and respiratory epithelium hyperplasia in nasoturbinal tissues were greater in high-exposure animals, but recovery occurred. None of the effects observed were considered toxicologically significant. The no-observable-adverse-effect level (NOAEL) for subchronic and neurotoxicity of LCCN-D was > or = 7500 ppm.

  3. 40 CFR 79.62 - Subchronic toxicity study with specific health effect assessments.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... references should be consulted. (1) 40 CFR 798.2450, Inhalation toxicity. (2) 40 CFR 798.2675, Oral Toxicity.../teratology guideline is found in § 79.63. (ii) Micronucleus (MN) Assay. The MN assay is an in vivo... vehicle/engine emissions. The MN assay detects damage to the chromosomes or mitotic apparatus of cells...

  4. 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.../teratology guideline is found in § 79.63. (ii) Micronucleus (MN) Assay. The MN assay is an in vivo... vehicle/engine emissions. The MN assay detects damage to the chromosomes or mitotic apparatus of cells...

  5. 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.../teratology guideline is found in § 79.63. (ii) Micronucleus (MN) Assay. The MN assay is an in vivo... vehicle/engine emissions. The MN assay detects damage to the chromosomes or mitotic apparatus of cells...

  6. Physical exercise prior and during treatment reduces sub-chronic doxorubicin-induced mitochondrial toxicity and oxidative stress.

    PubMed

    Marques-Aleixo, Inês; Santos-Alves, Estela; Mariani, Diogo; Rizo-Roca, David; Padrão, Ana I; Rocha-Rodrigues, Sílvia; Viscor, Ginés; Torrella, J Ramon; Ferreira, Rita; Oliveira, Paulo J; Magalhães, José; Ascensão, António

    2015-01-01

    Doxorubicin (DOX) is an anti-cancer agent whose clinical usage results in a cumulative and dose-dependent cardiotoxicity. We have previously shown that exercise performed prior to DOX treatment reduces the resulting cardiac(mito) toxicity. We sought to determine the effects on cardiac mitochondrial toxicity of two distinct chronic exercise models (endurance treadmill training-TM and voluntary free-wheel activity-FW) when used prior and during DOX treatment. Male-young Sprague-Dawley rats were divided into six groups (n=6 per group): SAL+SED (saline sedentary), SAL+TM (12-weeks TM), SAL+FW (12-weeks FW), DOX+SED (7-weeks of chronic DOX treatment 2mg/kg per week), DOX+TM and DOX+FW. DOX administration started 5weeks after the beginning of the exercise protocol. Heart mitochondrial ultrastructural alterations, mitochondrial function (oxygen consumption and membrane potential), semi-quantification of oxidative phosphorylation (OXPHOS) proteins and their in-gel activity, as well as proteins involved in mitochondrial oxidative stress (SIRT3, p66shc and UCP2), biogenesis (PGC1α and TFAM), acetylation and markers for oxidative damage (carbonyl groups, MDA,SH, aconitase, Mn-SOD activity) were evaluated. DOX treatment resulted in ultrastructural and functional alterations and decreased OXPHOS. Moreover, DOX decreased complex I activity and content, mitochondrial biogenesis (TFAM), increased acetylation and oxidative stress. TM and FW prevented DOX-induced alteration in OXPHOS, the increase in oxidative stress, the decrease in complex V activity and in complex I activity and content. DOX-induced decreases in TFAM and SIRT3 content were prevented by TM only. Both chronic models of physical exercise performed before and during the course of sub-chronic DOX treatment translated into an improved mitochondrial bioenergetic fitness, which may result in part from the prevention of mitochondrial oxidative stress and damage. PMID:25446396

  7. Toxicity evaluation of petroleum blending streams: inhalation subchronic toxicity/neurotoxicity study of a light catalytic reformed naphtha distillate in rats.

    PubMed

    Schreiner, C; Bui, Q; Breglia, R; Burnett, D; Koschier, F; Lapadula, E; Podhasky, P; White, R

    2000-08-11

    A 13-wk whole-body inhalation study was conducted with Sprague-Dawley CD rats (16/sex/group) exposed to a light catalytic reformed naphtha distillate (LCRN-D, CAS number 64741-63-5) at target concentrations of 0, 750, 2500, and 7500 ppm for 6 h/d, 5 d/wk. Sixteen rats per sex in the control and high-dose groups were maintained after final exposure for a 4-wk recovery period. The highest exposure concentration was 75% of the lower explosive limit. Standard parameters of subchronic toxicity were measured throughout the study; at necropsy, organs were weighed and tissues processed for microscopic evaluation. Neurotoxicity evaluations consisted of motor activity (MA) and a functional operational battery (FOB) measured pretest, throughout exposure and after the recovery period. Neuropathology was evaluated at termination. No test-related mortality or effects on physical signs, body weight, food consumption, or clinical chemistry were observed. In males exposed to 7500-ppm LCRN-D, a statistically significant decrease in white blood cell counts and lymphocyte counts was observed at the termination of exposure that was not present in animals after the 4-wk recovery period. However, mean corpuscular volume was slightly decreased in high-dose males after the recovery period. Statistically significant increases in kidney weights relative to body weights in 7500-ppm male rats correlated with microscopically observed hyaline droplet formation and renal tubule dilation, indicative of light hydrocarbon nephropathy, a condition in male rats that is not toxicologically significant for humans. Statistically significant decrease in absolute and relative spleen weights in 7500-ppm male rats correlated with decreases in hematologic parameters but had no microscopic correlate and was not observed in animals after 4 wk of recovery. This mild, reversible effect in white blood cell populations may relate to the presence of aromatics in the distillate. The only effect of LCRN-D on

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

    SciTech Connect

    Oikari, A.; Linstroem-Seppae, P.Ku.; 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.

  9. 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

  10. Does a concomitant exposure to lead influence unfavorably the naphthalene subchronic toxicity and toxicokinetics?

    PubMed

    Katsnelson, Boris A; Minigaliyeva, Ilzira A; Degtyareva, Tamara D; Privalova, Larisa I; Beresneva, Tatyana A

    2014-01-01

    Rats were given 20 times during 40 d either naphthalene per gavage or the same and lead acetate intraperitoneally in single doses corresponding to 5% of the respective 50% lethal doses. The concomitant exposure to lead not only added some typical indicators of lead toxicity to the moderate naphthalene intoxication picture but also exaggerated some less specific indices for intoxication. However, a number of such indices testified to attenuation of naphthalene's adverse effects under the impact of lead. Lead also lowered urinary excretion of both total and conjugated naphthalene, while the free- to total naphthalene ratio in urine sharply increased. These results corroborate implicitly the initial hypothesis that lead, being an inhibitor of cytochrome P450, hinders phase I of the naphthalene biotransformation and, thus, the formation of derivates which can be more toxic but are capable of entering into reactions of conjugation with resulting detoxication and elimination of naphthalene from the body.

  11. Oral subchronic toxicity of aqueous crude extract of Plantago australis leaves.

    PubMed

    Palmeiro, N M S; Almeida, C E; Ghedini, P C; Goulart, L S; Pereira, M C F; Huber, S; da Silva, J E P; Lopes, S

    2003-09-01

    The toxic effects of chronic oral administration (60 days) of aqueous crude extract (AE) of Plantago australis Lam. (Plantaginaceae) in rats at doses of 850 and 1700 mg/kg on biochemical (ALT, AST, creatinine, urea, glucose, alkaline phosphatase, total proteins and albumin), hematological (complete hemogram), and histopathological (heart, lung, liver, kidney, esophagus, stomach and gut) parameters were studied. All biochemical and hematological parameters were found to be in the normal range, but ALT in animals that received AE of 850 mg/kg was higher. Histopathological analysis of organs, especially the liver did not present alterations. PMID:12902047

  12. Subchronic inhalation toxicity of iron oxide (magnetite, Fe(3) O(4) ) in rats: pulmonary toxicity is determined by the particle kinetics typical of poorly soluble particles.

    PubMed

    Pauluhn, Jürgen

    2012-07-01

    Wistar rats were nose-only exposed to pigment-sized iron oxide dust (Fe(3) O(4) , magnetite) in a subchronic 13-week inhalation study according to the OECD testing guidelines TG#413 and GD#39. A 4 week pilot study with a 6 month post exposure period served as basis for validating the kinetic modeling approaches utilized to design the subchronic study. Kinetic analyses made during this post exposure period demonstrated that a diminution in particle clearance and lung inflammation occurred at cumulative exposure levels exceeding the lung overload threshold. Animals were exposed 6 h per day, five days per week for 13 consecutive weeks at actual concentrations of 0, 4.7, 16.6 and 52.1 mg m(-3) (mass median aerodynamic diameter ≈1.3 μm, geometric standard deviation = 2). The exposure to iron oxide dust was tolerated without mortality, consistent changes in body weights, food and water consumption or systemic toxicity. While general clinical pathology and urinalysis were unobtrusive, hematology revealed changes of unclear toxicological significance (minimally increased differential neutrophil counts in peripheral blood). Elevations of neutrophils in bronchoalveolar lavage (BAL) appeared to be the most sensitive endpoint of study. Histopathology demonstrated responses to particle deposition in the upper respiratory tract (goblet cell hyper- and/or metaplasia, intraepithelial eosinophilic globules in the nasal passages) and the lower respiratory tract (inflammatory changes in the bronchiolo-alveolar region). Consistent changes suggestive of pulmonary inflammation were evidenced by BAL, histopathology, increased lung and lung-associated-lymph node (LALN) weights at 16.6 and 52.1 mg m(-3) . Increased septal collagenous fibers were observed at 52.1 mg m(-3) . Particle translocation into LALN occurred at exposure levels causing pulmonary inflammation. In summary, the retention kinetics iron oxide reflected that of poorly soluble particles. The empirical

  13. Subchronic toxicity of triethylenetetramine dihydrochloride in B6C3F1 mice and F344 rats.

    PubMed

    Greenman, D L; Morrissey, R L; Blakemore, W; Crowell, J; Siitonen, P; Felton, P; Allen, R; Cronin, G

    1996-02-01

    Triethylenetetramine dihydrochloride (trien-2HCl; CAS No. 38260-01-04), a chelating agent used to treat Wilson's disease patients who are intolerant of the drug of choice, was tested for subchronic toxicity in B6C3F1 mice and F344 rats. Mice and rats received trien-2HCl in the drinking water at concentrations of 0, 120, 600, or 3000 ppm for up to 92 days. Twenty mice and 18 rats of each sex were assigned to each dose group fed either a cereal-based (NIH-31) or a purified (AIN-76A) diet, both containing nutritionally adequate levels of copper. An additional control group of rats and mice received a Cu-deficient AIN-76A diet. This low copper diet resulted in Cu-deficiency symptoms, such as anemia, liver periportal cytomegaly, pancreatic atrophy and multifocal necrosis, spleen hematopoietic cell proliferation, and increased heart weight, together with undetectable levels of plasma copper in rats but not in mice. Trien-2HCl lowered plasma copper levels some-what (at 600 and 3000 ppm) in rats fed the AIN-76A diet, but did not induce the usual signs of copper deficiency. Trien-2HCl caused an increased frequency of uterine dilatation at 3000 ppm in rats fed AIN-76A diet that was not noted in females fed the Cu-deficient diet. Trien-2HCl toxicity occurred only in mice in the highest dose group fed an AIN-76A diet. Increased frequencies of inflammation of the lung interstitium and liver periportal fatty infiltration were seen in both sexes, and hematopoietic cell proliferation was seen in the spleen of males. Kidney and body weights were reduced in males as was the incidence of renal cytoplasmic vacuolization. There were no signs of copper deficiency in mice exposed to trien-2HCl. The only effect of trien-2HCl in animals fed the NIH-31 diet was a reduced liver copper level in both rat sexes, noted at 3000 ppm.

  14. Subchronic toxicity of polyethylene glycol-g-polyvinyl alcohol grafted copolymer.

    PubMed

    Heuschmid, Franziska F; Schuster, Paul; Lauer, Birthe; Buesen, Roland; Mellert, Werner; Groeters, Sibylle; van Ravenzwaay, Bennard

    2013-07-01

    The safety of polyethylene glycol-g-polyvinyl alcohol (PEG-PVA) grafted copolymer was evaluated in a 13-week oral toxicity study in rats and in a 9-month oral toxicity study in dogs. Wistar rats were administered 600, 3000, or 15,000 ppm PEG-PVA grafted copolymer in their drinking water whereas beagle dogs were fed 3000, 10,000, or 30,000 ppm PEG-PVA grafted copolymer in the diet. There were no mortalities, no adverse clinical signs, no toxicologically adverse effects on body weight or body weight gain, feed consumption, hematological, clinical chemistry or urinary parameters, or histopathology in either species. In rats, no treatment-related effects were observed in the functional observational battery (FOB) or related measurements of motor activity. Increased water consumption observed in rats at the highest dose was the only test substance-induced effect noted. The no-observed-adverse-effect level (NOAEL) was the highest concentration tested in both species: 15,000 ppm in rats (corresponding to a daily intake of 1611 mg/kg bw for males and 2191 mg/kg bw for females) and 30,000 ppm in dogs (corresponding to a mean daily intake of 783 mg/kg bw for males and 811 mg/kg bw for females).

  15. 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.

  16. A 13-week subchronic toxicity study of madder color in F344 rats.

    PubMed

    Inoue, Kaoru; Shibutani, Makoto; Masutomi, Naoya; Toyoda, Kazuhiro; Takagi, Hironori; Uneyama, Chikako; Nishikawa, Akiyoshi; Hirose, Masao

    2008-01-01

    A 13-week repeated oral dose toxicity study of madder color (MC), a natural food colorant extracted from the roots of Rubia tinctorum L., was performed using F344 rats. Five groups of animals, each consisting of 10 males and 10 females, were fed diet containing 0, 0.6, 1.2, 2.5 or 5.0% MC for 13 weeks. During the experiment, lower body weight was evident from the 2.5% dose. Hematologically, fluctuation in red blood cell (RBC) parameters suggestive of weak anemia (females), and slight increases of platelet counts (both sexes) and white blood cell (WBC) counts (males) were observed at higher doses. Serum biochemically, slight fluctuations were observed in many parameters, including increased total protein (TP), conjugated bilirubin, Ca, and inorganic phosphate, and decrease of the albumin/globulin (A/G) ratio in both sexes, with dose-dependence for TP and A/G from 0.6% in females. Histopathological changes were mainly observed in the renal proximal tubules, such as microvesicular vacuolar degeneration in the cortex and karyomegaly in the outer medulla involving both sexes, lesions being evident even with 0.6%. In the outer medulla, elevation of cell proliferation activity as assessed with proliferating cell nuclear antigen was observed in males from 2.5%. Severity of focal necrosis of hepatocytes was increased only in females at 5.0%, while the increased relative liver weight as with the increased conjugated bilirubin was evident in both sexes from 1.2%. The results thus suggest that MC exerts mild toxicity, targeting liver, kidneys, and possibly RBCs and WBCs, some renal changes being evident from 0.6% in diet, that is attributable to be the lowest-observed adverse effect level (305.8-309.2mg/kg body weight/day). PMID:17881111

  17. A 13-week subchronic toxicity study of madder color in F344 rats.

    PubMed

    Inoue, Kaoru; Shibutani, Makoto; Masutomi, Naoya; Toyoda, Kazuhiro; Takagi, Hironori; Uneyama, Chikako; Nishikawa, Akiyoshi; Hirose, Masao

    2008-01-01

    A 13-week repeated oral dose toxicity study of madder color (MC), a natural food colorant extracted from the roots of Rubia tinctorum L., was performed using F344 rats. Five groups of animals, each consisting of 10 males and 10 females, were fed diet containing 0, 0.6, 1.2, 2.5 or 5.0% MC for 13 weeks. During the experiment, lower body weight was evident from the 2.5% dose. Hematologically, fluctuation in red blood cell (RBC) parameters suggestive of weak anemia (females), and slight increases of platelet counts (both sexes) and white blood cell (WBC) counts (males) were observed at higher doses. Serum biochemically, slight fluctuations were observed in many parameters, including increased total protein (TP), conjugated bilirubin, Ca, and inorganic phosphate, and decrease of the albumin/globulin (A/G) ratio in both sexes, with dose-dependence for TP and A/G from 0.6% in females. Histopathological changes were mainly observed in the renal proximal tubules, such as microvesicular vacuolar degeneration in the cortex and karyomegaly in the outer medulla involving both sexes, lesions being evident even with 0.6%. In the outer medulla, elevation of cell proliferation activity as assessed with proliferating cell nuclear antigen was observed in males from 2.5%. Severity of focal necrosis of hepatocytes was increased only in females at 5.0%, while the increased relative liver weight as with the increased conjugated bilirubin was evident in both sexes from 1.2%. The results thus suggest that MC exerts mild toxicity, targeting liver, kidneys, and possibly RBCs and WBCs, some renal changes being evident from 0.6% in diet, that is attributable to be the lowest-observed adverse effect level (305.8-309.2mg/kg body weight/day).

  18. Subchronic inhalation of diethylamine vapor in Fischer-344 rats: organ system toxicity.

    PubMed

    Lynch, D W; Moorman, W J; Stober, P; Lewis, T R; Iverson, W O

    1986-04-01

    Male and female Fischer 344 (F-344) rats were exposed at 0,25 or 250 ppm diethylamine (DEA) vapor, 6.5 hr per day, 5 days per week, for 24 weeks in order to assess cardiac and other organ system toxicity. Scheduled sacrifices were performed following 30, 60, and 120 days of exposure. During the first 2 weeks of exposure, the rats exposed at 250 ppm DEA did not gain weight. After 2 weeks, however, the rate of weight gain of these rats was greater than that of controls. Nevertheless, mean body weights for both sexes of rats exposed at 250 ppm DEA remained depressed compared to controls throughout the study. Sneezing, tearing, and reddened noses were seen in rats exposed at 250 ppm DEA. Histopathologic examinations revealed lesions of the nasal mucosa of rats exposed at 250 ppm DEA (rats exposed at 25 ppm were not evaluated). These lesions of the respiratory epithelium consisted of squamous metaplasia, suppurative rhinitis, and lymphoid hyperplasia. There were no pronounced treatment-related effects on organ weights, hematology, or clinical chemistry indices except for blood urea nitrogen which was evaluated in rats of both sexes exposed at 250 ppm DEA for 24 weeks. In contrast to the high-dose animals, no treatment-related effects were observed in rats intermittently exposed at 25 ppm DEA for up to 24 weeks. No evidence of cardiotoxicity was seen in rats exposed to either DEA concentration for up to 24 weeks. PMID:3699339

  19. Subchronic toxicity evaluation of γ-aminobutyric acid (GABA) in rats.

    PubMed

    Takeshima, Kazuhito; Yamatsu, Atsushi; Yamashita, Yusuke; Watabe, Kazuya; Horie, Noriko; Masuda, Kazuyuki; Kim, Mujo

    2014-06-01

    γ-Aminobutyric acid (GABA) is an amino acid compound contained in vegetables such as tomatoes and also widely distributed in mammals. GABA acts as an inhibitory neurotransmitter and promotes parasympathetic activity to provide several beneficial effects, for instance, relaxation, anti-stress, and insomnia. GABA, produced via a fermentation process, has been available as a functional food ingredient. As part of a program to assess its safety, GABA was administered by oral gavage at doses of 500, 1250, and 2500mg/kg body weight to groups of 10 male and 10 female Sprague-Dawley rats for 13weeks. Treatment was not associated with the test substance-related mortality and appeared to be well tolerated. There were no toxicologically and statistically significant changes in urinalysis, hematology, clinical chemistry parameters, and in necropsy findings. A few statistically significant changes in food consumption and body weights were noted in the male groups while any significant changes were not noted in female groups. There was no effect of treatment on organ weights or on the results of the histopathological examinations. The results of toxicity evaluation support the safety use of GABA and the potential use as a functional food ingredient.

  20. The subchronic toxicity of tetrachloroethylene (perchloroethylene) administered in the drinking water of rats.

    PubMed

    Hayes, J R; Condie, L W; Borzelleca, J F

    1986-07-01

    This study provides data on the effects of tetrachloroethylene in drinking solutions. The acute oral LD50 in male and female Charles River rats was found to be 3835 mg/kg for males and 3005 mg/kg for females. Male and female rats received theoretical daily doses of 14,400, and 1400 mg tetrachloroethylene/kg body wt/day for 90 consecutive days. There were no compound-related deaths. Body weights were significantly lower in male and female rats at the higher doses. There were no consistent dose-related effects on any of the hematological, clinical chemistry, or urinalysis parameters. 5'-Nucleotidase activity was increased in a dose-dependent manner, suggesting possible hepatotoxicity; however, other serum indicators of hepatic function were unaffected by the treatment. There were no gross pathological effects observed. Liver and kidney body weight ratios, but not brain weight ratios, were elevated at the higher doses. There was no other evidence of compound-related toxicity. These data suggest that exposure of humans to reported levels of tetrachloroethylene in drinking water (approximately 1 microgram/liter) does not constitute a serious health hazard.

  1. 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

  2. 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

  3. 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.

  4. Subchronic (12-week) inhalation toxicity study of methanol-fueled engine exhaust in rats

    SciTech Connect

    Maejima, Kazuhito; Suzuki, Tadao ); Numata, Hiroaki ); Maekawa, Akihiko ); Nagase, Sumi ); Ishinishi, Noburu )

    1994-01-01

    To evaluate the inhalation toxicity to rats of exhaust at low concentration for longer periods, Fischer 344 rats were exposed to 3 concentrations of exhaust generated by an M85 methanol-fueled engine (methanol with 15% gasoline) without catalyst for 8 h/d, 6 d/wk for 4, 8, or 12 wk. Concentration- and time-dependent increase carboxyhemoglobin in the erythrocytes and decrease in cytochrome P-450 in the lungs were observed in all treated groups. Furthermore, significant increases in plasma formaldehyde were observed in the group exposed to the highest concentration of exhaust (carbon monoxide, 89.8 ppm; formaldehyde, 2.3 ppm; methanol, 8.1 ppm; nitrogen oxides, 22.9 ppm; nitrogen dioxide, 1.1 ppm) for 8 or 12 wk. No change of plasma folic acid was observed in any group, and no methanol or formic acid was detected in the plasma in any animals. Histopathologically, exposure-related changes were found only in the nasal cavity of the high-concentration group. Slight hyperplasia/squamous metaplasias of the respiratory epithelium lining the nasoturbinate and maxilloturbinate were observed after 4 wk of exposure, and the incidences and degrees of these lesions increased slightly with the exposure time. No changes were found in the olfactory epithelium of the nasal cavity. As judged by optical microscopy, the exhaust concentration with no effect on the nasal cavity under the experimental conditions was concluded to be the medium concentration level containing 0.55 ppm formaldehyde. In the present study, however, concentration- and time-dependent increase of carboxyhemoglobin in the erythrocytes and decrease of the lung P-450 level were observed. Therefore, further study on more long-term inhalation of lower concentrations of exhaust might be needed. 31 refs., 2 figs., 3 tabs.

  5. Therapeutic value of Hippophae rhamnoides L. against subchronic arsenic toxicity in mice.

    PubMed

    Gupta, Richa; Flora, S J S

    2005-01-01

    The present study was planned to investigate the therapeutic efficacy of Hippophae rhamnoides L. against the toxic effects of arsenic in mice. H. rhamnoides L. is used as an herbal remedy for gastric ulcers, burns, and some skin and allergic diseases. Twenty-five Swiss albino mice were exposed to arsenic (25 ppm) in drinking water for 3 months. After 3 months different fruit extracts of H. rhamnoides L. (500 mg/kg for 10 days) were administered, the animals were sacrificed, and blood and tissues were assayed for various biochemical indicators of oxidative stress and whether arsenic was removed from tissues. Treatment with different fruit extracts of H. rhamnoides L. showed significant protection from arsenic inhibition of blood delta-aminolevulinic acid dehydratase activity and restored blood reduced glutathione levels. Other hematologic variables like white blood cell counts, hemoglobin, and hematocrit were partially protected by supplementation with a water extract of H. rhamnoides L. (HF-WRT). Significant protection was also observed in altered hepatic, renal, and brain reduced/ oxidized glutathione ratio and thiobarbituric acid-reactive substances levels. The aqueous extract of H. rhamnoides L. (HF-WRT) also provided protection against parameters indicative of liver injury such as aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase activities. There was also no effect on blood and tissue arsenic concentrations observed except some moderate depletion of blood arsenic concentrations, suggesting that the drug has no ability to chelate intracellular arsenic. It can be concluded from these results that post-treatment with an aqueous extract of H. rhamnoides L. (HF-WRT) significantly protects against arsenic-induced oxidative stress but does not chelate arsenic, suggesting it may have a beneficial role as a supplementing agent during chelation of arsenic by other means.

  6. 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

  7. 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. PMID:27635194

  8. 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.

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

    PubMed Central

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

    2015-01-01

    Abstract 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. Copyright © 2015. The Authors. Journal of Applied Toxicology Published by John Wiley & Sons Ltd. PMID:25982482

  10. Safety profile and gender specific differences of a methanol extract of Eriosema laurentii (Leguminosae) in acute and subchronic (28 days) oral toxicity studies in Wistar rats.

    PubMed

    Ateba, Sylvin Benjamin; Simo, Rudy Valdès; Mbanya, Jean Claude; Krenn, Liselotte; Njamen, Dieudonné

    2014-03-01

    Despite widespread use of Eriosema laurentii De Wild (Leguminosae) in West and Central Africa as herbal medicine and food additive the toxicity of this plant is unknown. Therefore, we performed the safety evaluation of a methanol extract (AEL). In acute toxicity, single oral administration of 2000mg/kg AEL caused neither toxicological symptoms nor mortality and the LD50 was estimated >5000mg/kg. In the subchronic oral toxicity, AEL induced no phenotypical signs of toxicity during and after treatment. Only a delayed decrease of relative spleen weight in males at the highest dose of 400mg/kg occurred. High density lipoprotein (HDL) increased significantly in females at 200 and 400mg/kg. Non-persistent increases in alanine aminotransferase activity within normal ranges were noted at 200mg/kg in males and at all doses in females. In males, AEL induced a decrease of white blood cell count at 400mg/kg, whereas lymphocytes increased at 200 and 400mg/kg and granulocytes at 400mg/kg. In females, no differences in haematological parameters occurred. Neither differences in bilirubin, creatinine and total protein levels were observed nor histological alterations in organs. The results indicate a broad safety margin for AEL.

  11. 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

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

    PubMed Central

    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 should

  13. Subchronic toxic effects of fluoride ion on the survival and behaviour of the aquatic snail Potamopyrgus antipodarum (Hydrobiidae, Mollusca).

    PubMed

    Alonso, Álvaro; Camargo, Julio A

    2011-04-01

    Short-term bioassays usually assess lethal effects of pollutants in animals, whereas subchronic bioassays are more suited for assessing effects on animal behaviour. Among them, videotaped bioassays are an improvement in the behavioural monitoring because they are easily and cheaply implemented. The present study focuses on the assessment of subchronic (14-day) effects of fluoride ion on the survival, proportion of dead plus immobile animals, and velocity (monitored by a videotaping and image analysis system) of the aquatic snail Potamopyrgus antipodarum (Hydrobiidae, Mollusca). One control and three nominal fluoride concentrations (5, 20, and 40 mg F(-)/l [actual mean concentrations of 5.2, 17.5, and 37.0 mg F(-)/l, respectively]) were used. Each treatment (including the control) was replicated 12 times. Mortality, number of dead plus immobile animals, and velocity were monitored after 0, 7, and 14 days of exposure. After 14 days, animals exposed to 40 mg F(-)/l showed higher mortality, number of dead, and immobile individuals than control animals. Snails exposed to 5 and 20 mg F(-)/l were not affected by fluoride ion regarding these endpoints. In contrast, snails exposed to 20 mg F(-)/l for 7 and 14 days showed lower velocity than control animals. Therefore, velocity was sensitive to environmental fluoride concentrations and as such is a useful parameter for ecologic risk assessment. In addition, videotaping allowed us to detect behavioural patrons in velocity at very short exposures (seconds) during the monitoring process by showing that the velocity of snails must be monitored at least during the course of several minutes. We conclude that in P. antipodarum, velocity is a more sensitive endpoint than the classic mortality and immobility endpoints.

  14. 90-day feeding and one-generation reproduction study in Crl:CD BR rats with 17 beta-estradiol.

    PubMed

    Biegel, L B; Flaws, J A; Hirshfield, A N; O'Connor, J C; Elliott, G S; Ladics, G S; Silbergeld, E K; Van Pelt, C S; Hurtt, M E; Cook, J C; Frame, S R

    1998-08-01

    Over the past several years, there has been increasing concern that chemicals and pesticides found in the environment may mimic endogenous estrogens, potentially producing adverse effects in wildlife and human populations. Because estrogenicity is one of the primary concerns, a 90-day/one-generation reproduction study with 17 beta-estradiol was designed to set dose levels for future multigenerational reproduction and combined chronic toxicity/oncogenicity studies. The purpose of these studies is to evaluate the significance of a range of responses as well as to provide benchmark data for a risk assessment for chemicals with estrogen-like activities. This 90-day/one-generation reproduction study was conducted in male and female Crl:CD BR rats using dietary concentrations of 0, 0.05, 2.5, 10, and 50 ppm 17 beta-estradiol. Endpoints were chosen in order to evaluate both subchronic and reproductive toxicity. In addition, several mechanistic/biochemical endpoints were evaluated for their usefulness in follow-up studies. In the P1 generation, dietary administration of 2.5, 10, and 50 ppm 17 beta-estradiol produced dose-dependent decreases in body weight, body weight gain, food consumption, and food efficiency. At 10 and 50 ppm 17 beta-estradiol, minimal to mild nonregenerative anemia, lymphopenia, decreased serum cholesterol (50 ppm only), and altered splenic lymphocyte subtypes were also observed in the P1 generation. Additionally, at these concentrations, there were changes in the weights of several organs. Evidence of ovarian malfunction, characterized by reduced numbers of corpora lutea and large antral follicles, was observed at 2.5 ppm 17 beta-estradiol and above. Other pathologic changes in males and females fed 10 and 50 ppm 17 beta-estradiol included centrilobular hepatocellular hypertrophy; diffuse hyperplasia of the pituitary gland; feminization of the male mammary glands; mammary gland hyperplasia in females; increased number of cystic follicles in the ovary

  15. 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.

  16. 12 CFR 220.117 - Exception to 90-day rule in special cash account.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Exception to 90-day rule in special cash... Exception to 90-day rule in special cash account. (a) The Board of Governors has recently interpreted... stock in a special cash account with a member firm on Day 1. On Day 3 customer sold the same stock at...

  17. 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...

  18. 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...

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

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 3 2013-04-01 2013-04-01 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...

  20. 19 CFR Annex Viii-A to Part 351 - Schedule for 90-Day Sunset Reviews

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 3 2012-04-01 2012-04-01 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...

  1. 19 CFR Annex Viii-A to Part 351 - Schedule for 90-Day Sunset Reviews

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 19 Customs Duties 3 2014-04-01 2014-04-01 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...

  2. 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

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

    PubMed

    Li, Ching-Hao; 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

  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-90 Day Gavage Safety Assessment of Boswellia serrata in Rats

    PubMed Central

    Singh, Pooja; Chacko, K. Mathai; Aggarwal, M. L.; Bhat, Binu; Khandal, R. K.; Sultana, Sarwat; Kuruvilla, Binu T.

    2012-01-01

    The present study deals with the evaluation and assessment of the safety/toxic potential of Boswellia serrata, a well known Ayurvedic herb used to treat disorders of digestive system, respiratory ailments and bone related diseases. A repeated dose oral (90 days) toxicity study of Boswellia serrata was carried out. For this, 10 rats of each sex were treated with the Boswellia serrata at three different doses i.e. 100, 500 and 1000 mg/kg B. wt. /day. As a control, 10 rats of each sex were treated with corn oil only which was the vehicle. Two groups consisting of five male and five female rats were kept as control recovery and high dose recovery group which were treated with the vehicle (corn oil) and the Boswellia serrata at the dose of 1000 mg/kg B. wt. Animals of control recovery and high dose recovery groups were further observed for 28 days without any treatment. From this study, it was found that the rats treated with high dose of the Boswellia serrata gained their body weight with much less rate than that of the control group. However, during the recovery period, the loss in body weight gain as observed during the study period exhibits a reversible effect on the metabolic activity and recovered. The results also indicate that Boswellia serrata is relatively safe in rat up to the dose of 500 mg/kg B.wt. as no adverse impact on health factors was observed. Thus, the No observed adverse effect level is 500 mg/kg B. wt. PMID:23293466

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. Subchronic and reproductive/developmental (screening level) toxicity of complexation products of iron trichloride and sodium tartrate (FemTA).

    PubMed

    Lynch, Barry; Emmen, Harry; van Otterdijk, Francois; Lau, Annette

    2013-09-01

    A complexation/reaction product, termed FemTA, of sodium tartrate [D(-)- and L(+)-tartaric acid and mesotartaric acid], sodium hydroxide, and iron trichloride may have use as an anticaking agent in salt preparations. FemTA is composed of about 4% sodium tartrate, approximately 10% mesotartaric acid, approximately 7% chloride, approximately 4% iron, approximately 7% sodium, approximately 0.3% sodium oxalate, and approximately 65% water. FemTA was tested in a 90-d oral toxicity study, which included a screening level reproductive/developmental toxicity phase, in Harlan Wistar rats. FemTA was administered by oral gavage at 500, 1000, and 2000 mg/kg body weight/d prior to and during mating, or about 20, 40, or 80 mg of iron/kg body weight/d, such that males received 90/91 d of treatment and females 104 to 109 d. Treatment was associated with inflammatory lesions of the lower GI tract at the mid- and high-dose levels, increased liver and kidney weights, increased serum bile acids and blood urea nitrogen, decreased chloride, and changes to hematological parameters consistent with inflammation. The effects were considered the result of iron overload. There were no effects on reproductive/developmental toxicity parameters. The no-observed-adverse-effect level (NOAEL), based on gastrointestinal tract effects was 500 mg/kg body weight/d. The NOAEL for reproductive/developmental toxicity was 2000 mg/kg body weight/d, the highest dose tested.

  11. 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

  12. 40 CFR 799.9310 - TSCA 90-day oral toxicity in rodents.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... be used throughout the duration of the study and the research sample should be stored under...) Clinical pathology. Hematology and clinical chemistry examinations must be made on all animals, including controls, of each sex in each group. The hematology and clinical chemistry parameters should be examined...

  13. 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... include calcium, phosphorus, fasting triglycerides, hormones, methemoglobin, and cholinesterases....

  14. 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... include calcium, phosphorus, fasting triglycerides, hormones, methemoglobin, and cholinesterases....

  15. 40 CFR 799.9310 - TSCA 90-day oral toxicity in rodents.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... test at one dose level of at least 1,000 mg/kg body weight (expected human exposure may indicate the...). Extrapolation from the results of this study to humans is valid only to a limited degree. However, it can useful... use in selecting dose levels for chronic studies and for establishing safety criteria for...

  16. 40 CFR 799.9310 - TSCA 90-day oral toxicity in rodents.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... occurring as a result of prolonged action on, or increased concentration of, the administered test substance... sacrifices are planned, the number must be increased by the number of animals scheduled to be sacrificed... oil and then solution in other vehicles. (ii) If possible, one lot of the......

  17. Acute, subacute and subchronic safety assessment of betalains rich Rivina humilis L. berry juice in rats.

    PubMed

    Khan, Mohammad Imtiyaj; Denny Joseph, K M; Muralidhara; Ramesh, H P; Giridhar, P; Ravishankar, G A

    2011-12-01

    Rivina humilis L. (Phytolaccaceae) accumulates vacuolar pigments betalains. These pigments are synthesized by plants of 11 families in the order caryophyllales. Red beet is the only industrial source of these hydrophilic and low acidic pigments. Betalains rich R. humilis berry juice (RBJ) could be used as alternative source of these pigments. However, there is no information on safety of these berries. In this research work, RBJ was fed to adult (single-dose: 1, 2 and 5 g RBJ/kg bw) and growing (repeated-dosing: 2.5 and 5 g RBJ/kg bw for 35 days; dietary feeding: 0.5%, 1% and 2% RBJ in diet, w/w for 90 days) male rats to assess acute, subacute and subchronic toxic responses. In all the three studies, RBJ was well tolerated plus the feed intake, body and organ weights of RBJ administered groups were comparable to that of untreated control rats. Data on hematology, histology of vital organs, biochemical measurements in serum and liver of RBJ treated rats were comparable to that of control in repeated-dosing and subchronic dietary study. These results suggest that intake of RBJ does not affect growth and normal biochemical homeostasis. Hence, RBJ is safe to consume without any adverse effects in the body. PMID:21914457

  18. Some patterns of metallic nanoparticles' combined subchronic toxicity as exemplified by a combination of nickel and manganese oxide nanoparticles.

    PubMed

    Katsnelson, Boris A; Minigaliyeva, Ilzira A; Panov, Vladimir G; Privalova, Larisa I; Varaksin, Anatoly N; Gurvich, Vladimir B; Sutunkova, Marina P; Shur, Vladimir Ya; Shishkina, Ekaterina V; Valamina, Irene E; Makeyev, Oleg H

    2015-12-01

    Stable suspensions of NiO and/or Mn3O4 nanoparticles with a mean diameter of 16.7 ± 8.2 nm and 18.4 ± 5.4 nm, respectively, prepared by laser ablation of 99.99% pure metals in de-ionized water were repeatedly injected IP to rats at a dose of 0.50 mg or 0.25 mg 3 times a week up to 18 injections, either separately or in different combinations. Many functional indices as well as histological features of the liver, spleen, kidneys and brain were evaluated for signs of toxicity. The accumulation of Ni and Mn in these organs was measured with the help of AES and EPR methods. Both metallic nanoparticles proved adversely bio-active, but those of Mn3O4 were found to be more noxious in most of the non-specific toxicity manifestations. Moreover, they induced a more marked damaging effect in the neurons of the caudate nucleus and hippocampus which may be considered an experimental correlate of manganese-induced parkinsonism. Mathematical analysis based on the Response Surface Methodology (RSM) revealed a diversity of combined toxicity types depending not only on particular effects these types are assessed for but on their level as well. The prognostic power of the RSM model proved satisfactory.

  19. 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

  20. 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

    2015-12-02

    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.

  1. 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

  2. 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.

  3. 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

  4. 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

    2014-07-14

    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

  5. 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

  6. Determination of LC50 and sub-chronic neurotoxicity of diesel exhaust nanoparticles.

    PubMed

    Durga, M; Devasena, T; Rajasekar, A

    2015-09-01

    Air pollution is a major problem faced globally and is seen associated with central nervous system (CNS) disorders like neuropathology and neuro-inflammation. Here, we investigated the CNS disorders as a result of sub-chronic exposure (90 days) to diesel exhaust nanoparticles (DENPs) and explored the minimal levels of DENPs needed to exhibit the early mediators of neuro-inflammation and neuropathology. Male and female wistar rats (6 rats per group) were exposed to DENPs (1/5th, 1/10th and 1/15th LC50) by inhalation for 4h per day, 5 days per week over 90 days and neurotoxicity end-points were analyzed. DENP exposure caused elevation in levels of pro-inflammatory cytokines, amyloid beta 42 (Aβ 42), reactive oxygen species (ROS), hydrogen peroxide (H2O2), nitrate (NO3(-)), nitrite (NO2(-)) and apurinic/apyrimidinic sites (AP) at varying degrees at different sections of rat brain. Hence, exposure to DENPs resulted in dose-dependent toxicity and was closely correlated to increased inflammation, DNA damage and oxidative stress.

  7. 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).

  8. A 90-day feeding study of glyphosate-tolerant maize with the G2-aroA gene in Sprague-Dawley rats.

    PubMed

    Zhu, Yaxi; He, Xiaoyun; Luo, Yunbo; Zou, Shiying; Zhou, Xin; Huang, Kunlun; Xu, Wentao

    2013-01-01

    Maize is not only a staple food crop but also an important raw material for feed and industry; however, the threat of weeds leads to a serious decline in its output and quality. The G2-aroA gene confers glyphosate herbicide tolerance to crops. In this study, the food safety of genetically modified (GM), glyphosate-tolerant maize with the G2-aroA gene was evaluated in a 90-day feeding study in Sprague-Dawley (SD) rats. Maize grain from GM or non-GM isogenic control lines were separately formulated into rodent diets at concentrations of 12.5% (low level), 25% (middle level), and 50% (high level). An additional group of rats were fed a commercialized diet as a control. The toxicological response variables, including body weights, food consumption, serum biochemistry, hematology, and absolute and relative organ weights, were compared between rats fed GM maize and those fed non-GM maize after consumption of test diets for 90days. In addition, gross and microscopic pathology were conducted among treatment groups. No adverse effects related to the consumption of GM maize were detected in the subchronic feeding study. These results indicated that the GM glyphosate-tolerant maize was as safe and nutritious as conventional maize.

  9. 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

  10. 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

  11. 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).

  12. A 90-day safety study of genetically modified rice expressing Cry1Ab protein (Bacillus thuringiensis toxin) in Wistar rats.

    PubMed

    Schrøder, Malene; Poulsen, Morten; Wilcks, Andrea; Kroghsbo, Stine; Miller, Andreas; Frenzel, Thomas; Danier, Jürgen; Rychlik, Michael; Emami, Kaveh; Gatehouse, Angharad; Shu, Qingyao; Engel, Karl-Heinz; Altosaar, Illimar; Knudsen, Ib

    2007-03-01

    An animal model for safety assessment of genetically modified foods was tested as part of the SAFOTEST project. In a 90-day feeding study on Wistar rats, the transgenic KMD1 rice expressing Cry1Ab protein was compared to its non-transgenic parental wild type, Xiushui 11. The KMD1 rice contained 15mg Bt toxin/kg and based on the average feed consumption the daily intake was 0.54mg Bt toxin/kg body weight. No adverse effects on animal behaviour or weight gain were observed during the study. Blood samples collected one week prior to sacrifice were analyzed and compared for standard haematological and biochemical parameters. A few parameters were significantly different, but all within the normal reference intervals for rats of this breed and age and not in relation to any other findings, thus not considered treatment related. Upon sacrifice a large number of organs were weighed, macroscopic and histopathological examinations were performed with only minor changes to report. The aim of the study was to use a known animal model in performance of safety assessment of a GM crop, in this case KMD1 rice. The results show no adverse or toxic effects of KMD1 rice when tested in the design used in this 90-day study. Nevertheless the experiences from this study lead to the overall conclusion that safety assessment for unintended effects of a GM crop cannot be done without additional test group(s).

  13. Human diets cooked by microwave or conventionally: comparative sub-chronic (13-wk) toxicity study in rats.

    PubMed

    Jonker, D; Til, H P

    1995-04-01

    To compare the possible effects of microwave and conventional cooking on a range of common dietary components, mixed human diets containing beef, potatoes and vegetables were fed to groups of 10 male and 10 female Wistar rats for 13 wk. The diet ingredients were cooked by either of the methods in a normal and an abused manner, the latter consisting of the normal treatment followed by two cycles of reheating to approximately 85 degrees C and cooling. The cooked ingredients were freeze-dried, ground and mixed with supplements of vitamins and minerals to meet the rat requirements. An additional control group was fed a cereal-based rodent diet. Criteria to assess toxicity included clinical observations, ophthalmoscopy, growth, food and water intake, haematology, clinical chemistry, urinalysis, organ weights, micronucleated erythrocytes in bone marrow, gross examination at autopsy and microscopic examination of a wide range of organs. The results indicate no adverse effects of the diets cooked by microwave compared with those cooked conventionally. PMID:7737598

  14. 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...

  15. 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...

  16. Toxicity and penetration of TiO2 nanoparticles in hairless mice and porcine skin after subchronic dermal exposure.

    PubMed

    Wu, Jianhong; Liu, Wei; Xue, Chenbing; Zhou, Shunchang; Lan, Fengli; Bi, Lei; Xu, Huibi; Yang, Xiangliang; Zeng, Fan-Dian

    2009-12-01

    The present study investigated the penetration and potential toxicity of titanium dioxide (TiO(2)) nanoparticles following its dermal exposure in vitro and in vivo. In vitro, after exposure to isolated porcine skin for 24h, titanium dioxide nanoparticles of carious sizes cannot penetrate through stratum corneum. Interestingly, when studied in vivo, quite different results were obtained. After topically applied on pig ear for 30 days, TiO(2) nanomaterials (4 nm and 60 nm) can penetrate through horny layer, and be located in deep layer of epidermis. Furthermore, after 60 days dermal exposure in hairless mice, nano-TiO(2) particles can penetrate through the skin, reach different tissues and induce diverse pathological lesions in several major organs. Notably, P25 (21 nm) TiO(2) nanomaterials shows a wider tissue distribution, and can even be found in the brain without inducing any pathological changes. Among all of the organs examined, the skin and liver displayed the most severe pathological changes that correspond to the significant changes in SOD and MDA levels. These results suggest that the pathological lesions are likely to be mediated through the oxidative stress induced by the deposited nanoparticles. Accordingly, the collagen content expressed as HYP content are also significantly reduced in mouse skin samples, indicating that topically applied nano-TiO(2) in skin for a prolonged time can induce skin aging. Altogether, the present study indicates that nanosize TiO(2) may pose a health risk to human after dermal exposure over a relative long time period.

  17. 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

  18. 12 CFR 220.117 - Exception to 90-day rule in special cash account.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 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...

  19. 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

  20. Effect of alpha-ketoglutarate on neurobehavioral, neurochemical and oxidative changes caused by sub-chronic cyanide poisoning in rats.

    PubMed

    Mathangi, D C; Shyamala, R; Vijayashree, R; Rao, K R; Ruckmani, A; Vijayaraghavan, R; Bhattacharya, R

    2011-03-01

    Recent studies revealed that alpha-ketoglutarate (A-KG) alone or with sodium thiosulfate (STS) provide significant protection against acute and sub-acute cyanide poisoning in rodents. This study addresses the protective effect of A-KG and/or STS in sub-chronic (90 days) cyanide poisoning. Wistar rats were divided into seven groups (n = 10): Control animals, potassium cyanide (KCN) A-KG, STS, KCN + A-KG, KCN + STS and KCN + A-KG + STS. Spontaneous motor activity and motor coordination were recorded every 15th day. Lipid peroxidation (LPO), reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) in blood, brain, liver and kidney, and glutamate, aspartate and dopamine in discrete regions of brain were measured following 90 days exposure. Cyanide significantly decreased motor coordination, accompanied by increase in LPO (blood, brain and liver) and dopamine (corpus striatum and cerebral cortex) levels, and depletion in GSH (blood, brain and liver), GPx (brain and liver), SOD (brain and liver), and CAT (blood and brain) levels. Although treatment of A-KG and STS alone significantly blunted the toxicity of KCN, concomitant use of both afforded the maximum protection. This study shows a promising role of A-KG and STS as treatment regime for long term cyanide exposure.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. A 90-day safety study of genetically modified rice expressing rhIGF-1 protein in C57BL/6J rats.

    PubMed

    Tang, Maoxue; Xie, Tingting; Cheng, Wenke; Qian, Lili; Yang, Shulin; Yang, Daichang; Cui, Wentao; Li, Kui

    2012-06-01

    Genetically modified plants expressing disease resistance traits offer new treatment strategies for human diseases, but at the same time present a challenge in terms of food safety assessment. The present 90-day feeding study was designed to assess the safety of transgenic rice expressing the recombinant human insulin-like growth factor-1 (rhIGF-1) compared to its parental wild rice. Male and female C57BL/6J rats were given a nutritionally balanced purified diet with 20% transgenic rhIGF-1 rice or 20% parental rice for 90 days. This corresponds to a mean daily rhIGF-1 protein intake of approximately 217.6 mg/kg body weight based on the average feed consumption. In the animal study a range of biological, biochemical, clinical, microbiological and pathological parameters were examined and several significant differences were observed between groups, but none of the effects were considered to be adverse. In conclusion, no adverse or toxic effects on C57BL/6J rats were observed in the design used in this 90-day study. These results will provide valuable information for the safety assessment of genetically modified food crops.

  8. 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

  9. 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.

  10. 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. PMID:27635133

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

    PubMed

    Clewell, Amy; Hirka, Gábor; Glávits, Róbert; Palmer, Philip A; Endres, John R; Murbach, Timothy S; Marx, Tennille; 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. PMID:27635133

  12. 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.

  13. 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

  14. 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.

  15. Toxicological investigations in the semiconductor industry: IV. Studies on the subchronic oral toxicity and genotoxicity of vacuum pump oils contaminated by waste products from aluminum plasma etching processes.

    PubMed

    Bauer, S; Wolff, I; Werner, N; Schmidt, R; Blume, R; Pelzing, M

    1995-01-01

    Dry etching processes in semiconductor manufacturing use ionized gases in closed reactors at pressures below 1 torr. Vacuum pump systems that service the reaction chambers are potential sources of exposure to complex mixtures of inorganic and organic compounds. These mixtures consist of unused process gases and process by-products that condense and accumulate in the vacuum pump oils. To evaluate potential hazards of dry etch vacuum equipment, a contaminated vacuum pump oil sample from a BCl3/Cl2 etching process was analyzed. The waste oil was administered by gavage for 14 or 28 days to male and female Wistar rats. Neither death nor behavioral changes occurred after subchronic treatment or during a 14-day posttreatment period. Only slight effects on body weights, clinical chemistry, and hematology data were seen in the exposed animals, although the livers of all waste oil-exposed rats of both sexes showed remarkable hypertrophic degenerations. Genotoxicological investigations were performed through the Ames assay (Salmonella assay) and the Micronucleus assay. The contaminated oil sample caused clear genotoxic effects in both test systems. PMID:8677517

  16. 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

  17. 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

  18. 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

  19. Comparative safety testing of genetically modified foods in a 90-day rat feeding study design allowing the distinction between primary and secondary effects of the new genetic event.

    PubMed

    Knudsen, Ib; Poulsen, Morten

    2007-10-01

    This article discusses the wider experiences regarding the usefulness of the 90-day rat feeding study for the testing of whole foods from genetically modified (GM) plant based on data from a recent EU-project [Poulsen, M., Schrøder, M., Wilcks, A., Kroghsbo, S., Lindecrona, R.H., Miller, A., Frenzel, T., Danier, J., Rychlik, M., Shu, Q., Emami, K., Taylor, M., Gatehouse, A., Engel, K.-H., Knudsen, I., 2007a. Safety testing of GM-rice expressing PHA-E lectin using a new animal test design. Food Chem. Toxicol. 45, 364-377; Poulsen, M., Kroghsbo, S., Schrøder, M., Wilcks, A., Jacobsen, H., Miller, A., Frenzel, T., Danier, J., Rychlik, M., Shu, Q., Emami, K., Sudhakar, D., Gatehouse, A., Engel, K.-H., Knudsen, I., 2007b. A 90-day safety in Wistar rats fed genetically modified rice expressing snowdrop lectin Galanthus nivalis (GNA). Food Chem. Toxicol. 45, 350-363; Schrøder, M., Poulsen, M., Wilcks, A., Kroghsbo, S., Miller, A., Frenzel, T., Danier, J., Rychlik, M., Emami, K., Gatehouse, A., Shu, Q., Engel, K.-H., Knudsen, I., 2007. A 90-day safety study of genetically modified rice expressing Cry1Ab protein (Bacillus thuringiensis toxin) in Wistar rats. Food Chem. Toxicol. 45, 339-349]. The overall objective of the project has been to develop and validate the scientific methodology necessary for assessing the safety of foods from genetically modified plants in accordance with the present EU regulation. The safety assessment in the project is combining the results of the 90-day rat feeding study on the GM food with and without spiking with the pure novel gene product, with the knowledge about the identity of the genetic change, the compositional data of the GM food, the results from in-vitro/ex-vivo studies as well as the results from the preceding 28-day toxicity study with the novel gene product, before the hazard characterisation is concluded. The results demonstrated the ability of the 90-day rat feeding study to detect the biological/toxicological effects of the

  20. 78 FR 46322 - Endangered and Threatened Species; 90-Day Finding on Petition To Delist the Southern Oregon...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-31

    ... artificially produced hatchery stocks (70 FR 37160; June 28, 2005). The SCWUA has previously submitted several... be warranted. Negative 90-day findings were published for these petitions on October 7, 2011 (76 FR 62375), January 11, 2012 (77 FR 1668), and September 10, 2012 (77 FR 55458). SCWUA Petition In this...

  1. 76 FR 36053 - Endangered and Threatened Wildlife and Plants; Revised 90-Day Finding on a Petition To Reclassify...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-21

    ...-day finding published on February 21, 2007 (72 FR 7843), constituted our compliance with the... Columbia vacated and remanded our February 21, 2007, not- substantial 90-day finding (72 FR 7843) back to... endangered species on June 4, 1973 (38 FR 14678), pursuant to the Endangered Species Conservation Act of...

  2. 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

    ... Biodiversity Project, and others requesting that the Pacific fisher (Martes pennanti pacifica) be listed as an... 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,...

  3. 75 FR 52928 - Endangered and Threatened Wildlife and Plants; Notice of 90-Day Finding for a Petition to List...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-30

    ... rockfish and tiger rockfish) was insubstantial and we therefore did not conduct status reviews (64 FR 33037... segments of Puget Sound/Georgia Basin distinct population segments of rockfish, 75 FR 22276 (April 28, 2010...; Notice of 90-Day Finding for a Petition to List Georgia Basin Populations of China Rockfish and...

  4. 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)...

  5. 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

    ... for feeding, breeding, and sheltering; (b) Genetics and taxonomy; (c) Historical and current range... Regional Office. On December 16, 2009 (74 FR 66866), we published a partial 90-day finding on the petition... from dog and horse waste, manipulation and alteration of streamflow by swimmers, and the trampling...

  6. 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...

  7. 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),...

  8. 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),...

  9. 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...

  10. 75 FR 23654 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition to List Hermes Copper...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-04

    ... finding (71 FR 44966, August 8, 2006) is limited to Marschalek and Deutschman's (2008) study of the effect... previous 90-day finding published in the Federal Register on August 8, 2006 (71 FR 44966). Previous Federal... Hermes copper (71 FR 44966) or Thorne's hairstreak butterflies (71 FR 44980) was warranted. (For...

  11. 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...

  12. 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

    ... assertion in the petition that mountain biking can cause soil erosion and compaction, degraded water quality... the western United States have been well documented, and include increased soil erosion, sedimentation... published two 90-day findings, on January 6, 2009 (74 FR 419), and February 5, 2009 (74 FR 6122)....

  13. 78 FR 13614 - Endangered and Threatened Wildlife; 90-Day Finding on a Petition To List the Humphead Wrasse as...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-28

    ..., delisting, and reclassifying a species under the ESA (``DPS Policy''; 61 FR 4722; February 7, 1996). A... publications, copies of reports or letters from authorities, and maps (50 CFR 424.14(b)(2)). At the 90-day..., including parts of Fiji, southwestern Indian Ocean and the South China Sea (Sadovy et al., 2003). Threats...

  14. 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..., and drought) rather than man-made factors are responsible for the decline in coho salmon...

  15. Low concentration toxic metal mixture interactions: Effects on essential and non-essential metals in brain, liver, and kidneys of mice on sub-chronic exposure.

    PubMed

    Cobbina, Samuel J; Chen, Yao; Zhou, Zhaoxiang; Wu, Xueshan; Feng, Weiwei; Wang, Wei; Mao, Guanghua; Xu, Hai; Zhang, Zhen; Wu, Xiangyang; Yang, Liuqing

    2015-08-01

    The deleterious effects of long term exposure to individual toxic metals in low doses are well documented. There is however, a paucity of information on interaction of low dose toxic metal mixtures with toxic and essential metals. This study reports on interactions between low dose mixtures of lead (Pb), mercury (Hg), arsenic (As) and cadmium (Cd) and toxic and essential metals. For 120d, six groups of forty mice each were exposed to metal mixtures, however, the control group was given distilled water. Exposure to Pb+Cd increased brain Pb by 479% in 30d, whiles Pb+Hg+As+Cd reduced liver Hg by 46.5%, but increased kidney As by 130% in 30d. Brain Cu, increased by 221% on Pb+Hg+As+Cd exposure, however, liver Ca reduced by 36.1% on Pb+Hg exposure in 60-d. Interactions within metal mixtures were largely synergistic. Principal component analysis (PCA) showed that low dose metal exposures influenced greatly levels of Hg (in brain and liver) and As (brain). The influence exerted on essential metals was highest in liver (PC1) followed by kidney (PC2) and brain (PC3). Exposure to low dose metal mixtures affected homeostasis of toxic and essential metals in tissues of mice.

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. Toxicity assessment of 4-amino-2-nitrotoluene.

    PubMed

    Houpt, John T; Leach, Glenn J; Williams, Larry R; Johnson, Mark S; Reddy, Gunda

    2013-01-01

    4-Amino-2-nitrotoluene (4A2NT; CAS 119-32-4) is a degradation product of 2,4-dinitrotoluene. The toxicity data on 4A2NT are limited. Therefore, we collected toxicity data from rats to assess environmental and human health effects from exposures. The approximate lethal dose for both sexes was 5000 mg/kg. A 14-day toxicity study in rats was conducted with 4A2NT in the feed at concentrations of 0, 125, 250, 500, 1000, and 2000 ppm. Based on a 14-day oral dose range toxicity study with 4A2NT in the feed, 2000 ppm was selected as highest concentration for a subsequent 90-day study. An oral 90-day subchronic toxicity study in rats was conducted with concentrations of 0, 500, 1000, or 2000 ppm of 4A2NT in the feed. The calculated consumed doses of 4A2NT in the feed were 0, 27, 52, or 115 mg/kg/d for males and 0, 32, 65, or 138 mg/kg/d for females. A no-observed adverse effect level could not be determined. The lowest observed adverse effect level was 27 mg/kg/d for males and 32 mg/kg/d for female rats based upon decreased body weight gain. The decreased body weight gain in male rats was the most sensitive adverse event observed in this study and was used to derive a benchmark dose (BMD). A BMD of 23.1 mg/kg/d and BMD with 10% effect level of 15.5 mg/kg/d were calculated for male rats, which were used to derive an oral reference dose (RfD). The human RfD of 1.26 μg/kg/d was derived using current United States Environmental Protection Agency guidelines.

  1. 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.

  2. 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......

  3. 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

  4. 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.

  5. Chronic kidney disease is associated with a higher 90-day mortality than other chronic medical conditions in patients with sepsis

    PubMed Central

    Mansur, Ashham; Mulwande, Evelyn; Steinau, Maximilian; Bergmann, Ingo; Frederik Popov, Aron; Ghadimi, Michael; Beissbarth, Tim; Bauer, Martin; Hinz, José

    2015-01-01

    According to previous studies, the clinical course of sepsis could be affected by preexisting medical conditions, which are very common among patients with sepsis. This observational study aimed at investigating whether common chronic medical conditions affect the 90-day mortality risk in adult Caucasian patients with sepsis. A total of 482 patients with sepsis were enrolled in this study. The ninety-day mortality was the primary outcome; organ failure was the secondary outcome. Sepsis-related organ failure assessment (SOFA) scores and the requirements for organ support were evaluated to assess organ failure. A multivariate Cox regression model for the association between the 90-day mortality risk and chronic preexisting medical conditions adjusted for all relevant confounders and mortality predictors revealed the highest hazard ratio for patients with chronic kidney disease (CKD) (hazard ratio, 2.25; 95% CI, 1.46-3.46; p = 0.0002). Patients with CKD had higher SOFA scores than patients without CKD (8.9 ± 4.0 and 6.5 ± 3.4, respectively; p < 0.0001). Additionally, an analysis of organ-specific SOFA scores revealed higher scores in three organ systems (kidney, cardiovascular and coagulation). Patients with CKD have the highest 90-day mortality risk compared with patients without CKD or with other chronic medical conditions. PMID:25995131

  6. Interaction of four low dose toxic metals with essential metals in brain, liver and kidneys of mice on sub-chronic exposure.

    PubMed

    Cobbina, Samuel Jerry; Chen, Yao; Zhou, Zhaoxiang; Wu, Xueshan; Feng, Weiwei; Wang, Wei; Li, Qian; Zhao, Ting; Mao, Guanghua; Wu, Xiangyang; Yang, Liuqing

    2015-01-01

    This study reports on interactions between low dose toxic and essential metals. Low dose Pb (0.01mg/L), Hg (0.001mg/L), Cd (0.005mg/L) and As (0.01mg/L) were administered singly to four groups of 3-week old mice for 120 days. Pb exposure increased brain Mg and Cu by 55.5% and 266%, respectively. Increased brain Mg resulted from metabolic activity of brain to combat insults, whiles Cu overload was due to alteration and dysfunction of CTR1 and ATP7A molecules. Reduction of liver Ca by 56.0% and 31.6% (on exposure to As and Cd, respectively) resulted from inhibition of Ca-dependent ATPase in nuclei and endoplasmic reticulum through binding with thiol groups. Decreased kidney Mg, Ca and Fe was due to uptake of complexes of As and Cd with thiol groups from proximal tubular lumen. At considerably low doses, the study establishes that, toxic metals disturb the homeostasis of essential metals.

  7. Compositional and toxicological analysis of a GM potato line with reduced α-solanine content--a 90-day feeding study in the Syrian Golden hamster.

    PubMed

    Langkilde, Søren; Schrøder, Malene; Frank, Thomas; Shepherd, Louise V T; Conner, Sean; Davies, Howard V; Meyer, Otto; Danier, Jürgen; Rychlik, Michael; Belknap, William R; McCue, Kent F; Engel, Karl-Heinz; Stewart, Derek; Knudsen, Ib; Poulsen, Morten

    2012-10-01

    Steroidal glycoalkaloids (GAs) are toxins, produced by plants of the Solanaceae family. The potato plant (Solanum tuberosum L.) and its tubers predominantly contain the two GAs α-chaconine and α-solanine. These compounds are believed to act in synergy, and the degree of toxicity may therefore depend on their ratio in the potato. To determine the influence of α-solanine: α-chaconine ratio in potatoes on toxicity, a GM potato line (SGT 9-2) with reduced α-solanine content, and the parental control line (Desirée wild-type) having a traditional α-solanine: α-chaconine ratio were (1) studied for compositional similarity by analysing for a range of potato constituents, and (2) used in a 90-day feeding trial with the Syrian Golden hamster to study differential toxicity. The animal feeding study used diets with up to 60% freeze-dried potato powder from either line. Whilst data indicated some compositional differences between the GM line and its wildtype control these did not raise concerns related to nutritional value or safety. Results of the feeding trials showed a low number of significant differences between potato lines with different α-solanine: α-chaconine ratio but none were considered to raise safety concerns with regard to human (or animal) consumption.

  8. 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.

  9. 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

  10. Subchronic toxicity study of 3-monochloropropane-1,2-diol administered by drinking water to B6C3F1 mice.

    PubMed

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

    2008-05-01

    3-Monochloropropane-1,2-diol (3-MCPD) is a food processing contaminant in a wide range of foods and ingredients and is a suspected cause of cancer. In this study, the 13-week toxicity of 3-MCPD was examined in B6C3F1 mice (10/sex/group) administered 3-MCPD doses of 0, 5, 25, 100, 200 and 400 ppm dissolved in their drinking water over a 13-week period. All the mice survived to the end of study. The mean body weight gains in the males and females given 400 ppm were significantly lower than those of the controls. The relative kidney weights of the males and females given 200 and 400 ppm were significantly higher than those of the controls without any corresponding histopathological changes. The sperm motility was lower in the 400 ppm group than the control, and there was a significant increase in the incidence of germinal epithelium degeneration in the 200 and 400 ppm groups. A delayed total estrus cycle length was observed in the 400 ppm group without any histopathological changes. Based on these results, the target organ was determined to be kidney, testis, and ovary. The no-observed-adverse-effect level (NOAEL) was found to be 100 ppm (18.05 mg/kg/day for males and 15.02 mg/kg/day for females).

  11. Neurological Toxicity of Individual and Mixtures of Low Dose Arsenic, Mono and Di (n-butyl) Phthalates on Sub-Chronic Exposure to Mice.

    PubMed

    Mao, Guanghua; Zhou, Zhaoxiang; Chen, Yao; Wang, Wei; Wu, Xueshan; Feng, Weiwei; Cobbina, Samuel Jerry; Huang, Jing; Zhang, Zhen; Xu, Hai; Yang, Liuqing; Wu, Xiangyang

    2016-03-01

    The objective of this study was to evaluate the toxicity of individual and mixtures of di(n-butyl) phthalates (DBP) and their active metabolite monobutyl phthalate (MBP) and arsenic (As) on spatial cognition associated with hippocampal apoptosis in mice. Mice were exposed, individually or in combination, to DBP (50 mg/kg body weight, intragastrically), MBP (50 mg/kg body weight, intragastrically), and As (10 mg/L, per os) for 8 weeks. The Morris water maze test showed that mice exposed to DBP/MBP combined with As exhibited longer escape latencies and the lower average number of crossing the platform. The As content in the hippocampus after As exposure increased as compared to those without As exposure. In mice exposed to DBP/MBP combined with As, pathological alterations and oxidative damage to the hippocampus were found. Expression of apoptosis-related protein: Bax and caspase-3 were significantly increased in the hippocampus, while there was no significant change in expression of Bcl-2. The results suggested that DBP and MBP combined with As can induce spatial cognitive deficits through altering the expression of apoptosis-related protein and As played a critical role in cognition impairments. And the joint exposure has antagonistic effect.

  12. 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

  13. 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

  14. 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

  15. Subchronic mycotoxicoses in Wistar rats: assessment of the in vivo and in vitro genotoxicity induced by fumonisins and aflatoxin B(1), and oxidative stress biomarkers status.

    PubMed

    Theumer, M G; Cánepa, M C; López, A G; Mary, V S; Dambolena, J S; Rubinstein, H R

    2010-01-31

    Some evidence suggests that fumonisin B(1) (FB(1)), a worldwide toxic contaminant of grains produced by Fusarium verticillioides, exhibits an oxidative stress mediated genotoxicity. We studied the DNA damage (by the alkaline comet and the micronucleus tests) and biomarkers of cellular oxidative stress (malondialdehyde, MDA; catalase, CAT; and superoxide dismutase, SOD) in spleen mononuclear cells of male Wistar rats subchronically (90 days) fed on a control experimental diet (CED) or poisoned with experimental diets contaminated with a culture material containing 100 ppm of FB(1) (FED), with 40 ppb of aflatoxin B(1) (a common toxic co-contaminant in cereals, AFB(1)ED), and with a mixture of both toxins (MED). The DNA damage was found in 13.7%, 81.7%, 98.0% and 99.3% (comet assay) and in 2.8%, 7.0%, 10.8% and 8.8% (micronucleus technique) in groups CED, FED, AFB(1)ED and MED, respectively. The MDA levels as well as the CAT and SOD activities were increased in all the poisoned animals. A similar behavior was observed in cells exposed in vitro to the toxins. These data support the hypothesis of an oxidative stress mediated genotoxicity induced by FB(1). Furthermore, the extent of DNA damage assessed by the comet assay suggests a possible protective effect of the fumonisins-AFB(1) mixtures in vitro against the genotoxicity induced individually by the toxins.

  16. 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.

  17. Effects of 90-day feeding of transgenic Bt rice TT51 on the reproductive system in male rats.

    PubMed

    Wang, Er Hui; Yu, Zhou; Hu, Jing; Xu, Hai Bin

    2013-12-01

    Rice is a staple food crop; however, the threat of pests leads to a serious decline in its output and quality. The CryAb/CryAc gene, encodes a synthetic fusion Bacillus thuringiensis (Bt) crystal protein, was introduced into rice MingHui63 to produce insect-resistant rice TT51. This study was undertaken to investigate potential unintended effects of TT51 on the reproductive system in male rats. Male rats were treated with diets containing 60% of either TT51 or MingHui63 by weight, nutritionally balanced to an AIN93G diet, for 90days. An additional negative control group of rats were fed with a rice-based AIN93G diet. Body weights, food intake, hematology, serum chemistry, serum hormone levels, sperm parameters and relative organ/body weights were measured, and gross as well as microscopic pathology were examined. No diet-related significant differences in the values of response variables were observed between rats that were fed with diet containing transgenic TT51, MingHui63 and the control in this 90-day feeding study. In addition, necropsy and histopathology examination indicated no treatment-related changes. The results from the present study indicated that TT51 does not appear to exert any effect on the reproductive system in male rats compared with MingHui63 or the control.

  18. 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.

  19. 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.

  20. 90-Day Cycle: Exploration of Math Intensives as a Strategy to Move More Community College Students out of Developmental Math Courses

    ERIC Educational Resources Information Center

    Sherer, Jennifer Zoltners; Grunow, Alicia

    2010-01-01

    The authors prepared this report after exploring programs using a 90-day cycle process borrowed from the Institute for Healthcare Improvement (IHI). The IHI 90-day cycle scans activity in the field as a "quick way to research innovative ideas and assess their potential for advancing quality improvement". The goal was to "get under the hood" of…

  1. 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

  2. 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

  3. 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.

  4. A 90-day safety study in Wistar rats fed genetically modified rice expressing snowdrop lectin Galanthus nivalis (GNA).

    PubMed

    Poulsen, Morten; Kroghsbo, Stine; Schrøder, Malene; Wilcks, Andrea; Jacobsen, Helene; Miller, Andreas; Frenzel, Thomas; Danier, Jürgen; Rychlik, Michael; Shu, Qingyao; Emami, Kaveh; Sudhakar, Duraialagraja; Gatehouse, Angharad; Engel, Karl-Heinz; Knudsen, Ib

    2007-03-01

    Genetically modified plants expressing insecticidal traits offer a new strategy for crop protection, but at the same time present a challenge in terms of food safety assessment. The present 90-day feeding study was designed to assess the safety of a rice variety expressing the snowdrop Galanthus nivalis lectin (GNA lectin), and forms part of a EU-funded project where the objective has been to develop and validate sensitive and specific methods to assess the safety of genetically modified foods. Male and female Wistar rats were given a purified diet containing either 60% genetically modified or parental rice for 90 days. This corresponds to a mean daily GNA lectin intake of approximately 58 and 67mg/kg body weight for males and females, respectively. Prior to the animal study comprehensive analytical characterization of both rice materials was performed. The chemical analyses showed a number of statistically significant differences, with the majority being within the ranges reported in the literature. In the animal study a range of clinical, biological, immunological, microbiological and pathological parameters were examined. A number of significant differences were seen between groups fed the two diets, but none of them were considered to be adverse. In conclusion, the design of the present animal study did not enable us to conclude on the safety of the GM food. Additional group(s) where the expressed gene products have been spiked to the diet should be included in order to be able to distinguish whether the observed effects were due to the GNA lectin per se or to secondary changes in the GM rice.

  5. 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

  6. A 90-day toxicology study of meat from genetically modified sheep overexpressing TLR4 in Sprague-Dawley rats.

    PubMed

    Bai, Hai; Wang, Zhixian; 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.

  7. Physico-chemical properties of a novel (-)-hydroxycitric acid extract and its effect on body weight, selected organ weights, hepatic lipid peroxidation and DNA fragmentation, hematology and clinical chemistry, and histopathological changes over a period of 90 days.

    PubMed

    Shara, Michael; Ohia, Sunny E; Schmidt, Robert E; Yasmin, Taharat; Zardetto-Smith, Andrea; Kincaid, Anthony; Bagchi, Manashi; Chatterjee, Archana; Bagchi, Debasis; Stohs, Sidney J

    2004-05-01

    Garcinia cambogia-derived (-)-hydroxycitric acid (HCA) is a popular and natural supplement for weight management. HCA is a competitive inhibitor of the enzyme ATP citrate lyase, which catalyzes the conversion of citrate and coenzyme A to oxaloacetate and acetyl coenzyme A (acetyl CoA) in the cytosol. Acetyl CoA is used in the synthesis of fatty acids, cholesterol and triglycerides, and in the synthesis of acetylcholine in the central nervous system. Studies have demonstrated the efficacy of a novel 60% calcium-potassium salt of HCA derived from Garcinia cambogia (HCA-SX, Super CitriMax) in weight management. Results have shown that HCA-SX promotes fat oxidation, enhances serotonin release and availability in the brain cortex, normalizes lipid profiles, and lowers serum leptin levels in obese subjects. Acute oral, acute dermal, primary dermal irritation and primary eye irritation toxicity, as well as Ames bacterial reverse mutation studies and mouse lymphoma tests have demonstrated the safety of HCA-SX. However, no detailed long-term safety of HCA-SX or any other HCA extract has been previously assessed. We evaluated the dose- and time-dependent effects of HCA-SX in Sprague-Dawley rats on body weight, selected organ weights, hepatic lipid peroxidation and DNA fragmentation, hematology and clinical chemistry over a period of 90 days. Furthermore, a 90-day histopathological evaluation was conducted. The animals were treated with 0, 0.2, 2.0 and 5.0% HCA-SX of feed intake and were sacrificed on 30, 60 or 90 days of treatment. The body weight and selected organ weights were assessed and correlated as a % of body weight and brain weight at 90 days of treatment. A significant reduction in body weight was observed in treated rats as compared to control animals. An advancing age-induced marginal increase in hepatic lipid peroxidation was observed in both male and female rats, while no such difference in hepatic DNA fragmentation was observed as compared to the control

  8. Report of an Expert Panel on the reanalysis by of a 90-day study conducted by Monsanto in support of the safety of a genetically modified corn variety (MON 863).

    PubMed

    Doull, J; Gaylor, D; Greim, H A; Lovell, D P; Lynch, B; Munro, I C

    2007-11-01

    MON 863, a genetically engineered corn variety that contains the gene for modified Bacillus thuringiensis Cry3Bb1 protein to protect against corn rootworm, was tested in a 90-day toxicity study as part of the process to gain regulatory approval. This study was reanalyzed by Séralini et al. who contended that the study showed possible hepatorenal effects of MON 863. An Expert Panel was convened to assess the original study results as analyzed by the Monsanto Company and the reanalysis conducted by Séralini et al. The Expert Panel concludes that the Séralini et al. reanalysis provided no evidence to indicate that MON 863 was associated with adverse effects in the 90-day rat study. In each case, statistical findings reported by both Monsanto and Séralini et al. were considered to be unrelated to treatment or of no biological or clinical importance because they failed to demonstrate a dose-response relationship, reproducibility over time, association with other relevant changes (e.g., histopathology), occurrence in both sexes, difference outside the normal range of variation, or biological plausibility with respect to cause-and-effect. The Séralini et al. reanalysis does not advance any new scientific data to indicate that MON 863 caused adverse effects in the 90-day rat study.

  9. 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

  10. 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.

  11. Anatomical sector analysis of load-bearing tibial bone structure during 90-day bed rest and 1-year recovery.

    PubMed

    Cervinka, Tomas; Rittweger, Jörn; Hyttinen, Jari; Felsenberg, Dieter; Sievänen, Harri

    2011-07-01

    The aim of this study was to investigate whether the bone response to long bed rest-related immobility and during subsequent recovery differed at anatomically different sectors of tibial epiphysis and diaphysis. For this study, peripheral quantitative tomographic (pQCT) scans obtained from a previous 90-day 'Long Term Bed Rest' intervention were preprocessed with a new method based on statistical approach and re-analysed sector-wise. The pQCT was performed on 25 young healthy males twice before the bed rest, after the bed rest and after 1-year follow-up. All men underwent a strict bed rest intervention, and in addition, seven of them received pamidronate treatment and nine did flywheel exercises as countermeasures against disuse-related bone loss. Clearly, 3-9% sector-specific losses in trabecular density were observed at the tibial epiphysis on average. Similarly, cortical density decreased in a sector-specific way being the largest at the anterior sector of tibial diaphysis. During recovery, the bed rest-induced bone losses were practically restored and no consistent sector-specific modulation was observed in any subgroup. It is concluded that the sector-specific analysis of bone cross-sections has potential to reveal skeletal responses to various interventions that cannot be inferred from the average analysis of the whole bone cross-section. This approach is considered also useful for evaluating the bone responses from the biomechanical point of view. PMID:21672131

  12. Results of a 90-day safety assurance study with rats fed grain from corn rootworm-protected corn.

    PubMed

    Hammond, B; Lemen, J; Dudek, R; Ward, D; Jiang, C; Nemeth, M; Burns, J

    2006-02-01

    The results of a 90-day rat feeding study with YieldGard (YieldGard Rootworm Corn is a registered trademark of Monsanto Technology, LLC.) Rootworm corn (MON 863) grain that is protected against feeding damage caused by corn rootworm larvae are presented. Corn rootworm-protection was accomplished through the introduction of a cry3Bb1 coding sequence into the corn genome for in planta production of a modified Cry3Bb1 protein from Bacillus thuringiensis. Grain from MON 863 and its near isogenic control were separately formulated into rodent diets at levels of 11% and 33% (w/w) by Purina Mills, Inc. Additionally, six groups of rats were fed diets containing grain from different conventional (non-biotechnology-derived) reference varieties. The responses of rats fed diets containing MON 863 were compared to those of rats fed grain from conventional corn varieties. All diets were nutritionally balanced and conformed to Purina Mills, Inc. specifications for Certified LabDiet 5002. There were a total of 400 rats in the study divided into 10 groups of 20 rats/sex/group. Overall health, body weight gain, food consumption, clinical pathology parameters (hematology, blood chemistry, urinalysis), organ weights, gross and microscopic appearance of tissues were comparable between groups fed diets containing MON 863 and conventional corn varieties. This study complements extensive agronomic, compositional and farm animal feeding studies with MON 863 grain, confirming that it is as safe and nutritious as existing conventional corn varieties.

  13. 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.

  14. A 90-day toxicology study of transgenic lysine-rich maize grain (Y642) in Sprague-Dawley rats.

    PubMed

    He, Xiao Yun; Tang, Mao Zhi; Luo, Yun Bo; Li, Xin; Cao, Si Shuo; Yu, Jing Juan; Delaney, Bryan; Huang, Kun Lun

    2009-02-01

    The gene for a lysine-rich protein (sb401) obtained from potatoes (Solanum berthaultii) was inserted into maize seed to produce Y642 transgenic maize. Compositional analysis of Y642 grain demonstrated that the concentrations of lysine and total protein were higher than those observed in maize grain from a near-isogenic non-genetically modified (non-GM) commercially available control quality protein maize (Nongda 108). The safety of Y642 maize grain was assessed by comparison of toxicology response variables in Sprague-Dawley (SD) rats consuming diets containing Y642 maize grain with those containing Nongda 108 maize grain. Maize grains from Y642 or Nongda 108 were incorporated into rodent diets at low (30%) or high concentrations (76%) and administered to SD rats (n=10/sex/group) for 90 days. An additional group of negative control group of rats (n=10/sex/group) were fed AIN93G diets. No adverse diet-related differences in body weights, feed consumption/utilization, clinical chemistry, hematology, absolute and relative organ weights were observed. Further, no differences in gross or microscopic pathology were observed between rats consuming diets with Y642 maize grain compared with rats consuming diets containing Nongda 108 maize grain. These results demonstrated that Y642 lysine-rich maize is as safe and nutritious as conventional quality protein maize.

  15. Results of a 90-day safety assurance study with rats fed grain from corn borer-protected corn.

    PubMed

    Hammond, B G; Dudek, R; Lemen, J K; Nemeth, M A

    2006-07-01

    The results of a 90-day rat feeding study with grain from MON 810 corn (YieldGard Cornborer -- YieldGard Cornborer is a registered trademark of Monsanto Technology, LLC) that is protected against feeding damage from corn and stalk boring lepidopteran insects are presented. Corn borer protection was accomplished through the introduction of cry1Ab coding sequences into the corn genome for in planta production of a bioactive form of Cry1Ab protein. Grain from MON 810 and its near-isogenic control was separately formulated into rodent diets at levels of 11% and 33% (w/w) by Purina Mills, Inc. (PMI). All diets were nutritionally balanced and conformed to PMI specifications for Certified LabDiet (PMI Certified LabDiet 5002 is a registered trademark of Purina Mills, Inc.) 5002. There were a total of 400 rats in the study divided into 10 groups of 20 rats/sex/group. The responses of rats fed diets containing MON 810 were compared to those of rats fed grain from conventional corn varieties. Overall health, body weight, food consumption, clinical pathology parameters (hematology, blood chemistry, urinalysis), organ weights, and gross and microscopic appearance of tissues were comparable between groups fed diets containing MON 810 and conventional corn varieties. This study complements extensive agronomic, compositional and farm animal feeding studies with MON 810 grain, confirming that it is as safe and nutritious as grain from existing commercial corn varieties.

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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 Department of Agriculture (Continued) FARM SERVICE AGENCY, DEPARTMENT OF AGRICULTURE SPECIAL PROGRAMS DIRECT LOAN SERVICING-SPECIAL Loan...

  1. The Value of ABCD2F Scoring System (ABCD2 Combined with Atrial Fibrillation) to Predict 90-Day Recurrent Brain Stroke

    PubMed Central

    Almasi, Mostafa; Ghasemi, Faeze; Chardoli, Mojtaba

    2016-01-01

    Background. The ABCD2 score is now identified as a useful clinical prediction rule to determine the risk for stroke in the days following brain ischemic attacks. Aim. The present study aimed to introduce a new scoring system named “ABCD2F” and compare its value with the previous ABCD2 system to predict recurrent ischemic stroke within 90 days of the initial cerebrovascular accident (CVA). Methods. 138 consecutive patients with the final diagnosis of ischemic CVA or TIAs who referred to emergency ward of Rasoul-e-Akram general hospital in Tehran from September 2012 to December 2013 were eligible. By adding a new score in the presence of atrial fibrillation to ABCD2 system, the new scoring system as ABCD2F was introduced and the risk stratification was done again on this new system. Results. The area under the curve for ABCD2 was 0.434 and for ABCD2F it was 0.452 indicating low value of both systems for assessing recurrence of stroke within 90 days of primary event. Multivariable logistic regression analysis showed that none of the baseline factors could predict 90-day recurrent stroke. Conclusion. ABCD2 and/or atrial fibrillation are not good scoring candidates for assessing the risk of recurrent stroke within first 90 days. PMID:27642521

  2. The Value of ABCD2F Scoring System (ABCD2 Combined with Atrial Fibrillation) to Predict 90-Day Recurrent Brain Stroke.

    PubMed

    Almasi, Mostafa; Hodjati Firoozabadi, Nader; Ghasemi, Faeze; Chardoli, Mojtaba

    2016-01-01

    Background. The ABCD2 score is now identified as a useful clinical prediction rule to determine the risk for stroke in the days following brain ischemic attacks. Aim. The present study aimed to introduce a new scoring system named "ABCD2F" and compare its value with the previous ABCD2 system to predict recurrent ischemic stroke within 90 days of the initial cerebrovascular accident (CVA). Methods. 138 consecutive patients with the final diagnosis of ischemic CVA or TIAs who referred to emergency ward of Rasoul-e-Akram general hospital in Tehran from September 2012 to December 2013 were eligible. By adding a new score in the presence of atrial fibrillation to ABCD2 system, the new scoring system as ABCD2F was introduced and the risk stratification was done again on this new system. Results. The area under the curve for ABCD2 was 0.434 and for ABCD2F it was 0.452 indicating low value of both systems for assessing recurrence of stroke within 90 days of primary event. Multivariable logistic regression analysis showed that none of the baseline factors could predict 90-day recurrent stroke. Conclusion. ABCD2 and/or atrial fibrillation are not good scoring candidates for assessing the risk of recurrent stroke within first 90 days. PMID:27642521

  3. The Value of ABCD2F Scoring System (ABCD2 Combined with Atrial Fibrillation) to Predict 90-Day Recurrent Brain Stroke

    PubMed Central

    Almasi, Mostafa; Ghasemi, Faeze; Chardoli, Mojtaba

    2016-01-01

    Background. The ABCD2 score is now identified as a useful clinical prediction rule to determine the risk for stroke in the days following brain ischemic attacks. Aim. The present study aimed to introduce a new scoring system named “ABCD2F” and compare its value with the previous ABCD2 system to predict recurrent ischemic stroke within 90 days of the initial cerebrovascular accident (CVA). Methods. 138 consecutive patients with the final diagnosis of ischemic CVA or TIAs who referred to emergency ward of Rasoul-e-Akram general hospital in Tehran from September 2012 to December 2013 were eligible. By adding a new score in the presence of atrial fibrillation to ABCD2 system, the new scoring system as ABCD2F was introduced and the risk stratification was done again on this new system. Results. The area under the curve for ABCD2 was 0.434 and for ABCD2F it was 0.452 indicating low value of both systems for assessing recurrence of stroke within 90 days of primary event. Multivariable logistic regression analysis showed that none of the baseline factors could predict 90-day recurrent stroke. Conclusion. ABCD2 and/or atrial fibrillation are not good scoring candidates for assessing the risk of recurrent stroke within first 90 days.

  4. 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...

  5. 41 CFR 302-7.9 - What are some reasons that would justify the additional storage beyond the initial 90-day limit?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... that would justify the additional storage beyond the initial 90-day limit? 302-7.9 Section 302-7.9 Public Contracts and Property Management Federal Travel Regulation System RELOCATION ALLOWANCES TRANSPORTATION AND STORAGE OF PROPERTY 7-TRANSPORTATION AND TEMPORARY STORAGE OF HOUSEHOLD GOODS AND...

  6. 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

  7. Rheumatoid arthritis is associated with higher 90-day Hospital Readmission Rates Compared to Osteoarthritis after Hip or Knee arthroplasty: A cohort study

    PubMed Central

    Singh, Jasvinder A.; Inacio, Maria C.S.; Namba, Robert S.; Paxton, Elizabeth W.

    2014-01-01

    Objective To examine if an underlying diagnosis of rheumatoid arthritis (RA) or osteoarthritis (OA) impacts the 90-day readmission rates after total hip or knee arthroplasty (THA or TKA). Methods Prospectively collected data from an integrated healthcare system Total Joint Replacement Registry of adults with RA or OA undergoing unilateral primary THA or TKA during 2009-2011 were analyzed. Adjusted logistic regression models for 90-day readmission were fit. Odds ratios with 95% confidence intervals (CI) were calculated. Study year was an effect modifier for the outcome, therefore separate analyses were conducted for each of the three study years. Results Of the 34,311 patients, 496 had RA and 33,815 had OA. Comparing RA and OA, there were: 73% and 61% women; 45% and 70% Caucasians; and the mean age was lower, 61 vs. 67 years (p<0.001). Respective crude 90-day readmission rates were 8.5% and 6.7%. The adjusted odds of 90-day readmission increased from year to year for RA compared to OA patients, from 0.89 (95% CI, 0.46-1.71) in 2009 to 1.34 (95% CI, 0.69-2.61) in 2010 to 1.74 (95% CI, 1.16-2.60) in 2011. The two most common readmission reasons were: joint prosthesis infection (10.2%) and septicemia (10.2%) in RA; joint prosthesis infection (5.7%) and other postoperative infection (5.1%) in OA. Conclusions RA is a risk factor for 90-day readmission after primary TKA or THA. An increasing risk of readmissions noted in RA in 2011 is concerning and indicates further studies should examine the reasons for this increasing trend. PMID:25302697

  8. 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

  9. Sub-chronic Hepatotoxicity of Anacardium occidentale (Anacardiaceae) Inner Stem Bark Extract in Rats.

    PubMed

    Okonkwo, T J N; Okorie, O; Okonta, J M; Okonkwo, C J

    2010-05-01

    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 LD(50)of 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.

  10. Evaluation of the oral subchronic toxicity of HHCB (1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-gamma-2 -benzopyran) in the rat.

    PubMed

    Api, A M; Ford, R A

    1999-12-20

    1,3,4,6,7,8-Hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-gamma-2-ben zopyran (HHCB) is used in a wide variety of fragrances in consumer products. Because of the widespread exposure to this material, a 90-day oral feeding study in accordance with OECD guidelines No. 408, with 4-week recovery periods for selected rats, was conducted. HHCB was added to the diet of rats at levels calculated to result in mean daily doses of 5, 15, 50 or 150 mg HHCB/kg. On completion of the treatment period, three males and three females from the high dose and control groups were maintained for a treatment free period of 4 weeks. No adverse effects were revealed from clinical examination or following extensive histopathological examinations. There were no significant findings at any dose level; a NOAEL of 150 mg/kg per day was concluded. As a supplement to the main study, histopathological examination of the prostate, seminal vesicles, mammary gland and testes of males and ovaries, mammary gland, uterus and vagina of females was undertaken on all animals in all test groups. This examination did not reveal any evidence of hormonal effects.

  11. 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.

  12. Prior statin use and 90-day mortality in Gram-negative and Gram-positive bloodstream infection: a prospective observational study.

    PubMed

    Mehl, A; Harthug, S; Lydersen, S; Paulsen, J; Åsvold, B O; Solligård, E; Damås, J K; Edna, T-H

    2015-03-01

    In several studies on patients with bloodstream infection (BSI), prior use of statins has been associated with improved survival. Gram-positive and Gram-negative bacteria alert the innate immune system in different ways. We, therefore, studied whether the relation between prior statin use and 90-day total mortality differed between Gram-positive and Gram-negative BSI. We conducted a prospective observational cohort study of 1,408 adults with BSI admitted to Levanger Hospital between January 1, 2002, and December 31, 2011. Data on the use of statins and other medications at admission, comorbidities, functional status, treatment, and outcome were obtained from the patients' hospital records. The relation of statin use with 90-day mortality differed between Gram-negative and Gram-positive BSI (p-value for interaction 0.01). Among patients with Gram-negative BSI, statin users had significantly lower 90-day total mortality [odds ratio (OR) 0.42, 95 % confidence interval (CI) 0.23-0.75, p = 0.003]. The association remained essentially unchanged after adjusting for the effect of sex, age, functional status before the infection, and underlying diseases that were considered confounders (adjusted OR 0.38, 95 % CI 0.20-0.72, p = 0.003). A similar analysis of patients with Gram-positive BSI showed no association of statin use with mortality (adjusted OR 1.22, 95 % CI 0.69-2.17, p = 0.49). The present study suggests that prior statin use is associated with a lower 90-day total mortality in Gram-negative BSI, but not in Gram-positive BSI.

  13. 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.

  14. A 90-day safety study in Sprague-Dawley rats fed milk powder containing recombinant human lactoferrin (rhLF) derived from transgenic cloned cattle.

    PubMed

    Zhou, Cui; Wang, Jian Wu; Huang, Kun Lun; He, XiaoYun; Chen, Xiu Ping; Sun, Hong; Yu, Tian; Che, Hui Lian

    2011-10-01

    Transgenic cloned animals expressing beneficial human nutritional traits offer a new strategy for large-scale production of some kinds of functional substances. In some cases, the required safety testing for genetically modified (GM) foods do not seem appropriate for human food safety, though regulations do not seem to provide alternatives. A 90-day rat feeding study is the core study for the safety assessment of GM foods. The test material in this 90-day study was prepared nonfat milk powder containing recombinant human lactoferrin (rhLF), which was expressed in transgenic cloned cattle. Groups of 10 male and female Sprague-Dawley rats were given a nutritionally balanced purified diet containing 7.5, 15, or 30% transgenic or conventional milk powder for 90 days. A commercial AIN93G diet was used as an additional control group. Clinical, biological, and pathological parameters were compared between groups. The only significant effect of treatment was higher mean ferritin and Fe(+) concentrations for both male and female rats fed the transgenic milk powder diets, as compared to rats fed nontransgenic milk diets or the commercial diet. The results of the present study are consistent with previous research, which indicates that milk powder containing rhLF derived from healthy transgenic cloned cattle is as safe as conventional milk powder.

  15. 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

  16. 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.

  17. 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.

  18. STS-90 Day 01 Highlights

    NASA Technical Reports Server (NTRS)

    1998-01-01

    On this first 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, can be seen performing pre-launch activities such as eating the traditional breakfast, crew suit-up, and the ride out to the launch pad. Also, included are various panoramic views of the shuttle on the pad. The crew is readied in the white room' for their mission. After the closing of the hatch and arm retraction, launch activities are shown including countdown, engine ignition, launch, and the separation of the Solid Rocket Boosters. The shuttle's payload bay doors are then opened in anticipation of the 16-day scientific mission. The astronauts then are seen readying the Spacelab module for various experiments.

  19. STS-90 Day 05 Highlights

    NASA Technical Reports Server (NTRS)

    1998-01-01

    On this fifth 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 perform tests associated with the STS-90 Neurolab Vestibular Team's efforts to gain insight into the balance organs in the ear and all the connections that system has to the eyes, brain, and muscles in adapting to the weightless condition in space and then readapts to the gravity environment found on Earth.

  20. 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.

  1. 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 ...

  2. 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

  3. Vertical jump performance after 90 days bed rest with and without flywheel resistive exercise, including a 180 days follow-up.

    PubMed

    Rittweger, Jörn; Felsenberg, Dieter; Maganaris, Constantinos; Ferretti, José Luis

    2007-07-01

    Muscle atrophy and neuromuscular de-conditioning occur in response to space flight and bed-rest. In this study, we investigated the efficacy of flywheel training to conserve jumping power and height during 90 days bed rest. Twenty-four young healthy men underwent strict bed-rest (-6 degrees head down tilt) for 90 days. Eight participants were assigned to a flywheel group (FW) and 16 to a control group (Ctrl). The ground reaction force was measured during vertical jump tests twice during baseline data collection, and on day 4, 7, 14, 90 and 180 of recovery. In half of the participants, jump tests were also performed within minutes after re-ambulation and on four more occasions during the first 2 days of recovery. Jump height was reduced from 40.6 cm (SD 6.1 cm) during the first baseline measurement to 27.6 cm (SD 5.6 cm) on day 4 of recovery in Ctrl, but only from 38.6 cm (SD 3.9 cm) to 34.4 cm (SD 6.5 cm) in FW (P < 0.001). At the same time, peak power was reduced from 47.4 W/kg (SD 8.0 W/kg) to 34.5 W/kg in Ctrl, but only from 46.2 W/kg (6.0 W/kg) to 42.2 W/kg SD 4.6 W/kg) in FW (P < 0.001). Jump height and peak power were completely recovered after 163 and 140 days in Ctrl, respectively, and after 72 and 18 days in FW (regression analysis). In conclusion, flywheel exercise could effectively offset neuromuscular de-conditioning during bed-rest, and led to full recovery at an earlier stage. These findings nourish the hope that adequate training paradigms can fully sustain neuromuscular function under microgravity conditions. PMID:17406887

  4. 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

    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 of

  5. 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

  6. 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.

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. A 90 day safety assessment of genetically modified rice expressing Cry1Ab/1Ac protein using an aquatic animal model.

    PubMed

    Zhu, Hao-Jun; Chen, Yi; Li, Yun-He; Wang, Jia-Mei; Ding, Jia-Tong; Chen, Xiu-Ping; Peng, Yu-Fa

    2015-04-15

    In fields of transgenic Bt rice, frogs are exposed to Bt proteins through consumption of both target and nontarget insects. In the present study, we assessed the risk posed by transgenic rice expressing a Cry1Ab/1Ac fusion protein (Huahui 1, HH1) on the development of Xenopus laevis. For 90 days, froglets were fed a diet with 30% HH1 rice, 30% parental rice (Minghui 63, MH63), or no rice as a control. Body weight and length were measured every 15 days. After sacrificing the froglets, we performed a range of biological, clinical, and pathological assessments. No significant differences were found in body weight (on day 90: 27.7 ± 2.17, 27.4 ± 2.40, and 27.9 ± 1.67 g for HH1, MH63, and control, respectively), body length (on day 90: 60.2 ± 1.55, 59.3 ± 2.33, and 59.7 ± 1.64 mm for HH1, MH63, and control, respectively), animal behavior, organ weight, liver and kidney function, or the microstructure of some tissues between the froglets fed on the HH1-containing diet and those fed on the MH63-containing or control diets. This indicates that frog development was not adversely affected by dietary intake of Cry1Ab/1Ac protein. PMID:25822065

  13. 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

  14. 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

  15. A 90 day safety assessment of genetically modified rice expressing Cry1Ab/1Ac protein using an aquatic animal model.

    PubMed

    Zhu, Hao-Jun; Chen, Yi; Li, Yun-He; Wang, Jia-Mei; Ding, Jia-Tong; Chen, Xiu-Ping; Peng, Yu-Fa

    2015-04-15

    In fields of transgenic Bt rice, frogs are exposed to Bt proteins through consumption of both target and nontarget insects. In the present study, we assessed the risk posed by transgenic rice expressing a Cry1Ab/1Ac fusion protein (Huahui 1, HH1) on the development of Xenopus laevis. For 90 days, froglets were fed a diet with 30% HH1 rice, 30% parental rice (Minghui 63, MH63), or no rice as a control. Body weight and length were measured every 15 days. After sacrificing the froglets, we performed a range of biological, clinical, and pathological assessments. No significant differences were found in body weight (on day 90: 27.7 ± 2.17, 27.4 ± 2.40, and 27.9 ± 1.67 g for HH1, MH63, and control, respectively), body length (on day 90: 60.2 ± 1.55, 59.3 ± 2.33, and 59.7 ± 1.64 mm for HH1, MH63, and control, respectively), animal behavior, organ weight, liver and kidney function, or the microstructure of some tissues between the froglets fed on the HH1-containing diet and those fed on the MH63-containing or control diets. This indicates that frog development was not adversely affected by dietary intake of Cry1Ab/1Ac protein.

  16. 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

  17. Ninety-day toxicity evaluation of 1,3,5-trinitrobenzene (Tnb) in Peromyscus leucopus

    SciTech Connect

    Reddy, T.V.; Torsella, J.; Daniel, F.B.; Olson, G.R.; Wiechman, B.; Reddy, G.

    1995-12-31

    The subchronic toxicity of TNB in P. leucopus was evaluated by feeding Certified Rodent Diet 5002 supplemented with TNB (0, 150, 375, and 750 mg of TNB/kg diet), for 90 days. The food and water consumption was not significantly different between dose groups (for either sex). The calculated average daily TNB intake for female and male P. leucopus respectively, was 0, 20, 65, 108 and 0, 23, 67, and 113 mg/kg body weight (BW). There were no differences in the absolute body weights between sexes as well as between dose groups. Similarly, the organ weights (absolute and relative) did not differ significantly between the dose groups (in both sexes) with an exception of male P. leucopus group receiving 750 mg TNB diet. In this group the spleen weights, both absolute and relative (g/100 g bw), were increased significantly. A significant increase in white blood cells and reticulocytes were detected. In addition, histopathological examinations in the aforementioned dose group revealed erythroid cell hyperplasia (spleen) and seminiferous tubular degeneration (testes). Although not significant, an increase in methemoglobin levels with an increased dose was evident. When the TNB concentration in the diet was increased to 1,200 and 1,800 mg/kg (used in the range finding study), the above indicated effects were much more prominent and were seen in both sexes. From this study a NOAEL of 20 mg/day/kg for female and 23 mg/day/kg for male is suggested.

  18. Spontaneous lesions in subchronic neurotoxicity testing of rats.

    PubMed

    Eisenbrandt, D L; Mattsson, J L; Albee, R R; Spencer, P J; Johnson, K A

    1990-01-01

    Male and female Fischer 344 rats, 30 weeks of age, were examined for neuropathologic changes after a 13-week inhalation neurotoxicologic study. Tissues were preserved by whole-body perfusion with 1.5% glutaraldehyde/4% formaldehyde solution. An extensive set of neural tissues was embedded in paraffin, sectioned, and stained with hematoxylin and eosin, luxol fast blue/periodic acid-Schiff/hematoxylin, Sevier-Munger silver, and cresyl echt violet. Lesions in the central and peripheral nervous system were comparable between sexes and between control and treated animals. Bilateral swollen axons were present in the medial aspect of the nucleus gracilis adjacent to the area postrema. Occasional swollen axons also were observed in the dorsal and ventral funiculi of the spinal cord. Degeneration of individual nerve fibers was present in the trapezoid body, vestibular nerve root, trigeminal nerve, cerebellar peduncles, and the funiculi of the spinal cord. Individual nerve fiber degeneration also was present in the spinal nerve roots, sciatic and tibial nerves. Nerve fiber degeneration was characterized by myelin disruption and degeneration, vacuoles and axonal fragmentation. Similar spontaneous neuropathology may be encountered in rats from other subchronic neurotoxicologic studies and must be differentiated from treatment-related toxicity.

  19. 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

  20. Structural changes in femoral bone tissue of rats after subchronic peroral exposure to selenium

    PubMed Central

    2013-01-01

    Background The role of selenium (Se) on bone microarchitecture is still poorly understood. The present study aims to investigate the macroscopic and microscopic structures of femoral bone tissue in adult male rats after subchronic peroral administration of Se. Methods Twenty one-month-old male Wistar rats were randomly divided into two experimental groups. In the first group (Se group) young males were exposed to 5 mg Na2SeO3/L in drinking water, for 90 days. Ten one-month-old males without Se administration served as a control group. At the end of the experiment, macroscopic and microscopic structures of the femurs were analysed using analytical scales, sliding instrument, and polarized light microscopy. Results The body weight, femoral length and cortical bone thickness were significantly decreased in Se group rats. These rats also displayed different microstructure in the middle part of the femur, both in medial and lateral views, where vascular canals expanded into the central area of the bone while, in control rats, these canals occurred only near the endosteal surfaces. Additionally, a smaller number of primary and secondary osteons was identified in Se group rats. Histomorphometric analyses revealed significant increases for area, perimeter, maximum and minimum diameters of primary osteons’ vascular canals but significant reductions for all measured variables of Haversian canals and secondary osteons. Conclusions Se negatively affected the macroscopic and microscopic structures of femoral bone tissue in adult male rats. The results contribute to the knowledge on damaging impact of Se on bone. PMID:23369508

  1. Subchronic inhalation neurotoxicity studies of ethyl acetate in rats.

    PubMed

    Christoph, Greg R; Hansen, John F; Leung, Hon-Wing

    2003-12-01

    Rats were exposed to 0, 350, 750 or 1500 ppm of ethyl acetate by inhalation for 6 h per day, 5 days per week for 13 weeks. Functional observational battery (FOB) and motor activity tests occurred on non-exposure days during weeks 4, 8 and 13, after which tissues were microscopically examined for neuropathology. A subset of rats was monitored during a 4-week recovery period. Exposure to 750 and 1500 ppm, diminished behavioral responses to unexpected auditory stimuli during the exposure session and appeared to be an acute sedative effect. There were no signs of acute intoxication 30 min after exposure sessions ended. Rats exposed to 750 and 1500 ppm had reduced body weight, body weight gain, feed consumption, and feed efficiency, which fully or partially recovered within 4 weeks. Reductions in body weight gain and feed efficiency were observed in male rats exposed to 350 ppm. The principal behavioral effect of subchronic exposure was reduced motor activity in the 1500 ppm females, an effect that was not present after the 4-week recovery period. All other FOB and motor activity parameters were unaffected, and no pathology was observed in nervous system tissues. Operant sessions were conducted in another set of male rats preconditioned to a stable operant baseline under a multiple fixed ratio-fixed interval (FR-FI) schedule of food reinforcement. FR response rate, FR post-reinforcement pause duration, and the pattern of FI responding were not affected during or after the exposure series. In contrast, within-group FI rate for the treatment groups increased over time whereas those of the controls decreased. A historical control group, however, also showed a similar pattern of increase, indicating that these changes did not clearly represent a treatment-related effect. Results from these studies indicate a LOEL of 350 ppm for systemic toxicity based on the decreased body weight gain in male rats, and a LOEL of 1500 ppm for neurotoxicity based on the transient reduction in

  2. 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

  3. 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.

  4. Effect of subchronic exposure to arsenic on levels of essential trace elements in mice brain and its gender difference.

    PubMed

    Wang, Xiaoxu; Zhang, Jian; Zhao, Lian; Hu, Shuhai; Piao, Fengyuan

    2013-02-01

    The interactions of toxic metals with essential metals may result in disturbances in the homeostasis of essential elements. However, there are few reports about toxic effect of arsenic (As) on the levels of essential trace elements in the central nervous system. To investigate whether subchronic exposure to As disturbs levels of main essential trace elements in the brain of mice and whether the gender difference in the response to As are altered, the concentrations of As, Iron (Fe), copper (Cu), selenium (Se), zinc (Zn) and Chromium (Cr) in the cerebrum and cerebellum of mice exposed to As subchronically were examined by inductively coupled plasma-mass spectrometry (ICP-MS). The gender difference in the changed levels of these essential trace elements was also statistically analyzed. The concentration of As was significantly higher in the cerebrum or cerebellum of mice exposed to As than that in control group (P < 0.05). It indicates that As can accumulate in brain of mice after subchronic exposure. The concentrations of Fe, Se and Cr in the cerebrum or cerebellum were significantly lower in mice exposed to As than those in control group (P < 0.05). On the contrary, the concentration of Cu in the cerebrum or cerebellum was significantly higher in mice exposed to As (P < 0.05). Our results indicate that subchronic exposure to As may decrease the levels of Fe, Se and Cr or increase the level of Cu in the brain of mice. Moreover, the significant gender difference was found relative to the effect of As on concentration of Se in cerebrum and concentrations of Cu and Se in cerebellum of mice. Therefore, more experiments are required to further understand mechanisms whereby As interacts with essential elements in brain and induces the gender difference.

  5. 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.

    PubMed

    Whittaker, Margaret H; Wang, Gensheng; Chen, Xue-Qing; 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.

  6. 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.

  7. 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

  8. Developmental sub-chronic exposure to chlorpyrifos reduces anxiety-related behavior in zebrafish larvae

    PubMed Central

    Richendrfer, Holly; Pelkowski, Sean D.; Colwill, Ruth M.; Créton, Robbert

    2013-01-01

    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

  9. 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.

  10. 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...

  11. Investigation of neurotoxic and immunotoxic effects of some plant growth regulators at subacute and subchronic applications on rats.

    PubMed

    Isik, Ismail; Celik, Ismail

    2015-12-01

    The present study was aimed to investigate the effects of subacute and subchronic treatment of some plant growth regulators (PGRs), such as abscisic acid (ABA) and gibberellic acid (GA3), on neurological and immunological biomarkers in various tissues of rats. The activities of acetylcholinesterase (AChE) and butrylcholinesterase (BChE) were selected as biomarkers for neurotoxic biomarkers. Adenosine deaminase (ADA) and myeloperoxidase (MPO) were measured as indicators for immunotoxic investigation purpose. Wistar albino rats were orally administered with 25 and 50 ppm of PGRs ad libitum for 25-50 days continuously with drinking water. The treatment of PGRs caused different effects on the activities of enzymes. Results showed that the administrations of ABA and GA3 increased AChE and BChE activities in some tissues of rats treated with both the dosages and periods of ABA and GA3. With regard to the immunotoxic effects, ADA activity fluctuated, while MPO activity increased after subacute and subchronic exposure of treated rat tissues to both dosages when compared with the controls. The observations presented led us to conclude that the administrations of PGRs at subacute and subchronic exposure increased AChE, BChE, and MPO activities, while fluctuating the ADA activity in various tissues of rats. This may reflect the potential role of these parameters as useful biomarkers for toxicity of PGRs.

  12. 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

  13. Sub-chronic exposure to methylmercury at low levels decreases butyrylcholinesterase activity in rats.

    PubMed

    Valentini, Juliana; Vicentini, Juliana; Grotto, Denise; Tonello, Raquel; Garcia, Solange C; Barbosa, Fernando

    2010-02-01

    In this study, we examined the effects of low levels and sub-chronic exposure to methylmercury (MeHg) on butyrylcholinesterase (BuChE) activity in rats. Moreover, we examined the relationship between BuChE activity and oxidative stress biomarkers [delta-aminolevulinic acid dehydratase (delta-ALA-D) and malondialdehyde levels (MDA)] in the same animals. Rats were separated into three groups (eight animals per group): (Group I) received water by gavage; (Group II) received MeHg (30 microg/kg/day) by gavage; (Group III) received MeHg (100 microg/kg/day). The time of exposure was 90 days. BuChE and ALA-D activities were measured in serum and blood, respectively; whereas MDA levels were measured in plasma. We found BuChE and ALA-D activities decreased in groups II and III compared to the control group. Moreover, we found an interesting negative correlation between plasmatic BuChE activity and MDA (r = -0.85; p < 0.01) and a positive correlation between plasmatic BuChE activity and ALA-D activities (r = 0.78; p < 0.01), thus suggesting a possible relationship between oxidative damage promoted by MeHg exposure and the decrease of BuChE activity. In conclusion, long-term exposure to low doses of MeHg decreases plasmatic BuChE activity. Moreover, the decrease in the enzyme is strongly correlated with the oxidative stress promoted by the metal exposure. This preliminary finding highlights a possible mechanism for MeHg to reduce BuChE activity in plasma. Additionally, this enzyme could be an auxiliary biomarker on the evaluation of MeHg exposure.

  14. 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

  15. 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

    2009-06-17

    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.

  16. Induction of oxidative stress in erythrocytes of male rats subchronically exposed to a mixture of eight metals found as groundwater contaminants in different parts of India.

    PubMed

    Jadhav, S H; Sarkar, S N; Aggarwal, M; Tripathi, H C

    2007-01-01

    Exposure of animals and humans to different metal components through contaminated drinking water can result in a wide range of adverse clinical conditions. Toxicological consequences arising from the concurrent repeated exposure to multiple metal contaminants are not known. The purpose of the present study was to evaluate the oxidative stress-inducing potential of a mixture of eight metals (arsenic, cadmium, lead, mercury, chromium, nickel, manganese, iron), representative of groundwater contamination in different areas of India, in erythrocytes of male rats subchronically exposed to environmentally relevant doses via drinking water. The selection of these metals, as determined by literature survey of groundwater contamination in India, was primarily based on the frequency of their occurrence and contamination level above World Health Organization maximum permissible limit (MPL) in drinking water. Male albino Wistar rats were exposed to the metal mixture at 0, 1, 10, and 100 times the mode concentrations (the most frequently occurring concentration) of the individual metals in drinking water for 90 days. In addition, one group of rats was also exposed to the mixture at a concentration equal to the MPL of individual components. The oxidative stress in erythrocytes was evaluated by assessing the magnitude of malondialdehyde production and reduced glutathione (GSH) content and the activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and glutathione reductase (GR) after 30, 60, and 90 days of exposure. MPL and 1x dose levels did not cause any changes. The mixture at 10x and 100x doses caused dose- and time-dependent effects. After 30 days, the 10x dose did not cause any changes except increase in SOD activity. The 100x dose increased the activities of SOD, catalase and GR and the GSH level, but caused no alterations in lipid peroxidation (LPO) and GPx activity. After 60 days, the 10x dose did not cause any changes. The 100x dose increased

  17. Olfactory neuron loss in adult male CD rats following subchronic inhalation exposure to hydrogen sulfide.

    PubMed

    Brenneman, K A; James, R A; Gross, E A; Dorman, D C

    2000-01-01

    Dysosmia and anosmia are reported to occur following human exposure to hydrogen sulfide (H2S) gas. The clinical association between H2S exposure and olfactory dysfunction in humans necessitates evaluation of the nasal cavity and olfactory system in experimental animals used to study H2S toxicity. The purpose of this study was to subchronically expose 10-week-old male CD rats to relatively low concentrations of H2S and to histologically evaluate the nasal cavity for exposure-related lesions. Rats (n = 12/group) were exposed via inhalation to 0, 10, 30, or 80 ppm H2S 6 h/d and 7 d/wk for 10 weeks. Following exposure to 30 and 80 ppm H2S, a significant increase in nasal lesions limited to the olfactory mucosa was observed. The lesions, which consisted of olfactory neuron loss and basal cell hyperplasia, were multifocal, bilaterally symmetrical, and had a characteristic rostrocaudal distribution pattern. Regions of the nasal cavity affected included the dorsal medial meatus and the dorsal and medial portions of the ethmoid recess. The no observed adverse effect level for olfactory lesions in this study was 10 ppm. For perspective, the American Conference of Governmental Industrial Hygienists threshold limit value (TLV) recommendation for H2S is currently 10 ppm (proposed revision: 5 ppm), so the concentrations employed in the present study were 3 and 8 times the TLV. These findings suggest that subchronic inhalation exposure to a relatively low level of H2S (30 ppm) can result in olfactory toxicity in rats. However, because of differences in the breathing style and nasal anatomy of rats and humans, additional research is required to determine the significance of these results for human health risk assessment.

  18. 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

  19. 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

  20. 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

  1. 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.

  2. Subchronic lead exposure, immunotoxicology and increased disease resistance in Japanese quail (Corturnix coturnix japonica).

    PubMed

    Nain, S; Smits, J E G

    2011-05-01

    The present study investigated the effects of lead (Pb) on immune responses in quail (Coturnix coturnix japonica) and the pathological impact of exposure to an infectious agent (E. coli O2). Fifty-four, 4-week-old quail were exposed to lead acetate in drinking water at 5 or 50 ppm. All birds were vaccinated with Newcastle Vaccine (NDV) during the third week of contaminant (Pb) exposure. In the fourth week, several arms of the immune response were tested using the T cell based phytohemagglutinin (PHA) skin test, the B cell mediated antibody response to NVD, and the chemiluminescence assay measuring innate immunity. Immunohistochemistry (IHC) was used to determine the expression of toll like receptor-3 (TLR-3) in the bursa of Fabricius. In the fifth week, quail were challenged with 200 μL of E. coli O2 (1×10(4) colony forming units (CFU)/mL). No clinical signs of Pb toxicity were observed. Morbidity/mortality subsequent to E. coli exposure was lowest in the high exposure group (27.8%) compared to low exposure (44.4%) and control (55.5%) groups. There was no difference in the T-cell-mediated PHA response, primary or secondary immune response or the innate response in Pb exposed groups; however, bursal TLR-3 increased (p<0.05) with higher Pb exposure. No evidence supported that subchronic Pb exposure was immunotoxic to quail at 5 or 50 ppm in drinking water. In contrast, our results provide evidence of a hormetic effect, with Pb exposed birds having lower morbidity and better survival than controls. Subchronic Pb exposure may be immunostimulatory rather than suppressive as predicted in earlier studies based on testing individual immune parameters.

  3. 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

  4. Effects of subchronic samarium exposure on the histopathological structure and apoptosis regulation in mouse testis.

    PubMed

    Zhang, De-Yong; Shen, Xiu-Ying; Ruan, Qin; Xu, Xiao-Lu; Yang, San-Ping; Lu, Yin; Xu, Hui-Ying; Hao, Fei-Lin

    2014-03-01

    To evaluate the reproductive toxicity of samarium, a widely used rare earth element, male ICR mice were orally exposed to samarium nitrate for 90 days for lesion evaluation in the testis. Decreased organ coefficients, disorganized seminiferous tubules, and decreased spermatogenic cells and sperm of the testis were observed extensively in the treated groups, indicating that the testis is a target organ of samarium. Electron microscopy confirmed that the lesions inside the spermatogenic cells and sperm mainly included mitochondrial swelling, mitochondrial vacuolization, fuzzy nuclear membranes, and marginated chromatin. Increased spermatogenic cell apoptosis rate in the testis was confirmed with a TUNEL assay. And expression up-regulation of p53 and Bax, and down-regulation of Bcl-2 were observed (p<0.05), indicating the apoptosis is related to p53 mediated pathway. PMID:24561534

  5. 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

  6. Genome-wide gene expression effects in B6C3F1 mouse intestinal epithelia following 7 and 90days of exposure to hexavalent chromium in drinking water.

    PubMed

    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 90days of exposure to 0, 0.3, 4, 14, 60, 170 or 520mg/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(50) values ranging from 10 to 100mg/L SDD. Only 16 genes satisfying the dose-dependent differential expression criteria had EC(50) values <10mg/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.

  7. Oxidative stress in female B6C3F1 mice following acute and subchronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

    PubMed

    Slezak, B P; Hatch, G E; DeVito, M J; Diliberto, J J; Slade, R; Crissman, K; Hassoun, E; Birnbaum, L S

    2000-04-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a highly persistent trace environmental contaminant and is one of the most potent toxicants known to man. Hassoun et al. (1998, Toxicol. Sci. 42, 23-27) reported an increase in the production of reactive oxygen species (ROS) in the brain of female B6C3F1 mice following subchronic exposure to TCDD at doses as low as 0.45 ng/kg/day. In the present study, oxidative stress was characterized in liver, spleen, lung, and kidney following subchronic (0.15-150 ng/kg; 5 days/week for 13 weeks, po) or acute exposure (0.001-100 microg/kg, po) to TCDD in order to investigate the interaction between tissue concentration and time for production of ROS. Seven days following acute administration of TCDD, mice were sacrificed; they demonstrated increases in liver superoxide anion production (SOAP) and thiobarbituric acid reactive substances (TBARS) at doses of 10 and 100 microg/kg, associated with hepatic TCDD concentrations of 55 and 321 ng/g, respectively. Liver obtained from mice following subchronic TCDD exposure demonstrated an increase in SOAP and TBARS above controls at doses of 150 ng/kg/day with liver TCDD concentration of only 12 ng/g. Interestingly, glutathione (GSH) levels in lung and kidney following sub-chronic TCDD exposure were decreased at the low dose of 0.15 ng/kg/day. This effect disappeared at higher TCDD doses. The data suggest that higher tissue TCDD concentrations are required to elicit oxidative stress following acute dosing than with subchronic TCDD exposure. Therefore, the mechanism of ROS production following TCDD exposure does not appear to be solely dependent upon the concentration of TCDD within the tissue. In addition, very low doses of TCDD that result in tissue concentrations similar to the background levels found in the human population produced an effect on an oxidative stress endogenous defense system. The role of this effect in TCDD-mediated toxicity is not known and warrants further investigation.

  8. Immunosuppressive effect of subchronic exposure to a mixture of eight heavy metals, found as groundwater contaminants in different areas of India, through drinking water in male rats.

    PubMed

    Jadhav, S H; Sarkar, S N; Ram, G C; Tripathi, H C

    2007-10-01

    Immunotoxicity is an important health hazard of heavy metal exposure. Because the risk of combined exposure in the population cannot be neglected, we examined whether subchronic exposure to a mixture of metals (arsenic, cadmium, lead, mercury, chromium, nickel, manganese, and iron) via drinking water at contemporary Indian groundwater contamination levels and at concentrations equivalent to the WHO maximum permissible limit (MPL) in drinking water can induce immunotoxicity in male rats. Data on groundwater contamination with metals in India were collected from literature and metals were selected on the basis of their frequency of occurrence and contamination level above the MPL. Male albino Wistar rats were exposed to the mixture at 0, 1, 10, and 100 times the mode concentrations (the most frequently occurring concentration) of the individual metals in drinking water for 90 days. In addition, one group was exposed to the mixture at a concentration equal to the MPL of the individual metal and another group was used as positive control for immune response studies. The end points assessed were weights of organs, hematological indices, humoral and cell-mediated immune responses, and histopathology of skin and spleen. The MPL and 1x doses did not significantly affect any of the parameters and none of the doses induced any significant changes after 30 days of exposure. The mixture at 10x and 100x doses increased the relative weight of the spleen, but that of thymus, adrenals, and popliteal lymphnodes were increased with the 100x dose. After 90 days, 10x and 100x doses decreased serum protein and globulin contents and increased the albumin:globulin ratio; the albumin level was decreased only with the 100x dose. After 60 days, the total erythrocyte count (TEC), hemoglobin (Hb) level, and packed cell volume (PCV) were decreased with the 100x dose, whereas after 90 days, 10x and 100x doses reduced the TEC, total leukocyte count, Hb level, PCV, mean corpuscular volume, and

  9. Subchronic treatment with antiepileptic drugs modifies pentylenetetrazol-induced seizures in mice: Its correlation with benzodiazepine receptor binding

    PubMed Central

    Rocha, Luisa

    2008-01-01

    Experiments using male CD1 mice were carried out to investigate the effects of subchronic (daily administration for 8 days) pretreatments with drugs enhancing GABAergic transmission (diazepam, 10 mg/kg, ip; gabapentin, 100 mg/kg, po; or vigabatrin, 500 mg/kg, po) on pentylenetetrazol (PTZ)-induced seizures, 24 h after the last injection. Subchronic administration of diazepam reduced latencies to clonus, tonic extension and death induced by PTZ. Subchronic vigabatrin produced enhanced latency to the first clonus but faster occurrence of tonic extension and death induced by PTZ. Subchronic gabapentin did not modify PTZ-induced seizures. Autoradiography experiments revealed reduced benzodiazepine receptor binding in several brain areas after subchronic treatment with diazepam or gabapentin, whereas subchronic vigabatrin did not induce significant receptor changes. The present results indicate differential effects induced by the subchronic administration of diazepam, vigabatrin, and gabapentin on the susceptibility to PTZ-induced seizures, benzodiazepine receptor binding, or both. PMID:18830436

  10. 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

  11. IS IT THE EXCEPTION OR THE RULE? DAILY CO-OCCURRENCE OF PHYSICAL, SEXUAL, AND PSYCHOLOGICAL PARTNER VIOLENCE IN A 90-DAY STUDY OF SUBSTANCE-USING, COMMUNITY WOMEN

    PubMed Central

    Sullivan, Tami P.; McPartland, Tara; Armeli, Stephen; Jaquier, Véronique; Tennen, Howard

    2013-01-01

    Objective This study aims to describe the daily co-occurrence of physical, sexual, and psychological intimate partner violence (IPV) among substance-using, community-based women currently experiencing IPV. Methods A micro-longitudinal study design was used to collect data daily from 49 women for 90 days. Results On the majority of days (62%), no IPV occurred; 27% of days were characterized by psychological IPV alone, followed by the co-occurrence of psychological and physical IPV (6% of IPV days). Results of person-level analyses showed comparable sized correlations between the proportion of days with physical and sexual IPV and the proportion of days with physical and psychological IPV. However, results of day-level analyses revealed that the association between physical and psychological IPV was much stronger than the association between physical and sexual IPV; Physical IPV was 64 times more likely to occur on days when psychological IPV occurred. Conclusions Results revealed new information about physical, sexual, and psychological IPV experiences and demonstrate the utility of a micro-longitudinal design among this high risk population. Implications for practice, future research, and the development of preventive interventions are noted, underscoring the importance of psychological IPV and the range of IPV experiences among women. PMID:24349863

  12. Toxicity test of a dental commercial composite

    PubMed Central

    Ponce-Bravo, Santa; Martínez-Rivera, José-Luis; Garcés-Ortíz, Maricela

    2015-01-01

    Background International rules must be followed for testing biosecurity in dental materials. A new brand of restorative material appeared in the market and regulations indicated that it should be tested for toxicity. Objectives The aim of this study was to determine the 90-day sub chronic toxicity of one triethylene glycol dimethacrylate containing composite (MEDENTAL Light-Cure Composite™) orally administered to rats according to Organization for Economic Co-Operation and Development no. 48 guidelines and the requirements specified in the ISO 10993-11. Material and Methods Wistar rats ate the polymerized composite during 90 days and were observed to determine changes in their behavior, eye and skin signs and other attitudes such as aggressiveness, posture, walking and response to handling. After 90 days were sacrificed to ascertain blood alterations, we did special hematological tests and assessed microscopic slides from 33 different organs. Results We recorded no significant changes in clinical behavior of the animals. Microscopic review of the H&E stained slides obtained from the analyzed organs showed no abnormal inflammatory or cytological changes and all hematological special tests were within normal limits. Conclusions Results of this study show that under our experimental conditions the MEDENTAL Light-Cure Composite™ does not produce inflammatory or cytological changes suggestive of toxicity. Key words:Dental materials, composite resin, toxicity, inflammation, TEGDMA. PMID:26155348

  13. 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

  14. Use of hydra for chronic toxicity assessment of waters intended for human consumption.

    PubMed

    Arkhipchuk, Victor V; Blaise, Christian; Malinovskaya, Maria V

    2006-07-01

    Methods developed with the cnidarian, Hydra attenuata (Pallas), have proven effective for screening acute toxicity in aqueous samples, whereas their use in revealing (sub)chronic toxic effects have had mitigated success. We therefore sought to explore manifestations of hydra mortality and abnormal morphological changes, as well as the reproductive capacity of hydras to further enhance the bioassay sensitivity and to assess (sub)chronic toxicity. These parameters were recorded following the onset of experiments after 8, 12 and 19-21 days of hydra exposure. Results obtained with potable waters (30 brands of bottled waters and artesian waters from 9 wells) showed chronic sublethal and lethal effects or reproduction rate inhibition for most samples. The effectiveness of the hydra toxicity test was demonstrated in comparison with other widely used bioassays. Our previous and present investigations suggest that hydra is a reliable and relevant test organism for the assessment of acute and chronic water toxicity.

  15. Subchronic Sleep Restriction Causes Tissue-Specific Insulin Resistance

    PubMed Central

    Neylan, Thomas C.; Grunfeld, Carl; Mulligan, Kathleen; Schambelan, Morris; Schwarz, Jean-Marc

    2015-01-01

    Context: Short sleep duration is associated with an increased risk of type 2 diabetes. Subchronic sleep restriction (SR) causes insulin resistance, but the mechanisms and roles of specific tissues are unclear. Objective: The purpose of this article was to determine whether subchronic SR altered (1) hepatic insulin sensitivity, (2) peripheral insulin sensitivity, and (3) substrate utilization. Design: This was a randomized crossover study in which 14 subjects underwent 2 admissions separated by a washout period. Each admission had 2 acclimatization nights followed by 5 nights of either SR (4 hours time in bed) or normal sleep (8 hours time in bed). Main Outcome Measure/Methods: Insulin sensitivity (measured by hyperinsulinemic-euglycemic clamp) and hepatic insulin sensitivity (measured by stable isotope techniques) were measured. In addition, we assayed stress hormone (24-hour urine free cortisol, metanephrine, and normetanephrine), nonesterified fatty acid (NEFA), and β-hydroxybutyrate (β-OH butyrate) levels. Resting energy expenditure (REE) and respiratory quotient (RQ) were measured by indirect calorimetry. Results: Compared to normal sleep, whole-body insulin sensitivity decreased by 25% (P = .008) with SR and peripheral insulin sensitivity decreased by 29% (P = .003). Whereas hepatic insulin sensitivity (endogenous glucose production) did not change significantly, percent gluconeogenesis increased (P = .03). Stress hormones increased modestly (cortisol by 21%, P = .04; metanephrine by 8%, P = .014; normetanephrine by 18%, P = .002). Fasting NEFA and β-OH butyrate levels increased substantially (62% and 55%, respectively). REE did not change (P = 0.98), but RQ decreased (0.81±.02 vs 0.75±0.02, P = .045). Conclusion: Subchronic SR causes unique metabolic disturbances characterized by peripheral, but not hepatic, insulin resistance; this was associated with a robust increase in fasting NEFA levels (indicative of increased lipolysis), decreased RQ, and

  16. 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

  17. 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

  18. 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.

  19. The effect of sub-acute and sub-chronic exposure of rats to the glyphosate-based herbicide Roundup.

    PubMed

    Cağlar, Sinan; Kolankaya, Dürdane

    2008-01-01

    Roundup is a glyphosate-based herbicide that includes 78.5% glyphosate and surfactant at lower toxic concentrations. Glyphosate is an organophosphorated non-selective agrochemical widely used in many countries including Turkey and acts after the sprout in a systemic way. The objective of this study was to analyze toxic effects of the herbicide Roundup in rat liver. Animals were treated with 56mg/kg (p.o.) and 560mg/kg (p.o.) of Roundup (78% glyphosate+surfactant) each day, during 5 and 13 weeks. Hepatotoxicity was monitored by quantitative analysis of the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) activities and measured amount of serum lipoprotein (LDL, HDL), total cholesterol and creatinine were used as the biochemical markers of liver damages. Besides the biochemical analysis, we also investigated liver tissues histopathologically. Sub-chronic treatment, starting from the low and high doses of Roundup, it was observed that there were mild effects on activity of ALT, AST and LDH enzymes indicating the hepatic toxicity induced by Roundup. It was found that the mild effects were different on the enzymes in male and female rats of treatment groups. Also it was found some difference in serum lipoprotein (LDL, HDL) and t-cholesterol. There was no difference creatinine value between control and treatment groups but it was observed that degenerative formation such as mononuclear cell infiltration and congestion of the liver tissues of treatment groups.

  20. 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.

  1. 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.

  2. Induction of depressive-like effects by subchronic exposure to cocaine or heroin in laboratory rats.

    PubMed

    Zilkha, Noga; Feigin, Eugene; Barnea-Ygael, Noam; Zangen, Abraham

    2014-08-01

    The effect of psychoactive drugs on depression has usually been studied in cases of prolonged drug addiction and/or withdrawal, without much emphasis on the effects of subchronic or recreational drug use. To address this issue, we exposed laboratory rats to subchronic regimens of heroin or cocaine and tested long-term effects on (i) depressive-like behaviors, (ii) brain-derived neurotrophic factor (BDNF) levels in reward-related brain regions, and (iii) depressive-like behavior following an additional chronic mild stress procedure. The long-term effect of subchronic cocaine exposure was a general reduction in locomotor activity whereas heroin exposure induced a more specific increase in immobility during the forced swim test. Both cocaine and heroin exposure induced alterations in BDNF levels that are similar to those observed in several animal models of depression. Finally, both cocaine and heroin exposure significantly enhanced the anhedonic effect of chronic mild stress. These results suggest that subchronic drug exposure induces depressive-like behavior which is accompanied by modifications in BDNF expression and increases the vulnerability to develop depressive-like behavior following chronic stress. Implications for recreational and small-scale drug users are discussed. In the present study, we examined the long-term effects of limited subchronic drug exposure on depressive-like symptoms. Our results demonstrate that short-term, subchronic administration of either cocaine or heroin promotes some depressive-like behaviors, while inducing alterations in BDNF protein levels similar to alterations observed in several animal models of depression. In addition, subchronic cocaine or heroin enhanced the anhedonic effect of chronic stress.

  3. 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

  4. 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

  5. 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

  6. Effects of subchronic exposure to 2,6-dinitrotoluene in the northern bobwhite (Colinus virginianus).

    PubMed

    Quinn, Michael J; Bazar, Matthew A; McFarland, Craig A; Perkins, Edward J; Gust, Kurt A; Gogal, Robert M; Johnson, Mark S

    2007-10-01

    Explosives and their breakdown products are commonly found in soils at U.S. military installations. Many areas where these compounds are found represent useful habitat for ground-foraging birds. Because these birds likely are exposed to such compounds, we evaluated the oral toxicity of 2,6-dinitrotoluene (DNT) in a representative ground-foraging species of management concern. Adult male and female northern bobwhite (Colinus virginianus) were exposed to either 0, 5, 10, 40, or 60 mg/kg/d via gavage for 60 d (subchronic) following determination of the median acute lethal dose (320 mg/kg). Circulating levels of red blood cells and hemoglobin were significantly decreased in a dose-dependent manner; however, levels remained within normal ranges. Plasma concentrations of total protein, albumin, globulin, aspartate aminotransferase, and potassium, sodium, and chlorine ions were significantly decreased, and circulating levels of uric acid were significantly increased. Decreased body weight, enlarged gallbladders, edematous gastrointestinal tracts, pale kidneys, pale and fibrous livers, and loose stools were consistent observations. The effects found in the clinical chemistries taken together with histopathological abnormalities observed in sections of hepatic and renal tissue suggest that the liver and kidneys are major targets for 2,6-DNT. Oral exposures to 2,6-DNT appear to affect northern bobwhite in a manner similar to that of the other main DNT isomer, 2,4-DNT, but in more subtle ways, adversely affecting the gastrointestinal system and leading to diarrhea and, ultimately, emaciation. The lowest-observed-adverse-effect level is 40 mg/ kg/d based on hematological measures, and the no-observed-adverse-effect level is 10 mg/kg/d based on the absence of results indicative of adverse effects.

  7. 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

  8. 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.

  9. Subchronic centrifugal mechanical assist in an unheparinized calf model.

    PubMed

    Wagner-Mann, C; Curtis, J; Mann, F A; Turk, J; Demmy, T; Turpin, T

    1996-06-01

    The purpose of this study was to determine whether the major centrifugal pumps currently in use in the United States (Medtronic, BioMedicus BioPump and Carmeda-coated BioPump, Sarns 3M centrifugal pump, and St. Jude Medical Lifestream) could function as left mechanical assist devices in the subchronic (72 h) unheparinized calf model. Calves were instrumented for left atrial to aorta ex vivo assist, and the pump flow was set at 3.5 +/- 0.4 L/min. Two calves (Sarns 3M and St. Jude) survived 72 h of pumping without clinical complications. The other 2 calves died at 62 and 66 h (Medtronic BioPump and Carmeda-coated BioPump, respectively); both had pelvic limb paralysis. The seal of the Sarns 3M pump head ruptured after approximately 36 h of pumping and required replacement. On postmortem examination, pump-associated thromboembolic lesions were detected in 3 of the 4 calves in one or more of the following organs: kidneys, pancreas, abomasum, duodenum, ileum, spleen, and lumbar spinal cord. The calf with the Sarns 3M pump had no discernable lesions. Because of the clinical abnormalities and postmortem lesions in the unheparinized calf model, it was suggested that anticoagulation is necessary for conducting centrifugal mechanical assist studies in calves using presently available technology.

  10. Subchronic hepatotoxicity of selenomethionine ingestion in mallard ducks

    USGS Publications Warehouse

    Hoffman, D.J.; Heinz, G.H.; LeCaptain, L.J.; Bunck, C.M.; Green, D.E.

    1991-01-01

    Twoyearold male mallards (Anas platyrhynchos) received a control diet (0.2 ppm Se) or diets containing 1, 2, 4, 8, 16, or 32 ppm Se as selenomethionine for 14 wk. Se accumulated readily in the liver in a dosedependent manner, reaching a mean concentration of 29 ppm (wet weight) in the 32 ppm group. Dietary Se of 2 ppm or greater increased plasma glutathione peroxidase activity. Mortality (10%) and histopathological effects, including bile duct hyperplasia and hemosiderin pigmentation of the liver and spleen, occurred in the 32 ppm group. These histopathological effects were accompanied by lower hemoglobin concentrations (16 and 32 ppm groups) and hematocrit (32 ppm group), and elevated plasma alkaline phosphatase activity (32 ppm group) indicative of cholestatic liver inJury. Other manifestations of hepatotoxicity included significant linear dose responses for hepatic oxidized glutathione (GSSG) concentrations and ratio of GSSG to reduced glutathione (GSH). Means for both of these responses differed from controls in groups receiving 832 ppm Se. Mean hepatic GSH and malondialdehyde (a measure of lipid peroxidation) concentrations were significantly elevated in the 16 and 32 ppm groups. Subchronic effects of selenomethionine, which occurs in vegetation, are of particular interest with respect to the health of wild aquatic birds in seleniferous locations.

  11. 40 CFR 798.6560 - Subchronic delayed neuro-toxicity of organophosphorus substances.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... diseases and medication and without abnormalities of gait should be acclimatized to the laboratory... observation of minimal responses. The hens should be weighed weekly. Any moribund hens should be removed and...) Test report. In addition to the reporting requirements specified under 40 CFR part 792, subpart J...

  12. 40 CFR 798.6560 - Subchronic delayed neuro-toxicity of organophosphorus substances.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... diseases and medication and without abnormalities of gait should be acclimatized to the laboratory... observation of minimal responses. The hens should be weighed weekly. Any moribund hens should be removed and...) Test report. In addition to the reporting requirements specified under 40 CFR part 792, subpart J...

  13. 40 CFR 798.6560 - Subchronic delayed neuro-toxicity of organophosphorus substances.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... diseases and medication and without abnormalities of gait should be acclimatized to the laboratory... observation of minimal responses. The hens should be weighed weekly. Any moribund hens should be removed and...) Test report. In addition to the reporting requirements specified under 40 CFR part 792, subpart J...

  14. 40 CFR 798.6560 - Subchronic delayed neuro-toxicity of organophosphorus substances.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... diseases and medication and without abnormalities of gait should be acclimatized to the laboratory... observation of minimal responses. The hens should be weighed weekly. Any moribund hens should be removed and...) Test report. In addition to the reporting requirements specified under 40 CFR part 792, subpart J...

  15. SUBCHRONIC MANCOZEB TREATEMENT INDUCED LIVER TOXICITY VIA OXIDATIVE STRESS IN MALE WISTAR RATS.

    PubMed

    Yahia, E; Aiche, M A; Chouabbia, A; Boulakoud, M S

    2014-01-01

    Mancozeb is a manganese/zinc ethylene-bis-dithiocarbamate fungicide that is widely used in agriculture to control a broad variety of fungal infections of both vegetables and ornamental plants. The present study has been carried out to investigate the possible effect of mancozeb on animal the oxidative stress and some of the biochemical markers in male Wistar rats. In this experiment, adult male rats weighing between 200 and 250 g were treated per os for 4 weeks with two different doses of 800 and 1200 mg/kg per day. Reduced glutathione (GSH) levels were decreased in all treated groups compared to control ones. It has been observed a significant increase in the fresh weight of liver in individuals of both doses. Moreover, mancozeb exposure caused a significant (p < 0.05) fall in aspartic aminotransferase (AST) and alanine aminotransferase (ALT) in group treated with 1200 and 800 mg/kg/day. Similarly, alkaline phosphatase (ALP) activity underwent a significant (p < 0.05) increase in both groups. The obtained observations clearly reveal hepatotoxic effects of mancozeb in rats and constitute, therefore, an environmental health risks to living organisms. PMID:26080489

  16. Evaluation of the subchronic toxicity of kefir by oral administration in Wistar rats.

    PubMed

    Diniz Rosa, Damiana; Gouveia Peluzio, Maria do Carmo; Pérez Bueno, Tania; Vega Cañizares, Ernesto; Sánchez Miranda, Lilian; Mancebo Dorbignyi, Betty; Chong Dubí, Dainé; Espinosa Castaño, Ivette; Marcin Grzes Kowiak, Lukasz; Fortes Ferreira, Célia Lucia de Luces

    2014-06-01

    Introducción: El kéfir es obtenido por fermentación de la leche con una población microbiana compleja presente en sus granos. Al consumo de kéfir se le atribuyen múltiples efectos beneficiosos sobre la salud. Objetivo: Evaluar la toxicidad subcrónica del kéfir en ratas Wistar, administrado por vía oral en dosis normal (normodosis) y sobredosis. Se evaluaron además, los parámetros de peso corporal, hematología, química sanguínea, translocación bacteriana e integridad de la mucosa intestinal. Métodos: Se conformaron tres grupos de seis animales de manera aleatoria: grupo control, recibió 0,7 mL de agua; grupo kéfir recibió 0,7 mL/día de kéfir (normodosis) y grupo Hkéfir recibió 3,5 mL/día de kéfir (dosis cinco veces superior). La administración se llevó a cabo mediante sonda. Los animales se alojaron individualmente, y se mantuvieron bajo las mismas condiciones de manejo y alimentación durante 4 semanas. Resultados: La administración de kéfir en dosis normal y sobredosis no afectó los parámetros evaluados en los animales, el peso corporal, indicadores hematológicos, de química sanguínea, y la patogenicidad potencial en los tejidos se encontraron dentro de límites normales, lo que demostró que el consumo de kéfir en dosis normal y sobredosis es seguro. Además, se evidenció que la administración de normodosis de kéfir redujo los niveles de colesterol y mejoró la mucosa intestinal de las ratas. Conclusión: Se demostró que el consumo de kéfir es seguro. Destacar que, la administración de sobredosis no evidenció daños, no obstante, se recomienda el consumo de normodosis, debido a los marcados efectos beneficiosos y de seguridad.

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

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... vehicle/engine emissions. The MN assay detects damage to the chromosomes or mitotic apparatus of cells in... chromosome. This assay uses peripheral blood lymphocytes isolated from an exposed rodent test species and...., motor disturbance) shall be recorded frequently enough to observe any abnormality, and not less...

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

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... vehicle/engine emissions. The MN assay detects damage to the chromosomes or mitotic apparatus of cells in... chromosome. This assay uses peripheral blood lymphocytes isolated from an exposed rodent test species and...., motor disturbance) shall be recorded frequently enough to observe any abnormality, and not less...

  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... and peripheral nerves. The spinal cord sections should be taken from the upper cervical bulb, the mid..., Washington, DC (1976). (4) Cavanaugh, J.B. “Peripheral neuropathy caused by chemical agents” Critical...

  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. Subchronic toxicology studies of hexachloro-1,3-butadiene (HCBD) in B6C3F1 mice by dietary incorporation

    SciTech Connect

    Yang, R.S.; Abdo, K.M.; Elwell, M.R.; Levy, A.C.; Brennecke, L.H. )

    1989-07-01

    Two-week repeated-dose and 13-week subchronic studies of HCBD were conducted in B6C3F1 mice. Groups of five mice/sex received 0, 30, 100, 300, 1,000, or 3,000 ppm HCBD in feed for 15 days. Toxic responses, primarily in the higher dose groups, included abnormal clinical signs (lethargy, hunched posture, rough coat, sensitivity to light, and/or incoordination), mortality (all mice in the top two dose groups died by day 7), body and organ weight depression, and gross and histopathological changes. The most prevalent microscopic lesion, seen in all HCBD-treated mice of both sexes, was renal tubular cell necrosis and/or regeneration. Regeneration was seen only in the lower dose groups. Thirteen-week studies were conducted in which groups of 10 mice/sex received 0, 1, 3, 10, 30, or 100 ppm HCBD in feed. No treatment-related clinical signs or mortality were observed. Body weight gain was reduced in the 30- and 100-ppm males (-49 and -56, respectively), and the 100-ppm females (-47). Significant reduction in kidney weights was seen in the 30- and 100-ppm males and 100-ppm females. A treatment-related increase in tubular cell regeneration in the renal cortex occurred in both male and female mice. This lesion was characterized by an increase both in number and basophilic staining intensity of the tubular epithelial cells. Regeneration was seen in the outer stripe of the outer medulla and extended into the medullary rays (pars recta); severity increased with dose. Female mice were more susceptible to the toxicity of HCBD than male mice. Although no adverse effects were observed at the 10-ppm level for male mice in the subchronic study, the regenerative lesion was present in female mice at 1 ppm, the lowest dose administered.

  2. 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,...

  3. 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...

  4. 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

  5. Acute and subchronic administration of anandamide or oleamide increases REM sleep in rats.

    PubMed

    Herrera-Solís, Andrea; Vásquez, Khalil Guzmán; Prospéro-García, Oscar

    2010-03-01

    Anandamide and oleamide, induce sleep when administered acutely, via the CB1 receptor. Their subchronic administration must be tested to demonstrate the absence of tolerance to this effect, and that the sudden withdrawal of these endocannabinoids (eCBs) does not affect sleep negatively. The sleep-waking cycle of rats was evaluated for 24h, under the effect of an acute or subchronic administration of eCBs, and during sudden eCBs withdrawal. AM251, a CB1 receptor antagonist (CB1Ra) was utilized to block eCBs effects. Our results indicated that both acute and subchronic administration of eCBs increase REMS. During eCBs withdrawal, rats lack the expression of an abstinence-like syndrome. AM251 was efficacious to prevent REMS increase caused by both acute and subchronic administration of these eCBs, suggesting that this effect is mediated by the CB1 receptor. Our data further support a role of the eCBs in REMS regulation.

  6. 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...

  7. Sub-chronic exposure to second hand smoke induces airspace leukocyte infiltration and decreased lung elastance

    PubMed Central

    Hartney, John M.; Chu, HongWei; Pelanda, Roberta; Torres, Raul M.

    2012-01-01

    Exposure to second hand tobacco smoke is associated with the development and/or exacerbation of several different pulmonary diseases in humans. To better understand the possible effects of second hand smoke exposure in humans, we sub-chronically (4 weeks) exposed mice to a mixture of mainstream and sidestream tobacco smoke at concentrations similar to second hand smoke exposure in humans. The inflammatory response to smoke exposures was assessed at the end of this time by enumeration of pulmonary leukocyte infiltration together with measurements of lung elastance and pathology. This response was measured in both healthy wild type (C57BL/6) mice as well as mouse mutants deficient in the expression of Arhgef1 (Arhgef1−/−) that display constitutive pulmonary inflammation and decreased lung elastance reminiscent of emphysema. The results from this study show that sub-chronic second hand smoke exposure leads to significantly increased numbers of airspace leukocytes in both healthy and mutant animals. While sub-chronic cigarette smoke exposure is not sufficient to induce changes in lung architecture as measured by mean linear intercept, both groups exhibit a significant decrease in lung elastance. Together these data demonstrate that even sub-chronic exposure to second hand smoke is sufficient to induce pulmonary inflammation and decrease lung elastance in both healthy and diseased animals and in the absence of tissue destruction. PMID:22934051

  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. The effect of subchronic supplementation with folic acid on homocysteine induced seizures.

    PubMed

    Rasic-Markovic, A; Rankov-Petrovic, B; Hrncic, D; Krstic, D; Colovic, M; Macut, Dj; Djuric, D; Stanojlovic, Olivera

    2015-06-01

    Influence of folic acid on the CNS is still unclear. Folate has a neuroprotective effect, while on the other hand excess folate can exacerbate seizures in epileptics. The aim of the present study was to examine the effect of subchronic administration of folic acid on behavioural and electroencephalographic (EEG) characteristics of DL homocysteine thiolactone induced seizures in adult rats. The activity of Na⁺/K⁺-ATPase and Mg²⁺-ATPase in different brain regions was investigated. Adult male Wistar rats were divided into groups: 1. Controls (C, 0.9% NaCl); 2. DL homocysteine-thiolactone 8.0 mmol/kg (H); 3. Subchronic supplementation with folic acid 5 mg/kg for 7 days (F) and 4. Subchronic supplementation with F + single dose of H (FH). Seizure behaviour was assessed by incidence, latency, number and intensity of seizure episodes. Seizure severity was described by a descriptive scale with grades 0-4. For EEG recordings, three gold-plated recording electrodes were implanted into the skull. Subchronic supplementation with folic acid did not affect seizure incidence, median number of seizure episodes and severity in FH, comparison with H (p > 0.05). The majority of seizure episodes in all groups were of grade 2. There were no significant differences in lethal outcomes at 24 h upon H injection in the FH vs. H group. The activity of Na⁺/K⁺-ATPase and Mg²⁺-ATPase was significantly increased in almost all examined structures in the FH vs. H group. Subchronic folic acid administration did not exacerbate H induced seizures and completely recovered the activity of ATPases.

  11. 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

  12. 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

  13. Toxic megacolon

    MedlinePlus

    ... disease - toxic megacolon; Crohn disease - toxic megacolon; Ulcerative colitis - toxic megacolon ... people with an inflamed colon due to: Ulcerative colitis , or Crohn disease that is not well controlled ...

  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. Effects of subchronic exposure of early life stages of white sturgeon (Acipenser transmontanus) to copper, cadmium, and zinc.

    PubMed

    Vardy, David W; Tompsett, Amber R; Sigurdson, Jacinda L; Doering, Jon A; Zhang, Xiaowei; Giesy, John P; Hecker, Markus

    2011-11-01

    Populations of sturgeon (Acipenseridae) are declining in many places in the world because of several potential factors, including overharvesting, habitat alteration, and pollution. In North America, populations of the white sturgeon (Acipenser transmontanus) have been experiencing poor annual recruitment in major river systems for more than three decades. Metal pollution has been hypothesized as a potential contributing factor to the poor recruitment in some of the water bodies. In general, little is known about the toxicity of metals such as Cu, Cd, and Zn to white sturgeon and their potential influence on survival of embryos and juveniles. The present study was conducted to establish baseline toxicity data for the subchronic exposure of early life stages of white sturgeon to Cu, Cd, and Zn that can be used in metal-related risk assessments. Embryos, larvae, and fry were exposed to increasing concentrations of dissolved Cu, Cd, or Zn for 66 d using laboratory-based flow-through exposure systems. Hatching success was greater than 79% for all controls, and no significant differences were observed among treatment groups or between treatments and controls. Chronic lethal concentrations at which 20% mortality occurred (LC20s) for Cd (1.5 µg/L), Cu (5.5 µg/L), and Zn (112 µg/L) obtained for white sturgeon in the present study were comparable to those of sensitive salmonid species. Based on LC20 values for 19 or 58 d posthatch white sturgeon, the United States national ambient water quality criteria and the Canadian water quality guidelines for the protection of aquatic life that have been established for Cd, Cu, and Zn protect white sturgeon early life stages.

  16. 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

  17. 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

  18. 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

  19. Another Alternative: A 90-Day Contractual Detoxification Treatment Program

    ERIC Educational Resources Information Center

    Kahn, Robert B.; And Others

    1978-01-01

    In May 1974, Fresno County's Narcotic Abuse Treatment Program began a 21-day outpatient methadone detoxification treatment modality. The purpose of this paper is to examine this alternative treatment modality, its characteristics, its therapeutic outcomes and the rationale for its use. (Author)

  20. Transcriptional responses in the rat nasal epithelium following subchronic inhalation of naphthalene vapor.

    PubMed

    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 30ppm for 6h/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 (0.1ppm). At the 1.0ppm 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 30ppm, 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 10ppm 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 3.7ppm, respectively, while the lowest female olfactory BMD values for pathways related to glutathione homeostasis, inflammation, and proliferation were 16.1, 11.1, and 8.4ppm, 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 0.3ppm, respectively, and the lowest male respiratory BMD values for pathways related to glutathione homeostasis, inflammation, and proliferation were 0.5, 0.7, and 0.9ppm, respectively

  1. 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.

  2. EPA's Reanalysis of Key Issues Related to Dioxin Toxicity and Response to NAS Comments (External Review Draft)

    EPA Science Inventory

  1. Systemic metabolic derangement, pulmonary effects, and insulin insufficiency following subchronic ozone exposure in rats.

    PubMed

    Miller, Desinia B; Snow, Samantha J; Henriquez, Andres; Schladweiler, Mette C; Ledbetter, Allen D; Richards, Judy E; Andrews, Debora L; Kodavanti, Urmila P

    2016-09-01

    Acute ozone exposure induces a classical stress response with elevated circulating stress hormones along with changes in glucose, protein and lipid metabolism in rats, with similar alterations in ozone-exposed humans. These stress-mediated changes over time have been linked to insulin resistance. We hypothesized that acute ozone-induced stress response and metabolic impairment would persist during subchronic episodic exposure and induce peripheral insulin resistance. Male Wistar Kyoto rats were exposed to air or 0.25ppm or 1.00ppm ozone, 5h/day, 3 consecutive days/week (wk) for 13wks. Pulmonary, metabolic, insulin signaling and stress endpoints were determined immediately after 13wk or following a 1wk recovery period (13wk+1wk recovery). We show that episodic ozone exposure is associated with persistent pulmonary injury and inflammation, fasting hyperglycemia, glucose intolerance, as well as, elevated circulating adrenaline and cholesterol when measured at 13wk, however, these responses were largely reversible following a 1wk recovery. Moreover, the increases noted acutely after ozone exposure in non-esterified fatty acids and branched chain amino acid levels were not apparent following a subchronic exposure. Neither peripheral or tissue specific insulin resistance nor increased hepatic gluconeogenesis were present after subchronic ozone exposure. Instead, long-term ozone exposure lowered circulating insulin and severely impaired glucose-stimulated beta-cell insulin secretion. Thus, our findings in young-adult rats provide potential insights into epidemiological studies that show a positive association between ozone exposures and type 1 diabetes. Ozone-induced beta-cell dysfunction may secondarily contribute to other tissue-specific metabolic alterations following chronic exposure due to impaired regulation of glucose, lipid, and protein metabolism. PMID:27368153

  2. Evaluation of the toxic and genotoxic potential of acid mine drainage using physicochemical parameters and bioassays.

    PubMed

    Netto, E; Madeira, R A; Silveira, F Z; Fiori, M A; Angioleto, E; Pich, C T; Geremias, R

    2013-05-01

    Carboniferous activity generates acid mine drainage (AMD) which is capable of unleashing toxic effects on the exposed biota. The aim of this study was to evaluate the toxic and genotoxic potential of untreated-AMD and AMD treated with calcinated sediment, using physicochemical parameters and bioassays. Results revealed that untreated-AMD presented low pH values and elevated concentrations of the metals Fe, Al, Mn, Zn and Cu. High acute toxicity was observed in Artemia sp. and Daphnia magna, and sub-chronic toxicity and genotoxicity in Allium cepa L. as well as scission of plasmid DNA exposed to untreated-AMD. Treatment of AMD with calcinated sediment promoted the reduction of acidity and the removal of metals, as well as a reduction in toxic and genotoxic effects. In conclusion, the calcinated sediment can be used as an alternative AMD treatment.

  3. Evaluation of the toxic and genotoxic potential of acid mine drainage using physicochemical parameters and bioassays.

    PubMed

    Netto, E; Madeira, R A; Silveira, F Z; Fiori, M A; Angioleto, E; Pich, C T; Geremias, R

    2013-05-01

    Carboniferous activity generates acid mine drainage (AMD) which is capable of unleashing toxic effects on the exposed biota. The aim of this study was to evaluate the toxic and genotoxic potential of untreated-AMD and AMD treated with calcinated sediment, using physicochemical parameters and bioassays. Results revealed that untreated-AMD presented low pH values and elevated concentrations of the metals Fe, Al, Mn, Zn and Cu. High acute toxicity was observed in Artemia sp. and Daphnia magna, and sub-chronic toxicity and genotoxicity in Allium cepa L. as well as scission of plasmid DNA exposed to untreated-AMD. Treatment of AMD with calcinated sediment promoted the reduction of acidity and the removal of metals, as well as a reduction in toxic and genotoxic effects. In conclusion, the calcinated sediment can be used as an alternative AMD treatment. PMID:23518284

  4. Route-to-route extrapolation of the toxic potency of MTBE.

    PubMed

    Dourson, M L; Felter, S P

    1997-12-01

    MTBE is a volatile organic compound used as an oxygenating agent in gasoline. Inhalation from fumes while refueling automobiles is the principle route of exposure for humans, and toxicity by this route has been well studied. Oral exposures to MTBE exist as well, primarily due to groundwater contamination from leaking stationary sources, such as underground storage tanks. Assessing the potential public health impacts of oral exposures to MTBE is problematic because drinking water studies do not exist for MTBE, and the few oil-gavage studies from which a risk assessment could be derived are limited. This paper evaluates the suitability of the MTBE database for conducting an inhalation route-to-oral route extrapolation of toxicity. This includes evaluating the similarity of critical effect between these two routes, quantifiable differences in absorption, distribution, metabolism, and excretion, and sufficiency of toxicity data by the inhalation route. We conclude that such an extrapolation is appropriate and have validated the extrapolation by finding comparable toxicity between a subchronic gavage oral bioassay and oral doses we extrapolate from a subchronic inhalation bioassay. Our results are extended to the 2-year inhalation toxicity study by Chun et al. (1992) in which rats were exposed to 0, 400, 3000, or 8000 ppm MTBE for 6 hr/d, 5 d/wk. We have estimated the equivalent oral doses to be 0, 130, 940, or 2700 mg/kg/d. These equivalent doses may be useful in conducting noncancer and cancer risk assessments.

  5. Sensitivity of isolated eggs of pond snails: a new method for toxicity assays and risk assessment.

    PubMed

    Liu, Tengteng; Koene, Joris M; Dong, Xiaoxiao; Fu, Rongshu

    2013-05-01

    The concentration of heavy metals in the environment is normally low. We here address whether using the development of isolated pond snail Radix auricularia eggs would provide a more sensitive endpoint and whether the gelatinous matrix of the egg mass surrounding the eggs indeed protects the snail embryos. In the present study, artificial removal of the gelatinous matrix of egg masses greatly increased the sensitivity of developing eggs to a heavy metal (cadmium). The sensitivity of isolated eggs to cadmium was determined using several convenient endpoints, including mortality, hatching rate, and heart rate, with an acute toxicity test and a subchronic test. In the acute toxicity test, a 96-h LC(50) value of 58.26 μg/L cadmium was determined. In the subchronic toxicity test, sublethal effects in terms of a significant reduction in hatching rate could be found in the 25-μg/L treatment, and a significant decrease of heart rate was observed in both treatments (5 and 25 μg/L). The high sensitivity of isolated eggs indicates that such tests can be efficient for toxicity assays and risk assessment, although one needs to keep in mind that the ecologically relevant measure of toxicity will be how eggs are affected when they are still inside the egg mass.

  6. 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...

  7. Evaluation of subchronic neurotoxicity of n-butyl acetate vapor.

    PubMed

    David, R M; Tyler, T R; Ouellette, R; Faber, W D; Banton, M I; Garman, R H; Gill, M W; O'Donoghue, J L

    1998-12-01

    n-Butyl acetate, a common industrial solvent, was selected by the US EPA as a chemical of concern for neurotoxicity as part of the Multisubstance Rule for the Testing of Neurotoxicity. The neurotoxic potential of n-butyl acetate was investigated in Sprague-Dawley rats using a functional observational battery, motor activity, neurohistopathology, and schedule-controlled operant behavior (SCOB) as indicators of neurotoxicity. Animals were exposed to concentrations of 0, 500, 1500, or 3000 ppm of n-butyl acetate for 6 hours per day for 65 exposures over 14 weeks. Functional observational battery and motor activity values for ad libitum-fed male and female rats were measured during Weeks -1, 4, 8, and 13. SCOB testing of food-restricted animals, using a multiple fixed ratio/fixed interval schedule, was conducted daily prior to each exposure to maintain the operant behavior; the data from Weeks -1, 4, 8, and 13 were evaluated for evidence of neurotoxicity. Transient signs of sedation and hypoactivity were observed only during exposure to the 1500 and 3000 ppm concentrations. The only signs of systemic toxicity were reduced body weights for the 3000 ppm ad libitum-fed groups and occasionally for the female 1500 ppm ad libitum-fed group. No evidence of neurotoxicity was seen during the functional observational battery examinations. Motor activity for the 3000 ppm male group was significantly (p < or = 0.05) higher than for the control group only during Week 4. No significant differences were observed among groups for Weeks 8 and 13. No significant differences in motor activity values were observed for female rats. No significant differences were seen in operant behavior at any test vapor concentration. Microscopic evaluations of sections from the brain, spinal cord (cervical and lumbar regions), dorsal and ventral spinal roots, dorsal root ganglia, sciatic nerve, and tibial nerve of animals in the control and 3000 ppm groups did not indicate any treatment-related effects

  8. Reduced toxicological activity of cigarette smoke by the addition of ammonia magnesium phosphate to the paper of an electrically heated cigarette: subchronic inhalation toxicology.

    PubMed

    Moennikes, O; Vanscheeuwijck, P M; Friedrichs, B; Anskeit, E; Patskan, G J

    2008-05-01

    Cigarette smoke is a complex chemical mixture that causes a variety of diseases, such as lung cancer. With the electrically heated cigarette smoking system (EHCSS), temperatures are applied to the tobacco below those found in conventional cigarettes, resulting in less combustion, reduced yields of some smoke constituents, and decreased activity in some standard toxicological tests. The first generation of electrically heated cigarettes (EHC) also resulted in increased formaldehyde yields; therefore, a second generation of EHC was developed with ammonium magnesium phosphate (AMP) in the cigarette paper in part to address this increase. The toxicological activity of mainstream smoke from these two generations of EHC and of a conventional reference cigarette was investigated in two studies in rats: a standard 90-day inhalation toxicity study and a 35-day inhalation study focusing on lung inflammation. Many of the typical smoke exposure-related changes were found to be less pronounced after exposure to smoke from the second-generation EHC with AMP than to smoke from the first-generation EHC or the conventional reference cigarette, when compared on a particulate matter or nicotine basis. Differences between the EHC without AMP and the conventional reference cigarette were not as prominent. Overall, AMP incorporated in the EHC cigarette paper reduced the inhalation toxicity of the EHCSS more than expected based on the observed reduction in aldehyde yields. PMID:18464053

  9. Acute and subchronic effects of Org 2305 and diazepam on psychomotor performance in man.

    PubMed Central

    Mattila, M J; Koski, J; Strömberg, C

    1987-01-01

    Three doses (15, 30 and 60 mg) of Org 2305 (O 15, O 30 and O 60 respectively), a novel anxiolytic drug chemically related to mianserin, were compared with placebo and 15 mg diazepam (DZ) on human psychomotor performance in a double-blind, cross-over study with 15 healthy volunteers. Objective measurements (choice reaction, tracking, flicker fusion, Maddox wing, digit symbol substitution, memory recall) and subjective assessments (visual analogue scales) were done at baseline and 2 and 13 h after the first dose. This testing procedure was repeated on day 7 when administering the seventh consecutive daily night-time dose. After the first dose O 15 did not differ from placebo and O 30 rarely differed from placebo. O 60 impaired various objective functions similarly to, or less than DZ. Subjectively, DZ and O 60 were felt as sedative. During subchronic treatment, DZ caused some impairment of baseline due to accumulation of bioassayable benzodiazepines, but significant responses to the last DZ dose were less than those to the first dose. DZ but not O 60 was reported to have caused lethargy and clumsiness during subchronic treatment. In the doses used Org 2305 impaired psychomotor performance less than diazepam did. A dose of 60 mg Org 2305 may offer some advantage over 15 mg diazepam, provided that their anxiolytic effects are about similar. PMID:2881574

  10. Subchronic phencyclidine in rats: alterations in locomotor activity, maze performance, and GABA(A) receptor binding.

    PubMed

    Beninger, Richard J; Beuk, Jonathan; Banasikowski, Tomek J; van Adel, Michael; Boivin, Gregory A; Reynolds, James N

    2010-02-01

    Phencyclidine (PCP), an antagonist at the N-methyl-D-aspartate subtype of ionotropic glutamatergic receptors, decreases gamma-aminobutyric acid (GABA)ergic inhibition, suggesting that changes in GABAergic receptor function underlie behavioral and cognitive deficits resulting from repeated administration of PCP. To test this hypothesis, male Sprague-Dawley rats treated with PCP (4.5 mg/kg, intraperitoneal, twice a day for 7 consecutive days) or saline were tested in behavioral and cognitive tasks 7 days after injections. The PCP group showed increased amphetamine (1.5 mg/kg)-stimulated locomotor activity, and exhibited a greater number of errors in the double Y-maze memory task, when compared with controls. Subchronic PCP treatment increased [H]muscimol-binding sites and decreased affinity for [H]muscimol binding in frontal cortex, hippocampus, and striatum in comparison with controls. There were no changes in the expression of glutamic acid decarboxylase or the GABA membrane transporter protein. These data show that subchronic PCP administration induces an impaired performance of a previously learned task and an enhanced response to amphetamine in the rat. The observed changes in GABAA receptors in the rat brain are consistent with the notion that alterations in GABAergic receptor function contribute to the behavioral and cognitive impairments associated with repeated exposure to PCP. PMID:19949321

  11. Sub-chronic exposure to paraoxon neither induces nor exacerbates diabetes mellitus in Wistar rat.

    PubMed

    Nurulain, Syed M; Petroianu, Georg; Shafiullah, Mohamed; Kalász, Huba; Oz, Murat; Saeed, Tariq; Adem, Abdu; Adeghate, Ernest

    2013-10-01

    There is an increasing belief that organophosphorus compounds (OPCs) impair glucose homeostasis and cause hyperglycemia and diabetes mellitus. The present study was undertaken to investigate the putative diabetogenic effect of sub-lethal and sub-chronic exposure to paraoxon (POX), an extremely hazardous OPC used in pesticides. The effect of paraoxon on streptozotocin-induced diabetic rats was also examined. Each rat was injected with 100 nmol of POX 5 days per week for 6 weeks. Blood glucose levels and red blood cell acetylcholinesterase activity were measured weekly. Biochemical analysis and morphological studies were performed at the end of the experiment. The results revealed that POX neither induces nor exacerbates diabetes mellitus in experimental rats. Liver and kidney/body weight ratios revealed statistically insignificant differences when compared with controls. Biochemical analysis of urine samples showed a small but not significant increase in protein level in all groups. Urine bilirubin was significantly higher in the diabetes + POX group when compared with the control group. The number of blood cells in urine was significantly higher in the POX-treated group compared with the control group. Hyperglycemia was noted in the diabetes and diabetes + POX groups, but neither in the saline control nor in POX-treated normal rats. Electron microscopy of POX-treated pancreas did not show any morphological changes in beta cells. These results suggest that POX does not cause diabetes mellitus at sub-lethal sub-chronic exposure.

  12. 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...

  13. 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...

  14. 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...

  15. 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 after exposures to Libby amphibole (LA). To support dosimetry model development and compare potency, a subchronic nose-only inhalation exposure study (6 hr/d, 5 d/wk, 13 wk) was conducted in male F344 rats. Rat...

  16. 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...

  17. 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,...

  18. FORMATION OF 8-OXO-7, 8-DIHYDRO-2'-DEOXYGUANOSINE IN RAT LUNG FOLLOWING SUB-CHRONIC INHALATION OF CARBON BLACK

    EPA Science Inventory

    ABSTRACT
    Formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine, an oxidative adduct in the lung DNA of rats following sub-chronic inhalation of carbon black. Gallagher, J., Sams II, R.L., Inmon, J., Gelein, R., Elder, A., Oberdorster, G., Prahalad, A. (2002). Toxicol. Appl. Pharm...

  19. Recovery by N-acetylcysteine from subchronic exposure to Imidacloprid-induced hypothalamic-pituitary-adrenal (HPA) axis tissues injury in male rats.

    PubMed

    Annabi, Alya; Dhouib, Ines Bini; Lamine, Aicha Jrad; El Golli, Nargès; Gharbi, Najoua; El Fazâa, Saloua; Lasram, Mohamed Montassar

    2015-01-01

    Imidacloprid is the most important example of the neonicotinoid insecticides known to target the nicotinic acetylcholine receptor in insects, and potentially in mammals. N-Acetyl-l-cysteine (NAC) has been shown to possess curative effects in experimental and clinical investigations. The present study was designed to evaluate the recovery effect of NAC against Imidacloprid-induced oxidative stress and cholinergic transmission alteration in hypothalamic-pituitary-adrenal (HPA) axis of male rats following subchronic exposure. About 40 mg/kg of Imidacloprid was administered daily by intragastric intubation and 28 days later, the rats were sacrificed and HPA axis tissues were removed for different analyses. Imidacloprid increased adrenal relative weight and cholesterol level indicating an adaptive stage of the general alarm reaction to stress. Moreover, Imidacloprid caused a significant increase in malondialdehyde level, the antioxidants catalase, superoxide dismutase and glutathione-S-transferase showed various alterations following administration and significant depleted thiols content was only recorded in hypothalamic tissue. Furthermore, the hypothalamic and pituitary acetylcholinesterase activity and calcium level were significantly increased highlighting the alteration of cholinergic activity. The present findings revealed that HPA axis is a sensitive target to Imidacloprid (IMI). Interestingly, the use of NAC for only 7 days post-exposure to IMI showed a partial therapeutic effect against Imidacloprid toxicity.

  20. Sub-Chronic Safety Evaluation of Ayurvedic Immunostimulant Formulation ‘Immuforte’ in Rats in Reverse Pharmacology

    PubMed Central

    Dhumal, Rohit; Patil, Prakash; Selkar, Nilakash; Chawda, Mukesh; Vahlia, Mahesh; Vanage, Geeta

    2013-01-01

    presence of heavy metals viz. lead (Pb), mercury (Hg), cadmium (Cd), and arsenic (As). Conclusion: The results of the present study demonstrated that Immuforte does not cause any observable toxicity at doses used in the study when administered for the period of 90 days and is safe for the human use and thus, Immuforte could be used safely for therapeutic use in humans. PMID:23833443

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. Acute and subchronic ozone inhalation in the rabbit: response of alveolar macrophages

    SciTech Connect

    Driscoll, K.E.; Vollmuth, T.A.; Schlesinger, R.B.

    1987-01-01

    Ozone is a potent oxidant gas and a common constituent of photochemical smog. This investigation evaluated the numbers and functional capabilities of alveolar macrophages (AM) recovered from rabbits undergoing acute and subchronic ozone exposure. Bronchoalveolar lavage was performed immediately, 24 h, and 7 d after acute (2-h) exposure to 0.1 or 1.2 ppm ozone, and on d 3, 7, and 14 during subchronic (2 h/d X 13 d) exposure to 0.1 ppm ozone. After acute exposure to 1.2 ppm, a marked increase in lavaged neutrophils was observed at 24 h. A single exposure to 0.1 ppm resulted in increased AM at 7 d, while repeated exposures resulted in an increase in AM and neutrophils on d 7 and 14. AM phagocytosis was depressed immediately and 24 h after acute exposure to 0.1 ppm, and at all time points after exposure to 1.2 ppm. Repeated exposures to 0.1 ppm produced reductions in the numbers of phagocytically active AM on d 3 and 7, with a return to control levels by d 14. Substrate attachment by AM was impaired immediately after exposure to 1.2 ppm; AM mobility was not altered by any of the ozone exposures. The results of these studies demonstrated significant alterations in the numbers and functional properties of AM as a result of single or repeated exposure to 0.1 ppm ozone, a level below the current National Ambient Air Quality Standard. These findings indicate that levels of ozone frequently encountered in areas of high photochemical air pollution can elicit a pulmonary inflammatory response and can impair pulmonary defense capabilities.

  7. Subchronic inhalation toxicology of ethylene glycol monoethyl ether in the rat and rabbit.

    PubMed Central

    Barbee, S J; Terrill, J B; DeSousa, D J; Conaway, C C

    1984-01-01

    The subchronic inhalation toxicology of ethylene glycol monoethyl ether (EGEE) was evaluated in rats and rabbits using a 13-week exposure regimen. Groups of 20 rabbits (10 M, 10 F) and 30 rats (15 M, 15 F) were exposed to a vapor of 25 ppm, 100 ppm, or 400 ppm, 6 hr/day, 5 days/week. The control groups received air only. Physical examinations and body weight measurements were conducted on all animals pretest and weekly throughout the study. Ophthalmoscopic examination was performed pretest and at termination. Evaluation of hematology and clinical che