Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to describe blood recipients and blood components transfused during the first 24 hours in 13 French hospitals. We included all blood recipients who had not had any blood transfusion within the past six months. Recipients were screened for red cell alloantibodies, the alanine aminotransferase activity and specific viral markers (hepatitis B and C, Human Immunodeficiency Virus). Eligible patients represented 47% of the all transfused. Among the 371 patients included, 57% were males and 71% were transfused in a surgical unit. Alloantibodies, non specific and specific viral markers were detected in 3%, 19% and 2% respectively. Among the patients included, 42 received 172 autologous units. In total, 1056 allogeneic units (an average of 3 units per patient) were transfused; blood products were leucocyte-depleted (49%) or leucocyte-poor (20%); 54% of red cell units were matched for antigens Rh and Kell. Neoplasms were the most frequently reported disease for which patients were transfused. This study provides baseline blood transfusion information on recipients and blood utilization for a specific period in French hospitals. Following this study, a national study will allow the clarification of the characteristics, for instance the surgical procedures requiring transfusion.
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PMID:[Pilot study of the characteristics of transfused patients and utilized labile blood products]. 952 18

Pyridine is used as a denaturant in alcohol and anti freeze mixtures, as a solvent for paint, rubber, and polycarbonate resins, and as an intermediate in the manufacture of insecticides, herbicides, and fungicides. It is used in the production of piperidine, an intermediate in the manufacture of rubber and mepiquat chloride, and as an intermediate and solvent in the preparation of vitamins and drugs, dyes, textile water repellants, and flavoring agents in food. Pyridine was nominated for study because of its large production volume and its use in a variety of food, medical, and industrial products. Male and female F344/N rats, male Wistar rats, and male and female B6C3F1 mice were exposed to pyridine (approximately 99% pure) in drinking water for 13 weeks or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, L5178Y mouse lymphoma cells, cultured Chinese hamster ovary cells, Drosophila melanogaster, and mouse bone marrow cells. 13-WEEK STUDY IN F344/N RATS: Groups of 10 male and 10 female F344/N rats were exposed to pyridine in drinking water at concentrations of 0, 50, 100, 250, 500, or 1,000 ppm (equivalent to average daily doses of 5, 10, 25, 55, or 90 mg pyridine/kg body weight). Two females exposed to 1,000 ppm died during week 1. Final mean body weights of 1,000 ppm males and females and 500 ppm females were significantly less than controls. Water consumption by female rats exposed to 1,000 ppm was less than that by controls. At study termination, evidence of anemia persisted in the 500 and 1,000 ppm males and all exposed groups of females. There was evidence of hepatocellular injury and/or altered hepatic function demonstrated by increased serum alanine aminotransferase and sorbitol dehydrogenase activities and bile acid concentrations in 500 and 1,000 ppm rats. The estrous cycle length of 1,000 ppm females was significantly longer than that of the controls. Liver weights of males and females exposed to 250 ppm or greater were significantly greater than controls. In the liver, the incidences of centrilobular degeneration, hypertrophy, chronic inflammation, and pigmentation were generally increased in 500 and 1,000 ppm males and females relative to controls. In the kidney, the incidences of granular casts and hyaline degeneration (hyaline droplets) were significantly increased in 1,000 ppm males and slightly increased in 500 ppm males; these lesions are consistent with 2u-globulin nephropathy. Additionally, there were increased incidences and/or severities of protein casts, chronic inflammation, mineralization, and regeneration primarily in 500 and 1,000 ppm males. 13-WEEK STUDY IN MALE WISTAR RATS: Groups of 10 male Wistar rats were exposed to pyridine in drinking water at concentrations of 0, 50, 100, 250, 500, or 1,000 ppm (equivalent to average daily doses of 5, 10, 30, 60, or 100 mg/kg). One male rat exposed to 500 ppm died during week 1. Final mean body weights of rats exposed to 250, 500, or 1,000 ppm were significantly less than those of the controls. Water consumption by rats exposed to 1,000 ppm was lower than that by controls. There was evidence of hepatocellular injury and/or altered hepatic function in the 500 and 1,000 ppm groups, similar to that observed in the 13-week study in F344/N rats. Incidences of centrilobular degeneration, hypertrophy, chronic inflammation, and pigmentation in the liver of rats exposed to 500 or 1,000 ppm were significantly increased relative to controls. 13-WEEK STUDY IN MICE: Groups of 10 male and 10 female B6C3F1 mice were exposed to pyridine in drinking water at concentrations of 0, 50, 100, 250, 500, or 1,000 ppm (equivalent to average daily doses of 10, 20, 50, 85, or 160 mg/kg for males and 10, 20, 60, 100, or 190 mg/kg for females). One female mouse exposed to 250 ppm died during week 2. Final mean body weights of female mice exposed to 1,000 ppm were significantly less than those of controls. Water consumption by exposed female mice was lower than that by controls at week 1 but generally slightly higher than controls at week 13. Sperm motirm motility in exposed male mice was significantly decreased relative to controls. Liver weights were significantly increased relative to controls in males exposed to 100 ppm or greater and in 250 and 500 ppm females. No chemical-related lesions were observed in male or female mice. 2-YEAR STUDY IN F344/N RATS: Groups of 50 male and 50 female F344/N rats were exposed to pyridine in drinking water at concentrations of 0, 100, 200, or 400 ppm (equivalent to average daily doses of 7, 14, or 33 mg/kg) for 104 (males) or 105 (females) weeks. Survival, Body Weights, and Water Consumption Survival of exposed males and females was similar to that of controls. Mean body weights of 400 ppm males and females were generally less than those of the controls throughout the study, and those of 200 ppm males and females were less during the second year of the study. Water consumption by males and females exposed to 200 or 400 ppm was generally greater than that by controls. Pathology Findings Incidences of renal tubule adenoma and renal tubule adenoma or carcinoma (combined) in male rats exposed to 400 ppm were significantly increased compared to controls and exceeded the historical control ranges. The findings from an extended evaluation (step section) of the kidneys did not reveal additional carcinomas, but additional adenomas were observed in each group of males. In the standard evaluation, an increased incidence of renal tubule hyperplasia was observed in 400 ppm males compared to controls. Incidences of mononuclear cell leukemia in female rats were significantly increased in the 200 and 400 ppm groups, and the incidence in the 400 ppm group exceeded the historical control range. Exposure concentration-related nonneoplastic liver lesions were observed in males and females, and the incidences were generally increased in groups exposed to 400 ppm. These included centrilobular cytomegaly, cytoplasmic vacuolization, periportal fibrosis, fibrosis, centrilobular degeneration and necrosis, and pigmentation. Bile duct hyperplasia occurred more often in exposed females than in controls. 2-YEAR STUDY IN MALE WISTAR RATS: Groups of 50 male Wistar rats were exposed to pyridine in drinking water at concentrations of 0, 100, 200, or 400 ppm (equivalent to average daily doses of 8, 17, or 36 mg/kg) for 104 weeks. Survival, Body Weights, and Water Consumption Survival of rats exposed to 200 or 400 ppm was significantly less than that of the controls. Mean body weights of rats exposed to 100, 200, or 400 ppm were significantly less than controls. Water consumption was similar by control and exposed rats. Pathology Findings The incidence of testicular interstitial cell adenoma in rats exposed to 400 ppm was significantly increased compared to controls. Incidences of interstitial cell hyperplasia were observed in control and exposed groups and were slightly, but not significantly, increased in rats exposed to 200 or 400 ppm. Severity of nephropathy was marked in all groups, and additional evidence of kidney disease, including mineralization in the glandular stomach, parathyroid gland hyperplasia, and fibrous osteodystrophy, was observed in 100 and 200 ppm rats. The incidences of hepatic centrilobular degeneration and necrosis, fibrosis, periportal fibrosis, and/or pigmentation were increased in one or more exposed groups. 2-YEAR STUDY IN MICE: Groups of 50 male B6C3F1 mice were exposed to pyridine in drinking water at concentrations of 0, 250, 500, or 1,000 ppm (equivalent to average daily doses of 35, 65, or 110 mg/kg) for 104 weeks, and groups of 50 female B6C3F1 mice were exposed to pyridine in drinking water at concentrations of 0, 125, 250, or 500 ppm (equivalent to average daily doses of 15, 35, or 70 mg/kg) for 105 weeks. Survival, Body Weights, and Water Consumption Survival of exposed males and females was similar to that of the controls. Mean body weights of 250 and 500 ppm females were less than controls. Water consumption by males exposed to 250 or 500 ppm was generally greater than that by controls during the last year of the study; male mice exposed to 1,000 ppm consumed less water than controls throughout the study. Water consumption by exposed females was generally lower than that by controls during the first year of the study, but greater than controls during the second year. Pathology Findings Hepatocellular neoplasms, including hepatoblastomas, in exposed male and female mice were clearly related to pyridine exposure. Additionally, many mice had multiple hepatocellular neoplasms. The incidences of hepatocellular neoplasms in exposed males and females generally exceeded the historical control ranges for drinking water studies. Neoplasms from control mice, 1,000 ppm males, and 500 ppm females were negative when stained for p53 protein. GENETIC TOXICOLOGY: Pyridine was not mutagenic in Salmonella typhimurium strains TA98, TA100, TA1535, or TA1537 or in L5178Y mouse lymphoma cells, with or without S9 metabolic activation, and it did not induce sister chromatid exchanges or chromosomal aberrations in cultured Chinese hamster ovary cells, with or without S9. Pyridine was tested for induction of sex-linked recessive lethal mutations in adult male Drosophila melanogaster, and mixed results were obtained. In one experiment, administration by injection gave negative results, but feeding produced an equivocal response. A second experiment generated negative results by injection and feeding. A third experiment showed significant increases in sex-linked recessive lethal mutations in flies treated with pyridine by injection but not by feeding. Overall, results of the sex-linked recessive lethal mutations test in Drosophila melanogaster were considered negative by feeding and equivocal by injection. Results of a single reciprocal translocation test in male Drosophila melanogaster were negative. No induction of chromosomal aberrations or micronuclei was noted in bone marrow cells of male mice administered pyridine via intraperitoneal injection. CONCLUSIONS: Under the conditions of these 2-year drinking water studies, there was some evidence of carcinogenic activity of pyridine in male F344/N rats based on increased incidences of renal tubule neoplasms. There was equivocal evidence of carcinogenic activity of pyridine in female F344/N rats based on increased incidences of mononuclear cell leukemia. There was equivocal evidence of carcinogenic activity in male Wistar rats based on an increased incidence of interstitial cell adenoma of the testis. There was clear evidence of carcinogenic activity of pyridine in male and female B6C3F1 mice based on increased incidences of malignant hepatocellular neoplasms. In F344/N rats, exposure to pyridine resulted in increased incidences of centrilobular cytomegaly and degeneration, cytoplasmic vacuolization, and pigmentation in the liver of males and females; periportal fibrosis, fibrosis, and centrilobular necrosis in the liver of males; and bile duct hyperplasia in females. In male Wistar rats, pyridine exposure resulted in increased incidences of centrilobular degeneration and necrosis, fibrosis, periportal fibrosis, and pigmentation in the liver, and, secondary to kidney disease, mineralization in the glandular stomach and parathyroid gland hyperplasia. Synonyms: Azabenzene, azine
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PMID:NTP Toxicology and Carcinogenesis Studies of Pyridine (CAS No. 110-86-1) in F344/N Rats, Wistar Rats, and B6C3F1 Mice (Drinking Water Studies). 1257 3

Monochloroacetic acid, a colorless crystalline material, is used as a postemergence contact herbicide and as an intermediate in the synthesis of other organic compounds. Toxicology and carcinogenicity studies were conducted by administering monochloroacetic acid (99% pure) in deionized water by gavage to groups of F344/N rats and B6C3F1 mice of each sex once daily, 5 days per week for 16 days, 13 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, mouse lymphoma L5178Y cells, Chinese hamster ovary cells, and Drosophila melanogaster. 16-Day Studies: Groups of five rats of each sex received 0, 7.5, 15, 30, 60, or 120 mg monochloroacetic acid/kg body weight. Doses administered to mice were 0, 15, 30, 60, 120, or 240 mg/kg to groups of five males and 0, 30, 60, 120, 240, or 480 mg/kg to groups of five females. One of five male rats given 120 mg/kg died during the studies. Clear nasal discharge, lacrimation, or both, were observed in all groups of male and female rats receiving monochloroacetic acid. No compound-related gross lesions were observed in rats. All male mice given 240 mg/kg and all females given 240 or 480 mg/kg died during the studies. Hypoactivity, piloerection, ataxia, and lacrimation were observed in mice given 240 or 480 mg/kg. No compound-related gross lesions were observed in mice at necropsy. 13-Week Studies: Groups of 20 rats of each sex received 0, 30, 60, 90, 120, or 150 mg/kg monochloroacetic acid, and groups of 20 mice of each sex received doses of 0, 25, 50, 100, 150, or 200 mg/kg. Three to five animals in each dose group were killed at weeks 4 and 8 for the evaluation of hematology parameters. Compound-related deaths occurred in rats in the three highest dose groups (all males given 120 or 150 mg/kg, 9/10 males given 90 mg/kg, and all females given 90 to 150 mg/kg) and in mice given 200 mg/kg (all males and 2/10 females). Final mean body weights of surviving rats and mice receiving monochloroacetic acid were similar to those of controls. In rats, dose-related increases in blood urea nitrogen, alanine aminotransferase, and aspartate aminotransferase levels were observed, and relative liver and kidney weights were elevated. There were no compound-related changes in the various hematologic or clinical pathology parameters in mice. A dose-related increase in the incidence and severity of cardiomyopathy was observed in male and female rats receiving monochloroacetic acid, and hepatocellular cytoplasmic vacuolization was observed in the high-dose mice that died during the studies. 2-Year Studies: Based on the mortality and compound-related histopathologic lesions observed in the 13-week studies, doses selected for the 2-year studies of monochloroacetic acid were 0, 15, or 30 mg/kg, administered to groups of 70 rats of each sex, and 0, 50, or 100 mg/kg, administered to groups of 60 mice of each sex. Interim evaluations were conducted on 10 rats per dose group after 6 months of treatment with monochloroacetic acid and on seven rats per dose group after 15 months of treatment. Body Weight and Survival in the 2-Year Studies: Mean body weights of low- and high-dose female and low-dose male rats receiving monochloroacetic acid were within 10% of those of controls throughout the studies; however, after week 30, the mean body weights of high-dose male rats were 4% to 8% less than those of controls. In mice, the mean body weights of dosed males were similar to controls, but those of low- and high-dose females were 6% to 10% less than control values after week 52. Survival of high-dose male and dosed female rats and high-dose male mice was significantly lower than that of controls (male rats: control, 27/53; low-dose, 21/53; high-dose, 16/53; female rats: 37/53; 19/53; 26/53; male mice: 46/60; 39/60; 21/60; female mice: 42/60; 40/60; 44/60). Neoplasms and Nonneoplastic Lesions in the 2-Year Studies: There was no compound-related increase in the incidence of neoplasms or nonneoplastic lesions in rats given monochloroacetic acid for 2 years. The incidence of uterine stromal polypss. The incidence of uterine stromal polyps in low- and high-dose female rats was slightly higher than that in controls (2/60; 7/57; 10/60). However, the incidence in the controls was unusually low, and those in the dosed groups were well within the range for NTP historical controls (mean: 21%, range: 10%-38%). Further, because the only malignant stromal neoplasm occurred in a control animal, the polyps were not considered to be related to the administration of monochloroacetic acid. Similarly, there was no monochloroacetic acid-related increase in the incidence of neoplasms in male or female mice, and malignant lymphoma occurred with a significant negative trend in dosed female mice. Increases in the incidence of inflammation of the mucosa of the nasal passages, respiratory epithelial metaplasia of the olfactory epithelium of the nose, and focal squamous cell hyperplasia of the forestomach occurred in dosed male and female mice. Genetic Toxicology: Monochloroacetic acid was not mutagenic in Salmonella typhimurium strains TA100, TA1535, TA1537, or TA98, with or without exogenous metabolic activation (S9). It induced trifluorothymidine resistance in L5178Y cells in the absence of S9 and induced sister chromatid exchanges without S9 in Chinese hamster ovary cells. Monochloroacetic acid did not induce a significant increase in chromosomal aberrations in Chinese hamster ovary cells, with or without S9. Monochloroacetic acid administered in feed was negative for the induction of sex-linked recessive lethal mutations in germ cells of male Drosophila melanogaster; however, when it was administered by injection, the results were equivocal. Conclusions: Under the conditions of these 2-year gavage studies, there was no evidence of carcinogenic activity for monochloroacetic acid in male or female F344/N rats given 15 or 30 mg/kg. There was no evidence of carcinogenic activity for monochloroacetic acid in male or female B6C3F1 mice given 50 or 100 mg/kg. Monochloroacetic acid administration was associated with inflammatory lesions of the nasal mucosa, metaplasia of the olfactory epithelium, and squamous cell hyperplasia of the forestomach in male and female mice. Synonyms: Chloroacetic acid, a-chloroacetic acid, chloroethanoic acid
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PMID:NTP Toxicology and Carcinogenesis Studies of Monochloroacetic Acid (CAS No. 79-11-8) in F344/N Rats and B6C3F1 Mice (Gavage Studies). 1263 63

1,2,3-Trichloropropane is a colorless liquid used as a paint and varnish remover, solvent, and degreasing agent, and as a crosslinking agent in the synthesis of polysulfides and hexafluoropropylene. 1,2,3-Trichloropropane may be found as an impurity in certain nematocides and soil fumigants and as a contaminant of drinking and ground water. Studies on the toxic and carcinogenic effects of 1,2,3-trichloropropane were initiated because of the close structural relationship of this chemical to other short-chain halogenated compounds that were demonstrated to be carcinogenic in experimental animals, and because of the potential for human exposure. Toxicology and carcinogenicity studies were conducted by administering 1,2,3-trichloropropane (greater than 99% pure) in corn oil by gavage to groups of F344/N rats and B6C3FI mice for 17 weeks and 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium strains, mouse lymphoma cells, and Chinese hamster ovary cells. 17-Week Studies: Groups of 20 male and 20 female rats received 1,2,3-trichloropropane in corn oil by gavage at doses of 8, 16, 32, 63, 125, or 250 mg/kg body weight 5 days per week for up to 17 weeks; 30 male and 30 female rats received corn oil alone and served as controls. Animals were evaluated at 8 or 17 weeks. All rats in the 250 mg/kg groups died by week 5. One male and four female rats in the 125 mg/kg groups died during the study. The mean body weight gains and final mean body weights of males receiving 63 mg/kg and of males and females receiving 125 mg/kg were lower than those of the controls. Hematocrit values, hemoglobin concentrations, and erythrocyte counts decreased with dose in males and females. Serum alanine aminotransferase, aspartate aminotransferase, and sorbitol dehydrogenase activities were significantly increased in some female rats receiving 125 mg/kg. Serum pseudocholinesterase activity decreased with dose in females. Increases in kidney and liver weights were related to chemical administration. The principal toxic lesions associated with the administration of 1,2,3-trichloropropane to rats were hepatocellular necrosis, karyomegaly, and biliary hyperplasia of the liver; renal tubule necrosis, regeneration, and karyomegaly of the kidney; and necrosis and inflammation of the nasal olfactory and respiratory epithelium. Groups of 20 male and 20 female mice received 1,2,3-trichloropropane in corn oil by gavage at doses of 8, 16, 32, 63, 125, or 250 mg/kg 5 days per week for up to 17 weeks; 30 male and 30 female mice received corn oil alone and served as controls. Sixteen male and seven female mice in the 250 mg/kg groups died by week 4. The final mean body weights and mean body weight gains of dosed mice were similar to those of the controls, except those of 250 mg/kg males, which were lower than those of controls. The principal toxic lesions associated with the administration of 1,2,3-trichloropropane were hepatocellular necrosis and karyomegaly of the liver; necrosis, regeneration, and hyperplasia of the bronchiolar epithelium in the lung; and acanthosis (hyperplasia) and hyperkeratosis of the forestomach epithelium. 2-Year Studies: Groups of 60 male and 60 female rats received 0, 3, 10, or 30 mg 1,2,3-trichloropropane/kg body weight in corn oil by gavage 5 days per week for up to 104 weeks. Selection of 30 mg/kg as the high dose in these studies was based on the following chemical-related effects in the 17-week studies: deaths and liver and kidney lesions at 125 and 250 mg/kg and reduced final mean body weights and mean body weight gains at 63 mg/kg or greater. Groups of 60 male and 60 female mice received 0, 6, 20, or 60 mg 1,2,3-trichloropropane/kg body weight in corn oil by gavage 5 days per week for up to 104 weeks. Selection of 60 mg/kg as the high dose was based on chemical-related deaths and lesions of the liver, lung, and forestomach at 125 and 250 mg/kg in the 17-week studies. 15-Month Interim Evaluations: Up to 10 rats and 10 mice from each dose group were evaluated at 15 months. Absolute and relative liver and kidned kidney weights of dosed rats were significantly greater than those of the controls. Chemical-related nonneoplastic lesions and neoplasms of the forestomach, oral mucosa, pancreas (males), kidney, mammary gland (females), preputial gland, and clitoral gland were observed in dosed rats. Chemical-related nonneoplastic lesions and neoplasms of the forestomach and liver (females) were observed in dosed mice. Survival and Body Weight in the 2-Year Studies: Survival of male and female rats receiving 10 or 30 mg/kg 1,2,3-trichloropropane was significantly lower than that of controls. Two-year survival rates of male rats were: control, 34/50; 3 mg/kg, 32/50; 10 mg/kg, 14/49; 30 mg/kg, 0/52; and of females were: 31/50, 30/49, 8/52, 0/52. At 30 mg/kg, survival was markedly reduced due to chemical-related neoplasms, and survivors were killed in weeks 67 (females) or 77 (males). Final mean body weights of 30 mg/kg rats were 13% lower for males and 12% lower for females than those of controls; mean body weights of 3 and 10 mg/kg rats were similar to controls. Survival rates of mice receiving 6, 20, or 60 mg/kg 1,2,3-trichloropropane were also significantly lower than those of controls. Two-year survival rates of male mice were: 42/52, 18/51, 0/54, 0/56; and of female mice were: 41/50, 13/50, 0/51, 0/55. Because of reduced survival at 20 and 60 mg/kg due to chemical-related neoplasms, survivors were killed in weeks 73 (60 mg/kg females), 79 (60 mg/kg males), or 89 (20 mg/kg males and females). Final mean body weights were 16% lower for 60 mg/kg males, 18~ lower for 60 mg/kg females, and 13% lower for 20 mg/kg males than those of controls. Final mean body weights of 6 mg/kg males and females and 20 mg/kg females were similar to controls. Neoplasms and Nonneoplastic Lesions in the 2-Year Studies: Administration of 1,2,3-trichloropropane to rats induced benign and malignant neoplasms of the oral mucosa (pharynx and tongue), forestomach, and preputial and clitoral glands in males and females; benign neoplasms of the exocrine pancreas and kidney in males, and malignant neoplasms of the mammary gland in females. The incidences of squamous cell papillomas and carcinomas of the oral mucosa were significantly increased in 10 and 30 mg/kg rats, while the incidences of squamous cell papillomas or carcinomas (combined) of the forestomach were significantly increased in all dosed groups. The incidence of pancreatic acinar adenoma was significantly increased in dosed males, but not in dosed females. Similarly, the incidence of adenoma of the kidney was significantly increased in 10 and 30 mg/kg male rats only. The incidences of adenoma or carcinoma (combined) of the preputial gland in 30 mg/kg males and of the clitoral gland in 10 and 30 mg/kg females (homologous organs) were significantly increased. The incidence of adenocarcinoma of the mammary gland was significantly increased in the 10 and 30 mg/kg females. The incidences of Zymbal's gland carcinomas were increased in 30 mg/kg males and females. Adenocarcinomas of the intestine occurred in small numbers of dosed rats and may have been chemical related. In mice, the incidence of squamous cell carcinoma of the oral mucosa was significantly increased only in 60 mg/kg females. In contrast, the incidences of squamous cell papilloma and carcinoma of the forestomach were significantly increased in all groups of dosed mice. The incidences of hepatocellular adenoma or carcinoma (combined) were significantly increased in all dosed groups of males and 60 mg/kg females. The incidences of harderian gland adenoma were significantly increased in 20 mg/kg males and in 60 mg/kg males and females. The incidences of uterine adenoma, adenocarcinoma, and stromal polyp were significantly increased in 60 mg/kg females. Genetic Toxicology: 1,2,3-Trichloropropane was mutagenic in vitro in the presence of S9 metabolic activation. At two laboratories, positive responses were obtained for mutagenicity in Salmonella typhimurium strains TA97, TA98, TA100, and TA1535 in the presence of S9; no mutagenic activity was observed in TA1537, with or without S9. 1,2,3-Trichloropropane induced trifluorothymidine resistance in L5178Y mouse lymphoma cells with, but not without, S9. In cultured Chinese hamster ovary cells, sister chromatid exchanges and chromosomal aberrations were induced by 1,2,3-trichloropropane; however, significant increases in the endpoints of both cytogenetic effects occurred only in the presence of S9. Conclusions: Under the conditions of these 2-year gavage studies, there was clear evidence of carcinogenic activity of 1,2,3-trichloropropane in male F344/N rats based on increased incidences of squamous cell papillomas and carcinomas of the oral mucosa and forestomach, adenomas of the pancreas and kidney, adenomas or carcinomas of the preputial gland, and carcinomas of the Zymbal's gland. Adenomatous polyps and adenocarcinomas of the intestine may have been related to chemical administration. There was clear evidence of carcinogenic activity of 1,2,3-trichloropropane in female F344/N rats based on increased incidences of squamous cell papillomas and carcinomas of the oral mucosa and forestomach, adenomas or carcinomas of the clitoral gland, adenocarcinomas of the mammary gland, and carcinomas of the Zymbal's gland. Adenocarcinomas of the intestine may have been related to chemical administration. There was clear evidence of carcinogenic activity of 1,2,3-trichloropropane in male B6C3F1 mice based on increased incidences of squamous cell papillomas and carcinomas of the forestomach, hepatocellular adenomas or carcinomas of the liver, and harderian gland adenomas. Squamous cell papillomas of the oral mucosa may have been related to chemical administration. There was clear evidence of carcinogenic activity of 1,2,3-trichloropropane in female B6C3F1, mice based on increased incidences of squamous cell carcinomas of the oral mucosa, squamous cell papillomas and carcinomas of the forestomach, hepatocellular adenomas or carcinomas of the liver, harderian gland adenomas, and uterine adenomas, adenocarcinomas, and stromal polyps. Nonneoplastic lesions associated with exposure to 1,2,3-trichloropropane included increased severity of nephropathy in male rats and increased incidences of basal cell and squamous hyperplasia of the forestomach, acinar hyperplasia of the pancreas, renal tubule hyperplasia, and preputial or clitoral gland hyperplasia in male and female rats. Increased incidences of squamous hyperplasia of the forestomach and eosinophilic foci in the liver in male and female mice were chemical related. Synonyms: Allyl trichloride, glycerol tnchlorohydrin, glyceryl tnchlorohydrin, trichlorohydrin
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PMID:NTP Toxicology and Carcinogenesis of 1,2,3-Trichloropropane (CAS No. 96-18-4) in F344/N Rats and B6C3F1 Mice (Gavage Studies). 1269 52