National Toxicology Program genetically modified model report最新文献

{"title":"Toxicology studies of pentaerythritol triacrylate (technical grade) (CAS No. 3524-68-3) in F344/N rats, B6C3F1 mice, and genetically modified (FVB Tg.AC hemizygous) mice (dermal studies).","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Pentaerythritol triacrylate is used in the production of ultraviolet-curable inks and coatings, electron beam irradiation- curable coatings, and radiation-cured and photocurable coatings of urethanes and epoxy resins; as a component of photopolymer and flexographic printing inks and plates and photoresists; as an ingredient of acrylic glues, adhesives, and anaerobic sealants; and as a modifier for polyester and fiberglass. It is also used in colloidal dispersions for industrial baked coatings, waterborne and solvent-based alkyds, vinyl/acrylic nonwoven binders, paper and wood impregnates, wire and cable extrusion, polymer-impregnated concrete, and polymer concrete structural composites. Pentaerythritol triacrylate was nominated by the National Cancer Institute for testing based on its high production volume and use, its potential for human exposure, and a lack of adequate testing of the chemical. Male and female F344/N rats and B6C3F(1) mice were administered technical grade pentaerythritol triacrylate (it is reactive and therefore not available as pure pentaerythritol triacrylate) in acetone dermally for 2 weeks or 3 months. Male and female Tg.AC hemizygous mice were administered technical grade pentaerythritol acrylate in acetone for 6 months. Genetic toxicology was evaluated in Salmonella typhimurium and in B6C3F(1) and Tg.AC hemizygous mouse peripheral blood erythrocytes. 2-WEEK STUDY IN RATS: Groups of five male and five female F344/N rats were administered 0, 12.5, 25, 50, 100, or 200 mg pentaerythritol triacrylate/kg body weight in acetone 5 days per week for 17 days. All rats survived to the end of the study; mean body weights of males administered 50 mg/kg or greater and 200 mg/kg females were significantly less than those of the vehicle controls. Irritation at the site of application occurred in all dosed groups except 12.5 mg/kg females. Epidermal hyperplasia, hyperkeratosis, sebaceous gland hyperplasia, ulcer, epidermal degeneration, parakeratosis, chronic active inflammation, and suppurative inflammation occurred at the site of application in most dosed groups of rats. 2-WEEK STUDY IN B6C3F(1) MICE: Groups of five male and five female B6C3F(1) mice were administered 0, 12.5, 25, 50, 100, or 200 mg pentaerythritol triacrylate/kg body weight in acetone 5 days per week for 17 days. All mice survived to the end of the study. The final mean body weight and body weight gain of 25 mg/kg males were significantly greater than those of the vehicle controls, as was the mean body weight gain of 50 mg/kg males. All dosed groups had irritation at the site of application. Thymus weights of males administered 50 mg/kg or greater and 200 mg/kg females were significantly less than those of the vehicle controls. Most dosed groups of mice had epidermal hyperplasia, hyperkeratosis, sebaceous gland hyperplasia, ulcer, epidermal degeneration, parakeratosis, chronic active inflammation, and suppurative inflammation at the site of application. 3-MONTH ","PeriodicalId":18898,"journal":{"name":"National Toxicology Program genetically modified model report","volume":" 4","pages":"1-190"},"PeriodicalIF":0.0,"publicationDate":"2005-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8950436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27668330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NTP toxicology studies of acesulfame potassium (CAS No. 55589-62-3) in genetically modified (FVB Tg.AC Hemizygous) mice and carcinogenicity studies of acesulfame potassium in genetically modified [B6.129-Trp53(tm1Brd) (N5) Haploinsufficient] mice (feed studies)mice.","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Unlabelled: </strong>Acesulfame potassium is an artificial sweetener used throughout the world in food and beverages. Acesulfame potassium was nominated by The Center for Science in the Public Interest because of its widespread use. Male and female Tg.AC hemizygous and p53 haploinsufficient mice were exposed to acesulfame potassium (at least 99% pure) in feed for 9 months. Genetic toxicology studies were conducted in mouse peripheral blood erythrocytes. 9-MONTH STUDY IN Tg.AC HEMIZYGOUS MICE: Groups of 15 male and 15 female Tg.AC hemizygous mice were fed diets containing 0%, 0.3%, 1%, or 3% acesulfame potassium (equivalent to average daily doses of approximately 420, 1,400, or 4,500 mg acesulfame potassium/kg body weight to males and 520, 1,700, or 5,400 mg/kg to females) for 40 weeks. Exposure to acesulfame potassium had no effect on survival or mean body weights. Feed consumption by the exposed groups was similar to that by the control groups throughout the study. There were no neoplasms or nonneoplastic lesions that were attributed to exposure to acesulfame potassium. 9-MONTH STUDY IN p53 HAPLOINSUFFICIENT MICE: Groups of 15 male and 15 female p53 haploinsufficient mice were fed diets containing 0%, 0.3%, 1%, or 3% acesulfame potassium (equivalent to average daily doses of approximately 475, 1,500, or 4,700 mg/kg to males and 570, 1,800, or 5,700 mg/kg to females) for 40 weeks. Exposure to acesulfame potassium had no effect on survival or mean body weights. Feed consumption by the exposed groups was similar to that by the control groups throughout the study. There were no neoplasms or nonneoplastic lesions that were attributed to exposure to acesulfame potassium.</p><p><strong>Genetic toxicology: </strong>Acesulfame potassium did not increase the frequency of micronucleated erythrocytes in peripheral blood of male or female Tg.AC hemizygous mice administered 0.3% to 3% in dosed feed. A similar study was conducted in p53 haploinsufficient mice, and a significant exposure concentration-related increase in the frequency of micronucleated erythrocytes was noted in males but not females.</p><p><strong>Conclusions: </strong>Under the conditions of this 9-month feed study, there was no evidence of carcinogenic activity of acesulfame potassium in male or female p53 haploinsufficient mice exposed to 0.3%, 1%, or 3%.</p>","PeriodicalId":18898,"journal":{"name":"National Toxicology Program genetically modified model report","volume":" 2","pages":"1-113"},"PeriodicalIF":0.0,"publicationDate":"2005-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8935293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27668328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxicology studies of trimethylolpropane triacrylate (technical grade) (CAS No. 15625-89-5) in F344/N rats, B6C3F1 mice, and genetically modified (FVB Tg.AC hemizygous) mice (dermal studies).","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Trimethylolpropane triacrylate is a multifunctional monomer with a wide range of industrial applications. It is used in the production of ultraviolet-curable inks, electron beam irradiation-curable coatings, and polymers and resins; as a component of photopolymer and flexographic printing plates and photoresists; and as an ingredient in acrylic glues and anaerobic sealants. The chemical is also used in paper and wood impregnates, wire and cable extrusion, polymer-impregnated concrete, and polymer concrete structural composites. Trimethylolpropane triacrylate was nominated by the National Cancer Institute for testing due to its high production volume and use, its potential for consumer exposure, and a lack of adequate testing of the chemical. Male and female F344/N rats and B6C3F(1) mice were administered technical grade trimethylolpropane triacrylate (it is reactive and therefore not available as pure trimethylolpropane triacrylate) in acetone dermally for 2 weeks or 3 months. Male and female Tg.AC hemizygous mice were administered technical grade trimethylolpropane triacrylate in acetone for 6 months. Genetic toxicology studies were conducted in B6C3F(1) and Tg.AC hemizygous mouse peripheral blood erythrocytes. 2-WEEK STUDY IN RATS: Groups of five male and five female F344/N rats were administered 0, 12.5, 25, 50, 100, or 200 mg trimethylolpropane triacrylate/kg body weight in acetone 5 days per week for 16 days. All rats survived to the end of the study, and mean body weights of dosed groups were similar to those of the vehicle controls. Dosed rats had irritation at the site of application; this clinical finding was most commonly seen in rats administered 50 mg/kg or greater. Male and female rats had epidermal hyperplasia, hyperkeratosis, sebaceous gland hyperplasia, inflammation of the epidermis and dermis, ulceration, epidermal degeneration, and parakeratosis at the site of application. 2-WEEK STUDY IN B6C3F(1) MICE: Groups of five male and five female B6C3F(1) mice were administered 0, 12.5, 25, 50, 100, or 200 mg trimethylolpropane triacrylate/kg body weight in acetone 5 days per week for 16 days. All mice survived to the end of the study. The final mean body weight gain of 200 mg/kg males was less than that of the vehicle controls; 100 and 200 mg/kg females had significantly increased final mean body weights. Irritation at the site of application occurred in all dosed males, all 100 and 200 mg/kg females, and one 50 mg/kg female. Thymus weights of males administered 50 mg/kg or greater were significantly decreased. Dosed male and female mice had epidermal hyperplasia, hyperkeratosis, chronic active inflammation of the dermis, sebaceous gland hyperplasia, ulcer, epidermal degeneration, parakeratosis, and/or suppurative inflammation of the epidermis at the site of application. Atrophy of the thymus occurred in 100 and 200 mg/kg male mice. 3-MONTH STUDY IN RATS: Groups of 10 male and 10 female F344/N rats were administered 0, 0.75, 1.5,","PeriodicalId":18898,"journal":{"name":"National Toxicology Program genetically modified model report","volume":" 3","pages":"1-195"},"PeriodicalIF":0.0,"publicationDate":"2005-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8935285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27668329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NTP report on the toxicology studies of aspartame (CAS No. 22839-47-0) in genetically modified (FVB Tg.AC hemizygous) and B6.129-Cdkn2atm1Rdp (N2) deficient mice and carcinogenicity studies of aspartame in genetically modified [B6.129-Trp53tm1Brd (N5) haploinsufficient] mice (feed studies).","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Unlabelled: </strong>Aspartame is an artificial sweetener used throughout the world in food and beverages. Conventional 2-year rodent cancer studies of aspartame are considered negative, although a small number of neoplasms of the brain were observed in a rat study (Fed. Regist., 1981a,b). The NTP has explored the use of genetically altered mouse models as adjuncts to the 2-year rodent cancer assay. These models may prove to be more rapid, use fewer animals, and provide some mechanistic insights into neoplastic responses. As part of the evaluation of new mouse cancer screening models, aspartame was tested for potential toxicity and carcinogenicity in two relatively well-studied models, the Tg.AC hemizygous strain and the p53 haploinsufficient strain, and an uncharacterized model, the Cdkn2a deficient strain. Male and female Tg.AC hemizygous, p53 haploinsufficient, and Cdkn2a deficient mice were given feed containing aspartame (greater than 98% pure) for 9 months. Genetic toxicology studies were conducted in Salmonella typhimurium, rat bone marrow cells, and mouse peripheral blood erythrocytes. 9-MONTH STUDY IN Tg.AC HEMIZYGOUS MICE: Groups of 15 male and 15 female Tg.AC hemizygous mice were fed diets containing 0, 3,125, 6,250, 12,500, 25,000, or 50,000 ppm aspartame (equivalent to average daily doses of approximately 490, 980, 1,960, 3,960, or 7,660 mg aspartame/kg body weight to males and 550, 1,100, 2,260, 4,420, or 8,180 mg/kg to females) for 40 weeks. Exposure to aspartame had no effect on survival. The mean body weights of 50,000 ppm females were greater than those of the controls from week 15 until the end of the study. Feed consumption by the exposed groups was similar to that by the control groups throughout the study. There were no neoplasms or nonneoplastic lesions that were attributed to exposure to aspartame. 9-MONTH STUDY IN p53 HAPLOINSUFFICIENT MICE: Groups of 15 male and 15 female p53 haploinsufficient mice were fed diets containing 0, 3,125, 6,250, 12,500, 25,000, or 50,000 ppm aspartame (equivalent to average daily doses of approximately 490, 970, 1,860, 3,800, or 7,280 mg/kg to males and 630, 1,210, 2,490, 5,020, or 9,620 mg/kg to females) for 40 weeks. Exposure to aspartame had no effect on survival or mean body weights. Feed consumption by the exposed groups was similar to that by the control groups throughout the study. No neoplasms or nonneoplastic lesions were attributed to exposure to aspartame. 9-MONTH STUDY IN Cdkn2a DEFICIENT MICE: Groups of 15 male and 15 female Cdkn2a deficient mice were fed diets containing 0, 3,125, 6,250, 12,500, 25,000, or 50,000 ppm aspartame for 40 weeks (equivalent to average daily doses of approximately of approximately 490, 960, 1,900, 3,700, and 7,400 mg/kg to males and 610, 1,200, 2,390, 4,850, and 9,560 mg/kg to females). Survival of all exposed groups was similar to that of the control groups. Mean body weights of 3,125 and 6,250 ppm males were less than those of the controls","PeriodicalId":18898,"journal":{"name":"National Toxicology Program genetically modified model report","volume":" 1","pages":"1-222"},"PeriodicalIF":0.0,"publicationDate":"2005-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27582598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}