国家毒理学计划技术报告:醋酸烯丙酯(CAS No. 591-87-7)、烯丙醇(CAS No. 107-18-6)和丙烯醛(CAS No. 107-02-8)灌胃对F344/N大鼠和B6C3F1小鼠的毒性比较研究。

Toxicity report series Pub Date : 2006-07-01
Rick D Irwin
{"title":"国家毒理学计划技术报告:醋酸烯丙酯(CAS No. 591-87-7)、烯丙醇(CAS No. 107-18-6)和丙烯醛(CAS No. 107-02-8)灌胃对F344/N大鼠和B6C3F1小鼠的毒性比较研究。","authors":"Rick D Irwin","doi":"","DOIUrl":null,"url":null,"abstract":"<p><p>Allyl acetate, allyl alcohol, and acrolein are used in the manufacture of detergents, plastics, pharmaceuticals, and chemicals and as agricultural agents and food additives. Male and female F344/N rats and B6C3F(1) mice received allyl acetate, allyl alcohol, or acrolein by gavage for 14 weeks. Genetic toxicology studies were conducted in Salmonella typhimurium, Drosophila melanogaster, cultured Chinese hamster ovary cells, rat bone marrow erythrocytes, and mouse peripheral blood erythrocytes. Groups of 10 male and 10 female rats were administered 0, 6, 12, 25, 50, or 100 mg allyl acetate/kg body weight, 0, 1.5, 3, 6, 12, or 25 mg/kg allyl alcohol, or 0, 0.75, 1.25, 2.5, 5, or 10 mg/kg acrolein in 0.5% methylcellulose by gavage, 5 days per week for 14 weeks. Groups of 10 male and 10 female mice were administered 0, 8, 16, 32, 62.5, or 125 mg/kg allyl acetate, 0, 3, 6, 12, 25, or 50 mg/kg allyl alcohol, or 0, 1.25, 2.5, 5, 10, or 20 mg/kg acrolein in 0.5% methylcellulose by gavage, 5 days per week for 14 weeks. In the allyl acetate rat study, all males and females in the 100 mg/kg groups died or were killed moribund by day 8; there were no other deaths. In the allyl alcohol study, all rats survived to the end of the study except one 6 mg/kg female. In the acrolein rat study, eight males and eight females in the 10 mg/kg groups died by week 9 of the study. Two males in the 2.5 and 5 mg/kg groups and one or two females in the 1.25, 2.5, and 5 mg/kg groups also died early; two of these deaths were gavage accidents. In the allyl acetate mouse study, all males and females in the 125 mg/kg group died during the first week of the study. All other early deaths, except five 62.5 mg/kg males and one 32 mg/kg female, were gavage accidents. In the allyl alcohol mouse study, one 50 mg/kg female died due to a gavage accident; all other animals survived to the end of the study. In the acrolein mouse study, all males and females administered 20 mg/kg died during the first week of the study. All other early deaths, except one male and one female administered 10 mg/kg, were unrelated to chemical administration. The concentration of 3-hydroxypropyl mercapturic acid (3-HPM) in the urine of rats and mice was determined after the first dose of chemical and at the end of the 14-week study. At both time points, the concentrations of 3-HPM in the urine of animals that received allyl acetate or allyl alcohol increased linearly with dose. In animals dosed with acrolein, the concentrations of 3-HPM exhibited a nonlinear increase with dose at the first time point. At the end of the study, the concentration of 3-HPM in the urine of animals dosed with acrolein was linear with dose except at the highest concentration administered. Since urine volumes were not recorded during the urine collection, complete quantitation of these data was not possible. The final mean body weights and mean body weight gains of male rats administered 12 or 50 mg/kg allyl acetate and of male and female rats administered 10 mg/kg acrolein were significantly less than those of the vehicle controls. The mean body weight gain of male mice in the 50 mg/kg group in the allyl alcohol study was also less than that of the vehicle controls. Final mean body weights and mean body weight gains of dosed female rats and male and female mice in the allyl acetate studies, male and female rats and female mice in the allyl alcohol studies, and male and female mice in the acrolein studies were generally similar to those of the respective vehicle controls. Clinical findings related to allyl acetate administration included pallor, eye or nasal discharge, ruffled fur, lethargy, diarrhea, and thinness among rats in the 100 mg/kg groups and lethargy, abnormal breathing, thinness, and ruffled fur among mice that died early. In the acrolein study, clinical findings included abnormal breathing, eye or nasal discharge, ruffled fur, thinness, and lethargy in rats in the 10 mg/kg groups. The liver weights of male rats administered 25 mg/kg allyl alcohol, female rats administered 50 mg/kg allyl acetate or 5 or 10 mg/kg acrolein, and male mice administered 10 mg/kg acrolein were significantly greater than those of the vehicle controls. Female rats administered 10 mg/kg acrolein had significantly lower absolute and relative thymus weights than did the vehicle controls. Female rats administered 25 mg/kg allyl alcohol spent more time in diestrus and less time in metestrus than the vehicle controls. The estrous cycles of female mice dosed with 16 or 32 mg/kg allyl acetate were significantly longer than that of the vehicle controls. Gross lesions related to allyl acetate treatment were observed in the liver, forestomach, and thorax/abdomen of male and female rats in the 100 mg/kg groups. Microscopically, the incidences of forestomach squamous epithelial hyperplasia were significantly increased in male rats administered 12 mg/kg or greater, female rats administered 25 or 50 mg/kg, male mice administered 32 or 62.5 mg/kg, and female mice administered 16, 32, or 62.5 mg/kg. Forestomach necrosis, hemorrhage, and inflammation were present in most rats in the 100 mg/kg groups, and the incidence of hemorrhage in 125 mg/kg male mice was increased; male mice in the 62.5 and 125 mg/kg groups and 125 mg/kg female mice had significantly increased incidences of glandular stomach hemorrhage. Increased incidences of several liver lesions occurred in male or female rats administered 50 or 100 mg/kg, and to a lesser extent in 25 mg/kg rats, 62.5 mg/kg male mice, and 125 mg/kg male and female mice. Bone marrow hyperplasia, hemorrhage or depletion in the mediastinal, mandibular, and mesenteric lymph nodes, hemorrhage and necrosis of the thymus, and hematopoietic cell proliferation of the red pulp were also observed in 100 mg/kg rats. Increased incidences of necrosis in the mandibular and mesenteric lymph nodes, spleen, and thymus were observed in 62.5 and 125 mg/kg mice. Male and female rats administered 6 mg/kg allyl alcohol or greater and male and female mice administered 12 mg/kg allyl alcohol or greater had significantly increased incidences of squamous hyperplasia of the forestomach epithelium. Female rats in the 25 mg/kg group had significantly increased incidences of bile duct hyperplasia and periportal hepatocyte hypertrophy in the liver. Incidences of portal cytoplasmic vacuolization were significantly increased in 50 mg/kg male mice and female mice in the 25 and 50 mg/kg groups. Gross lesions related to acrolein treatment were observed in the forestomach and glandular stomach of male and female rats in the 10 mg/kg groups and 20 mg/kg female mice. Microscopically, the incidences of squamous hyperplasia of the forestomach epithelium were significantly increased in male rats in the 5 and 10 mg/kg groups, female rats administered 2.5 mg/kg or greater, and male and female mice administered 2.5, 5, or 10 mg/kg. Male and female rats in the 10 mg/kg groups and 20 mg/kg male and female mice had significantly increased incidences of glandular stomach hemorrhage. Female mice in the 20 mg/kg group also had significantly increased incidences of glandular stomach inflammation and epithelial necrosis. Allyl acetate was mutagenic in S. typhimurium strains TA100 and TA1535, in the absence of S9 activation. With S9, no mutagenicity was detected in these two strains; negative results were obtained in strains TA97 and TA98, with and without S9. Allyl alcohol was not mutagenic in four strains of S. typhimurium, with or without S9 metabolic activation. Acrolein, tested in a preincubation protocol, was weakly mutagenic in S. typhimurium strain TA100 in the presence of 10% induced rat liver S9. Equivocal results were obtained in strains TA100 and TA1535 with 10% induced hamster liver S9. Negative results were obtained with TA97, TA98, and TA1538 under all test conditions, and acrolein gave negative results in all four S. typhimurium strains tested for mutation induction under a vapor protocol. No induction of micronuclei was noted in bone marrow erythrocytes of male rats administered allyl acetate by gavage three times at 24-hour intervals. No significant increases in micronucleated erythrocytes were noted in bone marrow samples from male rats administered allyl alcohol by intraperitoneal injection for 3 days. A small, but significant increase in the frequency of micronucleated normochromatic erythrocytes was observed in the peripheral blood of female mice administered allyl acetate by gavage for 14 weeks; no increase was observed in male mice. No increases in the frequencies of micronucleated normochromatic erythrocytes were observed in the peripheral blood of male or female mice administered allyl alcohol or acrolein by gavage for 14 weeks. Acrolein induced sister chromatid exchanges in cultured Chinese hamster ovary cells in the absence, but not the presence, of S9; it did not induce chromosomal aberrations, with or without S9. Results of three independent Drosophila melanogaster sex linked recessive lethal tests in which acrolein was administered to adult flies via feeding or injection and to larvae via feeding were negative.</p>","PeriodicalId":23116,"journal":{"name":"Toxicity report series","volume":" 48","pages":"1-73, A1-H10"},"PeriodicalIF":0.0000,"publicationDate":"2006-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"NTP Technical Report on the comparative toxicity studies of allyl acetate (CAS No. 591-87-7), allyl alcohol (CAS No. 107-18-6) and acrolein (CAS No. 107-02-8) administered by gavage to F344/N rats and B6C3F1 mice.\",\"authors\":\"Rick D Irwin\",\"doi\":\"\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Allyl acetate, allyl alcohol, and acrolein are used in the manufacture of detergents, plastics, pharmaceuticals, and chemicals and as agricultural agents and food additives. Male and female F344/N rats and B6C3F(1) mice received allyl acetate, allyl alcohol, or acrolein by gavage for 14 weeks. Genetic toxicology studies were conducted in Salmonella typhimurium, Drosophila melanogaster, cultured Chinese hamster ovary cells, rat bone marrow erythrocytes, and mouse peripheral blood erythrocytes. Groups of 10 male and 10 female rats were administered 0, 6, 12, 25, 50, or 100 mg allyl acetate/kg body weight, 0, 1.5, 3, 6, 12, or 25 mg/kg allyl alcohol, or 0, 0.75, 1.25, 2.5, 5, or 10 mg/kg acrolein in 0.5% methylcellulose by gavage, 5 days per week for 14 weeks. Groups of 10 male and 10 female mice were administered 0, 8, 16, 32, 62.5, or 125 mg/kg allyl acetate, 0, 3, 6, 12, 25, or 50 mg/kg allyl alcohol, or 0, 1.25, 2.5, 5, 10, or 20 mg/kg acrolein in 0.5% methylcellulose by gavage, 5 days per week for 14 weeks. In the allyl acetate rat study, all males and females in the 100 mg/kg groups died or were killed moribund by day 8; there were no other deaths. In the allyl alcohol study, all rats survived to the end of the study except one 6 mg/kg female. In the acrolein rat study, eight males and eight females in the 10 mg/kg groups died by week 9 of the study. Two males in the 2.5 and 5 mg/kg groups and one or two females in the 1.25, 2.5, and 5 mg/kg groups also died early; two of these deaths were gavage accidents. In the allyl acetate mouse study, all males and females in the 125 mg/kg group died during the first week of the study. All other early deaths, except five 62.5 mg/kg males and one 32 mg/kg female, were gavage accidents. In the allyl alcohol mouse study, one 50 mg/kg female died due to a gavage accident; all other animals survived to the end of the study. In the acrolein mouse study, all males and females administered 20 mg/kg died during the first week of the study. All other early deaths, except one male and one female administered 10 mg/kg, were unrelated to chemical administration. The concentration of 3-hydroxypropyl mercapturic acid (3-HPM) in the urine of rats and mice was determined after the first dose of chemical and at the end of the 14-week study. At both time points, the concentrations of 3-HPM in the urine of animals that received allyl acetate or allyl alcohol increased linearly with dose. In animals dosed with acrolein, the concentrations of 3-HPM exhibited a nonlinear increase with dose at the first time point. At the end of the study, the concentration of 3-HPM in the urine of animals dosed with acrolein was linear with dose except at the highest concentration administered. Since urine volumes were not recorded during the urine collection, complete quantitation of these data was not possible. The final mean body weights and mean body weight gains of male rats administered 12 or 50 mg/kg allyl acetate and of male and female rats administered 10 mg/kg acrolein were significantly less than those of the vehicle controls. The mean body weight gain of male mice in the 50 mg/kg group in the allyl alcohol study was also less than that of the vehicle controls. Final mean body weights and mean body weight gains of dosed female rats and male and female mice in the allyl acetate studies, male and female rats and female mice in the allyl alcohol studies, and male and female mice in the acrolein studies were generally similar to those of the respective vehicle controls. Clinical findings related to allyl acetate administration included pallor, eye or nasal discharge, ruffled fur, lethargy, diarrhea, and thinness among rats in the 100 mg/kg groups and lethargy, abnormal breathing, thinness, and ruffled fur among mice that died early. In the acrolein study, clinical findings included abnormal breathing, eye or nasal discharge, ruffled fur, thinness, and lethargy in rats in the 10 mg/kg groups. The liver weights of male rats administered 25 mg/kg allyl alcohol, female rats administered 50 mg/kg allyl acetate or 5 or 10 mg/kg acrolein, and male mice administered 10 mg/kg acrolein were significantly greater than those of the vehicle controls. Female rats administered 10 mg/kg acrolein had significantly lower absolute and relative thymus weights than did the vehicle controls. Female rats administered 25 mg/kg allyl alcohol spent more time in diestrus and less time in metestrus than the vehicle controls. The estrous cycles of female mice dosed with 16 or 32 mg/kg allyl acetate were significantly longer than that of the vehicle controls. Gross lesions related to allyl acetate treatment were observed in the liver, forestomach, and thorax/abdomen of male and female rats in the 100 mg/kg groups. Microscopically, the incidences of forestomach squamous epithelial hyperplasia were significantly increased in male rats administered 12 mg/kg or greater, female rats administered 25 or 50 mg/kg, male mice administered 32 or 62.5 mg/kg, and female mice administered 16, 32, or 62.5 mg/kg. Forestomach necrosis, hemorrhage, and inflammation were present in most rats in the 100 mg/kg groups, and the incidence of hemorrhage in 125 mg/kg male mice was increased; male mice in the 62.5 and 125 mg/kg groups and 125 mg/kg female mice had significantly increased incidences of glandular stomach hemorrhage. Increased incidences of several liver lesions occurred in male or female rats administered 50 or 100 mg/kg, and to a lesser extent in 25 mg/kg rats, 62.5 mg/kg male mice, and 125 mg/kg male and female mice. Bone marrow hyperplasia, hemorrhage or depletion in the mediastinal, mandibular, and mesenteric lymph nodes, hemorrhage and necrosis of the thymus, and hematopoietic cell proliferation of the red pulp were also observed in 100 mg/kg rats. Increased incidences of necrosis in the mandibular and mesenteric lymph nodes, spleen, and thymus were observed in 62.5 and 125 mg/kg mice. Male and female rats administered 6 mg/kg allyl alcohol or greater and male and female mice administered 12 mg/kg allyl alcohol or greater had significantly increased incidences of squamous hyperplasia of the forestomach epithelium. Female rats in the 25 mg/kg group had significantly increased incidences of bile duct hyperplasia and periportal hepatocyte hypertrophy in the liver. Incidences of portal cytoplasmic vacuolization were significantly increased in 50 mg/kg male mice and female mice in the 25 and 50 mg/kg groups. Gross lesions related to acrolein treatment were observed in the forestomach and glandular stomach of male and female rats in the 10 mg/kg groups and 20 mg/kg female mice. Microscopically, the incidences of squamous hyperplasia of the forestomach epithelium were significantly increased in male rats in the 5 and 10 mg/kg groups, female rats administered 2.5 mg/kg or greater, and male and female mice administered 2.5, 5, or 10 mg/kg. Male and female rats in the 10 mg/kg groups and 20 mg/kg male and female mice had significantly increased incidences of glandular stomach hemorrhage. Female mice in the 20 mg/kg group also had significantly increased incidences of glandular stomach inflammation and epithelial necrosis. Allyl acetate was mutagenic in S. typhimurium strains TA100 and TA1535, in the absence of S9 activation. With S9, no mutagenicity was detected in these two strains; negative results were obtained in strains TA97 and TA98, with and without S9. Allyl alcohol was not mutagenic in four strains of S. typhimurium, with or without S9 metabolic activation. Acrolein, tested in a preincubation protocol, was weakly mutagenic in S. typhimurium strain TA100 in the presence of 10% induced rat liver S9. Equivocal results were obtained in strains TA100 and TA1535 with 10% induced hamster liver S9. Negative results were obtained with TA97, TA98, and TA1538 under all test conditions, and acrolein gave negative results in all four S. typhimurium strains tested for mutation induction under a vapor protocol. No induction of micronuclei was noted in bone marrow erythrocytes of male rats administered allyl acetate by gavage three times at 24-hour intervals. No significant increases in micronucleated erythrocytes were noted in bone marrow samples from male rats administered allyl alcohol by intraperitoneal injection for 3 days. A small, but significant increase in the frequency of micronucleated normochromatic erythrocytes was observed in the peripheral blood of female mice administered allyl acetate by gavage for 14 weeks; no increase was observed in male mice. No increases in the frequencies of micronucleated normochromatic erythrocytes were observed in the peripheral blood of male or female mice administered allyl alcohol or acrolein by gavage for 14 weeks. Acrolein induced sister chromatid exchanges in cultured Chinese hamster ovary cells in the absence, but not the presence, of S9; it did not induce chromosomal aberrations, with or without S9. Results of three independent Drosophila melanogaster sex linked recessive lethal tests in which acrolein was administered to adult flies via feeding or injection and to larvae via feeding were negative.</p>\",\"PeriodicalId\":23116,\"journal\":{\"name\":\"Toxicity report series\",\"volume\":\" 48\",\"pages\":\"1-73, A1-H10\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2006-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Toxicity report series\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Toxicity report series","FirstCategoryId":"1085","ListUrlMain":"","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

摘要

醋酸烯丙酯、烯丙醇和丙烯醛用于制造洗涤剂、塑料、药品和化学品,并用作农业助剂和食品添加剂。雄性和雌性F344/N大鼠和B6C3F(1)小鼠分别灌胃醋酸烯丙酯、烯丙醇或丙烯醛14周。对鼠伤寒沙门菌、黑腹果蝇、培养的中国仓鼠卵巢细胞、大鼠骨髓红细胞和小鼠外周血红细胞进行遗传毒理学研究。每组10只雄性和10只雌性大鼠分别灌胃给药0、6、12、25、50或100 mg/kg体重的醋酸烯丙酯,0、1.5、3、6、12或25 mg/kg烯丙醇,或0、0.75、1.25、2.5、5或10 mg/kg含0.5%甲基纤维素的丙烯醛,每周5天,连续14周。每组10只雄性和雌性小鼠分别给予0、8、16、32、62.5或125 mg/kg醋酸烯丙酯,0、3、6、12、25或50 mg/kg烯丙醇,或0、1.25、2.5、5、10或20 mg/kg丙烯醛(0.5%甲基纤维素)灌胃,每周5天,连续14周。在醋酸烯丙酯大鼠研究中,100 mg/kg组雄性和雌性大鼠均在第8天死亡或死亡;没有其他人员死亡。在烯丙醇的研究中,除了一只6毫克/公斤的雌性大鼠外,所有大鼠都存活到研究结束。在丙烯醛大鼠研究中,10 mg/kg组的8只雄性和8只雌性在研究的第9周死亡。2.5和5 mg/kg组的2只雄性和1.25、2.5和5 mg/kg组的1或2只雌性也早死;其中两人死于灌胃事故。在醋酸烯丙酯小鼠研究中,125 mg/kg组的所有雄性和雌性在研究的第一周死亡。除了5名男性62.5 mg/kg和1名女性32 mg/kg外,所有其他早期死亡都是灌胃事故。在烯丙醇小鼠研究中,一只50 mg/kg雌性小鼠因灌胃事故死亡;所有其他动物都活到了研究结束。在丙烯醛小鼠研究中,给药20 mg/kg的所有雄性和雌性小鼠在研究的第一周死亡。除了一名男性和一名女性服用10毫克/公斤的药物外,所有其他早期死亡都与化学药物服用无关。在第一次给药后和14周研究结束时测定大鼠和小鼠尿液中3-羟丙基巯基酸(3-HPM)的浓度。在这两个时间点,服用醋酸烯丙酯或烯丙醇的动物尿液中3-HPM的浓度随剂量线性增加。在给药丙烯醛的动物中,3-HPM浓度在第一个时间点随剂量呈非线性增加。在研究结束时,丙烯醛给药动物尿液中3-HPM的浓度与给药剂量呈线性关系,最高给药浓度除外。由于尿液收集时未记录尿量,因此无法对这些数据进行完整的定量分析。给药12或50 mg/kg醋酸烯丙酯的雄性大鼠和给药10 mg/kg丙烯醛的雄性大鼠和雌性大鼠的最终平均体重和平均增重均显著低于载药对照组。在烯丙醇研究中,50 mg/kg组雄性小鼠的平均体重增加也小于载体对照组。在醋酸烯丙酯研究中,服用了剂量的雌性大鼠、雄性和雌性小鼠,在烯丙醇研究中,雄性和雌性大鼠和雌性小鼠,以及在丙烯醛研究中,雄性和雌性小鼠的最终平均体重和平均体重增加,大体上与各自的载体对照相似。与醋酸烯丙酯给药相关的临床表现包括100mg /kg组大鼠面色苍白、眼或鼻分泌物、绒毛皱褶、嗜睡、腹泻和消瘦,早期死亡小鼠嗜睡、呼吸异常、消瘦和绒毛皱褶。在丙烯醛研究中,10 mg/kg组大鼠的临床表现包括呼吸异常、眼或鼻分泌物、毛皱皱、消瘦和嗜睡。雄性大鼠给药25 mg/kg烯丙醇,雌性大鼠给药50 mg/kg醋酸烯丙酯或5、10 mg/kg丙烯醛,雄性小鼠给药10 mg/kg丙烯醛,肝脏重量均显著高于对照。给药10 mg/kg丙烯醛的雌性大鼠胸腺的绝对和相对重量明显低于对照。给药25 mg/kg烯丙醇的雌性大鼠在发情期的时间比对照大鼠长,而在发情期的时间比对照大鼠短。给药16或32 mg/kg醋酸烯丙酯后雌鼠的发情周期明显延长。100 mg/kg剂量组雄性和雌性大鼠肝脏、前胃和胸/腹部均观察到与醋酸烯丙酯处理相关的肉眼病变。 显微镜下,给药剂量为12 mg/kg及以上的雄性大鼠、给药剂量为25或50 mg/kg的雌性大鼠、给药剂量为32或62.5 mg/kg的雄性小鼠、给药剂量为16、32或62.5 mg/kg的雌性小鼠前胃鳞状上皮增生的发生率显著增加。100 mg/kg组大多数大鼠出现前胃坏死、出血和炎症,125 mg/kg雄性小鼠出血发生率增加;62.5、125 mg/kg组雄性小鼠和125 mg/kg组雌性小鼠腺性胃出血发生率显著增加。在给药50或100 mg/kg的雄性或雌性大鼠中,几种肝脏病变的发生率增加,在25 mg/kg的大鼠、62.5 mg/kg的雄性小鼠和125 mg/kg的雄性和雌性小鼠中发生率较低。100 mg/kg大鼠骨髓增生,纵膈、下颌骨、肠系膜淋巴结出血或衰竭,胸腺出血坏死,红髓造血细胞增殖。62.5和125 mg/kg小鼠下颌骨和肠系膜淋巴结、脾脏和胸腺坏死发生率增加。雄性和雌性大鼠给予6 mg/kg或以上烯丙醇,雄性和雌性小鼠给予12 mg/kg或以上烯丙醇,前胃上皮鳞状增生的发生率显著增加。25 mg/kg组雌性大鼠肝脏胆管增生和门静脉周围肝细胞肥大的发生率显著增加。50 mg/kg组雄性小鼠和50 mg/kg组雌性小鼠门静脉细胞质空泡的发生率显著增加。10 mg/kg剂量组和20 mg/kg剂量组雌雄大鼠前胃和腺胃均观察到与丙烯醛处理相关的大体病变。显微镜下,5、10 mg/kg剂量组雄性大鼠、2.5 mg/kg及以上剂量组雌性大鼠、2.5、5、10 mg/kg剂量组雄性和雌性小鼠前胃上皮鳞状增生的发生率均显著增加。10 mg/kg组和20 mg/kg组雄性和雌性大鼠胃腺出血发生率显著增加。20 mg/kg组雌性小鼠的胃腺炎和上皮坏死发生率也显著增加。在没有S9激活的情况下,醋酸烯丙酯对鼠伤寒沙门氏菌TA100和TA1535具有诱变作用。S9对两株均无致突变性;菌株TA97和TA98在含S9和不含S9的情况下均为阴性。烯丙醇对4株鼠伤寒沙门氏菌均无诱变作用,无论是否有S9代谢激活。丙烯醛,在孵育前测试方案中,在10%诱导的大鼠肝脏S9存在的情况下,对鼠伤寒沙门氏菌菌株TA100具有弱致突变性。TA100和TA1535菌株用10%诱导的仓鼠肝脏S9得到的结果不明确。TA97、TA98和TA1538在所有试验条件下均为阴性,丙烯醛在水蒸气诱导突变试验中对4株鼠伤寒沙门氏菌均为阴性。每隔24小时灌胃3次醋酸烯丙酯对雄性大鼠骨髓红细胞无诱导微核作用。雄性大鼠腹腔注射丙烯醇3天后,骨髓样品中微核红细胞未见明显增加。灌胃醋酸烯丙酯14周后,雌鼠外周血微核正染红细胞出现频率明显增加;在雄性小鼠中未观察到增加。经灌胃给予烯丙醇或丙烯醛14周后,雌雄小鼠外周血微核正染红细胞的频率均未见增加。丙烯醛在不存在S9的情况下诱导中国仓鼠卵巢细胞姊妹染色单体交换;无论有无S9,它都不会引起染色体畸变。在三种独立的黑腹果蝇性别相关隐性致死试验中,丙烯醛分别通过喂食或注射给成蝇和通过喂食给幼虫,结果均为阴性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
NTP Technical Report on the comparative toxicity studies of allyl acetate (CAS No. 591-87-7), allyl alcohol (CAS No. 107-18-6) and acrolein (CAS No. 107-02-8) administered by gavage to F344/N rats and B6C3F1 mice.

Allyl acetate, allyl alcohol, and acrolein are used in the manufacture of detergents, plastics, pharmaceuticals, and chemicals and as agricultural agents and food additives. Male and female F344/N rats and B6C3F(1) mice received allyl acetate, allyl alcohol, or acrolein by gavage for 14 weeks. Genetic toxicology studies were conducted in Salmonella typhimurium, Drosophila melanogaster, cultured Chinese hamster ovary cells, rat bone marrow erythrocytes, and mouse peripheral blood erythrocytes. Groups of 10 male and 10 female rats were administered 0, 6, 12, 25, 50, or 100 mg allyl acetate/kg body weight, 0, 1.5, 3, 6, 12, or 25 mg/kg allyl alcohol, or 0, 0.75, 1.25, 2.5, 5, or 10 mg/kg acrolein in 0.5% methylcellulose by gavage, 5 days per week for 14 weeks. Groups of 10 male and 10 female mice were administered 0, 8, 16, 32, 62.5, or 125 mg/kg allyl acetate, 0, 3, 6, 12, 25, or 50 mg/kg allyl alcohol, or 0, 1.25, 2.5, 5, 10, or 20 mg/kg acrolein in 0.5% methylcellulose by gavage, 5 days per week for 14 weeks. In the allyl acetate rat study, all males and females in the 100 mg/kg groups died or were killed moribund by day 8; there were no other deaths. In the allyl alcohol study, all rats survived to the end of the study except one 6 mg/kg female. In the acrolein rat study, eight males and eight females in the 10 mg/kg groups died by week 9 of the study. Two males in the 2.5 and 5 mg/kg groups and one or two females in the 1.25, 2.5, and 5 mg/kg groups also died early; two of these deaths were gavage accidents. In the allyl acetate mouse study, all males and females in the 125 mg/kg group died during the first week of the study. All other early deaths, except five 62.5 mg/kg males and one 32 mg/kg female, were gavage accidents. In the allyl alcohol mouse study, one 50 mg/kg female died due to a gavage accident; all other animals survived to the end of the study. In the acrolein mouse study, all males and females administered 20 mg/kg died during the first week of the study. All other early deaths, except one male and one female administered 10 mg/kg, were unrelated to chemical administration. The concentration of 3-hydroxypropyl mercapturic acid (3-HPM) in the urine of rats and mice was determined after the first dose of chemical and at the end of the 14-week study. At both time points, the concentrations of 3-HPM in the urine of animals that received allyl acetate or allyl alcohol increased linearly with dose. In animals dosed with acrolein, the concentrations of 3-HPM exhibited a nonlinear increase with dose at the first time point. At the end of the study, the concentration of 3-HPM in the urine of animals dosed with acrolein was linear with dose except at the highest concentration administered. Since urine volumes were not recorded during the urine collection, complete quantitation of these data was not possible. The final mean body weights and mean body weight gains of male rats administered 12 or 50 mg/kg allyl acetate and of male and female rats administered 10 mg/kg acrolein were significantly less than those of the vehicle controls. The mean body weight gain of male mice in the 50 mg/kg group in the allyl alcohol study was also less than that of the vehicle controls. Final mean body weights and mean body weight gains of dosed female rats and male and female mice in the allyl acetate studies, male and female rats and female mice in the allyl alcohol studies, and male and female mice in the acrolein studies were generally similar to those of the respective vehicle controls. Clinical findings related to allyl acetate administration included pallor, eye or nasal discharge, ruffled fur, lethargy, diarrhea, and thinness among rats in the 100 mg/kg groups and lethargy, abnormal breathing, thinness, and ruffled fur among mice that died early. In the acrolein study, clinical findings included abnormal breathing, eye or nasal discharge, ruffled fur, thinness, and lethargy in rats in the 10 mg/kg groups. The liver weights of male rats administered 25 mg/kg allyl alcohol, female rats administered 50 mg/kg allyl acetate or 5 or 10 mg/kg acrolein, and male mice administered 10 mg/kg acrolein were significantly greater than those of the vehicle controls. Female rats administered 10 mg/kg acrolein had significantly lower absolute and relative thymus weights than did the vehicle controls. Female rats administered 25 mg/kg allyl alcohol spent more time in diestrus and less time in metestrus than the vehicle controls. The estrous cycles of female mice dosed with 16 or 32 mg/kg allyl acetate were significantly longer than that of the vehicle controls. Gross lesions related to allyl acetate treatment were observed in the liver, forestomach, and thorax/abdomen of male and female rats in the 100 mg/kg groups. Microscopically, the incidences of forestomach squamous epithelial hyperplasia were significantly increased in male rats administered 12 mg/kg or greater, female rats administered 25 or 50 mg/kg, male mice administered 32 or 62.5 mg/kg, and female mice administered 16, 32, or 62.5 mg/kg. Forestomach necrosis, hemorrhage, and inflammation were present in most rats in the 100 mg/kg groups, and the incidence of hemorrhage in 125 mg/kg male mice was increased; male mice in the 62.5 and 125 mg/kg groups and 125 mg/kg female mice had significantly increased incidences of glandular stomach hemorrhage. Increased incidences of several liver lesions occurred in male or female rats administered 50 or 100 mg/kg, and to a lesser extent in 25 mg/kg rats, 62.5 mg/kg male mice, and 125 mg/kg male and female mice. Bone marrow hyperplasia, hemorrhage or depletion in the mediastinal, mandibular, and mesenteric lymph nodes, hemorrhage and necrosis of the thymus, and hematopoietic cell proliferation of the red pulp were also observed in 100 mg/kg rats. Increased incidences of necrosis in the mandibular and mesenteric lymph nodes, spleen, and thymus were observed in 62.5 and 125 mg/kg mice. Male and female rats administered 6 mg/kg allyl alcohol or greater and male and female mice administered 12 mg/kg allyl alcohol or greater had significantly increased incidences of squamous hyperplasia of the forestomach epithelium. Female rats in the 25 mg/kg group had significantly increased incidences of bile duct hyperplasia and periportal hepatocyte hypertrophy in the liver. Incidences of portal cytoplasmic vacuolization were significantly increased in 50 mg/kg male mice and female mice in the 25 and 50 mg/kg groups. Gross lesions related to acrolein treatment were observed in the forestomach and glandular stomach of male and female rats in the 10 mg/kg groups and 20 mg/kg female mice. Microscopically, the incidences of squamous hyperplasia of the forestomach epithelium were significantly increased in male rats in the 5 and 10 mg/kg groups, female rats administered 2.5 mg/kg or greater, and male and female mice administered 2.5, 5, or 10 mg/kg. Male and female rats in the 10 mg/kg groups and 20 mg/kg male and female mice had significantly increased incidences of glandular stomach hemorrhage. Female mice in the 20 mg/kg group also had significantly increased incidences of glandular stomach inflammation and epithelial necrosis. Allyl acetate was mutagenic in S. typhimurium strains TA100 and TA1535, in the absence of S9 activation. With S9, no mutagenicity was detected in these two strains; negative results were obtained in strains TA97 and TA98, with and without S9. Allyl alcohol was not mutagenic in four strains of S. typhimurium, with or without S9 metabolic activation. Acrolein, tested in a preincubation protocol, was weakly mutagenic in S. typhimurium strain TA100 in the presence of 10% induced rat liver S9. Equivocal results were obtained in strains TA100 and TA1535 with 10% induced hamster liver S9. Negative results were obtained with TA97, TA98, and TA1538 under all test conditions, and acrolein gave negative results in all four S. typhimurium strains tested for mutation induction under a vapor protocol. No induction of micronuclei was noted in bone marrow erythrocytes of male rats administered allyl acetate by gavage three times at 24-hour intervals. No significant increases in micronucleated erythrocytes were noted in bone marrow samples from male rats administered allyl alcohol by intraperitoneal injection for 3 days. A small, but significant increase in the frequency of micronucleated normochromatic erythrocytes was observed in the peripheral blood of female mice administered allyl acetate by gavage for 14 weeks; no increase was observed in male mice. No increases in the frequencies of micronucleated normochromatic erythrocytes were observed in the peripheral blood of male or female mice administered allyl alcohol or acrolein by gavage for 14 weeks. Acrolein induced sister chromatid exchanges in cultured Chinese hamster ovary cells in the absence, but not the presence, of S9; it did not induce chromosomal aberrations, with or without S9. Results of three independent Drosophila melanogaster sex linked recessive lethal tests in which acrolein was administered to adult flies via feeding or injection and to larvae via feeding were negative.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信