国家毒理学规划(NTP)关于F344/N大鼠和B6C3F1小鼠吸入甲酸毒性研究的技术报告(CAS No. 64-18-6)。

Toxicity report series Pub Date : 1992-07-01
Morrow Thompson
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引用次数: 0

摘要

甲酸存在于多种植物和水果、哺乳动物组织和昆虫毒液中。它在工业上用于制备各种药物、染料和化学品;作为脱钙剂;还有制革。甲酸也是一种空气和水的环境污染物,已被确定为甲醇中毒的有毒中间体(甲酸酯)。对F344/N大鼠和B6C3F1小鼠进行了2周和13周的甲酸毒性研究,方法是全身吸入甲酸蒸气。此外,鼠伤寒沙门氏菌进行了体外遗传毒性研究,有或没有代谢激活。甲酸在本实验中不具有诱变作用。在为期两周的研究中,每组5只F344/N大鼠和5只B6C3F1小鼠,每周5天,每天6小时暴露于浓度为0、31、62.5、125、250或500 ppm的甲酸中。暴露于百万分之500(大鼠和小鼠)和百万分之250(1只雌性小鼠)的动物发生死亡。暴露于62.5 ppm及更高浓度的大鼠和小鼠发生呼吸和嗅觉上皮显微病变,其严重程度与暴露浓度相关。病变包括鳞状化生、坏死和炎症。在为期两周的研究中,暴露对大鼠的凝血时间、血液pH值和电解质或尿液分析物的浓度和活性的影响很小或没有影响。在为期13周的研究中,每组10只动物,每种物种和性别,每周5天,每天6小时暴露在浓度为0、8、16、32、64和128 ppm的甲酸中。两只老鼠,一只雄性和一只雌性,在128ppm的浓度组中死亡。暴露于64 ppm和128 ppm甲酸的小鼠体重增加明显减少。大鼠和小鼠的微观变化从轻微到轻微的严重程度不等,通常仅限于128ppm组的动物。与暴露于甲酸相关的病变分别包括鳞状皮化生和呼吸上皮和嗅觉上皮的变性。中期和终末时间点的血液学和血清生化变化极小至轻微,通常与血液浓度一致。总的来说,甲酸的作用与吸入刺激性化学物质的作用一致。大鼠和小鼠呼吸损伤的未观察到不良反应水平(NOAEL)为32 ppm。在这些研究中没有明显的系统性毒性证据。同义词:氨基酸,甲酸,甲醇酸,氢羧酸。
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NTP technical report on the toxicity studies of Formic Acid (CAS No. 64-18-6) Administered by Inhalation to F344/N Rats and B6C3F1 Mice.

Formic acid occurs in a variety of plants and fruits, mammalian tissues, and insect venoms. It is used industrially in preparing a variety of drugs, dyes, and chemicals; as a decalcifier; and in leather tanning. Formic acid also is an environmental contaminant of air and water and has been identified as the toxic intermediate (formate) in methanol poisoning. Two- and 13-week toxicity studies of formic acid were conducted in male and female F344/N rats and B6C3F1 mice by whole body inhalation exposure to formic acid vapors. In addition, in vitro genetic toxicity studies were performed with Salmonella typhimurium, with or without metabolic activation. Formic acid was not mutagenic in this assay. In 2-week studies, groups of 5 F344/N rats and 5 B6C3F1 mice of each sex were exposed to formic acid for 6 hours a day, 5 days a week, at concentrations of 0, 31, 62.5, 125, 250, or 500 ppm. Deaths occurred in animals exposed to 500 ppm (rats and mice) and 250 ppm (1 female mouse). Microscopic lesions in the respiratory and olfactory epithelia occurred in rats and mice exposed to 62.5 ppm and higher concentrations, with the severity related to the exposure concentration. The lesions consisted of squamous metaplasia, necrosis, and inflammation. Exposures had minimal or no effects on coagulation times, blood pH and electrolytes, or on concentrations and activities of urine analytes in rats during the 2-week studies. In 13-week studies, groups of 10 animals of each species and sex were exposed to formic acid at concentrations of 0, 8, 16, 32, 64, and 128 ppm for 6 hours a day, 5 days a week. Two mice, 1 male and 1 female, died in the 128 ppm groups. Body weight gains were significantly decreased in mice exposed to 64 and 128 ppm formic acid. Microscopic changes in rats and mice ranged from minimal to mild in severity and generally were limited to animals in the 128 ppm groups. Lesions related to exposure to formic acid consisted of squamous metaplasia and degeneration of the respiratory and olfactory epithelia, respectively. Hematologic and serum biochemical changes at interim and terminal time points were minimal to mild and, generally, were consistent with hemoconcentration. Overall, the effects of formic acid were consistent with those of irritant chemicals administered by inhalation exposure. The no-observed-adverse-effect level (NOAEL) for respiratory injury was 32 ppm in rats and mice. There was no significant evidence of systemic toxicity in these studies. Synonyms: Aminic Acid, Formylic Acid, Methanoic Acid, Hydrogen Carboxylic Acid.

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Toxicity studies of acetoin and 2,3-pentanedione administered by inhalation to Wistar Han [Crl:WI(Han)] rats and B6C3F1/N mice. Toxicity studies of sodium metavanadate and vanadyl sulfate administered in drinking water to Sprague Dawley (Hsd:Sprague Dawley SD) rats and B6C3F1/N mice. Toxicity studies of (+)-usnic acid administered in feed to F344/N Nctr rats and B6C3F1/Nctr mice. Toxicity studies of Usnea lichens containing (+/-)-usnic acid administered in feed to F344/N Nctr rats and B6C3F1/Nctr mice. Toxicity studies of trans-resveratrol administered by gavage for two weeks or three months to F344/NTac rats, Wistar Han [Crl:WI(Han)] rats, and B6C3F1/N mice.
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