Evaluation of chronic toxicity and carcinogenicity of ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate in Sprague-Dawley rats.
Evaluation of chronic toxicity and carcinogenicity of ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate in Sprague-Dawley rats.
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DOI：
10.1016/j.toxrep.2015.06.001
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发表时间：
2015
影响因子：
--
通讯作者：
Kennedy GL
中科院分区：
文献类型：
--
作者：
Caverly Rae JM;Craig L;Slone TW;Frame SR;Buxton LW;Kennedy GL
在Sprague-Dawley大鼠2年经口给药研究中，检测了2，3，3，3-四氟-2-（七氟丙氧基）-丙酸铵（开发用作含氟聚合物生产中的聚合加工助剂）的潜在慢性毒性和致癌性。雄性大鼠每日给药剂量为0、0.1、1或50 mg/kg;雌性大鼠每日给药剂量为0、1、50或500 mg/kg。每天监测体重、摄食量和临床体征;在指定时间间隔进行临床病理学检查，并在给药12个月和24个月后对动物进行完整的病理学评价。在所有组中均观察到正常存活，未观察到异常临床体征，仅在500 mg/kg剂量组雌性大鼠中体重增加减少。高剂量组两种性别动物的红细胞量均轻度降低，雌性动物的降低更为明显。接受50 mg/kg剂量的雄性动物中存在指示肝损伤的临床病理学，并与组织形态学肝脏变化相关，包括肥大和退行性/坏死病变。在500 mg/kg剂量组雌性动物的肝脏中观察到相似的组织形态学病变。先前的短期毒性研究已将该化学品确定为一种PPARα激动剂，并且在50 mg/kg剂量组雄性和500 mg/kg剂量组雌性动物中发现的肝脏、胰腺和/或睾丸良性肿瘤与大鼠对过氧化物酶体增殖物的反应一致，并且与人类的相关性值得怀疑。仅在最高剂量500 mg/kg的雌性动物中观察到肾脏、舌和胃的变化。本研究中，雄性动物的无明显不良作用水平为1 - 50 mg/kg，雌性动物为50 - 500 mg/kg。
Ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate, developed for use as a polymerization processing aid in the manufacture of fluoropolymers, was tested for its potential chronic toxicity and carcinogenicity in a 2-year oral dosing study in Sprague–Dawley rats. Male rats were given daily doses of either 0, 0.1, 1 or 50 mg/kg; females were given either 0, 1, 50 or 500 mg/kg. Body weights, food consumption and clinical signs were monitored daily; clinical pathology was conducted at designated intervals and animals were given a complete pathological evaluation after 12 months and 24 months of dosing. Normal survival was seen in all groups, no abnormal clinical signs were seen, and body weight gain was reduced only in female rats at 500 mg/kg. Both sexes at the high dose had mild decreases in red cell mass which were somewhat more pronounced in females. Clinical pathology indicative of liver injury was present in males that received 50 mg/kg and correlated with histomorphological liver changes that included both hypertrophic and degenerative/necrotic lesions. Similar histomorphological lesions were seen in the livers of females at 500 mg/kg. Previous shorter term toxicity studies have identified this chemical as a PPARα agonist and the finding of benign tumors of the liver, pancreas and/or testes in males at 50 mg/kg and females at 500 mg/kg is consistent with the rat response to peroxisome proliferators and is of questionable human relevance. Changes in the kidney, tongue, and stomach were observed only at the highest dose of 500 mg/kg in females. The no-observed-adverse-effect-level in this study lies between 1 and 50 mg/kg for males and between 50 and 500 mg/kg for females.