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邻苯二甲酸二乙酯的慢性毒性——雄性 Wistar 大鼠三代泌乳和妊娠期暴露研究。

Chronic toxicity of diethyl phthalate-A three generation lactational and gestational exposure study on male Wistar rats.

机构信息

Department of Zoology, St. Xavier's College, Mumbai 400001, India.

出版信息

Environ Toxicol Pharmacol. 2007 May;23(3):319-27. doi: 10.1016/j.etap.2006.12.005. Epub 2007 Jan 8.

DOI:10.1016/j.etap.2006.12.005
PMID:21783775
Abstract

Diethyl phthalate (DEP) is widely used in the perfume industry as a vehicle for fragrances and in personal care products making human exposure of DEP significant to adults as well as neonatals, as confirmed by levels recorded in blood as well as breast milk samples of human populations in some parts of the world. Therefore, a study was undertaken to understand the toxic effect of DEP over three generations in male Wistar rats. Healthy male and female albino rats of Wistar strain weighing 75-100g (6-7 weeks old) were randomly assigned to two groups of six each. Group I (Control) male and female rats were fed on normal diet and water ad libitum. Group II (DEP) male and female rats were given DEP dissolved in corn oil mixed with the diet at 50mg/kg of the diet/day. Hundred days after the treatment, females were mated with males for 10 days. Exposure to DEP was continued throughout mating, gestation until termination at weaning, which was 150 days of total treatment period of the parental generation. The F1 and F2 generation pups were then segregated on the basis of their sex and six male and female pups of both generations were allowed to grow till they were 75-100g in weight. The treatment was then carried out similar to the parental generation but with reduced dose of 25mg/kg of the diet/day for F1 generation and 10mg/kg of the diet/day for F2 generation. Hundred days after the treatment, females were mated with males for 10 days. Exposure to DEP was continued throughout mating, gestation (21 days) until termination at weaning (21 days), which was 150 days of total treatment period of the F1 and F2 generation. Liver and serum ALT, AST and triglycerides were significantly increased over the three generations, which was much more significant in the F2 generation DEP treated group. The serum cholesterol and liver glutathione and glutathione reductase showed a significant decrease over the three generations, which was much more significant in the F2 generation DEP treated group as compared to the parental and F1 generation DEP treated rats. Histology of the liver showed remarkably enhanced fatty degeneration in the F2 generation DEP treated rats as compared to parental and F1 generation DEP treated rats. Vacuolations were much more significant in the F1 generation DEP treated rats as compared to the controls and F2 generation DEP treated rats. It can be concluded from this study, that continuous exposure through food, gestation and lactation over three generation's inspite of dose reduction of DEP leads to an enhanced toxic effect in the latter generations.

摘要

邻苯二甲酸二乙酯(DEP)广泛用于香水行业和个人护理产品中,这使得成人和新生儿都大量接触 DEP,这一点从世界某些地区的人群血液和母乳样本中的含量可以得到证实。因此,进行了一项研究,以了解 DEP 在雄性 Wistar 大鼠中经过三代的毒性作用。将 75-100g(6-7 周龄)重的健康雄性和雌性白化 Wistar 大鼠随机分为两组,每组 6 只。第 I 组(对照组)的雄性和雌性大鼠给予正常饮食和自由饮水。第 II 组(DEP 组)的雄性和雌性大鼠给予溶于玉米油的 DEP,与饮食混合,每日每公斤体重 50mg/kg。治疗 100 天后,雌性大鼠与雄性大鼠交配 10 天。交配、妊娠直至断奶(共 150 天的总治疗期)期间持续接触 DEP。然后根据性别将 F1 和 F2 代幼崽分开,每代 6 只雄性和雌性幼崽长到 75-100g 体重。然后以与亲代相同的方式进行治疗,但降低 F1 代饮食的剂量至 25mg/kg/天,F2 代饮食的剂量至 10mg/kg/天。治疗 100 天后,雌性大鼠与雄性大鼠交配 10 天。交配、妊娠(21 天)直至断奶(21 天)期间持续接触 DEP,这是 F1 和 F2 代的总治疗期为 150 天。三代大鼠的血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)和甘油三酯显著升高,F2 代 DEP 处理组更为显著。血清胆固醇和肝谷胱甘肽及谷胱甘肽还原酶显著降低,F2 代 DEP 处理组比亲代和 F1 代 DEP 处理组更为显著。与亲代和 F1 代 DEP 处理组大鼠相比,F2 代 DEP 处理组大鼠的肝组织显示出明显增强的脂肪变性。与对照组和 F2 代 DEP 处理组相比,F1 代 DEP 处理组的空泡化更为显著。从这项研究可以得出结论,尽管 DEP 的剂量减少,但通过食物、妊娠和哺乳连续暴露三代会导致后代毒性作用增强。

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