Ahmad Rahish, Verma Yogendra, Gautam Anil K, Kumar Sunil
Division of Reproductive and Cytotoxicology, National Institute of Occupational Health (ICMR), Ahmedabad, Gujarat, India.
Division of Reproductive and Cytotoxicology, National Institute of Occupational Health (ICMR), Ahmedabad, Gujarat, India
Toxicol Ind Health. 2015 Dec;31(12):1296-303. doi: 10.1177/0748233713491803. Epub 2013 Jul 5.
Phthalate compounds are widely used industrial chemicals; when incorporated into polyvinyl chloride, they are not covalently bound and released into the surrounding media. Some of them have estrogenic potential in vitro but data on in vivo studies are scanty. For the 3-day uterotrophic assay, di-n-butyl phthalate (DBP;10 and 100 mg/kg), butyl benzyl phthalate (BBP; 20 and 200 mg/kg), and diethylstilbestrol (DES, 40 µg/kg, positive control) were administered orally to immature female rats for three consecutive days from postnatal day (PND) 21. For the 20-day pubertal onset assay, DBP (10 and 20 mg/kg), BBP (20 and 200 mg/kg), and DES (6 µg/kg) were administered orally from PND 21 daily for 20 days. In the uterotrophic assay, in groups treated with higher dose of DBP and BBP, the uterine wet weight significantly decreased in the higher dose, and there were minor variations in the ovary wet weight, while the wet weight of these organs increased significantly in DES-treated group. In the 20-day pubertal assay, the weight of uterus and ovary declined significantly and changes in vaginal weight were nonsignificant in DBP- and BBP-treated groups. However, in DES-treated group nonsignificant elevation in vagina weight was observed. All the DES-treated animals showed the vaginal opening (VO) on day 26.17 ± 0.16. However, VO was not observed in any of the animals in control, vehicle control, BBP-, and DBP-treated groups up to PND 42, except in one animal each in vehicle control and DBP (100 mg/kg)-treated groups. The data indicated that both DBP and BBP were unable to induce elevation in the uterine and ovarian weight. While DES treatment can accelerate the growth of uterus and ovary and alter the onset of puberty and estrous cyclicity in prepubertal rats. These suggest that these compounds may not have estrogenic potential in vivo.
邻苯二甲酸酯类化合物是广泛使用的工业化学品；当它们被掺入聚氯乙烯中时，它们并非共价结合，而是会释放到周围介质中。其中一些在体外具有雌激素活性，但体内研究数据较少。在为期3天的子宫增重试验中，从出生后第21天（PND）开始，连续三天给未成熟雌性大鼠口服邻苯二甲酸二丁酯（DBP；10和100毫克/千克）、邻苯二甲酸丁苄酯（BBP；20和200毫克/千克）以及己烯雌酚（DES，40微克/千克，阳性对照）。在为期20天的青春期启动试验中，从PND 21开始，每天给大鼠口服DBP（10和20毫克/千克）、BBP（20和200毫克/千克）以及DES（6微克/千克），持续20天。在子宫增重试验中，在接受较高剂量DBP和BBP处理的组中，较高剂量下子宫湿重显著降低，卵巢湿重有微小变化，而在DES处理组中这些器官的湿重显著增加。在为期20天的青春期试验中，DBP和BBP处理组的子宫和卵巢重量显著下降，阴道重量变化不显著。然而，在DES处理组中观察到阴道重量有不显著的升高。所有DES处理的动物在第26.17±0.16天出现阴道开口（VO）。然而，在对照组、溶剂对照组、BBP和DBP处理组中，直到PND 42，除了溶剂对照组和DBP（100毫克/千克）处理组各有一只动物外，没有任何动物出现VO。数据表明，DBP和BBP均无法诱导子宫和卵巢重量增加。而DES处理可加速青春期前大鼠子宫和卵巢的生长，并改变青春期和发情周期的开始。这些表明这些化合物在体内可能没有雌激素活性。
