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Contamination of the environment with endocrine-disrupting chemicals (EDC) has raised concerns about potential health hazards for humans and wildlife. Human and wildlife exposure to one such ubiquitous chemical, p-tert-octylphenol (OP), are likely, due to its persistence in the environment and its presence in food, water, and items of daily use. OP is reported to bind to the estrogen receptor (ER) and alter expression of estrogen-responsive genes. Detrimental effects of OP exposures on the reproductive system have been observed in most, but not all, in vivo experiments. This study examined estrogenic effects of oral exposures of adult female rats to OP. In vitro, OP bound weakly to human ER and a co-activator protein, and accelerated proliferation of MCF-7 cells. Adult Sprague-Dawley rats were given OP by gavage daily for 35 d (25, 50, or 125 mg/kg/d). Body and organ weights and ovarian follicle populations were not significantly altered in OP-exposed adult rats, despite detectable levels of OP in reproductive organs. The estrous cycle of rats was slightly altered, but there were no significant estrogen-like changes in histomorphology or gene expression of the uterus. Prepubertal rats given 125 or 250 mg/kg OP by gavage for 3 d had reduced body weight compared to vehicle-exposed rats but failed to show any uterotrophic response, although 17α-ethinyl estradiol (EE, 10μg/kg/d, ip) induced a threefold increase in uterine weight. Overall, results suggest that toxicity will occur before estrogenic effects with oral exposures to OP. Relevant environmental exposures likely pose little risk for estrogenic effects. [ABSTRACT FROM AUTHOR]

Mammalian development is an extremely sensitive process and susceptible to a myriad of disruptions during various stages of embryonic and fetal development. Retinoic acid (RA), a variant of Vitamin A, is an essential component in normal mammalian development as well as adult growth and fluctuations in its levels during critical stages can result in a multitude of teratogenic/embryotoxic/toxic outcomes. An established teratogen, RA has been identified to affect neural tube and limb development. As a part of the developing reproductive-embryofetal toxicology facility at LAB Research Inc., timed-pregnant Sprague Dawley (SD) rats were orally administered (10 mL/kg) with 0, 5, 10, 20, 30 mg/kg RA in dimethylsulfoxide (DMSO; doses selected based on literature as well as a pilot study in non-pregnant adult female SD rats) from gestation day (GD) 6 to 17. Maternal body weights (BW) and food consumption (FC) were monitored throughout the gestation period. Pups were delivered by cesarean on GD21 and an external as well as internal exam was performed. RA treatment at 30mg/kg resulted in the death of 1 damon GD 14. The treated dams showed abnormal and uncoordinated behavior with salivation, decreased activity with partially closed eyes. RA treatment reduced maternal FC and consequently the BW between GD 7 to 12. BWs remained lower in RA treated animals throughout the remainder of gestation. At 30 mg/kg, RA resulted in a complete resorption of conceptus during early pregnancy. In the remaining treatment groups, up to 60-fold increase in the number of resorptions and 62-fold decrease in the number of live fetuses was noticed. The pups in the RA treated dams were relatively smaller in size and exhibited external malformations such as exencephaly, along with skeletal malformations in the rib cage and vertebral column. The above results were consistent with results published by other researchers and thus demonstrated that the laboratory’s procedures and evaluation methods were suitable for identification of RA induced effects on embryofetal development and maternal toxicity in Sprague Dawley rats. [ABSTRACT FROM AUTHOR]