Reproduction/Developmental Toxicity Screening Test in Rats with 1-hexene, with Cover Letter dated 11/7/95

摘要

The systemic, reproductive and developmental toxicity of 1-hexene (592-41-6) was evaluated in 4 groups of male and female Sprague-Dawley CD rats (12/sex/group) administered 5 mL/kg in corn oil by oral gavage. Doses of 0, 100, 500, and 1,000 mg/kg/day were dispensed to F0 males from 28 days prior to mating until euthanasia (44 days); gestation and lactation until euthanasia (41-55 days). The surviving F1 progeny were euthanized and necropsied on lactation Day 4. No mortality or clinical effects of treatment were noted at any dose level throughout study in the FO animals. Neither were there any statistically significant inconsistencies between treatment and control groups in mean bodyweights, weight gain, food consumption or organ weight. Reproductive measures, including copulation and fertility indices, precoital intervals, gestation lengths, and pregnancy rates were unremarkable, and no instances of prolonged delivery or unusual nesting behaviors were observed. Upon terminal necropsy, pitted kidneys were noted in treated F0 male rats of 500 and 1000 mg/kg groups. Microscopic examination of kidney tissue from male F0 rats at all treatment levels revealed inclusions (hyalin droplets) in epithelial cells of the proximal convoluted tubules. While no specific assay for alpha 2u-globulin was performed, researchers reported these findings compatible with an alpha 2u-globulin associated nephropathy specific to young adult male rats, but not reflective of a potential risk to humans. Microscopic examination of other select tissues, including ovaries, testes, epididymides, liver and peripheral (sciatic) nerve of control and treated F0 rats was negative. Likewise, the viability, bodyweight, developmental and necropsy data of F1 pups were comparable to those of controls.