REPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN RATS WITH ORALLYADMINISTERED 1-HEXENE

摘要

This study was conducted to provide screening information concerning the potential systemic, reproductive and developmental toxicity of 1-hexene when administered orally,by gavage, to male and female rats using a modified OECD 421 protocol. 1-Hexene was administered at doses of 100,500,and 1000mg/kg/day in corn oil;the control group received the vehicle at an equivalent volume. The males were treated for 28 days prior to mating and until euthanasia (44 days of dosing). The females were treated for 14 days prior to mating and during mating, gestation, and lactation until euthanasia (41-55 total days of dosing).Females were allowed to deliver and rear their offspring until lactation day 4. The parental rats were subject ot a gross and microscopic examination. Viability and deevelopment of the pups were followed through lactation day 4. There was no mortality, and there were no clinical signs of toxicity or differences in body weights, weight gain,feed consumption or organ weights. Copulation and fertility indices,precoital intervals,gestation lengths and preganancy rates were comparable among the groups,and no signs of prolonged delivery or unusual nesting behaviours were noted. Pud viability,body weights, external observations and necropsy data were comparable among the groups. Pitted kidneys were observed at necropsy for two parental males in the 500mg/kg/day group and three males in the 1000mg/kg/day group. Microscopic changes in the kidneys of some male rats from the 100,500,and 1000mg/kg/day groups consisted of dose-related accumulations of hyaline dropletsin the epithelial cells of theproximal convoluted tubules of the kidneys. In summary,the only treatment-related effect noted in this study was hydrocarbon nephropathy in male rats,which is not considered relevant for human health. The NOAEL for systemic and reproductive toxicity was 1000mg/kg/day,excluding the finding of male rat hydrocarbon nephropathy.