Combined repeated-dose and reproductive/developmental oral toxicity of 3-methylpentane, isooctane, and isononane in rats

ABSTRACT — 3-Methylpentane, isooctane, and isononane are acyclic branched saturated hydrocarbons with carbon numbers C6, C8, and C9, respectively. To assess human risk, we conducted a combined repeated-dose and reproductive/developmental oral toxicity studies in rats. [Organization for Economic Co-operation and Development (OECD) Test Guideline 422]. Each hydrocarbon was administered by gavage to rats at three doses (plus a control group). All three chemicals targeted the liver and kidney. An increase in liver weight without hepatic injury was observed as the adaptive response to the chemical treatments. Males treated by each chemical showed α2u-globulin nephropathy, which is a rat-specific finding that bears no human relevance. Reproduction/developmental toxicity parameters showed no treatment-related effects in parents or offspring at any dose for the three chemicals, except for the retardation of offspring bodyweight development which may be a secondary effect of a maternal systemic condition or direct effect on offspring in isononane. No observed adverse effect levels (NOAELs) of repeated toxicity in either sex were determined to be 300 mg/kg/day for 3-methylpentane, 100 mg/kg/day for isooctane, and 250 mg/kg/day for isononane. NOAELs of reproductive/developmental toxicity in parents and offspring were determined to be 1000 mg/kg/day for 3-methylpentane, and 300 mg/kg/day for isooctane. For isononane, NOAELs were determined to be 1000 mg/kg/day for reproduction, and 250 mg/kg/day for offspring development. These results provide new toxicological information and support the category assessment of published reports that evaluate the acyclic branched saturated hydrocarbons as low-toxicity substances.