Acute and subchronic toxicity of tetramethylcyclohexanes

The acute oral toxicity in rats was estimated for seven isomers or isomeric ratios of tetramethylcyclohexane (TMCH). Lack of sufficient mortality at the highest dosage test (15.8 g/kg) precluded evaluation of an LD50 for mixed cis, trans-isomers of 1,2,3,4-TMCH, 1,2,3,5-TMCH, 1,2,4,5-TMCH and 1,1,2,3-TMCH, for the separate cis- or trans-forms of 1,1,3,5-TMCH or a 1:1 mixture of c,t-1,1,3,5-TMCH and c,t-1,2,3,4-TMCH. Mixed (c,t-combined) isometric TMCH was administered orally to rats (30/group) and dogs (8/group) for 90 days at dietary levels of 0, 3000, 10,000 and 30,000 ppm TMCH and 0, 100, 300 and 1000 ppm TMCH, respectively. Administration of up to 30,000 TMCH to rats produced no discernible effects on survival, behavior, growth, food consumption, clinical blood picture or urine analysis. Absolute kidney weights of male but not female rats were elevated at all test levels. TMCH-related microscopic lesions were confined to the kidney of male rats in all treated groups. These histopathologic changes were characteristic of tubular nephrosis. No treatment-related effects were observed in groups of dogs fed up to 1000 ppm TMCH for 90 days.