Comparative chronic toxicities and carcinogenic potentials of 2-ethylhexyl-containing compounds in rats and mice

Four compounds containing a 2-ethylhexyl moiety [di(2-ethylhexyl)phthalate (DEHP), di(2-ethylhexyl)adipate (DEHA), tris(2-ethylhexyl)phosphate (TEHP), and 2-ethylhexyl sulfate (EHS)] were tested for carcinogenic and other chronic and subchronic toxic effects in 90-day and 2-year studies in male and female Fischer 344 rats and B6C3F1 mice. The low generalized toxic potencies of the test chemicals allowed relatively high doses of all of these compounds to be administered. Despite differences in chemical structure, all four chemicals were related to increased occurrences of hepatocellular neoplasms, principally carcinomas, in female mice. DEHA and DEHP also induced hepatocellular neoplasms in male mice, while DEHP caused hepatocellular neoplasms in both male and female rats. No other neoplasms were considered to be unequivocally related to compound administration in these studies. There was a positive correlation between the magnitude of the hepatocarcinogenic response in female mice and the probability of a hepatocarcinogenic response in male mice and in male and female rats, suggesting quantitative differences in the carcinogenic potentials of these agents. These results suggest that compounds containing a 2-ethylhexyl moiety (and 2-ethylhexanol, by implication) may possess some carcinogenic potential, especially for the rodent liver. No other organ-specific toxic effects common to two or more test chemicals were observed in these studies.