Lack of hepatic promotional activity by the peroxisomal proliferating hepatocarcinogen di(2-ethylhexyl)phthalate.

The hepatocarcinogenicity of di(2-ethylhexyl)phthalate (DEHP) was demonstrated in a recent bioassay in both rats and mice. Due to the negative genotoxicity of DEHP in both in vivo and in vitro assays, it was hypothesized that the positive carcinogenic response of DEHP may have been due to a promotional effect of DEHP on spontaneous foci. However, when DEHP was used in the promotion phase of a rat hepatic initiation-promotion system, no promotional activity could be demonstrated after either 3 or 6 months of feeding DEHP at a dietary concentration of 1.2%. No neoplasms or nodules were identified. In addition, DEHP did not increase the number of foci or the mean volume of the foci when foci were identified by six different histologic stains.