Di(2-ethythexyl)phthalate: lack of initiating activity in the liver of female F-344 rats

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Abstract
Di(2-ethylhexyl)phthalate (DEHP) is a peroxisome proliferator that was hepatocarcinogenic in female rats in a National Toxicology Program 2-year bioassay. However, DEHP was negative for promotional activity when tested using the same sex and strain of rat and dosing regimen that resulted in hepatocarcinogenicity. The carcinogenic response of peroxisome proliferators may be related to excess production of reactive oxygen species in the cell. In view of this and the negative promotion data, the initiating activity of DEHP was examined after single and sub-chronic dosing. No initiating activity was found when DEHP was administered in a single, oral dose (10 g/kg) or after 12 weeks of feeding at a dietary concentration of 1.2% when each was followed by a promotion regimen. There was no increase in number or mean volume of foci when liver sections were examined using multiple histologic markers and no tumors were identified.

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