title: Carcinogenicity testing of phthalate esters and related compounds by the National Toxicology Program and the National Cancer Institute.
abstract: Five phthalate ester and related compounds (phthalic anhydride, phthalamide, di(2-ethylhexyl) phthalate, di(2-ethylhexyl) adipate and butyl benzyl phthalate) have been tested for carcinogenic effects in standard lifetime rodent feeding studies. Groups of 50 male and female rats and mice were fed diets containing various concentrations of the test chemicals for 102-106 consecutive weeks. The dietary concentrations were estimated to be maximally tolerated doses and half maximally tolerated doses. All animals that died during the study and all survivors at the end of two years were examined grossly and microscopically for the presence of tumors. The incidences of animals with tumors at a specific anatomic site in the treated groups and the controls were compared statistically. Neither phthalamide nor phthalic anhydride increased tumor incidences in rats or mice. Di(2-ethylhexyl) phthalate increased the incidences of liver tumors in rats and mice of both sexes, while di(2-ethylhexyl) adipate caused liver tumors in male and female mice, only. Butyl benzyl phthalate did not cause tumors in male or female mice, but the incidence of myelomonocytic leukemia in butyl benzyl phthalate-treated female rats was significantly greater than that in the controls. Chemically induced early deaths in the butyl benzyl phthalate-treated male rats precluded an evaluation of carcinogenic potential in this sex. Under the conditions of these tests, di(2-ethylhexyl) adipate was considered to be carcinogenic in both rats and mice and di(2-ethylhexyl) adipate was considered to be carcinogenic in mice. The evidence for carcinogenic effects of butyl benzyl phthalate in female rats was judged to be equivocal because of the variable nature of the incidence of myelomonocytic leukemia in Fischer 344 rats. Phthalamide and phthalic anhydride did not exhibit carcinogenic effects in these studies.
mesh_terms: D000818:Animals; D002273:Carcinogens; D005260:Female; D008113:Liver Neoplasms / Q000139:chemically induced; D008297:Male; D051379:Mice; D009316:National Institutes of Health (U.S.); D009374:Neoplasms, Experimental / Q000139:chemically induced*; D010795:Phthalic Acids / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D013045:Species Specificity; D014481:United States
chemical_list: D002273:Carcinogens; D010795:Phthalic Acids