Abstract for TR-217

Carcinogenesis Bioassay of Di(2-ethylhexyl)phthalate in F344 Rats and B6C3F1 Mice (Feed Studies)

CASRN: 117-81-7
Chemical Formula: C24H38O4
Molecular Weight: 390.5602
Synonyms/Common Names: DEHP
Report Date: March 1982

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A bioassay of di(2-ethylhexyl)phthalate,the most commonly used plasticizer for polyvinylchloride polymers, forpossiblecarcinogenicity was conducted by feeding diets containing 6,000 or 12,000ppmof the test chemical to groups of 50 male and 50 female F344 rats and 3,000or6,000 ppm to groups of 50 male and 50 female B6C3F1 mice for 103 weeks.Controls consisted of 50 untreated rats and 50 untreated mice of eithersex.

Mean body weights of dosed male rats (high-and low-dose),high-dose female rats, and dosed female mice (high-and low-dose) were marginally-to-moderatelylower than those of the corresponding controls at the end of the chronic study,reflecting a decrease in body weight gain. Food consumption was reducedslightly in rats of either sex, whereas there was no apparent difference amongthe mouse groups.

Female rats and male and female mice administereddi(2-ethylhexyl)phthalate hadsignificantly higher incidences of hepatocellular carcinomas than thoseobserved in the controls (rats -- males: 1/50, 2%; 1/49, 2%; 5/49, 10%; females-- 0/50, 0%; 2/49, 4%; 8/50, 16%, P=0.003; mice -- males: 9/50, 18%; 14/48, 29%;19/50, 38%, P=0.022; females: 0/50, 0%; 7/50, 14%; P=0.006, 17/50, 34%,P<0.001). Further, a statistically significant positive trend forhepatocellular carcinomas occurred in female rats (P=0.002) and in male(P=0.018) and female (P<0.001) mice.

In addition, di(2-ethylhexyl)phthalatecaused a statistically significant increased incidence of male rats with eitherhepatocellular carcinomas or neoplastic nodules (3/50, 6%; 6/49, 12%; 12/49,24%; P=0.010).

Degeneration of the seminiferous tubules was observed in the high-dosemale rats (1/49, 2%; 2/44, 5%; 43/48, 90%) and in the high-dosemale mice (1/49, 2%; 2/48 4%; 7/49, 14%). Hypertrophy of cells in the anteriorpituitary was also found at increased incidences in the high-dosemale rats (1/46, 2%; 0/43, 0%; 22/49, 45%).

Under the conditions of this bioassay, di(2-ethylhexyl)phthalate wascarcinogenic for F344 rats and B6C3F1 mice, causing increased incidences offemale rats and male and female mice with hepatocellular carcinomas, andinducing an increased incidence of male rats with either hepatocellularcarcinomas or neoplastic nodules.

Levels of Evidence of Carcinogenicity:
Sex Species Results
Male Rats: Positive
Female Rats: Positive
Male Mice: Positive
Female Mice: Positive