The carcinogenicity of dietary di(2‐ethylhexyl) phthalate (DEHP) in fischer 344 rats and B6C3F1mice

Publisher Website
Google Scholar
Abstract
Groups of 50 male and female Fischer 344 rats and male and female B6C3Fl mice were fed diets containing 6000 or 12,000 (rats) or 3000 or 6000 (mice) mg di(2‐ethylhexyl) phthalate (DEHP)/kg feed for 103 consecutive wk. Concurrent controls (50 of each sex and species) were fed diet without the addition of DEHP. Treatment with DEHP did not affect survival rates for rats or mice, nor did it alter the amount of food consumed. Mean body weight gains of treated male rats (6000 and 12,000 mg/kg), female rats (12,000 mg/kg), and female mice (3000 and 6000 mg/kg) were less than those of the corresponding controls. Seminiferous tubular degeneration and hypertrophy of cells in the anterior pituitary were observed in male rats at 12,000 mg/kg, and chronic inflammation of the kidney and seminiferous tubular degeneration were observed in male mice at 6000 mg/kg. Neither clinical signs of toxicity nor nonneoplastic lesions were detected in the other treated groups at incidences greater than in the corresponding controls. Treatment with DEHP caused liver tumors in both sexes of mice and rats. The incidence of treated animals with hepatocellular carcinomas was significantly (p < 0.05) greater than that in controls for female rats ingesting 12,000 mg DEHP/kg diet, male mice ingesting 6000 mg/kg, and female mice ingesting 3000 or 6000 mg/kg. The combined incidence of animals with hepatocellular carcinomas or neoplastic nodules was significantly greater than that in controls for male rats ingesting 12,000 mg/kg and female rats ingesting 6000 mg/kg, while the combined incidence of animals with hepatocellular carcinomas or adenomas was significantly greater than that in controls for male mice ingesting 3000 mg/kg. Twenty of the 57 hepatocellular carcinomas diagnosed in DEHP‐treated mice (sexes and doses combined) had metastas‐ized to the lung. Pulmonary metastases were not observed in the control mice or in any of the rats. Male rats at the higher dose (12,000 mg/kg) had significantly lower incidences of pituitary tumors, thyroid C‐cell carcinomas, and testicular interstitial‐cell tumors. The incidence of testicular interstitial‐cell tumors was negatively correlated (p < 0.005) with either the presence of pituitary hypertrophy or the presence of testicular degeneration.