Carcinogenicity and chronic toxicity of di-2-ethylhexyl terephthalate (DEHT) following a 2-year dietary exposure in Fischer 344 rats

Abstract

The carcinogenicity and chronic toxicity potential of di-2-ethylhexyl terephthalate (DEHT) was assessed in F-344 rats (50/sex/dose) by dietary exposure for 104 weeks. Exposure levels of 0, 1500, 6000 or 12,000 ppm resulted in average daily doses of 79, 324 and 666 mg/kg/day for males and 102, 418 and 901 mg/kg/day for females. Animals were observed daily for clinical signs and detailed physical examinations were performed weekly. Body weight and food consumption were measured at scheduled intervals. During weeks 103–104, urine and blood samples were collected and analyzed. Eyes were examined during week 104 using a binocular indirect ophthalmoscope. At necropsy, organs were weighed and examined macroscopically and microscopically. No histological effects were noted in any organ at any dose and there was no increase in the incidence of any tumor types. Toxic responses were confined to lower weight gains and food conversion efficiency in males and females ingesting 6000 or 12,000 ppm. The severity of a normal geriatric degenerative retinal change was exacerbated in females exposed to 6000 or 12,000 ppm and in males exposed to 12,000 ppm. Therefore, the no-observed effect level (NOEL) for tumorigenicity was 12,000 ppm and the NOEL for chronic toxicity was 1500 ppm.