| Abstract |
To assess the potential reproductive effects over multiple generations, Diethylhexylphthalate (DEHP), CAS No. 117-81-7, was administered in the diet at concentrations of 1.5 (control), 10, 30, 100, 300, 1,000, 7500, and 10,000 ppm to groups of 17 male and 17 female Sprague-Dawley rats. The control dose level was set at 1.5 ppm as this was the amount of DEHP found in the control feed. Animals in the F0 generation began exposure as adults and were bred to produce the F1 generation (F1a, 1b, 1c), the F1 adults were bred to produce the F2 generation (F2a, 2b, 2c), and the F2 adults were bred to produce the F3 generation (F3a, 3b, 3c). Additional non-mating males (up to three per litter) were selected from the F1c, F2c, and F3c litters, and were maintained following similar procedures as those for mating males, except they were not cohabited with females. The 10,000 ppm animals only completed the F1 generation and were terminated due to the inability to produce any F2 generation animals. Parameters evaluated over the course of the study included body weights, feed consumption, clinical observations, reproductive performance, anogenital distance, pup survival, sexual development, estrous cyclicity, sperm endpoints, gross pathology, organ weights, and limited/selected histopathology. Based on measured feed consumption, mg/kg daily doses were calculated to be 0.12, 0.78, 2.4, 7.9, 23, 77, 592, and 775 mg/kg/day in the F0 animals; 0.09, 0.48, 1.4, 4.9, 14, 48, 391, and 543 mg/kg/day in the F1 animals; and 0.1, 0.47, 1.4, 4.8, 14, 46, 359 mg/kg/day in the F2 animals. |