Di-N-pentylphthalate (DPP) was tested using the Fertility Assessment by Continuous Breeding (FACB) protocol in Swiss CD-1 mice as part of a structure-activity evaluation of a variety of phthalates. Body weights, food and water consumptions, and clinical signs in a dose-range-finding study were used to set doses for the main study of 0.0, 0.5, 1.25, and 2.50% in feed. Measured feed consumption was increased by 8-35% at the highest concentration, but was unchanged in other DPP groups. Based on these measures, these concentrations produced calculated consumption estimates of nearly equal to 0.76, 2.16, and 4.8 g/kg/d.
During the continuous breeding phase (Task 2), all control pairs had at least 1 litter, while only 4 of 19 low dose pairs delivered a litter, and no middle dose or high dose pairs delivered a litter. In the 7 litters delivered at the low dose, the number of live pups/litter was reduced from control values by 90%; there were insufficient live pups to calculate pup weights adjusted for body weight.
At the end of Task 2, the control and high dose mice were cross-mated. The groups that contained either treated males, or treated females, gave birth to no live young, while 61% of cohabited control pairs bore live young.
The F0 control and high dose mice were necropsied after the crossover mating trial. The treated females weighed 9% less than their controls, while body-weight-adjusted liver weight was 56% greater than controls, and adjusted kidney weight was 12% less. Treated males weighed 10% less than controls, while adjusted liver weight was 55% greater. In males, adjusted kidney weights, seminal vesicles, and epididymal weights were reduced by 30%, 29% and 19% respectively. At the high dose, absolute testis weight was decreased by 78%, and there were no detectable epididymal sperm.
A second generation evaluation was not performed for DPP.
Thus, DPP at these concentrations sharply reduced litter size and number of litters/pair in the F0 mice.
NTIS# PB86118999