The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings were not evaluated in accordance with the levels of evidence for reproductive or developmental criteria established by NTP in March 2009. The findings and conclusions for this study should not be construed to represent the views of NTP or the U.S. Government.
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.