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.
Phenolphthalein administered via feed was tested for its effects on fertility and reproduction in Swiss CD-1 mice according to the Continuous Breeding protocol. A dose-finding study was not conducted; rather based on information available in the literature, 0.1, 0.7, and 3.0% levels were tested in the reproductive study. For F0 evaluation, male and female mice were continuously exposed for a 7-day precohabitation and a 98-day cohabitation period (Task 2). Subsequently, the control and 0.7% groups were used in a cross-over mating trial (Task 3) to determine the sex affected by chemical treatment. The F1 generation from control, 0.1, and 0.7% groups were also evaluated (Task 4).
Phenolphthalein with increasing dose and duration of exposure, caused a significant reduction in fertility, with a decrease in the number of litters per fertile pair in the 0.7 and 3.0% groups. Parental body weights were not affected by phenolphthalein treatment. The cumulative days to litter values were also increased in the 0.7 and 3% treated animals. In the cross-over mating trial, the treated females mated with control males delivered fewer live pups. There were no adverse effects in the litters from treated males mated with control females. At terminal necropsy, male kidneys were enlarged and right epididymis and testis weights were significantly lower than controls. Sperm morphology and vaginal cytology evaluation (SMVCE) results were parallel to subchronic study results in B6C3F1 mice; both sperm count (Task 3) and incidence of abnormal sperm (Tasks 3 and 4) were adversely affected. Reproductive performance of treated males, however, was similar to the corresponding control males.
The middle dose group was chosen for Task 3 crossover in the expectation (based on several previous RACB studies) that use of the high dose would indicate that both sexes were affected.
Similar to Task 2 results, fertility declined in F1 mice receiving 0.7% phenolphthalein. The number of live F2 pups per litter decreased as well. Also, in the F1 males in the 0.7% group, testis and epididymis weights were decreased, and the incidence of abnormal sperm was increased. Pathologic lesions in F1 males were similar to those found in the parental males.
Thus, phenolphthalein, administered in the feed at concentrations up to 3.0%, was clearly toxic to murine reproduction in both generations of treated mice.
NTIS # PB91178707