Ethylene Glycol Monophenyl Ether (EGPE), a common chemical and solvent used in industry and in consumer goods, was tested for reproductive toxicity in Swiss CD-1 mice using the RACB protocol. It was part of a series of glycol ethers and congeners evaluated for structure-activity correlations using this design. Data collected on body weights, clinical signs, and food/water consumption during the dose-range-finding segment (Task 1) were used to set concentrations for the main study (Task 2) at 0.0, 0.25, 1.25, 2.5% in feed. These concentrations produced calculated consumption estimates of nearly equal to 375, 1875, and 3700 mg/kg/day.
There were no effects on body weight during the continuous breeding phase of the study. Two control mice died, and one mouse and two mice died in the middle and high dose groups, respectively.
All pairs of mice in each group had at least 1 litter. There was no reduction in the mean number of litters/pair. The middle dose group had 5.00 litters/pair, while the control had a mean of 4.84; this difference was statistically significant, but biologically insignificant. The high dose group had 19% fewer live pups/litter than controls; the live pup weight (adjusted for litter size) was reduced by 4% and 10% in the middle and high dose groups, respectively.
Because of the reduction in pup number, a crossover mating trial was conducted, using one treated partner and one control partner. A separate group of re-randomized controls served as concurrent controls for this task. While there were no alterations in mating or fertility indices or in the number of live pups/litter seen in groups with a treated partner, live pup weight adjusted for litter size was reduced by 12% in the control male x 2.5% EGPE female group. Thus, there was a clear effect in treated females, but one probably related to developmental toxicity, rather than female fertility per se.
The control and high dose F0 mice were killed and necropsied. The treated males weighed 6% less than their controls, while their absolute liver weight was 14% greater. Female body weight was unchanged by EGPA, but absolute liver weight was increased by 55%. No other organ weights were affected. Sperm indices (% motile, epididymal concentration, morphology) were unaffected by EGPE treatment at 2.5%.
The last F1 litter from all dose levels in Task 2 was reared by the dams to weaning, and then dosed with EGPE at the same concentration provided to their parents. There was reduced body weight gain to weaning: the middle and high dose groups weighed 25% and 58% less than controls at weaning on pnd 21; on pnd 74, the weight differences were 11% and 17%, respectively. Mortality was also increased in the middle and high dose groups from weaning to mating at pnd 74. This was most pronounced in the high dose group: of the 56 pups weaned in this group, only a total of 6 survived to mating at pnd 74. This provided too few animals to analyze, and this group was omitted from the rest of the study.
At the mating of the second generation, there was no treatment-related effect on F2 pup number or sex ratio. F2 pup weight adjusted for litter size was reduced in the 1.25% group by 7%.
After the delivery of the F2 pups, the control and 1.25% group F1 mice were killed and necropsied. The 1.25% EGPE mice weighed 13% less than controls, their absolute testis weight was 16% less, and relative seminal vesicles weight was 14% less than controls. The 1.25% EGPE females weighed 7% less than controls; there were no adjusted weight changes in the treated females. There were no treatment-related alterations in epididymal sperm concentration, motility, or morphology.
In summary, EGPE produced significant reproductive and developmental toxicity at doses that increased liver weight in treated F0 mice. EGPE caused significant toxicity in growing animals, as evidenced by the reduced body weight in neonates in Tasks 2, 3, and 4, and the large increase in post-natal lethality as the F1 animals grew to the age of mating.
NTIS #PB85146140/AS