Propylene glycol monomethyl ether (PGME), a solvent used in industry, 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 0.5%, 1.0%, and 2.0% PGME in drinking water. These concentrations produced calculated consumption estimates of nearly equal to 0.95, 1.9, and 3.3 g/kg/d.
During Task 2, no changes in body weight or water consumption were found in any of the exposure groups. There was no reduction in the number of litters/pair, the number of live pups/litter, or the viability of those pups. Mean pup weight adjusted for litter size was reduced by 4% at the top dose level.
In the absence of an adverse effect on fertility, Task 3, the crossover test to identify the affected sex, was not conducted.
Task 4, the evaluation of the second generation, was conducted with the control and high dose groups only. The reduced pup weight at birth, noted in the first 4 litters, continued postnatally, with males and females weighing nearly equal to 14% less than controls during nursing. Male body weights were nearly equal to 8% lower than controls during the mating period, while female body weights during the mating period were not affected by PGME treatment. Mating and fertility indices were unaffected by PGME, as were the number and viability of the F2 offspring. After the F2 pups were delivered, evaluated, and killed, the adult F1 mice in the control and 2% PGME groups were killed and necropsied. While female body weight was not affected by PGME exposure, body-weight-adjusted liver weight was increased by 7.5%. Male body weights in the 2% PGME group were 8% lower than controls, while absolute testis, relative epididymis and prostate weights were reduced by 7% , 7% and 15%, respectively.
In summary, there was some evidence of probable developmental toxicity, expressed as reduced pup weights, but no evidence of reproductive toxicity expressed as reduced litters or pup numbers. This F1 pup weight effect was seen in the absence of an effect on F0 adult body weight.