Assessment of ethylene glycol monobutyl and monophenyl ether reproductive toxicity using a continuous breeding protocol in Swiss CD-1 mice

Abstract

A continuous breeding reproduction study design was utilized to examine the reproductive toxicity of ethylene glycol monobutyl ether (EGBE) and ethylene glycol monophenyl ether (EGPE). Swiss CD-1 mice were administered EGBE in drinking water (0, 0.5, 1.0, and 2.0%, i.e., 0.7, 1.3, and 2.1 g/kg body wt/day) and EGPE was administered via the feed (0, 0.25, 1.25, and 2.5%, i.e., 0, 0.4, 2.0, and 4 g/kg body wt/day). Both male and female mice were dosed for 7 days prior to and during a 98-day cohabitation period. EGBE was toxic at the high (2%) and mid dose (1%) to adult F 0 female mice: 13 out of 22 females at the high dose and 6 out of 20 at the mid dose died during the cohabitation period. Both the high- and mid-dose animals produced fewer litters/pair, fewer pups/litter, with decreased pup weight. These effects occurred in the presence of decreased body weight, decreased water consumption, and increased kidney weight. A crossover mating trial indicated that the reproductive effects could be attributed primarily to an effect on the female. This was substantiated at necropsy where testes and epididymis weights were normal as were sperm number and motility. Fertility of the offspring of the 0.5% group was normal in the presence of increased liver weights. With respect to EGPE, there was no change in the ability to produce five litters during the continuous breeding period. There was, however, a significant but small (10–15%) decrease in the number of pups/litter and in pup weight in the high-dose group. A crossover mating trial suggested a female component of the reproductive toxicity of EGPE. While fertility was only minimally compromised, severe neonatal toxicity was observed. By Day 21 there were only 8 out of 40 litters in the mid- and high-dose groups which had at least one male and female/litter. Second generation reproductive performance of the mid-dose group (1.25%) was unaffected except for a small decrease in live pup weight. In summary the reproductive toxicity of EGBE and EGPE was only evident in the female and occurred at doses which elicited general toxicity. EGBE was particularly toxic to adult female mice while EGPE was particularly toxic to immature mice of both sexes.