Reproductive toxicity of triethylene glycol and its diacetate and dimethyl ether derivatives in a continuous breeding protocol in Swiss CD-1 mice

Abstract

Triethylene glycol and two of its derivatives were evaluated for reproductive toxicity in a continuous breeding protocol with Swiss CD-1 mice. Triethylene glycol (TEG: 0, 0.3, 1.5, and 3%), triethylene glycol diacetate (TGD: 0, 0.75, 1.5, and 3%), and triethylene glycol dimethyl ether (TGDME: 0, 0.25, 0.5, and 1%) were administered in drinking water to breeding pairs (20 pairs per treatment group, 40 control pairs) during a 98-day cohabitation period. Reproductive function was assessed by the number of litters per pair, live pups per litter, proportion of pups born alive, and pup weight. There were no apparent effects on reproductive function in the animals receiving TEG or TGD at doses up to 3% in the drinking water (representing 6.78 or 5.45 g/kg, respectively). However, some developmental toxicity was demonstrated for both TEG and TGD. Continuous exposure of dams to 1.5 or 3% TEG significantly reduced live pup weight at birth compared to control and 0.3% TEG, while exposure to 3% TGD during lactation significantly (but reversibly) reduced pup body weights on Postnatal Days 14 and 21. In contrast, TGDME was toxic to the reproductive system as evidenced by decreases at the highest dose (1% TGDME; 1.47 g/kg) in the proportion of pairs that produced at least one litter, live pups per litter, and proportion of pups born alive, with dose-related trends seen in the latter two parameters. A crossover mating trial showed that TGDME was more toxic to the female than the male reproductive system. These data indicate that TGDME (1.47 g/kg) is a reproductive toxicant in Swiss mice while reproductive toxicity was not demonstrated in mice receiving TEG or TGD (at doses up to 6.78 or 5.45 g/kg, respectively).