DEVELOPMENTAL TOXICITY OF DIGLYME BY INHALATION IN THE RAT

Diglyme (Diethylene glycol dimethyl ether, CAS No. 111-96-6) is a glyc ol ether which has been used in solvent formulations. To assess the po tential developmental toxicity of this chemical, groups of pregnant Cr l:CD(R)BR rats were exposed to either 0 (control, room air only), 25, 100, or 400 ppm diglyme by inhalation for 6 hrs/day for Days 7 through 16 or gestation (day on which the copulation plug was detected was de signation Day I G). All female rats were euthanized on day 21G and the fetuses were examined. An additional group of rats was treated with 2 5 ppm 2-methoxethanol (2ME) to serve as a positive control and for com parison of relative potencies. Maternal toxicity evident as depressed feed consumption at 400 ppm and increased liver weights at 100 ppm. Th ere were no dams in the 400 ppm group with live fetuses (all litters c onsisted on resorbed conceptuses). Embryo viability was unaffected by concentrations of diglyme as high as 100 ppm. 2ME produced increased l iver weights and depressed feed consumption at 25 ppm. Embryo-fetal to xicity was evident as a concentration-related decrease in fetal weight at diglyme concentrations as high as 100 ppm (and with 2ME). There we re no fetuses derived from the 400 ppm diglyme-treated darns. A low in cidence of structural malformations was observed in all diglyme groups (as well as with 2ME). The incidence of variations, (primarily delaye d skeletal ossification and rudimentary ribs) was increased in the 25 and 100 ppm diglyme groups. The incidence and severity in the diglyme and 2ME groups exposed to 25 ppm was essentially the same suggesting s imilar potency for producing structural variations. In this study, dig lyme was embryolethal at 400 ppm; a level that otherwise was only marg inally toxic to the dam. Maternal and fetal toxicity also were demonst rated at 100 ppm. Although the fetal defects detected following diglym e exposure at 25 ppm were not significantly different from control val ues (with the exception of the incidence of skeletal developmental var iations), the pattern, type, and incidence of variations were similar to those seen at 100 ppm, suggesting that 25 ppm was an effect level t hat approaches the lower end of the developmental toxicity response cu rve. Therefore, the no-observable-effect level (NOEL) for diglyme expo sure in the dam is 25 ppm and a NOEL was not clearly demonstrated for the conceptus.