Developmental effects after inhalation exposure of gravid rabbits and rats to ethylene glycol monoethyl ether.

Abstract

The effects of ethylene glycol monoethyl ether (EGEE) were determined on development in utero. Pregnant New Zealand White rabbits were exposed to air or 160 or 617 ppm EGEE for 7 hr/day from 1 to 18 days of gestation (dg). Virgin Wistar rats were exposed to 150 or 649 ppm EGEE or air 5 days/week for the 3 weeks immediately preceding their breeding. Sperm-positive rats were subsequently exposed to air or 202 or 767 ppm EGEE for 7 hr/day from 1 to 19 dg. Group sizes were 29 to 38 per concentration for both species.Pregestational exposure of rats had no effect on mating success, and there was no effect of EGEE exposure on establishment of pregnancy in either species. Rabbits exposed to the both concentrations had decreased food intake and depressed weight gain. Exposure-related mortality occurred in the 617 ppm EGEE group of rabbits. The only toxic sign seen in rats was reduced weight gain after exposure to 767 ppm EGEE. Exposure induced high embryomortality at maternal toxic concentrations in rats and rabbits, while lower levels induced fetal growth retardation in rats but not in rabbits. Gestational exposure increased the incidence of anomalies and variations; these were primarily of soft tissues in rabbits and of skeleton in rats. Thus, significant evidence of terata, fetal growth retardation and embryomortality were induced in rabbits and rats at levels that were below or similar to those that induced maternal manifestation of toxicity. These data implicate EGEE as a teratogen.

Methoxyacetic acid and ethoxyacetic acid inhibit mitochondrial function in vitro

“…The teratogenicity of EGME was first reported in rats, mice, and rabbits by Nagano et a1 (8) and has been further elucidated by Hanley et a1 (9). Similar hematologic, testicular, and teratogenic effects have been reported following exposure to EGEE (4,8,(10)(11)(12)(13)(14)(15). Foster et a1 (4, 16) compared EGME-mediated testicular effects to those produced by EGEE in the rat.…”

Ethylene glycol monoethyl ether [MAK Value Documentation, 2008]

“…extra ribs and variations of sternebrae) were found in the maternally toxic range with clearly reduced feed consumption, but only slightly reduced body weight gains. The higher concentration of 617 ml/m 3 led to maternal mortality and total resorptions (Andrew and Hardin 1984; Table 4). …”

Occupational exposure to glycol ethers and human congenital malformations

“…Within each category a particular chemical is further distinguished by the length of its alkyl ether group (e.g., methyl ether, ethyl ether, propyl ether, and butyl ether). Glycol ether acetates are metabolized to the corresponding glycol ether, and ether acetates and ethers are considered equivalent from a toxicological viewpoint (ECETOC 1995;Andrew and Hardin 1984;Tyl et al 1988). …”

“…Yes (rats, mice, rabbits d ) Yes (rats, mice, rabbits) Wier et al 1987;Stenger et al 1971;Goad and Cranmer 1984;Hardin et al 1981;Andrew et al 1981;Andrew and Hardin 1984;Doe 1984;Hardin et al 1984;Nelson et al 1981;Nelson and Brightwell 1984;Schuler et al 1984;NIOSH 1983 EGEEA (ethyl;acetate) Yes (rats, rabbits)…”