title: Developmental toxicity evaluation of inhaled 2-ethoxyethanol acetate in Fischer 344 rats and New Zealand white rabbits.
abstract: Pregnant Fischer 344 rats and New Zealand white rabbits were exposed to 2-ethoxyethanol acetate (EEA; CAS No. 111-15-9) vapor by inhalation on Gestational Days 6 through 15 (rats) or 6 through 18 (rabbits) at concentrations of 0, 50, 100, 200, or 300 ppm, 6 hr/day. The animals were terminated on Gestational Day 21 (rats) or 29 (rabbits) and fetuses were examined for external, visceral, and skeletal malformations and variations. In rabbits, exposure to 100-300 ppm resulted in maternal toxicity: decreased weight gain at 100-300 ppm, clinical signs at 200-300 ppm, alterations in hematology at 100-300 ppm, reduced gravid uterine weight at termination at 200-300 ppm, and elevated absolute liver weight at 300 ppm. Developmental toxicity was observed at 100-300 ppm: an increased incidence of totally resorbed litters at 200-300 ppm, an increase in nonviable fetuses at 300 ppm, and a decrease in viable implants (live fetuses) per litter at 200-300 ppm. The incidence of fetal malformations (external, visceral, and skeletal) was increased at 200-300 ppm. The incidence of total malformations was 100% at 300 ppm and significantly increased at 200 ppm. Reduced fetal ossification was observed at 100-300 ppm. In rats, exposure to 100-300 ppm also resulted in maternal toxicity: reduced weight gain and reduced food consumption at 200-300 ppm and elevated relative liver weight and alterations in hematology at 100-300 ppm. Absolute maternal liver weight was increased at all EEA exposure concentrations; relative liver weight was increased at 100-300 ppm. Developmental toxicity was observed at 100-300 ppm: increased nonviable implantations/litter (300 ppm), reduced fetal body weight/litter (200-300 ppm), and increased incidence of external (300 ppm), visceral, and skeletal (100-300 ppm) variations indicative of toxicity. The incidence of visceral, skeletal, and total malformations was increased at 200-300 ppm. In conclusion, in both species, inhalation exposure to EEA during organogenesis produced maternal toxicity at 100-300 ppm and developmental toxicity at 100-300 ppm, including teratogenicity at 200-300 ppm. At 50 ppm in both species, there was no evidence of maternal or developmental toxicity, including teratogenicity.
authors.affiliation: Bushy Run Research Center, Export, Pennsylvania 15632.
authors.forename: R W
authors.initials: RW
authors.lastname: Tyl
authors.forename: I M
authors.initials: IM
authors.lastname: Pritts
authors.forename: K A
authors.initials: KA
authors.lastname: France
authors.forename: L C
authors.initials: LC
authors.lastname: Fisher
authors.forename: T R
authors.initials: TR
authors.lastname: Tyler
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005026:Ethylene Glycols / Q000633:toxicity*; D005260:Female; D005333:Fetus / Q000187:drug effects; D008297:Male; D011247:Pregnancy; D011817:Rabbits; D051381:Rats; D011916:Rats, Inbred F344; D013723:Teratogens
chemical_list: D005026:Ethylene Glycols; D013723:Teratogens; C021296:2-ethoxyethanol