Developmental Toxicity Evaluation of Inhaled 2-Ethoxyethanol Acetate in Ficher 344 Rats and New Zealand White Rabbits

Developmental Toxicity Evaluation of Inhaled 2–EthoxyethanolAcetate in Fischer 344 Rats and New Zealand White Rabbits. Tyl,R. W., Pritts, I. M, France, K. A., Fisher, L. C, and Tyler,T. R. (1988). Fundam. Appl. Toxicol. 10, 20–39. PregnantFischer 344 rats and New Zealand white rabbits were exposedto 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 Gesta–tionalDay 21 (rats) or 29 (rabbits) and fetuses were examined forexternal, visceral, and skeletal malformations and variations.In rabbits, exposure to 100–300 ppm resulted in maternaltoxic–ity: decreased weight gain at 100–300 ppm,clinical signs at 200–300 ppm, alterations in hema–tologyat 100–300 ppm, reduced gravid uterine weight at terminationat 200–300 ppm, and elevated absolute liver weight at300 ppm. Developmental toxicity was observed at 100–300ppm: an increased incidence of totally resorbed litters at 200–300ppm, an increase in nonviable fetuses at 300 ppm, and a decreasein viable implants (live fetuses) per litter at 200–300ppm. The incidence of fetal malformations (external, visceral,and skeletal) was increased at 200–300 ppm. The incidenceof total malformations was 100% at 300 ppm and significantlyincreased at 200 ppm. Reduced fetal ossification was observedat 100–300 ppm. In rats, exposure to 100–300 ppmalso resulted in maternal toxicity: reduced weight gain andreduced food consumption at 200–300 ppm and elevated relativeliver weight and alterations in hematology at 100–300ppm. Absolute maternal liver weight was increased at all EEAexposure concentrations; relative liver weight was increasedat 100–300 ppm. Developmental toxicity was observed at100–300 ppm: increased nonviable implantations/litter(300 ppm), reduced fetal body weight/litter (200–300 ppm),and increased incidence of external (300 ppm), visceral, andskeletal (100–300 ppm) variations indicative of toxicity.The incidence of visceral, skeletal, and total malformationswas increased at 200–300 ppm. In conclusion, in both species,inhalation exposure to EEA during organogenesis produced maternaltoxicity at 100–300 ppm and developmental toxicity at100–300 ppm, including teratogenicity at 200–300ppm. At 50 ppm in both species, there was no evidence of maternalor developmental toxicity, including teratogenicity.