Rw. Tyl et al., EVALUATION OF THE DEVELOPMENTAL TOXICITY OF ETHYLENE-GLYCOL AEROSOL IN CD-1 MICE BY NOSE-ONLY EXPOSURE, Fundamental and applied toxicology, 27(1), 1995, pp. 49-62
Ethylene glycol (EG; CAS No. 107-21-1) is teratogenic to mice by whole
-body (WE) exposure to aerosol (1000-2500 mg/m(3)). The WE results wer
e confounded by possible exposure from ingestion after grooming and/or
from percutaneous absorption. Therefore, CD-1 mice were exposed to EG
aerosol (MMAD 2.6 +/- 1.7 mu m) on Gestational Days (GD) 6 through 15
, 6 hr/day, by nose-only (NO) (0, 500, 1000, or 2500 mg/m(3)) or WB ex
posures (0 or 2100 mg/m(3), as positive control), 30/group. Five addit
ional ''satellite'' females each at 2500 mg/m(3) NO and 2100 mg/m(3) W
E were exposed on GD 6 for measurement of EG on fur. Control environme
nts were water aerosol (4200 mg/m(3) for NO; 2700 mg/m(3) for WB). Fem
ales were weighed and evaluated for clinical signs and water consumpti
on throughout gestation. On GD 18, maternal uterus, liver, and kidneys
(2) were weighed, with kidneys examined microscopically. Corpora lute
a and implantation sites were recorded. Live fetuses were weighed, sex
ed, and examined for structural alterations. For NO darns, kidney weig
hts were increased at 1000 and 2500 mg/m(3); no renal lesions and no o
ther treatment-related maternal toxicity were observed. There were no
effects on pre- or postimplantation loss; fetal body weights/litter we
re reduced at 2500 mg/m(3). At 2500 mg/m(3), incidences of fused ribs
and skeletal variations were increased. The 2500 mg/m(3) NO satellite
animals had similar to 330 mg/kg extractable EG. The WE group exhibite
d maternal and developmental toxicity including increased fetal skelet
al malformations and variations, confirming previous results, with 139
0 mg/kg extractable EG on fur. Therefore, exposure of CD-1 mice to a r
espirable EG aerosol during organogenesis by NO inhalation resulted in
minimal maternal toxicity at 1000 and 2500 mg/m(3) and developmental
toxicity at 2500 mg/m(3). The NOAEL was 500 mg/m(3) NO for maternal an
d 1000 mg/m(3) NO for developmental toxicity. This study supports the
interpretation of the initial EG WE results as due to systemic exposur
e from noninhalation routes since limiting noninhalation routes preven
ted almost all of the effects (including teratogenicity) observed in m
ice after WE exposure. (C) 1995 Society of Toxicology.