EVALUATION OF EXPOSURE TO WATER AEROSOL OR AIR BY NOSE-ONLY OR WHOLE-BODY INHALATION PROCEDURES FOR CD-1 MICE IN DEVELOPMENTAL TOXICITY STUDIES

This restraint versus whole-body exposure procedures in the absence of test chemical, and to determine the appropriate control environment ( water aerosol or air) for subsequent developmental toxicity studies of test materials administered as aerosols. Timed-pregnant CD-1 mice, 30 /group, were exposed to high concentrations of water aerosol or to air by whole-body or nose-only inhalation procedures on Gestational Days (GD) 6 through 15 for 6 hr per day. The group exposed to air by whole- body procedures was designated as the control group. Clinical observat ions and maternal body weights were recorded throughout gestation. At scheduled necropsy on GD 18, maternal animals were evaluated for body weight, gravid uterine weight, liver weight, number of ovarian corpora lutea, and status of uterine implantation sites. Fetuses were counted , weighed, and sexed and were examined for external, visceral (includi ng craniofacial), and skeletal alterations. Indices of maternal toxici ty were affected in both nose-only groups. Maternal body weights were reduced during and after the exposure period; maternal weight gain was reduced during the exposure period. Clinical signs observed, from ani mals struggling during restraint, were resolved by GD 18. At sacrifice on GD 18, maternal body weights and maternal gestational weight gains (both corrected for gravid uterine weights) and absolute liver weight s were reduced in both nose-only groups. Four females died (13.3%, all pregnant) in the air nose-only group, and maternal liver weight (rela tive to body weight) was reduced in the aerosol nose-only group. Gesta tional parameters were unaffected by any of the treatments. There were no statistically significant differences in the incidences of any ind ividual malformations or malformations by category (external, visceral , or skeletal) or of total malformations. However, exencephaly, low se t ears, cleft palate, and ventricular septal defect were observed only in both aerosol-exposed groups (whole-body and nose-only exposed). Th e incidences of individual external or visceral variations or of varia tions by category or of total variations were unaffected. The incidenc e of one skeletal variation, poorly ossified supraoccipital skull bone , was significantly increased in the aerosol nose-only group relative to the air whole-body controls. There were also increased incidences ( not statistically significant) of extra (14th) ribs in both aerosol gr oups. Therefore, maternal restraint (in both nose-only groups) during organogenesis produced indications of maternal toxicity, but restraint did not appear to affect normal embryo/fetal morphologic development. Maternal exposure to water aerosol (by whole-body or nose-only proced ures) resulted in small, biologically significant (but not statistical ly significant) increases in the incidences of fetal malformations and variations. In conclusion, for mice at least, nose-only exposures emp loying the present procedures can be used effectively, and water aeros ol is an appropriate control environment for developmental toxicity st udies of test materials administered as aerosols at high concentration s. (C) 1994 Society of Toxicology.