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DEVELOPMENTAL TOXICITY OF INHALED METHANOL IN THE CD-1 MOUSE, WITH APPLICATION OF QUANTITATIVE DOSE-RESPONE MODELING FOR ESTIMATION OF BENCHMARK DOSAGES
Citation:
Rogers, J., M. Mole, N. Chernoff, B. Barbee, C. Turner, T. Logsdon, AND R. Kavlock. DEVELOPMENTAL TOXICITY OF INHALED METHANOL IN THE CD-1 MOUSE, WITH APPLICATION OF QUANTITATIVE DOSE-RESPONE MODELING FOR ESTIMATION OF BENCHMARK DOSAGES. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-92/350 (NTIS PB93106979).
Description:
Pregnant CD-1 mice were exposed to 1,000, 2,000, 5,000, 7,500, 10,000 or 15,000 ppm on methanol for 7 hr/day on days 6-15 of gestation. n day 17 of gestation, remaining mice were weighed, killed and the gravid uterus was removed. umbers of implantation sites, live and dead fetuses and resorptions were counted, and fetuses were examined externally and weighed as a litter. alf of each litter was examined for skeletal morphology and the other half of each litter was examined for internal soft tissue anomalies using a freehand scalpel dissection. ignificant increases in the incidence of exencephaly and cleft palate were observed at 5,000 ppm and above, increased postimplantation mortality at 7,500 ppm and above (including an increasing incidence of full-litter resorption), and reduced fetal weight at 10,000 ppm and above. ose-related increase in cervical ribs or ossification sites lateral to the seventh cervical vertebra was significant at 2,000 ppm and above. hus, the NOAEL for the developmental toxicity iin this study is 1,000 ppm. og-logistic dose response model was applied to the incidence data for exencephaly, cleft palate, resorption and cervical rib, and maximum likelihood estimates (MLEs) and benchmark dosages (BDs, the lower 95% confidence interval of the MLEs) corresponding to 1% and 5% added risk were calculated. he MLE for 5% added risk of exencephaly, cleft palate or resorption was 3667 ppm, and the corresponding BD was 3078 ppm. or cervical rib, the 5% added risk values for the MLE and BD were 824 and 305 ppm, respectively. he BDs for 1% added risk were 1915 ppm for exencephaly, cleft palate or resorption, and 58 ppm for cervical rib. he results of this study indicate that inhaled methanol is developmentally toxic in the mouse at exposure levels which were not maternally toxic. itters of pregnant mice gavaged orally with 4 g methanol/kg displayed developmental toxic effects similar to those seen in the 10,000 ppm methanol exposure group.