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Toxicological Outcomes in Rats Exposed to Inhaled Ethanol During Gestation
Citation:
Beasley, T., P. Evansky, S. Martin, Kathy McDaniel, V. C. Moser, R. Luebke, J. Norwood, J. Rogers, C. Copeland, AND P. Bushnell. Toxicological Outcomes in Rats Exposed to Inhaled Ethanol During Gestation. NEUROTOXICOLOGY AND TERATOLOGY. Elsevier Science Ltd, New York, NY, 45:59-69, (2014).
Impact/Purpose:
The increased use of alternative fuels and the large population likely to be exposed to them argue for a need to understand their potential public health effects. Ethanol has been the forerunner for alternative fuels and in 2009 com starch-derived ethanol constituted 95% of the biofuel produced in the U.S. [26]. Robust evidence has identified ethanol as a known human teratogen and neurotoxicant. Ethanol consumption during pregnancy has been linked to fetal lcohol spectrum disorder (FASD), characterized as craniofacial malformations, persistent eurodevelopmental and neurocognitive deficits and immune system dysfunction in children 1,36,50]. The magnitude and severity of the deficits have been linked to the peak blood ethanol concentrations (BEC), but are·also influenced by the number of exposures and the developmental stage when exposure occurs [22,61,69].
Description:
Recent legislation has encouraged replacing petroleum-based fuels with renewable alternatives including ethanol, which is currently blended with gasoline in the United States at concentrations up to 15%. Efforts to increase the amount of ethanol in gasoline have prompted concerns about the potential toxicity of inhaled ethanol vapors from these fuels. The well-known sensitivity of the developing nervous and immune systems to ingested ethanol, and the lack of information about its toxicity by inhalation prompted the present work on its potential developmental effects in a rat model. Pregnant Long-Evans rats were exposed for 6.5 h/day on days 9-20 of gestation to clean air or ethanol vapor at concentrations of 5,000, 10,000, or 21,000 ppm, which resulted in estimated peak blood ethanol concentrations (BECs) of 2.3, 6.7, and 192 mg/dL, respectively. No overt toxicity in the dams was observed. Ethanol did not affect litter size or weight, or postnatal weight gain in the pups. Motor activity was normal in offspring through postnatal day (PND)29. On PND 62, the 5,000 and 21,000 ppm groups were more active than controls. On PND 29 and 62, offspring were tested with a functional observational battery, which revealed small changes in the neuromuscular and sensorimotor domains that were not systematically related to dose. Cell-mediated and humoral immunity were not affected by ethanol exposure in 6-week-old offspring. Systolic blood pressure was increased by 10,000 ppm ethanol in males at PND 90 but not at PND 180. No differences in lipoprotein profile, liver function, or kidney function were observed. In summary, prenatal exposure to inhaled ethanol caused some mild changes in physiological and behavioral development in offspring that were not clearly related to dose, and did not produce detectable changes in immune function. The low toxicity of inhaled ethanol may result from the slow rise in BEC by this exposure route.