You are here:
Selective Cognitive Deficits in Adult Rats after Prenatal Exposure to Inhaled Ethanol
Citation:
Oshiro, W., T. Beasley, Kathy Mcdaniel, Michele Taylor, P. Evansky, V. C. Moser, M. Gilbert, AND P. Bushnell. Selective Cognitive Deficits in Adult Rats after Prenatal Exposure to Inhaled Ethanol. NEUROTOXICOLOGY AND TERATOLOGY. Elsevier Science Ltd, New York, NY, 45(1):44-58, (2014).
Impact/Purpose:
The Energy Independence and Security Act (EISA), passed by Congress in 2007, mandated the United States to decrease dependence on foreign oil supplies, reduce energy consumption, and address climate change. The EISA required the Environmental Protection Agency (EPA) to revise the Renewable Fuel Standards (RFS) by requiring the volume of renewable fuel’ blended into transportation fuel to be increased from 9 billion gallons in 2008 to 36 billion gallons by 2022. In response to these new goals (RFS2), the demand for ethanol blended with gasoline has increased. In 2009,95% of renewable fuels produced in the U.S. were made from corn ethanol, and this trend is likely to continue as long as ethanol remains the dominant renewable fuel (EPA/600/R-l0/183F,2011). Indeed, the percentage of ethanol used in gasoline was recently approved for increase in the United States from 10% (ElO) to 15% (EI5) with some restrictions. In light of the potential benefits of these new fuels to energy independence and to climate change, it is important to assess the possible human health hazards associated with ethanol fuel blends, especially in sensitive populations.
Description:
Increased use of ethanol blends in gasoline suggests a need to assess the potential public health risks of exposure to these fuels. Ethanol consumed during pregnancy is a teratogen. However, little is known about the potential developmental neurotoxicity of ethanol delivered by inhalation, the most likely route of exposure from gasoline-ethanol fuel blends. We evaluated the potential cognitive consequences of ethanol inhalation by exposing pregnant Long Evans rats to clean air or ethanol vapor from gestational day 9-20, a critical period of neuronal development. Concentrations of inhaled ethanol (5,000, 10,000, or 21,000 ppm for 6.5 h/day) produced modeled peak blood ethanol concentrations (BECs) in exposed dams of 2.3, 6.8, and 192 mg/dL, respectively. In offspring, no dose-related impairments were observed on spatial learning or working memory in the Morris water maze or in operant delayed match-to-position tests. Two measures showed significant effects in female offspring at all ethanol doses: 1) impaired cue learning after trace fear conditioning, and 2) an absence of bias for the correct quadrant after place training during a reference memory probe in the Morris water maze. In choice reaction time tests, male offspring (females were not tested) from the 5,000 and 10,000 ppm groups showed a transient increase in decision times. Also, male offspring from the 21,000 ppm group made more anticipatory responses during a preparatory hold period, suggesting a deficit in response inhibition. The increase in anticipatory responding during the choice reaction time test shows that inhaled ethanol yielding a peak BEC of ~200 mg/dL can produce lasting effects in the offspring. The lack of a dose-related decrement in the effects observed in females on cue learning and a reference memory probe may reflect confounding influences in the exposed offspring possibly related to maternal care of altered anxiety levels in females. The surprising lack of more pervasive cognitive deficits, as reported by others at BECs in the 200 mg/dL range, may reflect route-dependent differences in the kinetics of ethanol. These data show that response inhibition was impaired in the offspring of pregnant rats that inhaled ethanol at concentrations at least 5 orders of magnitude higher than concentrations observed during normal automotive transport and fueling operations, which rarely exceed 100 ppb.