Influence of ALDH2 Polymorphism on Ethanol Kinetics and Pulmonary Effects in Male and Female Rats Exposed to Ethanol Vapors

Abstract

Ethanol is being added in various proportions to fuel in order to reduce greenhouse gas emissions. This is likely to result in involuntary exposure to ethanol vapors. Whether or not such exposure might cause health effects is still unknown. Acetaldehyde, an important metabolite of ethanol detoxified by aldehyde dehydrogenase (ALDH2) is more toxic that ethanol. This study assessed the impact of genetic ALDH2 polymorphism in male and female Sprague-Dawley rats on ethanol kinetics and pulmonary effects following sub-chronic exposure to ethanol vapors. Homozygote rats ALDH2^Q/2^Q (fast ALDH2 activity) and ALDH2^R/2^R (ALDH2 deficiency) were exposed to 1000 or 3000 ppm, 6 h/day, 5 days/week for 13 weeks. Blood ethanol concentrations (BEC) were measured at various post-exposure times. Cellularity in bronchoalveolar lavages (BAL) and lung histological evaluation were performed at week 13. Results showed that BEC in males were systematically lower than in females, e.g. BEC in ALDH2^Q/2^Q males (2 min, 1,000 ppm, day 1) was significantly (p < 0.05) lower (66.8 ± 10.7 μ M) compared to females (87.6 ± 15.3 μ M). BEC for ALDH2^Q/2^Q rats were different from ALDH2^R/2^R only for males exposed for more than 64 days. Repeated exposures resulted in a significant decrease of BEC, e.g. for ALDH2^Q/2^Q males (3,000 ppm) BEC on day 1 and day 85 were 324.6 ± 102.6 μ M and 187.5 ± 32.1 μ M, respectively. BAL and histological evaluation revealed no pulmonary toxicity for all groups. Overall, results showed that 3,000 ppm of ethanol vapors represents no observed adverse effect level (NOAEL) for pulmonary toxicity in the rat.