Humans are cumulatively exposed to acetaldehyde from various sources including 
alcoholic beverages, tobacco smoke, foods and beverages. The 
genetic-epidemiologic and biochemical evidence in ALDH2-deficient humans 
provides strong evidence for the causal relationship between 
acetaldehyde-exposure due to alcohol consumption and cancer of the upper 
digestive tract. The risk assessment has so far relied on thresholds based on 
animal toxicology with lower one-sided confidence limit of the benchmark dose 
values (BMDL) typically ranging between 11 and 63 mg/kg bodyweight (bw)/day 
dependent on species and endpoint. The animal data is problematic for regulatory 
toxicology for various reasons (lack in study quality, problems in animal models 
and appropriateness of endpoints - especially cancer - for transfer to humans). 
In this study, data from genetic epidemiologic and biochemical studies are 
reviewed. The increase in the daily exposure dose to acetaldehyde in 
alcohol-consuming ALDH2-deficients vs. ALDH2-actives was about twofold. The 
acetaldehyde increase due to ALDH2 inactivity was calculated to be 
6.7 μg/kg bw/day for heavy drinkers, which is associated with odds ratios of up 
to 7 for head and neck as well as oesophageal cancer. Previous animal toxicology 
based risk assessments may have underestimated the risk of acetaldehyde. Risk 
assessments of acetaldehyde need to be revised using this updated evidence.