The proposal for the harmonised classification and labelling (CLH) of acetaldehyde (EC 200-836-8; CAS 75-07-0) was submitted by the Dutch competent authority and was subject to a public consultation, which ended on 11 September 2015.
During its June meeting, the Committee for Risk Assessment (RAC) asked for further information to clarify the mode of action (MoA) of acetaldehyde – in particular, experimental and human studies that could clarify the influence of acetaldehyde dehydrogenase (ALDH2) genetic polymorphism on the physiological levels of acetaldehyde and possible health effects.
In humans, acetaldehyde is primarily produced by oxidation of ethanol through alcohol dehydrogenase (ADH) in the liver. Acetaldehyde also occurs endogenously. Acetaldehyde is further oxidised to acetic acid in an NAD-dependent reaction by aldehyde dehydrogenase (ALDH). Both ADH and ALDH exhibit human genetic polymorphisms and ethnic variations. A toxicologically relevant polymorphism involves the mitochondrial ALDH2, where the ALDH2*2 shows little or no catalytic activity. This inactive form is found in approximately 50% of the Asian population but is absent in Caucasians.
The genetic polymorphism impacts toxicokinetics, in particular the distribution of acetaldehyde in vivo. Conflicting results have been observed in in vivo mutagenicity studies, in particular on whether acetaldehyde is able to reach the germ cells. No reliable data are available on the latter nor on the half-life (and other toxicokinetics parameters) of acetaldehyde in humans with different genotypes of ALDH. Regarding cancer, a number of studies look at the link between genetic polymorphism and alcohol-related cancer risk. However, no direct association was found between acetaldehyde and cancer in humans.