Methanol Institute Comments on the Proposed Classification of Methanol as a Reproductive Toxicant Under the CLP Regulation

Rodents and non-rodent species metabolize methanol to formaldehyde to formic acid to carbon dioxide. There are two major differences, however. Rodents (mice and rats) metabolize methanol to formaldehyde using the enzyme catalase, whereas humans use alcohol dehydrogenase (ADH1). A byproduct of rodent methanol metabolism is hydrogen peroxide, a reactive oxygen species (ROS). ROS may be involved in the mode of action for methanol-induced adverse developmental effects in rodents. Secondly, in humans the conversion of formic acid to carbon dioxide is rate limited because humans have much lower levels of folate, a required component of this metabolic step, resulting in formic acid accumulation and toxicity. Thus, exposure to high levels of methanol result in increased ROS in rodents, and formic acid in humans.