US EPA

1010576 

Journal Article 

Hypothesis-Based Weight-of-Evidence evaluation of methanol as a human carcinogen 

Bailey, LA; Prueitt, RL; Rhomberg, LR 

2012 

Yes 

Regulatory Toxicology and Pharmacology
ISSN: 0273-2300
EISSN: 1096-0295 

62 

2 

278-291 

English 

22166730 

10.1016/j.yrtph.2011.11.015 

WOS:000301030000006 

Recent scientific debate has focused on the potential for exposure to methanol to cause lymphomas in humans. The concern stems from a few animal studies reporting an association, although evidence suggests the studies may have been confounded by chronic respiratory infection. Although the toxicological evidence for methanol carcinogenesis is weak, two modes of action have been put forth, one involving metabolism of methanol to formaldehyde, followed by formaldehyde induction of lymphoma, and another involving oxidative stress caused by hydrogen peroxide release during catalase-induced metabolism of methanol to formaldehyde. In this article, we apply our Hypothesis-Based Weight-of-Evidence (HBWoE) approach to evaluate the evidence regarding methanol exposure and lymphoma, attending to how human, animal, and mode-of-action results inform one another, tracing the logic of inference within and across all studies, and articulating how one could account for the suite of available observations. Upon comparison of alternative proposals regarding what causal processes may have led to the array of observations as we see them, we conclude that the apparent association between methanol exposure and lymphoma in some animal studies is weak and strains biological plausibility, and is better interpreted as due to confounding or to a mechanism not relevant in humans. 

Methanol; Formaldehyde; Lymphoma; Hazard identification; Human relevance; Risk assessment; Mode of action