In the first paper, Using mechanistic information to support evidence integration and synthesis: a case study with inhaled formaldehyde and leukemia, a critical evaluation of the plausibility of inhaled formaldehyde causing leukemia was conducted, focusing on currently postulated modes of action (MOAs) for leukemia. The paper includes the application of systematic review concepts to mechanistic studies, as well as the first attempt to apply a formal framework, specifically the World Health Organization (WHO) International Programme on Chemical Safety (IPCS) Mode of Action framework, in evaluating the evidence for the postulated MOAs for leukemia. As part of the application of the framework, the importance of the relative dosimetry of exogenous and endogenous formaldehyde is considered.
The case study demonstrates that current studies provide inconsistent evidence to support the postulated MOAs for leukemia, suggesting a lack of biological plausibility. It also provides an example that the IPCS framework will work in determining biological plausibility for endpoints for which data from multiple streams of evidence are inconsistent.
In a second paper, An updated mode of action and human relevance framework evaluation for formaldehyde-related nasal tumors, application of the IPCS mode of action framework is updated from a previous publication (McGregor et al. 2006) to evaluate the current mechanistic evidence relevant to understanding the MOA for formaldehyde-induced nasal tumors in rats and their human relevance. The newer studies further underscore the involvement of cytotoxicity and regenerative cell proliferation in the nasal carcinogenicity associated with formaldehyde exposure in rats and inform the genotoxic potential of inhaled formaldehyde.
Both of these studies lend additional support for the use of mechanistic data in the risk assessment of formaldehyde. Further, the results from these studies are highly relevant as the USEPA has designated formaldehyde as a high-priority substance for risk evaluation under the Toxic Substances Control Act (TSCA), a process that recommends that MOA or adverse outcome pathway (AOP) analyses be included as part of a risk evaluation.
Critical Reviews in Toxicology publishes research on toxicology and the application of toxicological information to assess human health hazards and risks.