Overall, the committee noted some recurring methodologic problems in the draft IRIS assessment of formaldehyde. Many of the problems are similar to those which have been reported over the last decade by other NRC committees tasked with reviewing EPA’s IRIS assessments for other chemicals. Problems with clarity and transparency of the methods appear to be a repeating theme over the years, even though the documents appear to have grown considerably in length. In the roughly 1,000-page draft reviewed by the present committee, little beyond a brief introductory chapter could be found on the methods for conducting the assessment. Numerous EPA guidelines are cited, but their role in the preparation of the assessment is not clear. In general, the committee found that the draft was not prepared in a consistent fashion; it lacks clear links to an underlying conceptual framework; and it does not contain sufficient documentation on methods and criteria for identifying evidence from epidemiologic and experimental studies, for critically evaluating individual studies, for assessing the weight of evidence, and for selecting studies for derivation of the RfCs and unit risk estimates. This summary highlights the committee’s substantive comments and recommendations that should be considered in revision of the draft IRIS assessment; more detailed comments and recommendations can be found at the conclusions of individual chapters or following the discussions on individual health outcomes.

The committee reviewed the extensive discussion on toxicokinetics of formaldehyde in the draft IRIS assessment and focused on several key issues: the implications of endogenous formaldehyde, the fate of inhaled formaldehyde, the systemic availability of formaldehyde, the ability of formaldehyde to cause systemic genotoxic effects, and the usefulness of various models.

Endogenous formaldehyde. Humans and other animals produce formaldehyde through various biologic pathways as part of normal metabolism. Thus, formaldehyde is normally present at low concentrations in all tissues, cells, and bodily fluids. Although there is some debate regarding interpretation of the analytic measurements, formaldehyde has been measured in exhaled breath and is most likely present normally at a concentration of a few parts per billion. The endogenous production of formaldehyde complicates the assessment of the risk associated with formaldehyde inhalation and remains an important uncertainty in assessing the additional dose received by inhalation, particularly at sites beyond the respiratory tract.

Fate of inhaled formaldehyde. Formaldehyde is a highly water-soluble, reactive chemical that has a short biologic half-life. Despite species differences in uptake due to differences in breathing patterns and nasal structures, formaldehyde is absorbed primarily at the site of first contact where it undergoes exten-