A committee of the National Research Council (NRC) will conduct an independent scientific review of the U.S. Environmental Protection Agency (EPA) draft human health assessment of formaldehyde for the Integrated Risk Information System (IRIS). The committee will provide a brief report that comments on EPA’s identification of potential adverse noncancer health effects, assessment of carcinogenic potential, exposure-response analysis for identified end points, quantitative risk assessment methods, and evaluation of sources of uncertainty in the health assessment. Specifically, the committee will address tasks such as the following:

Inhalation Reference Concentration for Formaldehyde

• Review and comment on the draft’s analysis of the potential noncancer health effects attributable to inhalation exposure to formaldehyde and answer the following questions: Has EPA fairly and soundly evaluated the weight of evidence that formaldehyde causes the effects identified in the assessment? Has it reached conclusions that can be supported by the available studies and appropriately identified and described the weaknesses of the studies?

• Review and comment on the draft’s evaluation of the studies used to identify the points of departure for quantitative derivation of the reference concentration and answer the following questions: Has EPA selected studies of suitable quality for the quantitative analysis? Has it appropriately determined the points of departure for the effects? In addition, review and comment on EPA’s determinations as to when and how to adjust appropriately for exposure duration and whether alternatives were adequately considered and presented.

• Review and comment on the draft’s evaluation of the studies used to determine the uncertainty factors for derivation of the reference concentration for the sensitive noncancer effects of formaldehyde. Also, review and discuss the evaluation of the extent to which the available studies capture the range of human variability in response to formaldehyde exposures; and review and discuss the completeness of the database used to identify the hazards of formaldehyde inhalation and to derive a reference concentration.

Carcinogenicity of Formaldehyde

• Comment on the cancer weight-of-evidence narrative in the draft, developed according to EPA’s 2005 Guidelines for Carcinogen Risk Assessment and answer the question, is the weight-of-evidence narrative scientifically supported?

• Review and comment on the draft’s reasonable upper estimates of the potential human cancer risk attributable to inhalation of formaldehyde at low concentrations.

• Review and comment on the scientific support for the choices made in developing the preferred quantitative estimates that are based on dose-response relationships between several cancers and cumulative inhalation exposure, and consider such issues as the appropriate dose metric given the study design, the alternative metrics, and the suitability of alternative metrics for use in evaluating environmental and residential inhalation exposures to formaldehyde.

• Review and comment on the scientific rationale for the choices made to develop the supportive estimates that are based on dose-response relationships from animal studies of nasal tumors, and consider the analysis of the sensitivity of low-dose estimates from biologically based dose-response models of formaldehyde for upper respiratory tract cancer to small changes in model design or model inputs.