Charge to the Expert Panel 

The NAS panel shall, based upon available literature, theory and experience use its best 

judgment, and rationale, to provide guidance to the Agency on the following areas of the human 

health risk assessment for inhalation exposures to formaldehyde: 1) identification of potential 

adverse non-cancer health effects; 2) assessment of carcinogenic potential; 3) exposure-response 

analysis for identified endpoints; 4) quantitative risk assessment methods; and 5) evaluation of 

sources of uncertainty in the health assessment. Specifically, the panel will address the 

following questions: 

(A) Inhalation Reference Concentration (RfC) for Formaldehyde 

1. Please review and comment on the draft’s analysis of the potential non-cancer health 

effects attributable to inhalation exposure to formaldehyde. Has EPA fairly and soundly 

evaluated the weight of the evidence that formaldehyde causes the effects identified in 

the assessment? Has it appropriately identified and noted the limitations of the available 

studies and the conclusions that can be supported by these studies? 

2. Please review and comment on the draft’s evaluation regarding which studies are 

informative as to the points of departure for the quantitative derivation of an Inhalation 

Reference Concentration (an estimate, with uncertainty spanning perhaps an order of 

magnitude, of a continuous inhalation exposure to the human population, including 

sensitive subgroups, that is likely to be without an appreciable risk of deleterious effects 

during a lifetime). Has it selected studies of suitable quality for the quantitative analysis 

done? Has it appropriately determined which levels to consider points of departure for 

those effects? Please review and comment on its determinations as to when and how to 

make appropriate adjustments for exposure duration and whether alternatives were 

adequately considered and presented. 

3. Please review and comment on the draft’s evaluation of the studies with respect to the 

development of uncertainty factors to derive an Inhalation Reference Concentration from 

points of departure from the sensitive non-cancer effects of formaldehyde. In doing so, 

please review and discuss the evaluation of the extent to which the available studies 

likely capture the range of human variability in response and the completeness of the 

database for purposes of identifying the hazards of formaldehyde inhalation and deriving 

a reference concentration. 

 

(B) Carcinogenicity of Formaldehyde 

1. Please comment on the cancer weight of evidence narrative in the draft, developed 

pursuant to the EPA’s 2005 Guidelines for Carcinogen Risk Assessment 

(www.epa.gov/iris/backgr-d.htm). Is the weight of evidence narrative scientifically 

supported? 

2. Please review and comment on the draft’s quantitative estimations of reasonable upper 

estimates of the potential human cancer risk attributable to inhalation of formaldehyde at 

low concentrations. 

a. The draft uses as its preferred quantitative estimates dose-response relationships 

between several cancers and cumulative inhalation exposure to formaldehyde. 
Please review and comment on the scientific support for the choices made in 

developing those estimates. Please include consideration of issues such 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. 

b. The draft provides, as partial supporting quantitative analysis, estimates of doseresponse quantification from animal studies of nasal tumors. Please review and 

comment on the scientific rationale for the choices made to develop those 

supportive estimates. In doing so, please consider the analysis of the sensitivity 

of low-dose estimates of potential biologically-based dose-response models of 

formaldehyde upper respiratory tract cancer to small changes in model design or 

model inputs.