Charge to the Expert Panel

The NAS panel shall, based upon available literatur e, 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. S pecifically, the panel will address the following questions:

(A) Inhalation Reference Concentration (RfC) for Formal dehyde

1. Please review and comment on the draft’s analysis o f the potential non-cancer health effects attributable to inhalation exposure to form aldehyde. Has EPA fairly and soundly evaluated the weight of the evidence that formaldeh yde causes the effects identified in the assessment? Has it appropriately identified an d noted the limitations of the available studies and the conclusions that can be supported b y 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 q uantitative derivation of an Inhalation Reference Concentration (an estimate, with uncertai nty spanning perhaps an order of magnitude, of a continuous inhalation exposure to t he human population, including sensitive subgroups, that is likely to be without a n appreciable risk of deleterious effects during a lifetime). Has it selected studies of sui table 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 de terminations 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 Inh alation Reference Concentration from points of departure from the sensitive non-cancer e ffects of formaldehyde. In doing so, please review and discuss the evaluation of the ext ent to which the available studies likely capture the range of human variability in re sponse 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 nar rative 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 scientifica lly supported?

2. Please review and comment on the draft’s quantitati ve estimations of reasonable upper estimates of the potential human cancer risk attrib utable to inhalation of formaldehyde at

low concentrations.

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

between several cancers and cumulative inhalation e xposure to formaldehyde.Please review and comment on the scientific support for the choices made in developing those estimates. Please include conside ration of issues such as the appropriate dose metric given the study design, the alternative metrics, and the suitability of alternative metrics for use in evalu ating environmental and residential inhalation exposures to formaldehyde.

b. The draft provides, as partial supporting quantitat ive analysis, estimates of doseresponse quantification from animal studies of nasa l 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-bas ed dose-response models of formaldehyde upper respiratory tract cancer to sma ll changes in model design or model inputs.