lifetime exposure to an agent; it is usually expressed in units of proportion (of a population) affected per milligram per kilogram of body weight per day. A unit risk is the upper bound on the excess lifetime cancer risk estimated to result from continuous exposure to an agent at a concentration of 1 μg/L in water or 1 μg/m3 in air. For example, a unit risk of 2 × 10-6 per microgram per liter is interpreted as 2 excess cancer cases (upper-bound estimate) expected to develop per 1,000,000 people if they are exposed to the chemical daily for a lifetime at 1 μg per liter of drinking water.
EPA requested that the National Research Council undertake an independent assessment of its draft Toxicological Review of Tetrachloroethylene (Perchloroethylene) (CAS No. 127-18-4) in Support of Summary Information on the Integrated Risk Information System (IRIS), hereafter called the draft IRIS assessment. The draft IRIS assessment proposes an RfC of 1.6 × 10-2 mg/m3, an RfD of 4 × 10-3 mg/kg-day, a range of inhalation unit risks of 2 × 10-6 to 2 × 10-2 per mg/m3, and a range of oral slope factors of 1 × 10-2 to 1 × 10-1 per mg/kg-day. EPA requested a review of those values and their scientific basis in 2006 but delayed public release of the draft IRIS assessment for additional evaluation within the agency. Therefore, the committee’s review did not begin until June 2008, when the draft was released.
A committee convened by the National Research Council was asked to conduct a scientific review—from toxicologic, epidemiologic, and human clinical perspectives—of EPA’s draft IRIS assessment of tetrachloroethylene that was made available for external review. The committee’s review was to include an evaluation of the adequacy of the assessment and the data and methods used for deriving the RfD and RfC of tetrachloroethylene and its oral and inhalation cancer unit risks. The committee was asked to evaluate whether the key studies underlying the draft IRIS assessment were of requisite quality, reliability, and relevance to support the derivation of the RfD, RfC, and oral and inhalation unit risks; to evaluate whether the scientific uncertainties in EPA's risk assessment were adequately described and, where possible, quantified; and to identify research that could reduce the uncertainties given the current understanding of human health effects associated with tetrachloroethylene exposure.
During the study course of the project, EPA submitted specific questions for the committee to address. The final list, submitted in February 2009, included the following questions:
General Charge Questions:
Does the draft IRIS assessment provide a scientifically sound, balanced, and transparent review and synthesis of the key scientific evidence on chronic noncancer and cancer hazard and risk?