Draft Charge to External Reviewers for the
IRIS Toxicological Review of Urea
June 2010
The U.S. Environmental Protection Agency (EPA) is seeking an external peer review of the
scientific basis supporting the human health assessment of urea that will appear on the Agency's
online database, the Integrated Risk Information System (IRIS). IRIS is prepared and
maintained by the EPA's National Center for Environmental Assessment (NCEA) within the
Office of Research and Development (ORD). Currently an IRIS assessment of urea does not
exist on the database.
The current draft health assessment includes an evaluation of the available data and a
determination that the data are insufficient for the derivation of toxicity values. A cancer
descriptor for urea is included. Below is a set of charge questions that address scientific issues in
the assessment of urea. Please provide detailed explanations for responses to the charge
questions. Please consider the accuracy, objectivity, and transparency of EPA's analysis and
conclusions in your review.
General Charge Questions:
1.	Is the Toxicological Review logical, clear and concise? Has EPA clearly synthesized the
scientific evidence for noncancer and cancer hazard?
2.	Please identify any additional studies that should be considered in the assessment of the
noncancer and cancer health effects of urea.
Chemical-Specific Charge Questions:
(A)	Oral reference dose (RfD) for urea
1. An RfD for urea was not derived. Is the rationale for not deriving an RfD scientifically
justified and clearly described? Please identify and provide the rationale for any studies that
should be selected as the principal study and any endpoint that should be considered as a critical
effect.
(B)	Inhalation reference concentration (RfC) for urea
1. An RfC for urea was not derived. Is the rationale for not deriving an RfC scientifically
justified and clearly described? Please identify and provide the rationale for any studies that
should be selected as the principal study and any endpoint that should be considered as a critical
effect?
(C)	Carcinogenicity of urea
1.	Under EPA's 2005 Guidelines for Carcinogen Risk Assessment (www.epa.gov/iris/backgr-
d.htm), the Agency concluded that there is inadequate information to access the carcinogenic
potential of urea. Is the choice of cancer descriptor scientifically justified and clearly described?
2.	EPA did not derive a quantitative estimate of the carcinogenic potential of urea. Do the data
support an estimation of a cancer slope factor for urea? If a quantitative estimate is proposed,
please identify the data set and a description of the method that should be used.
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