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() PRO' UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460

THE ADMINISTRATOR

Jonathan M. Samet, M.D. Chairman Clean Air Scientific Advisory Committee Science Advisory Board U.S. Environmental Protection Agency 1200 Pennsylvania Avenue, NW Washington, D.C. 20460

Thank you for your December 9, 2011, letter providing the Clean Air Scientific Advisory Committee Lead Review Panels comments on the U.S. Environmental Protection Agency's First External Review Draft Integrated Science Assessment for Lead, May 2011. We at the EPA greatly appreciate the panel's thorough review and constructive comments.

My staff carefully considered your comments and recommendations as well as the comments we received from the public. The EPA's revisions address both consensus and individual CASAC comments and also incorporate findings of additional studies published through September 2011. Attached is an overview of the major revisions in the Second External Review Draft of the Integrated Science Assessment for Lead. Some of the key changes made in response to the CASAC's comments are highlighted below.

The lead panel offered a number of recommendations to enhance the organization and presentation of the evidence in the ISA. Your committee provided similar recommendations regarding the First External Review Draft of the Integrated Science Assessment for Ozone. In response to these comments, we added a preamble, a preface and an executive summary. The restructuring was intended to bring the integrative overview discussion forward in the document and make it more accessible to the reader. The preamble is applicable to all ISAs and includes the more general sections on ISA development and the causality framework from chapter 2. The preface includes sections on legislative background, the history of previous reviews and the status of the current review. Chapter 2, the integrative summary, is now the first substantive chapter of the ISA.

The CASAC generally supported the EPA's conclusions on the health effects in the first draft of the lead ISA, and the major conclusions have not changed. However, the EPA modified the presentation of the evidence to reflect our rigorous "weight of the evidence" assessment approach and allow more transparency in the application of the framework for causal determination. Specifically, in chapters 2 and 5, we characterize the weight of evidence for each endpoint within a broad outcome category and specify the particular endpoints that contribute most heavily to the causal determination. We also more directly acknowledge uncertainties relating to the frequency, timing, duration and level of lead exposure

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who are likely to have had higher past than recent lead exposure. New sections that discuss the publichealth significance of findings were also added to the document in chapters 2 and 5. In chapters 2 and 5 we also strengthened our integration of epidemiologic and toxicological studies based on homologous endpoints, and we sharpened and focused our evaluation of the toxicological evidence to emphasize findings that were most relevant to human health, e.g., effects at low lead concentrations and dietary routes of exposure.

Chapter 3 integrates current findings with the science presented in the 2006 Air Quality Criteria Document to describe the state of the science on lead. Discussions were added or enhanced on monitoring technology, natural background lead concentrations, particle size distribution and on non-air sources of lead exposure. In chapter 4 we revised and expanded sections relating to biokinetic and exposure models, and we enhanced the discussion of the critical evaluation of studies of the relationship between air lead and blood lead.

In chapter 6 the CASAC panel's advice on the use of a broad definition of "susceptibility" has been carefully considered. As in the second draft ISA for ozone, we have used the term "at-risk" rather than susceptibility where an overarching term is appropriate and made several refinements to the discussion at the beginning of the chapter on Potentially At-Risk Populations.

In chapter 7 we revised the conclusions for ecological effects to consider effects in terrestrial and aquatic systems separately. Causal determinations are now accompanied by additional data on lead levels at which effects are observed. The determination of causality for bioaccumulation as it affects ecosystem services has been removed from the second draft.

We recognize that our efforts to protect the environment can be only as good as the science on which they are based. Independent critical reviews such as yours help to ensure that we use the best science to protect public health and our nation's environment. Please accept my appreciation for your hard work and thoughtful review.