THE ADMINISTRATOR OF THE ENVIRONMENTAL PROTECTION AGENCY 

H. Christopher Frey. Ph.D.· 

Chair 

Clean Air Scientific Advisory Committee 

Science Advisory Board 

U.S. Environmental Protection Agency 

1200 Pcnnsy 1 vania A venue. NW 

Washington. D.C. 20460 

Dear Dr. Frey: 

WASHINGTON. DC 20460 

SEP - 4 2013 

Thank you for your June 4, 2013, letter in which you provided the Clean Air Scientific Advisory 

Committee's comments and recommendations on the U.S. Environmental Protection Agency~s 

lntegraled Science Assessmentfor Lead, Third External Review Drqft, released in November 2012 for 

public comment and peer review. The EPA greatly appreciates your hard work. 

My staff carefully considered the paner s contments and recommend.ations and those we received from 

the puhlic. We made revisions, which include adding recently published papers you identified, to 

address the panel's consensus and individual comments as well as the public's comments. 

The CASAC panel recommended that the EPA revise the causal dctertnination for reduced kidney 

function from ""likely to be a causal relationship·· to ·"suggestive of a causal relationship." The EPA 

thoroughly evaluated the evidence for reduced kidney function as it relates to the EPA! s framework for 

ca~sal determinations. After considering the totality of the toxicological and epidemiologic evidence, 

with a particular focus on the potential· for reverse causation to influence study findings, the EPA agreed 

with CASAC's recommendation to revise the causal determination for reduced kidney function to 

Hsuggestive of a causal relationship.,. 

The panel noted that previous revisions successfully enhanced the clarity and transparency of the 

application of the causal fran1ework by defining specific endpoint groupings around which conclusions 

would be formed. The panel offered additional advice to refine certain health-outcome categories to 

increase their specificity. appropriately categorize several nervous-system endpoints~ adopt standard 

naming conventions for behavioral outcomes and enhance the evaluation of individual studies and the 

display of summary information. The EPA implemented these recommendations throughout the 

document by including new figures such as those showing various ecological effects as a function of 

exposure concentration, by identifying and clarifying attributes of the key evidence considered in 

fonning conclusions and by documenting the limitations and uncertainties of that evidence. 

The CASAC recognized that the draft ISA integrated ""an extraordinary amount of information about atrisk populations and employs a useful frame\vork'' for evaluation of potential at-risk populations and 

lifestages and recommended that the EPA add a table to include information on the relative magnitude 

of the effect modification from various risk factors. My staff compiled and evaluated quantitative risk 

Th1s paper 1s pnnted with veqetable-oil·based mks and 1S 100-percent postconsumer recycled material. chlorine-free-processed and recyclable. 
estimates tron1 health studies and found that there were few studies, and their results \\tere not always 

cotnparablc; thus. the information was incorporated in the text of the document where possible. rather 

than as a table. Given the characteristics of the available data we think this is an appropriate way to 

convey this information. 

I once again extend rny sincerest thanks to you and the pane) members for your hard work. We arc 

grateful for your independent critical reviews to help us ensure that the EPA uses the best science to 

protect public health and the environment.