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 Pcnnsy1 vania Avenue. NW Washington. D.C. 20460

Dear Dr. Frey: WASHINGTON. DC 20460 

## SEP

- 

## 4 2013

Thank you for yourJune 4, 2013, letter in which youprovided the Clean Air Scientific Advisory Committee'scomments and recommendations on the U.S. Environmental Protection**Agency~s** 

### lntegraledScienceAssessmentforLead, ThirdExternalReview Drqft, released in November2012 for public commentand peerreview. The EPA greatly appreciates yourhard work.

My staffcarefully considered the paners 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'sconsensus 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 ofa causal relationship." The EPA thoroughly evaluated the evidence for reduced kidney function as it relates to the EPA!s framework for**ca~sal** determinations. Afterconsidering the totality ofthe toxicological and epidemiologic evidence, with a particular focus on the potential·for reverse causation to influence study findings, the EPA agreed with CASAC'srecommendation to revise the causal determination for reduced kidney function to Hsuggestive ofa causal relationship.,.

The panel noted that previous revisions successfully enhanced the clarity and transparency ofthe application ofthe causal fran1ework 

### by defining specific endpoint groupings around which conclusions would be formed. Thepanel 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 ofindividual studies andthe display ofsummary information. TheEPA 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 ofthe key evidence considered in fonning conclusions and by documenting the limitations and uncertainties ofthat evidence.

The CASAC recognized that the draft ISA integrated ""an extraordinary amount ofinformation about atrisk populations and employs a useful frame\vork'' for evaluation ofpotential at-risk populations and lifestages and recommended that the EPA add a table to include information on the relative magnitude oftheeffect modification from various risk factors. My staffcompiled and evaluatedquantitative 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 ofthe document where possible. rather than as a table. Given the characteristics ofthe available data we think this is an appropriate way to convey this information.

Ionce again extend rny sincerest thanksto you and the pane) members for 

### yourhard 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.