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assessment , in a quantitative manner, data indicating that long

- lasting effects result from early life exposure to chlorpyrifos in children; ( 3 ) EPA disregarded data demonstrating that there is no evidence of a safe level of exposure during pre

- birth and early life stages; and ( 4 ) EPA failed to cit e or quantitatively incorporate studies and clinical reports suggesting potential adverse effects below 10% cholinesterase inhibition

. As I indicated in the December response, EPA has been working to complete an assessment that will evaluate the potentia l risks of volatilization from chlorpyrifos applications

. In early February 2013, we will publish a notice in the Federal Register announcing the availability of th is preliminary assessment for public comment. This assessment represents a significant advan cement in the evaluation of pesticide risks, as it will be the first probabilistic assessment of the risks posed by the post

- application volatilization of a semi

- volatile pesticide. Our approach builds upon the methodology we previously employed for volati le pesticides in the recent fumigant pesticide risk assessments 4 to assess bystander inhalation exposure from volatilization. In addition, it is consistent with the recommendations from the December 2009 Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) 5 meeting on the scientific issues associated with field volatilization of conventional (semi

- volatile) pesticides. The content of the preliminary volatilization assessment is further informed by Dow AgroSciences’ recently s ubmitted chlorpyrifos field volatility study 6 coupled with existing volatility data found in the open literature, and EPA modeling tools

. This assessment will supplement the July 2011 Preliminary Human Health Risk Assessment 7 (HHRA) and evaluates bystand er exposure from chlorpyrifos and chlorpyrifos

- oxon emitted from treated fields. Although the volatilization of chlorpyrifos was addressed in the preliminary HHRA , that analysis involved only a deterministic assessment based on limited monitoring data that did not attempt to evaluate a range of field conditions and

, therefore

, had correspondingly limited utility in a regulatory setting. Given the groundbreaking nature of th e

new assessment and its potential for use in guiding additional risk mitigation

, EPA believes it is critical to involve the public in the development of this assessment before it is finalized. Further, EPA is examining other semi

- volatile pesticides to determine if bystander volatilization
assessments are needed. Any comments received on this assessment will serve to inform those assessments as well. Accordingly, EPA will begin taking public comment on the draft version of the assessment in February 2013

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4 The assessments can be found in the dockets for each fumigant. Four of which ar e provided here chloropicrin

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5 U.S. EPA 2009 . FIFRA Science Advisory Panel Meeting Minutes

- Scientific Issues Associated with Field Volatilization of Conventional Pesticides

. Available at http://www.epa.gov/scipoly/sap/meetings/2009/december/120309meetingminutes.pdf
6 Rotondaro , A. and Havens, P. (2012). Direct Flux Measurement of Chlorpyrifos and Chlorpyrifos

- Oxo n Emissions Following Applications of Lorsban Advanced Insecticide to Alfalfa; Sponsor: Dow AgroSciences LLC, 9330 Zionsville Road Indianapolis, IN 46268

- 1054. EPA MRID 48883201

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these risks and

, if so, whether the nature of that risk supports the need to take action in advance of our complet ion of the final broader HHRA , currently scheduled for December 2013

. Regarding the remaining three petition issues addressing chlorpyrifos toxicity identi fied above, as we have indicated previously, the analysis is complicated and multifaceted because it involves many lines of scientific evidence , including many recently conducted studies and peer review evaluations and recommendations. That work includes c onsideration of : in vivo and in vitro experimental toxicology studies that evaluate neurodevelopmental effects in laboratory animals, adverse outcome pathway framework analyses, exposure, the results of multiple human epidemiology studies , and biomonitorin g data. Notwithstanding the complexity of this analysis, it was our hope to provide you with a written response last December that included our scientific conclusions on these issues. As you know, we convened a FIFRA SAP meeting in April 2012 8 to inform our work in generating a weight

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- evidence evaluation integrating the epidemiologic data with the experimental toxicology studies for the neurodevelopmental outcomes and acetylcholinesterase ( AChE ) inhibition. At the time EPA provided its part ial petition response to you in July 2012, EPA had just received the written SAP report from the April meeting

. EPA therefore ha d not ha d time to begin pursuing the SAP’s recommendation when EPA provided its response to you and to the 9th Circuit in our o ngoing litigation over this matter.

Thus far, EPA has not encountered epidemiological data of sufficient quality to support quantitative risk assessment of conventional pesticide chemicals. Before EPA decides how to use the epidemiological data on chlor pyrifos, we believe it is critical to attempt to resolve questions abo ut these studies regarding the extent of the cohort members’ exposures to chlorpyrifos, as well as the impact of exposure to other compounds capable of causing or contributing to the obs erved neurological outcomes. We acknowledge the lengthy conduct of our assessment, including multiple SAP reviews, but we believe the deliberate and considered approach we are taking is the most scientifically defensible method for re

- evaluating our curren t approach to assessing risks from chlorpyrifos and other organophosphorous pesticides generally, and, specifically, for evaluating the strengths and weaknesses of the epidemiological data.

The July 2012 SAP report is in accord with EPA’s assessment that the Agency should attempt to resolve certain key questions about the epidemiological data

. Specifically, the SAP recommended that EPA pursue a number of possible approaches for attempting to resolve whether the neurological outcomes observed in the studies occurred in the absence of AChE inhibition

– the effect EPA’s current regulatory approach is designed to preclude. Further, given that the women and children studied in the C olumbia University

- sponsored epidemiology study 9 were exposed to multiple chemicals (including other pesticides, polycyclic aromatic hydrocarbons and lead), the SAP cautioned the agency about attributing the outcomes to a single chemical based on the curre nt analysis conducted by Columbia University researchers. These statements by the SAP lead the agency to believe that we need to further explore the extent to

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9 Rauh, V., Arunajadai, S., Horton, M., Perera, F., Hoepner, L., Barr, D. B., & Whyatt, R. (2011). Seven

- year neurodevelopmental scores and prenatal exposure to chlorpyrifos, a common agricultural pesticide. Environ Health Perspect, 119(8), 1196

- 1201. doi: 10.1289/ehp.1003160; Rauh, V. A., Garfinkel, R., Perera, F. P., Andrews, H. F., Hoepner, L., Barr, D. B., Whyatt, R. W. (2006). Impact of prenatal chlorpyrifos exposure on neurodevelopment in the first 3 years of life among inner

- city children. Pediatrics, 118(6), e1845

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which the observed neurological outcomes were influenced by exposure to these other chemicals

. Following receipt of the report EPA began conducting a number of analyses to address these recommendations. As I indicated in our December response , we are making progress in conducting a dose

- reconstruction analysis of potential exposures to the women a nd children studied in the Columbia University

- sponsored epidemiology study 10 in order to assess the degree to which the individuals in the cohort may or may not have been exposed to chlorpyrifos levels high enough to cause AChE inhibition

. In addition to this assessment, to address the SAP recommendations EPA also intends in the coming months to complete an evaluation of cohort exposures to other chemicals. In order to complete both the dose reconstruction and analyses on other chemical e xposures , however, we will need to analyze the original data (“ raw data ”) from the Columbia University study to better understand the exposure to chlorpyrifos and other chemicals. To date, the study authors have declined our request to provide that informa tion to us, but we are continuing to discuss our need for evaluating these data with the study authors and we are hopeful that a resolution can be reached.

In addition to further analysis of the exposures in the Columbia study, EPA has also followed up on a recommendation that was brought up in the SAP’s oral deliberations regarding the administration and interpretation of diagnostic and analytic tools used to assess neuro and motor development in children like those used in the Columbia study. The SAP noted that it lacked expert i se in evaluating th e s e aspect s of the data. Because this expertise is relevant in assessing the potential for effects from exposures to other chemicals, between August and October 2012, we obtained additional peer review fr om scientists within the federal government who have expertise in this field. EPA will include consideration of the results of this peer review when it completes its assessment

, as further discussed below.

Finally, as o ur previous response indicated , las t fall, the Columbia University researchers published a new epidemiology st udy 11 describing the results of magnetic resonance imaging on a subset of children in the cohort

. We solicited comments b etween August 2012 and October 2012

, from scientists within the federal government who have expertise in th is scientific area and are currently evaluating this input to determine the extent to which this information informs the earlier Columbia University study results

. In light of our ongoing work described above

, we are not in a position to provide you with our conclusions on the three remaining toxicology issues in the petition at this time

, and it is difficult to provide a precise time frame for the completion of th at assessment. It is our hope that we can main tain our current schedule to complete the full chlorpyrifos HHRA by the end of 2013

10 Rauh, V., A runajadai, S., Horton, M., Perera, F., Hoepner, L., Barr, D. B., & Whyatt, R. (2011). Seven

- year neurodevelopmental scores and prenatal exposure to chlorpyrifos, a common agricultural pesticide. Environ Health Perspect, 119(8), 1196

- 1201. doi: 10.1289/ehp. 1003160; Rauh, V. A., Garfinkel, R., Perera, F. P., Andrews, H. F., Hoepner, L., Barr, D. B., Whyatt, R. W. (2006). Impact of prenatal chlorpyrifos exposure on neurodevelopment in the first 3 years of life among inner

- city children. Pediatrics, 118(6), e18 45

- 1859. doi: 10.1542/peds.2006

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. 11 Rauh VA, Perera FP, Horton MK, Whyatt RM, Bansal R, Hao X, Liu J, Barr DB, Slotkin TA, Peterson BS. Brain anomalies in children exposed prenatally to a common organophosphate pesticide. Proc Natl Acad Sci U S A. 201 2 May 15;109(20):7871

- 6. doi: 10.1073/pnas.1203396109. Epub 2012 Apr 30. PubMed PMID: 22547821; PubMed Central PMCID: PMC3356641.