2

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 

cite 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 potential risks of volatilization from chlorpyrifos applications.

In early February 2013, we will publish a notice in the Federal Register announcing the 

availability of this preliminary assessment for public comment. This assessment represents a 

significant advancement 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 volatile pesticides in the 

recent fumigant pesticide risk assessments4to 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 submitted chlorpyrifos field volatility study6coupled with existing 

volatility data found in the open literature, and EPA modeling tools.

This assessment will supplement the July 2011 Preliminary Human Health Risk 

Assessment7(HHRA) and evaluates bystander 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 the 

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, after publication of the Federal Register notice announcing its 

availability in docket number EPA-HQ-OPP-2008-0850.

Following completion of the public comment period and EPA’s subsequent evaluation of 

the comments, EPA will determine whether additional regulatory action is necessary to address 

 

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

EPA-HQ-OPP-2007-0350; dazomet - EPA-HQ-OPP-2005-0128; metam sodium/potassium - EPA-HQ-OPP-2005-

0125; and methyl bromide - EPA-HQ-OPP-2005-0123

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

6Rotondaro, A. and Havens, P. (2012). Direct Flux Measurement of Chlorpyrifos and Chlorpyrifos-Oxon Emissions 

Following Applications of Lorsban Advanced Insecticide to Alfalfa; Sponsor: Dow AgroSciences LLC, 9330 

Zionsville Road Indianapolis, IN 46268-1054. EPA MRID 48883201.

7 Available at http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPP-2008-0850-0025.
3

these risks and, if so, whether the nature of that risk supports the need to take action in advance 

of our completion of the final broader HHRA, currently scheduled for December 2013.

Regarding the remaining three petition issues addressing chlorpyrifos toxicity identified 

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 consideration 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 biomonitoring 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 20128to 

inform our work in generating a weight-of-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 partial petition response to 

you in July 2012, EPA had just received the written SAP report from the April meeting. EPA 

therefore had not had time to begin pursuing the SAP’s recommendation when EPA provided its 

response to you and to the 9th Circuit in our ongoing 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 chlorpyrifos, we believe it is critical to attempt to resolve 

questions about 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 observed 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 current 

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 Columbia University-sponsored epidemiology study9

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 current 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 

 

8 Available at http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPP-2012-0040-0029

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), e1845-1859. doi: 10.1542/peds.2006-0338. 
4

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 and children 

studied in the Columbia University-sponsored epidemiology study10 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 exposures, 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 information 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 expertise in evaluating these aspects 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 from 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 our previous response indicated, last fall, the Columbia University researchers 

published a new epidemiology study11 describing the results of magnetic resonance imaging on a 

subset of children in the cohort. We solicited comments between August 2012 and October 2012, 

from scientists within the federal government who have expertise in this 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 that assessment. It is our hope that 

we can maintain our current schedule to complete the full chlorpyrifos HHRA by the end of 2013

 

10 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), e1845-1859. doi: 10.1542/peds.2006-0338. 

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. 2012 May 15;109(20):7871-6. doi: 10.1073/pnas.1203396109. Epub 2012 Apr 30. 

PubMed PMID: 22547821; PubMed Central PMCID: PMC3356641.