UNITED STATES ENVIRONMENT AL PROTECTION AGENC Y WASH I NGTON , D

. C

. 20460

OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENT I ON

Aaron Colangelo, Esq. Senior Attorney N atu ral Resources Defense Counci l 1152 15th Street NW, Suit e 300 Washington, D.C. 20005 Margaret Reeves, Ph.D. 

## MAR 2 6 2015

Senior Scientist / Program Coordinator (Environmental Health and Worker:s' R i ghts) Pest i cide Action Network North America 49 Powell Street, Su ite 500 San Francisco, CA 94102 Re: Chl orpyrifos Petition Dated September 12 , 2007; March 2015 Provisional Response Dear Mr. Co l angelo and Dr. Reeves: This letter constitutes the U.S. Environmental Protection Agency ' s (EPA) provisional response to the Natural Resources Defense Council (NRDC) and Pest i cide Action Network North America's (PANNA) jointl y submitted September 12 , 2007 1 pe tition. The petiti on specifically requested that EPA revoke all to l erances and cancel all registrations for the insecticide chlorpyrifos

. This response incorporates EPA's two partia l responses of July 16, 2012 2
, and July 15 , 2014 3
, and describes EPA's provisional approach for addressing the three remaining claims in the petition. It also outlines the activities EPA expects to undertake to address the concerns identified in the Revised H uman Health Risk Assessment (RHHRA) 4

. As you are aware, while EPA has addressed seven of the ten claims raised in your petition through our July 16, 2012 and July 15 , 2014 partial petition responses, we determined that additional analyses were necessary to complete our respon se to your three interrelated claims ' regarding chlorpyrifos tox i cology and that it would be appropria t e to address those claims in the same tim e frame as the RHHRA for registration review. Specifically, the three remaining claims you raised in your petition were: ( 1) EPA fai led to incorporate into its risk assessment, in a quantitative manner, data indicating that long -lasting effects in children resu l t from ear l y li fe

1 Av a i lable at http: //www.regulations.gov /# !documentDetail;D= EPA-HO-OPP-2007- I 005-0005

. 2 Availabl e at http ;// www .regulations.gov /# !documentDetail;D = EPA-HQ-QPP-2007

- I005-0095

. 3 Av a ilable at http: //www.regu lations.gov /# !documentDetai l;D = EP A- H Q-OPP-2007- I005

- 0098

. 4 Av a ilable at http: //www.regu lations.gov/# !documentDetail;D=EPA

- HQ-OP P-2008-0850-0195

. 1exposure to chlorpyrifos; (2) E PA disr ega rded data d e mo nstra t ing that the r e is no evidence of a safe level of exposure during pre-birth and early life s tag es; and (3) EPA fa il ed to cite or quanti t atively inc o rpora t e studi es and clinical re p orts suggesting pote ntial adve rse effects below 10% c holinest erase inhibition

. On D ecember 31, 20 14 , EPA made the RHHRA av ailable for publi c r ev i ew and on January 14, 2015, EPA i ssued a Federal Register Notice 5 opening the public comment period for the RHHRA. In sum , the RHHRA sho ws some risks to worke rs who mix , loa d , and ap pl y c hl o rp yrifos pesticide products. The assessment also shows potential ri sks of concern in limited geographic areas from dri nkin g water in sma JJ watersheds. There were no additional risks of co ncern from p esticide exposure s in food o r ex p osu res to bystanders and worke rs from airborne chlorpyrifos

. This RHHRA is also among the first · assess ments informe d b y a physiologically based pharmacokin e ti c and pharmacodynamic (PB PK/PD) model. EPA is now taking comment on the asse ssmen t and will cons ider the comments rece i ve d and determin e whether additional refinements are necessary in light o f those comment s . Because we are taking co mment on the RHHRA , this document constitutes our provisional response to your petition. We i ntend to fina li ze our r espo n se late r thi s year fo ll owi n g review and analysis of comments received on the RHHRA. The Three Remaining P etition Claims The RHHRA addresses the issue s e mbodi e d in the three remainin g petition claims as interrelated que s ti ons regarding the poten tial for ne urodevelopmental effects to occur at leve l s lower than EP A's current regu latory point of departure

- 10 % acetyl c holinester as e (A ChE) inhi b ition. Below summarizes our po sition as presented in the RHHRA , but please refer to the RHHRA 6 for the e nt ire discussion. In short though , we do not believe that the clai m s raised in your petition establish a basis to revok e all chlorpyrifos tolerances and cancel all chlo rpyri fos registrations. In the RHHRA w e co nducted a weight-of-ev id ence (WOE) ana l ysis integrating recent e pidemiology s tudi es t hat inv olved chlorpyri fos exposures with chlorpyrifos expe rimental to x icology studies to eva luate the po tential for adverse neurodevelopm en tal outcomes. The WO E was also informed by E P A' s use of a ph ysiologicall y- ba se d pharmacokinetic-pharmacodynamic (PBPK

- PD ) model recently completed by Dow AgroSciences , one o f the c hl orpyrifos regis trant s. Fo ll owi ng EP A's quality assura nce evaluation , we used the r obust PBPK-PD model 7 to estimate human equivalent doses /concentra t ions which were used as the toxicological points of de pa rture (Po D s) and also to define inter- and intra- species facto rs fo r chlorp yri fos and/o r its oxon s pe c ifically tailored to a ll app licable exposure pathways for chlorpyrifos (e.g. food, water , occupational, re s id e nti a l)

.

5 Available at http : w ww .regulations.gov /# !documentD e tail;D = EPA-HQ-OPP-2008-0850-0200

. 6 Available at http : www . regulations.gov/# !documentDetail;D= EPA-HQ

- OPP-2008-0850-0195. 7 U.S. EPA 2011. FIFRA Science Advisory Pan el Meeting Minutes

- Chlorpyrifos Physiologically-Based Pharmacokinetic/ Pharmacodynamic (PB PK/PD) Modeling linked to the Cumula tive and Aggregate Risk Evaluation Syste m (C A RES). Available at http: //www.epa.gov/ s cipoly/ sap/ meetings/2011 / 021511 meeting.html. 2The key issues considered in the WOE were whether chlorpyrifos causes long-term effects from prenatal and/or early lifestage exposure and whether these adverse effects can be att ributed to doses lower than those which elicit 10 % inhibition ofRBC AChE. When taken to ge th er , the eviden ce from (1) the experimental tox i co logy studies evaluating outcomes such as behavior and cogni tive function; (2) mechanistic data on possible modes of action/ adverse outco me pathways (MOA/ AOP); and (3) ep id emi o logic and bi o monitoring stud ie s, indicate that chlorpyr ifo s like ly p l ayed a role in the neurodevelopmental outcomes reported by the Columbia University e pi <lemiologic st udy investigators. Uncertainties suc h as the lack of an establi shed MOA/ AOP for neurodevelopmental effect s, and the fact that the ep id e m iolog ic study cohorts were potentially exposed to m ultiple AChE-inhibiting pesticides preclude s definitive causal inference and precludes the use of the epidemiologic studies in a quantitative risk assessment. However, as d e tailed in the RHHRA, EPA believes there i s sufficient un certai nty in the human dose-response r e lati ons hip for neurodeve l opmental effects to preclud e u s from reducing or removing the statutory l 

### OX Food Quali ty Pro tect io n Act (FQPA) safety facto r. In addition , E PA bel i eves the evidence is insufficient to suggest altering the use of 1 0% AChE inhibit ion as th e point of departure. In 2008 8 and 2012 9 the Federal Insecticide , Fungicide , and Rodenticide Act (FIFRA) Scie ntific Advisory P anel (SAP) recommended that AChE data provide the most appropriate endpoint and dose-re spo nse data for deriving Po D s for purposes of risk assessment. EPA agrees with the SAP 's recommendation. While EPA believes that the e pidemiologic data give rise to a meas ure of uncertainty regarding the relationship between AChE inhi bition and certain adverse neurodev elop m e ntal outcome s, many of the same factor s that make these st udi es inappropriate for use in quantitative risk assessment also co unsel against their u se as a basis for departing from 10% AChE inhibition as a regulatory point of departure. A ltho ugh EPA's dose reconstructi on exercise certain ly suggests that it i s possible that the cohort members in the Columbia s tudy did not e xperie nce cho lin esterase inhibition , with no established MOA/ AOP for the observed neurodevelopmental effects, limited cohort exposure d ata, and possib le additive effects from co -exposures to other AChE inhi biting compounds, the re are s impl y too many uncertainties surrounding the neurodevelopmental data for E PA to conclude that our use of 10% AChE inhibition is n o l o n ger appropri ate. Accordingly, as provided in the RHHRA , EPA ha s retained AChE inhibition as the re gulatory point of de partur e. Provisional EPA R esponse For the reason s explained above, and as out li ned in our two part ial responses, EPA does not be l ieve the claims raised in your petition establish a basis to revoke all chlorpyrifos tolerances and cancel a ll ch lorpyrifos registration s. As set forth in the RHHRA , howev er , EPA has risk concerns stemmin g from routes of human exposure not addressed in y our petition, spec ifically from estimated drinking water expos ure and risks to workers (i.e., mixers, loaders , and app li cators). We are c urr ently tak ing pu bli c comment on the RHHRA

. Assuming that we do not receive any comments that persuade

8 U.S. EPA 2008. FlFRA Science Advisory Pan el Meeting Minutes -The Agency ' s Evaluation of the To xicity Profil e of Chlorpyrifos. Available at http: www.epa.gov/scipoly 1 sap/ meetings ' 2008 / september /sap0908reoort.pdf. 9 U.S. EPA 2012. FIFRA Science Advisory Panel Meeting Minute s - Scientific Issues Concerning Health Effects of C hlorpyrifos. Available at http: //www.epa . gov/ scipoly/ sap/ meetings/20 I 2 / april /0410 I 2minutes.pdf

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### 3us that exposures are acceptab le , we intend to seek any necessa ry labeling changes to currentlyregis tered chlorp yrifo s products to ensure that the continued use of chlorpyrifos is consistent with FIFRA and FFDCA sta ndards. Indee d , E PA has already begun discussions with the c hlorpyrifos regi s trant s r eg arding mitigation of worker risk. In additi on, over the coming months EPA will be working to refine the drinking water assessment ( DW A). The DWA co mpone nt of the RHHRA contained a national level screen , as well as a regional screen for two areas , t h e Pacific Northwest and the South Atlantic

- Gulf. The reg ional level methodology, which in volves using a drinkin g water intake watershed approach that accounts for geospatial di ffere nces and regional percent cropped area (PCA), will be expanded to e nco mp a s s the remaining regions of the co untry. The refine d DWA will also be informed by any mi ti gat ion addressing worker risks. Whi l e we agree wi th petitioner s that so me acti on should be taken to miti gate the ri sks of ch lorp yri fos, we do not believe that eith er revok in g all tolerances or cance lin g a ll c hlorp yrifo s products, the remedies sough t in your petition , will ultimate l y be necessary to appropriately mitigate t he se risks concerns. We believe these risks likely can be mitigated by appropri ate c hanges to the FIFRA label. According ly , should our position o n the risks fro m c hlorp y rifo s ex po sure and any necessary mitigation remain unchanged following our review of comments on the RHHRA, we intend to formally den y your petition to revoke all tol erances and cancel all regis tration s . However , s hould we be unabl e to work succ essfully with the c hlorpyrifos reg istrants to achieve necessary label mitigation , w e will take appropri ate acti on under the FFDCA and/or FIFRA to e n s ur e that expo sures to chlorpyrifos are consistent with the r equ irement s of those statutes
. While EPA in tends to work expeditiously to review the comments and complete any necessary revisions to its regulatory posit ion , EPA canno t at this point provide assurance that we wi ll co mpl ete the final response by the summer of this year as previously est imated, but we are continuing to work with t hat goal in mind and w ill be happy to provid e you with updates on our progress.

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