Page 1 of 4 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF

CHEMICAL SAFETY

AND

POLLUTION PREVENTION

MEMORANDUM

April 19, 2012

SUBJECT: Paraquat: Response to Comments on the Human Health Risk Scoping Document in Support of Registration Review

PC Code: 061601 DP Barcode: 399986 Decision No.: 448271 Registration No.: NA Petition No.: None Regulatory Action: Registration Review Assessment Type: Scoping Document Reregistration Case No.: NA

TXR No.: None CAS No.: 1910-42-5

MRID No.: None 40 CFR: 180.205

FROM: Rebecca Daiss, Biologist Thurston G. Morton, Chemist Carol H. Christensen, MPH Jessica Ryman, Ph.D., D.A.B.T., Toxicologist Health Effects Division (7509P)

THROUGH: Susan V. Hummel, Senior Scientist Elissa Reaves, PhD., Branch Chief

Risk Assessment Branch 4 Health Effects Division (7509P)

TO: Molly Clayton Chemical Review Manager

Pesticide Re-evalu ation Division Risk Management and Implementation Branch 3

Attached is Health Effects Division’s (HED) response to comments submitted by Syngenta Crop Protection, LLC on the human he alth risk assessment for paraquat which will be conducted as part of the registration review process (D392078, 12/6/11). A summary of submitted comments followed by HED’s response is provided below.Page 2 of 4 Comment: The required immunotoxicity study ha s been submitted (November 2011). Results from this study demonstrated that tr eatment with paraquat in the diet during 28 days at the dose levels concurred to by th e Dose Adequacy Review Team resulted in no suppression of the humoral (AFC) or innate components of the immune system of the

female B6C3F1 female mice.

HED Response: The Agency has received this study, appears to be acceptable, and there

is no evidence of immunotoxic ity in response to paraquat.

Comment: EPA stated that a developmental toxic ity study in the rabb it is required under 40 CFR Part 158. Developmental toxicity stud ies in the rat and the mouse demonstrated that paraquat does not produce developmenta l effects at dose levels which exclude maternal toxicity and there is no eviden ce of increase qualitat ive or quantitative susceptibility to the developing fetus at a ny of the doses evaluated. Data from the

scientific literature as well as studies conducte d internally indicate that the rabbit is not an appropriate animal model to use as a non-rodent alternative for paraquat toxicity testing. Due to the atypical response of the rabbit to paraquat exposure as compared to man and the unacceptable corrosive effects of paraqua t in rabbits, Syngenta does not concur that

there is benefit from the indicated rabbit developmental toxicity study.

HED Response: On April 14, 2012, the Agency’s Hazard Policy Council (HASPOC) reevaluated the data requirement for a deve lopmental toxicity study in rabbits. The HASPOC determined, based on a weight of the evidence, that this study was not likely to yield information that would impact the ri sk assessment. The developmental study in rabbits is no longer required.

Comment: Syngenta has provided a table with in formation to address uncertainty on product labels. Syngenta requests that this in formation be utilized to complete the human health and ecological risk assessments.

HED Response: HED appreciates this informati on and will use it in conducting the

human health risk assessment for Reregistration Review.

Comment: EPA indicates that lawns are a potential use site for paraquat. Paraquat is not approved for use in residentia l areas including lawns. In addition, Syngenta’s paraquat end-use product labels further minimize any potential for exposure to residential areas such as lawns. In light of the prohibiti ons against use in resi dential areas, Syngenta respectfully requests that lawn s be removed from the list of Non-Agricultural Use Sites.

HED Response: HED agrees there are no paraquat products registered for homeowner use and there are no products registered fo r application to residential areas.

Comment: Regarding the potential need for a by stander inhalation risk assessment, the physiochemical properties of paraquat make i nhalation exposure to paraquat for off-site resident bystanders very unlikely. Accord ingly, inhalation exposure assessments for bystanders are not warranted for paraquat.Page 3 of 4 HED Response: As noted in the HED Scoping Document, the Agency is in the process of examining its policies and refining the me thods used to complete residential exposure assessments. As part of this process, the potential need for a bystander inhalation risk assessment for paraquat will be examined during registration review and the information provided by Syngenta will be considered.

Comment: The Agency indicated that use of pass ive dosimetry data from HED’s generic pesticide exposure databases for the occupati onal exposure assessment may be preferable to the chemical-specific a pplicator biomonitoring expos ure data used to assess occupational exposure for the 2006 Paraquat Risk Assessment. The paraquat biomonitoring studies were conducted in accordan ce with scientific a nd ethical standards in place at the time. The studies account for chemical and pharmacodynamic properties of paraquat and are the best scientific sources of data for assessment of agricultural exposure scenarios. Syngenta supports con tinued reliance on these data to assess occupational exposures to paraquat.

HED Response: As noted in the HED Scoping Document , in the course of registration review EPA will reconsider these studies, as well as any other research involving intentional exposure of hu man subjects to paraquat or related chemicals brought to its attention. If EPA decides to rely on any of these studies, EPA will ensure that all applicable regulatory requirements are met, including but not limited to the requirements

for EPA ethics review and Human Studies Re view Board review of certain research involving intentional expos ure of human subjects.

Comment: The HED Scoping Document references recent findings from the Agricultural Health Study (AHS) concerning a possible association between paraquat use and Parkinson’s disease (PD). Other relevant epidemiologic data or a full evaluation of AHS study results were not presen ted in the scoping document.

HED Response: As part of the generation of th e HED Scoping Document, HED reviews findings of the AHS with respect to both can cer and non-cancer health outcomes. In this instance, two evaluations of PD were referenced in the HED Scoping document, in addition to other health endpoints. At this point in the process, the intention of HED is to note the availability of this information and to state the relevance of these data to informing the overall paraquat risk assessmen t. HED has not performed a full evaluation of available epidemiology studies nor have observational investiga tions outside of the AHS been referenced in the scoping documen t. When the paraquat risk assessment is generated, HED will consider the AHS and non-AHS epidemiology studies informative of the possible relation between paraquat use and PD, among other health outcomes. HED appreciates the provision by commenters of other possibly relevant epidemiology studies to inform the paraquat risk assessment and will consider this information in

concert with other relevant streams of data in the deve lopment of the paraquat risk

assessment in accordance with the draft Framework for Incorporating Epidemiology into Risk Assessment (US EPA, 2010).Page 4 of 4 Comment: The HED Scoping Document incorrectly states that paraquat was included

on the list of chemicals for which an orde r to conduct Tier 1 testing for endocrine disruption was issued. Paraquat was not in cluded in the Tier 1 list of chemicals.

HED Response: HED agrees. The statement in the HED Scoping document that “Paraquat was included on that list and has been issued an order to conduct the Tier 1 testing” was included in error.

Comment: Syngenta conducted a Paraquat Mark et Basket Survey (PMBS) on the frequency and magnitude of residues of para quat in single serving samples of various commodities. Syngenta is submitting this st udy for the Agency’s consideration during the registration review process.

HED Response: HED will review and consider the submitted PMBS data for potential use in assessing dietary exposure and risk for Registration Review of paraquat.

Reference:

U.S. Environmental Protection Agency. ( 2010). Draft Framework for Incorporating Human Epidemiologic and Incident Data in Health Risk Assessment, January 7,

2010.