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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-evaluation 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 health 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. 

 
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Comment: The required immunotoxicity study has been submitted (November 2011). 

Results from this study demonstrated that treatment with paraquat in the diet during 28 

days at the dose levels concurred to by the 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 immunotoxicity in response to paraquat. 

Comment: EPA stated that a developmental toxicity study in the rabbit is required under 

40 CFR Part 158. Developmental toxicity studies in the rat and the mouse demonstrated 

that paraquat does not produce developmental effects at dose levels which exclude 

maternal toxicity and there is no evidence of increase qualitative or quantitative 

susceptibility to the developing fetus at any of the doses evaluated. Data from the 

scientific literature as well as studies conducted 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 paraquat 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 developmental 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 risk assessment. The developmental study in 

rabbits is no longer required. 

Comment: Syngenta has provided a table with information to address uncertainty on 

product labels. Syngenta requests that this information be utilized to complete the human 

health and ecological risk assessments. 

HED Response: HED appreciates this information 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 residential 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 prohibitions against use in residential areas, Syngenta 

respectfully requests that lawns 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 for application to residential areas. 

Comment: Regarding the potential need for a bystander inhalation risk assessment, the 

physiochemical properties of paraquat make inhalation exposure to paraquat for off-site 

resident bystanders very unlikely. Accordingly, inhalation exposure assessments for 

bystanders are not warranted for paraquat. 
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HED Response: As noted in the HED Scoping Document, the Agency is in the process 

of examining its policies and refining the methods 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 passive dosimetry data from HED’s generic 

pesticide exposure databases for the occupational exposure assessment may be preferable 

to the chemical-specific applicator biomonitoring exposure data used to assess 

occupational exposure for the 2006 Paraquat Risk Assessment. The paraquat 

biomonitoring studies were conducted in accordance with scientific and 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 continued 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 human 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 Review Board review of certain research 

involving intentional exposure 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 presented in the scoping document. 

 

HED Response: As part of the generation of the HED Scoping Document, HED reviews 

findings of the AHS with respect to both cancer 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 assessment. HED has not performed a full evaluation 

of available epidemiology studies nor have observational investigations outside of the 

AHS been referenced in the scoping document. 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 development of the paraquat risk 

assessment in accordance with the draft Framework for Incorporating Epidemiology into 

Risk Assessment (US EPA, 2010). 
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Comment: The HED Scoping Document incorrectly states that paraquat was included 

on the list of chemicals for which an order to conduct Tier 1 testing for endocrine 

disruption was issued. Paraquat was not included 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 Market Basket Survey (PMBS) on the 

frequency and magnitude of residues of paraquat in single serving samples of various 

commodities. Syngenta is submitting this study 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.