UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

OFFICE OF CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

MEMORANDUM 

Date: December 12, 2011 

SUBJECT: Paraquat dichloride: Review of Human Incidents 

PC Code: 061601 DP Barcode: D 392273 

Decision No.: 452150 

Petition No.: NA 

Risk Assessment Type: NA 

TXRNo.: NA 

MRIDNo.: NA 

Registration No.: NA 

Regulatory Action: NA 

Case No.: NA 

CAS No.: 72963-72-5 

40CFR: NA 

FROM: Khin Swe Oo, Environmental Health Scientist ~ -o' 

Toxicology and Epidemiology Branch : ... -

Ver.Apr.08 

I 1 !I!.& /~-cfcv "''' 

Health Effect Division (7509P) {2 

THROUGH: David Miller, Acting Branch Chief rc/ // jtf/t{ 

Toxicology and Epidemiology Bran 

Health Effects Division (7509P) 

TO: Becky Daiss, Risk Assessor 

Risk Assessment Branch IV 

Health Effects Division (7509P) 

and 

Molly Clayton, Chemical Review Manager 

Risk Management & Implementation Branch III 

Pesticide Re-evaluation Division (7508P) 

I. CONCLUSION 

In general, a moderately large number of incidents have been reported involving paraquat 

dichloride. There were 46 cases reported for products containing paraquat dichloride present as 

a single chemical only; 73 cases reported for products containing paraquat dichloride as nonsingle active chemical, and 78 cases reported in Aggregate IDS. Human incident data may 

warrant further analysis for the risk assessment and/or risk management of paraquat dichloride. 

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II. ACTION REQUESTED 

This review is intended to fulfill our requirement to docket summaries of incident data that were 

reported to the Agency, as well as to ensure human incident data and the Agricultural Health 

Study (AHS) are part of the problem formulation phase of registration review. Reports of 

adverse health effects allegedly due to a specific pesticide exposure (i.e., an "incident") are 

largely self-reported and therefore, generally speaking, neither exposure to a pesticide or 

reported symptom (or the connection between the two) is validated. Typically, causation cannot 

be determined based on incident data. However, incident information can be an important source 

of feedback to the Agency - incidents of severe outcome, or a suggested pattern or trend among 

less severe incidents, can signal the Agency to further investigate a particular chemical or 

product. Observational epidemiology studies re late the risk of disease, e.g., cancer, and exposure 

to an agent such as a pesticide product in the general population or specific sub-groups like 

pesticide applicators. 

III. BACKGROUND 

For this evaluation, the OPP Incident Data System (IDS) was utilized for pesticide incident data 

on the active ingredient paraquat dichloride (PC Code 061601). The purpose of the database 

search is to identify potential patterns on the frequency and severity of the health effects 

attributed to paraquat dichloride exposure. The IDS includes reports of alleged human health 

incidents from various sources, including mandatory Federal Insecticide, Fungicide and 

Rodenticide Act (FIFRA) Section 6 (a) (2) reports from registrants, other federal and state health 

and environmental agencies and individual consumers. Since 1992, OPP compiles these reports 

in IDS. IDS contains reports from across the U.S. and most incidents have all relevant product 

information recorded. Reports submitted to the IDS represent anecdotal reports or allegations 

only, unless otherwise stated in the report. 

The AHS is a high quality, prospective epidemiology study evaluating the link between 

pesticide use and various health outcomes including cancer. The AHS includes private and 

commercial pesticide applicators and their spouses. If there are AHS findings relevant to a 

particular pesticide going through registration review, the Agency will ensure they are 

considered in the problem formulation/seeping phase of the process and, if appropriate, fully 

reviewed in the risk assessment phase of the process. The AHS includes information on use of 50 

different pesticide active ingredients commonly used in agriculture. 

IV. RESULTS/DISCUSSION 

IDS records incidents resulting in higher severity outcomes in more detail, in a module called the 

Main IDS module. This system stores incident data for death, major and moderate incidents, and 

it includes more details about the location, date and nature of the incident. Main IDS incidents 

involving only one pesticide are considered to provide more certain information about the 

potential effects of exposure from the pesticide, and therefore these incidents are listed in the 

Table 1 at the end of this report. Additionally, since higher severity incidents are generally of 

greater concern, incidents involving death and major outcomes include a narrative summary in 

Table 1. The less severe human incidents (minor, unknown, or no effects outcomes) are reported 

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by registrants as counts called aggregate summaries and are recorded in a separate module called 

Aggregate IDS. 

In Aggregate IDS, from January 1, 2006 to June 8, 2011, there are 78 incidents involving 

paraquat dichloride. Because it falls within the categories reported as counts (which includes 

minor, unknown or no effects), there is no unique report that provides details about the incident 

and single chemical incidents are not distinguished from multiple chemical incidents; however, a 

high frequency of incidents indicates there is a high potential for exposure and vice versa. For 

paraquat dichloride, there appears to be a moderately high potential for exposure. 

For the Main IDS, from January 1, 2006 to June 8, 2011, there are 119 cases reported that 

involve the pesticide products containing active ingredient paraquat dichloride. Seventy three 

cases reported for pesticide products containing paraquat dichloride as one of the active 

ingredients in the product, and 46 cases reported for single chemical paraquat dichloride only in 

the database. There is one HA (human death), 9 HB (human major), and 36 HC (human 

moderate). HA and HB incident descriptions are included in Table I. Among HB cases, 33.3% 

of cases were intentional ingestion, 22.2% were accidental ingestion, and 44.5% of cases were 

accidentally exposed to the product while using it. 

In the AHS, there have been five evaluations of various cancer and non-cancer endpoints in 

which authors reported notable associations with the herbicide paraquat: respiratory outcomes 

wheeze and chronic bronchitis (among non-smoking women); thyroid disease; Parkinson's 

disease (PD); and an evaluation of all cancers in relation to paraquat use over the lifetime. With 

the exception of the research study on Parkinson's disease, all investigations were preliminary, 

and not based upon prior knowledge of a role for paraquat (i.e. , no a priori) hypotheses. Animal 

studies and limited other epidemiologic evaluations have suggested a possible role for paraquat 

(and rotenone) in the etiology of Parkinson's disease. Strengths of this epidemiology study 

include its large sample size, and prospective nature of the data collection, as well as high 

response rate; limitations included the narrow generalizability of the results (primarily performed 

among white, male, pesticide applicators), and lack of knowledge of exposure periodicity and 

time of cessation of exposure. Results are briefly summarized below. 

In two AHS studies, modest associations were observed between paraquat, as well as other 

pesticides, and both wheeze (OR 1.27 (95% CI 1.04, 1.56), and chronic bronchitis (among nonsmoking women) (OR 1.91 (95% CI 1.02, 3.55)). Overall, these studies are not strongly 

supportive of a link between paraquat and respiratory health outcomes measured, exposure 

measurement error may explain these results; EPA will continue to monitor this literature 

through the regulatory review process. In addition, while there is limited a priori evidence as to a 

role for paraquat in thyroid disease, authors reported a statistically-significant elevated odds of 

hypothyroidism (under-active thyroid gland) among women who reported exposure to paraquat 

(OR 1.8 95% CI 1.1, 2.8). Alternative explanations may also exist at this time, and have not been 

completely investigated. Concerning Parkinson's disease, authors reported elevated odds ofPD 

among those who used paraquat in comparison to those who did not (OR 2.5 (95% CI 1.4, 4.7)). 

This result is supportive of the toxicological findings. In addition, AHS authors compared cancer 

incidence between users and non-users of paraquat, and did not observe strong evidence of an 

association between paraquat and any cancer outcome evaluated (including all cancers 

combined, prostate, lung, and colon). Elevated risks were observed with respect to non-Hodgkin 

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lymphoma (NHL) however, these results could be otherwise explained. As stated by the authors, 

"There was some suggestion of a possible link between paraquat exposure and NHL risk in 

humans, but the inconsistency in exposure level trend suggests that tbis could be a chance 

finding." In summary, based upon preliminary investigations within the AHS, authors observed 

some evidence of a possible role for paraquat in relation to wheeze as well as chronic bronchitis 

among non-smoking women, and thyroid disease. However, at this time other explanations 

cannot be excluded, and additional replication is needed. Authors did not observe strong 

evidence of an association with cancer. Concerning Parkinson's disease, recent evaluations 

support observations in experimental toxicology. 

In general, a moderately large number of incidents have been reported involving paraquat 

dichloride. There were 46 cases reported for pesticide products containing paraquat dichloride 

present as a single chemical only; 73 cases reported for pesticide products containing paraquat 

dichloride as non-single active chemical, and 78 cases reported in Aggregate IDS. Human 

incident data may warrant further analysis for the risk assessment and/or risk management of 

paraquat dichloride. 

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Table 1: Human Incidents (HA and HB) due to Paraquat dichloride. PC code 061601. 

Incident Page Incident Product Reg Location State Expo Incident Descrip

Package # Date Name Number sure 

number Type 

017507 - 16 5/18/200 GRAMOXON 000100- NEAR MD HB A 27 year old man, ingested 4 oz of 

00015 6 E INTEON 01217 PITTSFIELD He developed burning sensation in h

' also vomited several times. At the h

esophagogastroduodenoscopy was d

ulcerations in the esophagus, stomac

duodenum. He was discharged after 

to the ER, 4 days later with shortness 

hemoptysis (coughing blood). Chest 

lung infiltrates. A serum and urine pa

after the ingestion was 0.08 mcg/ml 

and 0.76 mcg/ml (asymptomatic spra

respectively. He was given methylpr

dexamethasone, cyclophosphamide, 

vit.E, Rapamycin and antibiotics. He 

hemodialysis for 6 days for kidney fa

to the inpatient psychiatric ward afte

lung and kidney symptoms. 

017862 - 47 8/1/2005 GRAMOXON NC HB A 56 year old male stated that he dev

00006 E (NON- breath, pain in chest/shoulders/neck

SPECIFIC) heart rate after using the product. H

hospital for 18 days. He used the pro

and came down with same symptom

WBC was 15,000 and erythrocyte se

97 (normal 15-20). However, physici

the cause of his symptoms. 

018909 - 49 8/24/200 PARAQUAT GOLDSBORO NC HA A 59 year old male died of cardiac ar

00001 7 (NON- organ failure in the hospital. It was n

SPECIFIC) product intentionally or not. 

018939 - 78 1/1/2006 GRAMOXON 000100- AR HB Adult (18-64) year old male stated th

00008 EMAX 01074 accidentally spilled on his hands sev

at work. He stated that he developed 

hands, and flakey fingernails, 

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018939 - 86 8/14/200 PARAQUAT sc HB A 52 year old male ingested about 60 

00013 7 (UNSPECIFI of 43.8% paraquat and 30 ml of wate

ED) performed about 1.5 hr post-ingestion

developed impaired lung, liver and kid

was put on hemoperfusion, and later 

He was also given cyclophosphamide 

methylprednisolone. Serum paraquat 

at about 4 hours after ingestion. He w

psychiatric unit about 2 weeks after th

020720 - 3 1/112009 PARQUAT DOYLESTOW PA HB A 50 year old female was admitted to 

00026 (NON- N failure. The doctors wanted to rule o

SPECIFIC) The cause remained unclear. 

020720 - 23 3/8/2009 GRAMOXON CA HB A 53 year old female accidentally ing

00027 E (NON- (about 1-2 tea spoon) which was plac

SPECIFIC) She developed oral swelling and was 

intensive care unit. Paraquat level at 

was 0.038mcg/ml; liver enzymes leve

Paraquat was not detected in the urin

days post-ingestion. She was intubat

machine for few days. She was disch

hospital after 3 weeks. 

021194 - 5 8114/200 GRAMOXON 000100- OTHELLO, WA HB A 49 year old male stated that he got 

00005 9 EMAX 01074 accidentally in his mouth while using 

(DISCONTIN swollen lips, tongue and ulcers in his 

UED) admitted to the ICU; found ulcers also 

was discharged from the hospital afte

021704 - 15 1/13/201 GRAMOXON CA HB A 44 year old male mistakenly drank 

00006 0 E developed difficulty in breathing and v

was admitted to the intensive care un

information. 

022354- 16 8/31/201 GRAMOXON 000100- GA HB Adult (16-64) year old worker, accide

00006 0 E INTEON 01217 (concentration,50/50) on his stomach 

was admitted to the Burn Center, and 

transplant. 

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