### UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460

OFFICE OF CHEMICAL SAFETY AND
POLLUTION PREVENTION



### MEMORANDUM

Date: May 21,2014



### SUBJECT: Paraquat D i chloride: Review of Human In gest i on Incid ents

PC Code: 061601 DP Barcode: 0420296

Decision No. : 491188

Pet i tion N o.: NA

Risk Assessme n t T y pe : N A

TXRNo.: NA

MRID No.: NA Registration No.: NA Regulator y Action: NA

Case No.: NA

CAS No.: 72963-72-5

40CFR: NA Ver.Apr.08



### FROM: E li zabe th Eva n s, Environmental Protect i o n Specia li st

, _ )

Toxico l ogy and Epidemiolo gy Branch

## ?:1;;**~~** Health Effects Di vis ion (7509P) 

# /1

. 

# /. I

,.,

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I, / ' • 'J 

### /.1. l..;/J 

### THROUGH: D avid J. Mi ll er, Acting Branch Chief [ 

# .._flj**~ ~**  ·I&

TO: T oxicology and Epidemiology Branch

Health Effects Division (7509P)

Elissa Reaves, Branch Chief

R i sk Assessment Bran ch IV

H ealth Effects D i vision (7509P)

Molly Clayton, Chemical Review Manager

Risk Management & 

### Im plementation Branch III

P esticide Re-Evaluation Division (7508P)

Summa ry and Conclusions

Three deaths due to accidental inges t ion of paraquat dich l or id e, occurring in th e Central Va ll ey of California, were br ought to the attention of EPA by the Director of the Ca li fornia Poison

Control System in a June 27

, 2013 letter to EPA's Office of P esticide Programs.' HED was requeste d by PRD to review its in

- house and external incident databases. As part ofthis review

,

1 Dr

. Gellar also notified the U.S. Consumer Product Safety Commission, who in forwarded the incident information

on the three ingestion deaths and one major severity ingestion to Norman Spurling for input into IDS.



### l i P age

### 2 | P a g e

several additional fatalit y reports involving paraquat dichloride ingestions were identified

. Two

of these subseque ntly identified deaths occurred in children, including a 15

- month old who drank Gramoxone from a Gatorade bottle and an 8 year old who drank the product from a Dr. Pepper

bottle.

Fatalities from paraquat dichloride ingestion and high severity ingestion cases are the focus of

this review which was re quested by PRD to determine if there i s a potential risk of concern for which mitigation actions might be considered

.

I. ACTION REQUESTED

On 6/27/13

, EPA/OPP received a letter from Dr. Richard Geller, Director of the California Poison Control System (CPCS)

. Dr. Geller provided case details for three fatal and one severe paraquat ingestion incidents that have occurred in the San Joaquin Valley of California in recent

years , all resultant from accidental ingestion of paraquat that had been illegally repackaged into beverage containers. The letter also cites an additional nine serious poisonings (including eight fatalities) from paraquat and diquat. Dr. Geller’s letter includes the following request:

“ These deaths, I believe with good reason, could have been prevented through reformulation of paraquat in a more dilute product.

Syngenta markets 3 Gramoxone products in the US, all of which contain paraquat dichloride in a 30.1% formulation. These are: Gramoxone Inteon (EPA Reg. No. 100

- 1217), Gramoxone SL (EPA Reg. No. 100

- 1217), and Gramoxone SL 2.0 (EPA Reg. No. 100

- 1431).

An accidental gulp of paraquat of say, 15 mL of the 30% product, would contain 4.5 grams of paraquat. A dose of 40 mg per kg, 2.8 grams in a 70 kg man, is widely considered to be fatal, while doses of less than 20 mg per kg, 1.4 grams in a 70 kg man, are much more likely to survive.

For safety reasons, paraquat in Japan is formulated in a 5% solution. A swallow of 15 mL thus results in an ingestion of only .75 grams, or 10.7 mg/kg in a 70 kg individual. This is a survivable ingestion. Even 30 ml of a 5% solution, 21.4 mg/kg, is more likely than not to survive.

I am writing to you because I believe that reformulation of Gramoxone to the Japanese standard could save

lives here in the US. This change, made in Japan in the 1980s, is credited with significantly decreasing the number of paraquat fatalities there. The following are vignettes of the 4 cases of accidental ingestion leading to fatality 2 we have seen at the Fresno/Madera Division of the California Poison Control System. We also have seen 9 other serious poisonings from paraquat and diquat with 8 fatalities, but these were deliberate ingestions/injections.”



### As part of an OPP effort to investigate this request

, HED performed this incident review of paraquat ingestion cases. For the purposes of this review, OPP’s Incident Data System (IDS),

t he Centers for D isease Control and Prevention/National Institute for Occupational Safety and Health (CDC/NIOSH) Sentinel Event Notification System for Occupational Risk (SENSOR)

- Pesticides

, National Pesticide Information Center ( NPIC ) , and the California Department of Pesticide Regulation ( CDPR) Pesticide Illness Surveillance Program ( PISP ) database s were queried

. The se quer ies were conducted to confirm that the reports from CPCS are included in IDS, search for case matches across databases, and review additional ingestion incidents. Only

2 Three of the four case reports are fatalities, but the fourth one appears to be a non

- fatal, high

- severity case

### 3 | P a g e

those cases occurring in the United States were considered in this analysis. Paraquat dichloride is widely used globally , poisonings result in a high pesticide mortality rate 3



### , and it is known to be a common agent for suicide. 4



### While this report focuse s on ingestion of paraquat dichloride

, it also summarizes all paraquat dichloride incidents identified in IDS and provides some information regarding occupational

incidents as well.

II. BACKGROUND

Paraquat dichloride is an herbicide registered to control weeds and grasses in many agricultural

and non

- agricultural (e.g., Rights

- of

- Way) use sites

. Tolerances are currently established for crop and livestock food commodities. Paraquat dichloride is also applied as a pre

- harvest

desiccation treatment on some crops including cotton. There are no products registered for homeowner use and no products registered for application to residential areas. (Paraquat Dichloride Final Work Plan, Docket # EPA

- HQ

- OPP

- 2011

- 0855)

Paraquat dichloride was first regist ered as a pesticide in the United States in 1964. In the 1960s

and 1970s there were a number of fatalities from accidental swallowing of paraquat. In 1988 the registrants added “safening” 5 

### agents into all of its paraquat formulations to avoid accidental ingestion and to deter misuse. These measures included the addition of blue dye, an alerting
agent (deterring odor) , and an emetic. Prior to this

, paraquat dichloride was brown in color like many cola beverages. The 1997 Paraquat Dichloride RED states t hat since these “safening” agents were added

, “ U.S. Poison Control Center data show a decline of almost 50% when comparing the proportion of all pesticide exposure due to paraquat ingestion for the four years

pre

- and post

- 1988

. ” 6



### Gramoxone Inteon (EP A Reg. No. 100

- 1217) was a formulation developed to decrease the acute oral toxicity in the event of ingestion by huma n s

. Gramoxone Inteon ("Inteon" technology) included a “gelling” agent designed to reduce absorption of paraquat dichloride into the p l asma following oral ingestion. However

, this gelling agent did not prove successful in saving lives and has since been removed from the subsequent product Gramoxone SL.

All paraquat dichloride products are classified as Restricted Use Products (RUP); mea ning that a certified pesticide applicator must apply or supervise the application of the product. Further, the product labels clearly and prominently prohibit pouring paraquat dichloride into food or beverage containers via the statement “NEVER PUT INTO FOOD, DRINK OR OTHER
CONTAINERS” and “DO NOT REMOVE CONTENTS EXCEPT FOR IMMEDIATE USE.”

3 Sittipunt, C. Teaching Case of the Month: Paraquat Poisoning . Respiratory Care, March 2005; Vol. 50 No. 3; 383

- 385.

4 Nagami, H. et al, Paraq uat Poisoning in Japan: A Hospital

- based Survey . J Rural Med 2007; 2: 85

- 92.

5 Found on the Syngenta

- sponsored Paraquat information website: http://paraquat.com/faq/accidental

- ingestion/q

- what

- has

- been

- done

- to

- prevent

- accidental

- swallowing

- of

- paraquat

6 EPA Paraquat Dichloride Registration Eligibility Decision (RED). EPA 738

- F

- 96

- 018. Found online at: http://www.epa.gov/oppsrrd1/REDs/0262red.pdf

### 4 | P a g e

According to Poisoning and Overdose, 6 th 

### edition Chapter 122. Paraquat and Diquat : “Ingestion of more than 40 mg/kg (~14 mL of a 20% solution in an adult) leads to corrosive GI injury, rapid onset of renal failure, myonecrosis, shock, and death within hours to a few days. Ingestion of

20

- 40 mg/kg causes a more indolent course evolving over several days, with most patients dying of pulmonary fibrosis after days to we eks. Patients with ingestions of less than 20 mg/kg usually recover fully.”

The mitigation actions required by the 1997 RED were specifically intended to lessen the occupational and ecological risks posed by paraquat and included: a reduction in maximum application rates ; additional PPE for mixers and loaders ; reduction of paraquat concentration in backpack sprayers ; and spray drift control measures.

In the 2011 Paraquat Dichloride Docket # EPA

- HQ

- OPP

- 2011

- 0855, the Human Health Risk Scoping Document f

ocused on inhalation exposure scenarios for registered uses, including occupational handler scenarios and residential bystander inhalation risk from off

- target drift

. Human incidents were reviewed and a moderately high frequency of incidents was found.

III. RESULTS/DISCUSSION

For the purposes of this review, OPP’s Incident Data System (IDS), Sentinel Event Notification System for Occupational Risk (SENSOR)

- Pesticides, National Pesticide Information Center (NPIC), and CDPR’s Pesticide Illness Surveillance P rogram (PI SP) database s were queried. The

quer ies were conducted to confirm the reports from C alifornia P oison C ontrol S ystem were included in IDS, search for case matches across databases, and review additional ingestion incidents. Only those cases oc curring in the United States were considered in this analysis. T his analysis is limited to paraquat dichloride (pc code 061601) as with the previous Human Incident

Review memo from 2009. 7



### a. IDS (Incident Data System) OPP’s 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. Sinc e 1992, OPP has compiled these reports in IDS. IDS conta ins reports from across the United States, and most incidents have all relevant product information recorded. Reports submitted to the IDS represent anecdotal reports or allegations only, unless othe rwise stated in the report.

IDS records incidents in one of two modules: Main IDS and Aggregate IDS:

o Main IDS contains incidents resulting in higher severity outcomes and provides more detail with regard to case specifics. This system stores inciden t data for death, major and moderate incidents, and it includes information about the

7 Paraquat (pc code 061603) has been cancelled and cases are not included.

### 5 | P a g e location, date and nature of the incident. Main IDS incidents involving only one active ingredient (as opposed to pesticide products with multiple active ingredients) ar e considered to provide more certain information about the potential effects of exposure from the pesticide.

o Aggregate IDS contains incidents resulting in less severe human incidents (minor, unknown, or no effects outcomes). These are reported by registr ants only as counts in what are aggregate summaries.

A query of (United States only) Main IDS from for all available years identifies a total of 276 incidents involving paraquat dichloride. A query of Aggregate IDS identifies a total of 342 incidents involving paraquat dichloride (Aggregate IDS cases do not include case descriptions and are not analyzed in this report).

Overall paraquat incident c ount information in IDS

Severity Code Severity Main

IDS Aggregate IDS Total

HA Death 2 7 2 7

HB Major 2 2 2 2

HC Moderate 181 181

HD Minor 26 326 352

HE human exposure 5 16 21

H human exposure 15 15

H

- A (death): If the person died;

H

- B (major): If the person alleged or exhibited symptoms which may have been life

- threatening,
or resulted in adverse reproductive effects or in residual disability; and

H

- C (moderate): If the person alleged or exhibited symptoms more pronounced, more prolonge d
or of a more systemic nature than minor symptoms, usually some form of treatment of the person
would have been indicated, symptoms were not life threatening and the person has returned to
his/her pre

- exposure state of health with no additional residual d isability.

H

- D (minor): If the person alleged or exhibited some symptoms, but they were minimally
traumatic, the symptoms resolved rapidly and usually involve skin, eye or respiratory irritation;

and

H

- E/H (unknown or no effects): If symptoms are unknown , unspecified or are alleged to be of a
delayed or chronic nature that may appear in the future.



### For the purposes of this special report

, deaths (HA) and high severity outcomes (HB) were analyzed in Main IDS

. Additionally, (HC) moderate severity health outcomes reported to Main

IDS since 2010 were reviewed.

A query of Main IDS from 1990

- February 2 0 1 4 , covering 24 years (all available years)

, identifies 27 deaths involving paraquat dichloride. Three fatalities match the three fatalities reported by Dr. Gellar from C alifornia P oison C ontrol S ystem ; the fourth case reported by Dr.

Gellar is coded a s “high” severity in Main IDS

.

### 6 | P a g e

Paraquat dichloride f

atalities in Main IDS

2 7 deaths involving paraquat dichloride were reported to Main IDS over the 24

- year period from

1990

- February 2014 :

 2 2 death reports involved ingestion of paraquat dichloride

o 11 deaths were from intentional ingestion

.

o Eight deaths were due to the accidental ingestion of paraquat dich loride ; all of these involved ingestion out of a reused beverage co ntainer containing the

chemical

o Three paraquat ingestion deaths were unclear as to whether they were intentional

or unintentional

 Two deaths from one incident (010677

- 00001) appear to be related to a drift event in which the farmer mistook Gramoxone for 2,4

- D

.

 Three deaths had unclear or unknown exposure circumstances

Table 1 describes seven accidental ingestion deaths reported in Main IDS. Table A

- 1 in Appendix A contains the full Main IDS tab le of all 2 7 reported deaths.

Table 1. Accidental Ingestion Deaths involving Paraquat Dichloride (pc code 061601)

Reported to Main IDS 1990

- February 201 4

Case ID Year Description

1 010077

- 00001 2000 15 month old child ingested paraquat product in a Gatorade container. Acute renal failure, nitric oxide used, sepsis set in and the child died

2 013569

- 00001 2002 Man ingested gulp of paraquat from Pepsi bottle. Was put on ventilator, given renal dialysis. Died

. 3 014885

- 00026 2003 Adult male was making an applicat ion of paraquat to his yard. He had two coffee cups in his garage, one contained coffee and the other contained paraquat. He accidentally took a sip of the paraquat and immediately spit it

out. About an hour later he started to feel si ck and drove himself to the hospital. His condition progressively got worse and he died on March 12, 2003. The cause of death established by the coroner was acute paraquat intoxication and multiple organ failure

. 4 016310

- 00001 2005 48 yr. old man was a pparently transferring straight product from a glass jar to a sprayer. He reportedly drank from that container by accident

. He thought he’d consumed tobacco spittle, so he didn’t seek medical attention immediately for the vomiting noted shortly afterward, according to the brother. Tested for drugs, apparently. Had been going through alcohol withdrawal according to brother. Never any mention of a suicide attempt.

5 025332

- 00001 2013 70 yr. old female ingested some contents of a re

- used iced tea bottle, whic h unknown to her contained Gramoxone. She presented awake and alert with persistent vomiting. Over the course of a 16 day admission she evolved the classic picture of paraquat ingestion: corrosive gastrointestinal injury plus renal and pulmonary failure le ading to death.

6 013372

- 00001 2002 The circumstances of exposure are unclear. On 10/2/02, caller indicated

w oman drank sips of paraquat by accident as she reached for her coffee. On 10/4/02, the history was altered, “During the night the patient got up to get some cough medicine which was sitting next to the product and took product by mistake”

.

### 7 | P a g e

7 0 25332

- 002 (update to

021704

- 00006) 2010 A 44 year old male mistakenly drank the product and developed difficulty in breathing and vomiting of blood. He was admitted to the intensive care unit.

Perished

8 016630

- 00001 2005 Man drank paraquat & organophosphates out of a bottle. Intubated at hospital, significant respiratory symptoms, blue sweat and urine. Accidental ingestion.

Perished



### High Severity Paraquat cases in Main IDS

A query of Main IDS over the 24

- year period from 1 990

- February 2014 identifies 22 major

severit y paraquat dichloride incidents:

 Four major severity cases were due to accidental ingestions

.

 Nine cas es were occupational incidents ; generally dermal exposures.

 One case was a suicidal ingestion

.

 One case related to bystand er drift has a lawsuit pending

.

 Seven cases are unclear or cas e descriptions were not found

.

Table 2 describes the four major severity accidental ingestions. Table 3 summarizes the nine occupational major severity incidents.

Table 2. Major Severity Accidental Ingestion Cases involving Paraquat Dichloride (pc code 061601) Reported to Main IDS 19 90

- February 201 4

Case ID Year Description

1 017507

- 0 0015 2006 A 27 year old man, ingested 4 oz of product (43% solution). He developed burning sensation in his chest and mouth; he also vomited several times. At the hospital esophagogastroduodenoscopy was done and found ulcerations in the esophagus, stomach and proximal duodenum. He was discharged after 24 hours. He returned to the ER, 4 days later with shortness of breath and hemoptysis (coughing blood). Chest X

- ray showed bilateral lung infiltrates. A serum and urine paraquat level four days after the ingestion was 0.08 mcg/ml (normal <0.06 mcg/ml), and 0.76 mcg/ml (asymptomatic sprayers up to 0.3 mcg/ml) respectively. He was given methylprednisolone, dexamethasone, cyclophosphamide, acetylcysteine, vit amin C, vit amin E, Rapamycin and antibiotics. He was put on hemodialysis for 6 days for kidney failure. He was transfered to the inpatient psychiatric ward after 39 days with residual lung and kidney symptoms.

2 018939

- 0 0 013 2007 A 52 year old male ingested about 60 ml of paraquat (30 ml of 43.8% paraquat and 30 ml of water). Gastric lavage was performed about 1.5 h ou r s post

ingestion. However, he developed impaired lung, liver and kidney functions. He was put on hemoperfusion, and later received he modialysis. He was also given cyclophosphamide and methylprednisolone. Serum paraquat level was 0.79 mcg/ml at about 4 hours after ingestion. He was transferred to the psychiatric unit about 2 weeks after the admission.

3 020720

- 00027 2009 A 53 year old female accidentally ingested the product (about 1

- 2 teaspoon) which was placed in the water bottle. She developed oral swelling and was admitted to the intensive care unit. Paraquat level at 22 hours post

- ingestion was 0.038mcg/ml; liver enzymes levels wer e also increased. Paraquat was not detected in the urine sample collected 4 days post

- ingestion. She was intubated and put on dialysis machine for few days. She was discharged from the hospital

after 3 weeks.

### 8 | P a g e

4 021194

- 0 0005 2009 A 49 year old male stated that he got the product accidentally in his mouth while using it, and developed swollen lips, tongue and ulcers in his mouth. He was admitted to the ICU; found ulcers also in the esophagus. He was discharged from the hospital after few days.

Table 3

. Major Severity Occupational Cases involving Paraquat Dichloride (pc code 061601) Reported to Main IDS 1990

- February 2014

Case ID Year Description

1 007791

- 00014 1998 An adult male was using 1% product in a backpack sprayer 3 days ago and fell during use causing him to get solution on his arm. He was not able to wash for about an hour. No irritation, noted that day some difficulty using that arm.

2 010749

- 00004 2000 Heart problems

3 013857

- 00018 2002 Caller is wife who states that husband was in field and exposed to product. Then spoke with patient (husband) who says he sprayed product on Nov 6th of ‘02. Says that he went out about 2

- 3 weeks later in field with cut on foot. Says that at beginning of new year he had some issues with the foot and p roblems that MD diagnosed. Wife of man afflicted called back. Says he has lost part of his foot due to this product. Wants medical expenses paid for by rancher boss.

4 015485

- 00013 2004 Two male workers

- one Hispanic and Spanish

- speaking, the other an African American with limited literacy skills

- were applying product one week prior to coming to the HCF 5 days ago. The wind was high and variable, so there were frequent dermal and inhalational exposures to product during the course of application. Dilu tion of product is not known and is difficult to determine given the communication limitations. Length of exposure was extended, but not exactly defined. The Hispanic male is more symptomatic, but both have had considerable respiratory, renal and Hepatic s ymptoms. The Hispanic male has received steroid and NAC therapies. The African American male had been receiving supp lemental care

5 017862

- 00006 2005 A 56 year old male stated that he developed shortness of breath, pain in chest/ shoulders/ neck, low fever and rapid heart rate after using the product. He was admitted to the hospital for 18 days. He used the product again this year and came down with same symptoms; lab results showed, WBC was 15,000 and erythrocyte sedimentation rate was 97 (normal 15

- 20). However, physicians were unable to find the cause of his symptoms

.

6 018939

- 00008 2006 Adult (18

- 64) year old male stated that the product accidentally spilled on his hands several times, while using it at work. He stated that he developed dry and flaky skin on hands, and flakey fingernails

.

7 021807

- 00004 1990 Caller has questions about intermittent, recurring exposure to Gramoxone products over the last many years. His last exposure to the product would have been to a mist of diluted product in April or May of 2009. He merely reports that he's been a little careless, with occasional dermal exposure to product mists on skin only, no ingestions. His symptoms started last year

-- nausea, dizziness, off balance, not sleeping as well. He originally a sked his MDs if these might be side effects of medications that he takes, and his doctors don't think so. He had his bladder removed due to cancer in the past. Since then, his doctors monitor his lungs and kidneys regularly and haven't reported any issues to him. He's just looking for more info on the Gramoxone.

8 022354

- 00006 2010 Adult (16

- 64) year old worker, accidentally spilled the product (concentration,50/50) on his stomach and genital areas. He was admitted to the Burn Center, and he received a skin transplant.

9 023072

- 00184 2011 Adult male was pouring Gramoxone into a sprayer and some of the Gramoxone spilled under his arm. This happened about 10:30 Thursday morning June 9. He

### 9 | P a g e did not change clothes and shower until that night. He didn't start feeling any symptoms until the next day around lunch. He noticed red sunburn like circle under his arm about 3 inches in diameter. On Saturday the area got worse. It was about 5 to 6 inches in diameter and turned a reddish purple color. On Saturday evening the blisters started to form. On Sunday the area affected continued to get larger. He said it was about 4 inches wide and 8 inches long

and the blisters became worse. This is when he had a doctor look at it. The local doctor recommended that he go to the bum center in Augusta, Georgia on Monday. He was diagnosed with second degree bums and treated. The Poison Control Center was contacted (but not Syngenta or Prosar). He is scheduled to go back to Augusta next Tuesday to have the area checked. He sai d they put some cadaver skin on the area on Monday and they are going to check it to see if they will have to do some skin grafting.



### Moderate Severity Paraquat Cases in IDS

A query of Main IDS from 1990

- February 2014 identifies a total of 181 moderate severity paraquat dichloride cases. For the purposes of this review, moderate severity incidents from

2010

- 2013, a total of 35 incidents, were analyzed in detail and are summarized in the Table

below . Moderate severity (HC) incidents in Main IDS are defi ned as follows : If the person alleged or exhibited symptoms more pronounced, more prolonged or of a more systemic nature than minor symptoms, usually some form of treatment of the person would have been indicated, symptoms were not life threatening and the person has returned to his/her pre

- exposure state of health with no additional residual disability.

All but one of the moderate severity incidents from 2010

- 2013 involved a Gramoxone product (Syngenta products account for 87% of paraquat market share in the United States; the products are a 30% AI concentration). Fourteen cases involved Gramoxone Inteon, six incidents involved Gramoxone 2.0 SL; and another 14 involved unspecified Gramoxone products. Two incidents involved multiple active ingredients but most included only paraquat dichloride or paraquat. This analysis reveals that moderate paraquat exposure incidents are typical handler/product user related exposures involving splashes, spills or equipment malfunction during the handling of the produc t, including mixing, loading or applying the product or cleaning application equipment. Most cases appear to have taken place on a farm, which often was the residence of the farmer/applicator; however location and occupational information was often sparse in the case reports. Information regarding the level of training of users is not available in IDS reports. The reports were primarily the patient treatment dialogue between the healthcare provider and case intake reporter (Syngenta contracts with Prosar ). Symptoms of the moderate severity paraquat incidents were typically dermal irritation including blisters, rashes, redness, followed by ocular exposures. Symptoms generally resolved within several days. However, there are a few reports

of skin irritat ion persisting over a long period of time following a paraquat application exposure. The Syngenta incident reports frequently state the following regarding exposure to paraquat, “Intact skin is an effective barrier to Paraquat exposure and systemic toxici ty is unlikely following brief dermal contact followed by appropriate decontamination. Concentrated solutions may result in irritation, blistering, or full thickness burns 1

- 3 days following exposure. Dilute solution may result in redness...”

### 10 | P a g e

There were al so a number of inhalation exposure incidents (or combination dermal and inhalation) resulting from the same type of handler exposure scenarios as outlined above. Two separate incidents involved 15

- year

- old children, one was splashed in the eye by the prod uct while applying with no PPE and the other child exposure report involved the accidental ingestion incident (mentioned above) where the child was orally exposed to the product when drinking from a Coke bottle, the child did not swallow the product and ma de a recovery. There are a total of 4 moderate severity cases in the above table that involved ingestion of small amounts of product; two of these cases involved drinking from mislabeled beverage containers.

In sum, moderate severity incidents are gene rally typical exposures involving the occupational risks involved with handling a pesticide product (dermal, inhalation and ocular exposure due to leaks, spills, splashes or mist inhalation). However, the ingestion of even a very small amount of

paraquat is highly toxic when ingested and may result in death or high severity health outcomes. See Appendix B for description of the moderate severity cases analyzed here.

b. SENSOR

- Pesticides

The SENSOR

- Pesticides database covers 11 states 8 

### from 1998

- 2010 , although reporting varies from state to state. Cases of pesticide

- related illnesses are ascertained from a variety of sources, including: reports from local Poison Control Centers, state Department of Labor workers’ compensation claims when reported by p hysicians, reports from State Departments of Agriculture, and physician reports to state Departments of Health. Although both occupational

and non

- occupational incidents are included in the database, SENSOR

- Pesticides focuses on occupational pesticide inci dents, and is of particular value in providing that information. The state coordinator at each of the 11 respective state Departments of Health conducts case follow

up activities such as obtaining medical records to verify symptoms and severity. Using

st andardized protocol and case definitions derived from poison center reporting, the state

SENSOR

- Pesticide coordinator enters the incident information into the state

- based system which is sent to NIOSH annually to be aggregated.

A query of SENSOR

- Pesticid es 1998

- 2010 identifies a total of 109 cases involving paraquat, stemming from 108 events. 87 of these cases involve a single active ingredient and 24 involved multiple active ingredients. There were two fatalities, two high severity cases, 25 moderate

s everity cases, and 80 low severity cases.

The most frequent route of exposure are dermal, ocular, and inhalation. Two cases reported an unknown route of exposure. Table 4 shows the frequency for the routes of exposure of the

paraquat cases.

8 California, Florida, Iowa, Louisiana, Michigan, North Carolina, New Mexico, New York, Oregon, Texas

, Washington

### 11 | P a g e

Table 4

. SENSOR

- Pesticides 1998

- 2010: Route of Exposure for Paraquat Cases

Route of Exposure Frequency

Dermal 54

Ocular 41

Inhalation 37

Unknown 2 Injection 0 *Cases may report multiple routes of exposure



### The most common reported health effects for paraquat cases are ocular, nervous system, and dermal symptoms. 66 of the 109 cases reported multiple types of health effects. Table 5 specifies all of the symptoms reported from SENSOR

- Pesticide cases.

Table 5. SENSOR

- Pesticides 1998

- 2010: Reported Health Effects for Paraquat Cases

Health Effect # of Times Reported

Ocular 51

Nervous System 47

Dermal 42

Respiratory 33

Gastrointestinal 29

Cardiovascular 14

Miscellaneous 9

Renal 4

* Cases may report multiple health effects



### 11 SENSOR

- Pesticides cases result ed from ingestion, including both of the fatalities. One fatality report was a suicide and the other involved a child who drank the paraquat out of a soda

bottle (see NC01163)

. Two ingestion cases involved siphoning of paraquat by mouth. All

available ingestion case descriptio ns are provided below in Table 6

.

### 12 | P a g e Table 6 . SENSOR

- Pesticides 1998

- 2010 Paraquat Ingestion Cases

Case ID Severity Case Description

NC01163 a Death An 8 year old child drank weed killer that had been put in a soda bottle and stored in garage. Further detail regarding this death was obtained from the SENSOR

Pesticides coordinator in North Carolina and stated the following, “8 year old boy ingested paraqua t from Dr pepper bottle on 7/29/08 and died at Duke medical center on 8/15/08. Family states older brother had used product on weeds around house and put it in a Dr. Pepper bottle in the garage and child found it on window sill. Older brother got it from a family friend who is a certified applicator. Dept of Ag asked to investigate and counsel father on pesticide storage. Family has 8 other children, Social Services on case as well as police. Staff medical epidemiologist reviewed case. Materials sent to family on proper pesticide storage. NIOSH notified.

NC00164 Death On August 25, 2007 59 year old man presents to Sampson Regional Medical Center ED jaundiced with c/o dysphasia, shortness of breath.

WS01693 Moderate Swallowed herbicide while siphonin g it to another container.

NC01865 Moderate 46 year old man ingested 1 cup of gramoxone (paraquat) in a suicide

attempt.

NC00881 Moderate Man was spraying paraquat around his home. Wind changed direction

and blew in mouth. Later told NCDA he swallowed it.

WA02854 Moderate Patient was attempting to siphon paraquat and ingested it

. OR01222 Moderate no mask was used. Br ought his own gloves & rubber suit, no rubber

boots.

WA01557 Low A 52 y/o male farmworker applied herbicides to raspberries and blackberries for 3 days without symptoms. He then developed respiratory symptoms and his employer provide he and his coworkers with PPE. His coworker felt better but he continued feeling badly. His symptoms improved after three weeks. However, he conti nued to have some respiratory symptoms and sought medical care.

FL01078 Low Patient started working for pesticide company 2 weeks ago and was spraying. He was spraying overhead so did get some on himself

CA07281 Low Spraying orange groves with roundup and without PPE. Exposed while spraying

. WA01991 Low Washing down tractor with a hose that had been used to fill a spray tank and splashed water back on herself.

SENSOR

- Pesticides Severity Index : KEY
Death Human Fatality High Life threatening, requires

treatment >5 days lost work/time

Moderate Involves systemic effects 3

- 5 days lost work/time

Minor Symptoms typically resolve

without treatment <3 days lost work/time

a. A 2009 American Academy of Pediatrics publication describes this case report and states the family believed the herbicide stored in the soda bottle to be Amoxone (2,4

- D). The patient was discharged after receiving supportive care in the hospital because he appeared well and 2,4

- D is a “relatively benign herbicide that may produce short

- term gastrointestinal symptoms” 9

9 Chen, et al, Paraquat Ingestion: A Challenging Diagnosis. Pediatrics 2010; 125; e1505. Found online at: http://pediatrics.aappublications.org/content/125/6/ e1505.full.pdf

### 13 | P a g e c. NPIC NPIC prepared a special report of paraquat incidents from 1/1/07

– 5/31/ 13 , there a total of four cases; no fatalities were reported, however, one case involved paraquat ingestion from a suicide

attempt.

d. CDPR/PISP CDPR is currently looking at all paraquat incidents reported to the Pesticide Illness Surveillance Program with the intent of putting out a Health and Safety Report. The report will be shared with EPA after it has been internally reviewed and cl eared at CDPR.

CDPR confirmed that from 1992

- 2010, there were a total of four paraquat ingestion cases reported (out of 101 total p araquat

- related cases reported)

, three of which resulted in death. (An additional ingestion death corresponding with Dr. Gellar’s report was reported in 2013 but is not yet available in the public dataset

. )

e. American Association of Poison Control Centers (AAPCC) In their 10/7/13 letter to EPA, the AAPCC noted a total of 50 paraquat deaths reported to the

National Poison Data System (NPDS) from 1983 to 201 1. Of the 50 deaths: 33 were suicides , 15

were due to unintentional exposures , and two were unknown. In the EPA response

, we requested

the case narratives for these fatalities. AAPCC has provided EPA with these narratives which are being reviewed. AAPCC also included this updated statement:

“Upon further examination, AAPCC has identified 51 US deaths attributed to paraquat published within the... annual reports between 1983 and 2011. Of these 51 deaths, we have been able t o locate the fatality reports for 38. These are attached for review by the EPA. The missing abstracts are from the earlier years of the database’s existence.”



### IV. Dataset Synopsis of Paraquat Dichloride Fatalities

 Main IDS identifies 2 7 deaths from 1990

- 2013 ; three accidental ingestions deaths reported by CPCS are included in this total

.

 SENSO R

- Pesticides 1998

- 2009 reports two deaths not found in IDS

, including one accidental ingestion by a child and one suicide.

 California PISP 2000

- 2010 identifies t hree deaths; at least two of which match with Dr. Gellar’s case reports.

 AAPCC reports 50 pa raquat fatalities from 1983

- 2011

.

V. CONCLUSION

The number of fatalities related to the ingestion of paraquat dichloride warrants closer

examination and discussion with PRD and the paraquat dichloride registrants

.

### 14 | P a g e 

# APPENDI X A

.

Table A

- 1. Main IDS Paraquat Dichloride (pc code 061601) Deaths from 1990

- Present (2/21/14)

Count Case ID Date State Severity Description

1 000741

- 0 0001 9/28/93 GA Death Man drank Gramoxone Extra to commit suicide: his stomach was lavaged & he was purged: he hemoperfused daily and died in hospital

. 2 001045

- 00001 4/16/94 SC Death 45 yr old man drank 2 swallows of Gramoxone: vomited: apnea, lung fibrosis, kidney disfunction: man died of respiratory f ailure

. 3 004599

- 0 0001 11/26/96 HI Death 75 yr. old Hawaiian man intentionally drank 30

- 60 ml of concentrated paraquat. He died 8 days later in hospital: renal failure, pulmonary

edema

. 4 007613

- 0 0001 8/5/98 LA Death Male ’ s 7 th beer was tainted with paraquat. Caused nausea and diarrhea. Male taken to ICU, treated w/ atropine & 2 PAM, but died.

5 009542

- 00001 9/1/99 DE Death 16 yr. old developed vomiting & renal failure. Lung biopsy revealed pulmonary fibrosis. Paraquat level 7+ times normal level in urine.

6 010077

- 00001 4/10/00 GA Death 15 month old child ingested paraquat product in a Gatorade container. Acute renal failure, nitric oxide used, sepsis set in and the child died.

7 010504

- 00001 7/22/00 PR Death Man ingested Gramoxone Super Herbicide and Roundup in an apparent suicide

. 8 010091

- 00001 3/1/00 CA Death Updates HB #010054

- 00002. 14 year old females presented with pulmonary fibrosis; later died.

9 010440

- 00001 7/7/00 PR Death Apparent suicide from ingestion of paraquat dichloride, Puerto Rico.

10 010666

- 00001 9/14/00 MS Death Man at Farmers Supply coop drank 1 cup of Gramoxone Extra in an apparent suicide. Died in Jackson University Hospital.

11 010677

- 00001 5/1/00 IL Death Farmer applied product within 100 ft. of 7 people. Wind blew mist, people washed, but death of 2 people , Dyspnea in several people.

12 010677

- 00001 5/1/00 IL Death Farmer applied product within 100 ft. of 7 people. Wind blew mist, people washed, but death of 2 people , Dyspnea in several people.

13 010591

- 00001 8/20/00 NM Death Suicide ingestion

. 14 011958

- 0 0001 8/11/01 PA Death 38 yr. old female argued with friend, intentionally drank alcohol, then drank Gramoxone, and jumped into pond. Died, multiple organs

failed.

15 013569

- 0 0001 11/10/02 OH Death man ingested gulp of paraquat from Pepsi bottle. Was put on ventilator, given renal dialysis. Died.

16 013372

- 00001 10/1/02 GA Death The circumstances of exposure are unclear. On 10/2/02, caller indicated soman drank sips of paraquat by accident as she reached for her coffee. On 10/4/02, the history was altered, “During the night the

### 15 | P a g e patient got up to get some cough medicine which was sitting next to the product and took product by mistake”

. 17 0 25332

- 004

( Update to

014885

- 00026 ) 3/5/03 CA Death An adult male was making an app lication of para quat to his yard. He

had two coffee cups in his garage, one containe d coffee and the other contained paraquat. He accidentally took a sip of the paraquat and

immediat e ly spit it out. About an hour later he started to feel sick and drove himself to the hospital. His condition progressively got worse and he died on March 12, 2003. The cause of de ath established by the coroner was acute paraquat intoxication and multiple organ failure.

18 015546

- 00001 9/9/04 TX Death Human death with possible paraquat exposure. Patient was seen in ER and treated. Patient later died from significant lung fibrosis.

19 016020

- 0 0001 2/24/05 CA Death It appears that the individual intentionally consumed a pesticide product from an unla belled container with the intention of harming himself. The patient developed symptoms that are consistent with paraquat ingestion and was treated at the hospital. The patient eventually expired. Analysis of the patient’s urine confirmed the presence of pa raquat; however, the exact formulation of herbicide that was ingested is unknown.

20 016630

- 00001 9/10/05 FL Death M an drank paraquat & organophosphates out of bottle. Intubated at hospital, signif

icant respiratory sympt oms, blue sweat & urine.

Accidental ingestion.

21 016310

- 0 0001 6/3/05 NC Death 48 yr. old man was apparently transferring straight product from a glass jar to a sprayer. He reportedly drank from that container by accident He thought he’d consumed tobacco spittle, so he didn’t seek medical attention immediately for the vomiting noted shortly afterward, according to the brother. Tested for drugs, apparently. Had been going through alcohol withdrawal according to brother. Never any mention of a suicide attempt.

22 018909

- 0 0001 8/24/07 NC Death A 59 year old male died of cardiac arrest and multi system organ failure in the hospital. It was not clear if he drank the product intentionally or not.

23 0 25332

- 00 002

( U pdate to 021704

- 00006) 1/13/10 CA Death A 44 year old male mistakenly drank the product and developed difficulty in breathi ng and vomiting of blood. He was admitted to the

intensive care unit.

24 023121

- 00001 7/12/11 SC Death Suicide, multiple products

. 25 025332

- 00001

( 0 25400

- 0000 1 updates this ) 6/1/13 CA Death 70 yr. old female ingested some contents of a re

- used ice d tea bottle, which unknown to her contained Gramoxone. She presented awake and alert with persistent vomiting. Over the course of a 16 day admission she evolved the classic picture of paraquat ingestion:

### 16 | P a g e corrosive gastrointestinal injury plus renal and pul monary failure leading to death.

26 025635

- 00001 8/19/13 NJ Death Gramoxone & iced tea ingestion in suicide case: 25 yr. old male at work as a landscaper. Discussed desire to commit suicide with

coworker. Drank out of 2

- 2.5 gallon canister. Vomited, became lethargic, taken to hospital for gastric lavage. Intubated, tachycardic, hypothermia, later died.

27 026120

- 00001 1/25/14 CA Death A m an drank paraquat while trying to kill himself. Drank an estimated

8

- 10 ounces from a cranberry juice bottle. Nausea, vomiting, diarrhea, bloody vomiting, died two days later.

.

### 17 | P a g e 

# APPENDIX B.

Moderate Severity (HC) Paraquat Incident Reports: Main IDS 2010

- 2013

Identification Incident

Date State Product Reg # Symptoms Description

1 0 21573

- 00 005 6/23/08 NE Gramoxone Inteon 100

- 1217 Dermal irritation Got product on hand 18 months prior

recurring/worsening dermal irritation

2 0 21807

- 00 005 3/19/10 AL Gramoxone Inteon +

Sevin 100

- 1217 High BP, bad taste

in mouth Inhaled mist in enclosed cab

3 0 21985

- 00 143 5/26/10 IN Gramoxone Inteon 100

- 1217 Rash, blisters Splash on leg

4 0 22107

- 00 007 6/15/10 NC Gramoxone Cornea burn, nose bleed, GI Splashed on face

5 0 22107

- 00 012 6/23/10 KY Gramoxone Inteon 100

- 1217 Oral burns, tongue

blisters 15

- yr

- old had some in mouth

- drank from a

Coke bottle

- full strength

- did not swallow

6 0 22107

- 00 067 6/25/10 AR Gramoxone Inteon 100

- 1217 Dermal redness May have gotten product on leg

- used 3 weeks prior

7 0 22281

- 00 028 8/16/10 AR Gramoxone Chest pain Wife inhaled spray

8 0 22281

- 00 029 8/19/10 TX Gramoxone Inteon Skin irritation Splashed on chest

9 0 22466

- 00 005 9/30/10 FL Gramoxone Inteon 100

- 1217 Dermal abrasion on face, bleeding Splashed on face while opening

10 0 23072

- 00 1 81 5/28/11 TN Gramoxone Farmer sprayed product in his eye

11 0 23072

- 00182 6/21/11 AR Gramoxone Rash, neurological Case inhaled product mist

– occurred on a

farm

12 0 23253

- 00 008 7/30/11 CA Gramoxone Inteon Ingestion from unmarked milk carton

- “intentional”

- CDPR report

13 0 23187

- 00 023 7/1/11 CA Gramoxone HB

14 0 23289

- 00 009 8/20/11 SC Gramoxone Inteon Skin blisters Got some product on gloves

15 0 23289

- 00 007 8/23/11 MS Gramoxone Blisters Sprayed on legs

16 0 23289

- 00 008 6/2010 GA Gramoxone Inteon 100

- 1217 Recurring dermal/

cardiovascular Truck driver spilled product onto his body

while transferring the product

17 0 2338 8

- 00 005 9/27/11 HI Gramoxone Throat swelling Drank ~1 tsp. of product

18 0 23490

- 00 008 10/3/11 TX Gramoxone Respiratory Mixing/loading splash

19 0 24040

- 00 097 4/19/12 PA Gramoxone 2.0 SL 100

- 1431 Rash Inhalation/dermal exposure

20 0 24040

- 00 095 4/6/12 TN Gramoxone 2.0 SL 100

- 1431 Blisters Splash

- equipment malfunction

21 0 24040

- 00 098 4/12/12 NC Gramoxone Stroke HB

22 0 24186

- 00 205 5/8/12 MO Gramoxone Inteon 100

- 1217 Blisters, dermal pain Occupational exposure to concentrate

- got a

drop on nose

### 18 | P a g e

23 0 24186

- 00 204 5/7/12 MD Gramoxone Numbness Applied weeks prior to symptoms; did not ingest, may have gotten some on skin or

inhaled fumes

24 0 24275

- 00 075 6/22/12 NC Gramoxone 2.0 SL 100

- 1431 C ough Inhalation

- mixed and applied product to a pasture, started coughing (has COPD)

25 0 24275

- 00 068 5/30/12 VA Gramoxone Inteon + glyphosate GI Application inhalation

26 0 24379

- 00 031 7/28/12 AR Gramoxone Ocular pain Splashed product in eye

27 0 24497

- 00 010 5/11/12 GA Product not specified Gastrointestinal,

shortness of breath Inhalation; occurred on farm

28 0 24497

- 00 009 ~8/23/12 TX Gramoxone 2.0 SL 100

- 1431 Headache, abnormal blood cell count,

fever Applying in enclosed cab

- stepped out and

inhaled mist

29 0 24539

- 00 007 9/6/12 CA Gramoxone Inhalation while spraying field

- no PPE

30 0 24807

- 00 006 ~11/4/12 MS Gramoxone Severe dermal, skin peeling Spilled product, soaked through gloves

31 0 24870

- 00 010 12/6/12 AL Gramoxone Inteon 100

- 1217 Neurological, cardiovascular, respiratory Inhalation and dermal exposure while

applying product

32 0 25215

- 00 016 4/6/13 TX Gramoxone Inteon 100

- 1217 Blisters, burns on

mouth Oral exposure from contaminated hose

33 0 25215

- 00 021 4/29/13 CA Gramoxone 2.0 SL 100

- 1431 Ocular, dermal Sprayed in the face from a leak in the hose of a spray tank, was wearing glasses

34 0 25458

- 00 007 6/12/13 AL Gramoxone 2.0 SL 100

- 1431 Ocular pain 15 year old was spraying crops, ocular

exposure 35 0 25458

- 00 011 ~6/24/13 GA Gramoxone Dermal Exposed when rinsing equipment