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

OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION

MEMORANDUM

Date : May 22, 2013

SUBJECT: Methyl Bromide: Review of Hum an Incidents

PC Co de: 053201 DP Barcode: 0411151 Decision No.: 476573 Petition No.: NA Risk Assessment Type: NA TXRNo.: NA MRID N o.: NA Registration No.: NA Regulatory Action: NA Case No. : NA CAS No.: 74-83-9 40CFR: NA Ver.Apr.08

Elizabeth Ev ans, Environm enta l Protection Specialist 

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Toxicology and E pidemiology Branch 

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Health Effects Division (7509P) l. 

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and Shanna Recore, Industrial H ygienist \**~** " 

### 1 ) Toxi colog y and Epidemiology Branch

## ~\.J.L~**ILC.~(JA...__,L** Health Effec ts Division ( 7509P ) ;{}

THROUGH: David J. Miller, Acting Branch

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TO: Matthew Lloyd, Risk Assessor R isk Assessment Branch VII Health Effects Division (7509P) and Susan Bartlow

, Chemical Review Manager Risk Management & Implementation Branch IV Pesticide R eevalua tion Di vision (7508P)

Su mmary and Con cJu sions

On December 1, 20 1 2 the final phase EPA-required new safety measures for soil fumigant pesticides (c hl oropicrin

, dazomet, metam sodium/potassium, and methyl bromide) went into effect. These safety measures are required to increase protections for agricultural workers and by stan ders. Due to the fact that these safety measures were only recently required, there is insufficient information available to determine if they have impacted the frequency of incidents

Pa ge 1 of 

### 11occurring

. However, the Age n cy w ill conti n ue to monitor the incident informa t ion and provide

a n updated rev i ew of i n cident, considering pre- and post- m itigation i ncidents separate l y, when the informa t ion becomes available

.

The Ag r icultural H ealth Study (AHS) is a l so a potent i a l source of i n format i o n associate d with human health effects associated with certa i n pesticides. Methyl bromide is included in t he AHS, and th i s report i ncludes a summary of evalua t ions of me t hyl bromide use i n association with

cancer outcomes reported in the AHS.

D etailed Review

I. ACTION REQUESTED

This r eview i s i nte n ded to fulfi ll our requirement t o docket summaries of incident data tha t were reported to the Agency, as well as to ensu r e h u man in ciden t data and the Agricu l tura l Health Study (AHS) are part ofthe prob l em formulation p h ase of registration r eview

. Reports of adverse health effects allegedly due to a specific pest i cid e exposure (i.e.

, an '" in cide n t") are largely self-reported and therefore, generally speaking, neither expos u re to a pesticide or reported symptom (or the connection between the two) is va li dated or otherw i se confirmed

. Typ i cally, causat i on cannot be determi n ed based on i ncident data. H owever, inc i dent information can be an important source of feedback to the Agency: incidents of severe outcome,

or a sugges t ed pa tt ern or trend among less severe inciden t s, can signal t h e Agency to further i nvest i gate a part i cu l ar chemical or p r od u ct. Observational epidemio l ogy studies r elate the r i s k of disease

, e.g., cancer, and exposure to an agen t such as a pesticide produc t in t he general population or specific sub-groups li ke pesticide applicators

.

II

. BACKGROUND

Methyl b r omide is a broad

- spectrum fumigant chemical that can be used as an acaricide, antimicrobial, fungic i de, herbicide, i nsecticide, nema t icide, and vertebra t e control agent. Methy l bromide's most prevalent use pattern i s as a soil fumigant. 1 Methy l brom i de i s commonly formulated as pressurized gas applied as a soil fumigant via soil injection or deep drip irrigation

. Methy l bromide can be used post-harvest v i a injection into an enclosure chamber, structure, or under a ta r p

. Met h yl bromide is r eg i stered fo r use on the so il s of all vegetable, fruit and nut crops, structural fum i gation, post harvest treatment of commod i t i es (e

. g. dates, figs, raisins,

wa l nuts) and non

- food uses (logs for export).

Th e 2006 T REDIRED found inha l at i on r isks of conce rn fo r occupat i ona l hand l ers i nvolved in methyl bromide applications and tarp perforation/removal activi t ies. Risks are also of concern for wor k ers w h o may r e-enter treated a r eas shortly after fumigat i on or tarp perforation h as been completed. Monitoring and modeling data indicate that there can be risks of concern associated wi t h methyl brom i de use at a broad range of distances from trea t ed fields, depending on

1 Methyl Bromide factsheet: http: // www.epa

. gov / oppsrrd I /REDs / factsheets / methylbromide-fs.pdf

Page 2 of11Page 3 of 11

application method, emission control methods employed, application rate, and size of the area treated. 2

For this evaluation, both the OPP Incident Data System (IDS) and the Centers for Disease Control and Prevention/Nationa l Institute for Occupational Safety and Health (CDC/NIOSH) Sentinel Event Notification System for Occupational Risk

- Pesticides (SENSOR) databases were consulted for pesticide incident data on the active ingredient Methyl bromide (PC Code: 0 53201 ). The purp ose of the database search is to identify potential patterns in the frequency and severity of the health effects attributed to Methyl bromide exposure.
In addition, findings from the AHS were reviewed. The Agricultural Health Study (AHS) is a high qual ity, prospective epidemiology study evaluating the link between pesticide use and various health outcomes including cancer. AHS authors have observed associations for certain cancer sites (gastric and prostate), as well as chronic bronchitis. These study r esults, as well as supporting information from studies performed external to the AHS, are summarized below.

III. RESULTS/DISCUSSION

a. IDS (Incident Data System)

OPP’s IDS includes reports of alleged human health incidents from various sources, including mandat ory 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 has compiled these reports in IDS. IDS contains r eports 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.

IDS records incidents in one of two modul es: 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 incident data for death, major and moderate incidents, and it includes informat ion about the location, date and nature of the incident. Main IDS incidents involving only one active ingredient (as opposed to pesticide products with multiple active ingredients) are considered to provide more certain information about the potential eff

ects 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 registrants only as counts in what are aggregate summaries.

For the Main IDS, from January 1, 2008 to February 19, 2013, there were there were 4 incidents reported for single chemical only in the database. There was 1 major severity incident, 1 moderate severity incident, 1 minor severity incident and 1 incident ha d no effects reported.

2 Ibid.Page 4 of 11

These incidents are further described in Table 1. There were 9 additional incidents reported involving more than one chemical. Overall, there are few incidents involving methyl bromide reported to IDS.

In Aggregate IDS, from January 1, 2008 to February 19, 2013, there were 4 reported incidents involving methyl bromide . These incidents were classified as minor severity.Page 5 of 11

Table 1. Main IDS Major Incidents for the single chemical Methyl Bromide Human Incident Chemical: Methyl Bromide PC Code: 053201

Incide nt Packa ge Repor t Inciden t Date Locati

on Reg Numb

er Product Name Exposu

re Severit y Codes Incident Description 01958 0

- 00001 4/15/20

08 Aubur n, WA METHYL

BROMIDE H Over fifty employees were exposed to methyl bromide in a building. No adverse reaction reported, only exposure.

01996 9

- 00001 8/16/20

08 NE 00578

5

- 00011 METH

- O

GAS 100 HB The owner of a pest control service company and an employee increased the pressure of the cylinder containing methyl bromide with nitrogen. This is a misuse that caused the methyl bromide cylinder to explode. Both individuals were taken to the hospital. Neither had clinical signs of methyl bromide exposure. One individual was released. The other individual had part of his leg amputated due to the fragmentation of the cylinder.

02150 8

- 00001 11/4/20

09 Mader a, CA 00885 3

- 00002

- 01122 0 M B C CONCENTR ATE HD An applicator was performing individual vine

- site fumigation with a hand

- held injection probe. During application the cylinder broke and a small amount of product sprayed the applicator who was wearing all required PPE. He immediately performed all on

- si te decontamination steps. He experienced eye and respiratory irritation and was taken to the hospital. After a 4

- hour observation period, the applicator was released and approved to go back to work.

02188 5

- 00001 1/1/201

0 Carson , CA 00578 5

- 00041 METH

- O

GAS Q HC Two cold storage employees reported adverse effects; possibly from methyl bromide off

- gassing from treated fruit (grapes). Both employees experienced difficulty breathing, sinus infections and respiratory irritation, unsteady gait, and diz ziness. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6027a4.htm?s_c id=mm6027a4_wPage 6 of 11 b. SENSOR

- Pesticides

The SENSOR

- Pesticides database covers 11 states from 1998

- 2009, 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 Depar tment of Labor workers’ compensation claims when reported by physicians, 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 data base, SENSOR

- Pesticides focuses on occupational pesticide incidents, 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 obtain ing medical records to verify symptoms and severity. Using standardized 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

- Pesticides 1998

- 2009 identifies a total of 119 cases, stemming from 67 events, involving methyl bromide. Ninety two percent of cases were work

- related. There were 3 fatalities, 2 high severity cases, 46 moderate severity cases and 68 low severity cases. Fifty

- six cases involved a single active ingredient and 57 cases involved a combination of methyl bromide and chloropicrin. Of the 56 single ai cases, there were two fatalities, two high severity cases, 21 moderate severity cases, and 31 low severity cases. Of th e 57 cases involving exposure to both methyl bromide and chloropicrin, there was one fatality, 20 moderate severity cases and 36 low severity cases. Symptoms reported for all cases are summarized in Table II.

Table II. SENSOR

- Pesticides 1998

- 2009: Repor ted Health Effects for

MeBr Cases N=119 Health Effect Count Dermal 39 Ocular 70 Respiratory 79 Gastrointestinal 53 Renal 2 Nervous System 65 Cardiovascular 15 Misc. 18 * Cases may report multiple health

effects

Fatality descriptions Two incidents from one event in Texas in 2002, single AI, relationship to pesticide exposure was coded as “definite;” however, intentional exposure was suspected but unknown as case 1 died, the following is case detail:Page 7 of 11

“ Details of exposure are unclear due to the fact that case died before explaining what happened. There were two cans of Methyl Bromide found outside the residence and all application devices were found hidden in garage. 2nd victim stated that case came home already exposed to chemical. 2nd vi ctim stated that he tried to help 1st victim and was exposed himself. Victim #1's 8 year old child came home, found dad in bed sick and laid next to him and became exposed. Victim's #1 & #2 both died from the exposure. (#1 died 2/5/02 and #2 died 3/24/02 )” A synopsis of the severe symptoms recorded for these two fatalities include: cardiac arrest, pulmonary edema, respiratory depression, ataxia, and seizure.

The third fatality occurred in California in 2009 and involved methyl bromide and chloropicrin,
p roduct name Helena MBC

- 33 soil fumigant (EPA Reg. No. 8853

- 3). A handler was filling a drum of MBC and chloropicrin and it ruptured and exploded.

Table II I . SENSOR

- Pesticides 1998

- 2009: MeBr Cases by Year

N=119 Year of Exposure Count 1998 8 1999 44* 2000 13 2001 10 2002 14 2003 2 2004 6 2005 2 2006 8 2007 1 2008 4 2009 7 *31 of these 1999 cases were attributable to one MeBr/Chloropicrin drift event described below.

Multiple case events In Florida in 1999: 31 individual cases were reported for one exposure event. Employees working at or near a tomato packing house received varied levels of exposure resultant from a MeBr/chloropicrin spill and drift. All 31 cases were low in severity and symptoms included respiratory irritation, headache and burning eyes.

Chloropicrin and MeBr Because chloropicrin and methyl bromide are often co

- formulated, the symptoms of these cases were reviewed to determine if the symptoms reported could be distinguished as attributabl e to either chloropicrin or methyl bromide.

O f the 57 methyl bromide and chloropicrin cases, the most commonly reported health effects involved the eye (n=46) such as eye irritation and lacrimation, also respiratory effects (n=46)Page 8 of 11

including upper respirat ory pain and cough. These symptoms are consistent with chloropicrin
exposure. 3 Of the 57 methyl bromide and chloropicrin cases, 29 reported a nervous system effect, generally a headache. Although it is difficult to determine which active ingredient was

r esponsible for the health effects, it appears that symptoms most frequently reported (burning, watery eyes and respiratory irritation) are consistent with chloropicrin exposure.

Soil Fumigation vs. Commodity Cases SENSOR

- Pesticides records the application site of the event, defined as “location where the application or event associated with the exposure took place.” Of the 119 methyl bromide cases reported in SENSOR

- Pesticides, 57 occurred on a farm. The remaining 62 occurred elsewhere, such as “industrial facilit ies” (n=35). This variation in location of the incidents is important because it shows that both soil fumigation and commodity incidents have both been reported. Some examples of commodity fumigation cas es are summarized here. Three Longshoremen were unloading imported logs that had been fumigated and were exposed. Another commodity case involved a shipping clerk unloading fumigated baskets from Asia.

c. Agricultural Health Study (AHS)

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 particu lar pesticide going through registration review, the Agency will ensure they are considered in the problem formulation/scoping phase of the process and, if appropriate, fully reviewed in the risk assessment phase of the process

. The AHS includes informatio n on use of 50 different pesticide active ingredients commonly used in agriculture.

In the Agricultural Health Study (AHS), researchers have identified an association between lifetime use of methyl bromide and both gastric and also prostate cancers, as we ll as prevalent chronic bronchitis among female spouses enrolled in the AHS. Given the low prevalence of fumigant use in the AHS, this Tier I summary also refers to studies outside of the AHS to provide a more accurate reflection of potential methyl bromid e carcinogenicity. Hughes

- Barry et al. (2012) reported an association between methyl bromide and gastric cancer. Using the intensity

- weighted exposure metric (adjusted for use of personal protective equipment), authors observed a three

- fold increased risk of gastric cancer comparing the upper methyl bromide group to the non

- exposed group (OR 3.13 (95% CI 1.25, 7.80), and researchers reported a significant monotonic increase in risk by increasing exposure (p for trend 0.02). In a study of California farm wor kers, Mills and Yang (2007) reported a link with gastric cancer and methyl bromide exposure of a similar magnitude and direction (OR 4 th quartile versus lowest methyl bromide exposure category 2.38 (95% CI 1.06, 5.37) (Mills and Yang et al. 2007).

Alavan ja et al. (2003) initially reported a link between methyl bromide and prostate cancer (Alavanja et al. 2003), however these finding were not replicated in more recent follow

- up analyses (Hughes

- Barry et al. 2012). In the early study, methyl bromide was amo ng only a few substances which were associated with prostate cancer regardless of a family history of prostate cancer among a first degree relative (top quintile versus no exposure: odds ratio (OR) 3.47 (95%

3 Recognition and Management of Pesticide Poisonings: 5 th Edition. Pg. 157Page 9 of 11

CI 1.57, 8.76), p for trend 0.004). Authors note that fumigant use in the AHS cohort is low due to crops typically grown in IA and NC, and the use of methyl bromide, while always low, decreased further over the time period since cohort enrollment (1993

- 2007). In the latter analysis, the authors did repl icate the earlier finding of an association with prostate cancer among those enrolled in the AHS cohort earlier (1993

- 1995) versus later (1995

- 1997) in cohort enrollment period, suggesting a link among those more highly exposed who enrolled in the study

ea rlier (Hughes

- Barry et al. 2012). It should be strongly noted that a lack of finding of an association with prostate cancer in the follow

- up analysis is not supportive of the conclusion of no association, since the prevalence of methyl bromide use is low, and decreasing in these study states. Methyl bromide use is greater in California than either of the two AHS study states. In a recent population

- based case control study (study period 2005

- 06), residential proximity to agricultural fields treated with met hyl bromide was associated with an increased risk of prostate cancer (OR 1.62 (95% CI 1.02, 2.56) ( Cockburn et al. 2011). The same authors also noted a non

significantly elevated risk of prostate cancer among farm workers in California (Mills and Yang 2003).

In a study of prevalent chronic bronchitis (questionnaire based self report outcome determination: “has a physician ever told you have chronic bronchitis?”), authors reported a link with methyl bromide (1.82 (95% CI 1.02, 3.24) controlling for age, state and other pesticide
exposures (Valcin et al. 2007) . This is a preliminary study and authors could not d iscern clearly between methyl bromide and other specific pesticide exposures and other correlated farm activities among female spouses due to the collection limited exposure information.

IV. CONCLUSION

On December 1, 2012 the final phase EPA

- required new s afety measures for soil fumigant pesticides (chloropicrin, dazomet, metam sodium/potassium, and methyl bromide) went into effect. These safety measures are required to increase protection for agricultural workers and bystanders. At the time of this repor t, there is insufficient information available to determine if the newly required safety measures have impacted the frequency of incidents occurring among soil fumigants including methyl bromide, since implementation. However, the Agency will continue to m onitor the incident information and provide an updated review of incident, considering pre

- and post

- mitigation incidents separately, when the information becomes available.

Only half the SENSOR

- Pesticides case s were exposed to methyl bromide on a farm ; 35 cases were exposed in an industrial facility. Therefore the commodity fumigation incidents are reported, while somewhat less than soil fumigation incidents, they warrant continue d monitoring as well as soil fumigation incidents.

In the AHS, authors noted a monotonically increasing trend of gastric cancer risk by increasing methyl bromide exposure; an association of a similar magnitude and direction was also reported among a highly exposed population of California farm workers. Early, strong associati ons with prostate cancer dissipated over time, perhaps due to decreasing prevalence of use of methyl bromide in the AHS cohort, as noted by the authors. However, a link with prostate cancer hasPage 10 of 11

been reported in both highly exposed samples of the general po pulation (California residents living near methyl bromide treated fields), and a California farm worker population in similar study periods. Other cancer

- methyl bromide links hypothesized in the open literature could not be evaluated in the AHS due to the small number of methyl bromide exposed testicular and lymphoma cancer cases. Fumigant use in the AHS is low; this obviates the ability the evaluate associations between methyl bromide use and many different anatomical cancer sites. Therefore, a lack of ass ociation should not be interpreted as evidence of no true association. Authors of studies in other highly exposed occupational and non

- occupational populations have reported similar associations to the AHS and will also be considered in EPA’s evaluation to provide a full evaluation of the carcinogenic potential of methyl bromide.Page 11 of 11

References

Alavanja MC, Samanic C, Dosemeci M, Lubin J, Tarone R, Lynch CF, Knott C, Thomas K, Hoppin JA, Barker J, Coble J, Sandler DP, Blair A. Use of agricultural pesticides and prostate cancer risk in the Agricultural Health Study cohort. Am J Epidemiol. 2003 May 1;157(9):800

- 14. PubMed PMID: 12727674.

Barry KH, Koutros S, Lubin JH, Coble JB, Barone

- Adesi F, Beane Freeman LE, Sandler DP, Hoppin JA, Ma X, Zheng T, Alavanja MC. Methyl bromide exposure and cancer risk in the Agricultural Health Study. Cancer Causes Control. 2012 Jun;23(6):807

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Cockburn M, Mills P, Z hang X, Zadnick J, Goldberg D, Ritz B. Prostate cancer and ambient pesticide exposure in agriculturally intensive areas in California. Am J Epidemiol. 2011 Jun 1;173(11):1280

- 8. doi: 10.1093/aje/kwr003. Epub 2011 Mar 28. PubMed PMID: 21447478; PubMed Centr al PMCID: PMC3121318.

Mills PK, Yang RC. Agricultural exposures and gastric cancer risk in Hispanic farm workers in California. Environ Res. 2007 Jun;104(2):282

- 9. Epub 2006 Dec 29. PubMed PMID: 17196584.

Mills PK, Yang R. Prostate cancer risk in California farm workers. J Occup Environ Med. 2003 Mar;45(3):249

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Valcin M, Henneberger PK, Kullman GJ, Umbach DM, London SJ, Alavanja MC, Sandler DP, Hoppin JA. Chronic bronchitis among nonsmoking farm women in the agricultural health study. J Occup Environ Med. 2007 May;49(5):574

- 83. PubMed PMID: 17495700; PubMed Central PMCID: PMC2074236.