UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: September 13, 20 13 

OFFICE OF CHEMICAL 

SAFETY AND POLLUTION PREVENTION 

SUBJECT: Methyl Bromide. Human Health Assessment Seeping Document in Support of 

Registration Review. 

PC Code: 05320 I 

Decision No.: 476573 

Petition No.: N/A 

Risk Assessment Type: N/ A 

TXRNo.: N/A 

MRID No.: N/A 

DP Barcode: 410208 

Registration No.: 7041-1 

Regulatory Action: Registration Review Scoping Document 

Case No.: 

CAS No.: 74-83-9 A () 

FROM: 

40CFR: 180 1~4~ 

MatthewLloyd,RiskAssessor ,q~ 0~._ y William 

William 

Irwin, 

Donovan, 

Ph.D, 

Chemist 

DABT, Toxicologist 

W .;}J4::.,._ -J-+,~ 

· ~ 

Risk Assessment Branch V Nil (RABV Nil) 

Health Effects Division (7509P) 

THROUGH: JeffDawson, Chemist 

HED Immediate Offic.e 

And 

Michael Metzger, Branch Chief 

Risk Assessment Branch V Nil ( 

Health Effects Division (7509P) 

TO: Sue Bartow, Chemical Review Manager 

Cathryn Britton, Team Leader 

Kevin Costello, Branch Chief 

Pesticide Re-Evaluation Division (7508P) 

Attached is HED's human-health risk assessment seeping document for methyl bromide to 

support registration review. 

Page 1 of32 
Page 2 of 32

Executive Summary

Methyl bromide is a broad-spectrum fumigant chemical that can be used as an acaricide, 

antimicrobial, fungicide, herbicide, insecticide, nematicide, and vertebrate control agent. It can 

be used for (1) pre-plant soil fumigant for food & ornamental crops; (2) structural & industrial

fumigations (e.g., flour mills); (3) post-harvest food & non-food commodity uses; and (4) other 

specialized fumigations (e.g., proposed quarantine anti-microbial fumigations). Under the Clean 

Air Act and the Montreal Protocol on Substances that Deplete the Ozone Layer, methyl bromide 

has been undergoing a phase-out process since 19951. There are several allowable exemptions to 

the phase out, based on technical and economic reasons (e.g., lack of suitable alternatives). 

Exemptions exist for use related to: 1) the Quarantine and Preshipment (QPS) exemption, to 

eliminate quarantine pests, and 2) Critical Use Exemption (CUEs), designed for users with no 

technically or economically feasible alternatives. The Health Effects Division (HED) considered 

the most recent human-health risk assessments for methyl bromide with respect to toxicity, 

exposure, and usage databases, and the most updated Agency science policy and risk assessment 

methodologies to determine the scope of work necessary to support registration review. 

The Tolerance Reassessment and Risk Management Decision (TRED) and Reregistration 

Eligibility Decision (RED) for methyl bromide’s commodity uses were issued in August, 20062

and the RED for methyl bromide’s soil and non-food structural uses was issued in July, 2008 and 

amended in May, 20093. The use categories (identified above) have been grouped for the 

purposes of this document as “soil uses”, “commodity uses”, and “space” uses (i.e., greenhouses, 

non-food durable goods, and commercial structural fumigations). Quarantine pre-shipment uses, 

typically conducted under USDA’s Animal and Plant Health Inspection Service Plant Protection

and Quarantine (APHIS PPQ) criteria, are generally covered under post-harvest & non-food 

commodity uses; APHIS PPQ’s treatment manual4outlines appropriate treatment regimes for 

listed commodities with the intent of preventing the movement of agricultural pests into or 

within the United States.

While no new uses of methyl bromide have been registered since the RED, HED recently 

completed evaluations on two 24c actions for methyl bromide: 1) for control of western flower 

thrips on berries in California for export to Asia; and 2) for eradication of a nematode threat in 

Idaho potato fields. Additionally, HED is currently evaluating a Section 18 request for 

quarantine treatment of various post harvest food commodities for USDA’s APHIS PPQ.

The toxicity database for methyl bromide is adequate for registration review and there are no 

toxicology data deficiencies. Inhalation is the primary exposure route and multiple inhalation 

toxicology studies have been performed in several species. The critical effects of methyl bromide 

exposure via the inhalation route are agenesis of the gall bladder and fused sternebrae observed 

 

1 Available: http://www.epa.gov/ozone/mbr/index.html

2 Available: http://www.epa.gov/oppsrrd1/REDs/methyl_bromide_tred.pdf

3 Available: http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPP-2005-0123-0716;oldLink=false

4 Available: http://www.aphis.usda.gov/import_export/plants/manuals/ports/downloads/treatment.pdf
Page 3 of 32

in the developmental toxicity study in rabbits, neurotoxicity effects (acute, sub-chronic and 

chronic studies), and nasal histopathology observed in the chronic toxicity/carcinogenicity study 

in rats. The hazard database included a developmental neurotoxicity study in rats conducted via 

the inhalation route of exposure. Data are available for both oral and inhalation routes. The 

inhalation database includes: acute neurotoxicity study in rats, developmental neurotoxicity in 

rats, developmental toxicity studies in rats and rabbits, sub-chronic toxicity studies in rats and 

dogs, and chronic studies in mice and rats. Four studies conducted via the oral route in rats and 

dogs are also available. The risk assessment team concluded that the 10X FQPA Safety Factor 

can be reduced to 1X. During registration review, the Agency may need to reevaluate the points 

of departure (PODs) and uncertainty factors (UFs) for the residential and occupational exposure 

assessments, although no modifications to the endpoint selections and safety factors are 

anticipated at this time. Methyl bromide is classified as “Not Likely to be Carcinogenic to 

Humans" based on a weight of evidence evaluation of the toxicity database including no 

indications of carcinogenesis observed in the chronic rodent bioassays. Methyl bromide is 

included in the Agricultural Health Survey (AHS), and the Agency intends to continue to 

evaluate the associations with carcinogenicity and other possible health effects through OPP’s 

framework for incorporating epidemiology into human health risk assessment5. 

The residue chemistry and dietary-exposure databases are adequate to support current 

registration requirements. Soil fumigation uses of methyl bromide have previously been 

determined to be non-food uses; post-harvest uses of methyl bromide are food uses and residue 

trials reflecting these uses form the basis for tolerances. OPP has been coordinating with the 

Methyl Bromide Industry Panel (MBIP) and USDA’s APHIS PPQ on a Section 18 request for 

quarantine commodity treatments that is under review concurrent with this scoping document. 

Depending on the outcome of this review or updated information during the registration review 

process, dietary contributions from food and drinking water may need to be updated during 

registration review. 

Several outstanding data gaps have been identified for the occupational and residential exposure 

database for registration review. An occupational exposure study for handheld probe applications 

was required for methyl bromide as part of the 2009 amended RED; a submission6is currently 

under review in HED7. Additionally, post-application exposure data for commodity fumigation 

was required. Data to measure ambient air concentrations are also outstanding. The Agency will 

review and incorporate review of these studies into the human health risk assessment during 

registration review. 

The following data deficiencies were identified for methyl bromide:

o 875.2500 [postapplication; inhalation exposure] – (off-gassing of previously 

fumigated commodities)8

 

5 Available: http://www.epa.gov/scipoly/sap/meetings/2010/020210meeting.html

6

Submission from TriCal, Inc. – submitted in August 2013

7

In 2013, HED issued a response for a methyl bromide waiver request of data requirement 875.1300 (GDCI053201-27007) associated with 2009 Registration Eligibility Decision.

8 GDCI-053201-26629; The Agency required protocol and consultation before the inititation of this study 

requirement.
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o Special Study– ambient air monitoring

 To address unique agricultural conditions (e.g., Siskiyou County, CA) and 

bystander exposure near active commodity fumigation sites 

1.0 Introduction

Methyl bromide is a broad-spectrum fumigant chemical that can be used as an acaricide, 

antimicrobial, fungicide, herbicide, insecticide, nematicide, and vertebrate control agent for soil 

fumigation uses, commodity fumigation, and structural fumigation9. As a soil fumigant, methyl 

bromide can be injected into soil in broadcast fashion or while forming raised beds at various 

depths using tractors equipped with shanks of various types. Use restrictions require all 

applications to be tarped, except for deep shank orchard replant [California only] and hand held 

tree-hole applications. Alternately, a less prevalent application method uses hot gas injection to 

force methyl bromide through a heat exchanger into drip tubing under tarps. Only a few hot gas 

applications will remain after December, 2013. According to the BEAD chemical profile10, 

critical use exemption (CUE) nominations have declined substantially but methyl bromide’s use 

at current levels for quarantine and preshipment is expected to continue into the future. For 

example, ornamental uses have CUEs that will expire in December, 2013.

As a commodity fumigant, methyl bromide gas can be injected into an enclosure, chamber, 

structure, or under a tarp to treat a broad range of post harvest commodities, both food and nonfood. In many cases, methyl bromide treatment is required by law for phytosanitation purposes, 

as per USDA’s Animal and Plant Health Inspection Service (APHIS) Plant Protection and 

Quarantine (PPQ) treatment manual11. Besides for post harvest commodity treatments, methyl 

bromide is also used for structural and industrial fumigation treatments of large food handling 

establishments (e.g., flour or grain mills).

The Tolerance Reassessment Eligibility Decision (TRED) and Reregistration Eligibility Decision 

(RED) for methyl bromide’s commodity uses were issued in August, 2006. The RED for Methyl 

Bromide’s soil and non-food structural uses was issued in July, 2008 and amended in May, 2009.

EPA also evaluates Critical Use Exemptions (CUEs), which are permitted under Section 604(d) 

of the Clean Air Act and the Montreal Protocol on Substances that Deplete the Ozone Layer. 

EPA entered into an agreement with CDPR on August 24, 2011 to resolve the civil rights

complaint in the Angelita C., et al. v. California Department of Pesticide Regulations case. 

Section 10 (Environmental Justice) provides additional information and references.

The OPP regulatory decision documents focused on the broad methyl bromide use patterns,

including: (1) use as a pre-plant soil fumigant for food & ornamental crops12; (2) structural &

 

9

Some methyl bromide product labels include antimicrobial claims; “...and some bacteria (e.g., Salmonella 

spp.)...” However, the antimicrobial applications are not separate treatments, and the antimicrobial action occurs 

during the conventional methyl bromide treatment. Therefore, the methyl bromide commodity treatments relevant to 

the antimicrobial claims (e.g., railroad cars, trucks, poultry houses) are covered under the Health Effects Division 

review and do not require separate review by OPP’s Antimicrobials Division. [Registrations 8622-55 (Metabrom Q) 

and 8536-29 (Methyl Bromide Quarantine Fumigant)]

10 Available: BEAD Chemical Profile for Registration Review: Methyl Bromide (053201). Chism, W. et. al.

11 Available: http://www.aphis.usda.gov/import_export/plants/manuals/ports/downloads/treatment.pdf

12 CUEs for ornamentals/shade trees expire in December, 2013
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industrial fumigations (e.g., flour mills); (3) post-harvest food & non-food commodity uses; and 

(4) other specialized fumigations (e.g., quarantine pre-shipment). These categories have been 

grouped broadly for the purposes of this document as “soil uses” and “commodity uses.” No new 

methyl bromide uses have been registered since the above mentioned regulatory decisions were 

issued. 

2.0 Hazard Identification/Toxicology

The toxicological database for methyl bromide is complete and sufficient for risk assessment 

purposes and includes a developmental neurotoxicity study in rats conducted via the 

inhalation route. The inhalation database includes: acute neurotoxicity study in rats, 

developmental neurotoxicity in rats, developmental toxicity studies in rats and rabbits, subchronic toxicity studies in rats and dogs, and chronic studies in mice and rats. Four studies 

conducted via the oral route in rats and dogs were also available. No modifications to the 

endpoint selections and safety factors are anticipated at this time.

Inhalation exposure is the key exposure pathway for methyl bromide use, regardless of use site. 

Methyl bromide has almost no odor even at physiologically hazardous concentrations. The 

critical effects of methyl bromide exposure via the inhalation route are agenesis of the gall 

bladder and fused sternebrae observed in the developmental toxicity study in rabbits, 

neurotoxicity effects (acute, sub-chronic and chronic studies), and nasal histopathology observed 

in the chronic toxicity/carcinogenicity study in rats. In the chronic rat inhalation study, there was 

increased incidence of basal cell hyperplasia of the nasal cavity in both sexes.

Developmental toxicity and neurotoxicity were the most commonly observed toxic effect in the 

toxicity data base and were observed in all tested species. Both acute and sub-chronic inhalation 

neurotoxicity studies in rats showed evidence of neurotoxic effects of methyl bromide 

characterized by decreased activity, tremors, ataxia and paralysis. Two sub-chronic studies 

demonstrated dogs to be the most sensitive species to the neurotoxic effects of methyl bromide. 

Neurotoxic effects were also seen in the chronic/carcinogenicity inhalation study in mice (ataxia, 

limb paralysis, degenerative changes in the cerebellum), the developmental inhalation study in 

rabbits (lethargy, right side head tilt, ataxia), and the developmental neurotoxicity (DNT) study 

in rats (decrease in motor activity). Developmental effects described as increased incidence of 

agenesis of the gallbladder and fused sternebrae were also seen in the developmental inhalation 

study in rabbits. In addition, the multi-generation reproduction toxicity study in rats revealed 

that methyl bromide exposure via the inhalation route resulted in decreases in pregnancy rates 

and body weights (pups and adults). The inhalation immunotoxicity study did not indicate 

immunotoxicity at doses up to 120 ppm. 

Four studies conducted via the oral route are available in the methyl bromide database. 

Effects noted after dietary exposure were primarily decreases in body weight gain, body 

weight, and food consumption. Evidence of stomach lesions was observed in the 90-day oral 

toxicity study in rats.

Several studies in the database indicate that methyl bromide is a genotoxic agent. The 

micronucleus genotoxicity study had positive responses, however at doses which also caused 
Page 6 of 32

mortality. However, no indications of carcinogenesis were observed in the chronic rodent 

bioassays, and methyl bromide is classified as “Not Likely to be Carcinogenic to Humans".

Acutely, methyl bromide is a low to moderate toxicant via the oral and inhalation routes of 

exposure (Toxicity Categories II and IV, respectively). In contrast, methyl bromide is highly 

irritating via both dermal and ocular routes of exposure (Toxicity Category I). Occupational 

exposure limits of methyl bromide are addressed by a number of different Agencies and 

expert panels, including other parts of EPA [EPA’s Acute Exposure Guideline Level (AEGL) 

Program13], OSHA14, CalOSHA15, NIOSH16, and the American Congress of Governmental 

Industrial Hygienists (ACGIH)17.

HED’s approach to estimating risks due to inhalation exposure is based on the guidance 

methodology developed by Office of Research and Development for the derivation of inhalation 

reference concentrations (RfCs) and human equivalent concentrations (HECs) for use in MOE 

calculations. Endpoint selection is based on the endpoints occurring at the lowest HECs (which 

may or may not be the lowest animal NOAEL) derived using the RfC methodology In this 

methodology, different HECs may be calculated for the same experimental NOAEL due to: 1) 

the different algorithms used to derive HECs for systemic versus portal of entry effects; or 2) the 

time adjustments conducted for non-occupational (commodity treatment facility bystander or 

agricultural setting bystander) versus occupational exposure scenarios. The HECs calculated for 

methyl bromide are consistent with the RfC methodology guidance and took the most sensitive 

population for each subgroup into account.

A detailed listing of the endpoints, doses, HECs and uncertainty factors selected for exposures is 

outlined in Attachment 3 of this document. For additional information on HEC calculations, 

refer to the previous risk assessments for methyl bromide (J. Dawson, DP Barcodes: D337288, 

D350818). All occupational and bystander endpoints were selected from inhalation studies, the 

predominant route of exposure. For acute exposures (agricultural and commodity bystanders, 

plus occupational), the Agency has selected the endpoint from the rabbit developmental 

inhalation study where agenesis of the gallbladder and fused sternebrae occurred. The short and 

intermediate-term inhalation endpoint was based on the sub-chronic inhalation study in dogs 

which caused decreased responsiveness in females, fecal effects and eye irritation. The long-term 

inhalation endpoint was based on the chronic inhalation study in rats where nasal lesions were 

observed. For the acute dietary scenario for females 13-50 years of age, the inhalation rabbit 

developmental study was selected for regulation. The acute dietary assessment for the general 

population utilized the inhalation acute neurotoxicity study for endpoint selection based on 

neurotoxicity signs. The chronic dietary scenario utilized the chronic rat study for endpoint 

selection based on decreased body weight, body weight gain and food consumption 

(encapsulated methyl bromide).

 

13 Available: http://www.epa.gov/oppt/aegl/pubs/rest113.htm

14 Available: http://www.osha.gov/dts/chemicalsampling/data/CH_251900.html

15 Available: http://www.dir.ca.gov/title8/5155table_ac1.html

16 Available: http://www.cdc.gov/niosh/idlh/74839.html

17 Available: http://www.acgih.org/Store/ProductDetail.cfm?id=1079
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The Food Quality Protection Act (FQPA) requires the Agency to consider special sensitivities 

of the young to chemical exposure. HED determined that the FQPA factor could be reduced to 

1X based on having a complete toxicological database and the adequacy of uncertainty factors 

assigned to chosen points of departure . Clear NOAELs were identified for all studies used for 

dietary endpoint selection, and their dose responses were well defined. Consequently, selected

points of departure (PODs) will not under-estimate the risk. An inhalation developmental 

neurotoxicity study (DNT) in rats has been received and reviewed by the Agency. Therefore, the 

database uncertainty factor of 10X previously retained for lack of the DNT has been removed 

for all risk assessments in accordance with current HED policy. In the rat developmental 

inhalation study there was no indication of susceptibility to the young, at doses up to 70 ppm. 

The rabbit inhalation developmental study also did not indicate susceptibility to the young; the 

dams and the offspring had identical NOAEL and LOAEL values. The inhalation 

developmental neurotoxicity study did show increased susceptibility in the young, as well as the 

rat inhalation reproduction study. It is noteworthy, however, that the use of inhalation studies to

assess dietary risks is a conservative approach since inhalation exposure is expected to lead to a

higher internal dose than dietary exposure since chemicals will enter the circulation before many

of the detoxification processes associated with oral exposure (e.g. first pass effect) occur. 

Moreover, chemicals in the respiratory tract generally enter the blood stream more readily than

chemicals in the gastrointestinal (GI) tract, since the alveolar space of the lung has less separation 

from the blood stream than the lumen of the GI tract from the blood stream. Finally, the most 

sensitive reproductive and offspring-specific endpoints and PODs from these studies were used 

to quantify short-, intermediate- and long-term risks. The methyl bromide risk assessment team 

has reviewed the entire database and determined there is no residual uncertainty regarding 

exposure to children at any developmental stage and recommends that the FQPA factor be 

reduced to 1X.

Conclusions: The toxicity database for methyl bromide is adequate for registration review, 

and includes a developmental neurotoxicity study in rats conducted via the inhalation route. 

Data are available for both oral and inhalation routes. During registration review, the Agency 

may need to reevaluate the points of departure (PODs) and uncertainty factors (UFs) for the 

residential and occupational exposure assessments based on current HED policy, although no

modifications to the endpoint selections and safety factors are anticipated at this time. 

3.0 Residue Chemistry

No new residue chemistry data deficiencies were identified during the scoping process. Soil 

fumigation uses of methyl bromide are classified as non-food uses. However, post-harvest uses 

are food uses and require tolerances. As of September 2013, recommendations to replace the 

current listings of inorganic bromide tolerances with methyl bromide tolerances, as requested in 

the residue chemistry chapter to the Reregistration Eligibility Decision (RED) (D271583, C.

Olinger, 2/22/2002), have not been implemented. Specifically, all tolerances listed under 40 

CFR §180.123 for inorganic bromides should be moved to §180.124. The existing tolerance 

expression and tolerance listed under 40 CFR §180.124 for cotton, undelinted seed is appropriate 

and should be retained. HED has conducted a preliminary re-evaluation of the recommended 

methyl bromide tolerances listed in the RED taking into consideration the recent Section 18 

request from USDA/APHIS. This process should be completed during registration review, and 
Page 8 of 32

the resulting recommendations should be incorporated into 40 CFR §180.124. At this time no 

other residue chemistry issues are pending resolution. 

Conclusions: The residue chemistry database for methyl bromide is adequate for registration 

review; there are no outstanding data requirements. This conclusion will be re-evaluated if new 

crop uses or higher use rates are requested in the future. 

4.0 Dietary Exposure

Acute and chronic aggregate dietary [food and drinking water] exposure and risk assessments 

were conducted using the Dietary Exposure Evaluation Model software with the Food 

Commodity Intake Database (DEEM-FCID) Version 3.16. This software uses 2003-2008 food 

consumption data from the U.S. Department of Agriculture’s (USDA’s) National Health and 

Nutrition Examination Survey, What We Eat in America, (NHANES/WWEIA). The analyses

were conducted in support of a human-health risk assessment for the proposed Section 18 uses 

on imported crops and foods that are fumigated under the USDA Animal and Plant Health 

Inspection Service (APHIS) program.

The methyl bromide dietary assessments were partially refined and considered exposure from 

food and drinking water. Although no percent crop treated information was used in the acute or 

chronic analyses, anticipated residues were used as a refinement to the residue levels in food. 

HED has considered the degradation or dissipation of methyl bromide during typical storage and 

transport of commodities (D279095, C. Olinger, 1/31/2002). Also, because methyl bromide is a 

gas at room temperature, HED has assumed that all methyl bromide will dissipate when heated. 

Accordingly, residues were assumed to be zero for all commodities that are heated during 

preparation or processing.

Based on the information detailed above, dietary exposure estimates were below the Agency’s 

level of concern. Since 2005, OPP’s evaluation of drinking water exposure has continued to 

evolve based on new information. Surface water estimated drinking water concentrations 

(EDWCs) for methyl bromide are considered de minimis based on representative half-life data 

for methyl bromide evaporation from water to air. Hence, the methyl bromide EDWC was from 

ground water estimates. Based on the data base of pesticides in ground water (U.S. EPA, 1992), 

2 wells in California (out of 20,429 wells monitored in Florida, California, and Hawaii) had 

methyl bromide levels of 2.5 and 6.4 μg/L. Thus, the highest ground water monitoring value of 

6.4 ppb was used in both the acute and chronic assessments. The available ground water 

monitoring data represent a conservative contribution to the dietary assessment because the 

monitoring was conducted when methyl bromide use was more prevalent in the U.S. than today.

Specifically, recent information from BEAD indicates that both agricultural (soil) and nonagricultural (post harvest) uses of methyl bromide are declining over the time period of 1998-

2011 (W. Chism, C. Doucoure, and D. Berwald, February, 2013). 

If the Environmental Fate and Effects Divison (EFED) determines that a new drinking water 

assessment is required in registration review, then the dietary assessment may need to be updated 

to incorporate inputs from the revised drinking water (i.e., ground water) assessment.
Page 9 of 32

Conclusions: The dietary exposure databases for methyl bromide are adequate for registration 

review. An updated dietary assessment may be required in registration review to incorporate any 

revisions to the methyl bromide drinking water assessment, or updated crop uses. 

5.0 TOLERANCE ASSESSMENT AND INTERNATIONAL HARMONIZATION

HED has conducted a preliminary tolerance reassessment for methyl bromide. This 

reassessment will be completed in registration review once the final list of crops intended for 

post-harvest treatment with methyl bromide is finalized with USDA/APHIS and the Methyl 

Bromide Industry Panel (MBIP).

Where possible, EPA encourages the harmonization of the US Tolerances and Maximum 

Residue Limits (MRLs). A table with the US tolerances, the Canada MRLs, Mexico MRLs and 

Codex MRLs for methyl bromide in registered RACs is provided in Appendix 4- International 

Tolerances and Maximum Residue Limits. EPA is currently in the process of converting 

inorganic bromide tolerances to methyl bromide tolerances. There are currently no established 

Codex, Canadian and/or Mexican MRLs for inorganic bromide. There are Codex MRLs for 

methyl bromide, but none for undelinted cotton seed, the only commodity with a methyl bromide 

tolerance in the USA. Therefore, at this time, there are no harmonization issues.

6.0 Residential Exposure

There are no residential uses of methyl bromide, but bystanders who live or work near fumigated 

fields or sites where commodity fumigation occurs are potentially exposed to fumigant emissions 

that travel off-site. When considering the potential risks to bystanders for single application

known sources (e.g., a farm field or a fumigated structure/commodity), HED used distributional 

modeling18 to calculate distances at which target concentrations are achieved at varied 

percentiles of exposure. Those “buffer zones” refer to the distances determined based on a target 

concentration defined by the HEC or Human Equivalent Concentration adjusted by an 

uncertainty factor.

HED also calculated ambient bystander exposure from regional sources that are not attributable 

to a specific application event. HED used ambient exposure data from various sources, including 

data generated by the Methyl Bromide Industry Panel, the California Air Resources Board 

(CARB), and the CARB Toxic Air Contaminant monitoring program (TAC) to calculate ambient 

bystander exposure for agricultural and non-agricultural urban environments, respectively.

For site-specific bystander assessments, the Agency has specifically focused on assessing acute 

methyl bromide inhalation exposures resulting because peak air concentrations typically occur in 

the first 24 or 48 hours after application. There is also the potential for inhalation exposure to 

methyl bromide via ambient air resulting from agricultural soil applications across larger regions. 

Exposures for all durations ranging from acute to chronic were considered from methyl bromide 

levels in ambient air. 

 

18 Probabilistic Exposure and Risk Model For Fumigants (PERFUM)
Page 10 of 32

The 2009 Amended RED required one methyl bromide residential exposure study relating to 

non-occupational exposure (GDCI-053201-836):

an ambient air monitoring study for methyl bromide (non-guideline) that 

addresses ambient exposures to both agricultural and commodity fumigations

from high use areas

At this time, the ambient air monitoring study identified above has not been submitted for 

Agency review. Those data will allow HED to refine the risk picture for agricultural areas with 

unique characteristics and active commodity fumigation sites. HED requires ambient air 

monitoring data from areas where areas where there is high use of methyl bromide. The 

monitoring sites selected should be selected based on the amount of methyl bromide used and the 

frequency of applications. The Agency intends to consider the study results and other available 

ambient air monitoring data during registration review. 

There are three recent documents that evaluated acute residential bystander inhalation exposure 

to methyl bromide based on numerous field volatility studies and PERFUM (Probabilistic 

Exposure and Risk model for Fumigants) air modeling for agricultural field applications.

Table 6.0 – Key Methyl Bromide Bystander Assessments

Memo Title Reference Description/Impact on Risk 

Assessment

Methyl Bromide: Phase 5 Health 

Effects Division (HED) Human Health 

Risk Assessment For Soil, Greenhouse, 

and Residential/Structural Uses. 

Dawson; D337288; 04/10/2007 Addresses non-food uses (i.e., soil, 

greenhouse, and structural uses)

Addenda to April 10, 2007 Phase 5 

Health Effects Division (HED) Human 

Health Risk Assessment For Soil, 

Greenhouse, and Residential/Structural 

Uses.

Dawson; D350818; 06/02/2008 An addendum to the Phase 5 risk 

assessment for methyl bromide soil and 

structural uses that do not have food 

tolerances; updated PERFUM analysis, 

first principles factors analysis 

Methyl Bromide: Health Effects 

Division (HED), Human Health Risk 

Assessment For Methyl Bromide Soil 

Uses Based On Methyl Bromide 

Industry Panel (MBIP) Studies In 

California and Florida.

Dawson; D375752; 01/06/11 Revised human health risk assessment 

based on the studies defined in the 

(MBIP) Methyl Bromide Industry Panel 

research plan (MBIP data for the TIF 

films conducted in CA and FL)

The results of the assessments identified in Table 6.0 (above) show that bystander inhalation 

exposure to methyl bromide after a soil fumigation application can vary depending on a variety 

of factors such as application method, agricultural tarps, water seals, and a number of soil 

parameters (i.e., soil moisture, organic content, etc.)19. For many application scenarios, the

PERFUM air modeling results showed that some buffer zone was required to obtain methyl 

bromide air concentrations that provided appropriate protection for residential bystanders. The 

2009 Amended Reregistration Eligibility Decision (RED) Document for methyl bromide

provides more information on buffer zone development for soil fumigations. 

 

19 Available: Dawson; D337288; 04/10/2007 and Dawson; D350818; 06/02/2008
Page 11 of 32

At this time, the Agency is in the process of implementing buffer zones for commodity 

fumigation. A summary of the changes required for methyl bromide commodity and structural 

fumigations can be found in docket EPA-HQ-OPP-2005-0123. In the human health risk 

assessments that support those regulatory decisions, PERFUM results (i.e., buffer zone 

distances) were presented based on a matrix of historical weather data, field sizes, applications 

rates and percentile of exposure for risk management purposes. A complete review of the 

modeling results is available in the Phase 5 risk assessment and its associated addendum.

Ambient exposures to methyl bromide are often difficult to trace back to single source events, 

and that is why HED used only monitoring data to evaluate ambient exposures. The same three 

documents referenced above (Table 6.0) analyzed ambient air inhalation exposure to methyl 

bromide based on numerous ambient air monitoring studies from the Western U.S. as a result of 

methyl bromide applications in agricultural areas or urban areas where commodity fumigation is 

conducted. The results of these assessments show that ambient air inhalation exposures to 

methyl bromide can occur for extended periods especially in areas of high use during the season 

of high use. 

The 2011 assessment was a revised human health assessment and data review from the MBIP 

research plan to evaluate soil emission reduction potential of various application techniques and 

sealing methods. The assessment used PERFUM buffer outputs in a similar manner to the 

previous pre-plant soil treatments and the results of the assessment indicated that overall 

emissions were reduced when the control measures (e.g., Totally Impermeable Film (TIF)

films20) were used compared to current common agricultural practices. 

Similarly, two recent documents addressed bystander inhalation exposure around more urban 

areas where commodity fumigation is commonplace and addressed ambient exposures to methyl 

bromide that relied on data from CARB’s Toxic Air Contaminant Program. See Table 6.1 

(below) for description of the documents.

Table 6.1 – Key Methyl Bromide Commodity Fumigation Assessments

Memo Title Reference Description/Impact on Risk 

Assessment

Methyl Bromide: Phase 5 Health 

Effects Division (HED) Human 

Health Risk Assessment For 

Commodity Uses. 

Dawson; D304623; 03/10/06 Phase 5 RA including key new 

sources of information: a recently 

submitted inhalation developmental 

neurotoxicity study in rats, 

comments pertaining to the inputs 

used for calculating exposures to 

bystanders from commodity uses 

(e.g., USDA/PPQ provided 

information that allowed port facility 

fumigation event modeling to be 

significantly refined), and revised 

PERFUM modeling for bystander 

 

20 i.e., a 5-layer EVAL-resin barrier film (EVAL is a specific product of EVOH resin manufactured by Kuraray Americas, 

Houston, Texas)
Page 12 of 32

risk estimates. 

Methyl Bromide: Addendum To 

Phase 5 Health Effects Division 

(HED) Human Health Risk 

Assessment For Commodity Uses. 

Dawson; D304619; 07/12/06 Minor corrections/clarifications to 

the Phase 5 Commodity RA

Methyl Bromide: Second Addenda 

To The 2006 (DP Barcode 304623) 

Phase 5 Human Health Risk 

Assessment For Commodity Uses.

Dawson; D304612; 11/26/08 Refined work on bystander aeration 

buffer zones both as addenda to the 

Phase 5 commodity risk assessment

Methyl Bromide: Analysis Of 

APHIS Specific Buffer Zone 

Considerations For Methyl Bromide 

Use In Commodity Treatments At 

Varied Port Facilities. 

Dawson; D304632; 08/30/07 Refined buffer zone calculations 

based on USDA PPQ site-specific 

conditions

Methyl Bromide: HED Review of 

MBIP Progress Report for 

Evaluating Worker Exposure 

Associated with Commodity 

Fumigation.

Dawson; D396565; 06/07/12 Review of MBIP Progress Report

Subsequent to the TRED in 2006, HED completed refined work on bystander aeration buffer 

zones both as addenda to the Phase 5 commodity risk assessment (Dawson; D304612; 11/26/08) 

and for some site specific conditions for OPP’s work with USDA APHIS PPQ (Dawson; 

D304632; 08/30/07). To date, HED continues to work on OPP’s effort for evaluating 

worker/bystander exposure and risk associated with methyl bromide commodity fumigation 

(Dawson; D396565; 06/07/12) and providing appropriate mitigation. HED addressed ambient air 

exposure potential in the documents described above in Table 6.0. 

Conclusions: 

The residential exposure databases for methyl bromide are adequate for registration review, with 

the exception of the outstanding exposure study (i.e., the ambient air study in Siskiyou County

and ambient air monitoring around commodity fumigation areas [e.g., Florida]) as required by 

the ambient air data call in21. HED will review and incorporate the ambient air monitoring study 

into human health risk assessments as appropriate, once it is submitted during registration 

review. Additional or updated PERFUM modeling and ambient air analyses may be required for 

either the soil or commodity uses during registration review if the points of departure (PODs) or 

uncertainty factors (UFs) for the residential exposure assessment are revisited during registration 

review, although that is not anticipated at this time. Changes in approaches for modeling 

bystander exposures may also necessitate further analysis.

During registration review, HED also plans to update the fumigant factors documents

22. The 

fumigant factors document provides a discussion of values and parameters used as the basis for 

buffer reduction credits (i.e., tarps) as well as for establishing good agricultural practices (i.e., 

soil moisture) for soil fumigant use. This document impacts all of the soil fumigants, including 

methyl bromide.

 

21 GDCI-053201-836. 

22 Dawson, Smith, and Shelat; D385314; 1/11/2011 ; Dawson and Smith; D362369; 05/14/2009
Page 13 of 32

7.0 Aggregate-Risk Assessment

HED conducted an aggregate risk assessment for methyl bromide as part of the Phase 5 Human 

Health risk assessment for commodity uses (Dawson; D304623; 03/10/06), and is completing a 

Section 18 commodity fumigation risk assessment concurrent with work on the methyl bromide 

scoping document. Based on current recommendations for ground water EDWCs and current 

crop and food uses, females 13-49 years old utilize 5.3% of the aPAD (D414652, W. Donovan, 

9/12/2013). EPA determined that because the dietary contribution to acute aggregate risk is small 

compared to the bystander contribution, the mitigation measures EPA is requiring to protect 

residential bystanders will ensure that acute aggregate risks do not exceed EPA’s level of concern.

EPA did not aggregate short-, intermediate-term, or chronic dietary and inhalation exposures to 

methyl bromide because endpoints for dietary and inhalation exposures for these durations are 

not based on common toxicological effects.

Conclusions: 

Dietary (food and water) exposure is a minor component of total methyl bromide aggregate risk 

relative to residential contribution to the aggregate risk assessment (i.e., bystander exposure). 

Changes in endpoint selection, HED policy, or the bystander exposure assessment may require a 

revised aggregate risk assessment.

8.0 Occupational Exposure

The regulatory decision documents for methyl bromide required occupational methyl bromide 

studies that have not yet been submitted to the Agency. 

The 2009 methyl bromide amended RED required one occupational exposure study (GDCI053201-27007):

applicator inhalation exposure study (handheld probe – orchard replant)23. 

HED recently initiated a review of a submission24 intending to address the

handheld probe data requirement.

The 2006 Tolerance Reassessment and Risk Management Decision required one occupational 

exposure study (GDCI-053201-26629):

post-application inhalation exposure study to address commodity fumigation. 

At this time, the post-application inhalation exposure data requirement has not 

been fulfilled. 

The four main categories of registered occupational uses of methyl bromide include the 

following: (1) use as a pre-plant soil fumigant for food, feed, and fiber crops; (2) structural, 

industrial, fumigation uses; (3) post-harvest food commodity uses; and (4) other specialized 

fumigations.

 

23 Available: Methyl Bromide. HED’s Response to the Registrant Submission to Address DCI GDCI-053201-

27007 (Hand-held Probe data requirement). May, 2013; D410712.

24 Submission from TriCal, Inc. – submitted in August 2013
Page 14 of 32

Occupational Handlers

There is potential for occupational handler inhalation exposure to methyl bromide for both soil 

and commodity uses. Dermal exposure is not expected given the high vapor pressure of methyl 

bromide and based on the application techniques used. Therefore, HED has not quantified 

occupational risk estimates for methyl bromide associated with dermal exposure. Because methyl 

bromide formulations are classified as Restricted Use Pesticides, it may only be applied under 

the direct supervision of a trained, certified applicator. There are several recent documents that 

analyzed and characterized occupational handler inhalation exposure associated with methyl 

bromide use. Besides the documents identified below, there are a number of recent reviews by 

HED detailing data submissions for commodity fumigations and “progress report” reviews of the 

Methyl Bromide Industry Panel’s multi-step plan for evaluating worker exposure associated with 

commodity fumigation.

Soil Uses:

Human Health Risk Assessment For Methyl Bromide Soil Uses Based On Methyl 

Bromide Industry Panel (MBIP) Studies In California and Florida

o Dawson; D375752; 01/06/2011

Addenda to April 10, 2007 Phase 5 Health Effects Division (HED) Human Health 

Risk Assessment For Soil, Greenhouse, and Residential/Structural Uses

o Dawson/Mendez; D350818; 06/02/08

Human Health Risk Assessment For Soil, Greenhouse, and Residential/Structural 

Uses. 

o Dawson; D337288; 04/10/07

Commodity Uses:

HED Review of Methyl Bromide Industry Panel Progress Report on Steps 1 to 4 of 

the Research Plan for Evaluating Worker Exposure Associated with Commodity 

Fumigation

o Dawson; D396565; 06/07/12

Further Characterization of Commodity Modeling Outputs Presented In 2008 

Second Addenda (D304612) To 2006 Risk Assessment (D304623)

o Dawson; D362979; 04/03/09

Health Effects Division (HED), Second Addenda To The 2006 (DP Barcode 

304623) Phase 5 Human Health Risk Assessment For Commodity Uses

o Dawson; D304612; 11/26/08

Methyl Bromide: Addendum To Phase 5 Health Effects Division (HED) Human 

Health Risk Assessment For Commodity Uses. 

o Dawson; D304619; 07/12/06

Methyl Bromide: Phase 5 Health Effects Division (HED) Human Health Risk 

Assessment For Commodity Uses. 

o Dawson; D304623; 03/10/06

Soil Uses:
Page 15 of 32

HED assessed acute and short-, intermediate-term, methyl bromide inhalation exposure for 

occupational handlers. Based on the cancer classification, no quantitative cancer assessment has 

been completed. After occupational risks of concern were identified for soil fumigation activities 

(2009 amended RED) like application and tarp/perforation/removal, and reentry into treated 

areas, OPP implemented a series of label changes and mitigation measures (worker PPE and 

administrative controls like buffer zones, rate reductions, and active monitoring during the 

operation) that addressed worker exposure concerns.

Commodity Uses:

Previous HED risk assessments indicate risks are of concern for all scenarios associated with 

commodity fumigation activities for all exposure durations if no respiratory protection is used 

(MOE <30 for acute & short-/intermediate-term and MOE <100 for chronic). Risks for the 

majority of commodity fumigation workers who use the air purifying respirator (PF 10) still 

exceed HED’s level of concern; however, short- and intermediate-term risks for forklift drivers 

and line workers who use the purifying respirator (PF 10) do not exceed HED’s level of concern 

(MOE >30). The 2006 Tolerance Reassessment and Risk Management Decision outlined a 

number of risk mitigation measures (e.g., respiratory requirements, fumigant management plans)

as well as air monitoring requirements. 

Occupational Post-Application

The bystander assessments conducted by HED are largely focused on non-occupational settings.

HED performed occupational bystander assessments based on available field volatility data for 

methyl bromide scenarios involving pre-plant methyl bromide applications (e.g., hole punching 

for planting in raised beds). Similarly, occupational bystander assessments were completed for 

workers involved near fumigated commodities (fork lift drivers and line workers) and structures.

Soil Uses:

HED previously determined there were inhalation risk concerns for workers reentering 

fumigated fields after application to complete tasks like tarp removal. As part of the 2009 

Amended RED, the Agency placed various restrictions (administrative controls and PPE) on 

reentry of workers into fumigated fields. With these restrictions, HED believes that risks to 

reentry workers will not exceed the HED’s level of concern. Between 2008 and 2011, HED has 

produced and revised several iterations of a document25 detailing the factors that impact soil 

fumigant (including methyl bromide) emissions and evaluating them for use in risk mitigation 

approaches (i.e. soil fumigant buffer zone credit factors). The document was revised over the 

post-RED comment period and provided values and parameters to be used as the basis for buffer 

reduction credits and outlined Good Agricultural Practices (GAPs) as they relate to pre-plant soil 

fumigations.

Commodity Uses:

 

25 Dawson and Smith; (2008) D306857; (2009) D362369; (2011) D385314.
Page 16 of 32

In the period since the 2006 Tolerance Reassessment Eligibility Decision, HED has evaluated a 

protocol for evaluating worker exposure resulting from commodity use, and been involved in 

discussion with MBIP on worker monitoring protocols to address worker exposure. At this time,

OPP is still actively working with the MBIP to implement appropriate label changes and 

mitigation measures. The Agency required data to better evaluate the exposures of workers who 

handle commodities and other materials that have been previously treated with methyl bromide 

after they are released into commerce in a July, 2009 Data Call In.

Conclusions: The occupational exposure database is sufficient for risk assessment to support the 

registration review process for the conventional uses of methyl bromide, although the postapplication data requirement [for commodity fumigation workers] is outstanding. HED will 

consider that bystander exposure data during registration review. HED may be required to 

update the occupational handler & occupational bystander assessments during Registration 

review if the points of departure (PODs) or uncertainty factors (UFs) for the occupational 

exposure assessment change based on the toxicological data required as part of the 2009 

Amended RED. While no additional data (beyond handler exposure data for the tree replant 

application scenario) are required for human health risk assessments associated with pre-plant 

soil applications, the good agricultural practices and risk mitigation measures are expected to 

lower handler exposure to methyl bromide. HED continues to play an active role in the risk 

mitigation discussions associated with commodity fumigation.

9.0 Public Health and Pesticide Epidemiology Data

As part of the scoping document, the Agency includes a summary of available epidemiological 

peer review literature. A complete review of the public health and pesticide epidemiology data 

for methyl bromide is available in a separate review26. In summary, there are fewer methyl 

bromide incidents in recent years compared to the last incident review27, possibly due to a 

combination of changing use patterns, state/local regulatory changes, and/or better worker 

education and outreach. In the case of methyl bromide, a number of studies were reviewed 

including studies involving California farmworkers, and several publication that were part of the 

Agricultural Health Study. During the registration review process, the Agency intends to 

continue to monitor and review available epidemiology literature.

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, two 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 the 57 cases involving exposure 

to both methyl bromide and chloropicrin, there was one fatality, 20 moderate severity cases and 

36 low severity cases. 

The Agricultural Health Study (AHS) is a high quality, prospective epidemiology study 

evaluating the potential associations between pesticide use and various health outcomes,

 

26 Evans, 2013; D411151

27 Blondell, 2002; D283047
Page 17 of 32

including cancer. The AHS includes private and commercial pesticide applicators and their 

spouses. The AHS includes information on use of 50 different pesticide active ingredients 

commonly used in agriculture, and methyl bromide is one of the pesticides which is included in 

the study and for which a number of AHS studies exploring potential associations between 

methyl bromide exposure and various cancer sites have been explored. 

As part of the AHS, Alavanja et al. (2003) initially reported an association between methyl 

bromide use and prostate cancer based on early results from the AHS (top quintile versus no 

exposure: odds ratio (OR) 3.47 (95% CI 1.57, 8.76), p for trend 0.004); however these finding 

were not replicated in more recent follow-up analyses (Hughes-Barry et al. 2012) which 

investigated methyl bromide use and prostate cancer risk but did not find statistically significant 

associations (in either magnitude or trend with increasing use) between methyl bromide 

exposure and prostate cancer among participants. The latter study, however, did re-affirm the 

earlier AHS finding of an association with prostate cancer among those enrolled in the AHS 

cohort earlier (1993-1995 cohort enrollment period) versus later (1995-1997 cohort enrollment 

period). The authors noted that in the AHS cohort, overall fumigant use is low because of the 

crops typically grown in Iowa and North Carolina. Additionally, the authors noted that and the 

use of methyl bromide, while always low, continued to decrease since cohort enrollment (1993-

2007). The authors concluded that the effect appeared to dissipate over time, and hypothesized 

decreasing prevalence of use of methyl bromide in the AHS cohort might suggest a possible link 

among those more highly exposed who enrolled in the study earlier. 

Several studies are available in the literature which focus on findings from studies of California 

farmworkers. In a recent population-based case control study (study period 2005-2006), 

residential proximity to agricultural fields treated with methyl bromide was associated with an 

increased risk of prostate cancer (OR 1.62 (95% CI 1.02, 2.56) (Cockburn et al. 2011). This 

study did not perform actual measurements of methyl bromide, but rather relied on historical 

data regarding self-reported residence location (i.e., whether or not the residence was located 

within 500 feet of a methyl bromide-treated field) and methyl bromide application data from the 

CA Pesticide Use Database. In an earlier study, Mills and Yang (2003) did not find a 

significantly elevated risk of prostate cancer among farm workers in California exposed to 

methyl bromide.

With respect to gastric cancer in a study of Hispanic California farm workers, Mills and Yang 

(2007) reported an association between disease and methyl bromide exposure (OR 4th quartile 

versus lowest methyl bromide exposure category 2.38 (95% CI 1.06, 5.37) when the OR was 

multivariate adjusted, but the authors found no statistically significant association when the OR 

was (only) age adjusted or when the no exposure group was instead used as the referent category. 

The authors state that they did not collect information on or control or adjust for dietary habits, 

family history, smoking, or alcohol consumption which may act as confounders and 

acknowledge that ORs for numerous pesticides were calculated and some statistically significant 

results may have occurred by chance. 

Hughes-Barry et al. (2012) reported a potential association between methyl bromide and gastric 

cancer as part of the AHS. Using the intensity-weighted exposure metric (adjusted for use of 

personal protective equipment), authors observed a three-fold increased risk of gastric cancer 
Page 18 of 32

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). The authors acknowledge that results are based on both declining methyl 

bromide use and a small number of exposed cases (5 to 10), and that these factors may have 

influenced their findings. They concluded that the association warrants re-evaluation in the AHS 

with longer follow up, and recommended that other epidemiologic studies investigating these 

associations be evaluated. 

At this time, none of the conclusions drawn by the authors have been evaluated according to the 

modified Bradford Hill criteria used by OPP for causation analysis and therefore have not 

received comprehensive internal OPP review28. EPA will continue to examine the available 

epidemiological literature as the registration review process moves forward and will be

considered in EPA’s evaluation to provide a full evaluation of the carcinogenic potential of 

methyl bromide.

10.0 Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in this 

human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions 

to Address Environmental Justice in Minority Populations and Low-Income Populations," 

http://www.epa.gov/compliance/resources/policies/ej/exec_order_12898.pdf. The Office of 

Pesticide Programs (OPP) typically considers the highest potential exposures from the legal use 

of a pesticide when conducting human health risk assessments, including, but not limited to, 

people who obtain drinking water from sources near agricultural areas, and the variability of 

diets within the U.S.. Should these highest exposures indicate potential risks of concern, OPP 

further refines the risk assessments to ensure that the risk estimates are based on the best 

available information.

The civil rights complaint Angelita C. v. California Department of Pesticide Regulation alleged

that California’s Department of Pesticide Regulation (CDPR) discriminated against Latino 

school children by allowing unhealthy levels of methyl bromide to be applied near schools 

populated by mostly Latino children. The complaint alleged that this pattern and practice of 

allowing methyl bromide to be applied near schools caused an unhealthy and racially 

discriminatory condition for Latino school children and their parents. U.S. EPA entered into an 

Agreement29 with the California Department of Pesticide Regulation (CDPR) to resolve a civil 

rights complaint filed under Title VI of the Civil Rights Act of 1964 (Title VI)30. CDPR has 

volunteered through this Agreement to expand on-going monitoring of methyl bromide air 

concentrations by adding a monitor at or near one of the schools named in the original 

complaint. The purpose of the additional monitor is to confirm that there will be no recurrence 

of earlier conditions. CDPR also has agreed to share the monitoring results with EPA and the 

public and will also increase its community outreach and education efforts to schools that are in 

 

28 The Agency laid out a framework involving modified Bradford Hill criteria that was reviewed by a FIFRA SAP 

Panel in February, 2010. Available: http://www.epa.gov/scipoly/sap/meetings/2010/february/020210agenda.pdf

29 Available: http://www.epa.gov/civilrights/TitleVIcases/

30 Available: http://www.epa.gov/civilrights/TitleVIcases/title6-c-factsheet.pdf
Page 19 of 32

high methyl bromide usage areas. EPA will consider any monitoring data provided during 

registration review. 

11.0 Cumulative

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a 

common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as 

to methyl bromide and any other substances. For the purposes of this assessment, therefore, EPA 

has not assumed that methyl bromide has a common mechanism of toxicity with other 

substances. For information regarding EPA’s efforts to determine which chemicals have a 

common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the 

policy statements released by EPA’s Office of Pesticide Programs concerning common 

mechanism determinations and procedures for cumulating effects from substances found to have 

a common mechanism on EPA’s website at http://www.epa.gov/pesticides/cumulative/.

11.0 Endocrine Disruption

As required by the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the Federal 

Food, Drug, and Cosmetic Act (FFDCA), EPA reviews numerous studies to assess potential 

adverse outcomes from exposure to chemicals. Collectively, these studies include acute, 

subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, 

developmental, reproductive, and general or systemic toxicity. These studies include endpoints 

which may be susceptible to endocrine influence, including effects on endocrine target organ 

histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, 

reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates 

acute tests and chronic studies that assess growth, developmental and reproductive effects in 

different taxonomic groups. As part of its most recent registration decision, EPA reviewed these 

data and selected the most sensitive endpoints for relevant risk assessment scenarios from the 

existing hazard database. However, as required by FFDCA section 408(p), methyl bromide is 

subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP). 

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

establish a dose-response relationship between the dose and the E, A, or T effect. 

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between 

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 

chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of 
Page 20 of 32

chemicals identified for EDSP screening was published on June 14, 201331 and includes some 

pesticides scheduled for registration review and chemicals found in water. For further 

information on the status of the EDSP, the policies and procedures, the lists of chemicals, future 

lists, the test guidelines and the Tier 1 screening battery, please visit our website.32

In the interim, EPA is making no human health or environmental safety findings associated with 

the EDSP screening of methyl bromide. Before completing this registration review, the Agency 

will make an EDSP FFDCA section 408(p) determination.

12.0 Human Studies

Methyl bromide risk assessments relied in part on data from a set of methyl bromide-specific, 

observational exposure studies where adults were involved. The relevant studies were reviewed 

and found to be in compliance with the appropriate guidance for protecting humans in research. 

In the case that additional exposure monitoring data are submitted to OPP, those studies should 

undergo an OPP ethics evaluation during the registration review process. A complete list of the 

review of human research that received OPP ethics review can be found in Attachment 5 of the 

Appendix to this document.

13.0 Risk Assessment Updates and Data Deficiencies

No data deficiencies outside those previously discussed in the 2006 TRED/2009 Amended RED 

were identified for methyl bromide. In December 2012, the Agency made some adjustments to 

the data requirements based on analysis and response to comments submitted by the MBIP. At 

that time, HED reaffirmed the need for ambient monitoring data in Siskiyou County, CA because 

of unique application circumstances (i.e., use pattern, weather, topographical differences from 

other use locations). At that time, the Agency changed its stance on the need for data from the 

methyl bromide soil uses in Florida because of the declining soil uses in Florida. Based on 

commodity fumigation issues, HED requires ambient air monitoring data from areas where areas 

where there is high use of methyl bromide. The monitoring sites selected should be selected 

based on the amount of methyl bromide used and the frequency of applications.

The following data deficiencies were identified for methyl bromide:

Toxicology: None

Residue Chemistry: None

 

31 See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0477-0074 for the final second list of 

chemicals.

32 http://www.epa.gov/endo/
Page 21 of 32

Occupational/Residential Exposure: Table 14 (below) outlines the outstanding data 

requirements for methyl bromide related to occupational and residential exposure. There 

are 3 Data Call-In’s associated with the data requirements

Table 14 – ORE-Related Data Requirements

DCI Guideline Number Study Title Comment

GDCI-053201-27007 875.1300 Applicator exposure –

handheld probe

(agricultural)

Orchard re-plant 

scenario

[occupational]

GDCI-053201-26629 875.2500 Inhalation exposure

(commodity)

Occupational Postapplication

[occupational]

GDCI-053201-836 SS-1076 Ambient Air 

monitoring

(agricultural/urban)

Community-based 

exposure assessment

(agricultural/urban 

areas like the 

Delaware River basin)

[residential

bystander]

EPA anticipates conducting the following assessments during registration review:

Toxicology: 

o None

Residue Chemistry: 

o Revised list of recommended tolerances to reflect list of crops intended for postharvest treatment with methyl bromide as being determined with USDA/APHIS

and MBIP.

Dietary Exposure:

o To include any changes in the crop list, recommended EDWCs, and/or PODs.

Occupational/Residential Exposure:

o Revised HED occupational handler/bystander risk assessments may be necessary 

based on the most recent exposure data, Agency policies, or if the toxicological 

reevaluation results in changes to the endpoints.

o Additional or revised HED residential bystander risk assessments may be 

necessary based on the most recent exposure data, Agency policies, or if the 

toxicological reevaluation results in changes to the endpoints.
Page 22 of 32

15.0 References

Memoranda Relevant to Registration review.

Author Barcode Date Title

W. Donovan D414652 9/12/2013

Methyl Bromide. Acute and Chronic Dietary (Food and Water) 

Exposure and Risk Assessments in Support of the Section 18 

Request from USDA/APHIS and the Section 3 Request from 

MBIP.

J. Dawson D350818 06/02/2008

Methyl Bromide, PC Code 053201, DP Barcode 350818; 

Addenda to April 10, 2007 Phase 5 Health Effects Division 

(HED) Human Health Risk Assessment For Soil, Greenhouse, and 

Residential/Structural Uses (i.e., 2007 Assessment DP Barcode 

D337288)

J. Dawson D337288 04/10/2007

Methyl Bromide: Phase 5 Health Effects Division (HED) Human 

Health Risk Assessment For Soil, Greenhouse, and 

Residential/Structural Uses. PC Code: 053201, DP Barcode: 

D337288

J. Dawson D375752 01/06/2011

Methyl Bromide, PC Code 053201, DP Barcode 375752; Health 

Effects Division (HED), Human Health Risk Assessment For 

Methyl Bromide Soil Uses Based On Methyl Bromide Industry 

Panel (MBIP) Studies In California and Florida

J. Dawson, and 

C. Smith, D306857 06/09/2008 Factors Which Impact Soil Fumigant Emissions - Evaluation For 

Use In Soil Fumigant Buffer Zone Credit Factor Approach

J. Dawson, and 

C. Smith, D362369 05/14/2009

Methyl Bromide (PC Code 053201), Chloropicrin (PC Code 

081501), Dazomet (PC Code 035602), Metam Sodium and 

Potassium (PC Codes 039003 & 039002), MITC (PC Code 

068103), DP Barcode 362369, Updated Health Effects Division 

Recommendations for Good Agricultural Practices and 

Associated Buffer Credits

J. Dawson, C. 

Smith, and S. 

Shelat

D385314 1/11/2011

Methyl Bromide (PC Code 053201), Chloropicrin (PC Code 

081501), Dazomet (PC Code 035602), Metam Sodium and 

Potassium (PC Codes 039003 & 039002), MITC (PC Code 

068103), DP Barcode 385314, Second Update To Health Effects 

Division Recommendations for Good Agricultural Practices and 

Associated Buffer Credits

J. Dawson D406462 12/12/2012

Methyl Bromide, PC Code 053201, DP Barcode 406462; Health 

Effects Division (HED), Review of Methyl Bromide Industry 

Data and Analysis In Response to Methyl Bromide DCI For 

Ambient Monitoring Studies In California and Florida

Dawson, Mendez D304623 03/10/2006

Methyl Bromide: Phase 5 Health Effects Division (HED) Human 

Health Risk Assessment for Commodity Uses. PC Code: 053201, 

DP Barcode: D304623 (March 10, 2006) 

Dawson, 

Mendez, 

Goodlow, 

Metzger

D304619 07/12/2006

Addendum To Phase 5 Health Effects Division (HED) Human 

Health Risk Assessment For Commodity Uses. PC Code: 053201, 

DP Barcode: D304619 (July 12, 2006) 

E. Evans D111151 05/23/2013 Methyl Bromide: Review of Human Incidents

J. Blondell D283047 06/15/2002 Methyl Bromide: Review of Human Incidents
Page 23 of 32

Attachments: 

Attachment 1: Chemical Identity Table.

Attachment 2: Metam Methyl Bromide Acute, Subchronic, and Chronic Toxicity Profile

Attachment 3: Methyl Bromide Endpoint Selection Tables.

Attachment 4: International Tolerances and Maximum Residue Limits.

Attachment 5: Complete Review of Human Research
Page 24 of 32

Attachment 1: Chemical Identity Table.

Table A.1: Methyl Bromide Nomenclature

Properties Methyl Bromide

Chemical Structure

 

Chemical Group Alkyl Bromide

Common Name Methyl Bromide

Molecular formula CH3Br

Molecular Weight 94.94

CAS No. 74-83-9

PC Code 053201

Table A.2: Physical and Chemical Properties of Methyl Bromide

Parameter Methyl Bromide

Appearance

colorless, odorless gas at normal temperatures and pressures and a 

liquified gas under moderate pressure

Boiling Point 3.6 °C

Vapor Pressure 1400 mm Hg at 20 °C

Partition Coefficient (log Pow) 1.19

Solubility in Water 1.75 g/100 mL at 20 °C
Page 25 of 32

Attachment 2: Methyl Bromide Acute, Subchronic, and Chronic Toxicity Profile

Table A.3: Acute Toxicity Data on Methyl

Bromide Technical

Guideline No. Study Type MRID # (s) Results Toxicity

Category

870.1100 Acute oral

(MeBr in

vegetable oil)

43510301 LD50 = 120-160 mg/kg (males) 

LD50 = 86 mg/kg (females)

II

870.1200 Acute dermal N/A

d N/Ad N/A

870.1300 Acute inhalation Kato et al (1986)

a LC50 = 3.03 mg/L, 4 hr exposure IV

870.2400 Primary

eye 

irritation

Alexeef, G.; Kilgore, W. 

(1983)band HezemansBoer et al (1988)

c

Severe irritation following accidental exposure 

to humans

I

870.2500 Primary

skin 

irritation

Alexeef, G.; Kilgore, W. 

(1983) and Hezemans-Boer 

et al (1988)

Severe irritation following accidental exposure 

to humans

I

870.2600 Skin sensitization N/A

d N/Ad N/A

a: Kato, N.; Morinobu, S.; Ishizu, S. (1986) Subacute inhalation Experiment for MeBr in Rats. Industr. Health. 24: 87-103.

b: Alexeef, G.; Kilgore, W. (1983) MeBr. In: Gunther, F.; Gunther, J., ed. Residue Reviews. Residues of Pesticides and Other Contaminants 

in the Total Environment, Vol. 88, p. 102-153. New York, Springer Verlag.

c: Hezemans-Boer, M; Toonstra, J.; Meulenbelt, J.; et al. (1988) Skin Lesions Due to Exposure to MeBr. Arch. Derm. 124:917-921.

d: N/A (Not Available): Acute dermal toxicity and dermal sensitization potential studies were not required because there is already a clear 

evidence that severe irritation to skin occurs after acute dermal exposure to MeBr.

Table A.4: Methyl Bromide Sub-chronic, Chronic and Other Toxicity

Guideline No./ Study

Type

MRID No. (year)/ 

Classification /Doses Results

870.3100

90-Day oral toxicity in rats

(peanut oil)

00154564 (1984) 

classification: no DER 

available.

NOAEL = 2 mg/kg/day

LOAEL = 10 mg/kg/day based on slight hyperplasia of the stratified 

squamous epithelium of the fore stomach. HDT was 50 mg/kg/day.

870.3150

4-week oral toxicity in rats

(capsule)

43776401 (1995)

acceptable/non-guideline

NOAEL = 0.835 mg/kg/day.

LOAEL = 7.99 mg/kg/day (HDT), based on slightly decreased body 

weight gain and food consumption.
Page 26 of 32

870.3465

Sub-chronic

Inhalation Toxicity in dogs

43386802 (1994)

acceptable/guideline

0, 5, 10/150, 25, 50 or 100 

ppm (actual mean 

concentrations 0, 5.3,

11.0/158.0, 26.0, 53.1 or

102.7 ppm; equivalent to

1.43, 2.97/42.7, 7.02, 14.3,

27.7 mg/kg/day). 7 hours/day

Systemic toxicity (7 weeks , 34 exposures)

NOAEL (threshold) = <5 ppm.

 LOAEL (threshold)= 5 ppm (0.021 mg/L), based on decreased responsiveness 

in females.

870.3700a 

Prenatal developmental in 

Wistar rats

(via inhalation)

00102990 (1981)

acceptable/guideline

0, 20 or 70 ppm (equivalent 

to 0, 20, or 71 mg/kg/day)–7

hrs/day; 5 days/wk

Maternal

NOAEL/ LOAEL > 70 ppm (HDT). Slightly increased 

incidence/severity of interstitial nephritis at 70 ppm may represent 

threshold effect.

Developmental 

NOAEL /LOAEL > 70 ppm (HDT)

870.3700b 

Prenatal developmental in 

rabbits (via inhalation)

41580401 (1990)

acceptable/guideline

0, 20, 40, or 80 ppm

(equivalent to 0, 7.1, 14 or 28 

mg/kg/day) - 6 hrs/day for 17 

days

Maternal

NOAEL = 40 ppm;

LOAEL = 80 ppm based on decreased appetite, lethargy, right side head

tilt, ataxia and lateral recumbency.

Developmental

NOAEL = 40 ppm

LOAEL = 80 ppm based on agenesis of the gall bladder, increased incidence of

fused sternebrae and decreased fetal body weight

870.3800

Reproduction and fertility 

effects in

CD rats

(via inhalation)

00160477 (1986)

acceptable/guideline

0, 3, 30, or 90 ppm for 6 

hours/day

(equivalent to males: 0, 2.4,

24 or 73 mg/kg/day; females:

0, 2.8, 28 or 85 mg/kg/day)

Parental/Systemic

NOAEL = 30 ppm

LOAEL = 90 ppm based on reduced body weight

Reproductive

NOAEL = 3 ppm

LOAEL = 30 ppm based on reduced pregnancy rates

(23%, F2b)

Offspring

NOAEL = 3 ppm

LOAEL = 30 ppm based on reduced pup weight on post-natal day 21 (F1a,

F2a, F2b generations) ranging from 10-20%.

870.4100b 

Chronic toxicity dogs

(fumigated feed)

43885201 (1996)

acceptable/guideline

0, 0.5, 1.5 or 5 ppm (M: 0,

0.06, 0.13 or 0.27; F: 0, 0.07,

0.12 or 0.27 mg/kg/day for 12 

months.

NOAEL/LOAEL > 5 ppm (HDT) (equivalent to 0.27 mg/kg/day)

It is noted that this study was conducted to establish a margin of safety for

human dietary exposure rather than to determine a LOAEL.

870.4300

Chronic toxicity

and carcinogenicity in rats

(micro-encapsulated)

44462501 (1997)

acceptable/guideline

0, 0.5, 2.5, 50, or 250 ppm

(M: 0, 0.02, 0.11, 2.2, or 11.1; 

F: 0, 0.03, 0.15, 2.92, and

15.12 mg/kg/day for 24

months

NOAEL = 50 ppm (2.2 mg/kg/day for males and 2.92 mg/kg/day for 

females). LOAEL = 250 ppm (11.1 mg/kg/day for males and

15.12 mg/kg/day for females), based on decreased body weight, body 

weight gain, and food consumption in males and females during the first

18 months of the study.

No evidence of carcinogenicity
Page 27 of 32

870.4300

Chronic toxicity

and carcinogenicity

(29-month) in rats (via 

inhalation)– Wistar rats

41213301 (1987); 42418301;

44359101 

acceptable/guideline

0, 3, 30 or 90 ppm (0, 0.0117,

0.117 or 0.335 mg/L) 

(equivalent to males: 0, 1.9,

19 or 58 mg/kg/day; females:

0, 2.2, 22 or 65 mg/kg/day)

Local irritation

NOAEL < 3 ppm (0.0117 mg/L);

LOAEL = 3 ppm (0.0117 mg/L), based on increased incidence of basal cell

hyperplasia of the nasal cavity in both sexes.

Systemic toxicity

NOAEL = 30 ppm (0.117 mg/L)

LOAEL = 90 ppm (0.335 mg/L), based on increased mortality, decreased

body weight and relative brain weight, hemothorax, increased incidence of

thrombus, cartilaginous metaplasia, myocardial degeneration and irritation

of the esophagus and fore stomach.

 No evidence of carcinogenicity

870.4300

Chronic toxicity

and carcinogenicity in mice –

B6C3F1 (via inhalation)–2 

years

National Toxicology Program

Study TR 385

42504101 (1992)

acceptable/guideline for 

carcinogenicity study.

0, 10, 33 or 100 ppm–6 

hrs/day; 5 days/week (0, 11.8,

38.9 or 118 mg/kg/day)

Local irritation

NOAEL/LOAEL = not reported

Systemic toxicity

NOAEL = 33 ppm (0.1279 mg/l)

LOAEL = 100 ppm

(0.3876 mg/l), based on mortality (males), neurological signs (abnormal 

posture, tremors, ataxia, limb paralysis and emaciation) decreased body 

weight/weight gain and microscopic lesions in the brain, heart, sternum and

olfactory epithelium.

No evidence of carcinogenicity

[No data on clinical chemistry, urinalysis, and gross findings]

Genotoxicity:

Rat testicular DNA

alkaline elution

assay

43180201 (1994) 

Acceptable/non-guideline 

Dose range: 0, 75, 150 or 250 

ppm (0, 291, 581 or 969 

mg/m

3

) for 6 hr/day over 5 

consecutive days

The test was positive.

870.5395

Cytogenetic

Micro nucleus assay in

mice and rats

43786501 (1986?) 

Acceptable/guideline

Dose range: 0, 154, 200, 260,

338 or 440 ppm (equivalent to

0, 0.597, 0.776, 1.008, 1.311 

or 1.706 mg/L) for 6 hrs/day,

5 days/week for 14 days, or

10 exposures.

The test was positive.

Micro nucleus (MN) induction was evaluated in bone marrow of rats and mice

and in peripheral blood of mice.

870.6200a

Acute neurotoxicity screening

battery in CD rats

(via inhalation)

42793601 (1993)

acceptable/guideline

0, 30, 100 or 350 ppm, for 6 

hrs

(M: 27, 90 or 314; F: 30, 101,

or 354 mg/kg/day).

NOAEL = 100 ppm

LOAEL = 350 ppm based on decreased activity and alertness as 

measured in a functional observation battery examination, decreased 

motor activity and decreased body temperature in males and females

were observed. A slight decrease in hind-limb grip strength in males may 

have been treatment-related. Effects were transient and all animals were

assessed to be normal by 1 week post-exposure.

870.6200b 

Sub-chronic neurotoxicity 

screening battery in rats (via

inhalation)

42964301; 43077401 

(1993) 

acceptable/guideline

0, 30, 70 or 140 ppm 6 hr/day,

5 days/week –13 weeks

(equivalent to males: 0, 19,

45, or 90 mg/kg/day; females:

0, 22, 51, 101 mg/kg/day)

NOAEL = 30 ppm (F)

LOAEL = 70 ppm (F) based on decreased body weight and motor 

activity.

NOAEL = 70 ppm (M)

LOAEL = 140 ppm (M) based on decreased body weight, increased mortality

(2 animals), convulsions (2 animals affected), effects on several FOB

parameters and brain histopathology in males.
Page 28 of 32

870.6300

Developmental

Neurotoxicity Study

46665001 (2004) 

Acceptable/non-guideline 

Doses: 0, 5, 25, or 50 ppm

Maternal

NOAEL = 50 ppm

LOAEL = not identified

Developmental

NOAEL =5 ppm

LOAEL = 25 ppm based on decreased motor activity on PND21

870.7485

Metabolism and 

pharmacokinetics

International Agency for 

Research on Cancer (IARC) 

Monographs Vol 41, p198

Rats received a single gavage dose (preparation of test solution was 

unspecified) of 24 mg/kg/b.w. 14C-MeBr. Over a 3-day period, the 

radioactivity recovered were as follows: carcass (14-17%), expired 

carbon dioxide (32%), urine (43%), and feces (less than 3%).

During a 6-hour exposure of rats to 4.75-9874 mg/cu.m 14C-MeBr vapor, 

approximately 27-50% of the compound inhaled was absorbed.

870.7800

Immunotoxicity

Rats

48510101

0, 20, 60 or 120 ppm, via 

inhalation 6 hours per day for 28 

consecutive days

Acceptable/Guideline

Immunotoxicity

NOAEL: 120 ppm (the highest dose tested)

LOAEL not established (>120 ppm)

Systemic Toxicity 

NOAEL: 60 ppm

LOAEL: 120 ppm, based on treatment related decreases in body weights and

body weight gains.

(*) A new 90-day inhalation study in rodents is not required for reregistration of MeBr. Acceptable rat chronic inhalation toxicity

(MRIDs 41213301, 42418301; reviewed in HED doc. nos. 007017, 007845, 009843 and 14130) and rat 90-day inhalation neurotoxicity 

(MRIDs 42933901 and 43077401; reviewed in HED doc. no. 010820) studies have been received. These studies provide adequate

descriptions of systemic toxicity to rodents from inhalation exposures of intermediate duration.

Table 4.2.4: Summary of Toxicological Dose and Endpoints for Use in the Methyl 

Bromide Oral Human Health Risk Assessments

Exposure

Scenario

Dose Used in Risk

Assessment, UF

FQPA SF* and Level of

Concern for Risk 

Assessment

Study and Toxicological Effects

Acute Dietary

(Females 13-50 years of age)

Dev. NOAEL = 14 

mg/kg/day

UF = 100

Acute RfD = 0.014 

mg/kg/day

FQPA SF = 1X

aPAD = acute RfD

FQPA SF

= 0.14 mg/kg/day

Developmental Toxicity - Rabbit (Inhalation) 

LOAEL = 28 mg/kg/day based on agenesis of 

the gall bladder and increased incidence of

fused sternebrae.

Acute Dietary (General

population including infants

and children)

NOAEL = 90 mg/kg/day

UF = 100

Acute RfD = 0.9 

mg/kg/day

FQPA SF = 1X

aPAD = acute RfD

FQPA SF

= 0.9 mg/kg/day

Acute neurotoxicity study --rat (Inhalation) 

LOAEL = 314 mg/kg/day based on decreased 

activity, increase in number of animals with 

drooping/half-closed eyelids and alertness as 

measured in the FOB, decreased rears, decreased

motor activity, increased piloerection and

decreased body temperature
Page 29 of 32

Chronic Dietary

(All populations)

NOAEL= 2.2 mg/kg/day

UF =100

Chronic RfD =

0.022 mg/kg/day

FQPA SF = 1X

cPAD = chronic RfD

FQPA SF

= 0.022 mg/kg/day

= 0.02 mg/kg/day

Chronic/carcinogenicity study -- rats

(Microencapsulated MeBr)

LOAEL = 11.1 mg/kg/day based on decreased 

body weight, body weight gain and food 

consumption

Cancer Classification: Not likely to be carcinogenic to humans
Page 30 of 32

Attachment 3: Methyl Bromide Endpoint Selection Tables.

Table A.6: Summary of Toxicological Dose and Endpoints for Use in Methyl Bromide Human Health Inhalation Risk Assessment

Risk Assessment* Study NOAEL/LOAEL Endpoints HED 

HECs

CPDR 

HECs¶

Acute Agricultural

Bystander (ambient;

24 hr exposure)

Developmental Study in

Rabbits

NOAEL = 40 

ppm

LOAEL = 80 

ppm

Developmental

effects: agenesis 

of gallbladder, 

fused sternebrae

10 ppm

UF = 30

21 ppm 

UF = 100 

(child & 

adult)

Greenhouse/Structural 

& Commodity

Bystander

Developmental Study in

Rabbits

NOAEL = 40 

ppm

LOAEL = 80 

ppm

Developmental

effects: agenesis 

of gallbladder, 

fused sternebrae

40 ppm

UF = 30

Occupational Developmental Study in

Rabbits

NOAEL = 40 

ppm

LOAEL = 80 

ppm

Developmental

effects: agenesis 

of gallbladder, 

fused sternebrae

30 ppm

UF = 30

Short- and

Intermediate

-Term Inhalation

(1 day to 6 

months)

Ambient Subchronic (5- to 7-

week) inhalation

toxicity study - dogs

NOAEL = 5 ppm

LOAEL = 10ppm

Decreased 

responsiveness in

females, fecal

effects and eye 

irritation

1.0 ppm

UF = 30

0.88 ppm

UF

= 100 (child)

Occupational Subchronic (5- to 7-

week) inhalation

toxicity study - dogs

NOAEL = 5 ppm

LOAEL = 10ppm

Decreased 

responsiveness in

females, fecal

effects and eye 

irritation

4.4 ppm

UF = 30

1.56 ppm 

UF = 100 

(adult)

Long-Term 

Inhalation (>6

months)

Ambient Chronic/Carcinogenicit

y

- rats

No NOAEL 

identified. 

LOAEL = 3 ppm

Nasal lesions 0.13 ppm

UF = 100

0.1 ppm 

UF = 100 

(child)

Occupational Chronic/Carcinogenicit

y

- rats

No NOAEL 

identified. 

LOAEL = 3 ppm

Nasal lesions 0.55 ppm

UF = 100

0.2 ppm 

UF = 100 

(adult)

Cancer Classification: Not likely to be carcinogenic to humans

* Agricultural bystander HECs have also been applied to 24 hour Time-Weighted-Average exposure concentrations measured

from ambient air. All bystander assessments are non-occupational, by definition. Commodity bystanders are all based on 8 hour

durations.

¶ Though CDPR and USEPA based their risk assessments on the same critical studies and endpoints, different algorithms were

used by each organization to calculate HECs. 
Page 31 of 32

Attachment 4: International Tolerances and Maximum Residue Limits.

Methyl Bromide (PC Code 053201; Date of Request 06/03/13)

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US [40 CFR §180.124] Canada Mexico1 Codex2

(a) General: methyl bromide None Residue definition 

not listed

Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico1 Codex2

Cotton, undelinted seed 150

MRLs With No US Equivalent

Bread and other cooked cereal 

products

0.01 (*)3

Cacao beans 5 Po4

Cereal grains 5 Po4

Cocoa products 0.01 (*) Po3

Dried fruits 0.01(*) Po3

2 Po4

Milled cereals products 0.01 (*) Po3

1 Po4

Peanut 0.01 (*) Po3

10 Po4

Tree nuts 0.01 (*) Po3

10 Po4

Completed: : M. Negussie; 06/05/2013

1 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.

2

* = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains. PoP = 

processed postharvest treated commodity, such as processing of treated stored wheat. (fat) = to be measured on the 

fat portion of the sample. MRLs indicated as proposed have not been finalized by the CCPR and the CAC.

3

= To apply to commodity at point of retail sale or when offered for consumption.

4

= To apply at point of entry into a country and, in case of cereal for milling, if product has been freely exposed to 

air for a period of at least 24 h after fumigation and before.
Page 32 of 32

Attachment 5: Complete Review of Human Research

The human health risk assessment for methyl bromide relies in part on data from studies in 

which adult human subjects were intentionally exposed to a pesticide. These studies, listed 

below, have received the appropriate ethical review.

Maddy, K.; Lowe, J.; Gibbons, D. et al. (1986) Studies of Methyl Bromide and 

Chloropicrin Used as Structural Fumigants in California, 1984. Unpublished study 

prepared by California Dept. of Food and Agriculture under Report No. HS-1352. 50 p. 

(MRID 159649)

Maddy, K.; Schneider, F.; Lowe, J.; et al. (1983) Monitoring Environmental Levels of 

Methyl Bromide during Commodity Fumigations. Unpublished study prepared by California 

Dept. of Food & Agriculture under Project No. HS-1078. 8 p. (MRID 159655)

Maddy, K.; Jacobs, K.; Frederickson, S. (1983) A Study of Inhalation Exposures of 

Tarpaulin Fumigation Workers to Methyl Bromide in Merced County, California in 

November 1982. Unpublished study prepared by California Dept. of Food & Agriculture 

under Project No. HS-1084. 6 p. (MRID 159656)

Maddy, K.; Fredrickson, S.; Jacobs, K. (1983) Inhalation Exposure of Tarpaulin Fumigation 

Workers to Methyl Bromide in Kern County, California in November 1982. Unpublished 

study prepared by California Dept. of Food & Agriculture under Project No. HS-1092. 6 p. 

(MRID 159657)

Maddy, K.; Lowe, J.; Fredrickson, S. (1984) Inhalation Exposure of Commodity Handlers to 

Methyl Bromide in Yolo County, California, October 1983. Unpublished study prepared by 

California Dept. of Food & Agriculture under Project No. HS-1168. 8 p. (MRID 159658)

Van Den Oever, R.; Roosels, D.; Lahaye, D. (1982) Actual Hazard of Methyl Bromide 

Fumigation in Soil Disinfection. British Journal Industrial Medicine 39(2):140-144. (MRID 

45581842)

Winegar, E. (1993) Methyl Bromide Tarpaulin Fumigation Monitoring at San Pedro Dock 

Berth 54. Unpublished study prepared by the Fresh Fruit Group. 18p. MRID 46854004.

Winegar, E.; Curtis, D.; Yates, M. (1995) Worker Health and Safety and Ambient Air 

Monitoring at Diamond Walnut Growers, Inc. Unpublished study prepared by Air Toxics 

Limited. 68p. MRID 46854007.

Winegar, E. (1992) Determination of Methyl Bromide Exposure During Dried Fruit and 

Tree Nut Fumigation Practices. Unpublished study prepared by Radian Corporation. 149p. 

MRID 46854008.