## 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: 05 3 20 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 Irwin, Ph.D, DABT, Toxicologist

## ·**~** William Donovan, Chemist 

# 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 1995 1 

## . 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

eli minate 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 r egistration review

.

The Tolerance Reassessment and Risk Management Decision (TRED) and Reregistration Eligibility Decision (RED) for methyl bromide’s commodity uses w ere issued in August, 2006 2



## and the RED for m ethyl b romide’s soil and non

- food structural uses was issued in July, 2008 and amended in May, 2009 3



## . The use ca tegories (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 c onducted 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 manual 4 

## outlines 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 ha ve been registered since the RED, HED recently completed evaluations on two 24c action s 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 trea tment of various post harvest food commodities for USDA ’s APHIS PPQ.

The toxicity database for methyl bromide is ade quate for r egistration r eview 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 m ethyl bro m ide exposure via t h e 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 develop m ental toxicity study in rabbits, neurotoxicity effects (acute, sub

- chronic and chronic studies), and nasal histopathology observed in the chronic toxicit y /carcinogenicity study

in rats. T he hazard database included a developmental neurotoxicity study in rats conducted via the inhalation route of exposure. Data are available for both oral and inhalation rou t es. The inhalation database includes: acute neurotoxicity study in rats, develop m enta l neurotoxicity in rats, develop m ental toxicity studies in rats and rabbits, sub

- chronic toxicity studies in rats and dogs, and chronic studies in m ice and rats. Four studies conducted via the oral route in rats and dogs a re also available. The risk asses sment team concluded that the 10X FQPA Safety Factor

can be reduced to 1X. During r egistration r eview, the Agency may need to reevaluate the points of departure (PODs) and uncertainty factors (UFs) for the residential and occupational exposure

assessments

, although n o 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

include d in the Agricultural Health Survey (AHS), and the Agency intends to continue to evaluate the associations with carcinogenicity and other possible health effec ts through OPP’s framework for incorporating epidemiology into human health risk assessment 5



## .

The residue chemistry and dietary

- exposure databases are adequate to support current registration requirements. Soil fumigation uses of methyl bromide have pre viously 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 , d ietary contributions from f ood 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 stud y for handheld probe applications

was required for methyl bromide as part of the 2009 amended RED ; a submission 6 

## is currently

under review in HED 7



## . 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/mee tings/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 (GDCI

053201

- 27007) associated with 2009 Registration Eligibility Deci sion.

8 

### GDCI

- 053201

- 26629; The Agency required protocol and consultation before the inititation of this study requirement.

## Page 4 of 32 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 a caricide, antimicrobial, fungicide, herbicide, insecticide, nematicide, and vertebrate control agent for soil fumigation uses, commodity fumigation, and structural fumigation 9



## . 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 requir e 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 dri p tubing under tarps . Onl y a few hot gas applications will remain after December, 2013

. According to the BEAD chemical profile 10



## , criti c al 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 non

food. 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 (P PQ) treatment manual 11



## . 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 Eligibilit y Decision (TRED) and Reregistration Eligibility Decision (RED) for methyl bromide’s commodity uses w ere 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 eval uates 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 crops 12 

## ; (2) structural &

9 

### Some methyl bromide product labels include antimicrobial claims; “...and some bacteria (e.g., Salmonella spp.)... ” However, the antimi crobial 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, po ultry 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

## Page 5 of 32

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 w ere issued.

2.0 Hazard Identification/Toxicology

The toxicological database for m ethyl bro m ide is complete and sufficient for risk assess m ent purposes and includes a develop m ental neurotoxicity study in rats conducted via the

inhalation route. The inha lation database includes: acute neurotoxicity study in rats, develop m ental neurotoxicity in rats, develop m ental toxicity studies in rats and rabbits, sub

chronic toxicity studies in rats and dogs, and chronic studies in m ice and rats. Four studies

conduct ed 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 m ethyl bro m ide exposure via t h e inhalation route are agenesis of the gall bladder and fused sternebrae observed in the develop m ental toxicity study in rab bits, neurotoxicity effects (acute, sub

- chronic and chronic studies) , and nasal histopathology observed

in the chronic toxicit y

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

inc r ea s ed i n cide n c e of basal cell h y p e r p lasia of the nasal ca v ity in both sexes.

Developmental toxicity and n eurotoxicity were the m ost co mm on ly observed toxic effect in the toxicity data base and w ere observed in all tested species. Both acute and sub

- chronic inhalation neurotoxicity studies in rats showed evidence of neurotoxic effects of m ethyl bro m ide characterized by decreased activity, tre m ors, ataxia and paralysis. Two sub

- chronic studies

de m onstrated dogs to be the m ost sensitive species to the neurotoxic e ff ects of m ethyl bro m ide.

Neurotoxic e ff

ects were also seen in the chronic/carcinogenicity inhalation study in m ice (ataxia,

li m b paralysis, degenerative changes in the cerebellu m ), the develop m ental inhalation study in rabbits (lethargy, righ t side head tilt, ataxia), and the develop m ental neurotoxicity (DNT) study in rats (decrease in m otor activity). Develop m ental effects described as increased incidence of agenesis of the gallbladder and fused sternebrae were also seen in the develop m ental inhalation study in rabbits. In addition, the m ulti

- generation reproduction toxicity study in rats revealed

that m ethyl bro m ide 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 m ethyl bro m ide database. Effects noted after dietary exposure were pri m a r ily decreases in body wei ght gain, body weight, and food consu m ption. Evidence of sto m ach lesions w as observed in the 90

- day oral toxicity study in rats.

Several studies in the database indicate that m ethyl bro m ide 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, m ethyl bro m i de is a low to m oderate tox i cant via the oral and inhalation routes of exposure (Toxicity Categories II and IV, respectively). In contrast, m ethyl bro m ide is highly irritating via both der m al and ocular routes of exposure (Toxicity Category I). Occupation al 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) Program 13 

## ], OSHA 14 

## , CalOSHA 15 

## , NIOSH 16 

## , and the American Congress of Governmental Industrial Hygienists (ACGIH) 17



## .

HED’s approach to esti m ating risks due to inhalation exposure is based on the guidance

m ethodology developed by O ffice of R esearch and D evelopment for the derivation of inhalation reference concentrations (RfCs) and hu m an e quivalent concentrations (HECs) for u s e in MOE

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

m ay or m ay not be the lowest ani m al NOAEL) derived using the RfC m ethodology In this

m ethodology, different HECs m ay be calculated for the sa m e experi m ental NOAEL due to: 1) the different algorith m s used to derive HECs for syste m ic versus portal of entry effects; or 2) the

ti m e adjust m ents conducted for non

- occupational (co mm odity treat m ent 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 sele cted 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 Barcode s : 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 select ed the endpoint from the rabb it 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 decrease d 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 u tilized 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/rest 113.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.o rg/Store/ProductDetail.cfm?id=1079

## Page 7 of 32

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 response s w ere well defined. Consequently, selected points of departure (PODs) will not under

- esti m ate 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 ass essments 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 y oung ; 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 us e 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 che m icals will enter the circulation before m any of the detoxification processes associated with oral exposure (e.g. first pass effect) occur. Moreover, che m icals in the respiratory tract generally enter the blood stream m ore readily than

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

from the blood stream than the lu m en of the GI tract from the blood strea m

. 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 toxi city database for methyl bromide is adequate for registration review

, and includes a develop m ental neurotoxicity study in rats conducted via the inhalation route

. Data are available for both oral and inhalation rou t es. During registration review , the Agen cy 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 antici pated 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 requir e tolerances. A s 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, a ll 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 consider ation the recent Section 18 request from USDA/ APHIS. This process shou ld be completed during r egistration r eview , 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 b romide 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 [ foo d 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. Depa rtment 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 assessment s w ere partially refined and considered exposure from

f ood 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

transp ort 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 informatio n

. Surface water estimated drinking water concentrations ( EDWCs ) for methyl bromide are considered de minim i s based on representative half

- life data

for methyl bromide evaporation from water to air

. Hence, the methyl bromide EDWC was from ground water es timates. 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 monitor ing value of 6.4 ppb was used in both the acute and chronic assessments. T he available ground water monitoring data represent a conservative contribution to the dietary assessment because the monitoring was conducted when methyl bromide use was more prev alent in the U.S

. than today. Specifically, recent information from BEAD indicates that both agricultural (soil) and non

agricultural (post harvest) uses of methyl bromide are declining over the time period of 1998

- 2011 (W. Chism, C. Doucoure, and D. Ber wald, February, 2013).

If the Environmental Fate and Effects Divison (EFED) determines that a new drinking water assessment is required in r egistration r eview, then the dietary assessment may need to be updated to incorporate inputs from the revised dri nking water (i.e., ground water ) assessment.

## Page 9 of 32

Conclusions: The dietary exposure database s for methyl bromide are adequate for r egistration

r eview. An updated dietary assessment may be required in r egistration r eview to incorporate any revisions to the methyl bromide drinking water assessment, or updated crop uses

.

5.0 T OLERANCE 

## A SSESSMENT AND 

## I NTERNATIONAL 

## H ARMONIZATION



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

reasses sment will be completed in r egistration r eview 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 un delinted cotton seed, the only commodity with a methyl bromide

tolerance in the USA. T herefore, 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 ne ar fumigated fields or sites where commodity fumigation occurs are potentially exposed to fumigant emissions

that travel off

- site. When considering the potentia l risks to bystanders for single application

known source s (e.g., a farm field or a fumigated st ructure/commodity )

, HED used distributional modeling 18 

## 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 t he HEC or Human Equivalent Concentration adjusted by an uncertainty factor.

HED also calculate d ambient bystander exposure from regional sources that are not attributable to a specific application event. HED use d 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

- agricult ural urban environments, respectively.

For site

- specific bystander assessments, t he Agency has specifically focused on assessing acute methyl bromide inhalation exposures resulting because peak air concentrations typically occur in

the first 24 or 48 hour s 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 m ethyl 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 stud y 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, th e ambient air monitoring study identified above has not been submitted for Agency review. Th ose 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

monito ring 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 ( P robabilistic

E xposure and R isk model for Fum igants) air modeling for agricultural field applicat ions

.

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

to lerances; 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 met hyl bromide provides more informa tion 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 st ructural fumigations can be found in docket EPA

- HQ

- OPP

- 2005

- 0123. In th e human health risk assessments that support th ose 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 a ir 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 brom ide 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 o verall

emissions were reduced when the control measures ( e

. g
., Totally Impermeable Film ( TIF )

films 20 

## ) 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 Commodi ty 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

info rmation 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 m anufactured 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 Comm odity 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 R efined 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 U SDA 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 r egistration 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 in 21



## . HED will review and incorporate the ambient air monitoring study

into human health r isk assessment s as appropriate, once it is submitted during r egistration

review

. Additional or updated PERFUM modeling and ambient air analyses may be required for either the soil or commodity uses during r egistration review if the points of departure (PO Ds) or uncertainty factors (UFs) for the residential exposure assessment are revisited during r egistration

review , although that is not anticipated at this time

. Changes in approaches for modeling bystander exposures may also necessitate further analysis.

During r egistration review , HED also plans to update the fumigant factors document s 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 g round 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 contributi on , 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

meth yl 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 )

. C hanges in endpoint selection, HED policy, or the bystander exposure assessment m ay require a revised aggregate risk assessment.

8 .0 Occupational Exposure

The regulatory decision documents for methyl bromide require d occupational methyl bromide

studies that have not yet been submitted to the Agency

. The 2009 methyl bromide amended RED required one occupational exposure study (GDCI

053201

- 27007):

applicator inhalation exposure study (handheld probe

– orchard replant) 23



## . HED recently initiated a review of a submission 24 

## intending to address the handheld probe data requirement.

The 2006 Tolerance Reassessment and Risk Management Decision required one occupation al 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) o ther specialized fumigations.

23 

### Available: Methyl Bromide

. HED’s Response to the Registrant Submission to Address DCI GDCI

- 053 201

- 27007 (Hand

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

24 

### Submission from TriCal, Inc.

– submitted in August 2013

## Page 14 of 32

Occupational Handlers

T here 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 ba sed 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 U se Pesticides, it may only be applie d 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 Assess ment 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 (D3046 12) 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 Pha se 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

, ra te 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 expo sure 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 co ncern; 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

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

a s 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 ass essments 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 control s and PPE) on reentry of workers into fumigated fields. With these restrictions, HED believes that risks to

re entry workers will not exceed the HED’s level of concern. Between 2008 and 2011, HED has produced and revised several iterations of a document 25 

## 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 factor s). 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 i nvolved 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 f or risk assessment to support the

r egistration review process for the conventional uses of methyl bromide , although the post

application data requirement [for commodity fumigation workers] is outstanding

. HED will

consider that bystander exposure data during r egistration 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 cha nge 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 ap plications, 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 Hea lth 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 review 26



## . In summary, there are fewer methyl

bromide incidents in recent years compared to the last incident review 27 

## , possibly due to a combination of changing use patterns, s tate/local regulatory changes, and/or better worker

education and ou treach. 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.

Th e 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 ingredien ts 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 potent ial 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 prosta te cancer based on early results from the AH S (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 canc er 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 a uthors note d that in the AHS cohort , overall fumigant use is low because of th e crops typically grown in Iowa and N orth C arolina. Additionally, the authors noted that and the use of methyl bromide, while always low, continued to decrease sinc e cohort enrollment (1993

- 2007). The authors concluded that the effect appeared to dissipa te 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 ea rlier.

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

farmworkers. In a recent population

- based case control study (study period 2005

- 20 06), 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 5 00 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 e xposed to methyl bromide.

With respect to gastric cancer i n a study of Hispanic California farm workers, Mills and Yang (2007) reported an association between disease and methyl bromide exposure (OR 4 th 

## quartile versus lowest methyl bromide exposure cate gory 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 sta te 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 signif icant 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 f actors 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 review 28



## . EPA will continue to examine the available epi demiological 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 lega l 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 allege d

that Calif ornia’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. T he 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 Agreement 29 

## with the California Department of Pestic ide 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 a t 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 wil l 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 m ethyl 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 statem ents 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/

.

1 1 .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

a dverse 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 select ed 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 wildlif e 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 batter y 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 cause d 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 cal l

- 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, 2013 31 

## and includes some pesticides scheduled for r egistrat ion review and chemicals found in water

. For further information on the status of the EDSP, the policies and procedures, the list s 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 r egistration review , the Agency will make an EDSP FFDCA section 408(p) determination.

1 2 .0 Human S tudies

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

under go 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.

1 3 .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 ma d e 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 ambi ent 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 bromid e soil uses in Florida because of the declining soil use s 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: Non e 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) outli nes 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 Post

application [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 assessment s during r egistration r eview: Toxicology:

o None Residue Chemistry:

o Revised list of recommended tolerances to reflect list of crops intended for post

harvest 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 Referenc es

Memoranda Relevant to Registration review

. Author Barcode Date Title

W. Donovan D 414652 9 / 1 2/201 3 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

Resident ial/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

Che m ical Structure

Che m ical Group Alkyl Bro m ide

Co mm on Na me Methyl Bro m ide

Molecular for m

ula CH 3 Br

Molecular W eight 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 nor m al te m peratures and pressures and a liquified gas under m oderate pressure

Boiling Point 3.6 ° C

Vapor Pressure 1400 m m Hg at 20 ° C

Partition Coe ff

icient (log P o w ) 1.19

Solubility in W ater 1.75 g/100 m L at 20 ° C

## Page 25 of 32

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

Table A. 3 : Acute Toxi c i t y Data on M e thy l

Bromide Technical

Guideline N o

. Study T y pe MRID # (s) Results Toxici t y Category

870.1100 Acute o r al

(MeBr in

v egetable oil) 43510301 LD 50 = 12 0

- 160 mg/kg (males)

LD 50 = 86 mg/ k g (f

e m a l e s) II

870.1200 Acute d ermal N/ A d N/ A d N/A

870.1300 Acute inhalation Kato et al (1 9 86 ) a L C 50 = 3.03 mg/L, 4 hr exposure IV

870.2400 Prima r y

e y e irritation Alexee f

, G

. ; K il gore, W

. (1983) b and Hezemans

Boer e t al (1 9 88 ) c Severe irritation following accidental exposure

to humans I

870.2500 Prima r y

skin

irritation Alexee f

, G

. ; K il gore, W

. (1983) and Hezemans

- Boer

et al (1988) Severe irritation following accidental exposure

to humans I

870.2600 Skin sensitizati o n N/ A d N/A d N/A

a: Kato, N.; Morinobu, S .; Ishizu, S. (1986) Subacute inhalation Experi m ent for MeBr in Rats. Industr. Health. 24: 87

- 103. b: Alexeef, G.; Kilgore, W. (1983) MeB r . In: Gunther, F.; Gunther, J., ed. Residue Reviews. Residues of Pesticides and Other Conta m inants

in the Total Environ m

ent, Vol. 88, p. 102

- 153. New York, Springer Verlag.

c: Heze m ans

- Boer, M ; Toonstra, J

. ; Meulenbelt, J.; et al. (1 9 88) Skin Lesions Due to Exposure to MeBr. Arch. Der m . 124:917

- 921. d: N/A (Not Available): Acute der m al toxicity and der m al sensitization potential studies were not required because there is already a clear

evi d ence that se v ere i r ritation to skin occ u rs aft e r acute der m al exposure to MeBr.

Table A. 4 : Methyl Bromide Sub

- chronic, Chronic and Other Toxicity

Guideline N o ./ Study

T y pe MRID No. ( y e a r)/

Classification /Doses Results

870.3100

90

- Day oral to xi city in r a ts ( p e anut oi l ) 00154564 (198 4 )

classif i ca t ion: n o DER

available. NOAEL = 2 mg/kg/day

LOAEL = 10 m g/kg/day based o n slight h y perplasia of the stratified

squamous epithelium of t h e fo re stomach. HDT w a s 50 mg/kg/day.

870.3150

4

- week o r al toxicity in r a ts ( capsul e ) 43776401 (199 5 )

acce p ta b l e /

n o n

- g u i d eli n e NOAEL = 0

. 835 mg/kg/da y

.

LOAEL = 7.99 mg/kg/day (HDT), b a sed on sli g htly d ecreased b o d y weight g a in and food consumpti o n.

## Page 26 of 32

870.3465

Sub

- chronic

Inhalation Toxicity in dogs 43386802 (199 4 )

ac c epta b l e /guid e line 0, 5

, 10/15 0

, 2 5 , 50 or 100

ppm (actual mean

conce n trations 0

, 5

. 3,

11.0/158. 0

, 2 6 .0, 53.1 or 102.7 ppm; equivale n t to 1.43, 2.97/4 2 .7, 7.02, 14. 3

, 27.7 mg/kg/da y )

. 7 hours/day S y stemic toxicity (7 weeks

, 34 exposures)

NOAEL (th r eshold) = <5 ppm. LOAEL (thres h old)= 5 ppm ( 0

. 0 21 mg/L), based on dec r eased responsiveness

in female s

.

870.3700a

P renat a l developmental in

Wist a r r a ts ( via inhalatio n ) 00102990 (198 1 )

ac c epta b l e /guid e line
0, 20 or 70 ppm (eq u ivalent

to 0, 20, or 71 mg/kg/da y )

– 7

hrs/da y ; 5 da y s /wk Maternal

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

inci d enc e /seve r i t y of i n terst i t i al n ephritis at 70 p p m may r e pre s e n t
threshold effect.

Develop m ent a l

NOAEL /LOAEL > 70 ppm (H D T)

870.3700b

P renat a l developmental in

rabbits ( via inhalatio n ) 41580401 (199 0 )

ac c epta b l e /guid e line 0, 2 0

, 4 0

, or 80 ppm (equivalent to 0, 7.1, 14 or 28 mg/kg/da y )

- 6 h rs/day for 17

da y s Maternal

NOAEL = 40 ppm;
L O AEL = 80 ppm based on decreased appe t it e , let h ar g y , rig h t si d e h e a d

ti l t, a tax i a and la t eral r e cu m ben c y

.

Developmental

NOAEL = 40 p p m LO A EL = 80 ppm based on agenesis of the g a ll b lad d er, inc r eased in ci den c e of

fused sternebrae and d e creased fet a l bo d y w e ig h t

870.3800

Reproduction a n d fert i li t y ef f ects i n CD rats ( via inhalatio n ) 00160477 (198 6 )

ac c epta b l e /guid e line
0, 3

, 3 0

, or 90 p pm for 6 hours/day (equivalent to males: 0, 2. 4

, 24 or 73 mg/kg/da y ; f

e males:

0, 2

. 8, 28 or 85 mg/kg/da y ) Pare n ta l / S y st e mic NOAEL = 30 ppm

LOAEL = 9 0 ppm based on reduced bo d y w e ight Reproductive

N OAEL = 3 ppm

LOAEL = 30 ppm based on red u ced pregna nc y r a tes (23%, F2b) Offspring

NOAEL = 3 ppm LOAEL = 30 ppm based on r educed p up weight on p o st

- natal day 21 (F1a, F2a, F2b g e neratio n s) ranging from 10

- 20%.

870.4100b

Chronic toxicity dogs ( fumigated f

ee d ) 43885201 (19 9 6)

ac c epta b l e /guid e line 0, 0. 5

, 1

. 5 or 5 ppm (M: 0,
0.06, 0.13 or 0

. 2 7; F: 0

, 0

. 07,

0.12 or 0.27 mg/kg/day for 12

months. NOAEL/LOAEL > 5 ppm (H D T) (eq u ivalent to 0.27 mg/kg/day)

It is n o ted th a t t

h is stu d y was co n ducted to esta b l i sh a m argin of s afe t y for

human dieta r y exposure rat h er than to determine a L OAE L

.

870.4300

Chronic toxicity and carcinogenicity in r a ts ( m i cro

- en c apsulat e d ) 44462501 (199 7 )

ac c epta b l e /guid e line 0, 0. 5

, 2

. 5, 50, o r 250 ppm (M: 0, 0.0 2

, 0

. 1 1

, 2

. 2, or 1 1 .1;

F: 0, 0

. 03, 0.1 5 , 2.92, and

15.12 mg/kg/day for 24

months NOAEL = 50 p pm (2.2 mg/kg/ da y 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), b a sed on d ec r eased bo d y weight, b od y weight g ai n
, and food consumption in males and females duri n g the first

18 months of t h e stu d y

. No evi d e n ce of car c i n oge n ici t y

## Page 27 of 32

870.4300

Chronic toxicity and carcinogenicity (29

- month) in ra ts (via inhalation)

– Wist a r r a ts 41213301 (198 7 ); 42418301;

44359101

ac c epta b l e /guid e line 0, 3

, 30 or 90 p p m (0, 0.011 7

, 0.117 or 0.335 mg/L) (equivalent to males: 0, 1. 9

, 19 or 58 mg/kg/da y ; f

e males: 0, 2

. 2, 22 or 65 mg/kg/da y ) Local ir r itation

NOAEL < 3 p p m (0.0117 mg/L);

LOAEL = 3 p pm (0.0117 mg/L ) , based on inc r ea s ed i n cide n c e of basal cell

h y p e r p lasia of the nasal ca v ity in both sexes.

S y stemic toxicity

NOAEL = 30 ppm (0.117 mg/L)

LOAEL = 9 0 ppm (0.335 mg/L )

, ba sed on i n creased mortalit y
, decreased

bo d y w e ig h t and relative brain weight, hemothorax, i n creased incidence of thrombus, cartila g inous metaplasia, m y o ca r dial dege n erati o n and irritation

o f the esophagus and f

ore stomach.

No evi d e n ce of car c i n oge n ici t y

870.4300

Chronic toxicity and carcinogenicity in mice

– B6C3 F 1 ( via inhalatio n )

– 2

y e a rs National Toxicolo g y Program Study TR 385 42504101 (199 2 )

ac c epta b l e /guid e line for carcinogenicity s tu d y

. 0, 1 0

, 33 or 100 ppm

– 6

hrs/da y ; 5 da y s /week ( 0

, 1 1 .8,

38.9 or 118 mg/kg/da y ) Loc a l ir r i t a tion

NOAEL/LOAEL = not repor t e d

S y stemic toxicity

NOAEL = 33 ppm (0.1279 mg/l)

LOAEL = 1 0 0 ppm (0.3876 mg/l )

, b a sed on mortality (males), neur ol ogical signs ( ab n ormal

posture, tre m ors, a t axi a , li m b pa r a l y s is and e m a ci a tion) de c reased bo d y weight/weight g ain and microscopic lesions in t h e brain, heart, sternum and

ol f act or y e p ithelium.

No evi d e n ce of car c i n oge n ici t y [ No data on c l i n ic a l c h e m ist r y
, u r i n al y sis, and g r oss findings]

Genotoxicity:

Rat testicular DNA

alk a line e lution

a ssay 43180201 (199 4 ) Accep t a bl e /non

- guideli n e Dose range: 0

, 7 5, 150 or 250

ppm (0, 291, 5 8 1 or 969
mg/ m 3 ) for 6 hr/day over 5

consecutive da y s The t e st w a s positive.

870.5395

C y to g enetic

Mic r o nucleus assay in

m ice and r a ts 43786501 (198 6 ? ) Accep t abl e /gui d eli n e
Dose range: 0, 1 54, 20 0

, 26 0

, 338 or 440 ppm (equivalent to 0, 0

. 597, 0.77 6

, 1.008, 1.311

or 1.706 mg/L) f

or 6 hrs/da y
, 5 da y s/week for 14 da y s, or 10 exposures. The t e st w a s positive.

Micro n u cleus ( MN) induction was eval u ated in bone marrow o f rats and mice

and in pe ri pheral blood of mice.

870.6200a

Acute n euroto x icity screening

b a tte r y in CD rats ( v ia inhalation ) 42793601 (199 3 )

ac c epta b l e /guid e line
0, 3 0

, 100 or 3 5 0 ppm, for 6

hrs (M: 27, 90 or 3 1 4; F: 3 0

, 10 1

,

or 354 mg/kg/da y )

. NOAEL = 100 p pm LOAEL = 350 p pm based on d ecreased activity and alertness as

m easured in a f

u nctio n al obser va t i on b a tte r y examination, decreased

m otor ac t ivi t y a nd dec r ea s ed b od y te m per a ture i n m a les and f

e m a les

were obser v ed. A slight d ec r ea s e in hind

- limb g r ip stren g th in males may have b een t r ea tm ent

- rel a te d

. E f fects w e re trans i ent and all a n i m als were

assessed to b e n ormal b y 1 week post

- exposure.

870.6200b

Sub

- chronic neurotoxicity screening b a tte r y in rats ( via

inhalatio n ) 42964301; 430 7 7401 (1993)

ac c epta b l e /guid e line
0, 3 0

, 70 or 140 ppm 6 hr/da y
, 5 da y s/week

– 13 weeks (equivalent to males: 0

, 1 9

, 45, or 90 mg/kg/da y ; f

e males: 0, 2 2

, 5 1

, 101 mg/kg/da y ) NOAEL = 30 p p m (F)

LOAEL = 70 p p m (F) based on d ecreased bo d y w e ight and motor

ac t ivi t y. NOAEL = 70 p p m (M)

LOAEL = 140 p pm (M) based o n dec r eased bo d y w eight, inc r ea s ed mortality (2 animals), conv u lsions (2 animals af f ected), ef f ects o n several FOB

parameters and b r ain histo p atholo g y in males.

## Page 28 of 32

870.6300

Developmental Neurotoxicity Stu d y 46665001 (200 4 ) Accep t a bl e /non

- guideli n e
Dose s : 0, 5, 2 5

, or 50 ppm Maternal

NOAEL = 50 ppm
L O AEL = not identified

Developmental

NOAEL =5 pp m LOAEL = 25 p pm based on d e creased m otor ac t ivi t y o n PND21

870.7485

Metabolism and pharmacokinetics Intern a tion a l A g en c y for

Research on C a n cer ( IARC) Monographs Vol 41, p198 Rats recei v e d a s ingle gava g e do s e (pre p ar a tion of test solution w a s unspecified) of 2 4 mg/kg/b.w. 14 C

- MeBr. Over a 3

- day p erio d

, t h e radioacti v ity recovered were as follows: ca r cass (14

- 17%), expi r e d

carbon d ioxi d e ( 32%), uri n e (4 3 %), and f eces (l e ss than 3% )

.

During a 6

- hour exposure of r a ts to 4

. 75

- 9874 m g/cu.m 14 C

- MeBr vapo r
, approximately 2 7

- 50% of t h e c o mpound 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

- da y in h a l a tion st ud y in ro d e nts is not req u ired for reregist r ation of MeBr. Acceptable r at chronic i n halation toxicity (MRIDs 41213301, 424 1 8301; re v iewed in HED doc. nos. 007017, 00784 5

, 009843 and 1 4 130) and rat 90

- day inhalation neurotoxicity (MRIDs 42933901 and 4 3077401; re v ie w ed in HED doc. no. 010820) stu d ies ha v e b een recei v e d. T h ese studies provi d e adequate
d e scriptions of s y stemic toxicity to rod e nt s from inhalati o n exposures of intermediate duration.

Table 4.2.4 : Summary of Toxi c ologi c al Dose and Endpoints for Use in the M e thyl

Bromide O r al Human H e alth Risk Asse ssme n ts

Exposure

S cen ario Dose Used in Risk

Assessme n t, UF FQPA SF* and Level of

Co n cern for Ris k

Asse ssme n t Study and Toxi c ologi c al Eff e c t s

Acute Dietary ( F e m ales 13

- 50 y ears of age) Dev. NOAEL = 14 mg/kg/day

UF = 100

Acute RfD = 0

. 014 mg/kg/day FQPA SF = 1X

aPAD = acute RfD

F Q P A S F

= 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

F Q P A S F

= 0.9 mg/kg/day A c ute n e u r otoxi c ity study

-- r at (Inhalation)

LOAEL = 314 mg/kg/day based on decreased

activit y
, increase in nu m

ber of ani m als with drooping/half

- closed e y elids and alertness as

m easured in the F OB, decreased rears
, decreased

m otor activit y
, 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

F Q P A S F 

### = 0.022 mg/kg/day

= 0.02 mg/kg/day C h ro n ic/carcinoge n icity st ud y

-- rats (Microenca p s u lated 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: Met hyl Bromide Endpoint Selection Tables.

Table A.6: Summary of Toxi c ologi c al Dose and Endpoints for Use in Methyl Bromide Human H e alth Inhalation Risk Ass e ssm e n t

Risk Assessment* Study NOAEL/LOAEL Endpoints HED

HECs CPDR

HECs ¶

Acute Agricultural

B y stander (a m

bient;

24 hr exposure) Developmental Study in

Rabbits NOAEL = 40

ppm LOAEL = 80

ppm Developmental

effect s : agenesis of gallbladder,

fused sternebrae 10 ppm

UF = 30 21 ppm

UF = 100 (child & adult)

Greenhouse/Structura l

& Co mm odity

B y stander Developmental Study in

Rabbits NOAEL = 40

ppm LOAEL = 80

ppm Developmental

effect s : agenesis of gallbladder,

fused sternebrae 40 ppm

UF = 30

Occupational Developmental Study in

Rabbits NOAEL = 40

ppm LOAEL = 80

ppm Developmental

effect s : agenesis of gallbladder,

fused sternebrae 30 ppm

UF = 30

Short

- and

Inter m ediate

- 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

fe m ales, fecal

effects and e y e 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

fe m ales, fecal

effects and e y e 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 b y stander HECs have also been applied to 24 hour Time

- Weighted

- Average exposure concentrations measured
from a m bient air. All b y stander assess m ents a r e non

- occupational, by definition. Co mm o d ity b y standers are all based on 8 hour
dur a tions.

¶ 

### Though CDPR and USEPA based their risk assessments on the same critical stud i es 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 Mexico 1 

### Codex 2



### (a) General : methyl bromide 

## None Residue definition

not listed

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

US Canada Mexico 1 

### Codex 2



### Cotton, undelinted seed 150

MRLs With No US Equivalent

Bread and other cooked cereal products 0.01 (*) 3



### Cacao beans 5 Po 4



### Cereal grains 5 Po 4



### Cocoa products 0.01 (*) Po 3



### Dried fruits 0.01(*) Po 3



### 2 Po 4



### Milled cereal s products 0.01 (*) Po 3



### 1 Po 4



### Peanut 0.01 (*) Po 3



### 10 Po 4



### Tree nuts 0.01 (*) Po 3



### 10 Po 4


### 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 Brom ide 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 Enviro nmental 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.; Jacob s, 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.; L owe, 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 De n 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.