BIOPESTICIDES REGISTRATION ACTION DOCUMENT



## Oil of Mustard and Ally Isothiocyanate (AITC)

PC Code: 004901

U.S. Environmental Protection Agency Office of Pesticide Programs Biopesticides and Pollution Prevention Division

(last updated September 26, 2013)Oil of Mustard and Allyl Isothiocyanate (AITC)

PC Code 004901 Biopesticides Registration Action Document

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### Table of Contents

I. EXECUTIVE SUMMARY .................................................................................................. 5

II. ACTIVE INGREDIENT OVERVIEW .............................................................................. 7

III. REGULATORY BACKGROUND...................................................................................... 7

A. Application for Pesticide Registration ............................................................................... 7

B. Food Clearances/Tolerances ............................................................................................... 8

IV. RISK ASSESSMENT ........................................................................................................... 8

A. Product Analysis Assessment (40 CFR § 158.2030) .......................................................... 8

B. Human Health Assessment.................................................................................................. 8

1. Tier I Toxi cology ............................................................................................................. .............................. 8

2. Tier II and Tier III T oxicity Studies ......................................................................................... ................. 10

3. Effects on the E ndocrine System ............................................................................................... ................. 10

4. Dose Response Assessment ...................................................................................................... ................... 11

5. Drinking Water Exposure a nd Risk Characterization ............................................................................ 11

6. Occupational, Residential, School and Day Care Exposure and Risk Characterization ...................... 11

a. Occupational Exposure and Risk Characterization ............................................................................... .. 11

b. Residential, School and Day Care Expo sure and Risk Characterization ............................................... 12

7. Aggregate Exposure from Multiple Routes Including Dermal, Oral, and Inhalation ........................... 12

a. Food Exposure ................................................................................................................. ............................ 12

b. Drinking Wat er Exposure ....................................................................................................... ................... 12

c. Other Non-occupational Exposure ............................................................................................... ............. 12

8. Cumulative Effects from Substances with a Common Mechanism of Toxicity ..................................... 13

9. Determination of Safety for United Stat es Population, Infa nts and Children ....................................... 13

10. Risk Characterization ......................................................................................................... ........................ 13

C. Environmental Assessment ............................................................................................... 13

1. Ecological Hazards ............................................................................................................ .......................... 13

2. Environmental Fate and Ground Water Data ...................................................................................... .... 13

3. Ecological Exposure and Risk Characterization ................................................................................. ..... 13

4. Endangered Species Assessment ................................................................................................. ............... 14

D. Product Performance Data ............................................................................................... 14

V. RISK MANAGEMENT DECISION ................................................................................. 14Oil of Mustard and Allyl Isothiocyanate (AITC)

PC Code 004901 Biopesticides Registration Action Document

3 A. Determination of Eligibility for Registration .................................................................. 14

B. Regulatory Decision ........................................................................................................... 14

C. Environmental Justice ....................................................................................................... 1 5

VI. ACTIONS REQUIRED BY REGISTRANTS.................................................................. 15

A. Reporting of Adverse Effects ............................................................................................ 15

B. Reporting of Hypersensitivity Incidents .......................................................................... 15

VII. APPENDIX A. DATA REQUIREMENTS (40 CFR PART 158-SUBPART U) .......... 16

VIII. APPENDIX B. REFERENCES ....................................................................................... 21

IX. GLOSSARY OF ACRONYMS AND ABBREVIATIONS ............................................. 22Oil of Mustard and Allyl Isothiocyanate (AITC)

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### BIOPESTICIDES REGISTRATION AC TION DOCUMENT (BRAD) TEAM

Branch Chief Linda A. Hollis, M.S.

Product Chemistry/Human Health Effects/Nontarget Organisms Russell Jones, Ph.D., Senior Scientist

Regulatory Action Leader Gina Burnett, M.S.Oil of Mustard and Allyl Isothiocyanate (AITC)

PC Code 004901 Biopesticides Registration Action Document

5 I. EXECUTIVE SUMMARY

Allyl isothiocyanate (AITC) is a naturally o ccurring component of Oil of Mustard, which was first registered by the Agency for pesticidal us e in 1962. As part of Oil of Mustard, AITC has been determined by the Agency to be the re sidue of concern and, as such, has been well characterized in the Reregistration Eligibility Decision for Flower and Vegetable Oils (EPA, 1993), the Biopesticides Registration Action Docu ment for Oriental Mustard Seed (PC Code 014921) (EPA, 2008), and the Vegetable and Flower Oil Summary Document for Registration Review (EPA, 2010). AITC is produced naturally when enzymes of the mustard plant, myrosinase and glucosolinate, are in the presence of water. In addition to its presence in mustard,

AITC can be found in food commodities such as cooked cabbage, kale, a nd horseradish. It is synthetically produced from allyl iodide and potassi um thiocyanate. In pesticidal products, AITC is used as an insect and animal repellent, f eeding suppressant, insectic ide, fungicide, herbicide

and nematicide.

The Agency has registered manufacturing- use product (MP), IR9804 (EPA Reg. No. 89285-1) and end-use product (EP), IRF135 (EPA Reg. No . 89285-2). These products contain synthetic AITC at 99.8% and 96.3%, respectively. IRF135 is intended for use as an insecticide, fungicide, herbicide and nematicide to be applied (1) by trac tor mounted shank injection at a depth of 8 to 15 inches, followed by tarp overlay, (2) by drip in jection, also covered by tarp overlay, and (3) by deep injection to depths gr eater than 17 inches, with no ta rp covering. This is the first proposed soil fumigant containing AITC as its active ingredient. IR9804 is intended for formulation into end-use products for soil treatm ent. The label application methods are for preplant applications, which would be considered a non-food use. No residual activity is expected and the active ingredient and its degredat es will dissipate prior to crop seeding.

The Agency has concluded that adequate mamm alian toxicology data ar e available to support AITC (EPA, 1993; EPA 2010). The oral LD 50 in rats is 339 mg/kg (EPA, 1993). Human exposure to AITC is expected to be minima l from the proposed MP and soil treatment EP, IR9804 (EPA Reg. No. 89285-1) and IRF135 (EPA Reg. No. 89285-2) (EPA, 2013). The active ingredient is not likely to result in adverse human health effects, based upon available reports

and information.

AITC rapidly degrades in the environment by normal biological, physical and/or chemical processes that can be reasonably expected to exist wh ere the pesticide is applied (EPA, 2013). In each case of registration of produc ts containing AITC, sufficient data or information has been

submitted to demonstrate that there will be no toxi city or adverse effects to nontarget organisms with the exception of certain insects and honey bees (EPA, 2008). The Agency has concluded that the honey bee toxicity issue can be appr opriately addressed thru end-use product label mitigation.

On October 1, 2009, the U.S. Environmental Prot ection Agency (EPA or the Agency) announced a policy to provide a more meaningful opportuni ty for the public to participate in major registration decisions before they occur. A ccording to this polic y, EPA provides a public comment period prior to making a registration decision for the follo wing types of applications: new active ingredients; first food uses; first outd oor uses; first resident ial uses; or any otherOil of Mustard and Allyl Isothiocyanate (AITC)

PC Code 004901 Biopesticides Registration Action Document

6 registration actions for which EPA believes there may be significan t public interest.

Consistent with the policy of making registration decisions more transparent, the public was provided 15 days in which to submit comments to the Agency regarding its pending decision to register products containing AITC for use as a pre-plant soil treatment. The following documents are available for comment in the docket, id entification number EPA-HQ-OPP-2013-0658: a draft of this Biopesticides Registration Action Docume nt (BRAD), the draft product labels for IR9804 (EPA Reg. No. 89285-1) and IRF135 (EPA Reg. No. 89285-2), and the Agency science review memorandum for these products (EPA, 2013). Th e public participation comment period was open from September 11, 2013 – September 25, 2013. No comments were received during this period.

Following the public participation comment pe riod, the draft BRAD was updated to include

additional information on AITC degredates and the draft pro duct label for IRF135 (EPA Reg. No. 89285-2) was revised to include: 1) a five day entry restricted pe riod, 2) directions on notification/sign posting before a pplication, 3) clarification of methods to determine soil and weather conditions, and 4) a table of contents.

It was determined that a fumigant management plan, as required for c onventional pesticide soil fumigant, will not be required for IRF135 (EPA Reg. No. 89285-2). AITC is not a restricted use pesticide, and all hazards will be mitigated by th e personal protective equipment, restricted entry period, and notification requireme nts included on the final version of the product label.

Altogether, the Agency believes that, based on the existing information in the Agency’s database

on AITC and the recent information submitted in s upport of the registration of pesticide products containing AITC for pre-plant soil treatment, it is in the best inte rest of the public to issue the registrations for IR9804 (EPA Reg. No. 89285-1) and IRF135 (EPA Reg. No. 89285-2). The

basis for this decision can be found in the sc ience review memorandums for these products (EPA, 2013a; EPA 2013b) and the existing information in the Agency’s database on AITC, all of

which are characterized in this BRAD.

For definitions of scientific terms, please refer to http://www.epa.gov/pesticides/glossary/

.Oil of Mustard and Allyl Isothiocyanate (AITC)

PC Code 004901 Biopesticides Registration Action Document

7 II. ACTIVE INGREDIENT OVERVIEW

Common Name: Oil of Mustard

Chemical Names: 1-Propene, 3-isothiocyanato- 2-Propenyl isothiochyanate 3-Isothiocyanato-1-propene Allyl isosulfocyanate Allyl isothiocyanate Allyl mustard oil

Trade & Other Names: Oil of Mustard Allyl isothiocyanate (AITC)

CAS Registry Number: 57-06-7

OPP Chemical Code: 004901

Type of Pesticide: Biochemical Pes ticide – insect and animal repellent, feeding suppressant, insecticide, fungicide, herbicide and

nematicide

Biochemical Classification

Oil of Mustard, containing the residue of con cern AITC, was first approved by the Agency for use in a registered product as a biochemical in secticide in 1962. For more information regarding product chemistry data requirements, please refer to Tables 1 thru 4 in Appendix A for this

document.

III. REGULATORY BACKGROUND

A. Application for Pesticide Registration

On August 29, 2012, Technology Sciences Group, Inc., on behalf of Isagro USA, Inc. (hereafter referred to as “Isagro” or “applicant”), 430 Davis Drive, Suite 240, Morrisville, NC, 27560, submitted applications to register a new bioc hemical pesticide products, IR9804 (EPA Reg. No. 89285-1) and IRF135 (EPA Reg. No. 89285-2), cont aining AITC as their active ingredient.

IRF135 is intended for use as an insecticide, fungicide, herbicide and nematicide to be applied to be applied (1) by tractor mounted shank injection at a depth of 8 to 15 inches, followed by tarp overlay, (2) by drip injection, also covered by tarp overlay, and 3) by deep injection to depths greater than 17 inches, with no tarp covering. IR 9804 is intended for formulation into end-use products for soil treatment.Oil of Mustard and Allyl Isothiocyanate (AITC)

PC Code 004901 Biopesticides Registration Action Document

8 B. Food Clearances/Tolerances

AITC is exempt from the requirement of a tolerance as stated at 40 CFR § 180.1167:

40 CFR § 180.1167 Allyl isothiocyanate as a component of food grade oil of mustard; exemption from the requirement of a tolerance.

The insecticide and repellent Allyl isothiocyanate is exempt from the requirement of a tolerance for residues when used as a component of food grade oil of must ard, in or on all raw agricultural commodities, when applied according to approved labeling.

The proposed end-use product, IRF135 (EPA Reg. No. 89285-2), is labeled for pre-plant soil application only. The active ingredient (synthetic AI TC) and its degradates will dissipate prior to planting. The Agency considers this to be a non-food use and, theref ore, a tolerance or exemption from the requirement of a tolerance is not required.

IV. RISK ASSESSMENT

A. Product Analysis Assessment ( 40 CFR § 158.2030 )

Biochemical pesticide product analysis data requirements include product chemistry and composition, analysis and certified limits, and physical and chemical characteristics. Product chemistry and composition data include informati on about the identity of the active ingredient, the manufacturing process, and discussion of the potential for formation of unintentional ingredients. Analysis and certifi ed limits data include information on analysis of samples and certification of limits. Physical and chemical charact eristics data describe basic characteristics of the registered pesticide products, including color, physical state, odor, stability, miscibility, pH, corrosion characteristics, viscosity and density.

All product chemistry data requirements have been satisfied for the activ e ingredient (Oil of Mustard/AITC) and the proposed products, IR 9804 (EPA Reg. No. 89285-1) and IRF135 (EPA Reg. No. 89285-2). Refer to Tables 1 thru 4 in Appendix A for a summary of product chemistry data specific to these products. Refer to the Vegetable and Flower Oil Summary Document for Registration Review (EPA, 2010) for a summary of product chemistry information for Oil of

Mustard/AITC.

B. Human Health Assessment

1. Tier I Toxicology

AITC has already been assessed by the Agency and the Agency has conc luded that adequate mammalian toxicology data are av ailable to support this bioc hemical pesticide (EPA, 1993; EPA, 2008; EPA 2010). In addition, adequate ma mmalian toxicology data and information are available to support registration of IR9804 (E PA Reg. No. 89285-1) and IRF135 (EPA Reg. No. 89285-2). This information is summarized below a nd listed in Table 5 in Appendix A of this

document.Oil of Mustard and Allyl Isothiocyanate (AITC)

PC Code 004901 Biopesticides Registration Action Document

9 Acute Toxicity for IR9804 (EPA Reg. No. 89285-1) and IRF135 (EPA Reg. No. 89285-2) (OCSPP Guideline Nos. 870.1100, 870.1200, 870.1300, 870.2400, 870.2500, and 870.2600; Master Record Identification (MRID) Nos. 488241-03 thru -07):

The acute oral toxicity in rats for IF9804 (EPA Reg. No. 89285-1), containing 99.8% AITC, is

LD 50 = 425.4 mg/kg. Acute dermal toxicity (rat) is LD 50 > 200 mg/kg, and acute inhalation toxicity (rat) is LC 50 > 0.21 mg/L. Therefore, IR9804 (EPA Reg. No. 89285-1) is categorized as Toxicity Category II for acute oral toxicity, acute dermal toxicit y, and acute inhala tion toxicity. It is categorized as Toxicity Category I for primary eye irrita tion and primary dermal irritation due to its corrosivity, and is classified as a de rmal sensitizer. No hypersensitivity incidents have been reported.

Guideline studies for acute human health toxici ty testing were not submitted for the EP, IRF135 (EPA Reg. No. 89285-2). In lieu of Guideline studi es, the applicant submitted a request to bridge the acute toxicity data submitted in suppor t of the TGAI/MP (containing 99.8% AITC) to support the acute toxicity data requirements for the EP (containing 96.5% AITC). The Agency has determined this request to be acceptabl e based upon the substantial similar formulation between these two products.

Subchronic Toxicity, Developmental Toxicity, and Mutagenicity Testing for IR9804 (EPA Reg. No. 89285-1) (Tier I) (OCSPP Guideline Nos. 870.3100, 870.3250, 870.3465; 870.3700, 870.5100, 870.5300, 870.5375; MRID No. 48824108):

A Guideline 90-day oral toxicity study was not su bmitted. In lieu of a study, the applicant cited a 90-day oral toxicity study conducted by th e National Toxicology Program (NTP, 1982) on F344/N rats dosed with 1.5 to 25 mg AITC/kg- body wgt/day, five days per week for 13 weeks

which had a No Observed Adverse Effect Le vel (NOAEL) of 25 mg AITC/kg-body wgt/day, the highest level tested. No mortal ities occurred during the course of the study and no treatmentrelated effects were observed on tissues obtained from the test animals when compared to nontreated controls. There were no differences in body weights between treated animals and nontreated controls (EPA, 2013a).

A Guideline 90-day dermal toxicity study was no t submitted. The applicant requested and was granted a waiver based on the fact that the produ ct is not intended for a pplication to human skin and prolonged or repeated dermal contact is not expected when EPs for pre-plant soil treatment are applied in accordance with Agency approved us e directions and PPE (for handlers: coveralls worn over long sleeve shirt and l ong pants, chemical resistant f ootwear plus socks, chemical resistant gloves, protective eyewear, and an air pu rifying respirator). Similarly, a Guideline 90- day inhalation toxicity study was not submitted. The applicant requested and was granted a waiver based on the fact that repeated inhala tion exposure to AITC aer osol, vapor or gas is highly unlikely and not expected, when the EPs for pre-plant soil treatment is applied in accordance with EPA approved label use directions and PPE.

A Guideline Prenatal Developmental Toxicity study was not submitted. In lieu of a study, the applicant cited a study in which AITC was one of 16 chemically-related compounds evaluated in order to correlate potential deve lopmental toxicity with molecu lar structure. In this study, noOil of Mustard and Allyl Isothiocyanate (AITC)

PC Code 004901 Biopesticides Registration Action Document

10 difference in the percentage of abnormal fetuse s in AITC-treated offspring were detected compared to control, and no difference between tr eated and control in the percentage of dead

fetuses was detected. The authors concluded that AITC did not di splay any teratogenic potential at the NOAEL of 60 mg/kg. The 60 mg/kg dose w ould be equivalent to 4.2 g AITC for a standard 70 kg human (EPA, 2013a).

Guideline Mutagenicity studies were not submitte d. In lieu of a study, the applicant cited a battery of mutagenicity studies on AITC conduc ted by the National Toxicology Program (NTP). In this battery, two reverse mutation studies confirmed that mutagenicity responses were negative in all strains te sted with and without S9 activation. In three in vitro mammalian gene mutation studies, a negative res ponse was observed in the first tr ial using mouse lymphoma cells

without S9 activation at concentrations ra nging from 0.05 to 0.8 mg/mL AITC. A second trial without S9 exhibited a significan t increase in average mutant fre quency and significant reduction in relative total growth at AITC concen trations of 0.4, 0.6, and 0.8 mg/mL; 1.0 mg/mL was cytotoxic. A third trial without S9 also exhibi ted a significant increase in average mutant frequency at concentrations of 0.6 to 1.4 mg /mL and a significant reduction in growth; a concentration of 1.6 mg/mL was cytotoxic. It is noted that the positive results were observed without S9 activation and in the pres ence of substantial cytotoxicity. An in vivo mammalian chromosome aberration study was conducted with mice dosed intraperitoneally with 0, 25, or 50 mg/kg AITC and compared against mice dosed with a positive control, dimethylbenzanthracine (DMBA). Increases in chromosome aberrations were not observed in AITC treated mice when compared to non-treated (negative) controls, while a positive response was observed in DMBAtreated mice. The Agency has determined that the weight of evidence demonstrates that AITC is not likely to be a mutagen. In addition, the method of application and rapid degradation rate for the proposed pre-plant soil treatment, together with appropriate PPE, mitigates exposure to humans (EPA, 2013a).

2. Tier II and Tier III Toxicity Studies

The biochemical pesticide Human Health Assessment data require ments for Tier II and Tier III were not required due to the low toxicity of th e active ingredient and the low levels of exposure expected from its intended uses in EP products.

3. Effects on the Endocrine System

As required under FFDCA section 408(p), EP A has developed the Endocrine Disruptor Screening Program (EDSP) to determine whether certain substances (inc luding pesticide active and other ingredients) may have an effect in humans or wildlife si milar 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 ap proach 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 estrog en, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go th rough Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stag e of the EDSP where EPA will determine which, if any, of th e Tier 2 tests are necessary base d on the available data. Tier 2 testing is designed to identify a ny adverse endocrine related eff ects caused by the substance, andOil of Mustard and Allyl Isothiocyanate (AITC)

PC Code 004901 Biopesticides Registration Action Document

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

Between October 2009 and February 2010, EPA issued test orders and data call-ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and nine inert ingredients.

This list of chemicals was selected based on th e potential for human exposure through pathways such as food and water, residen tial activity, and certain post-applic ation agricultural scenarios.

This list should not be construed as a lis t of known or likely e ndocrine disruptors.

AITC (as contained in Oil of Mustard) is not among the group of 58 pest icide active ingredients

on the initial list to be screened under the EDSP. Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Accordingly, EPA anticipates issuing future EDSP test orders and data call-ins for all pesticide active ingredients.

For further information on the status of the ED SP, the policies and procedures, the list of 67 chemicals, the test guidelines and the Tier 1 screening battery, pleas e visit our website: http://www.epa.gov/endo/

.

4. Dose Response Assessment

No toxicological endpoints have b een identified for Oil of Must ard or AITC; therefore, a doseresponse assessment was not required.

5. Drinking Water Exposure and Risk Characterization

No significant exposure from drinking water is expected when produc ts containing Oil of

Mustard or AITC are used according to the product label directions. AITC is a naturally occurring component of the human diet and degrad es rapidly in the soil with a short half-life (T1⁄2) ranging from 20 to 60 hours. AI TC transforms in sterilized soil at the same rate as intact soil, indicating that degreda tion is not dependent on soil microbial populations. Products containing AITC will not be directly applied to water. However, in an aqueous solution in the pH range between 6 and 8, AITC is proposed to degr ade completely. Within this pH range, the primary decomposition products identified were: a llyl thiocyanate (ATC); allylamine (AA); and carbon disulfide (CDS). ATC, an isomer of AITC, is expected to completely degrade in soil in approximately 4-5 days post application. Th e remaining two degradates, AA and CDS are expected to rapidly degrade by mi crobial activity in the soil in time frames that are much less than 5 days based on the weight of laboratory evidence. Should any amount of AITC or its degradates volatilize into the atmosphere, they wi ll be rapidly diluted a nd degraded via reaction with photochemically produced hydroxyl radicals (EPA, 2013a; EPA, 2013b).

6. Occupational, Residential, School and Day Care Exposure and Risk

Characterization

a. Occupational Exposure and Risk Characterization

Occupational exposure to the proposed soil trea tment EP, IRF135 (EPA Reg. No. 89285-2), is not expected due to mitigation through precautionary language and personal protectiveOil of Mustard and Allyl Isothiocyanate (AITC)

PC Code 004901 Biopesticides Registration Action Document

12 equipment (PPE) on the label.For other products containing AITC, the Agency has required labels to include the appropriate signal word a nd precautionary statements, as PPE if applicable, to mitigate any risk of exposure.

b. Residential, School and Day Care Ex posure and Risk Characterization

The proposed soil treatment EP, IRF135 (EPA Reg. No. 89285-2), is for agricultural use only. Previously approved AITC produc ts for outdoor residential use have been approved by the Agency based on minimal exposure to AITC when used according to label directions. No indoor residential, school, or day care uses are cu rrently approved for pr oducts containing AITC.

7. Aggregate Exposure from Multiple Routes Including Dermal, Oral, and Inhalation

There is reasonable certainty of no harm to U. S. populations, including infants and children, from aggregate exposures to residues of AITC when used as proposed. This includes all anticipated dietary exposures and all other expos ures for which there is reliable information. Moreover, potential non-occupational inhalation a nd dermal exposure is not likely to pose any adverse effects to exposed populations via aggregate and cumulative exposure.

a. Food Exposure

Dietary exposure of AITC is al ready occurring, given that this substance can be found in many foods commonly consumed by humans such as cooked cabbage, kale, horseradish, and mustard. AITC is exempt from the requirement of a tolera nce for residues when used as a component of food grade oil of mustard, in or on all raw agri cultural commodities, when applied according to approved labeling. Furthermore, the proposed use of synthetic AITC as a pre-plant soil treatment will not result on residues on food as the AITC, and its degradates, will readily degrade prior to planting (EPA, 2013a).

b. Drinking Water Exposure

The proposed use of synthetic AITC as a pre-plant soil treatment will not re sult in water residues because this biochemical degrades rapidly in the soil with a short half-lif e (T1⁄2) ranging from 20 to 60 hours. Products containing AITC will not be directly applied to wa ter. However, in an aqueous solution in the pH range between 6 a nd 8, AITC is proposed to degrade completely. Therefore, drinking water exposure from the propos ed used pattern is no t expected to pose incremental risk to adults, infants and children via drinking water consumption.

c. Other Non-occupational Exposure

The proposed soil treatment EP, IRF135 (EPA Reg. No. 89285-2), is for agricultural use only. Previously approved AITC produc ts for outdoor residential use have been approved by the Agency based on minimal exposure to AITC when used according to label directions. Other nonoccupational use is not expected for produc ts containing this ac tive ingredient.Oil of Mustard and Allyl Isothiocyanate (AITC)

PC Code 004901 Biopesticides Registration Action Document

13 8. Cumulative Effects from Substances wi th a Common Mechanism of Toxicity

AITC has no demonstrated subchronic toxicity; thus, there is no reason to expect cumulative effects of exposure to Pear Este r and to other substances with common mechanism of toxicity.

9. Determination of Safety for United St ates Population, Infants and Children

AITC is exempt from the requirement of a tolera nce for residues when used as a component of food grade oil of mustard, in or on all raw agri cultural commodities, when applied according to approved labeling. Therefore, it is expected that no harm will resu lt from aggregate exposure to the United States population, including infants an d children, to the residues of AITC on food commodities. This includes all anticipated diet ary exposures and all other exposures for which there is reliable information. Thus, there are not threshold effects of c oncern and consequently, provisions requiring additional margin of safety do not apply. Furthermore, the proposed use of synthetic AITC as a pre-plant soil treatment w ill not result on residues on food as the AITC, and its degradates, will readily degrade prior to planting (EPA, 2013a).

10. Risk Characterization

The Agency considered human exposure to AITC in light of the relevant sa fety factors in FQPA

and FIFRA. A determination has been made that no unreasonable adverse effects to the U.S. population in general, and to infants and children in particular, will result from the use of products containing AITC when label instructions are followed.

C. Environmental Assessment

1. Ecological Hazards

Oil of Mustard and AITC have already been assessed by the Agency and the Agency has concluded that adequate nontarge t organism toxicology data and information are available to support these ingredients (EPA , 1993; EPA, 2008; EPA 2010). In addition, adequate nontarget organism toxicology data information were to support registration of IR9804 (EPA Reg. No. 89285-1) and IRF135 (EPA Reg. No. 89285-2). This information is summarized in Table 6, in Appendix A of this document.

2. Environmental Fate and Ground Water Data

Environmental fate and groundwater data are not required at this time because the results of the nontarget organism toxicity assessment (Tier I da ta requirements) did not trigger these Tier II data requirements.

3. Ecological Exposure and Ri sk Characterization

Exposure and risk from the registered and propose d (pre-plant soil treatme nt) uses of AITC are expected to be minimal for nontarget organisms, with the exception of honey bees (EPA, 2013a). Exposure to honey bees will be mitigated by appr opriate label language on end-use products.Oil of Mustard and Allyl Isothiocyanate (AITC)

PC Code 004901 Biopesticides Registration Action Document

14 4. Endangered Species Assessment

The Agency believes that Oil of Mustard and AITC will have “No Effect” on any currently listed threatened and endangered species, or any designated critical habitat, as listed by the U.S. Fish and Wildlife Service (USFWS) and the Nationa l Oceanic and Atmospheric Administration’s (NOAA) National Marine Fisheries Service (N MFS) (EPA, 2010). EPA anticipates conducting no further analysis of potential risks to endangered or threatened species unless public comments during the Registration Review process alter the Agency’s cu rrent position. The Registration Review for these active ingredient s is ongoing as of the date of this document, September, 2013.

D. Product Performance Data

Product performance (efficacy) data must be devel oped for all pesticides to ensure that the products will perform as intended and that unn ecessary pesticide exposure to the environment

will not occur as a result of the use of ineffec tive products. The Agency reserves the right to require, on a case-by- case basis, the submissi on of efficacy data for any pesticide product registered or proposed for registration, but applic ations to register pes ticide products intended to control a pest of significance publ ic health importance, as defi ned in FIFRA section 28(d) and section 2(nn), must include such data. For further guidance on the product performance data requirement, refer to Pesticide Registration Noti ce (PR) Notices 96-7, 2002-1 and Explanation of Statutory Framework for Risk-Benefit Bala ncing for Public Health Pesticides (http://www.epa.gov/PR _Notices/pr1996-7.pdf ) (http://www.ea.gov/ PR_Notices/pr2002-1.pdf )

and ( http://www.epa.gov/pesticides /health/risk- benefit.htm ).

Oil of Mustard and AITC are not intended to be fo rmulated into products to control public health pests as defined in FIFRA section 28(d) and section 2(nn), and product performance (efficacy) was not evaluated by the Agency.

V. RISK MANAGEMENT DECISION

A. Determination of Eligibility for Registration

Section 3(c)(5) of FIFRA provides for pesticide product registration if it is determined that: (A) its composition warrants proposed claims; (B) its labeling and other materials comply with the requirements of FIFRA; (C) it will perform its intended function without unreasonable adverse effects on the environment; and (D) when used in accordance with widespread and commonly recognized practice, it will not ge nerally cause unreasonable adverse effects on the environment.

The four eligibility criteria have been satisfied for the proposed pesticid e products containing the active ingredient AITC (and for all previous registered pestic ide products containing AITC and Oil of Mustard).

B. Regulatory Decision

The data submitted fulfill the requirements fo r the unconditional registration IR9804 (EPA Reg. No. 89285-1) as an MP to be formulated into soil treatment products and IRF135 (EPA Reg. No.Oil of Mustard and Allyl Isothiocyanate (AITC)

PC Code 004901 Biopesticides Registration Action Document

15 89285-2) as an EP for pre-plant soil treatment. EPA is granting these unconditional registrations. For these product labels and for product-specif ic labels and information on other product containing Oil of Mustard and AITC, please refer to http://w ww.epa.gov/pesticides/pestlabels

.

C. Environmental Justice

EPA seeks to achieve environmen tal justice—the fair treatment and meaningful involvement of all people regardless of race, color, national or igin, or income—with respect to the development, implementation, and enforcement of environmental laws, regulations, and po licies. At this time, EPA does not believe that products containing the active ingredients Oil of Mustard or AITC, or the use of AITC for pre-plant soil treatment will cause harm or a disproportionate impact on atrisk communities. For additional information rega rding environmental justice issues, please visit

EPA’s website at http://www.epa.gov/compliance/en vironmentaljustice/index.html

.

VI. ACTIONS REQUIRED BY REGISTRANTS

EPA evaluated all data submitted in connection w ith the registration of AITC for pre-plant soil

treatment and determined that these data are sufficient to satisfy cu rrent registration data requirements. At this time, no additional data must be submitted to EPA for these particular products. For new uses and/or changes to existi ng uses, EPA may require additional data. Notwithstanding the information stated in the pr evious paragraph, it should be clearly understood that certain specific data are requi red to be reported to EPA as a requirement for maintaining the federal registration for a pesticide product. A br ief summary of these t ypes of data are listed

below.

A. Reporting of Adverse Effects

Pursuant to FIFRA section 6(a)(2), reports of al l incidents of adverse effects to the environment

must be submitted to EPA.

B. Reporting of Hypersensitivity Incidents

Under the provisions of 40 CFR Part 158.2050(d), all incidents of hypersensitivity (including both suspected and confirmed incidents) must be reported to the Agency.Oil of Mustard and Allyl Isothiocyanate (AITC)

PC Code 004901 Biopesticides Registration Action Document

16 VII. Appendix A. Data Requirements (40 CFR Part 158-Subpart U)

TABLE 1. Product Chemistry Data Requirements for IR9804 (99.8% AITC) (40 CFR § 158.2030)

OPPTS Guideline No. Study Results MRID

830.1550

to
830.1670 Product identity; Manufacturing process;

Discussion of formation of unintentional ingredients Submitted data satisfy the requirements for product identity, manufacturing process, and discussion of formation of impurities.

ACCEPTABLE 48824101

830.1700 Analysis of samples Submitted data satisfy the requirements for analysis of samples.

ACCEPTABLE 48824102

830.1750 Certification of limits Limits listed in the CSF are

A CCEPTABLE -

830.1800 Analytical method ACCEPTABLE 48824102Oil of Mustard and Allyl Isothiocyanate (AITC)

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17 TABLE 2. Physical and Chemical Properties of IR9804 (99.8% AITC) (40 CFR § 158.2030)

OPPTS Guideline

No. Property Description of Result MRID

830.6302 Color Colorless or pale yellow liquid 48824101

830.6303 Physical State Liquid 48824101

830.6304 Odor Very pungent, irritating aroma 48824101

830.6313 Stability to Normal and Elevated Temperatures, Metals and Metal Ions Reported stable. 48824101

830.6315 Flammability Flashpoint = 46°C 48824101

830.6317 Storage Stability Study in progress – anticipated completion date is the last quarter of 2013. 48824101

830.6319 Miscibility Not Applicable; TGAI/MP is not an emulsifiable liquid and is not diluted with petroleum

solvents. -

830.6320 Corrosion Characteristics Study in progress – anticipated completion date is the last quarter of 2013. 48824101

830.7000 pH 4-5 48824101

830.7050 UV/Visible Light Absorption Refractive index 1.524-1.531;

see http://www.fao.org/ag/agn/jef ca-flav/img/img/1560.gif for the absorbance spectrum 48824101

830.7100 Viscosity Not Applicable for TGAI/MP - 830.7200 Melting Point/Range -102.5°C 48824101

830.7220 Boiling Point/Range 150-151°C; 148-154°C 48824101

830.7300 Density 1.013-1.020; 1.0 48824101

830.7520 Particle Size, Fiber Length and

Diameter Distribution Not Applicable; TGAI/MP is

not fibrous -

830.7550

830.7560

830.7570 Partition Coefficient (n-Octanol/Water) Log P = 2.11 48824101

830.7840 Water Solubility Slightly soluble in water 48824101

830.7950 Vapor Pressure 1.33 kPa @ 38.3°C

0.493 kPa@ 20°C 48824101Oil of Mustard and Allyl Isothiocyanate (AITC)

PC Code 004901 Biopesticides Registration Action Document

18 TABLE 3. Product Chemistry Data Requirements fo r IRF135 (96.3% AITC ) (40 CFR § 158.2030)

OPPTS Guideline No. Study Results MRID

Method/Reference

830.1550

to
830.1670 Product identity; Manufacturing process;

Discussion of formation of unintentional ingredients Submitted data satisfy the requirements for product identity, manufacturing process, and discussion of formation of impurities.

ACCEPTABLE 489194-01

830.1700 Analysis of samples Not required for EP 489194-02

830.1750 Certification of limits Limits listed in the CSF are

ACCEPTABLE 489194-01

830.1800 Analytical method Not required for EP 489194-02Oil of Mustard and Allyl Isothiocyanate (AITC)

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19 TABLE 4. Physical and Chemical Prop erties of IRF135 (96.3% AITC) (40 CFR § 158.2030)

OPPTS Guideline

No. Property Description of Result MRID

830.6302 Color Not applicable per 40 CFR 158.2030(e)

– P r oduct is an EP. -

830.6303 Physical State Liqui d 489194-01

830.6304 Odor Not applicable per 40 CFR 158.2030(e)

– P r oduct is an EP. -

830.6313 Stability to Normal and Elevated Temperatures, Metals and Metal Ions Not ap p lica b le per 40 CFR 158.2030(e) – Product is an EP. -

830.6315 Flammability (flashpoint) 47oC 489194-02

830.6317 Storage Stability Study in progress

– anticipated completion date is the last quarter of
2013. 489194-01

830.6319 Miscibility N ot ap p lica b le per 40 CFR 158.2030(e)(10) – EP is not an emulsifiable liquid and is
not to be diluted with

p etroleum solvents. -

830.6320 Corrosion Characteristics Study in progress– anticipated completion date is the last quarter

of 2013. 489194-01

830.7000 pH 4.87 (1% soln) 489194-02

830.7050 UV/Visible Light Absorption N ot ap p lica b le per 40 CFR 158.2030(e) – Product is an
EP. -

830.7100 Viscosity 0.6 centistokes @ 40°C
0.8 centistokes @ 20°C 489194-02

830.7200 Melting Point/Range N ot ap p lica b le per 40 CFR 158.2030(e) – Product is an
EP. -

830.7220 Boiling Point/Range N ot ap p lica b le per 40 CFR 158.2030(e) – Product is an
EP. -

830.7300 Density 1.019 g/mL @ 20°C 489194-02

830.7520 Particle Size, Fiber Length and

Diameter Distribution N ot ap p lica b le per 40 CFR 158.2030(e) – Product is an
EP. -

830.7550

830.7560

830.7570 Partition Coefficient (nOctanol/Water) N ot ap p lica b le per 40 CFR 158.2030(e) – Product is an
EP. -

830.7840 Water Solubility N ot ap p lica b le per 40 CFR 158.2030(e) – Product is an
EP. -

830.7950 Vapor Pressure N ot ap p lica b le per 40 CFR 158.2030(e) – Product is an
EP. -Oil of Mustard and Allyl Isothiocyanate (AITC)

PC Code 004901 Biopesticides Registration Action Document

20 Table 5. Mammalian Toxicology Data Requirements for IR9804 (EPA Reg. No. 89285-1) (40 CFR § 158.2050)

Study/OPPTS Guideline No. Results Toxicity Category/Description MRID

Acute oral toxicity (rat) (870.1100) LD 50 = 425.4 mg/kg

ACCEPTABLE II 488241-03

Acute dermal toxicity (rat) (870.1200) LD 50 > 200 mg/kg

ACCEPTABLE II 488241-04

Acute inhalation toxicity (rat) (870.1300) LC 50 > 0.21 mg/L

ACCEPTABLE II 488241-05

Primary eye irritation (rabbit) (870.2400) Waiver due to observed corrosiveness on skin

ACCEPTABLE I 1

Primary dermal irritation (rabbit) (870.2500) Corrosive

ACCEPTABLE I 488241-06

Dermal sensitization (guinea pig) (870.2600) Sensitizer

ACCEPTABLE - 488241-07

Hypersensitivity incidents (885.3400) - - -

90-Day oral toxicity (870.3100) Rationale submitted

ACCEPTABLE 488241-08

90-Day dermal toxicity (870.3250) Rationale submitted

ACCEPTABLE 488241-08

90-Day inhalation toxicity (870.3465) Rationale submitted

ACCEPTABLE 488241-08

Mutagenicity (870.5100, 5300 and 5375) Rationale submitted

ACCEPTABLE 488241-08

Developmental toxicity (870.3700) Rationale submitted

ACCEPTABLE 488241-08

Table 6. Non-Target Organism Data Requirements for IR9804 (EPA Reg. No. 89285-1) (40 CFR § 158.2060)

Study/OPPTS Guideline No. Results Toxicity Category/Description MRID

Avian Acute Oral/OPPTS

850.2100 Rationale submitted
ACCEPTABLE No acute oral exposure based on application method and rapid environmental degradation 48824108, p. 18

Avian Dietary/OPPTS 850.2200 Rationale submitted
ACCEPTABLE No dietary exposure based on application method and rapid

environmental degradation 48824108, p. 20

Freshwater Fish LC50/OPPTS

850.1075 Rationale submitted

96-hr LC 50 = 0.077 ppm

ACCEPTABLE Very Highly Toxic, but no aquatic exposure based on application method and rapid

environmental degradation 48824108, pp. 22,

37-47

Freshwater Invertebrate/OPPTS

850.1010 Rationale submitted

48-hr EC 50 = 0.73 ppm

ACCEPTABLE Very Highly Toxic, but no aquatic exposure based on application method and rapid

environmental degradation 48824108, pp. 23,

216-221

Non-target Plants/OPPTS

850.4100 & 4150 Rationale submitted

ACCEPTABLE No non-target exposure based on application method and rapid environmental degradation 48824108, pp. 24-

27

Non-target Insects Rationale submitted

ACCEPTABLE No non-target exposure based on application method and rapid environmental degradation 48824108, pp. 28,

29Oil of Mustard and Allyl Isothiocyanate (AITC)

PC Code 004901 Biopesticides Registration Action Document

21 VIII. Appendix B. References

1. U.S. EPA, 1993. Registration Eligibility Decisi on (RED). Flower and Vegetable Oils. Office of Pesticide Programs. U.S. Environmenta l Protection Agency (U.S. EPA). December 1,

1993. Available at: http://www.epa.gov/opp00001/chem_search/reg_ actions/reregistration/red_G-114_01-Dec93.pdf

2. U.S. EPA, 2008. Oriental Mustard Seed (PC Code 014921). Biopest icides Registration Action Document. Office of Pesticide Program s. U.S. Environmental Protection Agency (U.S. EPA). December 17, 2008. Available at: http://www.epa.gov/pesticides/chem_search /reg_actions/regis tration/decision_PC014921_17-Dec-08.pdf

3. U.S EPA, 2010. Vegetable and Flower Oils Summary Document. Registration Review: Initial Docket. Office of Pesticide Programs. U.S. Environmental Protection Agency (U.S. EPA). March 29, 2010. Available at: http://www.regulations.gov/#!docum entDetail;D=EPA-HQ-OPP-2009-0904-0005

4. U.S. EPA, 2013a. Memorandum from Russell Jones, Ph.D. to Gina Burnett. Science Review in Support of the Registration of the T GAI/MP IR9804 and the EP, IRF 135, Respectively Containing 99.8% and 96.3% Allyl Isothiocyanate (AITC) As Th eir Active Ingredient. The TGAI/MP is an unregistered source of the ac tive ingredient. Office of Pesticide Programs. U.S. Environmental Protection Agency (U.S. EPA). May 15, 2013.

5. U.S EPA, 2013b. Memorandum from Russell Jones, Ph.D. to Gina Burnett. Revised Science Review in Support of the Registration of the TGAI/MP IR9804 and the EP, IRF 135, Respectively Containing 99.8% and 96.3% Allyl Isothiocyanate (AITC) As Their Active Ingredient. The TGAI/MP is an unregistered source of the active ingredient. Environmental Fate Addendum. Office of Pesticide Programs. U.S. Environmental Protection Agency (U.S. EPA). September 18, 2013.Oil of Mustard and Allyl Isothiocyanate (AITC)

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22 IX. GLOSSARY OF ACRONYM S AND ABBREVIATIONS

a.i. active ingredient BPPD Biopesticides and Pollu tion Prevention Division BRAD Biopesticide Registration Action Document bw body weight

CBI Confidential Business Information CFR Code of Federal Regulations

cm 3 cubic centimeter

CSF Confidential Statement of Formula °C degrees Celsius

EC 50 median effective concentra tion. A statistically derive d single concentration in environmental medium that can be expected to cause an effect in 50% of the test animals when administrated by the route in dicated (inhalation). It is expressed

as a concentration in ai r or water (e.g. mg/L). EDSP Endocrine Disrupt or Screening Program EDSTAC Endocrine Disruptor Screeni ng and Testing Advisory Committee EP end-use product EPA Environmental Protection Agency (the “Agency”) FDA Food and Drug Administration FFDCA Federal Food, Drug, and Cosmetic Act FIFRA Federal Insecticide, Fungicide, and Rodenticide Act FQPA Food Quality Protection Act FR Federal Register

g gram ha hectare kg kilogram Kow octanol-water partition coefficient

L liter

LC 50 median lethal concentration. A statistically derived singl e concentration in air or water that can be expected to cause d eath in 50% of the test animals when administrated by the route indicated (inhalation and environment). It is expressed as a concentration in air or water (e.g. mg/L).

LD 50 median lethal dose. A statistically de rived single dose that can be expected

to cause death in 50% of the test an imals when administered by the route indicated (oral and dermal). It is expressed as a weight of substance per unit weight of animal (e.g., mg/kg).

MRID No. Master Record Identification Number mg milligram mPa millipascal

mL milliliter MP manufacturing-use product N/A not applicable

NE “No Effect” NIOSH National Institute for Occupational Safety and HealthOil of Mustard and Allyl Isothiocyanate (AITC)

PC Code 004901 Biopesticides Registration Action Document

23 nm nanometer
NOEL no-observed-effect-level NOF notice of filing NOR notice of receipt OPP Office of Pesticide Programs

OCSPP Office of Chemical Safe ty and Pollution Prevention pa pascal PPE personal protective equipment PR Notice Pesticide Registration Notice

TGAI technical grade of the active ingredient ug microgram

USDA United Stat es Department of Agriculture

UV ultra-violet