Document ID: EPA-HQ-OPP-2013-0658-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2013-09-11T04:00Z

BIOPESTICIDES REGISTRATION ACTION DOCUMENT
                                       
                                       
                                       
                                       
                                       
                                       
                                       
                              Oil of Mustard and 
                          Ally Isothiocyanate (ATIC)
                                       
                               PC Code: 	004901 
               
                                       
                                       
                                       
                                       
                                       
                                       
                                       
                                       
                                       

   
	U.S. Environmental Protection Agency
	Office of Pesticide Programs
                Biopesticides and Pollution Prevention Division
                                       
                                       
                       (last updated September 11, 2013)
		
                                       
                               Table of Contents
I.	EXECUTIVE SUMMARY	5
II.	ACTIVE INGREDIENT OVERVIEW	6
III.	REGULATORY BACKGROUND	7
A.	Application for Pesticide Registration	7
B.	Food Clearances/Tolerances	7
IV.	RISK ASSESSMENT	7
A.	Product Analysis Assessment (40 CFR § 158.2030)	7
B.	Human Health Assessment	8
1.	Tier I Toxicology	8
2.	Tier II and Tier III Toxicity Studies	10
3.	Effects on the Endocrine System	10
4.	Dose Response Assessment	10
5.	Drinking Water Exposure and Risk Characterization	10

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 Exposure and Risk Characterization	11

7.	Aggregate Exposure from Multiple Routes Including Dermal, Oral, and Inhalation	11
a.	Food Exposure	11
b.	Drinking Water Exposure	12
c.	Other Non-occupational Exposure	12

8.	Cumulative Effects from Substances with a Common Mechanism of Toxicity	12
9.	Determination of Safety for United States Population, Infants and Children	12
10.	Risk Characterization	12
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	13
D.	Product Performance Data	13
V.	RISK MANAGEMENT DECISION	14
A.	Determination of Eligibility for Registration	14
B.	Regulatory Decision	14
C.	Environmental Justice	14
VI.	ACTIONS REQUIRED BY REGISTRANTS	14
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	22

BIOPESTICIDES REGISTRATION ACTION 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.

EXECUTIVE SUMMARY

Allyl isothiocyanate (AITC) is a naturally occurring component of Oil of Mustard, which was first registered by the Agency for pesticidal use in 1962. As part of Oil of Mustard, AITC has been determined by the Agency to be the residue 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 Document 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, and horseradish. It is synthetically produced from allyl iodide and potassium thiocyanate. In pesticidal products, AITC is used as an insect and animal repellent, feeding suppressant, insecticide, fungicide, herbicide and nematicide. 

Currently, pesticide product (MP), IR9804 (EPA File Symbol No. 89285-R) and end-use product (EP), IRF135 (EPA File Symbol 89285-E), are proposed to be registered. 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 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. IR9804 is intended for formulation into end-use products for soil treatment. The currently proposed label application methods are for pre-plant applications, which would be considered a non-food use. No residual activity is expected and the active ingredient and its degredates will dissipate prior to crop seeding.

The Agency has concluded that adequate mammalian toxicology data are available to support AITC (EPA, 1993; EPA 2010). The oral LD50 in rats is 339 mg/kg (EPA, 1993). Human exposure to AITC is expected to be minimal from the proposed MP and soil treatment EP, IR9804 (EPA File Symbol No. 89285-R) and IRF135 (EPA File Symbol 89285-E) (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 where the pesticide is applied (EPA, 2013). In each case of registration of products containing AITC, sufficient data or information has been submitted to demonstrate that there will be no toxicity 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 appropriately addressed thru end-use product label mitigation.

On October 1, 2009, the U.S. Environmental Protection Agency (EPA or the Agency) announced a policy to provide a more meaningful opportunity for the public to participate in major registration decisions before they occur. According to this policy, EPA provides a public comment period prior to making a registration decision for the following types of applications:  new active ingredients; first food uses; first outdoor uses; first residential uses; or any other registration actions for which EPA believes there may be significant public interest. 

Consistent with the policy of making registration decisions more transparent, the public is being 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, identification number EPA-HQ-OPP-2013-0658: a draft of this Biopesticides Registration Action Document (BRAD), the draft product labels for IR9804 (EPA File Symbol 89285-R) and IRF135 (EPA File Symbol 89285-E), and the Agency science review memorandum for these products (EPA, 2013). Note: The draft EP label will be revised, during this period, to include additional mitigation measures in accordance with those seen for similar application methods (soil fumigants) but as appropriate for this biopesticide. Intended revisions will include (1) an entry restricted period section on the label, (2) a fumigant management plan section, (3) clarification of restrictions for workers verses handlers, and (4) clarification of methods to determine soil and weather conditions. 

Altogether, the Agency believes that, based on the existing information in the Agency's database on AITC and the recent information submitted in support of the registration of pesticide products containing AITC for pre-plant soil treatment, it is in the best interest of the public to issue the registrations for IR9804 (EPA File Symbol 89285-R) and IRF135 (EPA File Symbol 89285-E). The basis for this decision can be found in the science review memorandum for these products (EPA, 2013) and the existing information in the Agency's database on AITC, both of which are characterized in this BRAD.  

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

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 Pesticide  -  insect and animal repellent, feeding suppressant, insecticide, fungicide, herbicide and nematicide
Biochemical Classification

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

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 biochemical pesticide products, IR9804 (EPA File Symbol 89285-R) and IRF135 (EPA File Symbol 89285-E), containing 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. IR9804 is intended for formulation into end-use products for soil treatment.

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 mustard, in or on all raw agricultural commodities, when applied according to approved labeling.
 
The proposed end-use product, IRF135 (EPA File Symbol 89285-E), is labeled for pre-plant soil application only. The active ingredient (synthetic AITC) and its degradates will dissipate prior to planting. The Agency considers this to be a non-food use and, therefore, a tolerance or exemption from the requirement of a tolerance is not required. 

 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 information about the identity of the active ingredient, the manufacturing process, and discussion of the potential for formation of unintentional ingredients. Analysis and certified limits data include information on analysis of samples and certification of limits. Physical and chemical characteristics 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 active ingredient (Oil of Mustard/AITC) and the proposed products, IR9804 (EPA File Symbol 89285-R) and IRF135 (EPA File Symbol 89285-E). 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. 

Human Health Assessment 

Tier I Toxicology 

AITC has already been assessed by the Agency and the Agency has concluded that adequate mammalian toxicology data are available to support this biochemical pesticide (EPA, 1993; EPA, 2008; EPA 2010). In addition, adequate mammalian toxicology data and information are available to support registration of IR9804 (EPA File Symbol No. 89285-R) and IRF135 (EPA File Symbol 89285-E). This information is summarized below and listed in Table 5 in Appendix A of this document.

Acute Toxicity for IR9804 (EPA File Symbol 89285-R) and IRF135 (EPA File Symbol 89285-E) (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 File Symbol 89285-R), containing 99.8% AITC, is LD50 = 425.4 mg/kg. Acute dermal toxicity (rat) is LD50 > 200 mg/kg, and acute inhalation toxicity (rat) is LC50 > 0.21 mg/L. Therefore, IR9804 (EPA File Symbol 89285-R) is categorized as Toxicity Category II for acute oral toxicity, acute dermal toxicity, and acute inhalation toxicity. It is categorized as Toxicity Category I for primary eye irritation and primary dermal irritation due to its corrosivity, and is classified as a dermal sensitizer. No hypersensitivity incidents have been reported.  

Guideline studies for acute human health toxicity testing were not submitted for the EP, IRF135 (EPA File Symbol 89285-E). In lieu of Guideline studies, the applicant submitted a request to bridge the acute toxicity data submitted in support 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 acceptable based upon the substantial similar formulation between these two products. 

Subchronic Toxicity, Developmental Toxicity, and Mutagenicity Testing for IR9804 (EPA File Symbol No. 89285-R) (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 submitted. In lieu of a study, the applicant cited a 90-day oral toxicity study conducted by the 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 Level (NOAEL) of 25 mg AITC/kg-body wgt/day, the highest level tested. No mortalities occurred during the course of the study and no treatment-related effects were observed on tissues obtained from the test animals when compared to non-treated controls. There were no differences in body weights between treated animals and non-treated controls (EPA, 2013).  

A Guideline 90-day dermal toxicity study was not submitted. The applicant requested and was granted a waiver based on the fact that the product is not intended for application 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 use directions and PPE (for handlers: coveralls worn over long sleeve shirt and long pants, chemical resistant footwear plus socks, chemical resistant gloves, protective eyewear, and an air purifying 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 inhalation exposure to AITC aerosol, 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 developmental toxicity with molecular structure. In this study, no difference in the percentage of abnormal fetuses in AITC-treated offspring were detected compared to control, and no difference between treated and control in the percentage of dead fetuses was detected. The authors concluded that AITC did not display any teratogenic potential at the NOAEL of 60 mg/kg. The 60 mg/kg dose would be equivalent to 4.2 g AITC for a standard 70 kg human (EPA, 2013).  

Guideline Mutagenicity studies were not submitted.  In lieu of a study, the applicant cited a battery of mutagenicity studies on AITC conducted by the National Toxicology Program (NTP). In this battery, two reverse mutation studies confirmed that mutagenicity responses were negative in all strains tested with and without S9 activation. In three in vitro mammalian gene mutation studies, a negative response was observed in the first trial using mouse lymphoma cells without S9 activation at concentrations ranging from 0.05 to 0.8 mg/mL AITC. A second trial without S9 exhibited a significant increase in average mutant frequency and significant reduction in relative total growth at AITC concentrations of 0.4, 0.6, and 0.8 mg/mL; 1.0 mg/mL was cytotoxic. A third trial without S9 also exhibited 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 presence 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 DMBA-treated 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, 2013). 

Tier II and Tier III Toxicity Studies

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

Effects on the Endocrine System	

As required under FFDCA section 408(p), EPA has developed the Endocrine Disruptor Screening Program (EDSP) to determine whether certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a "naturally occurring estrogen, or other such endocrine effects as the Administrator may designate." The EDSP employs a two-tiered approach to making the statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to identify any adverse endocrine related effects caused by the substance, and establish a dose-response relationship between the dose and the E, A, or T effect.
	
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 the potential for human exposure through pathways such as food and water, residential activity, and certain post-application agricultural scenarios.  This list should not be construed as a list of known or likely endocrine disruptors.
	
AITC (as contained in Oil of Mustard) is not among the group of 58 pesticide 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 EDSP, the policies and procedures, the list of 67 chemicals, the test guidelines and the Tier 1 screening battery, please visit our website:  http://www.epa.gov/endo/.

Dose Response Assessment

No toxicological endpoints have been identified for Oil of Mustard or AITC; therefore, a dose-response assessment was not required.  

Drinking Water Exposure and Risk Characterization

No significant exposure from drinking water is expected when products 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 degrades rapidly in the soil with a short half-life (T(1/2)) ranging from 20 to 60 hours. AITC transforms in sterilized soil at the same rate as intact soil, indicating that degredation 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 degrade completely. Within this pH range, the primary decomposition products identified were: allyl thiocyanate (ATC); allylamine (AA); and carbon disulfide (CDS). ATC, an isomer of AITC, was identified at each pH and sampling interval; AA is expected to biodegrade quickly in the environment, and so if it is formed following AITC treatment of soil, human and animal exposure is unlikely. CDS is naturally occurring in the environment, and is released from tree roots, tidal marshes and soil. CDS is considered ubiquitous in the environment, and so formation of carbon disulfide from treating soil with AITC would not increase exposure to non-target organisms over levels currently in the environment (EPA, 2013).

Occupational, Residential, School and Day Care Exposure and Risk Characterization

         a. Occupational Exposure and Risk Characterization

Occupational exposure to the proposed soil treatment EP, IRF135 (EPA File Symbol 89285-E), is not expected due to mitigation through precautionary language and personal protective equipment (PPE) on the label.For other products containing AITC, the Agency has required labels to include the appropriate signal word and precautionary statements, as PPE if applicable, to mitigate any risk of exposure. 

         b. Residential, School and Day Care Exposure and Risk Characterization

The proposed soil treatment EP, IRF135 (EPA File Symbol 89285-E), is for agricultural use only. Previously approved AITC products 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 currently approved for products containing AITC.

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 exposures for which there is reliable information.  Moreover, potential non-occupational inhalation and dermal exposure is not likely to pose any adverse effects to exposed populations via aggregate and cumulative exposure.

         c. Food Exposure 

Dietary exposure of AITC is already 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 tolerance for residues when used as a component of food grade oil of mustard, in or on all raw agricultural 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, 2013). 

         d. Drinking Water Exposure  

The proposed use of synthetic AITC as a pre-plant soil treatment will not result in water residues because this biochemical degrades rapidly in the soil with a short half-life (T(1/2)) ranging from 20 to 60 hours. 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 degrade completely. Therefore, drinking water exposure from the proposed used pattern is not expected to pose incremental risk to adults, infants and children via drinking water consumption.

         e. Other Non-occupational Exposure 

The proposed soil treatment EP, IRF135 (EPA File Symbol 89285-E), is for agricultural use only. Previously approved AITC products for outdoor residential use have been approved by the Agency based on minimal exposure to AITC when used according to label directions. Other non-occupational use is not expected for products containing this active ingredient.  

Cumulative Effects from Substances with a Common Mechanism of Toxicity
  
AITC has no demonstrated subchronic toxicity; thus, there is no reason to expect cumulative effects of exposure to Pear Ester and to other substances with common mechanism of toxicity. 

Determination of Safety for United States Population, Infants and Children

AITC is exempt from the requirement of a tolerance for residues when used as a component of food grade oil of mustard, in or on all raw agricultural commodities, when applied according to approved labeling. Therefore, it is expected that no harm will result from aggregate exposure to the United States population, including infants and children, to the residues of AITC on food commodities. This includes all anticipated dietary exposures and all other exposures for which there is reliable information. Thus, there are not threshold effects of concern and consequently, provisions requiring additional margin of safety do not apply. 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, 2013). 

Risk Characterization

The Agency considered human exposure to AITC in light of the relevant safety 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. 

Environmental Assessment

   1. Ecological Hazards

Oil of Mustard and AITC have already been assessed by the Agency and the Agency has concluded that adequate nontarget 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 File Symbol No. 89285-R) and IRF135 (EPA File Symbol 89285-E). This information is summarized in Table 6, in Appendix A of this document. 

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 data requirements) did not trigger these Tier II data requirements.  

Ecological Exposure and Risk Characterization

Exposure and risk from the registered and proposed (pre-plant soil treatment) uses of AITC are expected to be minimal for nontarget organisms, with the exception of honey bees (EPA, 2013). Exposure to honey bees will be mitigated by appropriate label language on end-use products. 

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 National Oceanic and Atmospheric Administration's (NOAA) National Marine Fisheries Service (NMFS) (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 current position. The Registration Review for these active ingredients is ongoing as of the date of this document, September, 2013.

Product Performance Data 

Product performance (efficacy) data must be developed for all pesticides to ensure that the products will perform as intended and that unnecessary pesticide exposure to the environment will not occur as a result of the use of ineffective products. The Agency reserves the right to require, on a case-by- case basis, the submission of efficacy data for any pesticide product registered or proposed for registration, but applications to register pesticide products intended to control a pest of significance public health importance, as defined 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 Notice (PR) Notices 96-7, 2002-1 and Explanation of Statutory Framework for Risk-Benefit Balancing 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 formulated 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.  

RISK MANAGEMENT DECISION

B. 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 generally cause unreasonable adverse effects on the environment. 

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

Regulatory Decision

The data submitted fulfill the requirements for the unconditional registration IR9804 (EPA File Symbol No. 89285-R) as an MP to be formulated into soil treatment products and IRF135 (EPA File Symbol 89285-E) as an EP for pre-plant soil treatment. For these product labels and for product-specific labels and information on other product containing Oil of Mustard and AITC, please refer to http://www.epa.gov/pesticides/pestlabels.

Environmental Justice

EPA seeks to achieve environmental justice -- the fair treatment and meaningful involvement of all people regardless of race, color, national origin, or income -- with respect to the development, implementation, and enforcement of environmental laws, regulations, and policies. 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 at-risk communities. For additional information regarding environmental justice issues, please visit EPA's website at http://www.epa.gov/compliance/environmentaljustice/index.html.

ACTIONS REQUIRED BY REGISTRANTS

EPA evaluated all data submitted in connection with the registration of AITC for pre-plant soil treatment and determined that these data are sufficient to satisfy current 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 existing uses, EPA may require additional data.  
Notwithstanding the information stated in the previous paragraph, it should be clearly understood that certain specific data are required to be reported to EPA as a requirement for maintaining the federal registration for a pesticide product. A brief summary of these types of data are listed below. 

C. Reporting of Adverse Effects

Pursuant to FIFRA section 6(a)(2), reports of all incidents of adverse effects to the environment must be submitted to EPA.

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. 

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 ACCEPTABLE
                                       -
                                   830.1800
Analytical method
                                  ACCEPTABLE
                                   48824102

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/jefca-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
                                   48824101

TABLE 3. Product Chemistry Data Requirements for 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
489194-02

TABLE 4. Physical and Chemical Properties 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)  -  Product is an EP.
                                       -
                                   830.6303
Physical State
 Liquid
                                   489194-01
                                       
                                   830.6304
Odor
 Not applicable per 40 CFR 158.2030(e)  -  Product is an EP.
                                       -
                                   830.6313
Stability to Normal and Elevated 
Temperatures, Metals and Metal Ions
 Not applicable 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
 Not applicable per 40 CFR 158.2030(e)(10)  -  EP is not an emulsifiable liquid and is not to be diluted with petroleum 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
 Not applicable 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
 Not applicable per 40 CFR 158.2030(e)  -  Product is an EP.
                                       -
                                   830.7220
Boiling Point/Range
 Not applicable 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
 Not applicable per 40 CFR 158.2030(e)  -  Product is an EP.
                                       -
                                   830.7550
                                   830.7560
                                   830.7570
Partition Coefficient (n-
Octanol/Water)
 Not applicable per 40 CFR 158.2030(e)  -  Product is an EP.
                                       -
                                   830.7840
Water Solubility
 Not applicable per 40 CFR 158.2030(e)  -  Product is an EP.
                                       -
                                   830.7950
Vapor Pressure
 Not applicable per 40 CFR 158.2030(e)  -  Product is an EP.
                                       -

Table 5. Mammalian Toxicology Data Requirements for IR9804 (EPA File Symbol 89285-R) (40 CFR § 158.2050)
                           Study/OPPTS Guideline No.
                                    Results
                         Toxicity Category/Description
                                     MRID
Acute oral toxicity (rat)
(870.1100)
                              LD50 = 425.4 mg/kg
                                  ACCEPTABLE
                                      II
                                   488241-03
Acute dermal toxicity (rat)	
(870.1200)
                              LD50 > 200 mg/kg
                                  ACCEPTABLE
                                      II
                                   488241-04
Acute inhalation toxicity	 (rat)
(870.1300)
                              LC50 > 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 File Symbol 89285-R) (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 LC50 = 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 EC50 = 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, 29

Appendix B. References

1. U.S. EPA, 1993. Registration Eligibility Decision (RED). Flower and Vegetable Oils. Office of Pesticide Programs. U.S. Environmental Protection Agency (U.S. EPA). December 1, 1993. Available at: http://www.epa.gov/opp00001/chem_search/reg_actions/reregistration/red_G-114_01-Dec-93.pdf
   
2. U.S. EPA, 2008. Oriental Mustard Seed (PC Code 014921). Biopesticides Registration Action Document. Office of Pesticide Programs. U.S. Environmental Protection Agency (U.S. EPA). December 17, 2008. Available at: http://www.epa.gov/pesticides/chem_search/reg_actions/registration/decision_PC-014921_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/#!documentDetail;D=EPA-HQ-OPP-2009-0904-0005

4. U.S. EPA, 2013. Memorandum from Russel Jones, Ph.D. to Gina Burnett. 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. Office of Pesticide Programs. U.S. Environmental Protection Agency (U.S. EPA). May 15, 2013.  
 
 

GLOSSARY OF ACRONYMS AND ABBREVIATIONS
      
   a.i.	active ingredient
   BPPD	Biopesticides and Pollution 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
   EC50	median effective concentration. A statistically derived single concentration in environmental medium that can be expected to cause an effect in 50% of the test animals when administrated by the route indicated (inhalation). It is expressed as a concentration in air or water (e.g. mg/L).
   EDSP	Endocrine Disruptor Screening Program
   EDSTAC	Endocrine Disruptor Screening 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
   LC50	median lethal concentration. A statistically derived single concentration in air or water that can be expected to cause death 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).
   LD50	median lethal dose. A statistically derived single dose that can be expected 
   	to cause death in 50% of the test animals 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 Health
   nm	nanometer
   NOEL	no-observed-effect-level
   NOF	notice of filing
   NOR	notice of receipt
   OPP	Office of Pesticide Programs
   OCSPP 	Office of Chemical Safety 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 States Department of Agriculture
       UV 	   ultra-violet