**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 )**Oil of Mustard and Allyl Isothiocyanate (AITC)**

PCCode 004901 **Biopesticides Registration Action Document** 

2 

### Table of Contents **I. EXECUTIVE SUMMARY**  **................................ ................................**  **................................ ..**  **5 II.**  **ACTIVE INGREDIENT OV ERVIEW**  **................................ ................................**  **............... 6**  **III. REGULATORY BACKGROUN**  **D ................................**  **................................ ......................**  **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.**  **Determ ination 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 DECI**  **SION ................................**  **................................ .................**  **14 Oil of Mustard and Allyl Isothiocyanate (AITC)** 

PCCode 004901 **Biopesticides Registration Action Document** 

3 **A. Determination of Eligibility for Registration**  **................................ ................................**  **.. 14**  **B. Regulatory Decision**  **................................ ................................**  **................................ ...........**  **14 C.**  **Environmental Justice ................................**  **................................ ................................**  **....... 14**  **VI. ACTIONS REQUIRED BY**  **REGISTRANTS ................................**  **................................ .**  **14 A.**  **R eporting of Adverse Effects**  **................................ ................................**  **............................ 15**  **B. Reporting of Hypersensitivity Incidents**  **................................ ................................**  **.......... 15**  **VII. APPENDIX A. DATA REQ**  **UIREMENTS (40 CFR PA RT 158**  **- SUBPART U)**  **.......... 16**  **VIII. APPENDIX B. REFERENC**  **ES ................................**  **................................ .......................**  **21 IX.**  **GLOSSARY OF ACRONYMS AND ABBREVIATIONS**  **................................ .............**  **22 Oil of Mustard and Allyl Isothiocyanate (AITC)** 

PCCode 004901 **Biopesticides Registration Action Document** 

4 

### BIOPESTICIDES REGISTRATION ACTION DOCUMENT **(BRAD) TEAM**  **Branch Chief** Linda A. Hollis, M.S. **Product Chemistry/ Hum**  **an Health Effects/Nontarget Organisms**  Russell Jones, Ph.D., Senior Scientist **Regulatory Action Leader**  Gina Burnett , M.S.**Oil of Mustard and Allyl Isothiocyanate (AITC)**

PCCode 004901 **Biopesticides Registration Action Document** 

5 **I. EXECUTIVE SUMMARY**  A llyl isothiocyanate (AITC) is a naturall y occurring component of Oil of Mustard , which was first registered b y the Agency for pesticidal use in 1962. As part of Oil of Mustard, AITC has been determined b y 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 naturall y when enzy mes of the mustard plant, my rosinase and glucosolinate, are in the presence of water. In addition to its presence in mustard, AI TC can be fo und in food commodities such as cooked cabbage, kale, and horseradish . It is sy ntheticall y produced from allyl iodide and potassium thiocyanate. In pesticidal products, AITC is used as an insect and animal repellent, feeding suppressant, insecticide, fungi cide, herbicide and nematicide. Currently , pesticide product (MP) , IR 9804 (EPA File Sy mbol No. 89285
- R) and end
- use product (EP), IRF 135 (EPA File Sy mbol 89285
- E) , are proposed to be registered. These product s contain sy nthetic AITC at 99.8 % and 96.3 %, respectivel y. IRF135 is intended for use as an insecticide, fungicide, herbicide and nematicide to be applied (1) b y tractor mounted shank injection at a depth of 8 to 15 inches, followed by tarp overlay , (2) by

drip injection, also covered b y t arp overlay , and ( 3) b y 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 b e 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 AI TC (EPA, 1993; EPA 2010) . The oral LD 50 in rats is 339 mg/kg (EPA, 1993) . Human exposure to AI TC is expected to be minimal from the proposed MP and soil treatment EP, IR9804 (EPA File Sy

mbol No. 89285
- R) and IRF135 (EPA File Sy mbol 89285
- E) (EPA, 2013)
. The active ingredient is not likely to result in adverse human health effects, based upon available reports and information. AI TC rapidl y degrades in the environment b y normal biological, phys ical and/or chemical processes that can be reasonably expected to exist where the p esticide 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**Oil of Mustard and Allyl Isothiocyanate (AITC)**

PCCode 004901 **Biopesticides Registration Action Document** 

6 registration actions for which EPA believes there may be significant public interest. Consistent with the policy of m aking registration decisions more transparent, the public is being provided 15 day s in which to submit comments to the Agency regarding it s 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 label s for IR9804 (EPA File Sy

mbol 89285
- R) and IRF135 (EPA File Sy mbol 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 appli cation methods (soil fumigants) but**  **as appropriate for this biopesticide. Intended revisions will include (1)**  **an entry restrict**  **ed period**  **section on the label, (2) a fumigant management plan**  **section , (3) clarification of**  **restrictions for workers verses handlers**  **, and (4) clarification of meth ods 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 product s containing AI TC for pre - plant soil treatment , it is in the best interest of the public to issue the registrations for IR9804 (EPA File Sy mbol 89285
- R) and IRF135 (EPA File Sy mbol 89285
- E)
. The basis for this decision can be found in the science review memorandum for th ese products (EPA, 2013) and the existing information in the Agency ’s database on AITC, both of which are c haracterized in this BRAD. For definitions of scientific terms, please refer to http://www .epa.gov/pesticides/glossary/
. **II. ACTIVE INGREDIENT OVERVIEW**  **Common Name:** Oil of Mustard **Chemical Names:** 1
- Propene, 3
- isothiocyanato 2
- Propenylisothiochyanate 3
- Isothiocyanato - 1
- propene Allyl isosulfocyanate Allyl isothiocyanate Allyl mustard oil **Trade & Other Names:** Oil of Mustard Allyl isothiocyanate (A IT C) **CAS Registry Number:** 57 - 06
- 7 **OPP Chemical Code:** 004901 **Type of Pesticide:** Biochemical Pesticide

– insect and animal repellent, feeding suppressant, in secticide, fungicide, herbicide and nematicide**Oil of Mustard and Allyl Isothiocyanate (AITC)**

PCCode 004901 **Biopesticides Registration Action Document** 

7 **Biochemical Classification**  Oil of Mustard , containing the residue of conern AITC, was first approved by the Agency

for use in a regi stered product as a biochemical insecticide in 1962. For more information regarding product chemistry

data requirements, please refer to Table s 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 Is agro USA , In c. (h ereafter referred to as “ Isagro ” or “applicant” ) , 430 Davis Drive, Suite 240, Morrisville, NC, 27560, submitted applications to register a new biochemical pesticide product s , IR 9804 (EPA File Sy mbol 89285
- R) and IRF135 (EPA File S ymbol 89285
- E) , co ntaining AITC as the ir 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 b y tarp overlay, (2) b y drip injection, also covered b y t arp overlay, and 3) b y 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
. **B. Food Clearances/Tolerances**  AI TC is exempt from the requirement of a tolerance as stated at 40 CFR § 180.1167: **40 CFR §**  **180.1167 Allyl isothiocyanate as a com** **ponent of food grade oil of m ustard; 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 Sy mbol 89285
- E), is labeled for pre
- plant soil application only
. The active ingredient (s ynthetic 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 re quirement of a tolerance is not required. **IV. RISK ASSESSMENT**  **A. Product Analysis Assessment (** 40 CFR § 158.2 03 0 **)** Biochemical pesticide product anal ys is data requirements include product chemistry and composition, analy sis and certified limits, and phy sical an d 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. Anal ys is and certified limits data include information on anal ysis of samples and certification of limits. Phy sical and chemi cal characteristics data describe basic characteristics of**Oil of Mustard and Allyl Isothiocyanate (AITC)**

PCCode 004901 **Biopesticides Registration Action Document** 

8 the registered pesticide products, including color, phy sical 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 Sy mbol 89285
- R) and IRF135 (EPA File Sy

mbol 89285
- E)
. Refer to Table s 1 thru 4 in Appendix A for a summ ary of product c hemistry 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** AI TC 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 addi tion, a dequate mammalian toxicology data and info rmation are available to support registration of IR 9804 (EPA File Sy mbol No. 89285
- R) and IRF135 (EPA File Sy mbol 89285
- E) . This information is summarized below and listed in Table 5 in Appendix A of this document
. **Acute Toxicity for**  **IR9804 (EPA File Symb ol**  **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 -**  **0 7**  **):** The acute oral toxicity in rats f or IF9804 (EPA File Sy

mbol 89285
- R), 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 L C 50 > 0.21 mg/L. Therefore, IR9804 (EPA File Sy mbol 89285
- R) is categorized as Toxicity Category

II for acute oral toxicity, acute dermal toxicity, and acute i nhalation toxicity
. It is categorized as Toxicity Category Ifor primary

eye irritation and primary dermal irri tation due to its corrosivity, and is classified as a dermal sensitizer. No hy persensitivity incidents have been reported. Guideline studies for acute human health toxicity testing were not submitted for the EP, IRF135 (EPA File Sy

mbol 89285
- E). In lieu of Guideline studies, the applicant submitted a request to bridge the a cute 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 u pon the substantial similar f o rmulation between these two products. **Sub c**  **hronic 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 to xicity

study was not submitted. Inlieu of a study , the applicant cited a 90
- day oral toxicity

study conducted by

the National Toxicology Program (NTP, 1982 ) on**Oil of Mustard and Allyl Isothiocyanate (AITC)**

PCCode 004901 **Biopesticides Registration Action Document** 

9 F344/N rats dosed with 1.5 to 25 mg AITC/kg
- body wgt/day , five day s 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 co mpared 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 tox icity

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 p rolonged 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 respirato r) . Similarly , a Guideline 90
- day inhalation tox icity

study was not submitted. The applicant requested and was granted a waiver based on the fact that repeated inhalation exposure to AI TC aerosol, vapor or gas is highl y unlikely and not expected, when the EP s for pre
- plant soil treatment is applied in accordance with EPA approved label use directions and PPE
. A Guideline Prenatal Developmental Tox icity study was not submitted. Inlieu of a study , the applicant cited a study in which AITC was one of 16 ch emicall y- related compounds evaluated in order to correlate potential developmental toxicity with molecular structure
. Inthis study , no difference in the percentage of abnormal fetuses in AITC
- treated offspring were detected compared to control, and no dif ference 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 s tudies 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 c onfirmed 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 ly mphoma cells without S9 activation at concentrations rangin g from 0.05 to 0.8 mg/mLAITC. 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 m g/mLw as cy totoxic. 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/mLwas cy totoxic. Itis noted that the positive results were observed without S9 activation and in the presence of substantial cy totoxicity . 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
tre ated mice. The Agency has determined that the weight of evidence demonstrates that AITC is not likely to be a mutagen. Inaddition, the method of application and rapid degradation rate for the proposed pre
- plant soil treatment , together with appropriate PP E, mitigates exposure to**Oil of Mustard and Allyl Isothiocyanate (AITC)**

PCCode 004901 **Biopesticides Registration Action Document** 

10 humans (EPA, 2013)
. **2. Tier II**  **and Tier III**  **Toxicity Studies** The biochemical pesticide Human Health Assessment data requirement s for Tier II and Tier III were not required due to the low toxicity of the active ingredient and the lo w levels of exposure expected from i ts intended uses in EP products
. **3. 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 des ignate.” The EDSP employ s a two - tiered approach to making the statutorily required determinations. Tier 1 consists of a battery of 11 screening assay s to identify the potential of a chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal sy stems. Chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal sy stems 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 an d 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 pathway s 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. AI TC (as contained in Oil of Mustard) is not among the grou p 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. Accordingl y, EPA anticipates issuing future EDSP test orders and data call
- ins for all pesti cide 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/
. **4. Dose Response Assessment**  No toxicolog ical endpoints have been identified for Oil of Mustard or AITC ; therefore, a dose
respon se assessment was not required. **5. Drinking Water Exposure and Risk Characterization**  No significant exposure from drinking water is expected when products containing Oil of**Oil of Mustard and Allyl Isothiocyanate (AITC)**

PCCode 004901 **Biopesticides Registration Action Document** 

11 Mustard or AI TC are used according to the product label directions. AI TC is a naturall y occurring component of the human diet and degrades rapidl y in the soil with a sh ort half
- life (T1⁄2) 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 directl y applied to water
. However, i n an aqueous solution in the pH range between 6 and 8, AITC is proposed to degrade compl etel y . 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 quickl y 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 env ironment, 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 AI TC would not increase exposure to non
- target organisms over levels currentl y in the environment ( EPA, 2013)
. **6. 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 Sy mbol 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 Sy mbol 89285
- E), is for agricultural use only . Previousl y approved AI TC products f or outdoor residential use have been approved by the Agency based on minimal exposure to AI TC when used according to label directions. No indoor residential, school, or day care uses are currentl y approved for products 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 AI TC 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.

**a. Food Exposure**  Dietary exposure of AI TC 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. A ITC is exempt from the requirement of a tolerance for residues when used as a component of**Oil of Mustard and Allyl Isothiocyanate (AITC)**

PCCode 004901 **Biopesticides Registration Action Document** 

12 food grade oil of mustard, in or on all raw agricultural commodities, when applied according to ap proved labeling. Furthermore, the proposed use of sy nthetic 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).

**b. Drinking Water Exposure**  The proposed use of s ynthetic AITC as a pre
- plant soil treatment will not result in water residues because this biochemical degrades rapidl y in the soil with a short half
- life (T1⁄2) 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.

**c. Other Non**  **- occupational Exposure**  The proposed soil treatment EP, IRF135 (EPA File Sy mbol 89285
- E), is for agricultural use only . Previousl y approved AI TC products for outdoor residential use have been approved b y the Agency based on minimal exposure to AI TC when used according to label di rections. Other non
occupational use is not expected for products containing this active ingredient. **8. Cumulative Effects**  **from Substances with a Common Mechanism of Toxicity** AI TC has no demonstrated subchronic toxicity ; thus, there is no reason to expe ct cumulative effects of exposure to Pear Ester and to other substances with common mechanism of toxicity
. **9. Determination of Safety for United States Population, Infants and Children**  A ITC is exempt from the requirement of a tolerance for residues when us ed 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 in fants 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 sy nthetic 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). **10. Risk Characterization**  The Agency

considered human exposure to AI TC 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.**Oil of Mustard and Allyl Isothiocyanate (AITC)**

PCCode 004901 **Biopesticides Registration Action Document** 

13 **C. Environmental Ass**  **essment 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; EP A 2010). In addition, adequate nontarget organism toxicology

data information were to support registration of IR9804 (EPA File Sy mbol No. 89285
- R) and IRF135 (EPA File Sy mbol 89285
- E) . T his informati on is summarized in Table 6 , in Appendix A of this docume nt. **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 data requirements) did not trigger these Tier II data requirements. **3. Ecological Exposure and Risk Characterization**  E xposure and risk from the registered and proposed (pre
- plant soil treatment) uses of AITC are expected to be m inimal for nontarget organisms, w ith the exception of honey bees (EPA, 2013)
. Exposure to honey

bees will be mitigated by appropriate label language on end
- use products. **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, o r 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 anal ys is 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, Sept ember, 2013. **D. 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 Allyl Isothiocyanate (AITC)**

PCCode 004901 **Biopesticides Registration Action Document** 

14 Oil of Mustard and AITC are not intended to be formulated into products to control publi c health pest s as defined in FIFRA s ection 28(d) and section 2(nn), and product performance (efficacy) was not evaluated b y 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 generally cause unreasonable adverse effects on the environment. The four eligibility criteria have been satisfie d for the proposed pesticide products containing the active ingredient AI TC (and for all previous registered pesticide products containing AITC and Oil of Mustard). **B. Regulatory Decision**  The data submitted fulfill the requirements for the unconditional reg istration IR 9804 (EPA File Sy mbol No. 89285
- R) as an MP to be formulated into soil treatment products and IRF135 (EPA File Sy mbol 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
. **C. 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 c ontaining the active ingredients Oil of Mustard or AITC, or the use of AI TC 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 EP A’s website at http://www.epa.gov/compliance/environmentaljustice/index.html
. **VI. ACTIONS REQUIRED BY REGISTRANTS**  EPA evaluated all data submitted in connection with the registrati on of AITC for pre
- plant soil treatment and determined that these data are sufficient to satisfy current registration data requirements. At this time, n o additional data must be submi tted 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 req uired to be reported to EPA as a requirement for maintaining the f ederal registration for a pesticide product. A brief summary of these types of data are listed**Oil of Mustard and Allyl Isothiocyanate (AITC)**

PCCode 004901 **Biopesticides Registration Action Document** 

15 below. **A. R** **eporting 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
. **B. Reporting of Hypersensitivity Incidents**  Under the provisions of 40 CFR Part 158.2050(d) , all incidents of hy persensitivity

(including both suspected and confirmed incidents) must be reported to the Agency
.**Oil of Mustard and Allyl Isothiocyanate (AITC)**

PCCode 004901 **Biopesticides Registration Action Document** 

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

**TABLE 1. Product Chemist ry Data Requirements for**  **IR9804 (99.8% AITC) (40 CFR § 158.2030)**  **OPPTS G**  **uideline N**  **o .**  **Study R**  **esults 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 im purities. **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** 48824102**Oil of Mustard and Allyl Isothiocyanate (AITC)**

PCCode 004901 **Biopesticides Registration Action Document** 

17 **TABLE 2. Physical an d 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 Phy sical State Liquid 48824101 830.6304 Odor Very pungent, irritating aroma 48824101 830.6313 Stability to Normal and Elevated

Tem peratures, 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 48824101**Oil of Mustard and Allyl Isothiocyanate (AITC)**

PCCode 004901 **Biopesticides Registration Action Document** 

18 **TABLE 3 . Product Chemistry Data Requirem**  **ents for IRF135 (96.3% AITC)**  **(40 CFR § 158.2030) OPPTS**  **G uideline**  **N o**  **. Study**  **R esults**  **MRID Me**  **thod/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

im purities. **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**Oil of Mustard and Allyl Isothiocyanate (AITC)**

PCCode 004901 **Biopesticides Registration Action Document** 

19 **TABLE 4. Physica l and Chemical Properties of**  **IRF135 (96.3% AITC) (40 CFR § 158.2030)**  **OPPTS Guideline No.**  **Property Description of Result**  **MRID** 830.6302 Color Not ap p lic a b l e per 40 CFR 15 8 .20 3 0(e)

– P roduct is an EP. - 830.6303 Phy sical State Li qu id 489194
- 01 830.6304 Odor Not ap p lic a b l e per 40 CFR 15 8 .20 3 0(e)

– P roduct is an EP. - 830.6313 Stability to Normal and E levated

Tem peratures, Metals and Metal I ons Not ap p lic a b l e per 40 CFR 15 8 .20 3 0(e)

– P roduct is an EP. - 830.6315 Flammability (flashpoint) 47oC 489194
- 02 830.6317 Storage Stability Study in progress

– anticip ated c o mp l e tion d ate is the last quarter of 2013. 489194
- 01
830.6319 Miscibility Not ap p lic ab l e per 40 CFR 15 8 .20 3 0(e)( 1 0)

– EP is not an emulsi f

iab le li quid and is n o t to be d i lut e d with petro l e um solvents. -
830.6320 Corrosion Characteristics Study in progress

– anticipat e d com

p l e tion d ate is th e last quarter o f 20 1 3. 489194
- 01
830.7000 pH 4.87 (1% soln) 489194
- 02 830.7050 UV/Visible Light Absorption Not ap p lic ab l e per 40 CFR 15 8 .20 3 0(e)

– P roduct is an EP. - 830.7100 Viscosity 0.6 centistokes @ 4 0 °C 0.8 centistokes @ 2 0 °C 489194
- 02 830.7200 Melting Point/Range Not ap p lic ab l e per 40 CFR 15 8 .20 3 0(e)

– P roduct is an EP. - 830.7220 Boiling Point/Range Not ap p lic ab l e per 40 CFR 15 8 .20 3 0(e)

– P roduct is an EP. - 830.7300 Density 1.019 g/mL @ 20 °C 489194
- 02 830.7520 Particle Size, Fiber Length and

Diameter Distribution Not ap p lic ab l e per 40 CFR 15 8 .20 3 0(e)

– P roduct is an EP. - 830.7550 830.7560 830.7570 Partition Coefficient (n
Octanol/Water) Not ap p lic ab l e per 40 CFR 15 8 .20 3 0(e)

– P roduct is an EP. - 830.7840 Water Solubility Not ap p lic ab l e per 40 CFR 15 8 .20 3 0(e)

– P roduct is an EP. - 830.7950 Vapor Pressure Not ap p lic ab l e per 40 CFR 15 8 .20 3 0(e)

– P roduct is an EP. -**Oil of Mustard and Allyl Isothiocyanate (AITC)**

PCCode 004901 **Biopesticides Registration Action Document** 

20 **Table 5. Mam**  **malian 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)** LD 50 = 425.4 mg/kg **ACCEPTABLE** II 488241
- 03 **Acute der**  **mal 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
- 0 8 **90 -**  **Day dermal toxicity (870.3250)**  Rationale submitted **ACCEPTABLE** 488241
- 0 8 **90 -**  **Day inhalation toxicity (870.3465)**  Rationale submitted **ACCEPTABLE** 488241
- 0 8 **Mutagenicity (870.5100, 5300 and 5375)**  Rationale submitted **ACCEPTABLE** 488241
- 0 8 **Developmental toxicity (870.3700)**  Rationale submitted **ACCEPTABLE** 488241
- 0 8

**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 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 E C 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, 29**Oil of Mustard and Allyl Isothiocyanate (AITC)**

PCCode 004901 **Biopesticides Registration Action Document** 

21 **VIII. A** **ppendix B.**  **R eferences**  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 , 20 08
. 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, Respectivel y 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. Env ironmental Protection Agency (U.S. EPA). May

15, 2013.**Oil of Mustard and Allyl Isothiocyanate (AITC)**

PCCode 004901 **Biopesticides Registration Action Document** 

22 **IX. 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 EC 50 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 Ac t 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 statistic ally 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). LD 50 me dian 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” NI OSH National Institute for Occupational Safety and Health**Oil of Mustard and Allyl Isothiocyanate (AITC)**

PCCode 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 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