BIOPESTICIDES REGISTRATION ACTION DOCUMENT



## Prohydrojasmon (PDJ)

PC Code: 028000

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

(last updated November 25, 2013)Prohydrojasmon (PDJ)

PC Code 028000 Biopesticides Registration Action Document

2 

### Table of Contents

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

II. ACTIVE INGREDIENT OVERVIEW .............................................................................. 6

III. REGULATORY BACKGROUND...................................................................................... 6

A. Application for Pesticide Registration ............................................................................... 6

B. Food Clearances/Tolerances ............................................................................................... 6

IV. RISK ASSESSMENT ........................................................................................................... 7

A. Product Analysis Assessment (40 CFR § 158.2030) .......................................................... 7

B. Human Health Assessment.................................................................................................. 7

1. Tier I Toxi cology ............................................................................................................. .............................. 7

2. Tier II and Tier III T oxicity Studies ......................................................................................... ................... 9

3. Effects on the E ndocrine System ............................................................................................... ................... 9

4. Dose Response Assessment ...................................................................................................... ................... 10

5. Drinking Water Exposure a nd Risk Characterization ............................................................................ 10

6. Occupational, Residential, School and Day Care Exposure and Risk Characterization ...................... 10

a. Occupational Exposure and Risk Characterization ............................................................................... .. 10

b. Residential, School and Day Care Expo sure and Risk Characterization ............................................... 10

7. Aggregate Exposure from Multiple Routes Including Dermal, Oral, and Inhalation ........................... 10

a. Food Exposure ................................................................................................................. ............................ 10

b. Drinking Wat er Exposure ....................................................................................................... ................... 10

c. Other Non-occupational Exposure ............................................................................................... ............. 11

8. Cumulative Effects from Substances with a Common Mechanism of Toxicity ..................................... 11

9. Determination of Safety for United Stat es Population, Infa nts and Children ....................................... 11

10. Risk Characterization ......................................................................................................... ........................ 11

C. Environmental Assessment ............................................................................................... 12

1. Ecological Hazards ............................................................................................................ .......................... 12

2. Environmental Fate and Ground Water Data ...................................................................................... .... 12

3. Ecological Exposure and Risk Characterization ................................................................................. ..... 12

4. Endangered Species Assessment ................................................................................................. ............... 13

D. Product Performance Data ............................................................................................... 13

V. RISK MANAGEMENT DECISION ................................................................................. 13

A. Determination of Eligibility for Registration .................................................................. 13

B. Regulatory Decision ........................................................................................................... 13Prohydrojasmon (PDJ)

PC Code 028000 Biopesticides Registration Action Document

3 C. Environmental Justice ....................................................................................................... 1 4

VI. ACTIONS REQUIRED BY REGISTRANTS.................................................................. 14

A. Reporting of Adverse Effects ............................................................................................ 14

B. Reporting of Hypersensitivity Incidents .......................................................................... 14

VII. APPENDIX A. DATA REQUIREMENTS (40 CFR PART 158-SUBPART U) .......... 15

VIII. APPENDIX B. REFERENCES ....................................................................................... 20

IX. GLOSSARY OF ACRONYMS AND ABBREVIATIONS ............................................. 21Prohydrojasmon (PDJ)

PC Code 028000 Biopesticides Registration Action Document

4 

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

Branch Chief Linda A. Hollis, M.S.

Product Chemistry/Human Health Effects/Nontarget Organisms Miachel Rexrode, Ph.D., Senior Scientist

Regulatory Action Leaders Gina Burnett, M.S., Regulatory Action Leader Leonard Cole, Jr., M.S., Seni or Regulatory SpecialistProhydrojasmon (PDJ)

PC Code 028000 Biopesticides Registration Action Document

5 I. EXECUTIVE SUMMARY

Prohydrojasmon (PDJ) is a synthetically made plant growth regulator that is structurally similar and functionally identical to jasmonic acid (JA), a naturally occurring plant regulator present in all vascular (higher) plants. The highest levels for JA are found in actively growing plant tissues such as leaves, flowers, and developing fruit, an d thus JA has always been a natural component of diets containing plant materials. The jasmonates, of which JA is a member, is a group of plant hormones involved in multiple stages of plant de velopment and defense, including the ability to stimulate fruit ripening. As a pesticide, PDJ is used to stimulate fruit ripening in apples and

grapes.

The new active ingredient application for PDJ contains a petition for the exemption from a requirement of a tolerance in or on apples a nd grapes pre-harvest, and two proposed products: the manufacturing-use product (MP), Prohydrojas mon Technical (EPA File Symbol 62097-EI) and the end-use product (EP), BLUSH (EPA File Symbol 62097-EO), containing 98% and 5.25% PDJ, respectively. Prohydrojasmon Technical is intended for formulating into EPs, including BLUSH, which will be applied pre-harves t as a foliar spray to apples and grapes.

Data derived from appropriate tests give no indication that PDJ is toxic to humans. No unreasonable adverse effects to humans are expected from its use as a fruit ripening agent. Furthermore, pesticide products containing PDJ are not likely to pose a risk to the environment, including nontarget organisms when us ed according to label instructions.

On October 1, 2009, EPA announced a new policy to provide a more meani ngful opportunity for the public to participate on major registration deci sions before they occur. According to this policy, EPA provides a public comment period prio r to making a registration decision for the following types of applications: new active ingredients, first f ood use, first outdoor use, first residential use; and any regist ration decisions for which the Agency believes there may be substantial public interest. Consistent with th e policy of making registration actions more transparent, PDJ was subject to a 15-day comm ent period as a “new active ingredient.” EPA established a comment period of 15 days on the basis of PDJ’s lack of toxicity and the determination that PDJ presents low risk of any adverse effects to human health and the environment. The notice for this comment peri od includes the draft Biope sticides Registration Action Document (BRAD), draft product labels for the Prohydroj asmon Technical (EPA File Symbol 62097-EI) and BLUSH (EPA File Sy mbol 62097-EO) and the science review memorandum for these products (EPA, 2013). The docket identification (ID) number for this action is EPA-HQ-OPP-2012-0831. No co mments were received in response to this public participation comment period.

The Agency believes that based on the risk asse ssment and information submitted in support of the registration of Prohydrojasmon Technical (EPA File Symbol 62097-EI) and BLUSH (EPA File Symbol 62097-EO), it is in the best interest of the public to issue these registrations and, therefore, EPA has registered these products. The basis for this decision can be found in the risk assessment for PDJ (EPA, 2013), which is characterized in this BRAD.

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

.Prohydrojasmon (PDJ)

PC Code 028000 Biopesticides Registration Action Document

6 II. ACTIVE INGREDIENT OVERVIEW

Common Name: Prohydrojasmon (PDJ)

Chemical Names: propyl-3-oxo-2-pentylcyclo-pentylacetate cyclopentaneacetic acid, 3-oxo-2-pentyl-, propyl ester

Trade & Other Names: Prohydrojasmon (PDJ)

CAS Registry Number: 158474-72-7

OPP Chemical Code: 028000

Type of Pesticide: Biochemical Pesticide – Plant growth regulator

III. REGULATORY BACKGROUND

On June 18, 2012, EPA received an application filed by SciReg, Inc., 12733 Director’s Loop, Woodbridge, VA 22192 on behalf of Fine Agro chemicals Ltd., Hill End House, Whittington, Worcester WR5 2RQ, United Kingdom, to regi ster the products, Pr ohydrojasmon Technical (EPA File Symbol 62097-EI), and BLUSH (EPA File Symbol 62097-EO), containing the new biochemical active ingredient, prohydrojasmon (P DJ), propyl-3-oxo-2-pentyl cyclo-pentylacetate. A notice of receipt (NOR) of this applicat ion, allowing for a 30-day comment period, was published in the Federal Register on Wednesday December 16, 2012 (75 FR 11175). No comments were received following this publication.

A. Classification

On September 22, 2008, the Biochemical Classifi cation Committee determined that PDJ was “biochemical like” and was eligible for a reduced data set. PDJ was classified as “biochemical

like” due to its non-toxic mode of action and beca use it is structurally similar and functionally identical to jasmonic acid (JA), a na turally occurring plant regulator.

B. Food Clearances/Tolerances

In the Federal Register of January 9, 2013, (Vol. 78 FR 1798) (FRL-9374-2), EPA issued a notice pursuant to FFDCA secti on 408(d)(3), 21 U.S.C. 346a(d)(3 ), announcing the filing of a pesticide tolerance petition (PP 2F8056) by Fine Agrochemicals Ltd. (the Petitioner), on behalf of SciReg, Inc., 12733 Director’s Loop, Woodbri dge, VA, 22192. The petition requested that 40 CFR part 180 be amended by establishing an exemp tion from the requirement of a tolerance for residues of prohydrojasmon (PDJ), propyl-3-oxo-2-pen tylcyclo-pentylacetate, in or on red apples and grapes. The notice referenced a summary of th e petition prepared by the Petitioner, which is available in the docket, http://www.regulations.gov . No substantive comments were received in response to the notice of filing.Prohydrojasmon (PDJ)

PC Code 028000 Biopesticides Registration Action Document

7 IV. RISK ASSESSMENT

A. Product Analysis Assessment ( 40 CFR § 158.2030 )

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

All product chemistry data requirements have been satisfied for the active ingredient, PDJ, and the pesticidal products, Prohydrojasmon Techni cal (EPA File Symbol 62097-EI), and BLUSH (EPA File Symbol 62097-EO). Refer to Tables 1 and 2 in Appendix A for a summary of product chemistry data.

B. Human Health Assessment

1. Tier I Toxicology

Adequate mammalian toxicology data/information ar e available to support registration of PDJ

. All toxicology data requirements for PDJ and the proposed products, Prohydrojasmon Technical (EPA File Symbol 62097-EI), and BLUSH (EPA File Symbol 62097-EO) have been satisfied. The following is a summary of EPA’s review of th e toxicity profile of this biochemical (also refer to Tables 3 and 4, in Appendix A of this document):

Acute Toxicity : Acute toxicity studies on the technical grade active ingredient (TGAI) for PDJ, containing 97.98% PDJ, confirm a low toxicity pr ofile. The acute toxicity data show virtual nontoxicity for all routes of exposure. Therefore, it can be concluded that any acute dietary risks associated with this plant re gulator would be negligible.

1. The acute oral median lethal dose (LD50) in rats was greater than 5,000 milligrams per kilogram (mg/kg) bodyweight, demonstrating ve ry low toxicity. There were no observed toxicological effects on the test subjects in the acute oral study submitted (MRID No. 47927825). PDJ is classified as Toxicity Category IV for acute oral toxicity.

2. The acute dermal LD50 in rats was gr eater than 2,000 mg/kg body weight (MRID 47927826), demonstrating low toxicity. PDJ is cla ssified as Toxicity Category III for acute dermal toxicity.

3. The acute inhalation median le thal concentration (LC50) was greater than 2.8 milligrams per liter (mg/L) in rats and showed no signifi cant inhalation toxicity (MRID 47927827). PDJ is classified as Toxicity Category IV for acute inhalation toxicity.Prohydrojasmon (PDJ)

PC Code 028000 Biopesticides Registration Action Document

8 4. A primary eye irritation study on rabbits indicate s that PDJ is minimally irritating to the eye (MRID 47927828). PDJ is classified as Toxicity Category IV for primary eye irritation.

5. A skin irritation study on rabbits indicates th at PDJ is not irritating to the skin (MRID 47927829). PDJ is classified as Toxicity Ca tegory IV for primary skin irritation.

6. Data indicate that PDJ is not a dermal sensitizer (MRID 47927830).

Mutagenicity : Two mutagenicity studies were performe d using the TGAI of PDJ (97.98% PDJ)

as the test substance:

1. In the Bacterial Reverse Gene Mutation Te st (MRID No. 47927833), th e number of mutant

bacterial colonies that were reverted back to their normal genetic profile (via gene mutation) were not significantly increased under PDJ treatment. Therefore, PDJ is considered to be nonmutagenic under the cond itions of this assay.

2. An in vitro Mammalian Cell Chromosome Aberrati on Test (MRID No. 47927834) tested PDJ genotoxicity on Chinese hamster lung cells (CHL /IU) up to the cytotoxic dose level of 80 micrograms per milliliter [μg/mL], without S9 ac tivation, and up to the limit concentration of 5000 μg/mL with S9 activation. None of the test substance concentrations induced a significant

increase in the incidence of cells with chromo somal abnormalities, eith er in the absence or presence of S9 activation and the test substan ce. Under the conditions of this assay, PDJ is considered to be non-mutagenic and does not cau se chromosome aberrations. Together, these

studies are sufficient to confirm that there are no expected dietary or non-occupational risks of mutagenicity with regard to food use of PDJ.

Subchronic Toxicity : In a subchronic oral t oxicity study using the TGAI of PDJ (97.98% PDJ) as the test substance, no clinically or toxicologically si gnificant effects were found in any treatment group (MRID 47927831). Therefore, the no observed a dverse effect level (NOAEL) for PDJ has been established as the highest test substan ce dose, 10,000 parts per million (ppm) (equivalent to 566 mg/kg bw/day for male test animals and 587 mg/kg bw/day for female test animals). A

lowest observed adverse effect level (LOAEL) was not establis hed, suggesting that the test animals could have tolerated a higher dose. In sum, the data submitted to the Agency indicate that PDJ has no subchronic dietary risk.

Developmental Toxicity : In a developmental toxicity study, using the TGAI of PDJ (97.98% PDJ) as the test substance (MRID 47927832), ther e were no treatment-related effects found at necropsy in maternal animals nor were there eff ects on copra lutei, number of implantations, sex ratio, fetal body weight, or prei mplantation embryonic mortality. The Agency does not consider the temporary decrease in body weight or food intake observed in the 500 mg/kg bw/day test group to be an adverse effect, as this is likely due to the palatabi lity of the food containing this high dose of test substance. Therefore, the Ag ency establishes the NOAEL for this study as 500 mg/kg bw/day. A LOAEL was not identified for matern al effects, suggesting that the test animals could have tolerated a higher dose. No treatm ent-related developmental effects were found on

external examination of the fetuses. Visceral examination showed a slight increase in the incidence of thymic remnants; however, the in crease was within the range of the performingProhydrojasmon (PDJ)

PC Code 028000 Biopesticides Registration Action Document

9 laboratories historical control da ta. Therefore, the Agency does not consider this a treatmentrelated effect. There was also a slight increase in the incidence of a 14 th rib, which is a common

variation in this strain of rat a nd is therefore not cons idered an adverse effect. This variation was not accompanied by an increased incidence of abnor mal embryos, either on external, skeletal, or visceral examination, and did not appear at a higher than normal rate. Based on the study results, the developmental effects NOAEL for the study is the highest dose tested 500 mg/kg bw/day. A

LOAEL was not identified for develo pmental effects, suggesting that the test animals could have tolerated a higher dose. In sum, the data subm itted to the Agency indicate that PDJ has no developmental toxicity risk.

2. Tier II and Tier III Toxicity Studies

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

3. Effects on the Endocrine System

As required under FFDCA section 408(p), EP A has developed the Endocrine Disruptor Screening Program (EDSP) to determine whether certain substances (inc luding pesticide active and other ingredients) may have an effect in humans or wildlife si milar to an effect produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator may designate.” The EDSP employs a two-tiered ap proach to making the statutorily required

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estrog en, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go th rough Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stag e of the EDSP where EPA will determine which, if any, of th e Tier 2 tests are necessary base d on the available data. Tier 2 testing is designed to identify a ny adverse endocrine related eff ects caused by the substance, 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 th e potential for human exposure through pathways such as food and water, residen tial activity, and certain post-applic ation agricultural scenarios.

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

PDJ is not among the group of 58 pe sticide active ingredie nts on the initial list to be screened under the EDSP. Under FFDCA section 408(p), the Ag ency must screen all pesticide chemicals. Accordingly, EPA anticipates issuing future EDSP te st orders and data call -ins for all pesticide active ingredients.

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

.Prohydrojasmon (PDJ)

PC Code 028000 Biopesticides Registration Action Document

10 4. Dose Response Assessment

No toxicological endpoints have b een identified for PDJ; theref ore, a dose-response assessment was not required.

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

Characterization

a. Occupational Exposure and Risk Characterization

Occupational exposure to PDJ is mitigated when re gistered products are used in accordance with EPA-approved labeling. Occupational exposures are not included under the Federal Food, Drug, and Cosmetic Act (FFDCA) in the assessment of aggregated exposures for the purpose of establishing tolerances and exemptions from tolerance.

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

Significant human exposure to PDJ is highly unlikely in residentia l, school and day care areas when end-use products are used in accord ance with EPA-approved labeling. This active ingredient is only approved for outdoor commercial agricultural us e as a plant growth regulator on apples and grapes, preharvest.

6. 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 PD J when used as proposed. This includes all anticipated dietary exposures and all other expos ures for which there is reliable information. Moreover, potential non-occupational inhalation a nd dermal exposure is not likely to pose any adverse effects to exposed populations via aggregate and cumulative exposure.

a. Food Exposure

Dietary exposure to residues of PDJ is expected to be insignificant. In a worst case scenario, such as no degradation of the app lied compound, PDJ residues consumed by a 70 kg person are four orders of magnitude below the No Observed Ad verse Effect Level (NOAEL) that was calculated for this compound (EPA, 2013). Furthermore, dietar y exposure to residues of PDJ from treated fruit is not expected to exis t above background levels of natu rally occurring JA (EPA, 2013).

b. Drinking Water Exposure

Exposure of humans to PDJ in drinking wate r is unlikely since products are labeled for application directly to terrestri al plants and because data demonstrate a soil half-life for this chemical from 1.6-2.3 hours, as well as rapid degradation in water (EPA, 2013). Furthermore, the expected concentrations in surface water ar e well below (6 to 7 orders of magnitude) the maximum doses used in laboratory testing, where no toxic effects were seen (i.e., Acute Oral Toxicity LD50 > 5,000 mg/kg; Developmental Toxicity NOAEL > 500 mg/kg) (EPA, 2013).Prohydrojasmon (PDJ)

PC Code 028000 Biopesticides Registration Action Document

11 c. Other Non-occupational Exposure

Non-occupational exposure is not expected because PDJ is no t approved for residential uses. The active ingredient is applied dir ectly to commodities and degrades rapidly; data demonstrate a soil

half-life for this chemical from 1.6-2.3 hours a nd a half-life in light-irradiated water from 54.0-

57.8 hours.

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

The EPA has not found PDJ to share a common mechanism of toxicity with any other substances, and PDJ does not appe ar to produce a toxic metabolit e produced by other substances. For the purposes of this toleran ce action, therefore, the EPA has assumed that PDJ does not have a common mechanism of toxicity with other subs tances. Following from this, the EPA concludes

that there are no cumulative eff ects associated with PDJ that need to be considered. For information regarding the EPA’s efforts to dete rmine chemicals that have a common mechanism of toxicity and to evaluate th e cumulative effects of such chem icals, see the EPA’s website at http://www.epa.gov/pesticides/cumulative.

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

EPA has determined that there are no foreseeab le dietary risks to th e U.S. population, including infants and children, from the use of PDJ as a pesticide (plant growth regulator) on apple and grape, when label instructions and good agricultural practices are followed. The available data and information indicate that the chemical (1 ) is of low toxicity and not a developmental toxicant, and (2) is structura lly similar and functionally identical to jasmonic acid (JA), a compound naturally occurring in the human diet. Wh en compared to the amount of JA that is likely already consumed in the human diet, dietar y exposure from pesticidal use of PDJ is not anticipated to significantly increase overall dietary exposure of infants and children.

Therefore, EPA concludes that there is a reasonable certainty that no harm will result to the U.S. population, including infants and chil dren, from aggregate exposure to the residues of PDJ when

it is used as labeled and in accordance with good agricultural practices. Such exposure includes all anticipated dietary exposures and all other exposures for which there is reliable information.

EPA has arrived at this conclusion because th e data and information available on PDJ do not demonstrate significant toxic potential to mammals, including infants and children.

9. Risk Characterization

The Agency has considered human exposure to PDJ in light of the relevant safety factors in FQPA and FIFRA. A determination has been made that no unreasonable a dverse effects to the U.S. population in general, and to infants and chil dren in particular, will result from the use of products containing PDJ when label instructions are follo wed. In addition, the Agency is establishing an exemption from the requirement of a tolerance for residues of the biochemical pesticide PDJ in or on apple and grape when used as a plant growth regulator pre-harvest and in

accordance with label directions and good agricultural practices.Prohydrojasmon (PDJ)

PC Code 028000 Biopesticides Registration Action Document

12 C. Environmental Assessment

1. Ecological Hazards

Adequate non-target toxicology da ta/information are available to support registration of PDJ; all biochemical pesticide non-targ et toxicology data requirement s have been satisfied. This information is summarized in Table 5, in Appendix A of this document.

2. Environmental Fate and Ground Water Data

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

3. Ecological Exposure and Ri sk Characterization

PDJ is not naturally-occu rring but is structurally similar to jasmonic acid (JA), which is an intermediate in the pathway to pl ant abscisic acid synthesis. JA can influence growth inhibition, senescence, and leaf abscission, and plays a ro le in wound response and systemic resistance. When plants are attacked by insects there is a rele ase of JA, which inhibits the insect’s ability to digest protein (EPA, 2013).

In order to evaluate risk of PDJ to terrestrial species, the Agency used calculated expected residues of PDJ in dietary exposure calculations for multiple weight classes of birds and mammals using the Terrestrial Residue Exposure Model (T-REX) Version 1.4.1. Expected

residues were calculated for avian and mammalia n food items along with di ssipation rates of PDJ when applied to foliar surfaces (single or multiple applications) in order to estimate worst case

scenarios. Calculations showed that PDJ (when applied at 0.009 lb s ai/A) has a low potential for toxic impact to birds and mammals that may be feeding in the area of ap plication (risk quotients equal to 0.00 for birds and mammals). With this information and PDJ’s non-toxic mode of action and biodegradability, the Agency has determined that exposure to PDJ will result in no risk to all non-target terrestri al organisms.

PDJ exposure to aquatic species is also expected to result in no toxicity effects. Estimated environmental concentrations (EECs) in aquatic sites from PDJ runoff after application to terrestrial crops were estimated using the GE Neric Estimated Environmental Concentration model (EPA, 2013). The model assumed 2 maximu m applications of end product at 0.009 lbs ai/A (4g ai/A) at 7 day intervals, a 10.7 day aquatic half-life, a 57.8 hours photodegradation halflife in water, and a 1.6 – 2.3 hour half-life in ae robic soil. Risk quotients for fish and aquatic invertebrates (0.0001 and 0.00005, respect ively) were three and four orders of magnitude below the Agency’s levels of concern (LOCs = 0.05 - 1) . The Agency has determined that exposure to PDJ presents no risk concerns for aquatic species.Prohydrojasmon (PDJ)

PC Code 028000 Biopesticides Registration Action Document

13 4. Endangered Species Assessment

The Agency has not conducted a risk assessmen t that supports a complete endangered species determination. The ecological risk assessment pla nned during Registration Review will allow the Agency to determine whether the uses of PDJ ha ve “no effect” or “may effect” federally listed threatened or endangered species (listed specie s) or their designated critical habitats.

D. Product Performance Data

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

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

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

PDJ is not intended to be formulated into product s to control public health pests as defined in FIFRA section 28(d) and section 2(nn), and prod uct performance (efficacy ) was not evaluated by the Agency.

V. RISK MANAGEMENT DECISION

A. Determination of Eligibility for Registration

Section 3(c)(5) of FIFRA provides for registration of a new pesticide active ingredient if it is determined that: (A) its composition warrants proposed claims; (B) its labeling and other materials comply with the requi rements of FIFRA; (C) it will perform its intended function

without unreasonable adverse eff ects on the environment; and (D) when used in accordance with widespread and commonly recogniz ed practice, it will not genera lly cause unreasonable adverse

effects on the environment. The f our eligibility criteria have b een satisfied for PDJ. Products containing PDJ are not expected to cause unreasonable adverse effect s, and are likely to perform as claimed when used according to label instructions. Therefore, the Agency has decided to register PDJ as a plant growth regulator on apples and grapes.

B. Regulatory Decision

The data submitted fulfill the requirements for the unconditional registration of Prohydrojasmon Technical (EPA File Symbol 62097-EI) and BLUSH (EPA File Symbol 62097-EO). For product-specific information, please refer to http://www.epa.gov/pe sticides/pestlabels

.Prohydrojasmon (PDJ)

PC Code 028000 Biopesticides Registration Action Document

14 C. Environmental Justice

EPA seeks to achieve environmen tal justice—the fair treatment and meaningful involvement of all people regardless of race, color, national or igin, or income—with respect to the development, implementation, and enforcement of environmental laws, regulations, and po licies. At this time, EPA does not believe that products c ontaining the active ingredient PDJ will cause harm or a disproportionate impact on at-risk communitie s. For additional information regarding environmental justice issues, please visit EPA’s website at http://www.epa.gov/compliance/en vironmentaljustice/index.html

.

VI. ACTIONS REQUIRED BY REGISTRANTS

EPA evaluated all data submitted in connection w ith the registration of PDJ as a plant growth regulator of use on apples and grapes and determ ined that these data are sufficient to satisfy current registration data requirement s. At this time, no additional data must be submitted to EPA for these particular products. For new uses a nd/or changes to existing uses, EPA may require

additional data.

Notwithstanding the information stated in the pr evious paragraph, it should be clearly understood that certain specific data are requi red to be reported to EPA as a requirement for maintaining the federal registration for a pesticide product. A br ief summary of these t ypes of data are listed

below.

A. Reporting of Adverse Effects

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

must be submitted to EPA.

B. Reporting of Hypersensitivity Incidents

Under the provisions of 40 CFR Part 158.2050(d), all incidents of hypersensitivity (including both suspected and confirmed incidents) must be reported to the Agency.Prohydrojasmon (PDJ)

PC Code 028000 Biopesticides Registration Action Document

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

TABLE 1. Product Chemistry Data Requirements for PDJ a (40 CFR § 158.2030)

OCSPP Guideline No. Study Results

830.1550

to
830.1670 Product identity; Manufacturing process;

Discussion of formation of unintentional ingredients The product identity and composition was adequately

addressed.

830.1700 Analysis of samples Analysis of samples was adequately addressed.

830.1750 Certification of limits The certifie d limits have been adequately addressed.

830.1800 Analytical method The Anal ytical method is acceptable.

a MRIDs 479278-01 thru -17Prohydrojasmon (PDJ)

PC Code 028000 Biopesticides Registration Action Document

16

TABLE 2. Physical and Chemi cal Properties for PDJ a,b (40 CFR § 158.2030)

OCSPP Guideline No./Property Description of Result Methods

830.6302 Color EP: Clear with very slight yellow coloring.

TGAI: Light yellow and clear. Visual observation at room
temperature

830.6303 Physical State EP: Clear, homogeneous mobile liquid.

TGAI: Oily liquid. Visual observation at room
temperature

830.6304 Odor EP: Sweet, fruity, solvent-like.

TGAI: No odor.

830.6313 Stability Not required for EP.

TGAI: Stable at room temperature and at 54°C for 14 days. Stable in contact with iron, zinc, aluminum, and their
acetates at room temperature and at 54°C for 14 days.

Degrades at 342°C and above. OCSPP 830.6313

OECD No. 113, 1981

830.6314 Oxidation/Reduction: Chemical Incompatibility Not applicable, the product does not contain an oxidizing or reducing agent.

830.6315 Flammability EP: flashpoint = 33.0°C.

EP: flashpoint = 33.5°C.

Not required for TGAI. Tag closed cup

Setaflash closed cup

830.6316 Explodability Not applicable, the product is not potentially explosive and has no explosive

characteristics.

830.6317 Storage Stability EP: stable at room temperature

for 36 months.

Not required for TGAI. Stored in polyethylene

containers in the dark at room temperature, and analyzed for active ingredient content after

22 and 36 months.

830.6319 Miscibility Not applicable, the product is not an emulsifiable liquid and

is not to be diluted with petroleum solvents.

830.6320 Corrosion Characteristics EP: no change in appearance of

containers after 36 months of storage at room temperature in

the dark.

Not required for TGAI. Stored in polyethylene

containers in the dark at room temperature, and appearance of

the container was examined

after 22 and 36 months.

830.6321 Dielectric Breakdown Voltage Not applicable, the product is

not for use around electrical equipment.

830.7000 pH EP: 6.1

TGAI: Not applicable, the product is not dispersible in Method based on Notification No. 71 of the Ministry of Agriculture, Forestry, andProhydrojasmon (PDJ)

PC Code 028000 Biopesticides Registration Action Document

17

TABLE 2. Physical and Chemi cal Properties for PDJ a,b (40 CFR § 158.2030)

OCSPP Guideline No./Property Description of Result Methods

water. Fisheries (February 3, 1960)

830.7100 Viscosity EP: at 20°C, mean viscosity ranges from 23.9 mPa at a spindle speed of 3.0 rpm to 23.5 mPa at a spindle speed of 25.0 rpm. At 40°C, mean viscosity ranges from 8.9 mPa at a spindle speed of 8.0 rpm to 9.1 mPa at a spindle speed of 60.0 rpm.

Not required for TGAI. Brookfield DVII+Pro Viscometer using a ULA adapter and spindle

830.7200 Melting Range Not applicable, the EP and TGAI are liquids.

830.7220 Boiling Range Not required for EP.

TGAI: 318°C. Differential thermal analysis (OECD No. 103, 1995)

830.7300 Density/Relative Density/Bulk Density EP: specific gravity = 0.955 at

20°C.

TGAI: 0.974 g/cm 3 at 25°C. Hydrometer method (JIS K0061)

Pycnometer (OECD No. 109, 1995)

830.7370 Dissociation Constant in Water Not required for EP.

TGAI: indeterminate. Conductometric method (OECD No. 112, 1981)

830.7550 Partition Coefficient Not required for EP.

TGAI: Not applicable, the product is partially/completely

soluble in water.

830.7840 Water Solubility Not required for EP.

TGAI: 60.2 mg/L at 25°C. Flask method (OECD No. 105)

830.7950 Vapor Pressure Not required for EP.

TGAI: 0.0167±0.00017 Pa at

25°C.

0.324±0.0221 Pa at 50°C b

. Gas saturation method (OECD No. 104, 1995)

a Data from MRIDs 47927804-10, 47927812-17, 47927843

b Prohydrojasmon Technical (EPA File Symbol 62097-EI ) requirements satisfied w ith technical grade active ingredient (TGAI) data; BLUSH (EPA File Symbol 62097-EO) requirements satisfied with EP specific data.Prohydrojasmon (PDJ)

PC Code 028000 Biopesticides Registration Action Document

18

Table 3. Human Health Toxicity Data for Prohydrojasmon Technical (EPA File Symbol 62097-EI) (40 CFR § 158.2050)

OCSPP Guideline No. Results/Toxicity Category MRIDs Study Conclusion

Acute Oral Toxicity

OCSPP 870.1100 LD 50 > 5000 mg/kg

IV 47927818,

47927825 Acceptable

Acute Dermal Toxicity

OCSPP 870.1200 LD 50 > 2000 mg/kg

III 47927818,

47927826 Acceptable

Acute Inhalation Toxicity

OCSPP 870.1300 LC 50 > 5.0 mg/L

IV 47927818,

47927827 Acceptable

Primary Eye Irritation

OCSPP 870.2400 slight eye irritation

IV 47927818,

47927828 Acceptable

Primary Dermal Irritation

OCSPP 870.2500 No skin irritation.

IV 47927818,

47927829 Acceptable

Dermal Sensitization

OCSPP 870.2600 Not a dermal sensitizer 47927818,

47927830 Acceptable

90-day Oral Toxicity-Rat

OCSPP 870.3100 NOEL= 1,000 ppm (56.6-58.7 mg/kg/day) 47927831 Acceptable

90-day Inhalation Toxicity

OCSPP 870.3465 Waiver Request 4 8869007 Acceptable

90-day dermal toxicity

OCSPP 870.3250 Waiver Request 4 8869006 Acceptable

Prenatal Developmental Toxicity Study - Rat

OCSPP 870.3700 Maternal NOEL > 500 mg/kg/day Developmental NOEL > 500 mg/kg/day 47927832 Acceptable

Bacterial Reverse

Mutation Test

OCSPP 870.5100 There was no evidence of

induced mutant colonies over background 47927833 Acceptable

In Vitro Mammalian

Chromosome Aberration

Tests

OCSPP 870.5375 There was no evidence of

cells with chromosomal

abnormalities 47927834 AcceptableProhydrojasmon (PDJ)

PC Code 028000 Biopesticides Registration Action Document

19

Table 4. Human Health Toxicity Data for BLUSH (EPA File Symbol 62097-EO) (40 CFR § 158.2050)

OCSPP Guideline No. LD 50 MRIDs Study Conclusion Acute Oral Toxicity

OCSPP 870.1100 LD 50 >5000 mg/kg

IV 47927818,

47927819 Acceptable

Acute Dermal Toxicity

OCSPP 870.1200 LD 50 >2000 mg/kg

III 47927818,

47927820 Acceptable

Acute Inhalation Toxicity

OCSPP 870.1300 LC 50 > 5.0 mg/L

IV 47927818,

47927821 Acceptable

Primary Eye Irritation

OCSPP 870.2400 Acute symptoms

were observed after

test material was administered, but resolved by day 7. BLUSH produces

reversible intense eye irritation

III 47927818,

47927822 Acceptable

Primary Dermal Irritation

OCSPP 870.2500 No skin irritation.

IV 47927818,

47927823 Acceptable

Dermal Sensitization

OCSPP 870.2600 Not a dermal

sensitizer 47927818,

47927824 Acceptable

TABLE 5. Non-Target Organism Toxicity Data for Prohydrojasmon Technical (EPA File Symbol 62097- EI) (40 CFR § 158.2060)

OCSPP Guideline No. Results/Toxicology Category MRID Study Conclusion

850.1010 Acute Toxicity Test, Daphnids EC 50 = 9.54 mg/L.

Moderately toxic 47927838 Acceptable

850.1075 Acute Toxicity Freshwater Fish Cyprinus carpio 96 hr LC 50 = 3.3 mg/L. Moderately toxic 47927837 Acceptable

850.2100 Avian Acute Oral Toxicity Bobwhite ( Colinus virginianus ) LD 50 >2000 mg/kg

Practically non-toxic 47927835 Acceptable

850.2200 Avian Dietary Toxicity Japanese quail ( Colinus virginianus ) LC 50 >5000 ppm

Practically non-toxic 47927836 Acceptable

Honey bee Acute Oral Toxicity LC 50 > 100 ug ai/bee 47927838 Acceptable

850.4100 Seedling Emergence and Seedling

Growth ER 50 > 1,140 g ai/ha (> 456 g ai/A) 48869004 Acceptable

850.3020 Acute Contact Honeybees LD 50 = 0.129 ug ai/bee (0.116 – 0.148 ug ai/bee) 48869002 Acceptable

850.4150 Terrestrial Plant Vegetative Vigor a ER 50 > 1,140 g ai/ha (> 456 g ai/A) 48869005 Acceptable

a Performed on the EP, BLUSH (62097-EO)Prohydrojasmon (PDJ)

PC Code 028000 Biopesticides Registration Action Document

20 VIII. Appendix B. References

EPA (2013) Environmental Protection Agency (EPA) Risk Assessment: Request for new registration for prohydroj asmon technical and product registration

Section 3 for BLUSH 5.25% ai with tolerance exemption. May 12, 2013.Prohydrojasmon (PDJ)

PC Code 028000 Biopesticides Registration Action Document

21 IX. GLOSSARY OF ACRONYM S AND ABBREVIATIONS

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

CBI Confidential Business Information CFR Code of Federal Regulations

cm 3 cubic centimeter

CSF Confidential Statement of Formula °C degrees Celsius

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

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

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

L liter

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

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

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

MRID No. Master Record Identification Number mg milligram mPa millipascal

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

NE “No Effect” NIOSH National Institute for Occupational Safety and HealthProhydrojasmon (PDJ)

PC Code 028000 Biopesticides Registration Action Document

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

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

TGAI technical grade of the active ingredient ug microgram

USDA United Stat es Department of Agriculture

UV ultra-violet