BIOPESTICIDES REGISTRATION ACTION DOCUMENT



# Homobrassinolide PC Code 067700

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

( last updated April 2 8 , 2010 )

This document is for informational purposes only and is representative of the Agency’s justification in registering

products containing this active ingredient. This is not a legal document.Homobrassinolide Page 2 of 16

Biopesticides Registration Action Docum ent TABLE OF CONTENTS I. BACKGROUND : ................................ ................................ ................................ .................. 4 II. ACTIVE INGREDIENT OV ERVIEW ................................ ................................ ............... 5 III. REGULATORY BACKGROUND ................................ ................................ ..................... 5 A. Classification ................................ ................................ ................................ ........................ 5 B. Food Clearances and Tolerances ................................ ................................ ........................ 5 IV. RISK ASSESSMENT ................................ ................................ ................................ ........... 6 A. Active Ingredient Characterization ................................ ................................ .................... 6 B. Human Health Assessment ................................ ................................ ................................ .. 6 1. Toxicity ................................ ................................ ................................ ............................... 6 2. Dose Response Assessment ................................ ................................ ............................... 6 3. Food Quality Protection Act (FQPA) Considerations ................................ ................... 7 4. Occupational, Residential, School and Day Care Exposure and Ris k Characterization.............................................................................................8 5. Cumulative Effects................................................................................. 8 6. Risk Characterization..............................................................................8 C. ENVIRONMENTAL ASSESSMENT ................................ ................................ ................ 9 1. Nontarget Organism Toxicology ................................ ................................ ..................... 9 2. Environmental Fate and Ground Water Data ................................ ............................... 9 3. Ecological Exposure and Risk Characteriz ation ................................ ........................... 9 4. Endangered Species Assessment................................................................10 D. PRODUCT PERFORMANCE DATA (EFFICACY) ................................ ..................... 10 V. RISK MANAGEMENT DECI SION ................................ ................................ ................. 10 A. Deter mination of Eligibility for Registration ................................ ................................ .. 10 B. Regulatory Decision ................................ ................................ ................................ ........... 11 VI. TERMS AND CONDITIONS OF THE REGISTRATION( S) ................................ ....... 11 VII . APPENDIX A. Data Requirements (40 CFR Part 158) ................................ ................... 13 VIII. APPENDIX B. Product Specific Information ............ ............ .................. ..... ... 16 IX . APPENDIX C. References ................................ ................................ ................................ ... 16Homobrassinolide Page 3 of 16

Biopesticides Registration Action Docum ent BIOPESTICIDES REGISTRATION ACTION DOCU MENT TEAM Office of Pesticide Programs: Biopesticides and Pollution Prevention Division Biochemical Pesticides Branch (BPB) John Fournier Regulatory Action L eader Li nda Hollis Branch Chief Miachel Rexrode, Ph.D. Senior BiologistHomobrassinolide Page 4 of 16

Biopesticides Registration Action Docum ent I. BACKGROUND : The active ingredient, h omobrassinolide, is a plant growth regulator and a sy nthesized homologue of brassinolide, a naturally occurring brassinosteroid. Brassinosteroids are a gro up of st eroidal plant hormones first discovered in 1973, when it wa s shown that pollen from Brassica napus could promote stem elongation and cell divisions and that the biologically active molecule was a steroid. They

are ubiquitously

distributed in the plant kingdom. Since their discovery, over 70 brassinosteroids have been isolated from plants. The occurrence of these steroids have been demonstrated in various plant parts, such as pollen, flower buds, fruits seeds, vascular cambium, leaves, shoots and roots. Studies on higher plants suggest that these steroids play a critical role in a range of developmental processes (i.e. stem elongation, root growth, floral initiation, etc. Homobrassinolide is a white to pale yellow powder that gives off a mild, characteristic odor. Th is application is for uses as a plant growth regulator includ es all agronomic and horticultural crops such as agricultural crops, greenhouse food uses and non

- food crops, and aquatic food and non

- food crops

. The Biopesticides and Pollution Prevention Division (BPPD) has reviewed the data required to support the registration of this biochemical active ingredient, under Section 3(c)(5) of the Federal In secticide, Fungicide and Rodenticide Act (FIFRA). Product chemistry data requirements were satisfied by

acceptable guideline studies. Acceptable mammalian toxicology waivers and information from scientific literature w ere submitted to support registration of h omobrassinolide. Acceptable acute toxicity guideline studies were submitted for the active ingredient. E cological effects data requirements for h omobrassinolide are fulfilled by acceptable guideline studies and acceptable waivers to support the remaining Tier I and Tier II requirements. Based on the data available , EPA determined that no unreasonable adverse effects to the U.S. population and th e environment will result from the use of the active ingredient when label instructions are followed and good agricultural practices are employed. Laboratory studies indicate that the active ingredient is not toxic following oral, inhalation or dermal exp osure . Brassinosteroids are found in all plants and there are no reports of adverse effects following human exposure. Moreover, the pesticidal usage of this biochemical will not have any harmful environmental effects. Since brassinosteroids are ubiquito us in the plant kingdom, mammals, birds, fish, a quatic invertebrates, insects, and non

- target plants all have a long history of exposure to them

. Due to the negligible risk concerns when used as a plant growth regulator, h omobrassinolide meets the criteria as specified in §3(c)(5) of the Federal Insecticide, Fungicide and Rodenti cide Act (FIFRA) , as amended, and is thus eligible for unconditional registration. Itwas determined that the data/information submitted adequately satisfy applicable data requi rements at 40 C.F.R. Subpart U §158.2000

.Homobrassinolide Page 5 of 16

Biopesticides Registration Action Docum ent II. ACTIVE INGREDIENT OVERVIEW Common Name: Homobrassinolide Chemical Names: Homobrassinolide (2α,3α,22S,23S,24S)

- 2,3,22,23
- tetrahydroxy

- 24
-

ethyl

- β

- homo

- 7
- oxa - 5α
- cholestan

- 6
- one) Trade & Other Names: Homobrassinolide CAS Registry Number: 80483
- 89
- 2 OPP Chemical Code: 067700 Type of Pesticide: Plant Growth Regulator III. REGULATORY BACKGROUND On November 16, 2007, Repar Corporation of Silver Spri ng, Maryland, submitted an application for the registration of the manufacturing

- use product (MP) Homobrassinolide Technical (69361

- RT) containing 80% homobrassinolide. A notice of receipt of the application for registration of homobrassinolide as a new a ctive ingredient was published in the Federal Register on February 13, 2008 (7 3 FR 8312 ) , with a 30

- day comment period. Two comments were received following this publication , but neither was related to the registration of homobrassinolide as a new active ingredient. Neither comment opposed the registration of homobrassinolide or provided any substantive basis supporting that position. The comments both referenced an unrelated pesticide product not related to homobrassinolide. The comment also did not provide any data or information calling into question EPA's risk assessment. All comments have been included in the docket. Consistent with the Agency ’s new policy for making pesticide registration a ctions more transparent, EPA will provid e a 30
- day publi c comment period on the decision to regist e r Homobrassinolide

. A. Classification On April 9, 2002, the Biochemical Classification Committee determined that Homobrassinolide is a biochemical pesticide due to its mode of action as a plant growth regulator and natural occurrence in the environment

. B. F ood Clearances/Tolerances The applicant filed a petition (PP 7F7296) proposing to establish an exemption from the requirement of a tolerance for residues of Homobrassinolide in or on all food commodities. A notice of filing was published on February 13, 2008 (73 FR 8312).Homobrassinolide Page 6 of 16

Biopesticides Registration Action Docum ent IV. RISK ASSESSMENT A. Active Ingredient Characterization H omobrassinolide (2α,3α,22S,23S,24S)

- 2,3,22,23
- tetrahydroxy

- 24
- ethyl

- β

- homo

- 7
- oxa - 5α
cholestan

- 6
- one) is a sy

nthesized ho mologue of brassinolide, a naturally

- occuring brassinosteroid. Brassinosteroids are a class of plant poly hydroxysteroids that are ubiquitously distributed in the plant kingdom. These compounds, when applied to plants, improve plants’ quality and yield

. They have been further researched for stress

- protective properties (i.e. cold, heat, salt, and heavy

metal exposure). Homobrassinolide is a plant growth regulator that can control or regulat e the growth and development of all higher and lower plants. The proposed uses include all agronomic and horticultural crops such as agricultural crops, greenhouse food uses and non

- food crops, and aquatic food and non

- food crops

.

T he description s of the product formulation and production process , as well as the formation of impurities, were examined by the Agency and found to meet current standards. A preliminary analysis was conducted to determine h omobrassinolide content in five batches of the product, and the results were determined to be acceptable by the A gency . The analy

tical method used to determine the content of the active ingredient is also acceptable. Physical and chemical properties submitted for the active ingredient were found to be adequate. Refer to Table 1 in Appendix A for a summary of produ ct chemistry

data requirements. Refer to Table 2 in Appendix A for the summary of physical and chemical characteristics of h omobrassinolide

. All product chemistry

data requirements for registration of homobrassinolide have been satisfied . B. Human He alth Assessment 1. Toxicity Adequate mammalian toxicology data /information are available to support registration of homobrassinolide

. All toxicology data requirements for homobrassinolide have been satisfied. For more information regarding the toxic ity data requirements, refer to Table 3 in Appendix A

. 2. Dose Response Assessment No toxicological endpoints were identified; therefore, a dose respon se assessment was not required.Homobrassinolide Page 7 of 16

Biopesticides Registration Action Docum ent 3. Food Quality Protection Act (FQPA) Considerations a. Dietary Ex posure and Risk Characterization The applicant provided information on the risk of homobrassinolide to human s. Although the metabolism of brassinosteroids is poorly understood, these plant steroids appear to be metabolized in plants to produce inactive f orms through transformation in the side chain or in the steroid skeleton. Brassinosteroids are present in all plants, resulting in ubiquitous exposure to humans and other organisms through the food chain without causing harm. The endogenous levels are in parts per million (ppm ) to parts per billion (ppb ) levels (i.e. brassinosteroids levels in pollen have measured at 200 ppb). The applicant claims that the small quantity ( less than 20 grams per acre ) of homobrassinolide that is proposed for application as a plant growth stimulant is unlikely

to increase levels of brassininosteroids in the treated plants. They reason that the amount of exogenenous brassinosteroid that is applied to a crop plant will be metabolized as the plant grows. L evels in the human diet are , therefore, unlikely to be affected. Calculations suggests that human exposure to homobrassinolide is expected to be low , with 20 grams per acre equivalent to 0. 459 m illigrams per square foot

. Potential toxicity is low with an acute oral toxicity value of less than five grams per kilogram of body weight and acute inhalation value of 2.2 milligrams per liter . This suggests that risk from exposure is very low at 20 grams per acre
. E ven if the entire acre of exposed plants were consumed (unlikely ) b y an individual, the toxicity from homobrassinolide is more than ten times below the toxicity values noted above. The applicant has requested tolerance exemption for residues of homobrassinolide in or on crops and use sites. The registrant also request s waivers for all tests for determining the residues including the analy tical method. Based on the available data, the Agency determined that there are reasonable grounds (as noted above) for tolerance exemption for the proposed uses of homobrassinolide in/on all raw agricultural commodities. The Agency also accepts the registrant’s argument that for low homobrassinolide toxicity and exposure to humans and feels that exemption from the required tolerance of residues in or on raw commodities is warranted. b . Drinking Water Exposure and Risk Characterization No significant drinking water exposure or residues are expect ed to result from the usage of h omobrassinolide as a plant growth regulator. The active ingredient (AI) is intended for use as a foliar appl ication on food commodities and not to be applied directly to water. If used in accordance with EPA

- approved labeling, the AI is not likely to accumulate in drinking water. In the unlikely

event that exposure via drinking water occur s from accidental sprayi ng , the health risk would be minimal, based on the low acute oral toxicity and the long history

of human exposure to brassinosteroids without adverse effects. It also seems unlikely that homobrassino lide concentrations would exceed levels that are currently ubiquitous to plants. Although environmental f ate information is not available, the compound is not soluble in water (water solubility

3.18%), and the log P ow = 3.96 , which suggests moderate binding to soil and a low probability

of ground water contam ination

. As a result, dietary

and drinking water exposure to residue s of h omobrassinolide are expected to be minimal

.Homobrassinolide Page 8 of 16

Biopesticides Registration Action Docum ent
c . Acute and Chronic Dietary Risks for Sensitive Subpopulations , Particularly Infants and Children FFDCA section 408 provides that the Agency shall apply

an additional tenfold margin of exposure (safety

) for infants and children in the case of threshold effects to account for pre

- and post - natal toxicity

and the completeness of the database , unless the Agency determines that a different margin of exposure (safety ) will be safe for infants and children. Margins of exposure (safety ) are often referred to as uncertainty (safety ) factors. In this instance, based on all the available information, the Agency has concluded that there is reasona ble certainty

that no harm to infants and children or adults will result from the use of h omobrassinolide when label instructions are followed. 4. Occupational, Residential, School and Day Care Exposure and Risk Characterization
a. Occupational Exposu re and Risk Characterization The potential for dermal, eye, and inhalation exposure to h omobrassinolide for handlers and applicators is mitigated as long as products are used according to label directions. The Agency will require labels to include the appropriate signal word, re

- entry interval and precautionary statements, including the requirement for personal protective equipment, to mitigate any risk of exposure . b. Residential, School and Day Care Exposure and Risk Characterization No indoor reside ntial, school, or day care uses are currently

approved for products containing h omobrassinolide

. Section 408(b)(2)(D)(v) of the FFDCA requires that, when considering whether to establish an exemption from a tolerance, the Agency consider “available inform ation concerning the cumulative effects of [a particular pesticide's] residues and other substances that have a common mechanism of toxicity .'' These considerations include the possible cumulative effects of such residues on infants and children. 5 . Cumul ative Effects EPA has considered the potential for cumulative effects of h omobrassinolide and other substances in relation to a common mechanism of toxicity . However, because of its low toxicity to mammal s and because it is readily metabolized by

plants into inactive forms , the Agency does not expect any

cumulative or incremental effects from exposure to residues of h omobrassinolide when applied/used as directed on the label and in accordance with good agricultural practices. 6 . Risk Characterization The Agency

considered human exposure to h omobrassinolide in light of the relevant safety factors in FQPA and FIFRA. EPA determined that no unreasonable adverse effects to the U.S. population in general, and to infants and children in particular, will res ult from the use of h omobrassinolide when label instructions are followed.Homobrassinolide Page 9 of 16

Biopesticides Registration Action Docum ent C. ENVIRONMENTAL ASSESSMENT 1. Nontarget Organism Toxicology Adequate non

- target toxicology data/information are availa ble to support registration of h omobrassinolide

. All non

- target toxicology data requirements for h omobrassinolide have been satisfied. There are no concerns for any non - target organisms when h omobrassinolide is applied in accordance with EPA

- approved label use directions. Toxicity studies on mammals show prac tically

no toxicity , and avian species have been environmentally exposed to the active ingredient since brassinosteroids are found in all plants. Application of the product in the environment is expected to be low at twenty grams per acre, with potential exposure to avian species at less than one m illigram per square foot. Additionally, th e product will be sprayed, not applied as a granular, resulting in decreased exposure. No toxic effects have been identified for non - target birds, non

- target plants, an d non

- target soil organism such as earthworms. Although h omobrassinolide is slightly toxic to fish and moderately toxic to aquatic invertebrates in laboratory

testing, as a result of the rapid metabolism of h omobrassinolide by crop plants under approved c onditions of use, calculated Risk Quotients (RQs) for fish and aquatic invertebrates are well below any

L evels of Concern (LOCs) for threatened and endangered species. There are no concerns for non

- target insects. Only insects that feed directly

on treat ed plant foliage or roots will be directly

exposed to h omobrassinolide at levels that will be pesticidal. These insects, however, also have been environmentally exposed to the active ingredient since it is ubiquitous in all plants and plant products (i.e. pollen) . Due to the rapid metaboliz ation of homobrassinolide by

crops, honey

bees and other pollinators that feed on nectar, and predators of insect pests are unlikely

to consume enough of the active ingredient to cause adverse effects. For more information regarding the non

- target toxicity data requirements, refer to Table 4 in Appendix A. 2. Environmental Fate and Ground Water Data Homobrassinolide is a plant growth regulator that is ubiquitous in the plant kingdom and rapidly metabolized by

crop plants , making it unlikely that concentrations of the active ingredient would exceed level s naturally

found in plants. As a result, h omobrassinolide is not likely to persist in the environment. The compound is not soluble in water and binds moderately to soil, resulting in a low probability

of ground water contamination. 3. Ecological Exposure and Risk Characterization The potential for exposure to non

- target wildlife is minimal. Based on the results/information presented in the Environmental Fate an d Groundwater Data section above, it is highly unlikely that non

- target organisms, particularly aquatic organisms, would be exposed to potentially toxic levels of h omobrassinolide via runoff and/or movement through the soil. The active ingredient in ubiqu itous in the plant kingdom and plants rapidly metabolize h omobrassinolide into inactive forms when it is applied. No unreasonable adverse effects to the environment are expected from the use of h omobrassinolide when label instructions are followed.Homobrassinolide Page 10 of 16

Biopesticides Registration Action Docum ent 4. Endangered Species Assessment A non
- target organism hazard assessment and an Endangered Species Assessment ha ve been conducted to support registration of Homobrassinolide Technical (80% h omobrassinolide manufacturing

- use product)

. There are no concerns for non

- target mammals and birds, including threatened and endangered species. Toxicity to mammals is in the slight to practically non - toxic range (LD 50 >1000 to 5000 mg/kg). Moreover, as brassinosteroids are ubiquitous in the plant kingdom and are readi ly

metabolized by

plants when applied as a plant growth regulator, they are not likely to persist in the environment. Due to the ubiquitous nature of the active ingredient in the natural world, birds, mammals, and insects have all been environmentally exp osed with no reported adverse effects. Based on submitted laboratory studies, no concerns were identified for non - target aquatic organisms, including threatened and endangered species. Calculated Risk Quotients (RQs) fish and aquatic invertebrates are we ll below any L evels of Concerns (LOCs) for threatened and endangered species. Using the acute endangered species level of concern (LOC) of 0.05 and the default slope of 4.5 , the chance of an individual mortality for aquatic endangered species is ~ 1 in 41 0,000,000 and for terrestrial endangered species is ~ 1 in 294,000. Because h omobrassinolide is not toxic to non

- target organisms based on its use pattern and use instructions, EPA has determined it will have "No Effect" on any currently listed threatene d or endangered species or any designated critical habitat

. D. PRODUCT PERFORMANCE DATA (EFFICACY) Submission of product performance data (OPPTS 810.3000) is listed as a requirement for all pesticide products. Customarily , the Agency requires efficacy data to be submitted for review only in connection with the registration of products directly pertaining to the mitigation of disease bearing human health organisms and certain designated quarantine p ests, i.e., ticks, mosquitoes, fleas, Mediterranean fruit flies, gyp sy m oths, Japanese b eetles , etc. For a list of organisms considered by

the Agency

as “public health pests”, please refer to Pesticide Registration Notice 2002

- 1 (http://www.epa.gov/PR_No tices/pr2002

- 1.pdf ). V. Risk Management Decision A. Determination of Eligibility for Registration Section 3(c)(5) of FIFRA provides for the registration of new active ingredients if it is determined that (A) its composition is such as to warrant the proposed claims for it; (B) its labeling and other materials required to be submitted 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 criteria of the Eligibility Determination for Pesticidal Active Ingredients are satisfied by the science assessments s upporting products containing h omobrassinolide . Such products are not expected to cause unreasonable adverse effects, and are likely to provide protection as claimed when used according to label instructions. Therefore, h omobrassinolide is eligible for re gistration for the labeled uses.Homobrassinolide Page 11 of 16

Biopesticides Registration Action Docum ent B. Regulatory Decision EPA has determined that h omobrassinolide presents no issues of toxicological, ecological, or environmental concern. As discussed above, acute toxicity data for h omobrassinolide demonstrate that i t is either toxicity category IV or III. H omobrassinolide does not demonstrate subchronic or developmental toxicity, and it is not mutagenic or genot o xic. EPA has no concerns for any

non - target organisms exposed to h omobrassinolide in accordance with app roved label directions. EPA has not identified any toxic effects for non

- target mammals, birds, plants, aquatic, or soil organisms. T here are no concerns for any threatened and endangered species. G iven that h omobrassinolide has very low toxicity

and presents little if any

risk to non

- target organisms, EPA concludes that it is in the best interests of the public and the environment to issue the registration for h omobrassinolide without delay

. Consistent with the Agency ’s new policy for making these re gistration actions more transparent, EPA will provide a 30
- day public comment period on the decision to regist e r h omobrassinolide. The data submitted fulfill the re quirements of registration of h omobrassinolide for use on all agricultural commodities (inc luding vegetables, fruits, nuts, outdoor and greenhouse ornamental and food crops ) as a plant growth regulator

. Refer to Appendix B for product

- specific information. 1. Conditional/Unconditional Registration All data requirements have been met and E PA has determined that unconditional registration of h omobrassinolide is appropriate

. 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

- in the development, implementation, and enforcement of environmental laws, regulations, and policies. At this time EPA does not believe that use of pesticide products containing h omobrassinolide will cause harm or a disproportionate impact on at - risk communities. For additional information regarding environmental justice issues, please visit EPA’s website at: http://www.epa.gov/compliance/environmentaljustice /index.html

. VI . TERMS AND CONDITIONS OF THE REGISTRATION(S) The Agency

evaluated all of the data submitted in connection with the initial registration of h omobrassinolide and determined that these data are sufficient to satisfy current registration dat a requirements. No additional data are required to be submi tted to the Agency at this time. For new uses and/or changes to existing uses, additional data may be required. Not withstanding the information stated in the previous paragraph, it should be clearly understood that certain, specific, data are required to be reported to the Agency as a requirement for maintaining the Federal registration for a pesticide product. A brief summary of these ty

pes of data are listed below.Homobrassinolide Page 12 of 16

Biopesticides Registration Action Docum ent
A. Reporting of Adver se Effects Reports of all incidents of adverse effects to the environment must be submitted to the Agency under the provisions stated in FIFRA, Section 6(a)(2). B. Reporting of Hypersensitivity Incidents Additionally , all incidents of hy persensitivity

( including both suspected and confirmed incidents) must be reported to the Agency under the provisions of 40 CFR Part 158.2050(d).Homobrassinolide Page 13 of 16

Biopesticides Registration Action Docum ent VI I . Appendix A. Data Requirements (40 CFR Part 158 - Subpart U ) *NOTE: Master Record I dentification ( MRID ) numbers listed i n the following tables are representative of supporting data for the original registration of the product containing this active ingredient. Subsequent to this registration, there may be additional MRIDs that support registration of other products contain ing this active ingredient. TABLE 1. Product Chemistry Data Requirem ents for hom obrassinolide (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 impurities. 47185101
- 04

830.1700 Analysis of samples Submitted data satisfy the requirements for analysis of samples. 4 7185106
- 08 830.1750 Certification of limits Limits listed in the CSF are adequate / acceptable. 47185110
- 17 830.1800 Analytical method Acceptable. 47208901
- 02Homobrassinolide Page 14 of 16

Biopesticides Registration Action Docum ent

TABLE 2. Physical and Chemical Properties of hom obrassinolide (40 CFR § 158.2030) OPPTS Gui deline No. Property Description of Result MRID 830.6302 Color White to pale yellow 47185104
830.6303 Physical State Powder 47185104 830.6304 Odor Mild, characteristic odor (1% suspension in ultrapure water) 47208901 830.6313 Stability to Normal and E levated

Tem peratures, Metals and Metal I ons Not applicable 830.6315 Flammability Not flammable at temperatures up to 100 0 C 47185114 830.6317 Storage Stability Stable for 14 days at 54 + 2 0 C and 62% relative humidity. 47185113 830.6319 Miscibility Not applicable, product is not to be mixed with petroleum solvents. 830.6320 Corrosion Characteristics Calculated corrosion rates based on mean weight loss of coupons exposed to the product for 14 days: Copper

- 0.00142 mm/year Aluminum

- 0.0540 mm/year. 47 185115

830.7000 pH 7.65 (1g in 100 ml of water) 47185112 830.7050 UV/Visible Light Absorption ^max = 1.2458 at 202 nm (10 mg in 50 ml methanol

HCL) 47185116

830.7100 Viscosity Not applicable, product is a solid 830.7200 Melting Point/Range 116
- 118 0 C 47175106 830.7220 Boiling Point/Range Not applicable, product is a solid 830.7300 Density Density = 0.7 g/ml at ambient temperature 47185107 830.7520 Particle Size, Fiber Length and

Diameter Distribution 830.7550 830.7560 830.7570 Partition Coeff icient (n

Octanol/Water) Log P ow = 3.96 47185111

830.7840 Water Solubility 3.18% in water 95.89% in acetone 99.89% in ethanol 47185108

830.7950 Vapor Pressure N/A, product is a solid and does not vaporize 47208902Homobrassinolide Page 15 of 16

Biopesticides Registration Action Docum ent

T ABLE 3. Mam malian Toxicology Data Re quirem ents for homobrassinolide (40 CFR § 158.2050) Study/OPPTS Guideline No. Results Toxicity Category/Description MRID Acute oral toxicity (rat) (870.1100) > 5,000 mg/kg Acceptable IV 47185118 47208903 Acute dermal toxicity (rat) (870.1200) > 2,000 mg/kg Acceptable III 47185120 Acute inhalation toxicity (rat) (870.1300) >2.26 mg/L Acceptable IV 47185121 Primary eye irritation (rabbit) (870.2400) Mild irritation Acceptable III 47185122 Primary dermal irritation (rabbit) (870.2500) Not an irritant Acceptable IV 47185123 Dermal sensitization (guinea pig) (870.2600) Not a sensitizer Acceptable IV 47185124 Hypersensitivity incidents (885.3400) Sufficient information has been submitted to support the waiver. Waiver Request Acceptable 47185131 90
- Day oral toxicity (870.3100) > 1,000 mg/L Acceptable III 47208906 90
- Day dermal toxicity (870.3250) Sufficient information has been submitted to support the waiver. Waiver Request Acceptable 47185136 90
- Day inhalation toxicity (870.3465) Sufficient information has been submitted to support the waiver. Waiver Request Acceptable 47185137 Developmental toxicity (870.3700) Sufficient information has been submitted to support the waiver. Waiver Request Acceptable 47185139 Bacterial Reverse Mutation Assay (870 .5100) Sufficient information has been submitted to support the waiver. Waiver Request Acceptable 47185139 In vivo Mammalian Cytogenetics

Erythrocyte Micronucleus Assay (870.5395) Not Cytotoxic Acceptable 47185127

In vitro Mammalian Cell Gene Mutation Te sting (870.5300) No potential for genotoxicity Waiver Request Acceptable 47185132

Mammalian Bone Marrow Chromosomal Aberration Test (870.5385) No chromosome aberrations in mice treated up to a single oral dose of 2000 mg/kg body

weight. Acceptable No Chr omosomal Aberrations 47208905

DNA Synthesis in Mammalian Cells in Culture (870.5550) Not required Waiver not needed 47185133

In vitro Mammalian Chromosomal Aberration Test (870.5375) Sufficient information has been submitted to support the waiver. Waiver Request Acceptable 47185134 Immunotoxicity (880.3550) No changes in organ weights or differential white blood cell counts of the treated animals which would indicate potential interference with normal immune function. Waiver Request Acceptable 47185135

Immune Response (880.3800) Sufficient information has been submitted to support the waiver. Waiver Request Acceptable 47185140 Chronic Exposure Sufficient information has been submitted to support the waiver. Waiver Request Acceptable 47185141 Carcinogen icity (870.4200) A carcinogenicity test is not required. Waiver not needed 47185142Homobrassinolide Page 16 of 16

Biopesticides Registration Action Docum ent

VII I . Appendix B. Product specific information is not available at this time as there are no currently registered products containing this active ingredient. When products containing homobrassinolide are registered with EPA, this document will be amended to include links to product specific information

. IX. Appendix C . REFERENCES Bajguz, A., 2000. Effect of brassinosteroids on nuclear acids and protein content in cultured cells of chlorella vulga ris. Plant Physiol. Biochem . 38, 209 - 215. Catterou, M., F. Dubois, H. Schaller, L . Aubanella, B. Vilcol, B. S. Sangwan

-Norrel, R.S. Sangwan, 2001. Brassinosteroids microtubules and cell elongation in Arabidopsis thaliana. II. Effects of brassinosteroids on microtubules and cell elongation in the b ull mutant. Planta , 212, 673 - 683. IE CVI .I

– In dividual Effects Chance Model Version 1.1. 2004. USEPA/OPP/EFED Seeta S.R.R., B.V.Vardhini, E. Sujatha, S. Anuradha. 2002. Brassinosteroids

- A new class of phy tohormones. Current Science , 82:12391245
. TABLE 4. Nontarget Organism Toxicity R equirem ents for active ingredient (40 CFR § 158.2060) Study/OPPTS Guideline No. /MRID No. Results Toxicity Category/Description MRID Avian acute oral toxicity Colinus virginianus (850.2100) Sufficient information has been submitted to support the waiver. Practically non

- toxic based on waiver information 47185143
Avian dietary toxicity Colinus virginianus (850.2200) Sufficient information has been submitted to support the waiver. Practically non

- toxic based on waiver information 47185144
Aquatic invertebrate acute toxicity ( Daphnia magna ) (850.1010) 48
- hr EC 50 = 8.9 mg/L Moderately Toxic 47185130

Freshwater fish LC 50 ( Oncorhynchus mykiss ) (850.1075) 96
- hr LC 50 = 24.56 mg/L 96
- hr LC 50 = 14.38 mg/L Slightly Toxic 47185129

Non
- target plant studies (850.4000

- 4800, as applicable) Sufficient information has been submitted to support the waiver. Waiver Request Acceptable 47185145 Non
- target insect testing (880.4350) Sufficient information has been submitted to support the waiver. Waiver Request Acceptable 47185146 Acute oral (mouse) toxicity ( 870.1100 ) LD 50 = >5000 mg/kg for female IV 47208903 90
- Day Oral Feeding (rat) (870.3100) NOAE L 1000 mg/kg/day No subchronic oral toxicity 47208906