BIOPESTICIDE REGISTRATION ACTION DOCUMENT Draft for Public ParticipationProcess

Laminarin
PC Code: 123200

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

Las t updated - November 30, 2009Laminarin Page 2

Biopesticide Registration Action Document TABLE OF CONTENTS I. EXECUTIVE SUMMARY II. ACTIVE INGREDIENT OVERVIEW III. REGULATORY BACKGROUND IV. RISK ASSESSMENT A. PRODUCT ANALYSIS ASSESSMENT 1. Product Chemistry and Composition 2 . Analysis and Certification of Limits 3. Physical and Chemical Characteristics B. HUMAN HEALTH ASSESSMENT 1. Toxicological Hazard Assessment 2. Dose Response 3. Dietary Exposure and Risk Characterization 4. Drinking Water Exposure and Ri sk Characterization 5. Ac ute and Chronic Dietary Exposure and Risks for Sensitive Subpopulations, Particularly Infants and Children 6. Occupational, Residential, School, and Daycare Exposure and Risk Characterization 7. Aggregate Exposur e from Multiple Routes Including Dermal, Oral, and Inhalation 8. Cumulative Effects 9. Risk Characterization C. ENVIRONMENTAL ASSESSMENT 1. Summary of Non - Target Organism Testing and Waiver Rationales 2. Environmental Effects Conclusion s 3. Threatened and Endangered Species Assessment V. ENVIRONMENTAL JUSTICE VI. RISK MANAGEMENT AND REGISTRATION DECISIONS A. DETERMINATION OF ELIGIBILITY B. REGULATORY DECISION C. LABELING VII. ACTIONS REQUIRED BY THE REGISTRANT A. REPORTING OF ADVERSE EFFECTS AND HYPERSENSITIVITY INCIDENTS VIII. GLOSSARY OF ACRONYMS AND ABBREVIATIONS IX. BIBLIOGRAPHY STUDIES SUBMITTED IN SUPPORT OF THIS REGISTRATION A. STUDIES SUBMITTED IN SUPPORT OF THIS REGISTRATION B. EPA RISK ASSESSMENT MEMORANDA APPENDIX - BIOCHEMICAL PESTICIDE DATA REQUIREMENTSLaminarin Page 3

Biopesticide Registration Action Document

BIOPESTICIDES REGISTRATION ACTION DOCUMENT TEAM

Office of Pesticide Programs Biopesticides and Pollution Prevention Division Biochemical Pesticides Branch (BPB) Chris Pfeifer Regulatory A ction Leader Linda Hollis Branch Chief Miachel Rexrode, Ph.D Senior Biologist Russell Jones, Ph.D Senior BiologistLaminarin Page 4

Biopesticide Registration Action Document I. EXECUTIVE SUMMARY Laminarin is a naturally

occurring pol ys accharide carboh ydrate (oliggosaccharide) found in all edible plants. It is a major constituent in cereal grains, and is consumed as an intentionally added ingredient in man y dietary supplements and texturing agents. Accordingl y, it is a regular part of the human diet. Laminarin is ty pica lly extracted from brown algae, where it is present in great quantit y as a storage glucan

– a carboh ydrate food reserve which can be converted to glucose when necessary . The extraction results in a low - odor white powder, which is extremely nutrient rich. Besides being the source for this biochemical pesticide, this algal extract is also a regular ingredient in the Japanese diet. As a biochemical active ingredient, L aminarin stimulates the natural d efense reactions of agricultural crops such as fruiting vegetables, tomato, eggplant, pepper, zucchini, cucurbits, watermelon, melons, grape, apple, pear, and strawberries against such disease organisms as gray mold, powdery

mildew, downy

mildew, fire blight, and bacterial spot. As a naturall y occurring oligosaccharide, residues of the active ingredient are undistinguishable from other naturall y occurring plant oligosaccharides. In addition to our long history of consumption of Laminarin without known tox icological effect, all the information submitted to the Agency

in conjunction with this exemption from a requirement of tolerance confirms that Laminarin is virtually non - toxic and poses no dietary risks to humans. Because Laminarin is considered to be “toxicologically innocuous,” no residue studies are required to support an exemption from the requirement of a tolerance. La minarin’s low toxicity profile notwithstanding, another justification for this exemption from the requirement of a tolerance is the unlikelihood of residues for this biochemical pesticide. Laminarin is intended for application as a S ys temic Acquired Resistance (SAR) inducer

– a preventative mode of action. As such, it is applied early in a crop’s life cycle

– in its growing stages - to help build immunity to disease organisms such as mold and bacterial infection. And as a biochemical, it biodegrade s rapidly . Data indicate that the active ingredient is more than 65% biodegraded after two weeks (MRID 47264954). Calculations indicate that it would be largel y biodegraded long before any final application would be practicable. Accordingly , no significant exposures are expected at the time of harvest. Acute, subchronic and developmental studies submitted in the application for registration provided sufficient information to satisfy all mammalian toxicology data requirements. No toxicological endpoints were established, and no adverse effects were observed with regard to mammalian health. No dietary

risks are expected with regard to the use of the active ingredient Laminarin. Significant dietary

exposures (including exposures via drinking water) are not expected for the active ingredient Laminarin. In the event of dietary exposure, the toxicological data demonstrate that Laminarin is not toxic or pathogenic to mammals. It is a regular constituent of the human diet; and there have been no health effects associated with its consumption by people . Furthermore, all data demonstrate that n o acute, sub - chronic, chronic, immune, or endocri ne disrupting effects are associated with the use of the active ingredient. Accordingl y, no harm toLaminarin Page 5

Biopesticide Registration Action Document infants, children, and the general U.S. population is anticipated with regard to dietary exposure. Because of the nontoxic profile and the lack of expected residue of the active ingredient, the risks associated with the proposed food uses of this active ingredient are expected to be negligible. The potential for aggregate, non - occupational exposure is expected to be insignificant as the active ingredient is largely biodegraded within two weeks, and applications of Laminarin occur earl y in the growing season . Moreover, given a lack of acute toxicological endpoints and because Laminarin is not known to share an y structural similarity to an y chemicals with c ommon mechanisms of toxicity , the likelihood of risks resulting from such de minimus exposures is negligible. Non - target organism and environmental fate data requirements were satisfied through a submission of studies. Laminarin occur s naturall y in the t errestrial environment, and is not associated with an y known detrimental effect. All information available to the Agency validates a non - toxic mode of action, and a lack of adverse effect relative to non - target organisms. In accordance with T - REX M odel , the Individual Effects Chance Model Version 1.1 and the non - target data submitted, the Agency has made a “No Effect” (NE) determination for direct and indirect effects to an y listed threatened and endangered species and their habitat as a result of the proposed uses of Laminarin . On October 1, 2009, EPA announced a new policy to provide a more meaningful opportunit y for the public to participate on major registration decisions before they occur. According to this new policy , EPA intends to provide a public comment period prior to making a registration decision for, at minimum, the following t ypes of applications: new active ingredients, first food use, first outdoor use, and first residential use. Consistent with the new policy of making registrat ion actions more transparent, Laminarin is subject to a 30 day

comment period as a “new active ingredient” whose registration would result in a “first outdoor use” and a “first food use .” While a final decision on registration is contingent upon review an d consideration of public comments, EPA presently believes that based on the risk assessment and information submitted in support of the registration of Laminarin that it is in the best interests of the public and the environment to issue the registration for Laminarin . The basis for this preliminary decision can be found in the risk assessment for Laminarin, which is characterized in this BRAD. As discussed above, acute toxicity data for Laminarin indicate a nontoxic profile. Laminarin does not demonstr ate subchronic or developmental toxicity , and it is not mutagenic or genotoxic. EPA has no concerns for an y non - target organisms exposed to Laminarin in accordance with approved label directions. EPA has not identified any toxic endpoints for non - target mammals, birds, plants, aquatic, or soil organisms. Nor are there concerns for an y threatened and endangered species. Thus, given that Laminarin has very low toxicity , and presents little if any risk to non - target organisms, and data confirm its effective nessLaminarin Page 6

Biopesticide Registration Action Document as a Sy stemic Acquired Response (SAR) Inducer, EPA concludes that it is in the best interests of the public and the environment to issue the registration for Laminarin . EPA reviewed data requirements for granting registration under Section 3(c)(5) of the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA). It was preliminarily determined that the data/information submitted fulfilled current data requirements (refer to 40 CFR Subpart U § 158.2000). If the Agency receives comments during the 30 day public comment period that inform EPA’s initial decision, EPA will address such new information and take appropriate action. II. ACTIVE INGREDIENT OVERVIEW Common Name: Laminarin Chemical Names: O ligosaccharide, Poly saccharide Carbohydrate, Glucan Trade & Other Names : Laminarin CAS Registry Number: 9008 - 22 - 4 OPP Chemical Code: 123200 Type of Pesticide: SAR Inducer III. REGULATORY BACKGROUND On July 31, 2008, EPA published in the Federal Register (Volume 74, Number 49) a notice announcing that Laboratoires Goemar SA, Z.AC La Madeline, Avenue General Patton, 35400 Saint - Malo, France c/o SciReg, Inc. 12733 Director's Loop, Woodbridge, VA 22192 , submitted an application to register a pesticide product (EPA File Sy mbol 83941 - E ) containing a new active ingredient ( Laminarin) not included in an y currentl y registered products . On March 16, 2009, EPA published in the Federal Register (Volume 74, Number 49) a notice announcing that Laboratoires Goemar SA, Z.AC La Madeline, Avenue G eneral Patton, 35400 Saint - Malo, France c/o SciReg, Inc. 12733 Director's Loop, Woodbridge, VA 22192 , submitted an application proposing to establish an exemption from the requirement of a tolerance for residues of the biochemical pesticide, Laminarin, in or on all food commodities (PP# 7E7276). No comments were received following the publications of either notice. A. CLASSIFICATIONLaminarin Page 7

Biopesticide Registration Action Document Laminarin is well recognized as a naturall y occurring pol ys accharide carbohydrate present in most plants. With regard to its active properties, it is considered to be a SAR inducer, bolstering plant defense mechanisms, protecting plants against attacks from mold, bacteria and fungi. It does not work directly

against pests, and is not associated with an y toxic mode of action. A ccordingl y, Laminarin is considered to be a biochemical pesticide due to its nontoxic mode of action to the target pest, natural occurrence in the environment, and its history of exposure to humans and the environment without known toxicity . B. FOOD CLEARAN CES/TOLERANCES This active ingredient is being preliminarily supported for food use. The Agency ’s risk assessment finds no evidence of dietary risk and supports Pesticide Petition# 7E7276, which proposes to establish an exemption from the requirement of a tolerance for residues of the biochemical pesticide, Laminarin, in or on all food commodities IV. RISK ASSESSMENT On October 26, 2007, the Agency issued a Final Rule in the Federal Register on the data requirements to support registration of biochemical and microbial pesticides, and updated the definitions for biochemical and microbial pesticides ( 72 FR 61002 ). The rule became effective on December 26, 2007. The data and information evaluated for this Biopesticides Registration Action Document (BRAD) were considered in light of these requirements. The classifications that are found for each data submission are assigned b y EPA science rev iewers and are an indication of the usefulness of the information contained in the documents for risk assessment. A rating of “ACCEPTABLE” indicates the study is scientifically

sound and is useful for risk assessment. A “SUPPL EMENTAL” rating indicates the data provide some information that can be useful for risk assessment. The studies may have certain aspects determined not to be scientifically acceptable (“SUPPLEMENTAL: UPGRADABLE”). If a study is rated as “SUPPLEMENTAL: UPGRADABLE,” the Environmental Pro tection Agency alway s provides an indication of what is lacking or what can be provided to change the rating to “ACCEPTABLE.” If there is simply a “SUPPLEMENTAL” rating, the reviewer will often state that the study

is not required by

the current 40 CFR Part 158. Both “ACCEPTABLE” and “SUPPLEMENTAL” studies may be used in the risk assessment process as appropriate. An “UNACCEPTABLE” rating indicates that new data need to be submitted. For the acute toxicity

data requirements, toxicity categories are assigne d for providing the appropriate precautionary labeling statement, based on the hazard(s) identified from studies and/or other information submitted to the Agency in support of a pesticide registration. The active ingredient or particular product is classi fied into Toxicity Category I , II, III, or IV, where Toxicity Category Iindicates the highest toxicity and Toxicity

Category IV indicates the lowest toxicity .Laminarin Page 8

Biopesticide Registration Action Document A. PRODUCT ANALYSIS ASESSMENT 1. Product Chemistry and Composition Laminarin is a naturally

occurring oligosaccharide that can be found in most plants. It serves plants as a storage glucan

– a carboh ydrate food reserve, which breaks down into glucose and provides plants energy

i n times of stress. Laminarin extract is derived from brown algae (Laminara digitata ), and is a low - odor white powder. Because of its nutrient richness and starch y character, Laminarin extract is commonly used as a dietary supplement, a food texturing age nt and an ingredient in some ethnic cuisines. All product chemistry

data requirements for Laminarin have been satisfied. As an active ingredient, Laminarin extract is indistinguishable from the oligosaccharide that is produced naturally in pants. The e xtract has a high degree of purity and contains no impurities of toxicological significance. All data requirements for phy sical and chemical characteristics have been adequatel y addressed. 2. Analysis and Certification of Limits The submitted data satisfied the requirement for Analy sis and Certification of L imits. Five batch anal ys es and the anal yt ical method used to determine the purity of Laminarin were examined and determined to be acceptable by the Agency . The certified limits for the active and inert ingredients fall within the ranges specified b y OPPTS Guideline 830 - 1750 . 3. Physical and Chemical Characteristics The Agency

has determined that the submitted data adequately describe the phy sical and chemical characteristics of Laminarin . Refer to Table 1 in Appendix A for The Series 830 phy sical and chemical properties. B. HUMAN HEALTH ASSESSMENT 1. Toxicological Hazard Assessment Adequate mammalian toxicology studies were provided in support of the registration of Laminari n for each data requirement . Acute toxicology data for Laminarin indicates that the active ingredient is virtually non - toxic to mammals, and that there are no toxicological endpoints relative to the use of Lamanarin as a SAR inducer. Accordingl y, the data submitted demonstrate that the proposed uses of Laminarin pose no significant risks to human health and support a finding of reasonable certainty that no harm to the general U.S. population, including infants and children, will result from exposure to thi s active ingredient.Laminarin Page 9

Biopesticide Registration Action Document Refer to Table 2 in Appendix A for a summary of the Toxicity

Data Requirements for this food use active ingredient.

a. Acute Toxicity

– Tier I (40 CFR § 158.2050) Acute Oral Toxicity

– Rat [OPPTS Guideline 870.1100; Master Rec ord Identification (MRID) Numbers (Nos.) 47264930 and 47264943 ] : An acute oral toxicity

study shows that the active ingredient Laminarin has an LD 5 0 of greater than 2 000 mg/Kg in rats. This was the maxi mum dose rate. T here were no observed toxicological effects on the test subjects at the maximum dose. The stud y supports the finding that this active ingredient poses no significant human health risk with regard to food uses. The stud y was found “ACCEPTABLE” and Laminarin was classified as TOXICITY CATE GORY III for this route of exposure when used as a SAR inducer. Acute Dermal Toxicity

– Rabbits (OPPTS Guideline 870.1200; MRID Nos. 47264931 and 47264974 ) : An acute oral toxicity

study shows that the active ingredient La minarin has an LD 5 0 of greater than 5000 mg/Kg in rats, which is considered to be virtually non - toxic . Data substantiate the active ingredient’s relative dermal non - toxicity to both occupational users and the general public. The study was found “ACCEPTABLE” and Laminarin was classifie d as TOXICITY CATEGORY IV for this route of exposure when used as a SAR inducer. Acute Inhalation Toxicity (OPPTS Guideline 870.1300; MRID Number (No.). 47264932) : An acute oral inhalation study shows that the active ingredient Laminarin has an LC 5 0 of g reater than 1.02 mg/L in rats, which shows no significant inhalation toxicity . This was the maximum dose rate, and no toxicological effects were observed on the test subjects. The study was found “ACCEPTABLE” and Laminarin was classified as TOXI CI TY CAT EGORY III for this route of exposure when used as a SAR inducer. Primary Eye Irritation (OPPTS Guideline 870.2400; MRID Nos. 47264933 and 47264976 ) : A primary ey e irritation study

on rabbits demonstrated Laminarin to be non - irritating . There were no o bserved effects for this route of exposure relative to the use of Laminarin. The study was found “ACCEPTABLE” and Laminarin was classified as TOXI CI TY CATEGORY IV for this route of exposure when used as a SAR inducer. Primary Dermal Irritation (OPPTS Guideline 870.2500; MRID No. 47264934 ) : A skin irritation study on rabbits demonstrated that Laminarin was not irritating to the skin. The findings are consistent with the other dermal studies and confirm that L aminarin is not toxic through this route of exposure. The study was found “ACCEPTABLE” and Laminarin was classified as TOXICITY CATEGORY IV for this route of exposure when used as a SAR inducer. Skin Sensitization (OPPTS Guideline 870.2600; MRID Nos. 47264935 and 47264978 ) : Data indicate Laminarin is not a dermal sensitizer. However, any reported incidents may

cause this position to be reconsidered.Laminarin Page 10

Biopesticide Registration Action Document Subchronic Testing (OPPTS Guideline 870.3100, 870.3250, 870.3465; MRID Nos. 47264937 , 47264938 and 47264939

) : In accordance with footnote seven and eight in the Biochemical Pesticides Human Health Assessment Data Requirements table in 40 CFR § 158.2050, subchronic dermal and subchronic inhalation testing were not required for a lack of exposure. Three subchronic oral tests were submitted in suppo rt of Laminarin’s food use. These studies satisfy the data requirement for subchronic oral testing and indicate that Laminarin has no subchronic toxicological effect through the oral route of exposure. A 28 - day oral toxicity

study found no toxicological e ffects regarding mortalit y, clinical observations, neurotoxicity assessment, body

weight, food consumption, hematology , clinical chemistry, organ weights, and macroscopic or microscopic observations. The NOELwas determined to be 1,000 mg/kg/day . A 90 - day oral toxicity

study found no statistical difference in hematology , clinical chemistry , or urinaly sis between test subjects and the control. The NOEL was determined to be 1,000 mg/kg/day . Another 90 - day oral toxicity

study also found no statistical diffe rence in hematology , clinical chemistry , or urinal ys is between test subjects and the control. And the NOEL was again determined to be 1,000 mg/kg/day. All subchronic oral toxicity studies indicate that Laminarin is not subchronically toxic through the or al route of exposure. Developmental Toxicity (OPPTS Guideline 870.3700; MRID Nos. 47264940 and 47264941 ) : Data submitted to the Agency satisfy the data requirement and support the Agency ’s conclusion that there is no risk of developmental toxicity assoc iated with the new food uses. A prenatal developmental toxicity

study on rats found no significant reproductive effects or fetal abnormalities, and established a NOAEL of 1,000 mg/kg/day . The findings suggest negligible risk with regard to developmental toxicity . Mutagenicity Testing (OPPTS Guidelines 870.5100, 870.5300, 870.5375; MRID Nos. 47264942, 4726493 and 47264944

) : Three genotoxicity

studies (a Bacterial Reverse Mutation Test, and an In Vitro Mammalian Cells in Culture Assay) were performed on the active ingredient Laminarin and satisfy

the data requirement . The Reverse Mutation Assay showed that the Laminarin did not induce mutant colonies over expected background levels. The In Vitro Mammalian Cells in Culture Assay

demonstrated that Laminarin did not damage to chromosomes or the mitotic apparatus of bone marrow cells . These mutagenicity studies are sufficient to confirm that there are no expected dietary , occupational, or non - occupational risks of mutagenicity with regard to Laminarin. b. Ac ute Toxicity

– Tier II and Tier III (40 CFR § 158.2050) The Tier II studies listed below were the onl y higher Tier studies required for Laminarin. No other studies were required based on a lack of acute toxicity in the Tier I studies and a lack of exposure relative to its use pattern as a SAR inducer Developmental Toxicity (OPPTS Guideline 870.3700; MRID No. 4726494 1 ) : Tier II data are required on the active ingredient for developmental toxicity if there might be regular exposure toLaminarin Page 11

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women. In that case , a second prenatal study using a different test subject is required . A second prenatal developmental toxicity study on rabbits also found no significant treatment - related reproductive effects or fetal abnormalities, and confirmed a NOAEL of 1,000 mg/kg/d ay . Data submitted to the Agency

confirm that Laminarin poses negligible risk with regard to developmental toxicity . Mutagenicity Testing (OPPTS Guidelines 870.5385; MRID No. 47264944 ) : Tier II data are required on the active ingredient for mutagenicity testing for the active ingredient. A bone Marrow Micronucleus Assay indicated that n o toxicity was noted in either sex at any dose up to the limit dose of 2000 mg/kg . This mutagenicit y s tudy , in conjunction with the Tier I mutagenicity

studies, satisfies the data requirement for mutagenicit y testing and is sufficient to confirm that there are no expected dietary , occupational, or non - occupational risks of mutagenicity

with regard to L aminarin. Immunotoxicity Testing (OPPTS Guidelines 880.3550; MRID No. 47 264945 ) : A w aiver request was accepted for immunotoxicity for the following reasons: 1) The potential for an y immunotoxic effect is precluded b y the Laminarin’s biodegradability . 2) Laminarin is not structurally

related to any

known immunotoxic chemical . 3) There is a long history of the consumption of L aminarin without known immunotoxicological incident. 4) The toxicological profile in acute toxicological studies, subchronic studies and developmental studies does not suggest an y immunotoxicity . All information points to the lack of dietary risk posed by

the immunotoxicity

of Laminarin residues, and supports the exemption from the requirement of a tolerance. c. Effects on the Endocrine System EPA will issue test orders between today and February 2010. The schedule for issuance of test orders, and details regarding status will be available at http://www.epa.gov/endo/ . EPA has also established a docket for the test orders in www.regulations.gov under docket number EPA - HQ OPP - 2009 - 0634. Data re quired under the test orders will provide information to help EPA identify whether chemicals have the potential to interact with the estrogen, androgen, and/or thy roid hormone sy stems, which regulate growth, metabolism, development, and reproduction. The data generated from the screens will provide robust and sy stematic scientific information that will help EPA identify

whether additional testing is necessary . Laminarin is a naturally

occurring carboh ydrate present in our fruits and vegetables. To date, there is no evidence to suggest that our natural exposure to Laminarin affects the immune sy stem, functions in a manner similar to any known hormone, or that it acts as an endocrine disruptor. Moreover, the use of Laminarin is not expected to result in any s ignificant exposures, effectivel y obviating an y opportunity for negative effects on humans or the environment. Therefore, it is unlikely

that Laminarin will have estrogenic or endocrine effects.Laminarin Page 12

Biopesticide Registration Action Document Because there is no available evidence demonstrating that Laminarin is an endocrine disruptor, the Agency

is not requiring information on the endocrine effects of Laminarin at this time. However, the Endocrine Disruption Screening Program (EDSP) has established a protocol, which guides the Agency in selecting s uspect ingredients for review; and the Agency reserves the right to require new information, should the program require it. Presently , based on the lack of exposure and the negligible toxicity profile of the extract, no adverse effects to the endocrine or immune sy stems are known or expected. 2. Dose Response Assessment No toxicological endpoints were identified; therefore, a dose response assessment was not required. 3. Dietary Exposure and Risk Characterization Exposure to residues of Laminarin on foods is expected to be negligible; and even in the event of dietary exposure, no dietary

risks are anticipated. Data submitted to the Agency show that Laminarin is 65% to 71% biodegraded within two weeks, and that it hydroly zes very rapidly into glucose. Because applications tend to occur earlier in the growing season (due to its mode of action as a SAR inducer), and given its short - lived presence on crops, no significant pesticidal residues are anticipated for harvested foods. E ven in the ev ent of exposure to residues, however, no dietary

risks are anticipated. Acute, subchronic, and teratogenicity studies support its non toxic profile. It is already present in the human diet

– especiall y in cereal grains - without any known detrimental eff

ect. Furthermore, it is approved by US FDA as a food additive, a dietary supplement and a texturing agent in processed foods in quantities greater than any expected pesticidal residues. T here is no information in the public literature suggesting any heal th issues to either animals or plants relative to this compound. In sum, no dietary exposure is expected; and an y potential dietary exposures would not be expected to pose any quantifiable risk, due to its nontoxic profile. 4. Drinking Water Exposure Risk Characterization Residues of Laminarin are not expected to be present in drinking water. Applications of Laminarin are made directly to terrestrial crops. These residues biodegrade rapidl y, and are not expected to percolate through soil. Even in the event of an errant spray drift or an extraordinary rainfall event, Laminarin does not persist in water due to its rapid hydrol yz ation into glucose. Moreover, risks from a miniscule aquatic exposure would be negligible, given Laminarin’s nontoxic prof

ile. Altogether, drinking water exposure is not expected to pose an y quantifiable risk due to a lack of residues, and the nontoxicity of Laminarin. 5. Acute and Chronic Dietary Exposure and Risks for Sensitive Subpopulations, Particularly Infants and C hildrenLaminarin Page 13

Biopesticide Registration Action Document Dietary exposure to humans, including infants and children, are considered negligible with regard to the pesticidal use of Laminarin. Because Laminarin is mostly biodegraded within two weeks and applications of Laminarin tend to occur earlier in the growing season with a minimum of ten day intervals between applications , no significant residues of Laminarin are expected on foods. Additionally , Laminarin is known to hydroly ze in water relativel y rapidly , and so what few residues might exist at harvest would be degraded into glucose during processing. In the event that there are an y residues, a cute toxicity studies indicate that Laminarin has negligible toxicity . It is ubiquitous in nature and present in all edible plants, and there is no history of toxicological incident involving its consumption. Its use is approved b y FDA as a food additive, a dietary supplement and as a texturing agent for processed foods. While no dietary exposures are expected, the Agency has determined there is a reasonab le certainty of no harm to the general US population, including infants and children, from exposure to this active ingredient. 6. Occupational, Residential, School and Day Care Exposure and Risk Characterization As an agricultural pesticide, some occupational exposure to Laminarin can reasonabl y be expected. Such occupational exposures are expected to be in significant because - by virtue of Laminarin’s mode of action as A SAR inducer - applications are directed and infrequent . The insignificance of an y exposure is even more pronounced for residential, school, or daycare are as . E ven in the event of incidental exposure, health risks to humans, including infants and children, are considered negligible , given Laminarin’s nontoxic profile.

a. Occupat ional Exposure and Risk Characterization Occupational exposures are expected to be minimal . As a biochemical with a preventative mode of action, applications of Laminarin will tend to be limited to earlier in the growing season when it can best bolster p lant defenses; and applications are expected to occur at more infrequent intervals than most other pesticides , as SAR induction requires time to be actualized in the plant s. Also, applications are expected to be foliarly directed in order to be most effec tive, further diminishing the chance of s pray drift associated with area - wide spray s. Regardless, requirements for the use of appropriate personal protective equipment and precautionary statements are required on product label s to mitigate any potential risks to pesticide handlers due to prolonged exposure. But even in the event of occupational exposure, an y health risks associated with regular exposure seem unlikely . People have regularl y consumed Laminarin in their fruits and vegetables with no history of detrimental effect s . Moreover, Laminarin has been approved b y FDA as a food additive and for use in ointments, suggesting a lack of risks for both the oral and the dermal routes of exposure. And with regard to pesticidal applications, a ll acute, subchronic, and developmental toxicity data sub mitted in support of this application for Laminarin confirm its lack of toxicity through all routes of exposure. Because of a lack of likel y exposure to residues and a well established nontoxic profile for Laminarin, no occupational risks are expected with regard to the use of this active ingredient.Laminarin Page 14

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b. Residential, School, and Daycare Exposure and Risk Characterization The Agency

does not expect any

risks to children (or adults) in any of these environments. Due to the agricultural use pattern of Laminarin , the potential for significant exposure is negligible. Even in the remote event of incidental residue, the active ingredient has a nontoxic profile for all routes of exposure and a long history of consumpt ion without incident. Due to limited exposure scenarios and negligible toxicity hazards, no risks are expected relative to these exposure scenarios. 7. Aggregate Exposure from Multiple Routes Including Dermal, Oral, and Inhalation The potential fo r aggregate exposure is expected to be insignificant. Directed Laminarin spray is not expected to result in significant amounts of respirable mist, and is not anticipated to be in non - occupational environments at all . Li kewise directed foliar application s, are not likel y to result in dermal exposures, especiall y in non - occupational environments. The chance of significant incidental residues, which could be consumed are also slight. Given a lack of any significant non - occupational exposure, a lack of conc ern regarding its naturally occurring background levels, and a lack of an y acute toxicological endpoints for Laminarin , the aggregate exposure scenario presents no significant concerns for risk. 8. Cumulative Effects Pursuant to FFDCA section 408(b)( 2)(D)(v), EPA has considered available information concerning the cumulative effects of Laminarin residues and other substances that have a common mechanism of toxicity . These considerations include the potential for cumulative effects on infants and children of Laminarin residues and other substances with a common me chanism of toxicity . Because Laminarin has a long history of dietary

consumption without incident, and because no toxicological endpoints have been established, the Agency concludes that Laminarin does not share a common mechanism of toxicity , and that there are no cumulative effects arising from Laminarin residues in or on food commodities . 9. Risk Characterization The Agency

considered human exposure to Laminarin in light of the relevant safet y factors in FQPA and FIFRA. A preliminary 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 Laminarin when label instructions ar e followed. C. ENVIRONMENTAL ASSESSMENTLaminarin Page 15

Biopesticide Registration Action Document 1. Ecological Hazards (Relative to the Biochemical Pesticides Nontarget Organisms and Environmental Fate Data Requirements - 40 CFR § 158.2060) Non - target organism and environmental fate data requirements we re satisfied through a s ubmission of studies. Laminarin is known to occur naturall y in the terrestrial and aquatic environment, and is not associated with an y known detrimental effect. All information available to the Agency

validates a non - toxic mode of action, a lack of persistence in the environment, and a lack of adverse effect relative to non - target organisms. In accordance with T - REX Model and the non - target data submitted, the Agency has made a “No Effect” (NE) determination for direct and i ndirect effects to an y listed threatened and endangered species and their habitat as a result of the proposed uses of Laminarin . Avian Testing (OPPTS Guidelines 850.2100, 850.2200; MRID Nos. 47 264950 and 47264951

) : No avian toxicity

is expected with regard to the pesticidal use of Laminarin. Inan acute oral toxicity study , groups of bobwhite s were administered single oral doses ranging up to 2000 mg/kg bod y weight Laminarin . They were observed for 14 day s. There were no mortalities and no signs of adve rse effects - all birds appeared healthy during the test, and macroscopic examination revealed no abnormalities in an y birds. The acute oral LD 50 was >2000 mg/kg, th e highest dose tested. In a dietary toxicity study on bobwhites , groups of chicks were pro vided a Laminarin - dosed diet for 5 day s, at concentrations ranging up to 5000 ppm per feeding. The diet was maintained for 5 days. There were no treatment - related effects on mortality , body weight, or feed consumption, and no clinical signs of toxicity . The dietary L D 50 was determined to be >5000 ppm . The exposure calculation suggests that even if a bird consumed an entire acre of the active ingredient , a toxic threshold would not occur. A lack of toxicological endpoints indicates that Laminarin is nont oxic to birds. Aquatic Organism Testing (OPPTS Guidelines 850.1010 , 850.10 75, 850.5400 ; MRID Nos. 47264947, 47264948, 47264949, and 47264953) : No risks are expected with regard to the exposure of aquatic organisms to Laminarin. Aquatic exposure is unli kely due to the rapid biodegradation and h ydroly sis of Laminarin. But in the event of aquatic exposures, no hazards are expected for aquatic organisms. In an acute toxicity test, groups of Daphnia magna were exposed to concentrations of Laminarin up to 1 00 mg/L Laminarin . No daphnid mortality or immobility

was seen in any

of the test groups after 24 or 48 hours. In this study , the 48 - hr NOEC and EC 0 were each ≥100 mg/L, and the LOEC and EC 50 were >100 mg/L. In an ac ute toxicity test , groups of zebrafish were exposed to a nominal concentration of 0 or 100 mg/L L aminarin for 96 hours. No mortality or adverse clinical signs were seen at an y intervals or in an y of the test groups. T he 96 - hr LC 50 for L aminarin in Zebra F ish was >100 mg/L. In a second toxicity test , groups of Rainbow T rout fry were exposed to a nominal concentration of 0 or 100 mg/L Laminarin for 96 hours. No mortality or adverse clinical signs were seen in any of the test groups. T he 96 - hr LC 50 for L aminarin in R ainbow T rout was >100 mg/L. A 72 - hour laboratory study was conducted to determine the effects of Laminarin (100 mg/L , nominal) on the growth ofLaminarin Page 16

Biopesticide Registration Action Document the unicellular freshwater green algae. An untreated control was also included in the test. At test end, cell growth and density were similar in the test material and control group. The 72 - hour EbC 50 and ErC 50 for H11 were >100 mg/L , and the NOECb and NOECr were >100 mg/L. The 4 studies altogether confirm a lack of toxicological endpoints, and indicate that Laminarin is nontoxic to aquatic org anisms Non - Target Plant Testing (OPPTS Guidelines 850.4100, 850.4150 ) : The data requirement was satisfied by

information demonstrating a lack of hazard to non - target plants relative to the active ingredient’s mode of action . The active ingredient is to be directed at agricultural crops ; incidental residues would be negli gible. To the degree that there is incidental exposure, Laminarin has been shown to have a non - toxic mode of action relative to plants. A s a SAR inducer, Laminarin bolsters plant health . Accordingl y, Laminarin would actually be expected to have a strengthening effect on non - target plants. Non - Target Insect Testing (OPPTS Guideline 880.4350, 850.3020 ); M RID No s . 47

264979 and 47264952 ) : Data indicate that the residues of Laminarin po se no risks of toxicity to non - target insects. In a laboratory

study , groups of male and female adult parasitic wasps were exposed for 48 hours to 37 g/L Laminarin spray ed on glass plates at varying rates up to 10.0 L/ha. Some issues of loss of fecundity were observed at the highest dose; but none were observed at the doses that were in line with the expected applications of the active ingredient. (The dose at which there was a loss of fecundit y was 10x greater than expected residues of Laminarin at the t ime of pesticidal application.) There was no statistically significant difference in mortalit y between the treated wasps and the untreated control groups. L imit tests were conducted to determine the acute oral and acute contact toxicity of Laminarin to the Honey Bee . Both tests us ed a nominal dose of 100.00 μg L aminarin/bee. In the oral toxicity test, groups of caged bees were provided the test material in a 50% w/v sucrose solution for six hours, and then monitored for mortality at intervals up to 48 hours. After 48 hours, there was no difference in mortality of the untreated control and test material groups. In the contact toxicity test, bees were anesthetized with carbon dioxide and received an individual application of Laminarin to the ventral thorax. In this test, the 48 - hr oral toxicity L D 50 for L aminarin was >118.64 μg/bee, and the 48 - hr contact toxicity L D 50 was >100.00 μg/bee. Data indicate that exposures to L aminarin are not expected to result in any

adverse effects to non - target insects. 2. Environmental Fate and Ground Water Data The need for environmental fate and groundwater data was not triggered because results of the acute toxicity

assessment did not trigger any additional Tier I studies. 3. Ecological Exposure and Risk Characterization The use of Laminarin is not expected to result in significant ecological exposures; and to the degree that there are an y incidental exposures, all data on file with the Agency demonstrate that Laminarin is nontoxic to non - target organisms. Laminarin is i ntended to be applied directly toLaminarin Page 17

Biopesticide Registration Action Document crops early

in the growing season at bi - monthly intervals . Biodegradability data show that it does not persist, and that it hydrol yz es rapidl y. (Laminarin is 65 - 71% biodegraded within two weeks.) When used according to the proposed label directions, no direct exposures are expected for non - target organisms. Laminarin is a naturally occurring carboh ydrate. Its presence in the environment has no known toxicological effect on animals or plants. Data submitted to satisfy the non - target organism data requirements confirm L aminarin’s lack of ecotoxicity . No adverse effects were observed on plants, insects, mammals, avian species and aquatic organisms ; and no toxicological endpoints were identified for an y of these organisms. No risks are expected to the environment with regard to the pesticidal use of Laminarin. 4. Threatened and Endangered Species Assessment Based on the available data, a No Effects (NE) determination was made for Laminarin on threatened and endangere d species when Laminarin is applied to crops as a SAR inducer. The Agency notes that all non - target organism data indicate no toxicity to non - target organisms. Laminarin has a non - toxic mode of action, which precludes toxic effects on plants. And Laminarin is intended to be applied as an agricultural product; accordingl y exposures to threatened and endangered species are expected to be negligible. The Agency used its T - REX Model and its In dividual Effects Chance Model Version 1.1 , in conjunction with data submitted on non - target organisms to quantifiably estimate the chance of risk to endangered/threatened avian and aq

uatic species from exposure to L aminarin. These values (avian risk at 1 in 294,000 and aquatic risk at 1 in 418,000,000) suggest that L ami narin should not cause toxic risk to endangered/threatened species. The calculated RQ values for endangered/threatened terrestrial (RQ = 0.00) and aquatic species (RQ = 0.0045) are below the Agency ’s LOCs of 0.1 and 0.5, respectivel y, supporting the Agency ’s finding that exposure to L aminarin will have No E ffect (NE) on threatened and endangered species . V. 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. To help address potential environmental justice issues, the Agency seeks information on any groups or segments of the population who, as a result of their location, cultural practices, or other factors, may have aty pical, unusually

high exposure to Laminarin , compared to the general population. Please comment if you are aware of any sub - populations that may have at ypica l, unusually

high exposure compared to the general population. VI. RISK MANAGEMENT AND REGISTRATION DECISIONS A. Determination of EligibilityLaminarin Page 18

Biopesticide Registration Action Document 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 requireme nts 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 th e environment. The four criteria of the Eligibility Determination for Pesticidal Active Ingredients are satisfied b y the science assessments supporting products containing Laminarin . Such products are not expected to cause unreasonable adverse effects, and are likel y to provide protection as claimed when used according to label instructions. Therefore, Laminarin is eligible for registration for the labeled uses. B. Regulatory Decision On October 1, 2009, EPA announced a new policy to provide a more me aningful opportunit y for the public to participate on major registration decisions before they occur. According to this new policy , EPA intends to provide a public comment period prior to making a registration decision for, at minimum, the following t ypes of applications: new active ingredients; first food use; first outdoor use; and first residential use. Accordingly, this pesticide is subject to a 30 - day comment period as a new active ingredient with both outdoor uses and residential uses. An y regulat ory decision will be informed by the comments EPA receives. At this time, EPA believes, the data submitted fulfill the requirements of registration for products containing Laminarin for use as a SAR inducer . Acute toxicity data for La minarin demonstrate that it is toxicity

category III and IV for all routes of exposure. (No toxicological endpoints were established.) Data confirm that L aminarin does not demonstrate subchronic or developmental toxicity , and it is not mutagenic or genotoxic. EPA has no con cerns for any non - target organisms exposed to Laminarin in accordance with its approved uses . EPA has not identified any toxic endpoints for non - target mammals, birds, plants, aquatic, or soil organisms. Nor are there concerns for an y threatened and endan gered species. Given, the non - toxic character of Laminarin , EPA supports its registration under Section 3(c)(5) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). Refer to Appendix B for product - specific information. 1. Conditional/U nconditional Registration All data requirements are fulfilled and EPA has preliminarily determined that an unconditional registration for Laminarin is warranted under Section 3(c)(5) of FIFRA. C. LabelingLaminarin Page 19

Biopesticide Registration Action Document Before releasing pesticide products containi ng Laminarin for shipment, the applicant is required to provide appropriate labels. VII. ACTIONS REQUIRED BY THE REGISTRANT The Agency

evaluated the data submitted in connection with the initial registration of Laminarin and preliminaril y determined th at these data fulfill current registration guideline requirements. No additional data are required to be submitted to the Agency at this time. Additional data may be required for new uses and/or changes to existing uses. Not withstanding the informati on 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 types of data are listed below. A. R eporting of Adverse Effects and Hypersensitivity Incidents 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). Additionall y, all incidents of hypersensitivity (including both suspected and confirmed incidents) must be reported to the Agency under the provisions of 40 CFR Part 158.2140 OPPTS Guideline reference number 885.3400 .Laminarin Page 20

Biopesticide Registration Action Document VIII. GLOSSARY OF ACRONYMS A ND ABBREVIATIONS BPPD Biopesticides and Pollution Prevention Division BRAD Biopesticide Registration Action Document CFR Code of Federal Regulations cm 3 cubic centimeter CSF Confidential Statement of Formula °C degrees Celsius EDSP Endocrine Disruptor Screening Program EDSTAC Endocrine Disruptor Screening and Testing Advisory Committee EPA Environmental Protection Agency (the “Agency”) FFDCA Federal Food, Drug, and Cosmetic Act FIFRA Federal Insecticide, Fungicide, and Rodenticide Act FQPA Food Qualit y Protection Act FR Federal Register g gram kg kilogram L liter LD 50 median lethal dose. A statistically derived single dose that can be expected to cause death in 50% of the test animals when administered by the route indicated (oral, dermal, or inhalation). 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 mL milliliter MP manufacturing - use product MPCA microbial pest control agent NE “No Effec t” NI OSH National Institute for Occupational Safet y and Health OPP Office of Pesticide Programs OPPTS Office of Prevention, Pesticides, and Toxic Substances PCR poly

merase chain reaction PPE personal protective equipment TGAI technical grade of the ac tive ingredientLaminarin Page 21

Biopesticide Registration Action Document IX. BIBLIOGRAPHY STUDIES SUBMITTED IN SUPPORT OF THIS REGISTRATION A. Studies Submitted in Support of this Registration . MRID Citation Receipt Date 47264900 Laboratoires Goemar S.A. (2007) Submission of Efficacy , Toxicity and Product

Chemistry

Data in Support of the Application for Registration of Vacciplant. Transmittal of 78 Studies. 24 - Oct 2007 47264901 Sm ith, F. (2007 ) Product Identity and Composition, Description of Beginning

Material, Manufacturing Process, and Discussion of Formation of Impurities: (Vacciplant). Unpublished study prepared by SciReg, Inc. 18 p. 24 - Oct 2007 47264902 Trebert, R. (2001) Laminarin - Ana lytical Profiles of Batches: (Final Report).

Project Number: BPL/200007/0395. Unpublished study prepared by Crepin Analyses & Controles. 84 p. 24 - Oct 2007 47264904 Cruz, F. (1998) Determination of Pure Laminarin: Global Method. Project Number:

FC98005. Un published study prepared by Laboratories GOEMAR. 8 p. 24 - Oct 2007 47264905 Trebert, R.; Cousin, C. (2002) Validation of the Method of the Dosage of Pure

Lam inarin: Global Method: (Final Report). Project Number: BPL/200107/1309. Unpublished study prepared by Crepin Analyses & Controles. 27 p. 24 - Oct 2007 47264906 Delolme, F. (2007) Analysis by MALDI - TOF Mass Spectrometry . Project Number: FC000828. Unpublished study prepared by SciReg, Inc. 7 p. 24 - Oct 2007 47264907 Sm ith, F. (2007) Summary of the OPPTS 83 0 Series Physical - Chemical Properties Test Guidelines: (Vacciplant). Unpublished study prepared by SciReg, Inc. 15 p. 24 - Oct 2007 47264908 Sm ith, F. (2007) Color, Odor, Physical State: (Vacciplant). Unpublished study

prepared by SciReg, Inc. 4 p. 24 - Oct 2 007 47264909 Trebert, R. (2002) G.L.P. Stability Study on Laminarin Code H 11 Batch N

S012000 According to EPA 830.6313: Final Report. Project Number: BPL/200112/0368. Unpublished study prepared by Crepin Analyses & Controles. 31 p. 24 - Oct 2007 47264910 Cuthbert, J. (2001) Laminarin: Determination of Spectra. Project Number:

1476/001VM. Unpublished study prepared by Safepharm Laboratories, Ltd. 24 p. 24 - Oct 2007 47264911 Luc, L. (2000) Laminarin - Oxidizing Properties. Project Number: 00/907005/020.

Unpubl ished study prepared by SEPC. 23 p. 24 - Oct 2007 47264912 Luc, L. (2007) Laminarin - Flammability of Solids. Project Number: 00/907005/016.

Unpublished study prepared by SEPC. 18 p. 24 - Oct 2007 47264913 Luc, L. (2000) Laminarin - Self- Ignition Temperature of Solids. Project Number:

00/907005/019. Unpublished study prepared by SEPC. 17 p. 24 - Oct 2007 47264914 Luc, L. (2000) Laminarin - Flammability in Contact with W ater. Project Number: 24 - Oct -Laminarin Page 22

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00/907005/017. Unpublished study prepared by SEPC. 18 p. 2007 47264 915 Luc, L. (2000) Laminarin - Explosive Properties (Solid). Project Number:

00/907005/018. Unpublished study prepared by SEPC. 25 p. 24 - Oct 2007 47264916 Luc, L. (2000) Laminarin - Melting Point. Project Number: 00/907005/003.

Unpublished study prepared by S EPC. 18 p. 24 - Oct 2007 47264917 Luc, L. (2000) Laminarin - Relative Density. Project Number: 00/907005/005.

Unpublished study prepared by SEPC. 21 p. 24 - Oct 2007 47264918 Claude, A. (2002) Laminarin - Relative Density. Project Number: 01/907005/002.

Unpubl ished study prepared by SEPC. 21 p. 24 - Oct 2007 47264919 Luc, L. (2002) Laminarin - Soulubility in W ater. Project Number: 00/907005/008.

Unpublished study prepared by SEPC. 43 p. 24 - Oct 2007 47264920 Martel, I. (2002) Determination of pH Values - (Lamina rin). Project Number:

01/907005/001. Unpublished study prepared by SEPC. 17 p. 24 - Oct 2007 47264921 Luc, L. (2001) Laminarin - Solubility in n - Heptane. Project Number: 00/907005/09,

SEP/00/068. Unpublished study prepared by SEPC. 41 p. 24 - Oct 2007 47264922 Luc, L. (2001) Laminarin - Solubility in Xylene. Project Number: 00/907005/010,

SEP/00/069. Unpublished study prepared by SEPC. 41 p. 24 - Oct 2007 47264923 Luc, L. (2001) Laminarin - Solubility in 1,2 Dichloroethane. Project Number:

00/907005/011, SEP/00/07 0. Unpublished study prepared by SEPC. 41 p. 24 - Oct 2007 47264924 Luc, L. (2001) Laminarin - Solubility in Methanol. Project Number: 00/907005/012,

SEP/00/071. Unpublished study prepared by SEPC. 41 p. 24 - Oct 2007 47264925 Luc, L. (2001) Laminarin - Solubili ty in Acetone. Project Number: 00/907005/013, SEP/00/072. Unpublished study prepared by SEPC. 41 p. 24 - Oct 2007 47264926 Luc, L. (2001) Laminarin - Solubility in Ethyl Acetate. Project Number:

00/907005/014, SEP/00/073. Unpublished study prepared by SEPC. 4 1 p. 24 - Oct 2007 47264927 Tremain, S. (2001) Laminarin: Determination of Vapour Pressure. Project

Number: 1303/005. Unpublished study prepared by Safepharm Laboratories, Ltd. and SEPC. 21 p. 24 - Oct 2007 47264928 Quintelas, G. (2001) Determination of the Partition Coefficient of Laminarin.

Project Number: SEP/00/074, 00/907005/015. Unpublished study prepared by Defitraces. 25 p. 24 - Oct 2007 47264929 Luc, L. (2000) Laminarin - Surface Tension. Project Number: 00/907005/007.

Unpublished study prepared by SEPC . 19 p. 24 - Oct 2007 47264930 Baudet, L. (2002) Phycarine 96S51: Acute Toxicity Study Safety Test in the Rat

by the Oral Route. Project Number: 20010618/ST. Unpublished study prepared by Centre de Recherches Biologiques. 27 p. 24 - Oct 2007 47264931 Audeval Gerald, C. (2001) H11 (Batch 99S24) Acute Dermal Toxicity Study in the 24 - Oct -Laminarin Page 23

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Rat. Project Number: 20000698/ST, 20000698/ST/TAUVD/H11. Unpublished study prepared by Centre de Recherches Biologiques. 30 p. 2007 47264932 Muller, W . (1999) Evaluation of Acu te Inhalation Toxicity with Phycarine in Rats.

Project Number: 980001/EX, TOXLABS/1998/7019/INH. Unpublished study prepared by Centre de Recherches Biologiques. 19 p. 24 - Oct 2007 47264933 Baudet, L. (2002) Phycarine 96S51: Ocular Primary Irritation in the Rabbit. Project

Number: 20010615/ST. Unpublished study prepared by Centre de Recherches Biologiques. 27 p. 24 - Oct 2007 47264934 Baudet, L. (2002) Phycarine 96S51: Cutaneous Primary Irritation in the Rabbit:

Final Report. Project Number: 20010617/ST/PSI/RABBIT/PHYCARIINE. Unpublished study prepared by Centre de Recherches Biologiques. 25 p. 24 - Oct 2007 47264935 Baudet, L. (2002) Phycarine 96S51: Study of Cutaneous Sensitization Using the

Magnusson and Kligman Maximisation Test in the Guinea Pig: Final Rep ort. Project Number: 20010616/ST. Unpublished study prepared by Centre de Recherches Biologiques. 39 p. 24 - Oct 2007 47264936 Delille, M. (1998) Acute Toxicity Study: Safety Test in the Rat by the

Subcutaneous Route: (Phycarine 96S51). Project Number: 9703 53/ST. Unpublished study prepared by Centre de Recherches Biologiques. 24 p. 24 - Oct 2007 47264937 Longobardi, C. (2000) 4489 - 1 (product H 11): 4 We ekOral Toxicity Study in Rats:

Final Report. Project Number: 7286, 7286/T/240/99. Unpublished study prepare d by Research Toxicology Centre, S.p.A.. 178 p. 24 - Oct 2007 47264938 Audeval Gerard, C. (2001) H11 (Batch 99S24): 90 - Day Repeated Dose Oral

Toxicity Study in the Rat. Project Number: 20000389/T. Unpublished study prepared by Centre de Recherches Biologiqu es. 237 p. 24 - Oct 2007 47264939 Audeval Gerard, C. (2001) 90 - Day Repeated Dose Oral Toxicity Study in the Dog. Project Number: 20000390/T. Unpublished study prepared by Centre de Recherches Biologiques. 257 p. 24 - Oct 2007 47264940 Audeval Gerard, C. (200 1) H11 (Batch 99S24): Study for the Effects on Embryo Foetal Development in the Rat by the Oral Route. Project Number: 20000387/T. Unpublished study prepared by Centre de Recherches Biologiques. 127 p. 24 - Oct 2007 47264941 Gerard, C. (2001) Study for the Effects on Embryo - Foetal Development in the

Rabbit by the Oral Route: H11 (Batch 99S24). Project Number: NO/20000388/T. Unpublished study prepared by CERB (Centre de Recherches Biologiques). 127 p. 24 - Oct 2007

47264942 Marzin, D. (2000) Mutagenicity Test on Bacteria (Salmonella typhimurium his and

Escherichia coli trp) Using B.N. Ames's Technique with H11. Project Number: IPL/R/991011/H11/GOEMAR/LABORATORY. Unpublished study prepared by Institut Pasteur de Lille. 38 p. 24 - Oct 2007 47264943 Haddouk, H. (20 02) In Vitro Mammalian Cell Gene Mutation Test in L5178Y TK

Mouse Ly mp homa Cells: Laminarin. Project Number: 22626/MLY. Unpublished study prepared by Centre International de Toxicologie. 47 p. 24 - Oct 2007Laminarin Page 24

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47264944 Haddouk, H. (2001) Bone Marrow Micronucle us Test by Oral Route in Mice:

Lam inarin. Project Number: 21149/MAS, 21149/MAS/LAMINARIN/LABORATOIRES/GOEMAR/SA. Unpublished study prepared by Centre International de Toxicologie. 37 p. 24 - Oct 2007 47264945 Sm ith, F. (2007) Toxicology Wa iver Request - Imm unotoxicit y (Lam inarin).

Unpublished study prepared by SciReg, Inc. 11 p. 24 - Oct 2007 47264946 Quintelas, G. (2001) Abiotic Degradation of Laminarin pH Dependent Hydrolysis

(Test C7). Project Number: SEP/00/075, SEPC/00/907005/025, 00/907005/025. Unpublis hed study prepared by Defitraces. 30 p. 24 - Oct 2007 47264947 Herti, J. (2001) Acute Toxicity of Laminarin to Daphnia magna in a 48 - Hour Semi Static Immobilization Test: Final Report. Project Number: PROJECT/10041220. Unpublished study prepared by Institut fuer Biologische Analytik und Consulting IBACON. 61 p. 24 - Oct 2007 47264948 Luc, L. (2001) Acute Toxicity in Freshwater Fish (96h): Oncorhynchus m yk iss

(Laminarin). Project Number: 00/907005/021. Unpublished study prepared by SEPC. 50 p. 24 - Oct 2007 472 64949 Luc, L. (2001) Acute Toxicity in Freshwater Fish (96h): Danio rerio: (Laminarin).

Project Number: 00/907005/022. Unpublished study prepared by SEPC. 49 p. 24 - Oct 2007 47264950 Rodgers, M. (2002) Laminarin: Acute Oral Toxicity (LD50) to the Bobwhite Quail.

Project Number: GOM/001, GOM/001/022173. Unpublished study prepared by Huntingdon Life Sciences, Ltd. 23 p. 24 - Oct 2007 47264951 Rodgers, M. (2002) Laminarin: Dietar y T oxicity (LC50) to the Bobwhite Quail.

Project Number: GOM/002, GOM/002/014410. U npublished study prepared by Huntingdon Life Sciences, Ltd. 21 p. 24 - Oct 2007 47264952 Kling, A. (2000) Assessment of Side Effects of Laminarin to the Honey Bee, Apis

me llifera L. in the Laboratory: Final Report. Project Number: 20001342/01/BLEU. Unpublis hed study prepared by Arbeitsgemeinschaft GAB Biotechnologie. 33 p. 24 - Oct 2007 47264953 Gnemi, P. (2000) H11: Algal Growth Inhibition Study. Project Number: 990714.

Unpublished study prepared by Istituto di Ricerche Biomediche Antoine Marxer RBM S.p.A. 2 7 p. 24 - Oct 2007 47264954 Luc, L. (2000) Ready Biodegradability Modified Strum Test: (Laminarin). Project

Number: 00/907005/024. Unpublished study prepared by SEPC. 24 p. 24 - Oct 2007 47264955 Sm ith, F. (2007) Product Identity and Composition, Description of Beginning

Materials, Description of Formulation Process, Discussion of Formation of Impurities, and Certified Limits (Vacciplant). Unpublished study prepared by SciReg, Inc. 57 p. 24 - Oct 2007 47264956 Sm ith, F. (2007) Summary of the OPPTS 830 Series P hysical - Chemical Properties Test Guidelines (Vacciplant). Unpublished study prepared by SciReg, Inc. 6 p. 24 - Oct 2007 47264957 Luc, L. (2001) Phyliq: Determination of pH Value of the Test Item . Project

Number: 00/907005/026. Unpublished study prepared by SEPC. 17 p. 24 - Oct 2007Laminarin Page 25

Biopesticide Registration Action Document
47264958 Luc, L. (2001) Phyliq: Determination of pH Value of a 1% Aqueous Dilution.

Project Number: 00/907005/028. Unpublished study prepared by SEPC. 17 p. 24 - Oct 2007 47264959 Luc, L. (2001) Phyliq: Determination of pH Value of the Test Item After an

Accelerated Storage Procedure at + 54 Degrees Celsius for 14 Days. Project Number: 00/907005/035. Unpublished study prepared by SEPC. 17 p. 24 - Oct 2007 47264960 Luc, L. (2001) Phyliq: Determination of pH Value of a 1% Aqueous Dilut ion After

an Accelerated Storage Procedure at + 54 Degrees Celsius for 14 Days. Project Number: 00/907005/037. Unpublished study prepared by SEPC. 17 p. 24 - Oct 2007 47264961 Luc, L. (2001) Phyliq: Viscosity. Project Number: 00/907005/029. Unpublished

stud y prepared by SEPC. 18 p. 24 - Oct 2007 47264962 Luc, L. (2001) Phyliq: Relative Density. Project Number: 00/907005/030.

Unpublished study prepared by SEPC. 20 p. 24 - Oct 2007 47264963 Luc, L. (2001) Phyliq: Storage Stability: Accelerated Procedure by Heati ng (at +54

Degrees Celsius for 14 Days). Project Number: 00/907005/034. Unpublished study prepared by SEPC. 39 p. 24 - Oct 2007 47264965 Luc, L. (2001) Phyliq: Low Temperature Stability. Project Number:

00/907005/040. Unpublished study prepared by SEPC. 18 p. 24 - Oct 2007 47264966 Luc, L. (2001) Phyliq: Dilution Stability. Project Number: 00/907005/033.

Unpublished study prepared by SEPC. 18 p. 24 - Oct 2007 47264967 Luc, L. (2001) Phyliq: Dilution Stability After an Accelerated Storage Procedure at

+54 (Degr ees) Celcius for 14 Days. Project Number: 00/907005/039. Unpublished study prepared by SEPC. 18 p. 24 - Oct 2007 47264968 Luc, L. (2001) Phyliq: Surface Tension. Project Number: 00/907005/031.

Unpublished study prepared by SEPC. 20 p. 24 - Oct 2007 47264969 Luc, L. (2001) Phyliq: Persistent Foaming. Project Number: 00/907005/032.

Unpublished study prepared by SEPC. 18 p. 24 - Oct 2007 47264970 Luc, L. (2001) Phyliq: Persistent Foaming After an Accelerated Storage

Procedure at +54 Degrees Celcius for 14 days. P roject Number 00/907005/038. Unpublished study prepared by SEPC. 18 p. 24 - Oct 2007 47264971 Luc, L. (2001) Phyliq: Free Acidity or Alkalinity. Project Number: 00/907005/027.

Unpublished study prepared by SEPC. 18 p. 24 - Oct 2007 47264972 Luc, L. (2001) Fr ee Acidity or Alkalinity After an Accelerated Storage Procedure at

+ 54 C for 14 Days. Project Number: 00/907005/036. Unpublished study prepared by SEPC. 17 p. 24 - Oct 2007 47264973 Audeval - Gerard, C. (2000) Acute Oral Toxicity Study in the Rat. Project Nu mb er

9912812, 990762T/Limvo/Phyliq. 27 p. 24 - Oct 2007 47264974 Audeval - Gerard, C. (2000) Acute Dermal Toxicity in the Rat. Project Number

9912812, 990763T/LIMVD/PHYLIQ. 28 p. 24 - Oct 2007Laminarin Page 26

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47264975 Sm ith, F. (2007) Toxicology Wa iver Request - Acute Inhalat ion Toxicity:

(Laminarin). Project Number: TOXLABS/1998/7020INH, 24634/61/5. Unpublished study prepared by SciReg, Inc. 81 p. 24 - Oct 2007 47264976 Audeval - Gerard, C. (2000) Acute Eye Irritation Study in the Rabbit. Project

Number: 990760T/IPOCH/PHYLIQ, 99 12812. Unpublished study prepared by Laboratories Goemar SA. 27 p. 24 - Oct 2007 47264977 Audeval - Gerard, C. (2000) Acute Skin Irritation Study in the Rabbit. Project

Number: 9912812, 990759T/IPCCH/PHYLIQ. Unpublished study prepared by Laboratories GOEMAR S A. 27 p. 24 - Oct 2007 47264978 Audeval - Gerard, C. (2000) Skin Sensitisation Study in the Guinea Pig

(Magnusson - Kligman Maximisation). Project Number: 990761/KINJCH/PHYLIQ, 9912812. Unpublished study prepared by Laboratories GOEMAR SA. 37 p. 24 - Oct 2007 47 264979 Tessier, C. (2001) The Effects of Phyliq (37 g/L Laminarin) on Aphidius

rhopalosiphi (Hy me noptera, Braconidae) on Artificial Substrate in Laborator y: LR 50 Estimation and Reproduction Assessment: Phyliq. Project Number: 01APGOL25. Unpublished study prepared by Promo - Vert S.A. 18 p. 24 - Oct 2007

47264980 Tessier, C. (2001) The Effects of Phyliq (37g/L Laminarin) on T yp hlodromus py ri

(Acari, Phytoseiidae) on Artificial Substrate in Laboratory: LR 50 Estimation and Reproduction Assessment . Project Numb er: 01T YGOL24. Unpublished study prepared by Promo - Vert S.A. 22 p. 24 - Oct 2007 47283300 Laboratories Goemar SA (2007) Submission of Product Chemistry Data in

Support of the Application for Registration of VacciPlant and the Petitions for Tolerance of Lami narin for Use on Food Crops. Transmittal of 2 Studies. 15 - Nov 2007 47283301 Trebert, R.; Cousin, C. (2002) Laminarin - Analytical Profile of One Batch 96S51.

Project Number: BPL/200111/0388. Unpublished study prepared by Crepin Analyses & Controles. 54 p. 1 5 - Nov 2007 47283302 Comb, A. (2006) Iodus 40: Two Year Storage Stability. Project Number:

GOM/005, GOM/005/063905. Unpublished study prepared by Huntingdon Life Sciences, Ltd. 32 p. 15 - Nov 2007 47391100 Laboratoires Goemar SA (2008) Submission of Product Chemistry and Toxicity Data in Support of the Application for Registration of VacciPlant and the Petition for Tolerance of Laminarin for Use on Food Crops. 02 - Apr 2008 47391101 Smith, F. (2008) Product Identity and Composition, Description of Beginning M aterials and Description of Formulation Process: (VacciPlant). Unpublished study

prepared by

SciReg, Inc. 52 p. 02 - Apr 2008 47391102 Smith, F. (2008) Toxicology Waiver Request - Acute Inhalation Toxicity : (VacciPlant). Unpublished study prepared by

SciReg, Inc. 65 p. 02 - Apr 2008 B. EPA Risk Assessment MemorandaLaminarin Page 27

Biopesticide Registration Action Document Rexrode, M. Science Review in Support of New Product Registration Human Tolerance Application for VacciPlant, an End - use Product Containing the Active Ingredient Laminarin (3.5%) dated October 23, 2009. Rexrode, M. Science Review in Support Support of a Tolerance Exemption Petition, R egistration of an End - Use Product for VacciPlant that C ontains L aminarin (3.5%) (3.5%) dated October 28, 2008. C. References U.S. EPA. 1998. Guidance for Ecologi cal Risk Assessment. Risk Assessment Forum. EPA/630/R - 95/002F, April 1998. U.S.EPA 2008. Terrestrial Residue Exposure Model (T - REX) Version 1.4.1. EFED/OPP/USEPA. U.S.EPA 2004. Individual Effects Chance Model Version 1.1. EFED/OPP/USEPA. U.S. EPA. 2004. Overview of the Ecological Risk Assessment Process in the Office of Pesticide Programs. Office of Prevention, Pesticides, and Toxic Substances. Office of Pesticide Programs. Washington, D.C. January 23, 2004.
APPENDIX A

– BIOCHEMICAL PESTICID E DATA REQUIREMENTS TABLE 1. Physical/Chemical Properties for Laminarin TABLE 1 .0 Physical and Chemical Properties for pure TGAI Laminarin a Guideline Reference No. Property Description of Result Methods 830.6302 Color White MRID 47264908 830.6303 Physical State Powder MRID 47264908 830.6304 Odor Low odor MRID 47264908 830.6313 Stability Stable after 14 days at 54°C in the presence of aluminum acetate or aluminum MRID 47264909 830.6314 Oxidation/Reduction:

Chemical Incompatibility No oxidizin g properties MRID 47264911Laminarin Page 28

Biopesticide Registration Action Document TABLE 1 .0 Physical and Chemical Properties for pure TGAI Laminarin a Guideline Reference No. Property Description of Result Methods 830.6315 Flammability None flammable; neither development nor ignition of gas were observed after contact with water. An exothermic reaction was observed at 236°C±3°C (mean value). No self

- ignition temperature was recorded up to 420°C. MRID 47264912 MRID 47264913 MRID 47264914

830.6316 Explodability Not explosive MRID 47264915, checking heat, friction, and shock sensitivity 830.6317 Storage Stability Not required for TGAI 830.6319 Miscibility Not applicable, product is not an emulsifiable liquid and will not be diluted with petroleum solvents. 830.6320 Corrosion

Characteristics Not required for TGAI 830.6321 Dielectric Breakdown

Voltage Not required for TGAI 830.7000 pH 6.25±0.02 at 23.2°C (1% w/v) MRID 4726 4920, by pH meter and a glass electrode 830.7100 Viscosity Not required for TGAI 830.7200 Melting Range No melting point could be determined. The test material became yellow at 204 - 215C, then it turned brown at 216 - 225.2C. At about 310.6 - 316.2C, the test material was completely retracted and blacked colored. The test material probably degraded during the test. MRID 47264916, by using an Electrothermal 8103 apparatus
830.7220 Boiling Range The test material is a powder. 830.7300 Relative Density D 4 20 = 1.515±0.04 - 1.502±0.06 MRID 47264917 and 47264918, by pycnometric method 830.7370 Dissociation Constant in

Water Can not be determined. 830.7550 Partition Coefficient Log P = - 1.6 MRID 47264928, by shake flask methodLaminarin Page 29

Biopesticide Registration Action Document TABLE 1 .0 Physical and Chemical Properties for pure TGAI Laminarin a Guideline Reference No. Property Description of Result Methods 830.7840 Water Solu bility > 88.6 g/L at 20°C;

< 10 mg/L (n - heptane); < 10 mg/L at 20°C (xylene, 1,2 - dichloroethane, and ethyl acetate); 60 mg/L (methanol); 21 mg/L at 20°C (acetone) MRID 47264919 MRID 47264921 MRID 47264922 MRID 47264923 MRID 47264924 MRID 47264925 MRID 4726 4926 by flask method 830.7950 Vapor Pressure < 2.6 x 10 - 5 Pa at 25°C MRID 47264927, using a vapor pressure balance system TABLE 2. Toxicity Data Requirements Summary Table 2. 0 Toxicological Results/ Category Guideline # Test Results/Toxi cology

Category MRID Study Conclusion 870.1100 Ac ute Oral LD 50 >2,000 mg/kg III 47264930

47264943 Acceptable 870.1200 Ac ute Dermal LD 50 >5,000 mg/kg IV 47264931

47264974 Acceptable 870.1300 Ac ute Inhalation > 1.02 mg/L III 47264932 Acceptable 870.2400 P rimary Eye Irritation Non irritating IV 47264933

47264976 Acceptable 870.2500 Primary Dermal Irritation - Rabbits Non - irritating IV 47264934 Acceptable 870.2600 Dermal Sensitization Not a sensitizer IV 47264935

47264978 Acceptable Ac ute Subcutaneous L D 50 >1,000 mg/kg 47264936 Acceptable 870.3050 28 day Oral Toxicity Rat NOEL=1,000 mg/kg/day 47264937 Acceptable 870.3100 90 day Oral Toxicity Rat NOEL=1,000 mg/kg/day 47264938 Acceptable 870.3150 Subchronic Oral Toxicity (gavage) - Dog NOEL=1,000 mg/kg/day 47264939 Acceptable 870.3700a Prenatal Developmental Toxicity Study - Rat Maternal NOEL > 1,000 mg/kg/day Developmental NOEL > 1,000 mg/kg/day 47264940 AcceptableLaminarin Page 30

Biopesticide Registration Action Document Table 2. 0 Toxicological Results/ Category Guideline # Test Results/Toxi cology

Category MRID Study Conclusion 870.3700b Prenatal Developmental Toxicity Study - Rabbit Maternal LOAEL = 1,000 m g/kg/day Developmental LOAEL = 1,000 mg/kg/day 47264941 Acceptable

870.5100 Bacterial Reverse Mutation Test There was no evidence of induced mutant colonies over background 47264942 Acceptable 870.5300 In Vitro Mammalian Cells in Culture Gene Mutati on Assay There was no evidence of induced mutant colonies over background. 47264943 Acceptable

870.5395 Bone Marrow Micronucleus assay in mo use No toxicity was noted in either sex at any dose up to the limit dose of 2000 mg/kg bw 47264944 Acceptable

8 70.7800 Immunotoxicity Waiver Request 47264945 Acceptable TABLE 3 . EcoToxicity Data Requirements Summary Table 3 .0 Ecotoxicity Data

Guideline # Test Results/Toxicology Category MRID Study Conclusion 850.1010 Ac ute Toxicity Test, Daphni ds EC 50 >100 mg/L. 47264947 Acceptable 850.1075 Ac ute Toxicity Freshwater Fish Danio rerio 96 hr LC 50 >100 mg/L. 47264948 Acceptable 850.1075 Fish Acute Freshwater Rainbow Trout Oncorhynchus mykiss 96 - hr LC 50 >100 mg/L. 47264949 Acceptable

850.2 100 Avian Acute Oral Toxicity Bobwhite ( Colinus virginianus ) LD 50 >2000 mg/kg 47264950 Acceptable 850.2200 Avian Dietary Toxicity Bobwhite ( Colinus virginianus ) LC 50 >5000 ppm 47264951 Acceptable 850.3020 Ac ute Contact Toxicity Honey bee (

Apis mellif

era) LD 50 >118.64 μg/bee

48 - hr contact LD 50 >100.00 μg/bee. 47264952 Acceptable 850.5400 Algal Toxicity, Tiers I and II Green alga Selenastrum capricornutum . E b C 50 , E r C 50 , NOECb, and NOECr for the test material at 24, 48, and 72 hours were each >100 mg/L 47264953 AcceptableLaminarin Page 31

Biopesticide Registration Action Document Table 3 .0 Ecotoxicity Data

Guideline # Test Results/Toxicology Category MRID Study Conclusion 835.3110 Biodegradability Biodegradation in the reference material and toxicity controls was 71% and 65%, respectively, after 14 days. Laminarin was concluded to be readily biodegradable under the test conditions. 47264954 Accept able

880.4350 Nontarget Insect Testing Exposure to 10.0 L/ha of the test material did significantly low er the fecundity of A. rhopalosiphi females compared to the untreated control. How ever, the product label for Vacciplant recommends an application rate of 9.7 to 14.4 oz/A, which the reviewer calculates to be equivalent to 0.7 to 1.05 L/ha, well below the 10.0 L/ha rate at which fecundity was affected. 47264979 Acceptable