Document ID: EPA-HQ-OPP-2009-0126-0007
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2010-08-27T04:00Z

BIOPESTICIDE REGISTRATION ACTION DOCUMENT 

 

Laminarin 

PC Code: 123200

U.S. Environmental Protection Agency

Office of Pesticide Programs

Biopesticides and Pollution Prevention Division

Last updated- February 13, 2010

TABLE OF CONTENTS

 TOC \f I.     EXECUTIVE
SUMMARY………………………………………………………
………..	p.4           

II.    ACTIVE INGREDIENT
OVERVIEW……………………………………………………p.6

III.   REGULATORY
BACKGROUND……………………………………………………
…..p.6

IV. RISK
ASSESSMENT……………………………………………………
…………………p.7

A. PRODUCT ANALYSIS
ASSESSMENT……………………………………………p.8

1.  Product Chemistry and
Composition…………………………………………….p.8

2.  Analysis and Certification of
Limits……………………………………………..p.8

3.  Physical and Chemical
Characteristics…………………………………………..p.8

B.  HUMAN HEALTH
ASSESSMENT………………………………………………..p.8

			1.  Toxicological Hazard
Assessment……………………………………………….p.8

			2.  Dose
Response………………………………………………………
………….p.12  

3.  Dietary Exposure and Risk
Characterization………………………………..….p.12

			4.  Drinking Water Exposure and Risk
Characterization…………………….…….p.12

			5.	Acute and Chronic Dietary Exposure and Risks for Sensitive 

                       Subpopulations, Particularly Infants and
Children………………………….…p.13

                  6.  Occupational, Residential, School, and Daycare
Exposure and Risk                                                       
                                                                        
                                                                        
                                          
Characterization………………………………………………
……………..…p.13                                                
                                                                        
                                                                      

			7.  Aggregate Exposure from Multiple Routes Including Dermal, Oral, 

and
Inhalation……………………………………………………
……………..p.14	

			8.  Cumulative
Effects………………………………………………………
……...p.14

			9.  Risk
Characterization………………………………………………
…………...p.14

		C.  ENVIRONMENTAL
ASSESSMENT……………………………………………..p.15

			1.  Summary of Non-Target Organism Testing and Waiver
Rationales……….…..p.15

                  2.  Environmental Fate and
Groundwater……………………………………….....p.16

                 	3.  Ecological Exposure and Risk
Characterization………………………….…….p.16  

                  4.  Threatened and Endangered Species
Assessment………………………....……p.17

V.     ENVIRONMENTAL
JUSTICE………………………………………………………
…p.17

VI.    RISK MANAGEMENT AND REGISTRATION
DECISIONS………………………..p.18

A. DETERMINATION OF
ELIGIBILITY……………………………………………p.18

B. REGULATORY
DECISION……………………………………………………….
p.18

C.
LABELING………………………………………………………
…………………p.19

VII.   ACTIONS REQUIRED BY THE
REGISTRANT……………………………………...p.19

A. REPORTING OF ADVERSE EFFECTS AND HYPERSENSITIVITY                    
                                          
INCIDENTS………………………………………………………
………….…….p.19

VIII.  GLOSSARY OF ACRONYMS AND
ABBREVIATIONS………………………….…p.19

IX.    BIBLIOGRAPHY STUDIES SUBMITTED IN SUPPORT OF THIS 

REGISTRATION……….…………………………………………
……………….……p.20

		A. STUDIES SUBMITTED IN SUPPORT OF THIS
REGISTRATION…………….p.26

		B. EPA RISK ASSESSMENT
MEMORANDA…...………………………………….p.26

APPENDIX A - BIOCHEMICAL PESTICIDE DATA
REQUIREMENTS…………….……p.27

 BIOPESTICIDES REGISTRATION ACTION DOCUMENT TEAM

Office of Pesticide Programs

Biopesticides and Pollution Prevention Division

Biochemical Pesticides Branch (BPB)

					Chris Pfeifer							Regulatory Action Leader

					Linda Hollis							Branch Chief

					Miachel Rexrode, Ph.D				Senior Biologist

Russell Jones, Ph.D					Senior Biologist

I.    EXECUTIVE SUMMARY tc "I.    EXECUTIVE SUMMARY/FACT SHEET" 

Laminarin is a common component of the human diet.  It is a naturally
occurring polysaccharide carbohydrate (oliggosaccharide) found in all
edible plants.  It is a major constituent in cereal grains, and is
consumed as an intentionally added ingredient in many dietary
supplements and texturing agents.  Laminarin is typically extracted from
brown algae, where it is present in great quantity as a storage glucan
– a carbohydrate food reserve that 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 pesticide active ingredient, Laminarin
stimulates the natural defense 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 naturally occurring oligosaccharide,
residues of the active ingredient are indistinguishable from other
naturally occurring plant oligosaccharides.  In addition to the long
history of human consumption of Laminarin without known toxicological
effect, data and information submitted to the Agency in conjunction with
the petition for the exemption from a requirement of tolerance confirm
that Laminarin is virtually non-toxic and poses no dietary risks to
humans.  

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. 

Because Laminarin is considered to be “toxicologically innocuous,”
no residue studies are required to support an exemption from the
requirement of a tolerance.  Laminarin’s low toxicity profile
notwithstanding, another justification for an exemption from the
requirement of a tolerance is the minimal likelihood of residues for
this biochemical pesticide.  Laminarin is intended for application as a
Systemic 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 biodegrades
rapidly.  Data indicate that the active ingredient is more than 65%
biodegraded after two weeks (MRID 47264954).  Calculations indicate that
it would be largely biodegraded long before any final application would
be practicable.  Accordingly, no significant exposures are expected at
the time of harvest.

	

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 no acute, sub-chronic, chronic, immune, or
endocrine-disrupting effects are associated with the use of the active
ingredient.  Accordingly, no harm to 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 early in the growing season. 
Moreover, given a lack of acute toxicological endpoints and because
Laminarin is not known to share any structural similarity to any
chemicals with common mechanisms of toxicity, the likelihood of risks
resulting from such de minimis exposures is negligible.

Non-target organism and environmental fate data requirements were
satisfied by valid studies.  Laminarin occurs naturally in the
terrestrial environment, and is not associated with any 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 Model, 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
any 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 opportunity for the public to participate on major
registration decisions before they occur.  According to this new policy,
EPA will provide a public comment period prior to making a registration
decision for, at minimum, the following types of applications: new
active ingredients, first food use, first outdoor use, first residential
use, and other actions for which we anticipate significant public
interest.  The registration application for Laminarin is for a “new
active ingredient” whose registration would result in a “first
outdoor use” and a “first food use.”  Therefore, consistent with
the new policy of making registration actions more transparent, the
Agency provided a 30-day comment period on the Laminarin application and
EPA's preliminary risk assessment.  EPA did not receive any comments
during the comment period.  

EPA believes, 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 demonstrate subchronic or
developmental toxicity, and it is not mutagenic or genotoxic.  EPA has
no concerns for any 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 any 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
effectiveness as a Systemic 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 determined that the data/information submitted
fulfilled current data requirements (refer to 40 CFR Subpart U §
158.2000).  

II.		ACTIVE INGREDIENT OVERVIEW

Common Name: 			Laminarin

Chemical Names: 		Oligosaccharide, Polysaccharide 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 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).  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 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 Symbol 83941-E) containing a new active ingredient (Laminarin) not
included in any currently registered products.  No comments were
received following the publication of either notice.  In addition, on
January 5, 2010, EPA provided the opportunity for a 30-day comment
period on the Agency’s draft risk assessment and intention to register
this pesticide product.  EPA has not received any comment on this
proposed action.

CLASSIFICATION 

Laminarin is a naturally occurring polysaccharide 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 any toxic mode of
action.  Accordingly, Laminarin is considered to be a biochemical
pesticide due to its nontoxic mode of action to the target pest, its
natural occurrence in the environment, and its history of exposure to
humans and the environment without known toxicity. 

FOOD CLEARANCES/TOLERANCES 

This active ingredient is being 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

 tc "III.  SCIENCE 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 (  HYPERLINK
"http://www.epa.gov/fedrgstr/EPA-TOX/2007/October/Day-26/t20828.htm"  72
FR 61002 ). The rule became effective on December 26, 2007. The data and
information evaluated for this Biopesticide Registration Action Document
(BRAD) were considered in light of these requirements.

Classifications for each data submission are assigned by EPA science
reviewers 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 “SUPPLEMENTAL” 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 Protection Agency
always 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
assigned 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 classified into Toxicity
Category I, II, III, or IV, where Toxicity Category I indicates the
highest toxicity and Toxicity Category IV indicates the lowest toxicity.
 

	A.  PRODUCT ANALYSIS ASESSMENT  tc "A.   Physical and Chemical
Properties Assessment " \l 2 

	

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 carbohydrate food
reserve - which breaks down into glucose and provides energy when plants
are stressed.  Laminarin extract is derived from brown algae (Laminara
digitata), and is a low-odor white powder.  Because of its nutrient
richness and starchy character, Laminarin extract is commonly used as a
dietary supplement, a food texturing agent 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 extract has a high degree of purity and contains no
impurities of toxicological significance.  All data requirements for
physical and chemical characteristics have been adequately addressed.   
 

2.  Analysis and Certification of Limits

The submitted data satisfied the requirement for Analysis and
Certification of Limits.  Five batch analyses and the analytical 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 by OPPTS Guideline
830-1750.   

3.  Physical and Chemical Characteristics

The Agency has determined that the submitted data adequately describe
the physical and chemical characteristics of Laminarin.  Refer to Table
1 in Appendix A for The Series 830 physical and chemical properties.   

	B.   HUMAN HEALTH ASSESSMENT 

	1.  Toxicological Hazard Assessment 

Adequate mammalian toxicology studies were provided in support of the
registration of Laminarin 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.  Accordingly, 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 this active ingredient.  

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 Record
Identification (MRID) Numbers (Nos.) 47264930 and 47264943]:  An acute
oral toxicity study shows that the active ingredient Laminarin has an
LD50 of greater than 2000 mg/Kg in rats.  This was the maximum dose
rate.  There were no observed toxicological effects on the test subjects
at the maximum dose.   The study supports the finding that this active
ingredient poses no significant human health risk with regard to food
uses.  The study was found “ACCEPTABLE” and Laminarin was classified
as TOXICITY CATEGORY 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 Laminarin has an LD50 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 classified 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 LC50 of greater 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 TOXICITY CATEGORY 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 eye irritation study on rabbits demonstrated
Laminarin to be non-irritating.  There were no observed effects for this
route of exposure relative to the use of Laminarin.   The study was
found “ACCEPTABLE” and Laminarin was classified as TOXICITY 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 Laminarin 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. 

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 support 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 effects regarding mortality, clinical
observations, neurotoxicity assessment, body weight, food consumption,
hematology, clinical chemistry, organ weights, and macroscopic or
microscopic observations.  The NOEL was determined to be 1,000
mg/kg/day. A 90-day oral toxicity study found no statistical difference
in hematology, clinical chemistry, or urinalysis 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 difference
in hematology, clinical chemistry, or urinalysis 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 oral 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 associated 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
Laminarin did not induce mutant colonies over expected background
levels. The In Vitro Mammalian Cells in Culture Assay demonstrated that
Laminarin did not damage 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.	Acute Toxicity – Tier II and Tier III (40 CFR § 158.2050)

The Tier II studies listed below were the only 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. 47264941): 
Tier II data are required on the active ingredient for developmental
toxicity if there might be regular exposure to women.  In that case, a
second prenatal study using a different test subject is required.  A
second prenatal developmental toxicity study on rabbits found no
significant treatment-related reproductive effects or fetal
abnormalities, and confirmed a NOAEL of 1,000 mg/kg/day.  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 no toxicity was noted in either sex at any dose up to the
limit dose of 2000 mg/kg. This mutagenicity study, in conjunction with
the Tier I mutagenicity studies, satisfies the data requirement for
mutagenicity testing and is sufficient to confirm that there are no
expected dietary, occupational, or non-occupational risks of
mutagenicity with regard to Laminarin.

Immunotoxicity Testing (OPPTS Guidelines 880.3550; MRID No. 47264945): 
A waiver request was accepted for immunotoxicity for the following
reasons:  1) The potential for any immunotoxic effect is precluded by
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 Laminarin without known immunotoxicological
incident.  4) The toxicological profile in acute toxicological studies,
subchronic studies and developmental studies does not suggest any
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 is in the process of issuing test orders for endocrine effects.  The
schedule for issuance of test orders, and details regarding status is
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 required under the test orders will provide information to help EPA
identify whether chemicals have the potential to interact with the
estrogen, androgen, and/or thyroid hormone systems, which regulate
growth, metabolism, development, and reproduction.  The data generated
from the screens will provide robust and systematic scientific
information that will help EPA identify whether additional testing is
necessary.

Laminarin is a naturally occurring carbohydrate present in our fruits
and vegetables.  To date, there is no evidence to suggest that our
natural exposure to Laminarin affects the immune system, 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 significant exposures, effectively obviating any opportunity for
negative effects on humans or the environment.  Therefore, it is
unlikely that Laminarin will have estrogenic or endocrine effects.

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 suspect 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 systems 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 hydrolyzes 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.  Even in the event 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 – especially in cereal grains - without any
known detrimental effect.  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. 
There is no information in the public literature suggesting any health
issues to either animals or plants relative to this compound.  In sum,
no dietary exposure is expected; and any 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 rapidly, 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
hydrolyzation into glucose.  Moreover, risks from a miniscule aquatic
exposure would be negligible, given Laminarin’s nontoxic profile. 
Altogether, drinking water exposure is not expected to pose any
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 Children 

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 hydrolyze in water relatively rapidly, and so what few residues
might exist at harvest would be degraded into glucose during processing.
 In the event that there are any residues, acute 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
by 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 reasonable 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 reasonably be expected.  Such occupational exposures are expected to
be insignificant because - by virtue of Laminarin’s mode of action as
a SAR inducer - applications are directed and infrequent.  The
insignificance of any exposure is even more pronounced for residential,
school, or daycare areas.  Even in the event of incidental exposure,
health risks to humans, including infants and children, are considered
negligible, given Laminarin’s nontoxic profile.  

	

			a. Occupational 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 early in the growing season when it can best bolster
plant 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 plants.  Also, foliar applications
are expected for the substance to be most effective, further diminishing
the chance of spray drift associated with area-wide sprays.  Regardless,
requirements for the use of appropriate personal protective equipment
and precautionary statements are required on product labels to mitigate
any potential risks to pesticide handlers due to prolonged exposure.
But, even in the event of occupational exposure, any health risks
associated with regular exposure seem unlikely.  Humans have long
consumed Laminarin in fruits and vegetables with no history of
detrimental effects.  Moreover, Laminarin has been approved by 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, all acute, subchronic, and developmental
toxicity data submitted in support of this application for Laminarin
confirm its lack of toxicity through all routes of exposure.  Because of
a lack of likely 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.

			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 consumption
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 for 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.  Likewise directed foliar
applications, are not likely to result in dermal exposures, especially
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 concern regarding its
naturally occurring background levels, and a lack of any 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
mechanism 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 safety factors in FQPA and FIFRA.  A determination has been
made that no unreasonable adverse effects to the U.S. population in
general, and to infants and children in particular, will result from the
use of Laminarin when label instructions are followed. 

	C.  ENVIRONMENTAL ASSESSMENT

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 were
satisfied by submission of studies.  Laminarin is known to occur
naturally in the terrestrial and aquatic environment, and is not
associated with any 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 effects 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
indirect effects to any 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. 47264950
and 47264951): 

No avian toxicity is expected with regard to the pesticidal use of
Laminarin.  In an acute oral toxicity study, groups of bobwhites were
administered single oral doses ranging up to 2000 mg/kg body weight
Laminarin.  They were observed for 14 days. There were no mortalities
and no signs of adverse effects - all birds appeared healthy during the
test, and macroscopic examination revealed no abnormalities in any
birds. The acute oral LD50 was >2000 mg/kg, the highest dose tested.  In
a dietary toxicity study on bobwhites, groups of chicks were provided a
Laminarin-dosed diet for 5 days, 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 LD50 was
determined to be >5000 ppm.  A lack of toxicological endpoints supports
the conclusion that Laminarin is nontoxic to birds.

 were each ≥100 mg/L, and the LOEC and EC50 were >100 mg/L.  In an
acute toxicity test, groups of zebrafish were exposed to a nominal
concentration of 0 or 100 mg/L Laminarin for 96 hours. No mortality or
adverse clinical signs were seen at any intervals or in any of the test
groups. The 96-hr LC50 for Laminarin in Zebra Fish was >100 mg/L.  In a
second toxicity test, groups of Rainbow Trout 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.
The 96-hr LC50 for Laminarin in Rainbow Trout was >100 mg/L.  A 72-hour
laboratory study was conducted to determine the effects of Laminarin
(100 mg/L, nominal) on the growth of 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 EbC50 and ErC50 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 organisms 

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 negligible.  To the degree that
there is incidental exposure, Laminarin has been shown to have a
non-toxic mode of action relative to plants.  As a SAR inducer,
Laminarin bolsters plant health.  Accordingly, Laminarin would actually
be expected to have a strengthening effect on non-target plants.  

Non-Target Insect Testing (OPPTS Guideline 880.4350, 850.3020); MRID
Nos. 47264979 and 47264952):  Data indicate that the residues of
Laminarin pose 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 sprayed on glass plates at
varying rates up to10.0 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 fecundity was 10x greater than
expected residues of Laminarin at the time of pesticidal application.) 
There was no statistically significant difference in mortality between
the treated wasps and the untreated control groups.  Limit tests were
conducted to determine the acute oral and acute contact toxicity of
Laminarin to the Honey Bee. Both tests used a nominal dose of 100.00 µg
Laminarin/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 LD50 for Laminarin was >118.64 µg/bee, and the 48-hr contact
toxicity LD50 was >100.00 µg/bee.  Data indicate that exposures to
Laminarin 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.

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 any incidental exposures,
all data on file with the Agency demonstrate that Laminarin is nontoxic
to non-target organisms.  Laminarin is intended to be applied directly
to crops early in the growing season at bi-monthly intervals. 
Biodegradability data show that it does not persist, and that it
hydrolyzes rapidly.  (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 carbohydrate.  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 Laminarin’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 any 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 endangered 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;
accordingly exposures to threatened and endangered species are expected
to be negligible.  The Agency used its T-REX Model and its Individual
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 aquatic species from exposure to
Laminarin. These values (avian risk at 1 in 294,000 and aquatic risk at
1 in 418,000,000) suggest that Laminarin 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, respectively,
supporting the Agency’s finding that exposure to Laminarin  will have
No Effect (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
atypical, unusually high exposure to Laminarin, compared to the general
population.  Please comment if you are aware of any sub-populations that
may have atypical, unusually high exposure compared to the general
population.

VI.   RISK MANAGEMENT AND REGISTRATION DECISIONS tc "V.   RISK
MANAGEMENT AND REGISTRATION DECISION" 

	A.  Determination of Eligibility 

 tc "A.  Determination of Eligibility " \l 2 

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 supporting products
containing Laminarin.  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, EPA
concludes that 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
meaningful opportunity 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 types of
applications:  new active ingredients; first food use; first outdoor
use; first residential use; and other actions for which the Agency
anticipates significant public interest.  Accordingly, this pesticide
was subject to a 30-day comment period as a new active ingredient with
both food uses and outdoor uses.  No comments were received during that
comment period.

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 Laminarin demonstrate that it is
toxicity category III and IV for all routes of exposure.  (No
toxicological endpoints were established.)  Data confirm that Laminarin
does not demonstrate subchronic or developmental toxicity, and it is not
mutagenic or genotoxic.  EPA has no concerns 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
any threatened and endangered 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/Unconditional Registration

All data requirements are fulfilled and EPA has determined that an
unconditional registration for Laminarin is warranted under Section
3(c)(5) of FIFRA. 

		C.  Labeling

Before releasing pesticide products containing 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 determined that 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 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
types of data are listed below.   

	A.  Reporting 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).

Additionally, 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.

VIII. GLOSSARY OF ACRONYMS AND ABBREVIATIONS

BPPD	Biopesticides and Pollution Prevention Division

BRAD	Biopesticide Registration Action Document

CFR	Code of Federal Regulations

cm3 	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 Quality Protection Act

FR	Federal Register

g 	gram

kg	kilogram

L                  liter

LD50	median lethal dose. A statistically derived single dose that can be
expected 

	to cause death in 50% of the test animals when administered by the
route 

	indicated (oral, 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 Effect”

NIOSH 	National Institute for Occupational Safety and Health

OPP	Office of Pesticide Programs

OPPTS 	Office of Prevention, Pesticides, and Toxic Substances

PCR	polymerase chain reaction 

PPE 	personal protective equipment

TGAI 	technical grade of the active ingredient

IX. BIBLIOGRAPHY STUDIES SUBMITTED IN SUPPORT OF THIS REGISTRATION

Studies Submitted in Support of this Registration.

  HYPERLINK "JavaScript:sortUpdate(document.sort,'1')"  MRID 	 
HYPERLINK "JavaScript:sortUpdate(document.sort,'2')"  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	Smith, 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 - Analytical 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. Unpublished 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 Laminarin: 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	Smith, F. (2007) Summary of the OPPTS 830 Series
Physical-Chemical Properties Test Guidelines: (Vacciplant). Unpublished
study prepared by SciReg, Inc. 15 p.	24-Oct-2007

47264908	Smith, F. (2007) Color, Odor, Physical State: (Vacciplant).
Unpublished study prepared by SciReg, Inc. 4 p.	24-Oct-2007

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. Unpublished 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 Water.
Project Number: 00/907005/017. Unpublished study prepared by SEPC. 18 p.
24-Oct-2007

47264915	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 SEPC. 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. Unpublished study prepared by SEPC. 21 p.	24-Oct-2007

47264919	Luc, L. (2002) Laminarin - Soulubility in Water. Project
Number: 00/907005/008. Unpublished study prepared by SEPC. 43 p.
24-Oct-2007

47264920	Martel, I. (2002) Determination of pH Values - (Laminarin).
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/00/070. 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-Solubility 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.
41 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 Rat. Project Number: 20000698/ST,
20000698/ST/TAUVD/H11. Unpublished study prepared by Centre de
Recherches Biologiques. 30 p.	24-Oct-2007

47264932	Muller, W. (1999) Evaluation of Acute 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 Report. 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: 970353/ST.
Unpublished study prepared by Centre de Recherches Biologiques. 24 p.
24-Oct-2007

47264937	Longobardi, C. (2000) 4489-1 (product H 11): 4 Week Oral
Toxicity Study in Rats: Final Report. Project Number: 7286,
7286/T/240/99. Unpublished study prepared 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 Biologiques. 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. (2001) 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. (2002) In Vitro Mammalian Cell Gene Mutation Test
in L5178Y TK Mouse Lymphoma Cells: Laminarin. Project Number: 22626/MLY.
Unpublished study prepared by Centre International de Toxicologie. 47 p.
24-Oct-2007

47264944	Haddouk, H. (2001) Bone Marrow Micronucleus Test by Oral Route
in Mice: Laminarin. Project Number: 21149/MAS,
21149/MAS/LAMINARIN/LABORATOIRES/GOEMAR/SA. Unpublished study prepared
by Centre International de Toxicologie. 37 p.	24-Oct-2007

47264945	Smith, F. (2007) Toxicology Waiver Request - Immunotoxicity
(Laminarin). 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. Unpublished 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 mykiss (Laminarin). Project Number: 00/907005/021.
Unpublished study prepared by SEPC. 50 p.	24-Oct-2007

47264949	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: Dietary Toxicity (LC50) to the
Bobwhite Quail. Project Number: GOM/002, GOM/002/014410. Unpublished
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 mellifera L. in the Laboratory: Final Report. Project
Number: 20001342/01/BLEU. Unpublished 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. 27 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	Smith, 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	Smith, F. (2007) Summary of the OPPTS 830 Series
Physical-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-2007

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 Dilution 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 study 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 Heating (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 (Degrees) 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. Project 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) Free 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 Number 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-2007

47264975	Smith, F. (2007) Toxicology Waiver Request - Acute Inhalation
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, 9912812. 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 SA. 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

47264979	Tessier, C. (2001) The Effects of Phyliq (37 g/L Laminarin) on
Aphidius rhopalosiphi (Hymenoptera, Braconidae) on Artificial Substrate
in Laboratory: 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
Typhlodromus pyri (Acari, Phytoseiidae) on Artificial Substrate in
Laboratory: LR 50 Estimation and Reproduction Assessment . Project
Number: 01TYGOL24. 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 Laminarin 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.	15-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 Materials 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 Memoranda

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, Registration of an End-Use Product for VacciPlant that
Contains Laminarin (3.5%) (3.5%) dated October 28, 2008.

C.  References

U.S. EPA.  1998.  Guidance for Ecological 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 PESTICIDE DATA REQUIREMENTS

TABLE 1. Physical/Chemical Properties for Laminarin

TABLE 1.0  Physical and Chemical Properties for pure TGAI Laminarina 

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 oxidizing properties	MRID 47264911

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 47264920, 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	D420 = 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 method

830.7840 	Water Solubility	> 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 47264926

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/Toxicology Category	MRID	Study Conclusion

870.1100

Acute Oral	LD50>2,000 mg/kg

III	47264930

47264943	Acceptable

870.1200

Acute Dermal	LD50>5,000 mg/kg

IV	47264931

47264974	Acceptable

870.1300

Acute Inhalation	> 1.02 mg/L

III	47264932

	Acceptable

870.2400

Primary 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 

Acute Subcutaneous 	LD50>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	Acceptable 

870.3700b 

Prenatal Developmental Toxicity Study - Rabbit

	Maternal LOAEL = 1,000 mg/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 Mutation Assay	There was no
evidence of induced mutant colonies over background.

	47264943	Acceptable

870.5395

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

870.7800

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

Acute Toxicity Test, Daphnids 	EC50 >100 mg/L.	47264947	Acceptable

850.1075 

Acute Toxicity Freshwater Fish

Danio rerio	96 hr LC50  >100 mg/L.	47264948	Acceptable

850.1075

Fish Acute Freshwater  

Rainbow Trout

Oncorhynchus mykiss 	96-hr LC50 >100 mg/L. 

	47264949	Acceptable

850.2100

Avian Acute Oral Toxicity 

Bobwhite (Colinus virginianus) 	LD50 >2000 mg/kg	47264950	Acceptable

850.2200

Avian Dietary Toxicity 

Bobwhite (Colinus virginianus)	LC50 >5000 ppm	47264951	Acceptable

850.3020

Acute Contact Toxicity 

Honey bee (Apis mellifera)	LD50 >118.64 µg/bee

 48-hr contact LD50 >100.00 µg/bee.	47264952	Acceptable

850.5400

Algal Toxicity, Tiers I and II

Green alga Selenastrum capricornutum.	EbC50, ErC50, NOECb, and NOECr for
the test material at 24, 48, and 72 hours were each >100 mg/L	47264953
Acceptable

	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	Acceptable

880.4350

Nontarget Insect Testing 	Exposure to 10.0 L/ha of the test material did
significantly lower the fecundity of A. rhopalosiphi females compared to
the untreated control. However, 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

Laminarin	           					Page   PAGE  7 		                             
                                  

Biopesticide Registration Action Document

 

 PAGE