**[\<]{.mark}EPA BIOPESTICIDES AND POLLUTION PREVENTION DIVISION COMPANY
NOTICE OF FILING FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL
REGISTER**

**(7/1/2007)**[\>]{.mark}

**[\<]{.mark}EPA Biopesticides and Pollution Prevention Division
contact: \[Linda Hollis; (703) 308-8733\][\>]{.mark}**

**[\<]{.mark}*INSTRUCTIONS:* Please utilize this outline in preparing
the pesticide petition. In cases where the outline element does not
apply, please insert "NA-Remove" and maintain the outline. Please do not
change the margins, font, or format in your pesticide petition. Simply
replace the instructions that appear in green, i.e., "****\[insert
company name\]," with the information specific to your
action.[\>]{.mark}**

**[\<]{.mark}*SUBMISSION:* E-mail the completed template to:
duggard.mari@epa.gov.[\>]{.mark}**

**[\<]{.mark}*TEMPLATE:*[\>]{.mark}**

**[\<]{.mark}\[Laboratoires Goëmar SA\][\>]{.mark}**

**[\<]{.mark}\[Insert petition number\][\>]{.mark}**

**[\<]{.mark}** EPA has received a pesticide petition **(****\[insert
petition number\])** from **\[Laboratoires Goëmar SA c/o SciReg, Inc.\],
\[12733 Director's Loop, Woodbridge, VA 22192\]** proposing, pursuant to
section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21
U.S.C. 346a(d), to amend 40 CFR part 180.**[\>]{.mark}**

**[\<]{.mark}(Options (pick one)[\>]{.mark}**

> [\<]{.mark} 1. by establishing a tolerance for residues of[\>]{.mark}
> **NA-remove**

**[\<]{.mark}** 2. to establish an exemption from the requirement of a
tolerance for**[\>]{.mark}**

[\<]{.mark} 3. to establish an amendment/expansion of an existing
tolerance exemption for the[\>]{.mark} **NA-remove**

**[\<]{.mark}(Options (pick one)[\>]{.mark}**

> [\<]{.mark} 1. microbial pesticide **\[NA-remove\]**[\>]{.mark}

**[\<]{.mark}** 2. biochemical pesticide **\[Laminarin\][\>]{.mark}**

[\<]{.mark} 3. plant-pesticide **\[NA-remove\]** in or on
**\[NA-remove\].**[\>]{.mark}

**[\<]{.mark}** Pursuant to section 408(d)(2)(A)(i) of FFDCA, as
amended, **\[Laboratoires Goëmar SA c/o SciReg, Inc.\]** has submitted
the following summary of information, data, and arguments in support of
their pesticide petition. This summary was prepared by **\[Laboratoires
Goëmar SA c/o SciReg, Inc.\]** and EPA has not fully evaluated the
merits of the pesticide petition. The summary may have been edited by
EPA if the terminology used was unclear, the summary contained
extraneous material, or the summary unintentionally made the reader
conclude that the findings reflected EPA's position and not the position
of the petitioner.**[\>]{.mark}**

**[\<]{.mark}I. \[Laboratoires Goëmar SA c/o SciReg, Inc.\] Petition
Summary[\>]{.mark}**

> [\<]{.mark} **\[Insert petition number\]**[\>]{.mark}

[\<]{.mark}*A. Product Name and Proposed Use Practices*[\>]{.mark}

**[\<]{.mark}** **\[The biopesticide, laminarin, is extracted from a
brown seaweed, *Laminaria digitata*. This brown seaweed grows attached
to the bedrock of the seashore on the sublittoral fringe (uncovered only
at spring tides). In France, it proliferates on the Brittany coastline.
*Laminaria digitata* is now the most farmed seaweed in France. The
harvest is regulated by Le Ministère de la Mer (French Ministry of the
Sea) and La Chambre Syndicale des Algues (Corporate Union for Algae).
*L. digitata* is also used in cosmetics as anti-cellulite and
anti-obesity treatments. It also has use in cancer treatment, and
treatments against bacterial, viral, and fungal infections.**

**Laminarin will be used to elicit the target crops' self-defense
mechanisms against such disease organisms as gray mold, powdery mildew,
downy mildew, fire blight, and bacterial spot.**

[]{.mark}

**For the first laminarin end-use product Goëmar intends to register
(VacciPlant), the concentration of laminarin will be 3.51% with an
application rate of 9.7 -- 14.4 fl. oz. per acre in 5-100 gallons of
water. Applications can be made aerially or via standard tractor-mounted
hydraulic sprayer.\][\>]{.mark}**

[\<]{.mark}*B. Product Identity/Chemistry*[\>]{.mark}

**[\<]{.mark}** 1. *Identity of the pesticide and corresponding
residues.* **\[Laminarin is one of the naturally-occurring glucans from
*L. digitata*. Glucans are polysaccharides of D-glucose monomers linked
by glycosidic bonds. β-glucans, of which laminarin is one, are found in
the bran of cereal grains, most abundantly in barley and oats and, to a
much lesser degree, in rye and wheat. They are useful in human nutrition
as texturing agents and as soluble fiber supplements. *L. digitata* is
used for sea-vegetable production in Ireland and France, and is an
important food item in Japan. []{.mark}**

[]{.mark}

**Laminarin appears to be a β-(1→3)-linked D-glucan with occasional
β-(1→6) linkage series of molecules, composed of a major M-series
containing 20-30 glucosyl residues linked to a mannitol terminal
residue, and a minor G-series containing 22-28 glucosyl residues. Both
series have a mean degree of polymerisation of 25 glucosyl pure
residues; an approximately 3:1 ratio of M-series to G-series molecules
is maintained across the range of molecular sizes. M-series molecules
contain 0 to 4 branches, with an average of 1.3 branches per molecule;
branched G-series molecules are also detected. This study also showed
that 75% of branches are single glucosyl residues.**

> []{.mark}

**Molecular formula: (C~6~H~12~O~6~)~n~ n = 25 to 30**

**Molecular mass: 4500 - 5000 g/mol\][\>]{.mark}**

**[\<]{.mark}** 2. *Magnitude of residues at the time of harvest and
method used to determine the residue.* **\[No magnitude of residue (MOR)
studies have been conducted on laminarin, as it is a naturally-occurring
plant extract (glucans, which are polysaccharides) which cannot be
differentiated from a plant's other naturally-occurring
oligosaccharides. Laminarin is also toxicologically innocuous (see
Toxicological Profile, pages 6-12). Further, OPPTS Guideline 860.1550
indicates that residue studies "will be waived for
toxicologically-innocuous active ingredients." As a tolerance exemption
is being sought, no magnitude of the residue studies or residue
analytical methods are being submitted\][\>]{.mark}**

**[\<]{.mark}** 3. *A statement of why an analytical method of detecting
and measuring the levels of the pesticide residue are not needed.*
**\[Laminarin is a naturally-occurring plant extract (glucans, which are
polysaccharides) which cannot be differentiated from a plant's other
naturally-occurring oligosaccharides. A tolerance exemption is being
sought for laminarin.\][\>]{.mark}**

**[\<]{.mark}***C. Mammalian Toxicological Profile***[\>]{.mark}**

1.  **[\<]{.mark}\[Acute oral toxicity**

**Report No. 20010618 ST**

**Guideline: 870.1100**

**Methods: Groups of five male and five female rats were exposed orally
to 2,000 mg/kg of laminarin (91% purity) in a volume of 10 ml/kg as a
suspension in water for injection. A group of control animals under the
same conditions as the test animals was treated with 10 ml/kg of water.
Animals were monitored daily for 14 days after administration of the
compound.**

**Findings: No mortalities occurred and no clinical signs were observed
throughout the observation period. No effects on body weight development
were noted. At gross necropsy, no visible lesions were observed.**

**Conclusion: The acute oral LD50 of laminarin to rats was determined to
be greater than 2,000 mg/kg, the highest dose level tested.**

2.  **Acute subcutaneous toxicity**

> **Report No. 970353 ST**

**Guideline: None**

**Methods: 1,000 mg/kg of laminarin (91% purity) was administered
subcutaneously in a volume of 5 ml/kg as a suspension in water to five
male and five female rats. A group of control animals under the same
conditions as the test animals was treated with 5 ml/kg of water.
Animals were monitored daily for 14 days after administration of the
compound.**

**Findings: No mortalities occurred, and no clinical signs were observed
throughout the observation period. No effects on body weight development
were noted. At gross necropsy, no visible lesions were observed.**

**Conclusion: The acute subcutaneous LD50 of laminarin to rats was
determined to be greater than 1,000 mg/kg, the highest dose level
tested.**

3.  **Acute dermal toxicity**

**Report No. 20000698 ST**

**Guideline: 870.1200**

**Methods: 5,000 mg/kg of laminarin (91% purity) was applied to the skin
in the dorsal region of each animal in a volume of 8 ml/kg as a
suspension in water to five male and five female rats. A group of
control animals under the same conditions as the test animals was
treated with 8 ml/kg of water. Animals were monitored daily for 14 days
after administration of the compound.**

**Findings: No mortalities occurred and no clinical signs were observed
throughout the observation period. No effects on body weight development
were noted. At gross necropsy, no visible lesions were observed.**

**Conclusion: Based on the above, the dermal LD50 of laminarin in rats
was determined to be greater than 5,000 mg/kg, the highest dose level
tested.**

**4. Evaluation of acute inhalation toxicity of laminarin in rats**

**Report No. 980001 EX**

**Guideline: 870.1300**

**Methods: Groups of five male and five female Charles River Wistar rats
were exposed (nose only) to laminarin (91% purity). The test article was
dissolved in distilled water at 10%, and was administered as an aerosol
of this aqueous solution for 4 hours with the maximum attainable
concentration of 1.02 mg/L. Animals were examined for mortality,
clinical signs, body weight gain, and pathological alterations of organs
at the end of a 14-day observation period.**

**Findings: No mortalities were observed. No clinical signs were
observed throughout the observation period. No effects on body weight
were noted. At gross necropsy, no visible lesions were observed.**

**Conclusion: The acute inhalation LC50 of laminarin in rats was
determined to be greater than 1.02 mg/L, the maximum attainable
concentration.**

**5. Primary eye irritation**

**Report No. 20010615 ST**

**Guideline: 870.2400**

**Methods: 0.1 g of laminarin (91% purity) was instilled into the
conjunctival sac of the left eye of each of three rabbits. The untreated
right eye served as a control.**

**Findings: The mean indices per parameter (24, 48, 72 h) were zero for
all three rabbits for chemosis, iris and cornea effects, and for one of
the three for redness. The mean index for redness in the other two
rabbits was 0.33.**

**Conclusion: Laminarin is considered non-irritating to the eyes of
rabbits.**

**6. Primary dermal irritation**

**Report No. 20010617 ST**

**Guideline: 870.2500**

**Methods: 0.5 g of laminarin (91% purity) was applied to the right
shaved flank of each of three rabbits. Adjacent surfaces of untreated
skin of each animal served as controls. The compound was moistened with
0.5 ml of water for injection in order to allow good contact between the
test substance and the skin. Semi-occlusive dressings held the compound
in place for 4 hours.**

**Findings: The mean indices per parameter (24, 48, 72 h) were zero for
all three rabbits for edema and for two of the three rabbits for
erythema. The third rabbit had a mean erythema index of 1.00.**

**Conclusion: Laminarin is considered non-irritating to the skin of
rabbits.**

**7. Dermal sensitization -- Magnusson and Kligman maximization test\
Report No. 20010616 ST**

**Guideline: 870.2600**

**Methods: The maximum slight to moderately irritating laminarin (91%
purity) concentration (based on the cutaneous reaction 24 hours after
intradermal administration) and used during the primary induction phase
was 25% (p/v) in water for injection.**

> **The maximum slight to moderately irritating laminarin concentration
> (based on the reading of cutaneous reactions 1 hour after removing the
> dressing of a 48-hour epicutaneous exposure and used during the second
> induction phase and the sensitization phase performed by the topical
> route) was 25% (p/v) in water for injection.**
>
> **The Maximum Non-Irritant Concentration (MNIC) determined by
> epicutaneous application (based on reading of cutaneous reactions 24
> and 48 hours after removing the dressing of a 24-hour exposure) and
> used during the challenge phase was 25% (p/v) in water for
> injection.**
>
> **Determination of the degree of allergenicity at 24 and 48 hours was
> based upon the percentage of animals in the group showing a reaction,
> rather than on its severity.**
>
> **The sensitivity and the reliability of the experimental method is
> verified, at least every six months, using a positive control group in
> which animals are treated with dinitrochlorobenzene (DNCB, 1%).**

**Findings: 100% of the positive control animals were sensitized at 24
hours and 80% at 48 hours. The laminarin-treated group had no sensitized
animals at either 24 or 48 hours.**

**Conclusion: Laminarin is considered a non-sensitizer to guinea pigs.**

**8. 4-week oral toxicity study in rats\
Report No. RTC 7286/T/240/99**

**Guideline: 870.3050**

**Methods: The toxicity of laminarin (97.6% purity), when given by daily
oral administration to rats, was investigated over a period of four
consecutive weeks.**

**A single group of 5 male and 5 female Sprague-Dawley rats received the
test substance daily by oral gavage at a dose level of 1,000 mg/kg for
28 consecutive days. A second similarly-constituted control group
received 0.5% carboxymethylcellulose in distilled water.**

**Findings: There were no toxicologically significant findings in
mortality, clinical observations, neurotoxicity assessment, body weight,
food consumption, hematology, clinical chemistry, organ weights, and
macroscopic or microscopic observations.**

**Conclusion: No toxicologically significant findings were observed in
any of the parameters investigated following treatment with laminarin at
a level of 1,000 mg/kg/day. The NOEL was determined to be 1,000
mg/kg/day.**

**9. 90-day oral toxicity study in rats**

**Report No. 20000389T**

**Guideline: 870.3100**

**Methods: Laminarin (94.9% purity) was administered daily by the oral
route for 90 consecutive days to one group of Sprague-Dawley rats
treated at the limit dose of 1,000 mg/kg/day. A group of control animals
was given the vehicle (water) under the same conditions. Each group
included 10 male and 10 female rats.**

**Examinations included: mortality, clinical observations of animals,
body weight changes, food and water consumption, clinical pathology,
ophthalmology, macroscopic findings, organ weights, and
histopathology.**

**Findings: No deaths occurred during the study.**

**No treatment-related clinical or macroscopic examination changes were
recorded and there was no change in functional tests/ophthalmology.
Treated animals had similar body weight changes, food and water
consumptions and organ weights to controls. There was no statistical
difference in hematology, clinical chemistry, or urinalysis. No
treatment-related histopathological changes were observed.**

**Conclusion: Laminarin administered for 90 consecutive days to male and
female Sprague-Dawley rats at 1,000 mg/kg was well tolerated.**

**The NOAEL was determined to be 1,000 mg/kg/day.**

**10. 90-day oral toxicity study in dogs**

**Report No. 20000390T**

**Guideline: 870.3150**

**Methods: Laminarin (94.9% purity) was administered daily by the oral
route for 90 consecutive days to one group of Beagle dogs treated at the
limit dose of 1,000 mg/kg/day. A group of control animals was given the
vehicle (water) under the same conditions. Each group included 4 male
and 4 female dogs.**

**Examinations included: mortality, clinical observations of animals,
body weight changes, food and water consumption, clinical pathology,
ophthalmology, macroscopic findings, organ weights, and
histopathology.**

**Findings: No treatment-related deaths occurred during the study. No
treatment-related clinical (except a slight increase of diarrhea and/or
soft stools common in young laboratory dogs in the treated group) or
macroscopic examination changes were recorded. There was no change in
functional tests/ophthalmology. Treated animals had similar body weight
changes, food and water consumption, and organ weights to controls.
There were no statistical differences in hematology, clinical chemistry,
or urinalysis. No treatment-related histopathological changes were
observed.**

**Conclusion: Laminarin administered for 90 consecutive days to male and
female Beagle dogs at 1,000 mg/kg was well tolerated.**

**The NOAEL was determined to be 1,000 mg/kg/day.**

**11. Ames mutagenicity test\
Report No. IPL-R 991011/H11**

**Guideline: 870.5100**

**Methods: Laminarin (97.6% purity) was tested with and without
metabolic activation (S-9) against *Salmonella typhimurium*: TA 1535, TA
1537, TA 98, TA 100 and *Escherichia coli*: WP2 (pKM101) and WP2uvrA
(pKM101) using the maximum concentration of 5,000 µg/plate and four
lower dilutions chosen according to a geometric ratio.**

**Findings: With and without metabolic activation in two independent
assays, no biologically significant increase in the number of revertants
was noted in the four *Salmonella typhimurium* and the two *Escherichia
coli* strains tested, in the presence of the test compound, laminarin.
It is noted that with metabolic activation, a slight, but statistically
significant, increase in the number of revertants was observed at the
maximum dose tested of 5,000 µg/plate in the first assay in *E. coli*
strains WP2 (pKM101) and WP2uvrA (pKM101) and at the three tested doses
of 150, 1,500 and 5,000 µg/plate in the second assay in the last strain,
WP2uvrA (pKM101). However, this effect was not biologically significant,
not dose-related, and as biological relevance should be considered first
according to OECD's recommendations, it was not attributed to mutagenic
activity.**

**Conclusion: Laminarin did not induce mutagenic activity in the four
*Salmonella typhimurium* and the two *Escherichia coli* strains
tested.**

**12. *In vivo* bone marrow micronucleus test**

**Report No. 21149 MAS**

**Guideline: 870.5395**

**Methods: After a preliminary test to define the dose levels, three
groups of five male and five female Swiss ICO: OF1 (IOPS Caw) mice
received two oral treatments of laminarin (94% purity) at 500, 1,000 and
2,000 mg/kg/day, at a 24-hour interval. All dose levels were corrected
for purity (94%). The top dose level for the cytogenetic test was
selected according to the criteria specified in the international
guidelines; since no observable toxic effects were noted in the
preliminary test, the top dose level selected for the definitive test
was 2,000 mg/kg/day. A control group received the vehicle (water) under
the same experimental conditions, and a positive control group received
cyclophosphamide at 50 mg/kg once.**

**The animals were sacrificed 24 hours after the last treatment. Bone
marrow smears were then prepared.**

**For each animal, the number of micronucleated polychromatic
erythrocytes (MPE) was counted in 2,000 polychromatic erythrocytes (PE).
The PE and normochromatic (NE) erythrocyte ratio was established by
scoring a total of 1,000 erythrocytes (PE+NE).**

**Findings: The mean values of MPE, as well as the PE/NE ratio for the
vehicle and positive controls, were consistent with the historical
data.**

**Cyclophosphamide induced a highly significant increase (p \< 0.001) in
the frequency of MPE, indicating the sensitivity of the test system
under these experimental conditions. The study was, therefore,
considered valid.**

**For both males and females, the mean values of MPE, as well as the
PE/NE ratio in the groups treated with the test substance, were
equivalent to those of the vehicle group.**

**Conclusion: Laminarin does not induce damage to the chromosomes or the
mitotic apparatus of mice bone marrow cells after two oral
administrations, with a 24-hour interval, at 500, 1,000 or 2,000
mg/kg/day.**

**13. *In vitro* mammalian cell gene mutation test in L5178Y TK+/- mouse
lymphoma cells**

**Report No. 22626 MLY**

**Guideline: 870.5300**

**Methods: After a preliminary screening assay, laminarin was evaluated
in two independent experiments. Five dose levels of laminarin (312.5,
625, 1250, 2500, and 5000 µg/ml; two cultures/dose level) were tested in
both test with and without metabolic activation (S-9).**

**Findings: Except for some sporadic decreases in the relative survival
(RS) or relative total growth (RTG), no noteworthy effects were induced
in either experiment. The test material did not induce any noteworthy
increases in the mutation frequency, either with or without S-9.**

**Conclusion: Laminarin did not show any mutagenic activity in the mouse
lymphoma assay.**

**14. Teratogenicity -- rat\
Report No. 20000387 T**

**Guideline: 870.3700**

**Methods: SPF (Specific Pathogen Free) Sprague-Dawley rats were used.
The study involved two groups: 1,000 mg/kg/day and a control. The test
substance was administered to 21 pregnant females at 1,000 mg/kg/day by
oral gavage at a volume of 5 ml/kg in sterile water. Control animals (23
pregnant females) were given sterile water under the same conditions.
Doses were prepared daily.**

**Findings: No treatment-related deaths occurred during the study. No
treatment-related clinical or macroscopic examination changes were
recorded. Treated animals had similar body weight changes, food and
water consumptions, and uterus weights when compared to controls. There
were no significant reproductive effects or fetal abnormalities.**

**Conclusion: Under the experimental conditions adopted, laminarin
administered to female rats at the limit dose of 1,000 mg/kg/day was
well tolerated. No major maternal toxicity and no external fetal
abnormalities were reported.**

> **The NOAEL was determined to be 1,000 mg/kg/day.**

**15. Teratogenicity -- rabbit\
Report No. 20000388 T**

**Guideline: 870.3700**

**Methods: Albino SPF (Specific Pathogen Free) New-Zealand White rabbits
were used. The study involved two groups: 1,000 mg/kg/day and a control.
The test substance was administered to 13 pregnant females at 1,000
mg/kg/day by oral gavage at a volume of 5 ml/kg in sterile water.
Control animals (16 pregnant females) were given sterile water under the
same conditions. Doses were prepared daily.**

**Findings: No treatment-related deaths occurred during the study. No
treatment-related clinical or macroscopic examination changes were
recorded. There were no statistically treatment-related significant
differences between the treated and control animals with regard to body
weight changes or food consumption. Treated and control animals had
similar water consumption and uterus weights. There were no significant
treatment-related reproductive effects or fetal abnormalities.**

**Conclusion: Under the experimental conditions adopted, laminarin
administered to female rabbits at the limit dose of 1,000 mg/kg/day was
well tolerated. No maternal toxicity and no treatment-related fetal
abnormalities were reported.**

> **The NOAEL was determined to be 1,000 mg/kg/day.\][\>]{.mark}**

**[\<]{.mark}***D. Aggregate Exposure***[\>]{.mark}**

-   **[\<]{.mark}** 1. *Dietary exposure.* **\[Considering laminarin's
    mode of action, its demonstrated lack of toxicity, its approval in
    Ireland, France, and Japan as a food source, its natural occurrence,
    and the fact that it hydrolyses to smaller-sized oligosaccharides
    and ultimately to glucose, it is unlikely that exposure to laminarin
    would have any negative impact on human health.\]**[\>]{.mark}

[\<]{.mark} i. *Food.* **\[Dietary exposure to laminarin should not be
of concern due to the low toxicity shown in the acute, subchronic, and
teratogenicity studies previously submitted. In addition, laminarin is
naturally occurring in foods. No adverse health issues to man, animals,
or plants have been associated with this compound. Exposure to laminarin
from its pesticidal use is anticipated to be very low to non-existent
due to its hydrolytic conversion to even smaller oligosaccharides and
ultimately to glucose.**

**During a meeting on October 14, 1997 the "Conseil Supérieur d'hygiène
publique de France" approved the use of laminar algae (*Laminaria
digitata* and *Laminaria saccharina*) in human nutrition. Approval was
subject to the following conditions:**

-   **For an adult, the recommended daily amount must be less than or
    equal to 30 mg of dry product (or 210 mg of fresh product).**

-   **For a child less than 4 years old, the recommended daily amount
    must be less than or equal to 15 mg of dry product (or 105 mg of
    fresh product).**

> **Pesticidal uses proposed for laminarin by Goëmar are expected to
> result in dietary exposure much lower than these.**

-   **The iodine and heavy metal limits previously set for laminar algae
    are to be applied: arsenic (As: 3 mg/8 kg), cadmium (Cd: 0.5 mg/kg),
    mercury (Hg: 0.1 mg/kg), iodine (I: 6,000 mg/kg), lead (Pb: 5
    mg/kg), tin (Sn: 5 mg/kg).**

```{=html}
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-   **The use of these algae must be in the form of food
    seasoning.\]**[\>]{.mark}

[\<]{.mark} ii. *Drinking water.* **\[*Laminaria digitata* is a
naturally-occurring brown seaweed. It is not considered to be a risk to
drinking water. Hydrolysis of laminarin to oligosaccharides and then to
glucose, percolation through soil, and municipal treatment of drinking
water would reduce or eliminate the possibility of exposure through
drinking water. Typical agricultural practices are carried out such that
spray drift is minimized. Although possible minimal spray drift may
contact drinking water, natural and water treatment steps would further
reduce or eliminate the possibility of exposure via potable water. The
end-use product, VacciPlant, is prohibited by the label from direct
application to water and, therefore, is not expected to be present at
significant concentrations in aquatic environments.\]**[\>]{.mark}

[\<]{.mark} 2. *Non-dietary exposure*. **\[The potential for
non-occupational, non-dietary exposure from laminarin to the general
population is not expected to be significant and is not expected to
present any risk of adverse health effects, especially given the lack of
acute and subchronic toxicity, acute irritation, mutagenic, and
teratogenic effects.**

***L. digitata* is used in the cosmetic industry, mainly in treatments
against cellulite and obesity, either alone or combined with other
extracts to enhance its activity, but also as a skin conditioner and
fragrance ingredient.\]**[\>]{.mark}

[\<]{.mark}*E. Cumulative Effects*[\>]{.mark}

[\<]{.mark} **\[VacciPlant (containing 3.51% laminarin) is applied using
a standard tractor-mounted field crop sprayer with hydraulic boom and
nozzles. VacciPlant may also be applied aerially. Only applications to
fruiting vegetables including tomatoes, eggplant, and peppers; cucurbits
including zucchini, cucumbers, watermelon, and melon; grapes;
apples/pears; and strawberries are intended at present.**

**There are no other products registered for food use that contain
laminarin as the active ingredient. As previously stated, the brown
seaweed from which laminarin is extracted, is used in sea-vegetable
production in Ireland and France, and is an important food item in
Japan. There are currently no known adverse effects associated with
laminarin consumption. Laminaria species are also harvested for the
extraction of alginate and have other medical and cosmetic uses. In
addition, the label will require pesticide applicators and other
handlers to wear personal protective equipment (PPE) to mitigate
exposure.\]**[\>]{.mark}

[\<]{.mark}*F. Safety Determination*[\>]{.mark}

[\<]{.mark} 1. *U.S. population.* **\[*Laminaria digitata* is a
naturally-occurring brown seaweed. The plant extract, laminarin, has low
toxicity as demonstrated by the acute, subchronic, teratogenicity, and
mutagenicity studies summarized above. Based on these results, the
aggregate exposure to laminarin over a lifetime should not change with
the pesticidal application of laminarin. Thus, there is a reasonable
certainty that no harm will result from aggregate exposure to
laminarin.\]**[\>]{.mark}

[\<]{.mark} 2. *Infants and children*. **\[Based on the natural
occurrence, current international food allowances, and lack of toxicity
of laminarin, there is reasonable certainty that no harm to infants and
children will result from aggregate exposure to laminarin. In addition,
the brown seaweed from which laminarin is extracted, is used in
sea-vegetable production in Ireland and France, and is an important food
item in Japan; there are currently no known adverse effects associated
with laminarin consumption. Laminarin is one of the naturally-occurring
glucans from *Laminaria digitata*. Glucans are polysaccharides of
D-glucose monomers linked by glycosidic bonds. β-glucans, of which
laminarin is one, are found in the bran of cereal grains, most
abundantly in barley and oats and, to a much lesser degree, in rye and
wheat. They are useful in human nutrition as texturing agents and as
soluble fiber supplements.**

**Laminarin hydrolyses to smaller-sized oligosaccharides and ultimately
to glucose, and the toxicity, mutagenicity, and teratology studies
summarized herein, show virtually no negative effects. Exempting
laminarin from the requirement of a tolerance should pose no significant
risk to humans or the environment and should be considered safe when
used on raw agricultural commodities.\][\>]{.mark}**

**[\<]{.mark}***G. Effects on the Immune and Endocrine
Systems***[\>]{.mark}**

[\<]{.mark} **\[There are no known effects on the immune and endocrine
systems, nor are any effects expected. Laminarin is not structurally
related to any known hormones, neurotoxins, or endocrine
disruptors.\]**[\>]{.mark}

**[\<]{.mark}***H. Existing Tolerances***[\>]{.mark}**

[\<]{.mark} **\[Laminarin does not have any existing U.S.
tolerances.\]**[\>]{.mark}

**[\<]{.mark}***I. International Tolerances***[\>]{.mark}**

**[\<]{.mark} \[There are no Codex Maximum Residue Levels or
international tolerance exemptions for laminarin.\][\>]{.mark}**