Document ID: EPA-HQ-OPP-2009-0189-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2009-04-08T04:00Z

<EPA BIOPESTICIDES AND POLLUTION PREVENTION DIVISION COMPANY NOTICE OF
FILING FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER  >

<EPA Biopesticides and Pollution Prevention Division contact: [insert
name and telephone number with area code]>

 

<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.>

<SUBMISSION: E-mail the completed template to: hollis.linda@epa.gov.>

<TEMPLATE:>

<[Valent BioSciences Corporation]>

<[# 73049-EUP-T]>

<	EPA has received a pesticide petition ([# 73049-EUP-T]) from [Valent
BioSciences Corporation], [870 Technology Way, Libertyville, IL 60048]
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.>

<(Options (pick one)>

<	3. to establish an amendment/expansion of an existing tolerance
exemption for the>

<(Options (pick one)>

<	1. microbial pesticide  [NA Remove]>

<	2. biochemical pesticide [S-Abscisic Acid;
(S)-5-(1-hydroxy-2,6,6-trimethyl-4-oxo-1-cyclohex-2-enyl)-3-methyl-penta
-(2Z,4E)-dienoic Acid]>

<	3. plant-pesticide [NA Remove] in or on 

			[Leafy Vegetables, (Crop Group 4)

			Herbs and Spices, (Crop Group 19)

			Pome Fruit, (Crop Group 11)

			Stone Fruit, (Crop Group 12)

			Pineapple].>

<	Pursuant to section 408(d)(2)(A)(i) of  FFDCA, as amended, [Valent
BioSciences Corporation] has submitted the following summary of
information, data, and arguments in support of their pesticide petition.
This summary was prepared by [Valent BioSciences Corporation] 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.>

<I. [Valent BioSciences Corporation]  Petition Summary>

<	[# 73049-EUP-T]>

<A. Product Name and Proposed Use Practices>

<	[Abscisic acid (ABA) is a hormone that has been found in all vascular
plants thus far analyzed as well as in algal plants.  Levels of ABA vary
from 3 to 5 ppb in aquatic plants to 10 ppm in avocado fruit.  ABA is
also produced by some phytopathogenic fungi including Cercospora cruenta
and Botrytis cinerea.

ABA is involved in many major processes during plant growth and
development including dormancy, germination, bud break, flowering, fruit
set, general growth and development, stress tolerance, ripening,
abscission and senescence.  One of the best-known roles of ABA is its
regulation of water loss through control of stomatal closure.  ABA is
one of the five major hormones found in plants.  In July of 2005 the
Agency classified ABA as a biochemical pesticide because of its
ubiquitous presence in nature.

Valent BioSciences Corp. is requesting a extension of the temporary
tolerance exemption for Abscisic Acid (ABA) for the use on grapes, to
also cover the listed crops; [Leafy Vegetables, (Crop Group 4), Herbs
and Spices, (Crop Group 19), Pome Fruit, (Crop Group 11), Stone Fruit,
(Crop Group 12), and Pineapple].

Proposed Applications, Rates, and Timings      

S-ABA will be applied in one to four applications of 100 to 2000 ppm
each in a water volume of up to 200 gallons per acre.]>

<B. Product Identity/Chemistry>

<	1. Identity of the pesticide and corresponding residues. [S-Abscisic
acid;
(S)-5-(1-hydroxy-2,6,6-trimethyl-4-oxo-1-cyclohex-2-enyl)-3-methyl-(2Z,4
E)-pentadienoic acid, (CAS #: [21293-29-8]) has been tested and
characterized.]>

<	2. Magnitude of residues at the time of harvest and method used to
determine the residue. [Residues of ABA from application to the listed
crops can be expected to rapidly dissipate to levels consistent with
those observed naturally in fruits and vegetables.]>

<	3. A statement of why an analytical method of detecting and measuring
the levels of the pesticide residue are not needed. [Residues of ABA
applied to plants are subject to rapid degradation and
photoisomerization, the route and rate of which is well understood. 
Because of the natural occurrence of ABA in all plant derived food or
feed items and the use rate and use pattern, no residues are expected be
present above the natural background levels of ABA at harvest. 
Analytical methods for the measurement of Abscisic acid in crop
materials are present in the literature.  A tolerance exemption petition
normally does not require submission of analytical methods to measure
residues for which a tolerance is not being established.]>

<C. Mammalian Toxicological Profile>

<	[Acute toxicity:   The acute oral toxicity determined using the rat
was greater than 5,000 mg/kg of body weight in female rats.  The acute
dermal toxicity using the rat, was greater than 5,000 mg/kg body weight
in male and female rats.  The acute inhalation toxicity was greater than
2.06 mg/L in male and female rats.>

Primary eye irritation, tested in rabbits, showed mild irritation to the
eye.  Iritis and conjunctivitis cleared after 24 hours.   Primary skin
irritation, tested in the rabbit, showed this material to be slightly
irritating.  This irritation cleared within 24 hours after treatment. 
ABA was tested for Sensitization in the Guinea Pig and found not to be a
skin sensitizer.  

Genotoxicity:   From three mutagenicity studies (Ames test, mouse
micronucleus assay, and unscheduled DNA synthesis assay in the rat), it
was determined that abscisic is not mutagenic.  

Subchronic Toxicity:  	Dermal exposure to S-ABA for 6 hours each day for
a period of 3 weeks resulted in all male and some female animals treated
at 1000 mg/kg/day, and a few animals treated at 300 mg/kg/day being
noted with very slight erythema (barely perceptible) at dose site on up
to 3 occasions during the study.  Increase in white blood cell count and
its associated parameters were observed in males treated at 1000
mg/kg/day, however, as examination of the blood smears revealed normal
morphology with no corroborating histological findings, the changes were
considered not to be toxicologically significant.

	In conclusion, under the conditions of this study, the No Observed
Adverse Effect Level (NOAEL) was considered to be 1000 mg/kg/day, the
limit dose.

	The test substance was administered to four groups of 20 Sprague-Dawley
rats (10 males and 10 females) at levels up to 20,000 ppm in the diet,
for 13-weeks.  No treatment related deaths occurred.  A
non-statistically significant slight reduction in mean body weight gain
and group mean bodyweight throughout treatment in males treated with
20,000 ppm and non-statistically significant reduction in group mean
bodyweight gain in females treated at 20,000 ppm. There was no effect on
food consumption.

	Increased covariant liver weights (without statistical significance)
noted in males treated at ≥ 6,000 ppm and females treated at 20,000
ppm, correlates with the slight change noted in cholesterol noted in
males, however triglycerides were decreased with no changes seen in the
proteins or liver enzymes and so these findings were not conclusive of
toxicity. Furthermore, there were no differences noted in clinical
pathology or histopathology of the liver.  All differences noted in the
covariant thyroid, liver, pituitary, spleen and adrenal gland weights in
males or females (without statistical significance) were not represented
in the clinical pathology or histopathology findings and therefore
considered not to be indicative  of toxicity from S-ABA.

	In conclusion, under the conditions of this study, the No Observed
Adverse Effect Level (NOAEL) was considered to be 20,000 ppm, the limit
dose.

Developmental:  A Prenatal Developmental Toxicity study of S-Abscisic
Acid was performed by orally gavage to 3 groups of 25 bred female
Crl:CD(SD) rats once daily from gestation days 6 through 19.  Dosage
levels were 500, 750 and 1000  mg/kg/day administered at a dosage
volume of 10 mL/kg to all groups.  

	All females in all groups survived to the scheduled necropsy on
gestation day 20.  No test article-related clinical findings were noted
in the 500 mg/kg/day group.  A transient mean body weight loss was
noted in the 1000 mg/kg/day group on the first day of dose
administration.  However, there was no corresponding reduction in food
consumption noted in this group and mean body weight gains in this group
were similar to the control group throughout the remainder of the
treatment period.  Furthermore, the decrease was not of sufficient
magnitude to affect the overall mean body weight gain when evaluated for
the entire period or mean body weights throughout the study.  Therefore,
the body weight loss on the first day of dose administration in the
1000 mg/kg/day group although considered test article-related was not
indicative of an adverse change.

	There were no test-article-related macroscopic findings noted for
females in any group at the scheduled necropsy.

	No test article-related effects were noted on intrauterine growth and
survival or fetal morphology at any dosage level.

	Based on the lack of adverse test article-related effects on maternal
animals and on prenatal development, a dosage level of 1000 mg/kg/day
(expressed as active moiety) was considered to be the
no-observed-adverse-effect level (NOAEL) for maternal toxicity and
prenatal developmental toxicity when S-Abscisic Acid was administered
orally by gavage to pregnant Crl:CD(SD) rats.]

<D. Aggregate Exposure>

<	1. Dietary exposure. [ABA is a natural biochemical plant growth
regulator present in all vascular plants, algae and some fungi.  It is
naturally present in fruits and vegetables at various levels, generally
not in excess of 10 ppm, and has always been a component of any diet
containing plant materials.  The proposed uses of this product are not
expected to results in residues in or on crops, above the natural
background levels typically found in other commonly consumed fruits and
vegetables.]>

<	i. Food. [Residues of ABA applied to grapes can be expected to rapidly
dissipate to levels consistent with those observed naturally.  Data
submitted confirm ABA’s dissipation through rapid metabolism,
photo-isomerization, and rapid degradation.  Because of its ability to
dissipate rapidly, ABA, when used in accordance with the terms of the
EUP, is not expected to results in residues in or on listed crops, above
the natural background levels typically found in other commonly consumed
fruits or vegetables.  As mentioned above, it is noted that ABA is
already commonly consumed.  It is naturally present in fruits and
vegetables at various levels (up to 10 ppm) and has always been a
component of any diet containing plant materials.]>

<	ii. Drinking water. [Applications are expected to be made using a
maximum rate of 2000 ppm using a maximum of 200 gallons per acre.  Due
to this low concentration and volume of application solution, leaching
into groundwater is unlikely.  Accidental application to lakes or steams
is unlikely.  However, even if ABA leached into groundwater, data show
that ABA is rapidly metabolized and photo-isomerized, further
diminishing the likelihood of any extra-normal ABA residues being
transferred to water.  Data also show ABA is naturally present in water.
 Residues resulting from the application of ABA to the listed crops are
not expected to result in any significant drinking water exposure beyond
natural background levels of ABA already present in water.]>

<	2. Non-dietary exposure. [The only non-dietary ABA exposure potential
would be to applicators.  Repeat dermal exposure was shown to not have a
toxic or deleterious response and inhalation exposure from typical
agricultural applications would be limited.  In addition, the protective
measures prescribed by the product’s label are expected to minimize
exposure and protect applicators during the label use of ABA.  The low
application rate, low toxicity and proposed use of ABA are not likely to
result in chronic exposure of workers or the public to ABA at levels
above what might be expected through natural occurrence.]>

<E. Cumulative Effects>

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, vegetables or any plant product, a common mechanism of toxicity with
any other substance is not relevant.  ABA has shown no toxicity in any
testing.]>

<F. Safety Determination>

<	1. U.S. population. [NA-Remove.]>

<	2. Infants and children. [NA-Remove.]>

<G. Effects on the Immune and Endocrine Systems>

<	[NA-Remove.]>

<H. Existing Tolerances>

<	[NA-Remove.]>

<I. International Tolerances>

<	[NA-Remove.]>

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