Document ID: EPA-HQ-OPP-2008-0810-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2008-12-03T05:00Z

<EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE
PETITIONS PUBLISHED IN THE FEDERAL REGISTER  (7/1/2007)>

<EPA Registration Division contact: Laura Nollen, (703) 305-7390>

 

<TEMPLATE:>

<Interregional Research Project #4 (IR-4)>

<Petition Number PP# 8E7445>

 -methyl-α- L
-manno-pyranosyl)oxy]-13-[[5-(dimethylamino)-tetrahydro-6-methyl-2H-pyra
n-2-yl]oxy]-9-ethyl-2,3,3a,5a,5b,6,9,10,11,12,13,14,16a,16b-tetradecahyd
ro-14-methyl-1H-as-Indaceno[3,2-d]oxacyclododecin-7,15-dione; and
Spinosyn D (Factor D; CAS # 131929–63–0) or 2-[(6-deoxy-2,3,4-tri- O
-methyl-α- L
-manno-pyranosyl)oxy]-13-[[5-(dimethyl-amino)-tetrahydro-6-methyl-2H-pyr
an-2-yl]oxy]-9-ethyl-2,3,3a,5a,5b,6,9,10,11,12,13,14,16a,16b-tetradecahy
dro-4,14-methyl-1H-as-Indaceno[3,2-d]oxacyclododecin-7,15-dione] in or
on the raw agricultural commodities Pomegranate at 0.3 parts per million
(ppm) and Date at 0.1 ppm and to increase the levels of existing
tolerances for Nut, tree, group 14 and Pistachio from 0.02 to 0.08 ppm
and Almond, hulls from 2.0 ppm  to 9.0ppm.  A reduction to a 1-day PHI
is supported with new MOR data for the increased tolerances in tree
nuts. >

<	EPA has determined that the petition contains data or information
regarding the elements set forth in section 408 (d)(2) of  FDDCA;
however, EPA has not fully evaluated the sufficiency of the submitted
data at this time or whether the data supports granting of the petition.
Additional data may be needed before EPA rules on the petition.

[The Agency has concluded that spinosad are considered toxicologically
identical to another pesticide, spinetoram. This conclusion is based on
the following: (1) Spinetoram and spinosad are large molecules with
nearly identical structures; and (2) the toxicological profiles for each
are similar (generalized systemic toxicity) with similar doses and
endpoints chosen for human-health risk assessment. Spinosad and
spinetoram should be considered toxicologically identical in the same
manner that metabolites are generally considered toxicologically
identical to the parent.	>

<A. Residue Chemistry>

<	1. Plant metabolism. Per the Federal Register: April 15, 1998 (Vol 63,
No 72) OPP-300644; FRL-5785-7, the nature of the residue of spinosad in
plants has been studied in several plants (apple, cabbage, cotton,
tomato and turnip) and is adequately understood.  EPA determined the
rotational crop study showed no carryover of measurable spinosad related
residues in representative test crops (lettuce, radish, and wheat). 
Tolerances for enforcement are established for spinosad based on the
residue definition of Spinosyn A (Factor A) plus Spinosyn D (Factor D).>

<	2. Analytical method. EPA has determined adequate analytical methods
are available for enforcement purposes for spinosad in plant and animal
matrices.  Methods include an immunoassay particle-based method 97.05
and an HPLC/UV method GRM 03.15 and a suite of specific crop methods:
GRM 94.02 (cottonseed and related commodities), GRM 95.17 (leafy
vegetables), GRM 96.09 (citrus), GRM 96.14 (tree nuts), GRM 95.04
(fruiting vegetables), GRM 94.02.S1 (cotton gin byproducts).  GRM 94.02
has a successful independent lab validation and was submitted for
inclusion in PAM II as Method I.  EPA recently concluded that for water,
residues should be estimated using total spinosad residue method (EPA,
DP # 316077, August 2, 2006).>

<	3. Magnitude of residues. The current tolerance for spinosad in tree
nutmeats was established for a 14-day PHI.  The revised tree nut
proposal is supported by a new IR-4 spinosad MOR study in almonds with a
1-day PHI and the recently submitted Dow AgroSciences spinetoram MOR
decline trial in almonds and pecans with a 1-day PHI time point (MRID
47468301).

The IR-4 spinosad MOR trial in almonds   DOCVARIABLE  Cr1lc  \*
MERGEFORMAT  supports a 1-day PHI.  Residues of spinosad were determined
following three foliar applications at five field locations in
California during the 2003 and 2004 growing seasons.  Spinosad was
applied at a target rate of 0.156 lb ai/A, for a total of approximately
0.468 lb ai/A.  Applications were made 6 to 7 days apart and timed so
that mature hulls and nutmeat were collected at both 1 and 3 days after
the final application (except at one trial at 4 days due to rainfall.)
Spinosad residues were determined by the IR-4 Western Region Satellite
Laboratory using a procedure derived from Dow AgroSciences method GRM
96.14.  The lowest level of method validation (LLMV) was 0.02 ppm.  All
spinosyn D residues were below the LLMV for the nutmeats.  Spinosyn D
residues in the hulls ranged from 0.0367 to 0.689 ppm for the 1-day PHI.
 Spinosyn A residues in nutmeat ranged from <0.02 to 0.0467 ppm. 
Spinosyn A residues in the hulls ranged from 0.255 to 4.42 ppm for the
1-day PHI.

The IR-4 MOR data supports a reduction of the PHI for spinosad to 1-day
in almonds and pistachios with a tolerance of 0.08 ppm in the nutmeats
and 9.0 ppm for almond hulls.  Full rationale for the full tree nut
group at 1-day PHI is provided by comparing data from four studies
conducted on almonds and/or pecans treated with spinosad or spinetoram. 
The data shows that the magnitude of residues on pecans is not
dissimilar from residues on almonds and supports bridging to pecans.

IR-4 supports bridging from the established spinosad tolerance for
avocado to pomegranate.  This translation is consistent with the
on-going discussions for crop groupings between IR-4, USDA and EPA. 
Pomegranate is scheduled to be placed into the inedible peel smooth skin
except papaya and banana tropical fruit crop subgroup E and the
representative crop for this subgroup will be avocado.

IR-4 requests that California (EPA Region 10) plum data for spinosad be
bridged over to dates.  The use pattern for dates will be the same as
for plums.  Five trials were conducted in California by Dow AgroSciences
and submitted to EPA (PP No. 8F5002, MRID No. 44597716). Three trials
were on plum and two trials were on prune type plums.  The plum residues
ranged from ND to 0.014 ppm with an average residue of 0.003 ppm. The
fresh prune-type plum residues ranged from 0.04 to 0.08 ppm with an
average of 0.063 ppm. The dried prune-type plum residues ranged from
0.03 to 0.08 ppm with an average of 0.058 ppm.  Concentration of
spinosad into dried prune type plums was not detected.>

<B. Toxicological Profile Per the Federal Register: April 15, 1998 (Vol
63, No 72) OPP-300644; FRL-5785-7, EPA determined the toxicological
profile and endpoints for spinosad are adequate for risk assessment
evaluations and determination of FQPA.  For recent spinosad decisions,
per Federal Register: December 5, 2007 (Volume 72, Number 233);
FRL-8339-8, EPA employed slightly revised endpoints based on their
decision that spinetoram is toxicologically identical to spinosad.  EPA
picked the lowest of the spinosad and spinetoram endpoints for each
exposure scenario.  A summary of the toxicological endpoints for
spinosad and spinetoram used for human risk assessment can be found at  
HYPERLINK "http://www.regulations.gov"  http://www.regulations.gov  in
docket EPA-HQ-OPP-2007-0310.  Relevant information is summarized below.>

<	1. Acute toxicity.  No appropriate endpoint attributable to a single
dose was identified; the EPA has not established an acute RfD for
spinosad or spinetoram.>

<	2. Genotoxicty. Assays for genotoxicity consisting of a bacterial
reverse mutation assay (Ames test), and in vitro assay for cytogenetic
damage using the Chinese hamster ovary cells, an in vitro mammalian gene
mutation assay using lymphoma cells, an in vitro assay for DNA damage
and repair in rat hepatocytes, and an in vivo cytogenetic assay in the
mouse bone marrow (micronucleus test) have been conducted with spinosad.
 These studies show a lack of genotoxicity.>

<	3. Reproductive and developmental toxicity. >Spinosad caused decreased
body weights in maternal rats given 200 mg/kg/day by gavage in a
developmental study (highest dose tested).  This was not accompanied by
either embryotoxicity, fetal toxicity, or teratogenicity.  The
no-observed-effect levels (NOELs) for maternal and fetal toxicity in
rats were 50 and 200 mg/kg/day, respectively.  A developmental study in
rabbits showed that spinosad caused decreased body weight gain and two
abortions attributed to inanition in maternal rabbits at 50 mg/kg/day
(highest dose tested).  Maternal toxicity was not accompanied by either
embryo toxicity, fetal toxicity, or teratogenicity.  The NOELs for
maternal and developmental effects in rabbits were 10 and 50 mg/kg/day,
respectively.  In a two-generation reproduction study in rats, parental
toxicity was observed in both males and females given 100 mg/kg/day
(highest dose tested).  Effects in the offspring (decreased litter size
and pup weight) at 100 mg/kg/day were attributed to maternal toxicity. 
The systemic and reproductive NOELs were both 10 mg/kg/day.  EPA has
determined that reliable data show that it would be safe for infants and
children to reduce the 10X FQPA safety factor to 1X.

<	4. Subchronic toxicity. Both Short-term endpoints (inhalation and
incidental oral) were established based on the Oral NOAEL of 4.9
mg/kg/day from the subchronic feeding study in dogs with spinosad and a
LOC for MOEs of 100.>

<	5. Chronic toxicity. EPA used the lowest NOAEL of 0.249 mg/kg/day from
the chronic toxicity study in dogs for spinetoram and a 100X UF to
establish a cRfD of 0.0249 mg/kg/day for both spinosad and spinetoram. 
Spinosad is considered ``Not likely to be Carcinogenic to Humans''.>

<	6. Animal metabolism. The nature of spinosad residue in animals is
understood based on livestock studies in ruminants (oral and dermal) and
poultry (oral) (DP # 316077, August 2, 2006).  ADME studies in rats
indicate spinosad is rapidly absorbed and extensively metabolized.  Also
the rat metabolism studies showed no major differences between the
bioavailability, routes or rates of excretion, or metabolism of Factor A
or Factor D.  Urine and fecal excretions were almost completed in
48-hours post-dosing.  In addition, the routes and rates of excretion
were not affected by repeated administration.  EPA recently indicated
that for fish/shellfish within the risk assessment estimates of the
total residue within edible tissues is applicable (EPA, DP # 316077,
August 2, 2006).  Total edible residues in fish have been extensively
characterized within BCF studies (MRID 43557601, 44557734, 47355801.>

<	7. Metabolite toxicology. Results of the plant and animal metabolism
studies and toxicity testing have been assessed.  Per Federal Register:
April 15, 1998 (Vol 63, No 72)  FRL-5785-7,  EPA concluded that the
spinosad metabolites/fermentation impurities (Factor B, Factor B of D,
Factor K, and other related Factors) were no more toxicological concern
than the two parent compounds.  Metabolite toxicity has been addressed
by establishment of the residue for tolerance purposes as the parent
materials.  In addition, for risk assessment purposes, the total residue
in water and edible fish is now conservatively considered.

>

<	8. Endocrine disruption. There is no evidence to suggest that spinosad
has an effect on any endocrine system.>

<C. Aggregate Exposure The agency conducted an assessment of the
aggregate exposure for spinosad and spinetoram in conjunction with the
establishment of the initial spinetoram tolerances reported in the
Federal Register of October 10, 2007 (  HYPERLINK
"http://www.epa.gov/EPA-PEST/2007/October/Day-10/p19947.htm"  72 FR
57492 ) (FRL-8149-9).  The EPA assumed toxicological equivalency of
spinosad and spinetoram in their aggregate exposure assessment. 
Anticipated exposure to spinosad was deemed acceptable.  The proposed
changes for nutmeat tolerances and the addition of dates and pomegranate
have little impact on the dietary exposure.  An evaluation of the animal
dietary burden indicates no impact on the animal meat or milk
tolerances.  No new aggregate assessments are warranted.>

<	1. Dietary exposure. i. Acute exposure. No quantitative acute dietary
exposure assessment has been required for spinosad.

ii. Chronic exposure.  Spinosad and spinetoram are deemed
toxicologically equivalent by EPA.  Based on the similarity of the
insecticides and the anticipated markets for each, it is unlikely that
spinosad and spinetoram will be applied to the same crop.  Hence, EPA
aggregated exposure by either assuming that all commodities contain
spinosad (because side-by-side spinosad and spinetoram residue data
indicated that spinetoram residues were less than or equal to spinosad
residues) or summing the percentage of a crop that would be treated with
spinosad and the percentage that would be treated with spinetoram.

Almond hulls are potential cattle feed items. However, a comparison of
their potential tolerance contribution to the higher values of other
roughage commodities already assumed in the theoretical animal dietary
burden calculations indicates no need to substitute almond hulls into
the spinosad cattle diets.  The potential exposure is already adequately
represented by other feed commodities in the calculation with higher
potential contributions.  Thus, there is no need for a revision of the
meat and milk animal commodity tolerances for spinetoram.>

<	i. Food. The chronic dietary exposure assessment (EPA, DP#33531,
September 12, 2007) was recreated in Dietary Exposure Evaluation Model -
Food Consumption Intake Database (DEEM-FCID) (version 2.16) which
incorporates the United States Department of Agriculture (USDA)
1994-1996 and 1998 Continuing Surveys of Food Intakes by Individuals
(CSFII).  The residues of livestock were refined through the
incorporation of a refined dietary burden (average field crop residues
and projected PCT) with average milk residues for spinosad from the
ruminant dermal MOR study.  The analysis assumed DEEM (ver 7.81) default
processing factors for many food commodities, EPA specified processing
factors for corn, grape, and wheat, 100% crop treated for food
commodities and used average field trial residues for several
commodities: apple, leafy vegetables, Brassica vegetables, citrus,
fruiting vegetables, herbs, banana and strawberry and tolerances values
for all others, except fish/shellfish which were conservatively
represented as 12.5 ppm (3X fold of the 4 ppm tolerance for spinosad.)>

<	ii. Drinking water. Drinking water estimates were determined based on
EPA screening models and concentrations were directly entered into the
dietary exposure model. For spinetoram, estimated environmental
concentrations (EECs) for chronic exposures are calculated to be 6.17
ppb for surface water using the First Index Reservoir Screening Tool
(FIRST) and 0.072 ppb for ground water using the Screening Concentration
in Ground Water (SCI-GROW) model.  For spinosad, average values of 10.5
ppb for surface water and 1.1 ppb for ground water were conservatively
estimated based on additional uses.  Thus, for the joint chronic dietary
risk assessment, EPA has used the water concentration value of 10.5 ppb
to assess the contribution to drinking water.>

<

	2. Non-dietary exposure. EPA has determined there is potential for
residential handler and post-application exposures to
spinosad/spinetoram.  Because spinosad and spinetoram control the
similar pests, EPA concluded these products will not be used in
combination with each other and combining the residential exposures is
unnecessary.  Per Federal Register of October 10, 2007 (  HYPERLINK
"http://www.epa.gov/EPA-PEST/2007/October/Day-10/p19947.htm"  72 FR
57492 ) (FRL-8149-9), short-term residential inhalation risks were
estimated for adult residential handlers, as well as short-term
post-application incidental oral risks for toddlers, based on
applications to home lawns, home gardens and ornamentals.>

<D. Cumulative Effects>

<	EPA has not made a common mechanism of toxicity finding as to spinosad
and any other substances and spinosad does not appear to produce a toxic
metabolite produced by other substances.  HED’s Hazard Assessment and
Policy Committee noted that toxicologically equivalent does not imply a
cumulative assessment which involves the concepts of mechanism of
toxicity and potency.  For the purposes of tolerance action, it is not
assumed that spinosad has a common mechanism of toxicity with other
substances.>

<E. Safety Determination The proposed actions of this petition have been
added via DEEM to EPA’s initial assessment for spinetoram/spinosad
(EPA, DP#33531, September 12, 2007).  The additional exposure is
estimated to be <0.1% of the cRfD.  Dow AgroSciences concludes with
reasonable certainty that no harm will result to the general population
or infants and children from the aggregate exposure to spinetoram
residues from these uses.>

<	1. U.S. population. The resulting dietary exposure estimates are not
of concern to HED; exposure for the general population is estimated as
<35% of the cPAD.  When the food and water exposure is summed with the
estimated residential inhalation exposure for youth (over 12 years old)
and adults, the resulting short term aggregate MOE values range from 650
to 710 (Federal Register: Dec 5, 2007 (Vol 72, No 233); FRL-8339-8).>

<	2. Infants and children. EPA has determined that reliable data allow a
reduction of the FQPA safety factor to 1X for infants and children.  The
resulting dietary exposure for the most exposed subpopulation (children
1 to 2 years) is estimated as <81% of the cPAD.  Short term
post-application risks were estimated for toddlers, based on application
to home lawn, home gardens and ornamentals and risks were not of concern
given resulting MOEs were >1200.  The resulting short term aggregate MOE
values were >180 and are, therefore, not of concern to HED.>

<F. International Tolerances>

<	A variety of international and CODEX MRLs are in place for spinosad. 
The third party database Homologa was queried for MRLs germane to this
petition.  IR-4 makes no claim regarding the verification of these
values relative to the national authorities.

h

h







CODEX	ALMONDS	0.01	PPM

CODEX	ALMONDS: HULLS	2	PPM

EU Harmonized	NUTS: all OTHER except almonds	0.05	PPM

EU Harmonized	POMEGRANATE	0.02	PPM

EU Harmonized	ALMONDS	1	PPM

EU Harmonized	DATES	0.02	PPM

]>

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