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Spinosad - Pesticide Petition Filing 9/98

[Federal Register: September 16, 1998 (Volume 63, Number 179)]
[Page 49568-49574]
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ENVIRONMENTAL PROTECTION AGENCY
[PF-830; FRL 6025-8]
Notice of Filing of Pesticide Petitions
AGENCY: Environmental Protection Agency (EPA).
ACTION: Notice.
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SUMMARY: This notice announces the initial filing of pesticide petitions
proposing the establishment of regulations for residues of certain

[[Page 49569]]

pesticide chemicals in or on various food commodities.
DATES: Comments, identified by the docket control number PF-830, must
be received on or before October 16, 1998.
ADDRESSES: By mail submit written comments to: Public Information and
Records Integrity Branch (7502C), Information Resources and Services
Division, Office of Pesticide Programs, Environmental Protection
Agency, 401 M St., SW., Washington, DC 20460. In person bring comments
to: Rm. 119, CM #2, 1921 Jefferson Davis Highway, Arlington, VA.
    Comments and data may also be submitted electronically to: opp-
docket@epamail.epa.gov. Follow the instructions under "SUPPLEMENTARY
INFORMATION." No confidential business information should be submitted
through e-mail.
    Information submitted as a comment concerning this document may be
claimed confidential by marking any part or all of that information as
Confidential Business Information (CBI). CBI should not be submitted
through e-mail. Information marked as CBI will not be disclosed except
in accordance with procedures set forth in 40 CFR part 2. A copy of the
comment that does not contain CBI must be submitted for inclusion in
the public record. Information not marked confidential may be disclosed
publicly by EPA without prior notice. All written comments will be
available for public inspection in Rm. 119 at the address given above,
from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal
holidays.

FOR FURTHER INFORMATION CONTACT: The product manager listed in the
table below:

------------------------------------------------------------------------
                                   Office location/
        Product Manager            telephone number          Address
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Beth Edwards,.................  Rm. 216, CM #2, 703-    1921 Jefferson
                                 305-5400; e-mail:       Davis Hwy.,
                                 edwards.beth@epamail.   Arlington, VA
                                 epa.gov.
Treva Alston,.................  Rm. 707B, CM #2, 703-   Do.
                                 308-8373; e-mail:
                                 alston.treva@epamail.
                                 epa.gov.
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SUPPLEMENTARY INFORMATION: EPA has received pesticide petitions as
follows proposing the establishment and/or amendment of regulations for
residues of certain pesticide chemicals in or on various food
commodities under section 408 of the Federal Food, Drug, and Comestic
Act (FFDCA), 21 U.S.C. 346a. EPA has determined that these petitions
contain data or information regarding the elements set forth in section
408(d)(2); 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 official record for this notice of filing, as well as the
public version, has been established for this notice of filing under
docket control number PF-830 (including comments and data submitted
electronically as described below). A public version of this record,
including printed, paper versions of electronic comments, which does
not include any information claimed as CBI, is available for inspection
from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal
holidays. The official record is located at the address in
"ADDRESSES" at the beginning of this document.
    Electronic comments can be sent directly to EPA at:
    opp-docket@epamail.epa.gov

    Electronic comments must be submitted as an ASCII file avoiding the
use of special characters and any form of encryption. Comments and data
will also be accepted on disks in Wordperfect 5.1/6.1 or ASCII file
format. All comments and data in electronic form must be identified by
the docket control number PF-830 and appropriate petition number.
Electronic comments on this notice may be filed online at many Federal
Depository Libraries.

List of Subjects

    Environmental protection, Agricultural commodities, Feed additives,
Food additives, Pesticides and pests, Reporting and recordkeeping
requirements.

    Dated: September 2, 1998.

James Jones,
Director, Registration Division, Office of Pesticide Programs.

Summaries of Petitions

    Petitioner summaries of the pesticide petitions are printed below
as required by section 408(d)(3) of the FFDCA. The summaries of the
petitions were prepared by the petitioners and represent the views of
the petitioners. EPA is publishing the petition summaries verbatim with
minor, non-substantive editorial changes. The petition summary
announces the availability of a description of the analytical methods
available to EPA for the detection and measurement of the pesticide
chemical residues or an explanation of why no such method is needed.

1. Dow AgroSciences

PP 8F5002

    EPA has received a pesticide petition (PP 8F5002) from Dow
AgroSciences, 9330 Zionsville Road, Indianapolis, IN 46254 proposing
pursuant to section 408(d) of the (FF DCA), 21 U.S.C. 346a(d), to amend
40 CFR part 180 by establishing a tolerance for residues of the
insecticide spinosad in or on the raw agricultural commodities corn
grain including field, sweet (K+CWHR), and pop at 0.02 part per million
(ppm); forage, fodder, straw, and hay of cereal grains at 1.0 ppm;
legume vegetables (succulent including soybeans) at 0.3 ppm; cucurbits
at 0.3 ppm; sorghum grain at 1.0 ppm; sorghum aspirated grain fractions
at 3.0 ppm; stone fruit at 0.2 ppm; and wheat grain at 0.02 ppm.
Because of the amount of spinosad residue found in corn, sorghum, and
wheat products used in animal feeds as well as those commodities with
existing residue tolerances that are potentially used in animal
rations, the following increases in livestock residue tolerances are
being proposed: livestock, meat residue tolerance of 0.1 ppm;
livestock, meat byproduct residue tolerance of 0.4 ppm; livestock, fat
residue tolerance of 1.5 ppm; a milk residue tolerance of 0.1 ppm; a
milk fat residue tolerance of 1.5 ppm. In addition, the following
poultry residue tolerances are being proposed: poultry, fat at 0.2 ppm;
poultry, meat and meat byproducts at 0.02 ppm; and eggs at 0.02 ppm. An
adequate analytical method is available for enforcement purposes. EPA
has determined that the petition contains data or information regarding
the elements set forth in section 408(d)(2) of the FFDCA; 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.

A. Residue Chemistry

    1. Plant metabolism. The metabolism of spinosad in plants (apples,
cabbage, cotton, tomato, and turnip) and animals

[[Page 49570]]

(goats and poultry) is adequately understood for the purposes of these
tolerances. A rotational crop study showed no carryover of measurable
spinosad related residues in representative test crops.
    2. Analytical method. There is a practical method (immunoassay) for
detecting 0.005 ppm and measuring 0.01 ppm levels of spinosad in or on
food with a limit of detection that allows monitoring of food with
residues at or above the levels set for these tolerances. The method
has had a successful method tryout in the EPA's laboratories.
    3. Magnitude of residues. Magnitude of residue studies were
conducted for stone fruit (7 sites for cherries, 6 sites for peaches, 4
sites for plums, and 2 sites for prunes); cucurbits (6 sites for
cucumbers, 6 sites for muskmelons, and 3 sites for summer squash);
sweet corn (12 sites); field corn (5 sites at 5 x label rate); legume
vegetables (11 sites for snap beans, 7 sites for snow peas, and 7 sites
at 5 x label rate for soybeans); sorghum (9 sites); and wheat (6 sites
at 5 x label rate). Residues found in these studies ranged from ND to
0.14 ppm on stone fruit; ND to 0.19 ppm in cucurbits; ND for field corn
grain and sweet corn (K=CWHR); 0.09 to 0.57 ppm for corn forage; 0.03
to 0.82 ppm for corn fodder; ND to 0.23 ppm for legume vegetables; 0.03
to 0.68 ppm for sorghum grain; 0.06 to 0.18 ppm for sorghum forage;
0.06 to 0.29 ppm for sorghum fodder; 2.02 ppm for sorghum aspirated
grain fractions; ND to 0.09 ppm for wheat grain; ND to 0.07 ppm for
wheat forage; 0.01 to 0.20 ppm for wheat hay; and 0.01 to 0.73 ppm for
wheat straw.

B. Toxicological Profile

    1. Acute toxicity. Spinosad has low-acute toxicity. The rat oral
LD50 is 3,738 milligram/kilogram (mg/kg) for males and >
5,000 mg/kg for females, whereas the mouse oral LD50 is >
5,000 mg/kg. The rabbit dermal LD50 is > 5,000 mg/kg and the
rat inhalation LC50 is > 5.18 mg/1 air. In addition,
spinosad is not a skin sensitizer in guinea pigs and does not produce
significant dermal or ocular irritation in rabbits. End use
formulations of spinosad that are water based suspension concentrates
have similar low acute toxicity profiles.
    2. Genotoxicty. Short-term assays for genotoxicity consisting of a
bacterial reverse mutation assay (Ames test), an in vitro assay for
cytogenetic damage using the Chinese hamster ovary cells, an in vitro
mammalian gene mutation assay using mouse 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
(highest dose tested). This was not accompanied by either embryo
toxicity, 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 teratology study in rabbits showed that
spinosad caused decreased body weight gain and a few abortions in
maternal rabbits given 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 fetal toxicity 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). Perinatal
effects (decreased litter size and pup weight) at 100 mg/kg/day were
attributed to maternal toxicity. The NOEL for maternal and pup effects
was 10 mg/kg/day.
    4. Subchronic toxicity. Spinosad was evaluated in 13-week dietary
studies and showed NOELs/no-observed-adverse-effect levels (NOAELs) of
4.89 and 5.38 mg/kg/day, respectively in male and female dogs; 6 and 8
mg/kg/day, respectively in male and female mice; and 33.9 and 38.8 mg/
kg/day, respectively in male and female rats. No dermal irritation or
systemic toxicity occurred in a 21-day repeated dose dermal toxicity
study in rabbits given 1,000 mg/kg/day.
    5. Chronic toxicity. Based on chronic testing with spinosad in the
dog and the rat, the EPA has set a reference dose (RfD) of 0.027 mg/kg/
day for spinosad. The RfD has incorporated a 100-fold safety factor to
the NOELs found in the chronic dog study to account for inter- and
intra-species variation. The NOELs shown in the dog chronic study were
2.68 and 2.72 mg/kg/day, respectively for male and female dogs. The
NOELs (systemic) shown in the rat chronic/carcinogenicity/neurotoxicity
study were 9.5 and 12.0 mg/kg/day, respectively for male and female
rats. Using the Guidelines for Carcinogen Risk Assessment published
September 24, 1986 (51 FR 33992), it is proposed that spinosad be
classified as Group E for carcinogenicity (no evidence of
carcinogenicity) based on the results of carcinogenicity studies in two
species. There was no evidence of carcinogenicity in an 18-month mouse
feeding study and a 24-month rat feeding study at all dosages tested.
The NOELs shown in the mouse oncogenicity study were 11.4 and 13.8 mg/
kg/day, respectively for male and female mice. A maximum tolerated dose
was achieved at the top dosage level tested in both of these studies
based on excessive mortality. Thus, the doses tested are adequate for
identifying a cancer risk. Accordingly, a cancer risk assessment is not
needed.
    6. Animal metabolism. There were no major differences in the
bioavailability, routes or rates of excretion, or metabolism of
spinosyn A and spinosyn D following oral administration in rats. 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.
    7. Metabolite toxicology. The residue of concern for tolerance
setting purposes is the parent material (spinosyn A and spinosyn D).
Thus, there is no need to address metabolite toxicity.
    8. Neurotoxicity. Spinosad did not cause neurotoxicity in rats in
acute, subchronic, or chronic toxicity studies.
    9. Endocrine effects. There is no evidence to suggest that spinosad
has an effect on any endocrine system.

C. Aggregate Exposure

    1. Dietary exposure. For purposes of assessing the potential
dietary exposure from use of spinosad on stone fruit, cucurbits, corn
(field, sweet, and pop), legume vegetables (succulent including
soybeans), sorghum, and wheat as well as from other existing spinosad
crop uses, a conservative estimate of aggregate exposure is determined
by basing the theoretical maximum residue concentrations (TMRC) on the
proposed tolerance levels for spinosad and assuming that 100% of these
proposed new crops and other existing (registered for use) crops grown
in the United States were treated with spinosad. The TMRC is obtained
by multiplying the tolerance residue levels by the consumption data
which estimates the amount of crops and related foodstuffs consumed by
various population subgroups. The use of a tolerance level and 100% of
crop treated clearly results in an overestimate of human exposure and a
safety determination for the use of spinosad on crops cited in this
summary that is based on a conservative exposure assessment.
    2. Drinking water. Another potential source of dietary exposure are
residues in drinking water. Based on the available environmental
studies conducted with spinosad wherein it's properties show little or
no mobility in soil, there is no anticipated exposure to residues of
spinosad in drinking water.

[[Page 49571]]

 In addition, there is no established maximum concentration level (MCL)
for residues of spinosad in drinking water.
    3. Non-dietary exposure. Spinosad is currently registered for use
on a number of crops including cotton, fruits, and vegetables in the
agriculture environment. Spinosad is also currently registered for
outdoor use on turf and ornamentals at low rates of application (0.04
to 0.54 lb active ingredient (a.i.) per acre) and indoor use for
drywood termite control (extremely low application rates used with no
occupant exposure expected). Thus, the potential for non-dietary
exposure to the general population is considered negligible.

D. Cumulative Effects

    The potential for cumulative effects of spinosad and other
substances that have a common mechanism of toxicity is also considered.
In terms of insect control, spinosad causes excitation of the insect
nervous system, leading to involuntary muscle contractions, prostration
with tremors, and finally paralysis. These effects are consistent with
the activation of nicotinic acetylcholine receptors by a mechanism that
is clearly novel and unique among known insecticidal compounds.
Spinosad also has effects on the Gamma aminobatopic acid (GABA)
receptor function that may contribute further to its insecticidal
activity. Based on results found in tests with various mammalian
species, spinosad appears to have a mechanism of toxicity like that of
many amphiphilic cationic compounds. There is no reliable information
to indicate that toxic effects produced by spinosad would be cumulative
with those of any other pesticide chemical. Thus it is appropriate to
consider only the potential risks of spinosad in an aggregate exposure
assessment.

E. Safety Determination

    1. U.S. population. Using the conservative exposure assumptions and
the proposed RfD described in Unit 1.B.5 of this document, the
aggregate exposure to spinosad use on stone fruit, cucurbits, corn
(field, sweet, and pop), legume vegetables (succulent including
soybeans), sorghum, and wheat and other existing crop uses will utilize
25.4% of the RfD for the U.S. population. A more realistic estimate of
dietary exposure and risk relative to a chronic toxicity endpoint is
obtained if average (anticipated) residue values from field trials are
used. Inserting the average residue values in place of tolerance
residue levels produces a more realistic, but still conservative risk
assessment. Based on average or anticipated residues in a dietary risk
analysis, the use of spinosad on the list in this unit of pending crop
uses and other existing crop uses will utilize 4.0% of the RfD for the
U.S. population. EPA generally has no concern for exposures below 100%
of the RfD because the RfD represents the level at or below which daily
aggregate dietary exposure over a lifetime will not pose appreciable
risks to human health. Thus, it is clear that there is reasonable
certainty that no harm will result from aggregate exposure to spinosad
residues on existing and pending crop uses.
    2. Infants and children. In assessing the potential for additional
sensitivity of infants and children to residues of spinosad, data from
developmental toxicity studies in rats and rabbits and a 2-generation
reproduction study in the rat are considered. The developmental
toxicity studies are designed to evaluate adverse effects on the
developing organism resulting from pesticide exposure during prenatal
development. Reproduction studies provide information relating to
effects from exposure to the pesticide on the reproductive capability
and potential systemic toxicity of mating animals and on various
parameters associated with the well-being of pups.
    FFDCA section 408 provides that EPA may apply an additional safety
factor for infants and children in the case of threshold effects to
account for pre- and post-natal toxicity and the completeness of the
database. Based on the current toxicological data requirements, the
database for spinosad relative to pre- and post-natal effects for
children is complete. Further, for spinosad, the NOELs in the dog
chronic feeding study which was used to calculate the RfD (0.027 mg/kg/
day) are already lower than the NOELs from the developmental studies in
rats and rabbits by a factor of more than 10-fold.
    Concerning the reproduction study in rats, the pup effects shown at
the highest dose tested were attributed to maternal toxicity.
Therefore, it is concluded that an additional uncertainty factor is not
needed and that the RfD at 0.027 mg/kg/day is appropriate for assessing
risk to infants and children.
    In addition, the EPA has determined that the 10 x factor to account
for enhanced sensitivity of infants and children is not needed because:
    i. The data provided no indication of increased susceptibility of
rats or rabbits to in utero and/or post-natal exposure to spinosad. In
the prenatal developmental toxicity studies in rats and rabbits and 2-
generation reproduction in rats, effects in the offspring were observed
only at or below treatment levels which resulted in evidence of
parental toxicity.
    ii. No neurotoxic signs have been observed in any of the standard
required studies conducted.
    iii. The toxicology data base is complete and there are no data
gaps.
    Using the conservative exposure assumptions previously described
(tolerance level residues), the percent RfD utilized by the aggregate
exposure to residues of spinosad on stone fruits, cucurbits, corn
(field, sweet, and pop), legume vegetables (succulent including
soybeans), sorghum and wheat and existing crop uses is 51.0% for
children 1 to 6 years old, the most sensitive population subgroup. If
average or anticipated residues are used in the dietary risk analysis,
the use of spinosad on these crops will utilize 9.2% of the RfD for
children 1 to 6 years old. Thus, based on the completeness and
reliability of the toxicity data and the conservative exposure
assessment, it is concluded that there is a reasonable certainty that
no harm will result to infants and children from aggregate exposure to
spinosad residues on the above proposed including existing crop uses.

F. International Tolerances

     There are no Codex Maximum Residue Levels established for residues
of spinosad on stone fruit, cucurbits, corn (field, sweet, and pop),
legume vegetables (succulent including soybeans), sorghum, and wheat or
any other food or feed crop. (Beth Edwards)