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Spinosad - Tolerance Petition Filing 11/96

[Federal Register: November 22, 1996 (Volume 61, Number 227)]
[Page 59437-59440]

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ENVIRONMENTAL PROTECTION AGENCY
[PF-674; FRL-5574-2]
Pesticide Tolerance Petition; Notice of Filing
AGENCY: Environmental Protection Agency (EPA).
ACTION: Notice of filing.

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SUMMARY: This notice is a summary of a pesticide petition proposing the
establishment of a regulation for residues of spinosad in or on cotton.

DATES: Comments, identified by the docket number [PF-674], must be
received on or before December 23, 1996.

ADDRESSES: By mail, submit written comments to: Public Response and
Program Resources Branch, Field Operations Division (7506C), Office of
Pesticide Programs, Environmental Protection Agency, 401 M St., SW.,
Washington, DC 20460. In person, bring comments to: Rm. 1132, Crystal
Mall #2, 1921 Jefferson Davis Highway, Arlington, VA 22202.
    Comments and data may also be submitted electronically by sending

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electronic mail (E-mail) to: 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 in 5.1 file format or ASCII file
formate. All comments and data on this notice of filing may be filed
online at many Federal Depository Libraries. In person, bring comments
to Rm. 1132, CM #2, 1921 Jefferson Davis Highway, Arlington, VA 22202.
    Information submitted as comments 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. 1132 at the address given above,
from 8 a.m. to 4:30 p.m., Monday through Friday, excluding legal
holidays.

For Further Information Contact: George LaRocca (PM 13), Rm. 204,
Crystal Mall #2, 1921 Jefferson Davis Highway, Arlington, VA 22202,
(703) 305-6100, e-mail: larocca.george@epamail.epa.gov.

SUPPLEMENTARY INFORMATION: EPA has received a pesticide petition (PP
6F4735) from DowElanco 9330 Zionsville Road, Indianapolis, IN 46268-
1054 proposing pursuant to section 408(d) of the Federal Food, Drug,
and Cosmetic Act, 21 U.S.C. section 346a(d), to amend 40 CFR part 180
by establishing a tolerance for residues of the insecticide spinosad in
or on the raw agricultural commodity cottonseed at 0.02 ppm. Spinosad
is a fermentation derived tetracyclic macrolide product produced by the
actinomycete, Saccharopolyspora spinosa and consists of two
structurally related compounds, namely spinosyn A and spinosyn D which
provide the insect control activity for this new product. The two
spinosyns only differ from each other in the substitution of a hydrogen
by a methyl group and have structures consisting of a basic amine
group, two sugars, and a larger complex hydrophobic ring. This new
active ingredient that has been accepted by EPA as a reduced risk
product is being proposed for registration as a broad spectrum worm
control product on cotton. The proposed analytical method is based on
high performance liquid chromatography (HPLC) with ultraviolet (UV)
detection.
    Pursuant to section 408(d)(2)(A)(i) of the FFDCA, as amended,
DowElanco has submitted the following summary of information, data, and
arguments in support of their pesticide petition. This summary was
prepared by DowElanco and EPA has not fully evaluated the merits of the
petition. EPA edited the summary to clarify that the conclusions and
arguments were the petitioner's and not necessarily EPA's and to remove
certain extraneous material.

I. Petition Summary

A. Residue Chemistry

    The metabolism of spinosad in plants (cotton) and animals (goats
and poultry) is adequately understood for the purposes of this
tolerance. A rotational crop study showed no carryover of measurable
spinosad related residues in representative test crops. Residues in the
magnitude of residue study were non-detectable in or on cottonseed.
Residues of spinosad did not concentrate in process fractions in
samples treated at a 6X application rate. There is a practical method
(HPLC with UV detection) for detecting (0.004 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
this tolerance. The method has had a successful method tryout in EPA's
laboratories.

B. Toxicological Profile

    1. Acute toxicity. Spinosad has low acute toxicity. The rat oral
LD50 is 3738 mg/kg for males and >5000 mg/kg for females, whereas the
mouse oral LD50 is >5000 mg/kg. The rabbit dermal LD50 is >5000 mg/kg
and the rat inhalation LC50 is >5.18 mg/l 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. Genotoxicity. 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 NOELs for maternal and
fetal effects 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 effects in rabbits were 10 and 50 mg/kg/day,
respectively. The NOEL found for maternal and pup effects in a rat
reproduction study was 10 mg/kg/day. Neonatal effects at 100 mg/kg/day
(highest dose tested in the rat reproduction study) were attributed to
maternal toxicity.
    4. Subchronic toxicity. Spinosad was evaluated in 13-week dietary
studies and showed NOELs of 4.9 mg/kg/day in dogs, 6 mg/kg/day in mice,
and 8.6 mg/kg/day in rats. No dermal irritation or systemic toxicity
occurred in a 21-day repeated dose dermal toxicity study in rabbits
given 1000 mg/kg/day.
    5. Chronic toxicity. Based on chronic testing with spinosad in the
dog and the rat, a reference dose (RfD) of 0.025 mg/kg/day is proposed
for spinosad. The RfD has incorporated a 100-fold safety factor to the
NOELs found in these two chronic tests. 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 shown in the rat chronic study were 2.4 and 3.0
mg/kg/day, respectively for male and female rats.
    6. Carcinogenicity. 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. The NOELs shown
in the rat chronic/oncogenicity study were 2.4 and 3.0 mg/kg/day,
respectively for male and female rats. A maximum tolerated dose was
achieved at the top dosage level tested in both of these

[[Page 59439]]

studies based on excessive mortality. Thus, the doses tested are
adequate for identifying a cancer risk. Accordingly, DowElanco
concludes that a cancer risk assessment should not be necessary.
    7. Neurotoxicity. Spinosad did not cause neurotoxicity in rats in
acute, subchronic, or chronic toxicity studies.
    8. Endocrine effects. There is no evidence to suggest that spinosad
has an effect on any endocrine system.
    9. 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. In
addition, the routes and rates of excretion were not affected by
repeated administration.
    10. Metabolite toxicity. The residue of concern for tolerance
setting purposes is the parent material (spinosyn A and spinosyn D).
Thus, DowElanco concludes there is no need to address metabolite
toxicity.

C. Aggregate Exposure

    1. Dietary exposure. For purposes of assessing the potential
dietary exposure from use of spinosad on cotton, a conservative
estimate of aggregate exposure is determined by TMRC assuming that 100%
of the cotton crop has a residue of spinosad at the tolerance level of
.02 ppm. The potential dietary exposure is obtained by multiplying the
tolerance residue level on cottonseed (0.02 ppm) by the consumption
data which estimates the amount of cottonseed products consumed by
various population subgroups. Cottonseed is fed to animals; thus
exposure to residues in cottonseed might result if such residues are
transferred to meat, milk, poultry, or eggs. However, based on the
results of animal metabolism studies in goat and poultry and the level
of spinosad residues expected in animal feeds (<0.02 ppm), DowElanco
concludes that there is no reasonable expectation that measurable
residues of spinosad will occur in meat, milk, poultry or eggs under
the terms of the proposed use of spinosad on cotton. There are no other
established U.S. tolerances for spinosad and no other registered uses
for spinosad on food or feed crops in the United States. 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 cotton that is based on a conservative exposure
assessment. 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 DowElanco concludes, there is no anticipated exposure
to residues of spinosad in drinking water. In addition, there is no
established Maximum Concentration Level for residues of spinosad in
drinking water.
    2. Non-dietary exposure. There are no other uses currently
registered for spinosad. The proposed use on cotton involves
application of spinosad to crops grown in an agriculture environment.
Thus, the potential for non-occupational exposure to the general
population is not expected to be significant.

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 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 DowElanco believes it is appropriate to
consider only the potential risks of spinosad in an aggregate exposure
assessment.

E. Safety Determinations

    1. U.S. population in general. Using the conservative exposure
assumptions and the proposed RfD described above, the aggregate
exposure to spinosad use on cotton will utilize 0.004% 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, DowElanco concludes that there
is reasonable certainty that no harm will result from aggregate
exposure to spinosad residues (<0.02 ppm) on cottonseed.
    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
data base. Based on the current toxicological data requirements, the
data base for spinosad relative to pre- and post-natal effects for
children is complete. Further, for spinosad, the NOELs in the chronic
feeding studies which were used to calculate the RfD (0.025 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, DowElanco concludes that an additional uncertainty factor is
not needed and that the RfD at 0.025 mg/kg/day is appropriate for
assessing risk to infants and children.
    Using the conservative exposure assumptions previously described,
the percent RfD utilized by the aggregate exposure to residues of
spinosad on cottonseed is 0.012% for children 1 to 6 years old, the
most sensitive population subgroup. Thus, based on the completeness and
reliability of the toxicity data and the conservative exposure
assessment, DowElanco concludes that there is a reasonable certainty
that no harm will result to infants and children from aggregate
exposure to spinosad residues on cottonseed.

F. International Tolerances

    There are no Codex maximum residue levels established for residues
of spinosad on cottonseed or any other food or feed crop.

II. Administrative Matters

    Interested persons are invited to submit comments on this notice of
filing. Comments must bear a notation indicating the docket control
number, PF-674. All written comments filed in response to this petition
will be available in the Public Response and Program Resources Branch,
at the address given above from 8 a.m. to 4

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p.m., Monday through Friday, except legal holidays.
    A record has been established for this notice under docket number
PF-674 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 a.m. to
4:30 p.m., Monday through Friday, excluding legal holidays. The public
record is located in the Public Response and Program Resources Branch,
Field Operations Division (7506C), Office of Pesticide Programs,
Environmental Protection Agency, Rm. 1132, Crystal Mall 2, 1921
Jefferson Davis Highway Arlington, VA 22202.
    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. The official
record for this rulemaking, as well as the public version, as described
above will be kept in paper form. Accordingly, EPA will transfer all
comments received electronically into printed, paper form as they are
received and will place the paper copies in the official rulemaking
record which will also include all comments submitted directly in
writing. The official rulemaking record is the paper record maintained
at the address in "ADDRESSES" at the beginning of this document.

List of Subjects

    Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.

    Dated: November 15, 1996.

Peter Caulkins,
Acting Director, Registration Division, Office of Pesticide Programs.

[FR Doc. 96-29929 Filed 11-21-96; 8:45 am]
BILLING CODE 6560-50-F