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Spinosad Pesticide Tolerance Petition Filing 12/96

[Federal Register: December 24, 1996 (Volume 61, Number 248)] [Notices]
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ENVIRONMENTAL PROTECTION AGENCY
[PF-684; FRL 5578-2]
DowElanco; Pesticide Tolerance Petition Filing
AGENCY: Environmental Protection Agency (EPA).
ACTION: Notice of Filing.
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SUMMARY: This notice is a summary of pesticide petitions proposing the
establishment of a regulation for residues of spinosad in or on apples,
brassica leafy vegetables, and fruiting vegetables (except cucurbits).

DATES: Comments, identified by the docket number [PF-684], must be received on
or before, January 23, 1997.

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 Street S.W., Washington, DC
20460. In person, bring comments to: Room 1132, Crystal Mall #2 , 1921
Jefferson Davis Highway Arlington, VA.

Comments and data may also be submitted electronically by sending 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
may be filed online at many Federal Depository Libraries. Additional
information on electronic submissions can be found below in this document.

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 Room 1132 at
the address given above, from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays.

FOR FURTHER INFORMATION CONTACT: By mail: George LaRocca, Product Manager (PM)
13, Registration Division (7505C), Office of Pesticide Programs, Environmental
Protection Agency, 401 M St., SW., Washington, DC 20460. Office location and
telephone number: Rm. 204, CM#2, 1921 Jefferson Davis Highway, Arlington, VA,
(703) 305-6100; e-mail: larocca.george@epamail.epa.gov.

SUPPLEMENTARY INFORMATION: EPA has received pesticide petition (PP) 7F4797
from DowElanco, 9330 Zionsville Road, Indianapolis, IN 46254, 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 tolerances
for residues of the insecticide spinosad in or on the raw agricultural
commodities apples at 0.2 parts per million (ppm), apple pomace (wet) at 0.5
ppm, head and stem brassica vegetables at 2.0 ppm, leafy brassica vegetables
at 15 ppm, and fruiting vegetables (except cucurbits) at 0.4 ppm. Because of
the amount of spinosad residue found in wet apple pomace and the amount of
apple pomace potentially included in cattle and dairy cow rations, the
following meat and milk tolerances for residues of spinosad are also being
proposed: meat at 0.05 ppm, kidney and liver at 0.2 ppm, fat at 1.0 ppm, milk
at 0.02 ppm, and milk fat at 0.5 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 the EPA as a reduced risk product is
being proposed for registration for insect control on apples, brassica leafy
vegetables, and fruiting vegetables (except cucurbits). The proposed
analytical method is based on high performance liquid chromatography (HPLC)
with ultraviolet (UV) detection.

Pursuant to the 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 petitions. This summary was prepared by DowElanco
and EPA has not fully evaluated the merits of these petitions. 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 (apples, cabbage, cotton, tomato, and
turnip) and animals (goats and poultry) is adequately understood for the
purposes of these tolerances. A rotational crop study showed no carry-over of
measurable spinosad related residues in representative test crops. Magnitude
of residue studies were conducted for apples, brassica leafy vegetables, and
fruiting vegetables (except cucurbits). Residues of spinosad did not
concentrate in tomato process fractions; however, there was a concentration of
spinosad residues in wet apple pomace, an animal feed process fraction. 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 the
EPA's laboratories.

B. Toxicological Profile

1. Acute toxicity. Spinosad has low acute toxicity. The rat oral LD50 is 3,738
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/ 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 no observed effect levels (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 1,000 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 in the Federal Register of 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 studies based on excessive mortality. Thus, the doses
tested are adequate for identifying a cancer risk. Accordingly, a cancer risk
assessment is not needed.

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 apples, brassica leafy vegetables, fruiting vegetables
(except cucurbits), meat, and milk, as well as cottonseed (included in a
previous submission under pesticide petition (PP) 6F4735), a conservative
estimate of aggregate exposure is determined by basing the theoretical maximum
residue contribution (TMRC) on the proposed tolerance levels for spinosad and
assuming that 100 percent of the cotton, apples, brassica leafy vegetables,
and fruiting vegetables (except cucurbits) grown in the U.S. 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 food
stuffs consumed by various population subgroups. 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 percent of crop treated clearly results in an over-estimate 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.
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 apples, brassica leafy vegetables, and fruiting
vegetables (except cucurbits), as well as a pending use on cotton involve
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
apples, brassica leafy vegetables, cotton, and fruiting vegetables (except
cucurbits) will utilize 9.1 percent 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 apples, brassica leafy vegetables, cotton, and fruiting
vegetables (except cucurbits) will utilize 2.1 percent of the RfD for the U.S.
population. EPA generally has no concern for exposures below 100 perecnt 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 on apples,
brassica leafy vegetables, cotton, and fruiting vegetables (except cucurbits).

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 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 (tolerance
level residues), the percent RfD utilized by the aggregate exposure to
residues of spinosad on apples, brassica leafy vegetables, cotton, and
fruiting vegetables (except cucurbits) is 20.6 percent 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 5.1 percent 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, DowElanco concludes that there is a
reasonable certainty that no harm will result to infants and children from
aggregate exposure to spinosad residues on apples, brassica leafy vegetables,
cotton, and fruiting vegetables (except cucurbits).

F. International Tolerances

There are no codex maximum residue levels established for residues of spinosad
on apples, brassica leafy vegetables, cotton, fruiting vegetables (except
cucurbits) 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 document control number, [PF-
684]. 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 8:30 a.m. to 4 p.m., Monday through Friday, except legal
holidays.

A record has been established for this notice under docket number [PF-684],
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 public record is located in: Public Response and Program
Resources Branch, Field Operations Division (7506C), Office of Pesticide
Programs, Environmental Protection Agency Room 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 ASCII file avoiding the use of
special characters and any for 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 Agency, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and recordkeeping
requirements.

Dated: December 13, 1996.
Peter Caulkins,
Acting Director, Registration Division, Office of Pesticide Programs.

[FR Doc. 96-32528 Filed 12-23-96; 8:45 am]