Spinosad - Tolerance Petition Filing 2/98
[Federal Register: March 4, 1998 (Volume 63, Number 42)]
ENVIRONMENTAL PROTECTION AGENCY
Notice of Filing of Pesticide Petitions
AGENCY: Environmental Protection Agency (EPA).
SUMMARY: This notice announces the initial filing of pesticide
petitions proposing the establishment of regulations for residues of
certain pesticide chemicals in or on various food commodities.
DATES: Comments, identified by the docket control number PF-794, must
be received on or before April 3, 1998.
ADDRESSES: By mail submit written comments to: Public Information and
Records Integrity Branch (7502C), Information Resources and Services
Division, Office of Pesticides 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-
email@example.com. Follow the instructions under "SUPPLEMENTARY
INFORMATION." No confidential business information should be submitted
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 Virginia 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
Product Manager telephone number Address
Beth Edwards.................. Rm. 206, CM #2, 703- 1921 Jefferson
305-5400, e-mail: Davis Hwy,
edwards.beth@epamail. Arlington, VA
Sidney Jackson................ Rm. 233, CM #2, 703- Do.
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
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-794] (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:
Electronic comments must be submitted as an ASCII file avoiding the
use of special characters and any form of encryption. Comment 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-794] and appropriate petition number.
Electronic comments on this notice may be filed online at many Federal
List of Subjects
Environmental protection, Agricultural commodities, Food additives,
Feed additives, Pesticides and pests, Reporting and recordkeeping
Dated: February 24, 1998.
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
without editing them in any way. 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.
EPA has received a pesticide petition (PP 8F4942) 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.
346a(d), to amend 40 CFR part 180 by establishing tolerances for
residues of the insecticide spinosad in or on the raw agricultural
commodity cotton gin byproducts at 1.5 parts per million (ppm). Because
of the amount of spinosad residue found in cotton gin byproducts as
well as wet apple pomace (pending tolerance under PP 6F4761) and almond
hulls and citrus dried pulp (pending tolerances under PP 7F4871) and
the amount of cotton gin byproducts, almond hulls, citrus dried pulp,
and apple pomace potentially included in livestock rations, a
livestock, fat residue tolerance of 0.8 ppm, a milk residue tolerance
of 0.05 ppm, and a milk fat residue tolerance of 0.7 ppm are also being
proposed. The following meat and milk tolerances for residues of
spinosad are presently pending under PP 6F4761 and PP 7F4871: meat at
0.04 ppm, kidney and liver at 0.2 ppm, fat at 0.7 ppm, milk at 0.04
ppm, and milk fat at 0.5 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 (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 (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 these tolerances.
The method has had a successful method tryout in the EPA's
3. Magnitude of residues. Magnitude of residue studies were
conducted for cotton gin byproducts at seven sites. Residues found in
these studies ranged from less than the limit of quantitation of the
analytical method to 0.9 ppm on cotton gin byproducts.
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 milligrams/
kilograms (mg/kg) for females, whereas the mouse oral LD50
is >5,000 mg/kg. The rabbit dermal LD50 is >2,000 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
3. Reproductive and developmental toxicity. Spinosad caused
decreased body weights in maternal rats given 200 milligrams/kilograms/
day (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 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 0.0268 mg/
kg/day for spinosad. The RfD has incorporated a 100-fold safety factor
to the NOELs found in the chronic dog study. 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. 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 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
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 cotton gin byproducts as well
as from other existing or pending uses, a conservative estimate of
aggregate exposure is determined by basing the TMRC on the proposed
tolerance levels for spinosad and assuming that 100% of the cotton gin
byproducts and other existing and pending crop uses 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 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. In addition, there is no established
Maximum Concentration Level for residues of spinosad in drinking water.
3. Non-dietary exposure. Spinosad is currently registered for use
on cotton with several crop registrations pending all of which involve
applications of spinosad in the agriculture environment. Spinosad is
also currently registered for use on turf and ornamentals at low rates
of application (0.04 to 0.54 lb a.i. per acre). Thus, the potential for
non-dietary exposure to the general population is not expected to be
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 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 above, the aggregate exposure to spinosad
use on cotton gin byproducts and other existing or pending crop uses
will utilize 20.6% 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 cotton gin
byproducts and other existing or pending crop uses will utilize 4.5% 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 cotton gin
products and other existing or 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.
Section 408 of the FFDCA 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 (0.0268 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 0.0268 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 cotton gin byproducts and other
existing or pending crop uses is 38.1% 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 11.1% 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 cotton gin
byproducts and other existing or pending crop uses.
F. International Tolerances
There are no Codex maximum residue levels established for residues
of spinosad on cotton gin byproducts or any other food or feed crop.