PMEP Home Page --> Pesticide Active Ingredient Information --> Insecticides & Miticides --> Insecticides, R to Z --> Spinosad --> Spinosad - Pesticide Petition Filing 4/99

Spinosad - Pesticide Petition Filing 4/99

[Federal Register: April 8, 1999 (Volume 64, Number 67)]
[Page 17171-17179]
-----------------------------------------------------------------------
ENVIRONMENTAL PROTECTION AGENCY
[PF-869; FRL-6071-2]
Notice of Filing of Pesticide Petitions
AGENCY: Environmental Protection Agency (EPA).
ACTION: Notice.
-----------------------------------------------------------------------

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-869, must
be received on or before May 10, 1999.

ADDRESSES: By mail submit written comments to: Public Information and
Records Integrity Branch, Information Resources and Services Division
(7502C), 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-
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
------------------------------------------------------------------------
Sidney Jackson................  Rm. 272, CM #2, 703-    1921 Jefferson
                                 305-7610, e-            Davis Hwy,
                                 mail:jackson.sidney@e   Arlington, VA
                                 pamail.epa.gov.
Lisa D. Jones.................  Rm. 259, CM #2, 703-    Do.
                                 308-9424, e-
                                 mail:jones.lisa@epama
                                 il.epa.gov. #
------------------------------------------------------------------------

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 support 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-869] (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 file format or ASCII
file format. All comments and data in electronic form must be
identified by the docket number (insert docket number) and appropriate
petition number. Electronic comments on notice may be filed online at
many Federal Depository Libraries.

List of Subjects

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

    Dated: April 2, 1999.

onald R. Stubbs, Acting

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

[[Page 17172]]

available to EPA for the detection and measurement of the pesticide
chemical residues or an explanation of why no such method is needed.

2. IR-4 Project

 PP 8E5034

    EPA has received a pesticide petition (8E5034) from the
Interregional Research Project Number 4 (IR-4), 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 a tolerance for
residues of the insecticide, spinosad in or on the raw agricultural
commodities (RAC) tuberous and corm vegetables (crop subgroup 1C) at
0.03 parts per million (ppm). 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
support granting of the petition. Additional data may be needed before
EPA rules on the petition. Spinosad is produced by Dow AgroSciences,
Inc. (Dow), the registrant,

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 this tolerance. 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 level set for this tolerance. The method has
had a successful method tryout in the EPA's laboratories.
    3. Magnitude of residues. Magnitude of residue studies were
conducted for potatoes at 14 sites. No quantifiable residues were
observed in treated field samples at an application rate of 0.11 pounds
active ingredient (lb a.i.) per acre or at an exaggerated application
rate of 0.55 lb a.i. per acre. A potato processing study is not
required because there were no quantifiable residues in the RAC even at
the 5x application rate (5x is the maximum theoretical concentration
factor for potato). Potato is the representative crop for the tuberous
and corm vegetables crop subgroup 1C.

B. Toxicological Profile

    1. Acute toxicity--Spinosad has low acute toxicity. The rat oral
lethal dose (LD)50 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 lethal concentration
(LC)50 is > 5.18 mg/liter(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. 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 (HTD). This was not accompanied by either embryo
toxicity, fetal toxicity, or teratogenicity. The no-observed adverse
effect levels (NOAELs) 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, HTD. Maternal toxicity was not
accompanied by either embryo toxicity, fetal toxicity, or
teratogenicity. The NOAELs for maternal and fetal toxicity in rabbits
were 10 and 50 mg/kg/day, respectively. In a 2-generation reproduction
study in rats, parental toxicity was observed in both males and females
given 100 mg/kg/day HTD. Perinatal effects (decreased litter size and
pup weight) at 100 mg/kg/day were attributed to maternal toxicity. The
NOAEL for maternal and pup effects was 10 mg/kg/day.
    4. Subchronic toxicity. Spinosad was evaluated in 13-week dietary
studies and showed 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.

[[Page 17175]]

    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 NOAELs found in the chronic dog study to account for inter- and
intra-species variation. The NOAELs shown in the dog chronic study were
2.68 and 2.72 mg/kg/day, respectively for male and female dogs. The
NOAELs (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 NOAELs shown in the mouse carcinogenicity 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 disruption. There is no evidence to suggest that
spinosad has an effect on any endocrine system.

C. Aggregate Exposure

    1. Dietary exposure--i. Food. For purposes of assessing the
potential dietary exposure from use of spinosad on tuberous and corm
vegetables as well as from other existing and pending spinosad crop
uses, a conservative estimate of aggregate exposure is determined by
basing the theoretical maximum residue concentration (TMRC) on the
proposed tolerance level for spinosad and assuming that 100% of these
proposed new crops and other pending and existing (registered for use)
crops grown in the United State 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. 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.
    ii. 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, Dow concludes that there is no anticipated
exposure to residues of spinosad in drinking water. In addition, there
is no established maximum concentration level (MCL) for residues of
spinosad in drinking water.
    2. 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 a.i. per acre) and indoor use for drywood termite control
(extremely low application rates used with no occupant exposure
expected). Thus, Dow believes that 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 Dow contends that 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 tuberous and corm vegetables and other pending and existing crop
uses will utilize 25.5% 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 tuberous and corm
vegetables and other pending and existing crop uses will utilize 4.1%
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, Dow believes 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 NOAELs in the dog
chronic feeding study which was used to calculate the

[[Page 17176]]

RfD (0.027 mg/kg/day) are already lower than the NOAELs 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 HDT were attributed to maternal toxicity. Therefore, the registrant
concludes 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 10x 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
two-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 tuberous and corm vegetables and
other pending and existing crop uses is 51.2% 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 9.4% 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, the registrant concludes that
there is reasonable certainty that no harm will result to infants and
children from aggregate exposure to spinosad residues on the above
proposed use including other pending and existing crop uses.

F. International Tolerances

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