[Federal Register Volume 61, Number 248 (Tuesday, December 24, 1996)]
[Notices]
[Pages 67801-67804]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-32528]


-----------------------------------------------------------------------

ENVIRONMENTAL PROTECTION AGENCY
[PF-684; FRL 5578-2]


DowElanco; Pesticide Tolerance Petition Filing

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice of Filing.

-----------------------------------------------------------------------

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: [email protected]. Electronic 
comments must be submitted as an

[[Page 67802]]

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: 
[email protected].

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.

[[Page 67803]]

    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

[[Page 67804]]

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:
    [email protected]
    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]
BILLING CODE 6560-50-F