[Federal Register Volume 65, Number 86 (Wednesday, May 3, 2000)]
[Notices]
[Pages 25721-25724]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-10772]


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

ENVIRONMENTAL PROTECTION AGENCY

[PF-939; FRL-6555-9]


Notice of Filing a Pesticide Petition to Establish a Tolerance 
for Certain Pesticide Chemicals in or on Food

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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

SUMMARY: This notice announces the initial filing of a pesticide 
petition proposing the establishment of regulations for residues of 
certain pesticide chemicals in or on various food commodities.

DATES: Comments, identified by docket control number PF-939, must be 
received on or before June 2, 2000.

ADDRESSES: Comments may be submitted by mail, electronically, or in 
person. Please follow the detailed instructions for each method as 
provided in Unit I.C. of the ``SUPPLEMENTARY INFORMATION.'' To ensure 
proper receipt by EPA, it is imperative that you identify docket 
control number PF-939 in the subject line on the first page of your 
response.

FOR FURTHER INFORMATION CONTACT:  By mail: William G. Sproat, Jr., 
Registration Division (7505C), Office of Pesticide Programs, 
Environmental Protection Agency, Ariel Rios Bldg., 1200 Pennsylvania 
Ave., NW., Washington, DC 20460; telephone number: (703) 308-8587; e-
mail address: [email protected].

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

    You may be affected by this action if you are an agricultural 
producer, food manufacturer or pesticide manufacturer. Potentially 
affected categories and entities may include, but are not limited to:

 
------------------------------------------------------------------------
                                                          Examples of
           Categories                 NAICS codes         potentially
                                                       affected entities
------------------------------------------------------------------------
Industry                          111                 Crop production
                                  112                 Animal production
                                  311                 Food manufacturing
                                  32532               Pesticide
                                                       manufacturing
------------------------------------------------------------------------

    This listing is not intended to be exhaustive, but rather provides 
a guide for readers regarding entities likely to be affected by this 
action. Other types of entities not listed in the table could also be 
affected. The North American

[[Page 25722]]

Industrial Classification System (NAICS) codes have been provided to 
assist you and others in determining whether or not this action might 
apply to certain entities. If you have questions regarding the 
applicability of this action to a particular entity, consult the person 
listed under ``FOR FURTHER INFORMATION CONTACT.''

B. How Can I Get Additional Information, Including Copies of this 
Document and Other Related Documents?

    1. Electronically. You may obtain electronic copies of this 
document, and certain other related documents that might be available 
electronically, from the EPA Internet Home Page at http://www.epa.gov/. 
To access this document, on the Home Page select ``Laws and 
Regulations'' and then look up the entry for this document under the 
``Federal Register--Environmental Documents.'' You can also go directly 
to the Federal Register listings at http://www.epa.gov/fedrgstr/.
    2. In person. The Agency has established an official record for 
this action under docket control number PF-939. The official record 
consists of the documents specifically referenced in this action, any 
public comments received during an applicable comment period, and other 
information related to this action, including any information claimed 
as confidential business information (CBI). This official record 
includes the documents that are physically located in the docket, as 
well as the documents that are referenced in those documents. The 
public version of the official record does not include any information 
claimed as CBI. The public version of the official record, which 
includes printed, paper versions of any electronic comments submitted 
during an applicable comment period, is available for inspection in the 
Public Information and Records Integrity Branch (PIRIB), Rm. 119, 
Crystal Mall #2, 1921 Jefferson Davis Highway, Arlington, VA, from 8:30 
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The 
PIRIB telephone number is (703) 305-5805.

C. How and to Whom Do I Submit Comments?

    You may submit comments through the mail, in person, or 
electronically. To ensure proper receipt by EPA, it is imperative that 
you identify docket control number PF-939 in the subject line on the 
first page of your response.
    1. By mail. Submit your comments to: Public Information and Records 
Integrity Branch (PIRIB), Information Resources and Services Division 
(7502C), Office of Pesticide Programs (OPP), Environmental Protection 
Agency, Ariel Rios Bldg., 1200 Pennsylvania Ave., NW., Washington, DC 
20460.
    2. In person or by courier. Deliver your comments to: Public 
Information and Records Integrity Branch (PIRIB), Information Resources 
and Services Division (7502C), Office of Pesticide Programs (OPP), 
Environmental Protection Agency, Rm. 119, Crystal Mall #2, 1921 
Jefferson Davis Highway, Arlington, VA. The PIRIB is open from 8:30 
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The 
PIRIB telephone number is (703) 305-5805.
    3.Electronically. You may submit your comments electronically by e-
mail to: ``[email protected],'' or you can submit a computer disk as 
described above. Do not submit any information electronically that you 
consider to be CBI. Avoid the use of special characters and any form of 
encryption. Electronic submissions will be accepted in Wordperfect 6.1/
8.0 or ASCII file format. All comments in electronic form must be 
identified by docket control number PF-939. Electronic comments may 
also be filed online at many Federal Depository Libraries.

D. How Should I Handle CBI That I Want to Submit to the Agency?

    Do not submit any information electronically that you consider to 
be CBI. You may claim information that you submit to EPA in response to 
this document as CBI by marking any part or all of that information as 
CBI. Information so marked will not be disclosed except in accordance 
with procedures set forth in 40 CFR part 2. In addition to one complete 
version of the comment that includes any information claimed as CBI, a 
copy of the comment that does not contain the information claimed as 
CBI must be submitted for inclusion in the public version of the 
official record. Information not marked confidential will be included 
in the public version of the official record without prior notice. If 
you have any questions about CBI or the procedures for claiming CBI, 
please consult the person identified under ``FOR FURTHER INFORMATION 
CONTACT.''

E. What Should I Consider as I Prepare My Comments for EPA?

    You may find the following suggestions helpful for preparing your 
comments:
    1. Explain your views as clearly as possible.
    2. Describe any assumptions that you used.
    3. Provide copies of any technical information and/or data you used 
that support your views.
    4. If you estimate potential burden or costs, explain how you 
arrived at the estimate that you provide.
    5. Provide specific examples to illustrate your concerns.
    6. Make sure to submit your comments by the deadline in this 
notice.
    7. To ensure proper receipt by EPA, be sure to identify the docket 
control number assigned to this action in the subject line on the first 
page of your response. You may also provide the name, date, and Federal 
Register citation.

II. What Action is the Agency Taking?

    EPA has received a pesticide petition as follows proposing the 
establishment and/or amendment of regulations for residues of a certain 
pesticide chemical 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 this petition contains 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 petition.

List of Subjects

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

    Dated: April 24, 2000.
James Jones,
Director, Registration Division, Office of Pesticide Programs.

Summary of Petition

    The petitioner summary of the pesticide petition is printed below 
as required by section 408(d)(3) of the FFDCA. The summary of the 
petition was prepared by the petitioner and represents the view of the 
petitioner. EPA is publishing the petition summary verbatim without 
editing it 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.

[[Page 25723]]

I. Elanco Animal Health, a Division of Eli Lilly and Company

OF6115

    EPA has received a pesticide petition OF6115 from Elanco Animal 
Health, a Division of Eli Lilly and Company, 2001 W. Main Street, 
Greenfield, IN 46140 proposing pursuant to section 408(d) of the 
Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to 
amend 40 CFR part 180 by establishing a tolerance for residues of 
spinosad in or on the raw agricultural commodity cattle meat, cattle 
meat by-products, cattle fat, milk, and milk fat at 0.45, 2.25, 5.75, 
0.75, and 8.0 parts per million (ppm), respectively. 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.

A. Residue Chemistry

    1. Analytical method. There are two practical methods immunoassay, 
high performance liquid chromotography (HPLC), for detecting (0.005 
ppm) and measuring (0.01 ppm) levels of spinosad in or on food with a 
limit of detection that allows for monitoring of food with residues at 
or above the levels set for these tolerances. The methods have had 
successful method tryout in EPA's laboratories.
    2. Magnitude of residues. A magnitude of the residue study was 
conducted in lactating dairy cattle after dermal application of 
spinosad, where spinosad residues were most concentrated in fat (approx 
1.3 ppm) and were much lower in the other edible tissues and milk (0/75 
ppm).

B. Toxicological Profile

    1. Acute toxicity. Spinosad has low acute toxicity. The rat oral 
LD50 is 3,738 milligrams/kilograms (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 milligrams/liter (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 (CHO) 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 (HDT)). 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 (HDT). 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. 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 in male and female 
dogs, respectively; 6 and 8 mg/kg/day in male and female mice, 
respectively; and 33.9 and 38.8 mg/kg/day in male and female rats, 
respectively. 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, 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 
NOAELs found in the chronic dog study to account for interspecies and 
intraspecies variation. The NOAELs shown in the dog chronic study were 
2.68 and 2.72 mg/kg/day for male and female dogs, respectively. The 
NOAELs (systemic) shown in the rat chronic/carcinogenicity/
neurotoxicity study were 9.5 and 12.0 mg/kg/day for male and female 
rats, respectively. 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 oncogenicity study were 11.4 and 13.8 mg/
kg/day for male and female mice, respectively. 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. Endocrine disruption. 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 the use of spinosad on cattle, and existing 
registered uses on cotton, fruit, and vegetable crops, a conservative 
estimate of aggregate exposure is determined by basing the theoretical 
maximum residue concentration (TMRC) on the proposed tolerance levels 
for spinosad and assuming that 100% of the proposed and registered uses 
on cattle and crops raised or 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 meat, 
crops and related foodstuffs consumed by various population subgroups. 
This conservative use of a tolerance level and 100% of the cattle and 
crops are treated with spinosad clearly results in an over estimation 
of human exposure.
    Using a more realistic analysis anticipated residues can be 
evaluated under a Tier II risk assessment taking into account a 
conservative percent of market share expected for the dermally applied 
spinosad to cattle (Extinosad). Assuming residues of spinosad in food 
commodities at the tolerance levels for commodities based on existing 
crop uses, and a 35% market share for the portion of the tolerance 
increasing in

[[Page 25724]]

commodities due to the new dermal application of spinosad to cattle, a 
Tier II dietary risk assessment can be calculated.
    2. Drinking water. Another potential source of dietary exposure are 
residues in drinking water. Based on the available environmental 
studies conducted with spinosad which shows 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 being submitted in this 
application for control of ectoparasites on cattle and agricultural 
premises. Spinosad is currently registered for use on a number of crops 
including cotton and various fruits and vegetables, all of which 
involve applications of spinosad in an 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 active 
ingredent per acre) and indoor use for drywood termite control 
extremely low application rates with no occupant exposure expected. 
Thus, the potential for non-occupational 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 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 (based on food 
and feed wherein potable water and non-occupational exposure is 
expected to be negligible) to spinosad use on cattle as well as 
existing registered crop uses will utilize 41.8% 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 market share 
percentage is applied to the tolerance levels to yield anticipated 
residue values. Inserting the anticipated residue values as a result of 
the percent market share, in place of tolerance residue levels produces 
a more realistic, but still conservative risk assessment. Based on 
anticipated residues which considers percent of market share in a 
dietary risk analysis, the use of spinosad on cattle and premises as 
well as existing registered crop uses will utilize 36.9% 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 all existing crop uses and the pending animal 
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 rats 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 prenatal and postnatal toxicity and the completeness of the 
data base. Based on the current toxicological data requirements, the 
data base for spinosad relative to prenatal and postnatal effects for 
children is complete. Further, for spinosad, the NOAEL in the chronic 
feeding study which was used to calculate the RfD (0.027 mg/kg/day) is 
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 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 
0.027 mg/kg/day is appropriate for assessing risk to infants and 
children. In addition, 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 postnatal exposure to spinosad. In 
the prenatal developmental toxicity studies in rats and rabbits and 2-
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 use of 
spinosad on cattle and premises as well as existing registered crop 
uses is 96.1% for children 1-6 years old, the most sensitive population 
subgroup. Based on anticipated residues which considers a percent of 
market share in a dietary risk analysis, the use of spinosad on cattle 
and premises as well as existing registered crop uses will utilize 
81.9% of the RfD for the children 1-6 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 the proposed crop uses, 
including all existing crop uses.

F. International Tolerances

    There are no Codex maximum residue levels established for residues 
of spinosad on any commodity.
[FR Doc. 00-10772 Filed 5-2-00; 8:45 am]
BILLING CODE 6560-50-F