[Federal Register Volume 65, Number 36 (Wednesday, February 23, 2000)]
[Notices]
[Pages 8970-8973]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-4242]


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ENVIRONMENTAL PROTECTION AGENCY

[PF-898; FRL-6390-1]


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.

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

DATES: Comments, identified by docket control number PF-898, must be 
received on or before March 24, 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-898 in the subject line on the first page of your 
response.

FOR FURTHER INFORMATION CONTACT:  By mail: Mary Waller, Fungicide 
Branch, Registration Division (7505C), Office of Pesticide Programs, 
Environmental Protection Agency, Ariel Rios Bldg., 1200 Pennsylvania 
Ave., NW., Washington, DC 20460; telephone number: (703) 308-9354; 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            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 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.''

[[Page 8971]]

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-898. 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 (CM #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-898 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, CM #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-898. 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 
pesticide chemical in or on various food commodities under section 408 
of the Federal Food, Drug, and Cosmetic 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: February 14, 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 views 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.

Gustafson LLC

PP 9F6036

    EPA has received a pesticide petition (9F6036) from Gustafson LLC, 
1400 Preston Road, Suite 400, Plano, Texas 75093 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 carboxin [5,6-dihydro-2-methyl-1,4-oxathiin-3-

[[Page 8972]]

carboxanilide] and its sulfoxide metabolite [5,6-dihydro-3-
carboxanilide-2-methyl-1,4-oxathiin-4-oxide], each expressed as the 
parent compound in or on the raw agricultural commodity canola 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 
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 carboxin in plants is 
adequately understood. The major metabolites in all commodities of 
wheat were carboxin sulfoxide and sulfone. Metabolites in cottonseed 
were at too low a level to be identified. The metabolism of carboxin in 
soybeans is characterized by the oxidation of sulfur (present as 
sulfoxides and sulfones), cleavage of the oxathiin ring, and 
conjugation with glucose.
    2. Analytical method. The analytical method employed for analysis 
of residues of carboxin in canola from the trials described below used 
a derivitization of the extracted carboxin residues, which were 
analyzed with a gas chromatograph with mass selective detector. The 
limit of quantitation is 0.025 ppm. The current method for the analysis 
of residues of carboxin in animal tissues, milk and eggs employs 
alkaline hydrolysis with the liberated aniline derivitized with 
heptafluorobutyric anhydride. Analysis is by gas chromatography of the 
derivitized aniline, with mass selective detection (GC/MSD). The limit 
of quantitation in all tissues was 0.02 ppm and the precision of the 
method as indicated by the coeficient of variation was 1.9%.
    3. Magnitude of residues. Gustafson LLC has submitted data to 
determine residues of carboxin in canola grown from seed, which was 
treated prior to planting with Vitaflo-280 Flowable fungicide. Four 
trials were conducted, three at the one X rate and the remaining at the 
3 X rate. Two trials were conducted in North Dakota and the remaining 
in Washington State. The residues detected were all less than the limit 
of quantitation (LOQ) of 0.025 ppm. The submitted field data indicate 
that residues of carboxin will not exceed the proposed tolerance of 
0.03 ppm in canola grown from treated seed.

B. Toxicological Profile

    1. Acute toxicity. Acute toxicity studies on carboxin demonstrate 
that the oral and dermal LD50 values for the technical 
material are 2.864 and >4.0 grams/kilograms (g/kg), respectively. The 
4-hour inhalation LC50 in rats is 4.7 milligrams/Liter (mg/
L). Irritation tests in rabbits showed carboxin to be a mild eye 
irritant and non-irritating to the skin. Carboxin did not cause skin 
sensitization in studies with guinea pigs.
    2. Genotoxicity. Bacterial/mammalian microsomal mutagenicity assays 
were performed and carboxin was found not to be mutagenic. Two 
chromosomal aberration assays were conducted, in Chinese hamster ovary 
cells and in mouse bone marrow in vivo, and were also negative. A study 
was performed in rat hepatocytes and demonstrated the induction of 
unscheduled DNA synthesis.
    3. Reproductive and developmental toxicity. In a developmental 
toxicity study in rats conducted in 1989, carboxin was administered by 
oral gavage to pregnant, Sprague Dawley rats at dosage levels of 10, 90 
and 175 mg/kg/day. Decreased maternal body weight gain was seen at dose 
levels of 90 and 175 mg/kg/day. The report states that there was a 
slightly reduced mean fetal body weight in the high dose group compared 
to controls (3.3 vs. 3.5 g). However, a recent evaluation of 59 studies 
of the historical control data in the final report shows that between 
10/83 and 4/87, the range for fetal weight was 3.1 to 5.1 g. Therefore, 
a mean fetal weight of 3.3 g in the 175 mg/kg/day group is within the 
historical control range. Maternal toxicity was also noted at this 
dosage level. Therefore, the no observable adverse effect level (NOAEL) 
for developmental toxicity is greater than 175 mg/kg/day and the NOAEL 
for maternal toxicity, based on decreased body weight gain, is 10 mg/
kg/day. In a developmental toxicity study in rabbits, carboxin was 
administered by oral gavage to pregnant White rabbits at dosage levels 
of 75, 375 and 750 mg/kg/day. There were no treatment related effects 
at any dose level with the exception of three abortions in the high 
dose group and one abortion in the mid dose group. An evaluation of 
historical control data from 28 studies conducted at that time shows 
abortion rates of 3/17 and 5/16 in two studies, as well as a number of 
studies in which there were 1 or 2 abortions each. Therefore, 
considering that there was no maternal toxicity at dose levels of 375 
or 750 mg/kg/day carboxin, it would have to be concluded that the 1/16 
and 3/16 abortions seen in the mid and high dose groups were 
spontaneous. The NOAEL for maternal and developmental toxicity was 
considered to be greater than 750 mg/kg/day. In a dietary 2-generation 
rat reproduction study, carboxin was fed to male and female Sprague 
Dawley rats at dietary concentrations of 20, 200 and 400 ppm in males 
and 20, 300 and 600 ppm in females. At the high dose level there was a 
decrease in body weight gain in parental males and females and a 
reduction in pup growth during lactation. No effects on reproduction 
were observed. The NOAEL for systemic, adult toxicity was 200 ppm (10 
mg/kg/day). The NOAEL for offspring growth was 300 ppm (15 mg/kg/day) 
and the NOAEL for reproductive effects was greater than 400 ppm (20 mg/
kg/day).
    4. Subchronic toxicity. A 13-week rat feeding study was conducted 
at dietary concentrations of 200, 800 and 2,000 ppm. A reduction in 
body weight gain was seen in males at 800 and 2,000 ppm and in females 
at 2,000 ppm. A reduction in blood levels of glucose, protein and/or 
globulin was seen in males at 800 and/or 2,000 ppm and an increase in 
urea nitrogen was seen in females at 2,000 ppm. Nephritis was seen in 
males and females given 800 and 2,000 ppm and in males given 200 ppm. 
The NOAEL for subchronic toxicity in rats was 200 ppm (10 mg/kg/day) in 
females and less than 200 ppm in males.
    5. Chronic toxicity. Carboxin was fed to Beagle dogs for 1-year at 
dietary concentrations of 40, 500 and 7,500 ppm. There was a reduction 
in body weight gain in females dogs at dose levels of 500 and 7,500 
ppm. At a dose level of 7,500 ppm there was a decreased hamatocrit in 
males and an increase in serum alkaline phosphates in males and 
females. The NOAEL for chronic toxicity was 1 mg/kg/day. Carboxin was 
fed to Sprague Dawley rats for 2 years at dietary concentrations of 20, 
200 and 400 ppm in males and 20, 300 and 600 ppm in females in a study 
completed in 1991. Survival was reduced in high dose males and body 
weight gain was significantly reduced in high males and females. 
Chronic nephritis was seen in mid and high dose rats, and this effect 
was more severe in males. There was no treatment-related increase in 
tumor incidence in rats. The NOAEL for chronic toxicity was 1 mg/kg/
day. Carboxin was fed to B6C3F1 mice for 18 months at dietary 
concentrations of 50, 2,500 and 5,000 ppm. At dosage levels of 2,500 
and 5,000 ppm there was an increased incidence of liver hypertrophy. 
There

[[Page 8973]]

was no treatment-related increase in tumor incidence.
    6. Animal metabolism. In the rat metabolism study, the percentage 
of dose did not exceed 0.21% in any tissue and the total percentage of 
dose in all tissues was 0.26-0.40%. The majority of the dose was 
excreted in the urine (about 80% within 72 hours). The predominant 
metabolite was p-hydroxy carboxin sulfide and the other major 
metabolite was 4-acetamidophenol. Unchanged carboxin was not detected 
in the excreta.
    7. Metabolite toxicity. Although no toxicology studies have been 
conducted on carboxin metabolites per se, none of these would be 
expected to have significant toxicity. The residue of concern is the 
parent compound only.
    8. Endocrine disruption. No specific studies have been conducted to 
evaluate potential estrogenic or endocrine effects; however, the 
standard battery of required studies has not demonstrated any evidence 
that is suggestive of hormonal effects. Evaluation of the rat multi-
generational study demonstrated no effect on the time to mating or on 
the mating and fertility indices. Chronic and sub-chronic toxicity 
studies in rats and dogs did not demonstrate any evidence of toxicity 
to the male or female reproductive tract or to any endocrine organ 
associated with endocrine disruption.

C. Aggregate Exposure

    1. Food. The potential dietary exposure from food was assessed 
using the conservative assumptions that all residues would be at 
tolerance levels (existing tolerances and a proposed tolerance on 
onions and the proposed tolerance on canola) and that all commodities 
would contain residues (100% crop treated). Although meal from canola 
is a livestock feed item, the 3X exaggerated rate study showed no 
residue at the LOQ. Thus, a processing study was not required and no 
additional residues are expected in livestock. The existing tolerances 
for animal commodities are adequate. Potential chronic exposures were 
estimated using NOVIGEN's Dietary Exposure Evaluation Model (DEEM 
Version 6.76), which uses USDA food consumption data from the 1989-1992 
survey. The total dietary exposure is estimated to be about 11% of the 
reference dose (RfD) for adults and 25% for infants and 23% for 
children. The chronic RfD is 0.01 mg/kg/day, based on the NOAEL of 1 
mg/kg/day in the rat and dog chronic studies and a 100-fold safety 
factor. The exposure contribution from canola will be less than 0.1% of 
the RfD.
    2. Drinking water. There are no established Maximum Concentration 
Levels (MCL's) for residues of carboxin in drinking water. Health 
Advisory (HA) Levels for carboxin drinking water for adults are 4 and 
0.7 mg/L (longer term and life time HA levels, respectively) and 1-day, 
10-day and longer term HA levels are all 1 mg/L for children. Seed 
treatment uses do not typically require a drinking water assessment. 
Use of carboxin as a seed treatment (at an application rate of 0.01 
ounce active ingredient per acre) is not expected to impact ground 
water or surface waters or result in significant human exposure.
    3. Non-dietary exposure. Carboxin is registered only for commercial 
agricultural use and not for homeowner use. Therefore,non-occupational 
exposure to the general population from carboxin is unlikely and is not 
considered in the aggregate exposure assessments.

D. Cumulative Effects

    The potential for cumulative effects of carboxin and other 
substances that have a common mechanism was considered. The mammalian 
toxicity of carboxin is well defined, with the kidney being identified 
as target organ. However, since the biochemical mechanism of toxicity 
of this compound is not known, it cannot be determined if toxic effects 
produced by carboxin would be cumulative with any other chemical 
compound. Thus, only the potential risk of carboxin is considered in 
the aggregate exposure assessment.

E. Safety Determination

    Exposure to carboxin would occur primarily from the dietary route. 
Maximum theoretical levels of carboxin in drinking water were well 
below drinking water levels of concern for adults and children. Non-
occupational exposure to the general population is not expected. 
Because calculation of the dietary exposure used tolerance levels for 
all crops and animal commodities and assumed 100% of the crop was 
treated, the exposure values are considered to be overestimates. 
Consideration of anticipated residues and actual percent crop treated 
would likely result in a significantly lower dietary exposure.
    1. U.S. population chronic dietary exposure. Chronic dietary 
exposure to the general U. S. population from existing uses and the 
proposed use on onions and canola is 11.6% of the RfD. The highest 
levels calculated are for non-nursing infants and children (1-6 years), 
the exposures are 23.2% and 26.6% of the RfD respectively. Therefore, 
there is a reasonable certainty that no harm will result from dietary 
exposure to carboxin residues.
    2. Infants and children. The potential for carboxin to induce toxic 
effects in children at a greater sensitivity than the general 
population has been assessed using the rat and rabbit developmental and 
two generation reproduction studies. There was no evidence of embryo 
toxicity or teratogenicity and no effects on reproductive parameters as 
a result of carboxin exposure. The lowest NOAEL for any developmental 
effect in these studies (15 mg/kg/day reduced pup growth during 
lactation in the rat reproduction study) is considerably greater than 
the NOAEL for systemic toxicity in rats (1 mg/kg/day for nephritis in 
the rat chronic feeding study). This result demonstrates that there is 
no prenatal or postnatal sensitivity to carboxin. Therefore, it is 
inappropriate to assume that infants and children are more sensitive 
than the general population to the effects from exposure to carboxin 
residues.

F. International Tolerances

    The Codex Alimentarius Commission has not established a maximum 
residue level for carboxin.
[FR Doc. 00-4242 Filed 2-22-00; 8:45 am]
BILLING CODE 6560-50-F