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 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: waller.mary@epa.gov.

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:

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.”

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: “opp-docket@epa.gov,” 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

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-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 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.