Environmental Protection Agency (EPA).
This notice announces the initial filing of a pesticide petition proposing the establishment of regulations for residues of a certain pesticide chemical in or on various food commodities.
Comments, identified by docket control number PF-1036, must be received on or before September 7, 2001.
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-1036 in the subject line on the first page of your response.Start Further Info
FOR FURTHER INFORMATION CONTACT:
By mail: Shaja R. Brothers, Registration Division (7505C), Office of Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460; telephone number: (703) 803-3194; e-mail address: firstname.lastname@example.org.End Further Info End Preamble Start Supplemental 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:
|Categories||NAICS codes||Examples of potentially affected entities|
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” “Regulation and Proposed Rules,” 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-1036. 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-1036 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, 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@example.com, 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-1036. 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. Start Printed Page 41594Information 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 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 support granting of the petition. Additional data may be needed before EPA rules on the petition.Start List of Subjects
List of Subjects
- Environmental protection
- Agricultural commodities
- Feed additives
- Food additives
- Pesticides and pests
- Reporting and recordkeeping requirements
Dated: July 27, 2001.
Acting 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.
Interregional Research Project #4 (IR-4)
EPA has received a pesticide petition [0E6214] from the Interregional Research Project #4 (IR-4), 681 US Highway #1 South, North Brunswick, NJ 08902 proposing, pursuant to section 408(d) of the FFDCA, 21 U.S.C. 346a(d), to amend 40 CFR part 180.492 by establishing a tolerance for residues of triflusulfuron methyl in or on the raw agricultural commodity chicory (root) at 0.05 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. This notice includes a summary of the petition prepared by Dupont, E.I. du Pont Nemours and Company, Agricultural Products, Wilmington, DE 19898.
A. Residue Chemistry
1. Plant metabolism. The metabolism and chemical nature of residues of triflusulfuron-methyl in plants is adequately understood.
2. Analytical method. High performance liquid chromatograph (HPLC) is the analytical method acceptable for determining residues of triflusulfuron-methyl in plants, and is available for enforcement purposes.
3. Magnitude of residues. The magnitude of residue data for triflusulfuron methyl in/on chicory is adequately understood. Residue field trials conducted in Washington and California have shown that the maximum residues in the raw agricultural commodity chicory and the processed commodities dry pulp and inulin were below the limit of detection (0.016 ppm). A tolerance for residues of triflusulfuron-methyl in chicory root at 0.05 ppm is consistent with the tolerances proposed by Du Pont for sugar beet roots and tops at 0.05 ppm.
B. Toxicological Profile
1. Acute toxicity. Based on EPA criteria, technical triflusulfuron methyl is in acute toxicity Category IV for oral and inhalation routes of exposure, and for dermal irritation. Triflusulfuron methyl is in acute toxicity Category III for dermal toxicity and for eye irritation. Acute oral toxicity in rats LD50 5,000 mg/kg; acute dermal toxicity in rabbits LD50 2,000 mg/kg; and acute inhalation toxicity in rats LC50 5.1 mg/L. Primary eye irritation in rabbits, non-irritant primary dermal irritation in rabbits, non-irritant dermal sensitization in guinea pigs, and non-sensitizer acute neurotoxicity no observed adverse effect level (NOAEL)= 2,000 mg/kg/day highest dose tested (HDT).
2. Genotoxicity. Mutagenicity data for technical triflusulfuron methyl include a reverse mutation assay (Ames Test) which was negative at concentrations up to 1,000μ mg/plate, the HDT; a Salmonella typhimurium plate incorporation assay which was negative at concentrations up to 3,000μ mg/plate, HDT; and a Chinese hamster ovary/hypoxanthine-guanine (CHO/HPRT) assay which was negative at concentrations up to 2,000 mg/kg/day, HDT. A chromosomal aberration/human lymphocyte assay was positive in the presence of metabolic activation at concentrations greater than or equal to 1,500μ mg/mL. A second chromosomal aberration/human lymphocyte assay was positive in the presence of metabolic activation at concentrations of 2,000μ mg/mL. Results in the absence of metabolic activation were inconclusive for both chromosomal aberration studies. The mouse bone marrow micronucleus test was negative at doses up to 5,000 mg/kg, HDT. In three Salmonella typhimurium plate incorporation assays, metabolites of triflusulfuron methyl were negative up to 5,000μ mg/plate, HDT.
3. Reproductive and developmental toxicity. In a 2-generation rat reproduction study, rats were fed dosages of 0, 0.588, 5.81, 44.0 and 89.5 mg/kg/day (males) and 0, 0.764, 7.75, 58.0, and 115 mg/kg/days (females) with a reproductive toxicity NOAEL equal to or greater than 89.5 and 115 mg/kg/day for males and females, respectively, based on the absence of reproductive Start Printed Page 41595effects in rats at the HDT. The NOAEL for systemic toxicity was 5.81 and 7.75 mg/kg/day for males and females, respectively based on decreased body weight/body weight gain (bwt/bwt gain) and food efficiency in males and females, and decreased weights of offspring from the F0 generation on days 14 and 21 post-partum at 44.0 and 58.0 mg/kg/day in males and females, respectively. Technical triflusulfuron methyl was evaluated for developmental toxicity potential in rats and rabbits. Rats were fed dosages of 0, 30, 120, 350, and 1,000 mg/kg/day with a developmental NOAEL equal to or greater than 1,000 mg/kg/day (HDT) and a maternal toxicity NOAEL of 120 mg/kg/day with a lowest observed adverse effect level (LOAEL) of 350 mg/kg/day based on reduced body weight gain in the 350 and 1,000 mg/kg/day animals, reduced food consumption in the 1,000 mg/kg/day animals and lower food efficiency in the 350 and 1,000 mg/kg/day. Rabbits were fed dosages of 0, 15, 90, 270, and 800 mg/kg/day with a NOAEL for developmental toxicity of 90 mg/kg/day with a LOAEL of 270 mg/kg/day based on the increase in abortions and a decrease in mean fetal body weight (bwt). The NOAEL for maternal toxicity is 90 mg/kg/day with a LOAEL of 270 mg/kg/day based on the maternal death and abortions, and increase in clinical signs noted in the mid-high and high dose groups, decreased food efficiency and increased post mortem finding describing gastrointestinal effects.
4. Subchronic toxicity. The subchronic toxicity of technical triflusulfuron methyl was evaluated in rabbits, rats, and dogs. In a 21-day dermal toxicity study with rabbits fed dosages of 50, 300, or 1,000 mg/kg/day, the systemic toxicity NOAEL was equal to or greater than 1,000 mg/kg/day for males and females. The dermal toxicity NOAEL was equal to or greater than 1,000 mg/kg/day for males and females.
Two 90-day studies were conducted in the rat. In one study, rats were fed dosages of 6.2, 127, 646, or 965 mg/kg/day (males) or 7.54, 150, 774, or 1,070 mg/kg/day (females). Triflusulfuron methyl exhibited subchronic toxicity at dietary concentrations of 2,000 ppm (127 and 150 mg/kg/day for males and females) or greater in the form of decreased body weights, decreased body weight gains, decreased food efficiency, increased mean relative liver weights, and regenerative anemia. The NOAEL was 6.2 mg/kg/day (males) and 7.54 mg/kg/day (females).
In another study, rats were fed dosages of 6.56, 133, 658, or 1,036 mg/kg/day (males) or 7.71, 153, 783, or 1,124 mg/kg/day (females). Triflusulfuron methyl showed subchronic toxicity at dietary concentrations of 2,000 ppm (133 and 153 mg/kg/day for males and females) or greater in the form of decreased body weight, decreased body weight gain, decreased food efficiency, and increased mean liver weights. The NOAEL was 6.56 mg/kg/day (males) and 7.71 mg/kg/day (females).
A subchronic neurotoxicity study with rats fed dosages of 0, 6.1, 46.1, 92.7, or 186.2 mg/kg/day (males) or 7.1, 51.6, 104.1, or 205.2 mg/kg/day (females), resulted in a NOAEL of 92.7 (males) and 7.1 mg/kg/ day (females). This was based on decreased body weight/body weight gain at the LOAEL of 186.2 mg/kg/day (males) and 51.6 mg/kg/day (females).
In another 90-day subchronic study, dogs were fed dosages of 3.87, 146.1, or 267.6 mg/kg/day (males) or 3.72, 159.9, or 250.7 mg/kg/day (females). Triflusulfuron methyl was found to be hepatotoxic at 4,000 ppm (146.1 mg/kg/day males and 159.9 mg/kg/day females), and greater elevated hepatic enzyme levels and postmortem evidence, including elevation in liver weights and microscopic evidence of bile stasis. Other microscopic findings considered to be treatment related were testicular atrophy and decreased testicular weights and hypercellularity of the sternal and femoral bone marrow, with a corresponding increase in reticulocyte and leukocyte counts seen in the high-dose males and females. Based on the microscopic findings in the liver and testes of the 4,000 ppm and greater treated animals, the NOAEL was 3.87 mg/kg/day (males) and 3.72 mg/kg/day (females).
5. Chronic toxicity. The chronic toxicity of technical triflusulfuron methyl was evaluated in dogs, mice, and rats. In a 1-year oral toxicity study with dogs fed dosages of 1.0, 26.9, 111.6 mg/ kg/day (males) and 1.2, 27.7, and 95.5 mg/kg/day (females), the NOAEL for males was 26.9 mg/kg/day; this was based on increases in alkaline phosphatase, liver weight, and incidence of minimal centrilobular hypertrophy at the LOAEL of 111.6. For females, the NOAEL was 27.7 mg/ kg/day; this was based on increased liver weight and increased incidence of minimal centrilobular hepatocellular hypertrophy at the LOAEL of 95.5 mg/kg/day.
In an 18-month carcinogenicity study, mice were fed dosages of 1.37, 20.9, 349, and 1,024 mg/kg/day (males) and 1.86, 27.7, 488, and 1,360 mg/kg/day (females). Male mice had statistically significant positive trends for hepatocellular adenomas and for combined adenoma/carcinoma (driven entirely by adenomas) at 349 and 1,024 mg/kg/day. These increases were not significant in pair-wise comparisons with control groups and were determined not to be carcinogenic effects by the Carcinogenicity Peer Review Committee (CPRC). The NOAEL was based on body and organ weight effects and was 20.9 mg/kg/day (males) and 27.7 mg/kg/day (females). In the combined chronic toxicity/carcinogenicity study, rats were fed dosages of 0, 0.406, 4.06, 30.6, and 64.5 mg/kg/day (males) and 0, 0.546, 5.47, 41.5, and 87.7 mg/kg/day (females). Male rats have a significant increasing trend and significant differences in pair-wise comparisons of the 30.6 and 64.5 mg/kg/day dose groups with controls for interstitial cell adenomas. This effect was determined to be a carcinogenic effect by the CPRC. No carcinogenic effects were noted in females up to and including 87.7 mg/kg/day HDT. The LOAEL for chronic toxicity is 30.6 mg/kg/day (males) and 41.5 (females) based on decreased body weight and body weight gain, alternations in the hematology parameters (males predominately) and an increased incidence of interstitial cell hyperplasia in males. The NOAEL for chronic toxicity is 4.06 mg/kg/day (males) and 5.47 mg/kg/day (females). This value is adjusted to the lowest concentration level of the chemical at this dosage (60%), resulting in NOAELs of 2.44 mg/kg/day (males) and 3.28 mg/kg/day (females).
6. Animal metabolism. For triflusulfuron methyl, in both the rat and the goat, a majority of the administrated dose was excreted in feces and urine. The biotransformation pathway for triflusulfuron methyl in the rat and the goat was similar. The major pathway was demethylation of the dimethylamino substituent on the triazine ring. The intermediate hydroxylated metabolite was also present. The secondary biotransformation pathway was clevage of the sulfonylurea bridge to form methyl saccharin, N-desmethyl triazine amine and N,N-bis-desmethyl triazine amine. In the lactating goat, triflusulfuron methyl was not excreted to any appreciable level in the milk. Levels of the ester carbonyl-derived residues were generally below the limit of reliable measurement (< 0.0006μ mg equivalent triflusulfuron methyl/mL) and triazine-derived residues reached a daily level of about 0.001 ppm. Therefore, the metabolic pathways in rats and lactating goats were very Start Printed Page 41596similar. There were no significant plant metabolites of triflusulfuron methyl that were not found in the rat or goat metabolism studies. In the unlikely event that triflusulfuron methyl were to enter the livestock diet, triflusulfuron methyl and its metabolites would be rapidly excreted and would not accumulate in meat, meat by-products, or milk.
7. Metabolite toxicology. The approximate lethal dose (ALD) of the degradation product, N,N-bis-desmethyl triazine amine, in male rats was 450 mg/kg/day. Rats were fed dose rates of 200, 300, 450, 670, 1,000, and 2,300 mg/kg of triflusulfuron methyl. Deaths occurred up to test day 7 in rats dosed at 450 mg/kg body weight and above. Clinical signs of toxicity were observed in lethally and nonlethally dosed rats. In an in vitro gene mutation study, N,N,-bis-desmethyl triazine amine was not mutagenic in Salmonella typhimurium up to a dose of 5,000μ mg/plate. For the degradation product, triazine amine, the ALD in male rats was 670 mg/kg/day. The test substance dose was 200, 300, 450, 670, 1,000, or 2,300 mg/kg. Deaths occurred up to test day 4 in rats dosed at 670 mg/kg and above. Clinical signs of toxicity were observed in lethally and nonlethally dosed animals. In an in vitro gene mutation study, triazine amine was not mutagenic in Salmonella typhimurium up to a dose of 5,000μ mg/plate.
8. Endocrine disruption. No special studies investigating potential estrogenic or other endocrine effects of methyl have been conducted. However, the standard battery of required toxicology studies have been completed. These include an evaluation of the potential effects on reproduction and development, and an evaluation of the pathology of the endocrine organs following repeated or long-term exposure to doses that far exceed likely human exposures. Based on these studies there is no evidence to suggest that triflusulfuron methyl has an adverse effect on the endocrine system.
C. Aggregate Exposure
1. Dietary exposure—i. Food. The acute dietary exposure was estimated for triflusulfuron methyl using the Dietary Exposure Evaluation Model (DEEM) (version 6.73) for a number of subpopulation groups. An acute Tier I dietary analysis was based upon the residues for sugar beet (root) at 0.05 ppm and sugar beet (top) at 0.05 ppm. The acute reference dose (aRfD) is 0.9 mg/kg bwt/day (based upon a NOAEL of 90 mg/kg bwt/day and a 100-fold safety factor). For triflusulfuron methyl, the predicated exposure for the U.S. population was 0.00460 mg/kg bwt/day (0.05 % of the aRfD) at the 95th percentile. The subpopulation with the highest predicted exposure was the non-nursing infants subgroup with an exposure of 0.00166 mg/kg bwt/day (0.19% of the aRfD) at the 95th percentile. Because the predicted exposures, expressed as percentages of the aRfD, are well below 100%, there is reasonable certainty that no acute effects would result from dietary exposure to triflusulfuron methyl.
The chronic dietary exposure was estimated for triflusulfuron methyl using the DEEM (version 6.74) for a number of subpopulation groups. A chronic Tier I dietary analysis was based upon residues for sugar beet (root) at 0.05 ppm and sugar beet (top) at 0.05 ppm. The chronic Reference dose (RfD) is 0.024 mg/kg bwt/day (based upon a NOAEL of 2.44 mg/kg bwt/day and a safety factor of 100). The estimated exposure for the U.S. population was 0.000146 mg/kg bwt/day (0.6% of the RfD). For the subpopulation with the highest level of exposure (non-nursing infants), the exposure was 0.000433 mg/kg bwt/day (<1.8% of the chronic reference dose (cRfD)). Because the predicted exposures, expressed as percentages of the cRfD, are well below 100%, there is reasonable certainty that no chronic effects would result from dietary exposure to triflusulfuron methyl. Even though very conservative assumptions were made in predicting acute and chronic exposures to triflusulfuron methyl, the predicted exposures expressed as percentages of the cRfD and aRfD values were found to be well within the acceptable range.
ii. Drinking water. Based on the available environmental studies conducted with triflusulfruon methyl, DuPont concludes that there is no anticipated exposure to residues of triflusulfuron methyl in drinking water. In addition, there is no established maximum concentration level (MCL) for residues of triflusulfuron methyl in drinking water.
2. Non-dietary exposure. Triflusulfuron methyl is not registered for any use that could result in non-occupational or non-dietary exposure to the general population.
D. Cumulative Effects
Triflusulfuron methyl belongs to the sulfonylurea class of crop protection chemicals. Other structurally similar compounds in this class are registered herbicides. However, the herbicidal activity of sulfonylureas is due to the inhibition of acetolacate synthase (ALS), an enzyme found only in plants. This enzyme is part of the biosynthesis pathway leading to the formation of branched chain amino acids. Animals lack ALS and this biosynthetic pathway. This lack of ALS contributes to the relatively low toxicity of sulfonylurea herbicides in animals. There is no reliable information that would indicate or suggest that triflusulfuron methyl has any toxic effects on mammals that would be cumulative with those of any other chemical.
E. Safety Determination
1. U.S. population. Based on the completeness and reliability of the toxicology data base and using the conservative assumptions presented earlier, EPA has established a cRfD of 0.024 mg/kg/day. This was based on the NOAEL for the 2-year chronic rat study (2.44 mg/kg/day) and a 100-fold safety factor. It has been concluded that the aggregate exposure was 0.6% of the cRfD. Generally, exposures below 100% of the cRfD are of no concern because it represents the level at or below which daily aggregate exposure over a lifetime will not pose appreciable risk to human health. Thus, there is reasonable certainty that no harm will result from aggregate exposures to triflusulfuron methyl residues.
2. Infants and children. In assessing the potential for additional sensitivity of infants and children to residues of triflusulfuron methyl, data from the previously discussed developmental and multi-generation reproductive toxicity studies were considered. Developmental studies are designed to evaluate adverse effects on the developing organism resulting from pesticide exposure during prenatal development. Reproduction studies provide information relating to reproductive and other effects on adults and offspring from the prenatal and postnatal exposures to the pesticide. The studies with triflusulfuron methyl demonstrated no evidence of developmental toxicity at exposures below those causing maternal toxicity. This indicates that developing animals are not more sensitive to the effects of triflusulfuron methyl administration than adults.
FFDCA section 408 provides that EPA may apply an additional uncertainty 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 current toxicological data requirements, the data base for triflusulfuron methyl relative to prenatal and postnatal effects for children is complete. In addition, the NOAEL of 2.44 mg/kg/day in the chronic rat study (and upon which the cRfD is based) is much lower than the Start Printed Page 41597NOAELs defined in the reproduction and developmental toxicology studies. The sub-population with the highest level of exposure was non-nursing infants, where exposure was < 1.8% of the cRfD. Based on these conservative analyses, there is reasonable certainty that no harm will result to infants and children from aggregate exposures to triflusulfuron methyl.
F. International Tolerances
There are no Codex Maximum Residue Levels established for triflusulfuron methyl.End Supplemental Information
[FR Doc. 01-19756 Filed 8-7-01; 8:45 am]
BILLIBG CODE 6560-50-S