Environmental Protection Agency (EPA).
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.
Comments, identified by docket control number PF-931, must be received on or before May 5, 2000.
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-931 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, Ariel Rios Bldg., 1200 Pennsylvania Ave., NW., Washington, DC 20460; telephone number: (703) 308-3194; 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” 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/. Start Printed Page 17873
2. In person. The Agency has established an official record for this action under docket control number PF-931. 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-931 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@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-931. 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 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.Start List of Subjects
List of Subjects
- Environmental protection
- Agricultural commodities
- Feed additives
- Food additives
- Pesticides and pests
- Reporting and recordkeeping requirements
Dated: March 28, 2000
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 petitioners. 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 Number 4
EPA has received a pesticide petition (5E4499) from Rutgers, the State University of New Jersey, 681 U.S. Highway No. 1 South, New Brunswick, NJ 08902 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 diflubenzuron in or on the raw agricultural commodity rangeland grass at 6.0 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 Uniroyal Chemical Company, 74 Amity Road, Bethany, CT 06525. Start Printed Page 17874
A. Residue Chemistry
1. Plant metabolism. The qualitative nature of the residue in plants is adequately understood based on data from soybeans, oranges, and rice metabolism studies.
2. Analytical method. A practical analytical method for detecting and measuring levels of diflubenzuron in or on food with a limit of detection that allows monitoring of the residue at or above the level set in the tolerance was used to determine residues in rangeland grass. Rangeland grass samples are analyzed by high performance liquid chromotography and detected by UV-absorption at 254 nanometers liquid chromatography for quantitation of diflubenzuron residues at a limit of quantitation (LOQ) for the method on rangeland grass of 0.05 ppm.
B. Toxicological Profile
1. Acute toxicity. Studies for diflubenzuron technical indicate the acute oral toxicity in rats and mice >4,640 milligrams/kilograms (mg/kg), and the acute dermal toxicity in rats is >10,000 mg/kg. The acute inhalation lethal concentration: (LC)50 in rats is >35 mg/L (6 hours). Diflubenzuron technical is not an eye or skin irritant to rabbits, and is not a dermal sensitizer in guinea pigs.
2. Genotoxcity. Diflubenzuron did not show any mutagenic activity in point mutation assays employing Salmonella typhimurium, S. cerevisiae, or L5178Y mouse lymphoma cells. Diflubenzuron did not induce chromosomal aberrations in Chinese hamster ovary cells and it did not induce unscheduled DNA synthesis in human WI-38 cells. Diflubenzuron was also negative in mouse micronucleus and mouse dominant lethal assays and it did not induce cell transformation in Balb/3T3 cells.
3. Reproductive and developmental toxicity. In a rat reproduction study, diflubenzuron was fed to 2 generations of male and female rats at dietary concentrations of 0, 10, 20, 40, and 160 ppm. No effects were seen on parental body weight gain and there were no reproductive effects. A subsequent study was conducted on 1-generation (one litter) of rats at dietary concentrations of 0, 1,000 and 100,000 ppm. Systemic effects were seen in adults at these doses but there was no effect on reproductive parameters. The no observed adverse effect level (NOAEL) for reproductive toxicity was greater than 100,000 ppm (5 mg/kg/day).
In a rat developmental toxicity study, diflubenzuron was administered by oral gavage to pregnant female rats at dosage levels of 0, 1, 2, and 4 mg/kg/day. No treatment related effects were seen. A subsequent study was conducted in pregnant Sprague Dawley rats at a dose of 0 and 1,000 mg/kg/day. No maternal toxicity was observed. The incidence of fetuses with skeletal abnormalities was slightly increased in the treated group, but was within historical background range. The NOAEL for maternal and developmental toxicity in rats was greater than 1,000 mg/kg/day.
Diflubenzuron was also administered by oral gavage to pregnant New Zealand white rabbits at dosage levels of 0, 1, 2, and 4 mg/kg/day. No treatment related effects were seen. A subsequent study was conducted in pregnant rabbits at doses of 0 and 1,000 mg/kg/day. No maternal or developmental toxicity was seen. The NOAEL for maternal and developmental toxicity in rabbits was greater than 1,000 mg/kg/day.
4. Subchronic toxicity. A 4-week inhalation study and a 3-week dermal study were conducted. In the inhalation study, rats were exposed (nose only) to 10, 30, or 100 mg/m3 for 6 hours per day, 5 days per week for 4 weeks. Treatment related findings were a slight reduction in erythrocytes, hemoglobin and hematocrit in male and female rats at a concentration of 100 mg/m3 and an increase in total bilirubin in high dose female rats. There was no effect on methemoglobin concentration at any dose level. The NOAEL for subchronic inhalation toxicity was 30 mg/m3.
5. Chronic toxicity. Diflubenzuron was given by capsule to male and female beagle dogs for 1-year at dose levels of 0, 2, 10, 50, and 250 mg/kg/day. Body weight gain was slightly reduced in females at 250 mg/kg/day. Absolute liver and spleen weights were increased in males given 50 and 250 mg/kg/day. A reduction in hemoglobin and mean corpuscular hemoglobin concentration, with an elevation in reticulocyte count, was seen at 50 and 250 mg/kg/day. Methemoglobin and sulfhemoglobin values were increased at doses of 10 mg/kg/day and greater. Histopathological findings were limited to pigmented macrophages and kupffer cells in the liver at doses of 50 and 250 mg/kg/day. The NOAEL for chronic toxicity in dogs was 2 mg/kg/day.
Diflubenzuron was fed to male and female Sprague Dawley rats for 2 years at dose levels of 0, 156, 625, 2,500, and 10,000 ppm. Methemoglobin values were elevated in female rats at all dose levels and in male rats at the two highest dose levels (HDL). Sulfhemoglobin was elevated in females, only, at dose levels of 2,500 and 10,000 ppm. Mean corpuscular volume (MCV) and reticulocyte counts were increased in high dose females. Spleen and liver weights were elevated at the two highest doses. Histopathological examination demonstrated an increase in hemosiderosis of the liver and spleen, bone marrow and erythroid hyperplasia and areas of cellular alteration in the liver. In another study, diflubenzuron was administered to male and female CD rats for 2 years at dose levels of 0, 10, 20, 40, and 160 ppm. Elevated methemoglobin levels were seen in high dose males and females. No additional effects, including carcinogenic findings, were observed. The NOAEL for chronic toxicity in rats was 40 ppm (2 mg/kg/day).
Carcinogenicity. A 91-week carcinogenicity study in CFLP mice was conducted at doses of 0, 16, 80, 400, 2,000, and 10,000 ppm. There was no increase in tumor incidence as a result of diflubenzuron administration. Target organ effects included: increased methemoglobin and sulfhemoglobin values, heinz bodies, increased liver and spleen weight, hepatocyte enlargement and vacuolation, extramedullary hemopoiesis in the liver and spleen, siderocytosis in the spleen and pigmented kupffer cells. A NOAEL for these effects was 16 ppm (2 mg/kg/day).
6. Animal metabolism. Diflubenzuron in rats at a single dose of 100 mg/kg and 5 mg/kg single and mutiple oral doses depicted limited absorption from the gastrointestinal tract. No major difference was observed between the single and multiple doses. In single dose treatments, after 7 days, 20 and 3% of the applied dose 5 and 100 mg/kg, respectively, were excreted in urine, while 79 and 98% of the applied dose 5 and 100 mg/kg, respectively, were eliminated in the feces. Very little bioaccumulation in the tissues was observed. In the feces, only unchanged parent compound was detected. Several metabolites were observed in the urine which are, among others, 2,6-diflurobenzoic acid (DFBA), 2,6-difluorophippuric acid, 2,6-difluorobenzamide (DFBAM), and 2-hydroxydiflubenzuron (2-HDFB). An unresolved peak that was characterized as p-chloroaniline (PCA) and/or p-chlorophenylurea (CPU) was found. This latter peak accounted for about 2% of the administered dose (5 mg/kg). To resolve if PCA and CPU are indeed metabolites of diflubenzuron, rats were administered a single oral dose, 100 mg/kg of 14C DFB. The major metabolites identified in rat urine were 4-chloroaniline-2-sulfate, accounting for almost 50% of the total radioactive residue (TRR) in the urine and N-(4-chlorophenyl)oxamic acid which Start Printed Page 17875accounted for about 15% of the TRR. Neither CPU, PCA nor their N-hydroxyl derivatives were found in rat urine at a limit of detection of 23 ppb. As in the previous study diflubenzuron was the only residue found in the feces.
7. Metabolite toxicology. PCA hydrochloride for male and female F344/N rats, and PCA hydrochloride for male B6C3F1 mice under the condition of a 2-year gavage study showed evidence of carcinogenic activity. In addition to PCA, 4-chlorophenylurea (CPU) is also a potential minor metabolite of diflubenzuron.
8. Endocrine disruption. The standard battery of required studies has been completed and evaluated to determine potential estrogenic or endocrine effects of diflubenzuron. These studies 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. These studies are generally considered to be sufficient to detect any endocrine effects. No such effects were noted in any of the studies with diflubenzuron.
C. Aggregate Exposure
1. Dietary exposure— i. Food. Since 1-day single dose oral studies in rats and mice indicated only marginal effects, an acute exposure risk assessment is not needed, as there were no significant acute effects observed.
a. Diflubenzuron. The chronic dietary exposure from diflubenzuron was estimated based on the average residue values from the various currently labeled raw agricultural commodities. Percent of crop treated was also factored into the estimate. The dietary exposure analysis was estimated based on 1989-92 USDA food consumption data.
The U.S. population (total), the dietary exposure of diflubenzuron was estimated as 0.000013 mg/kg/day. For nursing and non-nursing infants, the exposure was estimated as 0.000003 mg/kg/day and 0.000007 mg/kg/day, respectively. For children, the exposure was 0.000015 mg/kg/day and 0.000011 mg/kg/day for 1-6 year olds and 7-12 year olds, respectively.
b. p-Chloroaniline. The chronic dietary exposure from p-chloroaniline (PCA) which has been detected in some food products was also determined. Average residues from field trials for mushrooms and rice were used. Residues in liver were obtained from extrapolation of metabolism data to anticipated livestock dietary burdens. EPA has previously used a 2 percent in vivo conversion factor of DFB to PCA for foods derived from plant products. However, based on results of a recent rat metabolism study showing that no PCA is formed, this is no longer appropriate. The percent treated of each crop was also factored into the exposure estimate.
The U.S. population (total), the dietary exposure of PCA was estimated as <0.000001 mg/kg/day. For nursing and non-nursing infants, the exposure was estimated as <0.000001 mg/kg/day and 0.000001 mg/kg/day, respectively. For children 1-6 years old and 7-12 years old, the exposure was <0.000001 mg/kg/day.
ii. Drinking water. Diflubenzuron degrades in soil relatively quickly with aerobic half-life ranging from 3-7 days. Major degradates include difluorobenzoic acid (DFBA) and CPU. DFBA is further metabolized through decarboxylation and ring cleavage by soil microbes whereas CPU is slowly degraded to soil-bound entities. Under aerobic aquatic conditions, diflubenzuron has a half-life of 34 days with the main degradates being DFBA and CPU. In surface water, diflubenzuron is degraded by microbes with a half-life of 5-10 days. The soil mobility of diflubenzuron is considered quite limited based on a number of experimental studies as well as by computer modeling. CPU has also been shown to be relatively immobile in soil. Although DFBA shows mobility in soil, it is rapidly degraded. Therefore, based on results of laboratory and field studies, it is not likely that diflubenzuron or its degradates will impact ground water quality to any significant extent.
Based on EPA's PRZM/EXAMS modeling, the average annual mean concentration of diflubenzuron in surface water sources is not expected to exceed 0.05 ppb. The drinking water level of concern (DWLOC) for chronic (non-cancer) exposure to diflubenzuron in drinking water was determined as 699 parts per billion (ppb) for the U.S. population (total) and approximately 200 ppb for infants and children. The estimated maximum concentration of diflubenzuron in surface water (0.05 ppb) is much less than the DWLOCs as a contribution to chronic (non-cancer) aggregate exposure.
2. Non-dietary exposure. Diflubenzuron is a restricted use pesticide based on its toxicity to aquatic invertebrates. This restricted use classification makes it unavailable for use by homeowners. Occupational uses of diflubenzuron may expose people in residential locations, parks, or forests treated with diflubenzuron. Based on very low residues detected in forestry dissipation studies, low dermal absorption rate (0.05%), and extremely low dermal and inhalation toxicity, these uses are expected to result in insignificant risk, and will, therefore, not be included in the aggregate risk assessment.
D. Cumulative Effects
Uniroyal Chemical Company has considered the potential for cumulative effects of diflubenzuron and other substances with a common mechanism of toxicity. The mammalian toxicity of diflubenzuron is well defined. We are not aware of any other pesticide product registered in the U.S. that could be metabolized to p-chloroaniline. For this reason, consideration of potential cumulative effects of residues from pesticidal substances with a common mechanism of action as diflubenzuron is not appropriate. Thus, only the potential exposures to diflubenzuron were considered in the total exposure assessment.
E. Safety Determination
1. U.S. population. Dietary exposure to the U.S. population (total) from diflubenzuron was estimated at 0.000013 mg/kg/day. Based on the 0.02 mg/kg/day RfD (reference dose) derived from the dog chronic NOAEL of 2 mg/kg/day and a 100-fold safety factor, this dietary exposure is <0.1% of the RfD. Since estimated concentrations of diflubenzuron in drinking water are well below the drinking water levels of concern, aggregate exposure is not expected to exceed 100% of the RfD. Therefore, there is a reasonable certainty that no harm will result from aggregate exposure to diflubenzuron residues.
For PCA, dietary exposure to the U.S. population (total) was estimated as less than 0.000001 mg/kg/day. The risk from diflubenzuron-derived PCA can be estimated using a linear extrapolation of the dose-response from the rat chronic study conducted by the National Toxicology Program in which rats were dosed via gavage with p-chloroaniline [hydrochloride] for 24 months. EPA has determined the q1* as 0.0638, based on the combined sarcoma incidence in the spleen of male rats. In view of the results of recent CPU rat mechanistic and metabolism studies, and the diflubenzuron rat metabolism study, the dietary risk assessment included here considers only actual residues of PCA found in food and animal by-products. This is consistent with a parent compound, such as diflubenzuron, which is negative (Category E) for carcinogenicity. It is also consistent with EPA's manner of treatment of other active ingredients that are clearly negative for carcinogenicity. Using the q1* of 0.0638, the risk to the U.S. population (total) from dietary exposure Start Printed Page 17876to diflubenzuron-derived PCA is 1.31 x 10-8. This risk is below EPA's level of concern.
2. Infants and children. The same assumptions as for the U.S. population were used for the dietary exposure risk determination in infants and children. The dietary exposure of diflubenzuron was calculated as 0.000003 mg/kg/day and 0.000007 mg/kg/day respectively for nursing and non-nursing infants. These values are 0.2% and 0.4%, respectively of the RfD for diflubenzuron. The dietary exposure from diflubenzuron in children 1-6 and 7-12 years old was determined as 0.000015 mg/kg/day and 0.000011 mg/kg/day, respectively. These values are <0.1% of the RfD.
As previously discussed, the NOAELs for maternal and developmental toxicity in rats and rabbits were greater than 1,000 mg/kg/day, and the NOAEL for reproductive toxicity was greater than 5,000 mg/kg/day. Therefore, based on the completeness and reliability of the toxicity data and the conservative exposure assessment, Uniroyal concludes that there is reasonable certainty that no harm will result in infants and children from aggregate exposure to residues of diflubenzuron and its conversion products containing the p-chloroaniline moiety.
F. International Tolerances
There is no Codex Alimentarius Commission Maximum Residue Level for Residues of diflubenzuron on range grass.End Supplemental Information
[FR Doc. 00-8262 Filed 4-4-00; 8:45 am]
BILLING CODE 6560-50-F