65 FR 101 pgs. 33472-33479 - Tebufenozide; Benzoic Acid, 3,5-dimethyl-1-(1,1-dimethylethyl)-2-(4-ethylbenzoyl) hydrazide; Pesticide Tolerance
Type: RULEVolume: 65Number: 101Pages: 33472 - 33479
Docket number: [OPP-300999; FRL-6555-1]
FR document: [FR Doc. 00-13071 Filed 5-23-00; 8:45 am]
Agency: Environmental Protection Agency
Official PDF Version: PDF Version
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-300999; FRL-6555-1]
RIN 2070-AB78
Tebufenozide; Benzoic Acid, 3,5-dimethyl-1-(1,1-dimethylethyl)-2-(4-ethylbenzoyl) hydrazide; Pesticide Tolerance
AGENCY:
Environmental Protection Agency (EPA).
ACTION:
Final rule.
SUMMARY:
This regulation establishes tolerances for residues oftebufenozide [benzoic acid, 3,5-dimethyl-1-(1,1-dimethylethyl)-2-(4-ethylbenzoyl)hydrazide], in or on the tree nut crop group (including pistachios) at 0.1 part per million (ppm) and on almond hulls at 25 ppm. Rohm and Haas Company requested this tolerance under the Federal Food, Drug, andCosmetic Act, as amended by the Food Quality Protection Act of 1996.
DATES:
This regulation is effective May 24, 2000. Objections and requests for hearings, identified by docket control number OPP-300999, must be received by EPA on or before July 24, 2000.
ADDRESSES:
Written objections and hearing requests may besubmitted by mail, in person, or by courier. Please follow the detailed instructions for each method as provided in Unit VI. of the "SUPPLEMENTARY INFORMATION." To ensure proper receipt by EPA, your objections and hearing requests must identify docket control numberOPP-300999 in the subject line on the first page of your response.
FOR FURTHER INFORMATION CONTACT:
By mail: Joseph Tavano, Registration Division (7505C), Office of Pesticide Programs, EnvironmentalProtection Agency, Ariel Rios Bldg., 1200 Pennsylvania Ave., NW.,Washington, DC 20460; telephone number: (703) 305-6411 and e-mail address: tavano.joseph@epa.gov.
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does This Action Apply to Me?
You may be affected by this action if you sell, distribute, manufacture, or use pesticides for agricultural applications, process food, distribute or sell food, or implement governmental pesticide regulations. Potentially affected categories and entities may include, but are not limited to:
| Categories | NAICS codes | Examples of potentially affectedentities |
|---|---|---|
| Industry | 111 | Crop production |
| 112 | Animal production | |
| 311 | Food manufacturing | |
| 32532 | Pesticide manufacturing | |
| Agricultural Stakeholders | Growers/Agricultural Workers,Contractors (Certified/CommercialApplicators, Handlers, Advisors, etc.),Commercial Processors,Pesticide Manufacturers,User Groups,Food Consumers | |
| Food Distributors | Wholesale Contractors,Retail Vendors,Commercial Traders/Importers | |
| Inter governmental Stakeholders | State, Local, and/or Tribal GovernmentAgencies | |
| Foreign Entities | Governments, Growers, Trade Groups,Exporters |
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 inthe 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 actionmight apply to certain entities. If you have questions regarding the applicability of this action toa 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 OPP-300999. The official record consists of the documents specifically referenced in this action, 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 documentsthat 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 Hwy., 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.
II. Background and Statutory Findings
In the Federal Register of August 19, 1998 (63 FR 44439) (FRL 6019-6), and February 17, 1999 (64 FR 7883) (FRL 6060-1), EPA issued a notice pursuant to section 408 of theFederal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a as amended by the FoodQuality Protection Act of 1996 (FQPA) (Public Law 104-170) announcing the filing of apesticide petition (PP) 7F4815 for a tolerance by Rohm and Haas Company, 100 Independence MallWest, Philadelphia, 19106-2399. This notice included a summary of the petition prepared byRohm and Haas Company, the registrant. There were no comments received in response tothe notice of filing.
The petition requested that 40 CFR 180.482 be amended by establishingtolerances for residues of the insecticide tebufenozide in or on the tree nut crop group(including pistachios) at 0.1 ppm and on almond hulls at 25 ppm.
Section 408(b)(2)(A)(i) of the FFDCA allows EPA to establish tolerances (thelegal limit for a pesticide chemical residue in or on a food) only if EPA determines that thetolerance is "safe." Section 408(b)(2)(A)(ii) defines "safe" to mean that "there is a reasonablecertainty that no harm will result from aggregate exposure to the pesticide chemical residue,including all anticipated dietary exposures and all other exposures for which there is reliableinformation." This includes exposure through food and drinking water and in residential settings,but does not include occupational exposure. Section 408(b)(2)(C) requires EPA to give specialconsideration to exposure of infants and children to the pesticide chemical residue in establishinga tolerance and to "ensure that there is a reasonable certainty that no harm will result to infantsand children from aggregate exposure to the pesticide chemical residue * * *."
EPA performs a number of analyses to determine the risks from aggregateexposure to pesticide residues. For further discussion of the regulatory requirements of section408 and a complete description of the risk assessment process, see the final rule on BifenthrinPesticide Tolerances (62 FR 62961, November 26, 1997) (FRL-5754-7).
III. Aggregate Risk Assessment and Determination of Safety
Consistent with section 408(b)(2)(D), EPA has reviewed the available scientificdata and other relevant information in support of this action. EPA has sufficient data to assess thehazards of and to make a determination on aggregate exposure, consistent with section 408(b)(2),for tolerances for residues of tebufenozide on the tree nut crop group (including pistachios) at0.1 ppm and on almond hulls at 25 ppm. EPA's assessment of the exposures and risksassociated with establishing the tolerance follows.
A. Toxicological Profile
EPA has evaluated the available toxicity data and considered its validity, completeness, and reliability as well as the relationship of the results of the studies to human risk. EPA has also considered available information concerning the variability of the sensitivities of major identifiable subgroups of consumers, including infants and children. The nature of the toxic effects caused by tebufenozide are discussed in this unit.
B. Toxicological Endpoints
1. Acute toxicity -i. Acute toxicity studies with technical grade: Oral LD 50 in the rat is 5 grams formales and females-Toxicity Category IV; dermal LD 50 in the rat is = 5,000 milligrams/kilogram(mg/kg) for males and females-Toxicity Category III; inhalation LC 50 in the rat is 4.5 milligram/Liter (mg/L) -Toxicity Category III; primary eye irritation study in the rabbit is a non-irritant; primary skinirritation in the rabbit 5 mg/kg-Toxicity Category IV.Tebufenozide is not a sensitizer.
ii. In a 21-day dermal toxicity study, Crl:CD rats (6/sex/dose) received repeated dermaladministration of either the technical (96.1%) product (RH-75,992) at 1,000 (mg/kg/day) (Limit-Dose) or the formulation (23.1% active ingredient (a.i.)) product (RH-755,992 2F) at 0, 62.5, 250, or 1,000 milligram/kilogram/day(mg/kg/day), 6 hours/day, 5 days/week for 21 days. Under conditions of this study, RH-75,992Technical or RH-75,992 2F demonstrated no systemic toxicity or dermal irritation at the highestdose tested (HDT) 1,000 mg/kg during the 21-day study. Based on these results, the no-observed adverse effect level (NOAEL) forsystemic toxicity and dermal irritation in both sexes is 1,000 mg/kg/day HDT. A lowest-observed adverse effect level (LOAEL) forsystemic toxicity and dermal irritation was not established.
iii. A 1-year dog feeding study with a LOAELof 250 ppm (9 mg/kg/day for male and female dogs) based on decreases in RBC, HCT, andHGB, increases in Heinz bodies, methemoglobin, MCV, MCH, reticulocytes, platelets, plasmatotal bilirubin, spleen weight, and spleen/body weight ratio, and liver/body weight ratio.Hematopoiesis and sinusoidal engorgement occurred in the spleen, and hyperplasia occurred inthe marrow of the femur and sternum. The liver showed an increased pigment in the Kupffercells. The NOAEL for systemic toxicity in both sexes is 50ppm (1.9 mg/kg/day).
iv. An 18-month mouse carcinogenicity study with no carcinogenicity observed atdosage levels up to and including 1,000 ppm.
v. A 2-year rat carcinogenicity study with no carcinogenicity observed at dosage levelsup to and including 2,000 ppm (97 mg/kg/day and 125 mg/kg/day for males and females,respectively)
vi. In a prenatal developmental toxicity study in Sprague-Dawley rats (25/group),tebufenozide was administered on gestation days 6-15 by gavage in aqueous methyl cellulose atdose levels of 50, 250, or 1,000 mg/kg/day and a dose volume of 10 ml/kg. There was noevidence of maternal or developmental toxicity; the maternal and developmental toxicityNOAEL was 1,000 mg/kg/day.
vii. In a prenatal developmental toxicity study conducted in New Zealand white rabbits(20/group), tebufenozide was administered in 5 ml/kg of aqueous methyl cellulose at gavagedoses of 50, 250, or 1,000 mg/kg/day on gestation days 7-19. No evidence of maternal ordevelopmental toxicity was observed; the maternal and developmental toxicity NOAEL was1,000 mg/kg/day.
viii. In a 1993 2-generation reproduction study in Sprague-Dawley rats, tebufenozidewas administered at dietary concentrations of 0, 10, 150, or 1,000 ppm (0, 0.8, 11.5, or 154.8mg/kg/day for males and 0, 0.9, 12.8, or 171.1 mg/kg/day for females). The parental systemicNOAEL was 10 ppm (0.8/0.9 mg/kg/day for males and females, respectively) and the LOAELwas 150 ppm (11.5/12.8 mg/kg/day for males and females, respectively) based on decreasedbody weight, body weight gain, and food consumption in males, and increased incidence and/orseverity of splenic pigmentation. In addition, there was an increased incidence and severity ofextramedullary hematopoiesis at 2,000 ppm. The reproductive NOAEL was 150 ppm. (11.5/12.8mg/kg/day for males and females, respectively) and the LOAEL was 2,000 ppm (154.8/171.1mg/kg/day for males and females, respectively) based on an increase in the number of pregnantfemales with increased gestation duration and dystopia. Effects in the offspring consisted ofdecreased number of pups per litter on postnatal days 0 and/or 4 at 2,000 ppm (154.8/171.1mg/kg/day for males and females, respectively) with a NOAEL of 150 ppm (11.5/12.8mg/kg/day for males and females, respectively).
ix. In a 1995 2-generation reproduction study in rats, tebufenozide was administered atdietary concentrations of 0, 25, 200, or 2,000 ppm (0, 1.6, 12.6, or 126.0 mg/kg/day for males and0, 1.8, 14.6, or 143.2 mg/kg/day for females). For parental systemic toxicity, the NOAEL was25 ppm (1.6/1.8 mg/kg/day in males and females, respectively), and the LOAEL was 200 ppm(12.6/14.6 mg/kg/day in males and females), based on histopathological findings (congestion andextramedullary hematopoiesis) in the spleen. Additionally, at 2,000 ppm (126.0/143.2 mg/kg/dayin M/F), treatment-related findings included reduced parental body weight gain and increasedincidence of hemosiderin-laden cells in the spleen. Columnar changes in the vaginal squamousepithelium and reduced uterine and ovarian weights were also observed at 2,000 ppm, but thetoxicological significance was unknown. For offspring, the systemic NOAEL was 200 ppm(12.6/14.6 mg/kg/day in males and females), and the LOAEL was 2,000 ppm (126.0/143.2mg/kg/day in M/F) based on decreased body weight on postnatal days 14 and 21.
x. Several mutagenicity tests which were all negative. These include an Ames assaywith and without metabolic activation, an in vivo cytogenetic assay in rat bone marrow cells, and in vitro chromosome aberration assay in CHO cells, a CHO/HGPRT assay, a reverse mutationassay with E. Coli , and an unscheduled DNA synthesis assay (UDS) in rat hepatocytes.
xi. The pharmacokinetics and metabolism of tebufenozide were studied in femaleSprague-Dawley rats (3-6/sex/group) receiving a single oral dose of 3 or 250 mg/kg of RH-5992, 14 C labeled in one of three positions (A-ring, B-ring or N-butylcarbon). The extent of absorptionwas not established. The majority of the radio labeled material was eliminated or excreted in thefeces within 48 hours; small amounts (1 to 7% of the administered dose) were excreted in theurine and only traces were excreted in expired air or remained in the tissues. There was notendency for bioaccumulation. Absorption and excretion were rapid. A total of 11 metabolites,in addition to the parent compound, were identified in the feces; the parent compound accountedfor 96 to 99% of the administered radioactivity in the high dose group and 35 to 43% in the lowdose group. No parent compound was found in the urine; urinary metabolites were notcharacterized. The identity of several fecal metabolites was confirmed by mass spectral analysisand other fecal metabolites were tentatively identified by cochromatography with syntheticstandards. A pathway of metabolism was proposed based on these data. Metabolism proceededprimarily by oxidation of the three benzyl carbons, two methyl groups on the B-ring and an ethylgroup on the A-ring to alcohols, aldehydes or acids. The type of metabolite produced variesdepending on the position oxidized and extent of oxidation. The butyl group on the quaternarynitrogen also can be cleaved (minor), but there was no fragmentation of the molecule betweenthe benzyl rings.
No qualitative differences in metabolism were observed between sexes, when high or low dosegroups were compared or when different labeled versions of the molecule were compared.
xii. The absorption and metabolism of tebufenozide were studied in a group of males andfemale bile-duct cannulated rats. Over a 72-hour period, biliary excretion accounted for 30% females to 34% males of the administered dose while urinary excretion accounted for ? 55% of theadministered dose and the carcass accounted for 0.5% of the administered dose for both malesand females. Thus, systemic absorption (percent of dose recovered in the bile, urine and carcass)was 35% females to 39% males. The majority of the radioactivity in the bile (20% females to 24% males of theadministered dose) was excreted within the first 6 hours postdosing indicating rapid absorption.Furthermore, urinary excretion of the metabolites was essentially complete within 24 hourspostdosing. A large amount (67% males to 70% females) of the administered dose was unabsorbed andexcreted in the feces by 72 hours. Total recovery of radioactivity was 105% of the administereddose.
A total of 13 metabolites were identified in the bile; the parent compound was not identified (i.e.- unabsorbed compound) nor were the primary oxidation products seen in the feces in thepharmacokinetics study. The proposed metabolic pathway proceeded by primary oxidation ofthe benzylic carbons to alcohols, aldehydes or acids. Bile contained most of the other highlyoxidized products found in the feces. The most significant individual bile metabolites accountedfor 5% to 18% of the total radioactivity (males and/or females). Bile also contained the previouslyundetected (in the pharmacokinetics study) "A" Ring ketone and the "B" Ring diol. The othermajor components were characterized as high molecular weight conjugates. No individual bilemetabolite accounted for 5% of the total administered dose. Total bile radioactivity accountedfor ? 17% of the total administered dose. No major qualitative differences in biliary metaboliteswere observed between sexes. The metabolic profile in the bile was similar to the metabolicprofile in the feces and urine.
2. Short- and intermediate-term toxicity . No dermal or systemictoxicity was seen in rats receiving 15 repeated dermal applications of the technical (97.2%)product at 1,000 mg/kg/day (Limit-Dose) as well as a formulated (23% active ingredient (a.i)) product at 0, 62.5,250, or 1,000 mg/kg/day over a 21-day period. The Agency noted that in spite of the hematological effects seen in the dog study, similar effects were not seen in the rats receiving the compound via the dermal route indicating poor dermal absorption. Also, no developmental endpoints of concern were evident due to the lack of developmental toxicity in either rat or rabbitstudies. This risk is considered to be negligible.
3. Chronic toxicity . EPA has established the chronic population adjusted dose (cPAD) for tebufenozide at 0.018 mg/kg/day. This reference dose (RfD) is based on a NOAEL of 1.8 mg/kg/day and an uncertainty factor (UF) of 100. The NOAEL was established from the chronic toxicity study in dogs where the NOAEL was 1.8 mg/kg/day based on growth retardation, alterations in hematology parameters, changes in organ weights, and histopathological lesions in the bone, spleen and liver at 8.7 mg/kg/day.EPA determined that the 10x factor to protect children and infants (as required by FQPA) should be reduced to 1x. Therefore, the cPAD is thesame as the RfD: 0.018 mg/kg/day.
4. Carcinogenicity . Tebufenozide has been classified as a Group E, "no evidence of carcinogenicity for humans," chemical by EPA.
C. Exposures and Risks
1. Dietary - i. From food and feed uses . Tolerances have been established (40 CFR 180.482) for the residues of tebufenozide, in or on a variety of raw agricultural commodities. In today's action tolerances will be established for the residues of tebufenozide in or on the tree nut crop group including pistachios at 0.1 ppm, and on almond hulls at 25.0 ppm. Risk assessments were conducted by EPA to assess dietary exposures from tebufenozide as follows:
Section 408(b)(2)(F) states that the Agency may use data on the actual percent of food treated for assessing chronic dietary risk only if the Agency can make the following findings: Condition 1, that the data used are reliable and provide a valid basis to show what percentage of the food derived from such crop is likely to contain such pesticide residue; Condition 2, that theexposure estimate does not under estimate exposure for any significant subpopulation group; and Condition 3, if data are available on pesticide use and food consumption in a particular area, the exposure estimate does not understate exposure for the population in such area. In addition, the Agency must provide for periodic evaluation of any estimates used. To provide for the periodic evaluation of the estimate of percent crop treated (PCT) as required by section 408(b)(2)(F), EPA may require registrants to submit data on PCT.
a. Acute exposure and risk . Acute dietary risk assessments are performed for a food-use pesticide if a toxicological study has indicated the possibility of an effect of concern occurring as a result of a 1-day or single exposure. Neither neurotoxicity nor systemic toxicity was observed in rats given a single oral administration of tebufenozide at 0, 500, 1,000 or 2,000 mg/kg. No maternal or developmental toxicity was observed following oral administration of tebufenozide at 1,000 mg/kg/day (Limit-Dose) during gestation to pregnant rabbits. This risk is considered to be negligible.
b. Chronic exposure and risk . In conducting the DEEM (DietaryExposure Evaluation Model) analysis for chronic exposure to and risk from tebufenozide residues in food, the Agency used tolerance level residues and some PCT (Tier 2). For the subject crops, the tolerances used are: 0.1 ppm for tree nuts (including pistachios) and 25.0 ppm for almond hulls. The analysis evaluates individual food consumption as reported by respondents in the USDA, Continuing Surveys of Food Intake by Individuals conducted in 1989 through 1992. Summaries of the exposures and their representations as percentages of the cPAD for the general population and subgroups of interest are presented in Table 1.
| Population subgroup | Exposure(mg/kg/day) | cPAD% |
|---|---|---|
| U.S. population(48 continguous states) | 0.0026 | 14% |
| Non-nursing infants( 1 years old) | 0.0097 | 54% |
| Females (13+/nursing) | 0.0024 | 13% |
In the table, "cPAD%" means cPAD% = Exposure x 100% divide by cPAD.
The subgroups listed above are: (1) The U.S. population (48 continguous states ); (2) highest exposedpopulation subgroup that includes infants and children; and (3) females 13+.
This chronic dietary (food only) risk assessment should be viewed as conservative. Furtherrefinement using anticipated residue values and additional PCT information wouldresult in a lower estimate of chronic dietary exposure from food.
The estimates of PCT were used as follows. In all cases the maximum estimateswere used.
| Crop | Average | Maximum |
|---|---|---|
| Almonds | 1% | 1% |
| Apples | 1% | 2% |
| Beans/Peas, Dry | 0% | 1% |
| Cabbage, Fresh | 2% | 3% |
| Cole Crops | 1% | 2% |
| Cotton | 1% | 4% |
| Spinach, Fresh | 2% | 3% |
| Spinach, Processed | 20% | 29% |
| Sugarcane | 3% | 5% |
| Walnuts | 10% | 16% |
ii. From drinking water - a. Acute exposure and risk . Because no acute dietary endpointwas determined, the Agency concludes that there is a reasonable certainty of no harm fromacute exposure from drinking water.
b. Chronic exposure and risk . The Agency calculated the Tier I Estimated Environmental Concentrations (EECs) for tebufenozide using generic expected environmental concentration (GENEEC) (surface water) and screening concentration in ground water (SCI-GROW) (ground water) models for use inthe human health risk assessment. For chronic exposure, the worst case EECs for surface water and ground water were 16.5 parts per billion (ppb) and 1.04 ppb, respectively. These values represent upper-bound estimates of the concentrations that might be found in surface and ground water. These modelingdata were compared to the chronic drinking water levels of comparison (DWLOC) for tebufenozide in ground and surface water (SOP for Drinking Water Exposure and Risk Assessments, November 20, 1997).
For purposes of chronic risk assessment, the estimated maximum concentration for tebufenozide in surface and ground waters (16.5 ppb=16.5 m g/L) was compared to the back-calculated human health DWLOCs for the chronic (non-cancer) endpoint. These DWLOCs for various population categories are summarized in Table 2.
| PopulationCategory 2 | Chronic RfD(mg/kg/day) | Food exposure (mg/kg/day) | Max. waterexposure 3 (mg/kg/day) | DWLOC 4,5,6 ( m g/L) | EEC 7 calc. max.( m g/L) |
|---|---|---|---|---|---|
| U.S. population(48 continguous states) | 0.018 | 0.0026 | 0.0154 | 540 | 16.5 |
| Females (13+ years) | 0.018 | 0.0024 | 0.0156 | 470 | 16.5 |
| Non-nursing infants( 1 year) | 0.018 | 0.0097 | 0.0083 | 83 | 16.5 |
| 1 Values are expressed to 2 significant figures. | |||||
| 2 Within each of these categories, the subgroup with the highest food exposure was selected. | |||||
| 3 Maximum water exposure (chronic) (mg/kg/day) = Chronic PAD (mg/kg/day)-Food exposure (mg/kg/day). | |||||
| 4 DWLOC( m g/L) = Max. water exposure (mg/kg/day) x body wt (kg) ÷ [(10 -3 mg/ m g) x water consumed daily(L/day)]. | |||||
| 5 HED Default body weights are: General U.S. population, 70 kg; females (13+ years old), 60 kg; other adultpopulations, 70 kg; and, all infants/children, 10 kg. | |||||
| 6 HED Default daily drinking rates are 2 L/day for adults and 1 L/day for children. | |||||
| 7 EEC: Estimated Environmental Concentration. (Chronic 56-day value). | |||||
2. From non-dietary exposure . There is a potential for occupational exposure to tebufenozide during mixing, loading, and application activities. However, the Agency did not identify dermal or inhalation endpoints for tebufenozide and determined that risks from these routes of exposure are negligible.
3. Cumulative exposure to substances with a common mechanism oftoxicity . Section 408(b)(2)(D)(v) requires that, when considering whether to establish, modify, or revoke a tolerance, the Agency consider "available information" concerning the cumulative effects of a particular pesticide's residues and "other substances that have a commonmechanism of toxicity."
EPA does not have, at this time, available data to determine whether tebufenozide has a common mechanism of toxicity with other substances or how to include this pesticide in a cumulative risk assessment. Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, tebufenozide does not appear to produce a toxic metabolite produced by other substances. For the purposes of this toleranceaction, therefore, EPA has not assumed that tebufenozide has a common mechanism of toxicity with other substances. For information regarding EPA's efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the final rule for Bifenthrin Pesticide Tolerances (62 FR 62961, November 26, 1997).
D. Aggregate Risks and Determination of Safety for U.S. Population
1. Acute risk . The Agency did not identify an acute dietarytoxicological endpoint, therefore, the risk from this route of exposure is negligible.
2. Chronic risk . Using the exposure assumptions described above, and taking into account the completeness and reliability of the toxicity data, the Agency has concluded that dietary (food only) exposure to tebufenozide will utilize 14% of the cPAD for the U.S. population, and 54% of the cPAD for the most highly exposed population subgroup (non- nursing infants 1 yr). EPA generally has no concern for exposures below 100% of the cPAD. Submitted environmental fate studies suggest that tebufenozide is moderately persistent to persistent and mobile; thus, tebufenozide could potentially leach to ground water and runoff tosurface water under certain environmental conditions. The modeling data for tebufenozide indicate levels less than the Agency's DWLOCs. There are no chronic non- occupational/residential exposures expected for tebufenozide. Therefore, the Agency concludes that there is a reasonable certainty that no harm will result to adults, infants and children from chronic aggregate exposure to tebufenozide residues.
3. Short- and intermediate-term risk . There are potential non-occupational/residential short-term post application exposures (incidental non-dietary ingestion) to toddlers from the use of tebufenozide on ornamentals. However, since the Agency did not identify acute dietary endpoint, the short-term post application exposure risk assessment is expected to be negligible. Intermediate-term incidental non-dietary exposures are not expected.
4. Determination of safety . Based on these risk assessments, EPA concludes that there is a reasonable certainty that no harm will result from aggregate exposure to tebufenozide residues.
E. Aggregate Risks and Determination of Safety for Infants and Children
1. Safety factor for infants and children . In assessing the potential for additional sensitivity of infants and children to residues of tebufenozide, EPA considered data from developmental toxicity studies in the rat and rabbit and a 2-generation reproduction study in the rat. The developmental toxicity studies are designed to evaluate adverse effects on the developing organism resulting from maternal pesticide exposure gestation. Reproduction studies provide information relating to effects from exposure to the pesticide on the reproductive capability of mating animals and data on systemic toxicity.
FFDCA section 408 provides that EPA shall apply an additional tenfold margin of safety for infants and children in the case of threshold effects to account for prenatal and postnatal toxicity and the completeness of the data base unless EPA determines that a different margin of safety will be safe for infants and children. Margins of safety are incorporated into EPA risk assessments either directly through use of a margin of exposure (MOE) analysis or through using uncertainty (safety) factors in calculating a dose level that poses no appreciable risk to humans. EPA believes that reliable data support using the standard uncertainty factor (usually 100 for combined interspecies and intraspecies variability) and not the additional tenfold MOE/uncertainty factor when EPA has a complete data base under existing guidelines and whenthe severity of the effect in infants or children or the potency or unusual toxic properties of a compound do not raise concerns regarding the adequacy of the standard MOE/safety factor.
2. Conclusion . There is a complete toxicitydata base for tebufenozide and exposure data are complete or are estimated based on data thatreasonably accounts for potential exposures. For the reasons summarized above, the Agencyconcludes that an additional safety factor is not needed to protect the safety of infants andchildren.
3. Acute risk . Since no acute toxicological endpoints wereestablished, it is unlikely that acute aggregate risk exists.
4. Chronic risk . Using the exposure assumptionsdescribed above, and taking into account the completeness and reliability of the toxicity data, theAgency has concluded that dietary (food only) exposure to tebufenozide will utilize 14% of thecPAD for the U.S. population, and 54% of the cPAD for the most highly exposed population subgroup (non-nursing infants 1 yr). EPA generally has no concern for exposures below 100% of the cPAD.Despite the potential for exposure to tebufenozide in drinking water and from non-dietary, non-occupational exposure, EPA does not expect the aggregate exposure to exceed 100% of the RfD.
5. Short- or intermediate-term risk . Short- and intermediate-termrisks are judged to be negligible due to the lack of significant toxicological effects observed.
6. Determination of safety . Based on these risk assessments, EPAconcludes that there is a reasonable certainty that no harm will result to infants and children fromaggregate exposure to tebufenozide residues.
IV. Other Considerations
A. Metabolism in Plants and Animals
1. Nature of the residue - Plants .The qualitative nature of the residue in plants is adequately understood based upon acceptableapple, sugar beet, and rice metabolism studies. The Agency has concluded that the residue ofregulatory concern is tebufenozide per se .
2. Nature of the residue - Animal .The results of the ruminant and poultry metabolism studies have been reviewed by the Agencyand the determination was made that the tebufenozide residues of regulatory concern in animalsare the parent tebufenozide and the four metabolites designated: RH-2703 [benzoic acid, 3,5-dimethyl-1-(1,1-dimethylethyl)-2-((4-carboxymethyl)benzoyl)hydrazide], RH-9886 [benzoicacid, 3-hydroxymethyl,5-methyl-1-(1,1-dimethylethyl)-2-(4-ethylbenzoyl)hydrazide], the stearicacid conjugate of RH-9886, and RH-0282 [benzoic acid, 3-hydroxymethyl-5-methyl-1-(1,1-dimethylethyl)-2-(4-(1-hydroxyethyl) benzoyl)hydrazide].
B. Analytical Enforcement Methodology
1. Analytical methods - Plant tissues . The Rohm and Haas method TR 34-95-20, with minor modifications, was used to determine tebufenozide residue levels in/on pecansand almonds (MRID 44414304). This method has been validated by EPA and was submitted tothe Food and Drug Administration (FDA) for inclusion in PAM II. The method limit ofquantitation (LOQ) and limit of detection (LOD) for tebufenozide are 0.01 ppm and 0.003 ppm,respectively.
2. Analytical methods - Animal tissues . A submitted HPLC/UV Method, Rohm and HaasMethod TR 34-96-109, has been determined to be adequate for collecting data on residues oftebufenozide in animal tissues. The validated LOQ for tebufenozide in animal tissue is 0.02ppm. The LOQ for each of the metabolites studied are as follows: RH-2703 in liver, 0.02 ppm;RH-9886 and RH-0282 in meat, 0.02 ppm; RH-9526 in fat, 0.02 ppm. The LODs for the analytes are 0.006 ppm in tissues.
3. Multi-residue methods . Rohm and Haas has previously submitted data involvingmulti-residue method testing.
Adequate enforcement methodology (example-gas chromatography) is availableto enforce the tolerance expression. The method may be requested from: Calvin Furlow, PRRIB,IRSD (7502C), Office of Pesticide Programs, Environmental Protection Agency, Ariel RiosBldg., 1200 Pennsylvania Ave., NW., Washington, DC 20460; telephone number: (703)305-5229; e-mail address: furlow.calvin@epa.gov.
C. Magnitude of Residues
1. The petitioner submitted data from tests on pecans, almonds, and almond hulls.A bridging study was also submitted showing that there were no differences in the amount ofRH-5992 residues on pecans (nutmeat) from the two formulations. Residues of tebufenozidewere determined in/on nuts harvested 11-14 days following the last of 4 foliar applications oftebufenozide for a total of ~2.0lbs ai/acre per season (1x the proposed seasonal rate).Tebufenozide residues in/on pecans were below the LOQ of 0.01 ppm: values ranged from 0.003 ppm (the LOD) to 0.0058 ppm. Tebufenozide residues in/on almonds were 0.003-0.052 ppm, and in/on almond hulls were 7.880-19.9 ppm.
2. The inclusion of pistachios into the tree nut crop group without a change in therepresentative crops, pecans and almonds, has been recommended but has not as yet beenpublished. The submitted pecan, almond, and almond hull field trial residue studies are adequateto support the proposed 0.1 ppm tolerance for the tree nut crop group including pistachios andthe 25.0 ppm tolerance for almond hulls.
3. Processed food/feed . There are no tree nut (including pistachio) processed commodities of regulatory interest.
D. International Residue Limits
Codex MRLs have been established for residues of tebufenozide in/on pome fruit(1.0 ppm), husked rice (0.1 ppm) and walnuts (0.05 ppm). Tebufenozide is registered in Canada,and a tolerance for residues in/on apples is established at 1.0 ppm. EPA has set the pome fruittolerance at 1.0 ppm to harmonize with the Codex and Canadian levels.
E. Rotational Crop Restrictions
Since tree nuts and pistachios are perennial crops, rotational croprestrictions are not required for the tree nut crop group and pistachios.
V. Conclusion
Therefore, the tolerances are established for residues of tebufenozide, in or onthe tree nut crop group (including pistachios) at 0.1 ppm, and on almond hulls at 25 ppm.
VI. Objections and Hearing Requests
Under section 408(g) of the FFDCA, as amended by the FQPA, any person mayfile an objection to any aspect of this regulation and may also request a hearing on thoseobjections. The EPA procedural regulations which govern the submission of objections andrequests for hearings appear in 40 CFR part 178. Although the procedures in those regulationsrequire some modification to reflect the amendments made to the FFDCA by the FQPA of 1996,EPA will continue to use those procedures, with appropriate adjustments, until the necessarymodifications can be made. The new section 408(g) provides essentially the same process forpersons to "object" to a regulation for an exemption from the requirement of a tolerance issuedby EPA under new section 408(d), as was provided in the old FFDCA sections 408 and 409.However, the period for filing objections is now 60 days, rather than 30 days.
A. What Do I Need to Do To File an Objection or Request a Hearing?
You must file your objection or request a hearing on this regulation in accordance withthe instructions provided in this unit and in 40 CFR part 178. To ensure proper receipt by EPA,you must identify docket control number OPP-300999 in the subject line on the first page ofyour submission. All requests must be in writing, and must be mailed or delivered to the HearingClerk on or before July 24, 2000.
1. Filing the request . Your objection must specify the specific provisions in theregulation that you object to, and the grounds for the objections (40 CFR 178.25). If a hearing isrequested, the objections must include a statement of the factual issue(s) on which a hearing isrequested, the requestor's contentions on such issues, and a summary of any evidence relied uponby the objector (40 CFR 178.27). Information submitted in connection with an objection orhearing request may be claimed confidential by marking any part or all of that information asCBI. Information so marked will not be disclosed except in accordance with procedures set forthin 40 CFR part 2. A copy of the information that does not contain CBI must be submitted forinclusion in the public record. Information not marked confidential may be disclosed publicly byEPA without prior notice.
Mail your written request to: Office of the Hearing Clerk (1900), EnvironmentalProtection Agency, Ariel Rios Bldg., 1200 Pennsylvania Ave., NW., Washington, DC 20460.You may also deliver your request to the Office of the Hearing Clerk in Rm. C400, WatersideMall, 401 M St., SW., Washington, DC 20460. The Office of the Hearing Clerk is open from 8a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The telephone number for theOffice of the Hearing Clerk is (202) 260-4865.
2. Tolerance fee payment . If you file an objection or request a hearing, you must also pay the fee prescribed by 40 CFR 180.33(i) or request a waiver of that fee pursuant to 40 CFR 180.33(m). You must mail the fee to: EPA Headquarters Accounting Operations Branch, Officeof Pesticide Programs, P.O. Box 360277M, Pittsburgh, PA 15251. Please identify the fee submission by labeling it "Tolerance Petition Fees."
EPA is authorized to waive any fee requirement "when in the judgement of the Administrator such a waiver or refund is equitable and not contrary to the purpose of this subsection." For additional information regarding the waiver of these fees, you may contactJames Tompkins by phone at (703) 305-5697, by e-mail at tompkins.jim@epa.gov, or by mailing a request for information to Mr. Tompkins at Registration Division (7505C), Office of Pesticide Programs, Environmental Protection Agency, Ariel Rios Bldg., 1200 Pennsylvania Ave., NW., Washington, DC 20460.
If you would like to request a waiver of the tolerance objection fees, you must mail yourrequest for such a waiver to: James Hollins, Information Resources and Services Division(7502C), Office of Pesticide Programs, Environmental Protection Agency, Ariel Rios Bldg.,1200 Pennsylvania Ave., NW., Washington, DC 20460.
3. Copies for the Docket . In addition to filing an objection or hearing request with theHearing Clerk as described in Unit VI.A., you should also send a copy of your request to thePIRIB for its inclusion in the official record that is described in Unit I.B.2. Mail your copies,identified by docket control number OPP-300999, to: Public Information and Records IntegrityBranch, Information Resources and Services Division (7502C), Office of Pesticide Programs,Environmental Protection Agency, Ariel Rios Bldg., 1200 Pennsylvania Ave., NW.,Washington, DC 20460. In person or by courier, bring a copy to the location of the PIRIBdescribed in Unit I.B.2. You may also send an electronic copy of your request via e-mail to:opp-docket@epa.gov. Please use an ASCII file format and avoid the use of special charactersand any form of encryption. Copies of electronic objections and hearing requests will also beaccepted on disks in WordPerfect 6.1/8.0 file format or ASCII file format. Do not include anyCBI in your electronic copy. You may also submit an electronic copy of your request at manyFederal Depository Libraries.
B. When Will the Agency Grant a Request for a Hearing?
A request for a hearing will be granted if the Administrator determines that the materialsubmitted shows the following: There is a genuine and substantial issue of fact; there is areasonable possibility that available evidence identified by the requestor would, if establishedresolve one or more of such issues in favor of the requestor, taking into account uncontestedclaims or facts to the contrary; and resolution of the factual issue(s) in the manner sought by therequestor would be adequate to justify the action requested (40 CFR 178.32).
VII. Regulatory Assessment Requirements
This final rule establishes a tolerance under FFDCA section 408(d) in response to apetition submitted to the Agency. The Office of Management and Budget (OMB) has exemptedthese types of actions from review under Executive Order 12866, entitled Regulatory Planningand Review (58 FR 51735, October 4, 1993). This final rule does not contain any informationcollections subject to OMB approval under the Paperwork Reduction Act (PRA), 44 U.S.C. 3501 et seq ., or impose any enforceable duty or contain any unfunded mandate as described underTitle II of the Unfunded Mandates Reform Act of 1995 (UMRA) (Public Law 104-4). Nor doesit require any prior consultation as specified by Executive Order 13084, entitled Consultationand Coordination with Indian Tribal Governments (63 FR 27655, May 19, 1998); specialconsiderations as required by Executive Order 12898, entitled Federal Actions to AddressEnvironmental Justice in Minority Populations and Low-Income Populations (59 FR 7629,February 16, 1994); or require OMB review or any Agency action under Executive Order 13045,entitled Protection of Children from Environmental Health Risks and Safety Risks (62 FR 19885,April 23, 1997). This action does not involve any technical standards that would require Agencyconsideration of voluntary consensus standards pursuant to section 12(d) of the NationalTechnology Transfer and Advancement Act of 1995 (NTTAA), Public Law 104-113, section12(d) (15 U.S.C. 272 note). Since tolerances and exemptions that are established on the basis ofa petition under FFDCA section 408(d), such as the tolerance in this final rule, do not require theissuance of a proposed rule, the requirements of the Regulatory Flexibility Act (RFA) (5 U.S.C.601 et seq .) do not apply. In addition, the Agency has determined that this action will not have asubstantial direct effect on States, on the relationship between the national government and theStates, or on the distribution of power and responsibilities among the various levels ofgovernment, as specified in Executive Order 13132, entitled Federalism (64 FR 43255, August10, 1999). Executive Order 13132 requires EPA to develop an accountable process to ensure"meaningful and timely input by State and local officials in the development of regulatorypolicies that have federalism implications." "Policies that have federalism implications" isdefined in the Executive Order to include regulations that have "substantial direct effects on theStates, on the relationship between the national government and the States, or on the distributionof power and responsibilities among the various levels of government." This final rule directlyregulates growers, food processors, food handlers and food retailers, not States. This action doesnot alter the relationships or distribution of power and responsibilities established by Congress inthe preemption provisions of FFDCA section 408(n)(4).
VIII. Submission to Congress and the Comptroller General
The Congressional Review Act, 5 U.S.C. 801 et seq ., as added by the Small BusinessRegulatory Enforcement Fairness Act of 1996, generally provides that before a rule may takeeffect, the agency promulgating the rule must submit a rule report, which includes a copy of therule, to each House of the Congress and to the Comptroller General of the United States. EPAwill submit a report containing this rule and other required information to the U.S. Senate, theU.S. House of Representatives, and the Comptroller General of the United States prior topublication of this final rule in the Federal Register . This final rule is not a "major rule" asdefined by 5 U.S.C. 804(2).
List of Subjects in 40 CFR Part 180
Environmental protection, Administrative practice and procedure, Agriculturalcommodities, Pesticides and pests, Reporting and recordkeeping requirements.
Dated: May 10, 2000.
James Jones,
Director, Registration Division, Office of Pesticide Programs.
Therefore, 40 CFR chapter I is amended as follows:
PART 180-[AMENDED]
1. The authority citation for part 180 continues to read as follows:
Authority: 21 U.S.C. 321(q), (346a) and 371.
2. In § 180.482, by alphabetically adding the followingentries to the table in paragraph (a)(1) to read as follows.
§ 180.482 Tebufenozide; tolerances for residues.
* * * * *
(a) General . (1) ***
| Commodity | Parts per million |
|---|---|
| ***** | |
| Almond hulls | 25 |
| ***** | |
| Tree nut crop group includingpistachios | 0.1 |
| ***** |
[FR Doc. 00-13071 Filed 5-23-00; 8:45 am]
BILLING CODE 6560-50-F