Pesticides; tolerances in food, animal feeds, and raw agricultural commodities: Buprofezin,
[Federal Register: August 31, 2000 (Volume 65, Number 170)]
[Rules and Regulations]
[Page 52938-52947]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr31au00-10]
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-301040; FRL-6740-1]
RIN 2070-AB
Buprofezin (2-Tert-butylimino-3-isopropyl-5-phenyl-1,3,5- thiadiazinan-4-one); Time-Limited Pesticide Tolerances
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
SUMMARY: This regulation establishes time-limited tolerances for residues of buprofezin in or on lettuce, head; lettuce, leaf; and vegetables, cucurbits. Aventis CropScience requested these tolerances under the Federal Food, Drug, and Cosmetic Act, as amended by the Food Quality Protection Act of 1996. The tolerances will expire on December 31, 2004.
DATES: This regulation is effective August 31, 2000. Objections and requests for hearings, identified by docket control number OPP-301040, must be received by EPA on or before October 30, 2000.
ADDRESSES: Written objections and hearing requests may be submitted 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 number OPP-301040 in the subject line on the first page of your response.
FOR FURTHER INFORMATION CONTACT: By mail: Richard J. Gebken, Registration Division (7505C), Office of Pesticide Programs, Environmental Protection Agency, Ariel Rios Bldg., 1200 Pennsylvania Ave., NW., Washington, DC 20460; telephone number: (703) 305-6701; and e-mail address: gebken.richard@epa.gov.
SUPPLEMENTARY INFORMATION:
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General Information
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Does this Action Apply to Me?
You may be affected by this action if you are an agricultural producer, food manufacturer, or pesticide manufacturer. Potentially affected categories and entities may include, but are not limited to:
Examples of Categories
NAICS
Potentially Affected Entities
Industry
111
Crop production 112
Animal production 311
Food manufacturing 32532
Pesticide manufacturing
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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.
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How Can I Get Additional Information, Including Copies of this Document and Other Related Documents?
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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,'' Regulations 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/.
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In person. The Agency has established an official record for this action under docket control number OPP-301040. 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 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 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.
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Background and Statutory Findings
In the Federal Register of August 26, 1998 (63 FR 45483) (FRL-5791- 1), EPA issued a notice pursuant to section 408 of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a as amended by the Food Quality Protection Act of 1996 (FQPA) (Public Law 104-170) announcing the filing of a pesticide petition (PP) for tolerance by Aventis CropScience (formerly AgrEvo USA Company, 2 T.W. Alexander Drive, Research Triangle Park, N.C. 27709). This notice included a summary of the petition prepared by Aventis CropScience, the registrant. There were no comments received in response to the notice of filing.
The petition requested that 40 CFR 180.511 be amended by establishing a tolerance for residues of the insecticide buprofezin, in or on lettuce, head; lettuce, leaf; and vegetables, cucurbits at 5.0, 13.0, and 0.50 parts per million (ppm), respectively. The tolerances will expire on December 31, 2004.
Buprofezin is an insecticide which will be sold under the trade name of Applaud 70WP. Buprofezin is a new insect growth regulator used for the control of several species of Homoptera spp., such as planthoppers, mealybugs, leafhoppers, whiteflies and scales. It is currently registered in 76 countries mainly for use on vegetables, cotton, citrus, rice and ornamentals.
Section 408(b)(2)(A)(i) of the FFDCA allows EPA to establish a tolerance (the legal limit for a pesticide chemical residue in or on a food) only if EPA determines that the tolerance is ``safe.'' Section 408(b)(2)(A)(ii) defines ``safe'' to mean that ``there is a reasonable certainty 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 reliable information.'' This includes exposure through drinking water and in residential settings, but does not include occupational exposure. Section 408(b)(2)(C) requires EPA to give special consideration to exposure of infants and children to the pesticide chemical residue in establishing a tolerance and to ``ensure that there is a reasonable certainty that no harm will result to infants and children from aggregate exposure to the pesticide chemical residue. . . .''
EPA performs a number of analyses to determine the risks from aggregate exposure to pesticide residues. For further discussion of the regulatory requirements of section 408 and a complete description of the risk assessment process, see the final rule on Bifenthrin Pesticide Tolerances (62 FR 62961, November 26, 1997) (FRL-5754-7).
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Aggregate Risk Assessment and Determination of Safety
Consistent with section 408(b)(2)(D), EPA has reviewed the available scientific data and other relevant information in support of this action. EPA has sufficient data to assess the hazards of and to make a determination on aggregate exposure, consistent with section 408(b)(2), for a tolerance for residues of buprofezin on lettuce, head; lettuce, leaf; and vegetables, cucurbits at 5.0, 13.0, and 0.50 parts per million (ppm), respectively. EPA's assessment of exposures and risks associated with establishing the tolerance follows.
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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 toxicological data base for buprofezin is adequate for selecting toxicity endpoints according to the Agency guideline requirements for a food-use chemical by 40 CFR part 158. However, an additional developmental neurotoxicity study in rats is required to address Agency concerns raised from the presence of thyroid effects observed in rat and dog subchronic and/or chronic studies.
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Acute toxicity. Buprofezin is classified by the Agency as toxicity Category III for acute oral and toxicity category IV for acute dermal toxicity, acute inhalation toxicity, eye irritation and dermal irritation, and is not a dermal sensitizer. The nature of the toxic effects caused by buprofezin are discussed in the following Table 1 as well as the no observed adverse effect level (NOAEL) and the lowest observed adverse effect level (LOAEL) from the toxicity studies reviewed.
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Table 1.--Acute Toxicity Data on Buprofezin Technical*
Guideline No.
Study Type
Results
Toxicity Category
870.1100
Acute oral toxicity LD501,653 mg/kg males, III LD502,015 mg/kg females
870.1200
Acute dermal toxicity LD50> 5,000 mg/kg IV
870.1300
Acute inhalation
LC50> 4.21 mg/L
IV toxicity
(estimated)
870.2400
Acute eye irritation Mild
IV
870.2500
Acute dermal irritation Slight
IV
870.2600
Skin sensitization Negative
NA
*Buprofezin Technical (99% a.i.)
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Subcronic, chronic, and other toxicity. For subchronic toxicity, the primary effects of concern in the rat were increased microscopic lesions in male and female liver and thyroid, increased liver weights in males and females, and increased thyroid weight in males. Increased focal necrosis with an inflammatory infiltrate in the liver was observed in females following dermal subchronic exposure, as was increased acanthosis and hyperkeratosis in skin.
In chronic studies in the rat, an increased incidence of follicular cell hyperplasia and hypertrophy in the thyroid of males was reported. Increased relative liver weights were reported in female dogs. In the mouse, increased absolute liver weights in males and females, along with an increased incidence of hepatocellular adenomas and hepatocellular adenomas plus carcinomas in females were reported. The Agency has evaluated the carcinogenic potential of buprofezin, based on these liver tumors in female mice, and classified it as having ``Suggestive Evidence of Carcinogenicity, but not sufficient to assess human carcinogenic potential.''
The developmental toxicity study in the rat produced reduced ossification and reduced pup weight at maternally toxic doses (death, decreased pregnancy rates, and increased resorption rates). No developmental toxicity was observed in the rabbit at or below maternally toxic dose levels.
The reproductive toxicity study showed decreased pup body weights at dose levels where liver effects (increased relative and/or absolute liver weights) and decreased body weight gains were observed in the parental generations.
The data do not raise concern for susceptibility in offspring. The developmental and reproductive studies showed toxicity in the offspring only at dose levels that were toxic in the parent(s). The toxicity observed in the offspring was not more severe, qualitatively, than the toxicity observed in the parents.
The data do not indicate a basis for concern for neurotoxicity. Possible neurotoxicity (hunched positions, lethargy) was observed in the rat developmental toxicity study, at levels that caused death. In the 90-day rat subchronic study, a 24% decrease in plasma cholinesterase was reported in males and females at the high dose level. However, this was not correlated with any pathological observation or functional deficit. Neurotoxicity was not observed in any of the chronic studies in the rat, mouse, or dog.
There is no concern for mutagenic activity in several studies such as the Ames assay, forward mutation assay, mouse micronucleus assay, in vitro human cytogenetic assay, and unscheduled DNA synthesis.
A rat metabolism study indicated that 95% of the administered compound is recovered in the feces and urine within 72 hours, and that 45% is recovered as the parent compound, with the remainder as several metabolites. The nature of the toxic effects caused by buprofezin are discussed in the following Table 2 as well as the NOAEL and the LOAEL from the toxicity studies reviewed.
Table 2.--Subchronic, Chronic, and Other Toxicity
Guideline No.
Study Type
Results
870.3100
90-Day oral
NOAEL: 13.0 mg/kg/day toxicity rodents (Males or M); 16.3 (rat)
mg/kg/day (Females or F) LOAEL: 68.6 mg/kg/day (M); 81.8 mg/kg/day females based on increased relative thyroid weight males, increased liver weights M/F, increased microscopic lesions in liver and thyroid M/F
870.3200
24-Day dermal Systemic NOAEL: 300 toxicity (rat) mg/kg/day Dermal NOAEL: 300 mg/ kg/day Systemic LOAEL: 1,000 mg/kg/day based on increased focal necrosis with an inflammatory infiltrate in liver (F) Dermal LOAEL: 1,000 mg/kg/day based on increased acanthosis and hyperkeratosis in skin (F)
870.3700a
Developmental Maternal NOAEL 200 mg/ toxicity in
kg/day rodents (rat) Developmental NOAEL 200 mg/kg/day Maternal LOAEL 800 mg/ kg/day based on mortality, decreased pregnancy rates, increased resorption rates
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Developmental LOAEL 800 mg/kg/day based on reduced ossification, reduced pup weight, fetal edema
870.3700b
Developmental Maternal NOAEL 50 mg/ toxicity in non- kg/day rodents (rabbit) Developmental NOAEL 250 mg/kg/day Maternal LOAEL 250 mg/ kg/day based on decreased food consumption, decreased body weights. Developmental LOAEL, not established (> 250 mg/kg/day)
870.3800
Reproduction and Parental NOAEL 7.89 fertility
mg/kg/day effects in rats Reproductive/ Developmental NOAEL 7.89 mg/kg/day Parental LOAEL 81.47 mg/kg/day based on decreased body weight gain and on organ weight changes Reproductive/ Developmental LOAEL 81.47 mg/kg/day based on decreased pup weight.
870.4100
Chronic toxicity NOAEL 2 mg/kg/day in dogs LOAEL 20 mg/kg/day based on increased bile duct hyperplasia M/F, increased serum alkaline phosphatase activity M/F, increased relative and absolute liver weights and decreased liver function in females
870.4200
Carcinogenicity NOAEL 1.82/17.9 mg/kg/ study in mice day (M/F) LOAEL 17.40/191.0 mg/ kg/day (M/F) based on increased absolute liver weights in males and females, increased hepatocellular adenomas in females, increased hepatocellular adenomas + carcinomas in females
870.4300
Chronic toxicity/ NOAEL 1.0 mg/kg/day carcinogenicity in rodents (rat) LOAEL 8.7 mg/kg/day based on increased incidence of follicular cell hyperplasia and hypertrophy in thyroid in males No evidence of carcinogenicity
870.5100
Mutagenicity: Not mutagenic, with gene mutation or without Salmonella
activation tested up to cytotoxic levels
870.5300
Mutagenicity: Not mutagenic, with gene mutation or without mouse lymphoma activation tested up to cytotoxic levels
870.5300
Mutagenicity: in Negative for vitro human
chromosomal cytogenetic
aberrations tested assay
up to cytotoxic levels
870.5300
Mutagenicity: Negative for mouse
micronucleus micronucleus induction in bone assay
marrow cells of males and females tested up to cytotoxic levels
870.5300
Mutagenicity: Negative for DNA unscheduled DNA repair tested up to synthesis
cytotoxic levels
870.7485
Metabolism
79.1% recovered from feces, 12.9% from urine within 72 hr. 45.4% recovered as parent cpd, several metabolites identified
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Toxicological Endpoints
The dose at which no adverse effects are observed (the NOAEL) from the toxicology study identified as appropriate for use in risk assessment is used to estimate the toxicological level of concern (LOC). However, the lowest dose at which adverse effects of concern are identified (the LOAEL) is sometimes used for risk assessment if no NOAEL was achieved in the toxicology study selected. An uncertainty factor (UF) is applied to reflect uncertainties inherent in the extrapolation from laboratory animal data to humans and in the variations in sensitivity among members of the human population as well as other unknowns. An UF of 100 is routinely used, 10X to account for interspecies differences and 10X for intraspecies differences.
For dietary risk assessment (other than cancer), the Agency uses the UF to calculate an acute or chronic reference dose (acute RfD or chronic RfD) where the RfD is equal to the NOAEL divided by the appropriate UF (RfD=NOAEL/UF). Where an additional safety factor is retained due to concerns unique to the FQPA, this additional factor is applied to the RfD by dividing the RfD by such additional factor. The acute or chronic Population Adjusted Dose (aPAD or cPAD) is a modification of the RfD to accommodate this type of FQPA Safety Factor.
For non-dietary risk assessments (other than cancer), the UF is used to determine the LOC. For example, when 100 is the appropriate UF (10X to account for interspecies differences and 10X for intraspecies differences) the LOC is 100. To estimate risk, a ratio of the NOAEL to exposures (margin of exposure (MOE)=NOAEL/exposure) is calculated and compared to the LOC.
The linear default risk methodology (Q*) is the primary method currently used by the Agency to quantify carcinogenic risk. The Q* approach assumes that any amount of exposure will lead to some degree of cancer risk.
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A Q* is calculated and used to estimate risk which represents a probability of occurrence of additional cancer cases (e.g., risk is expressed as 1 x 10-6or one in a million). Under certain specific circumstances, MOE calculations will be used for the carcinogenic risk assessment. In this non-linear approach, a ``point of departure'' is identified below which carcinogenic effects are not expected. The point of departure is typically a NOAEL based on an endpoint related to cancer effects though it may be a different value derived from the dose response curve. To estimate risk, a ratio of the point of departure to exposure (MOEcancer=point of departure/exposures) is calculated. The doses and toxicological endpoints selected and the LOC for margins of exposure for various exposure scenarios are summaried in the following Table 3.
Table 3.--Toxicological Endpoint Summary for Use in Human Risk Assessment
Exposure Scenario
Dose (mg/kg/day)
Endpoint
Study
Acute Dietary
NOAEL = 200 UF = 100 LOAEL = 800 mg/kg/day Developmental toxicity based on skeletal
rabbit effects in offspring Acute RfD = 2.0 mg/kg NA (females 13 - 50); Acute RfD for general population including infants and children: None, no endpoint identified which was attributable to a single dose.
Chronic Dietary
NOAEL = 1.0 UF = 100 LOAEL = 8.7 mg/kg/day 2-year chronic toxicity/ based on increased oncogenicity in rat incidence of follicular cell hyperplasia and hypertrophy in the thyroid in males. Chronic RfD = 0.01 mg/ NA kg day
Short-term (dermal)
NOAEL = 300
LOAEL = 1,000 mg/kg/day 24-Day dermal rat based on an increase of focal necrosis with an inflammatory infiltrate in liver in females
Intermediate-term (dermal)
NOAEL = 300
LOAEL = 1,000 mg/kg/day 24-Day dermal rat based on an increase of focal necrosis with an inflammatory infiltrate in liver in females
Long-term (dermal)
Oral NOAEL = 1.0*
LOAEL = 8.7 mg/kg/day 2-Year chronic oral based on increased toxicity/oncogenicity incidence of
in rat follicular cell hyperplasia and hypertrophy in the thyroid in males. 30% dermal absorption estimated.
Short-term (inhalation)
Oral NOAEL = 200** LOAEL = 800 mg/kg/day Developmental toxicity based on skeletal
rat effects in offspring
Intermediate-term (inhalation)
Oral NOAEL = 13**
LOAEL = 68.6 mg/kg/day 90-Day oral subchronic abased on organ weight study in rat changes and microscopic findings in liver and thyroid (M and F) and kidney (M)
Long-term (inhalation)
Oral NOAEL = 1**
LOAEL = 8.7 mg/kg/day 2-Year chronic oral based on increased toxicity/oncogenicity incidence of
in rat follicular cell hyperplasia and hypertrophy in the thyroid in males.
*Since an oral NOAEL was selected, 30% dermal absorption was used. **Since an oral NOAEL was selected, 100% inhalation absorption was used.
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Exposure Assessment
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Dietary exposure from food and feed uses. Time-limited tolerances under section 18 emergency exemptions have been established (40 CFR 180.511(b)) for the residues of buprofezin, in or on a variety of raw agricultural commodities. The following time-limited tolerances for residues of buprofezin are established in connection with use of the pesticide under section 18 emergency exemptions: citrus fruit (2.0 ppm); citrus pulp dried (10 ppm); cotton seed (1.0 ppm); cotton gin byproducts (20 ppm); cucurbits (0.5 ppm); tomatoes (0.7 ppm); tomato paste (1.0 ppm); milk (0.03 ppm); and fat (0.02 ppm), meat (0.02 ppm), and meat byproducts (0.5 ppm) of cattle, goats, hogs, horses, and sheep. Risk assessments were conducted by EPA to assess dietary exposures from buprofezin in food as follows: i. Acute exposure. 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. The Dietary Exposure Evaluation Model (DEEMTM) analysis evaluated the individual food consumption as reported by respondents in the U.S. Department of Agriculture (USDA) 1989-1992 nationwide Continuing Surveys of Food Intake by Individuals (CSFII) and accumulated exposure to the chemical for each commodity. The following assumptions were made for the acute exposure assessments: The acute dietary exposure analysis assumed tolerance level residues and 100% crop treated for all registered and proposed commodities (Tier 1). For females 13-50 years old, 4% of the aPAD is occupied by dietary (food) exposure (no acute RfD established for the general population including infants and children). Therefore acute exposure to buprofezin, as a result of dietary exposure, is below the Agency's level of concern. The anticipated residues were used for evaluation. ii. Chronic exposure. In conducting this chronic dietary risk assessment, the DEEMTManalysis evaluated the individual food consumption as reported by respondents in the USDA 1989-1992 nationwide CSFII and accumulated exposure to the chemical
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for each commodity. The following assumptions were made for the chronic exposure assessments: Since there are no chronic residential exposure scenarios, the chronic aggregate risk assessment is concerned with food and water only. The chronic dietary exposure analysis incorporated anticipated residues calculated from field trial data and assumed 100% crop treated for all commodities except tomatoes (44% and 0.6% crop treated for the fresh market and for processing, respectively; Tier 2 analysis). Only 49% of the cPAD is occupied by dietary (food) exposure The buprofezin estimated environmental concentrations in surface and ground water are less than the Agency's DWLOC (for all population subgroups). Chronic risk for buprofezin, as a result of dietary (food and water) exposure, is below the Agency's level of concern. The Agency concludes with reasonable certainty that residues of buprofezin in food and drinking water do not contribute significantly to the acute or chronic aggregate human health risk at the present time. iii. Cancer. The Agency has evaluated the carcinogenicity potential of buprofezin, based on these liver tumors in female mice. Buprofezin was not carcinogenic to male and female rats. Administration of buprofezin in the diet was associated with increased incidence of liver tumors in female mice only because:
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There was a significant increase by pair-wise comparison with the controls for combined hepatocellular adenomas/carcinomas at 2,000 and 5,000 ppm (191.9 and 493 mg/kg/day, respectively) in females. The increased incidence of combined tumors was driven by the incidence of adenomas. There was a significant positive trend for combined tumors and a dose-related increase in the incidence at the two top doses. The increase in the combined incidence of liver tumors at 2,000 and 5,000 ppm was associated with non-neoplastic changes and the incidences were slightly outside the historical control range. The increased incidence of hepatocellular adenomas/carcinomas at 2,000 ppm in females was considered by the Agency to be biologically significant.
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In males, there was a significant increase by pair-wise comparison with the controls for combined adenomas/carcinomas of the lung at 20, 200 and 5,000 ppm (1.82, 17.4, or 481 mg/kg/day, respectively). Although there was evidence of a positive trend with increasing doses of buprofezin, the incidences in all dose groups were within the range for the historical controls. The Agency, therefore, concluded that the lung tumors in males were not treatment-related. The dosing at 5,000 ppm was considered to be adequate and not excessive based on increased liver weights in females, histopathological changes in the liver, and decreased body weight gains at 5,000 ppm in both sexes.
Although buprofezin was negative in in vitro and in vivo genotoxicity assays, the findings from the published literature indicate that it causes cell transformation and induces micronuclei in vitro. However, in the absence of a positive response in an in vivo micronucleus assay, the Agency concluded that buprofezin may have aneugenic potential which is not expressed in vivo.
Consistent with the EPA Guidelines for Carcinogen Risk Assessment (proposed July 1999), the Agency has classified buprofezin as having ``Suggestive Evidence of Carcinogenicity, but not sufficient to assess human carcinogenic potential.'' The Agency concluded that no quantification of cancer risk or assessment is appropriate, taking into account all of the evidence bearing on carcinogenicity including that a positive finding was limited to one sex of one species. iv. Anticipated residues. Section 408(b)(2)(E) authorizes EPA to use available data and information on the anticipated residue levels of pesticide residues in food and the actual levels of pesticide chemicals that have been measured in food. If EPA relies on such information, EPA must require that data be provided 5 years after the tolerance is established, modified, or left in effect, demonstrating that the levels in food are not above the levels anticipated. Following the initial data submission, EPA is authorized to require similar data on a time frame it deems appropriate. As required by section 408(b)(2)(E), EPA will issue a Data Call-In for information relating to anticipated residues to be submitted no later than 5 years from the date of issuance of this tolerance.
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Dietary exposure from drinking water. The maximum and average EECs for buprofezin in ground and surface water are less than the Agency's DWLOC for buprofezin as a contribution to acute and chronic aggregate exposure (for all population subgroups).
The Agency lacks sufficient monitoring exposure data to complete a comprehensive dietary exposure analysis and risk assessment for buprofezin in drinking water. Because the Agency does not have comprehensive monitoring data, drinking water concentration estimates are made by reliance on simulation or modeling taking into account data on the physical characteristics of buprofezin.
The Agency uses the Generic Estimated Environmental Concentration (GENEEC) or the Pesticide Root Zone/Exposure Analysis Modeling System (PRZM/EXAMS) to estimate pesticide concentrations in surface water and SCI-GROW, which predicts pesticide concentrations in ground water. In general, EPA will use GENEEC (a tier 1 model) before using PRZM/EXAMS (a tier 2 model) for a screening-level assessment for surface water. The GENEEC model is a subset of the PRZM/EXAMS model that uses a specific high-end runoff scenario for pesticides. GENEEC incorporates a farm pond scenario, while PRZM/EXAMS incorporates an index reservoir environment in place of the previous pond scenario. The PRZM/EXAMS model includes a percent crop area factor as an adjustment to account for the maximum percent crop coverage within a watershed or drainage basin.
None of these models include consideration of the impact processing (mixing, dilution, or treatment) of raw water for distribution as drinking water would likely have on the removal of pesticides from the source water. The primary use of these models by the Agency at this stage is to provide a coarse screen for sorting out pesticides for which it is highly unlikely that drinking water concentrations would ever exceed human health levels of concern.
Since the models used are considered to be screening tools in the risk assessment process, the Agency does not use EECs from these models to quantify drinking water exposure and risk as a %RfD or PAD. Instead drinking water levels of comparison (DWLOCs) are calculated and used as a point of comparison against the model estimates of a pesticide's concentration in water. DWLOCs are theoretical upper limits on a pesticide's concentration in drinking water in light of total aggregate exposure to a pesticide in food, and from residential uses. Since DWLOCs address total aggregate exposure to buprofezin, they are further discussed in the aggregate risk sections below.
Based on the GENEEC and SCI-GROW models the EECs of buprofezin in surface water and ground water for acute exposures are estimated to be 11.48 ppb for surface water and 0.04 ppb for ground water. The EECs for chronic exposures are estimated to be 1.80 ppb for surface water and 0.04 ppb for ground water.
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From non-dietary exposure. The term ``residential exposure'' is used in this document to refer to non-occupational, non-dietary exposure (e.g., for lawn and garden pest control, indoor pest control, termiticides, and flea and tick control on pets). Buprofezin is not registered for use on any sites that would result in residential exposure.
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Cumulative exposure to substances with a common mechanism of toxicity. 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 common mechanism of toxicity.''
EPA does not have, at this time, available data to determine whether buprofezin 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, buprofezin does not appear to produce a toxic metabolite produced by other substances. For the purposes of this tolerance action, therefore, EPA has not assumed that buprofezin 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).
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Safety Factor for Infants and Children
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Safety factor for infants and children--i. In general. 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 on toxicity and exposure 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.
ii. Prenatal and postnatal sensitivity. The Agency concluded that available toxicity data provide no indication of increased susceptibility of rats or rabbits following in utero exposure or of rats following prenatal/postnatal exposure to buprofezin. In the prenatal developmental toxicity study in rats, developmental effects were seen only in the presence of severe maternal toxicity including deaths. No developmental toxicity was seen at the highest dose tested in the prenatal developmental toxicity study in rabbits. And in the 2- generation reproduction study in rats, effects in the offspring were observed only at treatment levels which resulted in evidence of parental toxicity.
iii. Conclusion. The toxicology data base for buprofezin is complete for FQPA assessment. The developmental toxicity studies in rats and rabbits and the 2-generation reproduction study in rats are available and considered acceptable. Acute and subchronic neurotoxicity studies are not required for buprofezin.
The Agency determined that an additional developmental neurotoxicity study in rats is required based on the evidence of thyroid toxicity following subchronic and chronic exposures to rats as well as chronic exposures to dogs. In these studies, thyroid toxicity was characterized as decreases in serum thyroxine levels and increased thyroid weights in dogs and histopathological lesions in the subchronic and chronic toxicity studies in rats. While the Agency recognized the fact that thyroid toxicity was seen in the presence of hepatotoxicity, there was concern that thyroid effects were seen in two species following subchronic and chronic exposures. The Agency concluded that the DNT study is needed to further evaluate the hormonal responses associated with the developing fetal nervous system.
The Agency concluded that a safety factor is necessary for buprofezin since there is an additional developmental neurotoxicity characterization study needed in rats. This study is required due to the evidence of thyroid effects observed following subchronic and chronic exposures to rats and chronic exposure to dogs.
The safety factor was reduced to 3X because: There is no evidence of increased susceptibility to young rats or rabbits following in utero exposure or following prenatal and/or postnatal exposure to rats; Adequate actual data, surrogate data, and/or modeling outputs are available to satisfactorily assess dietary (food and water) exposure assessment; and there are no registered residential uses at the present time.
The FQPA safety factor for buprofezin is applicable to females 13- 50 and to infants and children due uncertainty resulting from an additional confirmatory developmental neurotoxicity study in rats. This additional study will characterize the potential for neurotoxic effects on fetal development and may provide data that could be used in the toxicology endpoint selection and further refine the dietary exposure risk assessments for these population subgroups.
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Aggregate Risks and Determination of Safety
To estimate total aggregate exposure to a pesticide from food, drinking water, and residential uses, the Agency calculates DWLOCs which are used as a point of comparison against the model estimates of a pesticide's concentration in water (EECs). DWLOC values are not regulatory standards for drinking water. DWLOCs are theoretical upper limits on a pesticide's concentration in drinking water in light of total aggregate exposure to a pesticide in food and residential uses. In calculating a DWLOC, the Agency determines how much of the acceptable exposure (i.e., the PAD) is available for exposure through drinking water e.g., allowable chronic water exposure (mg/kg/day) = cPAD - (average food + residential exposure). This allowable exposure through drinking water is used to calculate a DWLOC.
A DWLOC will vary depending on the toxic endpoint, drinking water consumption, and body weights. Default body weights and consumption values as used by the USEPA Office of Water are used to calculate DWLOCs: 2L/70 kg (adult male), 2L/60 kg (adult female), and 1L/10 kg (child). Default body weights and drinking water consumption values vary on an individual basis. This variation will be taken into account in more refined screening-level and quantitative drinking water exposure assessments. Different populations will have different DWLOCs. Generally, a DWLOC is calculated for each type of risk assessment used: acute, short-term, intermediate-term, chronic, and cancer.
When EECs for surface water and ground water are less than the calculated DWLOCs, OPP concludes with reasonable certainty that exposures to the pesticide in drinking water (when considered along with other sources of exposure for which OPP has reliable data) would not result in unacceptable levels of aggregate human health risk at this time. Because OPP considers the aggregate risk resulting from multiple exposure pathways associated with a pesticide's uses, levels of comparison in drinking water may vary as those uses change. If new uses are added in the future, OPP will reassess the potential impacts of residues of the pesticide in
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drinking water as a part of the aggregate risk assessment process.
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Acute risk. The acute dietary exposure analysis assumed tolerance level residues and 100% crop treated for all registered and proposed commodities (Tier 1). For females 13-50 years old, 4% of the aPAD (.67 ppm/day) is occupied by dietary (food) exposure (no acute RfD established for the general population including infants and children). The acute exposure to buprofezin as a result of exposure from residues in food is below the Agency's level of concern.
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Chronic risk. Since there are no chronic residential exposure scenarios, the chronic aggregate risk assessment is concerned with food and water only. The chronic dietary exposure analysis incorporated average residues calculated from field trial data and assumed 100% crop treated for all commodities except tomatoes (44% and 0.6% crop treated for the fresh market and for processing, respectively; Tier 2 analysis). Only 49% of the cPAD is occupied by dietary (food) exposure. The buprofezin EECs in surface and ground water are less than the Agency's DWLOC (for all population subgroups). Chronic risk for buprofezin, as a result of dietary (food and water) exposure, is below the Agency's level of concern. After calulating the DWLOCs and comparing them to the EECs for surface and ground water, EPA does not expect the aggregate exposure to exceed 100% of the cPAD, as shown in the following Table 4.
Table 4.--Aggregate Risk Assessment for Chronic (Non-Cancer) Exposure to Buprofezin
Subgroups exposure
(mg/kg/day)
% cPAD1
U.S. population
0.000957
29 all seasons.....................
All Infants
0.000452
14 (1 year)........................
Children
0.001615
49 (1-6 years).....................
Children
0.001305
40 (7-12 years)....................
Females
0.000871
26 (13-50 years)...................
Males
0.000858
26 (13-19 years)...................
Males
0.000818
25 (20+ years).....................
Seniors
0.000814
25 (55+)...........................
1cPAD = 0.0033 mg/kg/day
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Short-term risk. Short-term aggregate exposure takes into account residential exposure plus chronic exposure to food and water (considered to be a background exposure level). Buprofezin is not registered for use on any sites that would result in residential exposure. Therefore, the aggregate risk is the sum of the risk from food and water, which do not exceed the Agency's LOC.
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Intermediate-term risk. Intermediate-term aggregate exposure takes into account residential exposure plus chronic exposure to food and water (considered to be a background exposure level). Buprofezin is not registered for use on any sites that would result in residential exposure. Therefore, the aggregate risk is the sum of the risk from food and water, which do not exceed the Agency's LOC. 5. Aggregate cancer risk for U.S. population. Buprofezin has been classified as ``Suggestive Evidence of Carcinogenicity, but not sufficient to assess human carcinogenic potential'' based on liver tumors in female mice, according to the Agency's Cancer Risk Assessment Guidelines (proposed July 1999). The Agency concluded that no quantification of cancer risk is required. 6. Determination of safety. Based on these risk assessments, EPA concludes that there is a reasonable certainty that no harm will result to the general population, and to infants and children from aggregate exposure to buprofezin residues.
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Other Considerations
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Analytical Enforcement Methodology
Adequate enforcement methodology (example - gas chromatography) is available to enforce the tolerance expression. The method may be requested from: Calvin Furlow, PIRIB, IRSD (7502C), Office of Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460; telephone number: (703) 305-5229; e-mail address: furlow.calvin@epa.gov.
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International Residue Limits
No maximum residue limits (MRLs) are established for buprofezin in/on cucurbits or lettuce in Mexico or Canada. Codex has a buprofezin MRL of 1 ppm in/on cucumbers. The field trial data do not support harmonization.
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Conditions
Conditions for continued registration are as follows: A developmental neurotoxicity study in rats (OPPTS Guideline 870.6300) guideline requirement (40 CFR part 158) for food/feed use, validation of frozen storage intervals, petition method validation, an interference study, a confirmatory method, and additional cantaloupe and leaf lettuce field trials.
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Conclusion
Therefore, the tolerance is established for residues of buprofezin, 2-tert-butylimino-3-isopropyl-5-phenyl-1,3,5-thiadiazinan- 4-one, in or on lettuce, head; lettuce, leaf; and vegetables, cucurbits at 5.0, 13.0, and 0.50 ppm, respectively.
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Objections and Hearing Requests
Under section 408(g) of the FFDCA, as amended by the FQPA, any person may file an objection to any aspect of this regulation and may also request a hearing on those objections. The EPA procedural regulations which govern the submission of objections and requests for hearings appear in 40 CFR part 178. Although the procedures in those regulations require 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 necessary modifications can be made. The new section 408(g) provides essentially the same process for persons to ``object'' to a regulation for an exemption from the requirement of a tolerance issued by 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.
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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 with the instructions provided in this unit and in 40 CFR part 178. To ensure proper receipt by EPA, you must identify docket control number OPP-301040 in the subject line on the first page of your submission. All requests must be in writing, and must be mailed or delivered to the Hearing Clerk on or before October 30, 2000.
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Filing the request. Your objection must specify the specific provisions in the regulation that you object to, and the grounds for the objections (40 CFR
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178.25). If a hearing is requested, the objections must include a statement of the factual issues(s) on which a hearing is requested, the requestor's contentions on such issues, and a summary of any evidence relied upon by the objector (40 CFR 178.27). Information submitted in connection with an objection or hearing request may be claimed confidential 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. A copy of the information that does not contain CBI must be submitted for inclusion in the public record. Information not marked confidential may be disclosed publicly by EPA without prior notice.
Mail your written request to: Office of the Hearing Clerk (1900), Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460. You may also deliver your request to the Office of the Hearing Clerk in Rm. C400, Waterside Mall, 401 M St., SW., Washington, DC 20460. The Office of the Hearing Clerk is open from 8 a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The telephone number for the Office of the Hearing Clerk is (202) 260-4865.
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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, Office of 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 contact James 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, 1200 Pennsylvania Ave., NW., Washington, DC 20460.
If you would like to request a waiver of the tolerance objection fees, you must mail your request for such a waiver to: James Hollins, Information Resources and Services Division (7502C), Office of Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460.
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Copies for the Docket. In addition to filing an objection or hearing request with the Hearing Clerk as described in Unit VI.A., you should also send a copy of your request to the PIRIB for its inclusion in the official record that is described in Unit I.B.2. Mail your copies, identified by docket control number OPP-301040, to: Public Information and Records Integrity Branch, Information Resources and Services Division (7502C), Office of Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460. In person or by courier, bring a copy to the location of the PIRIB described 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 characters and any form of encryption. Copies of electronic objections and hearing requests will also be accepted on disks in WordPerfect 6.1/8.0 file format or ASCII file format. Do not include any CBI in your electronic copy. You may also submit an electronic copy of your request at many Federal Depository Libraries.
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When Will the Agency Grant a Request for a Hearing?
A request for a hearing will be granted if the Administrator determines that the material submitted shows the following: There is a genuine and substantial issue of fact; there is a reasonable possibility that available evidence identified by the requestor would, if established resolve one or more of such issues in favor of the requestor, taking into account uncontested claims or facts to the contrary; and resolution of the factual issues(s) in the manner sought by the requestor would be adequate to justify the action requested (40 CFR 178.32).
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Regulatory Assessment Requirements
This final rule establishes a tolerance under FFDCA section 408(d) in response to a petition submitted to the Agency. The Office of Management and Budget (OMB) has exempted these types of actions from review under Executive Order 12866, entitled Regulatory Planning and Review (58 FR 51735, October 4, 1993). This final rule does not contain any information collections 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 under Title II of the Unfunded Mandates Reform Act of 1995 (UMRA) (Public Law 104-4). Nor does it require any prior consultation as specified by Executive Order 13084, entitled Consultation and Coordination with Indian Tribal Governments (63 FR 27655, May 19, 1998); special considerations as required by Executive Order 12898, entitled Federal Actions to Address Environmental 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 Agency consideration of voluntary consensus standards pursuant to section 12(d) of the National Technology Transfer and Advancement Act of 1995 (NTTAA), Public Law 104-113, section 12(d) (15 U.S.C. 272 note). Since tolerances and exemptions that are established on the basis of a petition under FFDCA section 408(d), such as the tolerance in this final rule, do not require the issuance 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 a substantial direct effect on States, on the relationship between the national government and the States, or on the distribution of power and responsibilities among the various levels of government, as specified in Executive Order 13132, entitled Federalism (64 FR 43255, August 10, 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 regulatory policies that have federalism implications.'' ``Policies that have federalism implications'' is defined in the Executive Order to include regulations that have ``substantial direct effects on the States, on the relationship between the national government and the States, or on the distribution of power and responsibilities among the various levels of government.'' This final rule directly regulates growers, food processors, food handlers and food retailers, not States. This action does not alter the relationships or distribution of power and responsibilities established by Congress in the preemption provisions of FFDCA section 408(n)(4).
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Submission to Congress and the Comptroller General
The Congressional Review Act, 5 U.S.C. 801 et seq., as added by the Small Business Regulatory Enforcement Fairness Act of 1996, generally provides that before a rule may take effect, the agency promulgating the rule must submit a rule report, which includes a copy of the rule, to each House of the
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Congress and to the Comptroller General of the United States. EPA will submit a report containing this rule and other required information to the U.S. Senate, the U.S. House of Representatives, and the Comptroller General of the United States prior to publication of this final rule in the Federal Register. This final rule is not a ``major rule'' as defined by 5 U.S.C. 804(2).
List of Subjects in 40 CFR Part 180
Environmental protection, Administrative practice and procedure, Agricultural commodities, Pesticides and pests, Reporting and recordkeeping requirements.
Dated: August 22, 2000. Susan B. Hazen, Deputy Director, Office of Pesticide Programs.
Therefore, 40 CFR chapter I is amended as follows:
PART 180--AMENDED
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The authority citation for part 180 continues to read as follows:
Authority: 21 U.S.C. 321(q), (346a) and 371.
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Section 180.511 is amended by adding paragraph (a) to read as follows:
Sec. 180.511 Buprofezin; tolerances for residues.
(a) General. Tolerances are established for residues of buprofezin in or on the following food commodities:
Expiration/Revocation Commodity
Parts per million
Date
Lettuce, head
5.0
12/31/04 Lettuce, leaf
13.0
12/31/04 Vegetables, cucurbits
0.50
12/31/04
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[FR Doc. 00-22371Filed8-30-00; 8:45 am]
BILLING CODE 6560-50-S
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