Pesticides; tolerances in food, animal feeds, and raw agricultural commodities: Fluazinam,
[Federal Register: April 18, 2002 (Volume 67, Number 75)]
[Rules and Regulations]
[Page 19120-19130]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr18ap02-10]
ENVIRONMENTAL PROTECTION AGENCY
[OPP-2002-0003; FRL-6831-8]
RIN 2070-AB78
Fluazinam; Pesticide Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
SUMMARY: This regulation establishes an import tolerance for residues of fluazinam and its metabolite AMGT3-[[4-amino-3-[[3-chloro-5- (trifloromethyl)-2-pyridinyl] amino]-2-nitro-6-(trifluoromethyl) phenyl] thio]-2-(beta-D-glucopyranosyloxy) propionic acid) in or on
[wine grapes at 3.0 parts per million (ppm). ISK BioSciences Corporation requested this tolerance under the Federal Food, Drug, and Cosmetic Act, as amended by the Food Quality Protection Act of 1996.
DATES: This regulation is effective April 18, 2002. Objections and requests for hearings, identified by docket control number OPP-2002- 0003, must be received on or before June 17, 2002.
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-2002-0003 in the subject line on the first page of your response.
FOR FURTHER INFORMATION CONTACT: By mail: Cynthia Giles-Parker, Registration Division (7505C), Office of Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW.,Washington, DC 20460; telephone number: (703) 305-7740; e-mail address: giles-parker.cynthia@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 codes
potentially affected entities
Industry
111
Crop production 112
Animal production 311
Food manufacturing 32532
Pesticide manufacturing
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 theFederal Register listings at http://www.epa.gov/fedrgstr/. A frequently updated electronic version of 40 CFR part 180 is available at http://www.access.gpo.gov/ nara/cfr/cfrhtml_00/Title_40/40cfr180_00.html, a beta site currently under development. To access the OPPTS Harmonized Guidelines referenced in this document, go directly to the guidelines at http://www.epa.gov/ opptsfrs/home/guidelin.htm.
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In person. The Agency has established an official record for this action under docket control number OPP-2002-0003. 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 December 6, 2000 (65 FR 76253) (FRL- 6573-7), EPA
[[Page 19121]]
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 9F5079) by ISK BioSciences Corporation, 5970 Heisley Road, Suite 200, Mentor, Ohio, 44060. This notice included a summary of the petition prepared by ISK BioSciences Corporation, the registrant. There were no comments received in response to the notice of filing.
The petition requested that 40 CFR 180.574 be amended by establishing a tolerance for residues of the fungicide fluazinam, 3- chloro-N-[3-chloro-2,6-dinitro-4-(trifluoromethyl) phenyl]-5- (trifluoromethyl)-2-pyridinamine, in or on peanuts and potatoes at 0.02 part per million (ppm) and imported wine grapes at 3.0 ppm. In the Federal Register of September 7, 2001 (66 FR 46729) (FRL-6797-3), EPA established tolerances for peanuts and potatoes.
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 fluazinam and its metabolite AMGT on wine grapes at 3.0. 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 nature of the toxic effects caused by fluazinam and its metabolite AMGT 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.
Table 1.--Toxicological Profile of Fluazinam Technical
Guideline No.
Study Type
Results
870.3100
90-Day oral
NOAEL: Males = 3.8 toxicity rats mg/kg/day; Females = 4.3 mg/ kg/day LOAEL Males = 38 mg/kg/day; Females = 44 mg/ kg/day based on increased liver weights and liver histopathology in males, and increased lung and uterus weights in females.
870.3150
90-Day oral
NOAEL = 10 mg/kg/ toxicity dogs day LOAEL = 100 mg/kg/ day based on retinal effects, increased relative liver weight, liver histopathology and possible increased serum alkaline phosphatase in females and possible marginal vacuolation of the cerebral white matter (equivocal)
870.3200
21-Day dermal Systemic NOAEL = toxicity rats 10 mg/kg/day LOAEL = 100 mg/kg/ day based on increased AST and cholesterol levels in clinical chemistry determinations (males) Dermal NOAEL = not identified LOAEL = 10 mg/kg/ day based on erythema, acanthosis, and dermatitis
870.3250
90-Day dermal Not Available toxicity
870.3465
90-Day inhalation Not Available toxicity
[[Page 19122]]
870.3700
Prenatal
Maternal NOAEL = developmental 50 mg/kg/day toxicity rats LOAEL = 250 mg/kg/ day based on decreased body weight gain and food consumption and increased water consumption and urogenital staining Developmental NOAEL = 50 mg/kg/ day LOAEL = 250 mg/kg/ day based on decreased fetal body weights and placental weights, increased facial/ cleft palates, diaphragmatic hernia, and delayed ossification in several bone types, greenish amniotic fluid and possible increased late resorptions and postimplantation loss
870.3700
Prenatal
Maternal NOAEL = 4 developmental mg/kg/day toxicity rabbits LOAEL = 7 mg/kg/ day based on decreased food consumption and increased liver histopathology. Developmental NOAEL = 7 mg/kg/ day LOAEL = 12 mg/kg/ day based on an increase in total litter resorptions and possible fetal skeletal abnormalities
870.3700
Prenatal
Maternal NOAEL = 3 developmental mg/kg/day toxicity rabbits LOAEL = not identified (>3 mg/ kg/day) Developmental NOAEL = 3 mg/kg/ day LOAEL = not identified (>3 mg/ kg/day)
870.3800
Reproduction and Parental/Systemic fertility effects NOAEL = 1.9 mg/kg/ rats
day LOAEL = 9.7 mg/kg/ day based on liver pathology in F1males Reproductive NOAEL = 10.6 mg/kg/day LOAEL = 53.6 mg/kg/ day based on decreased number of implantation sites and decreased litter sizes to day 4 post-partum for F1 females (F2 litters). Offspring NOAEL = 8.4 mg/kg/day LOAEL = 42.1 mg/kg/ day based on reduced F1 and F2 pup body weight gains during lactation.
870.4100
Chronic toxicity NOAEL = Males: 1.9 rats
mg/kg/day; Females: 4.9 mg/ kg/day LOAEL = Males: 3.9 mg/kg/day; Females: not identified (4.9 mg/kg/ day) based on increased testicular atrophy in males and no effects in females
870.4100
Chronic toxicity NOAEL = 1 mg/kg/ dogs
day LOAEL = 10 mg/kg/ day based on gastric lymphoid hyperplasia in both sexes and nasal dryness in females
870.4200
Carcinogenicity NOAEL = Males:1.1 mice
mg/kg/day; Females: 1.2 mg/ kg/day LOAEL = Males: 10.7 mg/kg/day; Females: 11.7 mg/ kg/day based on increased incidences of brown macrophages in the liver of both sexes, eosinophilic vacuolated hepatocytes in males, and increased liver weight in females. Clear evidence of carcinogenicity (hepatocellular tumors) in male mice, but not in females
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870.4200
Carcinogenicity NOAEL = Males: mice
g/ml. Negative without S9 activation up to 0.3 g/ ml. Compound tested to cytotoxic concentrations.
870.5300
In vitro mammalian Negative with and gene mutation without S9 assay
activation up to 5 g/ml. Compound tested to cytotoxic concentrations.
870.5375
In vitro mammalian Negative with and chromosome
without S9 up to aberration (CHL cytotoxic cells)
concentrations. Cells harvested at 24 and 48 hours in nonactivated studies and at 24 hours in activated studies.
870.5395
Mammalian
Negative at 24 erythrocyte
hour sacrifice micronucleus test (500, 1,000, 2,000 mg/kg). Negative at 24, 48, and 72 hour sacrifices (2,000 mg/kg).
870.5550
UDS in primary rat Negative; however hepatocytes
there were several serious study deficiencies: Treatment time shorter than recommended, no data supporting the claim of cytotoxicity, data variability for major endpoints.
870.5550
Differential
Negative, however killing/growth only one inhibition in B. replicate plate/ subtilis
dose was used.
870.6200
Acute
Systemic NOAEL = neurotoxicity 50 mg/kg screening battery LOAEL = 1,000 mg/ rats
kg based on soft stools and decreased motor activity on day of dosing. Neurotoxicity NOAEL = 2,000 mg/ kg LOAEL = not identified (>2,000 mg/kg)
870.6200
Subchronic
Neurotoxicity neurotoxicity NOAEL = Males: screening battery 233 mg/kg/day; rats
Females: 280 mg/ kg/day LOAEL = not identified (Males: >233 mg/ kg/day; Females: >280 mg/kg/day)
870.6300
Developmental Not Available neurotoxicity
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870.7485
Metabolism and Only 33-40% of the pharmacokinetics administered dose rats
was absorbed. Most of the administered dose was recovered in the feces (>89%). Excretion via the urine was minor (*The reference to the FQPA Safety Factor refers to any additional safety factor retained due to concerns unique to the FQPA.
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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
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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. 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. A summary of the toxicological endpoints for fluazinam used for human risk assessment is shown in the following Table 2:
Table 2.--Summary of Toxicological Toxicological Doses and Endpoints for Fluazinam for Use in Human Risk Assessments1
Dose Used in Risk FQPA SF* and Endpoint Study and Toxicological Exposure Scenario
Assessment, UF
for Risk Assessment
Effects
Acute dietary females 13-50 years of Developmental
FQPA SF = 10
Developmental toxicity, age
NOAEL = 7 mg/kg/day.... aPAD = acute RfD/FQPA rabbits. UF = 100............... SF = 0.007 mg/kg/day. Developmental LOAEL = Acute RfD = 0.07 mg/kg/
12 mg/kg/day based on day.
increased incidence of total litter resorptions and possibly increased incidence of fetal skeletal abnormalities.
Acute dietary general population NOAEL= 50 mg/kg/day FQPA SF = 3
Acute neurotoxicity, including infants and children
UF = 100............... aPAD = acute RfD/FQPA rats. Acute RfD = 0.50 mg/kg/ SF = 0.167 mg/kg/day. LOAEL = 1,000 mg/kg/day day.
based on decreased motor activity and soft stools on day of dosing.
Exposure scenario
Dose used in risk
FQPA SF* and endpoint Study and Toxicological assessment, UF
for risk assessment Effects
Chronic dietary all populations
NOAEL= 1.1 mg/kg/day FQPA SF = 3
Carcinogenicity, mice. UF = 100............... cPAD = chr RfD = FQPA LOAEL = 10.7 mg/kg/day Chronic RfD = 0.011 mg/ SF 0.00367 mg/kg/day. based on liver kg/day.
histopathology and increased liver weight.
Chronic dietary all populations
NOAEL= 1.1 mg/kg/day FQPA SF = 3
Carcinogenicity, mice. UF = 100............... cPAD = chr RfD = FQPA LOAEL = 10.7 mg/kg/day Chronic RfD = 0.011 mg/ SF 0.00367 mg/kg/day. based on liver kg/day.
histopathology and increased liver weight.
Cancer (oral, dermal, inhalation) ``Suggestive evidence Quantification of human Increases in thyroid of carcino-genicity, cancer risk not
gland follicular cell but not sufficient to required. 2tumors in male rats; assess human
increases in carcinogenic
hepatocellular (liver) potential''2tumors in male mice.2
*The reference to the FQPA Safety Factor refers to any safety factor retained or reduced due to concerns unique to the FQPA. 1UF = uncertainty factor, FQPA SF = FQPA safety factor, NOAEL = no observed adverse effect level, LOAEL = lowest observed adverse effect level, PAD = population adjusted dose (a = acute, c = chronic), RfD = reference dose, LOC = level of concern, MOE = margin of exposure 2Cancer Assessment Document - Evaluation of the Carcinogenic Potential of Fluazinam, March 29, 2001, HED Doc. No. 014512.
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Exposure Assessment
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Dietary exposure from food and feed uses. Tolerances have been established for the residues of fluazinam in and or on potatoes and peanuts. Risk assessments were conducted by EPA on these crops and wine grapes to assess dietary exposures from fluazinam 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 one day or single exposure. The Dietary Exposure Evaluation Model (DEEM) analysis evaluated the individual food consumption as reported by respondents in the 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: A DEEM acute dietary exposure analysis was performed using tolerance residue levels and 100% CT data for all commodities (Tier 1). The DEEM defaults were used for all processing factors. The DEEM analysis included wine and sherry grapes, peanuts and potatoes using anticipated residues of fluazinam and its metabolite (AMGT) and processing factors for wine grapes (Tier 3).
ii. Chronic exposure. In conducting this chronic dietary risk assessment the Dietary Exposure Evaluation Model DEEM analysis evaluated the individual food consumption as reported by respondents in the USDA 1989-1992 nationwide CSFII and accumulated exposure to the chemical for each commodity. The following assumptions were made for the chronic exposure assessments: A DEEM chronic dietary exposure analysis was performed using tolerance residue levels and 100% CT data for all commodities (Tier 1). The DEEM defaults were used for all processing factors. The DEEM analysis included wine and sherry grapes, peanuts and potatoes using anticipated
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residues of fluazinam and its metabolite (AMGT) and processing factors for wine grapes.
iii. Cancer. Since fluazinam has been classified as ``Suggestive evidence of carcinogenicity, but not sufficient to assess human carcinogenic potential,'' an exposure assessment was not performed.
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Dietary exposure from drinking water. The Agency lacks sufficient monitoring exposure data to complete a comprehensive dietary exposure analysis and risk assessment for fluazinam 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 fluazinam.
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 Screening Concentrations in Ground Water (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 incorporate 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 estimated environmental concentrations (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 fluazinam they are further discussed in the aggregate risk sections below.
Based on the GENEEC and SCI-GROW models the EECs of fluazinam for acute exposures are estimated to be 18.0 parts per billion (ppb) for surface water and 0.10 ppb for ground water. The EECs for chronic exposures are estimated to be 3.15 ppb for surface water and 0.10 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).
Fluazinam 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 fluazinam 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, fluazinam 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 fluazinam 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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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.
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Prenatal and postnatal sensitivity. Qualitative evidence of increased susceptibility of fetuses to fluazinam was demonstrated in a developmental toxicity study in rats. Increased incidences of facial/ palate clefts and other rare deformities in the fetuses were observed in the presence of minimal maternal toxicity. In a developmental toxicity study in rabbits and in a 2-generation reproduction study in rats, neither quantitative nor qualitative evidence of increased susceptibility of fetuses or pups to fluazinam was observed. Because of the neurotoxic lesion observed in the white matter of the brain in mice, dogs and rats and the qualitative evidence of increased susceptibility of rat fetuses to fluazinam, a developmental neurotoxicity study will be required to be submitted to the Agency. Further, because of the lack of a developmental neurotoxicity study and the qualitative evidence of increased susceptibility of rat fetuses to fluazinam, the Food Quality Protection Act (FQPA) safety factor (SF) for protection of infants and children, as required by the FQPA of 1996, will be retained at 10X when assessing acute dietary exposure for ``females 13-50 years of age'' due to concern for the developing fetus. Additionally, the FQPA SF will be reduced to 3X when assessing exposures for ``all populations'' for all exposure durations (acute and chronic) because of uncertainty resulting from lack of a developmental neurotoxicity study.
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Conclusion. Because of the lack of a developmental neurotoxicity study and the qualitative evidence of increased susceptibility of rat fetuses to fluazinam, the Agency determined that the FQPA safety factor should be retained at 10X when assessing acute dietary exposure for ``females 13-50 years of age'' since, in addition to the need for a developmental neurotoxicity study, increased susceptibility of rat fetuses was observed following in utero exposure (an acute effect) in the rat developmental toxicity study resulting in concern for the developing fetus. The Agency also determined that the FQPA safety factor should be reduced to 3X
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when assessing exposure for ``all populations'' for all exposure durations (acute and chronic) since there is uncertainty due to the lack of a developmental neurotoxicity study. This study will further characterize the toxicity of fluazinam and may provide endpoints and NOAELs that could be used in risk assessments for any subpopulation/ exposure duration.
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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 groundwater 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 drinking water as a part of the aggregate risk assessment process.
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Acute risk. Using the exposure assumptions discussed in this unit for acute exposure, the acute dietary exposure to fluazinam from food will occupy 2% or less of the aPAD for the U.S. population, 60% of the aPAD for the most highly exposed population subgroup, females 13-50 years old. All other population subgroups occupy 2% or less of the aPAD. In addition, there is potential for acute dietary exposure to fluazinam in drinking water. After calculating DWLOCs and comparing them to the EECs for surface and ground water, EPA does not expect the aggregate exposure to exceed 100% of the aPAD, as shown in the following Table 3:
Table 3.--Aggregate Risk Assessment for Acute Exposure to Fluazinam
Surface Ground Population Subgroup
aPAD (mg/ % aPAD Water EEC Water EEC Acute DWLOC kg)
(Food) (ppb)
(ppb)
(ppb)
U.S. population
0.17
2%
18
0.10
5,800
Adult male 20+ yrs
0.17
2%
18
0.10
5,800
Adult female 13-50 yrs
0.007
60%
18
0.10
84
Children 1-6 yr
0.17
02 Potatoes.......................................
0.02
(a)(2) Tolerances are established for residues of fluazinam and its metabolite AMGT 3-[[4-amino-3-[[3-chloro-5-(trifloromethyl)-2- pyridinyl]amino]-2-nitro-6-(trifluoromethyl) phenyl] thio]-2-(beta-D- glucopyranosyloxy) propionic acid) in or on the following commodity:
Commodity
Parts per million
Wine grapes1...................................
3.0
1No US registration as of March 15, 2002.
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[FR Doc. 02-9497Filed4-17-02; 8:45 am]
BILLING CODE 6560-50-S
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