Pesticides; tolerances in food, animal feeds, and raw agricultural commodities: Fenhexamid,

[Federal Register: November 21, 2000 (Volume 65, Number 225)]

[Rules and Regulations]

[Page 69876-69883]

From the Federal Register Online via GPO Access [wais.access.gpo.gov]

[DOCID:fr21no00-10]

ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[OPP-301075; FRL-6752-4]

RIN 2070-AB78

Fenhexamid; Pesticide Tolerances for Emergency Exemptions

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

SUMMARY: This regulation establishes a time-limited tolerance for residues of fenhexamid in or on pears. This action is in response to EPA's granting of an emergency exemption under section 18 of the Federal Insecticide, Fungicide, and Rodenticide Act authorizing use of the pesticide on pears. This regulation establishes a maximum permissible level for residues of fenhexamid in this food commodity. The tolerance will expire and is revoked on December 31, 2002.

DATES: This regulation is effective November 21, 2000. Objections and requests for hearings, identified by docket control number OPP-301075, must be received by EPA on or before January 22, 2001.

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 VII. of the SUPPLEMENTARY INFORMATION. To ensure proper receipt by EPA, your objections and hearing requests must identify docket control number OPP-301075 in the subject line on the first page of your response.

FOR FURTHER INFORMATION CONTACT: By mail: Barbara Madden, Registration Division (7505C), Office of Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460; telephone number: (703) 305-6463; and e-mail address: madden.barbara@epa.gov.

SUPPLEMENTARY INFORMATION:

1. General Information

   1. Does this Action Apply to Me?

      You may be potentially 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.

   2. 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,'' ``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/. To access the OPPTS Harmonized Guidelines referenced in this document, go directly to the guidelines at http://www.epa.gov/opptsfrs/home/guidelin.htm.

      2. In person. The Agency has established an official record for this action under docket control number OPP-301075. 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, 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.

2. Background and Statutory Findings

   EPA, on its own initiative, in accordance with sections 408(e) and 408 (l)(6) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a, is establishing a tolerance for residues of the fungicide fenhexamid, (N-2,3-dichloro-4-hydroxyphenyl)-1-methyl cyclohexanecarboxamide), in or on pears at 15 parts per million (ppm). This tolerance will expire and is revoked on December 31, 2002. EPA will publish a document in the Federal Register to remove the revoked tolerance from the Code of Federal Regulations.

   Section 408(l)(6) of the FFDCA requires EPA to establish a time- limited tolerance or exemption from the requirement for a tolerance for pesticide chemical residues in food that will result from the use of a pesticide under an emergency exemption granted by EPA under section 18 of FIFRA. Such tolerances can be established without providing notice or period for public comment. EPA does not intend for its actions on section 18 related tolerances to set binding precedents for the application of section 408 and the new safety standard to other tolerances and exemptions. Section 408(e) of the FFDCA allows EPA to establish a tolerance or an exemption from the requirement of a tolerance on its own initiative, i.e., without having received any petition from an outside party.

   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

   [[Page 69877]]

   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. . . .''

   Section 18 of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) authorizes EPA to exempt any Federal or State agency from any provision of FIFRA, if EPA determines that ``emergency conditions exist which require such exemption.'' This provision was not amended by the Food Quality Protection Act (FQPA). EPA has established regulations governing such emergency exemptions in 40 CFR part 166.

3. Emergency Exemption for Fenhexamid on Pears and FFDCA Tolerances

   According to the Applicant, development of thiabenzadole resistance in California Botrytis populations has left packing houses without an effective tool to control the disease. Registered alternatives include thiabenzadole, captan, Bio-Save Pseudomonas syringae, Aspire Candida oleophila, chlorine and ozone. Testing in the laboratory and in the field suggests that thiabenzadole resistance may be developing above historic levels. Captan is not considered a viable alternative because several countries have banned the import of captan-treated fruit. The Applicant additionally claims that the unpredictable efficacy and results of biological controls have kept the pear industry from adopting this technology, and chlorine and ozone are claimed to burn the fruit. While the Agency does not fully agree with all of the arguments presented by the Applicant, EPA concurs that emergency conditions could exist for some packing houses in this State. On September 21, 2000, the Applicant availed of itself the authority to declare a crisis exemption under section 18 of FIFRA for the postharvest use of fenhexamid on pears to control gray mold.

   As part of its assessment of this emergency exemption, EPA assessed the potential risks presented by residues of fenhexamid in or on pears. In doing so, EPA considered the safety standard in FFDCA section 408(b)(2), and EPA decided that the necessary tolerance under FFDCA section 408(l)(6) would be consistent with the safety standard and with FIFRA section 18. Consistent with the need to move quickly on the emergency exemption in order to address an urgent non-routine situation and to ensure that the resulting food is safe and lawful, EPA is issuing this tolerance without notice and opportunity for public comment as provided in section 408(l)(6). Although this tolerance will expire and is revoked on December 31, 2002, under FFDCA section 408(l)(5), residues of the pesticide not in excess of the amounts specified in the tolerance remaining in or on pears after that date will not be unlawful, provided the pesticide is applied in a manner that was lawful under FIFRA, and the residues do not exceed a level that was authorized by this tolerance at the time of that application. EPA will take action to revoke this tolerance earlier if any experience with, scientific data on, or other relevant information on this pesticide indicate that the residues are not safe.

   Because this tolerance is being approved under emergency conditions, EPA has not made any decisions about whether fenhexamid meets EPA's registration requirements for use on pears or whether a permanent tolerance for this use would be appropriate. Under these circumstances, EPA does not believe that this tolerance serves as a basis for registration of fenhexamid by a State for special local needs under FIFRA section 24(c). Nor does this tolerance serve as the basis for any State other than California to use this pesticide on this crop under section 18 of FIFRA without following all provisions of EPA's regulations implementing section 18 as identified in 40 CFR part 166. For additional information regarding the emergency exemption for fenhexamid, contact the Agency's Registration Division at the address provided under FOR FURTHER INFORMATION CONTACT.

4. Aggregate Risk Assessment and Determination of Safety

   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).

   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 fenhexamid and to make a determination on aggregate exposure, consistent with section 408(b)(2), for a time-limited tolerance for residues of fenhexamid in or on pears at 15 ppm. EPA's assessment of the dietary exposures and risks associated with establishing the tolerance follows.

   1. Toxicological Endpoints

      The dose at which no observed adverse effect level (NOAEL) from the toxicology study identified as appropriate for use in risk assessment is used to estimate the toxicological endpoint. However, the lowest dose at which lowest observed adverse effect level (LOAEL) of concern are identified 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 level of concern (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-\6\ or 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

      [[Page 69878]]

      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 (MOE cancer= point of departure/exposures) is calculated. A summary of the toxicological endpoints for fenhexamid used for human risk assessment is shown in the following Table 1:

      Table 1. -- Summary of Toxicological Dose and Endpoints for Fenhexamid for Use in Human Risk Assessment

      FQPA SF* and Level of Exposure Scenario

      Dose Used in Risk

      Concern for Risk Study and Toxicological Assessment, UF

      Assessment

      Effects

      Acute Dietary females 13-50 years of None

      None

      None age

      Acute Dietary general population None

      None

      None including infants and children

      Chronic Dietary all populations

      NOAEL = 17 mg/kg/day UF FQPA SF = 3 cPAD = 1-Year Feeding Study in = 100 Chronic RfD = chronic RfD Dogs LOAEL = 124/133 0.17 mg/kg/day

      FQPA SF = 0.057 mg/kg/ mg/kg/day in males/ day

      females, based on decreased RBC counts, hemoglobin and hematocrit and increased Heinz bodies in RBC. Also, in females, increased absolute and relative adrenal weights correlated with histopathological observations of increases in incidence and severity of intracytoplasmic vacuoles in the adrenal cortex.

      Short-Term Dermal (1 to 7 days)

      Dermal NOAEL = 1,000 mg/ LOC for MOE = 300

      21-Day Dermal Study - (Residential)

      kg/day (limit dose) (Residential)

      Rabbits No rabbits (dermal absorption

      died during this rate = 20%)

      study. No skin irritation was observed in any treated animals. There were no compound related effects on clinical signs, body weight, food consumption, hematology, clinical chemistry, organ weights, or gross and histologic pathology. Dermal administration of fenhexamid was well tolerated by both sexes for 21-days at the limit dose of 1,000 mg/kg/day.

      Intermediate-Term Dermal (1 week to Dermal NOAEL = 1,000 mg/ LOC for MOE = 300

      21-Day Dermal Study - several months) (Residential)

      kg/day (limit dose) (Residential)

      Rabbits No rabbits (dermal absorption

      died during this rate = 20%

      study. No skin irritation was observed in any treated animals. There were no compound related effects on clinical signs, body weight, food consumption, hematology, clinical chemistry, organ weights, or gross and histologic pathology. Dermal administration of fenhexamid was well tolerated by both sexes for 21-days at the limit dose of 1,000 mg/kg/day.

      Long-Term Dermal (several months to None

      None

      None lifetime) (Residential)

      Short-Term Inhalation (1 to 7 days) None

      None

      None (Residential)

      Intermediate-Term Inhalation (1 week None

      None

      None to several months) (Residential)

      Long-Term Inhalation (several months None

      None

      None to lifetime) (Residential)

      Cancer (oral, dermal, inhalation) None

      None

      The Agency has classified Fenhexamid as a ``not likely'' carcinogen. This classification is based on the lack of evidence of carcinogenicity in male and female rats as well as in male and female mice and on the lack of genotoxicity in an acceptable battery of mutagenicity studies.

      *The reference to the FQPA Safety Factor refers to any additional safety factor retained due to concerns unique to the FQPA.

      [[Page 69879]]

   2. Exposure Assessment

      1. Dietary exposure from food and feed uses. Tolerances have been established (40 CFR 180.553) for the residues of fenhexamid, in or on a variety of raw agricultural commodities including grapes, raisins and strawberries. Risk assessments were conducted by EPA to assess dietary exposures from fenhexamid 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. No acute dietary endpoint has been identified. Therefore, no assessment was conducted for acute dietary exposures.

         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 Continuing Surveys of Food Intake by Individuals (CSFII) and accumulated exposure to the chemical for each commodity. The following assumptions were made for the chronic exposure assessments: use of tolerance level residues and 100% of the crop was treated.

         iii. Cancer. The Agency has classified fenhexamid as a ``not likely'' carcinogen. Therefore, no exposure assessment was conducted to assess cancer concerns.

      2. Dietary exposure from drinking water. The use pattern associated with the emergency exemption (use of fenhexamid as a postharvest treatment on pears) is not expected to impact water resources. However, the Agency is required to perform an aggregate risk assessment which includes all registered uses of fenhexamid that would lead to exposure to humans through drinking water. Therefore, the Agency estimated environmental concentrates in drinking water from the use of fenhexamid on strawberries to determine the aggregate risk assessment.

         The Agency lacks sufficient monitoring exposure data to complete a comprehensive dietary exposure analysis and risk assessment for fenhexamid 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 fenhexamid.

         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 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 fenhexamid they are further discussed in the aggregate risk sections below.

         Based on the GENEEC and SCI-GROW models the estimated environmental concentrations (EECs) of fenhexamid for chronic exposures are estimated to be 4.8 parts per billion (ppb) for surface water and 0.0007 ppb for ground water.

      3. 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). Fenhexamid is not registered for use on any sites that would result in residential exposure.

      4. 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 fenhexamid 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, fenhexamid 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 fenhexamid 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).

   3. Safety Factor for Infants and Children

      1. 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 MOE analysis or through using uncertainty (safety) factors in calculating a dose level that poses no appreciable risk to humans.

         ii. Developmental toxicity studies. In a developmental toxicity study in rats, maternal toxicity (marginally decreased body weight gain and decreased food consumption during the treatment period only) was observed at the LOAEL of 1,044 milligrams/kilograms/day (mg/kg/day) (only dose level tested). The NOAEL for maternal toxicity was 1,044 mg/kg/day). Although a NOAEL was not determined for maternal toxicity in this study, the study need not be repeated because the effects at the LOAEL were only marginal and of minimal toxicological concern.

         In a developmental toxicity study in rabbits, the NOAEL for maternal toxicity was 100 mg/kg/day and the LOAEL was 300 mg/kg/day, based on alterations of excretory products (discolored urine, scant feces, small scybala), decreased body weight gain and decreased food consumption (especially during the first week of dosing) and decreased placental weight. At the next higher dose level of 1,000 mg/kg/day, the maternal effects were increased in severity. A decreased gestation index, based on a slightly increased incidence of abortions and total litter resorptions, was not considered to be treatment-related because the incidences of abortions and resorptions fell within the historical control range submitted with the study. The NOAEL for developmental toxicity was 300 mg/kg/day and the LOAEL was 1,000 mg/kg/day, based on slightly decreased fetal body weights (1pups on postnatal days 14 and 21 and in F2pups on postnatal days 7, 14 and 21. At the next higher dose level of 1,814/2,043 mg/kg/day (M/F) (HDT), the decreased pup body weights were increased in severity. In addition, an increased mortality was observed among the post weaning F1 pups selected to be F1 parents (possibly due to the small size of the pups at weaning, which was 30% less than controls). The results in this reproduction study are equivocal with respect to evaluating the possibility of increased susceptibility of pups, as compared to adults, to fenhexamid. On the basis of NOAELs/LOAELs, no increased susceptibility of pups to fenhexamid was demonstrated in this study. However, the severity of the effects observed in the pups may have been greater than that observed in the adults at the same dose levels. In addition, several other toxicological considerations, including possibly increased intake of test material in pups resulting from intake in both milk and diet during the lactation period and possibly decreased levels of UDP-glucuronyltransferase enzyme in pups (a normally occurring phenomenon in rat pups) resulting in decreased metabolism or ``detoxification'' of test material, contributed to the uncertainty of the determination.

         iv. Prenatal and postnatal sensitivity. The available Agency Guideline studies indicate no increased susceptibility of rat or rabbit fetuses to in utero exposure to fenhexamid. In the prenatal developmental toxicity study in rats, no evidence of developmental toxicity was seen even at the highest dose tested. In the prenatal developmental toxicity study in rabbits, developmental toxicity was seen only in the presence of maternal toxicity. In the 2-generation reproduction study in rats, quantitatively (i.e., based on NOAELs/LOAELs in parental animals versus offspring), there was no evidence of increased susceptibility of the pups. Qualitatively, however, there was evidence of increased susceptibility based on the comparative severity of effects at the LOAEL (406 mg/kg/ day): Parental toxicity was characterized as alterations in clinical chemistry parameters and decreased organ weights without collaborative histopathology; while offspring toxicity was manifested as significantly decreased pup body weights in both generations during the lactation period (on lactation days 7, 14, and 21 in the F2 generation and lactation days 14 and 21 in the F1generation offspring)

         v. Conclusion. The Agency has determined that a safety factor is required for fenhexamid because qualitatively, there was evidence of increased susceptibility based on the comparative severity of effects in the 2-generation reproduction study in rats. The effects on pups were of concern because:

      1. Significant pup body weight decreases were observed in both the F1and the F2generations.

      2. The pup body weight decreases in the F2generation were observed during early lactation (lactation day 7 through day 21) when the pups are exposed to the test material primarily through the mother's milk.

      3. The pup body weight decreases in the F1generation were observed during late lactation (lactation days 14 through 21) when the pups are exposed to the test material through the mother's milk and through the feed.

      4. In the metabolism study on fenhexamid, glucuronidation of fenhexamid was clearly demonstrated to be the single major route of metabolism, detoxification and excretion of fenhexamid in adult male and female Wistar rats. The demonstrated poor glucuronidation capacity of rat pups between days 7 and 21 (in a referenced study) indicates a possibly increased sensitivity of pups and serves to support a concern for neonatal toxicity. However, the Agency has reduced the FQPA safety factor to 3x because:

      1. The toxicology data base is complete for the assessment of the effects of fenhexamid following in utero and/or postnatal exposure. 2. There is no indication of increased susceptibility of rat or rabbit fetuses to in utero exposure in the prenatal developmental toxicity studies with fenhexamid.

      3. The increased susceptibility demonstrated in the 2-generation reproduction study was only qualitative (not quantitative) evidence and was observed only in the presence of parental toxicity.

      4. The qualitative offspring effect was limited to decreased body weight and no other adverse effects (e.g., decreased pup survival, behavioral alterations, etc) were observed.

      5. Adequate data are available or conservative modeling assumptions are used to assess dietary food and drinking water exposure.

      6. There are currently no residential uses for fenhexamid.

         [[Page 69881]]

   4. 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 + chronic non-dietary, non-occupational 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 U.S. EPA Office of Water are used to calculate DWLOCs: 2 Liter(L)/70 kilogram (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 fenhexamid 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 fenhexamid on drinking water as a part of the aggregate risk assessment process.

      1. Acute 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 one day or single exposure. No acute dietary endpoint has been identified. Therefore, no risk assessment was conducted for acute dietary exposures.

      2. Chronic risk. Using the exposure assumptions described in this unit for chronic exposure, EPA has concluded that exposure to fenhexamid from food will utilize 7% of the cPAD for the U.S. population, 65% of the cPAD for all infants, less than 1 year old and 16% of the cPAD for children, 1-6 years old, the subpopulation of children at greatest exposure. There are no residential uses for fenhexamid that result in chronic residential exposure to fenhexamid. In addition, despite the potential for chronic dietary exposure to fenhexamid in drinking water, after calculating DWLOCs and comparing them to conservative model estimated environmental concentrations of fenhexamid in surface and ground water, EPA does not expect the aggregate exposure to exceed 100% of the cPAD, as shown in the following Table 2:

      Table 2. -- Aggregate Risk Assessment for Chronic (Non-Cancer) Exposure to Fenhexamid

      Ground Population Subgroup

      cPAD mg/kg/day % cPAD (Food) Surface Water EEC Water EEC Chronic (ppb)

      (ppb) DWLOC (ppb)

      U.S. Population

      0.057

      7

      4.8 0.0007

      1,900

      Children, 1-6 years

      0.057

      16

      4.8 0.0007

      480

      All infants, 00-29770Filed11-20-00; 8:45 am] BILLING CODE 6560-50-S