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CFR Citation: 40 CFR Part 180

OPP ID: [OPP-2003-0282; FRL-7324-6]

NOTICE: RULES

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

DOCUMENT ACTION: Final rule.

SUBJECT CATEGORY: Butafenacil; Pesticide Tolerance

DATES: This regulation is effective September 19, 2003. Objections and requests for hearings, identified by docket ID number OPP20030282, must be received on or before November 18, 2003.

DOCUMENT SUMMARY: This regulation establishes a tolerance for residues of butafenacil (1,1dimethyl2oxo2(2propenyloxy)ethyl 2chloro5[3,6 dihydro3methyl2,6dioxo4(trifluoromethyl)1(2H)pyrimidinyl]
benzoate) in or on cotton and livestock commodities. Syngenta Crop Protection, Inc. requested this tolerance under the Federal Food, Drug, and Cosmetic Act (FFDCA), as amended by the Food Quality Protection Act of 1996 (FQPA).

SUMMARY: Butafenacil,

SUPPLEMENTAL INFORMATION

A. 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 entities may include, but are not limited to: [sbull] Crop production (NAICS 111)
[sbull] Animal production (NAICS 112)
[sbull] Food manufacturing (NAICS 311)

[sbull] Pesticide manufacturing (NAICS 32532)

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 this unit could also be affected. The North American Industrial Classification System (NAICS) codes have been provided to assist you and others in determining whether this action might apply to certain entities. To determine whether you or your business may be affected by this action, you should carefully examine the applicability provisions in Unit II. If you have any questions regarding the applicability of this action to a particular entity, consult the person listed under FOR FURTHER INFORMATION CONTACT.
B. How Can I Get Copies of this Document and Other Related Information?

1. Docket. EPA has established an official public docket for this action under docket identification (ID) number OPP20030282. The official public docket consists of the documents specifically referenced in this action, any public comments received, and other information related to this action. Although a part of the official docket, the public docket does not include Confidential Business Information (CBI) or other information whose disclosure is restricted by statute. The official public docket is the collection of materials that is available for public viewing at the Public Information and Records Integrity Branch (PIRIB), Rm. 119, Crystal Mall 2, 1921 Jefferson Davis Hwy., Arlington, VA. This docket facility is open from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The docket telephone number is (703) 3055805.

2. Electronic access. You may access this Federal Register document electronically through the EPA Internet under the ``Federal 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/ Title40/40cfr18000.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.

An electronic version of the public docket is available through EPA's electronic public docket and comment system, EPA Dockets. You may use EPA Dockets at http://www.epa.gov/edocket/ to submit or view public comments, access the index listing of the contents of the official public docket, and to access those documents in the public docket that are available electronically. Although not all docket materials may be available electronically, you may still access any of the publicly available docket materials through the docket facility identified in Unit I.B.1. Once in the system, select ``search,'' then key in the appropriate docket ID number.

II. Background and Statutory Findings

In the Federal Register of February 26, 2003 (68 FR 8896) (FRL 72939), EPA issued a notice pursuant to section 408 of FFDCA, 21 U.S.C. 346a, as amended by FQPA (Public Law 104170), announcing the filing of a pesticide petition (PP 1F6309) by Syngenta Crop Protection, Inc., P.O. Box 18300, Greensboro, NC 274198300. That notice included a summary of the petition prepared by Syngenta Crop Protection, Inc., the registrant. There were no comments received in response to the notice of filing.

The petition requested that 40 CFR part 180 be amended by establishing a tolerance for residues of the herbicide butafenacil, the [2+2] cycloaddition dimer of butafenacil, and CGA293731 in or on cotton, undelinted seed at 0.5 parts per million (ppm); and in or on cotton, gin byproducts at 13.0 ppm.

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) of the FFDCA 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) of the FFDCA 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 of the FFDCA and a complete description of the risk assessment process, see the final rule on Bifenthrin Pesticide Tolerances (62 FR 62961, November 26, 1997) (FRL 57547).

III. Aggregate Risk Assessment and Determination of Safety

Consistent with section 408(b)(2)(D) of the FFDCA, EPA has reviewed the
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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) of the FFDCA, for a tolerance for residues of butafenacil and CGA293731 on cattle, kidney; goat, kidney; hog, kidney; horse, kidney; and sheep, kidney at 0.05 parts per million (ppm); in or on cattle, liver; goat, liver; hog, liver; horse, liver; and sheep, liver at 0.50 ppm; and tolerances for residues of butafenacil in or on cotton, undelinted seed at 0.50 ppm; and in or on cotton, gin byproducts at 10 ppm. EPA's assessment of exposures and risks associated with establishing these tolerances follows.

A. Toxicological Profile

EPA has evaluated the available toxicity data and considered its validity, completeness, and reliability as well as the relationship of the results of the studies to human risk. EPA has also considered available information concerning the variability of the sensitivities of major identifiable subgroups of consumers, including infants and children. The nature of the toxic effects caused by butafenacil are discussed in Table 1 of this unit 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.Acute Toxicity of Butafenacil Guideline number Study Type Results Toxicity Category 870.1100 Acute oral Lethal dose (LD)50 IV >5,000 milligrams/ kilogram (mg/kg) male and female (M/F) 870.1200 Acute dermal LD50 >2,000 mg/kg M/F III 870.1300 Acute inhalation Lethal concentration IV (LC)50 >5.10 milligrams per Liter (mg/L) 870.2400 Primary eye irritation Ocular irritation III resolved within 96 hours 870.2500 Primary skin irritation Not an irritant IV 870.2600 Dermal sensitization Not a sensitizer Not Applicable (NA) Table 2.Subchronic, Chronic, and Other Toxicity Guideline number Study Type Results 870.3100 90Day oral NOAEL = 300 ppm (dietary) (18.8/20.6 mg/kg/ toxicity rodents day M/F) (rat) LOAEL = 1,000 ppm (62.3/69.3 mg/kg/ day M/F), based on decreased body weight gains, decreased hemoglobin, hematocrit, mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), increased red cell volume, increased bone marrow hypercellularity; increased bilirubin and urobilinogen; increased alanine aminotransferase; hepatocyte necrosis; inflammatory liver cell infiltration 870.3100 90Day oral NOAEL = 30 ppm (4.11/ (dietary) 5.67 mg/kg/day M/F) toxicity in LOAEL = 100 ppm rodents (mouse) (13.8/20.1 mg/kg/ day M/F), based on hepatic histopathology: fatty change, glycogen deposition, and hypertrophy in both sexes
870.3150 90Day oral NOAEL = 200 mg/kg/ (capsule) day M/F toxicity in non LOAEL = 1,000 mg/kg/ rodents (dog) day M/F, based on decreases in MCV and MCH in males; increases in RDW, HDW, platelets and triglycerides in males; and hemosiderosis in spleen and liver and extramedullary hematopoiesis the spleen in males 870.3200 28Day dermal NOAEL = 1,000 mg/kg/ toxicity (rat) day
LOAEL = not determined 870.3700 Prenatal Maternal NOAEL = developmental 1,000 mg/kg/day toxicity in Maternal LOAEL = not rodents (rat) determined Developmental NOAEL = 1,000 mg/kg/day Developmental LOAEL = not determined 870.3700 Prenatal Maternal NOAEL = 100 developmental mg/kg/day toxicity in non Maternal LOAEL = rodents (rabbit) 1,000 mg/kg/day based on decreased body weight gains and food consumption during the treatment period, and on bloodstained vaginal discharge (related to total litter loss) in two doses
Developmental NOAEL = 100 mg/kg/day Developmental LOAEL = 1,000 mg/kg/day based on increased early resorptions and post implantation loss [[Page 54820]]
870.3800 2Generation Parental/systemic reproduction and NOAEL = 30 ppm (2.4/ fertility 2.5 mg/kg/day M/F) effects Parental/systemic LOAEL = 300 ppm (23.8/25.2 mg/kg/ day M/F), based on decreased body weights and food consumption and on increased incidences of bile duct hyperplasia and liver necrosis in males and females of both generations Offspring NOAEL = 300 ppm (23.8/25.2 mg/kg/day M/F) Offspring LOAEL = 1,000 ppm (79.6/ 83.8 M/F), based on decreased pup body weight and body weight gain in both generations Reproductive NOAEL = 30 ppm (2.4/2.5 mg/ kg/day M/F) Reproductive LOAEL = 300 ppm (23.8/25.2 mg/kg/day M/F) based on an increase in the number of days to mating in both generations 870.4100 1Year chronic NOAEL = 500 mg/kg/ oral (capsule) day M/F toxicity (dog) LOAEL = 1,000 mg/kg/ day M/F, based on decreased body weight gain in males, decreased MCV, MCH, and mean corpuscular hemoglobin concentration (MCHC); increased thrombocytes and red cell volume distribution width; hepatic histopathology: glycogen disposition, inclusion bodies in cytoplasm, and pigment disposition in both sexes, and focal vaculolation in females 870.4200 18Month NOAEL = 10 ppm (1.17/ carcinogenicity 1.20 mg/kg/day M/F) dietary study LOAEL = 60 ppm (6.96/ (mouse) 6.59 mg/kg/day M/ F), based on enlarged livers with increased weights, and hepatic microscopic lesions including Kupffer cell hyperplasia, inflammatory cell infiltration, and single cell necrosis in both sexes and on deposits of lipofuscin in males No evidence of carcinogenicity 870.4300 Combined 2Year NOAEL = 100 ppm chronic/ (3.76/4.43 mg/kg/ carcinogenicity day M/F) dietary study LOAEL = 300 ppm (rat) (11.4/13.0 mg/kg/ day M/F), based on minimal hepatic abnormalities in the females, including a fatty change and increased mitotic activity No evidence of carcinogenicity 870.5100 In vitro Negative in a bacterial gene reverse gene mutation mutation assay in strains TA98, TA100, TA102, TA1535, TA1537 of S. typhimurium and strain WP2(uvrA) of E. coli in the presence and absence of mammalian metabolic activation 870.5300 In vitro Evidence of mammalian cells borderline in culture induction of mutant colonies in presence of S9 in a mammalian cell gene mutation assay at the hypoxanthine guanine phophoribosyl transferase (HGPRT) locus of Chinese hamster V79 cells 870.5375 In vitro Negative. No mammalian evidence of cytogenetics increase in chromosome aberrations over background 870.5395 In vivo mammalian Negative. No cytogenetics increase in micronucleus frequency of assay (mouse) micronucleated polychromatic erythrocytes 870.5550 Other Negative. No genotoxicity evidence of unscheduled DNA induction of UDS; synthesis (UDS) no indications of in vivo/in vitro induction of DNA damage 870.5550 Other Negative. No genotoxicity evidence of UDS in vitro induction of UDS; no indications of induction of DNA damage in primary rat hepatocytes in culture 870.6200 Acute NOAEL = 2,000 mg/kg neurotoxicity LOAEL = Not screening determined battery (rat) No evidence of neurotoxicity 870.6200 Subchronic NOAEL = 300 ppm 21/ neurotoxicity 24 mg/kg/day M/F screening LOAEL = 1,000 ppm 72/ battery (rat) 76 mg/kg/day M/F, based on liver histopathology and decreased motor activity at week 13 in the males No evidence of neurotoxicity [[Page 54821]]
870.7485 Metabolism and Overall recovery of pharmacokinetics administered (rat) radioactivity exceeded 95%, most (7493%) of which was eliminated in the feces. Approximately 415% of the administered radioactivity was excreted in the urine over 168 hours while tissue residues were negligible, thereby implying limited absorption. No radioactivity was detected in expired air. Excretion of radioactivity was >90% complete by 48 hours. Up to six components were detected in the urine of rats from both dose groups, the most prevalent being an hydrolysis product, CGA293731 which represented >90% of urinary radioactivity. Urinary elimination of metabolites was quantitatively greater in female rats than in males. Only minor amounts (near detection limits) of parent compound were detected in the urine of highdose males. Based upon biliary elimination, 74 79% of the dose entered the hepatobiliary pathway but was eliminated via the feces. An increase in parent compound in feces of the highdose group was indicative of saturated absorption and/or saturated metabolism, but could not be definitively resolved due to the absence of biliary elimination studies at the high dose. Biliary elimination studies revealed that approximately 6064% of the administered low dose was detected in 04 hour pooled bile samples and that the majority of fecal radioactivity could be attributed to biliary metabolites 870.7485 Mechanistic Effects on enzymes studies of cultured mouse, rat, and/or human hepatocytes involved with heme biosynthesis 870.7485 Mechanistic Effects on liver studies microsomal and plasma protox activity and its metabolic conversion 870.7485 Mechanistic Effects on porphyrin studies profile in rats; treatment induced porphyria, consisting of accumulation of selected porphyrins in the liver, spleen, and plasma and increased excretion in urine and feces 870.7485 Mechanistic Test substance studies interferes with heme biosynthesis in rats, as evidenced by dose dependent, pronounced porphyria in the liver, spleen, and plasma; increased porphyrin excretion, and decreased activity of various isoenzymes of the hepatic microsomal cytochrome P450 system 870.7485 Mechanistic Test substance studies interferes with heme biosynthesis in mice, as evidenced by dose dependent, pronounced porphyria in the liver, spleen, and plasma; increased porphyrin excretion, and decreased activity of various isoenzymes of the hepatic microsomal cytochrome P450 system 870.7485 Mechanistic Effects on porphyrin studies profile in mice; treatment induced porphyria, consisting of accumulation of selected porphyrins in the tissue and plasma, and increased excretion of heme precursors B. Toxicological Endpoints

The dose at which the NOAEL from the toxicology study identified as appropriate for use in risk assessment is used to estimate the margin of exposure (MOE). 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. A 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 factors (SF) 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 SF.

For nondietary 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.

A summary of the toxicological endpoints for butafenacil used for human risk assessment is shown in Table 3 of this unit:
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Table 3.Toxicological Dose and Endpoints for Butafenacil Special FQPA SF* and Exposure Scenario Dose Used in Risk Level of Concern for Study and Toxicological Assessment, UF Risk Assessment Effects Acute dietary (General population None NA An endpoint including infants and children) attributable to a single dose is not available in the data base Chronic dietary (All populations) NOAEL= 1.2 mg/kg/day UF Special FQPA SF = 1 Mouse oncogenicity = 100 cPAD = chronic RfD..... study Chronic RfD = 0.012 mg/ Special FQPA SF = 0.012 The LOAEL is 6.96 mg/kg/ kg/day. mg/kg/day. day, based on enlarged livers with increased weights, and hepatic microscopic lesions including Kupffer cell hyperplasia, inflammatory cell infiltration, and single cell necrosis in both sexes and on deposits of lipofuscin in males Shortterm inhalation (1 to 30 days) Oral NOAEL = 18.8 mg/kg/ Residential LOC for MOE 90day rat feeding day = 100 study Occupational = 100..... The LOAEL for this study is 62.3 mg/kg/ day based on decreased hemoglobin, hematocrit, mean corpuscular hemoglobin, mean corpuscular volume, increased red cell volume distribution width, and increased incidence of bone marrow hypercellularity Shortterm incidental oral (1 to 30 NOAEL = 18.8 mg/kg/day Residential LOC for MOE 90day rat feeding days) = 100 study Occupational = NA...... The LOAEL for this study is 62.3 mg/kg/ day, based on decreased hemoglobin, hematocrit, mean corpuscular hemoglobin, mean corpuscular volume, increased red cell volume distribution width, and increased incidence of bone marrow hypercellularity Intermediateterm incidental oral (1 NOAEL = 18.8 mg/kg/day Residential LOC for MOE 90day rat feeding 6 months) = 100 study Occupational = NA...... The LOAEL for this study is 62.3 mg/kg/ day, based on decreased hemoglobin, hematocrit, mean corpuscular hemoglobin, mean corpuscular volume, increased red cell volume distribution width, and increased incidence of bone marrow hypercellularity Dermal (All durations) NA NA Quantification of dermal risk assessment is not required due to lack of concern for dermal, systemic or developmental toxicity Shortterm inhalation (1 to 30 days) Oral NOAEL = 18.8 mg/kg/ Residential LOC for MOE 90day rat feeding day = 100 study Occupational = 100..... The LOAEL for this study is 62.3 mg/kg/ day based on decreased hemoglobin, hematocrit, mean corpuscular hemoglobin, mean corpuscular volume, increased red cell volume distribution width, and increased incidence of bone marrow hypercellularity Intermediateterm inhalation (1 to 6 Oral NOAEL = 18.8 mg/kg/ Residential LOC for MOE 90day rat feeding months) day = 100 study Occupational = 100..... The LOAEL for this study is 62.3 mg/kg/ day, based on decreased hemoglobin, hematocrit, mean corpuscular hemoglobin, mean corpuscular volume, increased red cell volume distribution width, and increased incidence of bone marrow hypercellularity [[Page 54823]]
Longterm inhalation (>6 months) Oral NOAEL = 1.2 mg/kg/ Residential LOC for MOE Mouse oncogenicity day = 100 study Occupational = 100..... The LOAEL is 6.96 mg/kg/ day, based on enlarged livers with increased weights, and hepatic microscopic lesions including Kupffer cell hyperplasia, inflammatory cell infiltration, and single cell necrosis in both sexes and on deposits of lipofuscin in males Cancer (oral, dermal, inhalation) NA NA Classified as ``not likely to be carcinogenic to humans'' * The reference to the Special FQPA SF refers to any additional SF retained due to concerns unique to the FQPA. C. Exposure Assessment

1. Dietary exposure from food and feed uses. No tolerances have previously been established for butafenacil. Risk assessments were conducted by EPA to assess dietary exposures from butafenacil in food as follows:

i. Acute exposure. Quantitative acute dietary risk assessments are performed for a fooduse pesticide if a toxicological study has indicated the possibility of an effect of concern occurring as a result of a 1day or single exposure. No appropriate endpoint attributable to a single exposure was identified for butafenacil in either the general population or to the subpopulation of females 1350 years old, therefore no acute exposure assessment was performed.

ii. Chronic exposure. In conducting this chronic dietary risk assessment, the Dietary Exposure Evaluation Model Food Commodity Intake Database (DEEMFCID[reg]) analysis evaluated the individual food consumption as reported by respondents in the USDA 19941996, and 1998 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: The dietary exposure analysis assumed 100% crop treated and tolerance level residues or maximum field trial residues. Based on total food exposure for butafenacil, all population subgroups are below 1% cPAD.

iii. Cancer. Butafenacil showed no evidence of carcinogenicity in animal tests in two different species, and therefore, a quantitative cancer risk assessment was not performed.

2. Dietary exposure from drinking water. The Agency lacks sufficient monitoring exposure data to complete a comprehensive dietary exposure analysis and risk assessment for butafenacil 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 butafenacil.

The Agency uses the First Index Reservoir Screening Tool (FIRST) or the Pesticide Root Zone/Exposure Analysis Modeling System (PRZM/EXAMS), to produce estimates of pesticide concentrations in an index reservoir. The screening concentration in ground water (SCIGROW) model is used to predict pesticide concentrations in shallow ground water. For a screeninglevel assessment for surface water EPA will use FIRST (a Tier I model) before using PRZM/EXAMS (a Tier II model). The FIRST model is a subset of the PRZM/EXAMS model that uses a specific highend runoff scenario for pesticides. While both FIRST and PRZM/EXAMS incorporate an index reservoir environment, 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 LOC.

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 butafenacil they are further discussed in Unit III.E.

Based on the FIRST and SCIGROW models, the EECs of butafenacil for chronic exposures are estimated to be 0.049 parts per billion (ppb) for surface water and 0.00095 ppb for ground water.

3. From nondietary exposure. The term ``residential exposure'' is used in this document to refer to nonoccupational, nondietary exposure (e.g., for lawn and garden pest control, indoor pest control, termiticides, and flea and tick control on pets). Butafenacil is not proposed for registration for use on any sites that would result in residential exposure.

4. Cumulative effects from substances with a common mechanism of toxicity. Section 408(b)(2)(D)(v) of the FFDCA 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 butafenacil has a common mechanism of toxicity with other substances. Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as to butafenacil and any other substances
[[Page 54824]]
and butafenacil 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 butafenacil 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 policy statements released by EPA's Office of Pesticide Programs concerning common mechanism determinations and procedures for cumulating effects from substances found to have a common mechanism on EPA's website at http://www.epa.gov/pesticides/cumulative/. D. Safety Factor for Infants and Children

1. In general. Section 408 of the FFDCA 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.

2. Prenatal and postnatal sensitivity. There are no residual concerns regarding prenatal or postnatal toxicity or completeness of the toxicity or exposure data base.

3. Conclusion. There is a complete toxicity data base for butafenacil and exposure data are complete or are estimated based on data that reasonably accounts for potential exposures. EPA determined that the 10X SF to protect infants and children could be reduced to 1X. The FQPA factor was reduced because:
[sbull] There is no quantitative or qualitative evidence of increased susceptibility of rat and rabbit fetuses to in utero exposure in developmental studies or to in utero and postnatal exposure to rats in the 2generation reproduction study.
[sbull] There are no residential uncertainties for prenatal or postnatal toxicity.
[sbull] The toxicological data base is complete for the assessment of toxicity and susceptibility following prenatal and/or postnatal exposures. No clinical signs of neurotoxicity or neuropathology were observed in the data base, and the developmental neurotoxicity study was not required.
[sbull] There are no residual concerns regarding prenatal or postnatal toxicity or completeness of the toxicity or exposure data base.
[sbull] The dietary food exposure assessment is Tier I, screening level, which is based on tolerance level residues or maximum field trial residues and assumes 100% of all crops will be treated with chemical. By using these screening level assessments, actual exposures/ risks will not be underestimated.
[sbull] The dietary drinking water assessment utilizes water concentration values generated by health protective, highend estimates of water concentrations which will not likely be exceeded.
[sbull] There are currently no registered residential uses of butafenacil.
[sbull] These assessments will not underestimate the exposure/risks posed by current or proposed uses of butafenacil.

E. 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 EPA's Office of Water are used to calculate DWLOCs: 2 L/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 screeninglevel 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, shortterm, intermediateterm, chronic, and cancer.

When EECs for surface water and ground water are less than the calculated DWLOCs, EPA concludes with reasonable certainty that exposures to the pesticide in drinking water (when considered along with other sources of exposure for which EPA has reliable data) would not result in unacceptable levels of aggregate human health risk at this time. Because EPA 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, EPA will reassess the potential impacts of residues of the pesticide in drinking water as a part of the aggregate risk assessment process.

1. Acute risk. No acute risk from exposure to butafenacil is expected because there were no toxic effects of concern attributable to a single dose identified in available data.

2. Chronic risk. Using the exposure assumptions described in this unit for chronic exposure, EPA has concluded that exposure to butafenacil from food will utilize <1% of the cPAD for the U.S. population, <1% of the cPAD for infants ages 12, and <1% of the cPAD for children ages 35. There are no proposed residential uses for butafenacil that result in chronic residential exposure to butafenacil. In addition, there is potential for chronic dietary exposure to butafenacil in drinking water. After calculating DWLOCs and comparing them to the EECs for surface water and ground water, EPA does not expect the aggregate exposure to exceed 100% of the cPAD, as shown in Table 4 of this unit:
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Table 4.Aggregate Risk Assessment for Chronic (NonCancer) Exposure to Butafenacil Chronic Food Population cPAD (mg/kg/day) % cPAD (mg/kg/day) Exposure¹ (mg/kg/ Ground Water EEC² Surface Water EEC² Chronic DWLOC³ day) (ppb) (ppb) (ppb) General U.S. population 0.012 <1% 0.000041 0.00095 0.049 420 All infants (< 1 year old) 0.012 <1% 0.000014 0.00095 0.049 120 Children (12 years old) 0.012 <1% 0.000097 0.00095 0.049 120 Children (35 years old) 0.012

FOR FURTHER INFORMATION CONTACT Jim Tompkins, Registration Division (7505C), Office of Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 204600001; telephone number: (703) 3055697; email address: Tompkins.Jim@epa.gov.