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CFR Citation: 40 CFR Part 180

OPP ID: [OPP-2003-0315; FRL-7328-6]

NOTICE: RULES

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

DOCUMENT ACTION: Final rule.

SUBJECT CATEGORY: Sethoxydim; Pesticide Tolerance

DATES: This regulation is effective September 29, 2003. Objections and requests for hearings, identified by docket ID number OPP20030315, must be received on or before November 28, 2003.

DOCUMENT SUMMARY: This regulation establishes a tolerance for combined residues of sethoxydim (2[1(ethoxyimino)butyl]5[2(ethylthio)propyl]3 hydroxy2cyclohexen1one) and its metabolites containing the 2 cyclohexen1one moiety (calculated as the herbicide) in or on corn, sweet, forage; corn, sweet, stover; juneberry; lingonberry; pistachio; salal; and safflower and increases the tolerance on cattle, meat by products; corn, sweet, kernels plus cob with husk removed; goat, meat byproducts; hog, meat byproducts; horse, meat byproducts; milk; and sheep, meat byproducts. BASF Corporation requested the tolerances for corn, sweet, forage; corn, sweet, stover and the increase in tolerance for corn, sweet, kernels plus cob with husk removed; milk; and meat products under the Federal Food, Drug, and Cosmetic Act (FFDCA), as amended by the Food Quality Protection Act of 1996 (FQPA). Interregional Project 4 (IR4) requested the tolerances on juneberry, lingonberry, pistachio, salal, and safflower under the Federal Food, Drug, and Cosmetic Act (FFDCA), as amended by the Food Quality Protection Act of 1996 (FQPA).

SUMMARY: Sethoxydim,

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
[[Page 55859]]
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 OPP20030315. 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://. 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/.

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 January 18, 2000 (65 FR 2612) (FRL6486 4), August 7, 2002 (67 FR 51267) (FRL71913), and September 11, 2002 (67 FR 57593) (FRL719811), 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 pesticide petitions (9E6012, 9E6021, and 0E6150) by the Interregional Research Project Number 4, Technology Centre and Rutgers State University of New Jersey, 681 U.S. Highway 1 South, North Brunswick, NJ 089023390 and pesticide petition (2F4075) by BASF Corporation, P.O. Box 13528, Research Triangle Park, NC 277093528. These notices included summaries of the petitions prepared by BASF Corporation, the registrant. There were no comments received in response to these notices of filing.

These petitions requested that 40 CFR part 180 be amended to establish tolerances for cyclohexen1one moiety (calculated as the herbicide), in or on corn, sweet, forage at 3.0 parts per million (ppm); corn, sweet, stover at 3.5 ppm; lingonberry at 5.0 ppm; juneberry at 5.0 ppm; pistachios at 0.2 ppm; safflower at 15.0 ppm and salal at 5.0 ppm, and increase the tolerance in cattle, meat byproducts from 0.2 ppm to 1.0 ppm; corn, sweet, kernels plus cob with husk removed from 0.2 ppm to 0.4 ppm; goat, meat byproducts from 0.2 ppm to 1.0 ppm; horse, meat byproducts from 0.2 ppm to 1.0 ppm; milk from 0.05 ppm to 0.5 ppm, and sheep, meat byproducts from 0.2 ppm to 1.0 ppm. The tolerance increases were a result of a 15day reduction in the pre harvest interval for sweet corn requested by the registrant.

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 November 26, 1997 (62 FR 62961) (FRL 57547).

III. Aggregate Risk Assessment and Determination of Safety

Consistent with section 408(b)(2)(D) of the FFDCA, 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) of the FFDCA, for a tolerance for combined residues of the herbicide sethoxydim, (2[1(ethoxyimino)butyl]5[2
(ethylthio)propyl]3hydroxy2cyclohexen1one) and its metabolites containing the 2cyclohexen1one moiety (calculated as the herbicide), in or on corn, sweet, kernels plus cob with husk removed at 0.4 ppm; corn, sweet, forage at 3.0 ppm; corn, sweet, stover at 3.5 ppm; lingonberry at 5.0 ppm; juneberry at 5.0 ppm; milk at 0.5 ppm; cattle, meat byproducts at 1.0 ppm; goat, meat byproducts at 1.0 ppm; hog, meat byproducts at 1.0 ppm; horse, meat byproducts at 1.0 ppm and sheep meat byproducts at 1.0 ppm; pistachio at 0.2 ppm; safflower at 15.0 ppm and salal at 5.0 ppm. EPA's assessment of exposures and risks associated with establishing the tolerance follows.

A. Toxicological Profile

EPA has evaluated the available toxicity data and considered its validity, completeness, and reliability as well as the relationship of the results of the studies to human risk. EPA has also considered available information concerning the variability of the sensitivities of major identifiable subgroups of consumers, including infants and children. The natures of the toxic effects caused by sethoxydim are discussed in Table 1 of this unit as well as the no observed adverse effect level (NOAEL) and the lowest observedadverse effect level (LOAEL) from the toxicity studies reviewed.
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Table 1.Toxicology Profile for Sethoxydim Technical Guideline No. Study Type Results 870.1100 Acute oralrats LD50 = male (M): 3,125 milligram/ kilogram (mg/kg); female (F) 2,676 mg/ kg (category III) 870.1200 Acute dermal LD50 = > 5,000 mg/kg rats (category III) 870.1300 Acute inhalation LC50 = M: 6.03 meter/ rats Liter (m/L); F 6.28 m/L (category III) 870.2400 Primary eye No irritation irritationrabb (category IV) its
870.2500 Primary skin No irritation irritationrabb (category IV) its
870.2600 Dermal Waived based on lack sensitizationg of sensitization in uinea pigs guinea pigs with a formulated product 870.3100 90Day oral Males
toxicity rodents NOAEL = 60.4 (rats) LOAEL = 196.3 mg/kg/ day
Females NOAEL = 66.2 LOAEL = 200.5 mg/kg/ day Based on decreases in body weight, body weight gain, and food efficiency 870.3100 90Day oral Males
toxicity rodents NOAEL = 45.6 (mice) LOAEL = 137.1 mg/kg/ day
Females NOAEL = 52.7 LOAEL = 164.4 mg/kg/ day based on increased liver weight and histopathological evidence of hepatocellular hypertrophy 870.3150 90Day oral Males and females toxicity NOAEL not identified (nonrodents LOAEL = 3.4 mg/kg/ dogs) day (tentative) based on possible treatmentrelated clinical findings of cystitis of urinary bladders 870.3200 21Day dermal Males and females toxicity NOAEL = 1,000 mg/kg/ (rabbits) day higest dose tested (HDT) LOAEL not established. No localized or systemic effects 870.3465 4Week inhalation Males and females toxicity (rats) NOAEL = 0.3 mg/L (81 mg/kg/day) LOAEL of 2.4 mg/L (651 mg/kg/day), based on increased liver weight, clinical chemistry (increased total serum bilirobin), and liver histopathology 870.3700 Prenatal Maternal developmental NOAEL = 180 mg/kg/ toxicity (rats) day
LOAEL = 650 mg/kg/ day (irregular gaits, decreased activity, excessive salivation, and anogenital staining) Developmental NOAEL = 180 mg/kg/ day
LOAEL = 650 mg/kg/ day (2122% decrease in fetal weights, filamentous tail and lack of tail due to the absence of sacral, and/or caudal vertebrae, and delayed ossification in the hyoids, vertebral centrum, and/or transverse processes, sternebrae and/or metatarsals, and pubes) 870.3700 Prenatal Maternal developmental NOAEL = 320 mg/kg/ toxicity day
(rabbits) LOAEL = 400 mg/kg/ day, (based on 37% reduction in body weight gain without significant differences in group mean body weights, and decreased food consumption during dosing) Developmental NOAEL 320 mg/kg/day LOAEL = 400 mg/kg/ day HDT based on an increase in the incidence of incompletely ossified 6th sternebrae [[Page 55861]]
870.3800 Reproduction and Systemic fertility NOAEL >=150 mg/kg/ effects (rats) day
LOAEL >150 mg/kg/day Reproductive NOAEL >=150 mg/kg/ day
LOAEL >150 mg/kg/day Offspring NOAEL = 30 mg/kg/day LOAEL = 150 mg/kg/ day, based on decreased body weight in F2b pups during lactation and tail abnormalities seen in F1a and F1b offspring 870.4100 Chronic toxicity Males
(dogs) NOAEL = 17.5 mg/kg/ day
LOAEL = 110 mg/kg/ day
Females NOAEL = 19.9 mg/kg/ day
LOAEL = 129 mg/kg/ day, based on increase hemosiderosis in the spleen and depressed myeloid erythropoiesis in the sternal bone marrow, increased absolute and relative liver weights, increased alkaline phosphatase and ALT levels 870.4200 Carcinogenicity Males
(mice) NOAEL = 13.8 mg/kg/ day
LOAEL = 41.2 mg/kg/ day, based on early onset of liver effects including hepatocellular hypertrophy and fatty degeneration in male mice. No evidence of carcinogenicity 870.4300 Combined chronic/ Male
carcinogenicity NOAEL = 12 mg/kg/day (rats) LOAEL = 48 mg/kg/ day, based on liver toxicity (centrilobular hepatocellular hypertrophy) Females NOAEL = 66 mg/kg/day LOAEL = 204 mg/kg/ day, based on decreased body weight, body weight gain, liver toxicity (centrilobular hepatocellular hypertrophy), and lung lesions (heart failure cells and interstitial fibrosis) No evidence of carcinogenicity 870.5100 Bacterial reverse Negative mutation Concentrations 313 5,000 [mu]g/plate 870.5300 In vitro Negative mammalian cell Concentrations 500 gene mutation 5,000 [mu]g/mL 870.5300 In vitro Negative mammalian cell 10,000 mg/kg gene mutation
870.5300 In vitro Negative mammalian cell
gene mutation
870.5550 Unscheduled DNA Negative synthesis (rat Concentrations 10 to hepatocyte 507 [mu]g/mL cells)
870.5915 In vivo sister Negative chromatid Dose 0, 0.5, 1.67, 5 exchange gram (g)/kg (chinese hamster
bone marrow)
870.7485 Metabolism and Excretion is pharmacokinetics extremely rapid and (rats) tissue accumulation is negligible, assuming DMSO vehicle does not affect excretion or storage of NP55, 78% excreted into urine and 20.1% in feces
870.7485 Metabolism and Administration of pharmacokinetics radioactively (rats) labeled NP55 yielded 0.8% radioactivity in urine identified as hydroxymetabolites represented by 6OH M2SO2 and 2 other metabolites found by mass spectrometry were MSO and M1SO [[Page 55862]]

B. 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. A UF of 100 is routinely used, 10X to account for interspecies differences and 10X for intraspecies differences. Acceptable developmental toxicity studies were performed in rats and rabbits, with evidence of neurotoxicity in the rat study, and an acceptable 2generation reproduction study in rats. The developmental toxicity rabbit study did not exhibit either quantitative of qualitative susceptibility. Neurotoxicity studies are not available. Although, the Agency has concluded that there is a concern for prenatal and/or postnatal toxicity resulting from exposure to sethoxydim, the concern is reduced because the fetal effects in the developmental rat study were seen only at the high dose. Concern is also low because the LOAEL for offspring toxicity for the 2generation reproduction rat study is based on conservative determinations of offspring toxicity. However, due to lack of subchronic and developmental neurotoxicity studies with evidence of developmental (tail) abnormalities in the rat developmental and reproductive studies the additional 10X FQPA safety factor (SF) in the form of a data base UF was retained.

For dietary risk assessment (other than cancer) the Agency uses the UF to calculate an acute or chronic reference dose (aRfD or cRfD) where the reference dose (RfD) is equal to the NOAEL divided by the appropriate UF (RfD = NOAEL/UF). Where an additional 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 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 nonlinear 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 sethoxydim used for human risk assessment is shown in the following Table 2:
Table 2.Summary of Toxicological Dose and Endpoints for Sethoxydim for Use in Human Risk Assessment Special FQPA SF* and Exposure Scenario Dose Used in Risk Level of Concern for Study and Toxicological Assessment, UF Risk Assessmentk Effects Acute dietary (Females 1350 years of NOAEL = 180 mg/kg/day) Special FQPA SF = 1X Rat developmental age and including infants and UF = 1,000............. aPAD = acute RfD /..... toxicity children) Acute RfD = 0.18 mg/kg/ Special FQPA SF = 0.18 Developmental day. mg/kg/day. LOAEL = 650 mg/kg/day based on decreased fetal body weight, tail abnormalities, delayed ossification Acute dietary NOAEL = 180 mg/kg/day Special FQPA SF = 1X Rat developmental (General population)................. UF = 1,000............. aPAD = acute RfD /..... toxicity Acute RfD = 0.18 mg/kg/ Special FQPA SF = 0.18 Maternal day. mg/kg/day. LOAEL = 650 mg/kg/day based on irregular gait that was observed in 12/34 dams on the first day of dosing Chronic dietary NOAEL= 14 mg/kg/day Special FQPA SF = 1X Mouse carcinogenicity (All populations).................... UF = 1,000............. cPAD = chronic RfD /... study Chronic RfD = 0.014 mg/ Special FQPA SF = 0.014 LOAEL = 41 mg/kg/day kg/day. mg/kg/day. based on liver hypertrophy and fatty degeneration Shortterm NOAEL= 180 mg/kg/day Residential Rat developmental Incidental oral (130 days).......... LOC for MOE = 1,000.... toxicity Maternal LOAEL = 650 mg/kg/day based on irregular gait that was observed in 12/34 dams on the first day of dosing Intermediateterm NOAEL = 45.6 mg/kg/day Residential 90Day mouse oral Incidental oral (16 months)......... LOC for MOE = 1,000.... toxicity LOAEL = 137 mg/kg/day based on increased liver weight and hepatocellular hypertrophy [[Page 55863]]
Shortterm dermal (1 to 30 days) Dermal (or oral) study Residential Quantification of NOAEL= NA.............. LOC for MOE = NA....... dermal exposure risk assessment is not required because of lack of dermal and pre natal toxicity in rabbits, and the low dermal absorption physical and chemical properties of sethoxydim Intermediaterm dermal (1 to 6 Dermal (or oral) study Residential Quantification of months) NOAEL = NA............. LOC for MOE = NA....... dermal exposure risk assessment is not required because of lack of dermal and prenatal toxicity in rabbits, and the low dermal absorption physical and chemical properties of sethoxydim Longterm dermal > 6 months) Dermal (or oral) study Residential Quantification of NOAEL= NA.............. LOC for MOE = NA....... dermal exposure risk assessment is not required because of lack of dermal and prenatal toxicity in rabbits, and the low dermal absorption physical and chemical properties of sethoxydim Shortterm Inhalation study Residential 28Day rat inhalation Inhalation (1 to 30 days)............ NOAEL= 81 mg/kg/day.... LOC for MOE = 1,000.... LOAEL = 651 mg/kg/day based on increased liver weight, clinical chemistry (increased total serum bilirobin), and liver histopathology Intermediateterm Inhalation study Residential 28Day rat inhalation Inhalation (1 to 6 months)........... NOAEL = 81 mg/kg/day... LOC for MOE = 1,000.... LOAEL = 651 mg/kg/day based on increased liver weight, clinical chemistry (increased total serum bilirobin), and liver histopathology Cancer (oral, dermal, inhalation) ``Not likely human carcinogen'' based on the lack of evidence of carcinogenicity in rats and mice UF = uncertainty factor, FQPA SF = Special FQPA safety factor, NOAEL = noobservedadverseeffectlevel, LOAEL = lowestobservedadverseeffectlevel, PAD = populationadjusted dose (a = acute, c = chronic) RfD = reference dose, MOE = margin of exposure, LOC = level of concern, NA = Not Applicable. C. Exposure Assessment

1. Dietary exposure from food and feed uses. Tolerances have been established (40 CFR 180.412) for the combined residues of sethoxydim and its metabolites, in or on a variety of raw agricultural commodities. Tolerances are also currently established for secondary residues in meat, fat, and meat byproducts of cattle, goats, hogs, horses, poultry, and sheep at 0.2 ppm (except 2.0 ppm in poultry meat byproducts); eggs at 2.0 ppm, and milk at 0.05 ppm. Time limited tolerances (to expire by 12/31/03) are established for residues in milk at 0.5 ppm and the meat byproducts of cattle, goats, hogs, horses, and sheep at 1.0 ppm. Risk assessments were conducted by EPA to assess dietary exposures from sethoxydim in food as follows:

i. Acute exposure. 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 1 day or single exposure. This acute assessment used tolerance level residues for most of the crops but limited refinement was obtained though the incorporation of field trial data and experimental processing factors for some of the crops expected to be more highly associated with dietary exposure to sethoxydim. Specifically, field trial data were incorporated for apples, pears, and other pome fruits, grapes, oranges, potatoes, strawberries, peaches, succulent green peas, succulent green beans, and succulent lima beans. Empirical processing data for apples, grapes, tomatoes, potatoes and oranges were also used. The processing data for orange juice was also translated to other citrus juices. Percent crop treated (PCT) information was available for most crops and was used wherever possible to refine the assessment. Tolerance level residues were used for meat, poultry, milk and eggs. With the refinements incorporated in this assessment, the acute dietary analyses for sethoxydim show that the estimated risks from acute dietary exposure to sethoxydim are below <100% aPAD for the U.S. population.

ii. Chronic exposure. In conducting this chronic dietary risk assessment the Dietary Exposure Evaluation Model (DEEM^TM) analysis evaluated the individual food consumption as reported by respondents in the U.S. Department of Agriculture (USDA) 19891992 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 chronic analyses (limited refined dietary risk assessment) used tolerance level residues for all crops and the PCT for many crops. For the chronic analyses, refinement was obtained by calculation of anticipated residues for meat and
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milk, and without using field trial data. The results of this analysis indicate that the chronic dietary risk (food only) associated with existing uses of sethoxydim is below <100% cPAD for the U.S. population.

iii. Cancer. Sethoxydim is classified as ``not likely to be a human carcinogen''. Therefore, a quantitative assessment of aggregate cancer risk was not performed.

iv. Anticipated residue and PCT information. Section 408(b)(2)(E) of the FFDCA authorizes EPA to use available data and information on the anticipated residue levels of pesticide residues in food and the actual levels of pesticide chemicals that have been measured in food. If EPA relies on such information, EPA must require that data be provided 5 years after the tolerance is established, modified, or left in effect, demonstrating that the levels in food are not above the levels anticipated. Following the initial data submission, EPA is authorized to require similar data on a time frame it deems appropriate. As required by section 408(b)(2)(E) of the FFDCA, EPA will issue a Data CallIn for information relating to anticipated residues to be submitted no later than 5 years from the date of issuance of this tolerance.

Section 408(b)(2)(F) of the FFDCA states that the Agency may use data on the actual percent of food treated for assessing chronic dietary risk only if the Agency can make the following findings: Condition 1, that the data used are reliable and provide a valid basis to show what percentage of the food derived from such crop is likely to contain such pesticide residue; condition 2, that the exposure estimate does not underestimate exposure for any significant subpopulation group; and condition 3, if data are available on pesticide use and food consumption in a particular area, the exposure estimate does not understate exposure for the population in such area. In addition, the Agency must provide for periodic evaluation of any estimates used. To provide for the periodic evaluation of the estimate of PCT as required by section 408(b)(2)(F) of the FFDCA, EPA may require registrants to submit data on PCT.

The Agency used PCT information as follows.

Alfalfa 0.1%; apples 0.1%; apricot 0.02%; asparagus 5%; beans, lima 9%; beans/peas, dried 14%; beets, sugar 8%; broccoli 1%; cabbage 1%; canola 4%; cantaloupe 8%; carrots 2%; cauliflower 2%; cherries 0.4%; collards 2%; corn, field 0.1%; corn, sweet 0.5%; cotton 0.5%; cranberries 8%; cucumbers 6%; eggplant/peppers 5%; flax 38%; grapefruit 1%; grapes 1%; lemons 5%; lettuce 1%; nectarines 0.1%; oranges 3%; peaches 0.4%; peanuts 5%; peppers, bell 3%; peppers, chili 11%; pears 0.03%; peas, green 2%; potatoes 4%; potatoes, sweet 18%; pumpkins 8%; root/tuber vegetables (other than carrots, potatoes, and sugar beets) 5%; soybeans 2%; spinach 0.3%; squash 8%; strawberries 5%; sunflowers 14%; tomatoes 4%; vegetables, other 6%; watermelons 12%.

The Agency believes that the three conditions listed in Unit IV have been met. With respect to condition 1, PCT estimates are derived from Federal and private market survey data, which are reliable and have a valid basis. EPA uses a weighted average PCT for chronic dietary exposure estimates. This weighted average PCT figure is derived by averaging Statelevel data for a period of up to 10 years, and weighting for the more robust and recent data. A weighted average of the PCT reasonably represents a person's dietary exposure over a lifetime, and is unlikely to underestimate exposure to an individual because of the fact that pesticide use patterns (both regionally and nationally) tend to change continuously over time, such that an individual is unlikely to be exposed to more than the average PCT over a lifetime. For acute dietary exposure estimates, EPA uses an estimated maximum PCT. The exposure estimates resulting from this approach reasonably represent the highest levels to which an individual could be exposed, and are unlikely to underestimate an individual's acute dietary exposure. The Agency is reasonably certain that the percentage of the food treated is not likely to be an underestimation. As to conditions 2 and 3, regional consumption information and consumption information for significant subpopulations is taken into account through EPA's computerbased model for evaluating the exposure of significant subpopulations including several regional groups. Use of this consumption information in EPA's risk assessment process ensures that EPA's exposure estimate does not understate exposure for any significant sub population group and allows the Agency to be reasonably certain that no regional population is exposed to residue levels higher than those estimated by the Agency. Other than the data available through national food consumption surveys, EPA does not have available information on the regional consumption of food to which sethoxydim may be applied in a particular area.

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

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 Groundwater (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 1 model) before using PRZM/EXAMS (a Tier 2 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 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 percent reference dose (%RfD or percent population adjusted dose (%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 sethoxydim they are further discussed in the aggregate risk section Unit III. E.

Based on the FIRST and SCIGROW models the EECs of sethoxydim for [[Page 55865]]
acute exposures are estimated to be 100 parts per billion (ppb) for surface water and 1 ppb for ground water. The EECs for chronic exposures are estimated to be 20 ppb for surface water and 1 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). Sethoxydim is currently registered for use on the following residential nondietary sites: Ornamentals and flowering plants, recreational areas, and buildings/structures (nonagriculturaloutdoor). The risk assessment was conducted using the following exposure assumptions:

i. Residential handler. There is potential sethoxydim exposure to residential handlers who mix, load and apply sethoxydim for use on residential turf and ornamentals. Because dermal toxicity endpoints were not identified, only the following exposure scenarios were assessed:
[sbull] Adult inhalation exposure from mixing/loading/applying sethoxydim for spot treatment with a lowpressure handwand.
[sbull] Adult inhalation exposure from mixing/loading/applying sethoxydim for spot treatment with a hoseend sprayer.

ii. Residential postapplication. The labeled use pattern for sethoxydim only suggests spot treatments for nonagricultural sites (e.g., fence lines, at base of ornamental plantings, etc.). The Agency considered the potential residential postapplication exposure from spot treatment to be negligible. However, an exposure/risk assessment for broadcast turf treatment, using the applicable endpoints, was included in this assessment because there is no labeled recommendation against broadcast treatment of lawns. Sethoxydim treatment may take up to 3 weeks before visible burnback of turf is seen, and the previous risk assessment for other agricultural use sites included residential postapplication exposure from turf use.

Broadcast turf treatment would result in the potential for dermal (adults and children) and incidental oral exposure (children only) during postapplication activities. However, because the appropriate dermal toxicity endpoints for sethoxydim were not identified, and because inhalation is considered negligible for postapplication exposure, only the following postapplication exposure scenarios were assessed:

1. Incidental nondietary ingestion of pesticide residues on lawns from handtomouth transfer.

2. Incidental nondietary ingestion of residues from objectto mouth activities (pesticidetreated turfgrass).

3. Incidental nondietary ingestion of soil (base of pesticide treated ornamentals).

Postapplication exposures from various activities following lawn treatment are considered to be the most common and significant in residential settings.

The exposure via incidental nondietary ingestion involving other plant material (i.e., resulting from children's handling of treated ornamentals) may occur but is considered negligible.

The exposure and risk estimates for the three residential exposure scenarios are assessed for the day of application (day ``0'') because it is assumed that toddlers could contact the lawn immediately after application. On the day of application, it was assumed that 5% of the application rate is available from the turf grass as transferrable residue (20% for objecttomouth activities). Intermediateterm exposure is also expected (up to 6 months) because reapplications are not limited, and may be necessary to continue suppression of grass. The application rates used for turf and ornamental gardens are 0.33 and 0.49 lb active ingredient acres (ai/A) respectively.

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 sethoxydim 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 sethoxydim and any other substances and sethoxydim 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 sethoxydim 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 will 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.

2. Prenatal and postnatal sensitivity. EPA determined that there are no residual uncertainties for prenatal and/or postnatal toxicity based on the following:

i. There was evidence of qualitative susceptibility in the developmental rat study with the occurrence of more severe effects in the fetuses (tail abnormalities and delayed ossification) than the maternal animals (clinical signs of neurotoxicity). Tail abnormalities were also seen in the F1a and F1b offspring of the 2generation reproduction rat study. However, the degree of concern is low for the fetal effects in the developmental rat study since the fetal anomalies were seen only at the high dose 650 mg/kg/day which is close to the Limit Dose (LTD) (1,000 mg/kg/day). They were seen in the presence of maternal toxicity (clinical signs of neurotoxicity) and clear NOAELs/ LOAELs were established for maternal and developmental toxicities.

ii. Evidence of quantitative susceptibility was indicated in the 2 generation reproduction rat study, by a slightly higher decrease (11 13%) in the body weights of offspring during lactation as compared to an 810% decrease in the body weights of the parental animals. Again, the degree of concern is also low for the 2generation reproduction rat study since the LOAEL for offspring toxicity is based on a conservative determination of a minimal response in pup body weight decrements at the same dose that also caused decreases in body weights in the parental animals.

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iii. The developmental toxicity study in the rabbits did not exhibit either quantitative or qualitative susceptibility.

3. Conclusion. Exposure data for sethoxydim are complete or are estimated based on data that reasonably accounts for potential exposures. The toxicity data base, however, is not complete. Due to evidence of developmental (Tail) abnormalities in the rat developmental and reproductive studies, EPA has required submission of subchronic and developmental neurotoxicity studies. After reviewing the data base, EPA concluded that there was not a reliable basis for establishing an additional safety factor for the protection of children at a value different than the statutory default of 10X. Accordingly, EPA has retained the additional 10X FQPA safety factor in the form of a Data base Uncertainty Factor.

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 the U.S. EPA 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, OPP 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. Using the exposure assumptions discussed in this unit for acute exposure, the acute dietary exposure from food to sethoxydim will occupy 52% of the aPAD for the U.S. population, 92% of the aPAD for children aged 12 and 92% of the aPAD for children aged 3 5. In addition, there is potential for acute dietary exposure to sethoxydim 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 Sethoxydim Acute Food Surface Ground Population Subgroup aPAD (mg/ Exp mg/kg/ Water EEC Water EEC Acute DWLOC kg) day (ppb)¹ (ppb)¹ (ppb)² General U.S. population 0.18 0.096 100 1.0 2,940 Children 12 years 0.18 0.165 100 1.0 150 Children 35 years 0.18 0.165 100 1.0 152 ¹ The crop producing the highest risk level was used. ² Chronic DWLOC( [mu]g/L) = maximum chronic water exposure (mg/kg/day) x body weight (kg) water consumption (L) x 10³ mg/[mu]g.

2. Chronic risk. Using the exposure assumptions described in this unit for chronic exposure, EPA has concluded that exposure to sethoxydim from food will utilize 24% of the cPAD for the U.S. population, and 75% of the cPAD for infants <1 year old. Based on the use pattern, chronic residential exposure to residues of sethoxydim is not expected. In addition, there is potential for chronic dietary exposure to sethoxydim 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 cPAD, as shown in the following Table 4:
Table 4. Aggregate Risk Assessment for Chronic (NonCancer) Exposure to Sethoxydim. Chronic Surface Ground Chronic Population Subgroup cPAD (mg/ Food Exp mg/ Water EEC Water EEC DWLOC kg) kg/day (ppb)¹ (ppb)¹ (ppb)² General U.S. population 0.014 0.0038 20 1.0 358 Infants (<1 year) 0.014 0.0105 20 1.0 35.3 ¹ The crop producing the highest level was used. ² Chronic DWLOC ([mu]g/L) = [maximum chronic water exposure (mg/kg/day) x body weight (kg)] / [water consumption (L) x 10³ mg/[mu]g.]

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3. Shortterm risk (130 days). Shortterm aggregate exposure takes into account residential exposure plus chronic exposure to food and water (considered to be a background exposure level).

Sethoxydim is currently registered for uses that could result in shortterm residential exposure and the Agency has determined that it is appropriate to aggregate chronic food and water and shortterm exposures for sethoxydim.

Using the exposure assumptions described in this unit for short term exposures, EPA has concluded that food and residential exposures aggregated result in aggregate MOEs of greater than 1,000 for all exposure scenarios in children aged 12 years, which includes oral handtomouth, oral objecttomouth and soil ingestion. These aggregate MOEs do not exceed the Agency's level of concern for aggregate exposure to food and residential uses. Shortterm aggregate risk assessments were not calculated for adult handlers because oral and inhalation endpoints lack a common toxicity endpoint. The children 12 yearsof age scenario was chosen because it was the highest estimated food exposure and thus, also protective of children 35 years of age. In addition, shortterm DWLOCs were calculated and compared to the EECs for chronic exposure of sethoxydim in ground and surface water. After calculating DWLOCs and comparing them to the EECs for surface water and ground water, EPA does not expect shortterm aggregate exposure to exceed the Agency's level of concern, as shown in the following Table 5:
Table 5.A

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.