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This listing is not intended to be exhaustive, but rather provides a guide for readers regarding entities likely to be affected by this action. Other types of entities not listed in 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. 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 Access Electronic Copies of This Document and Other Related Information?

In addition to using EDOCKET (http://www.epa.gov/edocket/), 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 ECFR Beta Site Two at http://www.gpoaccess.gov/ecfr/. To access the OPPTS Harmonized Guidelines referenced in this document, go directly to the guidelines at http://www.epa.gpo/opptsfrs/home/guidelin.htm/ .

II. Background and Statutory Findings

In the Federal Register of June 2, 2004 (69 FR 31110) (FRL73611), EPA issued a notice pursuant to section 408(d)(3) of FFDCA, 21 U.S.C. 346a(d)(3), announcing the filing of pesticide petitions (PP 2E6363, 3E6781, 3E6800, 3E6805, 3E6806, 3E6807, 4E6819, and 0F6142) by Syngenta Crop Protection, Inc., P.O. Box 18300 Greensboro, NC 274198300, and Interregional Research Project 4 (IR4), 681 US Highway 1 South, North Brunswick, NJ 089023390. The petitions requested that 40 CFR 180.565 be amended by establishing tolerances for combined residues of the insecticide thiamethoxam, 3[(2chloro5thiazolyl)methyl]tetrahydro5 methylNnitro4H1,3,5oxadiazin4imine and its metabolite CGA322704 (N(2chlorothiazol5ylmethyl)N`methylN'`nitroguanidine), in or on legume vegetables group 6 at 0.02 parts per million (ppm) (3E6805), peppermint and spearmint at 4.0 ppm (2E6363); root vegetables (except sugar beet) crop subgroup 1B at 0.1 ppm and for radish tops at 0.80 ppm (4E6819); strawberry at 0.30 ppm (3E6800); cranberry at 0.01 ppm (3E6781); bushberry crop subgroup 13B and juneberry, lingonberry and salal at 0.25 ppm (3E6807); rapeseed seed, mustard seed, flax seed, safflower seed, crambe seed, and borage seed at 0.02 ppm (3E6806); and potato at 0.25 ppm (0F6142). In addition, due to the establishment of the individual tolerance for potato, it was requested that the tolerance expression for tuberous and corm crop subgroup 1C be revised to a tolerance expression for tuberous and corm (except potato) crop subgroup 1D. That notice included a summary of these petitions prepared by Syngenta Crop Protection, Inc. and IR4, the registrant. As a result of the residue data submitted to support these requests, the proposed tolerance level for peppermint and spearmint was subsequently revised to 1.5 ppm; the proposed tolerance level for root vegetables (except sugar beet) crop subgroup 1B was subsequently revised to 0.02 ppm; the proposed tolerance level for bushberry crop subgroup 13B and juneberry, lingonberry and salal was subsequently revised to 0.20 ppm; and the proposed tolerance for cranberry was revised to 0.02 ppm. There were no comments received in response to the notice of filing.

Section 408(b)(2)(A)(i) of 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 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 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 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 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 FFDCA, for a tolerance for combined residues of thiamethoxam and its metabolite CGA322704 on legume vegetables group 6 at 0.02 ppm, peppermint and spearmint at 1.5 ppm; root vegetables (except sugar beet) crop subgroup 1B at 0.02 ppm and for radish tops at 0.80 ppm; strawberry at 0.30 ppm; cranberry at 0.02 ppm; bushberry crop subgroup 13B and juneberry, lingonberry and salal at 0.20 ppm; rapeseed seed, mustard seed, flax seed, safflower seed, crambe seed, and borage seed at 0.02 ppm; and potato at 0.25 ppm. In addition, due to the establishment of the individual tolerance for potato, it was requested that the tolerance expression for tuberous and corm crop subgroup 1C be revised to a tolerance expression for tuberous and corm (except potato) crop subgroup 1D. EPA's assessment of exposures and risks associated with establishing the tolerance follows.

In assessing the human health risks associated with the existing and proposed uses of thiamethoxam, EPA has included exposure to thiamethoxam as well as its metabolite CGA322704 when evaluating exposure from the dietary (food only) pathway. This approach was developed when the Agency received the first fooduse request for registration of thiamethoxam and determined that the CGA322704 metabolite/degradate, as well as the parent compound, are residues of concern in food; no exposure to CGA322704 in drinking water was considered likely following application of thiamethoxam. At the time, toxicological information regarding CGA322704 was not available, and it was assumed that thiamethoxam and this metabolite are
toxicologically equivalent for estimation of dietary risk. Subsequently, the Agency received a petition requesting registration of the insecticide clothianidin. Upon review of that petition, the Agency discovered that CGA322704 and clothianidin are identical. With the registration of clothianidin uses, the Agency has largely complete toxicological databases for both thiamethoxam and CGA322704 (referred to in the remainder of this rule as clothianidin). While some of the toxic effects observed following dosing with the two active ingredients are similar, it is not clear that they are toxicologically equivalent.

To date, the Agency has not formally examined the toxicity data to determine if it is appropriate to separate exposure to the parent compound thiamethoxam
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from exposure to thiamethoxam's metabolite clothianidin when assessing the aggregate risk associated with thiamethoxam tolerances. Therefore, EPA has taken the very conservative approach of analzying the non cancer risk of thiamethoxam by both (1) aggregating exposure to thiamethoxam and its metabolite clothianidin resulting from use of thiamethoxam and clothianidin residues resulting from use of clothianidin as an active ingredient and comparing this aggregate exposure to relevant endpoints for thiamethoxam; and (2) aggregating exposure to clothianidin resulting from thiamethoxam use and from use of clothianidin as an active ingredient and comparing this aggregate exposure to relevant endpoints for clothianidin. EPA has taken the further conservative step of assuming that, in instances where both thiamethoxam and clothianidin are registered for use on a crop, both pesticides will, in fact, be used on that crop. Despite this very conservative approach, thiamethoxam noncancer risks (taking into account clothianidin exposure) are well below the Agency's level of concern (LOC).

Pending formal reconsideration of toxicological equivalency for thiamethoxam and the clothianidin metabolite, aggregate risks from both thiamethoxam and clothianidin are presented below.

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 thiamethoxam as well as the no observed adverse effect level (NOAEL) and the lowest observed adverse effect level (LOAEL) from the toxicity studies reviewed are discussed in the Federal Register of September 17, 2003 (68 FR 54386) (FRL73275). The nature of the toxic effects caused by the metabolite clothianidin are discussed in the Federal Register of May 30, 2003 (68 FR 32390) (FRL73068).

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 toxicological LOC. However, the LOAEL is sometimes used for risk assessment if no NOAEL was achieved in the toxicology study selected. An uncertainty factor (UF) is applied to reflect uncertainties inherent in the extrapolation from laboratory animal data to humans and in the variations in sensitivity among members of the human population as well as other unknowns. An UF of 100 is routinely used, 10X to account for interspecies differences and 10X for intraspecies differences.

Three other types of safety or uncertainty factors may be used: ``Traditional uncertainty factors;'' the ``special FQPA safety factor;'' and the ``default FQPA safety factor.'' By the term ``traditional uncertainty factor,'' EPA is referring to those additional uncertainty factors used prior to FQPA passage to account for database deficiencies. These traditional uncertainty factors have been incorporated by the FQPA into the additional safety factor for the protection of infants and children. The term ``special FQPA safety factor'' refers to those safety factors that are deemed necessary for the protection of infants and children primarily as a result of the FQPA. The ``default FQPA safety factor'' is the additional 10X safety factor that is mandated by the statute unless it is decided that there are reliable data to choose a different additional factor (potentially a traditional uncertainty factor or a special FQPA safety factor).

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 an UF of 100 to account for interspecies and intraspecies differences and any traditional uncertainty factors deemed appropriate (RfD = NOAEL/UF). Where a special FQPA safety factor or the default FQPA safety factor is used, 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 safety factor.

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). An example of how such a probability risk is expressed would be to describe the risk as one in one hundred thousand (1 x 10\5\), one in a million (1 x 10\6\), or one in ten million (1 x 10\7\). 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 thiamethoxam used for human risk assessment is shown in Table 1 of this unit:
Table 1.Summary of Toxicological Dose and Endpoints for Thiamethoxam for Use in Human Risk Assessment Dose Used in Risk FQPA SF and LOC for Study and Toxicological Exposure Scenario Assessment, UF Risk Assessment Effects Acute dietary (general population NOAEL = 100 mg/kg/day FQPA SF = 10 Acute mammalian including infants and children) UF = 100............... aPAD = acute RfD / FQPA neurotoxicity study in Acute RfD = 1 mg/kg/day SF. the rat = 0.1 mg/kg/day........ LOAEL = 500 mg/kg/day based on treatment related neurobehavioral effects observed in the FOB and LMA testing (drooped palpebral closure, decreased rectal temperature and locomotor activity, increased forelimb grip strength) [[Page 711]]
Chronic dietary (all populations) NOAEL = 0.6 mg/kg/day FQPA SF = 10 2Generation UF = 100............... cPAD = chronic RfD / reproduction study Chronic RfD = 0.006 mg/ FQPA SF. LOAEL = 1.8 mg/kg/day kg/day. = 0.0006 mg/kg/day.... based on increased incidence and severity of tubular atrophy in testes of F\1\ generation males. Oral nondietary (all durations) NOAEL = 0.6 mg/kg/day Residential LOC for MOE 2Generation = 1,000 reproduction study LOAEL = 1.8 mg/kg/day based on increased incidence and severity of tubular atrophy in testes of F\1\ generation males. Dermal (all durations) Oral study Resdiential LOC for MOE 2Generation NOAEL = 0.6 mg/kg/day = 1,000 reproduction study (dermal absorption LOAEL = 1.8 mg/kg/day rate = 27%). based on increased incidence and severity of tubular atrophy in testes of F\1\ generation males. Inhalation (all durations) Oral study NOAEL = 0.6 Residential LOC for MOE 2Generation mg/kg/day(inhalation = 1,000 reproduction study absorption rate = LOAEL = 1.8 mg/kg/day 100%) based on increased incidence and severity of tubular atrophy in testes of F\1\ generation males. Cancer (oral, dermal, inhalation) Likely carcinogen for humans based on increased incidence of hepatocellular adenomas and carcinomas in male and female mice. Quantification of risk based on most potent unit risk: Male mouse liver adenoma and/or carcinoma combined tumor rate. The upper bound estimate of unit risk, Q1* (mg/kg/day)\\2 is 3.77 x 10\\2 in human equivalents.

A summary of the toxicological endpoints for the metabolite clothianidin used for human risk assessment is shown in Table 2 of this unit:
Table 2.Summary of Toxicological Dose and Endpoints for Clothianidin for Use in Human Risk Assessment Dose Used in Risk Assessment,
Exposure Scenario Interspecies and Special FQPA SF and LOC Study and Toxicological Intraspecies and any for Risk Assessment Effects Traditional UF
Acute dietary (Females 1350 years of Developmental NOAEL = FQPA SF = 1 Developmental rabbit age) 25 mg/kg/day aPAD = acute RfD / FQPA study UF = 1,000............. SF. Developmental LOAEL = Acute RfD = 0.025 mg/kg = 0.025 mg/kg.......... 75 mg/kg/day based on an increased litter incidence of a missing lobe of the lung. Acute dietary (General population) NOAEL = 25 mg/kg/day FQPA SF = 1 Special Neurotoxicity/ UF = 1,000............. aPAD = acute RfD / FQPA Pharmacology Study in Acute RfD = 0.025 mg/kg SF. Mice and Rats = 0.025 mg/kg.......... LOAEL = 50 mg/kg based on transient signs of decreased spontaneous motor activity, tremors and deep respirations. Chronic dietary (All populations) Offspring NOAEL = 9.8 FQPA SF = 1 2Generation mg/kg/day cPAD = chronic RfD / Reproduction Study UF = 1,000............. FQPA SF = 0.0098 mg/kg/ Offspring LOAEL = 31.2 Chronic RfD = 0.0098 mg/ day. mg/kg/day based on kg/day. decreased mean body weight gain and delayed sexual maturation, decreased absolute thymus weights in F\1\ pups and an increase in stillbirths in both generations. Incidental Oral (All durations) NOAEL = 9.8 mg/kg/day Residential LOC for MOE 2Generation = 1,000 reproduction study Offspring LOAEL = 31.2 mg/kg/day based on decreased mean body weight gain and delayed sexual maturation, decreased absolute thymus weights in F\1\ pups and an increase in stillbirths in both generations. [[Page 712]]
Dermal (All durations) Oral study Residential LOC for MOE 2Generation NOAEL = 9.8 mg/kg/day = 1,000 reproduction study (dermal absorption Offspring LOAEL = 31.2 rate = 1%). mg/kg/day based on decreased mean body weight gain and delayed sexual maturation, decreased absolute thymus weights in F\1\ pups and an increase in stillbirths in both generations. Inhalation (All durations) Oral study Residential LOC for MOE 2Generation NOAEL = 9.8 mg/kg/day = 1,000 reproduction study (inhalation absorption Offspring LOAEL = 31.2 rate = 100%). mg/kg/day based on decreased mean body weight gain and delayed sexual maturation, decreased absolute thymus weights in F\1\ pups and an increase in stillbirths in both generations. Cancer (oral, dermal, inhalation) Classification: Not likely to be carcinogenic to humans. C. Exposure Assessment

1. Dietary exposure from food and feed uses. Tolerances have been established (40 CFR 180.565) for the combined residues of thiamethoxam and its metabolite clothianidin in or on a variety of raw agricultural commodities. Tolerances for thiamethoxam are established on barley, canola, cotton, sorghum, wheat, imported coffee, pecan, stone fruit, succulent bean, sunflower, tuberous and corm vegetables crop subgroup, fruiting vegetables, crop group, tomato paste, cucurbit vegetables crop group, pome fruits crop group, field corn forage, field corn stover, sweet corn stover, field corn grain, popcorn grain, sweet corn (kernal and cob with husk removed), milk, and the meat and meat by products of cattle, goats, horses, and sheep. Since clothianidin is a major metabolite of thiamethoxam, residues of clothianidin that would theoretically result from registered and pending uses of clothianidin and residues that would theoretically result from the metabolism of thiamethoxam are included in the analysis. Risk assessments were conducted by EPA to assess dietary exposures from thiamethoxam 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 1day or single exposure. In conducting the acute dietary risk assessment EPA used the Dietary Exposure Evaluation Model software with the Food Commodity Intake Database (DEEMFCID\TM\), which incorporates food consumption data as reported by respondents in the United States Department of Agriculture (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 acute exposure assessments: EPA conducted the acute dietary exposure analysis based on highly conservative assumptions. The residues of concern for the acute analysis are thiamethoxam and its metabolite clothianidin. The assessment for thiamethoxam assumed that 100% of the registered and proposed crops were treated and that all treated crops and livestock had residues of concern at the tolerance level. The general U.S. population and all population subgroups have exposure and risk estimates which are below EPA's LOC (i.e., the aPADs are all below 100%). The most highly exposed subgroup is children 1 to 2 years of age. The exposure estimate for children 1 to 2 years of age is 0.01099 mg/kg/day, which is equivalent to 11% of the aPAD.

For the metabolite clothianidin, the acute analysis is a conservative assessment that was based on tolerance level residues and the assumption of 100 percent crop treated (PCT) for established and proposed clothianidin uses. For the commodities that have both thiamethoxam tolerances and established or proposed clothianidin tolerances (i.e., sweet corn, field corn, pop corn, canola, milk, and pome fruit), the proposed clothianidin tolerances are added to the residues that could result from use of thiamethoxam. The general U.S. population and all population subgroups have exposure and risk estimates which are below EPA's LOC (i.e., the aPADs are all below 100%). The most highly exposed population subgroup is infants less than 1 year old, which utilizes 80% of the aPAD.

ii. Chronic exposure. In conducting the chronic dietary risk assessment EPA used the DEEMFCID\TM\, which incorporates food consumption data as reported by respondents in the USDA 19941996 and 1998 Nationwide CSFII, and accumulated exposure to the chemical for each commodity. The following assumptions were made for the chronic exposure assessments: The residues of concern for the chronic analysis are thiamethoxam and its metabolite clothianidin. The chronic analysis for thiamethoxam was based on anticipated residues in the form of average field trial residue values, and the analysis included percent crop estimates. The general U.S. population and all population subgroups have exposure and risk estimates which are below EPA's LOC (i.e., the cPADs are all below 100%). The most highly exposed subgroup is children 1 to 2 years of age. The exposure estimate for children 1 to 2 years of age is 0.000103 mg/kg/day, which is equivalent to 17% of the cPAD.

For clothianidin, the chronic analysis is a relatively conservative assessment that was based on tolerance level residues and the assumption of 100% crop treated for established and proposed clothianidin uses, with the exception of anticipated residues (AR) for apples and pears. For the commodities that have both thiamethoxam tolerances and established or proposed clothianidin tolerances (i.e., sweet corn, field corn, pop corn, canola, and milk), the
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proposed clothianidin tolerances are added to the residues that could result from use of thiamethoxam. For apples and pears, the highest average field trial (HAFT) levels from the residue field trials were added to the residues that could result from use of thiamethoxam. The general U.S. population and all population subgroups have exposure and risk estimates which are below EPA's LOC (i.e., the cPADs are all below 100%). The most highly exposed population subgroup is children 1 to 2 years of age, which utilizes 15% of the cPAD.

iii. Cancer. The residue of concern for the cancer analysis is thiamethoxam, per se. The residues of its metabolite clothianidin were removed from the cancer analysis because the metabolite was found to be ``not likely to be carcinogenic to humans'' when it was evaluated as an active ingredient. The cancer analysis was based on average field trial residue values as well as PCT estimates. The estimated dietary exposure to the U.S. population is 0.000263 mg/kg/day.

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 pursuant to section 408(f)(1) 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. For the present action, EPA will issue such data callins for information relating to anticipated residues as are required by FFDCA section 408(b)(2)(E) and authorized under FFDCA section 408(f)(1). Such data callins will be required to be submitted no later than 5 years from the date of issuance of this tolerance.

Section 408(b)(2)(F) of 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 FFDCA, EPA may require registrants to submit data on PCT.

The Agency used PCT information as follows:For existing uses, the Agency used estimates of PCT for the chronic exposure assessment which was determined using USDA's National Agricultural Statistics Service (NASS) Usage Data (19992003) and EPA Proprietary Usage Data (2001 2003). The chronic PCT estimates that were used for existing uses are shown in Table 3:
Table 3.Thiamethoxam Estimates of Crop Treated for Existing Uses Percent Crop Commodity Treated Apples............................................... 5 Barley............................................... 1 Canola............................................... 55 Cantaloupes.......................................... 13 Casabas.............................................. 44 Cottonseed........................................... 20 Crabapples........................................... 20 Cucumbers............................................ 5 Field corn, grain.................................... 6 Fruiting vegetables (except cucurbits Crop group 8) 15 Honeydew melons...................................... 13 Loquats.............................................. 53 Pears................................................ 9 Popcorn.............................................. 6 Potatoes............................................. 41 Pumpkins............................................. 44 Quinces.............................................. 53 Sorghum (including milo)............................. 9 Squash............................................... 44 Sunflowers........................................... 25 Sweet corn........................................... 6 Tuberous and Corm Vegetables Crop subgroup 1C 33 (except potatoes)...................................
Watermelons.......................................... 13 Wheat................................................ 2

For the new uses, the Agency used PCT estimates for the chronic exposure assessment based on usage data and market share projections as follows. Market share projections for the new uses for thiamethoxam were obtained from the registrant and compared to 19992003 USDA NASS Usage Data and EPA 20012003 Proprietary Usage Data for the historically, most widely used insecticide for control of insect pests for each crop. As a result of this comparison, the highest, most conservative PCT estimate for each crop was used for the chronic exposure assessment. These highly conservative estimates should not underestimate actual usage of thiamethoxam on the new crops/sites. To further support the reliability of these PCT estimates, as a condition of registration, the registrant will be required to agree to report annually on the market share attained for the new uses for which thiamethoxam is registered. As a condition of registration, they will also be required to agree to mitigate dietary risk as deemed appropriate by the Agency should the market share data raise a concern for increased dietary risk. The Agency will then compare that market share information with the PCT estimates used to evaluate potential dietary risk. In those instances where percent market share is approaching or exceeding the predicted PCT estimate used in the Agency's risk assessment, EPA will conduct a new dietary risk assessment to evaluate the new dietary risk. If the market share data raise a concern for increased pesticide risk, the Agency will act to mitigate that dietary risk and could employ several approaches, including but not limited to production caps, geographical limitations, removal of uses, or other means deemed appropriate by the Agency. The chronic PCT estimates that were used for existing uses are shown in Table 4:
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Table 4.Thiamethoxam Estimates of Crop Treated for New Uses Percent Crop Commodity Treated Beans, lima.......................................... 38 Beans, snap.......................................... 37 Bushberries.......................................... 55 Carrots.............................................. 20 Cranberries.......................................... 29 Mint................................................. 9 Peas, green processed................................ 36 Peas (including dried peas).......................... 44 Soybeans............................................. 11 Strawberries......................................... 46

The Agency believes that the three conditions listed in this Unit III. 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. 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 subpopulation 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 thiamethoxam 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 thiamethoxam 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 thiamethoxam.

The Agency uses the FQPA Index Reservoir Screening Tool (FIRST) or the Pesticide Root Zone Model/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 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. Both FIRST and PRZM/EXAMS incorporate an index reservoir environment, and both models include 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 screen for sorting out pesticides for which it is unlikely that drinking water concentrations would 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), which are the model estimates of a pesticide's concentration in water. EECs derived from these models are used 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 thiamethoxam they are further discussed in the aggregate risk sections in Unit E.

Based on the PRZM/EXAMS and SCIGROW models, the EECs of thiamethoxam for acute exposures are estimated to be 11.4 parts per billion (ppb) for surface water and 5 ppb for ground water. The EECs for chronic noncancer exposures are estimated to be 0.77 ppb for surface water and 1.94 ppb for ground water. The EECs for cancer exposures are estimated to be 0.31 ppb for surface water and 1.94 ppb for ground water.

Clothianidin is not a significant degradate of thiamethoxam in water. Therefore, residues of clothianidin in water were estimated based on applications of clothianidin as an active ingredient. Based on the FIRST and SCIGROW models, the EECs of clothianidin for acute exposures are estimated to be 7.29 parts per billion (ppb) for surface water and 5.84 ppb for ground water. The EECs for chronic exposures are estimated to be 1.35 ppb for surface water and 5.84 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). Thiamethoxam is not registered for use on any sites that would result in residential exposure.

Clothianidin is currently registered for use on turfgrasses. Exposures and risk resulting from clothianidin residues on turfgrasses are included in the aggregate risk assessment for clothianidin.

4. Cumulative effects from substances with a common mechanism of toxicity. Section 408(b)(2)(D)(v) of 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.''

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 thiamethoxam and any other substances and thiamethoxam 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 thiamethoxam has a common mechanism of toxicity with other substances. For information regarding EPA's efforts to determine
[[Page 715]]
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 OPP concerning common mechanism determinations and procedures for cumulating effects from substances found to have a common mechanism on EPA's Web site at http://www.epa.gov/pesticides/cumulative/ .

D. Safety Factor for Infants and Children

1. In general. Section 408 of 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 based on reliable data 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. In applying this provision, EPA either retains the default value of 10X when reliable data do not support the choice of a different factor, or, if reliable data are available, EPA uses a different additional safety factor value based on the use of traditional uncertainty factors and/or special FQPA safety factors, as appropriate.

2. Prenatal and postnatal sensitivity. The developmental toxicity studies indicated no quantitative or qualitative evidence of increased susceptibility of rat or rabbit fetus to in utero exposure based on the fact that the developmental NOAELs are either higher than or equal to the maternal NOAELs. However, the reproductive studies indicate effects in males rats in the form of increased incidence and severity of testicular tubular atrophy. These data are considered to be evidence of increased quantitative susceptibility for male pups when compared to the parents.

3. Conclusion. There is a complete toxicity data base for thiamethoxam and exposure data are complete or are estimated based on data that reasonably accounts for potential exposures. EPA determined that the 10X special safety factor to protect infants and children should be retained, based on the following factors: Effects on endocrine organs observed across species; the significant decrease in alanine amino transferase levels in the companion animal studies and in the dog studies; the mode of action of this chemical in insects (interferes with the nicotinic acetyl choline receptors of the insect's nervous system); the transient clinical signs of neurotoxicity in several studies across species; and the suggestive evidence of increased quantitative susceptibility in the rat reproduction study. 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 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 EPA's Office of Water are used to calculate DWLOCs: 2 liter (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. Using the exposure assumptions discussed in this unit for acute exposure, the acute dietary exposure from food to thiamethoxam will occupy 4% of the aPAD for the U.S. population, 2% of the aPAD for females 13 years and older, 10% of the aPAD for infants less than one year old, and 11% of the aPAD for children 1 to 2 years old. In addition, there is potential for acute dietary exposure to thiamethoxam 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 Table 5 of this unit:
Table 5.Aggregate Risk Assessment for Acute Exposure to Thiamethoxam Surface Ground Population Subgroup aPAD (mg/ % aPAD Water EEC Water EEC Acute DWLOC kg) (Food) (ppb) (ppb) (ppb) General U.S. Population........................ 0.1 4 11.4 5 3,400 All infants (less than one year old)........... 0.1 10 11.4 5 900 Children 12 years old......................... 0.1 11 11.4 5 890 Females 1349 years old........................ 0.1 2 11.4 5 2,900 [[Page 716]]

Sources of clothianidin residues in food include uses of both thiamethoxam and clothianidin. Toxicological doses and endpoints for clothianidin were used to calculate risk. The acute dietary exposure from food to the metabolite clothianidin will occupy 18% of the aPAD for the U.S. population, 12% of the aPAD for females 13 years and older, 80% of the aPAD for infants less than one year old, and 60% of the aPAD for children 1 to 2 years old. In addition, there is potential for acute dietary exposure to clothianidin 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 aPAD, as shown in Table 6 of this unit:
Table 6.Aggregate Risk Assessment for Acute Exposure to Clothianidin Surface Ground Population Subgroup aPAD (mg/ % aPAD Water EEC Water EEC Acute DWLOC kg) (Food) (ppb) (ppb) (ppb) General U.S. Population........................ 0.025 18 7.29 5.84 710 All infants (less than one year old)........... 0.025 80 7.29 5.84 48 Children 12 years old......................... 0.025 60 7.29 5.84 92 Females 1349 years old........................ 0.025 12 7.29 5.84 640

2. Chronic risk. Using the exposure assumptions described in this unit for chronic exposure, EPA has concluded that exposure to thiamethoxam from food will utilize 6% of the cPAD for the U.S. population, 11% of the cPAD for infants less than one year old, and 17% of the cPAD for children 1 to 2 years old. There are no residential uses for thiamethoxam that result in chronic residential exposure to thiamethoxam. In addition, there is potential for chronic dietary exposure to thiamethoxam 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 Table 7 of this unit:
Table 7.Aggregate Risk Assessment for Chronic (NonCancer) Exposure to Thiamethoxam Surface Ground Population Subgroup cPAD (mg/ % cPAD Water EEC Water EEC Chronic kg) (Food) (ppb) (ppb) DWLOC (ppb) U.S. population................................ 0.0006 6 0.77 1.94 20 All infants (less than one year old)........... 0.0006 11 0.77 1.94 5.4 Children 12 years old......................... 0.0006 17 0.77 1.94 5 Females 1349 years old........................ 0.0006 5 0.77 1.94 17

Sources of clothianidin residues in food include uses of both thiamethoxam and clothianidin. Toxicological doses and endpoints for clothianidin were used to calculate risk. Exposure to the metabolite clothianidin from food will utilize 6% of the cPAD for the U.S. population, 13% of the cPAD for infants less than one year old, and 15% of the cPAD for children 1 2 years old. Combined residential exposure estimates range from an MOE of 1,300 for combined oral and dermal exposure to toddlers (treated turf + treated soil + dermal) to 8,900 for dermal exposure to adults (application + postapplication) adults. In addition, there is potential for chronic dietary exposure to the metabolite clothianidin 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 Table 8 of this unit:
Table 8.Aggregate Risk Assessment for Chronic (NonCancer) Exposure to Clothianidin Surface Ground Population Subgroup cPAD (mg/ % cPAD Water EEC Water EEC Chronic kg) (Food) (ppb) (ppb) DWLOC (ppb) U.S. population................................ 0.0098 6 1.35 5.84 320 All infants (less than one year old)........... 0.0098 13 1.35 5.84 85 Children 12 years old......................... 0.0098 15 1.35 5.84 83 Females 1349 years old........................ 0.0098 5 1.35 5.84 280 Adults 50+ years old........................... 0.0098 5 1.35 5.84 330 [[Page 717]]

3. Shortterm risk. Shortterm aggregate exposure takes into account residential exposure plus chronic exposure to food and water (considered to be a background exposure level). Thiamethoxam is not registered for use on any sites that would result in residential exposure. Therefore, the aggregate risk is the sum of the risk from food and water, which do not exceed the Agency's LOC.

Shortterm aggregate exposures from the metabolite clothianidin result in aggregate MOEs of 5,900 for the general U.S. population, 1,100 for children 1 to 2 years old, and 6,200 for females 13 to 49 years old. These aggregate MOEs do not exceed the Agency's LOC for aggregate exposure to food and residential uses. In addition, short term DWLOCs were calculated and compared to the EECs for chronic exposure of clothianidin 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 LOC, as shown in Table 9 of this unit:
Table 9.Aggregate Risk Assessment for ShortTerm Exposure to Clothianidin Aggregate Surface Ground Population Subgroup MOE (Food + Aggregate Water EEC Water EEC ShortTerm Residential) LOC (ppb) (ppb) DWLOC (ppb) General U.S. population....................... 5,900 1,000 1.35 5.84 280 Children 12 years old........................ 1,100 1,000 1.35 5.84 8.7 Females 1349 years old....................... 6,200 1,000 1.35 5.84 250

4. Intermediateterm risk. Intermediateterm aggregate exposure takes into account residential exposure plus chronic exposure to food and water (considered to be a background exposure level). Thiamethoxam is not registered for use on any sites that would result in residential exposure. Therefore, the aggregate risk is the sum of the risk from food and water, which do not exceed the Agency's LOC.

Intermediateterm aggregate exposures from the metabolite clothianidin result in aggregate MOEs of 5,900 for the general U.S. population, 1,100 for children 1 to 2 years old, and 6,200 for females 13 to 49 years old. These aggregate MOEs do not exceed the Agency's LOC for aggregate exposure to food and residential uses. In addition, intermediateterm DWLOCs were calculated and compared to the EECs for chronic exposure of clothianidin in ground water and surface water. After calculating DWLOCs and comparing them to the EECs for surface water and ground water, EPA does not expect intermediateterm aggregate exposure to exceed the Agency's LOC, as shown in Table 10 of this unit: Table 10.Aggregate Risk Assessment for IntermediateTerm Exposure to Clothianidin Aggregate Surface Ground Intermediate Population Subgroup MOE (Food + Aggregate Water EEC Water EEC Term DWLOC Residential) LOC (ppb) (ppb) (ppb) General U.S. population..................... 5,900 1,000 1.35 5.84 280 Children 12 years old...................... 1,100 1,000 1.35 5.84 8.7 Females 1349 years old..................... 6,200 1,000 1.35 5.84 250

5. Aggregate cancer risk for U.S. population. In conducting the aggregate cancer risk assessment, only dietary and drinking water pathways of exposure were considered. At this time, there are no uses for thiamethoxam that would result in any nonoccupational, nondietary exposure (i.e., there are no dermal or inhalation routes of exposure that should be included in an aggregate assessment). A DWLOC was derived for the general U.S. population based on EPA's LOC for cancer or a risk in the range of 1 in 1 million. The DWLOC is compared to the estimated environmental concentrations of thiamethoxam in surface and ground water and is used to determine whether or not aggregate cancer exposures are likely to result in risk estimates that exceed EPA's LOC. Table 11 of this unit summarizes the drinking water estimated concentrations of thiamethoxam in surface water and ground water and the associated DWLOC for cancer:
Table 11.Aggregate Risk Assessment for Cancer Exposure to Thiamethoxam Maximum Maximum Food Water Cancer Ground Surface Population Subgroup Exposure mg/ Exposure mg/ Exposure mg/ DWLOC ppb Water EEC Water EEC kg/day kg/day kg/day ppb ppb General U.S. population...

FOR FURTHER INFORMATION CONTACT Dani Daniel, Registration Division (7505C), Office of Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 204600001; telephone number: (703) 3055409; email address: daniel.dani@epa.gov.