1 of 66 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D. C. 20460 OFFICE OF PREVENTION, PESTICIDES AND TOXIC SUBSTANCES Date: 7/ 13/ 06 MEMORANDUM SUBJECT: S metolachlor Human Health Risk Assessment for Proposed Section 18 Uses on Cilantro, Collards, Kale, and Mustard Greens; Section 3 Use on Pumpkin; and Tolerance on Winter Squash without a US Registration. PC Code: 108800 Smetolachlor & 108801 Metolachlor, ID#: 06OH05 & PP# 5E7015, DP Numbers: 329117 & 326011.

Regulatory Action: Section 18, Section 3, and Tolerance without US Registration Risk Assessment Type: Single Chemical Aggregate FROM: W. Cutchin, Chemist ARIA Team/ Technical Review Branch Registration Division ( 7505P)

THROUGH: Christina Swartz, Chief Registration Action Branch Health Effects Division ( 7509P)

TO: Barbara Madden/ A. Ertman PM 5 Risk Integration Minor Use and Emergency Response Branch Registration Division ( 7505P) 2 of 66 Table of Contents 1.0 Executive Summary................................................................................................................................ 3 2.0 Ingredient Profile......................................................................................................................................... 11 2.1 Summary of Registered/ Proposed Uses................................................................................................... 11 2.2 Structure and Nomenclature ................................................................................................................... 11 2.3 Physical and Chemical Properties ........................................................................................................... 12 3.0 Hazard Characterization/ Assessment ......................................................................................................... 12 3.1 Hazards and Dose Response Characterization ....................................................................................... 12 3.2 FQPA Considerations .............................................................................................................................. 17 3.3 Dose Response Assessment ...................................................................................................................... 17 3.4 Endocrine Disruption .............................................................................................................................. 21 4.0 Dietary Exposure/ Risk Characterization.................................................................................................... 21 4.1 Pesticide Metabolism and Environmental Degradation.......................................................................... 21 4.1.1 Metabolism in Primary Crops .......................................................................................................... 21 4.1.2 Metabolism in Rotational Crops ....................................................................................................... 22 4.1.3 Metabolism in Livestock ................................................................................................................... 22 4.1.4 Analytical Methodology .................................................................................................................... 22 4.1.5 Environmental Degradation.............................................................................................................. 23 4.1.6 Comparative Metabolic Profile......................................................................................................... 23 4.1.8 Pesticide Metabolites and Degradates of Concern............................................................................ 23 4.1.9 Drinking Water Residue Profile ....................................................................................................... 24 4.1.10 Food Residue Profile ....................................................................................................................... 25 4.2.11 International Residue Limits....................................................................................................... 27 4.3 Dietary Exposure and Risk...................................................................................................................... 27 5.0 Residential ( Non Occupational) Exposure/ Risk Characterization............................................................. 29 5.1 Residential Handler Exposure................................................................................................................. 29 5.2 Residential Postapplication Exposure ..................................................................................................... 29 5.3 Other ( Spray Drift, etc.) .......................................................................................................................... 30 6.0 Aggregate Risk Assessments and Risk Characterization............................................................................ 30 6.1 Acute Aggregate Risk .............................................................................................................................. 30 6.2 Short Term Aggregate Risk .................................................................................................................... 30 6.3 Intermediate Term Aggregate Risk ........................................................................................................ 31 6.4 Chronic Aggregate Risk........................................................................................................................... 31 6.5 Cancer Risk.............................................................................................................................................. 32 7.0 Cumulative Risk Characterization/ Assessment .......................................................................................... 32 8.0 Occupational Exposure/ Risk Pathway........................................................................................................ 32 8.1 Short/ Intermediate/ Long Term/ Cancer Handler Risk ........................................................................... 33 8.1.1 Data and Assumptions for Proposed Handler Exposure Scenarios ................................................. 33 8.1.2 Summary of Exposure Data for Handler Exposure Scenarios......................................................... 37 8.1.3 Non cancer S metolachlor Handler Exposure and Risk................................................................... 38 9.0 Data Needs and Label Requirements .......................................................................................................... 51 9.1 Toxicology................................................................................................................................................ 51 9.2 Residue Chemistry................................................................................................................................... 51 9.3 Occupational and Residential Exposure.................................................................................................. 52 References .......................................................................................................................................................... 52 Appendix A Table 1: Toxicity Profile for Metolachlor ( PC Code 108801)........................................................ 53 Appendix A Table 2: Toxicity Profile for S Metolachlor ( PC Code 108800) .................................................... 59 Appendix A Table 3: Structure of S Metolachlor ( PC Code 108800) and Metabolites..................................... 66 Appendix B International Residue Status Sheet............................................................................................... 67 3 of 66 1.0 Executive Summary Background The Ohio Department of Agriculture is requesting a specific exemption for the use of Smetolachlor formulated as Dual Magnum ® ( EPA Reg. No.: 100 816) for control of common purslane and prostrate pigweed on cilantro, collards, kale, and mustard greens. The Interregional Research Project Number 4 ( IR 4) has submitted data on the residues of S metolachlor formulated as Dual Magnum ® ( EPA Reg. No.: 100 816) on winter squash in support of the requested tolerance on winter squash, without a US registration, and the use on pumpkin.

Metolachlor is a racemic herbicide ( PC Code 108801) which consists of 50% each of the Renantiomer ( CGA 77101) and the S enantiomer ( CGA 77102, or alpha metolachlor). The Senantiomer is the herbicidally active isomer. An isomer enriched formula called S metolachlor ( 88% S isomer and 12% R isomer)( PC Code 108800) was submitted for reduced risk status based on similar efficacy at decreased application rates ( approximately 36 percent lower than that of metolachlor). In 1997, the EPA approved the registration of S metolachlor as a reducedrisk product.

Use Profile Metolachlor and S metolachlor are selective, chloroacetanilide herbicides used primarily for grassy weed control in many agricultural food and feed crops; residential lawns; commercial turf ( including golf courses, sports fields, recreation areas, and sod farms); ornamental plants, trees, and shrubs, and vines; hedge rows; and horticultural nurseries. Corn, sorghum, and soybean account for the majority of the use of both metolachlor and S metolachlor, followed by cotton, sweet corn, peanut, potato, and other minor field and vegetable crops.

Application rates for metolachlor and S metolachlor range from approximately one to four pounds active ingredient ( ai) per acre. Application is typically made pre emergence, one time per season.

The registrant, Syngenta, does not currently hold any active end use product registrations for metolachlor. S metolachlor is registered by Syngenta under the trade names of Dual MAGNUM ® , Pennant MAGNUM ® , Bicep MAGNUM ® , Boundary ® , and Medal ® . S metolachlor is formulated mainly as an emulsifiable concentrate. Other formulations include flowable concentrates, granular, and ready to use formulations. Application methods for agricultural uses includes ground application ( the most common application method), aerial application, irrigation systems, and chemigation ( center pivot only). A backpack sprayer, hose end sprayer, or handgun application may be used by professional applicators for application to residential lawns or turf. Residential applications to lawns and turf are intended for use by professional applicators only. The only currently active lawn/ turf label is an emulsifiable concentrate formulation for S metolachlor ( Pennant MAGNUM ® , EPA Reg. No. 100 950). 4 of 66 The Ohio Department of Agriculture requested use is for a single application, pre emergence using a ground sprayer on cilantro, collards, kale, and mustard greens, at 0.95 lb ai/ A to 1500 A in the state of Ohio. A total of 1425 lb ai ( 187 gal formulation) would be used as a result of this request. In order to harmonize with Pesticide Management Regulatory Agency ( PMRA), Canada, a revised Section B is required indicating the use on pumpkin as direct seeded treatment ( soil application, pre emergent to crop and weed) or post emergent treatment ( foliar application at the 1 2 leaf crop stage, prior to weed emergence) at a rate of 0.94 lb ai/ A ( 1.05 kg ai/ ha), and a PHI of 65 days. No US registration for winter squash is requested at this time.

Toxicity/ Hazard The toxicology database for metolachlor is complete for risk assessment purposes. Metolachlor is moderately acutely toxic ( toxicity category III) by the oral, dermal, and inhalation routes of exposure. It is not irritating to the skin or eyes, but is a dermal sensitizer. The Agency notes that recently reviewed acute toxicity studies from 1994 show metolachlor to be moderately acutely toxic ( toxicity category III) by the oral and dermal routes of exposure, and less toxic ( toxicity category IV) by the inhalation route of exposure. These 1994 studies also show metolachlor to be a mild eye irritant ( toxicity category III) and a minimal skin irritant ( toxicity category IV). In the subchronic and chronic toxicity studies, decreased body weight and body weight gain were the most commonly observed effects. There was no evidence that metolachlor was a reproductive or developmental toxicant. No systemic toxicity was observed when metolachlor was administered dermally at doses up to 1000 mg/ kg/ day. There was no evidence of mutagenic or cytogenetic effects in vivo or in vitro. Metolachlor has been classified as a Group C, possible human carcinogen based on liver tumors in rats at the highest dose tested. No cancer potency factor has been established, as risks calculated based on the chronic reference dose are predictive of cancer effects.

The toxicology database for S metolachlor, when bridged with the metolachlor database, is complete for risk assessment purposes. Bridging toxicology data from metolachlor, including acute toxicity, subchronic toxicity in rat and dog, developmental toxicity in rat and rabbit, mutagenicity, and metabolism studies are available. S metolachlor is moderately acutely toxic ( toxicity category III) by the oral and dermal route and relatively non toxic ( toxicity category IV) by the inhalation route of exposure. It causes slight eye irritation, and is non irritating dermally but is a dermal sensitizer. In the subchronic studies, body weight and body weight gain decreases were the most commonly observed effects. There was no evidence that S metolachlor was a developmental toxicant. There was no evidence of mutagenic or cytogenetic effects in vivo or in vitro with S metolachlor.

Tolerances are established for the combined residues ( free and bound) of metolachlor and its metabolites, determined as the derivatives 2[( 2 ethyl 6 methylphenyl) amino] 1 propanol ( CGA 37913) and 4( 2 ethyl 6 methylphenyl) 2 hydroxy 5 methyl 3 morpholinone ( CGA 49751), each expressed as the parent compound, in or on raw agricultural commodities ( 40 CFR § 180.368). The Metabolism Assessment Review Committee ( MARC) determined that the residues of concern for plant and animal commodities are metolachlor and its metabolites, 5 of 66 determined as the derivatives CGA 37913 and CGA 49751. Metabolites of metolachlor are assumed to be toxicologically equivalent to parent metolachlor. The residues of concern for Smetolachlor are the same as those for metolachlor.

Based on the Hazard Identification Assessment Review Committee ( HIARC) decision that metolachlor and S metolachlor are of comparable toxicity, studies of either chemical were used interchangeably for toxicology endpoint selection. Toxicological endpoints selected for risk assessment purposes are based on clinical signs of toxicity and decreased body weight gain. No evidence of neurotoxicity or neuropathology was seen in any of the available studies. A developmental neurotoxicity study is not required for metolachlor. Dermal absorption is calculated to be 58%, based on a dermal absorption study in rats, and inhalation absorption is assumed to be 100%.

In the case of metolachlor/ S metolachlor, risk assessments were conducted for the specific exposure scenarios listed below. Short and intermediate term dermal risk assessments were not conducted as no systemic toxicity was seen at the limit dose of 1000 mg/ kg/ day. A total uncertainty factor ( UF) of 100X was applied to the risk assessment to account for interspecies extrapolation ( 10X) and intraspecies variability ( 10X). The reference dose ( RfD) is equal to the No Observed Adverse Effect Level, or NOAEL, divided by the 100X uncertainty factor. The FQPA Safety Factor Committee has concluded that the FQPA safety factor for the protection of infants and children may be reduced to 1X ( i. e., removed) for the dietary and residential risk assessments. The Population Adjusted dose ( PAD) is equal to the RfD divided by the FQPA safety factor.

Acute Dietary ( general population): NOAEL= 300 mg/ kg/ day RfD= 3.0 mg/ kg/ day aPAD= 3.0 mg/ kg/ day Chronic Dietary: NOAEL= 9.7 mg/ kg/ day RfD = 0.1 mg/ kg/ day cPAD= 0.1 mg/ kg/ day Short term Incidental Oral: NOAEL= 50 mg/ kg/ day Target MOE= 100 Dietary Exposure The qualitative nature of metolachlor residues in plants is adequately understood based upon adequate corn, potato, and soybean metabolism studies. Residues of concern in plants include metolachlor and its metabolites, determined as the derivatives CGA 37913 and CGA 49751. The residues of concern for S metolachlor are the same as for metolachlor.

Adequate studies are available depicting the metabolism of metolachlor in ruminants and poultry. Metolachlor is rapidly metabolized and almost totally eliminated in the urine and feces of ruminants ( goats), non ruminants ( rats), and poultry. Metolachlor per se was not detected in any of the excreta or tissues. As in plants, metolachlor residues of concern in livestock commodities include metolachlor and its metabolites, determined as the derivatives CGA 37913 and CGA 49751. The residues of concern for S metolachlor in animals are the same as for metolachlor. 6 of 66 Adequate methodology is available for enforcing the current and proposed tolerances. The Pesticide Analytical Manual ( PAM, Vol. II) lists a GC/ NPD method ( Methods I) for determining residues in/ on plants and a GC/ MSD method ( Method II) for determining residues in livestock commodities. These methods determine residues of metolachlor and its metabolites as either CGA 37913 or CGA 49751 following acid hydrolysis. A modified version of this method ( Syngenta Method No. 1848 01) which uses LC/ MS/ MS has also been used. Adequate data are available on the recovery of metolachlor through Multi residue Method Testing Protocols. The FDA PESTDATA database indicates that metolachlor is completely recovered through Method 302, PAM Vol. I ( 3rd ed., revised 10/ 97).

Cilantro, Collards, Kale, and Mustard Greens: Previously submitted data from crop field trials conducted on spinach show that the combined residues of CGA 37913 and CGA 49751, each expressed as parent metolachlor, were < 0.08< 0.38 ppm in/ on samples harvested 34 69 days following a single pre emergence soil application of metolachlor at 1.0 lb ai/ A. Combined residues were also < 0.08 0.263 ppm in/ on spinach harvested 41 69 days following preemergence application at 2.0 lb ai/ A. These data would support a similar use of S metolachlor on spinach at a maximum rate of 0.6 lb ai/ A. The available data indicated that a tolerance level of 0.5 ppm would be appropriate for a tolerance on spinach. Considering the similarity between spinach and the subject crops and the higher proposed application rate for this Section 18, the data indicate that residues of S metolachlor are not likely to exceed 1.0 ppm as a result of the proposed use. A time limited tolerance of 1.0 ppm for the residues of S metolachlor on cilantro, collards, kale, and mustard greens would be appropriate.

Pumpkins and Winter Squash: Residue trials conducted jointly by IR 4 and the Pest Management Centre of Agriculture and Agri Food Canada ( PMC, AAFC) on behalf of the Canadian Horticultural Council, have been submitted for S metolachlor on winter squash. The residue study was arranged into four treatment scenarios: 1 pre emergent ( PRE) soil application at 0.64 0.69 lb ai/ A ( Treatment 2); 1 pre emergent soil application at 1.25 1.37 lb ai/ A ( Treatment 3); 1 post emergent ( POST) foliar application at 0.63 0.69 lb ai/ A ( Treatment 4); and 1 post emergent foliar application at 1.25 1.43 lb ai/ A ( Treatment 5). Winter squash fruit was harvested at pre harvest intervals ( PHIs) of 43 119 days ( PRE Treatments 2 and 3) or 31 105 days ( POST Treatments 4 and 5). The results from these trials show that maximum total residues of S metolachlor ( determined as CGA 37913 and CGA 49751) were < 0.08 ppm ( below the Lowest Limit of Method Validation, LLMV) in winter squash treated with either one preemergent soil application ( 0.72 1.54 kg ai/ ha or 0.64 1.37 lb ai/ A) or one post emergent foliar application ( 0.71 1.60 kg ai/ ha or 0.63 1.43 lb ai/ A), and harvested at PHIs of 31 119 days. Only one residue was detected above the LLMV ( CGA 49751 at 0.061 ppm). These data are sufficient to indicate that residues of S metolachlor on winter squash are not likely to exceed the proposed tolerance of 0.1 ppm as a result of the proposed use. According to the 2002 Reviewer's Guide, if winter squash data are submitted and found acceptable to support a winter squash tolerance then tolerances can be established on several Cucurbita spp. including pumpkin. The data submitted are sufficient to support the request for a tolerance on pumpkins. Tolerances of 0.1 ppm for the residues of S metolachlor on pumpkins and winter squash are appropriate. The tolerance on winter squash would be established without a US registration. 7 of 66 The proposed crop tolerances will have no impact on the maximum theoretical dietary burden ( MTDB) for livestock. Therefore, no changes are required in the tolerances for animal commodities as a result of the proposed Section 18s.

A drinking water assessment was conducted based on monitoring data from several sources, as well as on Tier 1 FIRST and SCI GROW modeling results. This assessment is a worst case scenario and demonstrates high end numbers. EECs for metolachlor and S metolachlor were calculated for both the parent compound and the ethanesulfonic acid ( ESA) and oxanilic acid ( OA) degradates. Although it was determined by the MARC that the ESA and OA metabolites appear to be less toxic than parent metolachlor, they are included in the risk assessment since they were found in greater abundance than the parent in water monitoring studies.

PRZM/ EXAMS and FIRST models were used to calculate the maximum peak and annual average concentrations of metolachlor/ S metolachlor in surface water. The SCI GROW screening model was used to estimate groundwater concentrations. As a result of the modeling results, the recommended total EEC's for surface water ( peak), surface water ( average), and groundwater ( peak and average) are 322 ppb ( 199 parent + 31.9 ESA+ 91.4 OA), 97 ppb ( 9.2 parent + 22.8 ESA + 65.1 OA), and 103 ppb ( 5.5 parent + 65.8 ESA + 31.7 OA), respectively.

Acute and chronic dietary risk assessments were conducted using the Dietary Exposure Evaluation Model ( DEEM FCID   , Version 2.03) which uses food consumption data from the USDA's Continuing Surveys of Food Intakes by Individuals ( CSFII) from 1994 1996 and 1998. Both the acute and chronic analyses assume tolerance level residues and 100 % CT data on all crops with established, pending, or proposed tolerances for metolachlor and/ or S metolachlor.

The acute dietary analysis for S metolachlor was conducted using the highest drinking water estimate for acute exposure, 322 ppb. The dietary exposure estimate to the U. S. population was < 1% aPAD and the most highly exposed subgroup, all infants < 1 yr old, at 2% aPAD. The results of the analysis indicate that acute risk from the dietary exposure to S metolachlor from the existing and requested uses did not exceed HED's level of concern for the U. S. population or any population subgroup.

A chronic dietary analysis for S metolachlor was conducted using the highest drinking water estimate for chronic exposure, 103 ppb. The dietary exposure estimate to the U. S. population was 4% cPAD and the most highly exposed subgroup, all infants < 1 yrs old, at 10% cPAD. The results of the analysis indicate that chronic risk from the dietary exposure to S metolachlor from the existing and requested uses did not exceed HED's level of concern for the U. S. population or any population subgroup.

Residential Exposure Metolachlor is a selective herbicide that was first registered in 1976 and consists of a Renantiomer and S enantiomer mixture in a ratio of 50: 50. Based on the enhanced herbicidal activity of the S enantiomer, metolachlor has recently been replaced in the market by Smetolachlor which has a S to R enantiomer ratio of 88: 12. Efficacy studies conducted by the registrant ( Syngenta) demonstrate that S metolachlor is needed in amounts 37% less than the 8 of 66 original metolachlor and this difference is reflected in the maximum application rates used in this assessment.

The formulated S metolachlor end use product is labeled under the trade name Pennant MAGNUMTM ( EPA Reg. No. 100 950) to distinguish the new product from the original metolachlor formulation named PennantTM ( EPA Reg. No. 100 691). Pennant MAGNUMTM ( 7.62 lbs. active ingredient per gallon) is labeled for use on commercial ( sod farm) and residential warm season turfgrasses and other noncrop land including golf courses, sports fields, and ornamental gardens. Although not labeled as a restricted use pesticide, Pennant MAGNUMTM, as currently marketed, is not intended for homeowner purchase or use ( intended for use by professionals). On this basis, with regard to the requirements of FQPA, metolachlor and S metolachlor are risk assessed for postapplication exposure only. Pennant MAGNUMTM and PennantTM are both emulsifiable concentrates ( EC).

For this risk assessment, small children are the population group of concern. Although the type of site that S metolachlor may be used on varies from golf courses to ornamental gardens, the scenario chosen for risk assessment ( residential turf use) represents what the Agency considers the likely upper end of possible exposure. Postapplication exposures from various activities following lawn treatment are considered to be the most common and significant in residential settings. Since toxicity was not observed in a dermal toxicity study, up to a dose level of 1,000 mg/ kg/ day, the only parameter of risk necessarily addressed in this assessment is the possible oral exposure of small children from treated turf, or soil.

The following postapplication exposure scenarios resulting from lawn treatment were assessed: ( 1) the incidental ingestion of metolachlor residues on lawns from a " hand to mouth" transfer, ( 2) the incidental ingestion of metolachlor residues from " object to mouth" activities ( in this case treated turfgrass), and ( 3) the incidental ingestion of metolachlor treated soil in residential areas. The term " incidental" is used to distinguish the inadvertent ( irregular) oral exposure of small children from the expected exposure from treated foods, or residue in drinking water. The exposure estimates of the three oral ingestion scenarios are combined to establish the possible ( if not likely) upper end of oral exposure from lawn ( or similar) use.

The current label specifies a 6 week interval before the re application of metolachlor and the registrant ( Syngenta) has indicated a label revision to limit application to once per season. On this basis, metolachlor risk is assessed for the time interval referred to as " short term" ( 1 30 days) and will not be assessed for a longer, or " intermediate term" duration. Also, since residents are not expected to re enter treated areas until the spray has dried ( as labeled), no inhalation exposure is expected, or assessed.

Based on the short term NOAEL of 50 mg/ kg/ day, the risk estimate for hand to mouth, objectto mouth, and soil ingestion combined ( on the day of treatment) is 0.046 mg/ kg/ day ( MOE = 1,100) for S metolachlor. 9 of 66 Aggregate Risk An acute aggregate risk assessment addresses potential exposure from combined residues of metolachlor/ S metolachlor on food and in drinking water ( both surface and ground water). Potential residential exposures are not incorporated into an acute aggregate risk assessment. Since the exposure from food and drinking water were already incorporated into the acute dietary risk assessment, no further aggregation is required. The dietary exposure estimate to the U. S. population was < 1% aPAD and the most highly exposed subgroup, all infants < 1 yr old, at 2% aPAD. The results of the analysis indicate that acute aggregate exposure risk to S metolachlor from the existing and requested uses did not exceed the Agency's level of concern for U. S. population or any population subgroup.

A short term aggregate risk assessment considers potential exposure from food, drinking water, and short term, non occupational ( residential) pathways of exposure for a duration of 1 to 30 days. For S metolachlor, potential short term, non occupational risk scenarios consist of oral exposure of children to treated lawns only. In this aggregate short term risk assessment, exposure from food, drinking water, and residential lawns has been considered. The exposure to food and water has already been considered in the chronic dietary risk assessment. The dietary exposure estimate was 4% cPAD for the U. S. population and 10% cPAD for the most highly exposed subgroup, all infants < 1 yrs old. Since only children have the potential for nonoccupational short term risk, they are the only population subgroup for which an aggregate short term risk assessment was conducted. Toddlers' S metolachlor incidental oral exposure is assumed to include hand to mouth exposure, object to mouth exposure and exposure through incidental ingestion of soil. The aggregate short term risk for exposure to S metolachlor for all infants < 1 yr old, the subgroup with the highest exposure, is MOE of 890, which does not reach the Agency's level of concern.

An intermediate term aggregate risk assessment considers potential exposure from food, drinking water, and non occupational ( residential) pathways of exposure for a duration of 30 to 180 days. However, for metolachlor/ S metolachlor, no intermediate term non occupational exposure scenarios are expected to occur; therefore, an intermediate term aggregate risk assessment is not required.

A chronic aggregate risk assessment considers chronic exposure from food, drinking water, and non occupational ( residential) pathways of exposure. For metolachlor and S metolachlor, there are no chronic ( greater than 180 days of exposure) non occupational exposure scenarios. Therefore, the chronic aggregate risk assessment considers exposure from food and drinking water only. Since the exposure from food and drinking water were already incorporated into the chronic dietary risk assessment, no further aggregation is required. The chronic dietary exposure estimate to the U. S. population was 4% cPAD and the most highly exposed subgroup, all infants < 1 yrs old, at 10% cPAD. The results of the analysis indicate that chronic aggregate risk from exposure to S metolachlor from the existing and requested uses did not exceed the Agency's level of concern for the U. S. population or any population subgroup.

Metolachlor has been classified as a Group C, possible human carcinogen based on liver tumors in rats at the highest dose tested. The chronic NOAEL of 15 mg/ kg/ day that was established 10 of 66 based on tumors in the rat ( seen at the highest dose tested of 150 mg/ kg/ day) is comparable to the NOAEL of 9.7 mg/ kg/ day selected for establishing the chronic reference dose for metolachlor. It is assumed that the chronic dietary PAD is protective for cancer dietary risk. Therefore, a separate cancer aggregate risk assessment was not conducted.

Occupational Exposure/ Risk This risk assessment incorporates the toxicological endpoints of concern as presented in the Report of the Hazard Identification Assessment Review Committee ( HIARC) September 28, 2001. No short or intermediate term dermal endpoint of concern was identified. The short term inhalation endpoint of concern ( NOAEL = 50 mg/ kg/ day) is based on increased incidence of clinical signs, decreased body weight and body weight gain, food consumption, and food efficiency from an oral prenatal developmental toxicity study in rats with S metolachlor. Since an oral study was selected, a 100% absorption factor should be applied and since the endpoint is from a prenatal developmental toxicity study, a body weight of 60 kilograms   the weight of an average female adult   was used. The intermediate term inhalation endpoint of concern ( NOAEL = 8.8 mg/ kg/ day) is based on decreased body weight gain from an oral subchronic ( 6 month) toxicity study in dogs with metolachlor. Since an oral study was selected, a 100% absorption factor should be applied and since the toxicological endpoint of concern is not sexspecific a body weight of 70 kilograms   the weight of an average adult   was used. Only inhalation Margins of Exposure ( MOE) were calculated, therefore, no aggregation of dermal and inhalation exposures was performed.

Occupational handler exposure was addressed using the Pesticide Handlers Exposure Database ( PHED ver. 1.1), and data from the Outdoor Residential Exposure Task Force ( ORETF). PHED data for mixing/ loading liquid formulations using closed systems were used as a surrogate for commercial impregnation of dry fertilizer with liquid S metolachlor. Dermal risks were not evaluated since no hazard was identified for quantification of risk following dermal exposure.

When data were available to assess risks, short and intermediate term inhalation risks to occupational handlers are below the Agency's level of concern for noncancer risk assessments ( i. e., MOE < 100) at baseline ( i. e., no respirator). HED has insufficient data to assess baseline and PPE levels of exposures to assess risks to pilots applying sprays with aerial equipment and assumes commercial mixer/ loaders impregnating dry bulk fertilizers ( using the PHED data) are using engineering controls. Therefore for these scenarios, only inhalation risks using engineering controls are assessed. The inhalation risks at the engineering control level of exposure were not a concern for these scenarios.

Since no post application dermal risks were calculated, the default restricted entry interval of 12 hours should be established for S metolachlor. EPA notes that S metolachlor does not qualify for consideration for a 4 hour restricted entry interval since it is classified as a dermal sensitizer.

The occupational risk assessment applied the latest exposure data, toxicology information, and usage data. The overall results indicate that the Agency has no risk concerns for S metolachlor use patterns involving agricultural crops or commercial uses. Occupational handler and 11 of 66 postapplication risks were not a concern at the lowest level of risk mitigation assessed for each scenario.

Recommendations Provided a revised Section B is received, ARIA concludes that there is a reasonable certainty that no harm will result to the U. S. Population, including infants and children, from acute, short and intermediate term, and chronic aggregate exposure to S metolachlor residues. ARIA recommends for time limited tolerances for the residues of S metolachlor on cilantro, collards, kale, and mustard greens at 1.0 ppm and permanent tolerances on pumpkin and winter squash at 0.1 ppm. The tolerance on winter squash does not have a US registration.

2.0 Ingredient Profile S metolachlor is a selective herbicide developed for the control of a large number of grassy weeds in corn, soybeans, sorghum and other crops. The S diastereomer of metolachlor has been shown to have greater biological efficacy than the R diastereomer.

2.1 Summary of Registered/ Proposed Uses Table 2.1 Summary of Directions for Use of S metolachlor.

Applic. Timing, Type, and Equip. Formulation [ EPA Reg. No.] Applic. Rate ( lb ai/ A) Max. No. Applic. per Season Max. Seasonal Applic. Rate ( lb ai/ A) PHI ( days) Use Directions and Limitations Cilantro, Collards, Kale, and Mustard Greens Pre emergence by broadcast or spot treatment ground sprayer Dual Magnum [ 100 816] 0.475 0.95 1 0.95 60 Do not apply through any type of irrigation system.

Pumpkin Broadcast ground sprayer either single application preemergence or post emergence. Dual Magnum [ 100 816] 0.94 1 0.94 65 Do not apply after two true leaf stage. Do not apply through any type of irrigation system.

Conclusions: The use directions for cilantro, collards, kale, and mustard greens are correct. The petitioner must correct Section B to a single application at 0.94 lb ai/ A either pre or postemergence with a 65 day PHI. A revised Section B is required.

2.2 Structure and Nomenclature TABLE 2.2 Test Compound Nomenclature 12 of 66 TABLE 2.2 Test Compound Nomenclature Compound S metolachlor C H 3 N O Cl CH 3 O C H 3 CH 3 Common name S metolachlor Company experimental name CGA 77102 IUPAC name 2 Chloro N( 2 ethyl 6 methylphenyl) N{ S( 2 methoxy 1 methylethyl)} acetamide CAS name Chloro N( 2 ethyl 6 methylphenyl) N( 2 methoxy 1 methylethyl) acetamide ( E) N{( 6 chloro 3 pyridyl) methyl} N' cyano N methylacetamidine CAS # 87392 12 9 End use product/( EP) Dual II MAGNUM ® ( EPA Reg. No. 100 816), Pennant MAGNUMTM ( EPA Reg. No. 100 950)

2.3 Physical and Chemical Properties TABLE 2.3 Physicochemical Properties of the Technical Grade Test Compound Parameter Value Reference Melting point/ range N/ A pH 7.8 at 25 ° C ( 1% aqueous dispersion)

Density 1.117 g/ cm3 at 20 ° C Water solubility ( 25 ° C) 0.48 g/ L Solvent solubility ( mg/ L at 25 ° C) Miscible with methanol, acetone, toluene, n octanol, nhexane ethyl acetate, dichloromethane Vapor pressure at 25 ° C 2.8 x 10 5 mm Hg Dissociation constant ( pKa) No dissociation constant in pH range 2 12 Octanol/ water partition coefficient Log( KOW) 3.0 at 25 ° C UV/ visible absorption spectrum Not Provided Registration Division: Physical and Chemical Characteristics ( DP Num: 225258)

3.0 Hazard Characterization/ Assessment 3.1 Hazards and Dose Response Characterization Metolachlor: 13 of 66 The metolachlor toxicology database is complete for risk assessment purposes. Metolachlor is moderately acutely toxic ( toxicity category III) by the oral, dermal, and inhalation routes of exposure. It is not irritating to the skin or eyes, but is a dermal sensitizer. The Agency notes that the reviewed acute toxicity studies from 1994 show metolachlor to be moderately acutely toxic ( toxicity category III) by the oral and dermal routes of exposure, and less toxic ( toxicity category IV) by the inhalation route of exposure. These 1994 studies also show metolachlor to be a mild eye irritant ( toxicity category III) and a minimal skin irritant ( toxicity category IV).

In the subchronic oral studies, the only evidence of toxicity was decreased body weight/ body weight gain at 259 mg/ kg/ day in female rats and at 29 mg/ kg/ day in male and female dogs. The respective No Observed Adverse Effect Levels ( NOAELs) for these studies were 23 mg/ kg/ day and 9 mg/ kg/ day. There was no evidence of systemic toxicity when 1000 mg/ kg/ day was applied topically to rabbits. Dermal irritation was observed at 10 mg/ kg/ day and above.

Similar effects were seen after long term administration of metolachlor. In the chronic dog study, the only adverse effect was decreased body weight gain in females at 33 mg/ kg/ day; the NOAEL was 10 mg/ kg/ day. In the mouse carcinogenicity study, possible treatment related deaths in females and decreased body weight/ body weight gain in both sexes were observed at 450 mg/ kg/ day; the NOAEL was 150 mg/ kg/ day. In the rat combined chronic toxicity/ carcinogenicity study, decreased body weight gain and food consumption were observed at 150 mg/ kg/ day; the NOAEL was 15 mg/ kg/ day. There was no evidence of carcinogenicity in mice; however, there were statistically significant increases in liver adenomas and combined adenomas/ carcinomas in female rats. In male rats, there was a statistically significant trend but not pair wise significance for liver tumors. There was no evidence of a mutagenic or cytogenetic effects in vivo or in vitro.

HED's Cancer Assessment Review Committee has classified metolachlor as a Group C carcinogen with risk quantitated using a non linear approach. The NOAEL of 15 mg/ kg/ day from the rat combined chronic toxicity/ carcinogenicity study is based on neoplastic nodules/ hepatocellular carcinomas seen at the highest dose tested of 150 mg/ kg/ day. The Agency notes that the tumor NOAEL of 15 mg/ kg/ day is comparable to the NOAEL of 9.7 mg/ kg/ day selected for establishing the chronic reference dose for metolachlor. The recommendation for a non linear approach should be followed since no new data were submitted for a re evaluation by the Cancer Assessment Review Committee.

The prenatal developmental studies in the rat and rabbit revealed no evidence of a qualitative or quantitative susceptibility in fetal animals. In the rabbit prenatal developmental toxicity study, at 360 mg/ kg/ day, maternal animals had persistent anorexia and decreased body weight gain; the NOAEL was 120 mg/ kg/ day. In the rat prenatal developmental toxicity study, frank toxicity [ death, clinical signs ( clonic and/ or tonic convulsions, excessive salivation, urine stained abdominal fur and/ or excessive salivation) and decreased body weight gain] was observed at the limit dose of 1000 mg/ kg/ day in maternal animals; the NOAEL was 300 mg/ kg/ day. The developmental effects at 1000 mg/ kg/ day included slightly decreased number of implantations per dam, decreased number of live fetuses/ dam, increased number of resorptions/ dam and significant decrease in mean fetal body weight. In the two generation reproduction study in rats, there was no evidence of parental or reproductive toxicity at approximately 80 mg/ kg/ day, the 14 of 66 highest dose tested. At this dose, there was a minor decrease in fetal body weight beginning at lactation day 4; the NOAEL was approximately 25 mg/ kg/ day. Since a similar body weight decrease was not seen on lactation day zero, the cause of the effect on later lactation days is most likely due to exposure of the pups to metolachlor in the diet and/ or milk and therefore is not evidence of an increased quantitative susceptibility in post natal animals.

A series of acute, subchronic, developmental ( rat) and mutagenicity studies were conducted on the ethane sulfonic acid ( ESA, or CGA 354743) and oxanilic acid ( OA, or CGA 51202) metabolites found in water. The MARC concluded that the ESA and OA metabolites appear to be less toxic than parent metolachlor/ S metolachlor, based on subchronic studies in the rat and dog ( ESA metabolite only) and developmental studies in the rat. No toxicity was observed in any of these studies at the limit dose( s) of 1000 mg/ kg/ day or greater. Since a dose for toxicity of the metabolites was not demonstrated, the degree of difference between metabolite and parent could not be established. Acute toxicity was essentially comparable, except both metabolites were moderate ( ESA) or severe ( OA) eye irritants, whereas the parent compound was not. However, the MARC concluded that the ESA and OA metabolites should be included in the water risk assessment ( not in the tolerance expression and not in the dietary food assessment) since they were found in greater abundance than the parent( s) in water monitoring studies and assuming the toxicity of the degradates are equivalent to metolachlor. In addition, parent metolachlor has been classified as a Group C carcinogen. Without long term studies in rats and mice with the metabolites, there are no data to substantiate that the metabolites are not carcinogenic.

One toxicology data gap exists for metolachlor, as there is concern for toxicity by the inhalation route following exposure on multiple days in a commercial setting. A 28 day inhalation study in rats with metolachlor should be conducted. Registrants are recommended to follow the protocol provided in OPPTS Guideline 870.3465 ( 90 day inhalation study) but cease exposure at 28 days. 15 of 66 The acute toxicity profile for metolachlor is presented in Table 3.1. a. For comparison purposes, the acute toxicity profile for metolachlor, based on the reviewed 1994 acute toxicity studies, is presented in Table 3.1. b.

Table 3.1. a Acute Toxicity Profile of Metolachlor ( PC Code 108801)

Guideline No. Study Type MRIDs # Results Toxicity Category 870.1100 Acute Oral Rats 00015523 LD50 = 2780 mg/ kg III 870.1200 Acute Dermal Rabbit 00015526 LD50 = > 10 mg/ kg III 870.1300 Acute Inhalation Rats 00015535 LC50 = > 1.75 mg/ L III 870.2400 Primary Eye Irritation Rabbits 00015528 non irritating IV 870.2500 Primary Skin Irritation Rabbits 00015530 non irritating IV 870.2600 Dermal Sensitization Guinea pigs 00015631 positive 870.6200 Acute Neurotoxicity  NA NA  study not required Table 3.1. b Acute Toxicity Profile of Metolachlor ( PC Code 108801) Based on 1994 Studies OPPTS Guideline No. Study Type MRIDs # Results Toxicity Category 870.1100 Acute Oral  Rat 43492001 LD50 = 3302 mg/ kg ( males); 2000 mg/ kg ( females); 2877 mg/ kg ( combined sexes) III 870.1200 Acute Dermal  Rabbit 43492002 LD50 = > 2000mg/ kg III 870.1300 Acute Inhalation  Rat 43492003 LC50 = > 4.33 mg/ L IV 870.2400 Primary Eye Irritation  Rabbit 43492004 mild irritant III 870.2500 Primary Skin Irritation  Rabbit 43492005 minimal irritant IV 870.2600 Dermal Sensitization  guinea pig 43492006 positive S metolachlor: The toxicology database for S metolachlor, when bridged with the metolachlor database, is complete for risk assessment purposes. Bridging toxicology data, including acute toxicity, subchronic toxicity in the rat and dog, developmental toxicity in the rat and rabbit, mutagenicity, and metabolism studies are available. S metolachlor is moderately acutely toxic ( Toxicity Category III) by the oral and dermal routes of exposure and relatively non toxic ( Toxicity Category IV) by the inhalation route of exposure. S metolachlor causes slight eye irritation and is non irritating dermally, but is a dermal sensitizer. 16 of 66 In one subchronic toxicity study in rodents with S metolachlor, no effects were observed in male and female rats at the high dose of approximately 225 mg/ kg/ day. In another subchronic toxicity study in rats, decreased body weight/ body weight gain, reduced food consumption and food efficiency and increased kidney weights in males were observed at 150 mg/ kg/ day; the NOAEL was 15 mg/ kg/ day. In the subchronic dog study, no effects were observed in dogs at the high dose of approximately 70 mg/ kg/ day.

There was no evidence of increased quantitative or qualitative fetal susceptibility in the prenatal developmental studies in rats and rabbits. In the rat, maternal toxicity [ increased clinical signs of toxicity ( pushing head through bedding) and decreased body weights/ body weight gains, food consumption and food efficiency] was observed at 500 mg/ kg/ day; the NOAEL was 50 mg/ kg/ day. There were no developmental effects at 1000 mg/ kg/ day, the highest dose tested. In the rabbit, clinical signs of toxicity ( little/ none/ soft stool) were observed at 100 mg/ kg/ day; the NOAEL was 20 mg/ kg/ day. No developmental effects were observed at 500 mg/ kg/ day, the highest dose tested. There was no evidence of mutagenic or cytogenic effects in vitro or in vivo studies with S metolachlor.

S metolachlor is extensively absorbed and metabolized following oral administration. Elimination is via the urine and feces. Tissue residues were highest in whole blood. Metabolism studies were inadequate for comparing the metabolic pathways of metolachlor and Smetolachlor However, based on a comparison of the findings in the available studies with both chemicals, it appears that S metolachlor is of comparable toxicity to the racemic mixture ( metolachlor).

One toxicology data gap exists for S metolachlor, as there is concern for toxicity by the inhalation route following exposure on multiple days in a commercial setting. A 28 day inhalation study in rats with S metolachlor should be conducted. The registrant is recommended to follow the protocol provided in OPPTS Guideline 870.3465 ( 90 day inhalation study) but cease exposure at 28 days.

The acute toxicity profile for S metolachlor is presented in Table 3.1. c.

Table 3.1. c Acute Toxicity Profile of S metolachlor ( PC Code 108800)

Guideline No. Study Type MRIDs # Results Toxicity Category 870.1100 Acute Oral Rats 43928915 LD50 = 3267 mg/ kg (%); 2577 mg/ kg/ day (&); 2672 mg/ kg/ day ( combined) III 870.1200 Acute Dermal Rabbit 43928916 LD50 = > 2000 mg/ kg III 870.1300 Acute Inhalation Rats 43928917 LC50 = > 2.91 mg/ L IV 17 of 66 870.2400 Primary Eye Irritation Rabbits 43928918 slight to moderate conjunctival irritation that cleared in 48 hours III 870.2500 Primary Skin Irritation Rabbits 43928919 non irritating IV 870.2600 Dermal Sensitization Guinea pigs 43928920 positive 870.6200 Acute Neurotoxicity  NA NA  study not required 3.2 FQPA Considerations The FQPA Safety Factor Committee met on November 5, 2001 to evaluate the hazard and exposure data for metolachlor and S metolachlor, and recommended that the FQPA Safety Factor for the protection of infants and children still be 1x ( based on the 2002 policy) for the following reasons ( Memorandum: Report of the FQPA Safety Factor Committee, Carol Christensen, 11/ 14/ 01): i. The toxicology database is complete for the FQPA assessment;

ii. There is no indication of quantitative or qualitative increased susceptibility of rats or rabbits to in utero and/ or postnatal exposure to metolachlor in the available toxicity data;

iii. A developmental neurotoxicity study is not required for metolachlor;

iv. The dietary ( food and drinking water) and non dietary exposure ( residential) assessments will not underestimate the potential exposures for infants and children from the use of metolachlor.

3.3 Dose Response Assessment Rationale for Endpoint Selection: HED's Hazard Identification Assessment Review Committee ( HIARC) met on September 6, 2001 and reviewed the toxicology databases for metolachlor and S metolachlor with regard to the acute and chronic reference doses ( RfDs) and the toxicological endpoint selection for use as appropriate in occupational/ residential risk assessments. The HIARC concluded that Smetolachlor and metolachlor have comparable toxicity profiles. Studies with both chemicals were used interchangeably for toxicology endpoint selection. This endpoint is applicable to the currently proposed uses.

A complete toxicology profile for both metolachlor and S metolachlor can be found in Tables 1 and 2 of Appendix A. A summary of the doses and endpoints selected for human health risk 18 of 66 assessment is presented in Table 3.3 of this document. A more thorough explanation of the rationale for endpoint selection is included below:

Acute Dietary Endpoint: The acute RfD of 3.0 mg/ kg/ day is based on a prenatal developmental toxicity study in rats with metolachlor, and is calculated as the NOAEL ( 300 mg/ kg/ day) divided by the total uncertainty factor of 100X ( 10X for interspecies extrapolation and 10X for intraspecies variability). The acute endpoint is based on an increased incidence of death, clinical signs of toxicity ( clonic and/ or tonic convulsions, excessive salivation, urine stained abdominal fur and/ or excessive lacrimation) and decreased body weight gain seen at the LOAEL of 1000 mg/ kg/ day. It is noted that although increased incidence of death is one of the effects seen, it was seen at a dose ( 1000 mg/ kg/ day) approximately three times higher than the dose ( 300 mg/ kg/ day) selected for risk assessment; therefore, the Agency is confident that adequate safety is provided to protect the public from dietary exposure to residues of metolachlor. Since the FQPA safety factor is reduced to 1X, the acute RfD is equal to the aPAD. The PAD is a modification of the acute or chronic RfD to accommodate the FQPA safety factor, and is calculated as the RfD divided by the FQPA safety factor.

Since clinical signs are observed after a single oral dose of metolachlor, the duration and route of administration are appropriate for the risk assessment. Salivation alone is seen at 300 mg/ kg/ day; however, as this effect is most likely due to gastric irritation and there is no other evidence of treatment related toxicity, the finding is not considered toxicologically significant. Developmental effects observed are not attributable to a single exposure and therefore, a separate acute endpoint has not been identified for females 13 50.

Chronic Dietary Endpoint: The chronic RfD of 0.10 mg/ kg/ day is based on a chronic toxicity study in dogs with metolachlor, and is calculated as the NOAEL ( 9.7 mg/ kg/ day) divided by the 100X UF. The chronic endpoint is based on decreased body weight gain in females at the LOAEL of 33.0 mg/ kg/ day. Since the FQPA safety factor is reduced to 1X, the chronic RfD is equal to the chronic PAD. The study duration and route of administration are appropriate for this risk assessment.

Short term Incidental Oral: The short term incidental oral NOAEL of 50 mg/ kg/ day, from a prenatal developmental toxicity study in rats with S metolachlor, is based on increased incidence of clinical signs, decreased body weight/ body weight gain, food consumption and food efficiency seen at the LOAEL ( 500 mg/ kg/ day) in maternal animals. The endpoint is appropriate for the population of concern ( infants and children). The Committee noted that the NOAEL ( 20 mg/ kg/ day) for the prenatal developmental toxicity study in rabbits with S metolachlor ( MRID 43928924) was lower than the 50 mg/ kg/ day from the rat developmental study. However, the endpoint was based on clinical signs of toxicity ( increase in little/ none/ soft stool observations) at 100 mg/ kg/ day. Although there was a dose related increase in this sign, it is not evidence of frank toxicity and was judged not be appropriate for risk assessment. Therefore, the rabbit study with S metolachlor was not selected for this exposure scenario.

Intermediate term Incidental Oral: The intermediate term incidental oral NOAEL of 8.8 mg/ kg/ day, from a subchronic toxicity study in dogs with metolachlor, is based on decreased 19 of 66 body weight gain seen at the LOAEL of 29.4 mg/ kg/ day. The endpoint and study duration are appropriate for the population of concern ( infants and children).

Dermal Absorption: A dermal absorption value of 58% has been selected, based on an available dermal absorption study in rats with metolachlor. The percentage of the applied dose found in blood, urine, feces, carcass and cage was increased during the period between skin wash ( 10 hours) and sacrifice ( 72 hours). During the same period, the levels in the skin decreased by a similar amount. This observation suggested that metolachlor retained in skin was absorbed during the pre sacrifice period. Therefore, the HIARC selected 58% dermal absorption value based on the combined values at 10 hours measurement ( 33%) and at the amount remaining on the skin ( 25%).

Short and Intermediate Term Dermal Endpoints: No hazard was identified for quantification of risk following dermal exposure. In a 21 day dermal toxicity study ( MRID 41833101), no systemic toxicity was seen following repeated dermal application of metolachlor ( 96.4% ai) to the intact skin of five New Zealand rabbits/ sex/ group at doses of 0, 10, 100 or 1000 mg/ kg/ day for 21 days. No prenatal developmental toxicity studies with metolachlor or S metolachlor were appropriate for this risk assessment. There was no evidence of developmental effects in rats or rabbits at maternally toxic doses with either metolachlor or S metolachlor, except in the rat prenatal developmental toxicity study. In this study, there were slightly decreased number of implantations per dam, decreased number of live fetuses/ dam, increased number of resorptions/ dam and significant decrease in mean fetal body weight but only at 1000 mg/ kg/ day which was extremely toxic to dams ( death, clinical signs of toxicity and decreased body weight gain).

Long term Dermal Endpoint: The long term dermal NOAEL of 9.7 mg/ kg/ day, from a chronic oral toxicity study in dogs with metolachlor, is based on decreased body weight gain in females at the LOAEL of 33.0 mg/ kg/ day. The treatment period ( 21 days) in the dermal toxicity study with metolachlor was not considered to be of sufficient duration for these compounds since effects seen in chronic oral studies could also be observed with long term dermal administration. Therefore, the HIARC selected an oral NOAEL for this exposure scenario, and since an oral study was selected, the dermal absorption factor ( 58%) should be applied.

Short term Inhalation Endpoint: The short term inhalation NOAEL of 50 mg/ kg/ day, from an oral prenatal developmental toxicity study in rodents with S metolachlor, is based on increased incidence of clinical signs, decreased body weight/ body weight gain, food consumption and food efficiency at the LOAEL of 500 mg/ kg/ day in maternal animals. Since an oral study was selected, a 100% absorption factor should be applied.

Intermediate Term Inhalation Endpoint: The intermediate term inhalation NOAEL of 8.8 mg/ kg/ day, from a subchronic oral toxicity study in dogs with metolachlor, is based on decreased body weight gain at the LOAEL of 29.4 mg/ kg/ day. Since an oral study was selected, a 100% absorption factor should be applied.

Long Term Inhalation Endpoint: The long term inhalation NOAEL of 9.7 mg/ kg/ day, from a chronic toxicity study in dogs with metolachlor, is based on decreased body weight gain in 20 of 66 females at the LOAEL of 33 mg/ kg/ day. Since an oral study was selected, a 100% absorption factor should be applied.

Target MOE for residential and aggregate exposure: A target MOE ( NOAEL/ exposure) is the level above which the Agency does not have a risk concern. For metolachlor, a target MOE of 100 is considered adequate for dermal and inhalation residential exposure, as well as for aggregate exposure. The target MOE of 100 includes the FQPA safety factor of 1X.

Table 3.3 Summary of Toxicological Dose and Endpoints for Metolachlor for Use in Human Risk Assessment Exposure Scenario Dose ( mg/ kg/ day) and Uncertainty Factor ( UF) Endpoint for Risk Assessment Study NOAEL = 300 UF = 100x FQPA Safety Factor = 1x death, clinical signs of toxicity ( clonic and/ or tonic convulsions, excessive salivation, urinestained abdominal fur and/ or excessive salivation) and decreased body weight gain Prenatal developmental toxicity study in rats with metolachlor Acute Dietary ( all population subgroups)

Acute PAD = 3.0 mg/ kg/ day NOAEL= 9.7 UF = 100 FQPA Safety Factor = 1x decreased body weight gain in females Chronic study in dogs with metolachlor Chronic Dietary ( all population subgroups)

Chronic PAD = 0.1 mg/ kg/ day Incidental Oral, Short Term ( one to 30 days) NOAEL = 50 Target MOE = 100 increased incidence of clinical signs, decreased body weight/ body weight gain, food consumption, and food efficiency Prenatal developmental toxicity study in rats with S metolachlor Incidental Oral, Intermediate Term ( one month to 180 days) NOAEL = 8.8 Target MOE = 100 decreased body weight gain Subchronic ( 6 month) toxicity study in dogs with metolachlor Dermal, Short and Intermediate Term Hazard was not identified for quantification of risk. No systemic toxicity was seen at the limit dose ( 1000 mg/ kg/ day) following dermal applications and there is no concern for developmental toxicity in rats or rabbits.

Dermal, Long Terma ( greater than 180 days) Oral NOAEL = 9.7 Target MOE = 100 decreased body weight gain in females chronic toxicity study in dogs with metolachlor 21 of 66 Table 3.3 Summary of Toxicological Dose and Endpoints for Metolachlor for Use in Human Risk Assessment Exposure Scenario Dose ( mg/ kg/ day) and Uncertainty Factor ( UF) Endpoint for Risk Assessment Study Inhalation, Short Termb Oral NOAEL = 50 Target MOE = 100 increased incidence of clinical signs, decreased body weight/ body weight gain, food consumption, and food efficiency Prenatal development toxicity study in rats with S metolachlor Inhalation, Intermediate Termb Oral NOAEL = 8.8 Target MOE = 100 decreased body weight gain subchronic ( 6 month) toxicity study in dogs with metolachlor Inhalation, Long Termb Oral NOAEL = 9.7 Target MOE = 100 decreased body weight gain in females chronic toxicity study in dogs with metolachlor * The reference to the FQPA Safety Factor refers to any additional safety factor retained due to concerns unique to the FQPA. a Since an oral NOAEL was selected, a dermal absorption factor of 58% should be used in route to route extrapolation.

b Since an oral NOAEL was selected, an inhalation factor of 100% should be used in route to route extrapolation.

3.4 Endocrine Disruption EPA is required under the FFDCA, as amended by FQPA, to develop a screening program to determine whether certain substances ( including all pesticide active and other ingredients) " may have an effect in humans that is similar to an effect produced by a naturally occurring estrogen, or other such endocrine effects as the Administrator may designate." Following recommendations of its Endocrine Disruptor and Testing Advisory Committee ( EDSTAC), EPA determined that there was a scientific basis for including, as part of the program, the androgen and thyroid hormone systems, in addition to the estrogen hormone system. EPA also adopted EDSTAC's recommendation that the Program include evaluations of potential effects in wildlife. For pesticide chemicals, EPA will use FIFRA and, to the extent that effects in wildlife may help determine whether a substance may have an effect in humans, FFDCA authority to require the wildlife evaluations. As the science develops and resources allow, screening of additional hormone systems may be added to the Endocrine Disruptor Screening Program ( EDSP).

In the available toxicity studies on S metolachlor, there was no estrogen, androgen, and/ or thyroid mediated toxicity. When additional appropriate screening and/ or testing protocols being considered under the Agency's EDSP are developed, S metolachlor may be subjected to further screening and/ or testing to better characterize effects related to endocrine disruption.

4.0 Dietary Exposure/ Risk Characterization 4.1 Pesticide Metabolism and Environmental Degradation 4.1.1 Metabolism in Primary Crops 22 of 66 The qualitative nature of metolachlor residues in plants is adequately understood based upon adequate corn, potato, and soybean metabolism studies. The metabolism of metolachlor involves conjugation with glutathione, breakage of this bond to form mercaptan, conjugation of the mercaptan with glucuronic acid, hydrolysis of the methyl ether, and conjugation of the resultant alcohol with a neutral sugar. A minor pathway may involve sugar conjugation of metolachlor directly to the corresponding oxo compounds. Residues of concern in plants include metolachlor and its metabolites, determined as the derivatives CGA 37913 and CGA 49751. The residues of concern for S metolachlor are the same as for metolachlor ( DP Num: 226780, L. Kutney, 11/ 12/ 96); however, the Agency is currently reviewing additional submitted data ( DP Num: 278742 and 279110). These data will be incorporated into future assessments for metolachlor and S metolachlor.

4.1.2 Metabolism in Rotational Crops HED has concluded that the confined rotational crop study for metolachlor was inadequate but potentially upgradable. Additional data are required characterizing the 14C residues in plants, along with information on the percentage of the 14C residues measured by the current enforcement method, supporting storage stability data, and sample storage conditions and intervals. The Agency notes that additional confined accumulation data in lettuce, radish and wheat rotational crops have been submitted and are currently under review. These data will be included in future assessments. Once the residue data requested by the TRED for rotational grains are submitted through the reregistration process, HED will determine whether any of the tolerances should be revised ( PP# 3E6787, DP Num: 304120, R. Loranger, 4/ 17/ 06).

4.1.3 Metabolism in Livestock Adequate studies are available depicting the metabolism of metolachlor in ruminants and poultry. Metolachlor is rapidly metabolized and almost totally eliminated in the urine and feces of ruminants ( goats), non ruminants ( rats), and poultry. Metolachlor per se was not detected in any of the excreta or tissues. As in plants, metolachlor residues of concern in livestock commodities include metolachlor and its metabolites, determined as the derivatives CGA 37913 and CGA 49751. The residues of concern for S metolachlor in animals are the same as for metolachlor; however, the Agency is currently reviewing additional submitted data ( D278742 and D279110). These data will be incorporated into future assessments for metolachlor and Smetolachlor

4.1.4 Analytical Methodology Adequate methodology is available for enforcing the current and proposed tolerances. The Pesticide Analytical Manual ( PAM, Vol. II) lists a GC/ NPD method ( Methods I) for determining residues in/ on plants and a GC/ MSD method ( Method II) for determining residues in livestock commodities. These methods determine residues of metolachlor and its metabolites as either CGA 37913 or CGA 49751 following acid hydrolysis. A modified version of this method ( Syngenta Method No. 1848 01) which uses LC/ MS/ MS has also been used. Adequate data are available on the recovery of metolachlor through Multi residue Method Testing Protocols. The 23 of 66 FDA PESTDATA database indicates that metolachlor is completely recovered through Method 302, PAM Vol. I ( 3rd ed., revised 10/ 97).

4.1.5 Environmental Degradation The environmental fate database is complete for metolachlor. Parent metolachlor/ S metolachlor appear to be moderately persistent to persistent, and range from mobile to highly mobile in different soils. Metolachlor/ S metolachlor have reportedly been detected as far as the 36 to 48 inch soil layer in some studies. Degradation appears to be dependent on microbially mediated and abiotic processes. The frequency of detection of metolachlor/ S metolachlor from evaluated monitoring data suggest that contamination in drinking water sources is widespread.

Environmental fate data comparing metolachlor and S metolachlor indicate that both are expected to have similar degradation pathways and rates in soil and water environments, and both are expected to be mobile to highly mobile in soil and water environments.

4.1.6 Comparative Metabolic Profile S metolachlor is extensively absorbed and metabolized following oral administration. Metolachlor is rapidly metabolized and almost totally eliminated in the urine and feces of ruminants ( goats), non ruminants ( rats), and poultry. Metolachlor per se was not detected in any of the excreta or tissues. Tissue residues were highest in whole blood. The metabolism of metolachlor in plants involves conjugation with glutathione, breakage of this bond to form mercaptan, conjugation of the mercaptan with glucuronic acid, hydrolysis of the methyl ether, and conjugation of the resultant alcohol with a neutral sugar. A minor pathway may involve sugar conjugation of metolachlor directly to the corresponding oxo compounds. Residues of concern in plants include metolachlor and its metabolites, determined as the derivatives CGA 37913 and CGA 49751.

4.1.8 Pesticide Metabolites and Degradates of Concern Table 4.1.8 Summary of Metabolites and Degradates to be included in the Risk Assessment and Tolerance Expression Matrix Residues included in Risk Assessment Residues included in Tolerance Expression Primary Crop Parent, CGA 37913 and CGA 49751 Parent, CGA 37913 and CGA 49751 Plants Rotational Crop Parent, CGA 37913 and CGA 49751 Parent, CGA 37913 and CGA 49751 Ruminant Parent, CGA 37913 and CGA 49751 Parent, CGA 37913 and CGA 49751 Livestock Poultry Parent, CGA 37913 and CGA 49751 Parent, CGA 37913 and CGA 49751 24 of 66 Table 4.1.8 Summary of Metabolites and Degradates to be included in the Risk Assessment and Tolerance Expression Matrix Residues included in Risk Assessment Residues included in Tolerance Expression Drinking Water Parent, ethanesulfonic acid ( ESA) and oxanilic acid ( OA) Not Applicable See Appendix A, Table 3 for chemical structures.

4.1.9 Drinking Water Residue Profile A drinking water assessment was conducted based on monitoring data from several sources, as well as on Tier 1 FIRST and SCI GROW modeling results. This assessment is a worst case scenario and demonstrates high end numbers. It is important to note that the analytical methods used to obtain the monitoring data are not able to distinguish between metolachlor and S metolachlor; therefore, the estimated environmental concentrations ( EECs) presented in this risk assessment are representative of both racemic metolachlor and S metolachlor.

EECs for metolachlor and S metolachlor were calculated for both the parent compound and the ethanesulfonic acid ( ESA) and oxanilic acid ( OA) degradates. Although it was determined by the MARC that the ESA and OA metabolites appear to be less toxic than parent metolachlor, they are included in the risk assessment since they were found in greater abundance than the parent in water monitoring studies.

The crops with the highest maximum seasonal application rates are turf ( S metolachlor only) and corn ( racemic metolachlor and S metolachlor) with a maximum seasonal application rate of 4.0 lbs ai/ A. Based on PRZM/ EXAMS modeling the maximum peak and annual average concentrations of metolachlor/ S metolachlor in surface water were 199 ug/ l and 9.2 ug/ l, respectively. Based on FIRST modeling results from the TRED, the estimate of the drinking water concentration from surface water sources of metolachlor ESA, a major degradate of metolachlor, is not likely to exceed 31.9 ug/ L for the annual peak concentration and 22.8 ug/ L for the annual average exposure for use on turf/ corn at a maximum annual application rate of 4.0 lbs ai/ A. Based on FIRST modeling results from the TRED the estimate of the drinking water concentration from surface water sources of metolachlor OA, another major degradate of metolachlor, is not likely to exceed 91.4 ug/ L for the annual peak concentration and 65.1 ug/ L for the annual average exposure for use on turf/ corn at a maximum annual application rate of 4.0 lbs ai/ A ( ground application with no spray drift).

SCI GROW screening model was used to estimate groundwater concentrations. The estimated concentration of metolachlor/ S metolachlor in drinking water from shallow groundwater sources is 5.5 ug/ l for application on corn at a seasonal maximum rate of 4.0 lbs ai/ A. This concentration is appropriate for both the peak and annual average exposures. The EEC for metolachlor degradate ESA use on turf/ corn is not expected to exceed 65.8 ug/ l for peak and annual average exposures. The EEC for metolachlor OA use on turf/ corn is not expected to exceed 31.7 ug/ l for peak and annual average exposures. 25 of 66 As a result of the above modeling results, the recommended total EEC's for surface water ( peak), surface water ( average), and groundwater ( peak and average) are 322 ppb ( 199 parent + 31.9 ESA+ 91.4 OA), 97 ppb ( 9.2 parent + 22.8 ESA + 65.1 OA), and 103 ppb ( 5.5 parent + 65.8 ESA + 31.7 OA), respectively.

Table 4.1.9 Metolachlor EEC's Surface Water ( peak) Surface Water ( average) Ground Water Parent 199 9.2 5.5 metolachlor ESA 31.9 22.8 65.8 metolachlor OA 91.4 65.1 31.7 Total EECs ( ppb) 322.3 97.1 103.0 4.1.10 Food Residue Profile S metolachlor is a selective, chloroacetanilide herbicide that is applied to a variety of crops as a preplant, preplant incorporated ( PPI), pre emergence, or post emergence application, primarily for the control of grass weeds. Permanent tolerances for the combined S metolachlor residues have been established in/ on plant commodities ranging from 0.1 ppm in/ on a variety of plant commodities to 15 ppm in/ on sugar beet tops [ 40 CFR § 180.368( a)( 2)].

The proposed crop tolerances will have no impact on the maximum theoretical dietary burden ( MTDB) for livestock. Therefore, no changes are required in the tolerances for animal commodities as a result of the proposed Section 18s.

Cilantro, Collards, Kale, and Mustard Greens The Ohio Department of Agriculture is requesting a specific exemption for the use of Smetolachlor formulated as Dual Magnum ® ( EPA Reg. No.: 100 816) for control of common purslane and prostrate pigweed on cilantro, collards, kale, and mustard greens. The requested use is for a single application, pre emergence using a ground sprayer, at 0.95 lb ai/ A to 1500 A in the state of Ohio. A total of 1425 lb ai ( 187 gal formulation) would be used as a result of this request.

Previously submitted data from 11 crop field trials ( MRID 44615401) conducted on spinach during 1994 and 1995 show that the combined residues of CGA 37913 and CGA 49751, each expressed as parent metolachlor, were < 0.08< 0.38 ppm in/ on 22 samples of spinach harvested 34 69 days following a single pre emergence soil application of metolachlor at 1.0 lb ai/ A. Combined residues were also < 0.08 0.263 ppm in/ on 10 samples of spinach harvested 41 69 days following an pre emergence application at 2.0 lb ai/ A. These data would support a similar use of S metolachlor on spinach at a maximum rate of 0.6 lb ai/ A. The available data indicated 26 of 66 that a tolerance level of 0.5 ppm would be appropriate for a tolerance on spinach. Considering the similarity between spinach and the subject crops and the higher proposed application rate for this Section 18, the data indicate that residues of S metolachlor are not likely to exceed 1.0 ppm as a result of the proposed use. A time limited tolerance of 1.0 ppm for the residues of Smetolachlor on cilantro, collards, kale, and mustard greens would be appropriate.

Pumpkins and Winter Squash Residue trials conducted jointly by the Interregional Research Project Number 4 ( IR 4) and the Pest Management Centre of Agriculture and Agri Food Canada ( PMC, AAFC) on behalf of the Canadian Horticultural Council, have been submitted for S metolachlor on winter squash and have been reviewed ( MRID 46707501, D. Dotson, in process).

Eleven trials were conducted in the United States and Canada. The residue study was arranged into four treatment scenarios: 1 pre emergent ( PRE) soil application at 0.64 0.69 lb ai/ A ( Treatment 2); 1 pre emergent soil application at 1.25 1.37 lb ai/ A ( Treatment 3); 1 postemergent ( POST) foliar application at 0.63 0.69 lb ai/ A ( Treatment 4); and 1 post emergent foliar application at 1.25 1.43 lb ai/ A ( Treatment 5). An adjuvant was not added to the spray mixture for any application. Winter squash fruit was harvested at pre harvest intervals ( PHIs) of 43 119 days ( PRE Treatments 2 and 3) or 31 105 days ( POST Treatments 4 and 5).

Residue analysis for S metolachlor in/ on winter squash was conducted using an analytical method entitled " Working Method for Analysis of CGA 37913 and CGA 49751 in Winter Squash." The working method ( HPLC/ MS/ MS) was adapted and modified from the datagathering enforcement Method AG 612 ( GC analysis) which was previously reviewed. Briefly, residues were extracted by reflux with hydrochloric acid. For CGA 37913, acidified extracts were cleaned up by partitioning in hexane and reconstituted in methanol. For CGA 49751, extracts were derivatized in 10% boron trichloride 2 chloroethanol ( 10%) solution, cleaned up by partitioning in dichloromethane and then reconstituted in ethyl acetate. Residues of CGA 37913 in sample extracts were analyzed using HPLC/ MS/ MS, while residues of CGA 49751 were analyzed according to the reference method No. AG 612 using GC NPD. Acceptability of the working method was confirmed by method validation and concurrent procedural recoveries of 70 120% ( ± 20% SD) measured during the residue study.

A freezer storage stability test was conducted in conjunction with the residue study in order to demonstrate residue stability for the trial samples. For the stability test, samples were fortified at 0.990 0.998 ppm and stored frozen (< 14 ° C) for up to 629 days ( 20 months). Although the test storage period ( 629 days) was shorter than the actual sample storage period ( 720 days), considering stored test samples were stable for 629 days ( 1.7 years), it is expected that residues remained stable up to 720 days ( 2 years).

The results from these trials show that maximum total residues of S metolachlor ( determined as CGA 37913 and CGA 49751) were < 0.08 ppm ( below the Lowest Limit of Method Validation, LLMV) in winter squash treated with either one pre emergent soil application ( 0.72 1.54 kg ai/ ha or 0.64 1.37 lb ai/ A) or one post emergent foliar application ( 0.71 1.60 kg ai/ ha or 27 of 66 0.63 1.43 lb ai/ A), and harvested at PHIs of 31 119 days. Only one residue was detected above the LLMV ( CGA 49751 at 0.061 ppm).

TABLE 4.2.10 Summary of Residue Data from Crop Field Trials with S metolachlor.

Residue Levels ( ppm) Commodity Total Applic. Rate lb ai/ A ( kg ai/ ha) PHI ( days)

n Min. Max. HAFT* Median ( STMdR)** Mean ( STMR)** Std. Dev.

Total combined residues, expressed as parent equivalents 0.64  0.69 ( 0.72  0.77) PRE 43  119 22 < 0.08 < 0.08 < 0.08 < 0.08 < 0.08

1.25  1.37 ( 1.40  1.54) PRE 43  119 20 < 0.08 < 0.08 < 0.08 < 0.08 < 0.08

0.63  0.69 ( 0.71  0.77) POST 31  105 22 < 0.08 0.091 0.086 0.08 0.081  Winter squash, fruit 1.25  1.43 ( 1.40  1.60) POST 31  105 22 < 0.08 < 0.08 < 0.08 < 0.08 < 0.08

PRE = preemergent ( to crop), POST = post emergent ( to crop) * HAFT = Highest Average Field Trial. ** STMdR = Supervised Trial Median Residue; STMR = Supervised Trial Mean Residue Conclusions: In order to harmonize with PMRA, a revised Section B is required indicating the use on pumpkin as direct seeded treatment ( soil application, pre emergent to crop and weed) or post emergent treatment ( foliar application at the 1 2 leaf crop stage, prior to weed emergence) at a rate of 0.94 lb ai/ A ( 1.05 kg ai/ ha), and a PHI of 65 days ( email: Denise MacGillivray Evaluation Officer, HED, PMRA, 6/ 26/ 06). No US registration for winter squash is requested at this time. The submitted data with the revised Section B are sufficient to indicate that residues of S metolachlor on winter squash are not likely to exceed the proposed tolerance of 0.1 ppm. According to the 2002 Reviewer's Guide, if winter squash data are submitted and found acceptable to support a winter squash tolerance then tolerances can be established on several Cucurbita spp. including pumpkin. The data submitted are sufficient to support the request for a tolerance on pumpkins. The proposed tolerances of 0.1 ppm for the residues of S metolachlor on pumpkins and winter squash are appropriate. The tolerance on winter squash would be established without a US registration.

4.2.11 International Residue Limits There are currently no Codex, Canadian or Mexican MRLs for S metolachlor; therefore there are no international harmonization issues for these actions.

4.3 Dietary Exposure and Risk Acute and chronic dietary risk assessments were conducted using the Dietary Exposure Evaluation Model ( DEEM FCID   , Version 2.03) which uses food consumption data from the 28 of 66 USDA's Continuing Surveys of Food Intakes by Individuals ( CSFII) from 1994 1996 and 1998. The analyses were performed to support Section 18 requests for the use of S metolachlor on cilantro, collards, kale, mustard greens, a Section 3 Use on Pumpkin; and Tolerance on Winter Squash without a US Registration.

Both the acute and chronic analyses assume tolerance level residues on all crops with established, pending, or proposed tolerances for metolachlor and/ or S metolachlor. In cases where separate tolerance listings occur for both metolachlor and S metolachlor on the same commodity, the higher value of the two is used in the analyses.

An acute dietary analysis for S metolachlor was conducted using tolerance levels and 100 % CT for all existing and proposed uses. The highest drinking water estimate for acute exposure, 322 ppb, was used in the analysis. The dietary exposure estimate to the U. S. population was < 1% aPAD and the most highly exposed subgroup, all infants < 1 yr old, at 2% aPAD. The results of the analysis indicate that acute risk from the dietary exposure to S metolachlor from the existing and requested uses did not exceed HED's level of concern for U. S. population or any population subgroup.

A chronic dietary analysis for S metolachlor was conducted using tolerance levels and 100 % CT data for all existing and proposed uses. The highest drinking water estimate for chronic exposure, 103 ppb, was used in the analysis. The dietary exposure estimate to the U. S. population was 4% cPAD and the most highly exposed subgroup, all infants < 1 yrs old, at 10% cPAD. The results of the analysis indicate that chronic risk from the dietary exposure to Smetolachlor from the existing and requested uses did not exceed HED's level of concern for the U. S. population or any population subgroup.

Table 4.3 Summary of Dietary Exposure and Risk for S metolachlor Acute Dietary ( 95th Percentile) Chronic Dietary Cancer Population Subgroup Dietary Exposure ( mg/ kg/ day) % aPAD Dietary Exposure ( mg/ kg/ day) % cPAD Dietary Exposure ( mg/ kg/ day) Risk General U. S. Population 0.019972 < 1 0.004113 4 All Infants (< 1 year old) 0.066430 2 0.010003 10 Children 1 2 years old 0.033427 1 0.007954 8 Children 3 5 years old 0.029665 < 1 0.007160 7 Children 6 12 years old 0.020708 < 1 0.004914 5 Youth 13 19 years old 0.016010 < 1 0.003352 3 Adults 20 49 years old 0.017578 < 1 0.003613 4 Adults 50+ years old 0.015963 < 1 0.003597 4 Females 13 49 years old 0.017453 < 1 0.003521 4 N/ A N/ A 29 of 66 5.0 Residential ( Non Occupational) Exposure/ Risk Characterization 5.1 Residential Handler Exposure There are no residential handler uses of S metolachlor and, therefore, no residential handler exposure assessment is required.

5.2 Residential Postapplication Exposure The formulated S metolachlor end use product is labeled under the trade name Pennant MAGNUMTM ( EPA Reg. No. 100 950) to distinguish the new product from the original metolachlor formulation named PennantTM ( EPA Reg. No. 100 691). Pennant MAGNUMTM ( 7.62 lbs. active ingredient per gallon) is labeled for use on commercial ( sod farm) and residential warm season turfgrasses and other noncrop land including golf courses, sports fields, and ornamental gardens. Although not labeled as a restricted use pesticide, Pennant MAGNUMTM, as currently marketed, is not intended for homeowner purchase or use ( intended for use by professionals). On this basis, with regard to the requirements of FQPA, metolachlor and S metolachlor are risk assessed for postapplication exposure only. Pennant MAGNUMTM and PennantTM are both emulsifiable concentrates ( EC).

For this risk assessment, small children are the population group of concern. Although the type of site that S metolachlor may be used on varies from golf courses to ornamental gardens, the scenario chosen for risk assessment ( residential turf use) represents what the Agency considers the likely upper end of possible exposure. Postapplication exposures from various activities following lawn treatment are considered to be the most common and significant in residential settings. Since toxicity was not observed in a dermal toxicity study, up to a dose level of 1,000 mg/ kg/ day, the only parameter of risk necessarily addressed in this assessment is the possible oral exposure of small children from treated turf, or soil.

The estimate for hand to mouth exposure on the day of treatment is 0.037 mg/ kg/ day ( MOE = 1,400) for S metolachlor and 0.06 mg/ kg/ day ( MOE = 840) for metolachlor. ( MOE estimates are based on the short term NOAEL of 50 mg/ kg/ day).

The estimate for object to mouth exposure on the day of treatment is 0.0092 mg/ kg/ day ( MOE = 5,400) for S metolachlor and 0.015 mg/ kg/ day ( MOE = 3,300) for metolachlor. ( MOE estimates are based on the short term NOAEL of 50 mg/ kg/ day).

The estimate for soil ingestion exposure on the day of treatment is 0.00012 mg/ kg/ day ( MOE = 400,000) for S metolachlor and 0.0002 mg/ kg/ day ( MOE = 250,000) for metolachlor. ( MOE estimates are based on the short term NOAEL of 50 mg/ kg/ day).

The estimate for hand to mouth, object to mouth, and soil ingestion combined ( on the day of treatment) is 0.046 mg/ kg/ day ( MOE = 1,100) for S metolachlor and 0.075 mg/ kg/ day ( MOE = 670) for metolachlor. ( MOE estimates are based on the short term NOAEL of 50 mg/ kg/ day). 30 of 66 The MOE estimates above are greater than 100 and indicate that the potential metolachlor/ Smetolachlor exposure ( to children) associated with residential use is not sufficient to require further assessment. Although considered an upper bound, the exposure estimate for the three scenarios, combined, is recommended for aggregate ( residential, food, and drinking water) risk estimates.

5.3 Other ( Spray Drift, etc.)

Spray drift is always a potential source of exposure to residents nearby to spraying operations. This is particularly the case with aerial application, but, to a lesser extent, could also be a potential source of exposure from the ground application method employed for S metolachlor. The Agency has been working with the Spray Drift Task Force, EPA Regional Offices and State Lead Agencies for pesticide regulation and other parties to develop the best spray drift management practices. The Agency is now requiring interim mitigation measures for aerial applications that must be placed on product labels/ labeling. The Agency has completed its evaluation of the new database submitted by the Spray Drift Task Force, a membership of U. S. pesticide registrants, and is developing a policy on how to appropriately apply the data and the AgDRIFT computer model to its risk assessments for pesticides applied by air, orchard airblast and ground hydraulic methods. After the policy is in place, the Agency may impose further refinements in spray drift management practices to reduce off target drift and risks associated with aerial as well as other application types where appropriate.

Please note that as indicated in this assessment, S metolachlor is directly applied to residential turf and does not result in exposures of concern. It is unlikely that the potential for risk of exposure to spray drift from agricultural uses would be higher than that estimated for the turf use of this chemical.

6.0 Aggregate Risk Assessments and Risk Characterization 6.1 Acute Aggregate Risk An acute aggregate risk assessment addresses potential exposure from combined residues of metolachlor/ S metolachlor on food and in drinking water ( both surface and ground water). Potential residential exposures are not incorporated into an acute aggregate risk assessment. Since the exposure from food and drinking water were already incorporated into the acute dietary risk assessment, no further aggregation is required. The dietary exposure estimate to the U. S. population was < 1% aPAD and the most highly exposed subgroup, all infants < 1 yr old, at 2% aPAD. The results of the analysis indicate that acute aggregate exposure risk to S metolachlor from the existing and requested uses did not exceed the Agency's level of concern for U. S. population or any population subgroup.

6.2 Short Term Aggregate Risk A short term aggregate risk assessment considers potential exposure from food, drinking water, and short term, non occupational ( residential) pathways of exposure for a duration of 1 to 30 31 of 66 days. For S metolachlor, potential short term, non occupational risk scenarios consist of oral exposure of children to treated lawns only. In this aggregate short term risk assessment, exposure from food, drinking water, and residential lawns has been considered. The exposure to food and water has already been considered in the chronic dietary risk assessment. The dietary exposure estimate was 4% cPAD for the U. S. population and 10% cPAD for the most highly exposed subgroup, all infants < 1 yrs old. Since only children have the potential for nonoccupational short term risk, they are the only population subgroup for which an aggregate short term risk assessment was conducted. Toddlers' S metolachlor incidental oral exposure is assumed to include hand to mouth exposure, object to mouth exposure and exposure through incidental ingestion of soil.

Table 6.2. Short Term Aggregate Risk Calculations Short  Term Scenario Population NOAEL mg/ kg/ day LOC1 Average Food & Water Exposure mg/ kg/ day Residential Exposure2 mg/ kg/ day Aggregate MOE ( food and residential) 3 All infants < 1 yr old 50 100 0.010003 0.046 890 1 The level of concern ( LOC) MOE is 100, based on inter and intra species safety factors totaling 100. 2 Residential Exposure = [ Incidental Oral exposure from all possible sources  combined hand to mouth, object tomouth and soil ingestion oral exposure]. No residential oral exposure is expected for adults 3 Aggregate MOE = [ NOAEL ÷ ( Avg Food & Water Exposure + Residential Exposure)]

The aggregate short term risk for exposure to S metolachlor for all infants < 1 yr old, the subgroup with the highest exposure, is MOE of 890, which does not reach the Agency's level of concern.

6.3 Intermediate Term Aggregate Risk An intermediate term aggregate risk assessment considers potential exposure from food, drinking water, and non occupational ( residential) pathways of exposure for a duration of 30 to 180 days. However, for metolachlor/ S metolachlor, no intermediate term non occupational exposure scenarios are expected to occur; therefore, an intermediate term aggregate risk assessment is not required.

6.4 Chronic Aggregate Risk A chronic aggregate risk assessment considers chronic exposure from food, drinking water, and non occupational ( residential) pathways of exposure. For metolachlor and S metolachlor, there are no chronic ( greater than 180 days of exposure) non occupational exposure scenarios. Therefore, the chronic aggregate risk assessment considers exposure from food and drinking water only. Since the exposure from food and drinking water were already incorporated into the chronic dietary risk assessment, no further aggregation is required. The chronic dietary exposure estimate to the U. S. population was 4% cPAD and the most highly exposed subgroup, all infants 32 of 66 < 1 yrs old, at 10% cPAD. The results of the analysis indicate that chronic aggregate risk from exposure to S metolachlor from the existing and requested uses did not exceed the Agency's level of concern for the U. S. population or any population subgroup.

6.5 Cancer Risk Metolachlor has been classified as a Group C, possible human carcinogen based on liver tumors in rats at the highest dose tested. The chronic NOAEL of 15 mg/ kg/ day that was established based on tumors in the rat ( seen at the highest dose tested of 150 mg/ kg/ day) is comparable to the NOAEL of 9.7 mg/ kg/ day selected for establishing the chronic reference dose for metolachlor. It is assumed that the chronic dietary PAD is protective for cancer dietary risk. Therefore, a separate cancer aggregate risk assessment was not conducted.

7.0 Cumulative Risk Characterization/ Assessment 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 S metolachlor and any other substances and S metolachlor 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 S metolachlor 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/.

8.0 Occupational Exposure/ Risk Pathway S metolachlor is a widely used herbicide in the United States   it is used in agricultural, commercial, and residential settings. S metolachlor is formulated as an emulsifiable concentrate and is applied with several types of application equipment. The major wide area methods are aerial, groundboom, and chemigation applications. Applications to smaller areas may be made with handheld equipment, including low pressure handwand sprayers, high pressure handwand sprayers, and handgun sprayers. S metolachlor can also be impregnated into dry bulk fertilizers. There is a potential for exposure to S metolachlor in occupational scenarios from handling Smetolachlor products during the application process ( i. e., mixer/ loaders, applicators, flaggers, and mixer/ loader/ applicators) and a potential for postapplication worker exposure from entering into areas previously treated with S metolachlor. As a result, risk assessments have been completed for occupational handler scenarios as well as occupational postapplication scenarios.

A chemical can produce different effects based on how long a person is exposed, how frequently exposures occur, and the level of exposure. HED classifies exposures up to 30 days as shortterm and exposures greater than 30 days up to several months as intermediate term. HED completes both short and intermediate term assessments for occupational scenarios in essentially all cases, because these kinds of exposures are likely and acceptable use/ usage data are not available to justify deleting intermediate term scenarios. Based on use data and label 33 of 66 instructions, HED believes that occupational S metolachlor exposures may occur over a single day or up to weeks at a time for many use patterns and intermittent exposures over several weeks also may occur. Some applicators may apply S metolachlor over a period of weeks, because they are custom or commercial applicators who are completing a number of applications for a number of different clients. Long term handler exposures are not expected to occur for Smetolachlor Different toxicological endpoints of concern have been selected for short and intermediate term inhalation exposures to S metolachlor; therefore the risk results for all inhalation durations of exposure are numerically distinct.

This risk assessment incorporates the toxicological endpoints of concern as presented in the Report of the Hazard Identification Assessment Review Committee ( HIARC) September 28, 2001. No short or intermediate term dermal endpoint of concern was identified. The short term inhalation endpoint of concern ( 50 mg/ kg/ day) is based on increased incidence of clinical signs, decreased body weight and body weight gain, food consumption, and food efficiency from an oral prenatal developmental toxicity study in rats with S metolachlor. Since an oral study was selected, a 100% absorption factor should be applied and since the endpoint is from a prenatal developmental toxicity study, a body weight of 60 kilograms   the weight of an average female adult   was used. The intermediate term inhalation endpoint of concern ( 8.8 mg/ kg/ day) is based on decreased body weight gain from an oral subchronic ( 6 month) toxicity study in dogs with metolachlor. Since an oral study was selected, a 100% absorption factor should be applied and since the toxicological endpoint of concern is not sex specific, a body weight of 70 kilograms   the weight of an average adult   was used. Only inhalation MOEs were calculated, therefore, no aggregation was performed.

The Agency's level of concern for noncancer risks ( i. e., target level for MOEs) is defined by the uncertainty factors that are applied to the assessment. The Agency applies a factor of 100 to account for inter species extrapolation to humans from the animal test species and to account for intra species sensitivity. The total uncertainty factor that has been applied to noncancer risk assessments is 100 for occupational scenarios.

8.1 Short/ Intermediate/ Long Term/ Cancer Handler Risk HED uses the term " handlers" to describe those individuals who are involved in the pesticide application process. HED believes that there are distinct job functions or tasks related to applications and that exposures can vary depending on the specifics of each task. Job requirements ( e. g., amount of chemical to be used in an application), the kinds of equipment used, the target being treated, and the level of protection used by a handler can cause exposure levels to differ in a manner specific to each application event.

8.1.1 Data and Assumptions for Proposed Handler Exposure Scenarios HED uses exposure scenarios to describe the various types of handler exposures that may occur for a specific active ingredient. The anticipated use patterns and current labeling indicate several 34 of 66 occupational exposure scenarios based on the types of equipment and techniques that can potentially be used for S metolachlor applications.

A series of assumptions and exposure factors served as the basis for completing the occupational handler risk assessments. Each assumption and factor is detailed below on an individual basis. The assumptions and factors used in the risk calculations include:

  Occupational handler exposure estimates were based on surrogate data from: ( 1) the Pesticide Handlers Exposure Database ( PHED) and ( 2) the Outdoor Residential Exposure Task Force ( ORETF).

  The adverse effects for the short term inhalation endpoint are based on an inhalation study where the effects were observed in females, therefore, the average body weight of an adult female handler ( i. e., 60 kg) is used to complete the short term inhalation noncancer risk assessment.

  The adverse effects for the intermediate term inhalation endpoint are based on an inhalation study where the effects were observed in males and females, therefore, the average body weight of an adult handler ( i. e., 70 kg) is used to complete the intermediate term inhalation noncancer risk assessment.

  Exposure factors used to calculate daily exposures to handlers are based on applicable data, if available.

  For non cancer assessments, HED assumes the maximum application rates allowed by labels in its risk assessments ( see Table 3).

  The average occupational workday is assumed to be 8 hours.

  The daily areas treated were defined for each handler scenario ( in appropriate units) by determining the amount that can be reasonably treated in a single day ( e. g., acres, square feet, cubic feet, or gallons per day). When possible, the assumptions for daily areas treated are taken from the Health Effects Division Science Advisory Committee on Exposure SOP # 9: Standard Values for Daily Acres Treated in Agriculture, which was completed on July 5, 2000. However, no standard values are available for numerous scenarios. Assumptions for these scenarios are based on HED estimates and could be further refined from input from affected sectors ( see Table 8.1.1).

Table 8.1.1 Summary of Maximum Application Rates for Proposed S Metolachlor Uses from Magnum Herbicide ( EPA Reg No. 100 816)

Crop or Target Application Rate ( lb ai/ acre) Application Equipment Area Treated Daily ( acres)

Agricultural Uses Sodfarms 2.5 lb ai/ acre Aerial 350 acres 35 of 66 Table 8.1.1 Summary of Maximum Application Rates for Proposed S Metolachlor Uses from Magnum Herbicide ( EPA Reg No. 100 816)

Crop or Target Application Rate ( lb ai/ acre) Application Equipment Area Treated Daily ( acres)

Chemigation Groundboom 80 acres Dry Bulk Fertilizers ( on farm) 80 acres 320 acres ( commercial applicator) 50 lb ai/ ton ( based on label recommendation of 100 pounds of fertilizer per acre) Dry Bulk Fertilizers ( commercial) 500  960 tons ( commercial mixer/ loader)

Aerial Chemigation 350 acres Groundboom 80 acres 2.5 lb ai/ acre Dry Bulk Fertilizers ( on farm) 80 acres 320 acres ( commercial applicator) Tabasco Peppers 25 lb ai/ ton ( based on label recommendation of 200 pounds of fertilizer per acre) Dry Bulk Fertilizers ( commercial) 500  960 tons ( commercial mixer/ loader)

Chemigation 60 acres Dry Bulk Fertilizers ( on farm) 60 acres Handgun Sprayer 5 acres High Pressure Handwand Sprayer 5acres 2.5 lb ai/ acre Low Pressure Handwand Sprayer 2 acres 320 acres ( commercial applicator) Nurseries 50 lb ai/ ton ( based on label recommendation of 100 pounds of fertilizer per acre) Dry Bulk Fertilizers ( commercial) 500  960 tons ( commercial mixer/ loader)

Aerial 1200 acres Chemigation 350 acres Groundboom 200 acres 1.9 lb ai/ acre Dry Bulk Fertilizers ( on farm) 160 acres 320 acres ( commercial applicator) Corn, Soybeans 19 lb ai/ ton ( based on label recommendation of 200 pounds of fertilizer per acre) Dry Bulk Fertilizers ( commercial) 500  960 tons ( commercial mixer/ loader)

Pod crops, 1.9 lb ai/ acre Aerial 350 36 of 66 Chemigation Groundboom 80 Dry Bulk Fertilizers ( on farm) 80 acres 320 acres ( commercial applicator) Peanuts, Potatoes, Safflowers, Brassica head and stem, Leaf petioles 19 lb ai/ ton ( based on label recommendation of 200 pounds of fertilizer per acre) Dry Bulk Fertilizers ( commercial) 500  960 tons ( commercial mixer/ loader)

Aerial 1200 acres Chemigation 350 acre Groundboom 200 acres 1.6 lb ai/ acre Dry Bulk Fertilizers ( on farm) 160 acres 320 acres ( commercial applicator) Grain/ Forage Sorghum 16 lb ai/ ton ( based on label recommendation of 200 pounds of fertilizer per acre) Dry Bulk Fertilizers ( commercial) 500  960 tons ( commercial mixer/ loader)

Aerial Chemigation 350 acres Groundboom 80 acres 1.6 lb ai/ acre Dry Bulk Fertilizers ( on farm) 80 acres 320 acres ( commercial applicator) Transplanted and Direct Seeded Vegetables 16 lb ai/ ton ( based on label recommendation of 200 pounds of fertilizer per acre) Dry Bulk Fertilizers ( commercial) 500  960 tons ( commercial mixer/ loader)

Aerial 1200 acres Chemigation 350 acres Groundboom 200 acres 1.3 lb ai/ acre ( based on label recommendation of 200 pounds of fertilizer per acre) Dry Bulk Fertilizers ( on farm) 160 acres 320 acres ( commercial applicator) Cotton 13 lb ai/ ton Dry Bulk Fertilizers ( commercial) 500  960 tons ( commercial mixer/ loader)

Chemigation 350 acres Pumpkins and Winter Squash 1.27 lb ai/ A Groundboom 80 acres Aerial Chemigation 350 acres Groundboom 80 acres Green and Dry Bulb onions, Vegetable root ( except sugar beet) 1.3 lb ai/ acre Dry Bulk Fertilizers ( on farm) 80 acres 37 of 66 320 acres ( commercial applicator) 13 lb ai/ ton ( based on label recommendation of 200 pounds of fertilizer per acre) Dry Bulk Fertilizers ( commercial) 500  960 tons ( commercial mixer/ loader)

Commercial Uses Residential and Commercial Turfgrass 2.5 Handgun Sprayer 5 acres Handgun Sprayer 5 acres High Pressure Handwand Sprayer 5 acres Landscape Plantings 2.5 Low Pressure Handwand Sprayer 2 acres 8.1.2 Summary of Exposure Data for Handler Exposure Scenarios HED uses unit exposure to assess handler exposures to pesticides. Unit exposures are estimates of the amount of exposure to an active ingredient a handler receives while performing various handler tasks and are expressed in terms of micrograms or milligrams of active ingredient per pounds of active ingredient handled. HED has developed a series of unit exposures that are unique for each scenario typically considered in our assessments ( i. e., there are different unit exposures for different types of application equipment, job functions, and levels of protection). The unit exposure concept has been established in the scientific literature and also through various exposure monitoring guidelines published by the U. S. EPA and international organizations such as Health Canada and OECD ( Organization for Economic Cooperation and Development).

Pesticide Handler Exposure Database ( PHED) Version 1.1 ( August 1998): PHED was designed by a task force of representatives from the U. S. EPA, Health Canada, the California Department of Pesticide Regulation, and member companies of the American Crop Protection Association. PHED is a software system consisting of two parts   a database of measured exposures for workers involved in the handling of pesticides under actual field conditions and a set of computer algorithms used to subset and statistically summarize the selected data. Currently, the database contains values for over 1,700 monitored individuals ( i. e., replicates).

Occupational handler exposure assessments are completed by HED using different levels of risk mitigation. Typically, HED uses a tiered approach. The lowest tier is designated as the baseline exposure scenario ( i. e., no respirator). If risks are of concern at baseline attire, then increasing levels of personal protective equipment or PPE ( e. g., respirators) are evaluated. If risks remain a concern with maximum PPE, then engineering controls ( e. g., enclosed cabs or cockpits, watersoluble packaging, and closed mixing/ loading systems) are evaluated. This approach is used to ensure that the lowest level of risk mitigation that provides adequate protection is selected, since the addition of PPE and engineering controls involves an additional expense to the user and   in the case of PPE   also involves an additional burden to the user due to decreased comfort and dexterity and increased heat stress and respiratory stress. 38 of 66 Surrogate Data: HED used surrogate data for some exposure scenarios.

HED generated MOEs to assess risk to commercial handlers engaged in impregnating Smetolachlor onto dry bulk fertilizer using inhalation unit exposure data from the Pesticide Handlers Exposure Database ( PHED), Version 1.1 ( August 1998). The PHED scenario for mixing/ loading liquids using a closed system were used as a surrogate to estimate these exposures. However, such an exposure surrogate is less appropriate for estimating exposures due to transferring the treated dry bulk fertilizer from an auger truck to the application equipment. There are no data or reasonable surrogate data available for this operation.

HED generated MOEs to assess risk to on farm handlers engaged in impregnating S metolachlor onto dry bulk fertilizer using inhalation unit exposure data from the Pesticide Handlers Exposure Database ( PHED), Version 1.1 ( August 1998). The PHED scenario for mixing/ loading liquids using an open system was used as a surrogate to estimate these exposures.

HED generated MOEs to assess risk to on farm and commercial applicators engaged in applying impregnated dry bulk fertilizer using inhalation unit exposure data from the Pesticide Handlers Exposure Database ( PHED), Version 1.1 ( August 1998). The PHED scenario for applying granular formulations with a tractor drawn spreader using an open cab was used as a surrogate to estimate these exposures.

8.1.3 Non cancer S metolachlor Handler Exposure and Risk The following equations and calculations were used in determining handler exposure and risk:

Daily Exposure: Daily inhalation handler exposures are estimated for each applicable handler task with the application rate, the area treated in a day, and the applicable inhalation unit exposure using the following formula:

     × × = day area Treated Area Daily area ai lb Rate n Applicatio handled ai lb ai mg Exposure Unit day ai mg Exposure Dailey Where:

Daily Exposure = Amount ( mg ai/ day) inhaled that is available for inhalation absorption; Unit Exposure = Unit exposure value ( mg ai/ lb ai) derived from August 1998 PHED data, from ORETF data, and from Proprietary data; Application Rate = Normalized application rate based on a logical unit treatment, such as acres, or tons. Maximum values are generally used ( lb ai/ A, lb ai/ ton); and Daily Area Treated = Normalized application area based on a logical unit treatment such as acres ( A/ day) or tons ( tons/ day).

Daily Dose: The daily inhalation dose is calculated by normalizing the daily exposure by body weight and adjusting, if necessary, with an appropriate inhalation absorption factor. For short term inhalation exposure scenarios for S metolachlor, an average adult female body weight of 60 kilograms was used, since the toxicological endpoint is sex specific. For intermediate term inhalation exposure scenarios for S metolachlor, an average adult body weight of 70 kilograms 39 of 66 was used, since the toxicological endpoint is not sex specific. Since the inhalation toxicological endpoints of concern are based on oral studies, an inhalation absorption factor of 100% is needed for the inhalation dose calculations. Daily dose was calculated using the following formula:

( )

    ×

    = ( kg) h Body Weigt (%/ 100) Factor Absorption day ai mg Exposure Daily mg/ kg/ day Dose Daily Average Where:

Average Daily Dose = Absorbed dose received from exposure to a pesticide in a given scenario ( mg pesticide active ingredient/ kg body weight/ day); Daily Exposure = Amount ( mg ai/ day) inhaled that is available for inhalation absorption; Absorption Factor = A measure of the amount of chemical that crosses a biological boundary such as the lungs (% of the total available absorbed); and Body Weight = Body weight determined to represent the population of interest in a risk assessment ( kg).

Margins of Exposure: Non cancer inhalation risks for each applicable handler scenario are calculated using a Margin of Exposure ( MOE), which is a ratio of the daily dose to the toxicological endpoint of concern. All MOE values were calculated for inhalation exposure levels using the formula below:

) ( mg/ kg/ day Dose Daily Average ) ( mg/ kg/ day LOAEL or NOAEL MOE=

Where:

MOE = Margin of Exposure, value used by HED to represent risk or how close a chemical exposure is to being a concern ( unitless); ADD = Average Daily Dose or the absorbed dose received from exposure to a pesticide in a given scenario ( mg pesticide active ingredient/ kg body weight/ day); and NOAEL or LOAEL = Dose level in a toxicity study, where no observed adverse effects ( NOAEL) or where the lowest observed adverse effects ( LOAEL) occurred in the study The short and intermediate term non cancer risk calculations for occupational S metolachlor handlers are presented in Table 8.1.3. Dermal risks were not evaluated since no hazard was identified for quantification of risk following dermal exposure. For both short term and intermediate term exposures, the following scenarios risks were not a concern at the baseline level ( no respirator) of exposure:

  Mixing/ Loading Emulsifiable Concentrates for Aerial Applications   Mixing/ Loading Emulsifiable Concentrates for Chemigation Applications   Mixing/ Loading Dry Bulk Fertilizers ( on farm, PHED)   Mixing/ Loading Emulsifiable Concentrates for Groundboom Applications   Applying Liquid Sprays via Groundboom Equipment   Applying Dry Bulk Fertilizers ( commercial, PHED)   Applying Dry Bulk Fertilizers ( on farm, PHED)   Flagging for Liquid Sprays via Aerial Equipment   Mixing/ Loading/ Applying Emulsifiable Concentrates with a Handgun Sprayer 40 of 66   Mixing/ Loading/ Applying Emulsifiable Concentrates with a Low Pressure Handwand HED has insufficient data to assess baseline and PPE levels of exposures to assess risks to pilots applying sprays with open cockpit aerial equipment   the only available data is for pilots using enclosed cockpits. In addition, HED assumes commercial mixer/ loaders impregnating dry bulk fertilizers ( using the PHED data) are using engineering controls ( i. e., closed systems). Therefore for these scenarios, only inhalation risks using engineering controls are assessed. The inhalation risks at the engineering control level of exposure were not a concern for these scenarios:

  Mixing/ Loading Dry Bulk Fertilizers ( commercial  PHED)   Applying Liquid Sprays via Aerial Equipment For most of the occupational handler scenarios for S metolachlor risks were not found to be a concern at the baseline attire exposure level. For those scenarios with only engineering control exposure data available, risks were not found to be a concern at that level of exposure. Therefore, the short and intermediate term inhalation handler risk assessment for S metolachlor does not indicate risk concerns for any of the handler scenarios.

The key data gap identified by HED for occupational handlers is exposures while transferring just impregnated dry bulk fertilizer into trucks. After impregnation, the treated fertilizer is gravity fed through a hopper onto a conveyor belt leading to a truck, which carries it to the field. There are no data or reasonable surrogates available for the transfer operation. In addition, data gaps exist for mixing/ loading and applying dry bulk fertilizers. HED has no data for these scenarios and has used surrogate PHED data from scenarios assumed to be similar.

In order to refine this occupational risk assessment, data on actual use patterns including rates, timing, and areas treated would better characterize S metolachlor risks. Exposure studies for many equipment types that lack data or that are not well represented in PHED ( e. g., because of low replicate numbers or data quality) should also be considered based on the data gaps identified above and based on a review of the quality of the data used in this assessment. 41 of 66 42 of 66 Table 8.1.3 S Metolachlor Short term and Intermediate term Inhalation Risks Unit Exposures ( Fg/ lb ai)

Exposure Scenario Crop or Target Application Ratea Area Treated Dailyb No Respiratorc ( unless noted) No Respirator ( unless noted)

Short term Dose ( mg/ kg/ day) No Respirator ( unless noted)

Short term MOEd No Respirator ( unless noted)

Intermediate term Dose ( mg/ kg/ day) No Respirator ( unless noted) Intermediate term MOEe Mixer/ Loader Tabasco Peppers,

Sodfarms 2.5 lb ai/ acre 350 acres 1.2 0.018 2900 0.015 590 Corn, Soybeans 1.9 lb ai/ acre 1200 acres 1.2 0.046 1100 0.039 230 Peanuts, Pod crops,

Potatoes, Safflowers,

Brassica head and stem, Leaf petioles 1.9 lb ai/ acre 350 acres 1.2 0.013 3800 0.011 770 Grain/ Forage Sorghum 1.6 lb ai/ acre 1200 acres 1.2 0.038 1300 0.033 270 Transplanted and Direct Seeded Vegetables 1.6 lb ai/ acre 350 acres 1.2 0.011 4500 0.0096 920 Cotton 1.3 lb ai/ acre 1200 acres 1.2 0.031 1600 0.027 330 Emulsifiable Concentrates ( Liquids) for Aerial Applications Green and Dry Bulb onions, Vegetable root ( except sugar beet) 1.3 lb ai/ acre 350 acres 1.2 0.0091 5500 0.0078 1100 Emulsifiable Concentrates Tabasco Peppers,

Sodfarms 2.5 lb ai/ acre 350 acres 1.2 0.018 2900 0.015 590 43 of 66 Table 8.1.3 S Metolachlor Short term and Intermediate term Inhalation Risks Unit Exposures ( Fg/ lb ai)

Exposure Scenario Crop or Target Application Ratea Area Treated Dailyb No Respiratorc ( unless noted) No Respirator ( unless noted)

Short term Dose ( mg/ kg/ day) No Respirator ( unless noted)

Short term MOEd No Respirator ( unless noted)

Intermediate term Dose ( mg/ kg/ day) No Respirator ( unless noted) Intermediate term MOEe ( Liquids) for Chemigation Applications Nurseries 2.5 lb ai/ acre 60 acres 1.2 0.003 17000 0.0026 3400 44 of 66 Corn, Peanuts, Pod crops, Potatoes,

Safflowers,

Soybeans, Brassica head and stem, Leaf petioles 1.9 lb ai/ acre 350 acres 1.2 0.013 3800 0.011 770 Grain/ Forage Sorghum,

Transplanted and Direct Seeded Vegetables 1.6 lb ai/ acre 350 acres 1.2 0.011 4500 0.0096 920 Cotton, Green and Dry Bulb onions,

Vegetable root ( except sugar beet) 1.3 lb ai/ acre 350 acres 1.2 0.0091 5500 0.0078 1100 Pumpkin and Winter Squash 1.27 lb ai/ acre 350 acres 1.2 0.0089 5,600 0.0076 1,200 Sodfarms, Nurseries 50 lb ai/ ton 960 tons 0.083 ( engineering controls) 0.066 ( engineering controls) 750 ( engineering controls) 0.057 ( engineering controls) 150 ( engineering controls)

Sodfarms, Nurseries 50 lb ai/ ton 500 tons 0.083 ( engineering controls) 0.035 ( engineering controls) 1,400 ( engineering controls) 0.03 ( engineering controls) 300 ( engineering controls)

Tabasco Peppers 25 lb ai/ ton 960 tons 0.083 ( engineering controls) 0.033 ( engineering controls) 1,500 ( engineering controls) 0.028 ( engineering controls) 310 ( engineering controls)

Dry Bulk Fertilizers ( commercial

PHED) Tabasco Peppers 25 lb ai/ ton 500 tons 0.083 ( engineering controls) 0.017 ( engineering controls) 2,900 ( engineering controls) 0.015 ( engineering controls) 590 ( engineering controls) 45 of 66 Corn, Peanuts, Pod crops, Potatoes,

Safflowers,

Soybeans, Brassica head and stem, Leaf petioles 19 lb ai/ ton 960 tons 0.083 ( engineering controls) 0.025 ( engineering controls) 2,000 ( engineering controls) 0.022 ( engineering controls) 410 ( engineering controls)

Corn, Peanuts, Pod crops, Potatoes,

Safflowers,

Soybeans, Brassica head and stem, Leaf petioles 19 lb ai/ ton 500 tons 0.083 ( engineering controls) 0.013 ( engineering controls) 3,800 ( engineering controls) 0.011 ( engineering controls) 780 ( engineering controls)

Grain/ Forage Sorghum,

Transplanted and Direct Seeded Vegetables 16 lb ai/ ton 960 tons 0.083 ( engineering controls) 0.021 ( engineering controls) 2,400 ( engineering controls) 0.018 ( engineering controls) 480 ( engineering controls)

Grain/ Forage Sorghum,

Transplanted and Direct Seeded Vegetables 16 lb ai/ ton 500 tons 0.083 ( engineering controls) 0.011 ( engineering controls) 4,500 ( engineering controls) 0.0095 ( engineering controls) 930 ( engineering controls)

Cotton, Green and Dry Bulb onions,

Vegetable root ( except sugar beet) 13 lb ai/ ton 960 tons 0.083 ( engineering controls) 0.017 ( engineering controls) 2,900 ( engineering controls) 0.015 ( engineering controls) 590 ( engineering controls)

Cotton, Green and Dry Bulb onions,

Vegetable root ( except sugar beet) 13 lb ai/ ton 500 tons 0.083 ( engineering controls) 0.009 ( engineering controls) 5,600 ( engineering controls) 0.0077 ( engineering controls) 1100 ( engineering controls)

Tabasco Peppers,

Sodfarms 2.5 lb ai/ acre 80 acres 1.2 0.004 13000 0.0034 2600 Nurseries 2.5 lb ai/ acre 60 acres 1.2 0.003 17000 0.0026 3400 Dry Bulk Fertilizers ( on farm  PHED) Corn, Peanuts,

Soybeans 1.9 lb ai/ acre 160 acres 1.2 0.0061 8200 0.0052 1700 46 of 66 Pod crops, Potatoes,

Safflowers, Brassica head and stem, Leaf petioles 1.9 lb ai/ acre 80 acres 1.2 0.003 16000 0.0026 3400 Grain/ Forage Sorghum 1.6 lb ai/ acre 160 acres 1.2 0.0051 9800 0.0044 2000 Transplanted and Direct Seeded Vegetables 1.6 lb ai/ acre 80 acres 1.2 0.0026 20000 0.0022 4000 Cotton 1.3 lb ai/ acre 160 acres 1.2 0.0042 12000 0.0036 2500 Green and Dry Bulb onions, Vegetable root ( except sugar beet) 1.3 lb ai/ acre 80 acres 1.2 0.0021 24000 0.0018 4900 Tabasco Peppers,

Sodfarms 2.5 lb ai/ acre 80 acres 1.2 0.004 13000 0.0034 2600 Corn, Soybeans 1.9 lb ai/ acre 200 acres 1.2 0.0076 6600 0.0065 1400 Peanuts, Pod crops,

Potatoes, Safflowers,

Brassica head and stem, Leaf petioles 1.9 lb ai/ acre 80 acres 1.2 0.003 16000 0.0026 3400 Grain/ Forage Sorghum 1.6 lb ai/ acre 200 acres 1.2 0.0064 7800 0.0055 1600 Transplanted and Direct Seeded Vegetables 1.6 lb ai/ acre 80 acres 1.2 0.0026 20000 0.0022 4000 Cotton 1.3 lb ai/ acre 200 acres 1.2 0.0052 9600 0.0045 2000 Emulsifiable Concentrates ( Liquids) for Groundboom Applications Green and Dry Bulb onions, Vegetable root ( except sugar beet) 1.3 lb ai/ acre 80 acres 1.2 0.0021 24000 0.0018 4900 47 of 66 Pumpkin and Winter Squash 1.27 lb ai/ acre 80 acres 1.2 0.0020 25,000 0.0017 5,100 Applicator Tabasco Peppers,

Sodfarms 2.5 lb ai/ acre 350 acres 0.068 ( engineering controls) 0.00099 ( engineering controls) 50,000 ( engineering controls) 0.00085 ( engineering controls) 10000 ( engineering controls)

Corn, Soybeans 1.9 lb ai/ acre 1200 acres 0.068 ( engineering controls) 0.0026 ( engineering controls) 19,000 ( engineering controls) 0.0022 ( engineering controls) 4000 ( engineering controls)

Peanuts, Pod crops,

Potatoes, Safflowers,

Brassica head and stem, Leaf petioles 1.9 lb ai/ acre 350 acres 0.068 ( engineering controls) 0.00075 ( engineering controls) 66,000 ( engineering controls) 0.00065 ( engineering controls) 14000 ( engineering controls)

Grain/ Forage Sorghum 1.6 lb ai/ acre 1200 acres 0.068 ( engineering controls) 0.0022 ( engineering controls) 23,000 ( engineering controls) 0.0019 ( engineering controls) 4700 ( engineering controls)

Transplanted and Direct Seeded Vegetables 1.6 lb ai/ acre 350 acres 0.068 ( engineering controls) 0.00063 ( engineering controls) 79,000 ( engineering controls) 0.00054 ( engineering controls) 16000 ( engineering controls)

Cotton 1.3 lb ai/ acre 1200 acres 0.068 ( engineering controls) 0.0018 ( engineering controls) 28,000 ( engineering controls) 0.0015 ( engineering controls) 5800 ( engineering controls)

Applying Liquid Sprays via Aerial Equipment Green and Dry Bulb onions, Vegetable root ( except sugar beet) 1.3 lb ai/ acre 350 acres 0.068 ( engineering controls) 0.00052 ( engineering controls) 97,000 ( engineering controls) 0.00044 ( engineering controls) 20000 ( engineering controls)

Tabasco Peppers,

Sodfarms 2.5 lb ai/ acre 80 acres 0.74 0.0025 20000 0.0021 4200 Corn, Soybeans 1.9 lb ai/ acre 200 acres 0.74 0.0047 11000 0.004 2200 Applying Liquid Sprays via Groundboom Equipment Peanuts, Pod crops,

Potatoes, Safflowers,

Soybeans, Brassica head and stem, Leaf petioles 1.9 lb ai/ acre 80 acres 0.74 0.0019 27000 0.0016 5500 48 of 66 Grain/ Forage Sorghum 1.6 lb ai/ acre 200 acres 0.74 0.0039 13000 0.0034 2600 Transplanted and Direct Seeded Vegetables 1.6 lb ai/ acre 80 acres 0.74 0.0016 32000 0.0014 6500 Cotton 1.3 lb ai/ acre 200 acres 0.74 0.0032 16000 0.0027 3200 Green and Dry Bulb onions, Vegetable root ( except sugar beet) 1.3 lb ai/ acre 80 acres 0.74 0.0013 39000 0.0011 8000 Pumpkin and Winter Squash 1.27 lb ai/ acre 80 acres 0.74 0.0013 40,000 0.0011 8,200 Tabasco Peppers,

Sodfarms, Nurseries 2.5 lb ai/ acre 320 acres 1.2 0.016 3100 0.014 640 Corn, Peanuts, Pod crops, Potatoes,

Safflowers,

Soybeans, Brassica head and stem, Leaf petioles 1.9 lb ai/ acre 320 acres 1.2 0.012 4100 0.01 840 Grain/ Forage Sorghum,

Transplanted and Direct Seeded Vegetables 1.6 lb ai/ acre 320 acres 1.2 0.01 4900 0.0088 1000 Applying Dry Bulk Fertilizers ( commercial

using PHED tractor drawn granular spreader data) Cotton, Green and Dry Bulb onions,

Vegetable root ( except sugar beet) 1.3 lb ai/ acre 320 acres 1.2 0.0083 6000 0.0071 1200 Tabasco Peppers,

Sodfarms 2.5 lb ai/ acre 80 acres 1.2 0.004 13000 0.0034 2600 Applying Dry Bulk Fertilizers ( on farm  using PHED tractor drawn granular spreader data) Nurseries 2.5 lb ai/ acre 60 acres 1.2 0.003 17000 0.0026 3400 49 of 66 Corn, Peanuts,

Soybeans 1.9 lb ai/ acre 160 acres 1.2 0.0061 8200 0.0052 1700 Pod crops, Potatoes, ,

Safflower, Brassica head and stem, Leaf petioles 1.9 lb ai/ acre 80 acres 1.2 0.003 16000 0.0026 3400 Grain/ Forage Sorghum 1.6 lb ai/ acre 160 acres 1.2 0.0051 9800 0.0044 2000 Transplanted and Direct Seeded Vegetables 1.6 lb ai/ acre 80 acres 1.2 0.0026 20000 0.0022 4000 Cotton 1.3 lb ai/ acre 160 acres 1.2 0.0042 12000 0.0036 2500 Green and Dry Bulb onions, Vegetable root ( except sugar beet) 1.3 lb ai/ acre 80 acres 1.2 0.0021 24000 0.0018 4900 Flagger Tabasco Peppers,

Sodfarms 2.5 lb ai/ acre 350 acres 0.35 0.0051 9800 0.0044 2000 Corn, Peanuts, Pod crops, Potatoes,

Safflowers,

Soybeans, Brassica head and stem, Leaf petioles 1.9 lb ai/ acre 350 acres 0.35 0.0039 13000 0.0033 2600 Flagging for Liquid Sprays via Aerial Equipment Grain/ Forage Sorghum,

Transplanted and Direct Seeded Vegetables 1.6 lb ai/ acre 350 acres 0.35 0.0033 15000 0.0028 3100 50 of 66 Cotton, Green and Dry Bulb onions,

Vegetable root ( except sugar beet) 1.3 lb ai/ acre 350 acres 0.35 0.0027 19000 0.0023 3900 Mixer/ Loader/ Applicator Mixing/ Loading/ Ap plying Emulsifiable Concentrates with a Handgun Sprayer ( LCO ORETF data) Turfgrass/ Nurseries/

Landscape plantings 2.5 lb ai/ acre 5 acres 1.8 0.00038 130000 0.00032 27000 Mixing/ Loading/ Ap plying Emulsifiable Concentrates with a High Pressure Handwand Nurseries/

Landscape plantings 2.5 lb ai/ acre 5 acres 120 0.025 2000 0.021 410 Mixing/ Loading/ Ap plying Emulsifiable Concentrates with a Low Pressure Handwand ( Residential ORETF data) Turfgrass/ Nurseries/

Landscape plantings 2.5 lb ai/ acre 2 acres 3.8 0.00032 160000 0.00027 32000 a Application rates are the maximum application rates determined from EPA registered labels for S metolachlor.

b Amount handled per day values are HED estimates of acres or tons treated applied based on Exposure SAC SOP # 9 " Standard Values for Daily Acres Treated in Agriculture," industry sources, and HED estimates.

c No Respirator: indicates baseline level risk mitigation with no respirator. When engineering controls are noted: closed mixing/ loading system and enclosed cockpits are assumed.

d Short term inhalation MOE = NOAEL ( 50 mg/ kg/ day) / inhalation daily dose ( mg/ kg/ day), where inhalation dose = daily unit exposure ( Fg/ lb ai) x application rate x amount handled per day x conversion factor ( 1mg/ 1,000 Fg)/ body weight ( 60 kg adult female).

e Intermediate term inhalation MOE = NOAEL ( 8.8 mg/ kg/ day) / inhalation daily dose ( mg/ kg/ day), where inhalation dose = daily unit exposure ( Fg/ lb ai) x application rate x amount handled per day x conversion factor ( 1mg/ 1,000 Fg) / body weight ( 70 kg adult female). 51 9.0 Data Needs and Label Requirements 9.1 Toxicology None 9.2 Residue Chemistry Deficiencies described in the last HED risk assessment remain ( PP# 3E6787, DP Num: 304120, R. Loranger, 4/ 17/ 06):

° Label amendments are required pertaining to the proposed uses on legume vegetables ( excluding soybean). Use directions on legume vegetables should be amended to prohibit applications to legume cultivars grown for the production of succulent shelled peas or beans, pending submission of adequate field trial data covering subgroup 6B.

° Label amendments are required pertaining to the proposed uses on bulb vegetables. The directions for bulb vegetables should be amended to indicate the correct crop group; bulb vegetables are in crop group 3, not crop group 8.