Summary of Petitions The petitioner summary of the pesticide petitions is printed below as required by FFDCA section 408 ( d) ( 3). The summary of the petitions is prepared by the petitioner and represents the view of the petitioner. The petition summary announces the availability of the description of the analytical methods available to EPA for the detection and measurement of the pesticide chemical residues or an explanation of why no such method is needed.

Interregional Research Project Number 4 ( IR 4)

PP# 3E6564, 3E6565 and 5E6914 EPA has received pesticide petitions ( PP# 3E6564, 3E6565 and 5E6914) from IR 4, 681 Highway 1 South, North Brunswick, NJ 08902 3390 proposing, pursuant to section 408( d) of the Federal Food, Drug, and Cosmetic Act ( FFDCA), 21 U. S. C. 346a( d), to amend 40 CFR part 180.345 by establishing tolerances for combined residues of the herbicide, ethofumesate ( 2 ethoxy  2, 3 dihydro 3, 3 dimethyl 5 benzofuranyl methanesulfonate) and its metabolites NC 8493 and NC 9607 ( both calculated as the parent compound)] in or on the raw agricultural commodities: carrots at 10 parts per million ( ppm) ( PP 3E6565), garden beets tops at 4 ppm, garden beet roots at 0.5 ppm ( PP 3E6564), onion dry bulb at 0.3 ppm ( PP 5E6914), garlic bulb at 0.3 ppm ( PP 5E6914), and shallots at 0.3 ppm ( PP 5E6914). Note that the carrots tolerance requested by IR 4 is with regional restriction, for use in Washington and Oregon only. EPA has determined that the petitions contain data or information regarding the elements set forth in section 408( d)( 2) of the FFDCA; however, EPA has not fully evaluated the sufficiency of the submitted data at this time or whether the data supports granting of the petition. Additional data may be needed before EPA rules on the petition. This notice includes a summary of the petitions prepared by Bayer CropScience, P. O. Box 12014, 2 T. W. Alexander Drive, Research Triangle Park, NC 27709.

A. Residue Chemistry 1. Plant metabolism. The metabolism of ethofumesate in plants is adequately understood. Studies have been conducted in sugar beet, annual ryegrass, cabbage, wheat and radish, all showing similar route of metabolism for ethofumesate. The major metabolites are NC 8493, NC 9607 ( the lactone analogue), NC 20645 ( the carboxy analogue) together with small amounts of the unchanged parent. Metabolite NC 20645 exists in equilibrium with NC 9607 and all recovered NC 20645 were derivatized and reported as NC 9607. From the studies, the residues of concern are the combined residues of ethofumesate and its metabolites NC 8493 and NC 9607.]

2. Analytical method. Analytical methods have been developed and validated for the determination of ethofumesate and its metabolites NC 9607, and NC 8493 in sugar beet ( roots and tops), meat and milk. The method has also been shown to capture NC 20645 as NC 9607 in sugar beet and milk. Therefore, reported residues of NC 9607 include any NC 20645 that may be present. Ethofumesate and its related residues are extracted in a two part process and quantified using gas chromatography equipped with flame photometric detector ( GC NPD) operated in sulfur mode. The method limit of quantification is 0.05 ppm. Therefore, adequate analytical methodology is available for enforcement purposes and it allows detection of residues at or above the proposed tolerances.

3. Magnitude of residues. Carrots   IR 4 received requests from Washington and Oregon for the use of ethofumesate on carrots. In support of the requests, magnitude of residue data were collected from three field trials in Washington. Samples were analyzed for residues of ethofumesate and its metabolites NC 9607 and NC 8493 ( results for NC 8493 were reported as NC 8906, a derivative of NC 8493). In treated carrot samples, the highest total residues measured for the three analytes ranged from 3.9 ppm to 6.3 ppm. The data support the proposed 10 ppm tolerance for the carrot roots.

Beets, garden   IR 4 received requests from New York and Oregon for the use of ethofumesate on garden beet. In support of the requests, magnitude of residue data were collected from a total of six field trials conducted in Texas, Oregon, New York, Wisconsin, Michigan, and Washington. Samples were analyzed for residues of ethofumesate and metabolites NC 9607 and NC 8493. In treated samples for the beet tops, the highest total residues measured for the three analytes ranged from about 1.0 ppm to 3.8 ppm. The total residues on the beet roots ranged from none detectable ( below the lowest level of method validation of 0.05 ppm for each of the three analytes) to a sum residue value of about 0.25 ppm. The data support the proposed tolerances for the garden beet tops ( 4 ppm) and the garden beet roots ( 0.5 ppm).

Onion dry bulb, garlic bulb, shallot bulb   IR 4 received requests from Oregon, Colorado, Idaho, North Dakota, Washington, California, Arizona, New Mexico, and Michigan for the use of ethofumesate on dry bulb onions. In support of the requests, magnitude of residue data were collected from a total of 10 field trials conducted in California, Idaho, Oregon, New York, Texas, Washington, Michigan, and Colorado. Samples were analyzed for residues of ethofumesate and metabolites NC 9607 and NC 8906 ( a derivative of NC 8493 metabolite). In treated samples for the dry bulb onions, the total residues measured for the three analytes ranged from none detectable ( below the lowest level of method validation of 0.05 ppm for each of the three analytes) to a sum residue value of about 0.196 ppm. The data support the proposed tolerances of 0.4 ppm for the dry bulb onion, garlic bulb, and shallot bulb.

B. Toxicological Profile 1. Acute toxicity. Ethofumesate is of low acute toxicity placing the active ingredient in Toxicity Category III and IV. Ethofumesate is non irritating to the eyes and skin and is not a skin sensitizer.

2. Genotoxicty. Ethofumesate has been evaluated through a full battery of mutagenicity assays. Ethofumesate was not mutagenic or genotoxic in any assay in either the presence or absence of metabolic activation.

3. Reproductive and developmental toxicity. i. Teratology  Rat Groups of 24 time mated female rats received ethofumesate by daily oral gavage at dose levels of 0, 10, 100, or 1000 mg/ kg/ day from day 6 to day 15 of gestation. All dams survived the study and no adverse effects on uterine/ implantation and fetal values or on the incidence of fetal defects were detected at any dose level. NOEL ( dam): 100 mg/ kg / day, based on body weight, food and water effects at 1000 mg/ kg/ day. NOEL ( fetus): 1000 mg/ kg / day, based on the absence of effects at the highest dose tested in the study.

ii. Teratology  Rabbit Groups of 16 mated female New Zealand White rabbits were dosed with ethofumesate orally by gavage at 0, 300, 600, or 1200 mg/ kg/ day from day 7 to 19 of gestation. Administration of ethofumesate led to maternal toxicity at 1200 mg/ kg/ day, which was characterized by reduced body weight gain, food consumption, and abortion in one animal. There was, however, no indication of an adverse effect on embryonic or fetal development at this dose. There were no significant maternal and fetal effects at doses of 300 and 600 mg/ kg/ day. NOEL ( dams): 600 mg/ kg/ day, based on maternal toxic effects at 1200 mg/ kg/ day. NOEL ( offspring): 1200 mg/ kg/ day, based on the absence of effects at the highest dose tested in the study.

iii. Two Generation Reproduction  Rat Groups of 25 males and 25 females Sprague Dawley rats were dosed with ethofumesate at 0, 3000, 10000, and 30000 ppm in the diet to assess reproductive performance over two successive generations. There were no treatment related mortalities or clinical observations. Mating performance, fertility, vaginal smear patterns, and macroscopic or microscopic findings were not affected by ethofumesate. Pup body weights, pup development, and litter size at 3000 ppm were not affected by ethofumesate. Pup survival, clinical conditions, and necropsy findings were not affected by treatment. NOEL ( all generations): 3000 ppm, corresponding to overall 245 and 296 mg/ kg/ day in males and females, respectively, based on reduction in body weight gain at 10000 ppm.

4. Subchronic toxicity.

i. 90 Day Dietary  Rat Groups of ten male and ten female Sprague Dawley CD rats received ethofumesate in the diet at dose levels of 0, 300, 3000, or 30000 ppm for 13 weeks. There were no deaths or treatmentrelated clinical findings during the course of the study. At 30000 ppm reduced body weight gain ( in females and in males to a lesser extent), lower food consumption ( in females) and utilization ( in both sexes), and marginally increased water consumption ( in males) were recorded. Increased liver weights were recorded in males and females. Increased kidney weights occurred among males with an associated incidence of irregular renal cortical scarring at post mortem examination. NOEL: 3000 ppm, corresponding to 190 and 230 mg/ kg/ day in males and females, respectively, based on the reduction in body weight and minor biochemical disturbances and kidney changes recorded at 30000 ppm.

ii. 90 Day oral  Dog Groups of four male and four female Beagle dogs received ethofumesate once daily by gavage at 0, 250, 750, or 1500 mg/ kg/ day for 13 weeks. There were no treatment related clinical signs, ocular changes, organ weight changes, or hematological changes. Body weights and body weight gains were unaffected by treatment and food consumption for all treated groups was comparable to that of the untreated group. NOEL: 250 and 750 mg/ kg/ day in males and females, respectively, based on the minor effects on clinical chemistry at 750 and 1500 mg/ kg/ day in males and females, respectively.

iii. 90 Day Dietary  Mouse Groups of ten male and ten female CD 1 mice received ethofumesate in the diet at concentrations of 0, 300, 3000 or 10000 ppm for 13 weeks. No treatment related clinical signs were observed and there was no treatment related effect on body weight gain. Food consumption of treated groups was similar to that of controls. There were no treatmentrelated macroscopic post mortem findings or histological changes. NOEL: 10000 ppm, corresponding to 2054 and 3103 mg/ kg/ day for males and females, respectively, based on the absence of toxic effects at the highest dose tested in the study.

5. Chronic toxicity.

i. Chronic Toxicity  Dog Groups of eight male and eight female beagle dogs received technical ethofumesate at dietary concentrations of 0, 800, 4000 or 20000 ppm for 104 weeks. At termination, liver weights were increased in both sexes at the highest dose level but there was no associated histopathological change. No observed adverse effect level: 4000 ppm, corresponding to 118 and 109 mg/ kg/ day for males and females, respectively, based on liver weight and clinical chemistry changes at 20000 ppm.

ii. Combined Chronic Toxicity/ Oncogenicity  Rat Groups of 50 male and 50 female Sprague Dawley rats were dosed daily for 104 weeks with ethofumesate via the diet at 0, 2000, 7000 or 20000 ppm. In males receiving 20000 ppm reduced body weight gain and reduced food consumption were recorded. At the same dose in females reduced body weight gain, increased liver weight, and histological changes in liver were seen. Reduced body weight gain ( females only) was seen at 7000 ppm. No effects considered to be of toxicological significance were recorded in males and females receiving 2000 ppm. NOEL: 2000 ppm, corresponding to 113 and 143 mg/ kg/ day in males and females, respectively.

iii. Oncogenicity  Mouse Groups of 50 male and 50 female CD 1 mice received ethofumesate in the diet at 0, 1000, 3000 or 10000 ppm for 80 weeks. The only treatment related changes observed were increased liver weights in all treated female groups. In the absence of histopathological changes in this organ, this effect was not considered to be of toxicological significance at any dose level and especially at 1000 ppm where the increase was only slightly more than 10%. NOEL: 1000 ppm, corresponding to 161 and 204 mg/ kg/ day in males and females, respectively, based the liver weight changes at 3000 ppm. 6. Animal metabolism. The metabolism of ethofumesate has been extensively studied in rats, ruminants and hens. Studies with radiolabelled ethofumesate in the rat show that the compound is rapidly and extensively absorbed. Ethofumesate is extensively metabolised mostly to the water soluble metabolite NC 20645 ( the carboxy analogue) that is excreted mainly in the urine. At higher dose levels there was an increase in excretion via the faeces. Most of the administered radiolabel was eliminated from the body within the first 24 hours after dosing. Tissue residue levels five or seven days after dosing were very low. Even at the high dose levels ( 100 or 500 mg/ kg) maximum levels were below 1 mg/ kg in most tissues. There was no evidence of selective accumulation in any tissue or organ. Three studies conducted with repeated dietary treatments showed no significant effect on the absorption, distribution, metabolism and excretion in the rat. A dairy cow was orally dosed twice daily with [ 14C] ethofumesate with a mean daily dose of 2.94 g ( equivalent to 5.0 mg/ kg body weight) for four consecutive days. This dose was equivalent to an exposure of 274 ppm in the diet. Radioactive residues were detectable in all edible tissues at between 0.033 and 1.863 mg equivalents/ kg tissue. In milk, residue levels rose rapidly reaching a maximum of 0.134 mg equivalents/ kg at 32 hours post administration of the initial dose. The highest residue levels were found in the kidney at 1.863 mg equivalents/ kg, followed by the liver at 0.661 mg/ equivalents/ kg. In most tissues the major component seen was the unchanged parent compound with small quantities of metabolites NC 8493, NC 9607 ( the lactone analogue) and NC 20645.

Three laying hens were orally dosed with [ 14C] ethofumesate at 1.50 mg per bird per day for ten consecutive days. The dose was equivalent to about 12 ppm in the diet. Following administration of the first dose of ethofumesate, elimination of the dosed radioactivity was rapid with 82% recovered within 24 hours. Residue levels of ethofumesate and/ or its metabolites in the edible tissues of the hen were low, with residue range from 0.002 ( egg whites) to 0.095 mg ( liver) equivalents/ kg tissue. Analysis of the nature of the residues showed that unchanged ethofumesate was present in all tissues and was the major residue identified in the egg yolks, fat and skin. NC 20645 was the major residue identified in the muscle and liver and was also present in the skin and egg yolks. NC 9607 was present in all tissues.

7. Endocrine disruption. No special studies have been conducted to investigate the potential of ethofumesate to induce estrogenic or other endocrine effects. However, no evidence of estrogenic or other endocrine effects has been noted in any of the standard toxicology studies that have been conducted with this product and there is no reason to suspect that any such effects would be likely.

C. Aggregate Exposure 1. Dietary exposure.

i. Food. Tier 1 dietary risk assessments were conducted for acute and chronic exposures. Dietary exposure estimates were based on tolerances that have been established ( 40 CFR 180.345) for combined residues of ethofumesate and metabolites in or on sugar beets and the proposed tolerances for minor crops use in onions, garlic and shallots ( 0.4 ppm), carrots ( 10.0 ppm) and garden beets ( 0.5 ppm). It was assumed that 100% of the crops were treated with ethofumesate. Dietary exposure estimates were calculated using the Dietary Exposure Evaluation Model software ( DEEM   , Exponent, Inc., formerly Novigen Sciences, Inc., Version 7.87) and the 1994 1996 and 1998 USDA Continuing Survey of Food Intake by Individuals ( CSFII) consumption data base. An acute reference dose ( RfD) of 6.0 mg/ kg/ day was used for the acute dietary assessment and was based on the results from a rabbit teratology study ( NOEL 600 mg/ kg/ day) and an uncertainty factor of 100 ( 10X for interspecies extrapolation and 10X for intraspecies variation). The U. S. population was estimated to have an acute dietary exposure of 0.010338 mg/ kg/ day ( 95th percentile) which occupies 0.17% of the acute RfD. The most highly exposed subpopulation was non nursing infants at 1.3% ( 0.079699 mg/ kg/ day) of the acute RfD.

Chronic dietary exposure was evaluated using a reference dose ( RfD) of 1.09 mg/ kg/ day, based on the results from a chronic dog study ( NOAEL of 109 mg/ kg/ day) and an uncertainty factor of 100 ( 10X for interspecies extrapolation and 10X for intraspecies variation). Chronic dietary exposure for the U. S. population was estimated to be 0.002060 mg/ kg/ day which occupies 0.2% of the chronic reference dose. The most highly exposed subpopulation was non nursing infants at 1.2% ( 0.012950 mg/ kg/ day) of the chronic reference dose. There is no concern for exposures occupying 100% or less of the RfD. Therefore, the acute and chronic dietary exposures for both the U. S. population and infants and children are well within acceptable levels.

ii. Drinking water. US EPA's Standard Operating Procedure ( SOP) for Drinking Water Exposure and Risk Assessments was used to perform the drinking water assessment. This SOP uses a variety of tools to conduct drinking water assessments. These tools include water models such as SCI GROW, FIRST, PRZMS/ EXAMS, and monitoring data. When monitoring data is not available, the models are used to predict potential residues in surface and ground water and the highest value is assumed to be the drinking water residue. In the case of ethofumesate, SCI GROW and PRZM/ EXAMS models were used to estimate a water residue. The estimated concentrations of the pesticide in surface water or ground water were calculated and then compared to the drinking water level of comparison ( DWLOC). The DWLOC is the concentration of a pesticide in drinking water that would be acceptable as an upper limit. These drinking water levels of comparison estimates are based on conservative dietary ( food) exposures and are expected to be much higher in real world situations.

For adults, the chronic DWLOC was 38,078 ppb and the acute DWLOC was 209,637 ppb. The chronic and acute DWLOCs for non nursing infants were 10,771 ppb and 59,204 ppb, respectively. The estimated environmental concentration ( EEC) for the worst case chronic scenario was 29 ppb ( PRZM/ EXAMS) and the acute EEC ( PRZM/ EXAMS) was 158 ppb. The DWLOCs are substantially greater than the high end estimated exposure from the surface water models indicating risk from potential drinking water exposure to ethofumesate is well within acceptable levels.

2. Non dietary exposure. Ethofumesate is an active ingredient in three products: Nortron  SC Herbicide, Progress, Herbicide, and Prograss, Herbicide. There are no residential uses of Nortron  SC Herbicide or Progress  Herbicide. Prograss ® Herbicide may be applied to residential lawns by professional lawn care operators. It is not intended for use by homeowners. Therefore, there is no exposure of homeowners to ethofumesate during the mixing, loading, and application of Prograss ® Herbicide to residential lawns. Post application exposure to adults and toddlers on lawns treated with Prograss ® Herbicide is possible, however. Tier I residential reentry assessments were prepared for adults and toddlers following treatment of residential lawns with Prograss ® Herbicide. Estimates were made for the worst case scenario, 3 applications of Prograss ® Herbicide at a rate of 3 lb ai/ A at 21 day intervals. Turf transferable residues were conservatively estimated using EPA default assumptions of 5% of application rate immediately after treatment, and 10% dissipation per day.

Using these assumptions, the residue was calculated to be 37.7 : g/ cm2 immediately after the third treatment. EPA Standard Operating Procedures ( SOPs) for Residential Exposure Assessment were used to complete the residential exposure estimates for adults and toddlers. Exposure of adults to ethofumesate is from the dermal route only. In addition to dermal exposure, toddlers may have oral exposure to ethofumesate during post application activities on treated turf via hand to mouth, object to mouth, and soil ingestion routes. Risk was estimated by calculating dermal margins of exposure ( MOEs) for adults and toddlers, and an oral MOE for toddlers. Dermal margins of exposure ( MOEs) were based on a rabbit 21/ 22 day dermal no observable adverse effect level ( NOAEL) of 1000 mg/ kg/ day. Oral MOEs were based on a rat 90 day oral NOAEL of 190 mg/ kg/ day. Dermal MOEs for adults and toddlers were 1280 and 765, respectively. The oral MOE for toddlers was 3015. The combined MOE for toddlers from dermal and oral exposure was 610. MOEs for adult and toddler activities on residential lawns following treatment with the maximum application of Prograss ® Herbicide are well above the target MOE of 100 when conservative Tier I assumptions were used in the assessment. This assessment indicates that there is a reasonable certainty of no harm to adults or toddlers from potential residential exposure to ethofumesate after application to homeowner lawns.

D. Cumulative Effects.

There is no reliable information to indicate that toxic effects of ethofumesate would be cumulative with those of another pesticide chemical. Thus, it is appropriate to consider only the potential risks of ethofumesate in an aggregate exposure assessment.

E. Safety Determination.

1. U. S. population. Acute dietary exposure for the U. S. population to residues of ethofumesate from current and proposed uses was estimated to occupy 0.2% of the acute RfD, which is well below levels expected to pose any appreciable risk to human health. Additionally, the acute DWLOC was calculated to be over 1300 fold greater than potential ethofumesate residues predicted in drinking water by the water models. Therefore, aggregate acute exposure to ethofumesate for proposed and current uses is within acceptable levels. Ethofumesate may be applied to residential lawns by professional lawn care operators which may result in postapplication exposure to adults on lawns treated with ethofumesate. Aggregate short term exposures were determined by combining chronic dietary ( food and water) exposures with shortterm residential exposures. The short term aggregate MOE for the general population of adults was calculated to be 1235 which is well above the acceptable level of 100. Therefore, aggregate short term exposure and risk for adults is expected to be well within acceptable levels. Using conservative exposure assumptions previously described, chronic dietary exposure to residues of ethofumesate from current and proposed uses was estimated to occupy 0.2% of the chronic RfD for the general U. S. population. The chronic DWLOC for adults was calculated to be over 1,300 fold greater that potential ethofumesate residue in drinking water predicted by conservative screening level models. Thus, based on the completeness and reliability of the toxicity data and the conservative exposure assessment it is concluded that there is a reasonable certainty that no harm will result to the general U. S. population from acute, short term or chronic aggregate exposures to ethofumesate residues from current and proposed uses.

2. Infants and children. Acute dietary exposure for the infants and children subpopulations to residues of ethofumesate from current and proposed uses was estimated to occupy 1.3% of the acute RfD, which is well below levels expected to pose any appreciable risk to human health. Additionally, the acute DWLOC was calculated to be over 375 fold greater than potential ethofumesate residues predicted in drinking water by the water models. Therefore, aggregate acute exposure to ethofumesate for proposed and current uses is within acceptable levels. Infants and children may experience short term dermal and oral exposure to ethofumesate as a result of postapplication activities on treated residential turf. Aggregate short term exposures were determined by combining chronic dietary ( food and water) exposures with short term residential exposures. The short term aggregate MOE was 560 for infants and children, which is well above the acceptable level of 100. Using conservative exposure assumptions previously described, chronic dietary exposure to residues of ethofumesate from current and proposed uses was estimated to occupy 1.2% of the chronic RfD for the most highly exposed subpopulation, non nursing infants . The chronic DWLOC for children was calculated to be over 350 fold greater than potential ethofumesate residues in drinking water predicted by conservative screening level models. Thus, based on the completeness and reliability of the toxicity data and the conservative exposure assessment it is concluded that there is a reasonable certainty that no harm will result to infants and children from acute, short term or chronic aggregate exposures to ethofumesate residues from current and proposed uses.

F. International Tolerances.

CODEX Maximum Residue Levels ( MRL) are not yet established for ethofumesate. European Union ( EU) has published its provisional MRLs for ethofumesate ( Directive 2003/ 60/ EC of June 18, 2003). These MRLs are established in accordance with Article 4 ( 1)( f) of Directive 91/ 414/ EEC; unless amended, the provisional MRLs will become definitive with effect from July 14, 2007. The EU MRLs are for crops of cereals, meat/ milk/ poultry commodities, fresh/ dry fruits and nuts, fresh vegetables and subgroups ( e. g., root and tuber vegetables, bulb vegetables), pulses, oil seed crops, potatoes, tea, and hops.