COMPANY FEDERAL REGISTER DOCUMENT SUBMISSION TEMPLATE

(7/1/2006) Pendimethalin, Increase Alfalfa Forage Tolerance, June 2009 EPA Registration Division contact: [ Philip V. Errico at 703 -30 5 - 6663 ]

INSTRUCTIONS: Please utilize this outline in preparing tolerance petition documents. In cases where the outline element does not apply please insert “NARemove” and maintain the outline. The comment notes that app ear on the left ma rgin represent hidden typesetting codes designed to expedite the processing of the Federal Register document. Please do not remove or alter these comment notes or change the margins, font, or format in your document. Simply replace the instructions that appear in italics and brackets, i.e., “[insert company name],” with the information specific to your action. ] TEMPLATE: [BASF Corporation ] [ PP-9F 7576 ] 21 U.S.C. 346 EPA has received a pesticide petition ( PP-9F7576 ] ) from [ BASF Corpo ration ] , [ 26 Davis Drive, Research Triangle Park, NC 27709 ] 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 180.361 by establishing a tolerance for the combined residues of [the herbicide pendimethalin, N- (1 - ethylpropyl) -3,4 - dimethyl2,6 - dinitrobenzenamine, and its metabolite 4 - [(1 - ethylpropyl)amino] -2 - methyl-3,5 - dinitrobenzyl alcohol] in or on the raw agricultural commodities [ alfalfa forage] at [3 . 5 ] parts per million (ppm) . EPA has determined that the petition contains data or information regarding the elements set forth in section 408 (d)(2) of the FDDCA; 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.

A. Residue Chemistry 1. Plant metabolism. [ The qualitative nature of the residues of pendimethalin in plants is understood based on adequate studies conducted with 14 C pendimethalin on various crops. Pendimethalin and its metabolite 4 - [(1 - ethylpropyl)amino] -2 - methyl-3,5 - dinitrobenzenamine are the residues of concern .]2. Analytical method. [ Section 408 (b)(3) of the amended FDCA requires EPA

to determine that there is a practical method for detecting and measuring levels of the pesticide chemical residue in or on food and that the tolerance be set at a level at or above of the limit of detection of the designated method. In plants the method is aqueous organic solvent extraction, column clean up, and quantitation by GC. The method has a limit of quantitation (LOQ) of 0.05 ppm for pendimethalin and the alcohol metabolite. ] 3. Magnitude of residues. [Fi eld trials in major growing areas across the US were carried out in order to determine the magnitude of residues in alfalfa commodities. EPA has determined that the petition contains data or information regarding the above aforementioned crops. Field trials were conducted on alfalfa targeting a pendimethalin ap plication rate of 2 lb ai/A with a 28 day pre- harvest interval (PHI) for alfalfa forage and hay] . B. Toxicological Profile 1. Acute toxicity. [ Pendimethalin (BAS 455 H) technical demonstrates low acute toxicity via the oral, dermal and inhalation route s of exposure. The acute toxicity studies place technical pendimethalin in toxicity category III for the acute oral, category IV for acute dermal, and category IV for acute inhalation. Technical pendimethalin is category IV for skin irritation and catego ry III for eye irritation. Pendimethalin did not cause skin sensitization in guinea pigs. Two formulated end use products are registered for use on crops, an Emulsifiable Concentrate (EC) and an Encapsulated Suspension (CS). The EC has an acute oral cate gory of III, acute dermal category of III, an acute inhalation category of III, eye and skin irritation of III, and is not a dermal sensitizer. The CS has an acute oral category of IV, an acute dermal category of IV, an acute inhalation category of IV, eye and skin irritation category of IV, and is not a dermal sensitizer. ] 2. Genotoxicty. [Extensive mutagenicity studies conducted to investigate point and gene mutations, DNA damage and chromosomal aberration, both using in vitro and in vivo test systems demonstrate pendimethalin to be non - genotoxic. Pendimethalin has been classified as a Group C "possible human carcinogen," based on a statistically significantly increased incidence of benign follicular cell adenomas of the thyroid gland in male and female rats at 5000 ppm (250 mg/kg b.w./day) (highest concentration tested). For risk assessment, OPP recommends using the RfD (non -linear) approach for quantification of human risk. The Agency Committee has determined that the hypothesis, that benign thyroi d tumors associated with pendimethalin are due to a thyroid-pituitary imbalance, can be supported. Finally, pendimethalin's mechanism of threshold oncogenic activity only occurs at high doses in rats, a mammalian species that is expected to be much more s ensitive than humans to the induction of thyroid tumors via conditions which result in hypothyroidism .] 3. Reproductive and developmental toxicity. [ Pendimethalin (BAS 455 H) is nota selective developmental toxicant. There is no indication of increased susceptibility

following prenatal/postnatal exposure to pendimethalin. In a developmental (teratology) toxicity study in the rat, the results demonstrated that the NOAELs for both maternal toxicity and fetal (prenatal)/developmental toxicity were 500 mg/kg b.w./day (highest dose tested) (HDT). In addition, there were no indications of any teratogenic effects in the rat fetuses at 500 mg/kg b.w./day (HDT). Therefore, pendimethalin is considered to be neither a developmental toxicant nor a teratogenic agent in the rat. In a developmental (teratology) toxicity study in the rabbit, the results demonstrated the NOAEL for maternal toxicity was 30 mg/kg b.w./day, based on increased clinical signs of toxicity and decreased body weight gain during the treatm ent period at 60 mg/kg b.w./day (HDT). T he NOAEL for fetal (prenatal)/developmental toxicity was 60 mg/kg b.w./day (HDT). I n addition, there were no indications of any teratogenic effects in the rabbit fetuses at 60 mg/kg b.w./day. T herefore, pendimethalin is considered to be neither a developmental toxicant nor a teratogenic agent in the rabbit. A two - generation reproductive toxicity study in the rat demonstrated an absence of increased sensitivity for the developing offspring to pendimethalin. The NOAEL for parental toxicity was 500 ppm (approximately 38.5 mg/kg b.w./day), based on reduced food consumption and decreased body weight/weight gain at 2500 ppm (mid- dietary concentration). The NOAEL for pup/offspring toxicity was also 500 ppm, based on dec reased pup body weight gain at 2500 ppm. Lastly, the NOAEL for reproductive toxicity was 2500 ppm (approximately 194 mg/kg b.w./day), based on reduced mean live litter size at 5000 ppm (highest concentration tested) (HCT). These reductions in mean live litter size and pup body weight gain were only observed at dietary concentrations that were parentally toxic. As such, there is no evidence that prenatal or postnatal exposure to pendimethalin results in an increased sensitivity to developing offspring. ] 4. Sub

- chronic toxicity. [ Sub - chronic (90 - day) feeding studies were conducted in rats and dogs. For the rat, the NOAEL for systemic toxicity was 500 ppm (41 mg/kg b.w./day), based on slightly decreased body weight, increased absolute and relative liver w eights, and liver histopathology (hepatocellular hypertrophy) in males and females at 5000 ppm (HCT). For the dog, the NOAEL for systemic toxicity was 2500 ppm (62.5 mg/kg b.w./day), based on decreased body weight at 10000 ppm (250 mg/kg b.w./day) .] 5. Chronic toxicity. [ The chronic Reference Dose (RfD) was established based on the results of sub - chronic special studies demonstrating the thyroid hormone related endpoint in rats. The NOAEL of 10 mg/kg b.w./day was established from the collective results of the sub - chronic oral 92 - day thyroid function study, the sub chronic oral 56 - day thyroid function study, and the 14 - day intrathyroidal metabolism study. A LOAEL of 31 mg/kg b.w./day was based on hormonal and histopathological changes in the thyroid glan d. The chronic RfD was calculated tobe 0.03 mg/kg b.w./day using an Uncertainty Factor (UF) of 30X (3X for interspecies

extrapolation and 10X for intraspecies variability) and a 10X database uncertainty factor (UFDB) retained pending receipt of a develop mental thyroid toxicity study. EPA/HED currently recommends a FQPA Safety Factor of 1X. Therefore, the chronic Population Adjusted Dose (PAD) is 0.03 mg/kg b.w./day. Chronic toxicity studies were conducted in rats, mice, and dogs. For the 2 -year rat fe eding study, the NOAEL for systemic toxicity was 500 ppm (25 mg/kg b.w./day), based on decreased body weight gain (approximately 20 -30%), increased clinical signs of toxicity, increased relative liver weights, and slight but statistical increase in the incidence of benign follicular cell adenomas of the thyroid gland in males and females at 5000 ppm (250 mg/kg b.w./day) (HCT). For the 18 - month mouse feeding study, the NOAEL for systemic toxicity was 500 ppm (75 mg/kg b.w./day), based on slightly decreased mean body weights and reduced survival at 5000 ppm (750 mg/kg b.w./day) (HCT). There were no oncogenic effects up to 5000 ppm (750 mg/kg b.w./day) (HCT). Lastly, for the 1 -year oral (via gelatin capsules) chronic dog study, the NOAEL for systemic toxicity was 200 mg/kg b.w./day, the highest dose tested .] 6. Animal metabolism. [Adequate goat and poultry metabolism studies are available for pendimethalin. The Agency has determined that there is no reasonable expectation of finite pendimethalin residues of concern in animal commodities as a result of use on multiple crops . However, tolerances for pendimethalin residues of concern in livestock commodities were proposed in a previous petition. In the rat, pendimethalin is metabolized mainly through oxidation of the 4 - methyl group attached to the benzene ring as well as oxidation of the alkyl side chain of the N- substituted dinitroaniline compound. When C14 -pendimethalin is administered to rats, about 70% of the radioactivity is excreted in feces and 20% is in the urine within 24 hours. Within 96 hours, the radioactivity found in the tissues was 0.3 ppm or less, except fat which is 0.9 ppm. The major portion of the radioactivity that was excreted in the feces was identified as the parent compound. ] 7. Metabolite toxicology

. [ The main pendimethalin plant metabolite, CL 202347, has been tested for toxicity. The acute oral toxicity in mice was determined to be 2140 mg/kg bw. An Ames assay showed the metabolite to be non - mutagenic. ] 8. Endocrine disruptio n . [It is known that pendimethalin affects the hypothalamus -pituitary-thyroid axis. However, as the chronic RfD (0.03 mg/kg b.w./day) is based on the thyroid hormone related endpoint in rats, as noted in the sub - chronic special studies in Section 5 above, which additionally demonstrated reversibility of the thyroid effects in the oral 56- day thyroid function study, these effects are already taken into consideration in the characterization of potential risks to humans. ] C. Aggregate Exposure 1. Dietary e

xposure. [ Pendimethalin is a pre- emergent herbicide used tocontrol broadleaf and grass weeds in food and non -food crops, as well as non agricultural use sites including residential lawns. In examining aggregate exposure, FQ PA directs EPA to consider avail able information concerning exposures from the pesticide residue in food (dietary) and all other non - occupational exposures. The primary non - food sources of exposure are through pesticide use in gardens, lawns, or buildings (residential and other indoor us es). The potential for aggregate exposure from all registered and proposed uses is discussed below .] i. Food. [An assessment was conducted to evaluate the potential risk due to chronic dietary exposure of the U.S. population to residues of pendimethalin (BAS 455 H). The current tolerance values are listed in the U.S. 40 CFR § 180.361. This analysis included all the crops with established tolerance values as of June 2009 , the proposed (pending at EPA) new tolerances forage grasses , crop group 17 , livestock commodities of 0.15 ppm in meat and 0.03 ppm in milk, and olives at 0.1 ppm, and the proposed increased tolerance for alfalfa forage to 3 . 5 ppm . No tolerances are proposed for poultry or eggs because grass forage and alfalfa forage are not feed item s for poultry. Acute Dietary Exposure Assessment An acute assessment was not needed since the U.S. EPA Toxicological Endpoint Selection (TES) Committee had previously evaluated the pendimethalin toxicity data and determined there was no relevant toxicological endpoints for acute dietary exposure and that a risk assessment was not required. Chronic Dietary Exposure Assessment The chronic dietary exposure estimates were based on established and proposed tolerance values, and 100% CT values. Default proces s factors were used with consumption data from the USDA Continuing Survey of Food Intake by Individuals (CSFII 1994 - 1996, 1998). T he EPA Food Commodity Ingredient Database (FCID) was also used in Exponent's Dietary Exposure Evaluation Module (DEEM-FCID) software. Secondary residues in meat and milk were included . Secondary residues for eggs and poultry were not included since it has been determined that there is no likelihood of residues in these animal commodities and therefore, a tolerance will not b e required by the EPA. Dietary exposure estimates were compared against the worst- case pendimethalin chronic Population Adjusted Dose (cPAD) of 0.03 mg/kg b.w./day for all populations subgroups. Results of the chronic dietary assessments are listed in the table below. The estimated chronic dietary exposure from crops (both established and proposed tolerances) was less than 20 % of the cPAD for all subpopulations. Additional refinements such as the use of anticipated residues and percent crop treated v alues for the established crop uses would further reduce the estimated chronic dietary exposure. The results in Table 1 below demonstrate there are no safety concerns for any subpopulation based on established and new uses, and that the results clearly me et the FQPA standard of reasonable certainty of no harm.Table 1. Summary of chronic dietary exposure assessment considering crops with established and proposed tolerances for pendimethalin. Population Subgroups Exposure Estimate (mg/kg b.w./day) %cPAD US Population 0.00207725 6.23 All infants (< 1 year) 0.00396 11.88 Children 1

- 2 0.0064085 19.23 Children 3

- 5 0.00508625 15.26 Children 6

- 12 0.00312325 9.37 Youth 13

- 19 0.00188925 5.67 Adults 20

- 49 0.0015675 4.70 Adults 50+ yrs 0.00142875 4.29 Fem ales 13

- 49 yrs 0.0015355 4.61 %cPAD = percent of chronic population adjusted dose Exposure estimates based on tolerance values and 100 % CT values ] ii. Drinking Water. [ There are no established maximum contaminant levels or health advisory levels for residues of pendimethalin (BAS 455 H) in drinking water. The drinking water exposure values used in this assessment were obtained from the most recent pendimethalin assessment conducted by EPA published on August 2, 2007. The pendimethalin water valu es were calculated using PRZM-EXAMS and SCI- GROW2. T he modeled chronic surface water concentrations were 6.0 ug/L, The modeled g roundwater concentration was 0.024 ug/L. Drinking water contributions were assessed based on the a pendimethalin water conc entration of 6.0 ug/L for chronic exposure and water consumption and body weights reported in CSFII, using DEEM- FCID software. T he chronic estimated water exposure values are summarized in Table 2. Table 2. Summary of chronic dietary exposure assessm ent for drinking water

considering direct and indirect sources. Population Subgroups Exposure Estimate (mg/kg b.w./day) %cPAD U.S. Population 0.000126 0.4 All Infants (< 1 year) 0.000415 1.2 Children 1

-2 years 0.000188 0.6 Children 3

- 5 years 0.000176 0.5 Children 6

- 12 years 0.000121 0.4 Youth 13

- 19 years 0.000091 0.3Adults 20

-49 years 0.000118 0.4 Adults 50+ years 0.000124 0.4 Females 13

– 49 years 0.000118 0.4 %cPAD = percent of chronic population adjusted dose Exposure based on the maximum estimated water concentration of 6.0 ug/L Acute Aggregate Exposure and Risk (Food and water) An acute assessment was not needed since the U.S. EPA Toxicological Endpoint Selection (TES) Committee had previously evaluated the pendimethalin toxicity data and determined there was no relevant toxicological endpoints for acute dietary exposure and that a risk assessment was not required. Short- and Intermediate- Term Aggregate Exposure and Risk (food, water, and residential) Short-term aggregate risk from pendimethalin takes into account exposures from dietary consumption (food and water) and residential exposure from turf use. P ost application exposure from the turf use is considered short-term. T he aggregate MOE from food, water, and residential exposure ar e 11 32 (children 1 -2 years) and 3 577 (US population) for the EC formulation and 6 78 (children 1 -2 years) and 2 358 (US population) for the CS formulation, respectively. These MOEs are greater than the target MOE of 300, which indicates there is no safety c oncern from the aggregate exposure from pendimethalin. The results of the analysis are shown in Tables 3 and 4. Table 3. Estimated short/intermediate term aggregate exposure and risk of

pendimethalin for the EC formulation. Population NOAEL

(mg/kg/day) Target

MOE 1 Food

Exposure (mg/kg/d ay) Water

Exposure (mg/kg/day) Residential

Exposure (mg/kg/day) Total

Exposure (mg/kg/day) MOE 2

US 10 300 0.00207725 0.00012625 0.000592 0.0027955 3577 Child 1

-2 yr old 10 300 0.0064085 0.0001875 0.002235 0.008831 113 2 1 Target MOE is 300. 2 Aggregate MOE = (NOAEL / (Food + Water + Residential Exposure) Table 4. Estimated short/intermediate term aggregate exposure and risk of

pendimethalin for the CS formulation. Population NOAEL

(mg/kg/day) Target

MOE 1 Food

Expo sure (mg/kg/day) Water

Exposure (mg/kg/day) Residential

Exposure (mg/kg/day) Total

Exposure (mg/kg/day) MOE 2

US 10 300 0.00207725 0.00012625 0.002038 0.0042415 2358 Child 1

-2 yr old 10 300 0.0064085 0.0001875 0.008148 0.014744 678 1 Target MOE is 300.2 Aggregate MOE = (NOAEL / (Food + Water + Residential Exposure)

Chronic Aggregate Exposure and Risk (food and water) The aggregate chronic risk includes residues of pendimethalin from food and water (Table 5). Exposures from residential uses are not included in the chronic aggregate assessment. T he results demonstrate there are no safety concerns for any subpopulation based on established and new uses, and that the results clearly meet the FQPA standard of reasonable certainty of no harm. Table 5. Estimated chronic aggregate exposure and risk of pendimethalin Population Subgroup cPAD (mg/kg/day) Food Exposure

(mg/kg/day) Water Exposure

(mg/kg/day) Total

Exposure (mg/kg/day) % cPAD U.S. Population 0.03 0.00207725 0.00012625 0.0022035 6.6 All Infants (< 1 yr old) 0.03 0.00396 0.000415 0.004375 13.1 Children 1

-2 years 0.03 0.0064085 0.0001875 0.006596 19.8 Children 3

- 5 years 0.03 0.00508625 0.00017625 0.0052625 15.8 Children 6

– 12 years 0.03 0.00312325 0.00012125 0.0032445 9.7 Youth 13

- 19 years 0. 03 0.00188925 0.00009125 0.0019805 5.9 Females 13

-49 years 0.03 0.0015355 0.0001175 0.001653 5.0 Adults 20

-49 years 0.03 0.0015675 0.0001175 0.001685 5.1 Adults + 50 0.03 0.00142875 0.00012375 0.0015525 4.7 ] 2. Non

-dietary exposure . [ The systemic exposure from the use of pendimethalin on residential turf was calculated following the current EPA Standard Operating Procedures (SOPs) for residential exposure assessment (EPA 1997b; EPA 1999a), as revised by EPA Policy 1 2 (EPA, 2001), and using the Resid ential Exposure Assessment Spreadsheet Tool (REx), Version 4.0G. E xposure values were derived from the use of a product- specific hand press study to estimate hand-to - mouth transfer in children and a formulation - specific turf transferable residue study to determine dermal exposure to adults and children. Residential exposure to both the Pendulum® 3.3 EC herbicide and Pendulum® AquaCapTM herbicide is presented below. The following table provides the route specific and aggregate exposure assessment results for each population subgroup, along with the percentage of the cPAD (0.03 mg kg BW/day) utilized, and MOE (NOAEL/Aggregate systemic Exposure).Table 6. Summary of residential exposure to pendimethalin following the use of the Pendulum® 3.3 EC herbicide formulation including the route specific and aggregate exposure assessment results for the population subgroups.

Table 7. Summary of residential exposure to pendimethalin following the use of

the Pendulum® AquaCap TM herbicide formulation including the route specific and aggregate exposure assessment results for the population subgroups.

] D. Cumulative Ef

fects [Exposure to Substances with Common Mechanism of Toxicity. The Agency has not yet published guidelines to determine whether pendimethalin has a common mechanism of toxicity with other substances or how to include this pesticide in a cumulative ris k assessment. Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, pendimethalin does not appear to produce a toxic metabolite produced by other substances. For the purposes of this tolerance action, therefore, it is assumed that pendimethalin does not have a common mechanism of toxicity with other substances. ] E. Safety Determination 1. U.S. population. [Based on these risk assessments, there is a reasonable certainty that no harm will result to the general population or any subpopulation Population subgroup Route of Exposure Route Specific Systemic Exposure (mg/kg BW/day) 1 Aggregate

Systemic Exposure (mg/kg BW/day) %cPAD MO E Adult (20

-49) Post

- application dermal 0.000592 0.000592 1.8 16892 Child (1

- 6) Post

- application dermal 0.000990 0.002235 6.7 4474

Post

- application (Hand to Mouth ingestion) 0.001245 1 Based 3% dermal absorption

Population subgroup Route of Exposure Route Specific Systemic Exposure (mg/kg BW/day) 1 Aggregate

Systemic Exposure (mg/kg BW/day) %cPAD MOE Adult (20

-49) Post

- application dermal 0.002038 0.002038 6.1 4907 Child (1

- 6) Post

- application dermal 0.003411 0.008148 24.4 1227

Post

- application (Hand to Mouth ingestion) 0.004737 1 Based 3% dermal absorptionfrom aggregate exposure to pendimethalin residues. ] 2. Infants and children

. [Based on these risk assessments, there is a reasonable certainty that no harm will result to infants or children, or any s ubpopulation from aggregate exposure to pendimethalin residues .] F. International Tolerances [ There are no CODEX, Canadian or Mexican International Maximum Residue Levels (MRL's) established for residues of pendimethalin in these crops at this time .]