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**COMPANY FEDERAL REGISTER DOCUMENT SUBMISSION TEMPLATE (7/1/2006)**  **EPA Registration Division contact: [**  **Kable Bo Davis at 703**  **- 30**  **6 -**  **0415 ]** 

**INSTRUCTIONS: Please utilize this outline in preparing tolerance petition**  **documents. In cases where the outline element does not apply please insert “NA****** **Remove” and maintain the outline. The comment notes that appear on the left ma**  **rgin represent hidd en 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 an d brackets, i.e., “[** **insert company name ],” with**  **the information specific to your action. ]**  **TEMPLATE: [**  **BASF Corporation ]**  **[Insert petition number, PP -** **xxxxxx]** 21 U.S.C. 346 EPA has received a pesticide petition **( [Insert petition number,**  **PP -** **xxxxxx ]**  **)** from **[ BASF Corporation**  **] ,**  **[ 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 amending the established tolerances for the combined residues of **[the herbicide pendimethalin,**  **N -**  **(1 -**  **ethylpropyl) -** **3,4 -**  **dimethyl -** **2,6dinitrobenzenamine, and its 3, 5 -**  **dinitrobenzyl alcohol metabolite (CL 202347)**  **]** in or on the raw agricultural commodities of **[ alfalfa,**  **forage ]**  at **[ 80**  **]** parts per million (ppm) and **[ alfalfa, hay** **]** at **[ 150**  **]** 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 plan ts is understood based on adequate studies conducted with 14 C**  **pendimethalin on various crops. Pendimethalin and its 3,5**  **- dinitrobenzyl alcohol**  **metabolite (CL202347) are the residues of concern .]** 2 2. Analytical method. **[ Section 408 (b)(3) of the amended F** **DCA 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 p lants 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 gro wing areas were**  **conducted in order to determine the magnitude of residues in the**  **alfalfa comm** **odities. Field**  **trials were carried out using the maximum number of applications, the maximum label rate and shortest pre** **- harvest interval (PHI)**  **in alfalfa at 14 da ys**  **. EPA has**  **determined that the petition contains data or information regarding the above aforementioned crops** 

. **]** B. Toxicological Profile 1. Acute toxicity. **[ Pendimethalin technical demonstrates low acute toxicity via**  **the oral, dermal ,**  **and inhalation r outes 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 ca tegory 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 category 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 syst ems 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 fe** **male 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 th** **yroid 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 mo**  **re sensitive than humans to the induction of thyroid tumors via conditions which result**  **in hypothyroidism .]**  3. Reproductive and developmental toxicity. **[ Pendimethalin is not a selective** 3

**developmental toxicant. There is no indication of increased suscept ibility 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**  **treatment peri od at 60 mg/kg b.w./day (HDT). The NOAEL for fetal**  **(prenatal)/developmental toxicity was 60 mg/kg b.w./day (HDT). In addition, there were no indications of any teratogenic effects in the rabbit fetuses at 60 mg/kg**  **b.w./day. Therefore, pendimethalin is c onsidered 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 decreased p up 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 si ze 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 weights, 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 s ub**  **- 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 gland. The chronic RfD was calculated to** 4

**be 0.3 mg/kg b.w./day using an Uncertainty Factor (UF) of 30X (3X for interspecies extrapolation and 10X for intraspecies variability)**  **. EPA/HED currently**  **recommends a FQPA Safety Factor of 1X. Therefore, the chronic Populati on**  **Adjusted Dose (PAD) is 0.3 mg/kg b.w./day. Chronic toxicity studies were conducted in rats, mice, and dogs. For the 2**  **- year rat**  **feeding study, the NOAEL for systemic toxicity was 500 ppm (25 mg/kg b.w./day), based on decreased body weight gain (approxi** **ma tely 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. 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 -** **pendi methalin is administered to rates, 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 2**  **140 mg/kg bw. An Ames assay showed the metabolite to be non -**  **mutagenic. ]**  8. Endocrine disruption

. **[ It is known that pendimethalin affects the**  **hypothalamus -** **pituitary -** **thyroid axis. However, as the chronic RfD (0.3 mg/kg b.w./day) is based on the thyroid h**  **ormone 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 considerat** **ion in the characterization of potential risks to humans.**  **]** C. Aggregate Exposure 1. Dietary exposure. **[ Pendimethalin is**  **a pre** **- emergent herbicide**  **used to**  **control 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 available information concerning exposures from the pesticide residue in food**  **and water (dietary) and all other non**  **- occupational**  **exposures. The primary non -**  **food sour ces of exposure are through pesticide use in** 5

**gardens, lawns, or buildings (residential and other indoor uses). The potential for aggregate exposure from all registered and proposed uses is discussed below**  **.]** i. Food. **[ An**  **assessment was**  **conducted to**  **evalua te**  **the potential**  **risk due**  **to chronic**  **dietary exposure**  **of the**  **U.S. population**  **to residues**  **of pendimethalin.**  **T he**  **current tolerance values are listed in the U.S. 40 CFR § 180.361. This analysis included**  **all the crops with esta** **blished tolerance values as of January**  **201 4**  **, the proposed**  **t olerances for**  **hops, dried cones at**  **1 .0 ppm**  **(pending EPA review, submitted October 2013), the**  **proposed crop group expansion**  **tolerances to replace current existing pendimethalin tolerances**  **including onion**  **- bulb subgroup 3**  **- 07A = 0.**  **10 ppm, onion -**  **green subgroup 3 -**  **07B = 0.20 ppm, low growing berry subgroup 13**  **- 07G = 0.10 ppm, vegetable** **- fruiting group 8**  **- 10 = 0.10 ppm, fruit** **- citrus**  **group 10 -**  **10, fruit -** **pome group 1 1**  **- 10 = 0.10 ppm, fruit** **- stone group 12**  **- 12 = 0.10**  **ppm , sunflower subgroup = 0.1**  **ppm (pending EPA review, submitted October**  **2013), and the proposed newly amended tolerances alfalfa .**  **Acute Dietary (food + drinking water)**  **Exposure Assessment An acute**  **dietary risk**  **assessment for females age 13** 

**– 49 years old is**  **not required**  **by EPA**  **bec ause**  **there i**  **s no**  **relevant toxicological**  **endpoints for**  **population sub**  **- group**  **. EPA**  **has determined**  **that an**  **acute dietary**  **assessment is**  **required for**  **all other**  **populations. The acute population adjusted dos e**  **(aPAD) is 1**  **mg ai/kg bw/day based**  **on a NOAEL = 100 mg /kg bw/day and a total safety factor of 100. The acute dietary**  **exposure to**  **pendimethalin residues**  **was low**  **for all**  **populations. T**  **he most**  **highly exposure sub**  **- populations was infants (< 1 year old) and utilized only**  **1.8 % aPAD.**  **Chronic Dietary (food + wat** **er) Exposure Assessment**  **The chronic**  **dietary exposure**  **estimates were**  **based on**  **established and**  **proposed tolerance**  **values, and**  **100% CT**  **values. Default**  **process factors**  **were used**  **with consumption**  **data from the USDA Continuing Survey of Food Intake by Individual s**  **(CSFII 1994**  **- 1996,**  **1998). T**  **he EP** **A Food**  **Commodity Ingredient**  **Database (FCID)**  **was also**  **used in**  **Exponent's Dietary**  **Exposure Evaluation**  **Module (DEEM** **- FCID)**  **software. Dietary**  **exposure estimates**  **were compared**  **against the**  **chronic Population**  **Adjusted Dose**  **(c PAD)**  **of 0.3**  **mg/kg b.w./day**  **for all**  **populations subgroups.**  **Results of**  **the chronic**  **dietary assessments**  **are listed**  **in T**  **able 1**  **below. The**  **estimated chronic**  **dietary exposure**  **from crops**  **and animals**  **(both established**  **and proposed**  **tolerances) was**  **less than**  **2.0% of**  **the cPAD**  **for all**  **subpopulations. Additional**  **refinements such**  **as the**  **use of**  **anticipated residues**  **and percent**  **crop treated**  **values for**  **the established**  **crop uses**  **would further**  **reduce the**  **estimated chronic**  **dietary exposure.**  **The results**  **in Table**  **1 below demonst** **rate 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.**6 **Table 1. Summary of Chronic D**  **ietary Ex** **posure (food + drinking water)**  **A sses**  **sm ent considering crops with established and proposed**  **tolerances for pendimethalin.**  **Population Subgroups**  **Exposure Estimate (mg/kg b.w./day)**  **%cPAD US Population**  **0.001984 0.6**  **Al l infants (< 1 year)**  **0.003665 1.1**  **Children 1 -** **2 0.006786**  **2.0 Children 3**  **- 5**  **0.0 05115**  **1.5 Children 6**  **- 12**  **0.002989 0.9**  **Youth 13 -**  **19 0.001679**  **0.5 Ad**  **ults 20 -** **49 0.001535**  **0.5 Ad**  **ults 50+ yrs 0.001438**  **0.4 Females 13**  **- 49 yrs**  **0.001502 0.5**  **%cPAD = percent of chronic population adjusted dose Exposure estim** **ates based on tolerance values and 100 % CT values**  **]** ii. Drinking Wa ter. **[ The**  **drinking water**  **exposure values**  **used in**  **this assessment**  **were obtained**  **from the**  **most recent**  **pendimethalin assessment**  **conducted by**  **EPA published**  **on February**  **23 ,**  **2012 .**  **The estimated**  **acute and**  **chronic surface**  **wate r**  **concentrations were**  **80.5μg/L and**  **6. 2μ**  **g/L, respectively.**  **The estimated**  **g roundwater**  **concentration was**  **0.0 36**  **μ g/L.**  **The estimated**  **drinking water**  **exposure was included in the dietary assessment. Acute Aggregate Exposure and Risk (Food and water)**  **The acute**  **dietary assessment**  **was conducted**  **including food**  **and drinking**  **water exposure.**  **Residential exposure**  **is not**  **included in**  **the acute**  **aggregate assessment.**  **The results**  **showed that**  **the acute**  **aggregate exposure**  **from pendimethalin**  **residues does not exceed the le** **vel of concern for any population.** 

**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**  **resident ial**  **exposure from**  **turf use.**  **P ost**  **application exposure**  **fr om**  **the turf**  **use is**  **considered short** **- term.**  **The residential**  **exposure used**  **in this**  **assessment is**  **from the**  **most recent**  **EP A**  **human health**  **risk assessment**  **published July**  **25, 2012.**  **T he**  **residential assessme**  **nt was**  **conducted using**  **the updated**  **Standard Operating**  **Procedures for**  **Residential Pesticide**  **Exposure Assessment.**  **The post** **- application**  **residential exposure**  **was determined**  **for the use on residential turf, residential gardens, and golf course turf. The highe st**  **post -**  **application exposure**  **from adults**  **was from**  **the garden**  **use and**  **residential turf**  **use for children 1 -** **2 years old. The children exposure included dermal and hand -** **to**   ** mouth** **exposure. T**  **he a**  **ggregate MOE**  **from food,**  **water, and**  **residential exposure** 7

**for child**  **ren 1**  **- 2**  **years old**  **was 9**  **2 and**  **for adult** **s was**  **12 5**  **. These**  **MOEs are**  **greater than**  **the target**  **MOE of**  **30, which**  **indicates there**  **is no**  **safety concern**  **from the**  **aggregate exposure**  **from pendimethalin.**  **The results**  **of the**  **analysis are**  **shown in**  **Tables 2.**  **Table 2**  **. E**  **stimated short/intermediate term aggregate exp osure and risk of** 

**pendimethalin .**  **Population NOAEL** 

**(mg/kg/day) Target** 

**MOE 1**  **Food + Drinking Water** 

**Exposure (mg/kg/day)**  **Residential**

**Exposure (mg/kg/day)**  **Total**

**Exposure (mg/kg/day)**  **MOE 2** 

**Adult 10**  **3 0**  **0.001984 0.078**  **0.079984 125**  **Child 1**  **- 2 yr old**  **10 30**  **0.006786 0.102**  **0.108786 92**  **1 Target MOE is 30.**  **2 Aggregate MOE = (NOAEL / (Food + Water + Residential Exposure)**  **Chronic Aggregate Exposure and Risk (food and water) The**  **aggregate chronic**  **risk inclu**  **des residues**  **of pendimethalin**  **from food**  **and water**  **(Table 1**  **). Exposures**  **fr om**  **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.**  **]** 2. Non

-dietary exposure . **[ The**  **post -**  **application short** **- term**  **dermal and**  **incidental oral**  **exposure and**  **risk assessment**  **was determined**  **for pendimethalin**  **use on**  **residen tial**  **turf, residential**  **gardens, and**  **golf course**  **turf. The**  **residential exposure**  **shown in**  **the Table**  **3 reflects**  **the most**  **recent EP** **A human**  **health risk**  **assessment published**  **on July**  **25 ,**  **201 2**  **. T**  **he residential**  **assessment was**  **conducted using**  **the updated**  **Standard O**  **perating Procedures**  **for Residential**  **Pesticide Exposure**  **Assessment. T**  **he calculated**  **MOEs are**  **all greater**  **than the**  **MOE level**  **of concern.**  **Table 3**  **. Pendimethalin**  **R esidential**  **Exposure after**  **the use**  **o n**  **Residential Turf,** 

**Residential Gardens, and Golf Course Tu rf.**  **Population Scenario**  **- Route**  **Exposure MOE**  **Adult Turf** **** **residential Dermal**  **0.032 313**  **Child 1 -** **2 Turf** **** **residential Dermal**  **0.06 167** 

**Hand to mouth 0.042**  **238 Object to mouth**  **0.0013 7692**  **soil ingestion 0.000065**  **153846 Granular**  **0.071 141** 8 **injestion Adult**  **Turf -**  **golf Dermal**  **0.0037 2703**  **Children 11 -**  **16 Turf**  **- Golf**  **Dermal 0.0043**  **2326 Children 6**  **- 11**  **Turf -**  **Golf Dermal**  **0.0051 1961**  **Adult Gardening**  **Dermal 0.078**  **128 Children 6**  **- 11**  **Gardening Dermal**  **0.053 189**  **]** D. Cumulative Effects **[ Exposure to Sub**  **stances 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 risk assessment. Unlike ot** **her 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, i** **t 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 po pulation or any subpopulation**  **from 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 subpopulation from aggreg**  **ate exposure to pendimethalin residues .]**  F. International Tolerances **[ There is**  **no CODEX, Canadian or Mexican International Maximum Residue Levels (MRL's) established for residues of pendimethalin in these crops at this**  **time .]**