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**EPA REGISTRATION**  **DIVISION -**  **COMPANY NOTICE**  **OF FILING**  **FOR PESTICIDE PETITION**  **Docket ID Number: EPA** **- HQ**  **- OPP**  **- 2014**  **- 0397**  **EPA Registration**  **Division contact:**  **Sidney Jackson (703)**  **305 -**  **7610 Interregional Research Project Number 4**  **Pesticide Petition Number**  **: 4**  **E8 282**  EPA has received a pesticide petition **( PP** **#) number**  **4E8282** from the Interregional Research Project Number 4 (IR

- 4), IR

- 4 Project Headquarters, Rutgers, The State University of New Jersey, 500 College Road East, Suite 201 W, Princeton, NJ 08450 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 residues of **the herbicide pendimethalin, including its**  **metabolites and degradates, in or on food commodities. Compliance with the**  **tolerance levels specified is to be determined by measuring only pendimethalin, N -**  **(1 -**  **ethylpropyl) -** **3,4 -**  **dimethyl -** **2,6dinitrobenzenamine, and its metabolite, 4 -**  **[(1 -**  **ethylpropyl)amino] -** **2 -**  **methyl -** **3,5 -**  **dinit robenzyl alcohol, calculated as the**  **stoichiometric equivalent of pendimethalin** in or on the raw agricultural commodities **caneberry, subgroup 13 -**  **07A** at **0.1** parts per million (ppm) , **bushberry subgroup 13 -**  **07B** at **0.1** ppm, and **nut, tree, group 14 -**  **12** at **0.1** ppm. **In addition, t he petitioner**  **proposes that upon approval of**  **the above mentioned**  **tolerances to remove**  **existing tolerance**  **s at 40 CFR 180.361 for**  **juneberry at 0.1 ppm, nut, tree,**  **group 1**  **4 at 0.1 ppm and pistachio at 0.1 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 support 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 14C pendimethalin**  **on various crops. Pendimethalin and its 3,5**  **- dinitrobenzyl alcohol metabolite**  **(CL202347) are the established 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 measu**  **ring 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 quantita** **tion by g**  **as**2

**c hromatography (**  **GC )**  **. The method has a limit of quantitation (LOQ) of 0.05 ppm for pendimethalin and the alcohol metabolite.**  3. Magnitude of residues. **Field trials in major growing areas were conducted in order to determine the magnitude of r** **esidues in caneberry and bushberry commodities. Field trials were carried out using the maximum label rate and**  **shortest pre -**  **harvest interval (PHI) in berries at 30 days. No field trial data were**  **generated in order to determine the magnitude of residues in**  **raw agricultural commodities in crop group 14**  **- 12 as EPA has determined that the tolerance on this**  **crop commodity may be safely extrapolated from the established tolerances for the crop group 14. EPA has determined that the petition contains data or inform**  **ation regarding the above aforementioned crops.**  B. Toxicological Profile 1. Acute toxicity. **Pendimethalin technical demonstrates low acute toxicity via the oral, dermal, and inhalation routes 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. The acute reference dose is based on reduced motor activity at Day 0 in the acute neurotoxicity study. Technical**  **pendimethalin i s category IV for skin irritation and category 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 Sus pension (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 o f 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, bot** **h 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 aden**  **omas of the thyroid gland in male and female rats at 5000 ppm (250 mg/kg body weight (** **b.w. )** **/day) (highest concentration tested). For risk assessment, OPP recommends using the**  **r eference**  **d ose (** **RfD )**  **non -** **linear approach for quantification of human risk. The**  **Agency Committee has determined that the hypothesis, that benign thyroid 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 hig** **h doses in rats, a mammalian species that is expected to be much more 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 dev** **elopmental toxicant. There is no indication of increased susceptibility following**3

**prenatal/postnatal exposure to pendimethalin. In a developmental (teratology) toxicity study in the rat, the results demonstrated**  **that the n**  **o -**  **o bserv** **ed -**  **a dverse** **- e**  **ffect -** **l evels (** **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). T**  **herefore, 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 period 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 indicatio ns of any teratogenic effects in the rabbit fetuses at 60 mg/kg**  **b.w./day. Therefore, 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 demonst rated 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 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 liv** **e 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 pos**  **tnatal 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 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 int** **rathyroidal metabolism study. The lowest** **- observed** **- adver** **se -**  **effect -** **level (** **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 be 0.3 mg/kg b.w./day using an Uncertainty Factor (UF) of 30X (3X for**4

**interspecies extrapolation and 1 0X for intraspecies variability). EPA/HED**  **currently recommends a FQPA Safety Factor of 1X. Therefore, the chronic Population 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 (approximately 20 -** **30%), increased clinical signs of toxicity, increased relative liver weights, and slight but statistical increase in**  **the i ncidence of benign follicular cell adenomas of the thyroid gland in males and**  **females at 5000 ppm (250 mg/kg b.w./day) , the highest concentration tested**  **(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 s**  **tudy, 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**  **- pendimethalin is administered to rats, about 70% of the administered**  **radioactivity is excreted via feces and 20% via urine within 24 hours. Within 96**  **hours, the total radioactive residues (TRR) found in the tissues was 0.3 ppm, except fat which was 0.9 ppm. The major portion of the radioactivity that was excreted in**  **the feces was identified as the unchange d parent compound. In the goat metabolism**  **study following administration of radiolabeled pendimethalin equivalent to 15.35 ppm in the diet for 5 consecutive days, approximately 94% of the administered**  **radioactivity was recovered in feces, urine and tissue s. Among the edible tissues,**  **only liver (0.32 ppm) and kidney (0.042 ppm) contained residues >0.01 ppm. With the exception of Metabolite 6 (13% TRR), no other component exceeded 10% of the**  **TRR in liver. The major metabolite (Metabolite 6) was identified in feces, bile and**  **urine by LC/MS and high resolution mass spectrometry. Only trace levels of unchanged parent were detected.**  7. Metabolite toxicology

. **The main pendimethalin plant metabolite, CL 202347, has been tested for acute oral toxicity in the m**  **ouse, as well as genotoxicity (Ames assay). The acute oral**  **lethal dose (** **LD )**  **50 in the mouse was determined to be 2140 mg/kg b**  **. w**  **. , which is considered to be “slightly toxic by ingestion in single**  **doses.” An Ames assay demonstrated that the plant metabolite is non**  **- mutagenic.**  **In addition, since goat Metabolite 6 was observed in a recent rat metabolism study, it is considered to have been evaluated in the existing mammalian toxicity database**  **for the active ingredient.** 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 hormone related endpoint in rats, as noted in the**5

**sub -**  **chronic special studies in Section 5 above, whic h 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 **Pendimethalin is a p re** **- 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, FQPA**  **directs EPA to consider available information concerning ex posures from the**  **pesticide residue in food and water (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 uses). The potential f or**  **aggregate exposure from all registered and proposed uses is discussed below .**  1. Dietary exposure. **The updated dietary assessments employed the EPA posted Dietary Exposure Evaluation Model** **- Fo**  **od Consumption Intake Database (DEEM** **- FCID) version 3.18 and**  **the residue input files from their July 2012 dietary assessment DP 401100 for any concentration factors as a starting point.**  i. Food. **An assessment**  **was conducted**  **to evaluate**  **the potential**  **risk due**  **to 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. T**  **he Tier**  **1 dietary**  **exposure estimates**  **were based**  **on established**  **and proposed**  **tolerance values,**  **and 100%**  **CT values.**  **A n**  **updated analysis**  **included all**  **the crops**  **with esta** **blished tolerance**  **values as**  **of May**  **2014 and:**  **the proposed**  **tolerances 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** **- fr** **uiting group 8**  **- 10 = 0.10 ppm, fruit** **- citrus group 10**  **- 10 = 0.10 ppm, fruit** **- pome group 11**  **- 10 = 0.10**  **ppm, fruit** **- stone**  **group 1**  **2 -**  **12 =**  **0.10 ppm,**  **and sunflower**  **subgroup =**  **0.1 ppm**  **(pending EPA**  **review, submitted**  **October 2013);**  **the proposed**  **amended tolerances**  **for alfalfa**  **forage and**  **hay (pending**  **EPA review,**  **submitted February**  **2014); the**  **proposed tolerances**  **on animal**  **commodities which**  **su pport**  **the proposed**  **am ended**  **tolerances on**  **forage grasses**  **(pending EPA**  **review, submitted**  **March 2014);**  **and the**  **proposed new**  **tolerances on**  **caneberry sub**  **group 13**  **- 07A**  **and bushberry**  **sub group**  **13 -**  **07B, and**  **the newly proposed**  **crop group**  **expansion tolerances**  **to repl**  **ace current**  **existing pendimethalin tolerances on tree nut group 14 -**  **12 = 0.10 ppm. Acute Dietary (food + drinking water) Exposure Assessment**  **No special**  **dietary assessment**  **for females**  **age 13** 

**– 49**  **years old**  **is required**  **by EPA**  **because no**  **endpoint was**  **identifi ed**  **for sensitive**  **populations. E**  **PA has**  **determined that an acute dietary assessment is required for the general populations which cover**  **infants and**  **children. The**  **acute population**  **adjusted dose**  **(aPAD) is**  **1 mg**  **active ingredient**  **( ai** **) /kg**  **b .** **w .** **/day based**  **on a**  **NOA EL**  **= 100**  **mg/kg b**  **. w**  **. /day**  **and a**  **total safety**  **factor of**  **100. T**  **he acute**  **dietary exposure**  **to pendimethalin**  **residues was**  **low for**  **all populations.**  **A t**  **the 95**  **th percentile,**  **the most**  **highly exposed**  **valid sub**  **-**6

**population was “Infants (<1 year old)” and this group ut ilized only 1.8% aPAD.**  **Chronic Dietary (food + water) Exposure Assessment Dietary**  **exposure estimates**  **were compared**  **against the**  **chronic Population**  **Adjusted Dose**  **(cPAD) of**  **0.3 mg/kg**  **b.w./day for**  **all populations**  **subgroups. Results**  **of the**  **chronic dietary**  **asse ssments**  **are listed**  **in Table**  **1 below.**  **The estimated**  **chronic dietary**  **exposure from**  **crops and**  **animals (both**  **established and**  **proposed tolerances)**  **was <** **2.2% of**  **the cPAD**  **for all**  **subpopulations. A** **dditional refinements**  **such as**  **the use**  **of anticipated**  **residues, PDP**  **data and**  **percent crop**  **treated values**  **for the**  **established crop**  **uses would**  **further reduce**  **the estimated**  **chronic dietary**  **exposure. The**  **results in**  **Table 1**  **below demonstrate**  **there are**  **no risk**  **concerns for**  **any subpopulation**  **based on**  **established and**  **new uses,**  **an d**  **that the**  **results clearly**  **meet the FQPA standard of reasonable certainty of no harm. Table 1. Summary of Chronic Dietary Exposure (food + drinking water)**  **Assessment considering crops with established and proposed tolerances**  **for pendimethalin. Populatio**  **n Subgroups**  **Exposure Estimate (mg/kg b.w./day)**  **%cPAD US Population**  **0.001928 0.6**  **Al l infants (< 1 year)**  **0.003616 1.2**  **Children 1 -** **2 0.006486**  **2.2 Children 3**  **- 5**  **0.004922 1.6**  **Children 6 -**  **12 0.002923**  **1.0 Youth 13**  **- 19**  **0.001635 0.5**  **Ad ults 20**  **- 49**  **0.001500 0.5**  **Ad ults 50+ yrs**  **. 0.001395**  **0.5 Females 13**  **- 49 yrs**  **. 0.001463**  **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**  **July 25,**  **2012. The**  **estimated acute**  **and chronic**  **surface water**  **concentrations from**  **EP A**  **models were**  **80.5 μg/L**  **and 6.2**  **μg/L, respectively.**  **The estimated**  **ground water**  **concentration was**  **0.036 μg/L.**  **T hese**  **estimated drinking**  **water exposures**  **were included**  **directly in**  **the dietary**  **assessments. The DEEM critical**  **exposure contribution analysis calculates estimated**  **model water**  **contributions (indirect**  **and direct)**  **makeup ov** **er 60%**  **of the**  **potential exposure**  **of pendimethalin**  **for infants**  **within the**  **acute assessment;**  **the modelled**  **water estimates are understood to be conservative.** 2. Non

-dietary exposure . **The post** **- application**  **short -** **term dermal**  **and**7

**incidental oral**  **exposure and**  **ri sk**  **assessment was**  **determined for**  **pendimethalin use**  **on residential**  **turf, residential**  **gardens, and**  **golf course**  **turf. The**  **residential exposure**  **shown in**  **the Table**  **2 reflects**  **the most**  **recent EP** **A human**  **health risk**  **assessment published**  **on July**  **25, 2012.**  **N o**  **new u**  **ses would**  **impact reuse**  **of this**  **assessment. T**  **he residential**  **assessment was**  **conducted using**  **the updated**  **Standard Operating**  **Procedures for**  **Residential Pesticide**  **Exposure Assessment.**  **T he**  **calculated ma**  **rgin of**  **exposures (** **MOEs )**  **are all**  **greater than**  **the MOE**  **leve l**  **of concern, which is a value of 30.**  **Table 2. Pendimethalin**  **Residential Exposure**  **after the**  **use on**  **Residential Turf,** 

**Residential Gardens, and Golf Course Turf. Population**  **Scenario -**  **Route Exposure**  **MOE Adult**  **Turf****** **residential Dermal**  **0.032 320**  **Child 1 -** **2 Turf** **** **residential Dermal**  **0.06 170** 

**Hand to mouth 0.042**  **240 Object to mouth**  **0.0013 7,700**  **soil ingestion 0.000065**  **150,000 Granular**  **in g**  **estion 0.071**  **140 Adult**  **Turf -**  **golf Dermal**  **0.0037 2,700**  **Children 11 -**  **16 Turf**  **- Golf**  **Dermal 0.0043**  **2,300 Children 6**  **- 11**  **Turf -**  **Golf Dermal**  **0.0051 2,000**  **Adult Gardening**  **Dermal 0.078**  **130 Children 6**  **- 11**  **Gardening Dermal**  **0.053 190**  **Acute Aggregate Exposure and Risk (Food and water) It**  **has been**  **previously determined**  **by EP** **A that**  **the acute**  **aggregate assessments**  **includes only**  **food and**  **drinking water**  **exposure (DP390457).**  **R esidential**  **exposure is**  **not included**  **in the**  **acute or**  **chronic aggregate**  **assessment. T**  **he results**  **showed that**  **the acute**  **aggregate exposure**  **from pendimethalin**  **residues does**  **not exceed**  **the level 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**  **residential exposure**  **from turf**  **use. P**  **ost application**  **exposure fr** **om the**  **turf use**  **is considered**  **short -** **term. T**  **he residential**  **exposure use**  **d in**  **this assessment**  **is from**  **the most**  **recent EP** **A human**  **health risk**  **assessment published July 25, 2012, no new residential uses impact the aggregate, so**  **only an update to the dietary components is needed. The residential assessment was conducted**  **using the**  **updated Standard**  **Operating Procedures**  **for Residential**  **Pesticide Exposure**  **Assessment. T**  **he post** **- application**  **residential exposure**  **was determined**  **for the**  **use on**  **residential turf,**  **residential gardens,**  **and golf**  **course turf.**  **The highest**  **post -**  **application exposur** **e from**  **adults was**  **from the**  **garden use**  **and**8

**residential turf**  **use for**  **children 1**  **- 2**  **years old.**  **T he**  **children exposure**  **included dermal**  **and hand** **- to**  **- mouth**  **exposure. T**  **he aggregate**  **MOE from**  **food, water,**  **and residential**  **exposure for**  **children 1**  **- 2**  **years old**  **was 92**  **an d**  **for adults**  **125. T**  **hese MOEs**  **are greater**  **than the**  **target MOE**  **of 30,**  **which indicates**  **there is**  **no risk**  **concern from**  **the aggregate**  **exposure from**  **pendimethalin. T**  **he results**  **of the**  **analysis are shown in Tables 3. Table 3.**  **Estimated short/intermediate term aggregate exposure 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**  **30 0.001928**  **0.078 0.079928**  **125 Child**  **1 -**  **2 yr old 10**  **30 0.006486**  **0.102 0.108486**  **92 1**  **HED’s LOC for the MOE is 30. 2**  **Aggregate MOE = (NOAEL / (Food + Water + Residential Exposure) Chronic Aggregate Exposure and Risk (food and water)**  **It has been previously determined by EPA that the chronic aggregate assessments includes only food and drinking water exposure (Table 1), because exposure is not**  **expected for residential (dermal and inhalation) exposure pathway (DP390457). Exposures from r** **esidential uses are not included in the chronic aggregate assessment. The results demonstrate there are no risk concerns for any**  **subpopulation based on established and new uses.** D. Cumulative Effects **Exposure to Substances with Common Mechanism of Tox icity. 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 other pesticides for which EPA has fol lowed 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 the aggregate exposure to the general population or any**  **subpopulation from pendimethalin residues does not result in an unacceptable risk.**  2. Infants and children

. **EPA has previously recommended the 10X FQPA**9

**safety factor be removed (reduced to 1X) based on reliable data. Based on these risk**  **assessments, there is a reasonable certainty that the aggregate exposure to infants or**  **children, or any subpopulation from pendimethalin residues does not result in an unacceptable risk** **.** F. International Tolerances **There are no CODEX, Canadian or Mexican International Maximum Residue Lev** **els (MRL's) established for residues of pendimethalin in these crops at this time**  **.**