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COMPANY FEDERAL REGISTER DOCUMENT SUBMISSION TEMPLATE 

(7/1/2006)

EPA Registration Division contact: [Kable Bo Davis at 703-306-0415]

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 appear on the left 

margin 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]

[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 plants 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.]
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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. [Field trials in major growing areas were conducted 

in order to determine the magnitude of residues in the alfalfa commodities. 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 days. 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 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. Technical pendimethalin is 

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 

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 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 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 high 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 
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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 

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 indications 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 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 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 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 sub-chronic oral 92-day thyroid function study, the subchronic 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 
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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 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 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-pendimethalin 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 2140 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 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 exposure. [Pendimethalin is a pre-emergent herbicide used to 

control broadleaf and grass weeds in food and non-food crops, as well as nonagricultural use sites including residential lawns. In examining aggregate exposure, 

FQPA 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 sources of exposure are through pesticide use in 
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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 evaluate the potential risk due to 

chronic dietary exposure of the U.S. population to residues of pendimethalin. 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 January 

2014, 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-fruiting group 8-10 = 0.10 ppm, fruit-citrus 

group 10-10, fruit-pome group 11-10 = 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 because there is 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 dose (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. The most highly 

exposure sub-populations was infants (< 1 year old) and utilized only 1.8% aPAD. 

Chronic Dietary (food + water) 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 Individuals 

(CSFII 1994 - 1996, 1998). The EPA 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 (cPAD) of 0.3 mg/kg b.w./day for all populations subgroups. Results of the 

chronic dietary assessments are listed in Table 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 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.
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Table 1. Summary of Chronic Dietary Exposure (food + drinking water)

Assessment 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

All infants (< 1 year) 0.003665 1.1

Children 1-2 0.006786 2.0

Children 3-5 0.005115 1.5

Children 6-12 0.002989 0.9

Youth 13-19 0.001679 0.5

Adults 20-49 0.001535 0.5

Adults 50+ yrs 0.001438 0.4

Females 13 - 49 yrs 0.001502 0.5

%cPAD = percent of chronic population adjusted dose 

Exposure estimates based on tolerance values and 100 % CT values

]

ii. Drinking Water. [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 water concentrations were 80.5μg/L and 6.2μg/L, respectively. The 

estimated groundwater concentration was 0.036μg/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 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. Post 

application exposure from the turf use is considered short-term. The residential 

exposure used in this assessment is from the most recent EPA human health risk 

assessment published July 25, 2012. The residential assessment 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 highest 

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-tomouth exposure. The aggregate MOE from food, water, and residential exposure 
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for children 1-2 years old was 92 and for adults was 125. 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. Estimated short/intermediate term aggregate exposure and risk of 

pendimethalin.

Population NOAEL 

(mg/kg/day)

Target 

MOE1

Food + Drinking Water 

Exposure 

(mg/kg/day)

Residential 

Exposure 

(mg/kg/day)

Total 

Exposure 

(mg/kg/day)

MOE2

Adult 10 30 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 includes residues of pendimethalin from food and water 

(Table 1). Exposures from residential uses are not included in the chronic aggregate 

assessment. The 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 residential turf, residential gardens, and golf course turf. The residential 

exposure shown in the Table 3 reflects the most recent EPA human health risk 

assessment published on July 25, 2012. The residential assessment was conducted 

using the updated Standard Operating Procedures for Residential Pesticide 

Exposure Assessment. The calculated MOEs are all greater than the MOE level of 

concern. 

Table 3. Pendimethalin Residential Exposure after the use on Residential Turf, 

Residential Gardens, and Golf Course Turf. 

Population Scenario- Route Exposure MOE

Adult

Turfresidential Dermal 0.032 313

Child 1-2 

Turfresidential 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
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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 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 risk 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 

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 

aggregate 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.]