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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

establishing a tolerance for the residues of [the herbicide pendimethalin, including its 

metabolites and degradates, in or on animal 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 animal metabolite 1-(1-

ethyl-propyl)-5, 6 dimethyl-7-nitro-1H-benzoimidazole, calculated as the 

stoichiometric equivalent of pendimethalin] in or on the raw agricultural animal 

commodities [milk] at [0.04] parts per million (ppm), [cattle, goat, horse, and sheep, 

fat] at [0.30] parts per million (ppm), [cattle, goat, horse, and sheep, liver] at [1.5] parts 

per million (ppm), [cattle, goat, horse, and sheep, meat] at [0.10] parts per million 

(ppm), and [cattle, goat, horse, and sheep, meat byproducts except liver] at [3.0] parts 

per million (ppm), and by amending the established tolerances for the combined residues 

of [the herbicide pendimethalin, including its metabolites and degradates, in or on 

feed commodities. Compliance with the tolerance levels specified is to be determined 

by measuring only pendimethalin, N-(1-ethylpropyl)-3,4-dimethyl2,6dinitrobenzenamine, and its metabolite, 4-[(1-ethylpropyl)amino]-2-methyl-3,5-

dinitrobenzyl alcohol, calculated as the stoichiometric equivalent of pendimethalin]

in or on the raw agricultural commodities of [Grass forage, fodder, and hay crop group 

17, forage] at [1000] parts per million (ppm), and [Grass forage, fodder, and hay crop 
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group 17, hay] at [2000] 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 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 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. In the animal commodity method D0405, pendimethalin and its 

metabolites (CL 202347 and Goat Metabolite 6) are extracted from milk and tissue 

with acidic aqueous methanol. An aliquot is taken from extract, diluted with water 

and then cleaned using a solid phase extraction column. The compounds are eluted 

from the column using methanol/water. The eluates are diluted with methanol/water 

for analysis via LC/MS/MS. The results are calculated separately by direct 

comparison of the sample peak responses to those of external standards. The 

method has a limit of quantitation (LOQ) of 0.01 in milk and 0.05 ppm in tissues for 

both pendimethalin and the goat metabolite 6. The method has undergone an 

independent laboratory validation.]

3. Magnitude of residues. [Field trials in major growing areas were conducted 

in order to determine the magnitude of residues in forage grass (MRID 47471701)

commodities. Field trials were carried out using the maximum number of 

applications, the maximum label rate and shortest pre-harvest interval (PHI) in 

forage grass at 0 day. Decline data indicated the average half-lives on the order of 10 

days in grass forage and hay. Two dairy cattle feeding studies are available to 

account for secondary transfer of pendimethalin residues occur from treated 

feedstuffs to bovine matrices. A recent dairy cattle feeding study was conducted for 

29 days with a pendimethalin concentration of 760 mg/kg-feed to cover the proposed 

use in grasses. This study also included a 10-day depuration phase to observe the 

withdrawal of the compound from milk and tissues following the last dosing 

interval. Observed residue levels of pendimethalin and goat metabolite 6 in milk 

and animal tissues support the proposed tolerances in animal matrices. A previous 

feeding study (MRID 46591234) was conducted three levels of 10, 30 and 100 mg/kgfeed; at these lower exposure levels, no residues in milk or any tissue were noted 

above the LOQ for pendimethalin, or two metabolite analytes at the highest dose 

level tested of 100 ppm. EPA has determined that the petition contains data or 
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information regarding the above aforementioned crops and animal feeding study.]

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 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 

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 
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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 

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 
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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 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 unchanged 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 tissues. 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 mouse, as well as genotoxicity 

(Ames assay). The acute oral LD50 in the mouse was determined to be 2140 mg/kg 

bw, 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 

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 [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, 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 

gardens, lawns, or buildings (residential and other indoor uses). The potential for 
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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- Food 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. The current 

tolerance values are listed in the U.S. 40 CFR § 180.361. The Tier 1 dietary 

exposure estimates were based on established and proposed tolerance values, and 

100% CT values. An updated analysis included all the crops with established 

tolerance values as of March 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-fruiting group 

8-10 = 0.10 ppm, fruit-citrus group 10-10, fruit-pome group 11-10 = 0.10 ppm, fruitstone group 12-12 = 0.10 ppm, 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); and the proposed new 

tolerances on animal commodities which support the newly proposed amended 

tolerances on forage grasses.

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 identified for sensitive populations. EPA 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 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. 

At the 95th percentile, the most highly exposed valid sub-population was “Infants 

(<1 year old)” and this group utilized 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 assessments 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. Additional 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, 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 0.001928 0.6

All 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

Adults 20-49 0.001500 0.5

Adults 50+ yrs 0.001395 0.5

Females 13 - 49 yrs 0.001463 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 July 25, 2012. The estimated acute and chronic 

surface water concentrations from EPA models were 80.5 μg/L and 6.2 μg/L,

respectively. The estimated groundwater concentration was 0.036 μg/L. These

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 over 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 

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 2 reflects the most recent EPA human health risk 

assessment published on July 25, 2012. No new uses would impact reuse of this 

assessment. 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, 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

Turfresidential Dermal 0.032 320

Child 1-2 Turf- Dermal 0.06 170
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residential

Hand to mouth 0.042 240

Object to mouth 0.0013 7,700

soil ingestion 0.000065 150,000

Granular 

injestion 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 EPA that the acute aggregate assessments 

includes only food and drinking water exposure (DP390457). Residential exposure 

is not included in the acute or chronic 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, 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. 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-to-mouth exposure. The aggregate MOE from food, water, and 

residential exposure for children 1-2 years old was 92 and for adults 125. These 

MOEs are greater than the target MOE of 30, which indicates there is no risk

concern from the aggregate exposure from pendimethalin. The 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)

MOE2

Adult 10 30 0.001928 0.078 0.079928 125
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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 residential 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 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 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 

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 Levels (MRL's) established for residues of pendimethalin in these crops at 

this time.]