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EPA REGISTRATION DIVISION - COMPANY NOTICE OF FILING FOR 

PESTICIDE PETITION 

EPA Registration Division contact: Sidney Jackson (703) 305-7610

Interregional Research Project Number 4 (IR-4)

Pesticide Petition Number: PP# 3E8212

EPA has received a pesticide petition (PP# 3E8212) from IR-4 Project 

Headquarters, Rutgers, The State University of NJ, 500 College Road East, Suite 

201 W, Princeton, NJ 08540 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 residues of the herbicide pendimethalin, [N- (1-

ethylpropyl)-3,4-dimethyl-2,6-dinitrobenzenamine], 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 

berry, low growing subgroup 13-07G at 0.1 ppm parts per million (ppm), fruit, citrus, 

group 10-10 at 0.1 ppm, fruit, pome, group 11-10 at 0.1 ppm, fruit, stone, group 12-12

at 0.1 ppm, hops, dried cones at 0.1, onion, bulb subgroup 3-07A at 0.1 ppm, onion, 

green subgroup 3-07B at 0.2 ppm, sunflower subgroup 20B at 0.1 ppm, and vegetable, 

fruiting, group 8-10 at 0.1 ppm. In addition, the petitioner proposes based upon the 

establishment of new tolerances above, removal of existing tolerances at 40 CFR 

180.361 on fruit, citrus, group 10 at 0.1 ppm, fruit, pome, group 11 at 0.1 ppm, fruit, 

stone, group 12 at 0.1ppm, garlic at 0.1 ppm, leek at 0.20 ppm, onion, bulb at 0.1

ppm, onion, green at 0.20 ppm, onion, welsh at 0.20 ppm, shallot at 0.2, strawberry at 

0.10 ppm, sunflower seed at 0.1 ppm and vegetable, fruiting, group 8 at 0.10 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 14 C 

pendimethalin on various crops. Pendimethalin and its and its 

metabolite, 4-[(1-ethylpropyl)amino]-2-methyl-3,5-dinitrobenzyl alcohol

are the residues of concern.

2. Analytical method. Section 408 (b)(3) of the amended FDCA requires EPA 

to determine that there is a practical method for detecting and measuring levels of 

the pesticide chemical residue in or on food and that the tolerance be set at a level at 

or above of the limit of detection of the designated method. In plants the method is 

aqueous organic solvent extraction, column clean up, and quantitation by GC. The 

method has a limit of quantitation (LOQ) of 0.05 ppm for pendimethalin and the 

alcohol metabolite.
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3. Magnitude of residues. Field trials in major growing areas were carried out 

in order to determine the magnitude of residues in the hops commodities. Field 

trials were carried out using the maximum number of applications, the maximum 

label rate and shortest pre-harvest interval (PHI). No field trial data were generated 

in order to determine the magnitude of residues in raw agricultural commodities in 

crop groups 8, 10, 11, and 12, or in crop subgroups 3-07A, 3-07B or 13-07G, and 

20B as EPA has determined that the tolerance on these crop commodities may be 

safely extrapolated from the established tolerances for the respective crop groupings 

and crop subgroups. 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 

milligram/kilogram body weight (mg/kg b.w.)/day) (highest concentration tested). 

For risk assessment, the EPA recommends using the RfD (non-linear) approach for 

quantification of human risk. The Agency 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. 
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In a developmental (teratology) toxicity study in the rat, the results demonstrated 

that the no-observed adverse effect level (NOAEL)s 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 (HDT). 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 (HDT). 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 lowest-observed adverse 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 interspecies extrapolation and 10X for intraspecies 

variability). EPA currently recommends a FQPA Safety Factor of 1X. Therefore, 

the chronic Population Adjusted Dose (PAD) is 0.3 mg/kg b.w./day.
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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) (HDT). 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) (HDT). There were no oncogenic effects up to 5000 ppm (750 mg/kg 

b.w./day) (HDT). Lastly, for the 1-year oral (via gelatin capsules) chronic dog study, 

the NOAEL for systemic toxicity was 200 mg/kg b.w./day, the highest dose tested.

6. Animal metabolism. Adequate goat and poultry metabolism studies are 

available for pendimethalin. The Agency has determined that there is no reasonable 

expectation of finite pendimethalin residues of concern in animal commodities as a 

result of use on multiple crops. 

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 

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.

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 October 

2012, and the proposed new tolerances for hops, dried cones at 1.0 ppm. Also, 

proposed new crop group tolerances to replace current existing pendimethalin 

tolerances. The current existing tolerances to be replaced are garlic at 0.1 ppm, leek 

at 0.20 ppm, onion-bulb at 0.10 ppm, onion-green at 0.20 ppm, shallot at 0.20 ppm, 

onion-welsh at 0.20 ppm, strawberry at 0.10 ppm, vegetable-fruiting group 8 at 0.10 

ppm, fruit, citrus group 10 at 0.10 ppm, fruit, pome group 11 at 0.10 ppm, fruitstone group 12 at 0.10 ppm, and sunflower seed at 0.1 ppm. The proposed new crop 

group tolerances are onion, bulb subgroup 3-07A at 0.10 ppm, onion-green 

subgroup 3-07B at 0.20 ppm, berry, low growing subgroup 13-07G at 0.10 ppm, 

vegetable-fruiting group 8-10 at 0.10 ppm, fruit-citrus group 10-10, fruit, pome 

group 11-10 at 0.10 ppm, fruit, stone group 12-12 at 0.10 ppm, and sunflower 

subgroup at 0.1 ppm. 

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 subgroup. 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% crop treated (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 (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 
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based on established and new uses, and 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. 

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 July 25, 2012. The estimated acute and chronic 

surface water concentrations were 80.5 microgram per liter (μg/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 
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use for children 1-2 years old. The children exposure included dermal and hand-tomouth exposure. The aggregate margin of exposure (MOE) from food, water, and 

residential exposure 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
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soil ingestion 0.000065 153846

Granular 

injestion 0.071 141

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 are no CODEX, Canadian or Mexican International Maximum 

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

this time.