COMPANY FEDERAL REGISTER DOCUMENT SUBMISSION TEMPLATE 

(7/1/2006) Pendimethalin, Increase Alfalfa Forage Tolerance, June 2009 

EPA Registration Division contact: [Philip V. Errico at 703-305-6663]

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TEMPLATE:

[BASF Corporation]

[ PP-9F7576]

21 U.S.C. 346 EPA has received a pesticide petition ( PP-9F7576]) 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 

combined residues of [the herbicide pendimethalin, N-(1-ethylpropyl)-3,4-dimethyl2,6-dinitrobenzenamine, and its metabolite 4-[(1-ethylpropyl)amino]-2-methyl-3,5-

dinitrobenzyl alcohol] in or on the raw agricultural commodities [alfalfa forage] at [3.5]

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 metabolite 4-[(1-

ethylpropyl)amino]-2-methyl-3,5-dinitrobenzenamine 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.]

3. Magnitude of residues. [Field trials in major growing areas across the US 

were carried out in order to determine the magnitude of residues in alfalfa 

commodities. EPA has determined that the petition contains data or information 

regarding the above aforementioned crops. Field trials were conducted on alfalfa 

targeting a pendimethalin application rate of 2 lb ai/A with a 28 day pre-harvest 

interval (PHI) for alfalfa forage and hay].

B. Toxicological Profile

1. Acute toxicity. [Pendimethalin (BAS 455 H) 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 (BAS 455 H) 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 

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 0.03 mg/kg b.w./day using an Uncertainty Factor (UF) of 30X (3X for interspecies 

extrapolation and 10X for intraspecies variability) and a 10X database uncertainty 

factor (UFDB) retained pending receipt of a developmental thyroid toxicity study. 

EPA/HED currently recommends a FQPA Safety Factor of 1X. Therefore, the 

chronic Population Adjusted Dose (PAD) is 0.03 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. 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. However, tolerances for pendimethalin residues of 

concern in livestock commodities were proposed in a previous petition.

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 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 (0.03 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 (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 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 (BAS 

455 H). 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 June 

2009, the proposed (pending at EPA) new tolerances forage grasses, crop group 17,

livestock commodities of 0.15 ppm in meat and 0.03 ppm in milk, and olives at 0.1 

ppm, and the proposed increased tolerance for alfalfa forage to 3.5 ppm. No 

tolerances are proposed for poultry or eggs because grass forage and alfalfa forage 

are not feed items for poultry. 

Acute Dietary Exposure Assessment

An acute assessment was not needed since the U.S. EPA Toxicological Endpoint 

Selection (TES) Committee had previously evaluated the pendimethalin toxicity 

data and determined there was no relevant toxicological endpoints for acute dietary 

exposure and that a risk assessment was not required. 

Chronic Dietary 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. Secondary residues in meat and milk were included. Secondary residues

for eggs and poultry were not included since it has been determined that there is no 

likelihood of residues in these animal commodities and therefore, a tolerance will 

not be required by the EPA. 

Dietary exposure estimates were compared against the worst-case pendimethalin 

chronic Population Adjusted Dose (cPAD) of 0.03 mg/kg b.w./day for all populations 

subgroups. Results of the chronic dietary assessments are listed in the table below. 

The estimated chronic dietary exposure from crops (both established and proposed 

tolerances) was less than 20% 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.
Table 1. Summary of chronic dietary exposure assessment considering crops 

with established and proposed tolerances for pendimethalin. 

Population

Subgroups

Exposure Estimate

(mg/kg b.w./day) %cPAD

US Population 0.00207725 6.23

All infants (< 1 year) 0.00396 11.88

Children 1-2 0.0064085 19.23

Children 3-5 0.00508625 15.26

Children 6-12 0.00312325 9.37

Youth 13-19 0.00188925 5.67

Adults 20-49 0.0015675 4.70

Adults 50+ yrs 0.00142875 4.29

Females 13 - 49 yrs 0.0015355 4.61

%cPAD = percent of chronic population adjusted dose 

Exposure estimates based on tolerance values and 100 % CT values

]

ii. Drinking Water. [There are no established maximum contaminant levels or 

health advisory levels for residues of pendimethalin (BAS 455 H) in drinking water. 

The drinking water exposure values used in this assessment were obtained from the 

most recent pendimethalin assessment conducted by EPA published on August 2, 

2007. The pendimethalin water values were calculated using PRZM-EXAMS and 

SCI-GROW2. The modeled chronic surface water concentrations were 6.0 ug/L, 

The modeled groundwater concentration was 0.024 ug/L. 

Drinking water contributions were assessed based on the a pendimethalin water 

concentration of 6.0 ug/L for chronic exposure and water consumption and body 

weights reported in CSFII, using DEEM-FCID software. The chronic estimated 

water exposure values are summarized in Table 2. 

Table 2. Summary of chronic dietary exposure assessment for drinking water 

considering direct and indirect sources. 

Population

Subgroups

Exposure Estimate

(mg/kg b.w./day)

%cPAD

U.S. Population 0.000126 0.4

All Infants (< 1 year) 0.000415 1.2

Children 1-2 years 0.000188 0.6

Children 3-5 years 0.000176 0.5

Children 6-12 years 0.000121 0.4

Youth 13-19 years 0.000091 0.3
Adults 20-49 years 0.000118 0.4

Adults 50+ years 0.000124 0.4

Females 13 – 49 years 0.000118 0.4

%cPAD = percent of chronic population adjusted dose 

Exposure based on the maximum estimated water concentration of 6.0 ug/L

Acute Aggregate Exposure and Risk (Food and water)

An acute assessment was not needed since the U.S. EPA Toxicological Endpoint 

Selection (TES) Committee had previously evaluated the pendimethalin toxicity 

data and determined there was no relevant toxicological endpoints for acute dietary 

exposure and that a risk assessment was not required. 

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 aggregate 

MOE from food, water, and residential exposure are 1132 (children 1-2 years) and 

3577 (US population) for the EC formulation and 678 (children 1-2 years) and 2358

(US population) for the CS formulation, respectively. These MOEs are greater than 

the target MOE of 300, which indicates there is no safety concern from the 

aggregate exposure from pendimethalin. The results of the analysis are shown in 

Tables 3 and 4. 

Table 3. Estimated short/intermediate term aggregate exposure and risk of 

pendimethalin for the EC formulation. 

Population NOAEL 

(mg/kg/day)

Target 

MOE1

Food 

Exposure 

(mg/kg/d

ay)

Water 

Exposure 

(mg/kg/day)

Residential 

Exposure 

(mg/kg/day)

Total 

Exposure 

(mg/kg/day)

MOE2

US 10 300 0.00207725 0.00012625 0.000592 0.0027955 3577

Child

1-2 yr old 10 300 0.0064085 0.0001875 0.002235 0.008831 1132

1 Target MOE is 300.

2 Aggregate MOE = (NOAEL / (Food + Water + Residential Exposure) 

Table 4. Estimated short/intermediate term aggregate exposure and risk of 

pendimethalin for the CS formulation. 

Population NOAEL 

(mg/kg/day)

Target 

MOE1

Food 

Exposure 

(mg/kg/day)

Water 

Exposure 

(mg/kg/day)

Residential 

Exposure 

(mg/kg/day)

Total 

Exposure 

(mg/kg/day)

MOE2

US 10 300 0.00207725 0.00012625 0.002038 0.0042415 2358

Child

1-2 yr old 10 300 0.0064085 0.0001875 0.008148 0.014744 678

1 Target MOE is 300.
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 5). 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. 

Table 5. Estimated chronic aggregate exposure and risk of pendimethalin 

Population Subgroup cPAD 

(mg/kg/day)

Food Exposure 

(mg/kg/day)

Water Exposure 

(mg/kg/day)

Total 

Exposure 

(mg/kg/day)

% cPAD

U.S. Population 0.03 0.00207725 0.00012625 0.0022035 6.6

All Infants (< 1 yr old) 0.03 0.00396 0.000415 0.004375 13.1

Children 1-2 years 0.03 0.0064085 0.0001875 0.006596 19.8

Children 3-5 years 0.03 0.00508625 0.00017625 0.0052625 15.8

Children 6 – 12 years 0.03 0.00312325 0.00012125 0.0032445 9.7

Youth 13-19 years 0.03 0.00188925 0.00009125 0.0019805 5.9

Females 13-49 years 0.03 0.0015355 0.0001175 0.001653 5.0

Adults 20-49 years 0.03 0.0015675 0.0001175 0.001685 5.1

Adults + 50 0.03 0.00142875 0.00012375 0.0015525 4.7

]

2. Non-dietary exposure. [The systemic exposure from the use of 

pendimethalin on residential turf was calculated following the current EPA 

Standard Operating Procedures (SOPs) for residential exposure assessment (EPA 

1997b; EPA 1999a), as revised by EPA Policy 12 (EPA, 2001), and using the 

Residential Exposure Assessment Spreadsheet Tool (REx), Version 4.0G. Exposure 

values were derived from the use of a product-specific hand press study to estimate 

hand-to-mouth transfer in children and a formulation-specific turf transferable 

residue study to determine dermal exposure to adults and children. Residential 

exposure to both the Pendulum® 3.3 EC herbicide and Pendulum® AquaCapTM 

herbicide is presented below. 

The following table provides the route specific and aggregate exposure assessment 

results for each population subgroup, along with the percentage of the cPAD (0.03 

mg kg BW/day) utilized, and MOE (NOAEL/Aggregate systemic Exposure). 
Table 6. Summary of residential exposure to pendimethalin following the use of 

the Pendulum®3.3 EC herbicide formulation including the route specific 

and aggregate exposure assessment results for the population subgroups.

Table 7. Summary of residential exposure to pendimethalin following the use of 

the Pendulum® AquaCapTM herbicide formulation including the route 

specific and aggregate exposure assessment results for the population 

subgroups.

]

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 

Population 

subgroup Route of Exposure

Route Specific 

Systemic Exposure 

(mg/kg BW/day) 1

Aggregate

Systemic Exposure 

(mg/kg BW/day)

%cPAD MOE

Adult 

(20-49) Post-application dermal 0.000592 0.000592 1.8 16892

Child 

(1-6)

Post-application dermal 0.000990

0.002235 6.7 4474 Post-application 

(Hand to Mouth ingestion) 0.001245

1 Based 3% dermal absorption

Population 

subgroup Route of Exposure

Route Specific 

Systemic Exposure 

(mg/kg BW/day) 1

Aggregate

Systemic Exposure 

(mg/kg BW/day)

%cPAD MOE

Adult 

(20-49) Post-application dermal 0.002038 0.002038 6.1 4907

Child 

(1-6)

Post-application dermal 0.003411

0.008148 24.4 1227 Post-application 

(Hand to Mouth ingestion) 0.004737

1 Based 3% dermal absorption
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.]