Page 3 of 18

observed thyroid effects in the rat because of several important quantitative dynamic 

differences between rats and humans with respect to thyroid function (Interim Guidance 

on Thyroid Disrupting Pesticides, dated 11/01/2005). The Points of Departures (PoDs) 

and endpoints of concern used for dietary and non-dietary (occupational and residential) 

risk assessments are presented in Table 1. The PoDs, endpoints, UFs, and FQPA Safety 

Factors will be re-evaluated during the preparation of the registration review risk 

assessment.

Endocrine Disruption Screening Program

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential 

adverse outcomes from exposure to chemicals. Collectively, these studies include acute, 

subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, 

developmental, reproductive, and general or systemic toxicity. These studies include 

endpoints which may be susceptible to endocrine influence, including effects on 

endocrine target organ histopathology, organ weights, estrus cyclicity, sexual maturation, 

fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological 

hazard assessments, EPA evaluates acute tests and chronic studies that assess growth, 

developmental and reproductive effects in different taxonomic groups. As part of its 

reregistration decision, EPA reviewed these data and selected the most sensitive 

endpoints for relevant risk assessment scenarios from the existing hazard database. 

However, as required by FFDCA section 408(p), pendimethalin is subject to the 

endocrine screening part of the Endocrine Disruptor Screening Program (EDSP). 

EPA has developed EDSP to determine whether certain substances (including pesticide

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a “naturally occurring estrogen, or other such endocrine effects as the 

Administrator may designate.” The EDSP employs a two-tiered approach to making the 

statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to 

identify the potential of a chemical substance to interact with the estrogen, androgen, or 

thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening and 

are found to have the potential to interact with E, A, or T hormonal systems will proceed 

to the next stage of the EDSP where EPA will determine which, if any, of the Tier 2 tests 

are necessary based on the available data. Tier 2 testing is designed to identify any 

adverse endocrine related effects caused by the substance, and establish a dose-response 

relationship between the dose and the E, A, or T effect.

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between 

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group 

of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. 

Pendimethalin is not among the group of 58 pesticide active ingredients on the initial list 

to be screened under the EDSP. Accordingly, as part of registration review, EPA will 

issue future EDSP orders/data call-ins, requiring the submission of EDSP screening 

assays for nitrapyrin. For further information on the status of the EDSP, the policies and 

procedures, the list of 67 chemicals, future lists, the test guidelines and the Tier 1 

screening battery, please visit our website: http://www.epa.gov/endo/.

Residue Chemistry
Page 4 of 18

The existing residue chemistry database for pendimethalin is adequate for risk assessment 

purposes. No additional data are required during the registration review process. The 

qualitative nature of the residue(s) of pendimethalin in plants and animals has been 

adequately identified/characterized and is understood. The residues of concern in plants 

and animals for tolerance enforcement and risk assessment are pendimethalin and its 3,5-

dinitrobenzyl alcohol metabolite. 

Dietary Exposure and Risk Assessment

The pendimethalin dietary exposure database is adequate to support the existing 

registrations. For the 2012 risk assessment, screening level acute and chronic dietary 

analyses were performed for pendimethalin using DEEM-FCID and assuming 100% crop 

treated. The results of aggregate dietary (food + drinking water) analysis show that the 

acute and chronic dietary risk for the general U.S. population and all population 

subgroups are below HED’s level of concern (<100% acute Population Adjusted Dose 

(aPAD) and chronic Population Adjusted Dose (cPAD)) at the 95th percentile of the 

exposure distribution.

Residential Exposure and Risk Assessment

Pendimethalin is currently registered for use on lawns, and landscape ornamentals and 

for weed control on non-cropland areas by commercial applicators and homeowners. 

Residential handler and post-application exposures were assessed for the 2012 risk 

assessment to reflect changes to the Standard Operating Procedures, body weight 

parameters, and toxicological information. Updated residential handler and postapplication risk estimates do not exceed HED’s level of concern (MOEs ≥ 30). 

Aggregate Exposure and Risk Assessment

The acute aggregate risk estimates associated with exposure to pendimethalin are 

equivalent to the acute dietary risk estimates. The acute dietary risk estimates from the 

2012 risk assessment do not exceed HED’s level of concern.

The short-term aggregate risk assessment was conducted for pendimethalin. The shortterm aggregate (residential exposure was combined with background food and water 

exposure) risk estimates from the 2012 risk assessment do not exceed HED’s level of 

concern (MOEs ≥ 30).

Chronic exposure is not expected for the residential exposure pathway. Therefore, the 

chronic aggregate risk would be equivalent to the chronic dietary exposure estimate. The 

chronic dietary risk estimates from the 2012 risk assessment do not exceed HED’s level 

of concern.

Occupational Exposure and Risk Assessment

HED updated the occupational exposure assessment for the 2012 pendimethalin Section 3 

for leaf lettuce, leafy brassica greens, melons, edamame, kiwi and other small fruit vines 

risk assessment to reflect current use information and policies. In addition to assessing

risk estimates for the proposed uses, the 2012 risk assessment document also assessed all 

currently registered occupational uses for pendimethalin. The results of the occupational 

handler exposure assessment indicate that there are potential risk estimates of concern for 

three uses of pendimethalin. Risk estimates for the alfalfa, sugarcane, and the turf and 
Page 5 of 18

ornamental scenarios do not exceed HED’s level of concern (MOE ≥ 30) with gloves 

and/or respirators. However, for the dry bulk fertilizer use, no additional PPE can be 

assumed because the commercial impregnation takes into account a closed system. 

In accordance with the updated Part 158 data requirements (2007), one or more DFR 

studies are required when a pesticide has residential or occupational uses that could result 

in post-application dermal exposure. As part of the recent revision to the Health Effects 

Division’s 2012 Standard Operating Procedures for Residential Pesticide Exposure 

Assessment, HED analyzed a number of DFR studies and selected a new default value for 

the fraction of the application rate available to be dislodged after a foliar application 

(FAR). This default value is 25%. Of the analyzed DFR studies, the maximum FAR value 

seen was 89% or 3.6 times higher than the default residue transfer value. Therefore, a 

calculated MOE of approximately 4 times higher than the LOC (i.e., an MOE > 120 for 

pendimethalin since the LOC = 30) using the default dislodged residue value would 

provide an adequate margin of safety for any potentially higher residues seen in a 

chemical-specific DFR study. 

Post-application worker risk estimates for all proposed and existing foliar uses were 

assessed in the 2012 risk assessment. The existing DFR study (MRID 44969902) does 

not represent foliar applications of pendimethalin and was, therefore, not used to 

calculate the post-application risk estimates for foliar applications. Post-application risk 

estimates using the default FAR value of 25% did not exceed HED’s level of concern 

(MOEs ≥ 30) however post-application MOEs for alfalfa and ornamentals (handset 

irrigation activity) and green onions and onions (hand weeding activity) are less than 120. 

As a result, a DFR study is required for pendimethalin at this time. This approach is 

documented in an HED HASPOC document entitled Guidance for Requiring/Waiving 

Turf Transferrable Residue (TTR) and Dislodgeable Foliar Residue (DFR) Studies (dated 

6/7/12).

Human Studies

The 2012 pendimethalin risk assessment relies in part on data from studies in which adult 

human subjects were intentionally exposed to a pesticide or other chemical. Studies such 

as the Pesticide Handlers Exposure Database and the Agricultural Handler Exposure Task 

Force, have been reviewed by the Agency and found on the basis of available evidence to 

have been neither fundamentally unethical nor significantly deficient relative to standards 

of ethical research conduct prevailing when they were conducted. There is no barrier in 

EPA's "Protection of Human Subjects" Regulation to reliance on these studies.

Public Health and Pesticide Epidemiology Data

An updated review of pendimethalin incident reports was recently prepared by HED (S. 

Recore, D403507, 07/10/2012). For this evaluation, the OPP Incident Data System (IDS) 

was consulted for pesticide incident data on the active ingredient pendimethalin. 

Pendimethalin is included in the Agricultural Health Study (AHS) and therefore 

information from the AHS on pendimethalin is included in the HED incident report.

The IDS includes reports of alleged human health incidents from various sources, 

including mandatory Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) 

Section 6 (a) (2) reports from registrants, other federal and state health and environmental 
Page 6 of 18

agencies and individual consumers. IDS contain reports from across the U.S. and most 

incidents have all relevant product information recorded. Reports submitted to the IDS 

represent anecdotal reports or allegations only, unless otherwise stated in the report. IDS 

records incidents resulting in higher severity outcomes in more detail, in a module called 

the Main IDS module. This system stores incident data for death, major and moderate 

incidents, and it includes more details about the location, date and nature of the incident.

In Aggregate IDS, from January 1, 2007 to February 22, 2012, there were 111 minor 

reported incidents involving pendimethalin. For the Main IDS, from January 1, 2007 to 

February 22, 2012, there were 24 incidents reported in the database. One incident was 

classified as major severity. Upon further review this incident involved more than one 

product; however, the other products were not identified. In addition, there was one more 

incident reported that involved pendimethalin and other chemicals. Overall, there are few 

incidents involving pendimethalin reported to IDS. 

The AHS is a high quality, prospective epidemiology study evaluating the link between 

pesticide use and various health outcomes including cancer. The AHS includes private 

and commercial pesticide applicators and their spouses. The AHS includes information 

on use of 50 different pesticide active ingredients commonly used in agriculture. There 

are AHS findings relevant to a pendimethalin that were summarized in the incident 

report. 

Within the AHS, there are several published investigations relevant to the hazard and 

exposure characterization of pendimethalin. Studies have noted a potential link of 

pendimethalin exposure related to various cancers and myocardial infarction. Of the 

studies discussed in the incident report, the authors of Hou et al. (2006) reported no 

compelling evidence that pendimethalin use was related to all cancers combined, or with 

many specific anatomical cancer sites including prostate cancer and melanoma. Alavanja 

et al. (2004) authors reported a significantly reduced risk of lung cancer when comparing 

all AHS participants with the general populations of the respective study states, but 

identified a 4-fold significantly increased risk of lung cancer among pendimethalin users. 

However, authors could not rule out a role of residual confounding by smoking in 

estimating the association, though, it is notable that this potential link with lung cancer 

has now been observed in two studies within the AHS, at two points in time, using 

similar data to measure exposure and co-variables including smoking. Authors also 

noted a significant association between users and pancreatic cancer, however, authors 

note there was no a priori hypothesis for this association, and many statistical tests were 

performed and not adjusted in final analyses. Additionally, an AHS study observed an 

association between users and myocardial infarction. Given the small number of 

pendimethalin exposed cases of MI, the correlated nature of many pesticides used by 

cohort members which is difficult to disentangle in statistical analyses only, and the lack 

of an a priori hypothesis and no known or hypothesized mechanism of action, these 

results should be interpreted with caution.

Based on the low frequency and generally low severity of incident cases reported for 

pendimethalin, there does not appear to be a concern at this time that would warrant 

further investigation based upon acute poisoning incident data. The Agency will continue 

to monitor the incident information and if a concern is triggered, additional analysis will 
Page 7 of 18

be included in the risk assessment.

Tolerance Assessment and International Harmonization

Tolerances are established under 40 CFR §180.440 for residues of pendimethalin, 

including its metabolites and degradates, in or on a variety of commodities. The Codex 

Alimentarius Commission and Mexico have not established maximum residue limits 

(MRLs) for pendimethalin. Included in Table 5 are the MRLs harmonized with Canada. 

Any pendimethalin tolerances reassessed during the registration review process will be 

considered for possible harmonization with international MRLs should they be 

established. (see Table 5)

The current tolerance expression as listed in the 40 CFR§180.361 (a) has been updated to 

reflect current HED policies and thus will not need to be revised during the registration 

review process. 

Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered 

in this human health risk assessment, in accordance with U.S. Executive Order 12898, 

"Federal Actions to Address Environmental Justice in Minority Populations and LowIncome Populations," 

http://www.epa.gov/compliance/resources/policies/ej/exec_order_12898.pdf. The Office 

of Pesticide Programs (OPP) typically considers the highest potential exposures from the 

legal use of a pesticide when conducting human health risk assessments, including, but 

not limited to, people who obtain drinking water from sources near agricultural areas, the 

variability of diets within the U.S., and people who may be exposed when harvesting 

crops. Should these high exposures indicate potential risks of concern, OPP will further 

refine the risk assessments to ensure that the risk estimates are based on the best available 

information.

Cumulative Risk Assessment

Unlike other pesticides for which EPA has followed a cumulative risk approach based on 

a common mechanism of toxicity, EPA has not made a common mechanism of toxicity 

finding as to pendimethalin and any other substances and pendimethalin does not appear 

to produce a toxic metabolite produced by other substances. For information regarding 

EPA’s efforts to determine which chemicals have a common mechanism of toxicity and 

to evaluate the cumulative effects of such chemicals, see the policy statements released 

by EPA’s Office of Pesticide Programs concerning common mechanism determinations 

and procedures for cumulating effects from substances found to have a common 

mechanism on EPA’s website at http://www.epa.gov/pesticides/cumulative/.

Data Requirements

HED requires a Dislodgeable Foliar Residue study to be submitted to refine the postapplication exposure risk estimates for foliar applications of pendimethalin. HED does 

not anticipate that additional residue chemistry or toxicology data will be required for the 

pendimethalin registration review process. 
Page 8 of 18

Barring submission of any data that would impact the outcome of the 2012 risk

assessment, HED does not anticipate the need for any updates to the pendimethalin risk 

assessment during registration review.
Page 9 of 18

Table 1: Toxicological Doses and Endpoints for Pendimethalin Human Health Risk 

Assessment (D390457; July 2012)

Exposure/Scenario Point of 

Departure

Uncertainty/FQPA 

Safety Factors

RfD, PAD, Level of Concern 

for Risk Assessment

Study and Toxicological 

Effects

Acute Dietary

(Females 13-49)

No appropriate endpoint was identified including developmental toxicity studies in rats and rabbits.

Acute Dietary

( General population 

including infants and 

children)

NOAEL=100 

mg/kg

UFA = 10X

UFH = 10X

FQPA SF = 1X

Total UF = 100X

Acute RfD = 1

mg/kg/day

aPAD = Acute RfD

 FQPA SF

= 1 mg/kg/day

Acute neurotoxicity study 

(MRID 48695601).

The LOAEL=300 mg/kg, based 

on reduced motor activity for 

males and females on Day 0.

Chronic Dietary (all 

populations) 

NOAEL = 10 

mg/kg/day

UFA = 3X 

UFH = 10X 

FQPA SF = 1X

Total UF = 30X

Chronic RfD = 0.3 

mg/kg/day

cPAD = Chronic RfD

 FQPA SF

= 0.3 mg/kg/day

92- Day thyroid function study 

in rats (MRID 42054601); 56-

day thyroid study in rats (MRID 

43135001); 14- day intra thyroid 

metabolism study in rats (MRID 

43135003).

LOAEL = 31 mg/kg/day based 

on hormonal and 

histopathological changes in the 

thyroid. 

Incidental Oral Exposure

Oral

Short- Term (1- 30 

days) 

Intermediate – Term

(1-6 months)

NOAEL = 10 

mg/kg/day

UFA = 3X 

UFH = 10X 

FQPA SF = 1X

Total UF = 30X 

Residential LOC = 30

Occupational LOC = 30

The same as the chronic dietary.

Dermal Exposure

Dermal 

Short- Term (1- 30 

days) 

Intermediate – Term

(1-6 months)

Long – Term

(>6 months)

NOAEL = 10 

mg/kg/day

UFA = 3X 

UFH = 10X 

FQPA SF = 1X

Total UF = 30X 

Dermal Absorption = 

3%

Residential LOC = 30

Occupational LOC = 30

The same as the chronic dietary.

Inhalation Exposure

Inhalation 

Short- Term (1- 30 

days) 

Intermediate – Term

(1-6 months)

Long – Term

(>6 months)

NOAEL = 10 

mg/kg/day

UFA = 3X 

UFH = 10X 

FQPA SF = 1X

Total UF = 30X

Inhalation 

Absorption = 100%

Residential LOC = 30

Occupational LOC = 30

The same as the chronic dietary.

Cancer

Cancer (oral, dermal, 

inhalation)

Group C, possible human carcinogen based on a statistically significant increased trend and pair-wise 

comparison between the high dose group and controls for thyroid follicular cell adenomas in male and 

female rats. A non-quantitative approach (i.e., non-linear, RfD approach) was recommended by the 

Cancer Peer Review Committee since mode of action studies are available.

UF = uncertainty factor, FQPA SF = FQPA safety factor, NOAEL = no observed adverse effect level, LOAEL = lowest observed 

adverse effect level, PAD = population adjusted dose (a = acute, c = chronic), RfD = reference dose, MOE = margin of exposure, LOC 

= level of concern, NA = Not Applicable. UFA= extrapolation from animal to human (interspecies), UFH = potential variation in 

sensitivity among members of the human population (intra-species). UFDB = to account for the absence of key data (i.e., lack of a 

critical study). 
Page 10 of 18

TABLE 2: Subchronic, Chronic and Other Toxicity Profile for Pendimethalin.

(D390457; July 2012)

Guideline 

Number

Study Type MRID Number 

& Classification

Dose Levels Results

870.3100 Subchronic oral 

[Rat] (30-day)

000106754 

Supplementary

0, 800, 1600, 3200 ppm

0, 80, 160, 320 

mg/kg/day

NOAEL = 160 mg/kg/day.

LOAEL = 320 mg/kg/day, 

based on increased liver 

weight.

870.3100 Subchronic oral 

[Rat] (13-week)

00156081 0, 100, 500, 5000 ppm

0, 10, 50, 500 mg/kg/day

NOAEL = 50 mg/kg/day.

LOAEL = 500 mg/kg/day, 

based on decreased body 

weight gain and food 

consumption, decreased 

hematocrit and hemoglobin 

with increases in platelets in 

males, increased liver weight, 

red thyroids, and hypertrophy 

of the liver.

870.3100 Subchronic oral 

[Rat] (13-week)

00059468

Supplementary

0, 25, 50, 100, 500, 2500

ppm

0, 2.5, 5, 10, 50, 250 

mg/kg/day

NOAEL = 250 mg/kg/day.

LOAEL was not determined.

870.3100 Subchronic oral

[Rat] (13 week)

00059469

Supplementary

0, 2500 ppm

0, 250 mg/kg/day

NOAEL = 250 mg/kg/day.

LOAEL was not determined.

870.3100 Subchronic oral 

[Rat] (92-day)

42054601 0, 100, 5000 ppm

0, 4.98, 245.4 mg/kg/day

NOAEL = 4.98 mg/kg/day.

LOAEL = 245.4 mg/kg/day, 

based on thyroid effects.

870.3100 Subchronic oral 

[Rat] (56-day)

43135001 0, 500, 5000 ppm

0, 31, 292 mg/kg/day

NOAEL was not determined.

LOAEL = 31 mg/kg/day, based 

on thyroid effects.

870.3100 Subchronic oral 

[Rat] (14-day)

43135003 0, 100, 500 ppm

0, 10, 500 mg/kg/day

NOAEL = 10 mg/kg/day.

LOAEL = 500 mg/kg/day, 

based on thyroid effects.

870.3100 Subchronic oral 

[Dog] (90-day)

00026672

Supplementary

0, 62.5, 250, 1000 

mg/kg/day NOAEL = 62.5 mg/kg/day.

LOAEL = 250 mg/kg/day, 

based on body weight loss.

870.3150 Subchronic oral 

[Mouse] (30-day)

000106754

Supplementary

0, 500, 1000, 2000 ppm

0, 75, 150, 300 

mg/kg/day

NOAEL = 300 mg/kg/day.

LOAEL was not determined.

870.3200 21-Day dermal 

toxicity [Rat]

00026663 0, 250, 500, 1000 

mg/kg/day NOAEL = 1000 mg/kg/day.

LOAEL was not determined.

870.3700a Prenatal 

developmental 

toxicity [Rat]

00025752

Supplementary, 

but satisfactory 

when considered 

0, 125, 250, 500 

mg/kg/day Maternal NOAEL = 500 

mg/kg/day (highest dose 

tested).
Page 11 of 18

TABLE 2: Subchronic, Chronic and Other Toxicity Profile for Pendimethalin.

(D390457; July 2012)

Guideline 

Number

Study Type MRID Number 

& Classification

Dose Levels Results

with the rabbit 

developmental.

Developmental NOAEL = 500 

mg/kg/day (highest dose 

tested).

870.3700b Prenatal 

developmental 

toxicity [Rabbit)]

00117444

Supplementary, 

upgradeable.

0, 15, 30, 60 mg/kg/day Maternal NOAEL = 60 

mg/kg/day (highest dose 

tested).

Developmental NOAEL = 60 

mg/kg/day (highest dose 

tested).

Note: a range finding study 

indicated doses ≥125 

mg/kg/day associated with 

increased mortality.

870.3800 Reproduction and 

fertility effects [Rat]

(2-generation 

reproduction)

41725203

Acceptable

0, 500, 2500, 5000 ppm

0, 34/43, 172/216, 346/436 

mg/kg/day (M/F)

HED RED

0, 25, 125, 250 mg/kg/day

HIARC Document

Note: Doses were obtained 

from an HED 

pendimethalin RED, and a 

HIARC document 

(4/18/2000) which resulted 

in different dose 

calculations for mg/kg/day. 

Consequently, doses 

are given as a range, based 

on calculations from actual 

chemical intake, and a 

generic ratio (1:20) of 

dietary intake.

Parental/Systemic 

NOAEL = 25-34/43 (M/F) 

mg/kg/day (500 ppm).

LOAEL = 125-172/216 (M/F) 

mg/kg/day (2500 ppm), based on 

decreased body weight gain and 

food consumption.

Reproductive/Offspring 

NOAEL = 25-34/43 (M/F) 

mg/kg/day (500 ppm).

Reproductive/Offspring 

LOAEL = 125-172/216 (M/F) 

mg/kg/day (2500 ppm), based on 

decreases in the number of pups 

born, and pup weights.

870.3800 Reproduction and 

fertility effects [Rat]

(3-generation 

reproduction)

00026671, 

0040304, 

00059470

Acceptable

0, 500, 5000 ppm

0, 25, 250 mg/kg/day

Parental/Systemic 

NOAEL = 25 mg/kg/day.

LOAEL = 250 mg/kg/day, based 

on decreased body weight.

Reproductive/Offspring 

NOAEL = 25 mg/kg/day.

Reproductive/Offspring 

LOAEL = 250 mg/kg/day, based 

on decreased pup body weight 

gain, and possible decreased pups 

born alive and pup survival.

870.4100b Chronic toxicity [Dog] 

(2-year oral)

00058657 0, 12.5, 50, 200 mg/kg/day NOAEL = 200 mg/kg/day.

LOAEL was not established. 
Page 12 of 18

TABLE 2: Subchronic, Chronic and Other Toxicity Profile for Pendimethalin.

(D390457; July 2012)

Guideline 

Number

Study Type MRID Number 

& Classification

Dose Levels Results

870.4200 Chronic toxicity/

carcinogenicity [Rat]

(2-year oral)

40174401

Acceptable

0, 100, 500, 5000 ppm

0, 5, 25, 250 mg/kg/day

NOAEL = 25 mg/kg/day.

LOAEL = 250 mg/kg/day, based 

on decreased survival and body 

weight gain, decreased food 

consumption, increased gamma 

glutamyl transferase, cholesterol 

and liver weights, and thyroid 

effects.

870.4200 Chronic toxicity [Rat] 

(2-year oral)

42027802

Acceptable

0, 1250, 2500, 3750, 5000 

ppm

0, 51, 103, 154, 213 

mg/kg/day

NOAEL was not determined.

LOAEL = 51 mg/kg/day, based on 

non-neoplastic thyroid follicular 

cell changes.

870.4300 Carcinogenicity 

[Mouse] (18-month 

oral)

40909901

Acceptable

0, 100, 500, 5000 ppm

0, 12.3/15.6, 62.3/78.3, 

622.1/806.9 mg/kg/day 

(M/F)

NOAEL = 62.3/78.3 mg/kg/day. 

LOAEL = 622./806.9 mg/kg/day, 

based on mortality, body weight 

decrease, organ weight changes, 

and amyloidosis.

870.5100 Reverse gene mutation 

assay [Bacterial 

strains of S. 

typhimurium]

00153768 50, 158, 500, 1581, 5000 

μg/plate Positive 

Evidence of a 2-fold increase in 

the number of induced mutant 

colonies over background (at all 

doses from 50 to 5000 μg/plate).

870.5100 Reverse gene mutation 

assay [Escherichia coli 

WP2]

43177801 25, 50, 100, 250, 500, 750 

μg/plate Negative

870.5100 Reverse gene mutation 

assay [Escherichia coli 

WP2]

43135005 50, 158, 500, 1581, 5000 

μg/plate or 1000 μg/paper 

disk/plate 

Negative

870.5100 Reverse gene mutation 

assay [Escherichia coli 

WP2]

43135006 50, 100, 250, 500, 750 

μg/plate Negative

870.5300 Mammalian cell gene 

mutation [Chinese 

hamster ovary]

43177802 1, 5, 7.5, 10, 20, 30, 40, 50 

μg/plate (-S9)

10, 25, 50, 75, 100, 125, 

150, 175 μg/plate (+S9)

Negative

870.5375 Chromosomal 

aberration [Chinese 

hamster ovary]

00153770 Doses ranging from 5-50 

μg/ml Negative

870.5395 Micronucleus study 

[Mouse]

42027801 313, 625, 1250 mg/kg Negative

870.5550 Alkaline elution assay 

[Rat]

43135007 1250, 2500, 5000 mg/kg Negative

870.6200 Acute neurotoxicity 48695601

Acceptable

0, 100, 300, or 1000 mg/kg NOAEL=100 mg/kg,

LOAEL= 300 mg/kg, based on 

reduced motor activity for males 

and females (↓19 and ↓51%, 
Page 13 of 18

TABLE 2: Subchronic, Chronic and Other Toxicity Profile for Pendimethalin.

(D390457; July 2012)

Guideline 

Number

Study Type MRID Number 

& Classification

Dose Levels Results

respectively, on Day 0.

870.6200 Subchronic 

neurotoxicity 

42054601

Acceptable

0, 42.0/50.1, 126.5 / 151.9, 

386.8/423.1 mg/kg bw/day 

[M/F]

NOAEL= 386.8/423.1 mg/kg/day 

(HDT).

LOAEL not established.

870.7800 Immuotoxicity 48608901

Acceptable

0, 38, 72, 276 mg/kg/day NOAEL=276 mg/kg/day (HDT)

LOAEL not established.

870.7485 Metabolism and 

pharmacokinetics 

[Rat]

00046275

Acceptable

NA* Pendimethalin is eliminated from 

the body within 24 hours, with 

70% being excreted in feces 

(primarily the parent compound), 

and 20% in urine.

NonguidelineDevelopmental 

Thyroid Study

48695603

Acceptable

0, 31, 62 or 186 mg/kg/day 

(GD 6 - PND 21)

Developmental thyroid function,

The thyroid function in fetuses or 

post partum day (PND 4) was not 

affected by the treatment of 

pendimethalin. 

Parental thyroid function,

Decreased thyroxine (T4) levels 

were observed in pregnant dams 

and PND 21 male and female pups 

at 31 mg/kg/day (LOAEL).
Page 14 of 18

TABLE 3: Toxicology Data Requirements for Pendimethalin.

Test Technical

Required Conducted

870.1100 Acute Oral Toxicity

870.1200 Acute Dermal Toxicity

870.1300 Acute Inhalation Toxicity

870.2400 Primary Eye Irritation

870.2500 Primary Dermal Irritation

870.2600 Dermal Sensitization

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.3100 Oral Subchronic (rodent)

870.3150 Oral Subchronic (non-rodent)

870.3200 21/28-Day Dermal

870.3250 90-Day Dermal

870.3465 90-Day Inhalation

yes

yes

yes

no

no

yes

yes

yes

no

no

870.3700a Developmental Toxicity (rodent)

870.3700b Developmental Toxicity (non-rodent)

870.3800 Reproduction

yes

yes

yes

yes

yes

yes

870.4100a Chronic Toxicity (rodent)

870.4100b Chronic Toxicity (non-rodent)

870.4200a Oncogenicity (rat)

870.4200b Oncogenicity (mouse)

870.4300 Chronic/Oncogenicity

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.5100 Mutagenicity—Gene Mutation (bacterial)

870.5300 Mutagenicity—Gene Mutation (mammalian)

870.5375 Mutagenicity—Structural Chromosomal Aberrations

870.5395 Mutagenicity—Other Genotoxic Effects 

870.5500 Mutagenicity—Other Genotoxic Effects

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.6100a Acute Delayed Neurotoxicity (hen)

870.6100b 90-Day Neurotoxicity (hen)

870.6200a Acute Neurotoxicity Screening Battery (rat)

870.6200b 90-Day Neurotoxicity Screening Battery (rat)

870.6300 Developmental Neurotoxicity

no

no

yes

yes

no

no

no

yes

yes

no

870.7485 General Metabolism

870.7600 Dermal Penetration 

870.7800 Immunotoxicity

yes

no

yes

yes

yes

yes
Page 15 of 18

Table 4: Physicochemical Properties of Pendimethalin.

Parameter Value Reference

Melting point/range 54-58 °C (TGAI) Product Chemistry Chapter of 

Pendimethalin RED, DP# 221531, 

12/8/1995, B. Cropp-Kohlligian

pH 4.7 (TGAI) CB# 789, 06/13/1986, G. Makhijani

Density 1.461 g/cm3 (at room temperature) DP#s 271502 and 317053, 

07/12/2006, W. Drew

Water solubility of PAI 0.275 ppm at 25 °C CB# 789, 06/13/1986, G. Makhijani

Solvent solubility of TGAI Solvent g/100 mL at 25 oC

n-Heptane 11.2 

2-Propanol 6.1 

Acetone 161.0

Toluene 128.4 

Methyl alcohol 5.5

Dimethyl sulfoxide 21.4 

Methylene chloride 232.0

CB# 789, 06/13/1986, G. Makhijani

Vapor pressure 1.24 x 10-8 Pa at 20 °C DP#s 271502 and 317053, 

07/12/2006, W. Drew

Dissociation constant, pKa Too small to measure CB# 789, 06/13/1986, G. Makhijani

Octanol/water partition 

coefficient, Log(KOW)

5.18 DP#s 271502 and 317053, 

07/12/2006, W. Drew

UV/visible absorption 

spectrum

UV molecular extinction =

3.81 x 104at 234 nm,

1.93 x 104at 280 nm. 

DP#s 271502 and 317053, 

07/12/2006, W. Drew
Page 16 of 18

Table 5: Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex

40 CFR 180.361:

Plant: 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

benzenamine, N-(1-

ethylpropyl)-3,4-dimethyl2,6-dinitro-, including the 

metabolite 

benzenemethanol, 4-[(1-

ethylpropyl)amino]-2-

methyl-3,5-dinitroNone

Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico1 Codex

Alfalfa, forage 3.5

Alfalfa, hay 4.0

Alfalfa, seed 0.10

Almond, hulls 0.4

Apple, wet pomace 0.20

Artichoke, globe 0.1

Asparagus 0.15

Beans 0.10

Beans, forage 0.10

Beans, hay 0.10

Brassica head and stem, subgroup 5-

A

0.1

Carrot 0.5

Citrus, oil 0.5

Corn, field, forage 0.1

Corn, field, grain 0.1 0.1 field corn

Corn, field, stover 0.1

Corn, pop, grain 0.1

Corn, sweet, forage 0.1

Corn, sweet, kernel plus cob with 

husks removed

0.1

Corn, sweet, stover 0.1

Cotton, gin byproducts 3.0

Cotton, undelinted seed 0.1

Crayfish 0.05

Fruit, citrus, group 10 0.1

Fruit, pome, group 11 0.10 0.1 apples

Fruit, stone, group 12 0.10 0.1apricots, nectarines, peaches, 

sweet cherries, tart cherries

Garlic 0.1

Grape 0.1

Grass forage, fodder, and hay crop 

group 17, forage

20

Grass forage, fodder, and hay crop 

group 17, hay

13

Grass forage, fodder, and hay crop 

group 17, straw

4.0

Juneberry 0.10

Leek 0.20

Nut, tree, group 14 0.1

Olive 0.1

Onion, bulb 0.1 0.1 dry bulb onions

Onion, green 0.20

Onion, welsh 0.20
Page 17 of 18

Table 5: Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex

Peanut 0.1

Peanut, hay 0.1

Peas (except field peas) 0.10

Peppermint, oil 1.0

Peppermint, tops 0.2

Pistachio 0.1

Pomegranate 0.10

Potato 0.1

Rice, grain 0.1

Rice, straw 0.1

Shallot 0.2

Sorghum, forage 0.1

Sorghum, grain, grain 0.1

Sorghum, grain, stover 0.1

Soybean, forage 0.1

Soybean, hay 0.1

Soybean, seed 0.1 0.1 dry soybeans 

Spearmint, oil 1.0

Spearmint, tops 0.2

Strawberry 0.10

Sugarcane, cane 0.1

Sunflower, seed 0.1

Vegetable, fruiting, group 8 0.10

Wheat, grain 0.10

Wheat, forage 3.0

Wheat, hay 0.60

Wheat, straw 0.30

Completed by: M. Negussie; 08/03/2012

(b) Section 18 emergency exemptions . Time-limited tolerances specified in the following table are 

established for combined 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, in or 

on the specified agricultural commodities, resulting from use of the pesticide pursuant to FIFRA section 18 

emergency exemptions. The tolerances expire and are revoked on the date specified in the table.

Commodity Parts per million Expiration/revocation date

Bermuda grass, forage 25 12/31/10

Bermuda grass, hay 60 12/31/10

1 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.

Table 6: HED Memoranda Relevant to Registration Review

Author Barcode/TXR # Date Title
Page 18 of 18

Table 6: HED Memoranda Relevant to Registration Review

Author Barcode/TXR # Date Title

S. Shelat D390457 07/25/2012 REVISED: Pendimethalin: Human 

Health Risk Assessment for Proposed 

Use on Leaf lettuce; Leafy brassica 

greens; Melons; Edamame; Kiwi and 

other small fruit vines

S. Recore D403507 07/10/2012 Pendimethalin: Review of Human 

Incidents