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5.4.4 Chronic Dietary Risk Assessment........................................................................... 23

5.4.5 Cancer Dietary Risk Assessment............................................................................. 23

5.4.6 Summary Table........................................................................................................... 24

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ......................................... 24

6.1 Residential Handler Exposure .................................................................................... 25

6.2 Post-Application Exposure .......................................................................................... 27

6.3 Combined Exposure..................................................................................................... 28

6.4 Residential Bystander Postapplication Inhalation Exposure................................... 29

6.5 Spray Drift.................................................................................................................... 29

7.0 Aggregate Exposure/Risk Characterization.................................................................. 29

7.1 Acute Aggregate Risk................................................................................................... 30

7.2 Short-Term Aggregate Risk ........................................................................................ 30

7.3 Chronic Aggregate Risk .............................................................................................. 31

7.4 Cancer Aggregate Risk ................................................................................................ 31

8.0 Cumulative Exposure/Risk Characterization ............................................................... 31

9.0 Occupational Exposure/Risk Characterization ............................................................ 31

9.1 Short-/Intermediate- Term Handler Risk.................................................................. 31

9.2 Short-/Intermediate-Term Post-Application Risk ................................................... 46

9.2.1 Dermal Post-application Risk.................................................................................. 46

9.2.2 Inhalation Postapplication Risk .............................................................................. 48

10.0 References......................................................................................................................... 49

Appendix A. Toxicology Profile and Executive Summaries ................................................. 50

A.1 Toxicology Data Requirements................................................................................... 50

A.2 Toxicity Profiles............................................................................................................ 51

A.3 Hazard Identification and Endpoint Selection .......................................................... 54

A.4 Executive Summaries................................................................................................... 57

Appendix B. International Residue Limits.............................................................................. 69

Appendix C. Physical/Chemical Properties............................................................................. 70

Appendix D. Review of Human Research................................................................................ 71
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1.0 Executive Summary

Pendimethalin (N-(1-ethylpropyl)-3,4-dimethyl-2,6-dinitrobenzenenamine) is a selective 

herbicide used for controlling annual grass and broadleaf weeds. It is a meristematic inhibitor 

that interferes with the plant’s cellular division of mitosis and is generally applied early in the 

growing season as a pre-emergent and early post-emergent herbicide. Pendimethalin is currently 

formulated into a variety of product formulations including; aqueous capsule suspension, 

granular, emulsifiable concentrate, and liquid formulations. Five new agricultural uses of 

pendimethalin have been proposed for the aqueous capsule suspension formulation of the enduse product Prowl ® H2O (38.7 % a.i.; EPA Registration Number: 241-418), a 3.8 lbs ai/gallon 

liquid formulation. The new uses include the following crops; leaf lettuce, leafy brassica greens, 

melons, vegetable soybean (edamame), kiwi and other small fruit vines. The maximum single 

proposed application rate is 1.0 lbs ai/A for leaf lettuce, leafy brassica greens, and melon 

production; 1.43 lbs ai/A for vegetable soybean (edamame); and 6.0 lb ai/A for kiwi and small 

fruit vines. Prowl ® H2O can be applied via ground or aerial application methods.

Use Profile 

End-use products containing pendimethalin are currently registered for use on the following

crops: alfalfa, artichoke, asparagus, bearing fruit and nut trees, brassica head and stem 

vegetables, carrots, carrots grown for seed, clover, corn, cotton, edible beans, fallow, forage 

legumes, fruiting vegetables, garlic, grain sorghum, grape, green onions, lentil and peas, mint, 

non-bearing fruit trees, olive trees, onions, peanuts, potatoes, rice, soybeans, strawberry, 

sugarcane, sunflowers, tobacco and wheat. In addition to agricultural crops, pendimethalin is 

registered for northern and southern grasses, for use on sod farms and for seed production. 

Additionally, pendimethalin is registered for use by commercial applicators and homeowners on 

lawns, parks, golf courses, in and around ornamentals, and weed control in non-cropland areas, 

such as landscape ground covers. Pendimethalin is also registered for use on container grown 

and field grown ornamentals, however, it is not to be used in greenhouses, shade houses, or other 

enclosed structures. 

Toxicity/Hazard

The risk assessment for pendimethalin is based on a well-characterized and complete toxicology 

database. In repeat-dose oral studies, the thyroid was consistently the target organ for 

pendimethalin toxicity. No developmental effects were seen in rabbit or rat developmental 

toxicity studies and no reproductive or offspring effects were seen in the 2-generation rat 

reproduction study. Based on the effects of hormonal changes (alterations in thyroid weights and 

histopathological lesions) observed in several studies following oral administration of 

pendimethalin, HED had a strong indication that pendimethalin may cause disruption to the 

endocrine system. Consequently, HED recommended that a developmental thyroid assay be 

conducted to evaluate the impact of pendimethalin on thyroid hormones, structure, and/or thyroid 

hormone homeostasis during development. A developmental thyroid study (MRID 48695603)

was submitted and demonstrated no developmental thyroid effect was observed. Pendimethalin 

is classified as a “possible human carcinogen.” 
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Pendimethalin has a low order of acute toxicity via oral, dermal and inhalation routes of 

exposure as demonstrated by the toxicity categories (III & IV). Pendimethalin is not an eye or 

skin irritant and is not a skin sensitizer. 

HED’s level of concern includes a 10X uncertainty factor (UF) for intraspecies extrapolation. 

This factor is used to account for human variability in toxicokinetics and toxicodynamics. 

However, the interspecies UF (used to account for animal to human differences in toxicokinetics 

and toxicodynamics) may be reduced to 3X with respect to 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 11/01/05). 

Additionally, HED has recommended the 10X FQPA safety factor be removed (reduced to 1X) 

due to no evidence of susceptibility. NOAELs were used for short-term, intermediate-term, and 

chronic risk assessments. The selected toxicity endpoints and PoDs for risk assessment are 

based on the most sensitive and relevant data. 

Dietary Exposure (Food and Water)

The residue chemistry data and environmental fate data are adequate to assess human exposure. 

The assessments are based on reliable data and will not underestimate exposure or risk. 

Estimated drinking water concentrations (EDWCs) were incorporated directly into the dietary 

exposure assessments. An unrefined acute dietary assessment was conducted assuming 100% 

crop treated (CT), tolerance-level residues, Dietary Exposure Evaluation Model (DEEM TM) 

default processing factors or empirical processing factors when available. The results of the 

acute dietary analysis for food and drinking water show that the acute dietary risk estimates are 

below the Agency’s level of concern (<100% of the acute population adjusted dose (aPAD)) for 

all population subgroups and were estimated at <1% of the aPAD for the U.S. general population 

and 2.0% of the aPAD for the most highly exposed population subgroup (infants < 1 years old). 

An unrefined chronic dietary assessment using tolerance-level residues, assuming 100% crop 

treated (CT) estimates and default DEEMTM processing factors or empirical processing factors 

were also conducted. The results of the chronic dietary analysis for food and drinking water 

indicate that the chronic dietary risk estimates are below the Agency’s level of concern (<100% 

of the chronic population adjusted dose (cPAD)) for all population subgroups and were estimated 

at <1% of the cPAD for the U.S. general population and 1.6% of the cPAD for the most highly 

exposed population subgroup (children 1-2 years old). Pendimethalin is classified as a “possible 

human carcinogen;” however, the chronic dietary risk assessment is considered to be protective 

of any cancer effects; therefore, a separate quantitative cancer aggregate risk assessment is not 

required

Residential Exposure

Although the proposed labels do not contain residential uses, pendimethalin is currently 

registered for use on lawns, landscape ornamentals, weed control non-cropland areas by 

commercial applicators and homeowners. Residential exposures were assessed in this document 

because changes in Standard Operating Procedures, body weight parameters, and toxicological 

information has changed since the last residential assessment (M. Collantes, Z. Figueroa; 

D325175; 04/02/07). Updated residential handler and post-application risk estimates do not 

exceed HED’s level of concern (MOEs ≥ 30). Updated residential exposure risk estimates are 

also considered in the aggregate risk assessment. 
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Occupational Exposure

Short- and intermediate-term dermal and inhalation exposure is expected for occupational 

handlers. The results of the occupational handler exposure and risk assessment estimates 

indicate that total short- and intermediate-term margins of exposure (MOEs) are not of concern 

to HED (i.e. MOE > 30) with baseline attire and varying levels of PPE with the exception of one 

use scenario. Occupational dermal post-application exposure is expected following foliar or 

post-emergent treatment of crops; however, short- and intermediate-term margins of exposure 

(MOEs) are not of concern to HED (i.e. MOE > 30). HED assumes that post-application 

inhalation exposures are minimal following applications of pendimethalin. Pendimethalin has 

low acute inhalation toxicity (Toxicity Category IV) and a vapor pressure of 3 x 10-5 mm Hg @ 

25.0°C, therefore, post-application inhalation exposures and risks were not quantitatively 

assessed. 

Review of Human Research

This risk assessment relies in part on data from studies in which adult human subjects were 

intentionally exposed to a pesticide or other chemical. These studies (Appendix D) have been 

determined to require a review of their ethical conduct, and one of these studies is also subject to 

review by the Human Studies Review Board. All of the listed studies have received the 

appropriate review.

2.0 HED Recommendations

HED recommends the registration request per the proposed labels be granted for applications of 

pendimethalin use on leaf lettuce, leafy Brassica greens, melon production, vegetable soybean 

(edamame), and kiwi and other small vine climbing fruit for the Prowl®H20 formulation of 

pendimethalin with the exception of one scenario: commercial impregnation for dry bulk 

fertilizer for grape, kiwi, and other small fruit vines (MOE = 26). Commercial bulk fertilizer 

application for the proposed use on kiwi and other small fruits resulted in MOEs that exceed 

HED’s level of concern (MOEs < 30). This scenario was assessed at the highest application rate 

and the highest amount (960 tons) bulk fertilizer treated per day. Bulk fertilizer impregnation at 

the lower range of 500 tons does not exceed HED’s LOC (MOEs ≥ 30). HED also recommends 

the tolerance expression for pendimethalin be updated to incorporate the tolerance revisions 

requested in Section 2.2.3. 

Existing uses of pendimethalin were also assessed. Most currently registered uses resulted in 

MOEs ≥ 30, and therefore are not of concern to HED, with the exception of the following 

exposure scenarios:

mixing and loading for chemigation and aerial application of alfalfa and sugarcane (MOE 

= 24)

mixing/loading/application with a handgun sprayer for drench application to turf grasses 

and ornamentals (MOE = 20)

These exposure scenarios were assessed with additional personal protective equipment. Risk 

estimates for these uses with gloves and/or respirators do not exceed HED’s level of concern 

(MOE ≥ 30) for the alfalfa, sugarcane, and the turf and ornamental scenarios.
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2.1 Data Deficiencies/Conditions of Registration

At this time, no data deficiencies have been noted.

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

Adequate enforcement methods are available and described in detail in the following references: 

1) Residue Chemistry Memo DP#s 271502; 310793; 311825; 314085; 314093; 317047; 317053, 

W. Drew, 12-Jul-2006 and 2) Residue Chemistry Memo DP# 238470, William Cutchin, 02-Aug1999 (PP#6E4603). These methods were adequate for data collection based on acceptable 

method validation and concurrent recovery data, and the fortification levels used in the method 

validation. The concurrent method recoveries were adequate to bracket expected residue levels 

and briefly described below.

Enforcement Methods: PAM Volume II lists four GC/ECD, methods for the determination of 

pendimethalin and its 3,5-dinitrobenzyl alcohol metabolite in plant commodities. Methods I and 

III determine residues of the parent, whereas Methods II and IV determine residues of the 3,5-

dinitrobenzyl alcohol metabolite. The LOQ of each method is 0.05 ppm. A confirmatory 

GC/MS method was subsequently submitted and was been found adequate (DP# 238470). 

2.2.2 International Harmonization

No Codex MRLs are established for these current new uses of pendimethalin, and there are 

currently no Canadian MRLs established for the proposed crops. However, an International 

Residue Limit Status Sheet (IRLS) follows the references and indicates that the MRLs on Onion, 

bulb, Fruit, pome group 11 and Fruit, stone group 12 is 0.1 ppm are harmonized. A table 

containing a summary of international tolerances and maximum residue limits can be found in 

Appendix B. 

2.2.3 Recommended Tolerances

Table 2.2.3 summarizes the registrant’s proposed tolerances and the Agency’s evaluations for 

tolerance recommendations. The tolerance expression for pendimethalin should read as follows:

Tolerances should be established for residues of the herbicide pendimethalin, including its 

metabolites and degradates, in or on the commodities listed below. Compliance with the 

tolerance levels specified below is to be determined by measuring pendimethalin and its alcohol 

metabolite, N-(1-ethylpropyl)-3,4-dimethyl-2,6-dinitrobenzenamine, and its metabolite (4-[(1-

ethyl propyl) amino]-2-methyl-3,5-dinitrobenzyl alcohol).
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Table 2.2.3. Tolerance Summary for Pendimethalin. 

Commodity Proposed

Tolerance 

(ppm)

Established/ 

Tolerance 

(ppm)

Recommended 

Tolerance 

(ppm)

Comments [Correct Commodity 

Definition]

Lettuce, Leaf 3.0 -- 4.0 Lettuce, leaf

Brassica, leafy greens, 

subgroup 5B

0.20 -- 0.20

Turnip greens 0.20 -- 0.20 Turnip, greens

Melon subgroup 9A 0.10 -- 0.10

Vegetable, soybean, 

succulent

0.10 -- 0.10 Vegetable, soybean (edamame)

Small fruit vine climbing 

subgroup 13-07E, except 

grape

0.10 -- 0.10 Fruit, small vine climbing, 

subgroup 13-07E, except grape

2.2.4 Revisions to Petitioned-For Tolerances

Combined residues of pendimethalin and CL 202,347 were quantifiable in/on samples of leaf 

lettuce and mustard greens, therefore the OECD tolerance calculation procedures were utilized in 

determining appropriate tolerance levels. Using the OECD tolerance calculation procedures, the 

recommended tolerances should be 4.0 ppm for leaf lettuce and 0.20 ppm for brassica leafy 

greens, subgroup 5B, mustard greens. HED attributes the difference in the proposed and 

recommended tolerances for leaf lettuce to the petitioner’s having used the North American Free 

Trade Agreement (NAFTA) tolerance calculation procedures in determining the proposed 

tolerance. 

 

2.3 Label Recommendations

2.3.1 Recommendations from Residue Reviews

860.1200 Directions for Use

The use directions for leaf lettuce, leafy brassica greens, melon, and kiwi and other small 

fruit vines must be amended to specify that no adjuvants may be added to the spray 

mixtures for these crops. 

The following revisions/clarifications are required for specific crops:

o For leafy brassica greens, the label revision must prohibit the use on turnip green 

varieties grown for roots or dual-purpose varieties grown for roots and tops. The 

label revision must further clarify that Pendimethalin may be used on cultivars of 

turnip green varieties grown for leaves only; the harvest of turnip green root for 

food/feed purposes is not supported by residue data or an established tolerance.
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o For applications to vegetable soybean (edamame), the petitioner must clarify 

whether aerial application is permitted (as per the supplemental label) or not (as 

per Section B). 

o A minimum retreatment interval (RTI) was not specified for cantaloupe. The 

label should be revised to specify a minimum retreatment interval of ≥17 days, 

based on the submitted crop field trial data.

860.1550 Proposed Tolerances

The tolerance for leaf lettuce should be established at 4.0 ppm, the proposed tolerance is 

3.0 ppm.

The petitioner should submit a revised Section F reflecting the recommended tolerances 

and commodity definitions presented in Table 2.2.3.

2.3.2 Recommendations from Occupational Assessment

No label recommendations based on the occupational assessment are required for the proposed 

pendimethalin uses. 

2.3.3 Recommendations from Residential Assessment

No label recommendations based on the residential assessment are required for the proposed 

pendimethalin uses. 

3.0 Introduction

Pendimethalin is a selective herbicide used for controlling annual grass and broadleaf weeds. It is 

a meristematic inhibitor that interferes with the plant’s cellular division of mitosis and is 

generally applied early in the growing season as a pre-emergent and early post-emergent 

herbicide. Pendimethalin is currently formulated into a variety of product formulations including; 

aqueous capsule suspension, granular, emulsifiable concentrate, and liquid formulations. Five 

new agricultural uses of pendimethalin have been proposed for the aqueous capsule suspension 

formulation of the end-use product Prowl ® H2O (38.7 % a.i.; EPA Registration Number: 241-

418), a 3.8 lbs ai/gallon liquid formulation. The new uses include the following crops; leaf 

lettuce, leafy brassica greens, melons, vegetable soybean (edamame), kiwi and other small fruit 

vines. The maximum single proposed application rate is 1.0 lb a.i./A for leaf lettuce, leafy 

brassica greens, and melon production; 1.43 lbs ai/A for vegetable soybean (edamame); and 6.0 

lbs ai/A for kiwi and small fruit vines. Prowl ® H2O can be applied via ground or aerial 

application methods.

The variety of end-use products containing pendimethalin currently registered are as follows; 

alfalfa, artichoke, asparagus, bearing fruit and nut trees, brassica head and stem vegetables, 

carrots, carrots grown for seed, clover, corn, cotton, edible beans, fallow, forage legumes, 

fruiting vegetables, garlic, grain sorghum, grape, green onions, lentil and peas, mint, non-bearing 

fruit trees, olive trees, onions, peanuts, potatoes, rice, soybeans, strawberry, sugarcane, 

sunflowers, tobacco and wheat. In addition to agricultural crops, pendimethalin is registered for 
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northern and southern grasses, for use on sod farms and for seed production. Pendimethalin is 

also registered for use by commercial applicators and homeowners on lawns, parks, golf courses, 

in and around ornamentals, and weed control in non-cropland areas, such as landscape ground 

covers. Pendimethalin is also registered for use on container grown and field grown ornamentals, 

however, it is not to be used in greenhouses, shade houses, or other enclosed structures. 

3.1 Chemical Identity

The chemical structure and nomenclature of pendimethalin are presented in Table 3.1.

Table 3.1 Test Compound Nomenclature and Structure for Pendimethalin and Metabolite

Empirical Formula

Pendimethalin

N-(1-ethylpropyl)-3,4-dimethyl-2,6-

dinitrobenzenamine

Metabolite CL 202347

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

dinitrobenzyl alcohol

Chemical Structure

Common Name Pendimethalin

Company experimental name BAS 455H (old CL 92533)

IUPAC name N-(1-ethylpropyl)-2,6-dinitro-3,4-xylidine

CAS Name N-(1-ethylpropyl)-3,4-dimethyl-2,6-dinitrobenzenamine

CAS Registry Number 40487-42-1; 56750-76-6

End-use product/EP Prowl® H2O Herbicide (EPA Reg. No 241-418)

Chemical Class Dinitroaniline Herbicides

3.2 Physical/Chemical Characteristics

Pendimethalin contains dinitroanilines; therefore, a discussion of the potential for formation of 

nitrosamines and analysis for the presence of nitrosamines formed during manufacture and 

storage of the product was required. Previously submitted data indicate that no volatile 

nitrosamines are present (<0.5 ppm) and that total nonvolatile nitrosamines were present at less 

than 100 ppm. These issues are mentioned for informational purposes and are addressed either in 

the evaluation of the technical grade of the active ingredient (TGAI) or in the registrants 

confidential statement of formula (CSF). Details of the physio-chemical properties are provided 

in Appendix C.

3.3 Pesticide Use Pattern

HN

CH3

CH3

O2N NO2

CH3

CH3
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IR-4 has submitted a Section B and draft supplemental labels for the proposed uses of the 3.8 lbs 

a.i./gal CS formulation of pendimethalin (Prowl® H2O Herbicide; EPA Reg. No. 241-418). The 

directions for use are presented in Table 3.3 for the proposed uses of the 3.8 lbs a.i./gal CS 

formulation on leaf lettuce, leafy brassica greens, melon, vegetable soybean (edamame), and 

kiwi and other small fruit vines. The established use directions were obtained from labels 

accepted 10/31/2011 for the CS formulation and 04/03/2009 for the EC formulation. Refer to 

section 2.3 for the recommended modifications to the proposed label. Table 3.3 provides the 

summary of the directions for use.

Table 3.3 Summary of Directions for Use of Pendimethalin.

Applic. Timing, Type, 

and Equip.

FormulationApplic. Rate

(lb a.i./A)

Max. No. 

Applic. 

per 

Season

Max. 

Seasonal 

Applic. Rate

(lb a.i./A)

RTI

(days)

PHI 

(days)

Use Directions and Limitations

Proposed Uses

Leaf Lettuce

Foliar, Broadcast,

Ground (min. 10 

gal/A) or air (min. 5 

gal/A)

3.8 lb 

a.i./gal 

CS

1.0 1 1.0 Not applicable 

(NA)

20 Apply to direct-seeded or 

transplanted leaf lettuce from the 

3-leaf stage until 20 days prior to 

harvest.

Leafy Brassica Greens: Mustard greens, broccoli raab, Chinese cabbage (bok choy), collards, kale, mizuna, mustard 

spinach, rape greens, and turnip greens

Foliar, Broadcast,

Ground (min. 10 

gal/A) or air (min. 5 

gal/A)

3.8 lb 

a.i./gal 

CS

1.0 1 1.0 NA 21 Apply to direct-seeded or 

transplanted Brassica leafy greens 

at the 4-leaf to 5-leaf stage. 

Melon: Cantaloupe, citron melon, muskmelon and watermelon

Preplant, retransplant, 

or Preemergence [1st

app.] or Postemergence, prior to 

vine running [2nd

app.], Shielded to row 

middles, Ground (min. 

10 gal/A)

3.8 lb 

a.i./gal 

CS

1.0 2 2.0 Not 

specified

(NS)

35 First application: Apply before 

melon transplanting, before seeded 

crop has emerged, or between 

rows covered with plastic mulch 

(prior to holes being punched for 

planting). Second application: 

Apply prior to vine running.

Do not feed forage or graze 

livestock in treated fields.

Vegetable Soybean (Edamame)

Preplant Surface,

Broadcast, Ground 

(min. 10 gal/A) or air 

(min. 5 gal/A)

3.8 lb 

a.i./gal 

CS

Coarse soil 

0.95

Medium 

1.2-1.4

Fine soil

1.4

Heavy clay 

1.5

1 Coarse soil 

0.95

Medium

1.4

Fine soil

1.4

Heavy clay 

1.5

NA 85 Apply up to 15 days prior to 

planting or up to 45 days prior to 

planting when used in a tank mix 

or applied sequentially with 

postemergence-applied herbicides. 

Do not exceed 1.0 lb a.i./A in 

Southern states. Do not use in 

CA.

Preplant incorporated,

Broadcast, Ground 

(min. 10 gal/A) or air 

(min. 5 gal/A)

Apply up to 60 days prior to 

planting. Do not exceed 1.0 lb 

a.i./A in Southern states. Do not 

use in CA.
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Table 3.3 Summary of Directions for Use of Pendimethalin.

Applic. Timing, Type, 

and Equip.

FormulationApplic. Rate

(lb a.i./A)

Max. No. 

Applic. 

per 

Season

Max. 

Seasonal 

Applic. Rate

(lb a.i./A)

RTI

(days)

PHI 

(days)

Use Directions and Limitations

Preemergence,

Broadcast, Ground 

(min. 10 gal/A) or air 

(min. 5 gal/A)

3.8 lb 

a.i./gal 

CS

Coarse soil 

0.71

Medium

0.95

Fine soil

0.95-1.2

1 Coarse soil 

0.71

Medium

0.95

Fine soil

1.2

NA 85 Apply at planting or up to 2 days 

after planting. Do not make 

applications north of Interstate 80, 

except in IN, MI, and OH.

Do not use in CA.

Kiwi and Other Small Fruit Vines:

Amur river grape, gooseberry, fuzzy kiwifruit, hardy kiwifruit, maypop, and Schisandra berry

Surface incorporated 

or preemergence,

Broadcast or banded, 

directly to the ground 

beneath vines or 

between rows,Ground

(min. 10 gal/A) or 

chemigation/

irrigation systems

3.8 lb 

a.i./gal 

CS

3.0-6.0 2 6.0 30 60 Apply after fall harvest, during 

winter dormancy, and in the 

spring.

Do not feed forage or graze 

livestock in treated vines.

Spray adjuvants were not used in the submitted crop field trials on leaf lettuce, mustard greens, 

cantaloupe, and kiwifruit. HED has concluded that spray adjuvant use must be prohibited on 

product labels when the field trials do not include adjuvants (Note: ChemSAC, 04/16/08). The 

use directions for leaf lettuce, leafy brassica greens, melon, and kiwi and other small fruit vines 

must be amended to specify that no adjuvants may be added to the spray mixtures for these 

crops. 

3.4 Anticipated Exposure Pathways

The Registration Division has requested an assessment of human health risk to support the 

proposed new uses of the CS formulation of pendimethalin on leaf lettuce, leafy brassica greens, 

melon, vegetable soybean (edamame), and kiwi and other small fruit vines. Humans may be 

exposed to pendimethalin in food and drinking water, since pendimethalin may be applied 

directly to growing crops and application may result in pendimethalin reaching surface and 

ground water sources of drinking water. There are residential uses of pendimethalin, so exposure 

to pendimethalin may occur in residential or non-occupational settings. In an occupational 

setting, handlers may be exposed while handling the pesticide prior to application, as well as 

during application. There is also a potential for post-application exposure for workers reentering treated sites. 

Risk assessments have been previously prepared for the existing uses of pendimethalin. This 

risk assessment considers all of the aforementioned exposure pathways based on the proposed 

new uses of pendimethalin, but also considers the existing uses as well, particularly for the 

dietary exposure and residential (non-occupational) risk assessment. 

3.5 Consideration of Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in this 
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human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions 

to Address Environmental Justice in Minority Populations and Low-Income Populations," 

(http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf. As a part of every pesticide risk 

assessment, OPP considers a large variety of consumer subgroups according to well-established 

procedures. In line with OPP policy, HED estimates risks to population subgroups from 

pesticide exposures that are based on patterns of that subgroup’s food and water consumption, 

and activities in and around the home that involve pesticide use in a residential setting. 

Extensive data on food consumption patterns are compiled by the USDA under the Continuing 

Survey of Food Intake by Individuals (CSFII) and are used in pesticide risk assessments for all 

registered food uses of a pesticide. These data are analyzed and categorized by subgroups based 

on age, season of the year, ethnic group, and region of the country. Additionally, OPP is able to 

assess dietary exposure to smaller, specialized subgroups and exposure assessments are 

performed when conditions or circumstances warrant. Whenever appropriate, non-dietary 

exposures based on home use of pesticide products and associated risks for adult applicators and 

for toddlers, youths, and adults entering or playing on treated areas postapplication are evaluated. 

Further considerations are currently in development as OPP has committed resources and 

expertise to the development of specialized software and models that consider exposure to 

bystanders and farm workers as well as lifestyle and traditional dietary patterns among specific 

subgroups.

4.0 Hazard Characterization and Dose-Response Assessment

4.1 Toxicology Studies Available for Analysis

The toxicology database is adequate to support the proposed uses for pendimethalin. The 

scientific quality of the database for pendimethalin is relatively high and the toxicity profile can 

be characterized for a wide range of effects, including potential developmental, reproductive, 

neurotoxic, and immunotoxic effects. 

4.2 Absorption, Distribution, Metabolism, & Elimination (ADME)

In a metabolism study (MRID 00046275), when {14C}pendimethalin was administered to rats, 

about 70% of the radioactivity was excreted in the feces and 20% in the urine within 24 hours. 

The excretion of radioactivity in the urine peaked at 6 to 12 hours wherein 11.2% of the dose 

was excreted. The maximum residual radioactivity in the tissues was found in the 6-hour samples 

(except for fat at 12 hours). The levels of radioactivity detected in liver, kidney, muscle, fat, and 

blood at 6 hours were 29.8, 16.9, 1.3, 12.2, and 5.4 ppm, respectively. Within 96 hours the 

radioactivity found in the tissues was 0.3 ppm or less, except for fat which was 0.9 ppm. The 

major portion of the radioactivity that was excreted in the feces was identified as the parent 

compound. Pendimethalin is metabolized in rats 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. 

4.2.1 Dermal Absorption
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There were no appropriate dermal absorption or toxicity studies available to allow an estimation 

of the dermal absorption by a route-to-route comparison of toxicity. In a previous risk 

assessment (HIARC doc. 04/18/2000), dermal absorption was estimated to be no greater than 

10%. This was based on structurally related chemicals (oryzalin, trifluralin and ethalfluralin) 

with dermal absorption studies (in monkeys) indicating absorption rates of 2.3%, ~1%, and 

2.8%, respectively. The solubility (water) for pendimethalin and these related chemicals are also 

similar at 0.5 ppm, 2.5 ppm, 0.3 ppm and < 1 ppm, respectively. The upper-bound value of 10% 

previously estimated for pendimethalin is considered very conservative. Therefore, for risk 

characterization purposes, a more appropriate estimate of 3% was applied. This absorption rate is 

comparable to those identified for related chemicals.

4.3 Toxicological Effects

Pendimethalin has a low acute toxicity via the oral, dermal, or inhalation route. It is not a dermal 

or eye irritant; and is not a dermal sensitizer. The thyroid is a target organ for pendimethalin. 

Thyroid toxicity in chronic and subchronic rat and mouse studies was manifested as alterations in 

thyroid hormones (decreased total T4, and T3, increased percent of free T4 and T3), increased 

thyroid weight, and microscopic thyroid lesions (including increased thyroid follicular cell 

height, follicular cell hyperplasia, as well as follicular cell adenomas).

Thyroid tumors were observed in both male and female rats in a chronic/carcinogenicity study. 

There were no tumors observed in the carcinogenicity study in mice. The Health Effects Division 

(HED) Cancer Peer Review Committee classified pendimethalin (03/18/92 and re-affirmed 

11/01/99) as a "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. The Committee also recommended a nonquantitative approach (i.e., non-linear, RfD approach) since mode of action studies are available 

that demonstrate that the thyroid tumors are due to a thyroid-pituitary imbalance, and also since 

pendimethalin was shown to be non-mutagenic in mammalian somatic cells and germ cells. The 

chronic risk assessment is considered to be protective of any cancer effects; therefore, a separate 

quantitative cancer aggregate risk assessment is not required. 

4.4 Safety factor for Infants and Children (FQPA Safety Factor)

There was no evidence of qualitative or quantitative susceptibility in a 2-generation reproduction 

study conducted in the rat, and there was no evidence of neurotoxicity in the acute and 

subchronic neurotoxicity studies. In a developmental thyroid study, there was no increased 

sensitivity to the offspring as compared to dams because thyroid hormones in fetuses and PND 4 

pups of exposed dams remained unaltered even when their mothers showed significantly 

decreased T4 levels. Only after exposure via the diet in addition to the milk, serum T4 levels of 

PND 21 pups were affected. Therefore, HED has recommended the 10X FQPA safety factor be 

removed (reduced to 1X).

4.4.1 Completeness of the Toxicology Database

The toxicology database for pendimethalin is complete and adequate to support risk assessments.
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4.4.2 Evidence of Neurotoxicity

There is no evidence of neurotoxicity for pendimethalin exposure. In an acute neurotoxicity 

study, FOB findings and reduced motor activity were observed on Day 0 only at 300 and 1000 

mg/kg. However, these findings were considered an impairment of the overall condition of the 

animals following treatment, rather than direct neurotoxic effects of the pendimethalin exposure 

based on the absence of any neurohistopathological changes in the treated animals and the 

transient nature of the observed FOB and neurobehavioral assessments. In a subchronic 

neurotoxicity study, no neurotoxic effects were observed in rats feeding pendimethalin up to 

5400 ppm for 90 days. In addition, the toxicology database does not reveal any evidence of 

neurotoxic clinical signs, changes in brain weight, or histopathology of the nervous system in 

any study with pendimethalin. 

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal

There was no indication of pre- and/or post-natal qualitative or quantitative increased 

susceptibility in the developmental studies in rats and rabbits or the 2-generation reproduction 

studies in rats. In addition, a developmental thyroid toxicity study demonstrated that there is no

potential thyroid toxicity following pre- and/or post-natal exposure to pendimethalin. Thyroid 

hormones in fetuses and PND 4 pups of exposed dams remained unaltered even when their 

mothers showed significantly decreased T4 levels. Only after exposure via the diet in addition to 

the milk, serum T4 levels of PND 21 pups were affected.

4.4.4 Residual Uncertainty in the Exposure Database

While some refinements were incorporated into the dietary exposure calculations, EPA is 

confident that the aggregate risk from exposure to pendimethalin in food, drinking water and 

residential pathways will not be underestimated. The acute dietary exposure assessment 

assumed 100% of the proposed and registered crops were treated, and utilized tolerance level 

residues for all existing and proposed commodities. The chronic dietary exposure assessment 

used tolerance level residues for all commodities, 100% crop treated (% CT) and empirical 

processing estimates when available or DEEMTM default processing factors. The drinking water 

assessment utilized water concentration values generated by models and associated modeling 

parameters which are designed to produce conservative, health protective, high-end estimates of 

water concentrations which are not likely to be exceeded. The dietary (food and drinking water) 

exposure assessment does not underestimate the potential exposure for infants, children, or 

women of child bearing age. 

In addition, the residential exposure assessment incorporates similarly conservative assumptions 

in the assessment of post-application exposure of children and in the incidental oral exposure 

assessment for children. These assessments will not underestimate the exposures and risks posed 

by pendimethalin. 

4.5 Toxicity Endpoint and Point of Departure Selections
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4.5.1 Dose-Response Assessment

The thyroid is the target organ for pendimethalin. Effects of hormonal changes (alterations in 

thyroid weights and histopathological lesions) were observed in several studies following oral 

administration of pendimethalin and it is likely that these changes may cause disruption in the 

endocrine system. On March 30, 2000, the HIARC re-affirmed (09/07/1999) that the NOAEL 

of 10 mg/kg/day selected from the 14-day intra-thyroidal study reflects a true NOAEL for 

thyroid effects since these effects have been demonstrated to have early onset (before 14 days). 

On this basis, all studies were considered together for establishing the NOAEL of 10 mg/kg/day. 

The LOAEL of 31 mg/kg/day, from the 56-day thyroid study, is based on several hormonal and 

histological thyroid changes and thyroid hormonal effects occurred as early as day 3. The 

estimated short- and intermediate-term dermal and inhalation NOAEL of 10 mg/kg/day for 

pendimethalin were selected from an oral study. Therefore, for risk characterization purposes, a 

dermal absorption factor of 3% and an inhalation absorption factor of 100% were used. Since 

both dermal and inhalation endpoints were based on the same toxicological effects these routespecific MOEs were combined into a total MOE. 

HEDs level of concern (LOC) for pendimethalin dermal and inhalation is 30 (i.e., a margin of 

exposure (MOE) less than 30 exceeds HED’s level of concern) for occupational scenarios. The 

level of concern includes a 10X uncertainty factor (UF) for intra-species extrapolation. This 

factor is used to account for human variability in toxicokinetics and toxicodynamics. However, 

the interspecies UF (used to account for animal to human differences in toxicokinetics and 

toxicodynamics) may be reduced to 3X with respect to 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).

4.5.2 Recommendation for Combining Routes of Exposures for Risk Assessment

Since the same three studies were used to select endpoints and doses for risk assessment for 

chronic dietary, dermal and inhalation routes of exposure (all durations), the risks from these 

exposure routes need to be aggregated. 

4.5.3 Cancer Classification and Risk Assessment Recommendation

Pendimethalin is classified as a “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 to demonstrate that the thyroid tumors are due to a thyroidpituitary imbalance, and also since pendimethalin was shown to be non-mutagenic in mammalian 

somatic cells and germ cells. The chronic risk assessment is considered to be protective of any 

cancer effects; such that, a separate quantitative cancer aggregate risk assessment is not required.

4.5.4 Summary of Points of Departure and Toxicity Endpoints Used in Human Risk 

Assessment
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Table 4.5.4.1 Toxicological Doses and Endpoint for Pendimethalin Human Health Risk Assessment

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). 

Table 4.5.4.2 Summary of Toxicological Doses and Endpoints for Pendimethalin for Use in Occupational 

Human Health Risk Assessments
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Exposure/ 

Scenario

Point of 

Departure

Uncertainty 

Factors

Level of Concern 

for Risk 

Assessment

Study and Toxicological Effects

Dermal ShortTerm (1-30 

days)

NOAEL=10

mg/kg/day

UFA=3x

UFH=10x

Occupational 

LOC for MOE 

=30

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.

Dermal 

IntermediateTerm (1-6 

months)

NOAEL=10

mg/kg/day

UFA=3x

UFH=10x

Occupational 

LOC for MOE 

=30

The same as above.

Inhalation 

Short-Term (1-

30 days)

NOAEL=10

mg/kg/day

UFA=3x

UFH=10x

Occupational 

LOC for MOE 

=30

The same as above.

Inhalation 

Intermediateterm (1-6 

months)

NOAEL=10

mg/kg/day

UFA=3x

UFH=10x

Occupational 

LOC for MOE 

=30

The same as above.

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.

Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data and used to 

mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL 

= no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UFA = 

extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity among members of the human 

population (intra-species). UFL = use of a LOAEL to extrapolate a NOAEL. UFS = use of a short-term study for long-term risk 

assessment. UFDB = to account for the absence of key data (i.e., lack of a critical study). MOE = margin of exposure. LOC = 

level of concern. N/A = not applicable.

5.0 Dietary Exposure and Risk Assessment 

5.1 Metabolite/Degradate Residue Profile

5.1.1 Summary of Plant and Animal Metabolism Studies

Plant Metabolism Studies

HED previously concluded that the nature of the residue in plants is understood, based on 

adequate studies conducted with [14C]-pendimethalin on potatoes and sweet corn. The results of 

these studies are supported by additional corn, cotton, dry bean, lima bean, peanut, potato, red 

table beet, rice, snap bean, soybean, sugarcane, and wheat metabolism data. These data are 

adequate to define the nature of the residue in all plants. The residues of concern in plant 

commodities are pendimethalin and its 3,5-dinitrobenzyl alcohol metabolite. The current 

tolerance expression for pendimethalin in 40 CFR §180.361 specifies the combined residues of 

pendimethalin and its 3,5-dinitrobenzyl alcohol metabolite. Refer the following document for 

additional details: 1) Residue Chemistry Memo DP# 329627, W. Drew, 07/12/2006 and 2) 

Residue Chemistry Chapter, Pendimethalin RED (DP# 221531, B. Cropp-Kohlligian, 

12/08/1995)

Livestock Metabolism Studies
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HED previously concluded that, pending resolution of residue characterization issues for goat 

kidney, the nature of the residue in animals is adequately understood based on acceptable goat 

and poultry metabolism studies. The data indicate that there is no reasonable expectation of 

finite residues (pendimethalin, Goat Metabolite 6, and the 3,5-dinitrobenzyl alcohol metabolite) 

in meat, milk, poultry and eggs (40 CFR §180.6[a][3]). Tolerances for pendimethalin in/on 

livestock commodities are not needed for the purpose of these proposals. Refer to the following 

referenced documents for the details: 1) Residue Chemistry Memo DP# 329627, W. Drew, 

07/12/2006 2) Residue Chemistry Memo DP#s 271502; 310793; 311825; 314085; 314093; 

317047; 317053, W. Drew, 07/12/2006 and 3) Residue Chemistry Chapter, Pendimethalin RED 

(DP# 221531, B. Cropp-Kohlligian, 12/08/1995).

5.1.2 Summary of Environmental Degradation

Pendimethalin dissipates in the environment by sorbing to soil, metabolizing by microbes, and 

by volatilizing into air as moisture content increases. Persistence decreased with increased 

temperature, increased moisture and decreased soil organic carbon. Pendimethalin residues in 

laboratory and field studies are tightly sorbed to soil and sediment particles, which is consistent 

with the laboratory mobility studies. 

Pendimethalin is stable to sterile hydrolysis, soil photolysis, and anaerobic soil metabolism, but 

degrades slowly under aqueous photolysis conditions with a calculated half-life of 17 days. 

Aerobic soil metabolism half-lives range from 42-1322 days with 172 days used for the purpose 

of exposure assessment. Pendimethalin forms many minor « 1 0% of applied) degradates that 

consist primarily of an intact benzene ring with rearranged alkyl groups. Anaerobic aquatic 

metabolism half-lives ranged from 6 to 105 days, and aqueous residues bind to sediment under 

this condition. This association with soil/sediment is consistent with soil mobility studies which 

indicated that pendimethalin is essentially immobile in all soils studied.

5.1.3 Comparison of Metabolic Pathways

Residue Chemistry Chapter, Pendimethalin RED (DP# 221531, B. Cropp-Kohlligian, 12/08/1995)

Pendimethalin IR-4 Tolerance Petition (DP# D329627, W. Drew, 07/12/2006)

The registrant has previously submitted acceptable studies depicting the metabolic fate of 

pendimethalin in plants, rats and livestock. All studies were conducted in a manner that is 

applicable and adequate for the proposed new uses. The residues identified in plant and animal 

metabolism studies include the parent pendimethalin and its 3,5-dinitrobenzyl alcohol 

metabolite.

Previously submitted adequate crop data are available to demonstrate that pendimethalin residues 

of concern do not concentrate in plant commodities derived from corn, and potatoes and that 

radioactive residues in/on crops will be extensively metabolized. Additionally, the nature of the 

residue of pendimethalin in animals is adequately understood. Previously submitted data from 

the goat metabolism study, along with data from a poultry metabolism study indicate that there is 

no reasonable expectation of finite in meat milk, poultry, nor eggs as a result of the current

registered uses and consequently the proposed new uses of pendimethalin.
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In a previously submitted rat metabolism study, radioactive pendimethalin as administered to rats 

indicated that about 70% of the radioactivity is excreted in the feces and 20% in the urine within 

24 hours. The major portion of the radioactivity that was excreted in the feces was identified as 

the parent compound. Pendimethalin is metabolized in rats mainly through oxidation of the 4-

methyl group attached to the benzene ring as well as oxidation of the alkyl side chain of the Nsubstituted dinitroaniline compound. 

5.1.4 Residues of Concern Summary and Rationale

As summarized in Table 5.1.4. The HED MARC recommends that the parent compound and its 

alcohol metabolite as the residues of concern for the tolerance expression and the risk 

assessment, it should be included for all plant commodities. However, there is no need for a 

residue assessment definition for livestock commodities (no reasonable expectation of finite 

residues). The drinking water values consider a total residue methodology analysis. 

Table 5.1.4 Summary of Metabolites and Degradates included in the Pendimethalin Risk Assessment and 

Tolerance Expression

Matrix

Residues included in Risk Assessment Residues included in

Tolerance Expression

Plants

Primary Crop Pendimethalin and 4-[(1-ethylpropyl)amino]-2-

methyl-3,5-dinitrobenzyl alcohol (CL 202347)

Pendimethalin 

and (CL 202347)

Rotational Crop

Livestock

Ruminant Not applicable - there is no reasonable expectation of finite residues in 

Poultry livestock.

Drinking Water Pendimethalin Not Applicable

5.2 Food Residue Profile

The specific details have been submitted in the following referenced documents: 1) DER 

Reference: 47891603.der3, 2) Residue Chemistry Memo DP# 372876, Y. Barnes, 03/10/2010, 3) 

Residue Chemistry Memo DP# 238469, W. Cutchin, 07/21/1999, and 4) Residue Chemistry 

Chapter, Pendimethalin RED (DP# 221531, B. Cropp-Kohlligian, 12/08/1995). The food residue 

profile (Table 5.2) for the new uses is described below.

The available and submitted concurrent storage stability data are adequate to support the 

submitted crop field trials. The data indicate that there are no storage stability issues, and no 

corrections for decline after storage are needed. 
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TABLE 5.2 Summaries of Residue Data from Field Trials with Pendimethalin.

Leaf Lettuce Crop Field Trials MRID 48489801

Commodity Analyte Total

Rate

(lb a.i./A)

PHI 

(days)

Residue Levels (ppm)1

n Sample 

Min.

Sample 

Max.

LAFT2 HAFT2 Median Mean Std. 

Dev.

Leaf lettuce Pendimetha

lin

0.98-1.03 18-21 9 <0.05 2.251 0.05 2.230 0.062 0.338 0.714

26-33 8 <0.05 1.191 0.05 1.010 0.05 0.174 0.338

CL 202347318-21 9 <0.05 <0.05 0.05 0.05 0.05 0.05 N/A

26-33 8 <0.05 <0.05 0.05 0.05 0.05 0.05 N/A

Combined 18-21 9 <0.10 <2.301 0.10 2.280 0.112 0.388 0.714

26-33 8 <0.10 <1.241 0.10 1.060 0.10 0.224 0.338

Mustard Greens Crop Field Trials MRID 48489802

Commodity Analyte Total

Rate

(lb a.i./A)

PHI 

(days)

Residue Levels (ppm)1

n Sample 

Min.

Sampl

e Max.

LAFT2 HAFT2 Media

n

Mean Std. 

Dev.

Mustard 

greens

Pendimetha

lin

0.48-0.53 21-35 8 <0.05 <0.05 0.05 0.05 0.05 0.05 N/A

0.97-1.04 13-35 <0.05 0.107 0.05 0.107 0.05 0.061 0.021

CL 20234730.48-0.53 21-35 8 <0.05 <0.05 0.05 0.05 0.05 0.05 N/A

0.97-1.04 13-35 <0.05 <0.05 0.05 0.05 0.05 0.05 N/A

Combined 0.48-0.53 21-35 8 <0.10 <0.10 0.10 0.10 0.10 0.10 N/A

0.97-1.04 13-35 <0.10 0.157 0.10 0.157 0.10 0.107 0.020

 Cantaloupe Crop Field Trials MRID 48489803

Commodity Analyte Total 

App. 

Rate

(lb 

a.i./A)

PHI 

(days)

Residue Levels (ppm)1

n Sample 

Min.

Sample 

Max.

LAFT

2

HAFT

2

Median Mean Std. 

Dev.

3.8 lb a.i./gal CS formulation

Cantaloupe Pendimethali

n

1.96-

2.02

35-47 8 <0.05 <0.05 0.05 0.05 0.05 0.05 N/A

CL 2023473<0.05 <0.05 0.05 0.05 0.05 0.05 N/A

Combined <0.10 <0.10 0.10 0.10 0.10 0.10 N/A

3.3 lb a.i./gal EC formulation

Cantaloupe Pendimethali

n

1.96-

2.00

47-49 2 <0.05 <0.05 0.05 0.05 0.05 0.05 N/A

CL 2023473<0.05 <0.05 0.05 0.05 0.05 0.05 N/A

Combined <0.10 <0.10 0.10 0.10 0.10 0.10 N/A

Kiwifruit Field Crop Trials MRID 48489801

Commodity Analyte Total

Rate

(lb 

a.i./A)

PHI 

(days)

Residue Levels (ppm)1

n Sampl

e Min.

Sample 

Max.

LAFT2 HAFT2 Media

n

Mean Std. 

Dev.

Kiwifruit Pendimethalin 6.09-

6.22

58-60 2 <0.05 <0.05 0.05 0.05 0.05 0.05 N/A

CL 20234732 <0.05 <0.05 0.05 0.05 0.05 0.05 N/A

Combined 2 <0.10 <0.10 0.10 0.10 0.10 0.10 N/A

1

 Except for sample min/max, values reflect per trial averages; n = no. of field trials. N/A = not applicable. 

2

 LAFT = lowest average field trial; HAFT = highest average field trial.
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3

 Residues of metabolite CL 202,347 were converted to parent equivalents; the molecular weight conversion factor 

is 0.9462.

No crop field trial data were submitted/or needed in support of the proposed use on vegetable 

soybean (edamame). The HED’s Chemistry Science Advisory Council (Note: ChemSAC, 

recommendations on 09/15/10 and 10/27/10) previously concluded that a tolerance for vegetable 

soybean (edamame) could be established at the same level as the established tolerances for bean 

(succulent) and pea (except field pea). 

5.3 Water Residue Profile

The drinking water residues used in the dietary risk assessment were provided by the 

Environmental Fate and Effects Division, EFED (Barcode: D390459, 02/23/2012, W. P. Eckel)

and incorporated directly into the dietary assessment.

This memorandum provided the estimates of human drinking water exposure to the herbicide 

pendimethalin from the proposed new uses on Kiwi/small fruits (Amur river grape, gooseberry, 

fuzzy kiwifruit, hardy kiwifruit, maypop, and Schisandra berry), Leaf lettuce, Leafy brassica 

greens, Melons (cantaloupe, citron melon, muskmelon, and watermelon) and Edamame (edible 

soybeans). The memorandum specifically referred to the details noted in the last drinking water 

assessment (DWA) for pendimethalin that was completed on February 23, 2009 for the proposed 

uses on olives and forage grasses (Barcodes D356491 and D355650). The results of the 

aforementioned assessment indicated that the EDWC remained the same as in the 05/08/2007

DWA (Barcode D334061). 

The EDWCs for the proposed new uses are 80.5 ppb (1-in-10 year annual peak acute 

concentration), 6.2 ppb (1-in-10 year annual mean chronic concentration), and 5.0 ppb (30-year 

annual mean (cancer) chronic concentration) for surface water (Table 5.3). These data are 

slightly higher than the 2007 results due to model changes and new environmental fate data. The 

ground water EDWC (SCIGROW model) remains unchanged at 0.036 ppb for a 6-pound/acre 

application (kiwi and small fruits). 

Table 5.3 provides a summary of the modeled drinking water concentrations. The model and 

its description are available at the EPA internet site: http://www.epa.gov/oppefed1/models/water/. 

Table 5.3

 Summary of Estimated Surface Water and Groundwater Concentrations for Pendimethalin

Scenario Surface Water Conc., ppb a Groundwater Conc., ppb b

Acute 80.5 0.036

Chronic (non-cancer) 6.2 0.036

Chronic (cancer) 5.0 NA

a

PRZM-EXAMS - Index Reservoir model. Input parameters are based on grapes in New York state (See May 8, 

2007 DWA, DP Barcode 334061, J. Breithaupt, EFED to D. Rosenblatt, RD).

b

From the SCI-GROW model assuming a maximum seasonal use rate of 6 lbs a.i./A (kiwi and small fruits)
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5.4 Dietary Risk Assessment

Pendimethalin Dietary Assessment (D401100.drs, Y. Barnes, 05/02/2012)

5.4.1 Description of Residue Data Used in Dietary Assessment

Acute and chronic aggregate dietary (food and drinking water) exposure and risk assessments 

were conducted using the Dietary Exposure Evaluation Model DEEM-FCIDTM, Version 2.03 

which uses food consumption data from the U.S. Department of Agriculture’s (USDA’s) 

Continuing Surveys of Food Intakes by Individuals (CSFII) from 1994-1996 and 1998. The 

deterministic acute and unrefined chronic analyses are based on tolerance-level residues, 100% 

crop treated assumptions for all of pendimethalin use commodities in this assessment and 

DEEMTM default processing factors or empirical processing factors where available. The 

drinking water estimates provided by EFED are modeled estimates, and were generated using the 

most conservative model available for the proposed crops and turf uses. The deterministic acute 

and unrefined chronic approach to dietary exposure analysis may overestimate risk to the general 

U.S. population.

5.4.2 Percent Crop Treated Used in Dietary Assessment

The acute and chronic assessments are based on the assumption that 100% for all pendimethalin 

use commodities, both recommended and registered were treated.

5.4.3 Acute Dietary Risk Assessment

The results for the most highly exposed subgroups for pendimethalin have an estimated exposure 

(food and water) as follows: 2.0 % of the aPAD for all infants, 1.4 % of the aPAD for children 1-

2 years old, and 1.2% of the aPAD for children 3-5 years old. For the general U.S. population the 

estimated exposure (food and water) from the use of pendimethalin result in an estimated risk 

equivalent to <1% of the acute population adjusted dose (aPAD) at the 95th percentile of 

exposure (Table 5.4.6). The acute dietary risk estimate is below HED’s level of concern at the 

95th percentile of exposure.

5.4.4 Chronic Dietary Risk Assessment

The results of the most highly exposed subgroups for pendimethalin have an estimated exposure 

(food and water) as follows: 1.0% of the cPAD for all infants, 1.6% of the cPAD for children 1-2 

years old, and 1.3% of the cPAD for children 3-5 years old. For the general U.S. population the 

estimated exposure (food and water) from the use of pendimethalin result in an estimated risk 

equivalent to <1% of the chronic population adjusted dose (cPAD), refer to Table 5.4.6. The 

chronic dietary risk estimate for food and drinking water are below HED’s level of concern. 

5.4.5 Cancer Dietary Risk Assessment

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 to demonstrate that the 

thyroid tumors are due to a thyroid-pituitary imbalance, and also since pendimethalin was shown 

to be non-mutagenic in mammalian somatic cells and germ cells. The chronic risk assessment is 
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considered to be protective of any cancer effects; therefore, a separate quantitative cancer 

aggregate risk assessment is not required.

5.4.6 Summary Table

Table 5.4.6 Summary of Dietary (Food and Drinking Water) Exposure and Risk for Pendimethalin

Population Subgroup

Acute Dietary1

(95th Percentile) Chronic Dietary1

Dietary Exposure 

(mg/kg/day) % aPAD* Dietary Exposure(mg/kg/day) % cPAD*

General U.S. Population 0.007460 <1 0.001621 <1

All Infants (< 1 year old) 0.019305 2.0 0.003067 1.0

Children 1-2 years old 0.014344 1.4 0.004677 1.6

Children 3-5 years old 0.011797 1.2 0.003840 1.3

Children 6-12 years old 0.009042 <1 0.002346 <1

Youth 13-19 years old 0.006621 <1 0.001500 <1

Adults 20-49 years old 0.006773 <1 0.001250 <1

Adults 50+ years old 0.006115 <1 0.001158 <1

Females 13-49 years old 0.006837 <1 0.001265 <1

*Note: HED is concerned when dietary risk estimates exceed 100% of the PAD. Values for the population with the 

highest risk are in bold type. 

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

Pendimethalin: Occupational and Residential Exposure/Risk Assessment for Registration Review and for new Proposed Use on 

Leaf lettuce; Leafy brassica greens; Melons; Edamame; Kiwi and other small fruit vines. S. Shelat, B. Bobowiec, DP402406, 

05/31/2012

Pendimethalin: REVISED Occupational and Residential Exposure Assessment for Proposed Section 3 Registration for Use on 

Mint, Citrus Fruits, Tree Nuts, and Carrots. M. Collantes, Z. Figeuroa, DP325175, 04/02/2007.

The proposed uses for pendimethalin do not include residential (non-occupational) uses. 

Although, the proposed uses for Prowl ® H2O are not anticipated to result in residential 

exposures, an updated residential handler and post-application assessment has been conducted 

due to changes in the Standard Operating Procedures for Residential Pesticide Exposure 

Assessment, body weights, as well as the incorporation of new toxicology data. Updated 

residential handler and post-application risk estimates do not exceed HED’s level of concern 

(MOEs ≥ 30). Updated residential exposure risk estimates are also provided for consideration in 

the aggregate risk assessment. 
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The residential scenarios addressed include uses on residential turf and ornamentals. Residential 

post-application scenarios include exposure from previously treated golf courses, turf in 

residential areas, and ornamentals. 

6.1 Residential Handler Exposure

The proposed uses of pendimethalin do not involve applications by homeowners or commercial 

applicators to residential settings. However, pendimethalin is currently registered for use on 

several residential/non-agricultural use sites: i.e., northern and southern grasses; sod farms; 

lawns; parks; golf courses; in and around ornamentals; and weed control in non-cropland areas, 

such as landscape ground covers. Pendimethalin is also registered for use on container grown 

and field grown ornamentals, however, it is not to be used in greenhouses, shade houses, or other 

enclosed structures. It is assumed that most residential use will result in short-term (1 to 30 

days) handler exposures. Residential handlers are assumed to be wearing short-sleeved shirts, 

short pants, shoes and socks during application of pendimethalin. Although PoDs from an oral 

study were used to assess residential handler dermal and inhalation risks for pendimethalin, HED 

does not believe this assessment is under-protective of adult handlers. 

HED’s level of concern for the MOE is defined by the uncertainty factors that are applied to the 

assessment. HED applies a 3X factor to account for interspecies extrapolation and a 10X factor 

to account for intra-species sensitivity. The total uncertainty factor that has been applied to the 

non-cancer risk assessment for pendimethalin is 30X for residential exposure. Residential 

exposure and risk estimates resulting in MOEs greater than or equal to 30 will not be of concern 

to HED. 

The worst case residential handler scenario is summarized in Table 6.1. The MOE was 670 for 

residential handlers loading and applying the granular formulation of pendimethalin, and is not 

of concern to HED (i.e. an MOE > 30). 
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Table 6.1: Short-Term Residential Handler Exposure and Risk Estimates for Pendimethalin

Exposure Scenario Target

MOE

Dermal Unit 

Exposure

Inhalation Unit 

Exposure

Application 

Rate a

Amount 

Treated 

or 

Handled 

Daily b

Dermal Inhalation Total

Dose c MOE d Dose e MOE f MOE g

Mixer/loader/Applicator

Loading/applying 

granulars with a 

belly grinder

30 360 0.039 4 lbs ai/acre 0.028 0.015 670 0.000054 180,000 670

a. Based on a review of the registered labels of pendimethalin for use in or around ornamentals

b. Belly grinder assumption of 1200 sq ft per day is calculated to be equivalent to 0.023 acres ((1200 sq ft/day ) x (43,560 sq ft/1 acre) = 0.023 acres/day)

c. Dermal Dose = Dermal Unit Exposure (mg/kg) x Application Rate (4lb ai/acre) x Amount Treated or Handled (0.023A /day) x DAF (3%)/BW (80kg)

d. Dermal MOE = Dermal NOAEL (10mg/kg/day)/Dermal Dose (mg/kg/day)

e. Inhalation Dose = Dermal Unit Exposure (mg/kg) x Application Rate (4lb ai/acre) x Amount Treated or Handled (0.023 A/day) /BW (80kg)

f. Inhalation MOE = Inhalation NOAEL (10 mg/kg/day)/ Inhalation Dose (mg/kg/day)

g. Total MOE = Total MOE = 1/[(1/Dermal MOE) + (1/Inhalation MOE)]
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6.2 Post-Application Exposure

Post-application short-term dermal and incidental oral exposure and risk estimates have been 

assessed for pendimethalin exposure from treated turf in residential settings (i.e., lawns and 

gardens) as well as from exposure to golf courses previously treated by a commercial applicator. 

When determining the potential for residential exposure, the Agency considers turf transferable 

residues, transfer coefficients, residue transfer to hands, residue transfer to objects, soil and 

granular ingestion rates, and exposure time. Two turf transferable residue studies were utilized 

in the determination of post-application exposure from pendimethalin treated turf. 

Determination of Transferable Turf Residue Dissipation from Turf Treated with 

Suspension Concentrate and Emulsifiable Concentrate Formulations of Pendimethalin

(MRID No.: 466841-02). Residues from the Georgia site were selected because they 

resulted in the highest Day 0 residues. 

Pendulum® WDG Herbicide (MRID No.44969901). The Day 0 residues detected were 

generally at or below the LOQ with the exception of 7 days after treatment when residues 

averaged 17.5 ng/cm2at the Pennsylvania site in MRID 44969901. Data from the 

Pennsylvania site was used in this assessment as it resulted in the only detectable residue 

after application.

Dermal and oral exposures were combined as the same study was used to identify the 

toxicological effects from the dermal and oral routes of exposure. The scenarios, routes of 

exposure and lifestages assessed include:

Physical activities on turf: adults (dermal) and children 1 < 2 years old (dermal and 

incidental oral);

Mowing: adults (dermal) and children 11 < 16 years old (dermal); and

Golfing: adults (dermal), children 11 < 16 years old (dermal), and children 6 < 11 years 

old (dermal).

Based on the Agency's current practices, a quantitative residential post-application inhalation 

exposure assessment was not performed for pendimethalin at this time primarily because 

pendimethalin’s vapor pressure (3 x 10-5 mm Hg @ 25 °C) and Henry's Law Constant (8.6 x 10-

07

atm m

3

/mol) indicate that the compound is relatively non-volatile under field conditions. The 

Agency sought expert advice and input on issues related to volatilization of pesticides from its 

Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in 

December 2009. The Agency received the SAP’s final report on March 2, 2010 

(http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The Agency is in the 

process of evaluating the SAP report and may, as appropriate, develop policies and procedures to 

identify the need for and, subsequently, the way to incorporate post-application inhalation 

exposure into the Agency's risk assessments. If new policies or procedures are put into place, the 

Agency may revisit the need for a quantitative post-application inhalation exposure assessment 

for pendimethalin

The MOEs for worst-case post-application dermal exposures are summarized in Tables 6.2. The 

MOEs ranged from 130 to 410,000 for both dermal exposure and incidental oral ingestion. All 
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assessed residential exposures and risk estimates resulted in MOEs of > 30; and therefore, are not 

of concern to HED. 

Table 6.2: Short- Term Residential Post-application Exposure and Risk Estimates for Pendimethalin 

Lifestage Post-application Exposure Scenario Dose (mg/kg/day) MOEs

Adult

Turf sprays –

physical activities on turf

Dermal 0.032 320

Child 1< 2

Dermal 0.060 170

Hand to Mouth 0.042 240

Object to Mouth 0.0013 7,800

Incidental Soil Ingestion 6.5E-05 150,000

Episodic Granular 

Ingestion 0.71 140

Adult

Turf sprays- Golfing

Dermal 0.0037 2,700

11 to <16 years Dermal 0.0043 2,300

6 to <11 years Dermal 0.0051 2,000

Adult Gardening spraysDermal 0.078 130

6 to <11 years Dermal 0.053 190

6.3 Combined Exposure

HED did not combine exposure resulting from adult handler and post-application exposure 

resulting from treated lawns and/or golfing because of the conservative assumptions and inputs 

within each estimated exposure scenario. HED believes that combining exposures resulting from 

handler and post-application activities would result in an overestimate of adult exposure. 

Therefore, HED selected the most conservative adult residential scenario, dermal postapplication exposure (MOE = 130) as the contributing source of residential exposure to be 

combined with the dietary exposure for the aggregate assessment.

The children’s oral exposure is based on post-application hand-to-mouth exposures (MOE = 

240). To include exposure from object-to-mouth and soil ingestion in addition to hand-to-mouth 

could result in a very conservative estimation of exposure, as it would overestimate the potential 

for oral exposure. However, there is the potential for co-occurrence of dermal and oral exposure, 

since the toxicological effects from the dermal and oral routes of exposure are the same. As a 

result, a combined residential exposure assessment is possible for children. Therefore, one 

children’s aggregate assessments is required (combined post-application dermal and oral 

combined with dietary exposure) to ensure no unacceptable risk will result to children when 

combining residential and dietary exposure for purposes of estimating an aggregate risk.

Table 6.3.1 summarizes the residential exposure scenarios that are to be used for estimating 

aggregate exposure. 

Table 6.3.1. Short-Term Residential Exposures for the Pendimethalin Combined Residential Risk Calculations

Population

Handler Exposure 

(mg/kg/day)1

Residential

Handler Total 

Exposure 

(mg/kg/day)3

Postapplication Exposure 

(mg/kg/day)2 Residential Postapplication Total 

Exposure (mg/kg/day)3 Dermal Inhalation Dermal Inhalation Oral

Adult 0.015 5.4E-05 0.015 0.078 N/A N/A N/A

Child N/A N/A N/A 0.060 N/A 0.042 0.102

1Handler exposure represents high end dermal exposure resulting from applying granular with a belly grinder

2

Postapplication exposure represents high end dermal and incidental oral exposure for the relevant exposure duration
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3

For adults, residential total exposure combines the highest dermal and inhalation exposures (Table 6.1), where applicable. For 

young children, total residential exposure combines high end post application incidental oral AND dermal exposure, where 

applicable (Table 6.2). Handler exposures should not routinely be combined with post-application exposures. NOTE: The 

highest estimated total residential exposure (for adults and child populations) should be used as the basis of the aggregate 

calculation in section 7.

6.4 Residential Bystander Postapplication Inhalation Exposure

Based on the Agency's current practices, a quantitative post-application inhalation exposure 

assessment was not performed for pendimethalin at this time primarily because of the low acute 

inhalation toxicity (Toxicity Category IV). However, volatilization of pesticides may be a 

source of post-application inhalation exposure to individuals nearby pesticide applications. The 

Agency sought expert advice and input on issues related to volatilization of pesticides from its 

Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in 

December 2009, and received the SAP’s final report on March 2, 2010 

(http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The Agency is in the 

process of evaluating the SAP report and may, as appropriate, develop policies and procedures to 

identify the need for and, subsequently, the way to incorporate post-application inhalation 

exposure into the Agency's risk assessments. If new policies or procedures are developed, the 

Agency may revisit the need for a quantitative post-application inhalation exposure assessment 

for pendimethalin.

6.5 Spray Drift

Spray drift is always a potential source of exposure to residents nearby to spraying operations. 

This is particularly the case with aerial application, but, to a lesser extent, could also be a 

potential source of exposure from the ground application method employed for pendimethalin. 

The Agency has been working with the Spray Drift Task Force, EPA Regional Offices and State 

Lead Agencies for pesticide regulation and other parties to develop the best spray drift 

management practices (see the Agency’s Spray Drift website for more information at 

http://www.epa.gov/opp00001/factsheets/spraydrift.htm). On a chemical by chemical basis, the 

Agency is now requiring interim mitigation measures for aerial applications that must be placed 

on product labels/labeling. The Agency has completed its evaluation of the new database 

submitted by the Spray Drift Task Force, a membership of U.S. pesticide registrants, and is 

developing a policy on how to appropriately apply the data and the AgDRIFT computer model to 

its risk assessments for pesticides applied by air, orchard airblast and ground hydraulic methods. 

After the policy is in place, the Agency may impose further refinements in spray drift 

management practices to reduce off-target drift with specific products with significant risks 

associated with drift.

Although a quantitative residential postapplication inhalation exposure assessment was not 

performed as a result of pesticide drift from neighboring treated agricultural fields, an inhalation 

exposure assessment was performed for flaggers. This exposure scenario is representative of a 

worse case inhalation (drift) exposure and may be considered protective of most outdoor 

agricultural and commercial postapplication inhalation exposure scenarios. 

7.0 Aggregate Exposure/Risk Characterization
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In accordance with the FQPA, HED must consider and aggregate (add) pesticide exposures and 

risks from three major sources: food, drinking water, and residential exposures. In an aggregate 

assessment, exposures from relevant sources are added together and compared to quantitative 

estimates of hazard (e.g., a NOAEL or PAD), or the risks themselves can be aggregated. When 

aggregating exposures and risks from various sources, HED considers both the route and 

duration of exposure. For pendimethalin, potential exposures from food , drinking water, and 

residential scenarios were aggregated. This assessment has considered the changes in the new 

Residential Standard Operating Procedures (SOPs) implemented in January of 2012. 

7.1 Acute Aggregate Risk

The aggregate acute risk estimates include exposure to residues of pendimethalin in food and 

water, and does not include dermal, inhalation or incidental oral exposure. The acute risk 

estimate for the U.S. population and all other population subgroups, resulting from aggregate 

exposure to pendimethalin in food and drinking water, is below the Agency’s LOC. The food 

and drinking water exposure estimates are < 1% of the aPAD for the U.S. general population, 

and 2.0% for the most highly exposed life stage, children < 1 years old. 

7.2 Short-Term Aggregate Risk

There is potential short-term exposure to pendimethalin via dietary (which is considered 

background exposure) and residential (which is considered primary) exposure pathways. For 

adults, these pathways lead to exposure via oral (background) as well as dermal and inhalation 

(primary) routes. The most conservative scenario was chosen for each population (i.e. combined 

hand-to-mouth and dermal exposure from treated turf for children 1< 2 years old). For a 

description of the residential exposure scenarios considered in the aggregate assessment, see 

Section 6.0.

The adult (dermal) aggregate MOE (for males and females) is 125, which indicates that exposure 

and risk do not exceed HED’s level of concern (MOE > 30). The aggregate MOE for children 

1< 2 years old, including dermal and incidental oral exposures from treated turf is 93, which 

indicates that exposure and risk do not exceed HED’s LOC (MOE > 30). Further refinement 

using additional % CT estimates or more refined EDWCs may need to be incorporated in future 

assessments. 

Table 7.2 Short-Term Aggregate Risk Calculations for Pendimethalin

Life stage

Short-Term Scenario

NOAEL 

mg/kg/day LOC1

Max 

Allowable 

Exposure2

mg/kg/day

Average 

Food and 

Water 

Exposure 

mg/kg/day

Residential 

Exposure 

mg/kg/day3

Total 

Exposure 

mg/kg/day4

Aggregate 

MOE (food, 

water, and 

residential)5

Adult 10 30 0.33 0.001621 0.078 0.080 125

Child 10 30 0.33 0.004677 0.102 0.107 93

1

Intraspecies factor= 10x; Interspecies factor = 3x

2 Maximum Allowable Exposure (mg/kg/day) = NOAEL (10 mg/kg/day)/LOC (30)
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3 Child Residential Exposure = [Oral exposure (0.042 mg/kg/day) + Dermal exposure (0.060 mg/kg/day) =0.102 

mg/kg/day (Table 6.3.1)

4 Total Exposure = Avg Food & Water Exposure + Residential Exposure)

5 Adult (10 mg/kg/day)/ (Total Exposure (0.08 mg/kg/day)]; Child Aggregate MOE= 

(10 mg/kg/day)/ (Total Exposure (0.107 mg/kg/day)]

7.3 Chronic Aggregate Risk

Chronic exposure is not expected for the residential (dermal and inhalation) exposure pathway. 

Therefore, the chronic aggregate risk would be equivalent to the chronic dietary exposure 

estimate. Refer to Section 5.4.3 for the chronic dietary (food and drinking water) exposure 

assessment. 

7.4 Cancer Aggregate Risk

Pendimethalin is considered a “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 to demonstrate that the thyroid tumors are due to a thyroid-pituitary 

imbalance, and also since pendimethalin was shown to be non-mutagenic in mammalian somatic 

cells and germ cells. The chronic dietary risk assessment is considered to be protective of any 

cancer effects; as a result, a separate quantitative cancer aggregate risk assessment is not required

8.0 Cumulative Exposure/Risk Characterization

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 the purposes of this tolerance action, therefore, 

EPA has not assumed that pendimethalin has a common mechanism of toxicity with 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/.

9.0 Occupational Exposure/Risk Characterization

Pendimethalin: Occupational and Residential Exposure/Risk Assessment for Registration Review and for new Proposed Use on 

Leaf lettuce; Leafy brassica greens; Melons; Edamame; Kiwi and other small fruit vines, S. Shelat; B. Bobowiec, DP402406, 

05/31/2012.

9.1 Short-/Intermediate- Term Handler Risk

Pendimethalin is a selective herbicide used for controlling annual grass and broadleaf weeds that 

is generally applied early in the growing season as a pre-emergent and early post-emergent

herbicide. Application methods, maximum application rates and use sites are summarized in 

Table 3.3. Based on the proposed use pattern of pendimethalin there is a potential for short- and 
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intermediate-term occupational exposure during handling (mixing & loading) and limited postapplication activities (irrigation, scouting, harvesting). Chronic exposure is not expected for the 

proposed use patterns. PPE was assessed at baseline (long pants, a long-sleeved shirt, shoes, 

socks, no chemical-resistant gloves, and no respirator) as well as varying levels of personal 

protective equipment. HED evaluated the proposed uses as well as existing uses of 

pendimethalin. 

HED’s level of concern for the MOE is defined by the uncertainty factors that are applied to the 

assessment. HED applies a 3X factor to account for interspecies extrapolation and a 10X factor 

to account for intra-species sensitivity. The total uncertainty factor that has been applied to the 

non-cancer risk assessment for pendimethalin is 30X for occupational exposure. Occupational 

exposure and risk estimates resulting in MOEs greater than or equal to 30 will not be of concern 

to HED.

A quantitative dermal and inhalation exposure assessment was performed. Summaries of the 

short- and intermediate-term risks for occupational handlers applying pendimethalin to proposed 

and registered crops are included in Table 9.1.1 and Table 9.1.2 (dry bulk fertilizer uses). The 

results of the occupational handler exposure and risk assessment indicate that total short- and 

intermediate-term MOEs are not of concern to HED (i.e. an MOE > 30) with baseline attire for 

most uses, exception of the following exposure scenarios:

mixing and loading for chemigation and aerial application of alfalfa and sugarcane (MOE 

= 24)

mixing/loading/application with a handgun sprayer for drench application to turf grasses 

and ornamentals (MOE = 20)

commercial impregnation for dry bulk fertilizer for grape, kiwi, and other small fruit 

vines (MOE = 26)

These exposure scenarios were assessed with additional personal protective equipment. Risk 

estimates for these uses with gloves and/or respirators do not exceed HED’s level of concern 

(MOE ≥ 30) for the alfalfa, sugarcane, and the turf and ornamental scenario, however, no 

additional PPE can be assumed for the dry bulk fertilizer use because the commercial 

impregnation takes into account a closed system. Table 9.1.3 presents the exposure and risk 

estimates of the aforementioned scenarios with the incorporation of personal protective 

equipment.
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Table 9.1.1. Short-/Intermediate-Term Occupational Exposure and Risk Estimates for Pendimethalin (with baseline protection). 

Exposure Scenario Crop or Target

Application 

Rate 2

lb ai/A

Area Treated or 

Amount 

Handled Daily3

Unit Exposure (mg/lb 

ai)1 Dose (mg/kg/day)4 Short- and Intermediate-term MOEs5

Combined Short 

and 

Intermediateterm MOEs 7

Baseline6

Dermal 

Baseline6

Inhalation 

Baseline 

Dermal 

Baseline 

Inhalation 

Baseline 

Dermal 

Baseline 

Inhalation 

Mixer/Loader

Mixing/Loading 

Liquids for Aerial, 

and/or Chemigation, 

Applications 

(AHETF)

Bearing fruit and nut trees, 

non bearing fruit and nut 

trees and nonbearing 

vineyards, olive trees, 

artichoke, asparagus, 

clover, Bermuda grass

4 350 acres

0.22 0.000219

0.12 0.0038 87 2600 84

Alfalfa, Sugarcane 4 1200 acres 0.4 0.013 25 760 24

Corn and Cotton 2 1200 acres 0.2 0.0066 51 1500 49

fruiting vegetables, garlic, 

onion mineral soil, peanuts, 

potato, strawberry, 

artichoke, edible beans, 

fallow, lentil and peas, 

tobacco

1.5 350 acres 0.043 0.0014 230 7000 220

Carrots, green onion, 

brassica and stem 

vegetables, leafy brassica 

greens

1 350 acres 0.029 0.00096 350 10000 340

Sunflowers 1.75 350 acres 0.51 0.0017 200 6000

190

Vegetable soybean 

(edamame) 1.43 350 acres 0.41 0.0014 240 7300

230

Mint 2 350 acres 0.58 0.0019 170 5200

170

Wheat 1.5 1200 acres 0.15 0.0049 67 2000

65

Bearing and non-bearing 

grape, kiwi and other small 

fruit vines

6 350 acres 0.17 0.0057 58 1700

56

Rice and soybeans 1 1200 acres 0.099 0.0033 100 3000

98
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Table 9.1.1. Short-/Intermediate-Term Occupational Exposure and Risk Estimates for Pendimethalin (with baseline protection). 

Exposure Scenario Crop or Target

Application 

Rate 2

lb ai/A

Area Treated or 

Amount 

Handled Daily3

Unit Exposure (mg/lb 

ai)1 Dose (mg/kg/day)4 Short- and Intermediate-term MOEs5

Combined Short 

and 

Intermediateterm MOEs 7

Baseline6

Dermal 

Baseline6

Inhalation 

Baseline 

Dermal 

Baseline 

Inhalation 

Baseline 

Dermal 

Baseline 

Inhalation 

Mixing/Loading 

liquids for 

groundboom 

applications 

(AHETF)

Carrots for seed production, 

mint, onion muck soil 2 80 acres 0.013 0.00044 760 23000 730

Carrots, Green Onion, 

brassica head and stem 

vegetables, leafy brassica 

greens, and melons

1 80 acres 0.0066 0.00022 1500 46000 1500

Corn and Cotton 2 200 acres 0.033 0.0011 300 9100 290

Rice, soybeans 1 200 acres 0.017 0.00055 610 18000 590

Bearing fruit trees, non 

bearing fruit trees, and 

nonbearing vineyards, 

Olive trees, artichoke, 

asparagus, clover, 

bermudagrass

4 80 acres 0.026 0.00088 380 11000 370

Alfalfa, Sugarcane` 4 200 acres 0.066 0.0022 150 4600 150

Bearing and nonbearing 

grape, citrus trees, and kiwi

and other small vines

6 80 acres 0.04 0.0013 250 7600 240

Sunflowers 1.75 80 acres 0.012 0.00038 870 26000 840

Wheat 1.5 200 acres 0.025 0.00082 400 12000 390

Fruiting vegetables, garlic, 

onion mineral soil, peanuts, 

potato, strawberry, 

artichoke, edible beans, 

fallow, grain sorghum, 

lentils and peas, tobacco

1.5 80 acres 0.0099 0.00033 1000 30000 980
Pendimethalin Human Health Risk Assessment DP No. 390457

Page 35 of 71

Table 9.1.1. Short-/Intermediate-Term Occupational Exposure and Risk Estimates for Pendimethalin (with baseline protection). 

Exposure Scenario Crop or Target

Application 

Rate 2

lb ai/A

Area Treated or 

Amount 

Handled Daily3

Unit Exposure (mg/lb 

ai)1 Dose (mg/kg/day)4 Short- and Intermediate-term MOEs5

Combined Short 

and 

Intermediateterm MOEs 7

Baseline6

Dermal 

Baseline6

Inhalation 

Baseline 

Dermal 

Baseline 

Inhalation 

Baseline 

Dermal 

Baseline 

Inhalation 

Mixing/Loading 

Liquids for open cab 

airblast (AHETF)

Grape and citrus fruit and 

nut trees, kiwi and other 

small vines

6 40 acres

1.77 0.00471

0.02 0.00066 510 15000 490

Olive trees, asparagus 4 40 acres 0.013 0.00044 760 23000 730

Mixing/Loading 

Liquids for Aerial 

Applications 

(AHETF)

Turf 2 350 acres

0.22 0.000219

0.058 0.0019 170 5200 170

Ornamentals 4 350 acres 0.12 0.0038 87 2600 84

Loading Granules for 

Tractor-drawn 

broadcast spreaders

Applications (PHED)

Turf 2 80 acres

0.0084 0.0017

0.0005 0.0034 20000 2900 2600

Ornamentals 4 80 acres 0.001 0.0068 9900 1500 1300

Mixing/Loading 

Liquids for 

Groundboom

Applications 

(AHETF) 

Turf 2 80 acres

0.22 0.000219

0.013 0.00044 760 2300 730

Ornamentals 4 80 acres 0.026 0.0009 380 11000 370

Applicator

Applying Sprays via 

Aerial Equipment 

(PHED)

(engineered control)

Artichoke, bermudagrass, 

perennial grass for seed, 

asparagus

4 350 acres

0.005 0.000068

0.0026 0.0012 3800 8400 2600

Brassica head and stem 

vegetables, carrots, green 

onions, leafy lettuce

1 350 acres 0.00066 0.0003 15000 34000 10000

Mint 2 350 acres 0.0013 0.0006 7600 17000 5200

Sunflowers 1.75 350 acres 0.0011 0.00052 8700 19000 6000

Alfalfa, Sugarcane 41200 acres 0.009 0.0041 1100 2500 760
Pendimethalin Human Health Risk Assessment DP No. 390457

Page 36 of 71

Table 9.1.1. Short-/Intermediate-Term Occupational Exposure and Risk Estimates for Pendimethalin (with baseline protection). 

Exposure Scenario Crop or Target

Application 

Rate 2

lb ai/A

Area Treated or 

Amount 

Handled Daily3

Unit Exposure (mg/lb 

ai)1 Dose (mg/kg/day)4 Short- and Intermediate-term MOEs5

Combined Short 

and 

Intermediateterm MOEs 7

Baseline6

Dermal 

Baseline6

Inhalation 

Baseline 

Dermal 

Baseline 

Inhalation 

Baseline 

Dermal 

Baseline 

Inhalation 

Wheat 1.5 1200 acres 0.0034 0.0015 3000 6500 2000

Corn, and Cotton 21200 acres 0.0045 0.002 2200 4900 1500

Rice and Soybeans 11200 acres 0.0023 0.001 4400 9800 3100

fruiting vegetables, garlic, 

onion mineral soil, peanuts, 

potato, strawberry, edible 

beans, fallow, grain 

sorghum, lentils and peas, 

onions and shallots, 

vegetable soybean 

(edamame)

1.5 350 acres 0.00098 0.00045 10000 22000

7000

Applying Sprays via 

Groundboom 

Equipment (AHETF)

Wheat 1.5 200 acres

0.0786 0.00034

0.0088 0.0013 1100 7800 990

Bearing and non bearing 

grape and citrus and nut 

trees and kiwi and other 

small vines

6 80 acres 0.014 0.002 710 4900

620

Edible bean, fruiting 

vegetables, garlic, grain 

sorghum, lentil and peas, 

onions mineral soil, 

peanuts, potatoes, 

strawberry, no till 

sunflowers, tobacco, 

artichoke, fallow, 

1.5

80 acres

0.0035 0.00051 2800 20000

2500

Mint and onions 280 acres 0.0047 0.00068 2100 15000 1900

Corn and Cotton 2200 acres 0.012 0.0017 850 5900 740

Brassica head and stem 

vegetables, carrots, green 

onions, leafy lettuce, melon

1 80 acres 0.0024 0.00034 4200 29000 3700

Rice and soybeans 1200 acres 0.0059 0.00085 1700 12000 1500

Alfalfa, Sugarcane 4200 acres 0.024 0.0034 420 2900 370
Pendimethalin Human Health Risk Assessment DP No. 390457

Page 37 of 71

Table 9.1.1. Short-/Intermediate-Term Occupational Exposure and Risk Estimates for Pendimethalin (with baseline protection). 

Exposure Scenario Crop or Target

Application 

Rate 2

lb ai/A

Area Treated or 

Amount 

Handled Daily3

Unit Exposure (mg/lb 

ai)1 Dose (mg/kg/day)4 Short- and Intermediate-term MOEs5

Combined Short 

and 

Intermediateterm MOEs 7

Baseline6

Dermal 

Baseline6

Inhalation 

Baseline 

Dermal 

Baseline 

Inhalation 

Baseline 

Dermal 

Baseline 

Inhalation 

Bearing fruit trees, non 

bearing fruit trees and 

nonbearing vineyards, olive 

trees, artichoke, 

bermudagrass, clover, 

asparagus, olive tress

4 80 acres 0.0094 0.0014 1100 7400 930

Sunflowers 1.75 80 acres 0.0041 0.0006 2400 17000 2100

Applying Sprays via 

Open Cab Airblast 

(AHETF)

Grape, citrus fruit and nut 

trees and kiwi and other 

small fruit vines

6

40 acres 1.77 0.00471

0.16 0.014 63 710 58

Bearing fruit trees, Olive 

trees, asparagus 4 0.11 0.0094 94 1100 86

Applying Sprays via 

Aerial Equipment 

(PHED)

( Engineered Control)

Turf 2 350 acres 0.005 0.000068 0.0013 0.0006 7600 17000 5200

Applying Sprays via 

Aerial Equipment 

(PHED)

(Engineered Control)

Ornamentals 4 350 acres 0.005 0.000068 0.0026 0.0012 3800 8400 2600

Applying Sprays via 

Groundboom 

Equipment (AHETF)

Turf 2

80 acres 0.0786 0.00034

0.0047 0.00068 2100 15000 1900

Applying Sprays via 

Groundboom

Equipment (AHETF)

Ornamentals 4 0.0094 0.0014 1100 7400 930

Applying Granules 

via open cab solid 

broadcast spreader 

(PHED)

Turf Landscaping 2

0.0099 0.0012

0.00059 0.0024 17000 4200 3300

Ornamentals 4 80 acres 0.0012 0.0048 8400 2100 1700

Applying Granules 

via hand (PHED) Turf Landscaping 2 1 acre 104 0.47 0.078 0.012 130 850 110
Pendimethalin Human Health Risk Assessment DP No. 390457

Page 38 of 71

Table 9.1.1. Short-/Intermediate-Term Occupational Exposure and Risk Estimates for Pendimethalin (with baseline protection). 

Exposure Scenario Crop or Target

Application 

Rate 2

lb ai/A

Area Treated or 

Amount 

Handled Daily3

Unit Exposure (mg/lb 

ai)1 Dose (mg/kg/day)4 Short- and Intermediate-term MOEs5

Combined Short 

and 

Intermediateterm MOEs 7

Baseline6

Dermal 

Baseline6

Inhalation 

Baseline 

Dermal 

Baseline 

Inhalation 

Baseline 

Dermal 

Baseline 

Inhalation 

Ornamentals 4 1 acre 0.16 0.024 64 430 56

Mixer/Loader/Applicator

Mixing/Loading/App

lying Liquids with 

Backpack Sprayer 

broadcast 

Landscaping (turf) 

outdoor residential 

areas (AHETF)

Turf 2

40 gallons or 1 

Acre

8.26 .000258 0.0062 .000065 1600 160000 1600

Mixing/Loading/App

lying Liquids with 

Backpack Sprayer 

broadcast

Landscaping, 

Christmas tree farms

Landscaping , Christmas 

Tree Farms 4 13.2 0.14 0.02 0.007 510 1400 370

Mixer / Loader / 

Applicator, Backpack 

Sprayer Soil directed 

(drench 

treatments)(MRID 

44339801)

Turf 2

8.26 0.00258

0.0062 .000065 1600 160,000 1600

Nurseries, landscaping, 

Christmas tree farms 4 0.012 .000013 810 78000 800

Mixing/Loading/App

lying Liquids with 

Manually-pressurized 

Handwand (PHED)

Turf 2

100 0.03

0.075 0.00075 130 13000 130

Ornamentals, Orchards 4 0.15 0.0015 67 6700 66

Mixing/Loading/App

lying Liquids with 

Mechanicallypressurized Handgun

Sprayer soil directed 

(drench treatments) 

(MRID 45773201)

Turf 2 5 acres 4.31 3.931 0.016 0.49 620 20 20

Mixer / Loader / 

Applicator, 

Olive trees, Orchards, 

Ornamentals 4 5 acres 1.3 0.0039 0.0029(PPE-G)* 0.00098 3400(PPE-G)* 10000 2600
Pendimethalin Human Health Risk Assessment DP No. 390457

Page 39 of 71

Table 9.1.1. Short-/Intermediate-Term Occupational Exposure and Risk Estimates for Pendimethalin (with baseline protection). 

Exposure Scenario Crop or Target

Application 

Rate 2

lb ai/A

Area Treated or 

Amount 

Handled Daily3

Unit Exposure (mg/lb 

ai)1 Dose (mg/kg/day)4 Short- and Intermediate-term MOEs5

Combined Short 

and 

Intermediateterm MOEs 7

Baseline6

Dermal 

Baseline6

Inhalation 

Baseline 

Dermal 

Baseline 

Inhalation 

Baseline 

Dermal 

Baseline 

Inhalation 

Mechanicallypressurized Handgun 

Sprayer broadcast 

orchards, landscaping 

(non turf) (PHED)

Kiwi, grape, citrus trees 6

0.0044 

(PPE-G)* 0.0015 2300 (PPE-G) * 6800

1700

Mixer / Loader / 

Applicator, 

Mechanicallypressurized Handgun 

Sprayer broadcast 

Liquids Turf 

(ORETF)

Turf 2 1.14 0.0019 0.0033

(PPE-G)* 0.0002 3000(PPE-G)* 42000 2800

Mixer / Loader / 

Applicator, 

Mechanicallypressurized Handgun 

Sprayer broadcast 

water-dispersible 

granules Turf 

(ORETF)

Turf 2 1.96 0.042 0.0053

( PPE-G)* 0.0053 1900 1900 950

Loader / Applicator 

Ground "push-type" 

rotary spreader

Ornamentals 4

5 acres 0.4 0.01

0.003 0.0025 3333 4000 1800

Loader / Applicator 

Ground "push-type" 

rotary spreader

Turf 2 0.0015 0.0013 6700 8000 3600

Loader / Applicator 

Ground belly 

grinder

Turf 2

1 acres 100 0.0620

0.075 0.0016 130 6500 130

Loader / Applicator 

Ground belly 

grinder

Ornamentals 4 0.15 0.0031 67 3200 65

Flagger

Flagging for Aerial 

Sprays Applications 

(PHED)

sugarcane, alfalfa, 

artichoke, asparagus, 

bermudagrass

4

350 acres 0.011 0.00035

0.0058 0.0061 1700 1600 840

Corn, and Cotton, mint, 

onions, 2 0.0029 0.0031 3500 3300 1700
Pendimethalin Human Health Risk Assessment DP No. 390457

Page 40 of 71

Table 9.1.1. Short-/Intermediate-Term Occupational Exposure and Risk Estimates for Pendimethalin (with baseline protection). 

Exposure Scenario Crop or Target

Application 

Rate 2

lb ai/A

Area Treated or 

Amount 

Handled Daily3

Unit Exposure (mg/lb 

ai)1 Dose (mg/kg/day)4 Short- and Intermediate-term MOEs5

Combined Short 

and 

Intermediateterm MOEs 7

Baseline6

Dermal 

Baseline6

Inhalation 

Baseline 

Dermal 

Baseline 

Inhalation 

Baseline 

Dermal 

Baseline 

Inhalation 

Edible bean, fruiting 

vegetables, garlic, grain 

sorghum, lentil and peas, 

onions mineral soil, 

peanuts, potatoes, 

strawberry, no till 

sunflowers, wheat, 

vegetable soybean 

(edamame)

1.5 0.0022 0.0023 4600 4400

2200

Carrots, Green Onion, 

Rice, soybeans, brassica 

head and stem vegetables, 

leafy vegetables, leaf 

lettuce, leafy brassica 

greens

1 0.0014 0.0015 6900 6500

3400

Sunflowers 1.75 0.0025 0.0027 4000 3700 1900

Turf 20.0029 0.0031 3500 3300 1700

Ornamentals 40.0058 0.0061 1700 1600 840

1. Unit Exposures are taken from “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (September 26, 2011). 

2. Application Rate. = Maximum rate listed from labels

3. Units Treated are taken from “Standard Values for Daily Acres Treated in Agriculture”; ExpoSAC SOP No. 9.1. Revised September 25, 2001

4. Dose (mg/kg/day) = Unit Exposure (mg/lb ai) * Application Rate * Area treated or Amount handled Body Weight (80 kg). 

5. MOE (Margin of Exposure) = NOAEL/ Dose. Dermal NOAEL(ST and IT) = 10 mg/kg bw/day , Inhalation NOAEL (ST and IT) = 10 mg/kg bw/day 

6. Baseline = Long-sleeve shirt, long pants, and no gloves (dermal); no respirator (inhalation).

7Combined MOE = 1/ ((1/dermal MOE)+ (1/ inhalation MOE))

Table 9.1.2. Short-/Intermediate-Term Occupational Exposure and Risk Estimates for Pendimethalin Use on Dry Bulk Fertilizer

Exposure 

Scenario Crops

Dermal 

Unit 

Exposure

(mg/lb 

ai)1

Inhalation 

Unit 

Exposure

(mg/lb ai)1

Applicatio

n Rate2

Amount 

Treated 

Daily3

Dose (mg/kg/day)4 MOE5

Combined Short 

and Intermediateterm MOEs 6

Dermal Inhalati

on

Dermal

(LOC 

=30)

Inhalation

(LOC =30)

Mixer/Loader Liquids
Pendimethalin Human Health Risk Assessment DP No. 390457

Page 41 of 71

Table 9.1.2. Short-/Intermediate-Term Occupational Exposure and Risk Estimates for Pendimethalin Use on Dry Bulk Fertilizer

Exposure 

Scenario Crops

Dermal 

Unit 

Exposure

(mg/lb 

ai)1

Inhalation 

Unit 

Exposure

(mg/lb ai)1

Applicatio

n Rate2

Amount 

Treated 

Daily3

Dose (mg/kg/day)4 MOE5

Combined Short 

and Intermediateterm MOEs 6

Dermal Inhalati

on

Dermal

(LOC 

=30)

Inhalation

(LOC =30)

Commercial 

Impregnation 

of Dry Bulk 

Fertilizers

Alfalfa, Artichoke, 

Asparagus, Bearing 

Fruit Nut Trees, Non 

bearing fruit trees, 

sugarcane

0.0086

(closed 

system)

0.000083

(closed 

system)

40 lb 

ai/ton

960 tons 0.13 0.1 79 97 44

500 tons 0.074 0.06 140 170

75

Carrots and Carrots 

grown for seed 

production, Corn, 

Cotton, Mint, and 

onions,

Northern Grasses, 

Southern Grasses

20 lb ai/ton

960 tons 0.071 0.058 140 170 78

500 tons 0.037 0.03 270 330

150

Grape, Kiwi and other 

small fruit vines 60 lb ai/ton

960 tons 0.21 0.17 47 58 26

500 tons 0.11 0.09 91 110 50

Edible beans, fallow, 

fruiting vegetables, 

garlic, grain sorghum, 

lentil and peas, 

peanuts, potatoes, 

tobacco, wheat

15 lb ai/ton

960 tons 0.053 0.043 190 230 100

500 tons 0.028 0.023 360 440

200

Brassica head and 

stem vegetables,

9.5 lb 

ai/ton

960 tons 0.034 0.027 300 370 160

500 tons 0.017 0.014 570 700 320

Clover 38 lb ai/ton

960 tons 0.13 0.11 75 91 41

500 tons 0.07 0.057 140 180 79

Forage legumes 12 lb ai/ton

960 tons 0.042 0.035 240 290 130

500 tons 0.022 0.018 450 560 250

Green Onions, rice, 

soybeans, leaf lettuce, 

melons,

10 lb ai/ton

960 tons 0.035 0.029 280 350 160

500 tons 0.018 0.015 540 670 300

Strawberry, vegetable 

soybean

14.2 lb 

ai/ton lb 

ai/ton

960 tons 0.05 0.041 200 240 110

500 tons 0.026 0.021 380 470 210

17 lb ai/ton 960 tons 0.06 0.049 170 200 92
Pendimethalin Human Health Risk Assessment DP No. 390457

Page 42 of 71

Table 9.1.2. Short-/Intermediate-Term Occupational Exposure and Risk Estimates for Pendimethalin Use on Dry Bulk Fertilizer

Exposure 

Scenario Crops

Dermal 

Unit 

Exposure

(mg/lb 

ai)1

Inhalation 

Unit 

Exposure

(mg/lb ai)1

Applicatio

n Rate2

Amount 

Treated 

Daily3

Dose (mg/kg/day)4 MOE5

Combined Short 

and Intermediateterm MOEs 6

Dermal Inhalati

on

Dermal

(LOC 

=30)

Inhalation

(LOC =30)

Sunflowers 500 tons 0.031 0.026 320 390 180

Golf Course 

(commercial) 30 lb ai/ton

960 tons 0.11 0.086 94 120 52

500 tons 0.055 0.045 180 220 100

On-farm 

Impregnation 

of Dry Bulk 

Fertilizers

Alfalfa, Artichoke, 

Asparagus, Bearing 

Fruit Nut Trees, Non 

bearing fruit trees, 

sugarcane, 

ornamentals

0.22

Baseline

0.000219

Baseline

4 lb ai/A

160 A 0.053 0.0018 190 5700 180

80 A 0.026 0.00088 380 1100 370

Carrots and Carrots 

grown for seed 

production, Corn, 

Cotton, Mint, onions,

Northern Grasses, 

Southern Grasses

2.0 lb ai/A

160 A 0.026 0.00088 380 1100 370

80 A 0.013 0.00044 760 23000 730

Grape, Kiwi and other 

small fruit vines 6.0 lb ai/A 160 A 0.079 0.0026 130 3800 120

80 A 0.04 0.0013 250 7600 240

Edible beans, fallow, 

fruiting vegetables, 

garlic, grain sorghum, 

lentil and peas, 

peanuts, potatoes, 

tobacco, wheat

1.5 lb ai/A

160 A 0.02 0.00066 510 15000 490

80 A 0.0099 0.00033 1000 30000 980

Brassica head and 

stem vegetables 0.95 lb 

ai/A

160 A 0.013 0.00042 800 24000 770

80 A 0.0063 0.00021 1600 48000 1500

Clover 3.8 lb ai/A

160 A 0.05 0.0017 200 6000 190

80 A 0.025 0.00083 400 12000 390

Forage legumes 1.2 lb ai/A 160 A 0.016 0.00053 630 19000 610

80 A 0.0079 0.00026 1300 38000 1200

Green Onions, rice, 

soybeans, leaf lettuce, 

melons

1.0 lb ai/A

160 A 0.013 0.00044 760 23000 730

80 A 0.0066 0.00022 1500 46000 1500

Strawberry, vegetable 

soybean

1.42 lb 

ai/A

160 A 0.019 0.00062 530 16000 520

80 A 0.0094 0.00031 1100 3200 1000

Sunflowers 1.7 lb ai/A 160 A 0.022 0.00074 450 13000 430
Pendimethalin Human Health Risk Assessment DP No. 390457

Page 43 of 71

Table 9.1.2. Short-/Intermediate-Term Occupational Exposure and Risk Estimates for Pendimethalin Use on Dry Bulk Fertilizer

Exposure 

Scenario Crops

Dermal 

Unit 

Exposure

(mg/lb 

ai)1

Inhalation 

Unit 

Exposure

(mg/lb ai)1

Applicatio

n Rate2

Amount 

Treated 

Daily3

Dose (mg/kg/day)4 MOE5

Combined Short 

and Intermediateterm MOEs 6

Dermal Inhalati

on

Dermal

(LOC 

=30)

Inhalation

(LOC =30)

80 A 0.011 0.00037 890 27000 860

Golf Course 

(commercial)

0.22

Baseline 

0.000219

Baseline 3.0 lb ai/A 160 A 0.04 0.0013 250 7600 240

80 A 0.02 0.00066 510 15000 490

Applicator

Commercial 

Impregnation 

of Dry Bulk 

Fertilizers 

320-160 Acres

And

On-Farm 

Impregnation 

of Dry Bulk 

Fertilizer at 

160 and 80 

Acres

Alfalfa, Artichoke, 

Asparagus, Bearing 

Fruit Nut Trees, Non 

bearing fruit trees, 

sugarcane, 

ornamentals

0.0099

Baseline 

0.0012

Baseline 

4.0 lb ai/A

320 A 0.0048 0.019 2100 520 420

160 A 0.0024 0.0096 4200 1000 840

80 A 0.0012 0.0048 8400 2100 1700

Carrots and Carrots 

grown for seed 

production, Corn, 

Cotton, Mint, onions,

Northern Grasses, 

Southern Grasses

2.0 lb ai/A

320 A 0.0024 0.0096 4200 1000 840

160 A 0.0012 0.0048 8400 2100 1700

80 A 0.00059 0.0024 17000 4200 3300

Grape, Kiwi and other 

small fruit vines 6.0 lb ai/A

320 A 0.0071 0.029 1400 350 280

160 A 0.0036 0.014 2800 690 560

80 A 0.0018 0.0072 5600 1400 1100

Edible beans, fallow, 

fruiting vegetables, 

garlic, grain sorghum, 

lentil and peas, 

peanuts, potatoes, 

tobacco, wheat

1.5 lb ai/A

320 A 0.0018 0.0072 5600 1400 1100

160 A 0.00089 0.0036 1100 2800 2200

80 A 0.00045 0.0018 22000 5600 4500

Brassica head and 

stem vegetables .95 lb ai/A

320 A 0.0011 0.0046 8900 2200 1800

160 A 0.00056 0.0028 18000 4400 3500

80 A 0.00028 0.0011 35000 8800 7000

Clover 3.8 lb ai/A

320 A 0.0045 0.018 2200 550 440

160 A 0.0023 0.0091 4400 1100 880

80 A 0.0011 0.0046 8900 2200 1800

Forage legumes 1.2 lb ai/A

320 A 0.0014 0.0058 7000 1700 1400

160 A 0.00071 0.0029 14000 3500 2800

80 A 0.00036 0.0014 28000 6900 5600

Green Onions, rice, 1.0 lb ai/A 320 A 0.0012 0.0048 8400 2100 1700
Pendimethalin Human Health Risk Assessment DP No. 390457

Page 44 of 71

Table 9.1.2. Short-/Intermediate-Term Occupational Exposure and Risk Estimates for Pendimethalin Use on Dry Bulk Fertilizer

Exposure 

Scenario Crops

Dermal 

Unit 

Exposure

(mg/lb 

ai)1

Inhalation 

Unit 

Exposure

(mg/lb ai)1

Applicatio

n Rate2

Amount 

Treated 

Daily3

Dose (mg/kg/day)4 MOE5

Combined Short 

and Intermediateterm MOEs 6

Dermal Inhalati

on

Dermal

(LOC 

=30)

Inhalation

(LOC =30)

soybeans, leaf lettuce, 

melons

160 A 0.00059 0.0024 17000 4200 3300

80 A 0.0003 0.0012 34000 8300 6700

Strawberry, vegetable 

soybean

1.42 lb 

ai/A

320 A 0.0017 0.0068 5900 1500 1200

160 A 0.00084 0.0034 12000 2900 2400

80 A 0.00042 0.0017 24000 5900 4700

Sunflowers 1.7 lb ai/A

320 A 0.002 0.0082 5000 1200 980

160 A 0.0012 0.0041 9900 2500 2000

80 A 0.0005 0.002 20000 4900 3900

Commercial 

Impregnation 

of Dry Bulk 

Fertilizers 

320-160 Acres

And

On-Farm 

Impregnation 

of Dry Bulk 

Fertilizer at 

160 and 80 

Acres

Golf Course 

(commercial)

3.0 lb 

ai/A3.0 lb 

ai/A

320 A 0.0036 0.014 2800 690 560

160 A 0.0018 0.0072 5600 1400 1100

80 A 0.00089 0.0036 1100 2800 2200

1 Based on “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (September 26, 2011); includes data from PHED/ORETF/AHETF

2 Based on proposed labels for Pendimethalin (see Table 3.1 and 3.2 in Section 3.0)

3 Exposure Science Advisory Council Policy #9.1 and industry information.

4 Dose = Unit Exposure (ug/lb ai) x CF (0.001 mg/ug) x Application Rate (lb ai/acre or lb ai/ton) x Area Treated or Amount Handled (A/day or tons/day) / BW (80 kg).

5 MOE (Margin of Exposure) = NOAEL/ Dose. Dermal NOAEL(ST and IT) = 10 mg/kg bw/day , Inhalation NOAEL (ST and IT) = 10 mg/kg bw/day 

6Combined MOEs = 1/ (1/dermal MOE) + (1/inhalation MOE)

Table 9.1.3. Short-/Intermediate-Term Occupational Exposure and Risk Estimates for Pendimethalin with Additional Personal Protective Equipment

Exposure Scenario Crop or Target Applicatio

n Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Unit Exposure (mg/lb 

ai)1 Dose (mg/kg/day)4

Short- and 

Intermediate-term 

MOEs5

Combined Short and 

Intermediate-term 

MOEs 6

PPE-G

Dermal Inhalation PPE-GDermal Inhalation PPE-G Dermal Inhalation 

Mixer/Loader/Applicator
Pendimethalin Human Health Risk Assessment DP No. 390457

Page 45 of 71

Table 9.1.3. Short-/Intermediate-Term Occupational Exposure and Risk Estimates for Pendimethalin with Additional Personal Protective Equipment

Exposure Scenario Crop or Target Applicatio

n Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Unit Exposure (mg/lb 

ai)1 Dose (mg/kg/day)4

Short- and 

Intermediate-term 

MOEs5

Combined Short and 

Intermediate-term 

MOEs 6

PPE-G

Dermal Inhalation PPE-GDermal Inhalation PPE-G Dermal Inhalation 

Mixing/Loading Liquids for Aerial, and/or 

Chemigation, Applications 

(AHETF)

Alfalfa, 

Sugarcane

(high yield 

crops)

4 lb ai/A 1200 

Acres 0.0376 0.000219(Baseline) 0.068 0.013(Baseline) 150 760(Baseline) 120

Mixing/Loading/Applying Liquids with 

Mechanically-pressurized Handgun Sprayer 

soil directed (drench treatments) (MRID 

45773201)

Turf 2 lb ai/A 5 Acres 4.31

0.789

(PPE-R 

80%)

0.0062

0.098

(PPE-R 

80%)

620

100

(PPE-R 

80%)

87

1. Unit Exposures are taken from “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (September 26, 2011). 

2. Applic. Rate. = Maximum rate listed from labels.

3. Units Treated are taken from “Standard Values for Daily Acres Treated in Agriculture”; ExpoSAC SOP No. 9.1. Revised September 25, 2001.

4. Dose (mg/kg/day) = Unit Exposure (mg/lb ai) * Application Rate * Area treated or Amount handled Body Weight (80 kg). 

5. MOE = Margin of Exposure = NOAEL/ Dose. Dermal NOAEL(ST and IT) = 10 mg/kg bw/day , Inhalation NOAEL (ST and IT) = 10 mg/kg bw/day 

6. Combined MOE = 1/ (1/dermal MOE) + (1/inhalation MOE)
Pendimethalin Human Health Risk Assessment DP No. 390457

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9.2 Short-/Intermediate-Term Post-Application Risk

9.2.1 Dermal Post-application Risk

Pendimethalin is mainly used as a pre-emergent or early post-emergent herbicide. Pendimethalin 

is registered for post-emergent applications to the following crops; alfalfa, bearing fruit trees, 

bermudagrass, brassica head and stem vegetables, carrots, clover, corn, cotton, garlic, grain 

sorghum, grape vines, green onion, lentils, mint, olive trees, potatoes, rice, and strawberries, 

sugarcane, tobacco, wheat. The following proposed new uses also include post-emergent 

applications; leaf lettuce, leafy brassica greens, melons, and kiwi and other small fruit vines. 

Most of the applications made to post-emergent crops are not of concern because the application 

method is ground directed layby or between rows of production. The labels direct users to avoid 

contact with buds, vines, and crop foliage to limit crop damage. Additionally applications, such 

as on corn are restricted to certain growth stages of the crop and therefore most post-application 

activity would unlikely result in post-application exposure with the exception of scouting. These 

restrictions suggest that only few post-emergent crop applications would result in postapplication exposure, these include alfalfa, clover, cotton, green onions, grain sorghum, onions, 

potatoes, rice, and wheat. Pendimethalin application to golf course use sites will also result in 

exposure to occupational post-application workers. Of the proposed uses, Prowl ® H2O use on 

leaf lettuce and brassica greens may occur in the early growth stages of the crops. 

Chemical-specific DFR data were available for pendimethalin on sugarcane and tobacco. Since 

DFR data are not available for the proposed uses, the available data were used as surrogates. 

Based on a review of the available data, it was decided that the DFR data for sugarcane treated 

with PROWL 3.3 EC Herbicide in North Carolina would be used to represent non-foliar 

pendimethalin applications. It is believed that the sugarcane and tobacco data are representative 

of the non-foliar applications because the layby application (ground-directed spray) of an 

aqueous solution of PROWL 3.3EC herbicide was made to established (10-leaf, vegetative stage) 

sugarcane plants and a tractor-mounted cone tank application to established tobacco (10-12 leaf 

stage) was made to the tobacco plants. 

The data shows that the residues were determined to be less than the LOQ in all cases except for 

one detected at the DAT 0.5 time point on one of the triplicate samples from the tobacco plant. 

This information verifies that negligible post-application exposure is expected from non-foliar 

applications of pendimethalin. 

The post-application exposure scenarios that resulted from the application of pendimethalin to 

post-emergent crops were performed by using the default DFR value. The fraction of a.i. 

retained on foliage is assumed to be 25% (0.25) on the day of application (= % DFR, after initial 

treatment) for agricultural crops. This fraction is assumed to further dissipate at the rate of 10% 

(0.1) per day on following days. These are default values established by HED’s Science 

Advisory Council (SAC) for Exposure.

Table 9.2.1 presents the risk estimates for each of the foliar application scenarios and the 

corresponding highest transfer coefficient activity. 
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Table 9.2.1 Summary of Occupational Postapplication Risk Estimates for Pendimethalin

Crop/Site

Highest Transfer Coefficient for 

Crop (cm2/hr)

and Associated Activity

DFR Day 0 MOE Day at which MOE 

≥ LOC

Leafy lettuce, leafy 

brassica greens

4,200

(hand weeding) 2.244 350 0

Alfalfa, Cotton, Clover, 

Rice, Wheat

1,900 (alfalfa)

(Irrigation) 35.901 49 0

Grain, Sorghum, 1,900 (Irrigation) 8.98 200 0

Green onions, Onions 

mineral and muck soil, 

Potatoes

4,200

(Hand Weeding) 8.975 88 0

Brassica head and stem 

vegetables

4200

(scouting, hand harvesting, hand 

weeding)

2.244 350 0

Ornamentals

1900

(Irrigation) 35.901 49 0

a. Default DFR = 25% (0.25) x Application Rate on the day of application (DAT 0) for agricultural crops. These are default 

values established by HED’s Science Advisory Council (SAC) for Exposure.

b. Dermal Dose = [DFR (ug/cm2) x TC (cm2/hr) x 0.001 mg/ug x 8 hrs/day] body weight (80 kg).

c. MOE = NOAEL (10 mg/kg/day)/ Dermal Dose (mg/kg/day). 

TTR studies were used to assess the liquid and granular formulation scenarios. For the liquid 

formulation Determination of Transferable Turf Residue Dissipation from Turf Treated with 

Suspension Concentrate and Emulsifiable Concentrate Formulations of Pendimethalin (MRID 

466841-02) was utilized. Data were collected at three sites in the TTR study including 

Pennsylvania, Georgia, and California. Data from the Georgia site was used in this assessment 

as it resulted in the highest predicted Day 0 residues. For the granular formulation scenarios, two 

TTR studies were available for use: Determination of Transferable Residues of Dimethenamid-P 

and Pendimethalin on Turf Treated with Tower Herbicide and Freehand Herbicide (MRID 

47901302) and Determination of Transferable Residues in Turf Treated with Pendulum® 2G or 

Pendulum® WDG Herbicide (MRID No.44969901). In both studies, the Day 0 residues 

detected were generally at or below the LOQ (4.31 ng/cm2) with the exception of 7 days after 

treatment when residues averaged 17.5 ng/cm2at the Pennsylvania site in MRID 44969901. 

Data from the Pennsylvania site was used in this assessment as it resulted in the only detectable 

residue after application.

Table 9.2.2 presents the risk estimates for turf application scenarios.

Table 9.2.2. Dermal Post-application Exposure and Risk Estimate for Turf Applications Using TTR Data

Crop Group Proposed Crop

Transfer 

Coefficients 

(cm2/hr)

DAT Study Test 

Site

TTRa

(ug/cm2)

Dermal Doseb

(mg/kg/day)

MOEc

Liquid

Turf/Sod Turf, golf course

3700

(maintenance) 0 Georgia 0.47 0.005 1900
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Table 9.2.2. Dermal Post-application Exposure and Risk Estimate for Turf Applications Using TTR Data

Crop Group Proposed Crop

Transfer 

Coefficients 

(cm2/hr)

DAT Study Test 

Site

TTRa

(ug/cm2)

Dermal Doseb

(mg/kg/day)

MOEc

Turf Turf, sod farms

6700

(Harvesting, 

maintenance, 

transplanting)

0 Georgia 0.31 0.006 1600

Granular

Turf/Sod Turf, golf course

3700

(maintenance) 0 Pennsylvania 0.018 0.0002 50,000

Turf Turf, sod farms

6700

(Harvesting, 

maintenance, 

transplanting)

0 Pennsylvania 0.012 0.00024 41,000

a. For the liquid formulation, TTR values resulting from golf course applications (3 lbs ai/acre) are 0.47 ug/cm2and sod farm or 

turf applications (2 lbs ai/acre) are 0.31 ug/cm2. For the granular formulation, TTR values resulting from golf course applications 

(3 lbs ai/acre) are 0.018 ug/cm2and sod farm or turf applications (2 lbs ai/acre) are 0.012 ug/cm2. 

b. Dermal Dose = [DFR (ug/cm2) x TC (cm2/hr) x 0.001 mg/ug x 8 hrs/day] body weight (80 kg).

c. MOE = NOAEL (10 mg/kg/day)/ Dermal Dose (mg/kg/day). 

9.2.2 Inhalation Postapplication Risk

Based on the Agency's current practices, a quantitative post-application inhalation exposure 

assessment was not performed for pendimethalin at this time primarily because of the low acute 

inhalation toxicity (Toxicity Category IV). However, there are multiple potential sources of 

post-application inhalation exposure to individuals performing post-application activities in 

previously treated fields. These potential sources include volatilization of pesticides and 

resuspension of dusts and/or particulates that contain pesticides. The Agency sought expert 

advice and input on issues related to volatilization of pesticides from its Federal Insecticide, 

Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and 

received the SAP’s final report on March 2, 2010 

(http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The Agency is in the 

process of evaluating the SAP report as well as available post-application inhalation exposure 

data generated by the Agricultural Reentry Task Force and may, as appropriate, develop policies 

and procedures, to identify the need for and, subsequently, the way to incorporate occupational 

post-application inhalation exposure into the Agency's risk assessments. If new policies or 

procedures are put into place, the Agency may revisit the need for a quantitative occupational 

post-application inhalation exposure assessment for pendimethalin.

Although a quantitative occupational postapplication inhalation exposure assessment was not 

performed, an inhalation exposure assessment was performed for occupational/commercial 

handlers. Handler exposure resulting from application of pesticides outdoors is likely to result in 

higher exposure than postapplication exposure. Therefore, it is expected that these handler 

inhalation exposure estimates would be protective of most occupational postapplication 

inhalation exposure scenarios.
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10.0 References

Residue Chemistry References

Pendimethalin. Human Health Assessment for the Proposed Food Uses of the Herbicide on 

Artichoke, Globe; Asparagus; Brassica Head and Stem Vegetables, Subgroup 5A; and Grape 

(PP#6E7129). PC Code 108501; DP Barcode D334062; D. Rate; 08/22/07.

Pendimethalin. Human Health Risk Assessment for the Proposed Food/Feed Use of the 

Herbicide (Associated with Section 18 Registration) on Bermuda Grass and Hay Fields in Texas. 

PC Code 108501; DP Barcode D349723; W. Drew; 05/20/08. 

Pendimethalin. Human Health Risk Assessment for the Proposed Tolerance in/on Crayfish. PC 

Code 108501; DP Barcode D350493; C. Olinger; 03/31/08.

Pendimethalin. Discussion of Impurities. PC Code 108501; DP Barcode D386760; F. Fort.; 

06/01/11.

Pendimethalin: Petition for the Establishment of Permanent Tolerances and Registration for 

Use on Lettuce, Leaf; Brassica, Leafy Greens, Subgroup 5B, and Turnip Greens; Melon 

Subgroup 9A; Vegetable, Soybean; and Small Fruit Vine Climbing Subgroup 13-07E, Except 

Grape. Submission of Crop Field Trial Data on Green Onion and Wheat Processing Data in 

Response to DP#s 271502; 310793; 311825; 314085; 314093; 317047; 317053, Submission of 

Citrus Fruit Crop Field Trial and Processing Data in Response to DP# 238469, and Submission 

of Limited Field Accumulation in Rotational Crop Data in Response to DP# 319412. Summary 

of Analytical Chemistry and Residue Data. DP Barcode 372189; Y. Barnes; 6/5/12.

Drinking Water Assessment

Drinking Water Assessment for Proposed New Uses of Pendimethalin on Kiwi/small fruits, Leaf 

lettuce, Leafy brassica, Melon, and Edamame (edible soybeans); IR-4 Tolerance Petition E7878. 

DP Barcode D390459; W. P. Eckel; 02/23/2012

Dietary Exposure Assessment

Pendimethalin: Acute and Chronic Dietary (Food and Drinking Water) Analysis and Risk 

Assessment to Support New Use on Lettuce, Leaf; Brassica, Leafy Greens, Subgroup 5B, and 

Turnip Greens; Melon Subgroup 9A; Vegetable, Soybean; and Small Fruit Vine Climbing 

Subgroup 13-07E, except Grape. DP Barcode 401100.drs; Y. Barnes; 05/02/2012.

Occupational/Residential Assessment 

Pendimethalin: Occupational and Residential Exposure/Risk Assessment for Registration 

Review and for new Proposed Use on Leaf lettuce; Leafy brassica greens; Melons; Edamame; 

Kiwi and other small fruit vines. S. Shelat, B. Bobowiec; DP402406, 05/31/2012.
Pendimethalin Human Health Risk Assessment DP No. 390457

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Appendix A. Toxicology Profile and Executive Summaries

A.1 Toxicology Data Requirements

The requirements (40 CFR 158.340) for pendimethalin are in Table 1. Use of the new guideline numbers does not 

imply that the new (1998) guideline protocols were used.

TABLE A.1 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
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A.2 Toxicity Profiles

Table A.2.1 Acute Toxicity Profile- Pendimethalin

Guideline No. Study Type MRID(s) Results Toxicity 

Category

870.1100 Acute oral [Rat] 00026657 LD50=1250 mg/kg (m)

=1050 mg/kg (f)

III

870.1200 Acute dermal [Rabbit] 00026657 LD50= >1250 mg/kg IV

870.1300 Acute inhalation [Rat] 00073342 LC50= 32 mg/L IV

870.2400 Acute eye irritation [Rabbit] 00026657 Slight conjunctival 

irritation

III

870.2500 Acute dermal irritation [Rabbit] 00026657 No dermal irritation IV

870.2600 Skin sensitization [Guinea pig] 00153767 Non- sensitizer -

TABLE A.2.2 Subchronic, Chronic and Other Toxicity Profile for Pendimethalin.

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.
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TABLE A.2.2 Subchronic, Chronic and Other Toxicity Profile for Pendimethalin.

Guideline 

Number

Study Type MRID Number 

& Classification

Dose Levels Results

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 

with the rabbit 

developmental.

0, 125, 250, 500 

mg/kg/day Maternal NOAEL = 500 

mg/kg/day (highest dose 

tested).

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 

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.
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TABLE A.2.2 Subchronic, Chronic and Other Toxicity Profile for Pendimethalin.

Guideline 

Number

Study Type MRID Number 

& Classification

Dose Levels Results

dietary intake.

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. 

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
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TABLE A.2.2 Subchronic, Chronic and Other Toxicity Profile for Pendimethalin.

Guideline 

Number

Study Type MRID Number 

& Classification

Dose Levels Results

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%, 

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).

* NA = Not Applicable. 

 Note: Some of the LOAELs/NOAELS were previously denoted as LOELs/NOELS in Data Evaluation Records 

(DERs). The language was updated to comply with current standards without re-examining effects.

A.3 Hazard Identification and Endpoint Selection
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A.3.1 Acute Reference Dose (aRfD) - Females age 13-49

Study Selected: None

MRID No.: N/A

Executive Summary: None

Comments about Study/Endpoint/Uncertainty Factor(s): No appropriate endpoint 

attributable to a single exposure (dose) was identified from the oral toxicity studies including 

developmental toxicity studies in rats and rabbits. Therefore, an acute RfD was not established.

A.3.2 Acute Reference Dose (aRfD) - General Population

Study Selected: Acute neurotoxicity study in rats

MRID No.: 48695601

Executive Summary: See appendix, Guideline 870.6200.

Dose and Endpoint for Risk Assessment: NOAEL= 100 mg/kg based on reduced motor 

activity on day 0 at LOAEL= 300 mg/kg/day

Comments about Study/Endpoint/Uncertainty Factor(s): The effects were seen after a single 

oral dose which is appropriate for this exposure period of concern. The uncertainty factor (UF)

includes a 10X for intraspecies extrapolation and a 10X for interspecies extrapolation (used to 

account for animal to human differences in toxicokinetics and toxicodynamics).

A.3.3 Chronic Reference Dose (cRfD)

Study Selected: 92-day thyroid function in rats

 56-day thyroid function in rats

14-day intra-thyroid metabolism study in rats

MRID No.: 420554601, 43135001, 43135003 

Executive Summary: See appendix, 

Dose and Endpoint for Risk Assessment: NOAEL= 10 mg/kg based on thyroid effects at 

LOAEL= 31 mg/kg/day

Comments about Study/Endpoint/Uncertainty Factor(s): These three studies were considered 

together to select the dose and endpoint for establishing the chronic reference dose (cRfD). The 

cRfD is derived from the NOAEL of 10 mg/kg/day for thyroid effects based on hormonal and 

histological changes in the thyroid observed at the LOAEL of 31 mg/kg/day. The HIARC reaffirmed (9/7/99) that the 14-day NOAEL of 10 mg/kg/day reflects a true NOAEL for thyroid 

effects since these effects have been demonstrated to have early onset (before 14 days). On this 

basis, all studies were considered together for establishing the LOAEL at 31 mg/kg/day and the 

NOAEL at 10 mg/kg/day. The uncertainty factor (UF) includes a 10X for intraspecies 

extrapolation and a 3X for interspecies extrapolation (used to account for animal to human 

differences in toxicokinetics and toxicodynamics). The interspecies UF can be rduced because of 

several important quantitative dynamic differences between rats and humans with respect to 

thyroid function (Interim Guidance on Thyroid Disrupting Pesticides, dated 11/1/05).

A.3.4 Incidental Oral Exposure (Short- and Intermediate-Term)

Study Selected: 92-day thyroid function in rats
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 56-day thyroid function in rats

14-day intra-thyroid metabolism study in rats

MRID No.: 420554601, 43135001, 43135003 

Executive Summary: See appendix. 

Dose and Endpoint for Risk Assessment: NOAEL= 10 mg/kg based on thyroid effects at 

LOAEL= 31 mg/kg/day.

Comments about Study/Endpoint/Uncertainty Factor(s): The 14-day NOAEL of 10 

mg/kg/day reflects a true NOAEL for thyroid effects since these effects have been demonstrated 

to have early onset (before 14 days). On this basis, all studies were considered together for 

establishing the LOAEL at 31 mg/kg/day and the NOAEL at 10 mg/kg/day. HEDs level of 

concern (LOC) for pendimethalin incidental oral exposure is 30 (i.e., a margin of exposure 

(MOE) less than 30 exceeds HED’s level of concern) for occupational scenarios. The level of 

concern includes a 10X uncertainty factor (UF) for intraspecies extrapolation and a 3X UF for 

interspecies (used to account for animal to human differences in toxicokinetics and 

toxicodynamics).

A.3.5 Dermal Exposure (Short-, Intermediate- and Long-Term)

Study Selected: 92-day thyroid function in rats

 56-day thyroid function in rats

14-day intra-thyroid metabolism study in rats

MRID No.: 420554601, 43135001, 43135003 

Executive Summary: See appendix. 

Dose and Endpoint for Risk Assessment: NOAEL= 10 mg/kg based on thyroid effects at 

LOAEL= 31 mg/kg/day.

Comments about Study/Endpoint/Uncertainty Factor(s): Based on the results of the thyroid 

studies in rats discussed above under chronic RfD, short-term (1-7 days), intermediate-term (one week to 

several months), and long-term/chronic (90 days or more) occupational and residential exposure estimates 

should be compared to the NOAEL of 10 mg/kg/day established in the 14-day intra-thyroidal study. The 

LOAEL of 31 mg/kg/day (LDT), from the 56-day thyroid study, is based on several hormonal and 

histological thyroid changes and thyroid hormonal effects occurred as early as day 3). Since an oral 

NOAEL was selected, 3% dermal absorption factor should be used for route-to-route 

extrapolation. HEDs level of concern (LOC) for pendimethalin dermal exposure is 30 (i.e., a 

margin of exposure (MOE) less than 30 exceeds HED’s level of concern) for occupational 

scenarios. The level of concern includes a 10X uncertainty factor (UF) for intraspecies 

extrapolation and a 3X for interspecies extrapolation (used to account for animal to human 

differences in toxicokinetics and toxicodynamics).

A.3.6 Inhalation Exposure (Short-, Intermediate- and Long-Term) 

Study Selected: 92-day thyroid function in rats

 56-day thyroid function in rats

14-day intra-thyroid metabolism study in rats

MRID No.: 420554601, 43135001, 43135003 

Executive Summary: See appendix. 

Dose and Endpoint for Risk Assessment: NOAEL= 10 mg/kg based on thyroid effects at 

LOAEL= 31 mg/kg/day
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Comments about Study/Endpoint/Uncertainty Factor(s): Except for an acute inhalation 

toxicity study (MRID# 00073342) for which pendimethalin was placed in toxicity Category IV 

(LC50 > 32 mg/L); no other studies are available via this route. HEDs level of concern (LOC) for 

pendimethalin inhalation exposure is 30 (i.e., a margin of exposure (MOE) less than 30 exceeds 

HED’s level of concern) for occupational scenarios. The level of concern includes a 10X 

uncertainty factor (UF) for intraspecies extrapolation and a 3X for interspecies extrapolation

(used to account for animal to human differences in toxicokinetics and toxicodynamics). Since 

the dose identified is from an oral study, route-to-route extrapolation is required as follows.

Step I: Convert the inhalation exposure (μg/lb ai) using 100% inhalation 

absorption rate, application rate and acres treated and to an oral

equivalent dose (mg/kg/day).

Step II: Convert the dermal exposure (mg/kg/day) using 3% dermal 

absorption rate, application rate and acres treated to an oral 

equivalent dose (mg/kg/day). This dose should be combined with 

the converted oral dose in Step I.

Step III: To calculate the MOE’s, the combined dose from Step II should 

then be compared to the oral NOAEL of 10 mg/kg/day for any 

time period. 

A.4 Executive Summaries

A.4.1 Subchronic Toxicity

In a special 92-day thyroid function feeding study (MRID 42054601), AC 92,553 

(pendimethalin, 92.6%, Lot #AC5213-72A) was administered to groups of 80 male 

CD[Crl:CD(SD)] rats at dose levels of 0, 100, or 5,000 ppm (corresponding to 0, 4.98, or 245.4 

mg/kg/day) for 92 days. Groups of 20 male rats were sacrificed at 15, 29, 57 and 92 days. At 100 

ppm there was decreased total T4, T3, total free T4 and increased percent T3, increased follicular 

cell height and decreased area occupied by colloid. At 5,000 ppm there were decreased body 

weight and food consumption compared to controls, increased thyroid weight, decreased total 

T4, total T3, rT3, total free T4 and [125I]-T4 to transthyretin bonding, increased percent free T4 , 

percent free T3 and [125I]-T4 to albumin binding, increased follicular cell height and decreased 

area occupied by colloid and ultrastructural thyroid changes. Most parameters were reversible 

after treatment subsided except for decreased body weight. The NOAEL was established at 100 

ppm (4.98 mg/kg/day). The LOAEL was determined to be 5000 ppm.

In a special 56-day feeding study (28-day treatment, 28-day recovery) to determine thyroid 

function (MRID 43135001), groups of 65- 70 (5-15 per sacrifice time) male Crl:CD(SD) rats 

were treated at dose levels of 0, 500 or 5000 ppm (0, 31 or 292 mg/kg/day) of AC 92,553 

(pendimethalin, 92.6%, Lot #AC5213-72A) in the diet for 28 days. A recovery period of up to 28 

days was employed. Animals were sacrificed at many time points during the study beginning as 

early as day 3.There were no deaths or clinical signs of toxicity during or after the treatment 

period at either dose. At 500 ppm there was decreased total T4 (38%), rT3 (25%) and total free 
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T4 (28%) and increased percent free T3 (13%), increased follicular cell height (40%) and 

decreased area occupied by colloid (51%) during treatment. At 5000 ppm, body weight (8%), 

body weight gain (29%) and food consumption (15%) were decreased compared to controls 

during the treatment period. Thyroid changes during treatment with 5000 ppm included: 

increased absolute (15%) and relative (23%) thyroid weight; decreased total T4 (74%), total T3 

(25%), rT3 (36%), total free T4 (40%), and [ 125 I]-T4 to transthyretrin binding; increased 

percent free T4 (117%), percent free T3 (26%) and [ 125 I]-T4 to albumin binding; increased 

follicular cell height (75%) and decreased area occupied by colloid (45%); ultrastructural thyroid 

changes were consistent with mild to moderate TSH stimulation except for the accumulation of 

dense-bodies in the cytoplasm which may be reaction products of AC 92,553. Many of these 

effects were observed as early as day 3. Most parameters were reversible post treatment except 

for a slight decreased body weight compared to controls (7%) at 5000 ppm. There were no 

changes in TSH, total free T3 or diameter of follicular cells. The LOAEL was 500 ppm (31 

mg/kg/day) based on thyroid effects. The NOAEL could not be determined.

In a special 14-day feeding study to determine thyroid function (MRID 43135003), AC 92,553 

(pendimethalin, 92.6%, Lot #AC5213-72A) was administered in the diet to groups of 10 male 

Crl:CD(SD) rats at dose levels of 0, 100 or 5,000 ppm (corresponding to 0, 10 or 500

mg/kg/day). At 5000 ppm AC 92, 533 for 14 days, TSH was increased and T4 and T3 were 

decreased. No treatment related effects were observed for rT3 levels, thyroid weight, 131I uptake 

in MIT, DIT or T4. There was a significant increase of 131I uptake by the thyroid of rats in the 

5000 ppm group and an increase in incorporation of 131I in T3. Total T3 and T4 levels in the 

thyroid were not affected by treatment at 5,000 ppm. The LOAEL is 5,000 ppm (500 

mg/kg/day) based on thyroid effects. The NOAEL is 100 ppm (10 mg/kg/day).

In a second special 14-day feeding study (MRID 43135004) to determine biliary excretion and 

hepatic metabolism, AC 92,553 (pendimethalin, 92.98%, Lot #AC6539-77A) was administered 

to groups of 10 male Crl:CD(SD) rats at dose levels of 0, 100, or 5,000 ppm (corresponding to 0, 

10, or 500 mg/kg/day). Ingestion of 5,000 ppm produced decreases in serum T3 and T4 with a 

compensatory increase in TSH. Also increased were liver weight, bile flow and cumulative 

biliary excretion of 125I-T4 with a slight increase in T4 -glucuronytransferase activity detected by 

generation of 125I-T4 glucuronide from 125I-T4 in vitro by hepatic microsomes. The increase in 

enzyme activity was also demonstrated in vivo by a significant increase in biliary excretion of 

125I-T4 -glucuronide. The LOAEL is 5,000 ppm (500 mg/kg/day) based on thyroid effects. 

The NOAEL is 100 ppm (10 mg/kg/day).

These studies are Acceptable when used in combination and satisfy the requirements for a 

chronic feeding study in rats. 

A.4.2 Prenatal Developmental Toxicity

870.3700a Prenatal Developmental Toxicity Study - Rat

In a developmental toxicity (MRID 00025752), pendimethalin (94.2% a.i.) was administered in 

corn oil to groups of 30 mated Sprague-Dawley CD strain rats by gavage at daily dose levels of 

0, 125, 250, or 500 mg/kg/day from gestation day 6 through 15. Females were observed for 
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signs of toxicity, and body weights were measured during gestation. Animals were sacrificed on 

gestation day 21 and examined grossly and microscopically. The uteri were examined for live 

fetuses and intra-uterine deaths. Fetuses were weighed, sexed, and examined for external, 

visceral, and skeletal alterations. There were no maternal or developmental effects noted at any 

dose level tested. Based on these results, the NOAELs for developmental and maternal 

toxicity are 500 mg/kg/day (highest dose tested).

This study is classified as acceptable and satisfies the Subdivision F guideline requirement for a 

prenatal developmental toxicity study in rats.

870.3700b Prenatal Developmental Toxicity Study - Rabbit

In a developmental toxicity (MRID 00117444), pendimethalin was administered in corn oil to 

groups of 20 artificially inseminated New Zealand White strain rabbits by gavage at dose levels 

of 0, 15, 30, or 60 mg/kg/day from gestation day 6 through 18. Females were observed for signs 

of toxicity, and body weights were measured during gestation. Animals were sacrificed on 

gestation day 29. The rabbits were examined grossly and microscopically. The uteri were 

examined for live fetuses and intra-uterine deaths. Fetuses were weighed, sexed, and examined 

for external, visceral, and skeletal alterations. No maternal toxicity was reported at doses 60 

mg/kg/day (highest dose tested). 

There was a slight increase in the mean incidence of skeletal anomalies in the mid- and highdose groups. These findings included less than twelve pairs of ribs (0/111, 1/118 and 4/107 

fetuses in the control, mid-, and high-dose groups, respectively, not statistically significant) 

and/or missing or incompletely ossified vertebrae (0/111, 1/118 and 7/107 fetuses in the control, 

mid and high dose groups, respectively). When compared to historical control data of the testing 

lab, skeletal anomalies observed in the mid- and high-dose groups were within the range and the 

mean of the historical incidence. Therefore, it was determined that these effects are not 

treatment-related. Consequently, the NOAEL for developmental toxicity was >60 mg/kg/day 

(HDT).

In the range-finding study (Accession No. 00248659), New Zealand White rabbits received 

pendimethalin in corn oil at doses of 0, 31.25, 62.5, 125, 250 or 500 mg/kg/day during gestation 

days 6 thru 18. Maternal toxicity was manifested as mortality and decreases in body weight gain 

at doses 62.5 mg/kg/day and above. Mortality occurred in 1/5 (20%) , 3/5 (60%) , 5/5 (100%) 

and 4/5 (80%) in the 62.5, 125, 250, and 500 mg/kg/day, respectively compared with 0/5 in the 

control group. In addition, the two remaining females at the 125 mg/kg/day group aborted prior 

to gestation day 29 and were sacrificed. Mean body weight losses for the control, 31.25, 62.5, 

125, 250, or 500 mg/kg/day groups were 56, 289, 242, 720, 918 and 492 grams, respectively. 

Thus, based on the mortality and the severe body weight losses, it is apparent that at dose levels 

of 125 mg/kg/day and above, pendimethalin is toxic to pregnant rabbits. Consequently, it was 

determined that the 60 mg/kg/day dose tested in the main study approached a maximum tolerated 

dose and the dams could not have tolerated higher doses.

A.4.3 Reproductive Toxicity
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In a 2-generation reproduction study (MRID 417252203), AC 92,533 (pendimethalin, 92.6%, 

Lot #AC5213-72A) was administered to groups of 25 male and 25 female Sprague-Dawley 

derived OFA-SD (IOPS-CAW) rats at dose levels of 0, 500, 2500 or 5000 ppm (corresponding to 

0, 25, 125 and 250 mg/kg/day). 

There were no clinical signs or changes in organ weight data. There was a minimal (5%) 

decrease in body weight gain and food consumption (possibly due to palatability) at 2500 ppm. 

At 5000 ppm, the decrease in body weight gain (13%) and food consumption (approximate 

8%/14% males/females, respectively). At 2500 mg/kg/day, body weight gain decreases (7%) 

were observed. There were decreases in food consumption of 10/15% in males/females, 

respectively). 

At 5000 and 2500 ppm, the mean numbers of pups born were significantly decreased compared 

to controls at 21% and 15%, respectively. Mean pup weights were decreased during lactation at 

5000 ppm (10 - 21%) and 2500 ppm (7 - 11%).

The parental NOAEL is 500 ppm (25 mg/kg/day), based on decreased body weight gain and 

food consumption at the LOAEL of 2500 ppm. The reproductive NOAEL is 500 ppm (25 

mg/kg/day), based on decreases in the number of pups born and pup body weights at the 

LOAEL of 2500 ppm (125 mg/kg/day).

This study is acceptable according to guidelines for a reproductive toxicity study in rats.

A.4.4 Chronic Toxicity

870.4100a (870.4300) Combined Chronic/Carcinogenicity – Rat

In a 2-year study in rats (MRID 40174401), AC 92,533 (pendimethalin, 91.9%, Lot #AC3528-

129-1), was administered to groups of 55 male and 55 female Crl:CD(SD)BR rats in the diet at 

levels of 0, 100, 500 or 5,000 ppm (corresponding to 0, 5, 25, or 250 mg/kg/day). Ten 

rats/sex/group were interim sacrificed as 12 months. At 5,000 ppm, survival in males was 

slightly decreased and body weight gain was decreased. There was decreased food consumption, 

increased gamma glutamyl transferase and cholesterol, increases in liver weight, as well as liver 

to body and/or brain weight ratios, generalized uterus, dark adipose tissue in females, diffusely 

dark thyroids, and follicular cell hyperplasia of the thyroid. At 500 ppm there was pigmentation 

of the thyroid follicular cells in males and females and follicular cell adenomas. The NOAEL is 

500 ppm (25 mg/kg/day). The LOAEL of 5000 ppm (250 mg/kg/day) is based on decreased 

survival, body weight gain and food consumption, increased gamma glutamyl transferase 

and cholesterol, increase in absolute and/or relative liver weight, generalized uterus, dark 

adipose tissue in females, diffusely dark thyroids and follicular cell hyperplasia of the 

thyroid. 

A.4.5 Carcinogenicity

870.4200a Carcinogenicity Study – rat
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See A.4.4

870.4200b Carcinogenicity (feeding) – Mouse

In an 18-month feeding study in mice (MRID 40909901),AC 92,533 (pendimethalin, 92.6%, Lot 

#AC5218-72A) was administered to groups of 65 male and 65 female Charles River CD-1 mice 

at dose levels of 100, 500, or 5,000 ppm (corresponding to 12.3, 62.3 and 622.1 mg/kg/day in 

males and 15.6, 78.3 and 806.9 mg/kg/day in females). There were 2 control groups consisting 

of 65 mice/sex. Ten mice/sex were sacrificed at 12 months in 1 control and all treated groups. 

(One control group only consisted of 55 mice/sex.) At 5,000 ppm there was increased mortality 

in females, decreased body weight in females, increased absolute thyroid, liver and gall bladder 

weights and/or relative body and brain weight ratios in males and females as well as amyloidosis 

in males. There were no tumors observed in mice. The LOAEL is 5,000 ppm (622.1 mg/kg/day 

[M]; 806.99 mg/kg/day [F]) based on mortality, body weight decrease, organ weight changes and 

amyloidosis. The NOAEL is 500 ppm (62.3 mg/kg/day [M]; 78.3 mg/kg/day [F]).

A.4.6 Mutagenicity

Mutagenicity tests were performed on pendimethalin and included acceptable studies for 

all three categories (gene mutations, structural chromosome aberrations and other genotoxic 

effects) which satisfied the 1991 mutagenicity guidelines. The Cancer Peer Review Committee

had reviewed these studies and concluded that it was not mutagenic in mammalian somatic cells 

and germ cells. The studies included 3 reverse gene mutation tests using Salmonella, 2 forward 

mutation studies using Chinese hamster ovary cells, 1 micronucleus test in mice, one dominant 

lethal assay, and one DNA repair test. All mutagenicity tests were negative for mutagenic 

effects.

Gene Mutation

870.5100, Reverse gene mutation assay 

[Bacterial strains of S. typhimurium]

MRID 00153768

μg/plate = 50, 158, 500, 1581, 5000

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]

MRID 43177801

μg/plate = 25, 50, 100, 250, 500, 750

Negative

870.5100, Reverse gene mutation assay 

[Escherichia coli]

MRID 43135005

50, 158, 500, 1581, 5000 μg/plate or 1000 

μg/paper disk/plate

Negative

870.5100, Reverse gene mutation assay 

[Escherichia coli WP2]

MRID 43135006

μg/plate = 50, 100, 250, 500, 750

Negative
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870.5300, Mammalian cell gene mutation 

[Chinese hamster ovary]

MRID 43177802

μg/plate = 1, 5, 7.5, 10, 20, 30, 40, 50 (-

S9)

μg/plate = 10, 25, 50, 75, 100, 125, 150, 

175 (+S9)

Negative

Cytogenetics

870.5395, Micronucleus study 

[Mouse]

MRID 42027801

313, 625, 1250 mg/kg

Negative

Chromsomal Aberration

870.5375, Chromosomal aberration 

[Chinese hamster ovary]

MRID 00153770

Dose ranging from 5-50 μg/mL

Negative

Other Genotoxicity

870.5550,Alkaline elution assay (Rat)

MRID 43135007

1250, 2500, 5000 mg/kg

Negative

A.4.7 Neurotoxicity

870.6200 Acute Neurotoxicity Screening Battery

In an acute neurotoxicity study (MRID 48695601), pendimethalin (BAS 455 H, 93.3±1.0 % a.i., 

batch # COD-001337) was administered by a single oral gavage (5 ml/kg) dose in corn oil to 

groups of male and female, non-fasted Wistar (Crl:WI, Han) rats (10/sex/dose) at doses of 0, 

100, 300, or 1000 mg/kg bw and observed for 14 days. Neurobehavioral assessment (functional 

observational battery and motor activity testing) was performed on all animals prior to test 

substance administration (Day -7), on the day of treatment (Day 0), and on Days 7 and 14. At

study termination (Day 15), 5 animals/sex/group were fixed by in situ perfusion under deep 

anesthesia with isoflurane and subjected to neuropathological examinations. The remaining 

animals were sacrificed using CO2 without further examination. The brain and peripheral 

nervous system tissues collected from the perfused animals in the control and 1,000 mg/kg 

groups were subjected to histopathological evaluation. 

All animals survived to the scheduled necropsy, except for one female in the 1,000 mg/kg group 

which was sacrificed due to moribund condition on Day 1.

No adverse, treatment-related effects were observed on general clinical observations or mean 

body weights at any dose level in males and females, throughout the study, however mean body 

weight gain between Days 0-7 in the male 1,000 mg/kg group was significantly lower (↓19%) 
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than the control group. Clinical signs were observed in only two females of the 1,000 mg/kg 

group and included abdominal position, red encrusted eye, labored respiration, semi-closed 

eyelids and poor general state. One of these two females was moribund and was sacrificed on 

Day 1 after treatment while the other female still showed slight poor general state but survived to 

scheduled sacrifice on Day 14.

Treatment-related FOB findings were observed in the 1,000 mg/kg group on Day 0 (post-dosing)

in males and females, but not on Days 7 and 14; thus, observed effects were transient. The 

following test substance-related findings were obtained in the 1,000 mg/kg group males: 

chromodacryorrhea, slight impairment of coordination, piloerection and urine discoloration. At 

300 mg/kg, urine discoloration occurred in one male rat on Day 0 and hypothermia was observed 

in another male on Day 7. At 100 mg/kg, accelerated respiration was observed in one male 

animal on Day 0 only, and vocalization was also noted in one male on Days 0 and 14, but not 

Day 7. These findings in the 100 mg/kg male group were considered to be incidental. In female 

animals, FOB findings were only observed on Day 0 at dose levels of 300 and 1,000 mg/kg and 

included squatting posture, slight eyelid closure, and slight impairment of coordination, severe 

reduced exploration of the area (apathetic animal) and urine discoloration. The eyelid closure and 

the discoloration of urine were observed in more animals in the 1,000 mg/kg group than the 300 

mg/kg group. All of these effects in females were reversible, as they were not present on Days 7 

and 14.

Forelimb grip strength was significantly (p≤0.01) reduced by ↓22% in males at the dose level of 

1,000 mg/kg on Day 0, but not in females at any dose level. In addition, hind limb grip strength, 

rearing and landing foot splay were unaffected by test substance in either sex throughout the 

exposure period. Only on Day 0, overall mean motor activity was significantly (p≤0.01) reduced 

by ↓59% in males at the dose level of 1,000 mg/kg and by ↓51% and ↓75% in females at dose 

levels of 300 and 1,000 mg/kg, respectively. These effects were also transient, as they had 

resolved by Day 7.

No test substance-related alterations were observed in gross histopathology observations or 

microscopic neurohistopathology in the 1,000 mg/kg male and female groups.

It is concluded that the reversible effects observed in males and females can be explained by 

impairment of the overall condition of the animals following treatment, rather than direct 

neurotoxic effects of the Pendimethalin exposure. This conclusion is based on the absence of 

any neurohistopathological changes in the treated animals and the transient nature of the 

observed FOB and neurobehavioral assessments. 

Based on the results of this study, the NOAEL for acute neurotoxicity of Pendimethalin is 

100 mg/kg body weight for males and females. The LOAEL for acute neurotoxicity is 300 

mg/kg body weight, based on reduced motor activity for males and females (↓19 and ↓51%, 

respectively, on Day 0. 

The study is classified as acceptable/guideline and satisfies the guideline requirement (OPPTS 

870.6200a; OECD 424) for an acute neurotoxicity study in rats.
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870.6200 Subchronic Neurotoxicity Screening Battery

In a subchronic neurotoxicity oral (dietary) study (MRID 48695602), pendimethalin (99.9% a.i., 

batch/lot # FH20726) was administered to Wistar (CrlGlxBrlHan:WI) rats (10/sex/group) at dose 

levels of 0, 600, 1800, or 5400 ppm (equivalent to 0, 42.0/50.1, 126.5 / 151.9, 386.8/423.1 mg/kg 

bw/day [M/F], respectively) for 3 months. Neurobehavioral assessment (functional 

observational battery and motor activity testing) was performed in all animals at pre-dosing (Day 

-7) and Days 1, 22, 50 and 85. Ophthalmology exams were conducted on all animals prior to 

dosing and on the control and 5000 group at the end of the study. Hematology and clinical 

chemistry parameters along with select organ weights and gross histopathology observations 

were also determined on 5/sex/group. At study termination, 5 animals/sex/group were 

euthanized and perfused in situ for neuropathological examination. The brain and peripheral 

nervous system tissues collected from the perfused animals in the control and 5400 ppm groups 

were subjected to microscopic histopathological evaluation. 

All animals survived to the scheduled necropsy. No adverse, permanent treatment-related effects 

were observed on general clinical observations, ophthalmology, FOB findings, or motor activity 

at any dietary concentration level in males and females. Only transient decreases (↓31%) in 

motor activity were observed only on Day 1 in males and females in the 5400 ppm groups. In 

addition, there were no test substance-associated alterations observed in brain weights, gross 

histopathology observations or microscopic neurohistopathology findings in the 5400 ppm (high 

dose) male and female groups.

Treatment-related effects on body weights and body weight gains were evident at the dietary 

concentration level of 5400 ppm in males and females throughout the study. Body weights were 

significantly (p≤0.05 or p≤0.01) reduced by 6%-12% and 7%-13% in males and females, 

respectively, throughout the treatment period. Body weight gains were also decreased (p≤0.01) 

in males (↓19% - 25%) and females (↓29% - 51%) throughout the treatment period. No 

significant differences in body weights were noted in males at dietary concentration level of 600 

or 1800 ppm. Body weight and body weight gains were also decreased in females in the 1800 

ppm group, but no differences were noted in the 600 ppm female group. 

Treatment related-effects on food consumption were noted at 5400 ppm in males (Days 7, 21-35, 

56 and 70) and females (Days 7 though 91). At 5400 ppm, lower (p≤0.05 or p≤0.01) food 

consumption ranged from ↓8% to ↓10% on Days 7, 21-35, 56 and 70 in males and from ↓16% to 

↓22% in females on Day 7 though the end of the treatment period (Day 91), when compared to 

the controls. No treatment-related effects on food consumption were observed at 600 and 1800 

ppm in males or at 600 ppm in females.

Treatment-related effects on hemoglobin, hematocrit and red blood cell count were noted in the 

1800 and 5400 ppm group females, but not in males. Higher (p≤0.01) cholesterol was noted in 

males (↑72 %) and females (↑62 %) at 5400 ppm. As well, significantly higher concentrations of 

albumin (↑9%), creatinine (↑16%) and total protein (↑9%) were noted in the 5400 ppm group 

males. Serum γ–glutamyltransferase activity and cholesterol were significantly higher in males 

and females at the dietary concentration level of 5400 ppm. No treatment-related changes were 
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observed in the other clinical chemistry parameters at any dietary concentration level in either 

males or females.

Treatment related effects on absolute and relative (to body) liver weights were noted at 1800 

ppm and 5400 ppm in males and females. However, there were no test substance-associated 

alterations observed in liver gross histopathology observations or microscopic histopathology 

findings in the 5400 ppm group males and females. These results, together with the increased 

serum γ–glutamyltransferase activity levels observed in the 5400 ppm males and females, 

suggest that the increase in liver weight observed in the high dose groups is due to an adaptive 

effect rather than a toxic response in this organ. 

It is concluded that pendimethain did not exhibit neurotoxic potential in this 3-month subchronic 

feeding study involving male and female Wistar rats at dietary concentration levels of 300, 1800 

and 5400 ppm, based on the lack of altered behavior in the FOB, only transient decreases in 

motor activity, and no effects on the macroscopic and microscopic pathology of nervous system 

tissues. However, systemic toxicity of Pendimethalin was apparent in males and females. This 

was characterized by decreased body weights, significant reductions in body weight gains and 

decreased food consumption, as well as altered hematologic and clinical chemistry parameters in 

both males and females.

Based on the results of this study, the NOAEL for subchronic neurotoxicity of 

Pendimethalin is 5400 ppm (equivalent to 386.8/423.1 mg/kg body weight/day for males 

and females, respectively). 

The NOAELs for systemic toxicity are 1800 ppm in males (equivalent to 126.5 mg/kg body 

weight/day) and 600 ppm in females (equivalent to 50.1 mg/kg body weight/day), based on 

significant reduction in body weights, body weight gains and food consumption, as well as 

altered hematologic and clinical chemistry parameters.

The study is classified as acceptable/guideline and satisfies the guideline requirement (OPPTS 

870.6200b) for a subchronic neurotoxicity study in rats.

A.4.8 Metabolism

870.7485 Metabolism - Rat

In a metabolism study (MRJD 00046275), {

14C}pendimethalin was administered to rats, about 

70% of the radioactivity was excreted in the feces and 20% in the urine within 24 hours. The 

excretion of radioactivity in the mine peaked at 6 to 12 horns wherein 11.2% of the dose was 

excreted. The maximum residual radioactivity in the tissues was found in the 6-hour samples 

(except for fat at 12 hours). The levels of radioactivity detected in liver, kidney, muscle, fat, and 

blood at 6 hours were 29.8, 16.9, 1.3, 12.2, and 5.4 ppm, respectively. Within 96 horns, the 

radioactivity found in the tissues was 0.3 ppm or less, except for fat which was 0.9 ppm. The 

major portion of the radioactivity that was excreted in the feces was identified as the parent 

compound. Pendimethalin is metabolized in rats 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 
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dinitroaniline compound. Pendimethalin is rapidly eliminated from the body with 70% being 

excreted in the feces primarily unchanged as parent compound and 20% in the urine within 24 

horns. It is mainly metabolized through oxidation of the 4-methyl group on the benzene ring and 

the alkyl side chain.

A.4.9 Immunotoxicity

870.7800 Immunotoxicity

In a 28-day dietary immunotoxicity study (MRID 48608901), pendimethalin, (93.3% a.i., Batch 

No. COD-001337) was administered in the diet to female Crl:WI(Han) rats (8/group) at dietary 

concentrations of 0, 500, 1000, or 3000 ppm (equivalent to 0, 38, 72 or 276 mg/kg/day, 

respectively) for 28 days. Animals in the positive control group (8/group) received 

cyclophosphamide (4.5 mg/kg/day) by gavage for 28 days. Animals in all study groups were 

immunized with sheep red blood cells (SRBC) by intraperitoneal injection (0.5 mL/animal, 4 x 

108SRBC/mL) six days prior to the scheduled sacrifice. At termination, blood was taken from 

the retroorbital venous plexus from fasted animals. The animals were anaesthetized using 

isoflurane. Measurement of the SRBC IgM antibody titers were performed at the end of the study 

with an Enzyme Linked Immunobsorbent Assay (ELISA). Additionally, all animals were 

assessed by gross pathology; the weights of liver, spleen and thymus were measured.

There were no test substance-related effects on mortality, clinical observations, hematology or 

mean absolute and relative (to terminal body weight) thymus weights in any group. Decreased 

mean body weight and body weight gains were observed at 3000 ppm. Increased liver weights 

were observed at 3000 ppm and were regarded as treatment-related, as previously observed in 

the overall mammalian toxicological profile of BAS 455 H (pendimethalin). 

Animals in the positive (cyclophosphamide) control group had decreases in mean absolute and 

relative (to terminal body weight) spleen and thymus weights when compared to vehicle control 

group. 

For systemic toxicity, the LOAEL is 3000 ppm (276 mg/kg/day) based on decreased mean 

body weights, body weight gains, and increased liver weights. The NOAEL for systemic 

toxicity in rats is 1000 ppm (72 mg/kg/day).

There were no significant differences in anti-SRBC IgM titers compared to the untreated control 

group at all dose levels tested. A high inter-individual variability was noted in all the treatment 

groups as well as in the control group. Evaluation of individual animal data of this study did not 

show any trend or distribution that would demonstrate significant suppression of anti-SRBC IgM 

response. Animals in the positive control group showed marked decreases in anti-SRBC IgM 

concentration. The positive control group confirmed the ability of the test system to detect 

immuno-suppressive effects and confirmed the validity of the study design.

The Natural Killer (NK) cells activity was not evaluated in this study. The toxicology database 

for pendimethalin does not reveal any evidence of treatment-related effects on the immune 
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system. The overall weight of evidence suggests that this chemical does not directly target the 

immune system. Under HED guidance, a NK cells activity assay is not required at this time.

For immunotoxicity, the NOAEL is 3000 ppm (276 mg/kg/day). The LOAEL could not be 

determined.

This 28-day dietary immunotoxicity study in the rat is acceptable/guideline and satisfies 

guideline requirement for an immunotoxicity study (OPPTS 870.7800).

A.4.9 Special/Other Studies 

Developmental Thyroid Study (non-guideline)

In a developmental thyroid study (MRID 48695603), pendimethalin (BAS 455 H , 99.9%; Batch 

# FH20726) was administered in the diet to naturally-mated presumed pregnant Sprague-Dawley

(Crl:CD(SD)) rats (35/dose) at doses of 0, 31, 62 or 186 mg/kg bw/day from gestation days 

(GD) 6-21. On GD 20, 10 dams/group were sacrificed and blood samples were withdrawn from 

dams and their fetuses for the determination of thyroid hormones. The fetuses were examined for 

external malformations and variations. The remaining dams were allowed to litter and rear their 

pups until PND 4 or PND 21. 

No mortality or clinical signs of toxicity were observed in this study. During the gestation 

period, mean body weights of dams administered 186 mg/kg bw/day were statistically 

significantly decreased 5-6% when compared to controls on GD 15 and 20. Body weight gain of 

the dams administered 186 mg/kg bw/day was statistically significantly decreased on GD 6-8 

and 17-20 by up to 16% when compared to controls. During the lactation period, Mean body 

weights of dams administered 186 mg/kg bw/day were statistically significantly decreased 6% 

when compared to controls on (post natal day) PND 7. They were still lower than controls at the 

end of the lactation period. During the gestation period mean food consumption was statistically 

significantly decreased in females administered 186 mg/kg bw/day by 16-29% when compared

to controls on GD 6-15 and GD 17-20. During the lactation period mean food consumption was 

statistically significantly decreased in females administered 62 mg/kg bw/day on GD 6-13 by 6-

10% when compared to controls Mean food consumption was also statistically significantly 

decreased in females administered 62 mg/kg bw/day on GD 6-13 by 6-10% when compared to 

controls.

T4 (thyroxine) levels were significantly decreased in all dose groups compared to the controls on 

Post Coital (PC) Day 20 and on PND 21. T4 levels were decreased 42, 58, and 61% when 

compared to controls on GD 20 at 31, 62, and 186 mg/kg/day, respectively. On PND 21, T4

levels were statistically significantly decreased 33, 49, and 68% when compared to controls at 

31, 62, and 186 mg/kg/day, respectively. Additionally, dams on PND 21 had statistically 

significantly decreased triiodothyronine (T3) levels by 9.5 and 16. 2% when compared to 

controls at 62 and 186 mg/kg/day, respectively.

The maternal toxicity LOAEL is 31 mg/kg bw/day based on decreased thyroxine (T4) 

levels. The maternal toxicity NOAEL is less than 31 mg/kg bw/day.
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Thyroid hormone levels were not affected in fetuses (GD 20) or pups on post-natal day (PND 4) 

by administration of the test substance. On PND 21, male pups had statistically significantly 

decreased T4 levels of 21, 22, and 37% when compared to controls at 31, 62, and 186 

mg/kg/day, respectively. On PND 21, female pups had statistically significantly decreased T4

levels of 14, 24, and 36% when compared to controls at 31, 62, and 186 mg/kg/day, respectively.

The offspring demonstrated there was no increased sensitivity as compared to dams because 

thyroid hormones in fetuses and PND 4 pups of exposed dams remained unaltered even when 

their mothers showed significantly decreased T4 levels. Only after exposure via the diet in 

addition to the milk, serum T4 levels of PND 21 pups were affected.

For thyroid function, the LOAEL was 31 mg/kg/day based on decreases in thyroxine (T4) 

levels in pregnant dams and 21 days old male and female pups. The NOAEL was not 

established. The thyroid function in fetuses or post partum day (PND 4) was not affected 

by the treatment of pendimethalin.

No treatment related effects were observed in altered growth, external developmental variations 

or external malformations.

The developmental LOAEL was not observed. The developmental NOAEL is 186 mg/kg 

bw/day.

This study is classified acceptable/non-guideline and can serve as a special study on thyroid 

function within the context of a developmental toxicity study.
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Appendix B. International Residue Limits

Pendimethalin (108501)

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico2 Codex3

40 CFR 180.361:

Plant: N-(1-ethylpropyl)-3,4-dimethyl-2,6-

dinitrobenzenamine and its metabolite, 4-

[(1-ethylpropyl)amino]-2-methyl-3,5-

dinitrobenzyl alcohol

Livestock: N-(1-ethylpropyl)-3,4-

dimethyl-2,6-dinitrobenzenamine and its 

metabolite, 4-[(1-ethylpropyl)amino]-2-

methyl-3,5-dinitrobenzyl alcohol

benzenamine, N-(1-

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

metabolite 

benzenemethanol, 4-[(1-

ethylpropyl)amino]-2-

methyl-3,5-dinitroNone

Commodity1 Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico2 Codex3

Lettuce, Leaf 4.0

Brassica, leafy greens, subgroup 5B 0.2

Turnip greens 0.2

Melon, subgroup 9A 0.1

Vegetable, soybean, succulent 0.1

Fruit, Citrus, Group 10-10 0.1

Citrus, Oil 0.5

Onion, bulb 0.1 0.1

Fruit, pome group 11 0.1 0.1

Fruit, stone group 12 0.1 0.1

Completed: M. Negussie and Y. Barnes; 12/05/2011 and 04/25/2012
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Appendix C. Physical/Chemical Properties

Appendix Table C.1. 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
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Appendix D. Review of Human Research

Studies reviewed for ethical conduct:

The PHED Task Force, 1995. The Pesticide Handlers Exposure Database, Version 1.1. 

Electronic Database. Task Force members Health Canada, U. S. Environmental Protection 

Agency, and the National Agricultural Chemicals Association, released February, 1995.

The Agricultural Handler Exposure Task Force (AHETF), 2011. The Occupational Handler 

Unit Exposure Surrogate Reference Table. U.S. Environmental Protection Agency. Released 

June 21, 2011. 

Data from the Outdoor Residential Exposure Task Force (ORETF).