Pendimethalin Human Health Risk Assessment DP No. 416285 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON. D.C. 20460 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

MEMORANDUM 

Date: 01/14/2015 

SUBJECT: PENDIMETHALIN -· Human Health Risk Assessment for New Use on Hops, 

and Crop Subgroup Conversions/Expansions for Low Growing Berr:y Subgroup 13-07G, Onion, 

Bulb Subgroup 3-07A, Onion, Green Subgroup 3-07B, and Sunflower Subgroup 20B; Crop 

Group Expansions for Citru~ Fruit, Group 10, Pome Fruit, Group 11 , Ston~ fruit, Group 12, and 

Fruiting Vegetable, Group 8.· · 

PC Code: 108501 

Decision No.: 484426 

Petition No.: PP# 3E8212 

Risk Assessment Type: New Use 

TXRNo.: NA 

MRIDNo.: 

DP Barcode: D416285 

Registration No.: 241-418 

Regulatory Action: NA 

Case No.: NA 

CAS No.: 40487-42-1 

40 CFR: 40 CFR §180.361 

F:ROM: P. Yvonne Barnes, Chemist and Risk Assessor 

s.umitra Bose-Biswas, Chemi · 

Bridget 

Yung Yan

Bob

g, 

ow

Ph.D.

iec, 

, 

Biolo

Toxico

gi

lo

st 

gist 

~ 

t17 6-

Risk Assessment Branch VI (/ 

Health Effects Division (7509P) 

THROUGH: Mohsen Sahafeyan, Chemist 1: 

DonnaS. Davis, acting Chief \{ 

Risk Assessment Branch VI 

Health Effects Division (7509P) 

TO: Sidney Jackson, Chemical Risk Manager 

Barbara Madden, Chief 

Registration Division (7505P) 

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~- . . 
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Table of Contents

1.0 Executive Summary............................................................................................................. 4

2.0 HED Recommendations....................................................................................................... 5

2.1 Deficiencies...................................................................................................................... 5

2.2 Tolerance Considerations................................................................................................. 6

2.2.1 Enforcement Analytical Method .................................................................................. 6

2.2.2 Recommended Tolerances............................................................................................ 7

2.2.3 Revisions to Petitioned For Tolerances........................................................................ 8

2.2.4 International Harmonization......................................................................................... 8

2.3 Label Recommendations.................................................................................................. 8

2.3.1 Recommendations from Residue Reviews................................................................... 8

2.3.2 Recommendations from Occupational Assessment ..................................................... 8

2.3.3 Recommendations from Residential Assessment......................................................... 8

3.0 Introduction.......................................................................................................................... 8

3.1 Chemical Identity ............................................................................................................. 8

3.2 Physical/Chemical Characteristics................................................................................... 9

3.3 Pesticide Use Pattern...................................................................................................... 10

3.4 Anticipated Exposure Pathways..................................................................................... 12

3.5 Consideration of Environmental Justice ........................................................................ 12

4.0 Hazard Characterization and Dose-Response Assessment................................................ 12

4.1 Summary of Toxicological Effects ................................................................................ 12

4.1.1 Absorption, Distribution, Metabolism, & Elimination (ADME) ............................... 13

4.1.2 Dermal Absorption ..................................................................................................... 13

4.2 Safety factor for Infants and Children (FQPA Safety Factor) ....................................... 13

4.2.1 Completeness of the Toxicology Database ................................................................ 14

4.2.2 Evidence of Neurotoxicity.......................................................................................... 14

4.2.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal............. 14

4.2.4 Residual Uncertainty in the Exposure Database......................................................... 14

4.3 Toxicity Endpoint and Point of Departure Selections.................................................... 15

4.3.1 Dose-Response Assessment ....................................................................................... 15

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

Assessment ............................................................................................................................... 16

4.3.3 Recommendation for Combining Routes of Exposures for Risk Assessment ........... 17

4.3.4 Cancer Classification and Risk Assessment Recommendation.................................. 17

4.3.5 Endocrine Disruption.................................................................................................. 18

5.0 Dietary Exposure and Risk Assessment ............................................................................ 19

5.1 Residues of Concern Summary and Rationale............................................................... 19

5.2 Food Residue Profile...................................................................................................... 19

5.3 Water Residue profile..................................................................................................... 19

5.4 Dietary Risk Assessment................................................................................................ 20
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5.4.1 Description of Residue Data Used in Dietary Assessment......................................... 20

5.4.2 Percent Crop Treated Used in Dietary Assessment.................................................... 20

5.4.3 Acute Dietary Risk Assessment ................................................................................. 20

5.4.4 Chronic Dietary Risk Assessment .............................................................................. 21

5.4.5 Cancer Dietary Risk Assessment................................................................................ 21

5.4.6 Summary Table........................................................................................................... 21

6.0 Residential (Non-Occupational) Exposure/Risk Characterization .................................... 21

6.1 Combined Exposure ....................................................................................................... 22

6.2 Residential Bystander Postapplication Inhalation Exposure.......................................... 23

6.3 Spray Drift...................................................................................................................... 23

7.0 Aggregate Exposure/Risk Characterization....................................................................... 23

7.1 Acute Aggregate Risk .................................................................................................... 24

7.2 Short-Term Aggregate Risk ........................................................................................... 24

7.3 Intermediate-Term Aggregate Risk................................................................................ 25

7.4 Chronic Aggregate Risk................................................................................................. 25

7.5 Cancer Aggregate Risk................................................................................................... 25

8.0 Cumulative Exposure/Risk Characterization..................................................................... 25

9.0 Occupational Exposure/Risk Characterization .................................................................. 26

9.1 Short-/Intermediate-Term Handler Risk ........................................................................ 26

9.2 Short-/Intermediate-Term Post-Application Risk .......................................................... 26

9.2.1 Dermal Post-application Risk..................................................................................... 26

9.2.2 Inhalation Post-application Risk................................................................................. 28

10.0 References.......................................................................................................................... 29

Appendix A. Toxicology Profile and Executive Summaries....................................................... 30

A.1 Toxicology Data Requirements...................................................................................... 30

A.2 Toxicity Profiles............................................................................................................. 31

Appendix B. International Residue Limits Table ...................................................................... 36

Appendix C. Physical/Chemical Properties................................................................................. 37

Appendix D. Occupational Handler Non-Cancer Exposure and Risk Estimates for 

Pendimethalin ............................................................................................................................... 38

Appendix E. Review of Human Research ................................................................................... 47
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1.0 Executive Summary

The Health Effects Division (HED) has evaluated the current databases for pendimethalin to 

support the registration review of this active ingredient. Pendimethalin (N-(1-ethylpropyl)-3, 4-

dimethyl-2,6-dinitrobenzenenamine) is a selective herbicide used for controlling annual grasses 

and broadleaf weeds. It is a meristematic inhibitor that interferes with the plant’s cellular 

division and it is generally applied early in the growing season as a pre-plant, pre-emergent 

and/or early post-emergent herbicide. It is registered for agricultural uses and is applied by

ground or aerial equipment.

BASF, jointly with the Interregional Research Project Number 4 (IR-4), is proposing a new use 

in/on hops (dried cones). In addition, IR-4 has proposed establishment of tolerances based on 

existing commodities, for low-growing berry (subgroup 13-07G), bulb onion (subgroup 3-07A), 

green onion (subgroup 3-07B), and sunflower (subgroup 20B). Furthermore, IR-4 has proposed 

crop group expansions/updates for crop Groups from group 8 to 8-10, group 10 to 10-10, group 

11 to 11-10 and group 12 to 12-12. 

The toxicology database for pendimethalin is complete, no additional data are required. 

Pendimethalin has low acute toxicity by the oral, dermal, or inhalation route of exposure. It is not 

an eye or skin irritant and is not a skin sensitizer. The target organ is the thyroid. 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). The Cancer Peer Review 

Committee (CARC) classified pendimethalin as a "Group C", possible human carcinogen and 

recommended a non-quantitative approach (i.e., non-linear, RfD approach) to risk assessment. 

There is no evidence that pendimethalin is a developmental, reproductive, neurotoxic, or 

immunotoxic chemical. The toxicity database is complete, there is no evidence of increased 

qualitative or quantitative susceptibility in the young, there is no evidence of neurotoxicity with 

pendimethalin, and exposure estimates are unlikely to underestimate risk; therefore, 10-fold 

FQPA Safety Factor to be reduced to 1x.

The residue chemistry database to support new agricultural uses of pendimethalin is complete. 

The nature and magnitude of the residue in plants, livestock, and rotational crops have been 

adequately delineated. Supporting storage stability data have been provided, and all methods 

used for analysis are acceptable. An adequate enforcement method is available. 

Acute and chronic dietary (food and water) risks assessment Using tolerance level residues, 

default processing factors, 100% crop treated assumptions and modeled water numbers were 

conducted to support the requested new uses. Acute and chronic dietary risk estimates are not of 

concern (<100% of the acute and chronic population adjusted doses (aPAD and cPAD)) for all 

populations.
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There are no proposed new residential uses for pendimethalin. Pendimethalin is registered for 

use in/on lawns, parks, golf courses, ornamentals, landscape ground covers, fruit bearing trees 

and nuts. Previously assessed residential handler and post-application risk estimates did not 

exceed HED’s level of concern (MOEs ≥ 30). 

The results of the occupational handler exposure and risk assessment indicate that total shortand intermediate-term margins of exposure (MOEs) are not of concern to HED (i.e., MOE > 30).

An occupational post-application exposure assessment is not required for hops. Post-application 

exposure was assessed for the proposed crop groups where post-emergent application is 

expected. Risk estimates did not exceed HED’s level of concern (MOEs ≥ 30) on day 0 (the day 

of application). For agricultural pesticides, the active ingredient classified as acute III or IV for 

acute dermal eye irritation and primary skin irritation are assigned a 12-hour REI. Therefore, the

REI of 12 hours on current pendimethalin labels is adequate to protect agricultural workers from 

post-application exposure to pendimethalin.

Acute and chronic aggregate exposures and risk assessments consider exposure to food and 

water only, and are not of concern (<100% of the aPAD or cPAD). HED has conducted shortand intermediate-term aggregate exposure and risk assessments which combined average food 

and water exposure and non-dietary (residential) sources of exposure to pendimethalin. The 

resulting short- and intermediate-term aggregate MOEs do not exceed HED’s level of concern, 

(MOEs ≥ 30). 

Environmental Justice

Potential areas of environmental justice concerns were considered in this human health risk 

assessment to the extent possible.

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. Studies that involve adult human subjects 

are subject to ethics review pursuant to 40 CFR 26, the studies relied on have received that 

review, and are compliant with applicable ethics requirements. 

2.0 HED Recommendations

There are no human health risk concerns that would preclude granting the requested new use on 

hops and establishment of the required tolerance. Additionally, there are no human health risk 

concerns that preclude the requested crop group expansions and extensions. 

2.1 Deficiencies

No toxicology, residue chemistry or occupational/residential exposure data deficiencies have 

been noted relative to these petitioned for actions. 
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2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

BASF has proposed BASF HPLC MS/MS Method D1005 as an enforcement method for hops. 

A method validation study (MRID No. 48860802) and an independent laboratory validation 

(ILV) (MRID No. 48860802) have been submitted. 

Briefly, residues of pendimethalin are extracted with acidified methanol (methanol: water: HCl, 

78:20:2, v/v/v). An aliquot of the extract is acidified, mixed 1:1 with HPLC water, and cleaned 

up by solid phase extraction. The eluted residues are brought to a final volume consisting of 

methanol: water (80:20, v/v) for HPLCMS/MS determination. Separation occurs on either a 

phenyl column or a C18 column. MS/MS detection in the positive ionization mode is used to 

monitor ion transitions from m/z 282 to 212 for pendimethalin and m/z 298 to 228 for CL 

202347. Quantitation is obtained using an external calibration curve of standards for each 

analyte. The LOQ is 0.05 ppm for each analyte in hops. The limit of detection (LOD) is 

approximately 20% of the LOQ, equivalent to 0.01 ppm for each analyte. BASF Method D1005 

includes a confirmatory method, has undergone successful independent laboratory validation, 

includes an extraction scheme that is similar to previously approved enforcement methods for 

pendimethalin and its regulated metabolite, and is suitable as an enforcement method for residues 

of pendimethalin in/on hops. 

The FDA PESTDATA database pesticide analytical manual (PAM Volume II, Appendix I) lists 

four gas chromatographs with electron capture detection (GC/ECD) methods for the 

determination of pendimethalin residues of concern in plant commodities. Methods I and III 

determine residues of the pendimethalin, and Methods II and IV determine the residues of the 

alcohol metabolite (CL 202,347). The LOQ of each method is 0.05 ppm. These GC/ECD 

methods are suitable to enforce the tolerances associated with the crop conversions and 

expansion. 

Conclusions: There are adequate analytical enforcement methods available to enforce the 

proposed tolerances. BASF Method D1005 is adequate to enforce the proposed tolerance for 

hops. Additionally, the FDA PESTDATA database pesticide analytical manual (PAM Volume 

II, Appendix I) lists four gas chromatographs with electron capture detection (GC/ECD) methods 

for the determination of pendimethalin residues of concern in plant commodities. These 

GC/ECD methods are suitable to enforce the tolerances associated with the crop conversions. 
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2.2.2 Recommended Tolerances

Table 2.2.2 summarizes the registrant’s petitioned for tolerances, established crop subgroup 

tolerance for petitioned for crop group conversions/expansions and the Agency’s 

recommendations. Tolerances established under 40 CFR §180.361 comply with the HED 

Interim Guidance on Tolerance Expressions (S. Knizner, 05/27/2009); no revisions are required 

to the existing residue definition. 

Table 2.2.2 Tolerance Summary for Pendimethalin.

Commodity

Proposed 

Toleranc

e (ppm)

Recommended 

Tolerance (ppm)

Correct Commodity 

Definition/Comments

To be established under 40 CFR §180.361 (a) General. (1)

Hop, dried cones 0.1 0.1

Onion, bulb subgroup 3-07A 0.1 0.1 Established tolerance for bulb

onion can be removed from the 

40CFR and replaced by this 

subgroup tolerance.

Onion, green subgroup 3-07B 0.2 0.2 Established tolerance for green

onion can be removed from the 

40CFR and replaced by this 

subgroup tolerance.

Vegetable, fruiting, group 8-10 0.1 0.1 Established tolerance for stone 

fruiting vegetable group 8 can be 

removed from the 40CFR and 

replaced by this group tolerance.

Fruit, citrus, group 10-10 0.1 0.1 Established tolerance for citrus 

fruit subgroup 10 can be removed 

from 40CFR and replaced by this 

group tolerance.

Fruit, pome, group 11-10 0.1 0.1 Established tolerance for pome 

fruit subgroup 11 can be removed 

from 40CFR and replaced by this 

group tolerance.

Fruit, stone, group 12-12 0.1 0.1 Established tolerance for stone 

fruit subgroup 12 can be removed 

from the 40CFR and replaced by 

this group tolerance.

Berry, Low growing subgroup 13-07G 0.1 0.1 Established tolerance for 

strawberry can be removed from 

the 40CFR and replaced by this 

subgroup tolerance.

Sunflower subgroup 20B 0.1 0.1 Established tolerance for sunflower 

seed can be removed from the 

40CFR and replaced by this 

subgroup tolerance.
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2.2.3 Revisions to Petitioned For Tolerances

None.

2.2.4 International Harmonization

The International Residue Limit (IRL) Status Sheet is attached. There are currently no 

established Codex, Canadian or Mexican maximum residue limits (MRLs) for the proposed new 

use of pendimethalin in/on hops. There are Canadian MRLs for commodities which are 

addressed by the U.S. crop group tolerances on pome fruit, onion, and stone fruit. The tolerance 

expression is harmonized between the U.S. and PMRA, and the tolerance levels are also 

harmonized as both countries will have MRLs/tolerances at 0.1 ppm for all commodities, except 

for the green onion subgroup 307B, which will be harmonized at the MRL/tolerance level of 0.2 

ppm. There are no issues of international harmonization raised by these petitions.

2.3 Label Recommendations

2.3.1 Recommendations from Residue Reviews

The proposed labels are adequate and supported by data. No revision to the labels is required. 

2.3.2 Recommendations from Occupational Assessment

There are no recommendations from the occupational assessment. The proposed label for the 

new use and crop expansions are adequate. 

2.3.3 Recommendations from Residential Assessment

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

pendimethalin uses. 

3.0 Introduction

3.1 Chemical Identity

The chemical structure and nomenclature of pendimethalin and its alcohol metabolite (CL 

202,347) are shown in Table 3.1, and the physicochemical properties of the technical grade of 

pendimethalin are given in Appendix C.
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Table 3.1 Pendimethalin Nomenclature.

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

End-use product (EP) 3.8 lbs. a.i. gal capsule suspension formulation (equivalent to 450 g a.i. L; 

Prowl® H2O Herbicide; EPA Reg. No 241-418)

Chemical structure of Metabolite CL 

202,347

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

CAS registry number 56750-76-6

3.2 Physical/Chemical Characteristics

Pendimethalin is an orange-yellow crystalline solid with a melting point of 54-58 oC. It is 

soluble in chlorinated hydrocarbons and aromatic solvents such as methylene chloride, acetone, 

and xylene, but relatively insoluble in water (<0.5 ppm) at 20 oC. Pendimethalin is stable under 

most acidic and alkaline conditions. The persistence of herbicides in the environmental and 

absorbed in the soil is correlated with solubility and vapor pressure. Pendimethalin is highly 

sorbed to the soil/sediment particles and non-volatile. Pendimethalin is stable to hydrolysis, soil 

photolysis, and anaerobic soil metabolism, but degrades slowly under the aqueous photolysis 

conditions with a calculated half-life of 17 days.

HN

CH3

CH3

O2N NO2

CH3

CH3
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3.3 Pesticide Use Pattern

BASF, jointly with the Interregional Research Project Number 4 (IR-4), is proposing a new use 

in/on hops (dried cones). In addition, IR-4 has proposed establishment of tolerances based on 

existing commodities, for low-growing berry (subgroup 13-07G), bulb onion (subgroup 3-07A), 

green onion (subgroup 3-07B), and sunflower (subgroup 20B). Furthermore, IR-4 has proposed 

crop group expansions/updates for crop Groups from group 8 to 8-10, group 10 to 10-10, group 

11 to 11-10 and group 12 to 12-12. 

A new use of Prowl® H2O on hops is proposed at a maximum single use rate of 4.0 lbs. a.i. per 

acre via ground only application in the states of Idaho, Oregon, and Washington. Application 

should be directed beneath vines and/or between rows. The proposed PHI is 90 days for hops.

Additionally, IR-4 has submitted supplemental labels for Prowl ® H2O for each petitioned for 

subgroup/group for EPA Registration Number 241-418. HED notes that the proposed use 

patterns for the new commodities added through the crop expansions are identical to the use 

pattern for the currently registered uses. Previously registered pendimethalin uses include;, 

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, kiwi and other small fruit vines, lentils 

and peas, leaf lettuce, leafy brassica greens, melons, mint, non-bearing fruit trees, olive trees,

onions, peanuts, potatoes, rice, soybeans, strawberry, sugarcane, sunflowers, tobacco, wheat, and

vegetable soybean (edamame). 

In addition to agricultural crops, the chemical pendimethalin is registered for northern and 

southern grasses, for use on sod farms and for seed production and for use by commercial 

applicators and residential applicators 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. The Prowl® H2O label requires 

applicators and other handlers to wear a long-sleeved shirt and long pants and shoes plus socks, 

plus chemical-resistant gloves. Table 3.3 summarizes the proposed new use and crop expansion 

label directions.
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Table 3.3. Summary of Proposed Directions for Use of Pendimethalin.

Commodity

Product 

Name 

(EPA 

Reg. 

No.)

Application

Equipment

Max. 

Single 

Applicatio

n Rate

(lbs.

a.i./A)

Max # 

Application

s

Per Season

Max 

Seasonal 

Application 

Rate

(lbs. a.i./A)

PHI1

(days)

Use Directions and 

Limitations

Hops

Prowl ®

H2O

(241-

418)

38.7 % 

a.i.

Aqueou

s 

Capsule 

Suspens

ion

Ground 4.0 2 4.0 90

Only for use in the states 

Idaho, Oregon, and 

Washington. 

Apply as broadcast or 

banded treatment. Apply 

directly to the ground 

beneath vines and/or in 

between rows. Do not 

apply over top of vines. Do 

not apply by chemigation.

Dry Bulb 

Onion 

subgroup 3-

07A Ground, 

Aerial, and 

Chemigatio

n

1.4 in 

mineral 

soil

and 1.9 in 

muck soils

2 1.9

45 and 

60 days 

in 

Californi

a

Apply to direct-seeded and 

transplanted dry bulb 

onions. Not for use in muck 

soils in California. Do not 

feed or graze crops.

Green 

Onion 

subgroup 3-

07B

1.0 2 1.9 30

Apply as broadcast spray to 

soil surface as postemergence to 2 to 3 true leaf 

stage. Do not feed forage or 

graze livestock 

Fruiting 

Vegetable 

Crop Group 

8-10

Ground or 

Aerial 1.4 1 1.4

21 for 

tomatoes 

70 for all 

other 

fruiting 

vegetable

s

Do not apply prior to directseeded fruiting vegetables. 

Do not apply postemergence. Do not plant 

lettuce within 6 months of 

application.

Citrus Fruit 

Crop Group 

10-10

Ground, 

Chemigatio

n, Flood, 

Flooded 

Basin, and 

Gravity 

Flow 

Irrigation 

6 2 6 1

Apply as broadcast to 

ground beneath the trees 

and/or in areas between 

rows. Do not apply over top 

of trees. Do not apply by 

air. Do feed forage or graze 

livestock. 

Pome Fruit 

Crop Group 

11-10 4 2 4 60

Stone Fruit 

Crop 12-12

LowGrowing 

Berry 

Subgroup 

13-07G

Ground, 

Aerial, 

Chemigatio

n

1.4 2 2.8 35

Do not feed forage or graze 

livestock in treated fields. 

Do not apply to new 

seasonal growth. Do not 

plant lettuce within 6 

months after application to 

strawberry beds. 

Sunflower 

Subgroup 

20B

Ground, 

Aerial

1.7

17 lb 

ai/ton 

fertilizer

1 1.7 NA

Do not apply postemergence. Do not feed 

forage or graze livestock. 

No not apply when air 

temperature is below 45 F. 

California pre-plant fall 

application for safflower 

production. 

1PHI = pre-harvest interval
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3.4 Anticipated Exposure Pathways

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 no proposed new residential uses 

of pendimethalin, however there are existing residential uses as listed in the previous section, so 

exposure to pendimethalin may occur in residential or non-occupational settings. Residential

handlers may be exposed by the dermal and oral routes from applying pendimethalin to home 

gardens, lawns, and ornamentals. Adults and may be exposed by the dermal and oral (children 

only through hand-to-mouth transfer) routes from activities on turf including mowing and 

golfing, and home gardens. In an occupational setting, handlers may be exposed while handling 

the pesticide prior to application, as well as during application. There is also an exposure for 

workers re-entering treated sites. 

3.5 Consideration of Environmental Justice

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

human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions 

to Address Environmental Justice in Minority Populations and 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 post-application 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 Summary of 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 the target organ for pendimethalin. 
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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).

The CARC classified pendimethalin (03/18/1992 and re-affirmed 11/01/1999) 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 non-quantitative approach (i.e., nonlinear, 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. There is no evidence that pendimethalin is a 

developmental, reproductive, neurotoxic, or immunotoxic chemical.

4.1.1 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 groups 

attached to the benzene ring as well as oxidation of the alkyl side chain of the N-substituted 

dinitroaniline compound.

4.1.2 Dermal Absorption

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. 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. Therefore, for risk assessment purposes, an estimate of 3% was applied. This 

dermal absorption rate is comparable to those identified for related chemicals.

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

The toxicity database is complete, there is no evidence of increased qualitative or quantitative 

susceptibility in the young, there is no evidence of neurotoxicity with pendimethalin and 
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exposure estimates are unlikely to underestimate risk; therefore, 10-fold FQPA Safety Factor to 

be reduced to 1x. 

4.2.1 Completeness of the Toxicology Database

The toxicology database for pendimethalin is complete and adequate to support risk assessments. 

4.2.2 Evidence of Neurotoxicity

There is no evidence of neurotoxicity resulting from 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. 

4.2.3 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.

4.2.4 Residual Uncertainty in the Exposure Database

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 previous 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.

 
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4.3 Toxicity Endpoint and Point of Departure Selections

4.3.1 Dose-Response Assessment

Acute Dietary Endpoint for the General Population: In an acute neurotoxicity study in rats 

(MRID 48695601), reduced motor activity was observed at 250 mg/kg (LOAEL) with a NOAEL 

of 100 mg/kg. The route and a single exposure of this study are appropriate for acute dietary risk 

assessment. The UF is 100x (10x for interspecies extrapolation, 10x for intraspecies variation, 

and 1x for FQPA Safety Factor). The acute population adjusted dose (aPAD) for the general

population is 1 mg/kg.

Acute Dietary Endpoint for Female 13-49 Years of Age: No appropriate endpoint was identified 

from any of the studies in the database, including developmental toxicity studies in rats and 

rabbits. Consequently, it was determined that there was no basis for selecting a dose and 

endpoint for an acute PoD for females 13-49 years of age.

Chronic Dietary Endpoint for the General Population: Three studies (a 92-day thyroid function 

study, a 56-day thyroid function study and a 14-day intra-thyroid metabolism study in rats) were

considered co-critical in establishing a PoD for chronic dietary risk assessment. All studies 

reflecting thyroid toxicity, HED has determined that these studies collectively support a NOAEL 

of 10 mg/kg/day and a LOAEL of 31 mg/kg/day for thyroid effects include several hormonal and 

histological thyroid changes and thyroid hormonal effects and should be used as the POD for all 

durations and exposure scenarios. An UF of 30x (3x for interspecies extrapolation and 10x for 

intraspecies variation) is applied to the NOAEL of 10 mg/kg/day to obtain a chronic reference 

dose (cRfD) of 0.3 mg/kg/day. The interspecies UF (used to account for animal to human 

differences in toxicokinetics and toxicodynamics) was 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). The FQPA factor is reduced to1x. The chronic population 

adjusted dose (cPAD) is 0.3 mg/kg/day.

Incidental Oral Exposure (Short- and Intermediate-Term): HED evaluated the toxicity database 

for pendimethalin and concluded that all available studies reflecting thyroid toxicity should be 

considered co-critical for selection of PODs, regardless of duration of exposure, since thyroid 

effects have a demonstrated early on-set (before 14 days). Therefore, HED has determined that 

these studies collectively support a NOAEL of 10 mg/kg/day and a LOAEL of 31 mg/kg/day for 

thyroid effects include several hormonal and histological thyroid changes and thyroid hormonal 

effects and should be used as the POD for all durations and exposure scenarios with the 

exception of the acute dietary endpoint.

Dermal Exposure (Short-, Intermediate-, and Long-Term): There was a 21-day dermal toxicity 

study available with a NOAEL of 1000 mg/kg (the limit dose); however, thyroid function was 

not measured in this study. Therefore, oral toxicity study was selected for this exposure scenario. 

The same rationale as stated in the incidental oral exposure section is applied to this exposure 
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scenario. These co-critical studies collectively support a NOAEL of 10 mg/kg/day and a LOAEL 

of 31 mg/kg/day for thyroid effects include several hormonal and histological thyroid changes 

and thyroid hormonal effects and should be used as the POD for all durations and exposure 

scenarios. Additionally, for risk assessment purposes, a dermal absorption factor of 3% should be 

used to estimate risk since these assessments for the routes of exposure are derived from POD 

selected from oral studies.

Inhalation Exposure (Short, Intermediate, and Long-Term): There was no inhalation study 

available except the acute inhalation study (Toxicity Category IV). Therefore, oral toxicity study 

was selected for this exposure scenario. The same rationale as stated in the incidental oral 

exposure section is applied to this exposure scenario. These co-critical studies collectively 

support a NOAEL of 10 mg/kg/day and a LOAEL of 31 mg/kg/day for thyroid effects include 

several hormonal and histological thyroid changes and thyroid hormonal effects and should be 

used as the POD for all durations and exposure scenarios. Additionally, for risk assessment 

purposes, an inhalation absorption factor of 100% should be used to estimate risk since these 

assessments for the routes of exposure are derived from POD selected from oral studies. 

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

Assessment

Table 4.3.2 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 from any of the studies in the database, 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

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.
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Table 4.3.2 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

(1-6 months)

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 

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

human population (intra-species), 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. 

4.3.3 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

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

routes should be aggregated. 

4.3.4 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.
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4.3.5 Endocrine Disruption

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

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

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive effects in different 

taxonomic groups. As part of its most recent re-registration decision for pendimethalin, EPA 

reviewed these data and selected the most sensitive endpoints for relevant risk assessment 

scenarios from the existing hazard database. However, as required by FFDCA section 408(p), 

pendimethalin is subject to the endocrine screening part of the Endocrine Disruptor Screening 

Program (EDSP). 

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

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

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

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

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance and 

establish a dose-response relationship between the dose and the E, A, or T effect. 

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

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 

chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of 

chemicals identified for EDSP screening was published on June 14, 20131and includes some 

pesticides scheduled for registration review and chemicals found in water. Neither of these lists 

should be construed as a list of known or likely endocrine disruptors.

For further information on the status of the EDSP, the policies and procedures, the lists of 

chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our 

website. 2

 

1 See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0477-0074 for the final second list of chemicals.

2 http://www.epa.gov/endo/
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5.0 Dietary Exposure and Risk Assessment 

5.1 Residues of Concern Summary and Rationale

The current tolerance expression for pendimethalin in 40 CFR §180.361 includes the combined 

residues of pendimethalin and its 3,5-dinitrobenzyl alcohol metabolite (CL 202,347) for plant 

commodities. Table 4.3 provides a summary. 

Matrix1 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

Drinking Water Pendimethalin Not Applicable

1 Livestock residues of concern are not considered in this action.

Livestock Matrix

There are no animal feed crops associated with the new use on hops. There is one new animal 

feed item, safflower meal, associated with the proposed crop group expansions (Sunflower 

subgroup 20B). Residues in safflower meal are likely to be the same as residues in sunflower. 

Sunflower meal has already been considered in the previous dietary burden calculations. 

Replacing sunflower with safflower has no impact on the dietary burden and animal tolerances. 

Therefore, a discussion of livestock metabolism is not required for these petitions.

5.2 Food Residue Profile

Pendimethalin is a registered herbicide for agricultural uses and is applied either pre or early post 

emergence. It is a meristematic inhibitor “growth retarder” that interferes with the plant’s 

cellular division of mitosis, controlling/preventing annual grasses and weeds. Once 

pendimethalin is absorbed by the roots or shoots, translocation to foliage is extremely limited. 

Residues of pendimethalin and/or its metabolite at harvest are usually very low or nondetectable, (e.g., below the level of quantification). 

5.3 Water Residue profile

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

Environmental Fate and Effects Division (EFED) in the following memorandum: “Tier II 

Estimated Surface Drinking Water Concentrations and Estimated Ground Water Concentration 

(EDWCs) for Pendimethalin for Use in Human Health Risk Assessment,” D334061, J. 

Breithaupt, 05/08/2007 (personal email: Ibrahim Abdel-Saheb 06/18/2014) and incorporated 

directly into the dietary assessment. Water residues were incorporated in the DEEM-FCID into 
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the food categories “water, direct, all sources” and “water, indirect, all sources.” The New York 

Grape Scenario yielded the highest drinking water residues (Table 5.3).

Table 5.3 Pendimethalin EDWCs for the New York Grape Scenario in Surface Water (2007)

Drinking Water 

Source

(Model) 

1 in 10-year annual peak 

concentration 

1 in 10-year annual 

mean concentration 

36-year annual mean 

concentration 

(μg/L) (μg/L) (μg/L)

Surface Water a

(PRZM-EXAMS) 77.7 6.0 4.8

a From the Tier II PRZM-EXAMS – (NY grape scenario)

Values used for risk assessment is bolded

5.4 Dietary Risk Assessment

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 for pendimethalin using the Dietary Exposure Evaluation Model software with 

the Food Commodity Intake Database (DEEM-FCID) Version 3.16. This software uses 2003-

2008 food consumption data from the U.S. Department of Agriculture’s (USDA’s) National 

Health and Nutrition Examination Survey, What We Eat in America, (NHANES/WWEIA). The 

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

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

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

drinking water point 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 analyses are based on tolerance-level residues; 100% 

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

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

drinking water point estimates provided by EFED are modeled estimates and were generated 

using the most conservative model available for the proposed crops and turf uses. 

5.4.2 Percent Crop Treated Used in Dietary Assessment

Percent crop treated information were not used in these assessments.

5.4.3 Acute Dietary Risk Assessment

The acute dietary risk estimate for the highest exposed population subgroup, all infants is 1.7% of 

the acute population adjusted dose (aPAD) and for the general U. S. population is <1.0% of the 

aPAD at the 95th percentile of exposure. HED is concerned when estimated dietary risk exceeds 

100%. There are no acute dietary risks of concern (Table 5.5.6). 
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5.4.4 Chronic Dietary Risk Assessment

The chronic dietary risk estimate for the highest exposed population subgroup, children 1-2 years 

old is 1.7% of the chronic population adjusted dose (cPAD) and for the general U. S. population 

is <1.0% of the cPAD. HED is concerned when estimated dietary risk exceeds 100%. There are 

no chronic dietary risks of concern (Table 5.4.6). 

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 dietary risk 

assessment is considered to be protective of any cancer effects. There are no chronic dietary 

risks of concern (Section 5.4.4); therefore there are no cancer dietary risks of concern for the 

existing and proposed uses of pendimethalin. 

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 Cancer

Dietary 

Exposure 

(mg/kg/day)

% 

aPAD*

Dietary 

Exposure

(mg/kg/day)

% 

cPAD*

Dietary 

Exposure

(mg/kg/day)

Risk

General U.S. Population 0.007311 < 1 0.001592 < 1

All Infants (< 1 year old) 0.017009 1.7 0.003195 1.1

Not 

applicable

Not 

applicable

Children 1-2 years old 0.015053 1.5 0.005043 1.7

Children 3-5 years old 0.011605 1.2 0.003987 1.3

Children 6-12 years old 0.007796 < 1 0.002329 < 1

Youth 13-19 years old 0.005430 < 1 0.001332 < 1

Adults 20-49 years old 0.005967 < 1 0.001256 < 1

Adults 50+ years old 0.005528 < 1 0.001191 < 1

Females 13-49 years old 0.006124 < 1 0.001248 < 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

There are no proposed new residential uses for pendimethalin; however, there are residential uses 

for pendimethalin currently registered. HED previously assessed short-term residential exposure 

and risk for the registered uses including; lawns, parks, golf courses, ornamentals, landscape 

ground covers, fruit bearing trees and nuts. (S. Shelat, 06/07/2012, D402406). 
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This assessment incorporated recent revisions to the Standard Operating Procedures for 

Residential Pesticide Exposure Assessment, body weights, as well as the new toxicology 

submitted data. The residential handler and post-application risk estimates did not exceed 

HED’s level of concern (MOEs ≥ 30). Details of the residential risk assessment can be found in 

the cited memorandum. Residential risk estimates for inclusion in the aggregate risk assessment 

are summarized below.

6.1 Combined Exposure

The following summarizes the results from the 2012 risk assessment memorandum (S. Shelat, 

D402406). HED did not combine adult residential exposure resulting from the handler and postapplication exposure because of the conservative assumptions and inputs within each estimated 

exposure scenario. HED believes that combining exposures resulting from adult handler and 

post-application activities would result in an overestimate of adult exposure. HED therefore, 

selected the most conservative adult dermal post-application exposure (0.078) as the contributing 

source of residential exposure to be combined with the dietary exposure for the aggregate 

assessment. However, the children’s oral exposure is based on combining the short term postapplication hand-to-mouth exposures (0.042) with the short term dermal post application 

exposure from activity on turf (0.060).

Table 6.1 reflects the residential exposure scenarios that are recommended for us in the 

aggregate assessment. 

 The recommended residential exposure for use in the adult aggregate assessment reflects 

most conservative adult residential scenario, short term duration dermal post-application 

exposure to gardening sprays (0.078). 

 The recommended residential exposure for use in the children 1<2 years old aggregate 

assessment reflects dermal, and hand-to-mouth exposures from short term duration postapplication exposure to turf applications 0.102).

Table 6.1. Combined Residential Exposure and Risk Estimates for use in Aggregate Pendimethalin Assessment

Lifestage

Handler Dermal Handler 

Inhalation

Post-application 

Dermale Hand-to-Mouth 

Combined 

Exposure Used for 

Aggregate

Dosea MOEb Dosec MOEd Dose MOE Dose MOE Total 

Dose

Total 

MOEf

Adults 0.015 670 5.4E-05 180,000 0.078 130 N/A 0.078 130

Children 1 

< 2 years 

old 

N/A N/A 0.060 170 0.042 240 0.102 100

a. Handler Dermal Dose = Dermal Unit Exposure (mg/kg) x Application Rate (4lbs ai/acre) x Amount Treated or Handled x DAF (3%)/BW (80kg) based on worst case scenario 

applications to ornamentals via belly grinder. 

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

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

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

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

f. Total Dose for aggregate= 1 ÷ (1/Dermal MOE) + (1/Inhalation MOE) + (1/Incidental Oral MOE), where applicable.
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6.2 Residential Bystander Postapplication Inhalation Exposure

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 has evaluated the SAP report and has developed a Volatilization Screening Tool and a 

subsequent Volatilization Screening Analysis (http://www.regulations.gov/#!docketDetail;D=EPA-HQOPP-2014-0219). During Registration Review, the agency will utilize this analysis to determine if 

data (i.e., flux studies, route-specific inhalation toxicological studies) or further analysis is 

required for pendimethalin.

6.3 Spray Drift

Spray drift is a potential source of exposure to those nearby pesticide applications. This is 

particularly the case with aerial application, but, to a lesser extent, spray drift can also be a 

potential source of exposure from the ground application methods (e.g., groundboom and 

airblast) employed for pendimethalin. The agency has been working with the Spray Drift Task 

Force (a task force composed of various registrants which was developed as a result of a Data 

Call-In issued by EPA), 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). 3 The agency has also developed a policy on how to 

appropriately consider spray drift as a potential source of exposure in risk assessments for 

pesticides. The potential for spray drift will be quantitatively evaluated for each pesticide during 

the Registration Review process which ensures that all uses for that pesticide will be considered 

concurrently. The approach is outlined in the revised (2012) Standard Operating Procedures. 

For Residential Risk Assessment (SOPs) - Residential Exposure Assessment Standard Operating 

Procedures Addenda 1: Consideration of Spray Drift. This document outlines the quantification 

of indirect non-occupational exposure to drift. It should be noted for current policy if the 

maximum application rate on crops adjusted by the amount of drift expected is less than or equal 

to existing turf registered application rates, the existing residential turf assessment is considered 

protective of spray drift exposure. 

7.0 Aggregate Exposure/Risk Characterization

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 

 

3 Available: http://www.epa.gov/opp00001/factsheets/spraydrift.htm 
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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 1.7% for the most highly exposed life stage, children < 1 years old. Therefore there are no 

acute aggregate risks of concern.

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 0.001256 0.078 0.080 130

Child 10 30 0.33 0.005043 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). 3 Child Residential Exposure = [Oral exposure (0.042 

mg/kg/day) + Dermal exposure (0.060 mg/kg/day) = 0.102 mg/kg/day (Table 6.1). 

4 Total Exposure = (Avg (Food & Water) Exposure + Residential Exposure). 5 Adult Aggregate MOE =

[NOAEL (10 mg/kg/day)/ (Total Exposure (0.08 mg/kg/day)]; Child Aggregate MOE= [NOAEL (10 mg/kg/day)/ (Total Exposure (0.107 mg/kg/day)]
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7.3 Intermediate-Term Aggregate Risk

Intermediate-term exposures to pendimethalin are not likely because of the intermittent nature of 

applications by homeowners (e.g., garden sprays).

7.4 Chronic Aggregate Risk

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

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

estimate. Refer to Section 5.4.4 for the chronic dietary (food and drinking water) exposure 

assessment. There are no chronic aggregate risks of concern.

7.5 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. Quantification of risk using a non-linear approach; i.e., RfD/PAD, will 

adequately account for all chronic toxicity, including carcinogenicity, that could result from 

exposure to pendimethalin. Since there are no chronic aggregate risks of concern (Section 7.4), 

there are no cancer aggregate risks of concern.

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/.
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9.0 Occupational Exposure/Risk Characterization

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 

intermediate-term occupational exposure during handling (mixing/ loading/applying) and 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) protection as well as varying levels of 

personal protective equipment. 

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

assessment. HED applied 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 

new use on hops and crop groups are included in Appendix D, Table D.1.1 - Table D.1.3. 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 

new uses. 

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. Most of the 

Prowl ® H2O applications made to post-emergent crops including the new use on hops 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, 

stunting, and reduced growth. Additionally, when applications are made to post-emergent crops 

there are growth stages restrictions which limit the number of likely post-application activities.

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 and 

tobacco treated with PROWL 3.3 EC Herbicide 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 
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aqueous solution of PROWL 3.3 EC 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 to the proposed use on hops and various crops expansion groups. 

Post application exposure to pendimethalin from application to the crop group

conversions/expansions; Dry Bulb Onion Subgroup 3-07A, Green Onion Subgroups 3-07B were 

performed by using the default DFR value. The existing DFR studies on sugarcane and tobacco 

are not considered to be representative of broadcast spray over post-emergent plants. 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 provide a summary of the exposures and risk estimates for occupational post 

application workers. Risk estimates (MOEs) for the crop group expansions dry bulb onion and 

green onion are ≥ 30 at day 0 of application. 

Table 9.2.1. Short Term Occupational Post-application Non-Cancer Exposure and Risk Estimates for 

pendimethalin new uses 

Crop/Site Activities Transfer Coefficient 

(TC) (cm2/hour) DFR1 Dermal Dose (mg/kg/day)2 MOE3

Post-Emergent Crop Application

Dry Bulb Onion 

Subgroup 3-07A Hand Weeding 4,200

5.33 0.07 150

Green Onion 

Subgroups 3-07B 2.80 0.04 280

1 DFR = Application Rate × F × (1-D)t × 4.54E8 μg/lb × 2.47E-8 acre/cm2; where F = 0.25 and D = 0.10 per day.

2 Daily Dermal Dose = [DFR (μg/cm2) × Transfer Coefficient × 0.001 mg/μg × 8 hrs /day × dermal absorption (%)]  BW (kg).

3 Day 0 MOE = POD (mg/kg/day) / Daily Dermal Dose. Daily Dermal Dose = [DFR/TTR (μg/cm2) × TC × 0.001 mg/μg × 8 hrs /day × dermal absorption factor (%)]  BW (kg).

Restricted Entry Interval

The REI specified on the proposed label is based on the acute toxicity of pendimethalin. 

Pendimethalin is classified as Toxicity Category IV via the dermal route and skin irritation 

potential. It is not a skin sensitizer. Short- and intermediate- term post-application risk estimates 

were not a concern on day 0 (12 hours following application) for all post-application activities. 

Under 40 CFR 156.208 (c) (2) (iii), a.i’s classified as Acute III or IV for acute dermal, eye 

irritation and primary skin irritation are assigned a 12-hour REI. Therefore, the [156 subpart K] 

Worker Protection Statement interim REI of 12 hours is adequate to protect agricultural workers 

from post-application exposures to pendimethalin.
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9.2.2 Inhalation Post-application 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) and low vapor pressure (1.24 x 10-8 Pa at 20 °C). 

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 re-suspension 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, 20104. The 

Agency is in the process of evaluating the SAP report as well as available post-application 

inhalation exposure data generated by the ARTF and may, as appropriate, develop policies and 

procedures, to identify the need for and, subsequently, the way to incorporate occupational postapplication 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 post-application 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 post-application exposure. Therefore, it is expected that these handler 

inhalation exposure estimates would be protective of most occupational post-application 

inhalation exposure scenarios.

 

4 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html
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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; 08/22/2007.

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; 05/20/2008. 

Pendimethalin. Human Health Risk Assessment for the Proposed Tolerance in/on Crayfish. PC Code 108501; DP 

Barcode D350493; C. Olinger; 03/31/2008.

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: D372189; Y. Barnes; 06/05/2012.

PENDIMETHALIN: Petition for the Establishment of Permanent Tolerances and Registration for New Use on 

Hops, and Crop Subgroup Conversions/Expansions for Low Growing Berry Subgroup 13-07G, Onion, Bulb 

Subgroup 3-07A, Onion, Green Subgroup 3-07B, and Sunflower Subgroup 20B; Crop Group Expansions for 

Citrus Fruit, Group 10, Pome Fruit, Group 11, Stone Fruit, Group 12, and Fruiting Vegetable, Group 8. Summary 

of Analytical Chemistry and Residue Data. DP# Barcode: D416576, Y. Barnes; 10/14/2014

Drinking Water Assessment

“Tier II Estimated Surface Drinking Water Concentrations and Estimated Ground Water Concentration (EDWCs) 

for Pendimethalin for Use in Human Health Risk Assessment,” (D334061, J. Breithaupt, 05/08/2007)

Dietary Exposure Assessment

Pendimethalin: Acute and Chronic Aggregate Dietary (Food and Drinking Water) Exposure and Risk 

Assessments in support of the Human Health Risk Assessment for New uses on Hops, Low Growing Berry 

Subgroups 13-07G, Onion, bulb subgroup 3-07A, Onion, green subgroup 3-07B, and Sunflower Subgroup 20B;

Crop Group conversions and expansions for Citrus Fruit Group 10, Pome Fruit Group 11, Stone Fruit Group 12, 

and Fruiting Vegetable Group 8. D416577.drs; Y. Barnes; 10/14/2014

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: Occupational and Residential Exposure Assessment for a Proposed Section 3 Use on Hops, Crop 

Expansion and Conversions of the Following: Low Growing Berry Subgroup 13-07, Onion Subgroups 3-07 A & 

B, Sunflower Subgroup 20B, Citrus Fruit Group 10-10, Pome Fruit Group 11-10, Stone Fruit Group 12-12, and 

Fruiting Vegetable Group 8-10.; D416578, 11/07/2014
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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 A.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.
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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 

[Rat] (14-day) 43135003

0, 100, 500 ppm

0, 10, 500 mg/kg/day

NOAEL = 10 mg/kg/day.

LOAEL = 500 mg/kg/day, based on 

thyroid effects.

870.3100 Subchronic oral 

[Dog] (90-day)

00026672

Supplementary

0, 62.5, 250, 1000 

mg/kg/day

NOAEL = 62.5 mg/kg/day.

LOAEL = 250 mg/kg/day, based on 

body weight loss.

870.3150

Subchronic oral 

[Mouse] (30-

day)

000106754

Supplementary

0, 500, 1000, 2000 ppm

0, 75, 150, 300 mg/kg/day

NOAEL = 300 mg/kg/day.

LOAEL was not determined.

870.3200 21-Day dermal 

toxicity [Rat] 00026663

0, 250, 500, 1000 

mg/kg/day

NOAEL = 1000 mg/kg/day.

LOAEL was not determined.

870.3700a

Prenatal 

developmental 

toxicity [Rat]

00025752

Supplementary, 

but satisfactory 

when considered 

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 

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

given as a range, based on 

calculations from actual 

chemical intake, and a 

generic ratio (1:20) of 

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).
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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

870.5100

Reverse gene 

mutation assay 

[Escherichia 

coli WP2]

43177801

25, 50, 100, 250, 500, 750 

μg/plate Negative

870.5100

Reverse gene 

mutation assay 

[Escherichia 

coli WP2]

43135005

50, 158, 500, 1581, 5000 

μg/plate or 1000 μg/paper 

disk/plate 

Negative

870.5100

Reverse gene 

mutation assay 

[Escherichia 

coli WP2]

43135006

50, 100, 250, 500, 750 

μg/plate Negative

870.5300

Mammalian 

cell gene 

mutation 

[Chinese 

hamster ovary]

43177802

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

50 μg/plate (-S9)

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

150, 175 μg/plate (+S9)

Negative

870.5375

Chromosomal 

aberration 

[Chinese 

hamster ovary]

00153770

Doses ranging from 5-50 

μg/ml Negative

870.5395

Micronucleus 

study [Mouse] 42027801 313, 625, 1250 mg/kg Negative

870.5550

Alkaline elution 

assay [Rat] 43135007 1250, 2500, 5000 mg/kg Negative

870.6200

Acute 

neurotoxicity

48695601

Acceptable

0, 100, 300, or 1000 

mg/kg

NOAEL=100 mg/kg,

LOAEL= 300 mg/kg, based on 

reduced motor activity for males 

and females (↓19 and ↓51%, 

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 Immunotoxicity

48608901

Acceptable

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

LOAEL not established.

870.7485

Metabolism and 

pharmacokineti

cs [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.
Pendimethalin Human Health Risk Assessment DP No. 416285

Page 35 of 47

TABLE A.2.2 Subchronic, Chronic and Other Toxicity Profile for Pendimethalin.

Guideline 

Number Study Type MRID Number & Classification Dose Levels Results

Nonguideline

Developmental 

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. 
Pendimethalin Human Health Risk Assessment DP No. 416285

Page 36 of 47

Appendix B. International Residue Limits Table 

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico2 Codex

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 Codex

Hop, dried cones 0.1

Citrus fruit group 10-10 0.1

Pome fruit group 11-10 0.1 0.1 apples

Onion, bulb subgroup 3-07A 0.1 0.1 dry bulb onions

Onion, green subgroup 3-07B 0.2

0.2 Beltsville bunching 

onions, elegans hosta, fresh 

(Chinese chive leaves, chive 

leaves, onions), fritillaria 

leaves, green onions, 

kurrats, lady's leeks, leeks, 

macrostem onions, shallot 

leaves, tree onion tops, 

Welsh onion tops, wild leeks

Sunflower subgroup 20B 0.1

Berry, low growing, subgroup 13-07G 0.1

Stone fruit group 12-12 0.1

0.1 apricots, nectarines, 

peaches, cherries (sweet and 

tart)

Fruiting vegetable group 8-10 0.1

Completed by: M. Negussie; 10/10/2014
Pendimethalin Human Health Risk Assessment DP No. 416285

Page 37 of 47

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
Pendimethalin Human Health Risk Assessment DP No. 416285

Page 38 of 47

Appendix D. Occupational Handler Non-Cancer Exposure and Risk Estimates for Pendimethalin

Table D.1.1. Occupational Handler Dermal and Inhalation Non-Cancer Exposure and Risk Estimates for Pendimethalin. 

Applicatio

n 

Equipment

Applicatio

n Type

Crop / Target 

Category

Application 

Rate2

Amount 

Handled 

/ Area 

Treated3

Dermal Unit Exposures 

(ug/lb ai)1

Inhalation Unit 

Exposures 

(ug/lb ai)1

Dermal Dose (mg/kg/day)4 Dermal MOE5

(LOC = 30)

Inhalation Dose 

(mg/kg-day)6

Inhalation MOE7

(LOC = 30)

Value

Units

Value

Units

SL/No 

G

SL/G EC No-R EC SL/No 

G

SL/G EC SL/No 

G

SL/G EC No-R EC No-R EC

Mixer/Loader

Aerial

Broadcast

Dry Bulb Onion 

Subgroup 3-07B

1.9

lb ai/acre

350

acres

220 37.6 8.6 0.22 0.08

0.06 0.01 0.002 180 1,100 4,700 0.002 0.0007 5,500 14,000

Green Onion Subgroup 

3-07B

1

lb ai/acre 0.03 0.005 0.001 350 2,000 8,800 0.001 0.0004 10,000 27,000

Low Growing Berry 

Subgroup 13-07 G

1.4

lb ai/acre 0.04 0.01 0.002 250 1,400 6,300 0.001 0.0005 7,500 20,000

Sunflower Subgroup 

20B

1.7

lb ai/acre

1200

acres

0.17 0.03 0.007 60 350 1,500 0.006 0.002 1,800 4,700

Chemigatio

n

Broadcast

Citrus Fruit Crop 

Group 11-10

6

lb ai/acre

350

acres

0.17 0.03 0.007 58 340 1,500 0.006 0.002 1,700 4,600

Dry Bulb Onion 

Subgroup 3-07B

1.9

lb ai/acre 0.05 0.01 0.002 180 1,100 4,700 0.002 0.0007 5,500 14,000

Green Onion subgroup 

3-07A

1

lb ai/acre 0.03 0.005 0.001 350 2,000 8,800 0.001 0.0004 10,000 27,000

Low Growing Berry 

Subgroup 13-07 G

1

lb ai/acre 0.04 0.007 0.0016 250 1,400 6,300 0.001 0.0005 7,500 20,000

Groundboo

m

Broadcast

Sunflower Subgroup 

20B

1.7

lb ai/acre

200

acres 0.03 0.005 0.001 360 2,100 9,100 0.001 0.0004 11,000 28,000

Dry Bulb Onion 

subgroup 3-07A

1.9

lb ai/acre

80

acres

0.01 0.002 0.0005 800 4,700 20,000 0.0004 0.0002 24,000 63,000

Green Onion 3-07B 1.

lb ai/acre 0.01 0.001 0.0003 1,500 8,800 39,000 0.0002 0.0001 46,000 120,000

Low Growing Berry 

Subgroup 13-07 G

1.4

lb ai/acre 0.01 0.002 0.0004 1,100 6,300 28,000 0.0003 0.0001 33,000 86,000

Hops, Pome Fruit Crop 

Group 11-10, Stone 

Fruit Crop 12-12

4

lb ai/acre 0.03 0.005 0.001 380 2,200 9,700 0.001 0.0003 11,000 30,000

Citrus Fruit Crop 

Group 10-10

6

lb ai/acre 0.04 0.007 0.002 250 1500 6500 0.001 0.0005 7,600 20,000

Applicator

Aerial

Broadcast

Dry Bulb Onion 

subgroup 3-07A

1.9

lb ai/acre 350

acres

2.08 0.005

0.0005 19,000 0.00004 250,00

0

Green Onion 3-07B 1.

lb ai/acre 0.0003 37,000 0.00002 470,000

Sunflower Subgroup 

20B

1.7

lb ai/acre

1200

acres

0.002 6,300 0.0001 80,000

Low Growing Berry 

Subgroup 13-07 G

1.4

lb ai/acre

350

acres

2.08 0.005 0.0004 26,000 0.00003 330,00

0

Groundboo

m

Dry Bulb Onion 

subgroup 3-07A

1.9

lb ai/acre

80

acres

78.6 16.1 5.1 0.34 0.04 0.004 0.001 0.0003 2,200 11,000 34,000 0.0007 0.0001 15,000 120,00

0
Pendimethalin Human Health Risk Assessment DP No. 416285

Page 39 of 47

Table D.1.1. Occupational Handler Dermal and Inhalation Non-Cancer Exposure and Risk Estimates for Pendimethalin. 

Applicatio

n 

Equipment

Applicatio

n Type

Crop / Target 

Category

Application 

Rate2

Amount 

Handled 

/ Area 

Treated3

Dermal Unit Exposures 

(ug/lb ai)1

Inhalation Unit 

Exposures 

(ug/lb ai)1

Dermal Dose (mg/kg/day)4 Dermal MOE5

(LOC = 30)

Inhalation Dose 

(mg/kg-day)6

Inhalation MOE7

(LOC = 30)

Value

Units

Value

Units

SL/No 

G

SL/G EC No-R EC SL/No 

G

SL/G EC SL/No 

G

SL/G EC No-R EC No-R EC

Broadcast Green Onion 3-07B 1.

lb ai/acre 0.002 0.0005 0.0001 4,200 21,000 65,000 0.0003 0.00004 29,000 230,000

Low Growing Berry 

Subgroup 13-07 G

1.4

lb ai/acre 0.003 0.0007 0.0002 3,000 15,000 47,000 0.0005 0.0001 21,000 170,000

Sunflower Subgroup 

20B

1.7

lb ai/acre

200

acres 0.01 0.002 0.001 1,000 4,900 15,000 0.001 0.0002 6,900 55,000

Hops, Pome Fruit Crop 

Group 11-10, Stone 

Fruit Crop 12-12

4

lb ai/acre 80

acres

0.01 0.002 0.0006 1,100 5,200 16,000 0.001 0.0002 7,400 58,000

Citrus Fruit Crop 

Group 10-10

6

lb ai/acre 0.014 0.003 0.0009 710 3,400 11,000 0.002 0.0003 4,900 39,000

Flagger

Aerial

Broadcast

Dry Bulb Onion 

subgroup 3-07A

1.9

lb ai/acre

350

acres

11 12 0.35 0.003 0.003 3,600 3,300 0.003 3,400

Green Onion 3-07B 1.

lb ai/acre 11 12 0.35 0.001 0.002 6,900 6,300 0.002 6,500

Low Growing Berry 

Subgroup 13-07 G

1.4

lb ai/acre 11 12 0.35 0.002 0.002 5,000 4,500 0.002 4,700

Sunflower Subgroup 

20B

1.7

lb ai/acre 11 12 0.35 0.002 0.003 4,100 3,700 0.003 3,800

Mixer/Loader/Applicator

Backpack

Citrus Fruit Crop 

Group 11-10

0.0000184

lb ai/gallon

40

gallons

8260 2.58

2.28E-06 4,400,000 2.38E-08 420,000,000

Hops, Pome Fruit Crop 

Group 11-10, Stone 

Fruit Crop 12-12

0.0000123 lb 

ai/gallon 0.000003 3,500,000 2.96E-08 340,000,000

Dry Bulb Onion 

subgroup 3-07A

0.00000583 lb 

ai/gallon 0.000001 14,000,000 7.53E-09 130,000,000

Green Onion 3-07B 0.00000307 lb 

ai/gallon 0.0000004 26,000,000 3.96E-09 2,500,000,000

Low Growing Berry 

Subgroup 13-07 G

0.0000043 lb 

ai/gallon 0.000001 19,000,000 5.55E-09 1,800,000,000

Sunflower Subgroup 

20B

0.00000522 lb 

ai/gallon 0.0000006 16,000,000 6.74E-09 1,500,000,000

Mechanical

lypressurized 

Handgun

Citrus Fruit Crop 

Group 11-10

0.0000184 lb 

ai/gallon

1000

gallons 1300 390 3.9

0.0000

1

0.00000

3

1,100,0

00 3,7000,00 0.000000898 11,000,000

Hops, Pome Fruit Crop 

Group 11-10, Stone 

Fruit Crop 12-12, 

0.0000123 lb 

ai/gallon

0.0000

1

0.00000

2

1,700,0

00 5,600,000 0.0000006

17,000,000

Dry Bulb Onion 

subgroup 3-07A

0.0000043 lb 

ai/gallon 0.0000

03

0.00000

09

3,500,0

00

12,000,00

0

0.000000

284 35,000,000

Green Onion 3-07B 0.00000307 

lb ai/gallon

0.0000

02

0.00000

05

6,700,0

00

22,000,00

0

0.000000

15 67,000,000

Low Growing Berry 

Subgroup 13-07 G

0.0000043 lb 

ai/gallon

0.0000

02

0.00000

1

48,00,0

00

16,000,00

0

0.000000

21 48,000,000

Sunflower Subgroup 

20B

0.00000522 lb 

ai/gallon

0.0000

03

0.00000

1

3,900,0

00

13,000,00

0

0.000000

255 39,000,000
Pendimethalin Human Health Risk Assessment DP No. 416285

Page 40 of 47

Table D.1.1. Occupational Handler Dermal and Inhalation Non-Cancer Exposure and Risk Estimates for Pendimethalin. 

Applicatio

n 

Equipment

Applicatio

n Type

Crop / Target 

Category

Application 

Rate2

Amount 

Handled 

/ Area 

Treated3

Dermal Unit Exposures 

(ug/lb ai)1

Inhalation Unit 

Exposures 

(ug/lb ai)1

Dermal Dose (mg/kg/day)4 Dermal MOE5

(LOC = 30)

Inhalation Dose 

(mg/kg-day)6

Inhalation MOE7

(LOC = 30)

Value

Units

Value

Units

SL/No 

G

SL/G EC No-R EC SL/No 

G

SL/G EC SL/No 

G

SL/G EC No-R EC No-R EC

Manuallypressurized 

Handwand

Citrus Fruit Crop 

Group 11-10

0.0000184 lb 

ai/gallon

40 

gallons

100,00

0

430 30

0.0000

3

0.00000

01 360,000 84,000000

0.000000

276 36,000,000

Hops, Pome Fruit Crop 

Group 11-10, Stone 

Fruit Crop 12-12

0.0000123 lb 

ai/gallon 0.0001 7.95E08 540,000 13,0000,000

0.000000

185 54,000,000

Dry Bulb Onion 

subgroup 3-07A

0.0000043 lb 

ai/gallon 0.0000

06

2.78E081,600,0

00

36,0000,0

00 6.45E-08 160,000,000

Green Onion 3-07B 0.00000307

lb ai/gallon

0.0000

05

1.98E082,200,0

00

510,000,0

00

0.000000

046 220,000,000

Low Growing Berry 

Subgroup 13-07 G

0.0000043 lb 

ai/gallon

0.0000

06

2.78E081,600,0

00

360,000,0

00 6.45E-08 160,000,000

1 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (March 2014); Level of mitigation: Baseline, PPE, and Eng. Controls. Shaded out cells suggest no data available or non-applicable. 

2 Based on registered or proposed label (Reg. No.241-418).

3 Exposure Science Advisory Council Policy #9.1.

4 Dermal Dose = Dermal Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A or gal/day) × DAF (%) ÷ 80 (kg).

5 Dermal MOE = Dermal NOAEL (mg/kg/day) ÷ Dermal Dose (mg/kg/day).

6 Inhalation Dose = Inhalation Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A or gal/day) ÷ 80 (kg).

7 Inhalation MOE = Inhalation NOAEL (mg/kg/day) ÷ Inhalation Dose (mg/kg/day).

8 SL/No G = Baseline PPE (long sleeved shirt, long pants, shoes and socks) no gloves
Pendimethalin Human Health Risk Assessment DP No. 416285

Page 41 of 47

Table D.1.2. Combined Occupational Handler Non-Cancer Exposure and Risk Estimates for Pendimethalin.

Application 

Equipment

Application 

Type

Crop / Target Category

Applic

ation 

Rate2

Amount 

Handle

d Area 

Treated

3

Dermal Unit 

Exposures (ug/lb ai)1

Inhalation Unit 

Exposures (ug/lb 

ai)1

Combined Dose (mg/kg-day) Combined MOE8

(LOC = 30)

Value

Units

Value

Units

SL/

No 

G

SL/G EC No-R EC SL/No G 

+ No-R

SL/G + 

No-R

EC SL/No G 

+ No-R

SL/G 

+ NoREC

Mixer/Loader

Aerial

Broadcast

Dry Bulb Onion Subgroup 3-

07B

1.9

lb 

ai/acre

350

acres

220 37.6 8.6 0.22 0.083

0.06 0.01 0.003 170 920 3,500

Green Onion Subgroup 3-

07B

1

lb 

ai/acre

0.03 0.01 0.0015 340 1,700 6,600

Low Growing Berry 

Subgroup 13-07 G

1.4

lb 

ai/acre

0.04 0.01 0.002 240 1,200 4,800

1200

acres

Sunflower Subgroup 20B

1.7

lb 

ai/acre

0.17 0.03 0.01 58 290 1,100

Chemigation

Broadcast

Citrus Fruit Crop Group 11-

10

6

lb 

ai/acre

350

acres

0.18 0.04 0.01 56 280 1,100

Dry Bulb Onion Subgroup 3-

07B

1.9

lb 

ai/acre

0.06 0.01 0.003 170 920 3,500

Green Onion subgroup 3-07A

1

lb 

ai/acre

0.03 0.01 0.0015 340 1,700 6,600

Low Growing Berry 

Subgroup 13-07 G

1

lb 

ai/acre

0.04 0.008 0.0021 240 1,200 4,800

Groundboom

Broadcast

Sunflower Subgroup 20B

1.7

lb 

ai/acre

200

acres

0.029 0.006 0.0015 350 1,800 6,900

Dry Bulb Onion subgroup 3-

07A

1.9

lb 

ai/acre

80

acres

220 37.6 8.6 0.22 0.083

0.0129 0.0026 0.00065 770 3,900 15,000

Green Onion 3-07B

1.

lb 

ai/acre

0.00682 0.0014 0.0003 1,500 7400 2,9000

Low Growing Berry 

Subgroup 13-07 G

1.4

lb 

ai/acre

0.00954 0.0019 0.0005 1,100 5,300 21,000
Pendimethalin Human Health Risk Assessment DP No. 416285

Page 42 of 47

Table D.1.2. Combined Occupational Handler Non-Cancer Exposure and Risk Estimates for Pendimethalin.

Application 

Equipment

Application 

Type

Crop / Target Category

Applic

ation 

Rate2

Amount 

Handle

d Area 

Treated

3

Dermal Unit 

Exposures (ug/lb ai)1

Inhalation Unit 

Exposures (ug/lb 

ai)1

Combined Dose (mg/kg-day) Combined MOE8

(LOC = 30)

Value

Units

Value

Units

SL/

No 

G

SL/G EC No-R EC SL/No G 

+ No-R

SL/G + 

No-R

EC SL/No G 

+ No-R

SL/G 

+ NoREC

Hops, Pome Fruit Crop 

Group 11-10, Stone Fruit 

Crop 12-12

4

lb 

ai/acre

0.0273 0.00583 0.00136 370 1,800 7,300

Citrus Fruit Crop Group 10-

10

6

lb 

ai/acre

0.0411 0.00806 0.00205 240 1,300 4,900

Applicator

Aerial

Broadcast

Dry Bulb Onion subgroup 3-

07A

1.9

lb 

ai/acre

350

acres

2.08 0.005 0.0006 18,000

Green Onion 3-07B

1.

lb 

ai/acre

350

acres

2.08 0.005 0.00029

5

34,000

Sunflower Subgroup 20B

1.7

lb 

ai/acre

1200

acres

2.08 0.005 0.00172 5800

Low Growing Berry 

Subgroup 13-07 G

1.4

lb 

ai/acre

350

acres

2.08 0.005 0.00041

3

24,000

Groundboom

Broadcast

Dry Bulb Onion subgroup 3-

07A

1.9

lb 

ai/acre

80

acres

78.6 16.1 5.1 0.34 0.04

0.005 0.002 0.0004 1,900 63,00 26,000

Green Onion 3-07B

1.

lb 

ai/acre

0.0027 0.001 0.0002 3,700 12,000 51,000

Low Growing Berry 

Subgroup 13-07 G

1.4

lb 

ai/acre

0.004 0.001 0.0003 2,600 8800 37,000

Hops, Pome Fruit Crop 

Group 11-10, Stone Fruit 

Crop 12-12

4

lb 

ai/acre

0.01 0.003 0.0008 960 3,100 13,000

Citrus Fruit Crop Group 10-

10

6

lb 

ai/acre 0.02 0.005 0.001 620 2,000 8,600

Sunflower Subgroup 20B

1.7

lb 

ai/acre

200

acres

0.01 0.003 0.001 870 2,900 12,000

Hops, Pome Fruit Crop 

Group 11-10, Stone Fruit 

Crop 12-12

4

lb 

ai/acre

80 acres 0.0108 0.00329 0.00078

4

960 3,100 13,000
Pendimethalin Human Health Risk Assessment DP No. 416285

Page 43 of 47

Table D.1.2. Combined Occupational Handler Non-Cancer Exposure and Risk Estimates for Pendimethalin.

Application 

Equipment

Application 

Type

Crop / Target Category

Applic

ation 

Rate2

Amount 

Handle

d Area 

Treated

3

Dermal Unit 

Exposures (ug/lb ai)1

Inhalation Unit 

Exposures (ug/lb 

ai)1

Combined Dose (mg/kg-day) Combined MOE8

(LOC = 30)

Value

Units

Value

Units

SL/

No 

G

SL/G EC No-R EC SL/No G 

+ No-R

SL/G + 

No-R

EC SL/No G 

+ No-R

SL/G 

+ NoREC

Citrus Fruit Crop Group 10-

10

6

lb 

ai/acre

0.0161 0.00494 0.00118 620 2,000 8,600

Flagger

Aerial

Broadcast

Dry Bulb Onion subgroup 3-

07A

1.9

lb 

ai/acre

350

acres

11 12 0.35

0.006 0.006 1,700 1,700

Green Onion 3-07B

1.

lb 

ai/acre

0.003 0.003 3,300 3,200

Low Growing Berry 

Subgroup 13-07 G

1.4

lb 

ai/acre

0.00417 0.00436 2,400 2,300

Sunflower Subgroup 20B

1.7

lb 

ai/acre

0.00506 0.00528 2,000 1,900

Mixer/Loader/Applicator

Backpack

Citrus Fruit Crop Group 11-

10

0.0000

184

lb 

ai/gallo

n

40

gallons 8260 2.58

0.000002 4,400,000

Hops, Pome Fruit Crop 

Group 11-10, Stone Fruit 

Crop 12-12

0.0000

123 lb 

ai/gallo

n

0.000003 3,500,000

Dry Bulb Onion subgroup 3-

07A

0.0000

0583 lb 

ai/gallo

n

0.000001 14,000,000

Green Onion 3-07B

0.0000

0307 lb 

ai/gallo

n

0.0000004 26,000,000

Low Growing Berry 

Subgroup 13-07 G

0.0000

043 lb 0.0000005 19,000,000
Pendimethalin Human Health Risk Assessment DP No. 416285

Page 44 of 47

Table D.1.2. Combined Occupational Handler Non-Cancer Exposure and Risk Estimates for Pendimethalin.

Application 

Equipment

Application 

Type

Crop / Target Category

Applic

ation 

Rate2

Amount 

Handle

d Area 

Treated

3

Dermal Unit 

Exposures (ug/lb ai)1

Inhalation Unit 

Exposures (ug/lb 

ai)1

Combined Dose (mg/kg-day) Combined MOE8

(LOC = 30)

Value

Units

Value

Units

SL/

No 

G

SL/G EC No-R EC SL/No G 

+ No-R

SL/G + 

No-R

EC SL/No G 

+ No-R

SL/G 

+ NoREC

ai/gallo

n

Sunflower Subgroup 20B

0.0000

0522 lb 

ai/gallo

n

0.0000007 16,000,000

Mechanicallypressurized 

Handgun

Citrus Fruit Crop Group 11-

10

0.0000

184 lb 

ai/gallo

n

1000

gallons

130

0

390 3.9

0.00001 0.00000

4

1,000,000 2,800,0

00

Hops, Pome Fruit Crop 

Group 11-10, Stone Fruit 

Crop 12-12 

0.0000

123 lb 

ai/gallo

n

0.000007 0.00000

2

1,500,000 4,200,0

00

Dry Bulb Onion subgroup 3-

07A

0.0000

043 lb 

ai/gallo

n 

0.000003 0.00000

114 3200,000 8,900,000

Green Onion 3-07B

0.0000

0307 

lb 

ai/gallo

n

0.000002 0.00000

06 6,100,000 17,000,000

Low Growing Berry 

Subgroup 13-07 G

0.0000

043 lb 

ai/gallo

n

0.000002 0.00000

084 4,400,000 12,000,000

Sunflower Subgroup 20B

0.0000

0522 lb 

ai/gallo

n

0.000003 0.00000

102 3500,000 9,800,000

Manuallypressurized 

Handwand

Citrus Fruit Crop Group 11-

10

0.0000

184 lb 

ai/gallo

n

40 

gallons

100,

000 430 30

0.00003 0.00000

04 360,000 2,500,0000

Hops, Pome Fruit Crop 

Group 11-10, Stone Fruit 

Crop 12-12

0.0000

123 lb 

ai/gallo

n

0.000018 0.00000

027 530,000 380,00,000

Dry Bulb Onion subgroup 3-

07A

0.0000

043 lb 0.000007 9.23E08 1,600,000 11,000,0000
Pendimethalin Human Health Risk Assessment DP No. 416285

Page 45 of 47

Table D.1.2. Combined Occupational Handler Non-Cancer Exposure and Risk Estimates for Pendimethalin.

Application 

Equipment

Application 

Type

Crop / Target Category

Applic

ation 

Rate2

Amount 

Handle

d Area 

Treated

3

Dermal Unit 

Exposures (ug/lb ai)1

Inhalation Unit 

Exposures (ug/lb 

ai)1

Combined Dose (mg/kg-day) Combined MOE8

(LOC = 30)

Value

Units

Value

Units

SL/

No 

G

SL/G EC No-R EC SL/No G 

+ No-R

SL/G + 

No-R

EC SL/No G 

+ No-R

SL/G 

+ NoREC

ai/gallo

n 

Green Onion 3-07B

0.0000

0307

lb 

ai/acre

0.000005 6.58E08 2,200,000 15,000

0,000

Low Growing Berry 

Subgroup 13-07 G

0.0000

043 lb 

ai/gallo

n

0.000007 9.23E08 1,600,000 110,00

0,000

1 Based on “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (March, 2014); includes data from PHED/ORETF/AHETF. 2 Based on proposed label (Reg. No.241-418). 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/ (dermal MOE) +inhalation MOE).
Pendimethalin Human Health Risk Assessment DP No. 416285

Page 46 of 47

Table D.1.3. Short-/Intermediate-Term Combined 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

Application 

Rate2

Amount 

Treated 

Daily3

Dose (mg/kg/day)4 MOE5 Combined 

Short and 

Intermediateterm MOEs 6

Dermal Inhalation Dermal

(LOC =30)

Inhalation

(LOC =30)

Mixer/Loader 

Commercial Impregnation of Dry 

Bulk Fertilizers

(closed system)

Sunflower 

Subgroup 

20B

0.0086 0.000083 

17 lb ai/ton

960 tons 0.06 0.049 170 200 92

500 tons 0.031 0.026 320 3,90 180

On-farm Impregnation of Dry 

Bulk Fertilizers

0.22

Baseline

0.000219

Baseline

160 A 0.022 0.00074 450 13,000 430

80 A 0.011 0.00037 890 27,000 860

Commercial Impregnation of Dry 

Bulk Fertilizers

(closed system) Bermudagra

ss

0.0086 0.000083

40 lb ai/ton

960 tons 0.13 0.1 79 97 44

500 tons 0.074 0.06 140 170 75

On-farm Impregnation of Dry 

Bulk Fertilizers

0.22

Baseline

0.000219

Baseline

160 A 0.053 0.0018 190 5,700 180

80 A 0.026 0.00088 380 1,100 370

Applicator

Commercial Impregnation of Dry 

Bulk Fertilizers 320-160 Acres

And

On-Farm Impregnation of Dry 

Bulk Fertilizer at 160 and 80 

Acres

Sunflower 

Subgroup 

20B 0.0099

Baseline 

0.0012

Baseline 

17 lb ai/ton

320 A 0.002 0.0082 5,000 1,200 980

160 A 0.0012 0.0041 9,900 2,500 2,000

80 A 0.0005 0.002 20,000 4,900 3,900

Bermudagra

ss

40 lb ai/ton

320 A 0.0048 0.019 2,100 520 420

160 A 0.0024 0.0096 4,200 1,000 840

80 A 0.0012 0.0048 8,400 2,100 1,700

1 Based on “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (March, 2014); includes data from PHED/ORETF/AHETF. 

2 Based on proposed label (Reg. No.241-418).

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/ (dermal MOE) +inhalation MOE).
Pendimethalin Human Health Risk Assessment DP No. 416285

Page 47 of 47

Appendix E. 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 data, which include studies from 

PHED 1.1; the AHETF database; the Outdoor Residential Exposure Task Force (ORETF) 

database; the ARTF database; are (1) subject to ethics review pursuant to 40 CFR 26, (2) have 

received that review, and (3) are compliant with applicable ethics requirements. For certain 

studies, the ethics review may have included review by the Human Studies Review 

Board. Descriptions of data sources, as well as guidance on their use, can be found at the 

Agency website: http://www.epa.gov/pesticides/science/handler-exposure-data.html and 

http://www.epa.gov/pesticides/science/post-app-exposure-data.html.