### 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 Ri s k A ss e ss ment for N e w U s e on Hop s, and Crop Subgroup Conver s ions/Expansion s for Low Growing Berr:y Subgroup 13-07G

, Onion

, Bulb Subgroup 3-07A

, Onion, Green Subgroup 3-07B, and Sunflower Subgroup 20B; Crop Group E xpan si ons for**Citru ~**  

### Fruit

, Group 10

, Pome Fruit

, Group 11

,**Ston ~**  

### fruit

, Group 12, and

Fruitin g V ege table

, Gr o up 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. 3 61

F:ROM : P. Yvonne Barnes, Chemi s t and Risk Asse ss or s.umitra Bo se -Biswas

,

## Chemi**·** Bridget Bob ow iec

, Biolo g i s t**~** 

### Yung Yan g, Ph.D.

, To x i co lo g i s t 

# t1 7 

# 6-

Ri s k A ss e ss ment Branch VI (/
Health Effect s Division (7509P)

THROUGH: Mohsen Sahafeyan, Chemi s t 

## 1:

DonnaS. D a vi s, acting Chi e f \{

Ri s k A ssess m e nt Branch VI

Health Eff ec t s Division (7509P)

TO : Sidney Jack s on, Chemical Ri s k Manager

Barbara Madden, Chief 

## Regi s tr a tion Di v ision ( 7505P)



## Page 1 of 47**~-** . .

### Pendimethalin Human Health Risk Assessment DP No. 416285

Page 2 of 47 Table of Contents

1.0 Executive Summary

................................ ................................ ................................ ............. 4
2.0 HED Recommendations

................................ ................................ ................................ ....... 5

2.1 De ficiencies

................................ ................................ ................................ ...................... 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 Phys ical/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

### Pendimethalin Human Health Risk Assessment DP No. 416285

Page 3 of 47 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

### Pendimethalin Human Health Risk Assessment DP No. 416285

Page 4 of 47 1.0 Executive Summary

The Health Effects Division (HED) has evaluated the current databases for p endimethalin 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. I t 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 to lerances 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 expan sions/updates for crop Groups from gro up 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 incr eased 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, t here is no evidence of increased qualitative or quanti tative 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 n ew 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 analysi s 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 population s.

### Pendimethalin Human Health Risk Assessment DP No. 416285

Page 5 of 47 There are no proposed new reside ntial 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).

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

and intermediate

- term margins of exposure (MOEs) are not of concern to HED (i.e.

, MOE > 30)

. An o ccupational 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 short

and intermediate

- term aggregate exposure and risk assessments which combined average food and water exposure and non

- dietary (residential) sources of exposure to pendimethalin. The
resultin g 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

ass essment 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. S tudies that involve adult human subjects are subject to ethics review pursuant to 40 C FR 26, the studies relied on have received that review, and are compliant with applicable ethics requirements.

2.0 H ED Recommendations

There are no human health risk concerns that would preclude granting the requested new use on hops and establishment of th e 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 n oted relative to these petitioned for actions.

### Pendimethalin Human Health Risk Assessment DP No. 416285

Page 6 of 47 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 d etermine 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 analytica l 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 ch romatographs 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.

### Pendimethalin Human Health Risk Assessment DP No. 416285

Page 7 of 47 2.2.2 Recommended Tolerances

Table 2.2. 2 summarizes the registrant’s petitioned for tolerance s , 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 T olerance 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

o nion 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

o nion 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.

### Pendimethalin Human Health Risk Assessment DP No. 416285

Page 8 of 47 2.2.3 Revisions to Petition ed 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, w hich 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 f rom Residential Assessment

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

3.0 In troduction

3.1 Chemical Identity

The chemical structure and nomencla ture 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.

### Pendimethalin Human Health Risk Assessment DP No. 416285

Page 9 of 47 Table 3.1 Pendimetha lin 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 lb s

. a.i. gal capsule suspension formulation (equivalent to 450 g a.i. L;
Prowl® H 2 O 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

a bsorbed 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 calculate d half

- life of 17 days.

### Pendimethalin Human Health Risk Assessment DP No. 416285

Page 10 of 47 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 us e of Prowl ® 

### H 2 

### O on hops is proposed at a maximum single use rate of 4.0 lb s

. 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 hop s

. Additionally, IR

- 4 has submitted supplemental labels for Prowl ® 

### H 2 

### O 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 exp ansions 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, c orn, 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 regis tered for use on container grown and field grown ornamentals . H owever , it is not to be used in greenhouses, shade houses, or other enclosed structures. The Prowl ® 

### H 2 

### O label requires applicators and other handlers to wear a long

- sleeved shirt and long pant s and shoes plus socks, plus chemical

- resistant gloves. Table 3.3 summarizes the proposed new use and crop expansion
label directions.

### Pendimethalin Human Health Risk Assessment DP No. 416285

Page 11 of 47 Table 3.3 . Summary of Proposed Directions for Use of Pendimethalin.

Commodity Product

Name (EPA Reg. No.) Application

Equipment Max.

Single Applicatio

n Rate (lb s.

a

. i

. /A) Max #

Application

s Per Season Max

Seasonal Application

Rate (lb s. a

. i

. /A) PHI 1

(days) Use Directions and

Limitations

Hops

Prowl ®

H 2 O (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 subgr oup 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 post

emergence 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 direct

seeded fruiting vegetables. Do not apply post

emergence. 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

Low

Growing 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 post

emergence. 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.

1 PHI = pre

- harvest interval

### Pendimethalin Human Health Risk Assessment DP No. 416285

Page 12 of 47 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 w ater 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 Justic e

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 a ccording 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 inv olve 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 a re 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 lifest yle 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 ey e irritant

, and is not a dermal sensitizer. The thyroid is the target organ for pendimethalin.

### Pendimethalin Human Health Risk Assessment DP No. 416285

Page 13 of 47 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/ 19 92 and re

- affirmed 11/01/ 19 99) as a "Group C", possible human carcinogen based on a statistically significant increased trend and pair

- wise comparison between the high dose group and controls for thyroid follicular cell adenomas in
male and female rats. The Commi ttee also recommended a non

- quantitative approach (i.e., non

linear, RfD approach) since mode of action studies are available that demonstrate that the thyroid tumors are due to a thyroid

- pituitary imbalance, and also since pendimethalin was shown to be

no n

- 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 pendimet halin is a developmental, reproductive, neurotoxic, or immunotoxic chemical.

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

In a metabolism study (MRID 00046275), when { 14 

### C} pendimethalin was administered to rats,
about 70% of the radioactivit y 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 we ll 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 compariso n 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 the se 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 Safet y 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

### Pendimethalin Human Health Risk Assessment DP No. 416285

Page 14 of 47 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 wer e 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 qu alitative 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 toxic ity 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

ass umptions 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.

### Pendimethalin Human Health Risk Assessment DP No. 416285

Page 15 of 47 4.3 Toxicity Endpoint and Point of Dep arture 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 obse rved 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 100 x (10x for interspecies extrapolation, 10x for int raspecies 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 wa s 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) wer e considered co

- critical in establishing a PoD for chronic dietary risk assessment . A ll stud ies reflecting thyroid toxicity, HED has determined that these studies collecti vely 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 (3 x for interspecies extrapo lation and 10x for intraspecies variation) is applied to the NOAEL of 1 0 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 re duced 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). Th e FQPA factor is reduced to1x

. The chronic popula tion 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 demonstrate d early on

- set (before 14 days). Therefore, HED has determined that
these studies collecti vely 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

e ffects 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

### Pendimethalin Human Health Risk Assessment DP No. 416285

Page 16 of 47 scen ario. T hese co

- critical studies collecti vely 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 durati ons 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 Exposur e (Short, Intermediate , and Long

- Term) : There was no inhalation study available except the acute inhalat ion 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. T hese co

- critical studies collecti vely 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 hormon al 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 de rived 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 UF A = 10X

UF H = 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 UF A = 3X

UF H = 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/d ay 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 UF A = 3X

UF H = 10X FQPA SF = 1X

Total UF = 30X Residential LOC = 30

Occupational LOC =

30 The same as the chronic dietary.

### Pendimethalin Human Health Risk Assessment DP No. 416285

Page 17 of 47 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 UF A = 3X

UF H = 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 UF A = 3X

UF H = 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 availa ble.
UF = uncertainty factor, UF A = extrapolation from animal to human (interspecies), UF H = potential variation in sensitivity among members of the human population (intra

- species), FQPA SF = FQPA safety factor, NOAEL = no observed adverse effect level, L OAEL = 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 a nd 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 no n

- 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 pendimet halin 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.

### Pendimethalin Human Health Risk Assessment DP No. 416285

Page 18 of 47 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, sex ual 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 secti on 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 eff ect 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 poten tial 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, 2013 1 

### and includes some pesticides sc heduled 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
chemic als, 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/

### Pendimethalin Human Health Risk Assessment DP No. 416285

Page 19 of 47 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.

Matrix 1 

### 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)

. R esidues 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.

R eplacing sunflower with saff lower 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 shoot s , transloca tion to foliage is extremely limited. Residues of pendimethalin and/or its metabolite at harvest are usually very low or non

detectable, (e.g., below the level of quantification).

5.3 Water Residue profile

The estimated drinking water residues used in the d ietary 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 H uman 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

### Pendimethalin Human Health Risk Assessment DP No. 416285

Page 20 of 47 the food categories “water, dire ct, 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)

Value s 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 Ag riculture’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 pendim ethalin 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 p rocessing 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 95 th 

### percentile of exposure. HED is concerned when estimated dietary risk exceeds 100%. There are no acute dietary risks of concern (Table 5. 5

. 6 ).

### Pendimethalin Human Health Risk Assessment DP No. 416285

Page 21 of 47 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 estim ated 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 a ction 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 consid ered 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 Dietary 1 (95th Percentile) Chronic Dietary 1 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/ 20 12, D 402406)

.

### Pendimethalin Human Health Risk Assessment DP No. 416285

Page 22 of 47 This assessment incorporated recent revisions to the Standard Operating Procedures for Residential Pesticide Exposure Asse ssment, 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 memora ndum. 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 post

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

assessment. However, t he children’s oral exposure is based on combining the short term post

application hand

- to

- mouth exposures ( 0.042 ) with the short term derm al 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 h and

- to

- mouth exposures from short term duration post

application 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

Dermal e Hand

- to

- Mouth Combined Exposure Used for Aggregate

Dose a MOE b Dose c MOE d Dose MOE Dose MOE Total
Dose Total

MOE f

Adults 0.015 670 5.4E

- 05 180,000 0.078 130 N/A 0.078 130

Children 1

< 2 y ears

o ld 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 (4lb s 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.

### Pendimethalin Human Health Risk Assessment DP No. 416285

Page 23 of 47 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

- HQ

OPP

- 2014

- 0219). 

### During Reg istration 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

S pray 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 fo r 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 regulat ion 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 applicati on 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 maj or 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

### Pendimethalin Human Health Risk Assessment DP No. 416285

Page 24 of 47 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 Ris k

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 ag gregate assessment, see
Section 6.0.

The adult (dermal) aggregate MOE (for males and females) is 12 5 , which indicates that exposure
and risk do not excee d 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 9 3 , which indicates that exposure and ri sk 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 LOC 1 Max

Allowable Exposure 2 mg/kg/day Average

Food and

Water Exposure mg/kg/day Residential

Exposure mg/kg/day 3 Total

Exposure mg/kg/day 4 Aggregate

MOE (food, water, and residential) 5

Adult 10 30 0.33 0.001256 0.078 0. 08 0 130

Child 10 30 0.33 0.005043 0.102 0.1 0 7 9 3

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 A ggregate MOE= [NOAEL (10 mg/kg/day)/ (Total Exposure (0.107 mg/kg/day)]

### Pendimethalin Human Health Risk Assessment DP No. 416285

Page 25 of 47 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 e xposure is not expected for the residential (dermal and inhalation) exposure pathway s

. 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 carc inogen” 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 r ecommended 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 o f 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 dete rmine 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 cumul ating effects from substances found to have
a common mechanism on EPA’s website at http://www.epa.gov/pesticides/cumulative/

.

### Pendimethalin Human Health Risk Assessment DP No. 416285

Page 26 of 47 9.0 Occupational Exposure/Risk Characterization

9.1 Short

- /Intermediate

- Term Han dler 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 rat es 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 post

application activities (irriga tion, 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 leve ls 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 applie d 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 pendim e thalin 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 use s

.

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 ® 

### H 2 

### O 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 tobac co. 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

### Pendimethalin Human Health Risk Assessment DP No. 416285

Page 27 of 47 aqueous solution of PROWL 3.3 EC herbicid e 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) (cm 2 /h ou r) DFR 1 Dermal Dose (mg/kg/day) 2 MOE 3

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/cm 2 ; where F = 0.25 and D = 0.10 per day.

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



### Restricted Entr y 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 intermedi ate

- 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

.

### Pendimethalin Human Health Risk Assessment DP No. 416285

Page 28 of 47 9.2.2 Inhalation Post

- applicatio n 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 pre ssure (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 pe sticides 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

P anel (SAP) in December 2009, and received the SAP’s final report on March 2, 2010 4 

### . 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, deve lop policies and procedures, to identify the need for and, subsequently, the way to incorporate occupational post

application inhalation exposure into the Agency's risk assessments. If new policies or procedures are put into place, the Agency may revisit the need for a quantitative occupational
post

- application inhalation exposure assessment for pendimeth a lin.

Although a quantitative occupational post

- application inhalation exposure assessment was not performed, an inhalation exposure assessment was perfo rmed 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 estimate s would be protective of most occupational post

- application inhalation exposure scenarios

.

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

### Pendimethalin Human Health Risk Assessment DP No. 416285

Page 29 of 47 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/ 20 07. Pendimethalin. Human Health Risk Assessment for the Proposed Food/Feed Use of the Herbicide (Associated with Section 18 Registr ation) on Bermuda Grass and Hay Fields in Texas. PC Code 108501; DP Barcode D349723; W. Drew; 05/20/ 20 08. Pendimethalin. Human Health Risk Assessment for the Proposed Tolerance in/on Crayfish. PC Code 108501; DP Barcode D350493; C. Olinger; 03/31/ 20 08. 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# 23846 9, and Submission of Limited Field Accumulation in Rotational Crop Data in Response to DP# 319412. Summary of Analytical Chemistry and Residue Data. DP Barcode : D 372189; Y. Barnes; 0 6/ 0 5 / 20 12

. 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 2 0B; 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. D P# Barcode: D 416576, 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. B reithaupt, 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. D 416577. 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, 05/31/20 12

. 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. ; D 416578, 11/07/2014

### Pendimethalin Human Health Risk Assessment DP No. 416285

Page 30 of 47 A ppendix 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

### Pendimethalin Human Health Risk Assessment DP No. 416285

Page 31 of 47 A.2 Toxicity Profile s

Table A.2.1 Acute Toxicity Profile

- Pendimethalin

Guideline No. Study Type MRID(s) Results Toxicity Category

870.1100 Acute oral [Rat] 00026657 LD 50 =1250 mg/kg (m) =1050 mg/kg (f) III

870.1200 Acute dermal [Rabbit] 00026657 LD 50 = >1250 mg/kg IV

870.1300 Acute inhalation [Rat] 00073342 LC 50 = 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.

### Pendimethalin Human Health Risk Assessment DP No. 416285

Page 32 of 47 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.

### Pendimethalin Human Health Risk Assessment DP No. 416285

Page 33 of 47 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).

### Pendimethalin Human Health Risk Assessment DP No. 416285

Page 34 of 47 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 Immu n otoxicity 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

Non

guideline 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

- examini ng effects.

### Pendimethalin Human Health Risk Assessment DP No. 416285

Page 36 of 47 A ppendix B. International Residue Limits Table

Summary of US and International Tolerances and Maximum Residue Limits Residue Definition :
US Canada Mexico 2 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

- dimethyl

2,6

- dinitro

- , including the metabolite benzenemethanol,

4

- [(1

- ethylpropyl)amino]

- 2

- methyl

- 3,5

- dinitro

None

Commodity 1 Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico 2 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 Appen dix 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/cm 3 (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, pK
a Too small t o measure CB# 789, 06/13/1986, G. Makhijani
Octanol/water partition coefficient, Log(K OW ) 5.18 DP#s 271502 and 317053, 07/12/2006, W. Drew
UV/visible absorption
spectrum UV molecular extinction =

3.81 x 10 4 at 234 nm,
1.93 x 10 4 at 280 nm. DP#s 271502 and 317053, 07/12/2006, W. Drew

### Pendimethalin Human Health Risk Assessment DP No. 416285

Page 38 of 47 A ppendix D

. Occupational Handler Non

- Cancer Exposur e and Risk Estimates for Pendime thalin

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

Rate 2 Amount

Handled
/ Area

Treated 3 Dermal Unit Exposures

(ug/lb ai) 1 Inhalation Unit Exposures (ug/lb ai) 1 Dermal Dose (mg/kg/day) 4 Dermal MOE 5
(LOC = 30) Inhalation Dose (mg/kg

- day) 6 Inhalation MOE 7
(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 46,000 120,00

0 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 470,00

0 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

Rate 2 Amount

Handled
/ Area

Treated 3 Dermal Unit Exposures

(ug/lb ai) 1 Inhalation Unit Exposures (ug/lb ai) 1 Dermal Dose (mg/kg/day) 4 Dermal MOE 5
(LOC = 30) Inhalation Dose (mg/kg

- day) 6 Inhalation MOE 7
(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 29,000 230,00
0 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 21,000 170,00

0

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 2,500,000,00

0 Low Growing Berry Subgroup 13

- 07 G 0.0000043 lb ai/gallon 0.000001 19,000,000 5.55E

- 09 1,800,000,00

0 Sunflower Subgroup

20B 0.00000522 lb

ai/gallon 0.0000006 16,000,000 6.74E

- 09 1,500,000,00

0

Mechanical ly

pressurized 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 0.000000
898 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 0.000000

6 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

Rate 2 Amount

Handled
/ Area

Treated 3 Dermal Unit Exposures

(ug/lb ai) 1 Inhalation Unit Exposures (ug/lb ai) 1 Dermal Dose (mg/kg/day) 4 Dermal MOE 5
(LOC = 30) Inhalation Dose (mg/kg

- day) 6 Inhalation MOE 7
(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

Manually

pressurized
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 84,00000
0 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 7.95E

08 540,000 13,0000,0
00 0.000000
185 54,000,000

Dry Bulb Onion subgroup 3

- 07A 0.0000043 lb ai/gallon 0.0000
06 2.78E

08 1,600,0
00 36,0000,0

00 6.45E

- 08 160,000,000

Green Onion 3

- 07B 0.00000307 lb ai/gallon 0.0000

05 1.98E

08 2,200,0

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 2.78E

08 1,600,0

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: Base line, PPE, and Eng. Controls. Shaded out cells suggest no data available or non

- applic able.

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 Am ount 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 Trea ted 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

Rate 2 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 MOE 8 (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

+ 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 0.083 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

Rate 2 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 MOE 8 (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

+ No

R EC

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

Rate 2 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 MOE 8 (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

+ No

R EC

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

Rate 2 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 MOE 8 (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

+ No

R EC

ai/gallo

n

Sunflower Subgroup 20B 0.0000
0522 lb ai/gallo

n 0.0000007 16,000,000

Mechanically

pressurized 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 8,900,0
00

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 9,800,0
00

Manually

pressurized
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 2,500,0

000

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 9.23E

08 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

Rate 2 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 MOE 8 (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

+ No

R EC

ai/gallo

n

Green Onion 3

- 07B 0.0000
0307
lb
ai/acre 0.000005 6.58E

08 2,200,000 15,000 0,000

Low Growing Berry Subgroup 13

- 07 G 0.0000
043 lb ai/gallo

n 0.000007 9.23E

08 1,600,000 110,00 0,000

1 Based on “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (March, 2014); includes data from PHED/ORET F/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 Hand led (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,

I nhalation NOAEL (ST and IT) = 10 mg/kg bw/day. 6 Combined 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

Expo sure Scenario Crops Dermal Unit Exposure (mg/lb ai) 1 Inhalation

Unit Exposure (mg/lb ai) 1 Application

Rate 2 Amount

Treated Daily 3 Dose (mg/kg/day) 4 MOE 5 Combined
Short and
Intermediate

term 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.

6 Combined 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 compli ant 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

.