UN I TED S T ATES ENVIRONMENTAL PROTECT I ON AGENCY

WAS H INGTON

, D

. C

. 20460

O FF I CE OF C H EM I CAL SAFETY

AN D PO L L U TIO N PR EVEN TIO N

MEMORANDUM

Date: 10-NOY-2015

SUBJECT: Pendimethalin

- Human Health Risk Assessmen t to Support the Proposed New

Uses on the Caneberry Subgroup 1 3-07 A and the Bushberry Subgroup l 3 -0 7B;
Amended Use on Grasses and Estab li shment of Tolerances for Pendimethalin

in/on Grass Forage

, Fodder

, and Hay (Crop Group 17) with New Ruminant Tolerances; and Crop Group Conver s ion for Tr ee Nut Crop Group 14.

PC Code: 10850 I DP Barcodc: D428265 Registration No.: 241-418 Regulator y Action: NA

CaseNo.: NA Decision No.: 490089

Petition No.: 4F8261

, 4E8282

Risk Assessment Type: New Use

TXR No.: NA CAS No.: 40487-42-1

MRID No.: NA 40 CFR: 40 CFR § 1 80

. 36 1

FROM:

. She il a Piper

, Risk

# Assessor**~~ ~/'** **~** Mohsen Sahafeyan

, Chemi s t**v""~e ~** **~** P. Yvonne Barnes

, Chem i st 

## ?,**~** 1
Bridget Bobowiec

, Biologist Yung Yang

, Ph.D.

, Toxicologist 

## th 6

,**~** Risk Assessment Branch Y l (]

- (/ v H ealth Effects Division (7509P)

THROUGH: Donna S. Davis

, Acting Chie @ tA/" 

## 0 rh\.,

, · ("

Ri s k Assessment Branch YI

## ~ Health Effects Division (7509P)

TO: Emily Schmidt

, Risk Manager Reviewer

Reuben Baris, Risk Manager

D an Kenny, C hi ef
Herbicide Branch Registration Division (7505P)

and

Page 1 of 42Pendimethalin Draft H uman Health Ri s k Assessment

Andy Ertman, Risk Ma n ager Barbara Madden, Team Leader

Marion Johnson, Branch Chief

Minor Use and Emergency Re s pon se Branch Regi s tration Divi sion (7505P)

Page 2of42 DP No. 0 428265Pendimethalin Human Health Risk Assessment DP No. D428265

Page 3 of 42 T able of Contents

1. 0 Executive Summary

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

................................ ................................ ................................ ....... 7
2.1 Deficiencies

................................ ................................ ................................ ...................... 7
2.2 Tolerance Considerations

................................ ................................ ................................ . 8
2.2.1 Enforcement Analytical Method

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

................................ ................................ ...... 11
2.3. Label Recommendations

................................ ................................ ................................ 11
3.0. Introduction

................................ ................................ ................................ ........................ 11
3.1. Chemi cal Identity

................................ ................................ ................................ ........... 12
3.2. Physical/Chemical Characteristics

................................ ................................ ................. 12
3.3. Pesticide Use Pattern

................................ ................................ ................................ ...... 13
3.4.1. Anticipated Exposure Pathways

................................ ................................ ..................... 15
3.5. Consideration of Environmental Justice

................................ ................................ ........ 15
4.0 Hazard Characterization and Dose

- Response Assessment

................................ ................ 15
4.2 Absorption, Distribution, Metabolism, & Elimination (ADME)

................................ ...... 16
4.2.1 Dermal Absorption

................................ ................................ ................................ ..... 16
4.4. 1 Completeness of the Toxicology Database

................................ ................................ 17
4.4.2. Evidence of Neurotoxicity

................................ ................................ .......................... 17
4.4.3. Evidence of Sensitivity/Susceptibility in the Developing or Young Animal

............. 17
4.4.4. Residual Uncertainty in the Exposure Database

................................ ......................... 17
4.5 Toxicity Endpoint and Point of Departure Selections

................................ .................... 18
4.5.1 Toxicity Endpoint and Point of Departure Selections

................................ .................... 18
4.5.2. Recommendation for Combining Routes of Exposures for Risk Assessment

........... 20
4.5.3. Cancer Classification and Risk Assessment Recommendation

................................ .. 20
4.6. Endocrine Disruption

................................ ................................ ................................ ........ 20
5.0 Dietary Exposure and Risk Assessment

................................ ................................ ............ 21
5.1 Residues of Concern Summary

................................ ................................ ...................... 21
5.2. Food Residue Profile

................................ ................................ ................................ ...... 22
5.3. Water Residue Profile

................................ ................................ ................................ .... 22
5.4. Dietary Risk Assessment

................................ ................................ ................................ 23
5.4.1. Description of Residue Data Used in Dietary Assessment

................................ ......... 23
5.4.2. Percent Crop Treated Used in Dietary Assessment

................................ .................... 23
5.4.3. Acute Dietary Risk Assessment

................................ ................................ ................. 24
5.4.4. Chronic Dietary Risk Assessment

................................ ................................ .............. 24
5.4.5. Cancer Dietary Risk Assessment

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

................................ ................................ ................................ ........... 24
6.0 Residential (Non

- Occupational) Exposure/Risk Characterization

................................ .... 25
6.1 Residential Risk Estimates for Use in Aggregate Assessment

................................ ...... 25
6.2 Spray Drift

................................ ................................ ................................ ...................... 26
6.3 Residential Bystander Post

- Application Inhalation Exposure

................................ ....... 27
7.0 Aggregate Exposure/Risk Char acterization

................................ ................................ ....... 27Pendimethalin Human Health Risk Assessment DP No. D428265

Page 4 of 42 7.1 Acute Aggregate Risk

................................ ................................ ................................ .... 27
7.2 Short

- Term Aggregate Risk

................................ ................................ ........................... 27
7.3 Intermediate

- Term Aggregate Risk

................................ ................................ ................ 28
7.4 Chronic Aggregate Risk

................................ ................................ ................................ . 28
7.5 Cancer Aggregate Risk

................................ ................................ ................................ ... 28
8.0 Cumulative Exposure/Risk Characterization

................................ ................................ ..... 28
9.0 Occupational Handler Exposure/Risk Estimates

................................ ............................ 29
9.2 Occupational Post

- application Exposure/Risk Estimates

................................ .............. 30
9.2.1 Occupational Post

- application Inhalation Exposure/Risk Estimates

.......................... 30
9.2.2 Occupational Post

- Application Dermal Exposure/Risk Estimates

............................. 31
10 .0 References

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

................................ ....................... 33
A.1 Toxicology Data Requirements

................................ ................................ ...................... 33
A.2 Toxicity Profiles

................................ ................................ ................................ ............. 34 Appendix B. Internation al Residue Limits Table

................................ ................................ ...... 39 Appendix C. Occupational Handler Non

- Cancer Exposure and Risk Estimates for
Pendimethalin

................................ ................................ ................................ ............................... 40 Appendix D. Review of Human Research

................................ ................................ ................... 42Pendimethalin Human Health Risk Assessment DP No. D428265

Page 5 of 42 Executive Summary

Pendimethalin is a selective herbicide used for controlling annual grasses and broadleaf weeds. It is a meristematic inhibitor that interferes with the plant’s cellular division and it is generally applied early in the growing season as a pre

- plant, pre

- emergent and/or early post

- emergent herbicide. It is registered for a variety of agricultural uses and non

- agricultural ones such as lawns, parks, golf courses, and ornamentals . The chemical can be applied by chemigation, ground , and aerial equipment.

The registrant

, BASF

, has requested a reduction of the pre

- harvest interval (PHI) for Bermuda grass and other perennial warm

- season grasses grown for forage, grazing, and hay production from 45 and 60 days to 0 d ays for the end

- use product Prowl® H 2 O (EPA Reg. no. 241

- 418; 38.7% a.i.)

. Amended tolerances on grass forage and hay were proposed to support the reduced

PHI. In addition, IR

- 4 has petitioned ( PP# 4E8282) for new uses in/on minor crops to include the

can eberry s ubgroup 13

- 07A

, and the b ushberry s ubgroup 13

- 07B , as well as conversion of the

t ree nut crop group 14 to the tree nut group 14

- 12. In support of its petition, field trial data for raspberry and bl ue berry w ere submitted . No new data for the tree n ut group 14 crop group
conversion w ere submitted or are needed.

The toxicology database for pendimethalin is complete, no additional data are required. The
target organ for pendimethalin is the thyroid. Thyroid toxicity in chronic and subchronic rat and mouse studies was manifested as alterations in thyroid hormones (decreased total T4, and T3, increased percent of free T4 and T3), increased thyroid weight, and microscopic thyroid lesions (including increased thyroid follicular cell height, follicular cel l hyperplasia, as well as follicular cell adenomas). 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.

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

. T here is no evidence of increased qualitative or quantitative susceptibility in the young and exposure estimates are unlikely to underestimate ri sk; therefore,
the FQPA Safety Factor is reduced to 1x.

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 assessm ent. The chronic risk assessment is considered to be pr otective of any cancer effects; therefore , a separate quantitative cancer aggregate risk assessment is not required.

A n endpoint/ PO D (point of departure) was selected from a rat a cute neurotoxicity stu dy for acute dietary risk assessment based on reduced motor activity with an uncertainty factor ( UF ) of 100x (10x for interspecies extrapolation, 10x for intraspecies variation, and 1x for FQPA Safety Factor). F or chronic dietary risk assessment and incide nt oral, dermal, inhalation exposure scenarios, t hree studies (a 92

- day thyroid function study, a 56

- day thyroid function study and a
14

- day intra

- thyroid metabolism study in rats) were considered as co

- critical in establishing aPendimethalin Human Health Risk Assessment DP No. D428265

Page 6 of 42 PO D . All studies reflectin g thyroid toxicity, HED has determined that these studies collectively support a NOAEL of 10 mg/kg/day and a LOAEL of 31 mg/kg/day for thyroid effects include several hormonal and histological thyroid changes and thyroid hormonal effects and should be
used as the POD for all durations and exposure scenarios. An UF of 30x (3x for interspecies extrapolation and 10x for intraspecies variati on) is applied

. The interspecies UF (used to account for animal to human differences in toxicokinetics and toxicodynamics) was reduced to 3X with respect to observed thyroid effects in the rat because of several important quantitative dynamic differences between rats and humans with respect to thyroid function (Interim Guidance on Thyroid Disrupting Pesticides, dated 11/01/2005). The FQPA factor is reduced to1x

.

The residue chemistry database to support new agricultural uses of pendimethalin is complete. The nature and magnitude of the res idue in plants, livestock, and rotational crops have been adequately delineated. The residues of concern (ROCs) in plants for primary and rotational crops for tolerance enforcement and risk assessment purposes are pendimethalin and its alcohol
metabolite (CL 202,347) and ruminants are pendimethalin and its metabolite, 1

- (1

- ethylpropyl)

- 5, 6

- dimethyl

- 7

- nitro

- 1H

- benzimidazole (metabolite 6)

. The available poultry metabolism data indicate that there is no reasonable expectation of finite residues of pendimet halin, and metabolites of concern in poultry and eggs [40 CFR §180.6(a)(3)] as a result of the registered

uses

. Adequate magnitude of residue data on requested uses and acceptable validated enforcement methods for plants , and livestock are available. Ade quate field trial data have been submitted for the new uses on caneberries and grasses. The studies were generated using validated data collection methods and are supported by storage stability data of appropriate duration and storage conditions. There a re no new poultry feed items associated with this action. Currently, there is no reasonable expectation of finite residues in poultry commodities ( 40CFR §180.6 ( a ) (3)). A significant increase in the ruminant dietary burden is expected as a result of the
0

- day PHI and post grazing interval; therefore

, a new ruminant feeding study was submitted.
HED has determined that new tolerances are needed in ruminant commodities as a result of the amended use on grasses.

Unrefined acute and chronic dietary (food and drinking water) risk assessment s w ere conducted using tolerance

- level residues, assuming 100% crop treated for all commodities, using default

pr ocessing factors, and incorporating modelled drinking water estimated exposure values

. The dietary fo od and drinking water risk estimate is < 2% of the acute and chronic population adjusted dose (aPAD/cPAD) for the U.S. population and all population subgroups.

There are no proposed new residential uses for pendimethalin. Existing pendimethalin
resident ial uses include use in/on lawns, parks, golf courses, ornamentals, landscape ground

covers, fruit bearing trees and nuts. Risk estimates for both residential handler and post application exposure from the last updated 2012 residential assessment were not of concern as

m argin s of exposure ( MOEs ) were greater or equal to 30 (S. Shelat, 06/07/2012, D 402406 )

.

The a cute aggregate risk assessment, by definition, includes food and water only, and as noted above is not of concern (< 100% of the aPAD). There are no long

- term residential exposurePendimethalin Human Health Risk Assessment DP No. D428265

Page 7 of 42 scenarios, therefore, the long

- term aggregate exposures and risk assessment is equivalent to the chronic dietary risk assessment, and is not of concern (<100% of the cPAD). HED has
conducted short

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

- dietary (residential) sources of exposure to pendi methalin. The resulting short

- term aggregate MOEs do not exceed HED’s level of concern, (MOEs ≥ 30)

. The
short

- term aggregate MOEs for adults is 130 and children 1

- 2 years old is 92. Intermediate

- term residential exposure is not anticipated; therefore a separate intermediate

- term assessment was not conducted.

HED previously conducted occupational han dler exposure and risk assessments for registration
review in 2012 (D402406) for several representative crops of the caneberry, bushberry, and tree nut crop group. T he proposed application rates and timing , and use pattern for those subgroups ( caneberry, bushberry, and tree nut ) are identical to those representative crops ; therefore, a new quantitative occupational handler assessment is not required

. In addition this action amends the PHI for Bermudagrass and other warm perennial grasses which was originally assessed for occupational exposure in 2009 (S. Shelat, 10/27/2009, D371025) . In the 2012 and the 2009

assessments s hort

- and intermediate

- term co mbined occupational handler dermal and inhalation margins of exposure (MOEs) were not of concern to HED (i.e., MOE > 30) with baseline attire and gloves personal protective equipment (PPE )

.

Post

- application exposure was no t assessed for the proposed crop groups due to the pre

- emergent and soil directed use pattern and review of chemical specific dislodgeable foliar residue (DFR) study on tobacco and sugarcane (MRID 44969901). The study exemplifies an appli cation
directed towards the soil to minimize contact with the actual crop. Pendimethalin application to Bermudagrass is expected to be a post emergent foliar spray and not represented by the DFR study. In 2009 the e stimated occupational dermal post application risks to treated Bermudagrass using de fault 25% dissipation did not exceed HED’s level of concern (MOE s ≥ > 30) on the day
of treatment for early post application activities including scouting and hand laying irrigation. All post

- application activities should comply with minimum 12

- hour re

- entry interval (REI) assigned to pendimethalin as it classified as Toxicity Category III and IV for acute dermal, dermal irritation and eye irritation.

This risk assessment relies , in part, on data from studies in which adult human subjects w ere intentionally exposed to a pesticide or other chemical. Studies that involve adult human subjects are subject to ethics review pursuant to 40 CFR 26, the studies have been review ed and are in compliant with applicable ethics requirements.

2.0 H ED R ecommendations

2.1 DeficienciesPendimethalin Human Health Risk Assessment DP No. D428265

Page 8 of 42 There are no data deficiencies relating to toxicology, occupational , and residential exposure with the current petition for uses of pendimethalin. The registrant should submit a revised Section F according to the recommend ed tolerances listed in Tables 2.2.2.A and 2.2.2.B. The registrant should also confirm the availability or replenish 1

- (1

- ethylpropyl)

- 5, 6

- dimethyl

- 7

- nitro

- 1H

benzimidazole ( metabolite 6 ) standards to the EPA Repository.

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

An adequate plant enforcement method is available for pendimethalin . T he PAM Volume II lists
four gas chromatography 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 parent, whereas Methods II and IV determine residues of the 3, 5

- dinitrobenzyl alcohol metabolite ( CL 202347 ) . The limit of quantitation ( LOQ ) of each method is 0.05 ppm. These met hods are appropriate for enforcement of the newly proposed cane and bushberry tolerances.

The proposed analytical method, BASF Method D0405

, is adequate to enforce the proposed
tolerance for ruminant matrices. BASF has proposed Method D0405 which is a high performance liquid chromatography with dual mass spectroscopic detection ( HPLC MS/MS )
method as an enforcement method for ruminant commodities. This method determines residues of pendimethalin and its metabolites CL 202,347 and Goat Metabolite 6 in m ilk and cow tissues. Method D0405 has undergone a successful independent laboratory validation ( ILV ) . The validated LOQ was 0.01 ppm for each analyte in milk and 0.05 ppm for each analyte in tissues.

2.2.2 Recommended Tolerances

T olerances are currently established for residues of the herbicide pendimethalin, including its metabolite and degradate, in or on the commodities in the 40 CFR §180.361. The tolerance expression listed in the 40 CFR §180.361 for plants does not comply wit h the HED interim tolerance expression policy (S. Knizner, 5/27/09) and should be changed to:

Tolerances are established for residues of the herbicide pendimethalin, including its metabolites and degradates, in or on the commodities. Compliance with the tolerance levels specified in the following table below is to be determined by measuring only the sum of pendimethalin, [ N

- (1

- ethylpropyl)

- 3,4

- dimethyl

- 2,6

- dinitrobenzenamine] and its metabolite, 4

- [(1

- ethylpropyl)amino]

- 2

- methyl

- 3,5

- dinitrobenzyl alcoho l, calculated as the stoichiometric equivalent of pendimethalin, in or on the commodity.

Furthermore, since tolerances for livestock are to be established now , t he “§180.361 (a)” in 40Pendimethalin Human Health Risk Assessment DP No. D428265

Page 9 of 42 CFR should be changed to “§180.361 (a) General. (1)”

Table 2.2.2.

- A b elow summarizes the plant tolerances for this action.

Table 2.2.2

- A T olerance Summary for Pendimethalin for Plants

.

Commodity Established
Tolerances (ppm) Proposed

Tolerances (ppm) HED

Recommended
Tolerance (ppm) Comment

Fruit, caneberry, subgroup13

-

07A None 0.1 0.10

Fruit, bushberry, subgroup13

-

07B None 0.1 0.10

Nut, tree group 14

- 12 None 0.1 0.10 Grass forage, fodder, and hay crop group 17, forage 20 1000 1000

Grass forage, fodder, and hay crop group 17, hay 13 2000 2000

Pistachio 0.1 None None Revoke: covered by
CG 14

- 12

Nut, tree group 14 0.10 None None Revoke: converted
to CG 14

- 12

Juneberry 0.10 None None Revoke: covered by
CG 13

- 07B Grass forage, fodder, and hay crop group 17, straw 4.0 None None Revoke: no longer a feed item

There are no ruminant tolerances currently established for pendimethalin. H ED recommends
that tolerances be established in 40 CFR §180.361 (a) (2) for residues of pendimethalin in
livestock commodities

. The residue definition for livestock commodities should be:

Tolerances are established for residues of the herbicide pendimethalin in or on livestock commodities, including its metabolites and degradates. Compliance with the tolerance levels is to be determined by measuring only the sum of pendimethalin (N

- (1

- ethylpropyl)

- 3,4

- dimethyl

- 2,6

- dinitrobenzenamine)) and its metabolite, 1

- (1

- ethylpropyl)

- 5, 6

- dimethyl

- 7

- nitro

- 1H

- benzimidazole (metabolite 6), calculated as the stoichiometric equivalent of pendimethalin, in or on the commodity.Pendimethalin Human Health Risk Assessment DP No. D428265

Page 10 of 42 Table 2.2.2

- B, below, summarizes the livestock tolerances for this action.

Table 2.2.2

- B T olerance Summary for Pendimethalin in Ruminants

. Commodity Proposed
Tolerances (ppm) HED

Recommended Tolerance (ppm) Comments

Milk 0.04 0.04 Cattle, fat 0.30 0.30 Cattle, meat 0.1 0 0.1 0 Cattle, meat byproduct None 3.0 Registrant proposed to exclude
liver. HED concludes liver
need not be excluded. Goats, fat 0.30 0.30
Goats, meat 0.1 0 0.1 0 Goats, meat byproduct None 3.0 Registrant proposed to exclude
liver. HED concludes liver
need not be excluded. Horse, fat 0.30 0.30
Horse, meat 0.1 0 0.1 0 Horse, meat byproduct None 3.0 Registrant proposed to exclude
liver. HED concludes liver
need not be excluded. Sheep, fat 0.30 0.30 Sheep, meat 0.1 0 0.1 0 Sheep, meat byproduct None 3.0 Registrant proposed to exclude
liver. HED concludes liver
need not be excluded. Cattle, meat byproduct except
liver 3.0 None Liver need not be excluded

Goat, meat byproduct except liver 3.0 None Liver need not be excluded Horse, meat byproduct except
liver 3.0 None Liver need not be excluded

Sheep, meat byproduct except
liver 3.0 None Liver need not be excluded

Cattle, liver 1.5 None Covered by tolerance for cattle meat byproduct. Goat, liver 1.5 None Covered by tolerance for goat meat byproduct. Horse, liver 1.5 None Covered by tolerance for horse meat byproduct. Sheep, liver 1.5 None Covered by tolerance for sheep meat byproduct.Pendimethalin Human Health Risk Assessment DP No. D428265

Page 11 of 42 2.2.3. Revisions to Petition ed For Tolerances

HED is r ecommending tolerance for “ meat byproduct ” (at 3.0 ppm) based on anticipated residues in kidney which contained the highest residue amongst all ruminant tissues and will
therefore cover anticipated residues in liver and fat. BASF proposed setting a tolerance on
“me at byproduct except liver” , also at 3.0 ppm based on anticipated residues in kidney with a separate lower tolerance on liver at 1.5 ppm . HED believes that anticipated residues in liver

versus k idney (on which the tolerance for meat byproduct is based on) are not significantly different given the limited number of data for each tissue and that both are greater than LOQ and
within about 1 ppm of each other

. Therefore, a single tolerance on “meat byproduct” without a separate tolerance on liver i s adequate

.

2.2.4. International Harmonization

The International Residue Limit (IRL) Status Sheet is attached in the Appendix B . There are currently no established Codex, Canadian, or Mexican maximum residue limits (MRLs) for the proposed new and amended uses , or for the crop group expansions . Therefore, there are no issues of international harmonization raised by these petitions.

2.3. Label Recommendations

None

.

3.0. In troduction

Pendi methalin (N

- (1

- ethylpropyl)

- 3, 4

- dimethyl

- 2,6

- dinitrobenzenenamine) is a selective herbicide used to control broadleaf weeds and grassy weed species in a number of crop and non

crop areas as well as on residential lawns and ornamentals. It is a meristematic inhibi tor that interferes with the plant’s cellular division of mitosis and is generally applied early in the growing season as a pre

- emergent and early post

- emergent herbicide

. Form ulations include liquid , solid, granular, emsulsifiable concentrate, and dry flo wables. Pendimethalin is applied by aerial, ground, chemigation , and handheld equipment

. Pendamethalin is registered by BASF Corporation and was first registered in March 1985. The most recent risk assessment was performed for hops (01/14/2015, D416285, P

. Y, Barnes)

.Pendimethalin Human Health Risk Assessment DP No. D428265

Page 12 of 42 3.1. Chemical Identity

Table 3.1 Pendimethalin Nomenclature.

Chemical structure

Common name Pendimethalin
Company experimental name BAS 455H (old CL 92533)

IUPAC name N

- (1

- ethylpropyl)

- 2,6

- dinitro

- 3,4

- xylidine

CAS name N

- (1

- ethylpropyl)

- 3,4

- dimethyl

- 2,6

- dinitrobenzenamine
CAS registry number 40487

- 42

- 1

End

- use product (EP) 3.8 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. Pendimethalin is highly ab sorbed to the soil/sediment particles and is non

- volatile. Pe ndimethalin 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. D428265

Page 13 of 42 Table 3.2 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 to 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

3.3. Pesticide Use Pattern

The subject petitions are for additions/rev isions to the Prowl® H 2 O (EPA Reg. no. 241

- 418; 38.7% a.i.) label only. Prowl® H 2 O is a 3.8 lbs. a.i./gal pendimethalin aqueous capsulated suspension (CS) formulation. The requested uses on caneberry subgroub 13

- 07A and bushberry subgroup 13

- 07B are for application by g round, chemigation, flood, flooded b asin , and gravity flow irrigation with the individual application rate between 2

- 6 lb ai/A/year, not to exceed the total maximum application rate of 6 lb ai/A/year ; the requested PHI is 30 days

. The reque sted
amended use on grass forage and hay only involves reduction of PHI 45 days (for forage and grazing) and 60 days (for hay) to 0

- day PHI for forage, hay and grazing. The application on grass may be by ground, aerial, c hemigation and with dry bulk ferti lizer between 1 to 4 lb ai/A/year,Pendimethalin Human Health Risk Assessment DP No. D428265

Page 14 of 42 not to exceed the total maximum application rate of 4 lb ai/A/year. There are no changes in the use rate for the nut tree crop group 14

- 12 and its use rate is the same as caneberry and bushberries but with 60

- day PHI. See following Table 3.3.1 below for use summary profile.

Table 3.3.1. Summary of Proposed Directions for Use of Pendimethalin.

Commodity Product

Name (EPA Reg. No.) Application

Equipment Max. Single

Application

Rate (lb a.i/A) Max. #

Applicatio

ns Per
Season Max.

Seasonal Application

Rate (lb a.i/A) Timing PHI 1 Use Directions and
Limitations

Caneberry Subgroup 2

13

- 07A

Prowl ®

H 2 O (241

- 418)
38.7 % a.i. Aqueous Capsule Suspension Ground,

Chemigation, Flood, Flooded Basin, and Gravity Flow Irrigation 6 lbs a.i/A

0.3 lb a.i/gallon at 20 gallons of

spray per acre 3 6 lbs a.i/A per

year Apply after pruning in

fall or spring but before new growth. Apply to surface beneath plants or between plants as surface incorporated or
before weed germination. App lication and incorporation must be
made before transplanting nonbearing crops. 30

Do not apply by air. Do not apply over the top of trees
or bushes. Do not feed forage or graze livestock in treated field or planting. Bushberry Subgroup 3

13

- 07B

Nut Tree Subgroup 4

14

- 12 60

Bermudagrass and other perennial

warm

- season
grasses grown for forage, hay production, pastureland or rangeland. Ground, Aerial, Chemigation, Dry Bulk
Fertilizer 4 lbs a.i/A

40 lbs a.i/ton
fertilizer 2 4 lbs a.i/A per

year Apply only to

established dormant perennial grasses before weed germination. 0 Apply uniformly as a broadcast spray. Do not apply after green up in spring before first cutting.

1 PHI = pre

- harvest interval 2. Caneberry Subgroup 13

- 07A includes; Blackberry, Loganberry, Raspberry black, red, and wild. 3 Bushberry Subgroup 13

- 07B includes; Aronia berry, Blueberry high and lowbush, Buffalo currant, Chilean guava, Cranberry highbush, Currant black and red , Elderberry, European barberry,
Go oseberry, Honeysuckle edible, Huckleberry, Jostaberry, Juneberry, Lingonberry, Native currant, Salal, Sea buckthorn. 4 Nut Tree Subgroup 14

- 12; includes,
African nut

- tree, Almond, Beechnut, Brazil nut, Brazilian Pine, Bunya, Bur Oak, Butternut, Cajou nut, Candlenut, Cashew, Chestnut, Chinquapin, Coconut, Coquito nut, Dika nut, Ginkgo, Guiana Chestnut, Hazelnut (filbert), Heartnut, Hickory nut, Japanese horse

- chestnut, Macadamia nut, Mongongo nut, Monkey

pot, Monkey puzzle nut, Okari nut, Pachira nut, Peach palm nut, Pecan, Pine nut, Pistachio, SapPendimethalin Human Health Risk Assessment DP No. D428265

Page 15 of 42 3.4.1. Anticipated Exposure Pathways

Humans may be exposed to pendimethalin in food and drinking water

, since pendimethalin may be applied directly to growing crops and application may result in pendimethalin reaching surface and ground water sources of drinking water

. E xposure to pendimethalin may also occur in residential or non

- occupational settings. Adults and may be exposed by to pendimethalin when applying th e pesticide to lawns and ornamental plants. Additionally, adults and older youth may be exposed to pendimethalin during activities on turf such as mowing or playing golf. Children may be exposed to pendimethalin when playing on lawns which have been trea ted with the pesticide. Occupational workers may be exposed to pendimethalin when mixing, loading or applying the pesticide or when reentering a treated area to conduct crop maintenance or harvest
activities.

3.5. Consideration of Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in this human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions to Address Environmental Justice in Minority Populations and L ow

- 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 acc ording 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 invol ve pesticide use in a residential setting. Extensive data on food consumption patterns are compiled by the USDA under the Continuing Survey of Food Intake by Individuals (CSFII) and are used in pesticide risk assessments for all registered food uses of a pesticide. These data are analyzed and categorized by subgroups based on age, season of the year, ethnic group, and region of the country. Additionally, OPP is able to assess dietary exposure to smaller, specialized subgroups and exposure assessments are performed when conditions or circumstances warrant. Whenever appropriate, non

- dietary exposures based on home use of pesticide products and associated risks for adult applicators and for toddlers, youths, and adults entering or playing on treated areas p ost

- 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 lifestyl e and traditional dietary patterns among specific subgroups.

4.0 Hazard Characterization and Dose

- Response Assessment

4.1 Toxicology Studies Available for Analysis

The toxicology database for pendimethalin is complete and adequate to support the propos ed

new uses

. Data requirements for the food uses of pendimethalin are listed in the Appendix A,Pendimethalin Human Health Risk Assessment DP No. D428265

Page 16 of 42 Table A. 1

. The studies used to evaluate the hazard potential of pendimethalin are listed in Appendix A, Table A.2

.

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

In a metaboli sm study (MRID 00046275), when ( 14 C) pendimethalin was administered to rats, about 70% of the radioactivity was excreted in the feces and 20% in the urine within 24 hours. The excretion of radioactivity in the urine peaked at 6 to 12 hours wherein 11.2% of the dose was excreted. The maximum residual radioactivity in the tissues was found in the 6

- hour samples (except for fat at 12 hours). The levels of radioactivity detected in liver, kidney, muscle, fat, and
blood at 6 hour s 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 t he parent compound. Pendimethalin is metabolized in rats mainly through oxidation of the 4 methyl groups
attached to the benzene ring as well as oxidation of the alkyl side chain of the N

- substituted dinitroaniline compound.

4 .2.1 Dermal Absorption

There were no appropriate dermal absorption or toxicity studies available to allow an estimation of the dermal absorption by a route

- to

- route comparison of toxicity. Based on structurally related chemicals (oryzalin, trifluralin, and ethalfluralin ) with dermal a bsorption studies (in monkeys) indicating absorption rates of 2.3%, ~1%, and 2.8%, respectively. The solubility (water) for pendimethalin and these related chemicals are also similar at 0.5 ppm, 2.5 ppm, 0.3 ppm and < 1 ppm, respectively. Therefore, for ri sk assessment purposes, an estimate of 3% was applied. This dermal absorption rate is comparable to those identified for related chemicals.

4.3 Toxicological Effect

A developmental thyroid study was conducted to see if there is a quantitative and/or qual itative effect between mothers and pups on thyroid response. The thyroid is the target organ for pendimethalin. Thyroid toxicity in chronic and subchronic rat and mouse studies was manifested as alterations in thyroid hormones (decreased total T4, and T3, increased percent of free T4 and T3), increased thyroid weight, and microscopic thyroid lesions (including increased thyroid follicular cell height, follicular cell hyperplasia, as well as follicular cell adenomas). Also, decreased body weights and increas ed absolute and relative liver weights were noted in animals exposed to pendimethalin. The results showed no differences between maternal and developmental effect on thyroid and dose response. A developmental thyroid study was
conducted to see if there is a quantitative and/or qualitative effect between mothers and pups on thyroid response. The results showed no differences between maternal and developmental effect on thyroid and dose response.

There is no evidence that pendimethalin is a developmental, reproductive, neurotoxic, or
immunotoxic chemical.Pendimethalin Human Health Risk Assessment DP No. D428265

Page 17 of 42 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 fol licular cell adenomas in male and female rats.

Pendimethalin has a low acute toxicity via the oral, dermal, or inhalation route (Toxicity Category III or IV) . It is not a dermal or eye irritant

, and is not a dermal sensitizer.

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

The toxicity database is complete, there is no evidence of increased qualitative or quantitative susceptibility in the young and exposure estimates are unlikely to underestimate risk; therefore,
10

- fold FQPA Safet y Factor is reduced to 1x.

4.4.1 Completeness of the Toxicology Database

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

4.4.2. Evidence of Neurotoxicity

There is no evidence of neurotoxicity resulting from pendimeth alin exposure. In an acute neurotoxicity study, FOB findings and reduced motor activity were observed on Day 0 only at 300 and 1000 mg/kg. However, these findings were considered an impairment of the overall condition of the animals following treatment, r ather than direct neurotoxic effects of the pendimethalin exposure based on the absence of any neuro

- histopathological changes in the
treated animals and the transient nature of the observed FOB and neurobehavioral assessments.
In a subchronic neurotoxicit y study, no neurotoxic effects were observed in rats feeding pendimethalin up to 5400 ppm for 90 days. In addition, the toxicology database does not reveal any evidence of neurotoxic clinical signs, changes in brain weight, or histopathology of the

nervous system in any study with pendimethalin.

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

There was no indication of pre

- and/or post

- natal qualitative or quantitative increased susceptibility in the developmental studies in rats and rabbits or the 2

- generation reproduction studies in rats. In addition, a developmental thyroid toxicity study demonstrated that there is no potential thyroid toxicity following pre

- and/or post

- natal exposure to pendimethalin.

4.4.4. Residual Uncertainty in the Exposure Database

There are no residual uncertainties in the exposure database. Since the dietary and non

- dietary exposure estimates were based on several conservative assumptions, HED does not believe the exposure assessment underestimates risk. T hese assumptions include tolerance

- level residues and 100% crop treated estimates for all commodities. Furthermore, conservative, upper

- bound assumptions were used to determine exposure through drinking water and residential sources, such that these expos ures have not been underestimated.Pendimethalin Human Health Risk Assessment DP No. D428265

Page 18 of 42 4.5 Toxicity Endpoint and Point of Departure Selections



### 4.5.1 Toxicity Endpoint and Point of Departure Selections

Acute Dietary Endpoint for the General Population : In an acute neurotoxicity study in rats (MRID 48695601), reduced motor activity was observed at 30 0 mg/kg (LOAEL) with a NOAEL of 100 mg/kg. The route and a single exposure of this study are appropriate for acute dietary risk assessment. The UF is 100x ( 10x for interspecies extrapolation, 10x for intraspecies variation, and 1x for FQPA Safety Factor). The acute population adjusted dose (aPAD) for the general population is 1 mg/kg.

Acute Dietary Endpoint for Female 13

- 49 Years of Age : No appropriate endpo int was identified from any of the studies in the database, including developmental toxicity studies in rats and rabbits. Consequently, it was determined that there was no basis for selecting a separate dose and endp oint for an acute PO D for females 13

- 49 years of age.

Chronic Dietary Endpoint for the General Population : Three studies (a 92

- day thyroid function study, a 56

- day thyroid function study and a 14

- day intra

- thyroid metabolism study in rats) were
considered co

- critical in establishing a P O D for c hronic dietary risk assessment . All studies reflecting thyroid toxicity, HED has determined that these studies collectively support a NOAEL of 10 mg/kg/day and a LOAEL of 31 mg/kg/day for thyroid effects include several hormonal and histological thyroid ch anges and thyroid hormonal effects and should be used as the POD for all durations and exposure scenarios. An UF of 30x (3x for interspecies extrapolation and 10x for intraspecies variation) is applied to the NOAEL of 10 mg/kg/day to obtain a chronic refer ence dose (cRfD) of 0.3 mg/kg/day. The interspecies UF (used to account for animal to human differences in toxicokinetics and toxicodynamics) was reduced to 3X with respect to observed thyroid effects in the rat because of several important quantitative dy namic differences between rats and humans with respect to thyroid function (Interim Guidance on Thyroid Disrupting Pesticides, dated 11/01/2005). The FQPA factor is reduced to1x

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

Incidental Ora l Exposure (Short and Intermediate

- Term) : HED evaluated the toxicity database for pendimethalin and concluded that all available studies reflecting thyroid toxicity should be
considered co

- critical for selection of PODs, regardless of duration of exposure, since thyroid effects have a demonstrated early on

- set (before 14 days). Therefore, HED has determined that these studies collectively support a NOAEL of 10 mg/kg/day and a LOAEL of 31 mg/kg/day for thyroid effects include several hormonal and histologic al thyroid changes and thyroid hormonal effects and should be used as the POD for all durations and exposure scenarios with the exception of the acute dietary endpoint.

Dermal Exposure (Short and Intermediate

- Term) : There was a 21

- day dermal toxicity stud y 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
scenario. T hese co

- critical studies collectively support a NOAEL of 10 mg/kg/day and a LOAELPendimethalin Human Health Risk Assessment DP No. D428265

Page 19 of 42 of 31 mg/kg/day for thyroid effects include several hormonal and histological thyroid changes and thyroid hormonal effects and should b e used as the POD for all durations and exposure scenarios. Additionally, for risk assessment purposes, a dermal absorption factor of 3% should be used to estimate risk since these assessments for the routes of exposure are derived from POD
selected from o ral studies.

Inhalation Exposure (Short and Intermediate

- Term) : There was no inhalation study available except the acute inhalation study (Toxicity Category IV). Therefore, oral toxicity study was selected for this exposure scenario. The same rationale as stated in the incidental oral exposure section is applied to this exposure scenario. T hese co

- critical studies collectively support a NOAEL of 10 mg/kg/day and a LOAEL of 31 mg/kg/day for thyroid effects include several hormonal and histological thyroid c hanges and thyroid hormonal effects and should be used as the POD for all durations and exposure scenarios. Additionally, for risk assessment purposes, an inhalation absorption factor of 100% should be used to estimate risk since these assessments for
the routes of exposure are derived from POD selected from oral studies.

Table 4. 5.1. Toxicological Doses and Endpoint for Pendimethalin Human Health Risk Assessment

Exposure/Scenario Point of

Departure Uncertainty/FQPA

Safety Factors RfD, PAD, Level of

Concern for Risk
Assessment Study and Toxicological
Effects

Acute Dietary (Females 13

- 49) No appropriate endpoint was identified 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 m g/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/day
based on hormonal and histopathological changes
in the thyroid.

Incidental Oral Exposure Oral
Short

- Term (1

- 30 days)

Intermediate

– Term (1

- 6 months) NOAEL = 10

mg/kg/day UF A = 3X

UF H = 10X FQPA SF = 1X

Total UF = 30X Residential LOC = 30

Occupational LOC = 30 The same as the chronic dietary.

Dermal
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. D428265

Page 20 of 42 Table 4. 5.1. Toxicological Doses and Endpoint for Pendimethalin Human Health Risk Assessment

Exposure/Scenario Point of

Departure Uncertainty/FQPA

Safety Factors RfD, PAD, Level of

Concern for Risk
Assessment Study and Toxicological
Effects

(1

- 6 months) Dermal Absorption
= 3%

Inhalation
Short

- Term (1

- 30 days)

Intermediate

– Term (1

- 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 available.
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, LOAEL = lowest observed adverse effect level, PAD = population adjusted dose (a = acute, c = chronic), RfD = reference dose, MOE = margin of exposure, LOC = level of concern, NA = Not Applicable.

4.5.2. Recommendation for Combining Routes of Exposures for Risk Assessment

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

, dermal and inhalation routes of exposure (all durations), the exposures and risks from these exposure routes should be aggregated.

4.5.3. Cancer Classification an d Risk Assessment Recommendation

The CARC classified pendimethalin (03/18/1992 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 Committee 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 d ue to a thyroid

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

non

- mutagenic in mammalian somatic cells and germ cells. The chronic risk assessment is considered to be protective of any cancer effects; therefore, a separate quantitative cancer aggregate risk assessment is not required.

4.6. 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 an d 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 targ et organ histopathology,Pendimethalin Human Health Risk Assessment DP No. D428265

Page 21 of 42 organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess growth, d evelopmental 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 e xisting hazard database. However, as required by FFDCA section 408(p), pendimethalin is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whether certain substances (incl uding pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator may designate.” The EDSP employs a two

- tiered app roach 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 tha t go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to identify any adverse endocrine

- related effects caused by the substance and
establish a dose

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

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/data call

- ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of chemicals identified for EDSP screening wa s published on June 14, 2013 1 and includes some pesticides scheduled for registration review and chemicals found in water

. Neither of these lists should be construed as a list of known or likely endocrine disruptors.

For further information on the status of the EDSP, the policies and procedures, the lists of chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our
website 2

.

5.0 Dietary Exposure and Risk Assessment

5.1 Residues of Concern Summary

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. The HED Pendimethalin team has reviewed the newly submitted ruminant feeding study and consulted with the co

- chairs of the Residue of Concern Knowledgebase Subcommittee (ROCKS ; DP428264, P.Y. Barnes, 08/06/2015) to determine that the residues of concern for
both t olerances setting and risk assessment in ruminants only is the parent compound,

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. D428265

Page 22 of 42 pendimethalin and its metabolite, 1

- (1

- ethylpropyl)

- 5, 6

- dimethyl

- 7

- nitro

- 1H

- benzimidazole ( also known as metabolit e 6). Table 5.1 provides a summary of the residues of concern for pendimethalin

. The dietary burden for poultry remains low, and based on the available metabolism data, HED concludes that residues in poultry commodities are not likely ( 40CFR §180.6 ( a )(3)).

5.2. Food Residue Profile

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

emergence . It is a meristematic inhibitor “growth retarder” that interferes with the plant’s cellular division of mitosis, controlling/preventing annual grasses and weeds. Once pendimethalin is absorbed by the roots or shoots, translocation to foliage is extremel y limited. Residues of pendimethalin and/or its metabolite at harvest are usually very low or non

detectable, (e.g., below the level of quantification). The study showed that the residues are
transferable to ruminant tissue and milk.

5.3. Water Residue P r ofile

The estimated drinking water concentrations (EDWCs) for pendimethalin were generated using the Surface Water Concentration Calculator (SWCC) computer model, the Pesticide Root Zone Model for Groundwater (PRZM

- GW), and the Screening Concentration in Ground Water (SCI

GROW) model. Both point estimates and distributions of water residues were provided. A comparison was made be t ween output from current EFED mode l s for pendimethalin for t h e
p r oposed u s es on caneberry

, bush berr y , t ree n ut group (6.0 lb s ai / A)

, and cool

- and warm s e a s on forage grasses (4.0 lb s ai / A) with the output from the currently registe r ed use on grapes (6.0 lb s ai / A) . Grapes has the highest application rate of all currently registered ( See Table 5.3 ). Table 5.1 Summary of Metabolites and Degradates included in the Pendimethalin Risk Assessment and Tolerance Expression

Matrix Residues included in Risk Assessment Residues included in Tolerance Expression

Plants Primary Crop Pendimethalin and alcohol metabolite, 4

- [(1

- ethylpropyl)amino]

- 2

- methyl

- 3,5

- dinitrobenzyl alcohol (CL 202347) Pendimethalin
and (CL 202347) Rotational Crop

Livestock Ruminant Pendimethalin and metabolite 6, 1

- (1

- ethylpropyl)

- 5, 6

- dimethyl

- 7

- nitro

- 1H

- benzimidazole) Pendimethalin and
metabolite 6

Water Pendimethalin Not applicablePendimethalin Human Health Risk Assessment DP No. D428265

Page 23 of 42 Table 5.3 EDWCs Scenario for Pendimethalin

Drinking Water
Source
(Model) 1 in 10 year Annual Peak
Concentration 1 in 10 year Annual
Mean Concentration Average Stimulation
Concentration

(μg/L) (μg/L) (μg/L)

Pendimethalin EDWCs for the New York Grape Scenario

Surface Water a (SWCC) 96.4 9.73 8.16

Ground Water b

PRZM

- GW b 4.38 E

- 09

-- 1.88 E

- 13

Pendimethalin EDWCs for the Cool and Warm Season Forage Grasses Scenario

Surface Water (SWCC) 21.9 1.47 1.25

Ground Water

PRZM

- GW 1.78 E

- 10

-- 3.09 E

- 13

a For the SWCC mode l

 The NY grape scenario was used to represent berr ies.

 The CA rangeland hay

, and the OR grass seed scenarios were used to represent forage grasses. The OR grass seed scenario resulted in higher EECs than the CA scena r io; and it is presented here.

b : For the PRZM

- GW model ; the following available scenarios were used to represent ornamentals and turf :

 FL potato, GA coastal, NC coastal, and WI sand. The NC scenario gave the highest EDWCs.

-- : The chemical did not r each groun dwater even after running the model with an extended 100

- year weather file.

5.4. Dietary Risk Assessment

5.4.1. Description of Residue Data Used in Dietary Assessment

A 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
unrefined acute and chronic analyses include all existing and proposed uses of pendimethalin and
are based on tolerance

- level residues; 100% crop treated assumptions for all of the pendimethalin use commodities in this assessment and DEEMTM default processing factors or empirical processing factors where available. The drinking water point estimates provided by EFED are
modeled estimates and wer e generated using the most conservative model available for the proposed crops. The acute and chronic approach to dietary risk exposure analysis will not underestimate risk to the general U.S. population or any population subgroup.

5.4.2. Percent Crop Treated U sed in Dietary AssessmentPendimethalin Human Health Risk Assessment DP No. D428265

Page 24 of 42 Percent crop treated refinements were not used in the acute or chronic dietary assessments..

5.4.3. Acute Dietary Risk Assessment

The acute aggregate (food and drinking water) dietary exposure estimates are below HED’s level
of concern ( i.e., <100% of the aPAD) for the U.S. population and all population subgroups. Combined dietary exposure from food and drinking water concentrations at the 95 th percentile of exposure is <1% of the aPAD for the U.S. population and 2% of the aPAD f or all infants <1 year old, the highest exposed population subgroup (See Table 5.4.6).

5.4.4. Chronic Dietary Risk Assessment

The chronic aggregate dietary exposure estimate for food and drinking water are below HED’s
level of concern. The estimated food and d rinking water is < 1% of the chronic population adjusted dose ( cPAD ) for the U.S. population and 2% of the cPAD (See Table 5.4.6).

5.4.5. Cancer Dietary Risk Assessment

A non

- quantitative approach was recommended by the Cancer Peer Review Committee since
mode o f action studies are available to demonstrate that the thyroid tumors are due to a thyroid

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

- mutagenic in mammalian somatic cells and germ cells. The chronic dietary risk assessment is con sidered to be protective of any cancer effects ; such that, a separate quantitative cancer aggregate risk assessment is not required.

5.4.6. Summary Table

Table 3. 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 0.009126 < 1 0.002074 < 1

Not applicable Not

applicable All Infants (< 1 year old) 0.020314 2.0 0.003844 1.3

Children 1

- 2 years old 0.017759 1.8 0.007019 2.3

Children 3

- 5 years old 0.013994 1.4 0.005254 1.8

Children 6

- 12 years old 0.009638 < 1 0.003130 1.0

Youth 13

- 19 years old 0.006663 < 1 0.001751 < 1Pendimethalin Human Health Risk Assessment DP No. D428265

Page 25 of 42 Table 3. 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

Adults 20

- 49 years old 0.007299 < 1 0.001609 < 1

Adults 50

- 99 years old 0.006631 < 1 0.001516 < 1

Females 13

- 49 years old 0.007416 < 1 0.001581 < 1 *The subpopulation(s) with the highest risk estimates are bolded

.

6.0 Residential (Non

- Occupational) Exposure/Risk Characterization

There are no proposed new residential uses for pendimethalin. Registered residential uses were assessed in the 2012 risk assessment and occupational and residential exposure assessment ( D40240 6) which reflected updates to HED’s 2012 Residential SOPs 2 along with policy changes for body weight assumptions. The 2012 assessment included short

- term dermal and inhalation risk estimates for residential handler applications of pendimethalin to gardens , ornamentals, and
lawns as well as short

- term dermal and oral post

- application risk estimates from physical activities on treated lawns, golfing, mowing, gardening, accidental granular ingestion, and hand

to

- mouth behavior. The residential handler and po st

- application risk estimates did not exceed HED’s level of concern (MOEs ≥ 30). The lowest MOE for adult residential handlers was from loading and applying granular pendimethalin with a belly grinder (MOE =670). The lowest margin of exposures for post a pplication activities were adult dermal exposure to treated gardens (MOE =130) and children ages 1 >2 years old physical activities on treated turf (dermal
MOE=170 and hand

- to

- mouth MOE =240).

6 .1 Residential Risk Estimates for Use in Aggregate Assessment

HED believes that combining exposures resulting from adult handler and post

- application activities would result in an overestimate of adult exposure. HED selected the most conservative adult dermal post

- application exposure (MOE = 130 ) as the representa tive source of residential exposure to be combined with the dietary exposure for the aggregate assessment. The children’s oral exposure is based on post

- application incidental oral hand

- to

- mouth exposures plus dermal
post

- application exposure from physical activities on turf ( MOE = 240 and 170, respectively ).
Table 6. 1 summarizes the residential exposure scenarios that are to be used for estimating
aggregate exposure.

2 Available: http://www.epa.gov/pesticides/science/residential

- exposure

- sop.htmlPendimethalin Human Health Risk Assessment DP No. D428265

Page 26 of 42 Table 6.1 . Combined Short

- Term Residential Exposure and Risk Estimates for Pen dimethalin

Use Site Handler

Dermal Handler Inhalation Post

application
Dermal Incidental Oral

Hand

- to

- Mouth Combined

Exposure for Aggregate Risk

Dose b MOE c Dose d MOE e Dose f MOE c Dose g MOE h Dose MOE i

Adults

– Ornamentals (Granular) via belly grinder
4 lb ai/acre a 0.015 670 5.4E

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

Children 1 <
2 Years Old

- Turf (Liquids) N/A N/A 0.060 170 0.042 240 0.102 100

a. Belly grinder assumption of 1200 sq ft per day is calculated to be equivalent to 0.023 acres ((1200 sq ft/day ) x (43,560 sq ft/1 acre) = 0.023 acres/day).
b. Handler Dermal Dose = Dermal Unit Exposure (mg/kg) x Application Rate (4 lb ai/acre) x Amount Treated or Handled x DAF (3%)/BW (80 kg).

c. Dermal MOE = Dermal NOAEL (10mg/kg/day)/Dermal Dose (mg/kg/day).
d. Handler Inhalation Dose = Dermal Unit Exposure (mg/kg) x Application Rate (4 lb ai/acre) x Amount Treated or Handled /BW (80 kg).

e. Handler Inhalation MOE = Inhalation NOAEL (10 mg/kg/day)/ Inhalation Dose (mg/kg/day)
f. Dermal Dose (mg/kg/day) = TTR ( μg/cm 2 ) x 0.001 (mg/μg) x short

- term TC (cm 2 /hr) x ET (hr/day) x DAF (3%) / BW (kg).

g. Hand

- to

- Mouth Dose (mg/kg/day) = E = [HR * ( F M * SA H ) * (ET * N_Replen) * (1

- (1

- SE ) (Freq_Replen/N

- Replens) )].
h. Oral MOE = NOAEL (18.8 mg/kg/day) / Oral Dose (mg/kg/day).
i. Adult Tot al MOE = Total MOE = 1/ [(1/Dermal MOE) + (1/Inhalation MOE)]. Children 1<2 years old Total MOE = 1/[(1/Dermal MOE) + (1/Incidental Oral MOE)] j. HED did not combine exposure resulting from adult handler and post

- application exposure resulting from treated lawns and/or golfing because of the conservative assumptions and inputs within each estimated exposure scenario.

6.2 Spray Drift

Spray drift is a potential source of exposure to those nearby pesticide applications. This is particularly the case with aer ial application, but, to a lesser extent, spray drift can also be a potential source of exposure from the ground application methods (e.g., groundboom and airblast) employed for pendimethalin. The Agency has been working with the Spray Drift Task Force (a task force composed of various registrants which was developed as a result of a Data
Call

- In issued by EPA), EPA Regional Offices and State Lead Agencies for pesticide regulation and other parties to develop the best spray drift management practices (see the Agency ’s Spray Drift website for more information). 3 The Agency has also developed a policy on how to appropriately consider spray drift as a potential source of exposure in risk assessments for pesticides. The potential for spray drift will be quantitatively evaluated for each pesticide during
the Registration Revie w process which ensures that all uses for that pesticide will be considered concurrently. The approach is outlined in the revised (2012) Standard Operating Procedures f or Residential Risk Assessment (SOPs)

- Residential Exposure Assessment Standard Operat ing Procedures Addenda 1: Consideration of Spray Drift. This document outlines the quantification
of indirect non

- occupational exposure to drift.

3 Available: http://www.epa.gov/opp0 0001/factsheets/spraydrift.htmPendimethalin Human Health Risk Assessment DP No. D428265

Page 27 of 42 6.3 Residential Bystander Post

- Application Inhalation Exposure

Volatilization of pesticides may be a sour ce 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 Ad visory 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

su bsequent Volatilization Screening Analysis (http://www.regulations.gov/#!docketDetail;D=EPA

- HQ

- OPP

- 2014

- 0219). During Registration Review, the Agency will utilize this analysis to determine if data (i.e., flux studies, route

- specific inhalation toxicolog ical studies) or further analysis is required for pendimethalin.

7.0 Aggregate Exposure/Risk Characterization

In accordance with the FQPA, HED must consider and aggregate (add) pesticide exposures and risks from three major sources: food, drinking water, and residential exposures. In an aggregate assessment, exposures from relevant sources are added together and compared to quantitative estimates of hazard (e.g., a NOAEL or PAD), or the risks themselves can be aggregated. When aggregating exposures and risks from various sources, HED considers both the route and duration of exposure. For pendimethalin, potential exposures from food, drinking water, and residential scenarios were aggregated.

7.1 Acute Aggregate Risk

The aggregate acute risk estimate , by definition include s exposure to residues of pendimethalin
in food and water only. The acute risk estimate for the U.S. population and all other population subgroups, resulting from aggregate exposure to pendimethalin in food and drinki ng water, is
below HED’s LOC. The food and drinking water exposure estimates are <1% of the aPAD for the U.S. general population, and 2% for the most highly exposed life stage, all infants <1 year
old . Therefore there are no acute aggregate risks of concern.

7.2 Short

- Term Aggregate Risk

There is potential short

- term exposure to pendimethalin via dietary (food and water) (which is

con sidered background exposure) and residential exposure pathways. For adults, these pathways lead to exposure via oral as well as dermal and inhalation routes. The most conservative scenario was chosen for each population (i.e. combined hand

- to

- mouth and d ermal exposure
from treated turf for children 1< 2 years old). For a description of the residential exposure scenarios considered in the aggregate assessment, see Section 6.0.Pendimethalin Human Health Risk Assessment DP No. D428265

Page 28 of 42 The adult aggregate MOE (for males and females) which combines average dietary residues with dermal exposure from post

- application exposure to treated ornamentals is 130, which indicates that exposure and risk do not exceed HED’s level of concern (MOE > 30). The aggregate MOE for children 1< 2 years old, which combines average diet ary residues with dermal and incidental oral exposures from treated turf is 9 2 , which indicates that exposure and risk do not exceed HED’s LOC (MOE > 30).

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 3 Residential

Exposure mg/kg/day 4 Total

Exposure mg/kg/day 5 Aggregate

MOE (food, water, and residential) 6

Adult 10 30 0.33 0.001609 0.078 0.080 130

Child 10 30 0.33 0.007019 0.102 0.109 92

1 Intraspecies factor= 10x; Interspecies factor = 3x 2 Maximum Allowable Exposure (mg/kg/day) = NOAEL (10 mg/kg/day)/LOC (30). 3 Average food and water exposure from chronic dietary exposure for adults 20

- 49 yrs and
children 1

- 2 yrs old (see table 5.4.6). 4 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)

. 5 Total Exposure = (Avg (Food & Water) Exposure + Residential Exposure). 6 Adult Aggregate MOE = [NOAEL (10 mg/kg/day)/ (Total Exposure (0.08 mg/kg/day)]; Child Aggregate MOE= [NOAEL (10 mg/kg/day)/ (Total Exposure (0.10 9 mg/kg/day)]



### 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). Therefore a separate intermediate term aggregate assessment was not conducted.

7.4 Chronic Aggregate Risk

Chronic exposure is not expected for the residential (dermal and inhalation) exposure pathways. Therefore, the chronic aggregate risk would be equivalent to the chronic dietary exposure
estimate. Refer to Section 5.4.4 for the chronic die tary (food and drinking water) exposure assessment. There are no chronic aggregate risks of concern.

7.5 Cancer Aggregate Risk

Pendimethalin is considered a “possible human carcinogen”

. Quantification of risk using a non

linear approach; i.e., RfD/PAD, will adequately account for all chronic toxicity, including carcinogenicity, that could result from exposure to pendimethalin. Since there are no chronic aggregate risks of concern (Section 7.4), there are no cancer aggregate risks of concern.

8.0. Cumulative Exposu re /Risk CharacterizationPendimethalin Human Health Risk Assessment DP No. D428265

Page 29 of 42 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 pendim ethalin 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 regar ding EPA’s efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the policy statements released by EPA’s Office of Pesticide Programs concerning common
mechanism determination s and procedures for cumulating effects from substances found to have
a common mechanism on EPA’s website at http://www.epa.gov/pesticides/cumulative/

.

9.0 Occupational Handler Exposure/Risk Estimates

HED uses the term handlers to describe those individuals who are involved in the pesticide application process. HED believes that there are distinct job functions or tasks related to applications and exposures can vary depending on the specific s of each task. Job requirements (amount of chemical used in each application), the kinds of equipment used, the target being treated, and the level of protection used by a handler can cause exposure levels to differ in a manner specific to each applicati on event.

Based on the anticipated use patterns and current labeling, types of equipment and techniques that can potentially be used, occupational handler exposure is ex pected from the proposed crop conversions and expansions. Pendimethalin application to Bermudagrass was originally assessed in 2009 (D371025). Occupational handler exposure risk estimates were calculated for total (combined dermal and inhalation) short

- and intermediate

- term exposures for the following exposure scenarios

.

 Mixing/load ing l iqui d formulations for ground, chemigation, and aerial a pplications

,

 Applying s prays via ground, and aerial a pplications , and

 Flagging for aerial spray a pplications

.

Estimates of dermal and inhalation exposure were calculated for various levels of PPE

. The
Prowl ® H 2 O product labels direct mixers, loaders, applicators and other handlers to wear long

sleeved shirt s and long pants, chemical

- resistant gloves, and shoes plus socks . The short

- and
intermediate term combined dermal and inhalation did n ot exceed HED’s level of concern (MOE ≥ 30) with label mandated PPE of single layer baseline and gloves. Body weight assumptions have increased from the 70 kg used in the 2009 assessment to 80 kg.

The proposed crop expansions to bushberries, caneberries, and tree nut subgroups are expected have identical handler exposure pattern (i.e., ground directed layby between rows) and maximum application rate (i.e., 6 lb ai/acre) as the previous citrus and other tree crops already assessed in the 2012 registration review (D402406). Occupational handler combined ( dermal and inhalation)
short

- and intermediate

- term exposure risk estimates were calculated for the following exposure
scenarios

.Pendimethalin Human Health Risk Assessment DP No. D428265

Page 30 of 42 1) Mixing/loading liquid formulations for ground and chemigation applicat ion s, 2 ) Applying s prays via groundboom equipment,
3 ) Mixing/loading/applying liquids via mechanically

- pressurized handgun

, 4 ) Mixing/loading/applying liquids vi a manually pressurized handwand, and 5) Mixing/loading/applying liquids via handgun sprayer

.

Combined dermal and inhalation risk estimates (MOEs) were not of concern (MOEs ≥ 30 ) with baseline dermal protection and gloves. See Table in Appendix D for a summary of the dermal
and inhalation exposures and risk estimates for Bermudagrass and crop grou ps oc cupational pesticide handlers.

9.2 Occupational Post

- application Exposure/Risk Estimates

HED uses the term post

- application to describe exposures that occur when individuals are present in an environment that has been previously treated with a pesti cide (also referred to as re

entry exposure). Such exposures may occur when workers enter previously treated areas to perform job functions, including activities related to crop production, such as scouting for pests or harvesting. Post

- application expos ure levels vary over time and depend on such things as the type of activity, the nature of the crop or target that was treated, the type of pesticide application, and the chemical’s degradation properties. In addition, the timing of pesticide applications

, relative to harvest activities, can greatly reduce the potential for post

- application exposure.

9.2.1 Occupational Post

- application Inhalation Exposure/Risk Estimates

There are multiple potential sources of post

- application inhalation exposure to indiv iduals performing post

- application activities in previously treated fields. These potential sources include volatilization of pesticides and resuspension of dusts and/or particulates that contain pesticides. The Agency sought expert advice and input on i ssues 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 Registration Review, the Agency will utilize this analysis to determine if data (i.e., flux studies, route

- specific inhalation toxicological studies) or further analysis is required for p endimethalin.

In addition, the Agency is continuing to evaluate the available post

- application inhalation exposure data generated by the Agricultural Reentry Task Force. Given these two efforts, the Agency will continue to identify the need for and, subsequently, the way to incorporate occupational post

- application inhalation exposure into the Agency 's risk assessments.

Although a quantitative occupational post

- application inhalation exposure assessment wa s not performed, an inhalation exposure assessment was performed for occupational/commercialPendimethalin Human Health Risk Assessment DP No. D428265

Page 31 of 42 handlers. Handler exposure resulting from application of pesticides outdoors is likely to result in higher exposure than post

- application exposure. Therefore, it is expected that these handler inhalation exposure estimates would be protective of most occupational post

- application inhalation exposure scenarios.

9

. 2 .2 Occupational Post

- A pplication Dermal Exposure/Risk Estimates

The proposed crop subgroups; b ushberry 13

- 07B, c aneberry 13

- 07A and t ree n ut 14

- 12 were not
assessed for dermal post

- application exposure because of use pattern and review of submitted chemical specific study. Pendimethalin is applied as a pre

- emergent/ early post

- emergent herbicide an d not directly applied to the foliage of the proposed crop groups but rather to the layby or between rows. T he chemical specific study on post

- application foliage supports that post application exposure to crops from pendimethalin layby application is neg ligible ( S ee Dislodgeable Foliar Residues section below).

The application to Bermudagrass is expected to be a post emergent foliar spray and not represented by the DFR study. The fraction of pendimethalin 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. In 2009 the estimated occupational dermal post application risks to tr eated Bermudagrass using
default dissipation assumptions did not exceed HED’s level of concern (MOEs ≥ 30) on the day of treatment for early post application activities including scouting and hand laying irrigation.

Dislodgeable Foliar Residues (DFR) :

Based on a review of the available data (C. Jarvis, 08/01/2001, D262264), it was decided that the DFR data for sugarcane and tobacco (MRID 44969902) treated with PROWL 3.3 EC Herbicide in Washington and Louisiana would be used to assess non

- foliar pendimet halin layby application s ( ground

- directed spray s ). However the DFR study residues were deter mined to be
less than the limit of quantitation ( LOQ ) in most samples.

Restricted Entry Interval

The REI specified on the proposed label is based on the acute toxicity of pendimethalin. Pendimethalin is classified as Toxicity Category IV via the dermal route and skin irritation potential. It is not a skin sensitizer. Under 40 CFR 156.208 (c) (2) (i ii), ai’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

.

10 ReferencesPendimethalin Human Health Risk Assessment DP No. D428265

Page 32 of 42 Residue Chemistry References
Pendimethalin. Human Health Risk Assessment for New Use on Hops, and Crop Subgroup Conversions/Expansions for Low Growing Berry Subgroup 13

- 07G, Onion, Bulb Subgroup 3

- 07A, Onion, Green Subgroup 3

- 07B, and Sunflower Subgroup 20B; Crop Group Expansions for Citrus Fruit, Group 10, Pome Fruit, Group 11, Stone Fruit, Group 12, an d Fruiting Vegetable, Group 8 ; DP Barcode 416285; P. Yvonne Barnes ; 01 / 14 /20 15

. Pendamethalin: Petition Section 3 Registration and Establishment of Permanent Tolerance of Pendimethalin for Uses on Caneberry S ubgroup 13

- 07A, Bushberry Subgroup 13

- 07B, and Livestock Commodities. Crop Group Conversion for Tree Nut Crop Group 14. Amend th e Pre

- Harvest I nterval and Establishment of T olerances for Pendimethalin in/on Grass Forage,

F odder, and Hay (Crop Group 17). Summary of Analytical Chemistry and Residue Data; DP
Barcodes D420013, M. Sahafeyan and P. Yvonne Barnes; 11/10 /2015
Pendimethali n: Pendimethalin Residues of Concern in Ruminant Commodities; DP# Barcode: D428264; P. Yvonne Barnes; 08/06/2015 Drinking Water Assessment Drinking Water Assessment for Proposed New Uses of Pendimet halin on Caneberry Subgroup 13

- 07 A, Bush berry Subgroup 13

- 07B, Crop Group Conversion for Tree N u t Group 14

- 12; and Cool

- and Warm Season Forage Grasses ; DP# Barcode: D 421275, 420012

, I. Abdel

- Saheb; 01/08/2015 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 Caneberry subgroup 13

- 07A, Bushberry subgroup 13

- 07B and Livestock commodities. Crop

g roup conversion for Tree Nut group 14. Amend the pre

- harvest interval and tolerances for Pendimethalin in/on Grass Forage, Fodder, and Hay (Crop Group 17); DP Barcode D428267;

P. Yvonne Barnes ; 11/3/2015

. Occupational/Residential Assessment
Pendimethali n: Occupational and Residential Exposure Assessment for a Proposed Section 3 Crop Expansions and Conversions of the Following: Bushberry Subgroup 13

- 07B, Caneberry Subgroup 13

- 07A, and Nut Tree Subgroup 14

- 12; DP# Barcode: D 420014

, B. Bobowiec;
03/03/2015 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; 06/07/12; D 40 2406 Secondary Review of Occup ational and Residential Exposure/Risk Assessment for Registration Review and for new Proposed Use on Leaf lettuce; Leafy PROWL ® 3.3 EC
Herbicide.” MRID 449699 01

- 02; DP Barcode D262264; C. Jarvis ; 08/01/2001

Pendimethalin: Occupational and Residential Exposure Assessment for Proposed Section 3 Registration for Use on Grasses Grown for Seed and Dormant Bermudagrass Pasture and Hay
Fields ; DP Barcode 371025; S. Shelat; 10/27/2009Pendimethalin Human Health Risk Assessment DP No. D428265

Page 33 of 42 Appendix A. Toxicology Profile and Executive Summaries

A.1 Toxicology Data Requirements

The requirements (40 CFR 158.340) for pendimethalin are in Table A.1. Use of the new guideline numbers does not imply that the new (1998) guideline protocols were used.

TABLE A.1 Toxicology Data Requirements for Pendimethalin.

Test Technical

Required Conducted

870.1100 Acute Oral Toxicity
870.1200 Acute Dermal Toxicity 870.1300 Acute Inhalation Toxicity 870.2400 Primary Eye Irritation 870.2500 Primary Dermal Irritation
870.2600 Dermal Sensitization yes
yes
yes
yes
yes
yes yes

yes
yes
yes
yes
yes

870.3100 Oral Subchronic (rodent) 870.3150 Oral Subchronic (non

- rodent)
870.3200 21/28

- Day Dermal
870.3250 90

- Day Dermal
870.3465 90

- Day Inhalation yes
yes
yes

no

no yes

yes
yes

no

no

870.3700a Developmental Toxicity (rodent) 870.3700b Developmental Toxicity (non

- rodent) 870.3800 Reproduction yes
yes
yes yes

yes
yes

870.4100a Chronic Toxicity (rodent) 870.4100b Chronic Toxicity (non

- rodent) 870.4200a Oncogenicity (rat) 870.4200b Oncogenicity (mouse) 870.4300 Chronic/Oncogenicity yes
yes
yes
yes
yes yes

yes
yes
yes
yes

870.5100 Mutagenicity

— Gene Mutation (bacterial) 870.5300 Mutagenicity

— Gene Mutation (mammalian) 870.5375 Mutagenicity

— Structural Chromosomal Aberrations 870.5395 Mutagenicity

— Other Genotoxic Effects 870.5500 Mutagenicity

— Other Genotoxic Effects yes
yes
yes
yes
yes yes

yes
yes
yes
yes

870.6100a Acute Delayed Neurotoxicity (hen)
870.6100b 90

- Day Neurotoxicity (hen) 870.6200a Acute Neurotoxicity Screening Battery (rat)
870.6200b 90

- Day Neurotoxicity Screening Battery (rat) 870.6300 Developmental Neurotoxicity no

no
yes
yes

no no

no
yes
yes

no

870.7485 General Metabolism
870.7600 Dermal Penetration 870.7800 Immunotoxicity yes

no
yes yes

yes
yesPendimethalin Human Health Risk Assessment DP No. D428265

Page 34 of 42 A.2 Toxicity Profiles

Table A.2.1 Acute Toxicity Profile

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

870.1100 Acute oral [Rat] 00026657 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.

870.3100 Subchronic oral

[Rat] (14

- day) 43135003 0, 100, 500 ppm NOAEL = 10 mg/kg/day.Pendimethalin Human Health Risk Assessment DP No. D428265

Page 35 of 42 TABLE A.2.2 Subchronic, Chronic and Other Toxicity Profile for Pendimethalin.

Guideline
Number Study Type MRID Number
& Classification Dose Levels Results

0, 10, 500 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 given as a range, based on
calculations from actual chemical intake, and a 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. D428265

Page 36 of 42 TABLE A.2.2 Subchronic, Chronic and Other Toxicity Profile for Pendimethalin.

Guideline
Number Study Type MRID Number
& Classification Dose Levels Results

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).

870.5100 Reverse gene

mutation assay [Escherichia coli WP2] 43177801 25, 50, 100, 250, 500, 750 μg/plate NegativePendimethalin Human Health Risk Assessment DP No. D428265

Page 37 of 42 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] 43135005 50, 158, 500, 1581, 5000 μg/plate or 1000 μg/paper disk/plate Negative

870.5100 Reverse gene

mutation assay [Escherichia coli WP2] 43135006 50, 100, 250, 500, 750 μg/plate Negative

870.5300 Mammalian

cell gene
mutation [Chinese hamster ovary] 43177802 1, 5, 7.5, 10, 20, 30, 40, 50 μg/plate (

- S9) 10, 25, 50, 75, 100, 125, 150, 175 μg/plate (+S9) Negative

870.5375 Chromosomal

aberration [Chinese hamster ovary] 00153770 Doses ranging from 5

- 50 μg/ml Negative

870.5395 Micronucleus

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

870.5550 Alkaline elution

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

870.6200 Acute

neurotoxicity 48695601

Acceptable 0, 100, 300, or 1000

mg/kg NOAEL=100 mg/kg,

LOAEL= 300 mg/kg, based on reduced motor activity for males and females (↓19 and ↓51%, respectively, on Day 0.

870.6200 Subchronic

neurotoxicity 42054601

Acceptable 0, 42.0/50.1, 126.5 /

151.9, 386.8/423.1 mg/kg bw/day [M/F] NOAEL= 386.8/423.1 mg/kg/day (HDT).

LOAEL not established.

870.7800 Immunotoxicity 48608901

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

LOAEL not established.

870.7485 Metabolism and

pharmacokineti cs [Rat] 00046275

Acceptable NA* Pendimethalin is eliminated from the body within 24 hours, with 70% being excreted in feces (primarily the parent compound), and 20% in
urine.

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.Pendimethalin Human Health Risk Assessment DP No. D428265

Page 38 of 42 TABLE A.2.2 Subchronic, Chronic and Other Toxicity Profile for Pendimethalin.

Guideline
Number Study Type MRID Number
& Classification Dose Levels Results

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. D428265

Page 39 of 42 Appendix 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: Pendimethalin

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, metabolite 6 “goat metabolite 6” (1

- (1

- ethylpropyl)

- 5, 6

- dimethyl

- 7

- nitro

- 1H

benzimidazole) 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 Fruit, caneberry, subgroup13

- 07A 0.10 Fruit, bushberry, subgroup13

- 07B 0.10 Nut, Tree group 14

- 12 0.10 Grass forage, fodder, and hay crop group 17, forage 1000.0 Grass forage, fodder, and hay crop group 17, hay 2000.0

Milk 0.10

Meat 0.10

Fat 0.3 Kidney 3.0

Liver 1.5 Meat byproducts except liver 3.0 Completed by: M. Negussie; 07/28/2015Pendimethalin Human Health Risk Assessment DP No. D428265

Page 40 of 42 Appendix C . Occupational Handler Non

- Cancer Exposure and Risk Estimates for Pendimethalin

Appendix D. Occupational Handler Dermal and Inhalation Non

- Cancer Exposure and Risk Estimates for Prowl ® H 2 O Pendimethalin on Proposed Crop Group Bushberries, Caneberries and Tree Nuts.

Application Equipment Crop /

Target Category App.

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) Total MOE 8

Value
Units Value

Units SL/No

G SL/G No

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

G SL/G No

- R No

- R SL/No
G and

No

- R SL/G

and

No

- R
Mixer/Loader Chemigation Bushberries,

Caneberries
and Tree

Nuts 6

lb
ai/acre 350 acres

220 220 0.219 0.17 0.03 58 340 0.006 1,700 56 280

Groundboom 80 acres 0.04 0.007 250 1,500 0.0013 7,600 240 1,300

40 acres 0.0198 0.00338 510 3,000 0.000658 15,000 490 2,500

Applicator

Groundboom Bushberries,

Caneberries
and Tree

Nuts 6

lb
ai/acre 80 acres

78.6 16.1 0.34 0.014 0.003 710 3,400 0.002 4,900 620 2,000

40 acres 0.00709 0.00145 1,400 6900 0.00102 9,800 1,200 4,000

Mixer/Loader/Applicator Mechanically

Pressurized Handgun
Ground soil

directed Bushberries,

Caneberries
and Tree

Nuts 0.3 lb

ai/gallo

n 1,000 gallon 1,300 390 3.9 0.146 0.0439 68 230 0.0146 680 62 170

Manually

Pressurized
Handwand 40 gallons 100,000 430 30 0.45 0.00194 22 5200 0.0045 2,200 22 1,500

Backpack
Ground soil

directed 8,260 2.58 0.0372 270 0.000388 26,000 270

1 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (March 2014); Level of mitigation: SL/N o G (single layer dermal), SL/G (single dermal layer with gloves), No

- R (baseline inhalation no respirator).
2 Based on proposed l abel (Prowl ® H 2 O Reg. No.241

- 418).
3 Exposure Science Advisory Council Policy #9.1.
4 Dermal Dose = Dermal Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A or gal/day) × DAF (3%) ÷ 80 (kg).
5 Dermal MOE = Dermal NOAEL (mg/kg/day) ÷ Dermal Dose (mg/kg/day).

6 Inhalation Dose = Inhalation Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal ) × Area Treated or Amount Handled (A or g al/day) ÷ 80 (kg).Pendimethalin Human Health Risk Assessment DP No. D428265

Page 41 of 42 7 Inhalation MOE = Inhalation NOAEL (mg/kg/day) ÷ Inhalation Dose (mg/kg/day).
8 Total MOE = NOAEL (10 mg/kg/day) ÷ Dermal Dose + Inhalation Dose.Pendimethalin Human Health Risk Assessment DP No. 416285

Page 42 of 42 Appendix D . 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 da tabase; are (1) subject to ethics review pursuant to 40 CFR 26, (2) have received that review, and (3) are compliant with applicable ethics requirements. For certain studies, the ethics review may have included review by the Human Studies Review
Board. D escriptions 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.ht ml