Linuron Human Health Risk Assessment DP No. D405828

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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF

CHEMICAL SAFETY AND

POLLUTION PREVENTION

MEMORANDUM

Date: September 18, 2013

SUBJECT: Linuron: Section 3 Human Health Risk Assessment for Proposed Use on 

Coriander, Dill, Horseradish, Parsley, Celeriac, Rhubarb, and Pea (Dry).

PC Code: 035506 DP Barcode: D405828

Decision No.: 469722 Registration No.: 61842-23

Petition No.: 2E8083 Regulatory Action: Section 3 Registration

Risk Assessment Type: Single Chemical Aggregate Case No.: 0047

TXR No.: NA CAS No.: 330-55-2

MRID No.: NA 40 CFR: §180.184

From: Kristin Rury, Biologist

Whang Phang, Senior Toxicologist

Nancy Tsaur, Chemist

Risk Assessment Branch III

Health Effects Division (7509P)

Through: Christine Olinger, Branch Chief

Risk Assessment Branch III

Health Effects Division (7509P)

To: Laura Nollen, Risk Manager

Risk Integration Minor Use and Emergency Response Branch

Division (7505P)

This document provides an assessment of the human health risk resulting from the proposed and 

registered uses of linuron. The toxicology reevaluation was performed by Whang Phang, the 

drinking water assessment was conducted by He Zhong (EPA Environmental Fate and Effects 

Division (EFED)), the review of the residue chemistry data was conducted by Nancy Tsaur, and 

the occupational, dietary, and human health risk assessments were conducted by Kristin Rury. 
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Table of Contents

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

2.0 HED Recommendations.................................................................................................... 6

2.1 Data Deficiencies ............................................................................................................ 6

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

2.2.1 Enforcement Analytical Method ............................................................................... 7

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

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

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

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

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

2.3.2 Recommendations from Occupational Assessment................................................. 9

3.0 Introduction........................................................................................................................ 9

3.1 Chemical Identity ........................................................................................................... 9

3.2 Physical/Chemical Characteristics ............................................................................. 10

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

3.4 Anticipated Exposure Pathways................................................................................. 11

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

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

4.1 Toxicology Studies Available for Analysis................................................................. 12

4.2 Absorption, Distribution, Metabolism, % Elimination (ADME) Data ................... 13

4.2.1 Dermal Absorption................................................................................................... 13

4.3 Toxicological Effects .................................................................................................... 13

4.4 Safety Factor for Infants and Children (FQPA Safety Factor) ............................... 14

4.4.1 Completeness of the Toxicology Database.............................................................. 14

4.4.2 Evidence of Neurotoxicity........................................................................................ 15

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal........ 15

4.4.4 Residual Uncertainty in the Exposure Database ................................................... 15

4.5 Toxicity Endpoint and Point of Departure Selections.............................................. 16

4.6 Cancer Classification ................................................................................................... 17

5.0 Dietary Exposure and Risk Assessment......................................................................... 18

5.1 Residues of Concern Summary and Rationale.......................................................... 18

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

5.3 Water Residue Profile.................................................................................................. 20

5.4.1 Description of Residue Data Used in Dietary Assessment.................................... 21

5.4.2 Percent Crop Treated Used in Dietary Assessment .............................................. 21

5.4.3 Acute Dietary Risk Assessment............................................................................... 21

5.4.4 Chronic Dietary Risk Assessment........................................................................... 22

5.4.5 Cancer Dietary Risk Assessment............................................................................. 22

5.4.6 Summary Table......................................................................................................... 22

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ............................. 23

6.1 Residential Bystander Post-application Inhalation Exposure ................................. 23

6.2 Spray Drift.................................................................................................................... 23

7.0 Aggregate Exposure/Risk Characterization.................................................................. 24

8.0 Cumulative Exposure/Risk Characterization ............................................................... 24

9.0 Occupational Exposure/Risk Characterization ............................................................ 24
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9.1 Short-Term Handler Risk ........................................................................................... 24

9.2 Short-Term Post-Application Risk............................................................................. 30

9.2.1 Dermal Post-Application Risk................................................................................. 30

9.2.2 Inhalation Post-Application Risk............................................................................ 31

10.0 References......................................................................................................................... 31

Appendix A. References for Published Toxicity Studies and Toxicology Profile ................ 33

Appendix B. Physical/Chemical Properties............................................................................. 40

Appendix C. Review of Human Research ............................................................................... 41
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1.0 Executive Summary

Introduction

Linuron is a selective phenylurea herbicide used to control broadleaf weeds and annual grasses 

by systemically inhibiting photosynthesis. It may be applied pre-plant, pre-emergence, postemergence or post-transplant to various field crops and noncrop areas.

The Interregional Research Project No. 4 (IR-4) submitted a petition (PP# 2E8083) to allow 

linuron use on coriander (fresh and seed), dill, horseradish, parsley, and dry pea. The proposed 

uses will be added to the technical product labels (Linuron Technical, EPA Reg. No. 61842-22; 

and Linuron Flake Technical, EPA Reg. No. 61842-24) and to the formulated end use product 

label (Lorox DF®, EPA Reg. No. 61842-23). HED previously evaluated the occupational 

exposure risk from linuron use on rhubarb and celeriac during tolerance reassessment (S. Recore, 

D281845, 03/27/2002) and these uses are also included in the currently proposed label. HED has 

reevaluated the exposure risk from linuron use on rhubarb and celeriac using current 

occupational exposure policies and inputs. 

Concomitant with this IR-4 petition, additional analytical method data have been submitted by

Tessenderlo Kerley to support the newly proposed uses. A new enforcement method for plant 

and livestock commodities was previously required as conditional data (K. Rury, DP375451, 

04/01/2010). A high performance liquid chromatography/tandem mass spectrometry

(HPLC/MS/MS) method based on extraction of residues and identification of parent and specific 

metabolites has been submitted. A method was also submitted that hydrolyzes commodities with 

base to transform the total linuron residue to 3,4-dichloroaniline (3,4-DCA). Gas

chromatography with mass spectrometry detection (GC/MS) is used to quantitate the 3,4-DCA. 

Independent laboratory validation of the latter method has been provided. In reviewing these 

data, HED has determined that the continued use of a common moiety definition (3,4-DCA) is 

appropriate, and that the validated GC/MS method for 3,4-DCA will be adequate for tolerance 

enforcement purposes. Thus, the requirement for additional enforcement analytical methods is 

fulfilled.

Use Profile

Lorox DF®is a water dispersible granular (WDG) formulation containing 50% linuron by

weight. Lorox DF® may be applied both before and after weed emergence and usually early in 

the crop growing season. The maximum single application rates are as follows: 2.0 lb product/A 

(1.0 lb ai/A) for coriander and dill; 3.0 lb product/A (1.5 lb ai/A) for celeriac, rhubarb, 

horseradish, and parsley; and 2.0 lb product/A (1.0 lb ai/A) for dry peas and parsley grown for 

seed in Oregon and Washington. The maximum seasonal application rates are as follows: 4.0 lb 

product/A for coriander and dill; 3.0 lb product/A for parsley, celeriac, rhubarb, and horseradish, 

and 2.0 lb product/A for dry pea and parsley grown for seed in Oregon and Washington. 

Hazard Assessment

With repeated dosing in test animals, linuron produces two primary effects: (1) changes in the 

hematopoetic system in rats, mice, and dogs; and (2) changes in the male reproductive system in 

developing rats. Linuron exhibits low acute toxicity via the oral (Toxicity Category III), dermal 

(Toxicity Category III), and inhalation (Toxicity Category IV) routes of exposure. Linuron is a 
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minimal eye irritant (Toxicity Category III), not a dermal irritant (Toxicity Category IV), and is 

not a dermal sensitizer. The HED Hazard and Science Policy Council (HASPOC) recently 

waived the requirement for a 28-day inhalation toxicity study, a 21-day dermal toxicity study, 

and a subchronic neurotoxicity study (TXR#0056666, TXR#0056436 and TXR#0056667). 

Based on the available hazard and exposure data, the Food Quality Protection Act (FQPA) safety

factor is reduced to 1X for all population subgroups and exposure scenarios. The level of 

concern (LOC) for non-cancer occupational risk assessment is a margin of exposure (MOE) of 

100 (i.e. an MOE < 100 is of concern). Linuron was classified as a Group C Carcinogen 

requiring no quantification of human cancer risk. Group C carcinogen classification is 

comparable to the current classification of “Suggestive Evidence of Carcinogenic Potential”.

Residential Exposure

There are no registered or proposed uses of linuron in residential settings. 

Dietary Exposure

The acute and chronic dietary (food and drinking water) exposure assessment for linuron 

assumed recommended tolerance-level residues for all food commodities, assumed that all of the 

proposed and registered crops were treated in the acute assessment (100% crop treated; %CT), 

incorporated estimated percent crop treated (%CT) values in the chronic assessment, and used 

default processing factors. Estimated drinking water concentrations (EDWCs) from EFED were 

also included. The results of the acute analysis indicate that the acute dietary (food and drinking 

water) exposure and risk does not exceed HED’s LOC [i.e., <100% acute population adjusted 

dose (aPAD)] for the general U.S. population, and all population subgroups, including females 

13-49 years old. At the 95th percentile of exposure, the resulting acute dietary (food and drinking 

water) risk estimates utilized 4.3% of the aPAD for the general U.S. population and 10% for all 

infants, the most highly exposed population subgroup. At the 95th percentile of exposure, the 

resulting acute dietary (food and drinking water) risk estimate utilized 5.7% of the aPAD for 

females 13-49 years old. 

The results of the chronic analysis indicate that chronic dietary (food and drinking water) 

exposure and risk does not exceed HED’s LOC [i.e., <100% chronic population adjusted dose 

(cPAD)] for the U.S. population and all population subgroups. The resulting chronic dietary

(food and drinking water) risk estimates utilized 22% of the cPAD for the general U.S. 

population and utilized 60% of the cPAD for children 1-2 years old, the most highly exposed 

population subgroup. 

Aggregate Exposure 

There are no registered or proposed residential uses of linuron; therefore aggregate exposure is 

equivalent to dietary (food + drinking water) exposure. 

Occupational Exposure 

There is potential for short-term occupational exposure to linuron during handling activities (e.g. 

mixing, loading, application) and during post-application activities. There are some risk 

estimates of concern for the proposed uses of linuron at baseline (no personal protective 

equipment; PPE), and with the label-specified PPE (coveralls/double layer and chemical resistant 

gloves). Mixing/loading for chemigation application to parsley, horseradish, celeriac, rhubarb, 
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dry pea, coriander, and dill required engineering control mitigation to be not of concern to HED 

(MOEs >100). Based on the results of the occupational exposure assessment, HED recommends 

that engineering controls (e.g., a closed mixing/loading system) be required on the Lorox DF®

label for mixing/loading for chemigation application to the proposed crops, or that the label 

restricts chemigation application. 

Some occupational short-term post-application risk estimates were of concern on the day of 

application. In order for MOEs to be greater than the LOC at the maximum single application 

rate, hand-set irrigation should occur 4 days after application for parsley, dill, coriander and 8 

days after application for celeriac. Since there were risk estimates of concern related to hand-set 

irrigation both on day 0 after application and at the label-specified restricted entry interval (REI),

HED recommends that the REI on the proposed label (12 hours) be revised to address those 

concerns.

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; and the ARTF database; are (1) subject to ethics review 

pursuant to 40 CFR 26, (2) have received that review, and (3) are compliant with applicable 

ethics requirements. For certain studies, the ethics review may have included review by the 

Human Studies Review Board. For citations of these data, see Appendix C. 

Environmental Justice Considerations

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

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

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

(http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf. 

2.0 HED Recommendations

HED has examined the residue chemistry, toxicity, and exposure databases for linuron and 

concluded that, provided a revised label and a revised Section F are submitted, there are no 

deficiencies that would preclude granting Section 3 registration for the requested crop 

commodity uses of linuron, or establishment of tolerances for residues of linuron. The specific 

tolerance recommendations are discussed in Section 2.1.2.

2.1 Data Deficiencies

Dislodgeable Foliar Residue (DFR) (158.1070)

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

required when a pesticide has residential or occupational uses that could result in postapplication dermal exposure. As part of the recent revision to the Health Effects Division’s 2012 

Standard Operating Procedures for Residential Pesticide Exposure Assessment, HED analyzed a 

number of DFR studies and selected a new default value for the fraction of the application rate 

available to be dislodged after a foliar application (FAR). This default value is 25% and is based 

on an analysis of 19 DFR studies where the FAR value ranged from 2% to 89%. This value is 
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recommended for use in both residential and occupational post-application assessments. Of the 

analyzed DFR studies, the maximum FAR value seen was 89% or 3.6 times higher than the 

default residue transfer value. Therefore, the HED has decided that a calculated MOE of 

approximately 4 times higher than the level of concern (e.g., an MOE > 400 if the LOC = 100) 

using the default dislodged residue values would provide an adequate margin of safety for any 

potentially higher residues seen in a chemical-specific DFR study (Guidance for 

Requiring/Waiving Turf Transferrable Residue (TTR) and Dislodgeable Foliar Residue (DFR) 

Studies. 06/07/2012, Exposure Science Advisory Council). A DFR study is required for linuron 

at this time since some of the dermal MOEs are less than 4 times the LOC based on default 

values for the fraction of application rate available for transfer after a foliar application. A 

previously submitted study evaluating residues on asparagus spears is not adequate to support the 

proposed and registered uses of linuron.

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

Various adequately validated analytical methods are now available for linuron.

For linuron residues of concern in plant commodities, Method ABC-68406-M is available and 

suitable for residue collection as well as enforcement of tolerances. This method involves reflux 

of crop samples in strong base to hydrolyze residues of linuron and its metabolites to 3,4-DCA, 

which is analyzed using GC/MS. Based on the lowest level of method validation (LLMV) from 

the independent laboratory validation (ILV) study, the validated limit of quantification LOQ is 

0.01 ppm for linuron and its metabolites hydrolyzable to 3,4-DCA. In addition, Method ABC65790 (LC/MS/MS) may be used as a confirmatory method. It is a multi-residue method that is 

suitable for screening for enforcement of tolerances for linuron residues in plant commodities. 

This method separately determines residues of linuron and metabolites 3-(3,4-dichlorophenyl)-1-

methylurea (DCPMU), N-(3,4-dichlorophenyl)urea (DCPU), and desmethyl linuron in crop 

commodities. 

For linuron residues of concern in livestock commodities, Method ABC-67638-M (GC/MS) is 

available and suitable for residue collection as well as enforcement of tolerances. Like the plant 

method, linuron and its metabolites are hydrolyzed to 3,4-DCA using strong base and then 

analyzed by GC/MS. 

2.2.2 Recommended Tolerances

In addition to the recommended tolerances listed below in Table 2.2.2, the tolerance with 

regional registration under 40 CFR §180.184(c) for parsley, leaves (0.25 ppm) should be deleted. 

Table 2.2.2. Tolerance Summary for Linuron.

Commodity Established/Proposed 

Tolerance (ppm)

HED-Recommended 

Tolerance (ppm)

Comments

(correct commodity definition)

Cilantro, fresh leaves 3.0 1.5

Cilantro, dried leaves 27 10

Coriander, seed 0.01 0.05
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Table 2.2.2. Tolerance Summary for Linuron.

Commodity Established/Proposed 

Tolerance (ppm)

HED-Recommended 

Tolerance (ppm)

Comments

(correct commodity definition)

Dillweed, fresh leaves 1.5 0.6

Dillweed, dried leaves 7.1 3.0

Dill, seed 0.3 0.5

Dill, oil 4.8 2.0

Horseradish 0.05 0.05

Parsley, leaves 3.0 4.0

Parsley, dried leaves 8.3 3.0

Pea, dry, seed 0.08 0.06

Note to RD: the tolerances of meat byproducts of cattle, goat, pork, and sheep should be updated 

to 2.0 ppm, instead of the current tolerance of 0.1 ppm. 

2.2.3 Revisions to Petitioned-For Tolerances

The revisions to the petitioned-for tolerances are described below. 

The Organization for Economic Cooperation and Development (OECD) tolerance calculation 

procedures were used to calculate the tolerance levels for the following three commodities: 

cilantro, fresh leaves; dillweed, fresh leaves; and pea, dry, seed. Based on the OECD 

calculations, all three tolerance levels should be decreased.

Instead of using the OECD calculator due to a limited number of field trials, the formula of 5X 

the mean was used to establish tolerance levels for the following three commodities: coriander, 

seed; dill, seed; and parsley, leaves. Based on this calculation method, all three proposed 

tolerance levels should be increased.

For the dried herbs (cilantro, dillweed, and parsley) and the dill oil, the formula of the highest 

average field trial (HAFT) multiplied by the concentration factor was used to calculate the 

recommended tolerance levels (the concentration factors were derived from dividing the average 

dried/oil commodity residue by the average fresh commodity residue). Based on this calculation 

method, all four tolerance levels should be decreased.

2.2.4 International Harmonization

There are no established maximum residue limits (MRLs) for linuron in Codex for any

agricultural commodity. Furthermore, no Canadian or Mexican MRLs have been established for 

linuron. Therefore, there are no harmonization issues.

2.3 Label Recommendations

2.3.1 Recommendations from Residue Reviews

Since there are livestock feed items associated with field pea, the following restriction should be 

added to the label: “Do not apply to field pea used for livestock feed.”
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2.3.2 Recommendations from Occupational Assessment

HED recommends that engineering controls (e.g., a closed mixing loading system) be required 

on the Lorox DF®label for mixing/loading for chemigation application to the proposed crops, or 

that chemigation is restricted from the proposed label. In addition, there were risk estimates of 

concern related to hand-set irrigation both on day 0 after application and at the label-specified 

REI; therefore, HED is recommending that the REI be revised on the label to address those 

concerns. In order for MOEs to be greater than the LOC at the maximum single application rate, 

the REI for hand-set irrigation should be 4 days for parsley, dill, and coriander, and 8 days for 

celeriac. 

3.0 Introduction

3.1 Chemical Identity

Table 3.1. Linuron Nomenclature.

Compound

Common name Linuron

Company experimental name DPX-Z0326

IUPAC name 3-(3,4-dichlorophenyl)-1-methoxy-1-methylurea

CAS name N‘-(3,4-dichlorophenyl)-N-methoxy-N-methylurea

CAS # 330-55-2

End-use product/EP

Metabolite

Common name DCPMU

Chemical name 3-(3,4-dichlorophenyl)-1-methylurea

Metabolite

Common name DCPU

Chemical name N-(3,4-dichlorophenyl)urea

N

H

Cl

Cl

O

N

O

CH3

CH3

N

H

Cl

Cl

O

N

H

CH3

N

H

Cl

Cl

O

NH2
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Table 3.1. Linuron Nomenclature.

Metabolite

Common name Desmethyl linuron

Chemical name N-(3,4-dichlorophenyl)-N‘-methoxyurea

3.2 Physical/Chemical Characteristics

Linuron is an off-white powder with a molecular weight of 249.1 g/mol, which indicates that the 

potential to cross biological barriers, such as the skin, is somewhat limited. Furthermore, the low 

log of the octanol/water partition coefficient (log Pow = 2.76 at 25C) suggests low potential for 

dermal absorption; the relatively low water solubility and low lipophilic potential, indicate that 

linuron is not likely to bioaccumulate. The vapor pressure for linuron is low (3.01×10-7 mm Hg 

at 25C), and linuron is considered relatively insoluble in water. The Henry’s Law constant was 

calculated to be 1.97×10-9atm·m

3

/mol. Thus, linuron is unlikely to volatilize significantly, and 

inhalation via chemical vaporization is unlikely. 

Linuron is moderately persistent with an aerobic soil metabolism half-life ranging from 57 to 100 

days. Because parent linuron is sufficiently persistent and may be mobile under certain 

environmental conditions, it has the potential to impact ground water quality. 

3.3 Pesticide Use Pattern

IR-4 is proposing new uses for the 50% DF formulation Lorox® DF (EPA Reg. No. 61842-23). 

The use directions are summarized below in Table 3.3.

Table 3.3. Summary of Proposed Directions for Use of Linuron (Lorox® DF, EPA Reg. No. 61842-23).

Application, 

Type, and 

Equipment

App Rate

(lb ai/A)

Timing

Max No. 

App per 

Season

Max. 

Seasonal 

App Rate

(lb ai/A)

PHI

(days) Product Use Directions and Limitations

Coriander (Cilantro)

Broadcast

Ground, 

Chemigation

0.5 - 1.0

preemergence

1

2.0

East of 

Rocky Mtns

1.5

West of 

Rocky Mtns

21

Do not apply by air. Do not apply to sand or loamy 

sand soil types to avoid crop injury. Do not use on 

soils with less than 1% organic matter to avoid crop 

injury. Do not exceed 4 lbs. LOROX® DF per acre 

per year East of Rocky Mountains. Do not exceed 3 

lbs. LOROX® DF per acre per year West of Rocky 

Mountains. Additional applications allowed, but do 

not exceed maximum rate. Do not apply within 155 

days of harvest for seed.

0.5 - 1.0

postemergence

2

Dill

N

H

Cl

Cl

O

N

H

O

CH3
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Table 3.3. Summary of Proposed Directions for Use of Linuron (Lorox® DF, EPA Reg. No. 61842-23).

Application, 

Type, and 

Equipment

App Rate

(lb ai/A)

Timing

Max No. 

App per 

Season

Max. 

Seasonal 

App Rate

(lb ai/A)

PHI

(days) Product Use Directions and Limitations

Broadcast

Ground, 

Chemigation

1.0

preemergence

1

2.0

East of 

Rocky Mtns

1.5

West of 

Rocky Mtns

21

Do not apply by air. Do not apply to sand or loamy

sand soil types to avoid crop injury. Do not use on 

soils with less than 1% organic matter to avoid crop 

injury. Do not exceed 4 lbs. LOROX® DF per acre 

per year East of Rocky Mountains. Do not exceed 3 

lbs. LOROX® DF per acre per year West of Rocky 

Mountains. Additional applications allowed, but do 

not exceed maximum rate.

0.5 - 1.0

postemergence

2

Parsley

Broadcast

Ground, 

Chemigation

0.5 - 1.5

preemergence

1 1.5

30

Do not apply by air. Apply after planting, but before 

the crop emerges. Do not exceed a total of 3 lbs. of 

LOROX® DF per acre per season. Use lower rates 

on coarse soils and higher rates on heavier soils. 0.5

postemergence

1 0.5

Parsley Grown for Seed (Oregon and Washington Only)

Broadcast

Ground, 

Chemigation

0.5 - 1.0

preemergence

2 2.0 NA

Do not apply by air. For best results apply 

preemergence to weeds or early postemergence 

while weeds are small. Wait at least 21 days 

between applications. Do not make more than two 

applications in the first growing season and do not 

make more than two applications in the second 

growing season.

Pea (Dry)

Broadcast

Ground, 

Chemigation

1.0

preemergence

1 1.0 NA

Do not apply by air. Do not apply to sand or loamy 

sand soil types. Do not use on soils with less than 

1% organic matter. Apply post planting but 

preemergence to the crop. Use lower rates on coarse 

soils and higher rates on heavier soils.

Horseradish

Broadcast

Ground, 

Chemigation

1.5

preemergence

1 1.5 NA

Do not apply by air. Apply after planting or during 

dormancy, but before the leaves emerge in spring. 

Use lower rates on lighter soils and higher rates on 

heavier soils.

3.4 Anticipated Exposure Pathways

Humans may be exposed to linuron in food and drinking water, since linuron may be applied as a 

spray over growing crops and these applications may result in linuron reaching surface and 

ground water. There are no registered residential uses of linuron, so exposure to residential 

handlers and those entering treated residential areas following application is not expected. In 

occupational settings, applicators may be exposed while handling linuron. There is also potential 

for post-application exposure for workers re-entering treated fields. Risk assessments have been 

completed for existing uses of linuron. This risk assessment considers all of the aforementioned 

exposure pathways based on the proposed new uses of linuron, but also considers existing uses 

of linuron, particularly in the dietary exposure assessment. 
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3.5 Consideration of Environmental Justice

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

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

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

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

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

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

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

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

Extensive data on food consumption patterns are compiled by the United States Department of 

Agriculture’s (USDA’s) National Health and Nutrition Examination Survey (NHANES), What 

We Eat in America (NHANES/WWEIA) 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 and ethnic group. 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 following application are evaluated. Further considerations 

are currently in development as OPP has committed resources and expertise to the development 

of specialized software and models that consider exposure to bystanders and farm workers as 

well as lifestyle and traditional dietary patterns among specific subgroups.

4.0 Hazard Characterization and Dose-Response Assessment

Since the last linuron risk assessment (D. Davis, D348519, 04/17/2008) an acute neurotoxicity

study and an immunotoxicity study have been submitted to the Agency. Additionally, the HED 

HASPOC waived the requirement for the subchronic neurotoxicity, subchronic dermal toxicity, 

and subchronic inhalation toxicity studies (TXR#0056667, TXR#0056666, and TXR#0056436). 

With the submission of the acute neurotoxicity study, the toxicity database of linuron has been 

reevaluated, and an acute dietary endpoint for the general U.S. population has been established.

4.1 Toxicology Studies Available for Analysis

The toxicological database for linuron is considered complete and the data requirements are 

satisfied. The toxicology database includes a 14-day inhalation study, 1-year and 2-year oral 

toxicity studies in dogs, chronic/carcinogenicity study in rats, a carcinogenicity study in mice, 

developmental toxicity studies in rats and rabbits, 2-generation and 3-generation reproduction 

studies in rats, metabolism studies in rats, a dermal penetration study in rats, an acute 

neurotoxicity study in rats, an immunotoxicity study in rats, a genotoxicity battery, and many 

published studies, which evaluate the androgenic effects and Leydig cell tumorigenesis produced 

by linuron (see Appendix A for literature references and the linuron toxicology profile). Waivers 

were granted for the required subchronic dermal and inhalation studies and the subchronic 

neurotoxicity study. 
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4.2 Absorption, Distribution, Metabolism, % Elimination (ADME) Data

With oral administration, linuron was extensively absorbed from the gastrointestinal (GI) tract,

metabolized, and eliminated. Total recovery was 96.1% of the administered dose in males and 

97.3% in females. In males and females, radioactivity remaining in the tissues and carcass 

represented <1% of the administered dose. The liver had the highest levels of radioactivity. The 

biological half-life (t1/2) of linuron differed between the low and high doses and between 

genders, ranging from 21 hours in low dose males to 56 hours in high dose females. The major 

route of elimination was via the urine (>80% of the radioactivity); fecal elimination accounted 

for approximately 15% of the administered dose. The major metabolites are hydroxy-norlinuron 

and norlinuron. The data also demonstrated that linuron exposure resulted in the induction of 

mixed-function oxidative enzymes. 

4.2.1 Dermal Absorption

A dermal absorption factor (normalized over 8-10 hours) of 16% was applied to the dermal 

exposure assessments. 

4.3 Toxicological Effects

With repeated dosing in test animals, linuron produces two primary effects: (1) changes in the 

hematopoetic system in rats, mice, and dogs and; (2) changes in the male reproductive system in 

developing rats. Lowest observed adverse effect levels (LOAELs) for hematological effects 

produced by linuron were substantially lower (40-fold lower) than LOAELs for reproductive 

effects. Dogs were shown to be most sensitive to the hematological effects, including hemolytic 

anemia characterized by slightly reduced hemoglobin, hematocrit, and erythrocyte counts 

accompanied by hemosiderin deposition in liver Kupffer cells. Secondary erythropogenic 

activity (erythroid hyperplasia of bone marrow) was also found. Systemic toxicity observed in 

mice included increased methemoglobin formation, vacuolation and hemosiderosis of the spleen, 

and decreased erythrocyte counts. In the chronic rat study, microscopic observations consistent 

with hemolysis (hemosiderin in Kupffer cells and increased hemosiderosis in bone marrow, 

spleen, and/or mesenteric lymph nodes) were found.

The rat developmental study showed increased post-implantation loss, fetal resorptions, 

decreased litter size, and decreased fetal body weight. In the rabbit developmental toxicity

study, an increased incidence of fetuses with skeletal skull variations was found. In the 

reproductive toxicity study, rats exposed to linuron during both development and adulthood had

gross lesions of the testes (including reduction in size); abnormally soft and small epididymides; 

deformities of the epididymides; decreased pup survival; decreased weanling body weights; 

decreased liver and kidney weights; and increased incidence of the liver atrophy in the offspring. 

The developmental effects on the reproductive system seen in the guideline studies are consistent 

with those reported in the published literature. The available data indicate that linuron inhibits

transcriptional activity of dihydrotestosterone (DHT), human androgen receptor (hAR) in vitro, 

and steroidogenic enzymes. Additional findings indicate linuron exposure decreases anogenital 

distance; may increase retention of areole/nipples in male rat offspring following in utero 
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exposure; increase luteinizing hormone (LH) levels in F0 and F1 male rats; reduces the size of 

androgen dependent tissues such as seminal vesicles, epididymis, and ventral prostate; and 

demonstrates a weak affinity for androgen receptors which may decrease fetal testosterone 

synthesis (Gray, et al., 1999; Hotchkiss, et al., 2004; Lambright, et al., 2000; McIntyre, et al, 

2000). It should be noted that most of the literature studies employed dose levels of 100 mg/kg 

or greater. At this time, linuron has not been demonstrated to be an estrogen receptor antagonist 

(Vinggaard, et al., 1999). It should be emphasized that the toxicity endpoints based on the 

hematological effects for chronic exposures were derived from the chronic (1-year) dog oral 

toxicity study. The point of departure (POD) for hematological effects was approximately 40-

fold lower than the LOAEL that caused the testicular effects seen in the rat reproduction toxicity

study. 

In rat and mouse carcinogenicity studies, linuron induced interstitial cell adenomas in the testes 

of rats and hepatocellular adenomas in mice. In a special study with aged rats, linuron induced 

hyperplasia and adenomas of the testes within 6 to 12 months. However, linuron was not 

mutagenic in bacteria or in cultured mammalian cells. There was also no indication of a 

clastogenic effect up to toxic doses in vivo. Linuron was classified as a Group C carcinogen by 

both the Cancer Assessment Review Committee (CARC), the Federal Insecticide, Fungicide, and 

Rodenticide Act (FIFRA) Science Advisory Panel (SAP), and the Hazard Identification 

Assessment Review Committee (HIARC Report, TXR#0050284, 11/20/2001). This is equivalent 

to the current classification of “Suggestive Evidence of Carcinogenic Potential”. No 

quantification of human cancer is recommended. 

The acute neurotoxicity study demonstrated that at 500 mg/kg, linuron produced many changes 

in the parameters of the field observation battery (FOB); these changes included rats holding 

their heads low, crusty deposits on the nose, impaired mobility, ataxia, low arousal, decreased 

rearing, no reaction to tail pinch or startle, decreased righting reflex, reduced or no hindlimb 

extensor strength, decreased grip strength in both hindlimbs and forelimbs, reduced rotarod 

performance, decreased hindlimb footsplay, and increased catalepsy. At 100 mg/kg, linuron 

produced decreases in motor activity and rearing. No effects were seen at 20 mg/kg (no 

observed adverse effect level; NOAEL). However, no compound-related changes in 

neurohistopathology were observed at any of the tested dose levels.

In addition, linuron did not show any immunotoxicity in the submitted immunotoxicity study up 

to the highest dose tested (1000 ppm or 92 mg/kg/day). 

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

HED has examined the currently available information on linuron and determined that the 

linuron database is adequate for assessing susceptibility of the young to linuron exposure. HED 

has determined that the linuron FQPA factor is reduced to 1X for the following reasons: 

4.4.1 Completeness of the Toxicology Database

Linuron toxicity database is robust and the study requirements are satisfied. The toxicology

database used to assess pre- and post-natal exposure to linuron is considered adequate. The 

following acceptable studies are available to support this determination: a rat developmental 
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toxicity study, a rabbit developmental toxicity study, a 3-generation rat reproductive toxicity

study, and a 2-generation rat reproductive toxicity study. In addition, the database includes an 

acute neurotoxicity study, and an immunotoxicity study. 

4.4.2 Evidence of Neurotoxicity

In an acute oral toxicity study, FOB findings of impaired mobility, alterations in gait, lack of 

coordination, lowered body temperature, no reaction to stimuli, low arousal, and decreases in 

motor activity were seen at the time of peak effect (7 hours post dosing) on study day 0. These 

observations were mostly seen in the 500 mg/kg group; and no pathological changes were found 

in nervous system tissues. A clear NOAEL (20 mg/kg/day) was established, and this NOAEL 

was approximately 2-26X greater than most of the PODs selected for risk assessment. The 

nervous system was not a target organ for linuron. Therefore, the concern for neurotoxicity is 

low. 

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

There is no qualitative/quantitative evidence of increased susceptibility of rabbit developmental 

study; developmental effects were seen at a dose higher than those causing maternal toxicity. In 

the rat developmental study, increases in post-implantation losses and increases in fetal

resorptions/litter were seen at a dose that caused decreases in maternal body weight and food 

consumption. Since increases in resorptions were marginal and there was no change in the 

number of live fetuses to corroborate the increases in post-implantation losses, these effects were 

not indicative of qualitative evidence of susceptibility (HIARC report, 11/20/2001).

There was no quantitative evidence of susceptibility either in the 2-generation or the 3-

generation reproduction studies. In the 2-generation study, reduced body weight gains of pups 

were seen at the same dose that caused decreases in parental body weights. In the 3-generation 

study, offspring effects (deceased pup survival and pup body weight) were seen a dose (44 

mg/kg/day) higher than the dose that caused decreases in body weight gain in the parental 

animals (9 mg/kg/day).

However, when the reproductive effects were examined, testicular atrophy was seen at the same 

dose (625 ppm, 45 mg/kg/day) in both studies. In both studies, while the F0 males were not 

affected, testicular lesions and reduced fertility were seen in the F1 males. This effect in the F1 

males is an indication of qualitative evidence of susceptibility. A clear NOAEL was established 

for the effects on the reproductive system. At this time, the PODs for risk assessment are 

protective of the effects seen on the male reproductive system. Therefore, a FQPA safety factor 

could be reduced to 1X.

4.4.4 Residual Uncertainty in the Exposure Database

There are no residual uncertainties in the linuron exposure database that would preclude granting 

the proposed uses of linuron. While some refinements were incorporated into the dietary

exposure calculations, EPA is confident that the risk from exposure to linuron in food and

drinking water will not be underestimated. The acute and chronic dietary (food) exposure 
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assessment utilized conservative upper-bound inputs including assuming tolerance-level residues 

for all existing and proposed commodities and used %CT estimates when available (Screening 

Level Usage Analysis (SLUA), 04/10/2013). Although the acute and chronic assessments 

included minor refinements, the use of field trial and %CT estimates ensures that actual 

exposures/risks from residues in food will not be underestimated. The drinking water assessment 

utilized water concentration values generated by models and associated modeling parameters 

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

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

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

women of child bearing age. 

4.5 Toxicity Endpoint and Point of Departure Selections

The previously selected toxicity endpoints have been re-evaluated in accordance with current 

policy. The details for toxicity endpoint selection are presented in the HIARC report (HIARC 

Report, TXR#0050284, 11/20/2001) and in the report: Summary of Toxicology Science Advisory 

Council Toxicology E-Review for Linuron (05/29/2013, internal memo). The toxicity endpoints 

and the PODs for risk assessment are presented below. It should be noted that since there were 

no guideline 28-day or 90-day oral toxicity studies conducted with linuron, the HIARC evaluated 

all the effects in the available database seen over approximately 30 days of treatment. The 

HIARC found that in the 2-generation rat reproduction study, body weight was significantly

decreased and considered adverse at 36 mg/kg/day (HIARC report, 11/20/2001); no effects were 

seen at doses less than 5.8 mg/kg/day (NOAEL). Therefore, the body weight decrease around 30 

days at 36 mg/kg/day could serve as the toxicity endpoint for short-term exposure. In addition at 

36 mg/kg/day, testicular effects were also found in F1 test animals at the end of the study. 

Therefore, 5.8 mg/kg/day was selected as the POD for short-term dermal and inhalation risk 

assessment (LOAEL = 36 mg/kg/day). 

Furthermore, the overall NOAEL/LOAEL for the 2-generation reproductive toxicity study as 

presented in Appendix A is different from that seen 30 days because the effect of body weight 

decrement was progressive with time; at the end of the study, this effect also occurred at the 

next lower dose level 5.8 mg/kg/day. Therefore, the overall maternal and offspring NOAEL and 

LOAEL were 0.74 mg/kg/day and 5.8 mg/kg/day, respectively (see Toxicity Profile in Appendix 

A).

Table 4.5. Summary of Toxicological Doses and Endpoints for Linuron for Use in Dietary and Occupational 

Human Health Risk Assessments.

Exposure/ 

Scenario

Point of 

Departure

Uncertainty/FQPA 

Safety Factors

RfD, PAD, 

Level of 

Concern for 

Risk 

Assessment

Study and Toxicological Effects

Acute Dietary 

(General 

Population, 

including 

Infants and 

Children)

NOAEL= 

20

mg/kg/day

UFA= 10x

UFH= 10x

FQPA SF= 1x

Acute RfD = 

0.2 mg/kg/day

aPAD = 0.2

mg/kg/day

Acute Neurotoxicity Study (Rat). LOAEL 

= 100 mg/kg based on decreases in rearing 

and in motor activity. 
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Table 4.5. Summary of Toxicological Doses and Endpoints for Linuron for Use in Dietary and Occupational 

Human Health Risk Assessments.

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 years of 

age)

NOAEL = 

12

mg/kg/day

UFA= 10x

UFH= 10x

FQPA SF= 1x

Acute RfD =

0.12 

mg/kg/day

Rat Developmental Toxicity. LOAEL = 

50 mg/kg/day based on increased postimplantation loss and fetal/litter 

resorptions.

Chronic 

Dietary (All 

Populations)

NOAEL=

0.77

mg/kg/day

UFA= 10x

UFH= 10x

FQPA SF= 1x

Chronic RfD 

= 0.0077

mg/kg/day

cPAD = 

0.0077

mg/kg/day

Chronic Oral Dog Study. LOAEL = 3.5 

mg/kg/day based on hematological effects 

(increased met- and sulf-hemoglobin 

levels). 

Dermal and 

Inhalation 

Short-Term1,2

(1-30 days)

NOAEL= 

5.8

mg/kg/day

UFA= 10x

UFH= 10x

FQPA SF= 1x

Occupational

LOC for 

MOE = 100

2-Generation Rat Reproduction Study. 

LOAEL = 36 mg/kg/day based on 

statistically and biologically significant 

decrease in premating body weights in F0 

and F1 animals. Histopathological 

changes in the testes were also seen at the 

end of the study in the F1 offspring.

Cancer (oral, 

dermal, 

inhalation)

Classification: Group C Carcinogen requiring no quantification of human cancer risk (HIARC 

Report, TXR# 0050284, 11/20/2001). Group C carcinogen classification is equivalent to the 

current classification of “Suggestive Evidence of Carcinogenic Potential”.

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

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

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

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

population (interspecies). RfD = reference dose. 

1 The dermal absorption factor of 16% (MRID No. 00163837) should be applied to extrapolate from the oral route to the dermal route.

2 Toxicity via the inhalation route is assumed to be equivalent to the oral route.

4.6 Cancer Classification

The linuron carcinogenicity data have been thoroughly reviewed by the Agency. There was a 

Special Review conducted by the Agency Carcinogen Assessment Group (CAG), and 

subsequently, the decision of the CAG and carcinogenicity studies were reviewed by the SAP. 

The CAG and SAP both classified linuron as a Group C carcinogen; the SAP recommended that 

no quantification of human cancer risk be conducted for linuron. Later, the CARC re-evaluated 

the carcinogenicity data for linuron and concluded that linuron is classified as a Group C 

carcinogen (a possible human carcinogen for which there is limited animal evidence) and no 

quantification of human cancer risk is required (HIARC Report, TXR#0050284, 11/20/2001). A 

Group C carcinogen classification is equivalent to the current classification of “Suggestive 

Evidence of Carcinogenic Potential”. 
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5.0 Dietary Exposure and Risk Assessment 

References:

- Linuron. Petition for the Establishment of Permanent Tolerances and Registration for Use on Coriander, Dill, 

Parsley, Pea (Dry), and Horseradish; and Submission of Residue Analytical Methods of Plants and Animal 

Matricies. Summary of Analytical Chemistry and Residue Data. N. Tsaur, DP#404359, DP#411652, 

08/14/2013.

- Linuron: Acute and Chronic Dietary (Food and Drinking Water) Exposure and Risk Assessment for the Section 

(3) Registration Action on Coriander, Dill, Horseradish, Parsley, Celeriac, Rhubarb, and Dry Pea. K. Rury, 

DP#411650, 09/04/2013.

5.1 Residues of Concern Summary and Rationale

The residue definitions for enforcement of tolerance and for risk assessment are identical, 

namely, linuron and metabolites convertible to 3,4-DCA.

The terminal residues of concern in plants and animals are linuron (parent) and metabolites 

convertible to 3,4-DCA including DCPMU, DCPU, desmethyl linuron, and hydroxy-norlinuron. 

3,4-DCA is not of regulatory concern in connection with the registered uses of linuron due to the 

very low levels at which the chemical is detected in plants and animals (<0.01ppm). Metabolites 

convertible to 3,4-DCA are not likely to be more toxic than the parent compound. Linuron can 

therefore, be regulated by using the enforcement analytical method in which known metabolites 

and unidentified polar components in plants and bound residues in animal tissues are hydrolyzed 

to 3,4-DCA. The total residue convertible to 3,4-DCA will be compared to the reference dose 

for parent linuron for purposes of dietary risk assessment. 

The linuron drinking water exposure assessment is based upon review of environmental fate 

studies for parent linuron, modeling and monitoring results for parent linuron, and modeling 

results for the degradates of linuron based upon parent linuron model input parameters. Parent 

linuron appears to be moderately persistent and relatively immobile. Water degradates identified 

in the linuron aerobic soil metabolism study are desmethyl linuron, DCPMU, and DCPU. The 

degradate 3,4-DCA was not included in the water assessment as it was not detected in the 

aerobic soil metabolism study (0.01 ppm detection limit). According to acceptable fate studies, 

3,4-DCA is formed under anaerobic aquatic conditions rarely found in the environment and is 

not relevant to drinking water assessment. The environmental fate assessment for linuron is 

incomplete and tentative because information on the persistence, mobility and dissipation 

pathways of several degradates of linuron is not available. However, none of the linuron water 

degradates are present at levels greater than 10% of the applied parent, and therefore are not 

considered major water metabolites. As shown in Table 5.1, the degradates are included by 

default (i.e. for risk assessment purposes, the residues included in the drinking water are linuron 

and metabolites convertible to 3,4-DCA as the validated analytical method determines linuron 

and metabolites convertible to 3,4-DCA).
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5.2 Food Residue Profile

No new metabolism data were submitted to support this registration request. The qualitative 

nature of the residue in plants and animals is adequately understood. The residue data on 

coriander, dill, parsley, pea (dry), and horseradish are adequate for tolerance assessment and for 

use in dietary risk assessment. Based on detectable residues found in forage/foliage of a few 

metabolism studies, linuron is assumed to have systemic activity in plants. Finite residues of 

linuron and/or its metabolites are anticipated on food and feed commodities, even from early 

season soil-directed applications. Transfer to livestock commodities has been demonstrated, 

although the residue is primarily metabolites and unidentified polar components. 

Crop Field Trials

All of the field trials were conducted according to the proposed label use directions in the 

appropriate representative geographical regions. Adjuvants were not used in any of the field 

trials. Residue decline studies were not conducted. The available residue data are acceptable and 

reflect the proposed use patterns provided in Section B. Furthermore, an acceptable method was 

used for residue quantitation and the data are supported by adequate storage stability data. The 

residue field trials are summarized in Table 5.2.

Table 5.2. Summary of Residues from Field Trials with Linuron.

Crop Matrix Analyteb Applic. Rate

(lb ai/acre)

PHI 

(days) n

Residuesa,b (ppm)

Min. Max. HAFT Mean SD

Coriander: Proposed Use = 2.0 lb ai/acre total application rate, 21-day PHI.

Fresh Leaves and Stems

Linuron 1.997 - 2.118

19-21 8 0.08 1.14 1.055 0.65 0.4

Dried Leaves and Stems 19 1 8.5 NA NA NA

Seed 155 2 <0.01 NA NA NA

Dill: Proposed Use = 2.0 lb ai/acre total application rate, 21-day PHI.

Fresh Leaves and Stems

Linuron 2.005 - 2.026

20 - 22 7 0.3 0.67 0.56 0.48 0.1

Dried Leaves and Stems 22 2 1.8 3.5 2.65 2.65 1.2

Seed 59 - 85 4 0.06 0.12 0.12 0.09 0.03

Oil 48 1 1.8 NA NA NA

Parsley: Proposed Use = 1.5 lb ai/acre total application rate, 30-day PHI.

Fresh Leaves and Stems Linuron 1.510 29 - 32 4 0.43 1.3 1.02 0.75 0.387

Dried Leaves and Stems 1.511 29 1 2.8 2.8 2.8 NA

Pea (Dry): Proposed Use = 1.0 lb ai/acre total application rate, unspecified PHI.

Pea (Dry) 0.972 - 1.015 65 - 92 12 <0.01 0.052 0.051 0.014 0.018

Horseradish: Proposed Use = 1.5 lb ai/acre total application rate, unspecified PHI.

Roots Linuron 1.43 – 1.55 77 - 100 <0.05 NA NA NA

aHAFT = highest average field trial. SD = Standard Deviation. For samples with no detectable residues (< 0.01 ppm) the LOQ value (0.01 ppm) 

was used to calculate the Mean and Standard Deviation.

bResidues were converted to and measured as 3,4-DCA. Values were converted to linuron equivalents.

Table 5.1. Summary of Metabolites and Degradates to be included in the Risk Assessment and Tolerance 

Expression.

Matrix Residues included in Risk Assessment Residues included in Tolerance 

Expression

Plants Primary Crop

linuron and

metabolites convertible to 3,4-DCA

linuron and metabolites convertible to 

3,4-DCA

Rotational Crop

Livestock Ruminant

Poultry

Drinking Water Not Applicable
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Meat Milk Poultry and Eggs

There are no feed items associated with this current petition. Cowpea commodities would affect 

the dietary burden of cattle but since they are a bean rather than a pea, they are not included in 

the petition for dry peas. Therefore, the previous livestock dietary intake calculations and 

resulting tolerance recommendations are not changed. However, since there are livestock feed 

items associated with field pea, the following restriction should be added to the label: “Do not 

apply to field pea used for livestock feed.”

Processing Data 

Data on dill oil and dried coriander, dill, and parsley indicate that linuron residues concentrate 

after processing. 

Storage Stability

Data showed that linuron residues were stable in all matrices under frozen storage for the 

duration of the storage period. The storage stability data are adequate to support the storage 

intervals and conditions for the residue samples of coriander, dill, parsley, pea (dry), and 

horseradish from the field trials and processing studies. 

5.3 Water Residue Profile

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

following memorandum: “Revised Linuron Drinking Water Assessment for an IR-4 New Use on 

Coriander, Dill, Celeriac, Horseradish, Parsley, Dry Peas, and Rhubarb” (H. Zhong, D405829, 

06/25/2013) and incorporated directly into this dietary assessment. Water residues were 

incorporated in the DEEM-FCID into the food categories “water, direct, all sources” and “water, 

indirect, all sources.” EFED assumed a total toxic residue approach. 

EDWCs in surface water and in ground water (Table 5.3) were generated for the proposed 

agricultural uses of linuron. The calculated estimated drinking water concentrations (EDWCs) 

from Tier-II Pesticide Root Zone Model/Exposure Analysis Modeling System (PRZM-EXAMS) 

and PRZM-Ground Water (PRZM-GW) supersede the previous upper bound EDWCs. 

The drinking water models and their descriptions are available at the EPA internet site: 

http://www.epa.gov/oppefed1/models/water/.
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Table 5.3. Summary of Estimated Surface Water and Groundwater Concentrations (EDWCs) for 

Linuron Used on Coriander, Dill, Celeriac, Horseradish, Parsley, Dry Peas, and Rhubarb.

Surface Water 

Conc., ppb a

Groundwater Conc., 

ppb b

Acute (non-cancer, peak exposure) 89.05

Chronic (non-cancer, post-breakthrough average) 48.69 48.8

Chronic (cancer, long-term mean) 30.81

a

Pesticide Root Zone Model (PRZM v3.12.2, May 12, 2005) and Exposure Analysis Modeling System (EXAMS 

v2.98.04.06, April 25, 2005), simulation models, were coupled with the input PE5.pl.shell. The model does incorporate a 

degradation component.

b

From the PRZM-GW model. 

Bolded values are used in the dietary exposure assessment.

5.4 Dietary Risk Assessment

5.4.1 Description of Residue Data Used in Dietary Assessment

HED used tolerance-level residues for the proposed and registered crops and maximum or 

average %CT for the registered crops when available; therefore, this assessment is considered 

conservative. Default processing factors were used for dried potato, corn syrup, and dried beef 

meat. Table 2.2.2 lists HED recommended tolerances for the proposed crops used in the dietary

assessment. 

5.4.2 Percent Crop Treated Used in Dietary Assessment

A SLUA entitled, “Usage Report Package in Support of a Tolerance Petition for the Herbicide 

Linuron, BEAN DP# 410336” (J. Alsadek, 04/10/2013) was provided by the Biological and 

Economic Analysis Division (BEAD). 

The acute dietary analysis incorporated 100%CT for all registered and proposed commodities.

The chronic dietary analysis incorporated average %CT data for asparagus (25%), carrots (85%), 

celery (25%), corn (1.0%), cotton (1.0%), potatoes (5.0%), sorghum (1.0%), soybeans (1.0%), 

sweet corn (1.0%), and wheat (1.0%); all other commodities were assumed to be 100%CT. 

5.4.3 Acute Dietary Risk Assessment

The acute dietary (food and drinking water) exposure assessments for linuron were considered 

slightly refined; the assessments incorporated recommended and/or established tolerance level 

residues, and used default processing factors. Maximum %CT estimates for registered crops 

were also incorporated into the assessment. The EDWC from EFED (89.05 ppb) was also 

included. Because different toxicological PODs were selected for females 13-49 years old and 

for the general U.S. population, two separate dietary exposure analyses were conducted. The 

results of the acute analyses indicate that the acute dietary (food and drinking water) exposure 

and risk estimates do not exceed HED’s LOC (i.e., <100% aPAD) for the general U.S. 

population, and all population subgroups, including females 13-49 years old. At the 95th

percentile of exposure, the resulting acute dietary (food and drinking water) risk estimates 
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utilized 4.3% of the aPAD for the general U.S. population and 10% for all infants, the most 

highly exposed population subgroup. At the 95th percentile of exposure, the resulting acute 

dietary (food and drinking water) risk estimate utilized 5.7% of the aPAD for females 13-49 

years old. 

5.4.4 Chronic Dietary Risk Assessment

The chronic dietary (food and drinking water) exposure assessment for linuron was also 

considered slightly refined; the assessment incorporated recommended and/or established 

tolerance-level residues and used default processing factors. Average %CT estimates provided 

by BEAD were incorporated into the assessment for the existing uses, along with the EDWC 

from EFED (48.8 ppb). The results of the chronic analysis indicate that chronic dietary (food 

and drinking water) exposure and risk does not exceed HED’s LOC (i.e., <100% cPAD) for the 

U.S. population and all population subgroups. The resulting chronic dietary (food and drinking 

water) risk estimates utilized 22% of the cPAD for the general U.S. population and utilized 60% 

of the cPAD for children 1-2 years old, the most highly exposed population subgroup. 

5.4.5 Cancer Dietary Risk Assessment

Linuron is classified as a “Group C Carcinogen” and quantification of human cancer risk is not 

required. A Group C carcinogen classification is equivalent to the current classification of 

“Suggestive Evidence of Carcinogenic Potential”.

5.4.6 Summary Table

Table 5.4.6. Summary of Dietary (Food and Drinking Water) Exposure and Risk Estimates

for Linuron.

Population Subgroup

Acute Dietary

(95

th Percentile) Chronic Dietary

Dietary 

Exposure 

(mg/kg/day)

% aPAD*

Dietary 

Exposure

(mg/kg/day)

% cPAD*

General U.S. Population 0.008606 4.3 0.001690 22

All Infants (< 1 year old) 0.020671 10 0.004298 56

Children 1-2 years old 0.016809 8.4 0.004586 60

Children 3-5 years old 0.013568 6.8 0.003114 40

Children 6-12 years old 0.008946 4.5 0.001981 26

Youth 13-19 years old 0.006172 3.1 0.001262 16

Adults 20-49 years old 0.006972 3.5 0.001466 19

Adults 50+ years old 0.006676 3.3 0.001463 19
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Table 5.4.6. Summary of Dietary (Food and Drinking Water) Exposure and Risk Estimates

for Linuron.

Population Subgroup

Acute Dietary

(95

th Percentile) Chronic Dietary

Dietary 

Exposure 

(mg/kg/day)

% aPAD*

Dietary 

Exposure

(mg/kg/day)

% cPAD*

Females 13-49 years old 0.006864 5.7 0.001443 19

*The values for the highest exposed population for each type of risk assessment are bolded.

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

There are no existing or proposed residential uses of linuron. Therefore, residential handler and 

post-application assessments are not required.

6.1 Residential Bystander Post-application Inhalation Exposure

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

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

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

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

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

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

December 2009, and received the SAP’s final report on March 2, 20101. The Agency is in the 

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

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

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

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

for linuron.

6.2 Spray Drift

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

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

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

airblast) employed for linuron. 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).

2

 The Agency is also taking means to qualitatively and 

qualitatively address spray drift as a potential source of exposure in risk assessments for 

pesticides through existing programs such as Ag Drift and chemical specific properties of 

 

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

2 Available: http://www.epa.gov/opp00001/factsheets/spraydrift.htm 
Linuron Human Health Risk Assessment DP No. D405828

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

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

concurrently. 

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. Because linuron is not registered for use in residential areas, the dietary

exposure assessments are equivalent to the aggregate exposure assessments. Refer to Section 5.0 

for the dietary exposure estimates. 

8.0 Cumulative Exposure/Risk Characterization

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

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

to linuron and any other substances. For the purposes of this tolerance action, therefore, EPA has 

not assumed that linuron has a common mechanism of toxicity with other substances. For 

information regarding EPA’s efforts to determine which chemicals have a common mechanism 

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

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

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

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

9.0 Occupational Exposure/Risk Characterization

References:

- Linuron. Occupational and Residential Exposure Assessment for Proposed Use on Coriander, Dill, Horseradish, 

Parsley, Celeriac, Rhubarb, and Pea (Dry). K. Rury, DP#405825, 09/04/2013.

9.1 Short-Term Handler Risk

HED has evaluated occupational exposure from the proposed uses of linuron. Application 

methods, maximum application rates, and use sites are summarized in Table 3.3. Aerial 

application is prohibited on the Lorox DF®label; however, linuron may be applied with 

chemigation, and ground equipment. Because linuron is an herbicide, and the proposed label 

specifies broadcast, banded, and over-the-row applications for the proposed crops, the use of 

handheld equipment is not expected and exposure from mixing/loading/applying using handheld 

equipment was not assessed. 

Based on the proposed and registered uses of linuron, only short-term exposures are expected for 

the following reasons: (1) only up to 2 applications per season are allowed for the proposed uses 

of linuron; and (2) as an early season herbicide, applications occur for only a short period in the 

growing season, limiting the potential for continuous occupational exposure over a duration 
Linuron Human Health Risk Assessment DP No. D405828

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longer than 30 days. The proposed label requires occupational mixer/loaders to wear long pants, 

long sleeved shirts, coveralls, chemical resistant gloves, shoes, socks, and a chemical resistant 

apron. Occupational applicators must wear coveralls, chemical resistant gloves, and chemical 

resistant footwear. 

HED’s LOC for the MOE is defined by the uncertainty factors that are applied to the assessment. 

HED applies a 10X factor to account for variability among species and a 10X factor to account 

for variability within species. The total uncertainty factor that has been applied to the handler 

assessment of linuron is 100X for occupational exposure. Occupational exposure and risk 

resulting in MOEs greater than or equal to 100 will not be of concern to HED. Dermal and 

inhalation risk estimates were combined in this assessment, since the toxicological effects for 

these exposure routes were similar. 

A summary of the short-term inhalation risks for occupational handlers applying linuron is 

provided in Tables 9.1.1, 9.1.2, and 9.1.3. There are some risk estimates of concern for the 

proposed uses of linuron at baseline (no PPE), and with the label-specified PPE (coveralls/double 

layer and gloves).

At baseline, all short-term occupational handler combined (dermal + inhalation) MOEs ranged 

from 19 to 900. With coveralls and gloves, all short-term occupational handler combined 

(dermal + inhalation) MOEs ranged from 56 to 4,900. Mixing/loading for chemigation 

application to parsley, horseradish, celeriac, rhubarb, dry pea, coriander, and dill required 

engineering control mitigation to be not of concern to HED (MOEs >100). With engineering 

controls for the specified crops, the occupational handler MOEs ranged from 490 to 740.
Linuron Human Health Risk Assessment DP No. D405828

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Table 9.1.1. Occupational Handler Short-Term Exposure and Risk Estimates for Linuron with Baseline Attire. 

Exposure Scenario Crop or 

Target

Dermal Unit 

Exposure (μg/lb 

ai)1

Inhalation Unit 

Exposure (μg/lb 

ai)1

Maximum 

Application 

Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Dermal Inhalation Total

Baseline Baseline Dose 

(mg/kg/day)4 MOE5 Dose (mg/kg/day)6 MOE7 MOE8

Mixer/Loader

Mixing/Loading for 

Chemigation Application

Parsley, 

Horseradish, 

Celeriac, 

Rhubarb

227 8.96

1.5 lb ai/A

350 Acres

0.238 24 0.0588 99 19

Dry Pea, 

Coriander, Dill 1.0 lb ai/A 0.159 36 0.0393 150 29

Parsley Grown 

for Seed 0.5 lb ai/A 0.0794 73 0.0196 300 59

Mixing/Loading for 

Groundboom Application

Dry Pea, Dill

227 8.96

1.0 lb ai/A 200 Acres 0.0908 64 0.0224 260 51

Parsley, 

Horseradish, 

Celeriac, 

Rhubarb

1.5 lb ai/A

80 Acres

0.0544 110 0.0135 430 88

Coriander 1.0 lb ai/A 0.0364 160 0.00896 650 130

Parsley Grown 

for Seed 0.5 lb ai/A 0.0182 320 0.00448 1,300 260

Applicator

Applying with 

Groundboom

Dry Pea, 

Coriander, Dill

78.6 0.34

1.0 lb ai/A 200 Acres 0.0314 180 0.00085 6,800 180

Parsley, 

Horseradish, 

Celeriac, 

Rhubarb

1.5 lb ai/A 80 Acres 0.0189 310 0.00051 11,000 300

Coriander 1.0 lb ai/A 0.0126 460 0.00034 17,000 450
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Table 9.1.1. Occupational Handler Short-Term Exposure and Risk Estimates for Linuron with Baseline Attire. 

Exposure Scenario Crop or 

Target

Dermal Unit 

Exposure (μg/lb 

ai)1

Inhalation Unit 

Exposure (μg/lb 

ai)1

Maximum 

Application 

Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Dermal Inhalation Total

Baseline Baseline Dose 

(mg/kg/day)4 MOE5 Dose (mg/kg/day)6 MOE7 MOE8

Parsley Grown 

for Seed 0.5 lb ai/A 0.00628 920 0.00017 34,000 900

1 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (May 2013); Level of mitigation: Baseline.

2 Based on registered or proposed label (Reg. No. 61842-23).

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 (16%) ÷ BW (80 

kg).

5 Dermal MOE = Dermal NOAEL (5.8 mg/kg/day) ÷ Dermal Dose (mg/kg/day).

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

7 Inhalation MOE = Inhalation NOAEL (5.8 mg/kg/day) ÷ Inhalation Dose (mg/kg/day).

8 Total MOE = NOAEL (5.8 mg/kg/day) ÷ Dermal Dose + Inhalation Dose.

Table 9.1.2. Occupational Handler Short-Term Exposure and Risk Estimates for Linuron with PPE Required on the Label (Chemical Resistant Gloves, Coveralls). 

Exposure Scenario Crop or 

Target

Dermal Unit 

Exposure 

(μg/lb ai)1

Inhalation Unit 

Exposure 

(μg/lb ai)1

Maximum 

Application 

Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Dermal Inhalation Total

Gloves, Coveralls Baseline Dose 

(mg/kg/day)4 MOE5 Dose (mg/kg/day)6 MOE7 MOE8

Mixer/Loader

Mixing/Loading for 

Chemigation Application

Parsley, 

Horseradish, 

Celeriac, 

Rhubarb

41.2 8.96

1.5 lb ai/A

350 Acres

0.0432 130 0.0588 99 56

Dry Pea, 

Coriander, Dill 1.0 lb ai/A 0.0288 200 0.0393 150 86

Parsley Grown 

for Seed 0.5 lb ai/A 0.0144 400 0.0196 300 170

Mixing/Loading for 

Groundboom Application

Dry Pea, Dill

41.2 8.96

1.0 lb ai/A 200 Acres 0.0165 350 0.0224 260 150

Parsley, 

Horseradish, 

Celeriac, 

Rhubarb

1.5 lb ai/A

80 Acres

0.00988 590 0.0135 430 250

Coriander 1.0 lb ai/A 0.0066 880 0.00896 650 370

Parsley Grown 0.5 lb ai/A 0.0033 1,800 0.00448 1,300 750
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Table 9.1.2. Occupational Handler Short-Term Exposure and Risk Estimates for Linuron with PPE Required on the Label (Chemical Resistant Gloves, Coveralls). 

Exposure Scenario Crop or 

Target

Dermal Unit 

Exposure 

(μg/lb ai)1

Inhalation Unit 

Exposure 

(μg/lb ai)1

Maximum 

Application 

Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Dermal Inhalation Total

Gloves, Coveralls Baseline Dose 

(mg/kg/day)4 MOE5 Dose (mg/kg/day)6 MOE7 MOE8

for Seed

Applicator

Applying with 

Groundboom

Dry Pea, Dill

78.6 0.34

1.0 lb ai/A 200 Acres 0.00504 1,200 0.000425 6,800 1,000

Parsley, 

Horseradish, 

Celeriac, 

Rhubarb

1.5 lb ai/A

80 Acres

0.00302 1,900 0.00051 11,000 1,600

Coriander 1.0 lb ai/A 0.00202 2,900 0.00034 17,000 2,500

Parsley Grown 

for Seed 0.5 lb ai/A 0.00101 5,700 0.00448 1,300 4,900

1 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (May 2013); Level of mitigation: Double Layer and Chemical Resistant Gloves.

2 Based on registered or proposed label (Reg. No. 61842-23).

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 (16%) ÷ BW (80 

kg).

5 Dermal MOE = Dermal NOAEL (5.8 mg/kg/day) ÷ Dermal Dose (mg/kg/day).

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

7 Inhalation MOE = Inhalation NOAEL (5.8 mg/kg/day) ÷ Inhalation Dose (mg/kg/day).

8 Total MOE = NOAEL (5.8 mg/kg/day) ÷ Dermal Dose + Inhalation Dose.

Table 9.1.3. Occupational Handler Short-Term Exposure and Risk Estimates for Linuron with Engineering Controls. 

Exposure Scenario Crop or 

Target

Dermal Unit 

Exposure (μg/lb 

ai)1

Inhalation Unit 

Exposure (μg/lb 

ai)1

Maximum 

Application 

Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Dermal Inhalation Total

Engineering 

Controls

Engineering 

Controls

Dose 

(mg/kg/day)4 MOE5 Dose (mg/kg/day)6 MOE7 MOE8

Mixer/Loader

Mixing/Loading for 

Chemigation Application

Parsley, 

Horseradish, 

Celeriac, 

Rhubarb

9.8 0.24 1.5 lb ai/A

350 Acres

0.0103 560 0.00158 3,700 490

Dry Pea, 

Coriander, Dill 1.0 lb ai/A 0.00686 850 0.00105 5,500 740
Linuron Human Health Risk Assessment DP No. D405828

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1 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (May 2013); Level of mitigation: Engineering Controls.

2 Based on registered or proposed label (Reg. No. 61842-23).

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 (16%) ÷ BW (80 

kg).

5 Dermal MOE = Dermal NOAEL (5.8 mg/kg/day) ÷ Dermal Dose (mg/kg/day).

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

7 Inhalation MOE = Inhalation NOAEL (5.8 mg/kg/day) ÷ Inhalation Dose (mg/kg/day).

8 Total MOE = NOAEL (5.8 mg/kg/day) ÷ Dermal Dose + Inhalation Dose.
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9.2 Short-Term Post-Application Risk

9.2.1 Dermal Post-Application Risk

Only short-term post-application exposure is expected for linuron based on the proposed use 

pattern, including that linuron is primarily applied in the early stages of the crop growth cycle 

and only once or twice per season. Because linuron is primarily applied in the early stages of the 

crop season, only post-application exposure from application to plants with minimum foliage 

was assessed. Chemical-specific DFR data have not been submitted for linuron. Therefore, this 

assessment uses HED’s default assumption that 25% of the application is available for transfer 

on day 0 following the application and the residues dissipate at a rate of 10% each following day.

The occupational short-term dermal post-application risk estimate MOEs ranged from 45 to 

3,700 on the day of application (Table 9.2.1); therefore, hand set irrigation to parsley, dill, 

coriander, and celeriac was of concern on day 0. The Lorox DF®label recommends that 

chemigation or rainfall occur within two weeks (14 days) after linuron application. However, in 

the Columbia River Basin, Lorox® DF is used only where the crop is sprinkler irrigated; 

increasing the likelihood for exposure via hand-set irrigation. In order for MOEs to be greater 

than the LOC at the maximum single application rate, hand-set irrigation should occur 4 days 

after application for parsley, dill, coriander and 8 days after application for celeriac. 

Table 9.2.1. Occupational Post-application Short-Term Dermal Exposure and Risk Estimates for Linuron.

Crop/Site Activities Transfer Coefficient 

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

Days Needed Following 

Application to Reach 

MOE > 100

Parsley, Dill, 

Coriander 

(1.0 lb ai/A)

Hand-Set 

Irrigation 1900

2.80

0.085 68 4

Transplanting 230 0.010 560

N/A

Scouting 210 0.0094 620

Thinning, Hand 

Weeding 70 0.0031 1,800

Parsley for Seed 

(0.5 lb ai/A)

Hand-Set 

Irrigation 1900

1.40

0.043 140

Transplanting 230 0.0052 1,100

Scouting 210 0.0047 1,200

Thinning, Hand 

Weeding 70 0.0016 3,700

Celeriac (1.5 lb 

ai/A)

Hand-Set 

Irrigation 1900

4.21

0.128 45 8

Scouting 210 0.014 410

Thinning, Hand N/A

Weeding 70 0.0047 1,200

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

2 Daily Dermal Dose = [DFR (μg/cm2) × Transfer Coefficient × 0.001 mg/μg × 8 hrs/day × dermal absorption (16%)]  BW (80 kg).

3 MOE = POD (5.8 mg/kg/day) / Daily Dermal Dose. Daily Dermal Dose = [DFR (μg/cm2) × TC × 0.001 mg/μg × 8 hrs/day × dermal 

absorption factor (16%)]  BW (80 kg).
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9.2.2 Inhalation Post-Application Risk

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

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

inhalation toxicity (Toxicity Category III and IV). However, there are multiple potential sources 

of post-application inhalation exposure to individuals performing post-application activities in 

previously treated fields. These potential sources include volatilization of pesticides and 

resuspension of dusts and/or particulates that contain pesticides. The Agency sought expert 

advice and input on issues related to volatilization of pesticides from its Federal Insecticide, 

Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and 

received the SAP’s final report on March 2, 20103. The Agency is in the process of evaluating 

the SAP report as well as available post-application inhalation exposure data generated by the 

ARTF and may, as appropriate, develop policies and procedures, to identify the need for and, 

subsequently, the way to incorporate occupational post-application inhalation exposure into the 

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

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

for linuron.

Although a quantitative occupational post-application inhalation exposure assessment was not 

performed, an inhalation exposure assessment was performed for occupational/commercial 

handlers. Handler exposure resulting from application of pesticides outdoors is likely to result in 

higher exposure than post-application exposure. Therefore, it is expected that these handler 

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

inhalation exposure scenarios.

10.0 References

D. Davis, D348519, 04/17/2008. Linuron: Human Health Risk Assessment to Support a Section 

18 Emergency Exemption for Use on Lentils in Washington and Idaho.

H. Zhong, D405829, 06/25/2013. Second Revision of Linuron Drinking Water Assessment for 

IR-4 New Use on Coriander, Dill, Celeriac, Horseradish, Parsley, Dry Peas, and Rhubarb. 

Revisions on 6/19/2013, and 4/30/2013.

J. Alsadek, D410336, 04/10/2013. Screening Level Usage Report In Support of a Tolerance 

Petition for the Herbicide Linuron.

J. Van Alstine, TXR#0056436, 10/26/2012. Linuron: Summary of Hazard and Science Policy

Council (HASPOC) Meeting of August 9, 2012: Recommendations on the Requirement of a 28-

Day Inhalation Study, 21-Day Dermal Toxicity Study, and a Subchronic Neurotoxicity Study.

J. Van Alstine, TXR#0056667, 06/12/2013. Linuron: Revision to Summary of Hazard and 

Science Policy Council (HASPOC) Meeting of August 9, 2013: Recommendation on the 

 

3 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html
Linuron Human Health Risk Assessment DP No. D405828

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Requirement of a 28-Day Inhalation Study, 21-Day Dermal Toxicity Study, and a Subchronic 

Neurotoxicity Study. 

J. Van Alstine, TXR#0056666, 06/12/2013. Linuron: Summary of Hazard and Science Policy

Council (HASPOC) E-Review on the requirement of a subchronic neurotoxicity study.

K. Rury, D375451, 04/01/2010. Linuron: Human Health Assessment Scoping Document in 

Support of Registration Review. Addendums: D378731, D380352.

K. Rury, D405825, 09/04/2013. Linuron: Occupational and Residential Exposure Assessment 

for the Proposed Use on Coriander, Dill, Horseradish, Parsley, Celeriac, Rhubarb, and Pea (Dry). 

K. Rury, D411650, 09/04/2013. Linuron: Acute and Chronic Dietary (Food and Drinking 

Water) Exposure and Risk Assessment for the Section (3) Registration Action on Coriander, 

Dill, Horseradish, Parsley, Celeriac, Rhubarb, and Dry Pea. 

N. Tsaur, D404359 and D411652, 08/14/2013. Linuron. Petition for the Establishment of 

Permanent Tolerances and Registration for Use on Coriander, Dill, Parsley, Pea (Dry), and 

Horseradish; and Submission of Residue Analytical Methods of Plants and Animal Matrices. 

Summary of Analytical Chemistry and Residue Data. 
Linuron Human Health Risk Assessment DP No. D405828

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Appendix A. References for Published Toxicity Studies and Toxicology Profile 

References for Published Studies

Gray, L; Wolf, C; Lambright, C; Mann, P; Price, M; Cooper, R; Ostby, J. 1999. Administration 

of potentially antiandrogenic pesticides (procymidone, linuron, iprodione, chlozolinate, 

p,p'-DDE, and ketoconazole) and toxic substances (dibutyl- and diethylhexyl phthalate, PCB 

169, and ethane dimethane sulphonate) during sexual differentiation produces diverse profiles of 

reproductive malformations in the male rat. Toxicol Ind Health, 15 (1-2):94-118.

Hotchkiss, A; Parks-Saldutti, L; Ostby, J; Lambright, C; Furr, J; Vandenbergh, J; & Gray, L. 

2004. A mixture of the “antiandrogens” linuron and butyl benzyl phthalate alters sexual 

differentiation of the male rats in a cumulative fashion. Biol. Of Reprod., 71:1852-1861. 

Lambright, C; Ostby, J; Bobseine, K; Wilson, V; Hotchkiss, A; Mann, PC; Gray, L. 2000. 

Cellular and molecular mechanisms of action of linuron: an antiandrogenic herbicide that 

produces reproductive malformations in male rats. Toxicol Sci. 56(2):389-99.

McIntyre, B; Barlow, N; Wallace, D; Maness, S; Gaido, K; Foster, P. 2000. Effects of in utero 

exposure to linuron on androgen-dependent reproductive development in the male 

Crl:CD(SD)BR rat. Toxicol Appl Pharmacol. 167(2):87-9.

Vinggaard, A; Hnida, C; Breinholt, V; Larsen, J. 2000. Screening of Selected Pesticidesfor 

Inhibition of CYP19 Aromatase Activity In vitro. Toxicol in Vitro. 14:227-234.

Vinggaard, A., Breinholt, V., and Larsen, J. 1999. Screening of selected pesticides for oestrogen 

receptor activation in vitro. Food Addit Contam. 16(12):533-542.

Wolf, C; Lambright, C; Mann, P; Price, M; Cooper, R; Ostby, J; Gray, D. 1999. Administration 

of potentially antiandrogenic pesticides (procymidone, linuron, iprodione, chlozolinate, p,p’-

DDE, and ketoconazole) and toxic substances (dibutylhexyl phthalate, PCB 169, and ethane 

dimethane sulphonate) during sexual differentiation produces diverse profiles or reproductive 

malformation in the male rats. Toxicol. Ind. Health 15:94-118.

Toxicological Profile for Linuron

Acute Toxicity for Linuron

Guideline No. Study Type MRID Results Tox. Category

870.1100 Acute Oral (Rat) 00027625 LD50 = 2600 mg/kg III

870.1200 Acute Dermal (Rabbit) 00027625 LD50> 2000 mg/kg III

870.1300 Acute Inhalation (Rat) 00053769 LC50 > 218 mg/L IV

870.2400 Primary Eye Irritation 42849001 Slight conjunctival redness at 24 

hrs; clear at 72 hrs

III

870.2500 Primary Skin Irritation 42849002 Not an irritant IV

870.2600 Dermal Sensitization 00146868 Not a sensitizer N/A
Linuron Human Health Risk Assessment DP No. D405828

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Repeated Dosing and Other Studies on Linuron

Guideline 

No. Study Type MRID No. (Year)/ Classification/Doses Results

Subchronic toxicity studies

870.3100 90-day oral- rat Requirement fulfilled by Chronic rat study

870.3150 90-Day oral toxicity-dog Requirement fulfilled by Chronic dog study- N/A

870.3200 21/28-Day dermal 

toxicity-rabbit

Waived (HASPOC, 10/26/20012; TXR: 0056436)

870.3250 90-Day dermal toxicity Waived (HASPOC, 10/26/20012; TXR: 0056436)

870.3465 90-Day inhalation toxicity Waived (HASPOC, 10/26/20012; TXR: 0056436)

Chronic toxicity studies

1-Year Feeding Study -

Dog

40952601 (1988)

Acceptable/Guideline

0, 10, 25, 125, 625 ppm

(M: 0, 0.29, 0.79, 4.17, 18.6 

mg/kg/day;

F: 0, 0.30, 0.77, 3.49, 16.1 

mg/kg/day)

NOAEL= 0.77 mg/kg/day

LOAEL = 3.49 mg/kg/day, based on 

hematological effects in males and females 

(increased methemoglobin and 

sulfhemoglobin levels)

2-Year Feeding Study -

Dog

00018374 (1963)

Unacceptable/Guideline

0, 25, 125, 625 ppm

(0, 0.6, 3.1, 16 mg/kg/day)

(1 ppm=0.025 mg/kg/day)

NOAEL= 3.1 mg/kg/day

LOAEL = 16 mg/kg/day, based on mild 

hemolytic anemia, slightly deceased 

hemoglobin, hematocrit, and RBC counts

870.4200 Oncogenicity Study -

Mouse

0124195 (1981)

Acceptable/Guideline

0, 50, 150, and 1500 ppm 

(M:0, 8, 23, and 261 mg/kg/day;

F: 0, 12, 35, and 455 mg/kg/day)

NOAEL= 23 mg/kg/day

LOAEL = 261 mg/kg/day, based on 

microscopic liver changes, 

methemoglobinemia, and deceased body 

weight gain throughout the study

Histopathology: hepatocytomegaly, 

hepatocellular cytoplasmic alterations, 

vacuolation, and necrosis in liver, slightly 

increased incidence of hemosiderosis in 

spleens of both sexes; Significant increase in 

hepatocellular adenomas in females

870.4100

870.4200

Combined Chronic 

Toxicity/ Carcinogenicity 

Study - Rat

0029680, 00029679 (1980)

00167411 (1986)

Acceptable/Guideline

0, 50, 125, 625 ppm

(M: 0,2.09, 5.11, 27.1 

mg/kg/day; 

F: 0, 3.13, 7.75, 48.3 mg/kg/day) 

NOAEL=2.09 mg/kg/day

LOAEL = 5.11 mg/kg/day, based on 

hematological effects, decreased body weight 

gains in both sexes, microscopic observations 

consistent with hemolysis (hemosiderin in 

Kupffer cells and increased hemosiderosis in 

bone marrow, spleen, and/or mesenteric 

lymph nodes)

Histopathology: Significant (p = 0.004) 

increase (27%, 5.7% control) in benign 

interstitial cell adenomas in testes incidences.

Developmental and reproductive toxicity studies

870.3700 Developmental Toxicity 

Study - Rat

00018167 (1979)

Acceptable/Guideline

0, 50, 125, 625 ppm

(0, 5.0, 12, 50 mg/kg/day)

Maternal Systemic

NOAEL= 12 mg/kg/day

LOAEL = 50 mg/kg/day, based on 

decreased maternal body weight (9%) and 

food consumption (7-8%).

Developmental

NOAEL= 12 mg/kg/day

LOAEL = 50 mg/kg/day, based on increased 

post-implantation loss and litters with early 

resorptions.

Developmental Toxicity -

Rabbit

00153867 (1985), 

40437201(1985)

Maternal Systemic

NOAEL= 5 mg/kg/day

LOAEL = 25 mg/kg/day, based on 
Linuron Human Health Risk Assessment DP No. D405828

Page 35 of 41

Guideline 

No. Study Type MRID No. (Year)/ Classification/Doses Results

Acceptable/Guideline

0, 5, 25, 100 mg/kg/day

decreased maternal body weight gain.

Developmental

NOAEL = 25 mg/kg/day

LOAEL = 100 mg/kg/day, based 

on alterations of the bones and skull 

(irregularly shaped fontanelle, hole in 

parietals, parietals contain intraparietals, and 

unossified).

870.3800 3-Generation

Reproduction - Rat

00146071 (1984)

00155168 (1985)

Acceptable/Guideline

0, 25, 125, 625 ppm

(M: 0, 2, 10-11, 48-50 mg/kg/day

F: 0, 2, 9, 44-50 mg/kg/day)

Parental

NOAEL= 2 mg/kg/day

LOAEL = 9 mg/kg/day, based on 

decreased body weight gains in males and 

females and anemia in females.

Reproductive

NOAEL = 10 mg/kg/day

LOAEL = 44 mg/kg/day based on 

reduced fertility, decreased pup survival, and 

lower pup body weights.

Offspring

NOAEL = 9 mg/kg/day 

LOAEL = 44 mg/kg/day, based on 

decreased pup survival, and lower pup body 

weights. 

2-Generation 

Reproduction - Rat

41463401 (1990)

41864701 (1991) 

Acceptable/Guideline

0, 12.5, 100, 625 ppm

(M: 0, 0.74, 5.8, 36 mg/kg/day

F: 0, 0.92, 7.3, 45 mg/kg/day) 

Parental NOAEL= 0.74 mg/kg/day; 

Parental LOAEL = 5.8 mg/kg/day, based on 

decreased body weight gains in males and 

females in both generations

Reproductive

NOAEL = 36 mg/kg/day

LOAEL = not established

Offspring

NOAEL= 0.74 mg/kg/day

LOAEL = 5.8 mg/kg/day, based on 

decreased pup body weights of F1 generation 

subsequent to 30days of treatment.

Metabolism and dermal absorption studies

870.7485 Metabolism Study - Rat 00146489 (1985), 40142401 

(1985)

41960001 (1991

42006801 (1991)

Linuron (single doses at 24 mg/kg and 400 

mg/kg) was administered by gavage to male 

and female rats. The biological half-lives 

ranged from 21 hr in the low dose males to 

56 hr in the high dose females. Total 

recovery of radioactivity was 96% in males 

and 97% in females, the majority of the 

administered C- linuron was eliminated in the 

urine (>80%) and, to a lesser extent, in the 

feces (~15%). Tissue and organ residues 

were very low (<l%) at both dose levels, and 

there was no indication of accumulation or 

retention of linuron or its metabolites. The 

major metabolites identified in the urine were 

hydroxy-norlinuron, desmethoxy linuron and 

norlinuron, and in feces, hydroxy-norlinuron, 

and norlinuron. Neither hydroxy-3,4-

dichloroanaline nor 3,4- dichloroanaline were 

present in any of the samples. Exposure to 

linuron appeared to induce mixed-function 

oxidative enzymes.

870.7600 Dermal Penetration - Rat 00163837 (1984) 

Acceptable/Guideline

Dermal absorption factor = 16% over 8 to 10 

hr (2%/hr).
Linuron Human Health Risk Assessment DP No. D405828

Page 36 of 41

Guideline 

No. Study Type MRID No. (Year)/ Classification/Doses Results

14C (2.35 Ci/mg)

0.12, 1.00, or 7.4 mg/2 in2 2.82, 

23.5, or 17.4 Ci

Dermal penetration studies 

(triple pack: in-vivo and 

in-vitro dermal penetration 

studies with rat and human 

skin)

Afalon SC Formulation 

48747806 (in-vivo rat) (2013)

48747807 (in-vitro rat & human 

skin) (2013)

48747807 (in-vitro rat & human 

skin) (2013)

In-vivo study was unacceptable/nonguideline.

The in-vivo study was unacceptable due to 

several deficiencies including exposure 

intervals, the recovery was too low for the 

low dose exposure (which was more relevant 

for establishing dermal absorption), the 

appropriate dermal absorption value was 

derived from only one animal, and 

insufficient reported data. 

Genotoxicity battery

870.5100 870.5100-Bacterial 

reverse gene mutation 

assay

MRID 00131738

Acceptable/Guideline

.5, 0.75, 1.0, 2.5, and 5.0 

g/plate(S9-mix)

1, 5, 10, 50, and 100 g/plate +S9 mix.

In a reverse gene mutation assay in bacteri, S. 

typhimurium strains TA98, TA100, TA1535, 

and TA1537 were exposed to Linuron (95-

97%, lot number not given) in 

dimethylsulfoxide at concentrations of 0 

There was no evidence of induced mutant 

colonies over background with or without S9 

activation. 

870.5300 CHO/HGPRT cell forward 

gene mutation assay

MRID 00137152

Acceptable/Guideline

0.05, 0.25, 0.35, 0.40, 0.45, and 

0.50 mM (S9- mix)

0.25, 0.50, 0.75, 0.90, and 1.0 

mM (+S9-mix)

In a mammalian cell gene mutation assay in 

vitro, triplicate (in the absence of activation) 

or duplicate (in the presence of activation) 

cultures of Chinese hamster ovary (CHO) 

CHO-K1-BH4 cells were exposed to Linuron 

(Lot No. 1N2-326-141, 94.5% a.i.) in F12 

medium. The S9-fraction was obtained from 

Aroclor 1254-induced 8 to 9 week-old male 

Charles River CD rats. Linuron was tested 

up to concentrations limited by cytotoxicity. 

Cytotoxicity was observed at 0.45 and 0.5 

mM under nonactivated conditions and at 

0.75 mM and above with 0.5 mg S9 

protein/mL and at 1.0mM and above with 1.0 

mg S9 protein/mL. (Percentage cell survival 

were not provided in the DER). There was 

no increase in mutant frequency in cells 

treated with linuron in either the presence or 

absence of metabolic activation. The positive 

(ethyl methane sulfonate (EMS) without S9-

mix and dimethylbenzanthracene with S9-

mix) and solvent (DMSO) controls responded 

appropriately. No evidence of an increased 

mutant frequency was observed in the 

presence or absence of metabolic activation.

870.5385

870.5395

In vivo bone marrow 

chromosomal aberration 

assay

MRID 00137153

Acceptable/Guideline

0, 100, 300, or 1000 mg/kg. 

In a mammalian cell cytogenetics 

chromosomal aberration assay in bone 

marrow cells of Sprague-Dawley rats, 5 rats 

per sex per harvest time were administered 

Linuron (94.5%, lot number not given) by 

single gavage at doses. Bone marrow cells 

were harvested 6-, 12-, 24-, or 48-hours after 

test compound administration and 48 hours 

after the positive control dose. The vehicle 

was corn oil (20 mL/kg) and the positive 

control was a single 40 mg/kg dose of 

cyclophosphamide.
Linuron Human Health Risk Assessment DP No. D405828

Page 37 of 41

Guideline 

No. Study Type MRID No. (Year)/ Classification/Doses Results

One high-dose rat in the 24-hour group was 

found dead and 8 of 10 high-dose rats in the 

48-hour group died prior to sacrifice on day 

2. Low- and mid-dose animals exhibited 

slight depression, ataxia, and/or prostration. 

Treated animals also had decreased body 

weights compared to controls. There was no 

significant increase in the frequency of 

aberrations in bone marrow cells of treated 

animals compared to controls at any sampling 

time. Values in treated animals ranged from 

0.3-0.8% aberrant cells/group; the positive 

control group had 19.6% aberrant cells, 

indicating that this control responded 

appropriately. There was no change in 

mitotic index of dosed groups compared to 

controls. There is no evidence that Linuron 

induced chromosomal aberrations in bone 

marrow cells of rats over background levels.

870.5300 Unscheduled DNA 

synthesis in mammalian 

cell culture

MRID 00132583

Acceptable/Guideline

0.00001, 0.0001, 0.001, 0.01, 0.1, 

1.0, 10, and 50.0 mM (trial 1)

0.01, 0.1, 1.0, 10, and 50.0 mM 

(trial 2)

In an unscheduled DNA synthesis assay, 

primary rat hepatocyte cultures were exposed 

to Linuron (94.5% a.i. in dimethylsulfoxide; 

Lot No. T80311-81) in Williams’ Medium E 

(WME) for 18 hours. There is no evidence 

that Linuron induced chromosomal 

aberrations in bone marrow cells of rats over 

background levelS

Neurotoxicity battery

870.6200a Acute Neurotoxcity studyrat (single gavage dose)49096701 (2013)

Acceptable/non-guideline

0, 20. 100, 500 mg/kg 

NOAEL = 20 mg/kg

LOAEL =100 mg/kg based on decreases in 

motor activity and rearing. At 500 mg/kg 

numerous changes in FOB parameters were 

found.

870.6200b Subchronic neurotoxicity 

study

The requirement of this study was waived by HASPOC, 6/12/2013

(TXR 0056666). 

870.6300 Developmental 

neurotoxicity study (DNT) 

A DNT study was not required because linuron affect testes and hematological 

parameters. but it did not produce increase susceptibility in young rats (TXR 

0050429)

Immunotoxicity study

870.7800 Immunotoxicity study-rats 48840401 (2012)

Acceptable/guideline

0, 150, 500, 1500/1000 ppm 

(1500 ppm was reduced to 1000 

ppm day 10 due to excessive 

weight loss)

M: 0, 13.3, 42.7, 132.1/92.1 

mg/kg/day)

F: 0, 13, 41.7, 130/92.8 

mg/kg/day

Systemic NOAEL = 41.7mg/kg/day

Systemic LOAEL = 92 based on decreases in 

body weight, body weight gains, and food 

consumption.

NOAEL for Immunotoxicity = 92 mg/kg/day 

(highest dose tested) based on no effects seen 

in T-cell dependent antibody response to 

antigen and natural killer cells

Special studies

Special Study - Leydig 

cell tumorigenesis in rats

41630101 (1990)

Acceptable/Nonguideline

(0 or 200 mg/kg/day for 14 days 

to 32 to 33 and 93 day old rats)

No treatment-related clinical signs of toxicity 

were observed. Body weight and body 

weight change were significantly less than 

controls and decreased accessory sex organ 

weights for growing and adult rats.

M: 0, 0.74, 5.8, 36 mg/kg/day; F: 

0, 0.92, 7.3, 45 mg/kg/day 

Selected animals from the 2-generation 

reproduction study were used to evaluate 

changes in serum hormone levels, accessory 
Linuron Human Health Risk Assessment DP No. D405828

Page 38 of 41

Guideline 

No. Study Type MRID No. (Year)/ Classification/Doses Results

F0 and F1 animals from 2-

generation reproduction study 

(41463401),

sex organ weights. Increased serum 

luteinizing hormone and estradiol levels were 

observed in F0 and F1 males.

High-dose F0 males had decreased absolute 

epididymides, dorsal lateral prostate, and 

levator ani muscle weights and increased 

relative testes, epididymides, and ventral 

prostate weights. Organ weights were 

unaffected in the two lower dose groups.

These data support the hypothesis that rats 

exposed to linuron could develop interstitial 

hyperplasia and subsequent adenomas 

(Leydig cell tumors) via a mechanism of 

sustained hypersecretion of luteinizing 

hormone induced by the antiandrogenic 

potential of linuron.

Special Study - Cross 

Mating - Rats

00159846 (1985)

Acceptable/Nonguideline

0, 625 ppm

(M: 0, 48 mg/kg/day

F: 0, 44 mg/kg/day)

The cross-mating results suggest that linuron 

may cause paternally-mediated effects based 

on decreased fertility and fecundity as well as 

maternally-mediated effects based on 

decreased pup viability and litter survival.

Special Study - Aged male 

rats

45506501 (1986)

Acceptable/Nonguideline

0, 625 ppm

(0, 22 mg/kg/day)

Linuron induced hyperplasia and adenomas 

of the testes in aged rats. In addition, lifetime feeding was not necessary to induce 

oncogenic responses in this tissue. Exposure 

duration was 6 to 12 months.

Special Study -

Biochemical and 

Histopathological effects

164093 (1986)

Acceptable/Nonguideline

0, 12.5, 100, 625 ppm

(M: 0, 0.75, 4.1, 22 mg/kg/day

F: 0, 1.1, 6.1, 37 mg/kg/day)

The biochemical and histopathological data 

presented in this report suggest that linuron 

may affect testosterone metabolism in horse 

testicular microsomes for a range of 

concentrations which overlap the dose levels 

given rats chronically. However, the net 

effect of these enzyme changes and the 

relevance to the rat in vivo are uncertain. 

Evidence in young and old rats exposed 

repeatedly (3-7x) or for 11 or 19 months 

suggests that Leydig cell incubates are 

differentially altered in their sensitivity to 

LH. Microscopic lesions in the testes and 

cervix have been confirmed in other studies.
Linuron Human Health Risk Assessment DP No. D405828

Page 39 of 41

Toxicology Data Requirements

The requirements (40 CFR 158.340) for food use for linuron are shown below in Table 1. Use of the new guideline 

numbers does not imply that the new (1998) guideline protocols were used.

Test Technical Linuron

Required Satisfied

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 (nonrodent).........................................

870.3200 21/28-Day Dermal .........................................................

870.3250 90-Day Dermal ..............................................................

870.3465 90-Day Inhalation..........................................................

yes

yes

yes

CR

CR

+

+

waiveda

waiveda

waiveda

870.3700a Developmental Toxicity (rodent)...................................

870.3700b Developmental Toxicity (nonrodent).............................

870.3800 Reproduction .................................................................

yes

yes

yes

yes

yes

yes

870.4100a Chronic Toxicity (rodent)..............................................

870.4100b Chronic Toxicity (nonrodent)........................................

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...

870.5550 Mutagenicity—Other Genotoxic Effects.......................

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

--

--

yes

waived b

--

870.7485 General Metabolism ......................................................

870.7600 Dermal Penetration........................................................

870.7800 Immunotoxicity...............................................

yes

yes

yes

yes

yes

yes

+: Satisfied by the availability of the chronic toxicity study.

a

: HASPOC, 10/26/12; TXR#0056436, 06/12/2013; TXR#0056436

b

: HASPOC, 6/12/13; TXR#0056666
Linuron Human Health Risk Assessment DP No. D405828

Page 40 of 41

Appendix B. Physical/Chemical Properties

Table B. Physicochemical Properties of the Technical Grade Test Compound Linuron.

Parameter Value Reference

Molecular weight (g/mole) 249.1 MRID 42213301

Melting point/range 91-94±1°C MRID 42213301

pH 6.98, 7.09 for a 0.2% solution and 9.38, 

9.41, for a 2.5% solution at 22.5±0.5C

MRID 42213301

Density 1.4963 g/mL at 22.3±0.5C 

(air comparison pycnometer) MRID 42213301

Water solubility (20.5 ± 0.5 C) 5.88×10-3

g/100 mL MRID 42213301

Solvent solubility (20 C)

dichloromethane 44.1 g/100 mL

toluene 7.91 g/100 mL

methanol 12.6 g/100 mL

hexane 0.220 g/100 mL

MRID 42213301

Vapor pressure at 25°C 4.015×10-5

Pa

3.01×10-7 mm Hg MRID 42213303

Henry’s Law Constant at 25°C 1.97×10-9atm·m3/mol http://toxnet.nlm.nih.gov

Dissociation constant (pKa)

dissociation constant could not be 

determined; physical and chemical 

properties deemed all methods in OECD 

guidelines inappropriate

MRID 42213302

Octanol/water partition coefficient 

Log(KOW)

8.2×102at 23±1C (GC method)

log Pow = 2.76 MRID 42213301
Linuron Human Health Risk Assessment DP No. D405828

Page 41 of 41

Appendix C. Review of Human Research

The PHED Task Force, 1995. The Pesticide Handlers Exposure Database, Version 1.1. 

Electronic Database. Task Force Members: Health Canada, U.S. EPA, and the National 

Agricultural Chemicals Associations, released February 1995. 

The Agricultural Handler Exposure Task Force (AHETF), 2011. The Occupational Handler Unit 

Exposure Surrogate Reference Table. U.S. EPA. Released June 21, 2011.