UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: December 9, 2015 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

SUBJECT: Diuron. Human Health Assessment Scoping Document in Support of 

Registration Review. 

PC Codes: 035505 

Decision No.: 496087 

Petition No.: NA 

Risk Assessment Type: NA 

TXRNo.: NA 

MRID No.: NA 

DP Barcode: D42323 l 

Registration No.: NA 

Regulatory Action: Registration Review 

Case No.: 0046 

CAS No.: 330-54-1 

40 CFR: 180. 106 

FROM: Karlyn Middleton, Toxicologist/Risk ass ssor , 

Zaida Figueroa, Industrial Hygienist 

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William Drew, Chemist ~,.- ) 1

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Katelynn King, Chemist (HED, Tfis1 11A~e~~ Branch 7) /vii( /ARisk Assessment Branch II 

Health Effects Division (7509P) 

Office of Pesticide Programs ~ ~..O 

Timothy Dole, Industrial Hygienist 0 ~, ~ C!, .J-"() '-( 

Jonathan Chen, Toxicologist 4':~ 

Risk Assessment Science Support Branch 

Antimicrobials Division (75 1 OP) 

Office of Pesticide Programs 

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TO: Katherine St. Clair, Chemical Review Manager 

Pesticide Re-Evaluation Division (7508P) 

Office of Pesticide Programs 

San Yvette Williams, Chemical Review Manager 

Antimicrobials Division (75 1 OP) 

Office of Pesticide Programs 

Page I of 31 
The Health Effects Division (HED) and Antimicrobials Division (AD) human health risk assessment 

scoping document for diuron to support registration review is presented below. HED reviewed the 

conventional uses of diuron, while AD reviewed the antimicrobial uses [note: although HED evaluated the 

mildewcide use (paints and stains) previously (2003), during registration review the use pattern falls under 

the purview of AD]. This document summarizes HED's and A D's evaluation of the data available for 

assessing human health risk from exposure to diuron, as well as any data needed to support registration 

review. 

Executive Summa ry 

The Health Effects Division (l IED) and the Antimicrobials Division (AD) have evaluated the 

available data, exposure information, and the most recent human health risk assessment for the 

herbicide diuron. This evaluation was performed in order to determine the scope of work 

necessary to support the established tolerances and existing registrations for diuron. The primary 

sources of information were recent human health risk assessments (D335228; C. Swartz; 

511512007 and D403844; D. McNeilly; 8/29/2012), the Revised HED Chapter of the 

Reregistration Eligibility Decision (RED) document for diuron (0291546; C. Christenson; 

9/8/2003), and toxicity and residue studies submitted as required during registration. HED and 

AD have evaluated this information for diuron in association with the updates to toxicity, 

exposure, and usage databases to determine if sufficient data are available and if further updates 

are needed to support registration review. 

Diuron [3-(3,4-Dichlorophenyl)-l ,l-dimethylurea] is a pre- and post-emergent herbicide used to 

control annual and perennial broad leaf and grassy weeds in a variety of agricultural crops, 

ornamental trees and non-crop sites. It is also used as a mildewcide in paints and stains, and as 

an algaecide in commercial fish production. Products containing diuron are used in occupational 

settings, including agricultural food crops and non-food crops, ornamental trees, flowers and 

shrubs, paints and coatings, ornamental fish ponds and catfish production, rights-of-way and 

industrial sites. Residential uses of diuron include ponds, aquariums and paints. There is also a 

Special Local Need (SLN) use in Georgia on Cotton. 

The toxicology database for diuron is not complete. The Hazard and Science Policy Council 

(HASPOC) determined that an acute neurotoxicity (ACN) study is needed for diuron. In the 

absence of an ACN study, the I OX FQPA factor would be retained as a database uncertainty 

factor and appli ed to the acute dietary risk assessment (only). The immunotoxicity and 

subchronic neurotoxicity studies are not available for diuron; however, the HASPOC has 

determined that these studies are not needed based on a weight of evidence approach, 

considering the available hazard and exposure information (TXR# 0057097). 

The target organs for diuron are the hematopoietic system, bladder, and kidney. No evidence of 

increased susceptibility was observed in the available developmental and reproduction toxi city 

studies. Diuron is classified as a '·known/likely" human carcinogen, based on urinary bladder 

carcinomas in both sexes of the Wistar rat, kidney carcinomas in the male rat and mammary 

gland carcinomas in the female NMRI mouse. A linear low dose extrapolation model (QI*) was 

recommended for the quantification of human cancer risk, based on the urinary bladder 

carcinomas in the rat. Since the last assessment, a mode of action (MOA) has been proposed by 

Page 2of3 1 
Page 3 of 31

the registrant for the rat bladder tumors and mechanistic studies have been submitted to support 

the proposed MOA. 

In the most recent assessments (D335228; 5/15/2007 and D403844; 8/29/2012), the 10X Food 

Quality Protection Act (FQPA) Safety Factor was retained (LOAEL to NOAEL extrapolation)

for chronic dietary, incidental oral (intermediate) and inhalation exposure since a NOAEL was 

not determined in the rat chronic/carcinogenicity study used for risk assessment. The FQPA 

factor was reduced to 1X for all other scenarios. 

HED has not revised the endpoints, doses, and safety factors for the purpose of this scoping 

assessment for registration review. However, new toxicity data (dermal, inhalation, subchronic 

rat, chronic dog, and mutagenicity studies) as well as mechanistic data (for rat bladder tumors)

are available for diuron and are currently under review. Therefore, future assessments should 

take into consideration the findings from the new data and determine the appropriateness of the 

existing endpoints and doses selected for risk assessment, based on science policies and risk 

assessment methodologies in place at the time of registration review. The FQPA factor should 

also be revisited in light of any revised endpoints and points of departure. 

The residue chemistry database is largely complete but there are outstanding data. The 

metabolism of diuron in crops and livestock is adequately understood. Adequate enforcement 

methods are available for crops; however, an independent laboratory validation (ILV) of the 

enforcement method for livestock commodities, and multi-residue method (MRM) testing for 

diuron in livestock commodities, are required. The tolerance expressions (as stated in 40CFR 

§180.106[a] and [c]) are not in accord with current guidance, as they do not contain the 

appropriate coverage and compliance statements; they should be revised (as detailed below) 

during registration review to comply with HED’s guidance on tolerance expressions. There are 

no Codex maximum residue limits (MRLs) established for diuron, so there are no harmonization 

issues with regard to Codex. US tolerances are generally not harmonized with Canadian MRLs, 

with the exception of asparagus at 7 ppm (mg/kg). Further harmonization with Canadian MRLs 

may be possible during registration review. It is possible that HED will conduct a new dietary 

risk assessment with revised estimated drinking water concentrations (EDWCs) during 

registration review. Additional work related to residue chemistry is expected, reviewing 

submitted magnitude of residue (MOR) and MRM testing data, as well as the required ILV.

HED agrees with the registrant’s proposed waiver of the requirement of additional data on field 

accumulation in rotational crops. 

The residential exposure database is complete for the conventional uses. Diuron is registered for 

use in residential settings (i.e., ponds and aquariums) and used by homeowners and commercial 

handlers applying diuron directly into the water or as a foliar application to emergent aquatic 

vegetation. HED conducted residential non-cancer and cancer handler assessments for the 

aquatic uses (i.e., recreational fish and backyard ponds) and the risk estimates were not of 

concern. During registration review, HED will update the residential handler assessments based 

on revised toxicological endpoints, inputs, assumptions, and scientific procedures (e.g., Aquatic 

Use Residential SOP). Also, HED will conduct quantitative residential non-cancer and cancer 

post-application assessments for the aquatic use to reflect current exposure assumptions and 

science methodology for aquatic assessments (e.g., Aquatic Use Residential SOP). However, no 

risks of concern are anticipated. In addition, the Agency will consider the potential for exposure 

through spray drift and volatilization.
Page 4 of 31

In addition to conventional applications, there are antimicrobial uses of diuron that result in 

residential exposure. Diuron is registered for use as a material preservative in paints films, 

coatings, stains, mastics, caulks and polymer lattices. The paint use (with the highest exposure 

scenario) which is protective of the other uses, was evaluated in the RED for residential handler 

inhalation exposure when applying paint using airless sprayers and brushes and rollers; noncancer risk estimates were not of concern. These risk estimates will need to be reevaluated 

during registration review to account for any updates in toxicological endpoints and to account 

for the inhalation exposure - indoor study that is needed for the antimicrobial uses to assess 

handler exposures during material preservation and use of preserved materials.

Cancer risk estimates were also evaluated and were not of concern given the conservative nature 

of the exposure assumptions used. Although residential post-application exposures to paint 

vapors were evaluated for the RED using an oral endpoint and the risks were not of concern, 

these exposures may need to be re-evaluated during registration review to account for any 

updates in toxicological endpoints.

The most recent aggregate risk assessment was performed in conjunction with the 2007 human 

health risk assessment. Updated chronic and cancer dietary assessments were conducted to 

include the newly proposed tolerances. Because residential exposure to diuron was considered 

negligible, the dietary (food + water) assessments served as the aggregate risk estimates. The 

diuron chronic dietary risk estimates were all below HED’s level of concern. A new aggregate 

assessment for diuron will be required during registration review that includes current use 

patterns and incorporates any changes in endpoint selection, safety factors, and updated dietary 

and residential exposure estimates. 

There is sufficient information available to assess occupational exposure and risk from the 

conventional registered uses. Based on existing registrations, the previous assessments identified 

most of the anticipated occupational handler and post-application exposure scenarios. During 

registration review, a dislodgeable foliar residue (DFR) study is required to refine postapplication (cancer) exposures to support the registered uses. New occupational handler and 

post-application assessments will be conducted for existing uses based on updated scientific 

procedures for dermal and inhalation risk assessment, the required DFR data as well as any 

changes to the toxicology endpoints.

The structure and chemical names, as well as the chemical and physical properties for diuron can 

be found in the tables in Attachment 1.

 

Hazard Identification/Toxicology

The toxicology database for diuron is incomplete. The Hazard and Science Policy Council 

(HASPOC) concluded that the acute neurotoxicity (ACN) study is needed for diuron since 1) 

neurotoxic effects were observed in an acute oral lethality study with diuron; 2) significant 

neurotoxic effects were seen in an ACN study with a structurally related chemical, and 3) 

findings in an ACN study could potentially result in the need for an acute dietary risk 

assessment. In the absence of the study, the 10X FQPA factor would be retained as a database 

uncertainty factor and applied to the acute dietary risk assessment (only). Immunotoxicity and 

subchronic neurotoxicity studies are also not available for diuron. Additionally, the available 
Page 5 of 31

developmental rat study was classified as unacceptable since the test article concentrations in the 

top two doses were highly variable. However, the HASPOC determined that the immunotoxicity 

and the subchronic neurotoxicity studies are not needed at this time, based on a weight of 

evidence approach, considering the available hazard and exposure information. The HASPOC 

also concluded that a new rat developmental study is not needed and HED has upgraded the 

classification of the available study to acceptable/nonguideline (TXR# 0057097). 

The mechanism of herbicidal action for diuron is the inhibition of photosynthesis. The

mammalian mode of action is unknown. The target organs for diuron are the hematopoietic 

system, bladder, and kidney. In toxicity studies, erythrocyte damage resulted in hemolytic 

anemia and compensatory hematopoiesis. Significantly decreased erythrocyte counts, 

hemoglobin levels, and hematocrit were observed. Additionally, increased mean corpuscular 

volume (MCV), mean corpuscular hemoglobin (MCH), and abnormal erythrocyte forms were 

seen, as well as increased reticulocyte and leukocyte counts. These observations of erythrocytic 

regeneration were consistently seen in oral chronic toxicity studies in rats, mice and dogs. Gross 

pathology findings in chronic rat and mouse studies showed increased incidences of urinary 

bladder edema and wall thickening at high doses. Microscopic evaluation showed dose-related 

increases in the severity of epithelial focal hyperplasia of the urinary bladder and renal pelvis in 

both sexes. A summary of the available toxicity data on diuron is provided in Attachment 2. 

Dermal exposure to diuron did not result in systemic toxicity in a previously reviewed rabbit 

dermal study or the new rat dermal study at doses up to the limit dose. Inhalation exposure to 

diuron resulted in hemolytic anemia and decreased thyroid hormones (T3 and T4) in rats at the 

mid and high doses; piloerection was observed at the high dose. No effects were seen at the low 

dose. 

No evidence of increased susceptibility (qualitative or quantitative) was seen following in utero 

and/or pre-/post-natal exposure in developmental or reproduction studies. No evidence of 

neurotoxicity was observed in the available toxicity studies. 

Administration of diuron in the diet to rats and mice resulted in increases in several tumor types 

(kidney, bladder, and mammary gland). Corroborative non-neoplastic lesions (epithelial focal 

hyperplasia) were also observed in the kidney and bladder. Grossly, increased incidences of

urinary bladder edema and wall thickening were seen. Diuron is classified as a “known/likely” 

human carcinogen, based on urinary bladder carcinomas in both sexes of the Wistar rat, kidney 

carcinomas in the male rat and mammary gland carcinomas in the female NMRI mouse. 

Quantification of cancer risk was performed using a linear-low dose extrapolation based on the 

incidence of urinary bladder carcinomas in the rat with a cancer potency factor (Q1* of 1.91 x 10-

2

(mg/kg/day)-1). There is no mutagenicity concern for diuron. Since the last risk assessment, 

mechanistic data have been submitted to address the bladder tumors observed in chronic studies 

with diuron. The studies are currently under review; however, if the registrant would like the 

Agency to consider a proposed mode of action for diuron, a formal request for cancer 

reclassification should be submitted. 

Metabolism data in the rat indicates that diuron is absorbed and metabolized within 24 hours 

post-dose at the low dose and within 48 hours post-dose at the high dose. The urine is the major 

route of excretion in both sexes; a small amount of diuron is detected in the feces. No apparent 

difference was observed between single and multiple low oral doses. There was no apparent sex-
Page 6 of 31

related difference in either absorption or elimination. The highest tissue residue levels were 

found in the liver and kidneys 4 days post exposure. 

Diuron has low acute toxicity (Toxicity Category 3 or 4) by the oral, dermal, or inhalation 

exposure routes. Diuron is not an eye irritant or skin sensitizer.

Endpoints currently selected for the most recent human health risk assessment are shown in 

Attachment 3. An acute dietary assessment was not conducted since an appropriate single-dose 

endpoint was not identified. However, the need for an acute dietary risk assessment should be 

revisited after the ACN study is received and reviewed. Chronic dietary and incidental oral risk 

assessments were conducted. Incidental oral risk assessments were done for both short-term and 

intermediate-term exposure. However, based on the registered uses only short-term incidental 

oral exposure is anticipated. Therefore, this should be reflected in the updated endpoints and 

doses for risk assessment during registration review. Residential and occupational risk 

assessments for dermal and inhalation exposure were also conducted. A new rat dermal study 

and inhalation study are available for diuron. Therefore, the endpoints/PODS for dermal and 

inhalation exposure should be revisited after completion of the data review. Based on a cursory 

review of the new rat dermal and inhalation studies, HED does not anticipate conducting a 

dermal risk assessment. However, the inhalation study should be used for assessing risks 

associated with inhalation exposure.

In the previous risk assessment (D335228), the 10X Food Quality Protection Act (FQPA) Safety 

Factor was retained for chronic dietary and intermediate-term incidental oral and inhalation risk 

assessments. The factor was retained for LOAEL to NOAEL extrapolation since a NOAEL was 

not determined in the study selected (rat chronic/carcinogenicity) for the risk assessments. The 

FQPA factor was reduced to 1X for all the other scenarios based on the following: 1) the 

toxicology database is adequate to assess pre- and post-natal toxicity; 2) there was no evidence 

of increased susceptibility following in utero exposure to rat and rabbits and pre/post-natal 

exposure to rats; 3) there was no concern for potential developmental neurotoxicity, and a 

developmental neurotoxicity study is not required; and 4) there are no residual uncertainties 

identified in the exposure databases. The dietary (food and drinking water) and non-dietary 

(residential) exposure assessments will not underestimate the potential exposures for infants and 

children.

Conclusions for Hazard Identification/Toxicology of Diuron (Conventional and Antimicrobial 

Uses)

Additional toxicology data are required for diuron to support registration review. An acute oral 

neurotoxicity study in the rat (870.6200) is required since 1) neurotoxic effects were observed in 

an acute oral lethality study with diuron; 2) significant neurotoxic effects were seen in an ACN

study with a structurally related chemical, and 3) findings in an ACN toxicity study could 

potentially result in the need for an acute dietary risk assessment. In the absence of an ACN 

study, the 10X FQPA factor would be retained as a database uncertainty factor and applied to the 

acute dietary risk assessment (only). A subchronic neurotoxicity study is not required, it is 

unlikely to provide a lower POD or a more sensitive endpoint than those currently used for risk 

assessment. Also, an immunotoxicity is not required, based on lack of evidence of potential 

immunotoxicity at relevant dose levels. 
Page 7 of 31

During registration review, HED and AD recommend reevaluation of the following points,

which should take into consideration the results of the additional studies received for diuron and 

ensure consistency with science policies/guidance in effect at the time of review: (1) endpoints 

and doses for risk assessment, and (2) reconsideration of safety/uncertainty factors, including the 

FQPA safety factor.

New mechanistic studies have been submitted to address the bladder tumors observed after 

exposure to diuron. However, if the registrant would like the Agency to consider a proposed 

mode of action for diuron, a formal request for cancer reclassification should be submitted. 

Residue Chemistry and Dietary Exposure

Residue Chemistry - Conventional Uses: The metabolism of diuron in crops and livestock is 

adequately understood. HED concluded that the residues of concern in plant and animal 

commodities (for tolerance expression and risk assessment purposes) are defined as diuron and 

its metabolites convertible to 3,4-dichloroaniline (3,4-DCA), mostly comprised of 

dichlorophenylurea (DCPU) and dichlorophenylmethylurea (DCPMU). HED previously 

concluded the residues of concern in drinking water (for risk assessment) are parent, DCPMU 

and monochlorophenyldimethylurea (mCPDMU). Although phenyldimethylurea (PDMU) and 

monochlorophenylmethylurea (mCPMU) were also identified as major degradates in water, they 

were not included as residues of concern; the Metabolism Assessment Review Committee 

(MARC) did not provide a rationale for this decision (D275688; J.S. Punzi; 10 August 2001), 

and therefore for the purpose of registration review, HED consulted with EFED to determine if 

the residues of concern for drinking water need to be revisited. PDMU, also known as fenuron 

(an obsolete phenylurea herbicide with very low toxicity to animals), occurs at roughly 13% 

under anaerobic aquatic conditions only. Similarly, mCPMU occurs at approximately 21% 

under anaerobic aquatic conditions only. Results from a DEREK analysis (which compares the 

toxicity of metabolites and/or degradates relative to the parent compound, based on structural 

similarities and differences) of mCPMU did not indicate any toxicity that would differ from that 

of the parent compound, diuron. HED has determined that neither PDMU nor mCPMU are 

considered residues of concern in drinking water since there is no concern for increased toxicity 

(relative to the parent compound) and the degradates are only present under anaerobic aquatic 

conditions. Note that 3,4-DCA is not a residue of concern in plants, animals or drinking water 

because it is a minor metabolite/degradate. 

Most of the established tolerances for residues of diuron are supported by adequate data, 

however the existing residue chemistry database for diuron is incomplete. Field trial residue data 

were previously requested for globe artichoke; barley hay; cotton gin byproducts; field corn 

aspirated grain fractions (AGF) and other processed fractions, forage and stover; filbert; grass 

forage, hay, straw and seed screenings; pear; oat forage and hay; olive; field pea vines and hay; 

sorghum AGF, stover and forage; and wheat forage and hay, as listed in the revised residue 

chemistry chapter for the diuron Reregistration Eligibility Decision (RED) document (D291550; 

S.L. Kinard; 7/9/2003). 

Additional field trial data, as mentioned above, were previously requested in the HED chapter of 

the RED document (D291546; C. Christenson; 8 September 2003) to complete the residue 

chemistry database. Adequate analytical methods exist for data collection and tolerance 

enforcement in plant commodities. An ILV of the enforcement method for livestock 
Page 8 of 31

commodities was requested, and MRM testing for diuron was requested for both plant and 

livestock commodities (D291550; S.L. Kinard; 7/9/2003).

The requested field trial residue data were not submitted for cotton gin byproducts, nor grass 

straw and seed screenings; residue data were received for all other requested commodities. 

However, tolerances in grass straw and seed screenings are established only if the petitioner 

submits data for these commodities, and requests said tolerances. These data were not 

submitted, nor were tolerances proposed; therefore, residue data for grass straw and seed 

screenings are not required. Also, HED has determined that previously requested crop field trial 

data for cotton gin byproducts are not needed (refer to the rationale in Appendix A). 

Studies addressing all of the other requested residue data requirements were submitted by the 

registrants, along with MRM testing (in grapes), and an ILV of the enforcement method for plant 

commodities (in grapes, olives and wheat grain). These submitted studies are adequate with 

regard to regulatory requirements. However, studies addressing both ILV of the livestock 

enforcement method and MRM testing for diuron in livestock commodities remain outstanding 

data requirements. 

Results from animal feeding studies suggested that tolerances may be necessary in eggs, poultry 

commodities, and/or milk. Residue data were previously unavailable for several potential feed 

items. Based on the recently submitted field trial studies, it is unlikely that the maximum 

reasonably balanced dietary burdens would increase when recalculated with all potential feed 

items. Therefore, the established tolerances for residues in livestock commodities would not 

need to be revised 

Field rotational crop trials were conducted on representative crops at less than the maximum 

application rates with 1-year plant-back intervals (PBIs), and some labels indicate a 2-year PBI. 

HED previously recommended that the registrants provide additional data to support the higher 

application rate, and advised the registrant that a 2-year PBI is not considered practical. HED 

also recommended that the registrants remove the 2-year PBI from the registered labels, and 

provide data to support application at the rate of 3.2 pounds of active ingredient per acre (lb ai/A) 

and a 1-year PBI (D291550; S.L. Kinard; 7/9/2003). The Agency subsequently issued a Data 

Call-In (DCI) Notice (GDCI-035505-26943) for diuron, requesting additional data on field 

accumulation in rotational crops. The time frame allotted for submission of the additional data 

was 36 months. In response, DuPont submitted a request and rationale (MRID #47127101) for a 

waiver of the requirement for additional field accumulation in rotational crops data. This waiver 

request is adequate with regard to regulatory requirements; further field accumulation testing in 

rotated crops is not required. 

The tolerance expression for diuron (cited in 40CFR §180.106[a] and [c]) is not in accord with 

current guidance, as it does not contain the appropriate coverage and compliance statements. It 

should be revised during registration review to comply with HED’s guidance on tolerance 

expressions (S. Knizner; 27 May 2009). The tolerance expression for diuron in 40CFR 

§180.106[a] should be revised to state: 

Tolerances are established for residues of the herbicide diuron, including its 

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

Compliance with the tolerance levels specified below is to be determined by 
Page 9 of 31

measuring only diuron (3-(3,4-dichlorophenyl)-1,1-dimethylurea) and its 

metabolites convertible to 3,4-dichloroaniline, calculated as the stoichiometric 

equivalent of diuron. 

The tolerance expression for diuron in 40CFR §180.106[c] should be revised to state: 

Tolerances with a regional registration as defined in §180.1(l) are established 

for residues of the herbicide diuron, including its metabolites and degradates, 

in or on the commodities listed in the table below. Compliance with the 

tolerance levels specified below is to be determined by measuring only diuron 

(3-(3,4-dichlorophenyl)-1,1-dimethylurea) and its metabolites convertible to 

3,4-dichloroaniline, calculated as the stoichiometric equivalent of diuron. 

There are no Codex MRLs established for diuron, so there are no harmonization issues with 

regard to Codex. US tolerances are generally not harmonized with Canadian MRLs, with the 

exception of asparagus at 7 ppm (mg/kg). Further harmonization with Canadian MRLs may be 

possible during registration review. 

Dietary Exposure - Conventional Uses: 

The Environmental Fate and Effects Division (EFED) is conducting a new drinking water 

assessment for diuron, in order to account for new modeling techniques introduced since the 

previous risk assessment. This new drinking water assessment will include the current residues 

of concern (parent, DCPMU and mCPDMU). If the new assessment results in significant 

increases in the EDWCs, HED may complete a new dietary exposure assessment during 

registration review; this dietary exposure assessment would include updated consumption 

information and the latest version of the dietary model. 

In the most recent human health risk assessment (D335228; C. Swartz; 5/15/2007), chronic and 

cancer dietary (food + water) assessments were conducted for diuron and residues convertible to 

3,4-DCA. Additionally, a separate assessment was done for the water degradate, MCPDMU 

[N’-(3-chlorophenyl)-N,N-dimethyl urea], in fish and drinking water. The MCPDMU degradate 

is structurally similar to monuron, which is no longer registered in the U.S., but is a carcinogen 

with a cancer potency factor. There were no chronic or cancer dietary (food + water) risk 

estimates of concern for diuron, residues convertible to 3,4-DCA or MCPDMU. The dietary 

(food + water) estimates serve as the aggregate risk estimates. 

Dietary Exposure - Antimicrobial Uses:

EPA has not established tolerances or tolerance exemptions for residues for the antimicrobial 

uses of diuron. Diuron has not been cleared as a food additive by the US Food and Drug 

Administration (US FDA) under the Federal Food, Drug, and Cosmetic Act (FFDCA) Section 

409. There are no currently registered antimicrobial uses that could result in direct or indirect 

food contact since the only uses (adhesives, coatings, and materials preservatives) are under the 

jurisdiction of FDA and they have not been cleared for food-contact. Therefore, a dietary 

exposure assessment will not be conducted for the antimicrobial uses of diuron during 

registration review.
Page 10 of 31

Conclusions for Residue Chemistry and Dietary Exposure - Conventional and Antimicrobial 

Uses

In order to complete the residue chemistry database, an ILV of the livestock enforcement 

method, as well as MRM testing for diuron in livestock commodities are required. Additional 

work related to residue chemistry is expected for the conventional uses (reviewing the adequate 

submitted MOR and MRM testing data). It is possible that HED will conduct a new dietary risk 

assessment for the conventional uses with revised EDWCs during registration review. EPA does 

not plan to conduct a dietary exposure assessment for the antimicrobial uses. 

Residential Exposure

There are potential residential exposures from activities associated with: 1) ponds and aquariums

and 2) paint uses. The registered uses of diuron in residential settings result in potential 

exposure to homeowners who apply the products, and to adults and children who come into 

contact with treated areas while doing maintenance or playing close to treated areas. Products 

intended for residential use may be applied using handheld equipment, a spoon, by hand, by 

airless sprayer, or by paintbrush/roller. Residential exposure is expected to be short-term in 

duration.

There are new dermal and inhalation toxicity studies available for diuron. HED and AD do not 

anticipate conducting a dermal risk assessment based on a cursory review of the data which 

indicate that both systemic toxicity, which is evaluated by HED and AD, and dermal irritation, 

which is evaluated by AD, were not observed at the limit dose. However, HED and AD do 

anticipate using the inhalation study for assessing inhalation exposure which will require new 

risk estimates. 

Residential Handler Exposure – Conventional Uses

Residential exposures from the aquatic uses (i.e., ponds and aquariums) were previously 

considered for homeowners and commercial handlers applying diuron directly into the water or 

as a foliar application to emergent aquatic vegetation (D291546; C. Christensen; 9/8/2003). 

Since some end-use products are formulated as tablets/blocks and dissolve in less than 5 minutes, 

the exposure from the block/tablet forms of diuron are expected to be less than the exposure from 

the end-use products formulated as liquids (i.e., measuring and pouring the liquid into the 

aquarium or pond). Therefore, the liquid formulations were considered protective of the 

exposures from the tablets/blocks products. Residential (inhalation) non-cancer handler risk 

estimates were not of concern (D291546).

Although a quantitative non-cancer residential (dermal) handler risk assessment was not 

conducted as part of the RED (D291546) due to the lack of toxicity via the dermal route, 

calculations of daily dermal exposure and daily dermal dose were conducted for purposes of the 

residential cancer handler risk assessment. Cancer risk assessments for residential handlers were 

completed and presented as total cancer risk estimates at baseline clothing for each exposure 

scenario. Cancer risk estimates for residential handlers for the aquatic uses were completed and 

presented as total cancer risk estimates for each residential exposure scenario. The cancer risks 

ranged from 1.1 x 10-6to 3.0 x 10-10 (D291546; C. Christensen; 9/8/2003). 
Page 11 of 31

During registration review, HED anticipates that residential handler exposure assessment for the 

aquatic use will need to be updated to reflect any changes in the toxicology endpoints, current 

exposure assumptions and science methodology for aquatic assessments (e.g., Aquatic Use 

Residential SOP). 

Residential Post-application Exposure – Conventional Uses

Uses of diuron in aquatic sites around residential settings result in potential post-application 

exposures to adults and children. The exposures to adults and children from the aquatic uses 

(i.e., ponds and aquariums) were previously considered (D291546; C. Christensen; 9/8/2003), 

and were determined to be minimal. During registration review, HED anticipates conducting

quantitative non-cancer and cancer post-application exposure assessments for the aquatic use to 

reflect current exposure assumptions and methodology for aquatic assessments (e.g., Aquatic 

Use Residential SOP). 

Residential Handler Exposure – Antimicrobial Uses

A residential handler assessment was conducted for inhalation exposure when applying paint 

using airless sprayers and brushes and rollers (D291546; C. Christensen; 9/8/2003). Risk 

estimates were calculated using the oral NOAEL of 10 mg/kg/day for short term exposures and 

they exceeded the target LOC of 100 and were not of concern. These risk estimates will need to 

be reevaluated during registration review to account for any changes in the toxicology endpoints.

In addition, an inhalation exposure - indoor study (guideline 875.1400) is needed to assess 

residential handler inhalation exposures during the brush/roller and airless spray application of 

diuron preserved paint. These data are anticipated to be used to revise the previous assessments.

Residential cancer handler risk estimates for the antimicrobial uses were also evaluated and were 

in the range of 1.0 to 3.0 x 10-6. These cancer risk estimates were considered conservative given 

that it was assumed that a homeowner would paint their house every year for 50 years out of a 70 

year lifespan.

Residential Post-application Exposure – Antimicrobial Uses

Residential post-application exposures to paint vapors were evaluated by HED for the RED 

using an oral endpoint and the risks were determined to be not of concern (D291546; C.

Christensen; 9/8/2003). In general, AD only evaluates vapor exposures for chemicals that have 

vapor pressures that are greater than 1 x 10-4 mm hg at room temperature (i.e. 25 C). Because 

diuron has a vapor pressure of 3.9 x 10-8 mm hg at 25 C, AD does not anticipate re-evaluating 

the post application exposures to paint vapors. 

Spray Drift and Volatilization – Conventional Uses

Residential bystander exposures resulting from off-site transport (e.g., spray drift or 

volatilization) may occur as a result of the conventional applications of diuron. The potential for 

spray drift will be quantitatively evaluated for each pesticide during the Registration Review 

process which ensures that all uses for that pesticide will be considered concurrently. The 

approach is outlined in the revised (2012) Standard Operating Procedures for Residential Risk 
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Assessment (SOPs) – Residential Exposure Assessment Standard Operating Procedures Addenda 

1: Consideration of Spray Drift. This document outlines the quantification of indirect nonoccupational exposure to drift. In terms of volatilization, the agency has developed a 

Volatilization Screening Tool and a subsequent Volatilization Screening Analysis1. During 

Registration Review, the agency will utilize this analysis to determine if data (i.e., flux studies, 

route-specific inhalation toxicological studies) or further analysis is required for diuron.

Spray Drift and Volatilization – Antimicrobial Uses

Residential bystander exposures resulting from off-site transport (e.g., spray drift or 

volatilization) are not anticipated for the antimicrobial uses of diuron because these uses do not 

include the outdoor applications to soil or foliage that are associated with the conventional uses 

of diuron.

Conclusions for Residential Exposure – Conventional and Antimicrobial Uses

The residential exposure database is adequate to support the existing diuron conventional and 

antimicrobial registrations. HED previously conducted residential exposure assessments for the

aquatic and paint uses. The risk estimates were not of concern. However, during registration 

review, HED will update the exposure assessment for the aquatic use and AD will update the 

exposure assessment for the paint use as needed based on revised inputs, indoor inhalation 

exposure data from required studies, assumptions, and Residential SOPs. HED will also 

consider the potential for exposure through spray drift and volatilization from the conventional 

uses in accordance with any new policies in place.

Furthermore, a rat subchronic inhalation exposure study is now available for diuron. Since 

inhalation risks were previously assessed using an endpoint and dose from an oral study, revised 

residential handler exposure assessments (non-cancer) will be required under registration review 

to incorporate new inhalation toxicological data. An updated exposure assessment will be 

provided based on an endpoint and dose selected from the inhalation study.

 

1 Volatilization Screening Tool Analysis available at: http://www.regulations.gov/#!docketDetail;D=EPA-HQ-OPP2014-0219.
Page 13 of 31

Aggregate Risk Assessment

The most recent aggregate risk assessment was performed for the conventional uses in 

conjunction with the 2007 human health risk assessment. Updated chronic and cancer dietary 

assessments were conducted to include the newly proposed tolerances. In addition to the chronic 

and cancer dietary (food + water) assessments conducted for diuron and residues convertible to 

3,4-DCA, a separate assessment was completed for the water degradate, MCPDMU [N’-(3-

chlorophenyl)-N,N-dimethyl urea], in fish and drinking water. The MCPDMU degradate is 

structurally similar to monuron, which is no longer registered in the U.S., but is a carcinogen 

with a cancer potency factor. However, based on a very conservative estimate of residues in fish 

and monitoring data for the degradate in drinking water, a cancer assessment assuming 

equivalent potency to monuron resulted in cancer risks below HED’s level of concern. Since 

residential exposure to diuron was considered negligible, the dietary (food + water) assessments 

served as the aggregate risk estimates in past assessments. The diuron dietary/cancer risk 

estimates were all below HED’s level of concern. 

Conclusions for Aggregate Assessment – Conventional Uses

The diuron chronic dietary/cancer risk estimates were all below HED’s level of concern in the 

most recent risk assessments. At the time of registration review, HED will conduct a new 

aggregate risk assessment based on any potential updates to points of departure or exposure 

estimates from food and drinking water, as well as residential sources of exposure.

Conclusions for Aggregate Assessment – Antimicrobial Uses

There are no dietary exposures for the antimicrobials uses and the residential exposures are 

limited to handler inhalation exposures from the application of diuron preserved paints. The 

need for including the paint handler inhalation exposure in an aggregate risk assessment will be 

determined in conjunction with the updates to the toxicological points of departure.

Occupational Exposure 

Occupational Handler Exposure – Conventional Uses

Occupational (non-cancer and cancer) handler exposures are expected based on the registered 

agricultural uses of diuron. Diuron is used to control annual and perennial broadleaf and grassy 

weeds in occupational settings, including agricultural food crops and non-food crops/areas, 

ornamental trees, flowers and shrubs, ornamental fish ponds and catfish production, rights-ofway and industrial sites. Diuron is formulated as a granule, water dispersible granule, dry 

flowable, emulsifiable concentrate, liquid flowable concentrate, soluble concentrate and readyto-use solution. It is applied using aerial, ground and a variety of handheld equipment. There is 

also a Special Local Need (SLN) use in Georgia on Cotton. Based on the registered use pattern 

and agricultural practices, occupational exposure from the registered food uses is expected to be 

short-term (i.e., 1-30 days) and intermediate-term (i.e., 1-6 months) in duration for all scenarios. 

Long-term exposures (i.e., more than 6 months) are not anticipated. Maximum single 

application rates range from 0.8 lbs active ingredient (ai)/acre for corn to 87.1 lbs ai/acre for noncrop areas (e.g., utility and industrial areas).
Page 14 of 31

There are new dermal (rat) and inhalation toxicity studies are available for diuron. Therefore, 

the dermal and inhalation toxicological endpoints will be revisited during registration review. 

Based on a cursory review of the new dermal study, HED does not anticipate conducting a 

dermal risk assessment. However, the inhalation study will be used for assessing risks associated 

with inhalation exposure.

In all past risk assessments, no chemical-specific data were available with which to assess 

potential exposure to pesticide handlers; therefore, occupational handler assessments were based 

primarily on surrogate unit exposures from the Pesticide Handlers Exposure Database (PHED). 

Previous risk calculations were based on the maximum application rates and assuming maximum 

area treated per day. Handler’s exposure and risk were calculated at baseline clothing (i.e., long 

pants, a long-sleeved shirt, no chemical-resistant gloves, and no respirator) and with personalprotective equipment (PPE) when necessary (e.g., respirators and engineering controls). 

Based on existing registrations, the previous assessments (D291546; D335228; D403844) 

identified all of the anticipated occupational handler exposure scenarios. All the relevant

occupational handler scenarios were assessed, resulting in non-cancer risk estimates not of 

concern (MOEs > 100; LOC = 100) for most scenarios at some level of personal protective 

equipment (PPE). 

Since no systemic toxicity following repeated dermal dosing was seen in the rabbit dermal 

toxicity study, a quantitative non-cancer dermal risk assessment was not previously conducted as 

part of the RED (D291546). However, calculations of daily dermal exposure and daily dermal 

dose were included for purposes of the cancer risk assessment. Cancer risk assessments for 

occupational handlers were completed and presented as total cancer risk estimates at multiple 

levels of PPE and mitigation for each exposure scenario as needed.

During registration review, occupational (non-cancer and cancer) handler scenarios will be

reassessed to address updates to toxicity endpoints, exposure policies, including updates to 

default exposure data used for handler scenarios and assumptions for body weights.

Occupational Post-application Exposure – Conventional Uses

Occupational (non-cancer and cancer) post-application exposures are expected based on the 

registered agricultural uses of diuron. Occupational (non-cancer) post-application risk estimates 

were not quantitative assessed, because no dermal toxicological endpoint of concern was 

identified. However, a quantitative post-application (cancer) exposure assessment was 

conducted to address potential cancer risks resulting from the registered uses (D291546). Cancer 

risk assessments for occupational post-application activities were completed and presented as 

total cancer risk estimates at baseline clothing, multiple levels of PPE and risk mitigation for 

each exposure scenario as needed (e.g., engineering controls). The cancer risk assessment was 

conducted using dislodgeable foliar residue (DFR) default values at day 0 (i.e., 12 hours 

following application).

In the absence of toxicity via the dermal route, a quantitative non-cancer post-application risk 

assessment will not be required for the registered uses. However, a quantitative cancer postapplication risk assessment will be required for workers conducting post-application activities. 

In accordance with the updated Part 158 data requirements (2007), one or more DFR studies are 
Page 15 of 31

required when a pesticide has occupational uses that could result in post-application dermal 

exposure. Since the RED, no dislodgeable foliar residue (DFR) studies have been submitted for 

diuron. In accordance with the 40 CFR DFR data requirement, based on the existing use pattern, 

a DFR study is required to refine cancer post-application exposure assessments and add 

appreciably to our overall understanding of the availability of dislodgeable foliar pesticide 

residues for diuron. 

The restricted entry interval (REI) of 12 hours currently on the registered labels is based on the 

acute toxicity of the technical ingredient and it is considered adequate to protect workers from 

post-application exposures to diuron.

There are multiple potential sources of inhalation exposure to individuals performing postapplication activities in previously treated fields. These potential sources include volatilization 

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

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

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

and received the SAP’s final report on March 2, 2010. The Agency has evaluated the SAP report 

and has developed a Volatilization Screening Tool and a subsequent Volatilization Screening 

Analysis. During registration review, the Agency will utilize this analysis to determine if data 

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

for diuron.

In addition, the Agency is continuing to evaluate the available post-application inhalation 

exposure data generated by the Agricultural Reentry Task Force. Given these two efforts, the 

Agency will continue to identify the need for and, subsequently, the way to incorporate 

occupational post-application inhalation exposure into the Agency’s risk assessments.

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

previously performed, an inhalation exposure assessment was performed for occupational 

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 the handler 

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

inhalation exposure scenarios.

Occupational Handler Exposure – Antimicrobial Uses

Occupational handler inhalation exposures are also expected based on the registered 

antimicrobial uses of diuron. Diuron is used as an industrial mildewcide for the control of fungal 

and algal growth in paint films, coatings, stains, sealants, mastics caulks and polymer lattices. 

These exposures can occur while open pouring diuron into the paints and coatings being 

preserved and while applying the preserved paints and coatings using airless sprayers and 

brushes and rollers. Based on the registered use pattern and industrial practices, occupational 

exposure from the antimicrobial uses is expected to be short-term (i.e., 1-30 days) and 

intermediate-term (i.e., 1-6 months) in duration for all scenarios. Long-term exposures (i.e., 

more than 6 months) are not anticipated because the use data indicate that diuron usage is low 

compared to other paint mildewcide. The application rates range from 0.06 % to 0.475% ai by 

weight, and the maximum rate is specified for exterior paints used in high humidity, high 
Page 16 of 31

temperature environments. If it is assumed that the paint density is 11.2 lb per gallon, then the 

use rate is 0.0532 lb a.i. per gallon of paint. 

Occupational handler exposure for the antimicrobial uses were assessed for the RED (D291546; 

C. Christensen; 9/8/2003) using a maximum single application rate of 0.0532 lb ai per gallon. 

Occupational non-cancer and cancer occupational risk estimates were assessed.

The occupational non-cancer handler risk estimates were not of concern at some level of PPE 

(i.e., PF5 respirator) for most exposure scenarios except for airless spraying indoors where the 

intermediate-term MOE of 56 was of concern even with PF5 respirators (LOC=100). Cancer 

risk assessments for occupational handlers were also completed and presented as total cancer risk 

estimates at multiple levels of PPE and mitigation for each exposure scenario as needed.

The non-cancer inhalation risks will need to be reassessed to address the inhalation toxicity study 

that was submitted after the RED and both the non-cancer and cancer risks will need to be 

reassessed to address the inhalation exposure - indoor study (875.1400) that is needed. In 

addition, AD will revisit the assumption that respiratory protection and gloves are used during 

airless sprayer application of diuron preserved paints. This update is necessary for the risk 

assessment to reflect current regulatory policy (i.e., preserved paints are treated articles rather 

than pesticide products and thus they do not have pesticide labeling that requires PPE). 

Alternatively, it may be appropriate to register diuron containing paints as pesticide products, 

when diuron functions as a thin film mildewcide that controls mildew after the paint is applied 

rather than only as an in-can preservative that protects paints before it is applied.

Occupational Post-application Exposure – Antimicrobial Uses

Occupational exposures to paint vapors during paint manufacturing were determined to be 

minimal based on the low vapor pressure of diuron (D291546; C. Christensen; 9/8/2003). In 

general, AD only evaluates vapor exposures for chemicals that have vapor pressures that are 

greater than 1 x 10-4at room temperature (i.e., 25◦C), thus AD does not anticipate re-evaluating 

vapor exposures for diuron which has a vapor pressure of 3.9 x 10-8 mm hg at 25 C. 

Conclusions for Occupational Exposure –Conventional and Antimicrobial Uses

The previous occupational (non-cancer and cancer) assessment covered the relevant exposure 

scenarios and did not result in risk estimates of concern at some level of PPE. Updated 

occupational handler and post-application (non-cancer and cancer) assessments will be necessary 

during registration review to include revised surrogate unit exposures for occupational handlers2, 

updated exposure methodologies, the required DFR data for post-application (cancer) 

assessments and any changes in the toxicity endpoints.

The occupational exposure database for the antimicrobial uses is currently being updated by the 

Antimicrobials Exposure Assessment Task Force (AEATF) and this new database could be used 

to satisfy the requirement for the inhalation exposure - indoor study (875.1400) for diuron if data 

compensation issues are appropriately addressed. In addition, the assumption that respirators and 

gloves are used during airless sprayer application of preserved paints will need to be revisited 

 

2 Outlined in the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” available at: 

http://www2.epa.gov/sites/production/files/2015-09/documents/handler-exposure-table-2015.pdf.
Page 17 of 31

because it does not reflect current science policy. Any changes in the toxicological endpoints 

will also be incorporated.

Risk Assessment Updates, Data Deficiencies, and Label Revisions

Toxicology

 870.6200 Acute oral neurotoxicity study. An acute oral neurotoxicity study in the rat 

(870.6200) is required for conventional and antimicrobial uses since 1) neurotoxic effects 

were observed in an acute oral lethality study with diuron; 2) significant neurotoxic 

effects were seen in an ACN study with a structurally related chemical, and 3) findings in 

an ACN study could potentially result in the need for an acute dietary risk assessment. In 

the absence of the study, the 10X FQPA factor would be retained as a database 

uncertainty factor and applied to the acute dietary risk assessment (only).

 HED and AD will consider the appropriateness of the existing endpoints based on the 

new data and current policies and risk assessment methodologies. 

 A formal request for cancer reclassification should be submitted to the Agency. 

Residue Chemistry:

 860.1340 Residue analytical method. An ILV of the livestock enforcement method is 

required for conventional uses. 

 860.1360 Multi-residue method. MRM testing for diuron in livestock commodities is 

required for conventional uses. 

Dietary Exposure:

 Revised dietary exposure analyses might be required for the conventional uses to reflect 

updated dietary exposure models and updated drinking water estimates.

 A dietary exposure assessment is not needed for the antimicrobial uses because these uses 

do not result in dietary exposure.

Occupational/Residential Exposure:

 875.2100 Dislodgeable Foliar Residue (DFR) Dissipation Study. DFR data are required

for certain registered conventional uses (e.g., agricultural food crops and ornamental 

trees).

 875.1400 Inhalation Indoor Exposure Study. This study is needed to evaluate the 

antimicrobial material preservation uses. The scenarios that need to be evaluated in this 

study include: (1) Mixing/loading liquids for material preservation, (2) Brush/roller and 

airless sprayer application of preserved paints. Surrogate exposure data from the 

Antimicrobial Exposure Assessment Task Force (AEATF) can be used to satisfy the data 

need if data compensation issues are appropriately addressed.
Page 18 of 31

 HED and AD anticipate conducting revised non-cancer and cancer occupational and 

residential handler exposure assessments to reflect the use of the most recent handler 

exposure data, the toxicity studies and updated exposure inputs.

 HED anticipates conducting quantitative residential non-cancer and cancer postapplication exposure assessments for the aquatic use to reflect updates in toxicological 

endpoints and current exposure assumptions and methodology for aquatic assessments 

(e.g., Aquatic Use Residential SOP). 

Label Revisions:

None.

Endocrine Disruption

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

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

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

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

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

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

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

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

taxonomic groups. As part of its most recent registration and reregistration decisions for diuron,

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

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

diuron is subject to the endocrine screening part of the Endocrine Disruptor Screening Program 

(EDSP). 

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

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

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

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

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

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

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

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

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

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

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

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

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

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

of chemicals identified for EDSP screening was published on June 14, 20133and includes some 

 

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

list of chemicals.
Page 19 of 31

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

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

Diuron is on List 2. List 2 represents the next set of chemicals for which EPA intends to issue 

test orders/data call-ins in the near future. For further information on the status of the EDSP, the 

policies and procedures, the lists of chemicals, future lists, the test guidelines and the Tier 1 

screening battery, please visit our website.4

Public Health and Pesticide Epidemiology Data

For this evaluation, the Agency consulted the OPP Incident Data System (IDS), the Centers for 

Disease Control and Prevention/National Institute for Occupational Safety and Health 

(CDC/NIOSH) Sentinel Event Notification System for Occupational Risk-Pesticides (SENSOR), 

and the National Pesticide Information Center (NPIC) databases for pesticide incident data on 

the active ingredient diuron (D428534, S. Recore, 8/6/2015). Diuron is not included in the 

Agricultural Health Study (AHS); therefore, that study does not provide information for this 

document.

For the Main IDS, from January 1, 2009 to August 12, 2014, there were 3 incidents reported 

involving diuron. They were classified as moderate severity. 

In Aggregate IDS, from January 1, 2009 to August 12, 2014, there were 49 incidents reported 

involving diuron. Thirty six of these incidents were classified as minor severity. Thirteen 

incidents were classified having no or unknown effects. Overall, there are few incidents

involving diuron reported to IDS. A query of SENSOR-Pesticides from 1998-2010 identified 92 

cases involving diuron (pc code 035505) stemming from 49 events. Of these 92 cases, nine 

cases stemming from five events involve a single active ingredient and were analyzed for this 

memo. All nine cases were low in severity. Two cases were occupational and seven cases were 

non-occupational. Five of the non-occupational cases (all five cases resulted from one event) 

occurred after one Right-of-way application was made to a railroad track in Oregon in 2000. 

These five cases each individually crossed railroad tracks that had been treated with Direx 80 

DF, EPA reg #1812-362. Another non-occupational case occurred when an individual swam in a 

pond that had been treated with diuron, which is an illegal use of the pesticide. No further 

information was provided regarding this case. The seventh non-occupational case involved a 

child near his father when applying the pesticide and the dust got into the child’s eye. The two 

occupational cases involved pesticide applications, one of which was a Right-of-Way applicator, 

the second occupational case did not include a case description. In sum, a total of six out of the 

nine single ai cases were exposed as a result of Right-of-way applications. The leading health 

system effected involved the nervous system; the chief symptom reported among cases 

headache. 

The National Pesticide Information Center or NPIC was also consulted for diuron. The NPIC is 

a cooperative effort between Oregon State University and EPA which is funded by EPA to serve 

as a source of objective, science-based pesticide information and respond to inquiries from the 

public and to incidents. From 2009 to June 30, 2014, 6 incidents were reported to NPIC 

involving diuron. NPIC estimates a certainty index as to whether an incident (including reported 

 

4 http://www2.epa.gov/endocrine-disruption
Page 20 of 31

symptoms) was either definitely, probably, possibly, or unlikely to have been caused by the 

reported exposure to a pesticide, or whether the incident was unrelated to pesticides or if the 

incident was unclassifiable. Of the 6 reported incidents, 3 were reported as symptomatic and 

classified as probably related to the diuron exposure, 2 cases were classified as unlikely and 1 

case was unclassifiable. The three probable incidents were classified as minor severity.

Based on the low frequency and low severity of incident cases reported for diuron in IDS, 

SENSOR-Pesticides, and NPIC there does not appear to be a concern at this time that would 

warrant further investigation. The Agency will continue to monitor the incident information and 

if a concern is triggered, additional analysis will be included in the risk assessment.

Tolerance Assessment and International Harmonization

Tolerances for diuron are established under 40CFR §180.106 for residues resulting from 

applications of the herbicide to various crops. The tolerance expression is not in accord with 

current policy, as it does not contain the appropriate coverage and compliance statements. It 

should be revised during registration review to comply with HED’s policy on tolerance 

expressions, as stated above in the residue chemistry section. 

There are no Codex MRLs established for residues of diuron at this time. Canadian MRLs exist 

for several commodities with US tolerances; the residue definitions are not the same for the US 

and Canada. For commodities with listings in each country, US tolerances are generally not 

harmonized with Canadian MRLs, with the exception of asparagus at 7 ppm (mg/kg). During

registration review, HED will examine the basis for the US tolerances and, to the extent possible, 

harmonize with Canadian MRLs. The International Residue Limit Status sheet is attached to this 

document as Attachment 2. 

There are no pending requests for the establishment of new tolerances for diuron.

Environmental Justice

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

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.hss.energy.gov/nuclearsafety/env/guidance/justice/eo12898.pdf). The OPP 

typically considers the highest potential exposures from the legal use of a pesticide when 

conducting human-health risk assessments, including, but not limited to, people who obtain 

drinking water from sources near agricultural areas, the variability of diets within the U.S., and 

people who might be exposed when harvesting crops. Should these highest exposures indicate 

potential risks of concern, OPP further refines the risk assessments to ensure that the risk 

estimates are based on the best available information.

Cumulative Risk Assessments 

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 diuron and any other substances, and diuron does not appear to produce a toxic metabolite

produced by other substances. For the purposes of this action, therefore, EPA has not assumed 
Page 21 of 31

that diuron 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://www2.epa.gov/pesticide-science-and-assessing-pesticiderisks/cumulative-assessment-risk-pesticides.

Human Studies

The previous diuron risk assessments relied 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 the Pesticide Handlers Exposure 1.1 (PHED) Database, Outdoor Residential 

Exposure Task Force (ORETF) database, Agricultural Handler Exposure Task Force (AHETF) 

database, are (1) subject to ethics review pursuant to 40 CFR 26, (2) have received that review, 

and (3) are compliant with applicable ethics requirements. For certain studies, the ethics review 

may have included review by the Human Studies Review Board. Descriptions of data sources, 

as well as guidance on their use, can be found at the Agency website5. In addition, the new 

studies that are being performed by the Antimicrobial Exposure Assessment Task Force 

(AEATF) are being reviewed by the Human Studies Review Board (HSRB) as they are designed 

and completed. The recommendations made by the HSRB are being implemented to ensure that 

AEATF study participants are fully informed and protected as required by the “Protection of 

Human Subjects” regulation.

References

Author Barcode Date Title

S. Recore D428534 8/6/2015 Diuron: Review of Human Incidents.

D. Mcneilly 403844 8/29/2012 Diuron. Human Health Risk Assessment for the Special Local 

Need (SLN) Use of Direx 4L on Cotton. GA-120001.

C. Swartz D335228 5/15/2007 Diuron. Updated Aggregate Risk Assessment to Support

Permanent Tolerances for Residues in Cactus, Peppermint

Tops, Spearmint Tops, and Fish.

C. Christensen D291546 9/08/2003 DIURON: The REVISED HED Chapter of the Reregistration 

Eligibility Decision Document (RED).

Attachments

Attachment 1. Chemical Identity Table for Diuron

Attachment 2. Summary of Acute, Subchronic and Chronic Toxicity Profile

Attachment 3. Summary of Diuron Toxicological Doses and Endpoints for Use in Human 

Health Risk Assessments

Attachment 4. International Residue Limit Status

Attachment 5. Rationale for Waiving the Requirement for Magnitude of Residue Data in Cotton 

Gin Byproducts.

 

5 Available at: http://www2.epa.gov/pesticide-science-and-assessing-pesticide-risks/occupational-pesticide-handlerexposure-data and http://www2.epa.gov/pesticide-science-and-assessing-pesticide-risks/occupational-pesticide-postapplication-exposure.
Page 22 of 31

Attachment 1. Chemical Identity Table for Diuron

Table A.1. Diuron Nomenclature. 

Chemical structure

Common name Diuron

Molecular formula C9H10Cl2N2O

Molecular weight 233.1 amu

IUPAC name 3-(3,4-dichlorophenyl)-1,1-dimethylurea

CAS name N′-(3,4-dichlorophenyl)-N,N-dimethylurea

CAS registry number 330-54-1

End-use product (EP) Not applicable for this document. 

Table A.2. Physicochemical Properties of Diuron (Technical Grade). 

Parameter Value Reference

Melting point/range (oC) 156.4 ± 0.7 DuPont-197861

pH (25oC) 6.19 ± 0.05 (aqueous 1%, w/w)

Density (g/cm3at 20.6 ± 0.4oC) 1.5249 ± 0.0040

Water solubility (g/L at 20oC) 0.0394

Solvent solubility (g/L at 20oC) Acetone 47.2

Acetonitrile 15.5

Dichloromethane 20.5

Ethyl acetate 19.0

n-Hexane 0.0386

Methanol 36.5

n-Octanol 17.7

Toluene 1.55

Xylene 1.47

DuPont-190612

Vapor pressure (25oC) 5.18 x 10-6 Pa (3.89 x 10-8 mm Hg) DuPont-197861

Dissociation constant (pKa) No dissociation at environmentally 

relevant pH levels.

Octanol/water partition coefficient

(Log [KOW] at 20oC)

2.81 ± 0.013

UV/visible absorption (max, λ) 211 nm , 248 nm (secondary) DuPont-196713

1. Diuron (DPX-14740): Laboratory Study to Determine Physical Properties, DuPont-19786; E.I. 22uPont de 

Nemours and Company, Wilmington DE; A.L. Tunink (2006). 

2. Diuron (DPX-14740): Laboratory Study of Solubility in Organic Solvents, DuPont-19061; E.I. 22uPont de 

Nemours and Company, Wilmington DE; K.R. Serak (2006). 

3. Diuron (DPX-14740): Laboratory Study ofUV/Visible Absorption and Molar Absorptivity, DuPont-19671; E.I. 

22uPont de Nemours and Company, Wilmington DE; J.A. Hahn (2006). 
Page 23 of 31

Attachment 2. Summary of Acute, Subchronic and Chronic Toxicity Profile

Acute Toxicity of Diuron

Guideline No. Study Type MRID # Results

Toxicity 

Category

870.1100 Acute Oral 00146144

00146145

LD50 = 4721 mg/kg (M)

 >5000 mg/kg (F)

LD50 = >5000 mg/kg (M/F)

III

870.1200 Acute Dermal 00146146 LD50 >2000 mg/kg III

870.1300 Acute Inhalation 40228803 LC50 >7.1 mg/L IV

870.2400 Primary Eye Irritation 00146147 At 48 hrs, all irritation had 

cleared.

III

870.2500 Primary Skin Irritation 00146148 All irritation had cleared by 

72 hrs.

IV

870.2600 Dermal Sensitization 00146149 Nonsensitizer N/A

870.6200 Acute Neurotoxicity N/A Not available N/A

Diuron Subchronic, Chronic and Other Toxicity*

Guideline #/ Study Type MRID # (year)/ 

Classification/Doses

Results

870.3100

90-Day oral toxicity in 

rats 

MRID 40886502 (1988)

Acceptable/Nonguideline

0, 4, 10, or 25 ppm (0, 

0.3, 0.7, or 1.6 mg/kg/day 

for males and 0, 0.3, 0.8, 

1.8 mg/kg/day for 

females)

The NOAEL cannot be determined based on equivocal 

findings in the urinary bladder including blood vessel 

dilation, reduced transparency, and increased firmness.

870.3100

90-Day oral toxicity in 

rats

MRID 47800101 Submitted since last risk assessment, needs to be 

reviewed by HED.

870.3200

21/28-Day dermal 

toxicity in rabbits

MRID 42718301 (1992)

Acceptable/Guideline

0, 50, 500, or 1200 

mg/kg/day 

Systemic toxicity NOAEL =1200 mg/kg/day (HDT)

870.3200

90 day dermal toxicity in 

rats

MRID 46943902 Submitted since last risk assessment, needs to be 

reviewed by HED.

870.3465

21-Day inhalation 

toxicity

MRID 47169502 (1986)

6.6, 47,6, 311 mg/m3

Submitted since last risk assessment, needs to be 

reviewed by HED.

870.3700a

Prenatal developmental 

toxicity in rats

MRID 40228801 (1986)

Unacceptable/Guideline

0, 16, 80, or 400 

mg/kg/day

Maternal toxicity NOAEL = 16 mg/kg/day. Maternal 

toxicity LOAEL = 80 mg/kg/day, based on decreased 

body weight gain and food consumption.

Developmental toxicity NOAEL= 80 mg/kg/day.

Developmental toxicity LOAEL = 400 mg/kg/day, based 

on whole litter resorption, reduced fetal body weights, 

and delayed ossification of the vertebrae and sternebrae.

870.3700b

Prenatal developmental 

toxicity in rabbits

MRID 40228802 (1986)

Acceptable/Guideline

0, 2, 10, or 50 mg/kg/day

Maternal toxicity NOAEL = 10 mg/kg/day. Maternal 

toxicity LOAEL = 50 mg/kg/day, based on decreased 

body weight and food consumption.
Page 24 of 31

Diuron Subchronic, Chronic and Other Toxicity*

Guideline #/ Study Type MRID # (year)/ 

Classification/Doses

Results

Developmental toxicity NOAEL = 50 mg/kg/day (HDT).

870.3800

Reproduction and 

fertility effects in rats

MRID 41957301 (1990)

Acceptable/Guideline

0, 10, 250, or 1750 ppm. 

(0, 0.58, 14.8, or 101 

mg/kg/day for males and 

0, 0.71, 18.6, or 132 

mg/kg/day for females, 

respectively.

Parental NOAEL = 250 ppm (18.6 mg/kg/day).

Parental LOAEL =1750 ppm (132 mg/kg/day) based on 

decreased body weight, body weight gain, food 

consumption and food efficiency in both generations. 

Reproductive NOAEL = 1750 ppm (HDT).

Offspring NOAEL = 250 ppm (18.6 mg/kg/day). 

Offspring LOAEL = 1750 ppm (132 mg/kg/day) based 

on decreased body weight of the F1 and F2 pups during 

lactation.

870.4100

Chronic toxicity in dogs

MRID 00091192 (1964)

Unacceptable/Guideline

0, 25, 125, 250, or 

2500/1250 ppm (0, 1.8, 

9.4, 18.8, or 93.8 

mg/kg/day by conversion 

factor of 0.075) for 24 

months.

NOAEL = 125 ppm (9.4 mg/kg/day) in males and 250 

ppm (18.8 mg/kg/day) for females.

LOAEL = 250 ppm (18.8 mg/kg/day) for males and 

1250 ppm (93.8 mg/kg/day) for females based on anemia 

and body weight losses.

870.4100

Chronic toxicity in dogs

MRID 46943901 Submitted since last risk assessment, needs to be 

reviewed by HED.

870.4200

Combined Chronic/

Carcinogenicity in rats

MRID 

40886501,43871901, 

43804501, 44302003 

(1986)

Acceptable/Guideline

0, 25, 250, 2500 ppm (0, 

1.0, 10, or 111 mg/kg/day 

for males and 0, 1.7, 17, 

or 203 mg/kg/day for 

females) for 24 months. 

NOAEL = Not established.

LOAEL = 25 ppm (1.0 mg/kg/day for males and 1.7 

mg/kg/day for females) based on evidence of hemolysis 

and compensatory hematopoiesis (decreased erythrocyte 

counts, increased reticulocyte counts, increased spleen 

weight and bone marrow activation).

Dosing was considered adequate.

870.4200

Carcinogenicity in mice 

MRID 42159501 (1983)

Acceptable/Guideline

0, 25, 250, or 2500 ppm 

(0, 5.4, 50.8, or 640.13 

mg/kg/day for males and 

0, 7.5, 77.5, or 867.0 

mg/kg/day for females) 

for 24 months

NOAEL = 250 ppm (50.8 and 77.5 mg/kg/day) for males 

and females.

LOAEL = 2500 ppm (640.1 and 867.0 mg/kg/day) for 

males and females based on hemolytic anemia and liver 

toxicity in both sexes and urinary bladder toxicity in 

females.

Dosing was considered adequate.

870.5100

Gene mutation

Salmonella typhimurium

reverse gene mutation

MRID 00146608 (1985), 

40228805 (1991)

Acceptable/Guideline

Independent trials were negative in S. typhimurium

strains TA1535, TA97, TA98 and TA100 up to the 

highest doses tested (10 μg/plate –S9; 250 μg/plate +S9); 

higher concentrations (50 μg/plate –S9; 500 μg/plate 

+S9) were cytotoxic.

870.5100

Gene mutation

Salmonella typhimurium

reverse gene mutation

MRIDs 48337412

48337413

Submitted since last risk assessment, needs to be 

reviewed by HED.

870.5300

Gene mutation 

Chinese hamster ovary 

(CHO)/ HGPRT cell 

MRID 00146609 (1985)

Acceptable/Guideline

Independent tests were negative up to cytotoxic doses 

without S9 activation (1.250 mM, 291 μg/mL) and with 

S9 activation (0.5 mM  117 μg/mL).
Page 25 of 31

Diuron Subchronic, Chronic and Other Toxicity*

Guideline #/ Study Type MRID # (year)/ 

Classification/Doses

Results

forward gene mutation 

assay

870.5375

Chromosomal aberration 

in vivo rat bone marrow 

cytogenetic assay

MRID00146611 (1985)

MRID 44350301 (1997) 

(revised)

Acceptable/Guideline

The test was negative in Sprague Dawley rats up to

cytotoxic doses. A significant (p<0.05) increase in the 

percentage of abnormal cells and the average number of 

aberrations per cell was seen but only when the data 

were combined for the high-and mid-dose males and 

females at the 48-hour sampling time. A significant 

positive linear trend was also recorded for the combined 

(by sex) aberrations per cell and percentage abnormal 

cells. Nevertheless, the values fell well within the range 

of historical control ranges.

870.5375

Chromosomal aberration

MRID 48337411 Submitted since last risk assessment, needs to be 

reviewed by HED.

870.5375

Mouse Bone Marrow 

Micronucleus 

MRID 45494502 (1995) 

80% ai, 45494503 (1995) 

42.4% ai, 45494504 

(1996) 80% ai, 45494505 

(1998) 98.1% ai

Acceptable/Guideline

Preliminary review indicates no evidence of cytogenetic 

effect in mice administered either technical grade or 

formulated diuron.

870.5375

In Vitro Cytogenetics 

MRID 47169501 Submitted since last risk assessment, needs to be 

reviewed by HED.

870.5550

Unscheduled DNA 

Synthesis

MRID 00146610 (1985)

Acceptable/Guideline

The test was negative up to cytotoxic doses (0.33 mM, 

equivalent to 76 μg/mL).

870.5550

Unscheduled DNA 

Synthesis

MRID 47169503 Submitted since last risk assessment, needs to be 

reviewed by HED.

870.7485

Metabolism and 

pharmacokinetics

MRID 42010501 (1996)

Acceptable/Guideline

Metabolism data in the rat indicates that diuron is 

absorbed and metabolized within 24 hours post-dose at 

the low dose and within 48 hours post-dose at the high 

dose. The urine is the major route of excretion in both 

sexes; a small amount of diuron is detected in the feces. 

No apparent difference was observed between single and 

multiple low oral doses. There was no apparent sexrelated difference in either absorption or elimination. 

The highest tissue residue levels were found in the liver 

and kidneys 4 days post exposure. 

Nonguideline: Time 

course of early effects of 

diuron on the bladder 

epithelium of male 

Wistar rats.

MRID 48801301 Submitted since last risk assessment, needs to be 

reviewed by HED.

Nonguideline: Diuron 

Technical: Mechanistic 

Study in Sprague-Dawley 

and Wistar Rats

MRID 46480301 Submitted since last risk assessment, needs to be 

reviewed by HED.
Page 26 of 31

Diuron Subchronic, Chronic and Other Toxicity*

Guideline #/ Study Type MRID # (year)/ 

Classification/Doses

Results

Nonguideline: The 

Toxicological 

significance of IN-V3362 

(2-chloro-N,N-dimethyl4-nitroaniline) in diuron 

technical

MRID 48819002 Submitted since last risk assessment, needs to be 

reviewed by HED.

* The table has not been updated to the current version.
Page 27 of 31

Attachment 3. Summary of Diuron Toxicological Doses and Endpoints for Use in Human 

Health Risk Assessments

Summary of Toxicological Doses and Endpoints for Diuron for Use in Dietary and Non-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 No appropriate endpoint attributed to a single dose was identified. Therefore, an acute RfD was 

not established.

Chronic Dietary 

(All Populations)

LOAEL= 1 

mg/kg/day

UFA= 10x

UFH=10x

FQPA SF= 10x [UFL]

Chronic RfD = 

0.001

mg/kg/day

cPAD = 0.001 

mg/kg/day

Chronic toxicity/carcinogenicity 

study in rats

LOAEL = 1 mg/kg/day based 

on evidence of hemolytic 

anemia and compensatory 

hematopoiesis

Incidental Oral 

Short-Term (1-30 

days)

NOAEL= 10 

mg/kg/day

UFA= 10x

UFH=10x

FQPA SF= 1x

Residential LOC 

for MOE = 100

Developmental toxicity study in 

rabbits

LOAEL = 50 mg/kg/day based 

on decreased body weight and 

food consumption.

Incidental Oral 

Intermediate-Term 

(1-6 months)

NOAEL =1 

mg/kg/day

UFA= 10x

UFH=10x

FQPA SF= 1X

Residential LOC 

for MOE = 100

Chronic toxicity/carcinogenicity 

study in rats

LOAEL=10 mg/kg/day based 

on altered hematological 

parameters observed at 6 

months.

Dermal ShortTerm and 

Intermediate-Term

No systemic toxicity was seen following repeated dermal dosing at 1200 mg/kg/day in the 

rabbit dermal toxicity study. A dermal risk assessment was not conducted.

Inhalation ShortTerm (1-30 days)NOAEL= 10 

mg/kg/day

UFA= 10x

UFH=10x

FQPA SF= 1x

Residential LOC 

for MOE = 100

Developmental toxicity study in 

rabbits

LOAEL = 50 mg/kg/day based 

on decreased body weight and 

food consumption.

Inhalation 

Intermediate-Term 

(1-6 months)

NOAEL= 1 

mg/kg/day

UFA= 10x

UFH=10x

FQPA SF= 1x

Residential LOC 

for MOE = 100

Chronic toxicity/carcinogenicity 

study in rats

LOAEL=10 mg/kg/day based 

on altered hematological 

parameters observed at 6 

months.

Cancer (oral, 

dermal, 

inhalation)

A cancer slope factor of 1.91 x 10-2 has been established based on urinary bladder carcinomas 

in both sexes of the Wistar rat, kidney carcinomas in the male rat (a rare tumor), and mammary 

gland carcinomas in the female NMRI mouse.

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

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

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

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

population (intraspecies). UFL = use of a LOAEL to extrapolate a NOAEL. FQPA SF = FQPA Safety Factor. PAD = 

population adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of concern. 

N/A = not applicable. 
Page 28 of 31

Summary of Toxicological Doses and Endpoints for Diuron for Use in Occupational Human Health Risk 

Assessments

Exposure/

Scenario

Point of 

Departure

Uncertainty 

Factors

Level of Concern 

for Risk 

Assessment

Study and Toxicological Effects

Dermal (Shortand 

IntermediateTerm)

No systemic toxicity was seen following repeated dermal dosing at 1200 mg/kg/day in the 

rabbit dermal toxicity study. A dermal risk assessment was not conducted.

Inhalation 

Short-Term 

(1-30 days)

NOAEL= 10 

mg/kg/day

UFA= 10x

UFH=10x

Occupational LOC 

for MOE = 100

Developmental toxicity study in 

rabbits

LOAEL = 50 mg/kg/day based on 

decreased body weight and food 

consumption.

Inhalation 

Intermediateterm (1-6 

months)

NOAEL= 1 

mg/kg/day

UFA= 10x

UFH=10x

Occupational LOC 

for MOE = 100

Chronic toxicity/carcinogenicity 

study in rats

LOAEL = 10mg/kg/day based on 

altered hematological parameters 

observed at 6 months.

Cancer (oral, 

dermal, 

inhalation)

A cancer slope factor of 1.91 x 10-2 has been established based on urinary bladder 

carcinomas in both sexes of the Wistar rat, kidney carcinomas in the male rat (a rare 

tumor), and mammary gland carcinomas in the female NMRI mouse.

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

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

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

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

population (intraspecies). MOE = margin of exposure. LOC = level of concern. N/A = not applicable. 
Page 29 of 31

Attachment 4. Diuron International Residue Limit Status

Summary of US Tolerances and International MRLs

Diuron (PC Code 035505)

Residue Definitions

US Canada Mexico1 Codex2

3-(3,4-dichlorophenyl)-1,1-dimethylurea and its 

metabolites convertible to 3,4-dichloroaniline. 

N’-(3,4-dichlorophenyl)-N,NdimethylureaNone

Commodity Tolerance (ppm)/MRL (mg/kg)

US Canada Mexico1 Codex2

40CFR §180.106(a) General

Alfalfa, forage 3.0 

Alfalfa, hay 2.0 

Apple 0.1 

Artichoke, globe 1 

Asparagus 7 7

Banana 0.1 

Berry group 13 0.1 

Cattle, fat 1 

Cattle, meat 1 

Cattle, meat byproducts 1 

Citrus, oil 3.0 

Corn, field, grain 0.1 1 (Corn)

Corn, pop, grain 0.1 

Cotton, undelinted seed 0.2 

Fish - freshwater finfish, farm raised 2.0 

Fruit, citrus, group 10, except lemon 0.05 1 (Citrus fruits)

Goat, fat 1 

Goat, meat 1 

Goat, meat byproducts 1 

Grain, aspirated fractions 5.0 

Grape 0.05 1

Grass, forage, except bermudagrass 2 

Grass, hay, except bermudagrass 2 

Hazelnut 0.1 

Hog, fat 1 

Hog, meat 1 

Hog, meat byproducts 1 

Horse, fat 1 

Horse, meat 1 

Horse, meat byproducts 1 

Lemon 0.5 1 (Citrus fruits)

Nut, macadamia 0.05 

Olive 1 

Papaya 0.5 

Peach 0.1 

Pear 1 

Pea, field, seed 0.1 

Pea, field, vines 2 

Pea, field, hay 2 

Pecan 0.05 

Peppermint, tops 1.5 

Pineapple 0.1 1

Pineapple, process residue 0.4 

Sheep, fat 1 

Sheep, meat 1 

Sheep, meat byproducts 1 
Page 30 of 31

Summary of US Tolerances and International MRLs

Diuron (PC Code 035505)

Residue Definitions

US Canada Mexico1 Codex2

3-(3,4-dichlorophenyl)-1,1-dimethylurea and its 

metabolites convertible to 3,4-dichloroaniline. 

N’-(3,4-dichlorophenyl)-N,NdimethylureaNone

Commodity Tolerance (ppm)/MRL (mg/kg)

US Canada Mexico1 Codex2

Sorghum, grain, forage 2 

Sorghum, grain, grain 0.5 

Sorghum, grain, stover 2 

Spearmint, tops 1.5 

Sugarcane, cane 0.2 

Sugarcane, molasses 0.7 

Walnut 0.05 

Wheat, bran 0.7 

Wheat, forage 2 

Wheat, grain 0.5 1

Wheat, hay 2 

Wheat, straw 1.5

40CFR §180.106(c) Tolerances with regional 

registrations

Barley, bran 0.7 

Barley, grain 0.2 

Barley, hay 2 

Barley, straw 1.5 

Cactus 0.05 

Clover, forage 0.1 

Clover, hay 1.0 

Oat, forage 2 

Oat, grain 0.1 

Oat, hay 2 

Oat, straw 1.5 

Trefoil, forage 0.1 

Trefoil, hay 1.5 

Vetch, forage 0.1 

Vetch, hay 1.5 

MRLs with No US Equivalent

1 (Potato)

Completed: 21 November 2014

1. Mexico adopts US tolerances and/or Codex MRLs for its export purposes. 

2. There are no Codex MRLs established for diuron. 
Page 31 of 31

Attachment 5:Rationale for Waiving the Requirement for Magnitude of Residue Data in 

Cotton Gin Byproducts

Most gin trash used as livestock feed is generated in the TX/OK/NM area where stripper cotton 

is grown. These areas produce 38% of total feedlot beef. It is fed only to feedlot beef as 

roughage, at a maximum of 5% of the diet when available at harvest time. Picker cotton growing 

areas produce much less per acre. Technological harvesting advances in both stripper and picker 

types have decreased amounts available per season. Diuron is taken up by and translocated thru 

the roots and, to a lesser extent, thru the stems and leaves. Current tolerances for diuron in 

grains and seeds, and in their corresponding roughage commodities are:

1. Grains and seeds at 0.1-0.5 ppm; 

2. hay, straw, forage, stover and vines at 1.0-2.0 ppm;

3. aspirated grain fractions (AGF) at 5.0 ppm, and;

4. cottonseed at 0.2 ppm.

It would seem reasonable to assume that residues in gin trash would likely be less than 5.0 ppm; 

however, diuron residues were conservatively assumed to be present at 10 ppm in the gin 

trash. Based on calculation of the dietary burden to beef cattle from the 2003 RED document 

(D291550; S.L. Kinard; 9 July 2003), and incorporating cotton gin byproducts at 5% of the diet,

the dietary burden to beef cattle would rise from 6.0 to 6.2 ppm. For this small increase, there 

would be no need to revise the tolerances in ruminant commodities. Additionally, if the 

calculated dietary burden were based on current guidance, even with the exaggerated residue 

assumption of 10 ppm in cotton gin byproducts, it would most likely be lower than that derived 

in 2003 due to the use of median residue levels for blended/processed feedstuffs (a grouping 

which includes cotton gin byproducts).