UNIT E D STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON

, D .C. 20460

MEMORANDUM

Date: December 9, 2015 OFF I CE OF CHEMICAL SAFETY
AND POLLUTION PREVENTION

SUBJECT: Diuron

. Human Health Assess m e nt Scop in g D oc ument i n Support of Regis t ration R eview.

PC Codes: 035505
Deci s ion No.: 496087
Petition No.: NA

Ri s k A ss e ss ment Type: NA

TXRNo.: NA

MRID No .: NA DP Barcode: D4 2323 l Registration No.: NA Regulatory Action: Registration Rev i ew Case No.: 0046
CAS No.: 330

- 54 -1
40 CFR: 1 80. 1 06

FROM: Kar l yn Middleton

, To x ic o l og i s t / Ri s k ass ssor , Za i da Figueroa

, I ndustr i a l Hy g i e ni s t
7 

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William Dr ew, Chemist

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### j //,

Katel y nn King

, Chemis t ( H ED,

## Tfis1**11**

## A~e~~ Br anch 7) 

## /vi i(/ARi sk Assessment Branch II

H ea lth Effec t s Division (7509P)

Office of P es ti c id e Pr ograms**~ ~..O**  T imoth y D o l e , I ndu s tri al Hy g i e ni st 0

### ~,**~** 

## C!, .J-"() '-( Jonathan Chen

, Tox i cologist**4':~** Risk Assessme n t Science Suppo rt Bran ch
Antim i crobia l s Division (75 1 O

P )
Office of P es tic id e Program s



### THROUGH: Chris tin a Swartz, Branch C hi ef {:\,

# ~ Risk Assessment Branch II**~** Dana Voge l

, D ivisio n Direct o r Jess Rowland

, Deputy Division Dir ecto r

### ~~**~** H ea l th Effec t s Di v i s ion (7509P)**~ ~**  / ,.-- S t

eve Weiss

, Branch Chief

### ~ (,,,,V..ec./ Risk Assessmen t Scie n ce Suppo r t Branch

An timi crob i als Division (751 O P )
Office of P es ti cide Program s

TO: Katherine St. C l a ir

, Chemi ca l Rev i ew Mana ge r P

es ticid e R e-Eva luation Di vis i o n (7508 P )
Office of Pestic i de Program s San Yvette Williams

, Chem i cal R ev iew Manager
Ant imicrobi als Di v ision (75 1 O

P )
Office of P es ti cide Pr ogra m s

Pa ge I of 3 1Th e Health Effects Division ( HED) and Antimicrobials Division (A D ) human h ea lth risk assessment scopi n g document for diuron to support r eg i strat ion r eview is presented below. HED rev i ewed the

convent i onal uses of diuron

, whi le AD reviewed the antimicrobial uses [note: a lthough H ED eva luated the

mild ewc ide u se (paints and s tains) previ o u s ly (2003), during regi s tration revi ew the use patt e rn falls und er the purview of AD]. This do cume nt s ummarizes HED ' s and A D ' s eva luation of th e data available for assessing human health risk from exposure to diur on , as we ll as any data ne eded to suppo rt r egistrat i on

r ev i ew.

Exec uti ve S umma ry

The H ealth Effec t s Di visio n ( l IED) and the Ant imicrobi als Division ( A D ) have evaluated th e available data

, expos ur e information

, and th e most r ecent human h ealt h risk assessmen t for the

herbicide diuron. This eva l uation was performed in order to determine the scope of work

necessary to suppo rt the established tol era nce s and ex i s tin g registrations for diuron. The primary

sou r ces of inform a ti on we r e recent hum a n h ea lth r i sk assessmen t s (D335228 ; C. Swartz ; 511512007 and D403844; D. McNeilly; 8 / 29 / 2012)

, the Revised HED C hapt er of the

R e r eg i strat i on E ligibility D ec i s ion (RED) document for diuron (0291546; C. C hri ste nson ;
9 / 8 / 2003), and toxicity and r es idue studies su bmitted as required during regi s tration. H ED and

AD have evaluated this info r mation for diuron in association with the updates to to xicity,

expos ure , and usage databa ses to determin e if sufficie nt data are ava i lable and if further updates

are n ee ded to s upport regi s tration revie w.

Diuron [3

- (3

, 4-Dichlorophenyl)-l

, l-dim e th y lurea] is a pre- and post-emergent h erbici de u sed t o

con tr ol annual and perennial broad leaf and grassy weeds in a var i ety of agricultural crops , ornamental trees a nd non- c r op s ite s

. It i s a l so u sed as a mildewcide in paints and sta ins

, and as

an algaecide in co mmercial fish product i on. Product s containing diuron are u sed in occupational

se ttin gs, includin g agricultural food crop s and non-food crops, ornamenta l tre es, flow e rs and

shrubs

, paints and coat in gs , orname nt al fish ponds and catfish production, ri gh t s

- of

- way and

indu stria l sites. Residential uses of diuron includ e ponds

, aquariums a nd paints. The r e is a l so a Spec ial Local Need (S LN) u se in Geor g i a o n Cotton.

The toxicology database for diuron is n o t co mplet e. Th e Hazard and Sc ienc e Policy Counc il ( H AS POC ) determined that an ac ute n euro t oxic it y (ACN) s tud y i s needed for diuron. In th e absence of an ACN study

, th e I OX FQPA factor would be retained as a database uncertainty

factor and app li e d to the acute dietary ri s k assessment (on ly). The immunotoxicit y and

subchronic n e urotoxicit y s tudi es are not ava ilable for diuron ; how eve r , the HASPOC ha s dete rm ined that these studies are not needed based on a weight of evide nc e approach

,

co n sider ing the avai labl e hazard a nd exposure information ( TXR # 0057097).

Th e target organs for diuron are the hemat o poietic sys te m , bladder

, and kidney

. No evidence of

in c r ease d s u scep tibilit y was obse r ved in th e available developmental and reproduction toxi c it y stud i es. Diuron i s c l assified as a ' ·kn own/l ik ely " human carc ino ge n , based on urinary bladder

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

g l and carcinomas in the female NMR I mou se. A lin ea r low dose ex trapolation model (QI*) was

rec o mm e nded fo r th e quantification of human cancer ri sk

, based on the urinary bladder

ca r c in o mas in th e rat. Since th e last assessment

, a mode of action (MOA) ha s been proposed by

Page 2of3 1Page 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 assessment s ( D3 35228 ; 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 ris k assessment. The FQPA
factor was reduced to 1X for all other scenarios.

HED has not revised t he 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 fin dings 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
als o 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 m ethod (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; t hey 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
ri sk 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 I LV. 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., recreati onal fish and backyard ponds) and t he 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 assessment s for the aquatic use to reflect current exposure assumptions and science methodology for aquatic a ssessments (e.g., Aquatic Use Residential SOP). H owever , 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 , t here are an timicrobial 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 p rotective of the other uses, was evaluated in the RED for residential handler inhalation exposure when applying paint using airless sprayers and brushes and rollers ; non

cancer risk estimates were not of concern. These risk estimates will need to be reevaluated during registration review to account for any update s 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 estimate s were also evaluated and were not of concern given the conservative nature of the exposure assumption s used. Although residential post

- application exposures to paint vapors were evaluated for the RED u sing 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 w ith 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 se rved 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 a ny 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 post

application (cancer) exposures to support the registered uses

. N ew occupational handler and
post

- application assessments will be conducted for existing uses based on updated scientific procedures for dermal and inhalation risk assessment

, t he 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 A ttachment 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 A C N 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 wou ld be retained as a database uncertainty factor and applied to the acute dietary risk assessment (only). I mmunotoxicity and subchronic neurotoxicity studies are also not available for diuron . Additionally, the availablePage 5 of 31

developmental rat study was clas sified 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

, b ased o n a weight of
evide nce approach, considering the available hazard and expo sure 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 a cceptable/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, e rythrocyte 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 erythr ocyte 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 mou se 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 Attachmen t 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 dose s ; p iloerection was observed at the high dose. No effects were seen at the low
dose.

No e vidence 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 t he 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. D iuron 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 fem ale 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 ( Q 1 * of 1.91 x 10

-

2 (mg/kg/day)

- 1 ). There is no mutagenicity co ncern 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, i f 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, derma l, 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 appropria te 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 assessment s 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. R esidential and occupational risk assessments for dermal and inhalation exposure were also conducted. A n ew rat dermal study
and inhalation stud y are available for diuron. Therefore, the endpoints/PODS for dermal a nd 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 u sed 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 int ermediate

- term incidental oral and inhalation risk

as sessments . 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 a nd 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. Th e dietary (food and drinking water) and non

- dietary (residential) exposure assessments will not underestimate the potential exposures for infants and
children.

Conclusions for Haza rd 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) significan t 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 tha n those currently used for risk assessment. Also, an i mmunotoxicity is not required, based on lack of evid ence of potential immunotoxicity at relevant dose levels.Page 7 of 31

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

,

w hich 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) re consideration of sa fety/uncertainty factors, including the FQPA safety factor.

New mechanistic studies have been submitted to address the bladder tumors observed after exposure to diuron. However, i f the registrant would like the Agency to consider a proposed
mode of actio n 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 conver tible 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 monochlorophenyldime thylurea (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 provid e 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 fenur on (an obsolete phenylurea herbicide with very low toxicity t o animals ), occurs at roughly 13% under anaerobic aquatic conditions only. Similarly, mCPMU occurs at approximate ly 2 1% under anaerobic aquatic conditions only. Results from a DEREK analysis (w hich compares the toxicity of metabolites and/or degradates relative to the parent compound, b ased on structural
similarities and differences ) of mCPMU did not indicate any toxicity that would differ from that of the parent compound , diuron

. HED has deter mined 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 th e existing residue chemist ry 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
fo rage, 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)

.

A dditional 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 livestockPage 8 of 31

commodities was requested, and MRM testin g 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 n ot 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 need ed (refer to the ratio nale in A ppendix 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 r epresentative 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 pe r 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 da ta. 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 guid ance , 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 40CF R §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 belo w is to be determined byPage 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. Complian ce 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
incr eases 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 healt h 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

- chl orophenyl)

- 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 (FF DCA) 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 cle ared 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 or der 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 (review ing 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 f or the antimicrobial uses

.

Residential Exposure

There are potential residential exposures from activities associated with: 1) pond s and aquarium s and 2) paint use s

. 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 us ing 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. Christe nsen; 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 r isk esti mates 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

- 6 to 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 toxicolog y 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 conduct ing quantitative non

- cancer and cancer post

- application exposure assessment s 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 t oxicology endpoints

. In addition, an inhalation exposure

- indoor stud y (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 antic ipated 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 exp osures 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 f or Residential RiskPage 12 of 31

Assessment (SOPs)

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

occupational exposure to drift. In terms of volatilization, the agency has developed a
Vola tilization Screening Tool and a subsequent Volatilization Screening Analysis 1 . 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, assumpti ons, 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 tox icological 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

- OPP

2014

- 0219.Page 13 of 31

Aggregate Risk Assessment

The most recent aggregate risk assessment was performed for the conventional uses in conjunctio n 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 residu es 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 t he 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 c ancer 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

The re 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 aggre gate 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, f

lowers and shrubs, ornamental fish ponds and catfish production, rights

- of

way and industrial sites. Diuron is formulated as a granule, water dispersible granule, dry flowable, emulsifiable concentrate, liquid flowable concentrate, soluble concentrate and ready

to

- 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 fr om 0.8 lbs active ingredient (ai)/acre for corn to 87.1 lbs ai/acre for non

crop areas (e.g., utility and industrial areas)

.Page 14 of 31

There are n ew dermal (rat) and inhalation toxicity studies are available for diuron. Therefore,
the dermal and inhalation toxicol ogical endpoints will be revisited during registration review

. Based on a cursory review of the new dermal stud y , 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 th e 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 personal

protective equipment (PPE) when necessary (e.g., respirators and engineering controls).

Based on existing registrations, the previous assessments ( D2915 46 ; D335228 ; D 403844 ) 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 scenario s at some level of personal protective equipment (PPE).

Since no systemic toxicity following repeated dermal dosing was seen in th e rabbit dermal toxicity study, a quantitative non

- cancer dermal risk assessment was not previously conducted as part of th e 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 toxic ity 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 expe cted 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

- applicati on (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 post

application risk assessment will be required for workers conducting post

- application activities

. In accordance with the updated Part 158 data requirements (2007), one or mo re DFR studies arePage 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

. I n accordance with the 40 CFR DFR data r equirement

, 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 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 re port 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 Reentr y 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 expos ure 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

Occu pational 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 patter n 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, highPage 16 of 31

temper ature environments. If it is assumed that the paint density is 1 1.2 lb per gallon, then the
use rate is 0.0 532 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 n on

- cancer and cancer occupational risk estimate s 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 al so 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 dur ing 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 pestici de 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

O ccupational 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

- 4 at 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 e xposures for occupational handlers 2

, 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 bein g 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 f or 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 T ask 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 stud ies and updated exposure inputs

.

 HED anticipates conducting quantitative residential non

- cancer and cancer post

application exposure assessments for the aquatic use to reflect updates in toxicologica l 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, neurotoxici ty, 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 maturat ion, 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 sectio n 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 h umans 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 cons ists 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

- relate d effects caused by the substance, and
establish a dose

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

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

- ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of chemicals identified for EDSP screening was published on June 14, 2013 3 and 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 schedu led 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 ( D 428534 , S. Recore

, 8 /6 /2015 ). Diuron is not included in the Agricultural Health S tudy (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 identifie d 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 w ere 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 w as 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 tr eated 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. T he 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 Righ t

- 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 b etween 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 fr om the public and to incidents. From 2009 to June 30, 2014, 6 incidents were reported to NPIC
i nvolving diuron. NPIC estimates a certainty index as to whether an incident (including reported

4 http://www2.epa.gov/endocrine

- disruptionPage 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 unrela ted 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 pr obable 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 establ ished 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 commodit ies 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, “Fede ral 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 expo sures 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 e xposed 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 to xic metabolite produced by other substances. For the purposes of this action, therefore, EPA has not assumedPage 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 substance s found to have a common mechanism on
EPA’s website at http://www2.epa.gov/pesticide

- science

- and

- assessing

- pesticide

risks/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

s tudies from the Pest icide 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 website 5

. 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

H uman S ubjects ” regulation.

References

Author Barcode Date Title

S. Recore D 428534 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 Re sidues in Cactus, Peppermint Tops, Spearmint Tops, and Fish.

C. Christensen D2915 46 9 /0 8 /2003 DIURON: The REVISED HED Chapter of the Reregistration Eligibility Decision Document (RED).

Attachment s

Attachment 1. Chemical Identity Table for Diuron
Attachment 2. Summary of Acute, Subchronic and Chronic Toxicity P rofile
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

- handler

exposure

- data and http://www2.epa.gov/pesticide

- science

- and

- assessing

- pesticide

- risks/occupational

- pesticide

- post

application

- exposure.Page 22 of 31

Attachment 1

. Chemical Identity Table for Diuron

Table A.1

. Diuron Nomenclature.

Chemical structure

Common name Diuron

Molecular formula C 9 H 10 Cl 2 N 2 O 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

- 19786 1 pH (25oC) 6.19 ± 0.05 (aqueous 1%, w/w) Density (g/cm 3 at 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

- 19061 2

Vapor pressure (25oC) 5.18 x 10

- 6 Pa (3.89 x 10

- 8 mm Hg) DuPont

- 19786 1 Dissociation constant (pK
a ) No dissociation at environmentally relevant pH levels. Octanol/water partition coefficient (Log [K OW ] at 20oC) 2.81 ± 0.013

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

- 19671 3

1. Diuron (DPX

- 14740): Laboratory Study to Determine Physical Properties , DuPont

- 19786; E.I. 22 uPont 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. 22 uPont 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.

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

Attachment 2

. Summary of Acute, S ub chronic and Chronic T oxicity Profile

Acute Toxicity of Diuron

Guideline No

. Study Type MRID # Results Toxicity Category

870.1100 Acute Oral 00146144

00146145 LD 50 = 4721 mg/kg (M)

>5000 mg/kg (F)

LD 50 = >5000 mg/kg ( M/ F) III

870.1200 Acute Dermal 00146146 LD 50 >2000 mg/kg III

870.1300 Acute Inhalation 40228803 LC 50 >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 tran sparency, 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/m 3 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 effici ency 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 F 1 and F 2 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
Ge ne 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 MRID s 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 dete cted in the feces. No apparent difference was observed between single and multiple low oral doses. There was no apparent sex

related difference in either absorption or elimination. The highest tissue residue levels were found in the liver and kidneys 4 da ys 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: Mechani stic Study in Sprague

- D a w ley
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

T oxicological significance of IN

- V3362 (2

- chloro

- N,N

- dimethyl

4

- 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 UF A = 10x

UF H =10x FQPA SF= 10x [UF L ] 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 UF A = 10x

UF H =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 UF A = 10x

UF H =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 Short

Term 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 Short

Term (1

- 30 days) NOAEL= 10

mg/kg/day UF A = 10x

UF H =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 UF A = 10x

UF H =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 a ssociated with lower environmentally relevant human exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential va riation in sensitivity among members of the human population (intraspecies). UF L = 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 expo sure. 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 (Short

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
Short

- Term (1

- 30 days) NOAEL= 10

mg/kg/day UF A = 10x

UF H =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
Intermediate

term (1

- 6

m onths) NOAEL= 1

mg/kg/day UF A = 10x

UF H =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. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (intraspecies). MOE = margin of exposure. L OC = 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 Mexico 1 Codex 2

3

- (3,4

- dichlorophenyl)

- 1,1

- dimethylurea and its metabolites convertible to 3,4

- dichloroaniline. N’

- (3,4

- dichlorophenyl)

- N,N

dimethylurea None

Commodity Tolerance (ppm)/MRL (mg/kg)
US Canada Mexico 1 Codex 2 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 1Page 30 of 31 Summary of US Tolerances and International MRLs

Diuron (PC Code 035505)
Residue Definitions
US Canada Mexico 1 Codex 2

3

- (3,4

- dichlorophenyl)

- 1,1

- dimethylurea and its metabolites convertible to 3,4

- dichloroaniline. N’

- (3,4

- dichlorophenyl)

- N,N

dimethylurea None

Commodity Tolerance (ppm)/MRL (mg/kg)
US Canada Mexico 1 Codex 2 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 f ed 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 w ould 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
calculat ed dietary burden were based on current guidance , even with the exaggerated residue assumption of 10 ppm in cotton gin byproducts, i t 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 byprod ucts).