UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

DATE: August 5, 2014 

OFFICE OF CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

SUBJECT: Diclofop-methyl: Human Health Assessment Scoping Document in Support of 

Registration Review. 

PC Code: 11 0902 

Decision Nos.: 490582 

Petition Nos.: NA 

Risk Assessment Type: Single Chemical 

Aggregate 

TXRNo.: NA 

MRIDNo.: NA 

FROM: Sheila Piper, Chemist bh~~ 

DP Barcodes: 0419904 

Registration No.: 241-427 

Regulatory Action: Registration 

Review 

CaseNo.: NA 

CAS No.: 51338-27-3 

40 CFR: 180.385 

Yung Yang, Ph.D., Toxicologist td(J 6 - (;/e>?7 . ~ 1 • 

Monica Hawkins, Ph.D., M.P.H., Bbv1ronme~tal Health Scientist AA \}~fin»J~ Risk Assessment Branch VI 

1 

v~ Health Effects Division (7509P) 

THROUGH: Donna Davis, Acting Branch Chief ~tJJ../2~ Risk Assessment Branch VI 

Health Effects Division (7509P) 

TO: Marianne Mannix, Chemical Review Manager 

Pesticide Re-Evaluation Division (7505P) 

Risk Management & Implementation Branch 3 (RMIB3) 

Executive Summary 

The Health Effects Division (HED) Diclofop-methyl Registration Review Team has evaluated 

the status of the human health risk assessment for diclofop-methyl to determine the scope of 

work necessary to support Registration Review. The primary source of information for this 

evaluation was the most recent human health risk assessment written for diclofop-methyl 

(Memo, D268403, C. Jarvis, 08/1 0/2000). 

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Diclofop-methyl Registration Review Human Health Seeping Document 

Diclofop-methyl was first registered in 1982 as an herbicide that controls wild oats and annual 

grassy weeds in wheat and barley, as well as in established bermuda grass turf on golf courses. 

Exposures can be expected to occur via the dietary, drinking water, and occupational (handler 

and post-application) routes. There are no registered residential uses of diclofop-methyl; 

however, there is the potential for residential exposure to golfers from contact with turf treated 

by commercial applicators. 

The toxicology database for diclofop-methyl is complete; no additional data are required to 

support the registration review. The diclofop-methyl registration review team has evaluated the 

toxicity database and reviewed the endpoints, doses and safety/uncertainty factors selected for 

this chemical and finds them to reflect current policies. No new data is anticipated and no 

further review of the points of departure of SFIUFs are required for this chemical. 

There are no outstanding residue chemistry data. The dietary exposure database is adequate to 

support the registration review of diclofop methyl. No dietary (food and water) risks of concern 

were identified; however, EFED has indicated that an updated drinking water assessment is 

required. Should the revised drinking water concentrations significantly increase, a revised 

dietary risk assessment may be required. 

Based on current HED policy, a turf transferrable residue (TTR) study is required for diclofopmethyl to support the use on golf courses. An updated residential exposure assessment will be 

required under registration review which incorporates the findings of the TTR study and the most 

updated residential standard operating procedures (SOPs) to address post-application exposure to 

adults and children golfing on commercially treated turf. 

An updated aggregate risk assessment will be required in registration review which incorporates 

updated drinking water estimates and revised residential post-application exposure estimates 

from the established golf course use. 

The current tolerance expression should be updated to comply with HED's current policy on 

tolerance expressions during registration review. The residue definition in the US is harmonized 

with the Canadian Maximum Residue Limit (MRL) expression; Codex has no MRLs for diclofopmethyl. The barley and wheat tolerances at 0.1 ppm are harmonized with Canada. Mexico adopts the 

standards of the US for its export purposes. 

Dislodgeable Foliar Residue (DFR) studies (wheat/barley) are required for diclofop-methyl at 

this time based on HED policy. An updated occupational handler exposure assessments will be 

required based upon revisions to the Agency's scenario-specific surrogate handler exposure data. 

Introduction 

HED has evaluated the most recent complete human health risk assessment for diclofop-methyl 

to determine if sufficient data are available and if updates are needed to support registration 

review. The latest risk assessment was conducted in 2000 (C. Jarvis, 0268403, 08/1 0/2000). 

HED has also considered updates to its toxicity, exposure and usage databases, and the latest 

Agency science policy and risk assessment methodologies. 

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Diclofop-methyl Registration Review Human Health Scoping Document 

Diclofop-methyl is classified by the Agency as a restricted use pesticide due to carcinogenicity in 

laboratory mice, and may be purchased and used only by certified applicators. Diclofop-methyl 

may be applied pre-plant, pre-emergent, or post-emergent, and is applied by fixed-wing aircraft 

and tractor-drawn equipment, as well as by hand held equipment. The registered product is 

emulsifiable concentrate (EC) formulations and the maximum label rate is 1.0 lb. ai!acre for 

wheat and barley, and 1.02 lb. ai/acre for golf course turf. There is a maximum of one 

application per growing season. 

Information on the chemical identify of diclofop-methyl is included in Attachment 1. 

Hazard ldentificationffoxicology 

Diclofop Methyl Herbicide is a member of the aryloxphenoxypropionate class of herbicides that 

is an inhibitor of acetyl CoA carboxylase. 

The toxicology database for diclofop-methyl is complete, no additional data are required. While 

the current 40 CFR Part 158 Toxicology Data Requirements include subchronic inhalation, 

immunotoxicity, and neurotoxicity (acute and subchronic) studies, these studies were not 

submitted for diclofop-methyl. However, the Hazard and Science Policy Council (HASPOC) 

determined that based on a weight-of-evidence (WOE) approach, considering all the available 

hazard and exposure information for diclofop-methyl, subchronic inhalation, immunotoxicity, 

and neurotoxicity (acute and subchronic) studies are not required to support the registered uses of 

diclofop-methyl (TXR#0056963, 5/8/2014). 

Diclofop-methyl exhibits moderate to low acute toxicity via the oral and dermal routes of 

exposure (toxicity category II and III, respectively), but is less toxic by the inhalation route of 

exposure (toxicity category IV). In primary irritation studies, diclofop-methyl produced moderate 

ocular irritation (toxicity category III) and slight dermal irritation (toxicity category IV). It was 

considered to be a moderate to severe sensitizer in a maximization test; the Buehler test was 

negative. 

Diclofop-methyl toxicity database identified the liver as the target organ. Liver weights were 

increased in treated animals in all ofthese studies. In the two-generation study, increased liver 

weights were observed across generations in both sexes; in some cases, pup liver weights were 

also affected. Histological examination of the livers revealed an increased incidence of hepatic 

lesions following subchronic oral and dermal exposure and multi-generational exposure. 

Carcinogenicity studies in the rat and mouse showed increased incidence of adenomas and 

carcinomas of the liver. No evidence of mutagenicity was seen in any study. The Agency's 

Cancer Assessment Review Committee classified diclofop-methyl as a Group C carcinogen 

(possible human carcinogen) with a Q1* of2.3 x 10-1 (mg/kg/dayy1 based on 

hepatocarcinogenesis in the mouse carcinogenicity study. 

Developmental toxicity studies were conducted in the rat and rabbit. In the rat study, 

developmental toxicity was observed only at maternally toxic doses. Systemic maternal toxicity 

was observed at the lowest dose tested and consisted of increased absolute and relative liver 

weights. At the mid-dose level, decreased fetal body weight and decreased crown-rump length, 

Page 3 of20 
Diclofop-methyl Registration Review Human Health Scoping Document 

distended ureters, and skeletal abnormalities were observed. In the rabbit study no developmental 

toxicity was seen; maternal toxicity, consisting of increased liver and kidney weights, decreased 

body weights, and reduced food consumption, was observed only at the high dose. 

The acute reference dose (RID) ofO.l mg/kg/day (NOAEL=10 mg/kg/day) for females 13-50 

years old is derived from the developmental toxicity study in the rat, based on significant 

decreases in fetal body weight and crown-rump length, distended ureters, and skeletal 

abnormalities at the LOAEL of 32 mg/kg/day. No appropriate endpoint was identified for the 

U.S. general population, including infants and children. The chronic RID of 0.0023 mg/kg/day 

(NOAEL= 0.23 mglkg/day) is derived from a combined chronic feeding/carcinogenicity study in 

the rat, based on increased absolute and relative liver and kidney weights, increased ALT (alanine 

aminotransferase), AST (aspartate aminotransferase), and AlkP (alkaline phosphatase) activities, 

impaired lipid and protein metabolism, and histopathology (hypertrophy, lipofuscin storage) in 

males and females at the LOAEL of2.3 mg/kg/day. The short- and intermediate-term dermal risk 

assessment was based on a 21 -day dermal toxicity study in the rat with a NOAEL of 5 

mg/kg/day, the LOAEL was 25 mg/kg/day based on increased liver enzymes, proteins, and 

absolute and relative liver weights. A dermal absorption factor (after 10 hours of exposure) of 

15% will be used to convert the oral dose to an equivalent dermal dose for the cancer risk 

assessment only. No inhalation study is available except the acute inhalation study. The 

subchronic feeding study in the rat with NOAELILOAEL of 1.6/6.3 mg/kg/day, respectively is 

selected for short- and intermediate-term inhalation risk assessment since the effect (liver 

toxicity) is consistent with the other studies in both rats and mice. The current use pattern for 

diclofop-methyl does not indicate a concern for long-term inhalation or dermal exposure. 

There is no evidence for increased quantitative or qualitative susceptibility of the young 

following in utero and pre-and post-natal exposure to diclofop-methyl based on the results from 

developmental studies conducted with rats and rabbits, as well as a two-generation reproduction 

study conducted with rats. The risk assessment team concluded that the FQPA Safety Factor 

could be reduced to 1. 

Metabolism studies in the rat indicate that diclofop-methyl is extensively absorbed, metabolized 

and excreted through the feces (69.7 to 77.9%) while less was eliminated in the urine (16.4 to 

18.9%); no measurable amount(< 0.01%) ofradioactivity was found in expired air. Residual 

radioactivity was found mainly in the liver, kidney and digestive tract; the highest levels of 

radioactivity were found in the fat. Two metabolites were identified in both the urine and feces 

as hydroxylated and de-esterified parent compounds. 

Conclusions for Hazard Identification/Toxicology 

The toxicology database for diclofop-methyl is complete, no additional data are required. The 

HASPOC determined that based on a weight-of-evidence (WOE) approach considering all the 

available hazard and exposure information for diclofop-methyl, subchronic inhalation, 

immunotoxicity, and neurotoxicity (acute and subchronic) studies are not required to support 

registered use of diclofop-methyl at this time. The selected PODs and toxicological endpoints 

from the most recent human health risk assessment are summarized in the attachment. 

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Diclofop-methyl Registration Review Human Health Scoping Document 

No new data have been reviewed since the last toxicological assessment for diclofop-methyl. 

Additionally, the team has reviewed the points of departures and safety factors and concluded 

that they consider all appropriate data and are consistent with current science policy. 

Dietary Exposure 

The existing residue chemistry database for diclofop-methyl is adequate for risk assessment 

purposes. Tolerances are established for diclofop-methyl under 40 CFR § 180.385 in/on barley 

and wheat commodities. The nature of the residue in plants is adequately understood. The 

residues of concern in plants is diclofop-methyl (parent), diclofop acid, and hydroxyl diclofop 

(free and conjugated). Based on the results of metabolism studies in ruminants, and a poultry 

feeding study, tolerances are required for residues in meat and milk as a result of ingestion of 

diclofop-methyl residues in the livestock feed. Tolerances have been proposed for barley hay, 

wheat forage, wheat hay, and livestock commodities and should be included in the 40 CFR for 

diclofop-methyl. Tolerances are not required for residues of diclofop-methyl in eggs and poultry 

tissues. Acceptable_ analytical methods are available to enforce tolerances for residues of 

diclofop-methyl in plant and livestock commodities. 

The most recent dietary exposure and risk assessment was conducted in 2000 (D267649, R. 

Griffin, 08/03/00). HED conducted a partially refined, acute and chronic dietary risk 

assessments for diclofop-methyl using anticipated residues, percent crop treated, and included 

modeled estimated drinking water concentrations. The Environmental Fate and Effects Division 

(EFED) provided a refined surface water and a Tier 1 groundwater analysis for diclofop-methyl, 

using computer modeling, existing monitoring data, and a small scale prospective groundwater 

study which were incorporated into the most recent risk assessment for this chemical. The 

residues of concern for drinking water are diclofop-methyl (parent) and its metabolite, 2-[ 4-(2,4-

dichlorophenoxy)phenoxy ]propanoic acid. PRZMIEXAMS and SCI-GROW modeling 

estimates, as well as monitoring data from the prospective groundwater study, are based on 

parent diclofop-methyl and its acid metabolite. EFED has indicated that updated drinking water 

exposure estimates are needed for diclofop-methyl during registration review. 

The acute dietary assessment was limited to the females 13-49 years of age population subgroup. 

This is the only population subgroup for which an appropriate toxic endpoint attributable to a 

single dose was identified. For females 13-49 years of age, acute dietary (food and water) risk 

was S 8% of the acute population adjusted dose (aPAD). Estimated chronic dietary (food and 

water) risks for the U.S population and all regulated population subgroups were S 1% of the 

chronic PAD (cP AD). Carcinogenic risk for diclofop-methyl is quantified, based on the 

estimated average dietary exposure of the general U.S. population (5x1o-6 mg/kg bw/day) 

multiplied by the upper-bound potency factor (Q1*) of2.3 x10-1 (mg/kg/dayy1. On this basis, the 

upper-bound carcinogenic risk estimate for diclofop-methyl is calculated to be 1.2 x 1 o-6). 

Conclusions for Dietary Exposure 

The residue chemistry database is considered complete and the dietary exposure database is 

adequate to support the existing registration. Tolerances have been proposed for barley hay (6 

ppm); wheat forage (12 ppm); wheat hay (1 ppm); meat by-products, excluding kidney (7 ppm); 

Page 5 of20 
Diclofop-methyl Registration Review Human Health Scoping Document 

kidney (25 ppm); milk (4 ppm); and in the meat and fat of cattle, goat, horses, and sheep (1 ppm) 

and should be included in the 40 CFR for diclofop-methyl. An updated dietary (food and 

drinking water) risk assessment may be conducted during registration review process should the 

updated drinking water exposure values vary significantly from the values used in the current 

assessment. 

Residential (Non-Occupational) Exposure and Risk 

Diclofop-methyl, an emulsifiable concentrate, is a restricted use pesticide that is currently 

registered for use on golf course turf. Diclofop-methyl is restricted from use on residential 

turf/lawns, however there is the potential for residential exposure from contact with turf treated 

by commercial applicators during golfing activities; however, based on the use on golf courses, 

adults and older children may experience exposure to diclofop-methyl as a result of contacting 

commercially treated turf (i.e., residential post-application exposure). 

Residential Handler 

Diclofop-methyl is a restricted use pesticide. Label language restricts the sale and use of this 

pesticide to licensed applicators. There are no residential handler exposure scenarios expected 

for diclofop-methyl and residential handler exposure assessments were not conducted and are not 

required. 

Residential Post-Application 

In accordance with 40CFR158, TTR data are required for all occupational (e.g., sod farms, golf 

courses, parks, and recreational areas) or residential turf uses that could result in post-application 

exposure to turf. HED developed a waiver policy for TTR studies. The MOEs from the 

assessment, using default TTR values are evaluated. If those are 1 0 times higher than the level 

of concern (LOC) the TTR studies can be waived. Residential MOEs for post-application 

exposure are shown in the table below. 

Golfing 

Formulation Lifestage TTR, Weight Transfer Hours of Exposure Absorbed Dermal Dermal 

(ug/cm2) unit Coefficient Exposure (mg/day) Dose MOE MOE 

conversio (cm2/hr) (hr) (mglkg/day) (rounded) 

n factor 

(mg/ug) 

Liquids Adult 0.11 0.001 5,300 4 2.3564 0.02945475 169.75 170 

11 to 0.11 0.001 4,400 4 1.9562 0.03432 145.69 150 

<16 

years 

6 to <11 0.11 0.001 2,900 4 1.2893 0.04029185 124.09 120 

years 

Since the estimated residential turf post-application exposure for golf course using default TTR 

values for diclofop-methyl is not minimal in comparison to the level of concern (i.e., the 

calculated MOE is not greater than 10 times higher than the level of concern, MOE= 120 

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Diclofop-methyl Registration Review Human Health Seeping Document 

compared to the LOC of 100, future refmements of this post-application exposure for diclofopmethyl may be necessary due to increased use of diclofop-methyl or advances in EPA risk 

assessments. Therefore, EPA is requiring the 40CFR TTR data requirement for diclofop-methyl 

as part of registration review. 

An updated residential post-application assessment will be required for registration review which 

incorporates the required TTR data using the updated 2012 residential SOPs 

(http://www.epa.gov/pesticides/science/residential-exposure-sop.html). 

Spray Drift/Volatilization Residential bystander exposures resulting from off-site transport (e.g., 

spray drift or volatilization) may occur as a result of applications of diclofop-methyl. The 

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

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

concurrently. The approach is outlined in the revised (2012) Standard Operating Procedures For 

Residential Risk Assessment (SOPs) - Residential Exposure Assessment Standard Operating 

Procedures Addenda 1 : Consideration of Spray Drift 

(http://www.regulations.gov/#!docketDetail;D=EPA-HQ-OPP-2013-0676). This document 

outlines the quantification of indirect non-occupational exposure to drift. In terms of 

volatilization, the agency has developed a Volatilization Screening Tool and a subsequent 

Volatilization Screening Analysis (http://www.regulations.gov/# !docketDetail;D=EPA-HQOPP-2014-0219). During Registration Review, the agency will utilize this analysis to determine 

if data (i.e., flux studies, route-specific inhalation toxicological studies) or further analysis is 

required for dicloflop-methyl. 

Conclusions for Residential Exposure 

There is insufficient information available to assess residential post-application exposure. In 

accordance with the updated Part 158 data requirements (2007), a ITR study is required for all 

occupational (e.g., sod farms, golf courses, parks, and recreational areas) or residential turf uses 

that could result in post-application exposure to turf. Based on HED policy, a TTR study is 

required for diclofop-methyl. The study will affect the occupational post-application assessment 

that will be conducted for golf courses. A revised residential exposure assessment (cancer and 

non-cancer) may be required under registration review that includes post-application exposure to 

adults and children golfing on commercially treated turf. This assessment should incorporate, as 

necessary, updated human factors (e.g., body weight) assumptions, and the 2012 Revised 

Residential SOPs. The potential for residential exposures resulting from off-site transport (e.g., 

spray drift or volatilization) will need to be evaluated for diclofop-methyl during the registration 

review process. 

Aggregate Risk Assessment 

In accordance with the Food Quality Protection Act (FQPA), HED must consider and aggregate 

pesticide exposures and risks from three major sources: food, drinking water, and direct 

residential exposures. 

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Diclofop-methyl Registration Review Human Health Scoping Document 

The acute (females only) and chronic aggregate risk assessments for diclofop-methyl included 

food and drinking water only. As discussed above, there were no aggregate acute or chronic 

risks identified in the most recent dietary assessment. An updated dietary risk assessment will 

only be required if there is a significant change to the drinking water concentration. A shortterm aggregate risk assessment considering exposure from food, water, and non-occupational 

(residential) sources of exposure did not exceed HED' s level of concern. An intermediate-term 

aggregate risk assessment was not conducted for diclofop-methyl. The cancer aggregate risk 

estimate to diclofop-methyl addresses carcinogenic exposure from food, drinking water, and 

residential exposure to golferS is 3.2 X 1 o-6. 

Conclusions for Aggregate Risk Assessment 

No acute or chronic aggregate risks have been identified for diclofop-methyl. An updated 

dietary risk assessment will only be required during registration review if there is a significant 

change to the drinking water concentration. While there are no registered residential uses for 

diclofop-methyl, there is the potential to residential post-application exposure from contact with 

turf from commercial application to golf courses. Therefore, an updated short- and intermediateterm as well as cancer aggregate risk assessments will be required for registration review for 

diclofop-methyl. 

Occupational Exposure 

As previously mentioned, diclofop-methyl is currently registered for use on agricultural crops 

such as wheat and barley and on golf course turf. It is applied pre-plant, pre-emergent, or postemergent by groundboom and aerial for wheat/barley and hand-held equipment for golf courses. 

The maximum application rate is 1 lb ai/ A for wheat and barley and 1.0 lb ai/ A for golf course 

turf. Occupational handler and post-application exposures are expected based on the registered 

uses of diclofop-methyl. For labels where diclofop-methyl is applied to wheat and barley, 

engineering controls are used by applicators and flaggers. Mixer/loaders must use a closed 

system as instructed by the currently approved labels. Mixer/loaders must also use a chemicalresistant apron and chemical-resistant gloves. For labels where diclofop-methyl is applied to golf 

courses, the PPE for mixers/loaders is baseline PPE (long-sleeved shirt, and long pants, 

chemical-resistant footwear plus socks), chemical-resistant apron and gloves, and a NIOSH 

approved respirator with an organic vapor cartridge or canister. 

Occupational Handlers 

For occupational handlers, the major exposure scenarios identified and assessed previously 

include: mixing/loading liquids for groundboom application, mixing/loading liquids for aerial 

application, mixing/loading liquids for hand gun sprayer application, applying liquids with a 

groundboom sprayer, applying liquids with fixed-wing aircraft, applying liquids with hand gun 

sprayer, and flagging for liquids application. Occupational handler exposures are expected to be 

short- and intermediate-term in duration. All of the MOEs for the combined dermal and 

inhalation exposure are greater than 1 00 with maximum risk reduction measures (personal 

Page 8 of20 
Diclofop-methyl Registration Review Human Health Scoping Document 

protective equipment (PPE) or engineering controls) for all of the short- and intermediate-term 

occupational exposure scenarios listed above (D267650, Tadayon, S., 8/2/2000). 

The cancer risk estimates for occupational handler dermal and inhalation exposure range from 

1.4 x 10·

2 to 5.1 x 10·6 at the baseline level, 8.4 x 10·5 to 6.0 x 10-7 with PPE, and 5.8 x 10·5 to 1.4 

x 10-6 at the engineering control level (D267650, Tadayon, S., 8/2/2000). In 2000, diclofopmethyl was classified as a "possible human carcinogen" by the Carcinogenicity Peer Review 

Committee (CARC) based on liver adenomas and carcinomas with significant trend and pairwise comparisons, as seen in a mouse carcinogenicity study. The Q1 * was determined to be 2.3 

x 10-1 (mg/kg/day)"1 human equivalents to assess its cancer risks. The CARC reconvened on 

January 5, 2000 and it was decided that the Q1 * remain unchanged (D267650, Tadayon, S., 

8/2/2000). 

Recommended unit exposures for occupational handler assessments have generally been derived 

only from the Pesticide Handlers Exposure Database (PHED). However, recently both the 

Outdoor Residential Exposure Task Force (ORETF) and the Agricultural Handler Exposure Task 

Force (AHETF) have produced pesticide handler exposure monitoring data that the Agency is 

using in place ofPHED (http://www.epa.gov/pesticides/science/handler-exposure-data.html). As 

more reliable data become available, the Agency will continue to replace existing data. 

Reviewers should incorporate new exposure monitoring data, as necessary, during registration 

rev1ew. 

Occupational Post-Application 

In accordance with 40CFR158, DFR data are required for all occupational (e.g., crop, nursery, 

greenhouse use sites) or residential (e.g., ornamental and vegetable gardens, pick your own 

farms, retail tree farms) uses that could result in post-application exposure to foliage. HED 

developed a waiver policy for DFR studies. The MOEs from the assessment, using default 

values are evaluated. If those are 2 times higher than the LOC the DFR studies can be waived. 

Occupational MOEs for post-application exposure are shown in the table below. 

Occupational Post-application Non-Cancer Dermal Exposure and Risk Estimates 

Crop/Site Activities Transfer Coefficient ·Dermal Dose MOE (cm2

/hr) (mglkglday) 

Barley Scouting 1,100 0.278 18 

Wheat, Spring Scouting 1,1 00 0.278 18 

Wheat, Winter Scouting 1,100 0.278 18 

Since the highest estimated occupational post-application exposure using default DFR values for 

diclofop-methyl is not minimal in comparison to the level of concern (i.e., the calculated MOE is 

not greater than 2 times higher than the level of concern, MOE = 18 (at Day 1 (restricted-entry 

interval (REI) = 24 hours) compared to the LOC of 1 00); EPA is requiring the 40CFR DFR data. 

Therefore, EPA is requiring the 40CFR DFR data requirement to facilitate any necessary 

exposure assessments refinements and to further EPA's general understanding of the availability 

of dislodgeable foliar pesticide residues. 

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Diclofop-methyl Registration Review Human Health Seeping Document 

There may be the potential for post-application dermal exposure to workers following 

applications of diclofop-methyl to agricultural crops (wheat/barley) and to golf course turf. As 

noted above, application can be made either pre-plant, pre-emergent, or post-emergent. 

Recommended transfer coefficients for occupational post-application assessments are derived 

from Agricultural Reentry Task Force (ARTF) exposure monitoring studies 

(http://www.epa.gov/pesticides/science/post-app-exposure-data.html). These transfer 

coefficients have been updated in 2012 based on a reanalysis and submission of new monitoring 

data. Reviewers should incorporate new exposure monitoring data, as necessary, during 

registration review. 

Conclusions for Occupational Exposure 

There is insufficient information available to assess occupational exposure. In accordance with 

the updated Part 158 data requirements (2007), one or more Dislodgeable Foliar Residue (DFR) 

studies are required when a pesticide has residential or occupational uses that could result in 

post-application dermal exposure. Based on HED policy, a DFR is required for diclofop-methyl 

at this time for wheat/barley. In accordance with the updated Part 158 data requirements (2007), 

a TurfTransferrable Residue (TTR) study is required for all occupational (e.g., sod farms, golf 

courses, parks, and recreational areas) or residential turf uses that could result in post-application 

exposure to turf. Based on HED policy, a TTR study is required for diclofop-methyl. An 

updated occupational handler and post-application assessment will be required under registration 

review if warranted by any significant changes in exposure assessment methodology and any 

new data that is submitted. 

Public Health and Pesticide Epidemiology Data 

HED has completed its review of incident data that were reported to the Agency, the findings in 

the Agricultural Health Study (AHS) as part of the diclofop-methyl seeping process (S. Recore, 

05/29/14, D420493). There does not appear to be a concern at this time that would warrant 

further investigation, sincere there were no incidents involving diclofop-methyl. The Agency 

will continue to monitor the incident information and if a concern is triggered, additional 

analysis will be included in the preliminary risk assessment. 

Page 10 of20 
Diclofop-methyl Registration Review Human Health Scoping Document 

Tolerance Assessment and International Harmonization 

Tolerances are currently established under 40 CFR §180.385 for the herbicide diclofop-methyl 

(methyl 2-[ 4-(2,4-dichlorophenoxy)phenoxy ]propanoate) and its metabolites 2-[ 4-(2,4-

dichlorophenoxy)phenoxy ]propanoic acid and 2-[ 4-(2,4-dichloro-5-

hydroxyphenoxy)phenoxy ]propanoic acid in or on barley grain, barley straw, wheat grain and 

wheat straw at 0.1 ppm. Only tolerances for plant commodities are presently established, and 

none have been established for livestock commodities. Tolerances have been proposed for 

barley hay (6 ppm); wheat forage (12 ppm); wheat hay (1 ppm); meat by-products, excluding 

kidney (7 ppm); kidney (25 ppm); milk ( 4 ppm); and in the meat and fat of cattle, goat, horses, 

and sheep (1 ppm) and should be included in the 40 CFR for diclofop-methyl. Tolerances are 

not required for residues of diclofop-methyl in eggs and poultry tissues. 

HED recommend that 40 CFR §180.385(a) should be further subdivided into 40 CFR 

§ 180.385(a)(1) and 40 CFR § 180.385(a)(2) for separate designations of diclofop residues of 

concern in plants and animals, respectively. 

The current tolerance expressions are not in compliance with BED's Interim Guidance on 

Tolerance Expressions (5/27/09, S. Knizner) and should be revised during registration review. 

The residue definitio·n in the US is harmonized with the Canadian Maximum Residue Limit (MRL) 

expression; Codex has no MRLs for diclofop-methyl. The barley and wheat tolerances at 0.1 ppm 

are harmonized with Canada. Mexico adopts the standards of the US for its export purposes. 

Therefore, there are no harmonization issues with Canada, Codex, or Mexico. The International 

Residue Limit Status Sheet is attached to the document as Attachment 5. 

International or Intergovernmental Work Sharing 

HED is not currently involved in any joint international review projects that involve the active 

ingredient, diclofop-methyl. Additionally, HED is unaware of any ongoing international 

assessments for diclofop-methyl. Given the limited use pattern for this chemical and the lack of 

any identified new work, HED has not identified any potential work sharing opportunities for 

diclofop-methyl. 

Cumulative 

The Food Quality Protection Act (FQP A) requires the Agency to consider the cumulative risks of 

chemicals sharing a common mechanism of toxicity. 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 diclofop-methyl and any other substances, 

and diclofop-methyl does not appear to produce a toxic metabolite produced by other substances. 

Therefore, a cumulative risk assessment has not been performed for these compounds. 

Human Studies 

There are no diclofop-methyl specific human studies that require an ethics review at this time. 

Previous HED risk assessments relied in part on data from studies in which adult human subjects· 

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Diclofop-methyl Registration Review Human Health Scoping Document 

were intentionally exposed to a pesticide or other chemical. These data, which include studies 

from PHED 1.1; the AHETF database; the Outdoor Residential Exposure Task Force (ORETF) 

database; the ARTF database; are (1) subject to ethics review pursuant to 40 CFR 26, (2) have 

received that review, and (3) are 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' 

Data Requirements 

Toxicity Studies 

• None 

Residue Chemistry Studies 

• None 

Occupational/Residential Studies 

• Chemical-specific TTR study (875.2100) 

• Chemical-specific DFR study (875.2100) 

References 

Table 1: HED Memoranda Relevant to Registration Review 

Author BarcodeffXR # Date Title 

Uma Habiba TXR No. 0056963 06/14 Diclofop-methyl: Summary of Hazard 

and Science Policy Council 

(HASPOC) Meeting of May 8, 2014: 

Recommendations on the 

Requirement of a Subchronic 

Inhalation Study, Neurotoxicity 

(acute and subchronic) Studies, and 

an lmmunotoxicity Study 

Shanna Recore D420493 05/29/14 Diclofop-methyl: Tier 1 Review of 

Human Incidents 

Seyed Tadayon D267650 08/02/00 Revised Occupational and Residential 

Exposure Assessment and 

Recommendations for the 

Reregistration Eligibility Document 

for Diclofop-methyl 

1 http://www.epa.gov/pesticides/science/handler-exposure-data.html and 

http://www.epa.gov/pesticides/science/post-app-exposure-data.html 

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Diclofop-methyl Registration Review Human Health Seeping Document 

Table 1: HED Memoranda Relevant to Registration Review 

Author BarcodeffXR # I Date 

Christina Jarvis D268403 08/10/00 

Richard Griffin D267649 08/03/00 

Sheila Piper D265277 05/02/00 

Attachments 

Attachment 1. Chemical Identity 

Attachment 2. Toxicology Data Requirement 

Attachment 3. Toxicity Profile Tables 

Attachment 4. Endpoint Tables 

Attachment 5. International Residue Limits Table 

Attachment 1. Diclofop-methyl Chemical Identity 

Table 1.1 Diclofop-methyl Nomenclature 

Compound 

Common name Diclofop-methyl 

Title 

Diclofop-methyl Revised HED 

Chapter of the Reregistration 

Eligibility Decision Document (RED) 

Diclofop-methyl. Revised Anticipated 

Residue Estimates and Dietary Risk 

Assessment 

Diclofop-methyl. Product and 

Residue Chemistry Chapters for the 

Reregistration Eligibility Decision 

Document (RED) 

TUPAC name methyl (RS)-2-[4-(2,4-dichlorophenoxy)phenoxy)propionate 

CAS name methyl 2-[4-(2,4-dichlorophenoxy)phenoxy]propanoate 

CAS registry number 51338-27-3 

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Diclofop-methyl Registration Review Human Health Scoping Document 

Table 1.2. Physicochemical Properties of the Technical Grade of Diclofop-methyl 

Parameter Value Reference 

Melting point (range) 39-41 c 

pH 5.7 

Density 1.30+0.05 g/cm3 at 40 C 

Water solubility 0.005g/l00mL 

Solvent solubility xylene - 253 g/1 OOmL 

ethanol - 11 g/1 OOmL 

acetone- 249 g/IOOmL D265277, S .Piper, 5/02/00 

Vapor pressure 1. 9 x 1 0~ mm Hg at 20 C 

Dissociation constant, pKa pKa = 3.43 

Octanol/water partition 37,800 

coefficient, 

Log(Kow) 

UV /visible absorption spectrum Not available 

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Diclofop-methyl Registration Review Human Health Scoping Document 

Attachment 2. Toxicology Data Requirement 

Test Technical 

Required Conducted 

870.1100 Acute Oral Toxicity yes yes 

870.1200 Acute Dermal Toxicity yes yes 

870.1300 Acute Inhalation Toxicity yes yes 

870.2400 Primary Eye Irritation yes yes 

870.2500 Primary Dermal Irritation yes yes 

870.2600 Dermal Sensitization yes yes 

870.3100 Oral Subchronic (rodent) yes yes 

870.3150 Oral Subchronic (non-rodent) yes yes 

870.3200 21/28-Day Dermal yes yes 

870.3250 90-Day Dermal no no 

870.3465 90-Day Inhalation no waived 

870.3700a Developmental Toxicity (rodent) yes yes 

870.3700b Developmental Toxicity (non-rodent) yes yes 

870.3800 Reproduction yes yes 

870.4100a Chronic Toxicity (rodent) yes yes 

870.41 OOb Chronic Toxicity (non-rodent) yes yes 

870.4200a Oncogenicity (rat) yes yes 

870.4200b Oncogenicity (mouse) yes yes 

870.4300 Chronic/Oncogenicity yes yes 

870.5100 Mutagenicity- Gene Mutation (bacterial) yes yes 

870.5300 Mutagenicity- Gene Mutation (mammalian) yes yes 

870.5375 Mutagenicity- Structural Chromosomal Aberrations yes yes 

870.5395 Mutagenicity-Other Genotoxic Effects yes yes 

870.5500 Mutagenicity-Other Genotoxic Effects yes yes 

870.6100a Acute Delayed Neurotoxicity (hen) no no 

870.6100b 90-Day Neurotoxicity (hen) no no 

870.6200a Acute Neurotoxicity Screening Battery (rat) yes waived1 

870.6200b 90-Day Neurotoxicity Screening Battery (rat) yes waived 1 

870.6300 Developmental Neurotoxicity no no 

870.7485 General Metabolism yes yes 

870.7600 Dermal Penetration no yes 

870.7800 Immunotoxicity yes waived 1 

. . . . 1

The 90-day mha1at10n, acute/subchromc neurotoxicity, and 1mmunotoXICity studies are not requrred at th1s trrne . 

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Diclofop-methyl Registration Review Human Health Scoping Document 

Attachment 3. Toxicity Profile Tables 

Table 3.1. Acute Toxicity Profile for Diclofop-metbyl 

Guideline Study Type MRID(s) Results Toxicity 

Number Category 

870.1100 Acute oral [Rat] 41476001 LDso = 512 ( 428-636) mg/kg (M/F) II 

92036052 

870.1200 Acute dermal [Rat] 00071522 LDso > 2000 mg/kg (M/F) III 

92036013 

870.1300 Acute inhalation [Rat] 41573304 LCso > 4.75 mg/L (MIF) IV 

870.2400 Acute eye irritation [Rabbit] 42428601 Slight ocular irritant, conjunctival redness III 

and discharge at 24 hr, cleared by 72hr 

870.2500 Acute dermal irritation [Rabbit] 40213506 Slight irritation reported IV 

870.2600 Skin sensitization [Guinea pig] 41476003 Buehler: Negative 

41476002 Maximization: Moderate to severe sensitizer 

41476003 

Table 3.2. Subcbronic, Chronic and Other Toxicity Profile for Diclofop-metbyl 

Guideline Number/ MRID(s)/ Results Study Type Classification 

870.3150 42573301-02 NOAEL=l.6/1.8 mg/kg/day [MIF] 

90-Day oral toxicity Acceptable/Guideline LOAEL= 6.317.1 mg/kg/day (M!F] based on clinical 

[rat] chem, perox proliferation, liver hypertrophy 

870.3150 42593901 NOAEL not established 

90-Day oral toxicity Acceptable/Guideline LOAEL= 0.3/0.4 mg/kg/day [MIF] based on clinical 

[mouse] chem, perox proliferation, liver necrosis 

870.3200 41476004 Systemic NOAEL= 5 mg/kg/day 

28-day dermal toxicity Acceptable/guideline Systemic LOAEL= 25 mg/kg/day based on 

[rat) increased liver enzymes, proteins, and absolute 

and relative liver weights 

Dermal irritation NOAEL= 125 mg/kg/day; LOAEL>l25 

mg/kg/day 

870.3700a 92036043 Maternal NOAEL = 0.3 mg/kg/day 

Prenatal Acceptable/Guideline LOAEL = 3.0 mg/kg/day Based on significantly 

developmental increased absolute liver and kidney weights, 

[rabbit] decreased body weight gain, and reduced food 

consumption. 

Developmental NOAE= 3.0 mg/kg/day. 

LOAEL could not be determined. 

870.3700c 92036042 Maternal NOAEL =not established. 

Prenatal Acceptable/Guideline LOAEL = 10 mg/kg/day based on reductions in food 

developmental consumption, mean body weights and body weight gain. 

[rat] Developmental NOAEL= I 0 mg/kg/day 

LOAEL = 32 mg/kg/day based on decreased fetal body 

weights and crown-rump length, distended ureters, 

skeletal abnormalities. 

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Diclofop-methyl Registration Review Human Health Scoping Document 

Table 3.2. Subcbronic Chronic and Other Toxicity Profile for Diclofop-metbyl 

Guideline Number/ MRID(s)/ Results Study Type Classification 

870.3800 42543 101 Parental/Systemic NOAEL = 0.3 mglkglday 

Reproduction and Acceptable/Guideline LOAEL = 3.0 mglkglday based on liver weight increases 

fertility effects and histopathological lesions in liver and kidney. 

[rat] Reproductive/Developmental 

NOAEL = 3 .l/2.5 mglkg/day [M/F] 

LOAEL = 7.3/8.4 mglkglday [M/F] based on reduced fetal 

body weights and delayed !>hysical development. 

870.4100b 92036039 NOAEL = 2.0/0.2 mglkg/day [MIF] 

Chronic toxicity (dog] Acceptable/Guideline LOAEL = not established/0.63 mglkg/day [M/F] based on 

Clinical chem, perox proliferation, liver histopathology. 

870.4100a 43927302 NOAEL = 0.23/0.3 mglkglday [M/F] 

Chronic toxicity/ Acceptable/Guideline LOAEL = 2.32/3.05 mg/kglday [M/F] based on Increased 

Carcinogenicity liver and kidney weights, hepatocellular hypertorphy , 

[rat] histopathology (lipofusin storage). 

Evidence of significant (p<O.O I) increases (both pair-wise 

and trend) of hepatocellular adenomas and carcinomas in 

males as well as combined adenomas/carcinomas in both 

sexes. 

870.4300 92036058 NOAEL = 0.24/0.25 mglkglday (M/F] 

Carcinogenicity Acceptable/Guideline LOAEL [systemic] = 0.76/0.77 mglkg/day [MIF] based on 

[mouse] Clinical chem, perox proliferation, liver hypertrophy. 

Statistically significant trends were evident in both sexes 

for hepatocellular adenomas, carcinomas and combined 

adenomas/carcinomas. 

870.5100a 000719004 Dose range: 0 to 500 uglmL, +/- S9 

Gene Mutation Acceptable Negative 

Bacterial reverse 

mutation test in 

Salmonella 

typhimurim 

870.5300a 4 1573305 Dose range: 2 to 500 J.lg/mL +/- S9 

In vitro mammalian Acceptable Test was negative up to cytotoxic doses (200 J.lg/mL, - cell gene mutation test S9; 300 J.lg/mL, +S9). in Chinese hamster 

lung fV79] cells 

870.5375a 41476004 Dose range: I to 500 J.lg/mL +/- S9 

ln vitro mammalian Acceptable Test was negative over the dose range ( +S9) chromosome 

aberration test in 

primary human 

hepatocytes 

870.5385 41737901 Dose range: 0, 200, 1000, and 2000 mg/kg 

In vitro Acceptable Chromosomal analysis did not show any treatmentcytogenetic related cytogenetic aberrations 

test in bone 

marrow cells 

of the Chinese 

hamster 

870.5550 41996902,42437801 Dose range: 0.5 to 50 J.lg/mL, cytotoxicity at 100 J.lg/mL 

Unscheduled Acceptable Did not induce significant increases in nuclear labeling 

DNA synthesis in ofprimary rat hepatocytes. 

A549 human lung 

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Diclofop-methyl Registration Review Human Health Scoping Document 

Table 3.2. Subchronic, Chronic and Other Toxicity Profile for Diclofop-methyl 

Guideline Number/ MRID(s)/ Results Study Type Classification 

carcinoma in 

vitro 

870.5550 41996902,42437801 Dose range: 0.03 to 100 J.lg/mL ± S9 

Unscheduled Acceptable Did not induce significant increases in nuclear labeling 

DNA synthesis in human lung cancer cells. 

A549 human lung 

carcinoma in 

vitro 

Mutagenicity 0087820 Dose range: 250, 500, 1000 J.lg/mL ± S9 

-Other Acceptable Mitotic gene conversions not increased in yeast strain 

genotoxic over spontaneous rate ± S9 

effects 

870.7485 41573306 Diclofop-methyl is extensively absorbed, metabolized and 

Metabolism Acceptable/Guideline excreted through the feces and the urine; no measurable 

[rat) amount(< 0.01%) of radioactivity was found in expired 

air. Residual radioactivity was found mainly in the liver, 

kidney and digestive tract; the highest levels of 

radioactivity were found in the fat. Two metabolites were 

identified in both the urine and feces as hydroxylated and 

de-esterified parent compounds. 

870.7600 42364601 Dermal absorption factor = 15% at 10 hours 

Dermal penetration Acceptable/guideline 

[rat] 

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Diclofop-methyl Registration Review Human Health Scoping Document 

Attachment 4: Diclofop-methyl Endpoint Selection Table 

Table 4. Toxicolotdcal Doses and Endpoints for Use in Diclofop-metby) Human Health Risk Assessments. 

Exposure Point of Departure, RID, PAD, Level Study and Toxicological Effects 

Scenario Uncertainty/FQPA Safety of Concern for 

Factors Risk Assessment 

Acute Dietary NOAEL- 10 mg/kg/day aPAD= 0.1 Developmental toxicity study in the rat 

(Females 13-49) UFA =lOx mg/kg/day (MRlD 92036042) 

UFH = lOx Developmental LOAEL= 32 

FQPA SF= I mg/kg/day based on decreased fetal 

body wts, distended ureters, skeletal 

abnormalities. These effects could be 

attributed to a single dose. 

Acute Dietary No endpoint attributable to a single dose was identified. 

(General 

Population) 

Chronic Dietary NOAEL - 0.23 mglkg/day cPAD = 0.0023 Carcinogenicity study in rats. 

(All Populations) UFA =lOx mglkg/day (MRID 43927302) 

UFH = lOx LOAEL = 2.32 mglkg/day, based on 

FQPA SF = lx increased relative liver and kidney wts, 

liver enzymes, liver histopathology 

(hypertrophy, lipofuscin storage). 

Effects and NOAEL consistent with 

other studies in mouse and dog. 

Dermal Short- and NOAEL= 5 mg/kg/day LOC for 21-Day Dermal Toxicity Study in the 

Intermediate-Term UFA = lOx MOE=IOO Rat 

UFH = lOx (MRID 41476004) 

FQPASF = lx LOAEL= 25 mglkg/day based on 

Dermal absorption factor: increased liver enzymes, proteins, and 

15% absolute and relative liver weights. 

Dermal Long-Term No long-term exposure anticipated from currently use pattern. 

(>6 Months) 

Inhalation Short- Oral, NOAEL= 1.6 mg/kg/day LOC for Subchronic Oral Toxicity Study in the 

and intermediated- (inhalation toxicity assumed MOE=IOO Rat (MRID 42573301) 

Term to be equivalent to oral LOAEL= 6.3 mglkg/day based on 

toxicity 100%) increased liver enzymes, proteins, and 

absolute and relative liver weights. 

Inhalation Long- No long-term exposure anticipated from currently use pattern. 

Term 

{>6 Months) 

Cancer (Oral, Classification: Group C carcinogen (possible human carcinogen) with a Q l * of2.3 x 10·1 

Dermal, Inhalation) (mg/kg/day)-1 based on hepatocarcinogenesis in the mouse carcinogenicity study. 

Pomt of Departure (POD) = data pomt or estimated pomt, denved 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). FQPA SF= FQPA Safety Factor. PAD= 

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

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Diclofop-methyl Registration Review Human Health Scoping Document 

Attachment 5. International Residue Limits Table 

Table 5. Summary of US and International Tolerances and Maximum Residue Limits for 

Diclofop-Methyl 

Residue Definition: 

us Canada Mexico1 Codex 

40 CFR § 180.385 propanoic acid, 2-[ 4-(2,4- None 

Plant: Diclofop-methyl (methyl 2-[ 4- dichlorophenoxy) phenoxy)-, 

(2,4-dichlorophenoxy) methyl ester, including the 

phenoxy ]propanoate) and its metabolites propanoic acid, 2-

metabolites 2-[ 4-(2,4- [4-(2,4-

dichlorophenoxy)phenoxy ]propanoic dichlorophenoxy)phenoxy ]- and 

acid and 2-[ 4-(2,4-dichloro-5- propanoic acid, 2-[ 4-(2,4-

hydroxyphenoxy)phenoxy]propanoic dichloro-5-hydroxyphenoxy) 

acid phenoxy]-

Livestock: None 

Commodity Tolerance (ppm) /Maximum Residue Limit (m vkg) 

us Canada Mexico' Codex 

Barley, grain 0.1 0.1 

Barley, straw 0.1 

Wheat, grain 0.1 0.1 

0.1 triticale 

Wheat, straw 0.1 

Completed: M. Negussie; 05/29/14 1 Mex1co adopts US tolerances and/or Codex MRLs for 1ts export purposes. 

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