### UNITED STATES ENVIRONMENT AL PROTE CT ION AGENCY

WASHINGTON, D. C. 20460

MEMORANDUM

DATE : 

### 23-APR-2015 OFFICE OF CHEMICAL SAFETY AND

POLLUTION PREVENTION



### SUBJECT: 

### Propanil: R eg i strat i on Review Human Health Scoping D ocument



### PC Code: 028201



### MRIDNo.: NA



### Petition No.: NA



### Assessment Type: Single Chemical/ Agg regat e 

### DP Barcode: D4 2 4441 

### Registration No .: NA 

### Regulatory Action: Registration Review 

### Reregi s tration Case N o

. : 226



### TXR No.: NA CAS No.: 709- 98-8



### REVIEWERS: Mohsen Sahafeyan, Chemist and Risk Assessor 

# ,,,//<: ' L 

# JLL.eEv1sabel C r aig, Ph.D .,DA BT

, Tox1co l og 1st 

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# y.

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Shalu S h e l at

, Indu strial Hygieni st 

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## P u
,., . '-

. ·**~** Ri s k Asses s ment Branch VI 

## W 

# 0

Health Effects Di v ision (7509 P )

THROUGH: Donna D av i s, Acting Branc h Chi ef

Risk Assessment Branch VI

H ea lth E ffects Division ( 7509P)

TO: Joel Wolf

, C hemical Review Manager

A nd

K evin Coste ll o, Bra nch C hief

Ri sk Management and Implementation Branch II

Pesticide Re-Evaluation Division (7508P)



### E xecutive S ummary

The Heal t h E ffe cts Divi s i o n (HED) Propanil Registration Revi ew Team ha s eva luated the

stat us of th e human health assess m e nt s for propanil to determ ine the scope of work

necessary to support R egistrati on R ev i ew. Prop anil i s a selective pos t emergence
herbicide registered for u s e on rice. The H E D Revised c h apte r for Re gistra t ion

E ligibility Decision (RED) fo r propanil was completed on February 28th, 2002.

Propanil is avai lable as an em ulsifiabl e co ncentr ate 

### li q uid

, water dispersible granule 

### (dry
flowable)

, solub le concentrate liquid

, and flowabl e c o ncentrate liquid and is app lied as a
bro adca st treatment by groun d and aerial equipment. The principal toxic effect of

Page 1 of24

### Page 2 of 24

propanil is methemoglobinemia and hemolytic anemia, which is seen in different species (rats, mice and dogs) in oral studies of vary ing durations

.

The current toxicology database for propanil is incomplete. The subchronic inhalation

and acute neurotoxicity studies are required but have not been submitted

. A waiver for the inhalation and acute toxicity studies was not granted and thu s, these studies are still outstanding ( J. Leshin, TXR# 0057107 , 2/27/2015 ). Once new data are submitted, t he propanil registration review tea m will re

- evaluate th e toxicity database and update the points of departure (PoDs) and safety factors/uncertainty factors (SFs/UFs) used in the

most recent risk assessment for this chemical , as needed

.

The residue chemistry database for propanil is adequate to support the registration review process for propanil. However, the dietary risk assessment may need to be updated to directly incorporate estimated drinking water concentrations, include updated percent crop treated and consumption information, using updated PoDs and SFs/UFs.

T here are no residential use s for propanil

. There is the potential for non

- occupational exposure from nearby agricultural applications of propanil to rice

. T he need for spray

drift and volatilization risk assessment s for propanil will be examined during R egistration

R eview

.

The current occupational exposure database for pro panil is incomplete. A chemical

specific DFR study in rice as well as a worker exposure study for a closed mixing and loading system with the dry flowable formulation is required

. In the 2011 assessment

, HED estimated the risks to mixers/loaders, groundbo om applicators, aerial applicators, and flaggers who are involved in applications of propanil to rice. The risk estimates were based on a propanil

- specific use survey and updated surrogate exposure data. F or many scenarios , the resulting risk estimates w ere of concern
, particularly for individuals handling higher amounts of propanil. The post

- application risk estimates calculated in

2002 were based on transfer coefficients and default fraction of available residue that have since been updated. Post

- application risk estimates based on the current inputs also

result in risk estimates of concern. The occupa tional handler and post

- application exposure assessment may need to be updated during the r egistration r eview process to include changes in use pattern , the inclusion of additional data

, and also to comply with new guidelines and policies.

As there are no residential uses for propanil, the aggregate risk assessment includes food and water only. As noted above, updated assessments may be required for registration

review.

Current tolerances are for rice and livestock are established under 40 CFR §180.274 and are adequate

. The t olerance expression should be updated in accordance with HED’s current guidance. As there are no international maximum residue limits (MRLs) established for propanil, there is no issue with harmonization of US tolerances with

inte rnational MRLs.

### Page 3 of 24

1.0 I ntroduction

Propanil N

- (3,4

- dichlorophenyl)propanamide is a selective postemergence herbicide registered for use on rice to control broadleaf and grass weeds. Propanil is available as an emulsifiable concentrate (EC), a liquid or dry flowable (DF), and a low volume (LV) formulation and is typically applied as a broadcast treatment by ground and aerial equipment . There are currently 35 active end use product registrations and one experimental use permit. Propanil belongs to the ac etanilide class of pesticides and, acting primarily in the leaves, is a strong inhibitor of the Hill reaction, disrupting normal photosynthesis. The chemical structure and nomenclature of propanil and the physicochemical properties of technical grade propa nil are presented in Attachment 1

.

The Reregistration Eligibility Decision (RED) document for propanil was signed on 9/30/2003. The Agency amended the Propanil RED in March 2006 as a result of its review of the public comments and review of additional d ata submitted by the Propanil

Task Force to refine the exposure estimates for workers handling propanil

. By 2006, uses

on barley, oats, and wheat had also been voluntarily cancelled

. The most recent human health risk assessment was performed in 2003 (R. Griffin, D289785, 3/14/2003) and a follow up addendum was completed in 2011 (C. Smith, D293904, 6/14/2011)

. There are currently no pending PRIA actions for propanil. HED has reviewed the most recent exposure and risk assessments for propanil, as well as toxicity data, exposure and usage databases, and the latest Agency science policy and risk assessment methodologies to determine if sufficient data are available and if updates are needed to support registration

review.

2.0 Hazard Identification/ Toxi cology

The toxicology database for prop anil is incomplete (See Attachment 2). Although the current 40 CFR Part 158 Toxicology Data Requirements include subch ronic inhalation

, and neurotoxicity (acute and subchronic) studies, these studies were not submitt ed for

prop anil

. B ased on a weight

- of

- evidence (WOE) approach that considers all the available hazard and exposure information for propanil,

, the Hazard and Science Policy Council (HASPOC) determined that the subchronic inhalation, and acute neurotoxicity studies are required to support the registered uses of propanil. The Council also determined that the subchronic neurotoxicity study for propanil is not required at this time ( J. Leshin, TXR#

0057107 , 2/27/2015 ).

In a metabolism study in rats, the majori ty of propanil and its metabolites were excreted in the urine within 24 hours, with only 2

- 13% excreted in the feces and minimal retention in the carcass or internal organs. In addition to the parent compound, six metabolites were recovered in the urine ( four derivatives of 3,4

- dichloroaniline and two derivatives of

2

- hydroxy

- 4,5

- dichloroaniline), which account for >40% of the radioactivity. Four metabolites were recovered in feces and two organic solvent soluble compounds were

recovered from the rat live r. The metabolites 3, 4

- dichloroaniline (DCA), and its N

hydroxy and 6

- hydroxy derivatives have been associated with methemoglobin formation in open literature studies.

### Page 4 of 24

The principal toxic effect s of propanil are methemoglobinemia and hemolytic anemia,

wh ich are seen in different species (rats, mice and dogs) in oral studies of varying

durations . Other than slightly decreased fetal body weights (with or without accompanying delays in skeletal ossification)

, there was no apparent adverse effect of in

utero propanil exposure on the morphological development of the fetuses in the prenatal developmental toxicity studies in rats and rabbits. Effects observed in the two generation reproduction study in rats included delayed vaginal perforation, delayed balanopr eputial separation, and decreased mean sperm count. This is consistent with results from an in

vitro rat prostate androgen receptor competitive binding assay reviewed by EPA in 2012 (TXR# 0051481), which shows that propanil is a weak binder of the rat andr ogen receptor. Propanil is not immunotoxic or mutagenic. The Health Effects Division ( HED ) Cancer Peer Review Committee has classified propanil into the category termed “Suggestive evidence of carcinogenic potential by all routes of exposure, but not suffi cient to assess human carcinogenic potential ” based on testicular interstitial adenomas observed in male rats and malignant lymphomas in female mice.

Propanil has low acute toxicity, with toxicity categories of III (oral) and IV (dermal, inhalation and pr imary skin irritation). No dermal sensitization was observed; however, primary eye irritation is observed in rabbits (toxicity category II ).

In the previous r isk assessment (2002), the point of departure (PoD) for all exposure scenarios (chronic dietary; short

- and intermediate

- term incidental oral ; and short, intermediate and long

- term dermal and inhalation exposures) were based on the LOAEL

of 9.0 mg/kg/day (methemoglobinemia) from the chronic toxicity/c arcinogenicity study

in rats. A NOAEL was not dete rmined . For dietary and residential exposures, an addendum to the 2002 risk assessment, based on a Hazard Identification Assessment Review Committee (HIARC) report (dated May 14, 2003; TXR#0051852) set an uncertainty factor of 1000X (10X for interspecies extrapolation, 10X for intraspecies variability, 3X for LOAEL

- to

- NOAEL extrapolation and 3X because of the lack of data on the potential anti

- androgenic activity of propanil). For occupational exposures, the uncertainty factor was 300X (10X for interspeci es extrapolation, 10X for intraspecies variability and 3X for LOAEL

- to

- NOAEL extrapolation).

In the 2002 risk assessment, t he Food Quality and Protection Act safety factor (FQPA SF) was reduced to 1X. A 1X FQPA SF was considered appropriate because the

t oxicology database was adequate for assessing FQPA , a developmental neurotoxicity study was not required for this chemical and there is was no evidence of increased quantitative susceptibility of the young following in utero , pre

- or post

- natal exposure to propanil. Although there was evidence in the 2

- generation reproduction study in rats

which indicate d qualitative susceptibility of the offspring, the concern was low because the effects noted were well characterized, occurred only at the highest dose test ed and did not appear to have any long

- term effects in reproductive function. Also, there was no residual uncertainty in the exposure database.

Conclusions: The toxicology database for prop anil is incomplete

. The subchronic inhalation, and acute neurotoxicity studies are required to support registered use of propanil

. As part of registration review, upon receipt of the required toxicity data, the

### Page 5 of 24

endpoints, doses, and safety factors used in the most recent risk assessment will be re

evaluated acco rding to current HED policy.

3.0 Residue Chemistry

The residue chemistry database is adequate for dietary risk assessment for propanil. Tolerances are established under 40 CFR §180.274 for the combined residues of the herbicide propanil (3′, 4′

- dichloropropionanilide) and its metabolites convertible to 3, 4

- dichloroaniline (3,4

- DCA), in or on rice, crayfish and livestock commodities. No r esidue chemistry deficiencies were cited in 2003 RED for rice

. Since 2003, uses on barley, oats,

and wheat have been voluntarily cancelled

.

The qualitative nature of the residue in plants and livestock is adequately understood based on acceptable metab ol ism studies conducted on rice, wheat , ruminant and poultry and crayfish

.

The HED Metabolism Assessment Review Committee (MARC) has reviewed the propanil toxicology and metabolism data (meeting dates of 1/16/96) and concluded that for plants and livestock the residues of concern for enforcement and human health risk

assessment are propanil (parent), 3,4

- dichloroaniline, and related residues convertible to 3,4

- dichloroaniline (3,4

- DCA ).

Water metabolism was subsequently submitted to the MARC on August 7, 2001. The committee concluded that parent and the metabolite 3, 4

- DCA should be included in risk

assessment.

Based on metabolism data, 3,4

- DCA is also a metabolite of two other pesticides, linuron and diuron. However, the MARC does not recommend aggregating residues of 3,4

- DCA for the propanil, linuron and diuron risk assessments. While 3,4

- DCA is a potential degradate of all three pestic ides, it is such a small portion of the terminal residues in linuron and diuron ( <l% of the TRR), that linuron and diuron

- derived 3,4

- DCA is not likely to contribute significantly to the overall 3,4

- DCA exposure The analytical method for quantifying residu es of concern from linuron and diuron converts all residues to 3,4

- DCA as a convenience , but 3,4

- DCA was not a significant residue in any metabolism or hydrolysis study. Therefore, the MARC recommended that all residues convertible to 3,4

- DCA would be incl uded in the tolerance expression for linuron and diuron only because no validated enforcement method was available for the quantification of individual components of the residues of concern.

Adequate residue analytical methods are available for tolerance enforcement

. For plants,

a n adequately

- validated gas chromatography with nitrogen

- phosphoros detector ( GC/NPD ) method, designated as EN

- CAS Method No. ENC

- 9/ 90, or Method TR 34

- 93

- 99 was submitted to EPA by the registrant . Residues are determined as 3,4

- DCA, and calculated as the parent, propanil; the limit of quantitation (LOQ) is 0.01 ppm for this

method

. The method has been previously described and deemed adequate for data collection on rice and wheat matrices. It has been subjected to a successful in dependent laboratory validation (ILV) trial as required by PR Notice 96

- 1 and was a dequately

radiovalidated using 14 

### C

- labeled samples from the confined rotational crop study (MRID

### Page 6 of 24

42963001). For livestock commodities , the current prefer red enforcement method is the gas chromatography with electron

- capture detector (GC /ECD ) method listed in PAM

Volume II as Method I. As with the plant analytical enforcement method, r esidues are determined as 3,4

- DCA, and calculated as the parent, propanil; the limit of q uantitation (LOQ) is 0.01 ppm for this method. The reported LOQ of Method I is 0.05 ppm. The reregistration requirements for multi

- residue method testing for residues of propanil and 3,4

- DCA are satisfied.

Ade quate studies on magnitude of residue in ric e, processing, storage stability , confined rotational crop, and ruminant and poultry feeding studies have been submitted. In addition, a dequate metabolism, magnitude of residue and storage stability data for crayfish have also been submitted. These data s upport the existing tolerance on rice, livestock and crayfish.

As data depicting magnitude of the residue in catfish and in crops irrigated by water from

treated rice field were not available, in the Addendum to the RED (2006)

, the registrant was required to put restriction on all rice labels for use of water from treated rice field s for catfish farming , irrigation of other crops, or release to flowing or standing water within a 1⁄2 mile of a potable water intake

.

Conclusions: T he residue chemistry database is adequate to support the current registrations for propanil

. No additional data are required to support the registration review of propanil.

4.0 Dietary Exposure and Risks

Dietary exposure and risk were last assessed in 2003 fo r chronic dietary food using Dietary Exposure Evaluation Model software with the Food Commodity Intake Database (DEEM

- FCIDTM, Version 1.3). Acute dietary risk for propanil was not assessed since no appropriate endpoints (effects) attributable to a si ngle exposure (dose) were identified in any toxicological study . In the previous dietary assessment, e xposure through drinking

water

, modeled for rice application

, were assessed by the Drinking Water Level of Comparison ( DWLOC ) method and the estimated en vironmental concentration ( EEC ) estimates for propanil per se and 3,4

- DCA (combined) were less than the estimated

DWLOC

.

T he 2003 chronic dietary risk for (food only) assessment was partially refined us ing anticipated residues from field trial data, percent crop treated for rice ( 9%CT) and processing factor in for mation. That assessment also included barley, oats, and wheat

uses which were voluntarily c ancelled later. The assessment concluded that for all supported registered commodities, the estimated chronic dietary risks associated with the use of propanil do not exceed HED’s level of concern ( < 100% chronic population adjusted dose (c PAD) for the general U.S. population and all population subgroups

inclu ding the most highly exposed population subgroups, all infants <1 year of age

, children 1

- 2 years old, and children 3

- 5 years old , each at 4% cPAD

.

Subsequent to the 2003 dietary risk assessment, HED has updated the consumption data

used in DEEM and drin king water estimated exposures are now directly incorporated in the dietary exposure assessment. Upon receipt of the required toxicity data, and update

### Page 7 of 24

of the points of departure (PoDs) and safety factors (SFs) for risk assessment, the dietary

risk assess ment may need to be updated to include updated percent crop treated information and to directly incorporate updated estimates of residues in drinking water, as well as updated consumption information.

Conclusions: A n n updated dietary exposure and risk assessment , which incorporates changes to PoDs and UFs, includes updated drinking water estimates, as well as updated percent crop treated information may need to be completed to support registration review.

5.0 Residential Exposure and Risks

Currently, there are no registered residential uses for propanil , therefore , a quantitative residential exposure and risk assessment has not been conducted and will not be required for Registration Review.

Spray Drift and Volatilization Residential bystander exposures resulting from off

- site transport (e.g., spray drift or volatilization) may occur as a result of applications of propanil . 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 Exposu re 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 Volatilization Screening T ool and a subsequent Volatilization Screening Analysis (http://www.regulations.gov/#!docketDetail;D=EPA

- HQ

- OPP

- 2014

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

- specific inhalation toxicological studies) or fu rther analysis is required for propanil

.

Conclusions: Currently, there are no registered uses at residential sites, therefore

residential handler and residential post

- application assessments are not required. T he

need for spray drift and volatilization risk assessment s for propanil will be examined during R egistration R eview

.

6.0 Aggregate Risk Assessment

The aggregate risk assessment evaluates the combined risk from dietary exposure (food and water) and any non

- occupatio nal (residential) uses. However, there are currently no

residential uses for propanil ; therefore the propanil aggregate risk assessment includes only dietary exposure ( food and water ) which may need to be updated (see dietary exposure and risk section)

.

Conclusions: The aggregate risk assessments for propanil , which includes food and water only, may need to be reassessed during Registration Review as noted in Section

4.0.

### Page 8 of 2 4

7.0 Occupational Exposure and Risks

Propanil is currently registered for use on rice, therefore handler and post

- application exposures are expected. I n 2011 , HED completed an addendum to the 2002 occupational and residential exposure (ORE) assessment for propanil ( C. Smith, D293904, 6/14/20 11 )

. That addendum included two main updates: 1) inclusion of data on typical application rates and acres treated per day that were collected during a survey of 50 aerial application firms in 2007 and 58 in 2008 and 2) inclusion of HED’s new s cenario

- speci fic surrogate

handler exposure table.

Occupational Handlers

HED ha d estimated the risks to mixers/loaders, groundboom applicators, aerial applicators, and flaggers who are involved in applications of propanil to rice. The risk

estimates for the mixer/l oader scenarios and an applicator scenario result ed in risk

estimates of concern . Mixer/loader risk estimates ranged from 32 to 1100 and applicator risk estimates ranged from 67 to 1900 at engineering controls. As a result of the previous risk assessment, the registrant has agreed to submit a worker exposure study to address the occupational handler risk issues identified. In addition, HED’s exposure policies have been updated since the 2011 assessment was compl eted , including updates to the exposure data used for handler scenarios and body weight assumptions.

Occupational Post

- application : The most recent post

- application assessment for propanil was completed in 2002 (S. Recore, D280853, 2/8/2002) which used the default dislodgeable foliar residue (DFR) fraction of application rate (F AR 

### ) value (20%)

. At that time, t he resulting MOE of 293 for the currently reg istered rice use at the maximum rate (6 lbs ai/acre) exceeded HED’s level of concern (LOC ) of 300 (MOE < LOC)

. The current default F AR 

### value for post

application activities is 25%. With the use of the current F AR 

### value, as well as updated

transfer coefficient (TC) values, the resulting risk estimates for post

- application exposure

from the ri ce application at the maximum rate of 6 lbs ai/acre range from 24 to 38 0.

Since the highest estimated occupational post

- application exposure using default DFR

and TC values for propanil 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 = 600 compared to the LOC of 300; EPA is requiring the 40CFR §158 DFR data. S ee Attachment 6 for additional information regarding updated risk estimate s and DFR data requirement.

Conclusions: A chemical

- specific DFR study in rice is required for propanil in

accordance with 40 CFR § 158, additionally

, the registrant has agreed to submit a worker exposure study to address the occupational handler risk issues that were previously

identified. The o ccupational exposure/risk assessments for propanil may also need to be

reassessed during Registration Review to address updates to HED’s exposure policies

, including updates to exposure data used for handler scenarios

, post

- application transfer coefficients, transferable residue assumptions, and assumptions for body weights

. Occupational exposure/risk assessments may also need to be reassessed if changes to the toxicity endpoints or uncertainty factors are made during Registration Review.

### Page 9 of 24

8.0 P ublic Health and Pesticide Epidemiology Data

For the M ain Incident Data System (IDS) 2010

- 20 14, and Sentinel Event Notification System for Occupational Risk

- Pesticides (SENSOR

- Pesticides ) 1998

- 2010 , there has been a total of 13 cases involving propanil; only two cases involved single active ingredient; other cases involved multiple ingredients. T hese incidents were classified as

low to moderate in severity. Propanil is not included in the Agricultural Health Study ( AHS ) , and therefore this study does not provide information that needs to be considered under registration review

.

Based on the low frequency and low severity of incident cases reported for propanil in

both IDS and SENSOR

- Pesticides, 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.

9 .0 Tolerance Assessment and International Harmonization

Permanent Tolerances are established under 40 CFR §180.274 for the combined residues

of the herbicide propanil (3′, 4′

- dichloropropionanilide) and its metabolites convertible to 3, 4

- dichloroaniline (3, 4

- DCA), in or on rice, crayfish and livestock commodities.

The t olerance expression should be updated in accordance with HED’s Interim Guidance

on Toleran ce Expressions (5/27/09, S. Knizner) as the following:

Tolerances are established for residues of propanil (3′, 4′

- dichloropropionanilide)

, including its metabolites and degradates

, in or on the commodities in the table below. Compliance with the toleranc e levels specified below is to be determined by measuring only those propanil residues convertible to 3, 4

- dichloroaniline (3,

4

- DCA) , expressed as the stoichiometric equivalent of propanil , in or on the commodity.

The Codex Alimentarius Commission , Canad a and Mexico have not established maximum residue limits (MRLs) for propanil and therefore there is no issue with

harmonization of US tolerances with international MRLs.

1 0 .0 Cumulative Risk Assessment

Propanil has not been included in a cumulative assessment group or cumulative risk

assessment.

1 1 .0 Risk Assessment Updates and Data Deficiencies

 The subchronic inhalation (guideline 870.3465), and acute neurotoxicity (guideline 870.6200) studies are required to support registered use of propanil.

 A propanil specific worker exposure study using closed

- system application equipment (guideline 875.1100) had been required during the RED mitigation

process ; Data Call

- In (DCI) has already been issued.

### Page 10 of 24

 A propanil specific dislodgeable foliar residue study (guideline 875.2100) in rice is required.

1 2 .0 References

Memoranda Relevant to Registration Review

Author Barcode/TXR # Date Title

Charles Smith D293904 6/14/2011 Propanil: Addendum to the 2002 Occupational and Residential Exposure

Assessment.

S. Recore D280853 2/8/2002 Occupational and Residential Exposure

Assessment and Recommendations for the Reregistration Eligibility Decision (RED) Document for Propanil (1st Revision)

Sherrie L.

Kinard D280854 2/28/2002 Propanil . Revised Residue Chemistry Chapter for the Reregistration Eligibility

Decision

Richard Griffin D281147 2/28/2002 Propanil . Human Health Risk Assessment (Revised)

Richard Griffin D289785 5/14/2003 Propanil . Addendum to the Revised

Human Health Risk Assessment

Shanna Recore D424891 1/8/2015 Propanil : Review of Human Incidents

OPP No DP Barcode

Docket ID: EPA

- HQ

- OPP

2003

- 0348 3/7/2006 Amendment to Reregistration Eligibility Decision (RED) for Propanil (March 2006) and the Propanil RED (September 2003)

J. Leshin TXR# 0057107 2/27/ 2015 Propanil: Summary of Hazard and Science Policy Council (HASPOC) Meeting of January 8, 2015:

Recommendations on the requirements of subchronic inhalation and neurotoxicity (acute and subchronic) studies.

Christina

Swartz D222631 2/20/1996 Propanil. List A Reregistration Case

No. 0226/Chemical ID No. 028201. Outcome of the 1/16/96 meeting of

the HED Metabolism Committee.

Sherrie L.

Kinard D277494 8/31/2001 Propanil. Outcome the HED

Metabolism Assessment Review

Committee to discuss degradates in drinking water on August 7, 2001

.



### Attachments:

Attachment 1: Chemical Identity Table. Attachment 2: Toxicology data requirements

Attachment 3 : Propanil Toxicity Profile Tables

Attachment 4 : Propanil Toxicological Doses a nd Endpoints for Risk Assessment

Attachment 5 : Summary of Occupational Registered Propanil Uses

Attachment 6: Dislodgable Foliar Residue Data Requirement Criteria

Attachment 7 : Propanil International Residue Limit Status Sheet

### Page 11 of 24

Attachment 1: Chemical Identity Table s

.

Attachment Table 1.1: 

### Propanil Nomenclature

Chemical structure

Common name Propanil

IUPAC name 3',4'

- dichloropropionanilide

CAS name N

- (3,4

- Dichlorophenyl)propanamide

CAS # 709

- 98

- 8

Trade Name Stam® and SuperWham®

Attachment Table 1.2; 

### Physicochemical Prop erties of Technical Grade Propanil

Parameter Value Reference

Melting range 92 °C ChemIDplus ( http://chem.sis.nlm.nih.gov/ch emidplus/rn/709

- 98

- 8 )

Amendment to the Propanil RED (March 7, 2006) Water solubility 152 m g/L at 25 °C

Vapor pressure 9.08x10

- 6 mmHg at 25  C

Octa nol/water partition coefficient log ( K OW ) 3.07

Stability Active ingredient hydrolyzes in strong

acid or base

Density 1.25 g/ml

### Page 12 of 24

Attachment 2. Toxicology Data Requirement s

Atttachment 2.1: Toxicology Data Requirements for Propanil

Test Technical

Required Conducted

870.1100 Acute Oral Toxicity 870.1200 Acute Dermal Toxicity

870.1300 Acute Inhalation Toxicity 870.2400 Primary Eye Irritation 870.2500 Primary Dermal Irritation

870.2600 Dermal Sensitization yes

yes

yes

yes

yes

yes yes

yes

yes

yes

yes

yes

870.3100 Oral Subchronic (rodent) 870.3150 Oral Subchronic (non

- rodent)

870.3200 21/28

- Day Dermal

870.3250 90

- Day Dermal

870.3465 90

- Day Inhalation yes

yes

yes

no CR yes

yes

yes

no

no

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

- rodent) 870.3800 Reproduction yes

yes

yes yes

yes

yes

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

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

yes

yes

yes

yes yes

yes

yes

yes

yes

870.5100 Mutagenicity

— Gene Mutation (bacterial) 870.5300 Mutagenicity

— Gene Mutation (mammalian) 870.5375 Mutagenicity

— Structural Chromosomal Aberrations 870.5395 Mutagenicity

— Other Genotoxic Effects 870.5500 Mutagenicity

— Other Genotoxic Effects yes

yes

yes

yes

yes yes

yes

yes

yes

yes

870.6100a Acute Delayed Neurotoxicity (hen)

870.6100b 90

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

870.6200b 90

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

no

ye s

yes CR no

no

no waived 1

no

870.7485 General Metabolism

870.7600 Dermal Penetration

870.7800 Immunotoxicity yes

CR

yes yes

yes

yes CR = conditionally required

1 Data requirement waived by HASPOC for t he subchronic n eurotoxicity study ( TXR# 0057107 )

.

### Page 13 of 24

Attachment 3. Propanil Toxicity Profile Tables

Table 3.1. Acute Toxicity Profile for Prop anil

Guideline

No. 

### Study Type MRID # Results Toxicity Category

81

- 1 Acute Oral [rats] 41360801 LD 50 = 1080 mg/kg III

81

- 2 Acute Dermal [rabbits] 41360901 LD 50 > 2000 mg/kg IV

81

- 3 Acute Inhalation [rats] 41265901 LC 50 = 6.1 mg/L IV

81

- 4 Primary Eye Irritation

[rabbits] 41360501 Iritis, conjunctivitis present in all rabbits, cleared by day 14; corneal opacity cleared by 4 days II

81

- 5 Primary Dermal Irritation

[rabbits] 41360601 Slightly irritating

P.I.I. = 0.2/4.0 IV

81

- 6 Dermal Sensitization

[guinea pigs] 40070204 Negative N/A



### Table 3.2. Subchronic, Chronic and Other Toxicity Profile for Propanil

Guideline

No. Study Type MRID No. /(year)/

Doses Results

870.3100 90

- Day oral

toxicity rodents (Wistar rat) MRID 00015459,

00046259 (1961) 0, 0.01, 0.033, 0.10, 1.0, 5.0 % (diet) (0, 10, 33, 100, 1000, 5000 mg/kg/d) NOAEL = 33 mg/kg/day LOAEL = 100 mg/kg/day based on increased relative spleen weight in females and decreased hemoglobin in

males.

870.3100 90

- Day oral

toxicity rodents (CD

- 1 mouse) MRID 40402901 (1983)

0, 25, 200, 1600, 12800 ppm (diet) (M: 0, 6.6, 49, 442, 5325 mg/kg/d) (F: 0, 9.6, 78, 566, 6467 mg/kg/d) NOAEL = 6.6/9.6 (M/F) mg/kg/day LOAEL = 49/78 (M/F) mg/kg/day based on histopathological findings in the liver (hepatocytic pleomorphism and hepatocytic multifocal necrosis).

870.3200 21

- Day dermal

toxicity (NZW rabbit) MRID 41777001,

41961800 (1990) 0, 250, 500, 1000 mg/kg/d 6 hrs/day; 5 days/week NOAEL = 250 mg/kg/day LOAEL = 500 mg/kg/day based on decreased body weight gain (day 20) and decreased food consumption (days 14

- 20).

### Page 14 of 24

Table 3.2. Subchronic, Chronic and Other Toxicity Profile for Propanil

Guideline

No. Study Type MRID No. /(year)/

Doses Results

870.3700a Prenatal

developmental toxicity in

rodents MRID 00058588 (1980)

0, 0.8, 4.0, 20, 100 mg/kg/d Gavage; GD 6

- 15 Maternal NOAEL = 20 mg/kg/day LOAEL = 100 mg/kg/day based on decreased body weight gain during treatment. Developmental NOAEL = 20 mg/kg/day LOAEL = 100 mg/kg/day based on decreased mean fetal weight and delayed ossification in the sternebrae and

cervical vertebrae.

870.3700b Prenatal

developmental toxicity in

nonrodents (NZW rabbit) MRID 00058589 (1980)

0, 4, 20, 100 mg/kg/d Gavage; GD 6

- 18 Maternal NOAEL = 20 mg/kg/day LOAEL = 100 mg/kg/day based on mortality, clinical signs of toxicity, and weight loss during treatment. Developmental NOAEL = 20 mg/kg/day LOAEL = 100 mg/kg/day based on slightly decreased mean fetal weight.

870.3800 Reproduction

and fertility effects (SD rats,

2

- generations) MRID 44604301 (1998)

0, 60, 150, 600 ppm (diet) (F0 M: 0, 4, 11, 43 mg/kg/d) (F0 F: 0, 5, 13, 51 mg/kg/d) Parental/Systemic NOAEL = 11/13 (M/F) mg/kg/day LOAEL = 43/51 (M/F) mg/kg/day based on decreased body weight, body weight gain, and food consumption, increased absolute and/or relative spleen weights, and increased incidence and severity of pigmented macrophages in the spleen. Reproductive NOAEL = 11/13 (M/F) mg/kg/day LOAEL = 43/51 (M/F) mg/kg/day based on delayed vaginal perforation and balanopreputial separation in F1 adolescents, and decreased mean testicular sperm count and production rate in F1 adult males. Offspring NOAEL = 11/13 (M/F) mg/kg/day LOAEL = 43/51 (M/F) mg/kg/day based on reduced F1 and F2 pup weights, delayed vaginal perforation and balanopreputial separation in F1 adolescents, and organ weight changes in F2 weanlings (increased absolute and relative spleen weights and decreased relative pituitary weights in females, de creased absolute and/or relative liver and kidney weights in males and females).

870.4100a Chronic toxicity

rodents See 870.4300, Combined chronic toxicity/carcinogenicity

### Page 15 of 24

Table 3.2. Subchronic, Chronic and Other Toxicity Profile for Propanil

Guideline

No. Study Type MRID No. /(year)/

Doses Results

870.4100b Chronic toxicity

dogs (beagles,

1

- yr) MRID 42962901 (1993)

0, 200, 1600, 2300 ppm (diet) (M: 0, 5, 45, 79 mg/kg/d) (F: 0, 6, 42, 85 mg/kg/d) NOAEL = < 5/6 (M/F) mg/kg/day LOAEL = 5/6 (M/F) mg/kg/day based on macrocytic, regenerative, methemoglobinemia (decreased erythrocytes, hemoglobin, hematocrit, and mean cellul ar hemoglobin concentration; increased mean cell volume, methemoglobin, and reticulocytes.; increased Heinz bodies in females at week 51), and endogenous pigment (hemosiderin) in the kidney of both sexes and the liver

of males

870.4200 Carcinogenicity

(CD

- 1 mice;

104

- wk) MRID 43391701 (1994)

0, 500, 1000 ppm (diet) (M: 0, 74.9, 150 mg/kg/d) (F: 0, 88.6, 174.1 mg/kg/d) NOAEL = < 74.9/88.6 (M/F) mg/kg/day LOAEL = 74.9/88.6 (M/F) mg/kg/day based on methemoglobinemia (increased methemoglobin and

Heinz bod ies in males) and blue discoloration of the

extremities. Evidence of carcinogenicity: malignant lymphomas in females at 174.1 mg/kg/d

870.4300 Combined

chronic toxicity/carcino genicity (SD rat; 104

- wk) MRID 43303201 (1994)

0, 200, 600, 1800 ppm (diet) (M: 0, 9.0, 27.7, 88 mg/kg/d) (F: 0, 11.5, 38.3, 145 mg/kg/d) NOAEL = < 9.0/11.5 (M/F) mg/kg/day LOAEL = 9.0/11.5 (M/F) mg/kg/day based on clinical chemistry findings in both sexes (increased methemoglobin at weeks 13, 26, and 52; decreased packed cell volume and red blood cells at weeks 26and 52), increased spleen weight in females at 52 weeks, and

gross

- and histo

- pathological findings at 104 weeks (enlarged spleen in females, small seminal vesicles and

p rostate in males, hemosiderosis in spleen of males, brown pigment [probably hemosiderin] in proximal convoluted tubules of females and endometrial polyps in females). Evidence of carcinogenicity: testicular interstitial cell

adenomas in males at 27.7 and 8 8 mg/kg/d.

870.5100 Gene Mutation

Bacterial

reverse gene mutation assay MRID 00155085 (1980) Propanil was negative in Salmonella typhimurium strains TA1535, TA1537, TA1538, TA98 and TA100

and in Escherichia coli WP2 up to cytotoxic doses
(  1,000 μg/plate +/

- S9) in independent trials.

870.5100 Gene Mutation

Bacterial

reverse gene mutation assay MRID 00028625 (1979) Independent trials were negative in Salmonella typhimurium strains TA1535, TA1537, TA1538, TA98

and TA100 up to cytotoxic doses (  1,000 μg/plate +/

- S9) and in Escherichia coli WP2 up to the highest dose tested (1,000 μg/plate +/

- S9).

### Page 16 of 24

Table 3.2. Subchronic, Chronic and Other Toxicity Profile for Propanil

Guideline

No. Study Type MRID No. /(year)/

Doses Results

870.5300 Gene Mutation

In vitro

mammalian cell gene mutation

test MRID 00155084 (1984) In a Chinese Hamster Ovary (CHO)/HGPRT cell forward gene mutation assay, independent tests were negative up to cytotoxic doses without S9 activation (125 μg/mL) and with S9 activation (175 μg/mL).

870.5385 Cytogenetics

Mammalian

bone marrow

chromosome

aberration test MRID 00155083 (1983) An in vivo bone marrow cytogenetic assay was negative

in CD

- 1 male mice administered 0, 26.5, 106, or 265 mg/kg/day by oral gavage once or once daily for 5 consecutive days. Doses selected for this study represented 1/4, 1/10 or 1/40 of the acute LD 50 , respectively. Overt toxicity was manifested as decreas ed spontaneous motor activity, lethargy and piloerection in animals receiving  106 mg/kg/day in both dosing regimens. No data were provided to support the claim of decreased metaphases in the high dose animals, and this deficiency compromised the acceptab ility of the study. However, since there was a clear indication of toxicity to the test animals, and no differences in LOAELs between

male and female mice were seen in the subchronic or chronic studies, the doses should be considered adequate.

870.5500 Other

Genotoxicity

Bacterial DNT damage or repair tests MRID 00028625 (1979) Propanil was negative for differential cytotoxicity in

Escherichia coli strains W3110/p3478 (pol A +/

- ) up to an equivalent cytotoxic dose (5 μg

- S9) but was positive for the induction of preferential inhibition of repair

- deficient Bacillus subtilis M45 (rec

- ) at 0.01

- 5 μg without S9: S9 activation was not included in this study.

870.5550 Other

Genotoxicity

Unscheduled DNA synthesis

in mammalian

cells in culture MRID 00028625 (1979) In an unscheduled DNA synthesis assay in WI

- 38 human fibroblasts, propanil was negative up to an insoluble level (1000 μg/mL).

### Page 17 of 24

Table 3.2. Subchronic, Chronic and Other Toxicity Profile for Propanil

Guideline

No. Study Type MRID No. /(year)/

Doses Results

870.5575 Other

Genotoxicity Mitotic gene

conversion in Saccharomyces

cerevisiae MRID 00028625 (1979) In a D3 mitotic recombination assay, propanil was negative for the induction of mitotic recombinants at doses up to 0.1 % with or without S9 mix. Independent trials were performed.

870.7485 Metabolism and

pharmacokineti cs (SD rat) MRID 41796400,

41796402 (1991) A: single oral low dose (2.5 mg/kg) B: multiple oral low dose (2.5 mg/kg for 15 days) C: single oral high dose (300 mg/kg) D: intravenous dose (0.7 mg/kg in saline) The majority of the radioactivity (78

- 90%) was excreted

in the u rine, and 2

- 13% was excreted in the feces. Most of the radioactivity was eliminated within 24 hours for all except the high oral dose where it took 48 hours to eliminate 90%. For the i.v. data, females excreted 10% in the feces, while males excreted 2%. The carcass

contained 0.18

- 0.71% of the radioactivity, with the liver having the highest residue.

Of the total of 13 metabolites identified, three major

metabolites accounted for 17

- 44% of the radioactivity and were involved in hydroxylation and oxidatio n of the propanamide moiety. Other metabolites included 3,4 dichloroaniline, and its N

- hydroxy and 6

- hydroxy derivatives, which are associated with methemoglobin

formation.

870.7800 Immunotoxicity

(SD rats) MIRD 47162901 (2007)

0, 50, 200, 600 ppm (diet) (M: 0, 4, 16, 48 mg/kg/d) (F: 0, 5, 19, 56 mg/kg/d) Systemic NOAEL = 200 ppm (16/19 mg/kg/d) Systemic LOAEL = 600 ppm (48/56 mg/kg/d) based on significantly decreased body weight in both sexes and

mild anemia in females.

Immunotoxicity NOAEL = 600 ppm (48/56 mg/kg/d) Immunotoxicity LOAEL = not determined

### Page 18 of 24

Attachment 4. Propanil Toxicological Doses and Endpoints for Risk Assessment

Point of d eparture (Po D) = 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 Table 4.1. Summary of Toxicological Doses and Endpoint for Prop anil for Use in Dietary and Non

Occupational Human Health Risk Assessments

Exposure

Scenario PoD Uncertainty/ FQPA SFs RfD, PAD, Level of

Concern for Risk

Assessment Study and Toxicological Effects

Acute Dietary

females 13

- 50 years of age No appropriate endpoint attributed to a single dose was identified. An acute RfD was no

established.

Acute Dietary general population including infants

and children N ot applicable

Chronic Dietary all populations LOAEL = 9.0

mg/kg/day UF A = 10x

UF H = 10x

UF L = 3x

UF DB = 3x

Chronic RfD = 0.009 mg/kg/day

cPAD = 0.009 mg/kg/day Chronic toxicity/carcinogenicity

study in rats (MRID 43303201)
Increased methemoglobin in both sexes, increased spleen weight in

females and small seminal vesicles/prostate in males.

Incidental oral

Short

- term and

intermediate term LOAEL = 9.0

mg/kg/day UF A = 10x

UF H = 10x

UF L = 3x

UF DB = 3x

LOC for MOE = 1000 Chronic toxicity/carcinogenicity

study in rats (MRID 43303201)
Increased methemoglobin in both sexes, increased spleen weight in

females and small seminal vesicles/prostate in males.

Dermal a

Short

- term and

intermediate term LOAEL = 9.0

mg/kg/day UF A = 10x

UF H = 10x

UF L = 3x

UF DB = 3x

LOC for MOE = 1000 Chronic toxicity/carcinogenicity

study in rats (MRID 43303201)
Increased methemoglobin in both sexes, increased spleen weight in

females and small seminal vesicles/prostate in males.

Inhalation b

Short

- term and

intermediate term LOAEL = 9.0

mg/kg/day UF A = 10x

UF H = 10x

UF L = 3x

UF DB = 3x

LOC for MOE = 1000 Chronic toxicity/carcinogenicity

study in rats (MRID 43303201)
Increased methemoglobin in both sexes, increased spleen weight in

females and small seminal vesicles/prostate in males.

Cancer (oral, dermal, inhalation) Classification: "Suggestive evidence of carcinogenic potential by all routes of exposure, but not sufficient to assess human carcinogenic potential”.

### Page 19 of 24 observed adverse effect level. UF = uncertainty factor. FQPA SF = FQPA Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose. LOC = level of concern.

a An oral endpoint was used for dermal e xposure: dermal absorption factor of 20% of oral exposure shall

be used.

b An oral endpoint was used for inhalation exposure: inhalation exposure assumed equivalent to oral exposure; a 100% absorption rate is applied.



### Table 4.2. Summary of Toxic ological Doses and Endpoints for Propanil for Use in Occupational Human Health Risk Assessments

Exposure/

Scenario Point of

Departure (PoD) Uncertaint

y Factors Level of

Concern for

Risk

Assessment Study and Toxicological Effects

Dermal a

Short

- term
and

intermediate

term LOAEL =

9.0 mg/kg/day UF A =10x

UF H =10x

UF L =3x Occupational

LOC for MOE

= 3 00 Chronic toxicity/carcinogenicity study

in rats (MRID 43303201)
Increased methemoglobin in both sexes, increased spleen weight in

females and small seminal vesicles/prostate in males.

Dermal a Long

- term (> 6 months) LOAEL =

9.0 mg/kg/day UF A =10x

UF H =10x

UF L =3x Occupational

LOC for MOE

= 3 00 Chronic toxicity/carcinogenicity study

in rats (MRID 43303201)
Increased methemoglobin in both sexes, increased spleen weight in

females and small seminal vesicles/prostate in males.

Inhalation b

Short

- term
and

intermediate

term LOAEL =

9.0 mg/kg/day UF A =10x

UF H =10x

UF L =3x Occupational

LOC for MOE

= 3 00 Chronic toxicity/carcinogenicity study

in rats (MRID 43303201)
Increased methemoglobin in both sexes, increased spleen weight in

females and small seminal vesicles/prostate in males.

Inhalation b
Long

- term (> 6 months) LOAEL =

9.0 mg/kg/day UF A =10x

UF H =10x

UF L =3x Occupational

LOC for MOE

= 3 00 Chronic toxicity/carcinogenicity study

in rats (MRID 43303201)
Increased methemoglobin in both sexes, increased spleen weight in

females and small seminal vesicles/prostate in males.

Cancer (oral, dermal, inhalation) Classification: "Suggestive evidence of carcinogenic potential by all routes of

exposure, but not sufficient to assess human carcinogenic potential”.

Point of d eparture (Po D) = 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. FQPA SF = FQPA Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose. LOC = level of concern.

a An oral endpoint was used for dermal exposure: dermal absorption factor of 20% of oral exposure shall

be used.

b An oral endpoint was used for inhalation exposure: inhalation exposure assumed equivalent to oral exposure; a 100% absorption rate is applied.

### Page 20 of 24

Attachment 5 : Summary of Occupational Registered Propanil Uses

Attachment Table 5.1 Summary of Occupational Registered Propanil Uses 1

EPA Reg

No. Use

Site Application Equipment Application Timing Max App

Rate (lb ai/A) REI Comments

19713

- 576 RICE Aircraft. Weed postemergence. 6.00696 24 hr PHI: 60 day(s) preharvest interval.

Ground.

71085

- 16 RICE Aircraft. Weed postemergence. 6 24 hr PHI: 60 day(s) preharvest interval. PGI: 80 day(s) pregrazing interval.,80 day(s) prefeeding interval. Ground.

71085

- 2 RICE Aircraft. Weed postemergence. 5.800725 24 hr PHI: 60 day(s) preharvest interval.

Ground.

71085

- 20 RICE Aircraft. Weed postemergence. 5.905125 24 hr PHI: 60 day(s) preharvest interval.

Ground.

71085

- 22 RICE Aircraft. Weed postemergence. 6 24 hr PHI: 60 day(s) preharvest interval. PGI: 60 day(s) pregrazing interval. Ground.

71085

- 23 RICE Aircraft.

6 24 hr PHI: 80 day(s) preharvest interval. PGI: 80 day(s) pregrazing interval Ground.

Aircraft. PHI: 60 day(s) preharvest interval. PGI: 60 day(s) pregrazing interval. Ground.

71085

- 25 RICE Ground. Early postemergence.

6.07986 24 hr PHI: 65 day(s) preharvest interval.,270 day(s) preharvest interval. PGI: 270 day(s) pregrazing interval Weed preemergence.

Early postemergence.
Weed preemergence.

71085

- 26 RICE Aircraft. Weed postemergence. 6.4887 24 hr PHI: 60 day(s) preharvest interval. Ground.

71085

- 29 RICE Aircraft.

Weed postemergence. 6.128715 48 hr PHI: 60 day(s) preharvest interval. Low pressure ground

sprayer.

71085

- 3 RICE Aircraft. Weed postemergence. 6 24 hr PHI: 60 day(s) preharvest interval.
Ground.

71085

- 30 RICE Aircraft. Weed postemergence. 4.368525 24 hr PHI: 60 day(s) preharvest interval. Ground.

71085

- 31 RICE Aircraft. Weed postemergence. 6.04404 24 hr PHI: 48 day(s) preharvest interval. Ground.

71085

- 32 RICE Aircraft. Weed postemergence. 6 24 hr PHI: 69 day(s) preharvest interval. PGI: 60 day(s) pregrazing interval. Ground.

Aircraft. Weed postemergence. 6 24 hr PHI: 60 day(s) preharvest interval. PGI: 60 day(s) pregrazing interval. Ground.

71085

- 36 RICE Aircraft. Weed postemergence. 5.99424 24 hr PHI: 60 day(s) preharvest interval. PGI: 60 day(s) prefeeding interval.,60 day(s) pregrazing interval. Ground.

71085

- 38 RICE Aircraft. Weed postemergence. 6.075 24 hr PHI: 60 day(s) preharvest interval. PGI: 60 day(s) pregrazing interval.

71085

- 39 RICE Aircraft. Weed postemergence. 6.0858 24 hr PHI: 60 day(s) preharvest interval. PGI: 60 day(s) prefeeding interval.,60 day(s) pregrazing interval. Ground.

71085

- 5 RICE Aircraft. Weed postemergence. 6 24 hr

### Page 21 of 24

Attachment Table 5.1 Summary of Occupational Registered Propanil Uses 1

EPA Reg

No. Use

Site Application Equipment Application Timing Max App

Rate (lb ai/A) REI Comments

Ground.

71085

- 6 RICE Aircraft. Weed postemergence. 6 24 hr PHI: 60 day(s) preharvest interval. PGI: 60 day(s) pregrazing interval. Ground.

71085

- 9 RICE Aircraft. Weed postemergence.

6.00696 24 hr PHI: 80 day(s) preharvest interval. PGI: 80 day(s) pregrazing interval. Ground.

Aircraft. Weed postemergence. PHI: 60 day(s) preharvest interval. PGI: 60 day(s) pregrazing interval. Ground.

86363

- 19 RICE Aircraft. Weed postemergence. 6.075 24 hr PHI: 60 day(s) preharvest interval. PGI: 60 day(s) pregrazing interval. Ground.

87290

- 17 RICE Aircraft. Weed postemergence. 6.075 24 hr PHI: 60 day(s) preharvest interval. PGI: 60 day(s) pregrazing interval. Ground.

87290

- 18 RICE Aircraft. Weed postemergence. 6.04854 24 hr PHI: 60 day(s) preharvest interval. PGI: 60 day(s) pregrazing interval. Ground.

87290

- 32 RICE Aircraft. Weed postemergence. 6.01398 24 hr PHI: 60 day(s) preharvest interval. PGI: 60 day(s) pregrazing interval

. Ground.

1. Propanil (028201) Label Use Report Package in Support of Registration Review, L. Dobbins,

12/2/2014

### Page 22 of 24

Attachment 6: Dislodgeable Foliar Residue Data Requirement Criteria

Updated post

- application exposure and risk estimates were calculated to evaluate the impact of updates to the F AR 

### and transfer coefficient values since the last occupational and residential assessment was completed. The values are presented below:

Attachment Table 6.1 Occupational Post

- application Non

- Cancer Exposure and Risk Estimates for Propanil

Crop/Site Activities Max Application

Rate Transfer Coefficient

(cm 2 /hr) DFR/TTR 1 Dermal Dose (mg/kg/day) 2 MOE 3

Short

- term

/ Intermediate

- term

Rice Scouting
4 lbs ai/acre 1100
11.2 0.247 36

Wedding, Hand 70 0.016 570

Scouting
6 lbs ai/acre 1100
16.83 0.370 24

Wedding, Hand 70 0.024 380

1 DFR = Application Rate × F × (1

- D) t × 4.54E8 μg/lb × 2.47E

- 8 acre/cm 2 ; where F = 0.25 and D = 0.10 per day

2 Daily Dermal Dose = [DFR (μg/cm 2 ) × Transfer Coefficient × 0.001 mg/μg × 8 hrs/day × dermal absorption ( 20 %)]  BW ( 80 kg).

3 MOE = POD ( 9 mg/kg/day) / Daily Dermal Dose. Daily Dermal Dose = [DFR/TTR (μg/cm 2 ) × TC × 0.001 mg/μg × 8 hrs/day × dermal absorption factor ( 20 %) ]  BW ( 80 kg)

.



### In accordance with 40CFR § 158, 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. In the absence of chemical

- sp ecific DFR data, EPA uses default values. The 2012 Standard Operating Procedures for Residential Pesticide Exposure Assessment includes an analysis of a number of DFR studies, which resulted in the selection of a

revised default values for the fraction of the application rate available for transfer after a foliar application (F AR 

### ). This value is based on an analysis of 19 DFR studies. Since that time, the Agricultural Re

- entry Task Force has submitted information (MRID 49299201)

that corrects an application rate error made in the original submission of “ARF039

– Determination of Dermal and Inhalation Exposure to Reentry Workers During Chrysanthemum Pinching in a Greenhouse” (EPA MRID 45344501). As a result of this submission, the default value of 25% was not changed as it still reflects a high

- end, conservative value. However, it is important to note that the range of F AR 

### values was

revised from 2%

- 89% to 2%

- 47%. In the data, a large range of transferability is observed and this variability can potentially be attributable to many factors such as active ingredient; formulation; field conditions in the studies; weather conditions (e.g., humidity); or many other difficult to quantify factors. Although witnessed across multiple chemicals, this r ange in F AR 

### values is not expected when considering DFR data for a single chemical. Because DFR data are not available for propanil, EPA is using the

default value of 25%. Although there may be a small degree of uncertainty in the use of

the default DFR value for propanil (i.e., there is a small chance that the F AR 

### value may exceed the applicable default value ), it is likely that the health

- protective aspects of EPA’s occupational post

- application assessment methodology will more than compensate

for this potential uncertainty. For example, when assessing residential and occupational

post

- application exposure to gardens and ornamentals, EPA assumes the following:

exposures occur to zero

- day (i.e., day of application ) residues every day of the assessed exposure duration (i.e., EPA assumes that no dissipation or degradation occurs, it doesn’t rain, etc); individuals perform the same post

- application activities performed in the

### Page 23 of 24

transfer coefficient study day after day (e.g., weeding, harvesting, pruning, e tc.); and individuals engage in these post

- application activities for a high

- end amount of time every day (represented by data reflecting time spent gardening based on survey data).

Given the conservatisms discussed above and the potential compounding nat ure of these conservatisms, EPA is able to rely upon the calculated exposure estimates with confidence that exposure is not being underestimated.

Since the highest estimated occupational post

- application exposure using default DFR

values for propanil 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 = 600 compared to the LOC of 300 ; 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.

### Page 24 of 24

Attachment 7 : Propanil International Residue Limit Status Sheet



## Propanil (PC Code 028201; 12/18/14)

Summary of US and International Tolerances and Maximum Residue Limits Residue Definition :
US Canada Mexico 1 Codex
40CFR§180.274

combined residues of the herbicide propanil (3′, 4′

- dichloropropionanilide) and its metabolites convertible to 3, 4

- dichloroaniline (3, 4

- DCA) None None



### Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico 1 

### Codex
Cattle, fat 0.10
Cattle, meat 0.05 Cattle, meat byproducts 1.0 Crayfish 0.05 Egg 0.30
Goat, fat 0.10
Goat, meat 0.05 Goat, meat byproducts 1.0 Hog, fat 0.10 Hog, meat 0.05 Hog, meat byproducts 1.0
Horse, fat 0.10
Horse, meat 0.05 Horse, meat byproducts 1.0

Milk 0.05 Poultry, fat 0.05 Poultry, meat 0.10 Poultry, meat byproducts 0.50
Rice, bran 40 Rice, grain 10
Rice, hulls 30
Rice, straw 75 Sheep, fat 0.10 Sheep, meat 0.05 Sheep, meat byproducts 1.0

Completed: M. Negussie; 12/30/2014

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