# . .

# ~~) UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460

Office of Chemical Safety and Pollution Prevention



### Date: Septembet·2s, 2014

Subject:Paraquat Dichloride. Request For Expansion of the Potato Tolerance to Crop Subgroup
1C.

-

PC Code: 061601

Decision No.: 483239

Petition No.: 3E8201

Risk Assessment Type: NA

TXRNo.: NA DP Barcode: D419828
Registration No.: None
Regulatory Action: Section 3 Registration

Case No.: 0262

CAS No.: 1910-42-5

MRID No.: None 40 CFR: 180.205 

# /d--

From: Thurston G. Morton, Chemist

# ~**~.....r** Risk Assessment Branch IV

Health Effects Division (7509P)

Through: Elissa Reaves, PhD, Branch Chief

Risk Assessment Branch IV

Health Effects Division (7509P)

To: Andrew Ertman

Barbara Madden

Risk Integration, Minor Use & 

### Emergency Response Branch Registration Division (RD) (7505P)

1 

### of 11Paraquat Dichloride Summary of Analytical Chemistry and Residue Data Barcode: D419828

Executive Summary

Paraquat dichloride (hereafter in this document referred to solely as paraquat) is a non-selective

herbicide currently registered for the control of weeds and grasses in agricultural and nonagricultural areas, and for use as a defoliant, desiccant, and plant growth regulator. The Paraquat Reregistration Eligibility Decision (RED) Document (EPA 738-F-96-018) was issued in August

1997. The Product and Residue Chemistry Chapters of the RED were completed in July of 1995 (D217262, D. Miller). Currently all registered end-use products are formulated as paraquat dichloride, and the active ingredient is expressed in terms of the paraquat cation.

The Interregional Research Project No.4 (IR-4), in PP#3E8201, has proposed the expansion of

the potato tolerance for residues of the herbicide paraquat (1,1 '-dimethyl-4,4'-bibyridinium ion)

derived from the application of the dichloride salt (calculated as the cation) to Tuberous and

Corm Vegetables Subgroup 1 C.

Tolerances for residues of paraquat have been established under 40CFR§180.205

. The

tolerances are expressed in terms of residues of paraquat derived from application of either the bis(methyl sulfate) or the dichloride salt (both calculated as the cation). Because there are currently no registered products containing paraquat dimethyl sulfate, the tolerance expression

listed under 40CFR§180.205(a) and §180.205(c) should be revised to remove reference to the bis(methyl sulfate) salt of**paraq~t.** This was previously recommended by HED in 2006. In

2009 HED issued guidance on tolerance expressions (S. Knizner, 2009). We now conclude the

tolerance expression should be as follows: Tolerances are established for residues of paraquat, including its metabolites and degradates, in or on the commodities in the table below. Compliance with the tolerance levels specified below is to be determined by measuring only

paraquat dichloride and calculated as the paraquat cation.

General tolerances have been established under 40CFR§180.205(a), and range from 0.01 ppm for

egg and milk to 210 ppm for Animal feed, nongrass, group 18, hay. Tolerances with regional registration have been established under 40CFR§ 180.205( c) at 0.05 ppm for cassava, pigeon pea seed, tanier, tyfon, and true yam, and at 0.1 ppm for taro corm.

The qualitative nature of paraquat residues in plant commodities is understood based upon studies depicting the metabolism of paraquat in carrots and

. lettuce folloWing preemergence

treatment and in potatoes and soybeans following desiccant treatment. The residue of concern in plants is the parent, paraquat. The qualitative nature of residues in livestock is adequately

understood based on the combined results of studies conducted with ruminants (goats and cows),
swine, and poultry. The residue of concern in eggs, milk, and poultry and livestock tissues is

also parent paraquat.

An adequate spectrophotometric method, Method I of the Pesticide Analytical Manual (PAM)

Vol. II, is available for enforcing tolerances for residues of paraquat in/on plant commodities.

For the method, samples are heated at reflux with 0.5 M sulfuric acid and then applied to a cation exchange column. Paraquat residues are eluted with saturated ammonium chloride solution.

Cotton seed samples are first subjected to Soxhlet extraction in hexane, and the hexane extract is

refluxed with sulfuric acid and then applied to the cation exchange column. An aliquot of the

column eluate is mixed with 0.2% (w/v) sodium hydrosulftte in 0.3 M sodium hydroxide, which

reduces paraquat to a free radical. Residues are determined using a variable wavelength

2 of11Paraquat Dichloride Summary of Analytical Chemistry and Residue Data Barcode: D419828



### 3 of 11 spectrophotometer, measuring the light absorption of the paraquat free radical. The validated limits of quantitation (LOQ) vary from 0.01 ppm up to 0.5 ppm.

PAM Vol. II lists a spectrophotometric method, designated as Method Ia (LOD = 0.005 ppm), as available for the enforcement of tolerances for paraquat resi dues in animal commodities. In addition, an adequate HPLC/UV method is available for the enforcement of tolerances for paraquat residues in livestock tissues and eggs (RAM 004/04, MRID 43226902; this method has not yet been published in P AM Vol. II); the reported LOQ is 0.005 ppm for livestock tissues and

eggs.

Adequate storage stability data are available indicating that residues of paraquat are stable under frozen storage conditions in/on representative examples of the following crop groups for at leas t
18 months: non

- oily grains , including corn grain; leafy vegetables , including corn forage, fodder, and silage ; root crops ; and fruits or fruiting vegetables. In addition, residues of paraquat have been found to be stable in/on cantaloupe stored frozen for up to 3.7 months, cucumber stored frozen for up to 4.0 months, summer squash stored frozen for up to 2.6 months, ginger root stored frozen for up to 2.4 months , and okra pod stored frozen for up to 7.3 months. It was previously concluded that storage stability data for corn grain may be translated to oilseeds.

T he available ruminant and poultry feeding study data indicate that the tolerance recommendations of the RED Document (8/97) are appropriate

, and that increased tolerances for

livestock commod ities are not needed to support the requested expansion to crop group 1C

.

Regulatory Recommendations and Residue Chemistry Deficiencies

Pending the submission of a revised Section F, t here are no residue chemistry issues that woul d preclude granting a registration for paraquat on the Crop Subgroup 1C , as follows:

In 2009 HED issued guidance on tolerance expressions (S. Knizner, 2009). We now conclude the tolerance expression should be as follows: Tolerances are established for r esidues of

paraquat, including its metabolites and degradates, in or on the commodities in the table below. Compliance with the tolerance levels specified below is to be determined by measuring only paraquat dichloride and calculated as the paraquat cation

.Paraquat Dichloride Summary of Analytical Chemistry and Residue Data Barcode: D419828



### 4 of 11 Table 1. Tolerance Summary for Paraquat Dichloride

Commodity Tolerance (ppm) Comments ( correct commodity definition ) Established Proposed Recommended

Tolerances to be established under 40 CFR ' 180.205(a):

Tuberous and corm vegetables subgroup 1 C -- 0.5 0.50

Potato 0.5 Revoke Covered by Tuberous and corm vegetables subgroup 1C

Tolerances to be revoked under 40 CFR ' 180.205(c):

Cassava 0.05 Revoke Covered by Tuberous and corm vegetables subgroup 1C

Tanier 0.05 Revoke Covered by Tuberous an d corm vegetables subgroup 1C

Yam, true, tuber 0.05 Revoke Covered by Tuberous and corm vegetables subgroup 1C



### Background

IR

- 4 has submitted a petit ion (PP# 3 E 8201 ) requesting for the expansion to tuberous and corm vegetables subgroup 1C using the cur rent potato tolerance. Potato is the representative crop for subgroup 1C. The PC Code, nomenclature, and chemical structure of paraquat are listed below in Table 1. The physicochemical properties of paraquat are listed in Table 2.

Table 1. Nomenclat ure of Paraquat Dichloride

. Compound

Common name Paraquat dichloride

IUPAC name 1,1’

- dimethyl

- 4,4’

- bypyridinium dichloride

CAS name 1,1’

- dimethyl

- 4,4’

- bypyridinium dichloride

CAS registry number 1910

- 42

- 5 (4685

- 14

- 7 for the cation)

End

- use product (EP) 2.0 lb paraquat cation/gal SC (Gramoxone Inteon; EPA Reg. No. 100

- 1217)Paraquat Dichloride Summary of Analytical Chemistry and Residue Data Barcode: D419828



### 5 of 11 Table 2. Physicochemical Properties of Technical Grade Paraquat Dichloride.

Parameter Value Reference

Melting point/range decomposes at ca. 340 °C Product Chemistry Chapter

o f the Paraquat Dichloride Update, 10/10/91 pH 6.4 at 20 °C

Density 1.5 g/cm 3 at 25 °C

Water solubility (20 °C) freely soluble in water:

618

- 620 g/L at pH 5.2, 7.2, and 9.2

Solvent solubility (20 °C) <0.1 g/L in acetone, dichloromethane, toluene, et hyl acetate, and hexane; 143 g/L in methanol

Vapor pressure <<10

- 8 kPa at 25 °C

Octanol/water partition coefficient, Log(K OW ) log K OW =

- 4.5 at 20 °C

Dissociation constant, pK
a 0.95 (pure active ingredient) Product Chemistry Chapter of the Paraquat

R eregistration Standard,

11/25/85

UV/visible absorption spectrum Not availableParaquat Dichloride Summary of Analytical Chemistry and Residue Data Barcode: D419828



### 6 of 11 860.1200 Directions for Use

IR

- 4 has submitted a petition (PP#3E8201) for expansion of the use on potato to Crop Subgroup 1C. The product to be used is Gramoxone SL 2.0 (EPA Reg. No. 100

- 1431), an emulsifiable concentrate (EC) formulation which contains 2 lb paraquat cation/gal. Gramoxone SL 2.0 is proposed for pre plant or preemergence directed spray to tuberous and corm vegetables subgroup 1C. Maximum application rate is 0.5 lb a.i./A. A maximum of three applications is proposed. No pre

- harvest interval (PHI) is specified.

Table 3. Summary of Proposed End

- Use Product.

Trade Name Reg.

No. ai (% of formulation) Formula

tion Type Target Crops Target Pests Label Dat e

Gramoxone

SL 2.0 100

-

1 431 2 lb
paraquat cation/gal E C Tuberous and Corm Vegetables Subgroup 1C A variety of small

annual weeds (broadleaves and grasses), and perennial weeds; also

used as a harvest aid

and desiccant. Proposed

supplemental label + regis tered label

Table 4. Summary of Proposed Directions for Use of Gramoxone Inteon (100

- 1217).

Application Timing Application

Rate (lb ai/A) Max. No.

Applic.

per Season RTI 1

(days) Max.

Seasonal Applic. Rate (lb ai/A) PHI

(days) Use Directions and other

L imitations

Tuberous and Corm Vegetables Subgroup 1C

Preplant or Preemergent Broadcast

spray 0. 25

- 0. 5 3 28 NS NS Apply up to ground cracking before crop has emerged using ground equipment in a minimum of 10 gal/A or aerial in 5 gal/A

.
1 RTI = Retreat ment intervalParaquat Dichloride Summary of Analytical Chemistry and Residue Data Barcode: D419828



### 7 of 11 The supplemental label specifies that preplant and preemergence applications must be made prior to crop emergence. Intentional or accidental contact (including drift) with the crop may result in severe damage or loss of the crop.

The cur rent product label prohibits application through any type of irrigation system . All rotational crops may be planted immediately after the last application.

Conclusion s

. The proposed use directions are adequate to allow evaluation of the available residue data relative to the proposed use.

860.1300 Nature of the Residue

- Plants

The r esidue c hemistry c hapter of the RED (D217262, D. Miller, 7/28/95) concluded that

, f or the purposes of reregistration and risk assessment, the qualitative nature of the residue in plants is adequately understood based on studies depicting the metabolism of paraquat in carrots and lettuce following preemergence treatment and in potatoes and soybeans following desiccant

treatment. The residue of concern in plants is parent paraquat.

860.1300 Nature of the Residue

- Livestock

The r esidue c hemistry c hapter of the RED (D217262, D. Miller, 7/28/95) concluded that f or purposes of reregistration and risk assessmen t, the qualitative nature of the residue in animals is adequately understood based on the combined results of studies conducted with ruminants (goats and cows), swine, and poultry. The residue of concern in eggs, milk, and poultry and livestock

tissues is parent paraquat.

860.1340 Residue Analytical Methods

Plant commodity method

PAM Vol. II lists a spectrophotometric method, designated as Method I (LOD = 0.01

- 0.06 ppm), as available for the enforcement of tolerances in plant commodities. Several modif ications of Method I have been developed for analysis of specific crops, and these modified methods have

been used for data collection.

The RED Document ( EPA 738

- F

- 96

- 018, 8/ 97) reported that radiovalidation data had been provided for Method 1B of the e nforcement method using radiolabeled samples. The Agency tentatively concluded that Method 1B adequately recovers paraquat cation residues from samples of potat oes and soybeans treated with [ 14 

### C]paraquat. At the time of the RED document, t he registrant h a d recently submitted representative spectra and other supporting raw data from the radiovalidation study (MRID 43954002). I t was concluded that

, upon the Agency’s review of this additional information, the requirements for residue analytical methods for plant

commodities would be considered fulfilled for reregistration purposes. HED has not conducted a formal review of the data. A preliminary review has been conducted, however, and the data are considered to be adequate for the purposes of these toleran ce petitions.Paraquat Dichloride Summary of Analytical Chemistry and Residue Data Barcode: D419828



### 8 of 11 Conclusions

. The existing spectrophotometric method (Method I of PAM Vol. II) is adequate for collecting data on residues of paraquat in/on plant commodities. The method is adequate for tolerance enforcement purposes for these commodities.

Animal commodity method

PAM Vol. II lists a spectrophotometric method, designated as Method Ia (LOD = 0.005 ppm), as being available for the enforcement of tolerances in animal commodities. The registrant has submitted description s and adequate independent laboratory validation data for a high

performance liquid chromatography method (HPLC; designated as Method 4B) to determine paraquat residues in animal tissues and eggs. The method has been validated by the Analytical Chemistry Branch (ACB) . T he registrant wa s reque ste d to make minor changes in the method

write

- up. A revised version of the method has been submitted (RAM 004/04; MRID 43226902) and is now available for enforcement purposes

. The reported LOQ is 0.005 ppm for live stock tissues and eggs

.

860.1360 Multiresidue Methods

The FDA PESTDATA database (dated 11/01 ) does not have an entry for paraquat. The r esidue

c hemistry c hapter of the RED (D217262, D. Miller, 7/28/95) concluded that the existing FDA multiresidue methods are not likely to recover residues of paraquat because of i ts ionic nature.

860.1380 Storage Stability

This guideline is not relevant to the current petition.

860.1400 Water, Fish, and Irrigated Crops

This guideline is not rele vant to the current petition.

860.1460 Food Handling

This guideline is not relevant to the current petition.

860.1480 Meat, Milk, Poultry, and Eggs

This guideline is not relevant to the current petition.

860.1500 Crop Field Trials

No residue field t rial data have been submitted for this petition.

The registrant is requesting for the expansion to tuberous and corm vegetables subgroup 1C using the current potato tolerance. Potato is the representative crop for subgroup 1C.Paraquat Dichloride Summary of Analytical Chemistry and Residue Data Barcode: D419828



### 9 of 11 860.1520 Processed Food an d Feed

This guideline is not relevant to the current petition.

860.1650 Submittal of Analytical Reference Standards

paraquat dichloride, Syngenta, expiration date

10/31/2016 paraquat impurity 2,2.6,2" terpyridine, Syngenta, expiration date

10/1/2009 paraquat impurity 2,3,diphenylquinoxaline, Syngenta, expiration date

4/1/2002

The registrant must submit paraquat dichloride a nalytical reference standards when required to :

Theresa M. Cole US EPA National Pesticide Standard Repository

Environmental Science Center

7 01 Mapes Road Fort Meade, MD 20755

- 5350 Cole.Theresa@epa.gov (410) 305

- 2907

860.1850 /1900 Confined /Field Accumulation in Rotational Crops

This guideline is not relevant to the current petition.

860.1550 Proposed Tolerances

HED pr eviously determined that the residue of concern for paraquat in/on plant and animal commodities is paraquat per se (D217262, D. Miller, 7/28/95) . Because there are currently no registered products containing paraquat dimethyl sulfate, the tolerance expres sion listed under 40

CFR § 180.205(a) and § 180.205(c) should be revised to remove reference to the bis(methyl sulfate) salt of paraquat.

In 2009 HED issued guidance on tolerance expressions (S. Knizner, 2009). We now conclude the tolerance expression sho uld be as follows: Tolerances are established for residues of

paraquat, including its metabolites and degradates, in or on the commodities in the table below. Compliance with the tolerance levels specified below is to be determined by measuring only

paraq uat dichloride and calculated as the paraquat cation.

A summary of the recommended tolerances for the current petition is given in Table 6

.Paraquat Dichloride Summary of Analytical Chemistry and Residue Data Barcode: D419828



### 10 of 11 Table 6 . Tolerance Summary for Paraquat Dichloride

Commodity Tolerance (ppm) Comments ( correct commodity

d efinition ) Established Proposed Recommended

Tolerances to be established under 40 CFR ' 180.205(a):

Tuberous and corm vegetables subgroup 1C -- 0.5 0.50

Potato 0.5 Revoke Covered by Tuberous and corm vegetables subgroup 1C

Tolerances to be revoked under 40 CFR ' 180.205(c):

Cassava 0.05 Revoke Covered by Tuberous and corm vegetables subgroup 1C

Tanier 0.05 Revoke Covered by Tuberous and corm vegetables subgroup 1C

Yam, true, tuber 0.05 Revoke Covered by Tuberous and corm vegetables subgroup 1C



### Codex/International MRL Harmonization

The Codex Alimentarius Commission has established a maximum residue limit (MRLs) for paraquat residues in root and tuber vegetables . The Codex and U.S. tolerance s are in harmony with respect to MRL/tolerance expres sion; both regulate the parent paraquat cation only. The Agency cannot harmonize with the Codex MRL of 0.0 5 ppm since residues of paraquat dichloride in potatoes occurred above the Codex MRL of 0.05 ppm

. A comparison of the Codex

MRLs and the proposed U. S. tolerances is presented in the following table

.

No Canadian or Mexican MRLs have been established for paraquat. R egistered food/feed uses of paraquat exist in Canada . T hese uses presumably fall under the PMRA General MRL of 0.1 mg/kg

. Regulation B.15.002(1) of the Canadian Food and Drugs Regulations (FDR) establishes 0.1 ppm as the General Maximum Residue Limit. This regulation states that a food is adulterated if it contains residues of a pesticide at a level greater than 0.1 ppm unless a specif ic MRL has been established in Table II, Division 15 of the FDR.Paraquat Dichloride Summary of Analytical Chemistry and Residue Data Barcode: D419828



### 11 of 11 

### International Residue Limits

Paraquat Dichloride (060601; 04/30/2014)

Summary of US and International Tolerances and Maximum Residue Limits Residue Definition :
US Canada Mexico 2 Codex 3

40 CFR 180.205:

Plant: paraquat (1,1′

- dimethyl

- 4,4′

- bipyridinium

- ion) derived from application of either the bis(methyl sulfate) or the dichloride salt (both calculated as the cation) 4,4'

- bipyridinium,
1,1'

- dimethyl

Paraquat cation



### Commodity 1 

### Tolerance (ppm) /Maximum Res idue Limit (mg/kg)

US Canada Mexico 2 

### Codex
Tuberous and corm vegetables subgroup 1C 0.50 0.05 root and tuber vegetables

Completed: M. Negussie; 04/30/14

1 Includes only commodities of interest for this action. Tolerance val ues should be the HED recommendations and not those proposed by the applicant.

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



### References

Paraquat Dichloride. (061601) Product Che mistry Chapter and Residue Chemistry Chapter for the Reregistration Eligibility Document: CBRS No. 15906; Rereg. Case No. 0262 , D217262,

D. Miller

, 7/2 8 /95