## UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON

, D

. C

. 20460



## MEMORANDUM

Dat e : 04-FEB-2016 OFFICE OF C H EM I CA L SAFETY AN D POLL T I ON P REVENT I ON



## SUBJECT: Triclopyr

. P eti tion to Amend To l e rance Expr ess ion s to Includ e T riclop y r Choline Sa lt ; and P etition t o R e move Gr az in g R est riction s fo r D a iry Cattle.


## S umm ary o f Ana l ytical and Re s idue C h e mi s t ry Data.

P C Co d es: 1 16000

, 1 1600 I

, I 1 60 0 2, 1 16004

D ecisio n No.: 488478

Petition Nos.: 4F8249 & 

### 4 F 8279
Ri sk Assessme n t Type: 

### NA

TXR No.: 

### NA

MRIO No.: 4974 1901 DP No.: 0419487

R eg i s tration Nos.: 62719-37

, 62719-53

, 627 19-8 7,
62719

- 552

, 62719

- 637

, 62719-AIT (687)

R eg ul ator y Act i on: Section 3
Case No.: 2710
CAS Nos.: 55335-06 -3

, 5 72 1 3-69- 1

, 64700-56-7

, I 

### 0483 7 3- 85-8


### 40 CF R : 

### § 180 .4 1 7



## F rom: J e nnifer R. Ty ler

, C h e mi st 

# C**~rc11** Risk Assess m e nt Branch I 

## (RA B 1 )



## Through:

To: Health Effec t s Di v ision ( H E D

, 7509P)

Mindy Ondish, Ri sk R ev i ewe r Reuben Bari s , Product Man age r 25
Herbicide Branch ( HB) Registrati o n Division (RD

, 7505P)



## Exec uti ve S ummarv

Dow AgroSc i e nces ha s su bmitted 1 ) a p e titi o n to amend th e t o l e rance exp r ess i o n s for triclop y r t o includ e a new formulation

, tric l opyr cholin e sa lt (PP # 4F8 2 79) ; and 2) a petition to remove the grazing r estrict ion for la c t a tin g dairy catt l e , and establish a tol e rance for residue s in milk

, fat ( 0.70 ppm ) as we ll a s incr ease d tolerances for r es idue s in milk (0 .60 ppm )

, m ea t ( 0.08 ppm ), 

## fat ( 0.09 ppm )

, and meat b ypro duct s (0

. 7 ppm) (P P # 4F8249). Th e company su bmitted the re s ult s of a liv es t ock feeding study in s upport of PP # 4F8249.

Currently

, pennanent toleranc es are establi s hed for the combin e d r es idue s of triclopyr 

## per se, as

a result of the application/use of butoxyeth y l es ter of triclop y r a nd triethylamine s alt of tr i clop y r , in or on eggs; fish; grass forage and ha y; milk ; p o ultr y fat, m eat

, and meat b y products

, except
kidne y ; ri ce , g rain and s tr aw ; a nd shellfish [ 40 CF R 

## § 18 0.417 (a)( l ) ]. In addition

, permanent toleran ces a re established for re s idues of triclopyr acetic ac id a nd its metab o l it e 3

, 5

, 6

- trichloro-2- pyridinol (TC P ) as a r es ult of the applicat i on/use of butox ye th y l este r of triclopyr and

Page I of7

### Triclopyr Summary of Analytical Chemistry and Residue Data DP# 419487

Page 2 of 7 

## triethylamine salt of triclopyr, in or on the meat, fat, and meat byproducts of cattle

, goats, hogs, horses, and sheep [40 CFR §180.417 (a)(2)].

Regulatory Recomm endations and Residue Chemistry Deficiencies

Pending submission of a revised Section F (see requirements under Proposed Tolerances), there are no residue chemistry issues that would preclude granting the following:

PP# 4F8279: An updated tolerance expre ssion in 40 CFR §180.417(a) to state:

40 CFR 180.417(a)(1): “Tolerances are established for residues of the herbicide triclopyr, including its metabolites and degradates, in or on the commodities in the table below resulting from the application of the b utoxyethyl ester of triclopyr, triethylamine salt of triclopyr, or choline salt of triclopyr. Compliance with the tolerance levels specified below is to be determined by measuring only triclopyr (2

- [(3,5,6

- trichloro

- 2

- pyridinyl)oxy]acetic acid)

. ”

40 CFR 180.417(a)(2): Tolerances are established for residues of the herbicide triclopyr, including its metabolites and degradates, in or on the commodities in the table below resulting from the application of the butoxyethyl ester of triclopyr, triethyla mine salt of triclopyr, or choline salt of triclopyr. Compliance with the tolerance levels specified below is to be determined by measuring the combined residues of triclopyr (2

- [(3,5,6

- trichloro

- 2

- pyridinyl)oxy]acetic acid) and its metabolite 3,5,6

- trich loro

- 2

- pyridinol (TCP) , calculated as the stoichiometric equivalent of triclopyr .”

PP# 4F8249: The removal of the grazing restriction for lactating dairy cattle as well as the
establishment of th e following permanent tolera nces :

Milk 1 

## 0.60 ppm Meat* 2 

## 0.10 ppm Fat* 2 

## 0.10 ppm Meat byproducts* 2 

## 0.50 ppm * of cattle, goat, hog, horse

, and sheep.

1 40 CFR §180.417 (a)(1)

2 40 CFR §180.417 (a)(2)



## 860.1550 Proposed Tolerances

A summary of the recommended tolerances along with recommendations for commodity definitions are presented in Table 6 . The petitioner is requested to submit a revised Section F to
reflect the recommendations in Table 6

. A human health risk assessment wil l be prepared as a separate document (DP# 426071 )

.

Background

Triclopyr, triclopyr TEA, and triclopyr BEE products are used as selective herbicides to control broadleaf weeds and woody brush . Triclopyr products are registered for use on rice as well as a variety of non

- agricultural sites including rights of way, pasture and rangelands, forests, and turf (including home lawns), golf courses, cemeteries, parks, lakes, bayous, ponds, reservoirs, marshes, roadsides, fence rows, canals, ditch banks, athletic fields, storage yards, industrial sites, trails, patios, camp areas, homes and cabins (outdoor), and christmas tree plantings. Triclopyr

### Triclopyr Summary of Analytical Chemistry and Residue Data DP# 419487

Page 3 of 7 

## products are formulated as soluble concentrates, emulsifiable concentrates, liquids (pressurized and ready

- to

- use), gr anules, wettable powders, and pellets.

PP# 4F8279

Dow AgroSciences has submitted a petition to amend the tolerance expressions for triclopyr to
include a new formul ation, triclopyr choline salt. The company proposes that the tolerance expression in 40 CFR §180.417(a) be updated to state:

40 CFR 180.417(a)(1): “Tolerances are established for residues of the herbicide triclopyr (2

- [(3,5,6

- trichloro

- 2

- pyridinyl)oxy]acetic acid), including its metabolites and degradates,
in or on the commodities in the ta ble below resulting from the application of the butoxyethyl ester of triclopyr, triethylamine salt of triclopyr, or triclopyr choline. Compliance with the tolerance levels specified below is to be determined by measuring only triclopyr. ”

and,

40 CFR 180. 417(a)(2): Tolerances are established for residues of the herbicide triclopyr (2

- [(3,5,6

- trichloro

- 2

- pyridinyl)oxy]acetic acid), inclu ding its metabolites and degradates,
in or on the commodities in the table below resulting from the application of the
bu toxyethyl ester of triclopyr, triethylamine salt of triclopyr, or triclopyr choline. Compliance with the tolerance levels specified below is to be determined by measuring the combined residues of triclopyr and its metabolite 3,5,6

- trichloro

- 2

- pyridinol (TC P).”

In a memo dated 22

- MAR

- 2012, HED reviewed a request to determine the bioequivalence between triclopyr and triclopyr choline salt, and agreed that bioequivalence was supported by the currently available information (Memo, G. Kramer, D399410). Therefo re, HED recommends in favor of the request to amend the tolerance expressions for triclopyr to include triclopyr choline
salt.

PP# 4F8249

49741901 der.doc



## Dow AgroSciences has submitted a petition to remove the grazing restriction for lactating dairy
cattle on several registered labels for triclopyr (see Table 1 )

.

Table 1. Summary of Existing and Proposed Grazing Restrictions for Triclopyr.

Use Site Formulation (EPA Reg. No.) Existing Use
Directions and

Limitations Proposed Use Directions and
Limitations

Land Grazed by Lactating Dairy Animals (Rangelands, Pastures, CRP Acres, Non

- Crop Areas, Forestry) TEA MUP (EPA Reg. No. 62719

- 53) BEE MUP (EPA Reg. No. 62719

- 87)
Garlon ® 3A (EPA Reg. No. 62719

- 37) Remedy ® Ultra (EPA Reg. No. 62719

- 552)
PastureGard ® HL (EPA Reg. No. 62719

- 637) Do not allow lactating dairy animals to graze
treated areas until the next growing season.

PHI (hay): 14 days. Grazing or harvesting green forage: There are no grazing or haying restrictions for livestock including dairy animals on treated area.

Haying (harvesting of dried forage): Do not harvest within 14 days after application.

### Triclopyr Summary of Analytical Chemistry and Residue Data DP# 419487

Page 4 of 7 

## In addition, the company has also proposed the establishment of a tolerance for residues in milk, fat (0.70 ppm) as well as increased tolerances for residues in milk (0.60 ppm), meat (0.08 ppm), fat (0.09 ppm), and meat byproducts (0.7 ppm).

The ruminant feed items associated with triclopyr are grass forage and hay, and rice grain. Using residues from previously submitted magnitude of the residue studies on grass and rice

, HED
recalculated the maximum reasonable dietary burden ( MRDB ) for dairy cattle to include these commodities (see Table 2 ).

Table 2

. Calculation of MRDB of Beef/Dairy Cattle for Triclopyr.

Feed Commodity Feedstuff Type 1 % Dry
Matter 2 % Diet 2 Residue (ppm) 3 MRDB (ppm) 4

Beef Cattle (R=15%; CC=80%; PC=5%)
Grass hay R 88 15 173 (highest residue) 29.489

Rice grain CC 88 20 0.109 (average residue) 0.025

Untreated PC/CC NA 65 NA

- Total 29.513 Dairy Cattle (R=45%; CC=45%; PC=10%) Grass forage R 25 45 697 (highest residue) 1254.6

Rice grain CC 88 20 0.109 (average residue) 0.025

Untreated PC NA 35 NA

- Total 1255

1. CC = carbohydrate concentrate; R = roughage; PC = protein concentrate.
2. Table 1 (860.1000 OP PTS Test Guidelines; June 2008 Revisions of Livestock Diets Percents Reasonable Balanced Diets.
3. Highest residue of 173 ppm used for grass hay [ 1974 Study cited on pg. 16 of Section E of petition; residues in grass forage were determined following application at 1.5 lb ae/A; residues were extrapolated to 2 lb ae/A (labeled rate)]. Highest residue of 697 ppm used for grass forage (MRID# 41961001). Average residue of 0.109 ppm used for rice grain [used in D275030 (Memo, W. Donovan;
16

- APR

- 2002)].
4. Contribution = [tolerance /% DM (if cattle)] X % diet.



## The company submitted the results of a new livestoc k feeding study in support of PP# 4F8249 (MRID# 4974190 1 ) , and the study is considered to be scientifically acceptable and adequate to support the proposed petition

. In this study, lactating Friesian/Holstein dairy cattle were dosed orally with triclopyr for 28

- 29 consecutive days. The doses were administered on two occasions each day (AM and PM). The cows were divided into 5 treatment groups: control group (3 cows) ; 50

- ppm dose group (0.04x, 4 cows); 100 ppm dose group (0.08x, 4 cows); 500 ppm dose group (0.4x, 4 cows), and 1000 ppm dose group (0.8x, 16 cows). Twelve of the cows in the 0.84x treatment group were used to generate depuration data (3, 7, 14, and 21 da ys). At the end of the dosing, these cows were transferred to the control diet to measure the decline in residues following withdrawal of triclopyr from the diet. Residues of triclopyr and the metabolite TCP in tissues (muscle, liver, kidney, subcutaneou s fat, mesenteric fat, and perirenal fat) and milk (whole milk, skimmed milk, and cream) were determined using a high

- performance liquid chromatography (HPLC)/mass spectrometry (MS)/MS method. The limit of detection ( LOD )
and limit of quantitation ( LOQ ) f or each analyte were 0.003 ppm and 0.01 ppm, respectively. Residues of triclopyr and TCP from the 1000

- ppm dose group, including residues following a 3

- day depuration period, are summarized in Table 3

.

### Triclopyr Summary of Analytical Chemistry and Residue Data DP# 419487

Page 5 of 7 Table 3 . Triclopyr and TCP Residues in New Dairy Cattle Feeding Study at 1000

- ppm Dose (MRID#
4974190 1 ).

Matrix 1 

### Triclopyr TCP Triclopyr + TCP Average
Residue

(ppm) Maximum
Residue

(ppm) Average
Residue

(ppm) Maximum
Residue

(ppm) Average
Residue

(ppm) Maximum
Residue

(ppm) Whole Milk (Days 8

- 29 ) 0.071 0.216

- - - - Whole Milk (+3 days) 2 

### ND 4 

### ND

- - - - Skimmed Milk (Day 22) 0.044 0.161

- - - - Cream (Day 22) 0.028 0.095

- - - - Muscle 0.353 0.610 1.18 1.36 1.54 1.97 Muscle (+3 days) 2 

### ND 4 

### ND <LOQ <LOQ <0.0 15 <0.0 15 Composite/Average Fat 3 

### 1.65 2.35 4.64 7.67 6.29 10.0 Composite/Average Fat (+3 days) 2,3 

### 0.018 0.023 0.04 5 0.050 0.064 0.073

Liver 1.14 1.76 15.5 16.6 16.6 17.5 Liver (+3 days) 2 

### ND ND 0.197 0.249 <0.20 2 <0.25 4 Kidney 41.6 74.7 28.8 31.7 70.4 106 Kidney (+3 days) 2 

### <LOQ <LOQ 0.153 0.181 <0.163 <0.191

1. Residue of concern in milk is triclopyr only. Residues of concern in all other livestock commodities are triclopyr and metab olite TCP.
2. Residue levels after 3 days of depuration.
3. Composite fat residue values were calculated as the average of the triclopyr concentration in the corresponding subcutaneous, mesenteric, and perirenal fat samples.
4. < LOQ = limit of quantitation ( < 0.01 ppm); ND = not detect ed (<0.003 ppm) . For residues <LOQ, LOQ (0.01 ppm was used for
calculation. For ND r esidues, 1/2 LOQ (0.005 ppm) used for calculations.



## Current triclopyr labels contain the following pre

- slaughter interval: During the season of application, withdraw livestock from grazing treated grass a t least 3 days before slaughter.
Based on this r estriction, coupled with the fact that the majority of the livestock diet ary burden is from treated grass ( >99% of the dietary burden ) the company recommends using the residue data
from the 3

- day depuration period to determine appropriate tolerance levels for residues in/on
livestock m eat, fat, and meat byproducts. ChemSAC agreed with this proposal ( 18

- NOV

- 2015 ChemSAC Meeting Minutes ). In addition, ChemSAC recommended the pre

- slaughter interval listed on current triclopyr labels be amended to include a restriction against feeding treated grass
to livestock a t least 3 days before slaughter.

The anticipated residues for livestock commodities were determined using the Langmuir Model (see Table 5). The maximum percent residue s remaining following the 3

- day depuration period

were then used , as appropriate, to the determined the appropriate tolerances for livestock
commodities

.

Table 5 . Tolerance Calculation Pr oposal Using Langmuir Model and 3

- Day Depuration Data

. Dose Level (ppm) Commodity
Milk Muscle Fat Liver Kidney

54.8 0.01 0.314 0. 744 2.43 5.33
109.6 0.038 0.1 93 1.13 3.55 8.34
538.7 0.138 1.19 5.01 11.7 53.8
1057.4 0.517 1.97 10 17.5 106

Livestock Dietary Burden (ppm) Anticipated Residues 1 

### (ppm)

Dairy Cattle 1255 0.56 2.2 12 19 126 Depuration from 0 to 3 days Max % Remaining

- 0.76 0.7 3 1.45 0.1 8 Dairy Cattle

- 0.016 0 .087 0. 275 0.226

Tolerance 0.60 0.0 2 0.1 0 0.3 0 0. 30

1. Residue of concern in milk is triclopyr only. Residues of concern in all other livestock commodities are triclopyr and metabolite TCP.

### Triclopyr Summary of Analytical Chemistry and Residue Data DP# 419487

Page 6 of 7 

## Although p reviously submitted livestock feeding studies for triclopyr showed concentration of triclopyr in milk fat ( MRID# 00071808), residues did not concentrate in milk fat in the current study. Based on the high residues in kidney and liver and ionic nature of triclopyr, HED has determined that a tolerance for milk fat is not required.

HED reco mmends the tolerances listed in Table 6. A summary of current U.S. tolerances and Canadian maximum residue limits (MRLs) for tric lopyr can be found in Attachment 1. The recommended U.S. tolerances and Canadian maximum limits (MRLs) for milk is not harmonized. The removal of the grazing restriction necessitates higher tolerance level for milk. During Registration Review, HED will consider the possibility of harmonizing with Canada for the commodities with differing tolerances.

Table 6. Tolerance Summary for Triclopyr.

Commodity Established
Tolerance

(ppm) Proposed
Tolerance

(ppm) Recommended
Tolerance

(ppm) Canadian MRL (ppm) Comments
Correct Commodity Definition 40 CFR §180.417 (a)(1)
Milk 1 

### 0.01 0.60 0.60 0.01 Milk, fat 1



### - 0.70

- - 40 CFR §180.417 (a)(2)

Meat 2,3 

### 0.05 0.08 0.10 0.1

Fat 2,3 

### 0.05 0.09 0.1 0 0.1
Liver 2,3 

### 0.5

- NA

- Kidney 2,3 

### 0.5

- NA

- Meat byproducts, except kidney
and liver 2,3 

### 0.05

- NA

-

Meat byproducts 2,3



### - 0.7 0.5 0 0.5

1 Triclopyr only.
2 Triclopyr and TCP.
3 Meat fat, liver, kidney, and meat byproducts of cattle, goats, horses, hogs, and sheep.



## A revised Section F should b e submitted to include the recommended tolerances listed in
Table 6.

RDI: RAB1 Chemists ( 1 2 / 09 /201 5 ) ; G. Kramer (2/4/2016 ) cc: J. Tyler J. Tyler :S10943:PY

- S:(703)305

- 5564 :7509P:RAB1

### Triclopyr Summary of Analytical Chemistry and Residue Data DP# 419487

Page 7 of 7 

## Attachment 1: Triclopyr International Residue Limit Status Sheet

.

Summary of US and International Tolerances and Maximum Residue Limits. Residue Definition : US Canada Mexico 1 Codex US [40 CFR §180.417 (1) Tolerances for residues of the herbicide triclopyr per se, as a result of the application/use of butoxyethyl ester of triclopyr and triethylamine salt of triclopyr 3,5,6

- trichloro

- 2

- pyridyloxyacetic acid, including the metabolite 3,5,6

- trichloro

- 2

- pyridinol Milk: 3,5,6

- trichloro

- 2

- pyridyloxyacetic acid None

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

US Canada Mexico 1 Codex Egg 0.05
Fish 3.0 Grass, forage 700.0 Grass, hay 200.0
Milk 0.01 0.01 Poultry, fat 0.1 Poultry, meat 0.1 Poultry, meat byproducts, except kidney 0.1 Rice, grain 0.3 Rice, straw 10.0
Shellfish 3.5 US [40 CFR §180.417 (2) Canada Mexico 1 Codex 2

Livestock: (2) Tolerances for the combined residues of the herbicide triclopyr ((3,5,6

- trichloro

- 2

- pyridinyl)oxy) acetic acid and its metabolite 3,5,6

- trichloro

- 2

- pyridinol (TCP), as a result of the application/use of butoxyethyl ester of triclopyr or the triethylam ine salt of triclopyr 3,5,6

- trichloro

- 2

- pyridyloxyacetic acid, including the metabolite 3,5,6

- trichloro

- 2

- pyridinol Milk: 3,5,6

- trichloro

- 2

- pyridyloxyacetic acid None

Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg)
US Canada Mexico 1 Codex 2 Cattle, fat 0.05 0.1 Cattle, kidney 0.5 0.5 Cattle, liver 0.5 0.5 Cattle, meat 0.05 0.1 Cattle, meat byproducts, except kidney and liver 0.05 0.1 Goat, fat 0.05 0.1 Goat, kidney 0.5 0.5 Goat, liver 0.5 0.5 Goat, meat 0.05 0.1 Goat, meat byproducts, except kidney and liver 0.05 0.1 Hog, fat 0.05 0.1 Hog, kidney 0.5 0.5 Hog, liver 0.5 0.5 Hog, meat 0.05 0.1 Hog, meat byproducts, except kidney and liver 0.05 0.1 Horse, fat 0.05 0.1 Horse, kidney 0.5 0.5 Horse, liver 0.5 0.5 Horse, meat 0.05 0.1 Horse, meat byproducts, except kidney and liver 0.05 0.1 Sheep, fat 0.05 0.1 Sheep, kidney 0.5 0.5 Sheep, liver 0.5 0.5 Sheep, meat 0.05 0.1 Sheep, meat byproducts, except kidney and liver 0.05 0.1 Completed: M. Negussie; 02/19/2014

1 

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

### Triclopyr (PC Code I 1 6001 )/Dow AgroSciences



## B.7.8 Live s tock Feeding Studies (Annex IIA 6.4; Annex IHA 8.4)

8.7

. 8.1 Cattle

Document ID: MRTD No. 49741901 

## Report: Rawle, N. (2015) Triclopyr Livestock Feeding Study : Magnitude of the
Residue in Milk

, Muscle, Liver, Kidne y and Fat of Lactatin g Dairy Cattle. Report Nos. CEMS-6356

, 131285, CE MR 6356. Unpublished study prepared by Dow AgroSciences D anmark A/S. 672 p. 

## Guidelines: EPA OCSPP Harm onized Test Guideline 860.1480 Meat/Milk/Poultry / Eggs (August 1996)

PMRA Reg ul ato r y Directiv e D JR 98-02

- Residu e Chemistry Guidelines

, Section 8

- Meat/Milk/Poultry/Eggs
OECD Guideli n e 505 Residues in Livestock (January 2007) 

## GLP Compliance: No deviations from U.S. EPA regulatory requirements were reported
which wou ld hav e an impact on the validity of the study. 

## Acceptability: The srudy is con s idered scie ntificall y acceptable. The acceptability of this

stu d y for regulatory purposes i s addres se d in the forthcoming U.S. EPA

Residu e Chemistry Summary Document

, DP # 419487.**~** 

## E valuator: Jennifer R. Tyler

, Chem i st

## ~~.-,.//...c;::>• 

# _,_... Registration Action Branch I / Health E ffects Di v ision**~** 

## / (RAB 1 / HED, 7509P)

Note: Thi s Data Evaluation Record (DER) was o ri ginally prepared under contract by Versar, Inc

. (68 5 0 Ver sa r Ce nt er.

pringfield. VA 2215 I: submined I 2 / 30 / 15 ). The D E R has been reviewed b y 1-1 ED and r evised to reflect current Office of
Pesticide Programs (OPP) policies.



## EXECUT IVE SUMMARY

Dow AgroSciences has submitted a cattle feeding st udy with triclopyr [2-[(3,5,6-trichloro-2- pyridinyl)oxy ]acetic acid ). In the study

, four groups of dairy cows (4 cows/g roup) were dosed orally via ge latin capsule, twice daily after milking for 28

- 29 consecutive days

, with triclopyr at 1.646, 3

. 265, 15.905

, and 34.391 m g/kg bw / day (Groups B

, C, D

, and E). Ba sed on the average feed consumpt i o n , the actual mean daily dose level s were equivalent to 54.8, 109.6

, 538.7, and
1057.4 ppm in the diet (dry -w e ight ba s i s). Twelve additional cows in Group E were dosed to obta in depuration data. One group of three control cows (Gro up A) received capsules containing

no triclopyr. The in-life pha se of the study was conducted at ADAS Drayton (S tratford-onAvon, Warwickshir e, UK), and the analytical phase was conducted by CEM Analytical Se r vices (CEMAS; Wokinghan1

, Berkshire

, UK).

Cows were m il ked twice daily

, prior to dosing (PM and AM) and samp l es were collected for analys i s on Study Days -1(pre-dosing) ,2, 6

, 8, 10

, 14

, 18

, 22

, 26, and 28 or 29. In addition

, milk was collected from the depuration cows on Study Da ys 29, 31

, 33, 35, 38, 40. 42

, 45

, 48

, and49( 1 ,3, 5, 7, 10, 12, 14

, 17

, 20,and21 daysafterthefinaldose). E xtra milk collected on D ays 22 and 26 (proportional composite of previous day P M and that day AM sample) was used
for preparation of cr e am and skim milk samples. Animals that were not included in the depuration study were sacr ifi ced

- 3

- 6 hours after the final dose on Study Da ys 28 (Groups C and E) and 29 (Gro u ps B and D ). Sam ples of liver

, kidney

, 

## fat (subcutaneous

, mesenteric, and

MRlD # 49741901 Page I of24

### Triclopyr [PC Code 116001]/Dow AgroSciences

MRID# 49741901 Page 2 of 24 

## perirenal ) , and muscle (composite of hind leg or flank, loin, and diaphragm) were collected from
each cow.

Samples were stored frozen (≤

- 18 °C) at the test facility, during shipping, and at the analytical laboratory until analysis

. Maximum s torage durations were : 57 days (1.9 months) for whole milk; 79 days (2.6 months) for ski m milk; 152 days (5.0 months) for cream; 111 days (3.7 months) for triclopyr and 150 days (4.9 months) for 3,5,6

- trichloro

- 2

- pyridinol (TCP) for liver; 99 days (3.3 months) for kidney; 98 days (3.2 months) for fat; and 106 days (3.5 months) for
muscle. Th e intervals between extraction and analysis were not reported. To support sample storage durations, a concurrent storage stability study was conducted with the feeding study reflecting three storage intervals : 0 ; 30, 32, or 63 ; and 105

- 171 days for sampl es of whole milk, skim milk, cream, and all tissues fortified with both analytes . The data demonstrate that residues of triclopyr and TCP [3,5,6

- trichloro

- 2

- pyridinol] are stable for up to: 168 days in whole milk ; 110 days in skim milk; 153 days in crea m; 171 days in liver; 105 days in kidney; 159 days in fats; and 160 days in muscle. These data are adequate to support the study.

Samples were analyzed for residues of triclopyr an d metabolite TCP using two high

- performance liquid chromatography methods with tandem mass

- spectrometry detection (LC/MS/MS) based on the methods described in Dow AgroSciences Study ID 130961 for whole milk, skim milk

, and tissues and in Study ID 120588 for cream. The limit of quantitation (LOQ; determined as
the lowest level o f method validation, LLMV) was 0.01 ppm for each analyte in each bovine
matrix ; t he combined LOQ was 0.02 ppm. The methods were adequate for data collection based on acceptable concurrent recovery data from samples fortified with each analyte at: 0.01

- 1. 0 ppm for whole milk

, skim milk

, and cream; 0.01

- 20 ppm for liver; 0.01

- 75 ppm for kidney; 0.01

- 10 ppm for fat; and 0.01

- 2.0 ppm for muscle. The fortification levels used in concurrent method recovery were adequate to bracket expected residue levels (with in an order of magnitude for fat)

. Concurrent recoveries were corrected for apparent residues in controls; residues in the treated samples were not corrected for residues in controls. Quantifiable residues of TCP were converted to parent equivalents by the study reviewer using a molecular weight conversion factor of 1.3 (MW triclopyr 256.46 ÷ MW TCP 198.44).

Combined residues of triclopyr and TCP were below the LOQ in all samples of cream and near or below the LOQ in whole milk and skim milk (residues r anged <0.02

- <0.0 37 ppm) at the 54.8

- ppm dose level. At the 109.6

- and 538.7

- ppm dose levels, combined residues in whole milk plateaued by Study Day s 6

- 8; at the 1057.4

- ppm dose level, residues of triclopyr plateaued by Day 8, but residues of TCP continued to increase through the study. Residues of TCP in milk exceeded those of triclopyr at the 109.6

- , 538.7

- , and 1057.4

- ppm dose levels, respectively, by up to 3.2x (average 1.9x), 18x (average 8.8x), and 15x (average 6.1x). Combined residues of triclopyr and TCP at the 109.6

- , 538.7

- , and 1057.4

- ppm dose levels, respectively, were: <0.026

- 0.065, 0.094

- 0.377, and 0.184

- 0.602 ppm in whole milk; <0.029

- 0.049, 0.123

- 0.314, and
<0.235

- 0.615 ppm in skim milk; and <0.02

- <0.028, <0.069

- 0.177, and <0.114

- 0.339 ppm in

cream.

Quantifiable residues triclopyr and TCP were observed in tissues at all dosing levels , with the highest residues observed in kidney, then liver, and the lowest residues observed in muscle.
Ratios of residues in tissues to those in feed were re latively consistent across feeding levels except for those in liver, which declined steadily with increasing feeding level. Residues of TCP exceeded those of triclopyr in liver (average 1 5

- 26x), fat (1.6

- 4.0x), and muscle (1.7

- 3.7x) but

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MRID# 49741901 Page 3 of 24 

## were lower than th ose of triclopyr in kidney (0.3

- 0.8x). Combined residues of triclopyr and TCP
at the 54.8

- , 109.6

- , 538.7

- , and 1057.4

- ppm dose leve l s , respectively, were : 0.929

- 2.43, 2.46

- 3.55, 10.3

- 11.7, and 14.3

- 17.5 ppm in liver; 2.77

- 5.33, 6.46

- 8.34, 28.2

- 53.8, and 48.3

- 106 ppm in kidney; 0.058

- 0.744, 0.130

- 1.13, 1

. 26

- 5.01, and 3.25

- 10.0 ppm in composite fat (calculated by the petitioner as the average of analyte concentrations in the corresponding samples of individual fats); and 0.040

- 0.134, 0.147

- 0.193, 0.975

- 1.1 9, and 1.29

- 1.97 ppm in muscle.

The depuration study indicated that f ollowing removal of the test substance from the diet, residue
levels decreased in milk and all tissues, with residues decreasing most rapidly in milk and muscle and least rapidly in live r. C ombined residues of triclopyr and TCP in whole milk and muscle
decreased to below the LOQ (<0.02 ppm) by Study Day 31 (Depuration Day 3). Combined
residues were near or below the LOQ in kidney by Study Day 42 (Depuration Day 14) and in fats by Study Day 49 (Depuration Day 21). Average combined residues were <0.031 ppm in liver by Study Day 49.

Linear

- regression analysis demonstrated a generally linear relationship between dose level and resulting residues in milk and tissues, with a better correlat ion observed for TCP than for triclopyr.

I. MATERIALS AND METHOD S

A. MATERIALS

Table B.7.8.1

- 1

. Nomenclature for Triclopyr and Compounds of Interest.

Common name Triclopyr Identity [(3,5,6

- Trichloro

- 2

- pyridinyl)oxy]acetic acid

CAS no. 55335

- 06

- 3 Company experimental name Not applicable Other synonyms (if applicable) Not applicable

Metabolite TCP Identity 3,5,6

- trichloro

- 2

- pyridinol

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## B. STUDY DESIGN

1. Test Procedure

Four groups of dairy cows (4 cows/group) were dosed orally via gelatin capsule, twice daily after milking for 28

- 29 consecutive days, with triclopyr at 1.646, 3.265, 15.905, and 34.391 mg/kg bw/day (Groups B, C, D, and E). Based on the average feed consumption, the actual mean daily dose levels were equivalent to 54. 8, 109.6, 538.7, and 1057.4 ppm in the diet (dry

- weight basis). Twelve additional cows in Group E were dosed to obtain depuration data. One group of three control cows (Group A) received capsules containing no triclopyr. The in

- life phase of the study

w as conducted at ADAS Drayton (Stratford

- on

- Avon, Warwickshire, UK)

Livestock

Table B.7.8.1

- 2 . Description of Livestock Used in the Feeding Study.
Species Breed Age (Years) Weight at Study Initiation (kg) Health Status Description of Housing/Holding Area

Bos taurus Friesian/
Holstein 3.5

- 7.5 526

- 828 (Study Day

- 1) All health issues were relatively minor and typical for cows of this

age Individual stalls (3.75 m x 3.45 m) Natural light with artificial lighting as necessary, naturally ventilated. Min/max temperatures &
R.H. were recorded daily but were not reported

.



## Diet

Table B.7.8.1

- 3 . Test Animal Dietary Regime. Composition of Diet Feed Consumption 1 ( Avg. kg/ cow/wk ) Water Acclimation Period Predosing

Grass silage ( ad libitum ); Pelleted dairy compou nd: ~11 kg/day split into 3 feedings Group A: 18.06

- 20.58 Group B:17.95

- 19.93 Group C: 18.71

- 20.90 Group D: 17.75

- 19.71 Group E: 19. 0 2

- 21.21 Ad libitum 14 days None

1 The petitioner noted that cows in all groups had slightly lower intake in week three compared to the rest of the study. The level of dosing did not seem to affect food intakes.



## Treatment

Table B.7.8.1

- 4 . Dosing Regime.

Treatment Group (Cow #s) Treatment Type Level of
Administered Dose

(mg/ kg b w / day) Residue
Intake in Diet (ppm) Vehicle Timing/ Duration (days)

Group A (1, 2, 3) Oral 0 0 Gelatin capsule N/A Group B (4, 5, 6, 7) 1.646 54.8 29 Group C (8, 9, 10, 11) 3.265 109.6 28 Group D (12, 13, 14, 15) 15.905 538.7 29 Group E (16, 17, 18, 19) 1 34.391 1057.4 28

1 Group E also contained cows (20, 21, 22), (23, 24, 25), (26, 27, 28), and ( 29, 30, 31) for the depuration study.

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## Sampling

Table B.7.8.1

- 5 . Sample Collection.

Milk Collected Urine, Feces, Cage
Was h Collected Interval From Last
Dose to Sacrifice Tissues Harvested and Analyzed

Milk was collected twice daily. Milk
collected in the PM was combined with milk collected the following morning to generate daily samples. Skim milk and cream were generated from milk samples collected as above on Study Days 22 and 26 Not collected Feeding study:
3

- 5.5 hours

Depuration study:
3

- 21 days Liver Kidney Fat ( s ubcutaneous, m esenteric, perirenal )
Muscle (comprised of equal pieces of hind leg or flank, loin, and diaphragm muscle)



## Sample Handling and Preparation

Milk was collected twice daily, prior to dosing (PM and AM) on Study Days

- 1 (pre

- dosing), 2, 6, 8, 10, 14, 1 8 , 22, 26

, and 28. In addition, milk was collected from the depuration cows on Study Days 29, 31, 33, 35, 38, 40, 42, 45, 48, and 49 (1, 3, 5, 7, 10, 12, 14, 17, 20, and 21 days after the final dose). For each cow, milk from the PM collection was stored refrigerat ed (5 ± 3 °C) overnight until it was composited with the following day’s AM sample to produce a daily sample. The composited samples were then stored frozen (<

- 18 °C). Average milk yields for the respective dose levels (0

- 1057.4 ppm) were: 24.4, 23.3, 2 2.4, 24.4, and 26.2 kg/day. Extra milk collected on Days 22 and 26 (proportional composite of previous day PM and that day AM sample) was centrifuged to separate cream and skim milk.

Animals that were not included in the depuration study were sacrificed ~3

- 6 hours after the final dose on Study Days 28 (Groups C and E) and 29 (Groups B and D) . For the depuration study, three cows were terminated on each of Study Days 31, 35, 42, and 49 (Depuration Days 3, 7, 14, and 21). Samples of liver, kidney, fat (su bcutaneous, mesenteric, and perirenal), and muscle
were collected from each cow

. Tissue samples were placed in frozen storage (<

- 18 °C) within 3
hours of collection

.

The petitioner stated that no adverse treatment

- related effects were observed on body weight, feed consumption

, or milk production, and that no treatment

- related behavioral reactions or systemic signs of toxicity were noted. Gross necropsies showed no effects that appeared to be

treatment

- related.

Samples were shipped frozen by ground tra nsport within 1

- 20 days of collection to the analytical laboratory (CEMAS) , where they were stored frozen (≤

- 18 °C) until preparation for analysis. Samples of liver, kidney, and fat were prepared for analysis by homogenizing in the presence of dry ice; dr y ice was not needed for homogenization of muscle samples, and no preparation was needed for whole milk, skim milk, or cream.

2. Description of Analytical Procedures

Samples were analyzed for residues of triclopyr and metabolite TCP using two LC/MS/MS methods, based on the methods described in Dow AgroSciences Study ID 130961 for whole milk, skim milk

, and tissues and in Study ID 120588 for cream. Brief descriptions of the methods, including modifications for method 120588 were included in the submiss ion.

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## Briefly, samples of milk, skim milk, and tissues were extracted with methanol:2.5 N NaOH (90:10, v:v). An aliquot of the extract was acidified with 1.0 N HCl, then purified through a

reverse

- phase polymeric solid phase extraction (SPE) column. Resi dues were eluted with acetonitrile (ACN)/water/1 N HCl, and the eluate was diluted with a solution containing stable isotope standards of triclopyr and TCP in water:acetic acid (99 .9 : 0. 1, v:v) for analysis by
LC/MS/MS.

Samples of cream were extracted with water:ACN (1:1, v:v) and QuEChERS extraction salts (MgSO 4 

## :NaCl:sodium citrate:disodium citrate sesquihydrate (4:1:1:0.5, w:w:w:w)), and the ACN phase was placed in a freezer overnight to precipitate fat. An aliquot of the resulting extract was centrifuge d if necessary and combined with water/0.1% acetic acid and stable isotope internal standard solution. The mixture was filtered (0.4 5 μm) for analysis by LC/MS/MS.

The methods monitor the following ion transitions for quantitation of triclopyr and TCP,

r espectively: m/z 254.1 → 196.0 and m/z 197.7 → 106.8. The methods do not provide for conversion of metabolite residues to parent equivalents; therefore, quantifiable residues of TCP were converted to parent equivalents by the study reviewer using a molec ular weight conversion factor of 1.3 (MW triclopyr 256.46 ÷ MW TCP 198.44).

The LOQ (determined as the LLMV) was 0.01 ppm for each analyte in each bovine matrix; the combined LOQ was 0.02 ppm. The limit of detection (LOD) for each analyte was 0.003 ppm.

II. RESULTS AND DISCUSSION

Method performance was evaluated during method validation and by use of concurrent recovery samples . For method validation, samples of skim milk, cream, and muscle were fortified with each analyte at 0.01 and 0.10 ppm; for concurrent recoveries, samples were fortified with each analyte at: 0.01, 0.10, 0.50, and 1.0 ppm for whole milk; 0.01, 0.10, and 1.0 ppm for skim milk and cream; 0.01, 0.10, 1.0, 10, and 20 ppm for liver; 0.01, 0.10, 1.0, 10, and 75 ppm for kidney; 0.01, 0.1, 0.5, 1.0, 5.0 and/or 10 ppm for fat; and 0.01, 0.10, and 2.0 ppm for muscle. Recoveries were generally within the acceptable range of 70

- 120%; therefore, the method s w ere considered valid for the analysis of triclopyr and TCP resid ues in bovine matrices (Table B.7.8.1

- 6). The
fortification levels bracketed the measured residues (within an order of magnitude for fat)

. Concurrent recoveries were corrected for apparent residues in controls.

The detector response was linear for all matrices (coefficient of determination, r 2 

## ≥ 0.9968 ) within the range of 0.05

- 10 ng/mL . Representative chromatograms of control samples, fortified samples

, and treated samples were provided. The control chromatograms generally had no peaks
of inte rest above the chromatographic background. The fortified sample chromatograms contained only the analyte of interest, and peaks were symmetrical and well defined

. Apparent
residues in controls were below the LOQ (<0.01 ppm) for each analyte in all contro l samples of whole milk, skim milk, cream, kidney, fat, and muscle. Residues of triclopyr were below the LOQ in all control samples of liver; however, apparent residues of TCP were observed at 0.023

- 0.048 ppm

. To investigate whether TCP may have formed d uring storage or when samples were thawed for preparation or analysis, retain samples were analyzed with extra precautions taken to keep them as cold as possible; however, TCP was also found in control retain samples. The petitioner concluded that it was “unclear what was responsible for the TCP residues in control
liver.” The reported residue values were not corrected for apparent residues in controls.

### Triclopyr [PC Code 116001]/Dow AgroSciences

MRID# 49741901 Page 7 of 24 

## Quantifiable r esidues of TCP were converted to parent equivalents by the study reviewer using a molecular weight conversion factor of 1.3 (MW triclopyr 256.46 ÷ MW TCP 198.44).

Table B.7.8.1

- 6. Summary of Method Validation and Proce dural/Concurrent Recoveries of Triclopyr and
TCP from Bovine Matrices

. Matrix Analyte Fortifi

cation
Level (ppm) Samp le size (n) Quantitation 1 Confirmation 1

Recoveries 2 (%) Mean ± Std.
Dev. (%) Recoveries 2 (%) Mean ± Std.
Dev. (%)

Method Validation

Skim milk Triclopyr 0.01

- 0.10 10 78

- 88 83 ± 3.6 80

- 87 83 ± 2.5

TCP 0.01

- 0.10 10 71

- 90 85 ± 6.4 73

- 87 82 ± 5.4

Cream Triclopyr 0.01

- 0.10 10 95

- 108 101 ± 3.6 96

- 105 101 ± 2.6

TCP 0.01

- 0.10 10 71

- 86 76 ± 6.9 70

- 86 77 ± 7.9

Muscle Triclopyr 0.01

- 0.10 10 72

- 88 83 ± 5.5 73

- 85 81 ± 4.3

TCP 0.01

- 0.10 10 76

- 90 82 ± 6.4 73

- 85 79 ± 4.5

Concurrent Recoveries

Whole milk Triclopyr 0.01

- 1.0 86 70

- 112 93 ± 7.9

TCP 0.01

- 1.0 71 69, 69 ; 71

- 111 86 ± 11

Skim milk Triclopyr 0.01

- 1.0 19 88

- 105 97 ± 5.5

TCP 0.01

- 1.0 19 71

- 104 86 ± 11

Cream Triclopyr 0.01

- 1.0 16 97

- 109 102 ± 3.6

TCP 0.01

- 1.0 16 66 ; 72

- 95 83 ± 8.8

Liver Triclopyr 0.01

- 20 25 92

- 106 97 ± 3.3

TCP 0.1

- 20 15 72

- 97 84 ± 7.2 Kidney Triclopyr 0. 0 1

- 75 25 83

- 112 105 ± 7.8

TCP 0.01

- 75 25 72

- 120; 121, 127 98 ± 17
Fat,
subcutaneous Triclopyr 0.01

- 5.0 12 71

- 90 83 ± 5.7

TCP 0.01

- 5.0 12 73

- 99 84 ± 8.4
Fat, mesenteric Triclopyr 0.01

- 10 21 86

- 108 98 ± 5.4

TCP 0.01

- 10 21 70

- 100 86 ± 8.6 Fat, perirenal Triclopyr 0.01

- 10 12 89

- 107 98 ± 5.2

TCP 0.01

- 10 12 87

- 113 102 ± 7.2

Muscle Triclopyr 0.01

- 2.0 21 88

- 110 98 ± 5.5

TCP 0.01

- 2.0 21 69, 69 ; 70

- 94 82 ± 8. 0

1 The methods monitor the following ion transitions for quantitation of triclopyr and TCP, respectively: m/z 254.1 → 196.0 and m/z 197.7 → 106.8; confirmation transitions were not reported.

2 Concurrent recoveries were corrected for apparent residues in controls ; values include f resh fortification recoveries for storage stability.



## Samples were stored frozen (≤

- 18 °C) at the test facility, during shipping, and at the analytical laboratory until analysis. Maximum storag e durations were: 57 days (1.9 months) for whole milk; 79 days (2.6 months) for skim milk; 152 days (5.0 months) for cream; 111 days (3.7 months) for triclopyr and 150 days (4.9 months) for TCP for liver; 99 days (3.3 months) for kidney; 98 days (3.2 mont hs) for fat; and 106 days (3.5 months) for muscle (Table B.7.8.1

- 7a). The intervals between extraction and analysis were not reported. To support sample storage durations, a concurrent storage stability study was conducted with the feeding study reflecti ng three storage intervals: 0; 30, 32, or 63; and 105

- 171 days for samples of whole milk, skim milk, cream, and all tissues fortified with both analytes (Table B.7.8.1

- 7b). The data demonstrate that residues of triclopyr and TCP are stable for up to: 16 8 days in whole milk; 110 days in skim milk; 153 days in cream; 171 days in liver; 105 days in kidney; 159 days in fats; and 160 days in muscle. These data are adequate to support the study. The petitioner also investigated the

### Triclopyr [PC Code 116001]/Dow AgroSciences

MRID# 49741901 Page 8 of 24 

## storage stability of resid ues of triclopyr in extracts of milk and tissues stored refrigerated (4 °C)
for 7

- 8 days. The results indicated that residues were stable for all matrices.

Table B.7.8.1

- 7 a . Summary of Storage Conditions.

Matrix Analyte Storage Temperature (°C) Actual Storage Duration 1 Interval of Demonstrated Storage Stability 2

Whole milk Triclopyr & TCP ≤

- 18 8

- 57 days (0.3

- 1.9 months) 168 days

Skim milk Triclopyr & TCP 75

- 79 days (2.5

- 2.6 months) 110 days

Cream Triclopyr & TCP 148

- 152 days (4.9

- 5.0 months) 153 days

Liver Triclopyr 90

- 111 days (3.0

- 3.7 months) 171 days

TCP 129

- 150 days (4.2

- 4.9 months) Kidney Triclopyr & TCP 78

- 99 days (2.6

- 3.3 months) 105 days

Fats Triclopyr & TCP 71

- 98 days (2.3

- 3.2 months) 159 days

Muscle Triclopyr & TCP 85

- 106 days (2.8

- 3.5 months) 160 days

1 Interval from collection/sacrifice to extraction. The intervals between extraction and analysis were not reported.

2 Based on a concurrent storage stability study (refer to Table B.7.8.1

- 7b).



### Table B.7.8.1

- 7b. Stability of Triclopyr and TCP Residues in Bovine Matrices During Frozen Storage (≤

- 18
°C )

. Commodity Analyte Spike
Level (ppm) Storage
Interval (days) Fresh Fortification Recoveries (%) [Avg.] Stored Sample Recoveries (%) Mean Recovery (%) Corrected % Recovery 1

Whole milk Triclopyr 0.10 0 87, 83, 85 [85] 86, 87, 87 87 102

32 96, 93, 95 [95] 101, 100, 103 101 107

168 80, 82, 81 [81] 81, 78, 80 80 98

TCP 0.10 0 77, 78, 73 [76] 83, 78, 80 80 106

32 78, 71, 73 [74] 81, 80, 78 80 108

168 69, 69, 77 [72] 65, 71, 65 67 93

Skim milk Triclopyr 0.10 0 88, 91, 88 [89] 90, 88, 90 89 100

32 100, 104, 102 [102] 106, 107, 97 103 101

110 100, 102, 100 [101] 99, 97, 98 98 97

TCP 0.10 0 76, 82, 77 [78] 77, 77, 76 77 98

32 76, 75, 75 [75] 82, 85, 73 80 106

110 71, 77, 78 [75] 72, 74, 80 75 100

Cream Triclopyr 0.10 0 99, 103, 104 [102] 102, 103, 104 103 101

63 102, 100, 103 [102] 112, 113, 109 111 110

153 107, 104, 111 107 105

TCP 0.10 0 66, 73, 72 [70] 75, 73, 76 75 106

63 75, 75, 80 [77] 76, 71, 71 73 95

153 74, 78, 75 76 98

Liver Triclopyr 0.10 0 97, 95, 98 [97] 96, 97, 99 97 101

30 97, 94, 100 [97] 112, 105, 108 108 112

171 99, 97, 97 [98] 92, 89, 92 91 93

TCP 0.10 0 73, 72, 76 [74] 77, 79, 77 78 105

30 85, 82, 83 [83] 100, 94, 89 94 113

171 83, 81, 83 [82] 63, 60, 64 62 76
Kidney Triclopyr 0.10 0 90, 83, 89 [87] 90, 86, 82 86 98

30 101, 101, 103 [102] 96, 107, 105 103 101

105 108, 110, 111 [110] 108, 108, 105 107 98

TCP 0.10 0 75, 72, 84 [77] 78, 71, 71 73 95

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Table B.7.8.1

- 7b. Stability of Triclopyr and TCP Residues in Bovine Matrices During Frozen Storage (≤

- 18
°C )

. Commodity Analyte Spike
Level (ppm) Storage
Interval (days) Fresh Fortification Recoveries (%) [Avg.] Stored Sample Recoveries (%) Mean Recovery (%) Corrected % Recovery 1

30 79, 79, 8 1 [80] 81, 83, 83 82 103

105 81, 80, 83 [81] 75, 78, 80 78 95

Fat Triclopyr 0.10 0 99, 98, 94 [97] 98, 101, 95 98 101

32 92, 95, 98 [95] 103, 103, 105 104 109

159 100, 97, 100 [99] 100, 99, 100 100 101

TCP 0.10 0 81, 81, 86 [83] 87, 87, 84 86 104

32 72, 70, 73 [72] 76, 76, 85 79 110

159 89, 85, 86 [87] 81, 80, 78 80 92

Muscle Triclopyr 0.10 0 110, 89, 98 [99] 88, 92, 90 90 91

32 88, 91, 91 [90] 95, 97, 94 95 106

160 92, 95, 96 [94] 97, 99, 99 98 104

TCP 0.10 0 86, 87, 88 [87] 87, 82, 82 84 96

32 71, 76, 70 [72] 77, 75, 76 76 105

160 88, 81, 83 [84] 78, 80, 83 80 96

1 Corrected for recovery in freshly fortified samples.



## The results from the submitted f eeding study are presented in Tables B.7.8.1

- 8 (whole milk, skim milk, and cream), B.7.8.1

- 9 (tissues)

, B.7.8.1

- 10 (residue summary) , and B.7.8.1

- 11 (depuration results)

. Combined residues of triclopyr and TCP were below the LOQ in all samples of cream
and near or below t he LOQ in whole milk and skim milk (residues ranged <0.02

- <0.037 ppm) at
the 54.8

- ppm dose level. At the 109.6

- and 538.7

- ppm dose levels, combined residues in whole milk plateaued by Study Days 6

- 8; at the 1057.4

- ppm dose level, residues of triclopyr pla teaued by Day 8, but residues of TCP continued to increase through the study (see Figure B.7.8.1

- 1). Residues of TCP in milk exceeded those of triclopyr at the 109.6

- , 538.7

- , and 1057.4

- ppm dose levels, respectively, by up to 3.2x (average 1.9x), 18x (av erage 8.8x), and 15x (average 6.1x). Combined residues of triclopyr and TCP at the 109.6

- , 538.7

- , and 1057.4

- ppm dose levels, respectively, were: <0.026

- 0.065, 0.094

- 0.377, and 0.184

- 0.602 ppm in whole milk; <0.029

- 0.049, 0.123

- 0.314, and <0.235

- 0.615 p pm in skim milk; and <0.02

- <0.028, <0.069

- 0.177, and
<0.114

- 0.339 ppm in cream

.

Quantifiable residues triclopyr and TCP were observed in tissues at all dosing levels, with the highest residues observed in kidney, then liver, and the lowest residues observed in muscle. Ratios of residues in tissues to those in feed were relatively consistent across feeding levels except for those in liver, which declined steadily with increasing feeding level. Residues of TCP exceeded those of triclopyr in liver (av erage 15

- 26x), fat (1.6

- 4.0x), and muscle (1.7

- 3.7x) but were lower than those of triclopyr in kidney (0.3

- 0.8x). Combined residues of triclopyr and TCP
at the 54.8

- , 109.6

- , 538.7

- , and 1057.4

- ppm dose levels, respectively, were: 0.929

- 2.43, 2.46

- 3.55, 10.3

- 11.7, and 14.3

- 17.5 ppm in liver; 2.77

- 5.33, 6.46

- 8.34, 28.2

- 53.8, and 48.3

- 106 ppm in kidney; 0.058

- 0.744, 0.130

- 1.13, 1.26

- 5.01, and 3.25

- 10.0 ppm in composite fat (calculated by the petitioner as the average of analyte concentrations in the corres ponding samples of individual fats); and 0.040

- 0.134, 0.147

- 0.193, 0.975

- 1.19, and 1.29

- 1.97 ppm in muscle.

The depuration study indicated that following removal of the test substance from the diet, residue levels decreased in milk and all tissues, with r esidues decreasing most rapidly in milk and muscle

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## and least rapidly in liver. Combined residues of triclopyr and TCP in whole milk and muscle decreased to below the LOQ (<0.02 ppm) by Study Day 31 (Depuration Day 3). Combined
residues were near or below the LOQ in kidney by Study Day 42 (Depuration Day 14) and in fats by Study Day 49 (Depuration Day 21). Average combined residues were <0.031 ppm in liver by Study Day 49.

Linear

- regression analysis demonstrated a generally linear relationship between d ose level and resulting residues in milk and tissues, with a better correlation observed for TCP than for triclopyr ; see Figures B.7.8.1

- 2 (whole milk), B.7.8.1

- 3 (liver); B.7.8.1

- 4 (kidney); B.7.8.1

- 5 (subcutaneous fat); and B.7.8.1

- 6 (muscle)

.

Table B.7 .8.1

- 8

. Whole Milk, Skim Milk, and Cream Residue Data From Ruminant Feeding Study with Triclopyr

. Animal I D # Collection
Time (study day) Feeding
Level (ppm) Residues 1 (ppm parent equivalents) Triclopyr TCP Combined [Avg.] 2

Whole milk
4, 5, 6, 7 2 54.8 (0.003 ), ( 0.008 ), ( 0.004 ), ND ND, (0.005 ), ( 0.006 ), ( 0.004) <0.02, <0.02, <0.02, <0.02 [<0.02]

6 (0.003 ), ( 0.006 ), ( 0.003 ), ( 0.004) (0.006 ), ( 0.01 ), ( 0.009 ), ( 0.006) <0.02, <0.02, <0.02, <0.02 [<0.02]

8 3 ND, (0.003 ), ND, ND (0.004 ), ( 0.008 ), ( 0.008 ), ( 0.003) <0.02, <0.02, <0.02, <0.02 [<0.02]

10 (0.004 ), ( 0.006 ), ( 0.004 ), ND (0.005 ), 0.014

, ( 0.009 ), ( 0.004) <0.02, <0.024, <0.02, <0.02 [<0.021]

14 (0.004 ), ( 0.007 ), ( 0.004 ), ( 0.003) (0.004 ), 0.016

, (0.008 ), (0.004) <0.02

, <0.026

, <0.02

, < 0.02 [<0.021]

18 (0.005 ), ( 0.008 ), ( 0.007 ), ( 0.004) (0.006 ), 0.018

, (0.01 ), (0.005) <0.02, 0.028, <0.02, <0.02 [<0.022]

22 ND, (0.003 ), ( 0.004 ), ( 0.004) (0.006 ), 0.021

, (0.008 ), (0.004) <0.02, <0.031, <0.02, <0.02 [<0.023]

26 (0.004 ), ( 0.004 ), ( 0.004 ), ( 0.003) (0.008 ), 0.022

, (0.01 ), (0.005) <0.02, <0.032, <0.02, <0.02 [<0.023]

29 (0.003 ), ( 0.008 ), ( 0.005 ), ( 0.004) (0.006 ), 0.016

, (0.007 ), (0.005) <0.02, <0.026, <0.02, <0.02 [<0.021]

8 3 , 9, 10, 11 2 109.6 (0.008 ), ( 0.007 ), 0.012

, ( 0.006) (0.007 ), 0.016

, 0.01 3

, ( 0.009) <0.02, <0.026, 0.025, <0.02 [<0.02 3 ]

6 

### ( 0

. 0 0 7 ), ( 0

. 0 0 7 ), 0

. 02 2

, ( 0

. 0 0 6 ) 0.016

, 0.027

, 0.023

, 0.019 <0.026, <0.037, 0.045, <0.029 [<0.034]

8 3 (0.005 ), ( 0.005 ), 0.012

, ( 0.004) 0.018

, 0.027

, 0.019

, 0.017 <0.028, < 0.037, 0.031, <0.027 [<0.031]

10 (0.007 ), (0.006 ), 0.014

, ( 0.006 ) 0.016

, 0.030

, 0.017

, 0.016 <0.026, <0.040, 0.031, <0.026 [<0.030]

14 (0.007 ), (0.006 ), 0.022

, ( 0.007) 0.017

, 0.028

, 0.016

, 0.017 <0.027, <0.038, 0.038, <0.027 [<0.032]

18 (0.01 ), 0.013

, 0.038

, 0.011 0.018

, 0.039

, 0.027

, 0.019 < 0.028

, 0.052

, 0.065

, 0.030 [ < 0.044]

22 (0.008 ), (0.008 ), 0.015

, 0.013 0.018

, 0.025

, 0.025

, 0.017 <0.028, <0.035, 0.040, 0.030 [ < 0.033]

26 (0.008 ), (0.008 ), 0.015

, 0.011 0.021

, 0.032

, 0.027

, 0.030 <0.031, < 0.042, 0.042, 0.041 [<0.039]

28 0.015

, 0.010

, 0.030

, 0.016 0.022

, 0.031

, 0.026

, 0.028 0.037

, 0.041

, 0.056

, 0.044 [0.045]
12, 13, 14,
15 2 538.7 0.057

, 0.037

, 0.019

, 0.034 0.045

, 0.080

, 0.083

, 0.032 0.102

, 0.117

, 0.102

, 0.066 [0.097]

### Triclopyr [PC Code 116001]/Dow AgroSciences

MRID# 49741901 Page 11 of 24

Table B.7 .8.1

- 8

. Whole Milk, Skim Milk, and Cream Residue Data From Ruminant Feeding Study with Triclopyr

. Animal I D # Collection
Time (study day) Feeding
Level (ppm) Residues 1 (ppm parent equivalents) Triclopyr TCP Combined [Avg.] 2

6 0.024

, 0.027

, 0.011

, 0.013 0.105

, 0.173

, 0.164

, 0.068 0.129

, 0.200

, 0.175

, 0.081 [0.146]

8 3 0.020

, 0.138

, ( 0.005 ), (0.008) 0.129

, 0.239

, 0.168

, 0.110 0.149

, 0.377

, <0.178

, <0.120 [<0.206]

10 (0.007 ), 0.016

, 0.013

, 0.018 0.098

, 0.177

, 0.142

, 0.076 <0.108

, 0.193

, 0.155

, 0.094 [<0.138]

14 0.015

, 0.020

, ( 0.007 ), 0.015 0.112

, 0.193

, 0.162

, 0.083 0.127

, 0.213

, <0.172

, 0.098 [<0.152]

18 0.036

, 0.016

, 0.024

, 0.039 0.141

, 0.256

, 0.174

, 0.140 0.177

, 0.272

, 0.198

, 0.179 [0.206]

22 0.037

, 0.025

, 0.014

, 0.029 0.112

, 0.199

, 0.198

, 0.115 0.149

, 0.224

, 0.212

, 0.144 [0.182]

26 0.027

, 0.029

, 0.012

, 0.025 0.131

, 0.244

, 0.220

, 0.114 0.158

, 0.273

, 0.232

, 0.139 [0.200]

29 0.028

, 0.024

, 0.011

, 0.013 0.163

, 0.233

, 0.185

, 0.110 0.191

, 0.257

, 0.196

, 0.123 [0.192]
16, 17, 18,
19 (20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31) 4 2 1057.4 0.118

, 0.059

, 0.312

, 0.051 0.147

, 0.110

, 0.171

, 0.145 0.265

, 0.169

, 0.483

, 0.196 [0.278]

6 0.059

, 0.018

, 0.147

, 0.028 0.317

, 0.181

, 0.335

, 0.318 0.376

, 0.199

, 0.482

, 0.346 [0.351]

8 0.058

, 0.041

, 0.138

, 0.051 0.309

, 0.182

, 0.331

, 0.306 0.367

, 0.223

, 0.469

, 0.357 [0.354]

10 0.024

, 0.035

, 0.107

, 0.053 0.213

, 0.149

, 0.289

, 0.176 0.237

, 0.184

, 0.396

, 0.229 [0.262]

14 0.041

, 0.023

, 0.156

, 0.037

, 0.092, 0.172, 0.051, 0.041, 0.094, 0.041, 0.114, 0.102, 0.297, 0.039, 0.040, 0.029 0.317

, 0.168

, 0.273

, 0.341

, 0.309, 0.265, 0.417, 0.262, 0.324, 0.208, 0.385, 0.304, 0.045, 0.142, 0.239, 0.279 0.358

, 0.191

, 0.429

, 0.378

, 0.401, 0.437, 0.468, 0.303, 0.418, 0.249, 0.499, 0.406, 0.342, 0.181, 0.279, 0.308 [0.353 ]

18 0.097

, 0.019

, 0.198

, 0.040 0.355

, 0.190

, 0.287

, 0.286 0.452

, 0.209

, 0.485

, 0.326 [0.368]

22 0.032

, 0.022

, 0.216

, 0.101

, 0.517, 0.130, 0.089, 0.059, 0.074, 0.119, 0.087, 0.167, 0.039, 0.069, 0.075, 0.033 0.473

, 0.230

, 0.386

, 0.379

, 0.469, 0.375, 0.512, 0.342, 0.424, 0.211, 0.429, 0.381, 0.371, 0.226, 0.339, 0.395 0.505

, 0.252

, 0.602

, 0.480

, 0.986, 0.505, 0.601, 0.401, 0.498, 0.330, 0.516, 0.548, 0.410, 0.295, 0.414, 0.428 [0.486 ]

26 0.065

, 0.034

, 0.104

, 0.035 0.465

, 0.222

, 0.362

, 0.433 0.530

, 0.256

, 0.466

, 0.468 [0.430]

28 0.061

, 0.046

, 0.096

, 0.052

, 0.128, 0.055, 0.031, 0.032, 0.084, 0.066, 0.179, 0.122, 0.044, 0.037, 0.032, 0.044 0.455

, 0.256

, 0.408

, 0.420

, 0.349, 0.350, 0.710, 0.476, 0.470, 0.230, 0.443, 0.403, 0.258, 0.240, 0.309, 0.419 0.516

, 0.302

, 0.504

, 0.472

, 0.477, 0.405, 0.741, 0.508, 0.554, 0.296, 0.622, 0.525, 0.302, 0.277, 0.341, 0.463 [0.457 ]

Skim milk
4, 5, 6, 7 22 54.8 ND, ND, ( 0.004 ), ( 0.003) (0.009 ), 0.02 7

, 0.0 17

, (0.006) <0.02, <0.037, <0.027, <0.02 [ <0.026]

26 (0.004)

, ND, ( 0.004 ), ( 0.003) (0.009 ), 0.022 (0.010 ), ( 0.005) <0.02

, <0.032

, <0.02

, <0.02 [ <0.023]
8, 9, 10, 11 22 109.6 (0.007 ), ( 0.006 ), 0.015

, 0.012 0.025

, 0.039

, 0.034

, 0.025 <0.035

, <0.049

, 0.049

, 0.037 [<0.042]

26 (0.005 ), ( 0.007 ), 0.014 (0.007) 0.021

, 0.032

, 0.025

, 0.019 <0.031

, <0.042

, 0.039

, <0.029 [<0.035]

### Triclopyr [PC Code 116001]/Dow AgroSciences

MRID# 49741901 Page 12 of 24

Table B.7 .8.1

- 8

. Whole Milk, Skim Milk, and Cream Residue Data From Ruminant Feeding Study with Triclopyr

. Animal I D # Collection
Time (study day) Feeding
Level (ppm) Residues 1 (ppm parent equivalents) Triclopyr TCP Combined [Avg.] 2

12, 13, 14,
15 22 538.7 0.029

, 0.014 (0.009 ), 0.019 0.163

, 0.300

, 0.237

, 0.142 0.192

, 0.314

, <0.247

, 0.161

, [<0.228]

26 0.014

, 0.013 (0.005 ), 0.013 0.137

, 0.292

, 0.218

, 0.110 0.151

, 0.305

, <0.228

, 0.123 [<0.202]
16, 17, 18,
19 22 1057.4 0.017

, (0.008 ), 0.161

, 0.058 0.536

, 0.278

, 0.454

, 0.467 0.553

, <0.288

, 0.615

, 0.525 [<0.495]

26 0.029

, (0.006 ), 0.045

, 0.020 0.470

, 0.225

, 0.376

, 0.405 0.499

, <0.235

, 0.421

, 0.425 [< 0.395]

Cream
4, 5, 6, 7 22 54.8 ND, ND, ND , ND (0.004 ), ( 0.009 ), ( 0.006)
ND <0.02

, <0.02

, <0.02

, <0.02 [<0.02]

26 ND, ND, ND , ND (0.004 ), ( 0.009 ), ( 0.005 ), ( 0.003) <0.02

, <0.02

, <0.02

, <0.02 [<0.02]
8, 9, 10, 11 22 109.6 (0.003) ND, ( 0.007 ), ( 0.005) (0.009 ), 0.017

, 0.018

, (0.01) <0.02

, <0.027

, <0.028

, <0.02 [<0.024]

26 ND, ( 0.004 ), ( 0.007 ), ( 0.003) (0.009 ), 0.016

, 0.01 7

, (0.009) <0.02

, <0.026

, <0.027

, <0.02 [<0.023]
12, 13, 14,
15 22 538.7 0.012

, 0.011 (0.008 ), ( 0.009) 0.070

, 0.165

, 0.124

, 0.059 0.082

, 0.176

, <0.134

, <0.069 [ <0.115]

26 (0.008 ), 0.011 (0.007 ), ( 0.007) 0.077

, 0.166

, 0.126

, 0.059 < 0.087

, 0.177

, < 0.136

, < 0.069

, [<0.117]
16, 17, 18,
19 22 1057.4 0.015 (0.007 ), 0.095

, 0.032 0.242

, 0.121

, 0.244

, 0.234 0.257

, < 0.131

, 0.339

, 0.266 [< 0.248]

26 0.020 (0.005 ), 0.025

, 0.016 0.244

, 0.104

, 0.220

, 0.208 0.264

, < 0.114

, 0.245

, 0.224 [<0.212]

1 ND = not detected (<LOD). The LOD was 0.003 ppm, and the LOQ was 0.01 ppm for each analyte. Values between the LOD and LOQ are reported in parenthesis. Quantifiable residues of TCP were converted to parent equivalents using a molecular weight conversion factor of 1.3 (MW triclopyr 256.46 ÷ MW TCP 198.44). Combined residu es and averages were calculated by
the study reviewer using the LOQ for all residues reported as <LOQ.

2 Combined residues of triclopyr and TCP

. 3 Day 8 milk samples for cows in dose groups 54.8, 109.6, and 538.7 reflecting AM milk sampling only.

4 Samples for cows 20

- 31 in the dose group 1057.4 were taken o n days 14, 22, and 28 days only.



### Table B.7.8.1

- 9. Tissue Residue Data From Ruminant Feeding Study with Triclopyr

. Animal
Identification # Collection
Time Feeding
Level (ppm) Residues 1 (ppm parent equivalents)
Triclopyr TCP Combined [Avg.] 2

Liver
4, 5, 6

, 7 Sacrifice 54.8 0.084

, 0.094

, 0.086

, 0.075 1.28

, 2.34

, 1.29

, 0.854 1.37

, 2.43

, 1.38

, 0.9 29 [1.53]
8, 9, 10, 11 109.6 0.199

, 0.119

, 0.137

, 0.080 3.14

, 3.43

, 2.32

, 3.31 3.34

, 3.55

, 2.46

, 3.39 [3.18]
12, 13, 14, 15 538.7 0.562

, 0.958

, 0.301

, 0.727 9.71

, 9.93

, 11.43

, 9.80 10.27

, 10.89

, 11.73

, 10.53 [10.85]
16, 17, 18, 19 1057.4 1.764

, 1.102

, 0.903

, 0.795 15.63

, 13.24

, 16.62

, 16.40 17.39

, 14.34

, 17.52

, 17.20 [16.61.] Kidney
4, 5, 6

, 7 Sacrifice 54.8 2.935

, 3.713

, 2.960

, 2.293 0.943

, 1.62

, 0.806

, 0.478 3.88

, 5.33

, 3.77

, 2.77 [3.94]
8, 9, 10, 11 109.6 5.667

, 5.372

, 4.902

, 3.481 2.43

, 2.97

, 1.99

, 2.98 8.10

, 8.34

, 6.89

, 6.46 [7.45]

### Triclopyr [PC Code 116001]/Dow AgroSciences

MRID# 49741901 Page 13 of 24

Table B.7.8.1

- 9. Tissue Residue Data From Ruminant Feeding Study with Triclopyr

. Animal
Identification # Collection
Time Feeding
Level (ppm) Residues 1 (ppm parent equivalents)
Triclopyr TCP Combined [Avg.] 2

12, 13, 14, 15 538.7 19.696

, 37.819

, 14.031

, 26.713 17.3

, 16.0

, 14.1

, 13.4 36.98

, 53.82

, 28.16

, 40.13 [39.77]
16, 17, 18, 19 1057.4 74.654

, 31.272

, 36.205

, 24.253 30.9

, 31.7

, 28.8

, 24.0 105.51

, 62.97

, 65.01

, 48.28 [70.44]
Fat, subcutaneous
4, 5, 6

, 7 Sacrifice 54.8 0.077

, 0.141

, 0.028

, 0.036 0.181

, 0.377

, 0.067

, 0.043 0.258

, 0.518

, 0.095

, 0.079 [0.238]
8, 9, 10, 11 109.6 0.223

, 0.138

, 0.172

, 0.035 0.392

, 0.609

, 0.408

, 0.134 0.615

, 0.747

, 0.580

, 0.169 [0.528]
12, 13, 14, 15 538.7 0.209

, 0.712

, 0.481

, 0.374 1.33

, 2.04

, 2.97

, 1.64 1.54

, 2.75

, 3.45

, 2.01 [2.44]
16, 17, 18, 19 1057.4 0.556

, 0.819

, 0.738

, 0.464 1.64

, 3.18

, 3.40

, 2.18 2.20

, 4.00

, 4.14

, 2.64 [3.25] Fat, mesenteric
4, 5, 6

, 7 Sacrifice 54.8 0.085

, 0.145

, 0.038

, 0.026 0.158

, 0.439

, 0.070

, 0.028 0.243

, 0.584

, 0.108

, 0.054 [0.247]
8, 9, 10, 11 109.6 0.163

, 0.198

, 0.134

, 0.014 0.397

, 0.876

, 0.266

, 0.062 0.560

, 1.07

, 0.400

, 0.076 [0.528]
12, 13, 14, 15 538.7 0.268

, 1.321

, 0.700

, 0.255 1.66

, 2.93

, 3.34

, 0.632 1.92

, 4.25

, 4.04

, 0.887 [2.77]
16, 17, 18, 19 1057.4 1.157

, 1.463

, 2.213

, 0.472 2.81

, 4.55

, 8.39

, 2.40 3.97

, 6.01

, 10.61

, 2.88 [5.87] Fat, perirenal
4, 5, 6

, 7 Sacrifice 54.8 0.256

, 0.399

, 0.148

, 0.016 0.350

, 0.729

, 0.136

, 0.025 0.606

, 1.13

, 0.284

, 0.041

, [0.515]
8, 9, 10, 11 109.6 0.266

, 0.517

, 0.201

, 0.050 0.521

, 1.04

, 0.335

, 0.096 0.787

, 1.56

, 0.536

, 0.146 [0.757]
12, 13, 14, 15 538.7 0.209

, 2.749

, 1.482

, 0.275 1.27

, 4.57

, 6.07

, 0.604 1.48

, 7.32

, 7.55

, 0.879 [4.31]
16, 17, 18, 19 1057.4 4.274

, 2.742

, 4.103

, 0.828 5.58

, 6.92

, 11.2

, 3.39 9.85

, 9.66

, 15.32

, 4.22 [9.76] Fat, composite 3

4, 5, 6

, 7 Sacrifice 54.8 0.139

, 0.228

, 0.071

, 0.026 0.230

, 0.516

, 0.090

, 0.032 0.369

, 0.744

, 0.161

, 0.058 [0.333]
8, 9, 10, 11 109.6 0.217

, 0.284

, 0.169

, 0.033 0.437

, 0.843

, 0.336

, 0.097 0.654

, 1.13

, 0.505

, 0.130 [0.604]
12, 13, 14, 15 538.7 0.229

, 1.594

, 0.888

, 0.301 1.419

, 3.181

, 4.125

, 0.959 1.65

, 4.77

, 5.01

, 1.26 [3.17]
16, 17, 18, 19 1057.4 1.996

, 1.675

, 2.351

, 0.588 3.343

, 4.884

, 7.669

, 2.657 5.34

, 6.56

, 10.02

, 3.25 [6.29]

Muscle
4, 5, 6

, 7 Sacrifice 54.8 0.026

, 0.038

, 0.033

, 0.019 0.045

, 0.096

, 0.047

, 0.021 0.071

, 0.134

, 0.080

, 0.040 [0.081]
8, 9, 10, 11 109.6 0.066

, 0.039

, 0.050

, 0.027 0.127

, 0.140

, 0.111

, 0.120 0.193

, 0.179

, 0.161

, 0.147 [0.170]
12, 13, 14, 15 538.7 0.188

, 0.356

, 0.161

, 0.281 0.885

, 0.832

, 0.840

, 0.694 1.07

, 1.19

, 1.00

, 0.975 [1.06]
16, 17, 18, 19 1057.4 0.610

, 0.276

, 0.291

, 0.233 1.361

, 1.018

, 1.229

, 1.131 1.97

, 1.29

, 1.52

, 1.36 [1.54]

1 Quantifiable residues of TCP were converted to parent equivalents using a molecular weight conversion factor of 1.3 (MW triclopyr 256.46 ÷ MW TCP 198.44). Combined residues and averages were calculated by the study reviewer.

2 Combined residues of triclopyr and TCP

. 3 Calculated by the petitioner as the average of analyte concentrations in the corresponding samples of individual fats.

### Triclopyr [PC Code 116001]/Dow AgroSciences

MRID# 49741901 Page 14 of 24

Table B.7.8.1

- 10 . Summary of Residue Data From Ruminant Feeding Study with Triclopyr

. Matrix Feeding Level (ppm) Residue s of Triclopyr and TCP ( ppm parent equivalents ) 1 T issue
R esidue: F eeding

L evel R atio 2 n Min. Max. Median Mean Std. Dev.

Triclopyr

Whole milk 3 (Days 8, 10, 14, 18, 22, 26, 29) 54.8 28 <0.01 <0.01 0.01 0.01 NA

109.6 28 <0.01 0.038 0.01 0.013 0.007

538.7 28 <0.01 0.138 0.019 0.024 0.024

1057.4 64 0.019 0.517 0.059 0.084 0.077

Skim milk 54.8 8 <0.01 <0.01 0.01 0.01 NA

109.6 8 <0.01 0.015 0.01 0.011 0.002

538.7 8 <0.01 0

. 029 0.014 0.015 0.006

1057.4 8 <0.01 0.161 0.025 0.044 0.050

Cream 54.8 8 <0.01 <0.01 0.01 0.01 NA

109.6 8 <0.01 <0.01 0.01 0.01 NA

538.7 8 <0.01 0.012 0.01 0.011 0.001

1057.4 8 <0.01 0.095 0.018 0.028 0.028

Liver 54.8 4 0.075 0.094 0.085 0.085 0.008 0.0017

109.6 4 0.080 0.199 0.128 0.134 0.050 0.0018

538.7 4 0.301 0.958 0.645 0.637 0.277 0.0018

1057.4 4 0.795 1.76 1.00 1.14 0.434 0.0017 Kidney 54.8 4 2.29 3.71 2.95 2.98 0.581 0.0677

109.6 4 3.48 5.67 5.14 4.86 0.969 0.0517

538.7 4 14.0 37.8 23.2 24.6 10.2 0.0702

1057.4 4 24.3 74.7 33.7 41.6 22.6 0.0706 Fat, composite 4 54.8 4 0.026 0.228 0.105 0.116 0.088 0.0042

109.6 4 0.033 0.284 0.193 0.176 0.106 0.0026

538.7 4 0.229 1.59 0.595 0.753 0.634 0.0030

1057.4 4 0.588 2.35 1.84 1.65 0.761 0.0022

Muscle 54.8 4 0.019 0.038 0

. 030 0.029 0.008 0.0007

109.6 4 0.027 0.066 0.045 0.046 0.017 0.0006

538.7 4 0.161 0.356 0.235 0.247 0.089 0.0007

1057.4 4 0.233 0.610 0.284 0.353 0.173 0.0006

TCP

Whole milk 3 (Days 8, 10, 14, 18, 22, 26, 29) 54.8 28 <0.01 0.022 0.01 0.012 0.003

109.6 28 0.016 0.039 0.021 0.023 0.006

538.7 28 0.076 0.256 0.152 0.158 0.051

1057.4 64 0.045 0.710 0.32 8 0.328 0.110

Skim milk 54.8 8 <0.01 0.027 0.010 0.014 0.007

109.6 8 0.019 0.039 0.025 0.027 0.007

538.7 8 0.110 0.300 0.191 0.200 0.073

1057.4 8 0.225 0.536 0.429 0.401 0.105

Cream 54.8 8 <0.01 <0.01 0.01 0.01 NA

109.6 8 <0.01 0.018 0.013 0.013 0.004

538.7 8 0.059 0.166 0.100 0.106 0.046

1057.4 8 0.104 0.244 0.227 0.202 0.057

Liver 54.8 4 0.854 2.34 1.29 1.44 0.632 0.0427

109.6 4 2.32 3.43 3.22 3.05 0.500 0.0313

538.7 4 9.71 11.4 9.86 10.2 0.813 0.0212

1057.4 4 13.2 16.6 16.0 15.5 1.55 0.0157 Kidney 54.8 4 0.478 1.62 0.875 0.962 0.480 0.0296

### Triclopyr [PC Code 116001]/Dow AgroSciences

MRID# 49741901 Page 15 of 24

Table B.7.8.1

- 10 . Summary of Residue Data From Ruminant Feeding Study with Triclopyr

. Matrix Feeding Level (ppm) Residue s of Triclopyr and TCP ( ppm parent equivalents ) 1 T issue
R esidue: F eeding

L evel R atio 2 n Min. Max. Median Mean Std. Dev.

109.6 4 1.99 2.98 2.70 2.59 0.476 0.0272

538.7 4 13.4 17.3 15.1 15.2 1.76 0.0321

1057.4 4 24.0 31.7 29.8 28.8 3.43 0.0300 Fat, composite 4 54.8 4 0.032 0.516 0.160 0.217 0.216 0.0094

109.6 4 0.097 0.843 0.386 0.428 0.311 0.0077

538.7 4 0.959 4.13 2.30 2.42 1.49 0.0077

1057.4 4 2.66 7.67 4.11 4.64 2.22 0.0073

Muscle 54.8 4 0.021 0.096 0.046 0.052 0.031 0.0018

109.6 4 0.111 0.140 0.123 0.124 0.012 0.0013

538.7 4 0.694 0.885 0.836 0.813 0.083 0.0016

1057.4 4 1.02 1.36 1.18 1.18 0.146 0.0013 Combined triclopyr + TCP

Whole milk 3 (Days 8, 10, 14, 18, 22, 26, 29) 54.8 28 <0.02 <0.032 0.02 0.022 0.003

109.6 28 <0.026 0.065 0.036 0.036 0.010

538.7 28 0.094 0.377 0.177 0.182 0.062

1057.4 64 0.18 1 0. 986 0. 412 0.412 0.1 40

Skim milk 54.8 8 <0.02 <0.037 0.02 0.024 0.007

109.6 8 <0.029 0.049 0.038 0.039 0.007

538.7 8 0.123 0.314 0.210 0.215 0.071

1057.4 8 <0.235 0.615 0.462 0.445 0.131

Cream 54.8 8 <0.02 <0.02 0.02 0.02 NA

109.6 8 <0.02 <0.028 0.023 0.023 0.004

538.7 8 <0.069 0.177 0.110 0.116 0.046

1057.4 8 <0.114 0.339 0.251 0.230 0.074

Liver 54.8 4 0.929 2.43 1.37 1.53 0.639 0.0443

109.6 4 2.46 3.55 3.36 3.18 0.491 0.0324

538.7 4 10.3 11.7 10.7 10.9 0.636 0.0217

1057.4 4 14.3 17.5 17.3 16.6 1.52 0.0166 Kidney 54.8 4 2.77 5.33 3.82 3.94 1.06 0.0973

109.6 4 6.46 8.34 7.49 7.45 0.912 0.0761

538.7 4 28.2 53.8 38.6 39.8 10.6 0.0999

1057.4 4 48.3 106 64.0 70.4 24.5 0.1002 Fat, composite 4 54.8 4 0.058 0.744 0.265 0.333 0.303 0.0136

109.6 4 0.130 1.13 0.57 9 0.604 0.412 0.0103

538.7 4 1.26 5.01 3.21 3.17 1.99 0.0093

1057.4 4 3.25 10.0 5.95 6.29 2.84 0.0095

Muscle 54.8 4 0.040 0.134 0.075 0.081 0.039 0.0024

109.6 4 0.147 0.193 0.170 0.170 0.020 0.0018

538.7 4 0.975 1.19 1.04 1.06 0.095 0.0022

1057.4 4 1.29 1.97 1.44 1.54 0.304 0.0019

1 n = No. of samples. For calculation of median, mean, and standard deviation, the LOQ (0.01 ppm for each analyte) was used for residues reported as ND or <LOQ. NA = Not applicable

2 Referred to as the transfer coefficient (TC) or transfer factor (T f ); to be used in the calculation of residues anticipated at the dietary burden. The maximum factor for each tissue is bolded

. 3 Data for whole milk are summarized for days after residues had reached a plateaus (based on 538.7

- ppm dose level).

4 Calculated by the petitioner as the average of analyte concentrations in the corresponding samples of individual fats.

### Triclopyr [PC Code 116001]/Dow AgroSciences

MRID# 49741901 Page 16 of 24 

## F igure B.7.8.1

- 1. Combined Residues of Triclopyr and TCP in Whole Milk as a Function
of Time.

0 0.05

0.1 0.15

0.2 0.25

0.3 0.35

0.4 0.45

0.5

0 5 10 15 20 25 30Average Combined Residue (ppm)



### Study Day 54.8-ppm Dose Group

109.6-ppm Dose Group

538.7-ppm Dose Group

1057.4-ppm Dose Group

### Triclopyr [PC Code 116001]/Dow AgroSciences

MRID# 49741901 Page 17 of 24 

## Figure B.7.8.1

- 2. Linear Regressio n of Triclopyr and TCP in Whole Milk vs. Dosing Level.

### Triclopyr [PC Code 116001]/Dow AgroSciences

MRID# 49741901 Page 18 of 24 

## Figure B.7.8.1

- 3. Linear Regression of Triclopyr and TCP in Liver vs. Dosing Level.

### Triclopyr [PC Code 116001]/Dow AgroSciences

MRID# 49741901 Page 19 of 24 

## Figure B.7.8.1

- 4. Linear Regression of Triclopyr and TCP in Kidney vs. Dosing Level.

### Triclopyr [PC Code 116001]/Dow AgroSciences

MRID# 49741901 Page 20 of 24 

## Figure B.7.8.1

- 5. Linear Regression of Triclopyr and TCP in Subcutaneous Fat vs. Dosing
Level.

### Triclopyr [PC Code 116001]/Dow AgroSciences

MRID# 49741901 Page 21 of 24 

## Figure B.7.8.1

- 6. Linear Regression of Triclopyr and TCP in Muscle vs. Dosing Level.

### Triclopyr [PC Code 116001]/Dow AgroSciences

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## Depuration Period

Table B.7.8.1

- 11. Summary of Residues of Triclopyr in Whole Milk and Tissues of Cattle From the Depuration Study: 1057.4

- ppm Feeding Level.

Matrix Animal ID # Study Day Depuration Day Residues 1 (ppm parent equivalents) Triclopyr TCP Combined [Avg] 2

Whole milk 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31 29 1 0.036, 0.032, 0.017, 0.014, 0.037, 0.030, 0.061, 0.080, 0.027, 0.025, 0.021, 0.027 0.278, 0.289, 0.644, 0.278, 0.381, 0.184, 0.393, 0.358, 0.202, 0.178, 0.279, 0.385 0.314, 0.321, 0.661, 0.292, 0.418, 0.214, 0.454, 0.438, 0.229, 0.203, 0.300, 0.412 [0.355]
20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31 31 3 ND, ND, ND, ND, ND, ND, ND, ND, ND, ND, ND, ND (0.004), (0.004), (0.008), (0.005), (0.007), (0.006), 0.016, (0.005), (0.004), (0.003), (0.006), (0.007) <0.02, <0.02, <0.02,

< 0.02, <0.02, <0.02, <0.026, <0.02, <0.02, <0.02, <0.02, <0.02 [<0.02]

23, 24, 25, 26, 27,

28, 29, 30, 31 33 5 ND, ND, (0.004), ND, ND, ND, ND, ND, ND ND, ND, ND, ND, ND, ND, ND, ND,
ND <0.02, <0.02, <0.02, <0.02, <0.02, <0.02, <0.02, <0.02, <0.02 [<0.02]
23, 24, 25, 26, 27,

28, 29, 30, 31 35 7 ND, ND, ND, ND, ND, ND, ND, ND, ND, ND, ND, ND, ND, ND, ND, ND, ND,
ND <0.02, <0.02, <0.02, <0.02, <0.02, <0.02, <0.02, <0.02, <0.02, [<0.02]
26, 27, 28, 29, 30,
31 38 10 ND, ND, ND, ND, ND, ND ND, ND, ND, ND, ND, ND <0.02, <0.02, <0.02, <0.02, <0.02, <0.02 [<0.02]
26, 27, 28, 29, 30,
31 40 12 ND, ND, ND, ND, ND, ND ND, ND, ND, ND, ND, ND <0.02, <0.02, <0.02, <0.02, <0.02, <0.02 [<0.02]
26, 27, 28, 29, 30,
31 42 14 ND, ND, ND, ND, ND, ND ND, ND, ND, ND, ND, ND <0.02, <0.02, <0.02, <0.02, <0.02, <0.02 [<0.02]
29, 30, 31 45 17 ND, ND, ND ND, ND, ND <0.02, <0.02, <0.02 [<0.02]
29, 30, 31 48 20 ND, ND, ND ND, ND, ND <0.02, <0.02, <0.02 [<0.02]
29, 30, 31 49 21 ND, ND, ND ND, ND, ND <0.02, <0.02, <0.02 [< 0.02]

Liver 20, 21, 22 31 3 ND, ND, ND 0.163, 0.180, 0.249 <0.173, <0.190,
<0.259 [<0.207]
23, 24, 25 35 7 ND, ND, ND 0.039, 0.066, 0.032 <0.049, <0.076, <0.042 [<0.056]
26, 27, 28 42 14 ND, ND, ND 0.039, 0.054, 0.032 <0.049, <0.064,
<0.042 [<0.052]
29, 30, 31 49 21 ND, ND, ND 0.028 (0.008), 0.023 <0.038, <0.020,
<0.033 [<0.031]

### Triclopyr [PC Code 116001]/Dow AgroSciences

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Table B.7.8.1

- 11. Summary of Residues of Triclopyr in Whole Milk and Tissues of Cattle From the Depuration Study: 1057.4

- ppm Feeding Level.

Matrix Animal ID # Study Day Depuration Day Residues 1 (ppm parent equivalents) Triclopyr TCP Combined [Avg] 2
Kidney 20, 21, 22 31 3 (0.007), (0.005), (0.004) 0.181, 0.100, 0.178 <0.191, <0.110,
<0.188 [<0.163]
23, 24, 25 35 7 (0.004) 0.011 (0.004) 0.017, 0.032, 0.017 <0.027, 0.043, <0.027 [<0.032]
26, 27, 28 42 14 (0.003) ND, (0.004) (0.007), (0.006), (0.005) <0.02, <0.02, <0.02 [<0.02]
29, 30, 31 49 21 ND, ND, ND (0.004), (0.004), (0.004) <0.02, <0.02, <0.02 [<0.02]
Fat,
subcutaneo

us 20, 21, 22 31 3 0.015, 0.038, 0.031 0.036, 0.083, 0.076 0.051, 0.121, 0.107 [0.093]
23, 24, 25 35 7 0.015, 0.017, (0.004) 0.018, 0.030, ND 0.033, 0.047, <0.02 [<0.033]
26, 27, 28 42 14 0.011, (0.009), 0.015 0.017, 0.017, (0.009) 0.028, 0.027, <0.025 [<0.027]
29, 30, 31 49 21 ND, ND, 0.014 (0.005), ND, 0.023 <0.02, <0.02, 0.037 [<0.026]
Fat,
mesenteric 20, 21, 22 31 3 0.024, 0.024, (0.006) 0.041, 0.045, 0.027 0.065, 0.069, <0.037 [<0.057]
23, 24, 25 35 7 0.022, 0.018, (0.005) 0.026, 0.022, ND 0.048, 0.040, <0.02 [<0.036]
26, 27, 28 42 14 0.032, (0.009), 0.022 0.032, (0.006), (0.009) 0.064, <0.02, <0.032 [<0.039]
29, 30, 31 49 21 0.018, ND, ND 0.022, ND, ND 0.040, <0.02, <0.02 [<0.027]
Fat, perirenal 20, 21, 22 31 3 0.013, (0.008), (0.006) 0.032, 0.023, 0.047 0.045, <0.033, < 0.057 [<0.045]
23, 24, 25 35 7 (0.007), 0.012, (0.009) (0.009), 0.018
ND <0.02, 0.030, <0.02 [<0.023]
26, 27, 28 42 14 0.012, (0.008), (0.004) (0.008), ND, (0.005) <0.022, <0.02, <0.02 [<0.021]
29, 30, 31 49 21 ND, ND, ND ND, ND, ND <0.02, <0.02, < 0.02 [<0.02]
Fat, composite 3 20, 21, 22 31 3 0.017, 0.023, 0.014 0.036, 0.050, 0.050 0.053, 0.073, 0.064 [0.064]
23, 24, 25 35 7 0.015, 0.016, (0.006) 0.018, 0.023, ND 0.033, 0.039, < 0.02 [ < 0.031]
26, 27, 28 42 14 0.018, (0.009), 0.014 0.019, (0.006), (0.008) 0.037, <0.02, <0.024 [<0.027]
29, 30, 31 49 21 (0.006), ND, (0.005) (0.007), ND, (0.006) <0.02, <0.02, <0.02 [<0.02]

Muscle 20, 21, 22 31 3 ND, ND, ND (0.005), (0.005), (0.009) <0.02, <0.02, <0.02 [<0.02]
23, 24, 25 35 7 ND, (0.003) ND ND, (0.004) ND <0.02, <0.02, <0.02 [<0.02]
26, 27, 28 42 14 (0.003), ND, ND (0.003), ND, ND <0.02, <0.02, <0.02 [<0.02]
29, 30, 31 49 21 ND, ND, N D ND, ND, N D <0.02, <0.02, <0.02 [<0.02]

1 ND = Not detected (< LOD). The LOD was 0.003 ppm, and the LOQ was 0.01 ppm for each analyte. Values between the LOD and LOQ are reported in parenthesis. Quantifiable residues of TCP were converted to parent equivalents using a molecular weight conversion factor of 1.3 (MW t riclopyr 256.46 ÷ MW TCP 198.44). Combined residues and averages were calculated by the study reviewer using the LOQ for all residues reported as <LOQ.

2 Combined residues of triclopyr and TCP.

### Triclopyr [PC Code 116001]/Dow AgroSciences

MRID# 49741901 Page 24 of 24 3 Calculated by the petitioner as the average of analyte concentrations in the corresponding samples of individual fats.



## III. CONCLUSIONS

The cattle feeding study is considered to be scientifically acceptable. Combined residues of triclopyr and TCP were below the LOQ in all samples of cream and near or below the LOQ in whole milk and skim milk (residues ranged <0.02

- <0.037 ppm) at the 54.8

- ppm dose level. At
the 109.6

- and 538.7

- ppm dose levels, combined residues in whole milk plateaued by Study Days 6

- 8; at the 1057.4

- ppm dose level, residues of triclopyr plateaued by Day 8, but residues of TCP continued to increase through the study. Residues of TCP in milk exceeded those of triclopyr at the 109.6

- , 538.7

- , and 1057.4

- ppm dose levels, respectively, by up to 3.2x (average 1.9x), 18x (average 8.8x), and 15x (average 6.1x). Combined residues of triclopyr and TCP at
the 109.6

- , 538.7

- , and 1057.4

- ppm dose levels, respectively, were: <0.026

- 0.065, 0.094

- 0.377,
and 0.184

- 0.602 ppm in whole milk; <0.029

- 0.0 49, 0.123

- 0.314, and <0.235

- 0.615 ppm in skim milk; and <0.02

- <0.028, <0.069

- 0.177, and <0.114

- 0.339 ppm in cream

.

Quantifiable residues triclopyr and TCP were observed in tissues at all dosing levels, with the highest residues observed in kidney, then li ver, and the lowest residues observed in muscle. Ratios of residues in tissues to those in feed were relatively consistent across feeding levels except for those in liver, which declined steadily with increasing feeding level. Residues of TCP
exceeded th ose of triclopyr in liver (average 15

- 26x), fat (1.6

- 4.0x), and muscle (1.7

- 3.7x) but were lower than those of triclopyr in kidney (0.3

- 0.8x). Combined residues of triclopyr and TCP
at the 54.8

- , 109.6

- , 538.7

- , and 1057.4

- ppm dose levels, respectively, were: 0.929

- 2.43, 2.46

- 3.55, 10.3

- 11.7, and 14.3

- 17.5 ppm in liver; 2.77

- 5.33, 6.46

- 8.34, 28.2

- 53.8, and 48.3

- 106 ppm in kidney; 0.058

- 0.744, 0.130

- 1.13, 1.26

- 5.01, and 3.25

- 10.0 ppm in composite fat (calculated by the petitioner as the average of analyte concentrations in the corresponding samples of individual fats); and 0.040

- 0.134, 0.147

- 0.193, 0.975

- 1.19, and 1.29

- 1.97 ppm in muscle.

The depuration study indicated that following removal of the test substance from the diet, residue
levels decreased in milk and all tissues, with residues decreasing most rapidly in milk and muscle and least rapidly in liver. Combined residues of triclopyr and TCP in whole milk and muscle decreased to below the LOQ (<0.02 ppm) by Study Day 31 (Depuration Day 3). Combine d residues were near or below the LOQ in kidney by Study Day 42 (Depuration Day 14) and in fats by Study Day 49 (Depuration Day 21). Average combined residues were <0.031 ppm in liver by Study Day 49.

A cceptable method s w ere used for residue quantitatio n, and adequate storage stability data have been submitted to support sample storage durations and conditions.

REFERENCES

None.