  SEQ CHAPTER \h \r 1 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

OFFICE OF

CHEMICAL SAFETY AND

 

POLLUTION PREVENTION

  SEQ CHAPTER \h \r 1 MEMORANDUM

Date:  October 7, 2010

SUBJECT:	    Tetrachlorvinphos.  Cattle Oral/Dermal and Poultry Dermal
Studies.  Summary of Residue Data Submitted in Support of
Reregistration.

PC Codes:  083701/083702	DP Barcodes:  D320848, D320858, D320859, and
381350

Decision Nos.:  359964, 359967, 386529	Registration No.:  None

Petition No.:  NA	Regulatory Action:  Other Reregistration

Risk Assessment Type:  NA  	Case No.:  0321

TXR No.:  NA	CAS No.:  22248-79-9

MRID Nos.:  47193001, 47369201, and 47589301	40 CFR:  §180.252



	From:	Christine L. Olinger, Chemist

		Risk Assessment Branch VII

		Health Effects Division (7509P)

	Through:	Donna S. Davis Chemist

		Risk Assessment Branch VII

		Health Effects Division (7509P)

		Michael S. Metzger, Chief

		Risk Assessment Branch VII

		Health Effects Division (7509P)

	To:	James Parker

		Risk Management and Implementation Branch I

		Pesticide Re-evaluation Division (7508P)

  SEQ CHAPTER \h \r 1 This document was originally prepared under
contract by Dynamac Corporation (1901 Research Boulevard, Suite 220;
Rockville, MD 20850).

Dynamac Program Manager:		Date:  04/01/2009

	Danilo Martinez

	

The document has been reviewed by the Health Effects Division (HED) and
revised to reflect current Office of Pesticide Programs (OPP) policies.

Executive Summary

Tetrachlorvinphos is an insecticide registered for use as a feed-through
(oral) larvicide for livestock and for direct treatment of beef cattle,
dairy cattle, horses, poultry, swine, and livestock premises to control
nuisance and public health pests such as flies.  No plant uses of
tetrachlorvinphos are currently registered.

EPA has completed its reregistration eligibility review and decisions on
tetrachlorvinphos (EPA 738-R-95-041, September 1995).  The Residue
Chemistry Science Chapter for Tetrachlorvinphos Reregistration
Eligibility Decision (RED) was issued 7/6/94 (DP# 199644, F. Suhre). 
According to the Residue Chemistry Chapter, the formulations registered
for use on animals include the granular (G), wettable powder (WP),
impregnated material (Impr), dust (D), ready-to-use (RTU), and
emulsifiable concentrate (EC).  These formulations may be applied
directly as a spray, backrubber solution, dust-bag, and dust.  The G
formulations are registered as feed supplements to control fecal flies
(oral larvicide); the D, WP and EC formulations are registered for
animal premise treatments, and/or topical treatments.

In response to the Tetrachlorvinphos RED, KMG Bernuth, Inc., has
submitted the results of magnitude of the residue studies on cattle and
poultry as well as a storage stability study and a residue analytical
method.  These studies have been reviewed by HED.  This document
summarizes the adequacy of these data in fulfilling reregistration
requirements.  It is noted that the Tetrachlorvinphos RED also required
a new magnitude of the residue study on swine which remains outstanding.
 The swine study was required in lieu of a swine metabolism study.  For
the purpose of this action, the end-use product labels registered to KMG
Bernuth were re-examined.  Based on the results of the reviewed studies,
HED is requiring label revisions for certain products.

Tolerances for residues of tetrachlorvinphos are established under 40
CFR §180.252.  The current tolerance expression is for the combined
residues of tetrachlorvinphos
[(Z)-2-chloro-1-(2,4,5-trichlorophenyl)vinyl dimethyl phosphate] and its
metabolites, 1-(2,4,5-trichlorophenyl)-ethanol (free and conjugated
forms), 2,4,5-trichloroacetophenone, and
1-(2,4,5-trichlorophenyl)-ethanediol.  Time limited tetrachlorvinphos
tolerances are established for the animal commodities under 40 CFR
§180.252 and were based on the available metabolism data.  In the RED
HED recommended time-limited tolerances to allow time for the registrant
to submit new magnitude of residue studies.  There are no Codex maximum
residue limits (MRLs) established or proposed for residues of
tetrachlorvinphos.

The qualitative nature of the residue in ruminants following oral or
dermal dosing, and in poultry following dermal application is adequately
understood based on previously submitted studies.  The Agency has
determined that the residues of concern are tetrachlorvinphos,
des-O-methyl tetrachlorvinphos, 1-(2,4,5-trichlorophenyl)ethanol (free
and conjugated forms), 2,4,5-trichloroacetophenone, and
1-(2,4,5-trichlorophenyl)ethanediol.

A gas liquid chromatography (GLC) method for the determination of
tetrachlorvinphos per se in animal commodities is described in the
Pesticide Analytical Method (PAM), Vol. II, as Method I.  The registrant
has submitted a method for the determination of tetrachlorvinphos and
its metabolites, which uses LC/MS/MS, LC/MS, GC/ECD, and GC/MS methods. 
An independent laboratory validation (ILV) must be submitted.

Samples collected from the animal studies were analyzed for all
tetrachlorvinphos residues of concern using LC/MS/MS, LC/MS, GC/ECD or
GC/MS methods.  The limit of quantitation was 0.01 ppm for each analyte
and was defined as the lowest fortification level at which acceptable
recovery data are obtained.  The methods used for analysis of cattle
matrices were adequately validated by fortifying control matrices with
each analyte at 0.01-0.6 ppm, while the method for the poultry matrices
was validated at 0.01 and 0.1 ppm.  

No data pertaining to the behavior of regulated tetrachlorvinphos
metabolites using FDA's multiresidue protocols have been submitted.  As
requested in the 1994 Residue Chemistry Chapter, the regulated
metabolites of tetrachlorvinphos should be analyzed using the FDA
multiresidue protocols as appropriate to ascertain if the methods are
capable of accurately quantifying all residues of concern.

Samples collected from the magnitude of the residue study on cattle were
stored frozen for up to 50 days for milk and cream, 54 days for liver,
fat, and kidney, and 63 days for muscle prior to residue analysis. 
Samples collected from the magnitude of the residue study on poultry
were estimated (information regarding dates of sample collection and
analysis was not provided) to be stored frozen for up to 144 days for
eggs and 59 days for tissues prior to analysis.  Although a companion
storage stability study was included in support of the cattle study, the
submitted data were deemed inadequate because of the study design. 
Selected samples of various matrices were re-assayed after the initial
analysis.  Considerable degradation may have occurred prior to the
initial analysis of storage stability samples.  Many of the matrices did
not have quantifiable residues of one or more of the analytes at the
time of initial analysis, so potential degradation upon storage cannot
be accurately assessed.  A new storage stability study should be
conducted with quantifiable (i.e., fortified) residues of all analytes
in all cattle and poultry matrices.  In addition, the registrant needs
to submit information pertaining to dates of treatment, collection,
extraction, and analysis to verify the maximum storage intervals of all
samples collected from both the cattle and poultry studies.

The submitted magnitude of the residue study on cattle is inadequate but
upgradeable pending submission of supporting storage stability data. 
The residue data reflect a combination of two treatments:  oral
administration of tetrachlorvinphos for 29-31 days at actual rates of
1.512-1.555 and 4.630 g ai/750 kg BW per day (6.3-6.5x and 19.3x,
respectively, the maximum registered rate of 0.24 g ai/750 kg BW for
feed-through treatment) and dermal spray treatments on three occasions,
at ~14 day intervals, at actual rates of 10.111 and 19.166-19.493 g ai
per animal per dose (~0.5 and 1.0x, respectively, the maximum registered
rate of 18.9 g ai/animal for direct animal spray treatment).  At the
treatment regime approximating the registered uses (6.5x oral + 1x
dermal), the maximum total residues of concern (with the maximum
residues of the parent in parentheses) were:  0.072 (0.036) ppm for
milk, 0.078 (<0.01) ppm for cream, 0.158 (<0.01) ppm for liver, 0.278
(0.015) ppm for kidney, 0.272 (0.212) ppm for muscle, 0.842 (0.558) ppm
for subcutaneous fat, and 0.747 (0.340) ppm for peritoneal fat.  These
data will support the registered feed-through (oral) and direct animal
spray uses of tetrachlorvinphos on cattle.

The submitted magnitude of the residue study on poultry is inadequate
but upgradeable pending submission of storage stability
data/information.  The residue data reflect 6-7 dermal spray treatments
of laying hens with an EC formulation, made at two-week retreatment
intervals, at rates of 0.0908, 0.1816, or 0.5448 g ai/hen/application. 
These application rates, respectively, correspond to ~0.5x, 1.0x, or
2.9x the maximum registered direct spray treatment rate of 0.19 g
ai/bird daily.  At ~1.0x, the maximum total residues of concern (with
the maximum residues of the parent in parentheses) were:  0.288 (0.026)
ppm for egg, 0.517 (0.016) ppm for liver, 0.583 (0.022) ppm for kidney,
0.396 (0.082) ppm for muscle, 19.405 (6.030) ppm for skin with fat, and
1.298 (0.099) ppm for abdominal fat.  

No data were submitted reflecting application of tetrachlorvinphos as a
backrubber treatment, direct animal dusting and/or premise spray
treatment; also no data were submitted directly reflecting the use of
cattle ear tag uses which may still be registered to other companies. 
The OPPTS 860.1480 Guideline states that when a pesticide may be applied
by more than one mode of treatment, separate studies are required;
however, only oral and dermal spray studies were required in the TCVP
RED.  Because the oral and dermal treatments are expected to result in
the highest residue levels, no additional data will be required to
support backrubber or premise spray treatments.  Data from wetting
sprays may be accepted in lieu of data from dust treatments.

Analytical standards for tetrachlorvinphos are currently available in
the EPA National Pesticide Standards Repository; however, no reference
standards are available for the metabolites which are also regulated
(TCVPdeme, TCPEone, TCPEol, and TCPEdiol).

Regulatory Recommendations and Residue Chemistry Deficiencies

The submitted magnitude of the residue studies on cattle and poultry are
inadequate but upgradeable.  Since a swine magnitude of residue study
has not been submitted, the existing time limited tolerances based on
the goat metabolism study should remain until the new study has been
submitted.  The poultry and cattle tolerances will need modification;
refer to Table 9 for tolerance reassessment summary.

It is noted that the metabolite des-O-methyl tetrachlorvinphos is not
included in the current tolerance expression as determined by the
Agency; therefore 40 CFR §180.252 should be amended to include the
TCVPdeme metabolite.  HED recommends that the tolerance definition
should be modified as follows. 

Tolerances are established for residues of the insecticide
tetrachlorvinphos, 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 the sum of
tetrachlorvinphos [(Z)-2-chloro-1-(2,4,5-trichlorophenyl)vinyl dimethyl
phosphate) and its metabolites chloro- 1
-(2,4,5-trichlorophenyl)-vinylmonomethyl phosphate,
1-(2,4,5-trichlorophenyl)-ethanol (free and conjugated forms),
2,4,5-trichloroacetophenone, and 1-(2,4,5-trichlorophenyl)-ethanediol,
calculated as the stoichiometric equivalent of tetrachlorvinphos, in or
on the commodity.

A list of the outstanding residue chemistry deficiencies is presented
below.  

860.1200  Directions for Use

•	Based on the magnitude of the residue study on cattle, the product
labels with direct animal spray uses on cattle (EPA Reg. Nos. 61483-43
and 61483-50) should be amended to specify a maximum of three
applications, with two-week retreatment intervals, at 19 g
ai/animal/dose.  The product label for Ravap (EPA Reg. No. 61483-50)
should also be amended to provide conversion factors to allow
calculation of direct animal spray treatment rate in terms of g
ai/animal.  

•	Based on the magnitude of the residue study on poultry, the product
labels with direct animal spray uses on poultry (EPA Reg. Nos. 61483-43
and 61483-50) should be amended to specify a maximum of seven
applications (with two-week retreatment intervals) at 0.18 g
ai/hen/application.  Note that the label should specify the weight or
volume of the product to be applied.

860.1340 Residue Analytical Methods

•	An Independent Laboratory Validation (ILV) must be submitted for the
proposed tolerance enforcement method.  

860.1360 Multiresidue Methods

•	No data pertaining to the behavior of regulated tetrachlorvinphos
metabolites using FDA's multiresidue protocols have been submitted.  As
requested in the 1994 Residue Chemistry Chapter, the regulated
metabolites of tetrachlorvinphos should be analyzed by the FDA
multiresidue protocols as appropriate to ascertain that the methods are
capable of accurately quantifying all residues of concern.  See Decision
Tree for MRM in Appendix II-2 of PAM Vol. I for more information.

860.1380 Storage Stability

•	New storage stability studies should be conducted with quantifiable
(i.e., fortified) residues of all analytes in all cattle and poultry
matrices.  In addition, the registrant needs to submit information
pertaining to dates of treatment, collection, extraction, and analysis
to verify the maximum storage intervals of all samples collected from
both the cattle and poultry studies.

860.1480 Meat, Milk, Poultry, and Eggs

•	A magnitude of the residue study on swine is required.

860.1650 Submittal of Analytical Reference Standards

•	The registrant must submit reference standards for the TCVP
regulated metabolites (TCVPdeme, TCPEone, TCPEol, and TCPEdiol) to the
Analytical Chemistry Lab.

Background

The chemical names and structures of the regulated residues are
presented in Table 1.  The physicochemical characteristics of the
technical grade of tetrachlorvinphos are presented in Table 2.

 

Common name	Tetrachlorvinphos

Company experimental name	TCVP

IUPAC name	(Z)-2-chloro-1-(2,4,5-trichlorophenyl) vinyl dimethyl
phosphate

CAS registry number	22248-79-9

End-use products registered to KMG Bernuth, Inc.

	Rabon 50 WP Insecticide (EPA Reg. No. 61483-43, 50% WP);

Rabon 3% Insecticide Dust EPA Reg. No. 61483-45, 3% D); 

Rabon 97.3 Oral Larvicide (EPA Reg. No. 61483-47, 97.3% G); 

Rabon 7.76 Oral Larvicide Premix (EPA Reg. No. 61483-48, 7.76% G); and

 

Common name	TCPEone	TCPEdiol

Chemical name	2,4,5-trichloroacetophenone
1-(2,4,5-trichlorophenyl)ethanediol



Table 2.   Physicochemical Properties of the Technical Grade Test
Compound: Tetrachlorvinphos. 

Parameter	Value	Reference 1

Melting point/range	94.5 ºC	(MRID 41222503)

pH	5.5; 1% solution	(MRID 41222503)

Density	0.83 g/mL	(MRID 41222503)

Water solubility	(25°C) 0.00116 g/100g	(MRID 41222503)

Solvent solubility	(mg/100mg at 25°C)

chloroform		80

methanol			21

acetone			44

hexane			0.8

toluene			28	(MRID 41222503)

Vapor pressure	(25°C) 2.6 x 10-7 mm Hg	(MRID 41222503)

Dissociation constant, pKa	non-ionizable	(MRID 41222503)

Octanol/water partition coefficient, Log(KOW)	3350 average KOW at 25 ºC
(MRID 41222503)

UV/visible absorption spectrum	Not available

	1  Cited reference was reviewed under CB No. 7468, 4/3/91, R. Perfetti.

860.1200  Directions for Use

A search of EPA’s PPLS database conducted 02/04/2009 identified five
tetrachlorvinphos end-use products registered to KMG Bernuth, Inc. for
use as an oral larvicide for livestock or direct treatment of beef
cattle, lactating cattle, horses, poultry, swine, and livestock
premises.  These products are listed in Table 3A.  Only those end-use
products registered to the technical registrant, KMG-Bernuth, are
considered in this table.

Table 3A.   List of Tetrachlorvinphos End-Use Products Registered to KMG
Bernuth, Inc.

Trade Name	EPA Reg. No.	Acceptance Date	ai (% of formulation)
Formulation Type

Rabon 50 WP Insecticide	61483-43	4/17/2006	50%	WP

Rabon 3% Insecticide Dust	61483-45	10/23/2008	3%	D

Rabon 97.3 Oral Larvicide	61483-47	09/18/2007	97.3%	G

Rabon 7.76 Oral Larvicide Premix	61483-48	05/04/2006	7.76%	G

Ravap EC Livestock, Poultry & Premise Insecticide Spray 1	61483-50
11/30/2007	23%	EC

1 Also contains 5.3% dichlorvos.

The tetrachlorvinphos products listed above may be applied directly to
livestock via various methods or used as a feed-through (oral
supplement).  It may also be applied to their living quarters.  A
summary of the directions for use for ruminants, poultry, and swine,
which are the subject of the residue data reviewed herein, are presented
in Table 3B.  Example calculations for application rates are presented
in Table 3C for the product, Rabon 50 WP Insecticide (EPA Reg. No.
61483-43), that leads to the maximum application rate.

Table 3B.   Summary of Registered Directions for Use of
Tetrachlorvinphos. 1

Application Type/Mode	Formulation

[EPA Reg. No.]	Application Rate	Use Directions and Limitations

Cattle, Beef

Direct animal spray 	50% WP

[61483-43]	0.5-1.0 gal of 0.35-0.5% solution/animal;

(equivalent to a maximum rate of 18.9 g ai/animal)  

	Apply as a low pressure coarse spray and apply only to point before
runoff.  No retreatment restrictions are specified.  There is no
withholding period from last application to slaughter.  

	23% EC

[61483-50]	0.5-1.0 gal of a spray solution per animal with spray
solution made by diluting 1 gal of 23% EC in 75 to 200 gal of water

(equivalent to 11 g ai/animal)	Do not treat more often than every 10
days.  Do not apply to calves under 6 months of age.  Brahman and
Brahman-cross cattle should not be treated as they may show
hypersensitivity to organophosphate pesticides.  Do not apply in
combination with other organophosphate pesticides (e.g., trichlorfon). 
There is no withholding period from last application to slaughter.

Feed through (oral) 	7.76% G

[61438-48]	70 mg/100 lb BW/day

(equivalent to 0.24 g ai/750 kg BW)	For use as an oral larvicide in
cattle feeds to prevent the development of flies in the manure of
treated cattle.  Concentrate must be mixed with feed.

Direct animal dusting	3% D

[61483-45]	1.7-3.4 g ai/animal	Apply to the upper portions of the back,
neck, and poll by hand dusting or self-treating dust bag.  Repeat as
necessary.

Cattle, Lactating

Direct animal spray	23% EC

[61483-50]	0.5 gal of a spray solution per animal with the spray
solution made by diluting 1 gal of 23% EC in 200 gal of water

(equivalent to 4 g ai/animal)	Repeat as necessary (general label
directions specify do not apply more than once a day).  Do not apply to
calves under 6 months of age.  No milk discard is required.  Care should
be taken that the spray does not come in direct contact with the cow’s
teats unless they are washed with an approved cleansing solution and
dried before milking.  Apply the spray at least 20 minutes prior to
milking or after milking has been completed.

Feed through (oral)	97.3% G

[61483-47]

7.76% G

[61438-48]	70 mg/100 lb BW/day

(equivalent to 0.24 g ai/750 kg BW

	For use as an oral larvicide in cattle feeds to prevent the development
of flies in the manure of treated cattle.  Concentrate must be mixed
with feed.

Direct animal dusting	3% D

[61483-45]	1.7-3.4 g ai/animal	Apply to the upper portions of the back,
neck, and poll by hand dusting or self-treating dust bag.  Repeat as
necessary.

Poultry

Direct animal spray 	50% WP

[61483-43]

	1.0 gal of 0.5% solution/100 birds (equivalent to a maximum rate of
0.19 g ai/bird)	Spray the vent and fluff of wire cages from below. 
Repeat when necessary but do not repeat more than every 14 days. 

	23% EC

[61483-50]	1.0 gal of a spray solution per 100 birds with the spray
solution made by diluting 1 gal of 23% EC in 50 gal of water

	Direct animal dusting	3% D

[61483-45]	0.03 lb ai/300 birds	For individual treatment of poultry in
wire cages.  Direct dust to vent and fluff area.  Group treatment may be
preferred.  Dust should reach skin.  Wire rungs and corners should also
be treated.

Swine

Direct animal spray 	50% WP

[61483-43]	0.25 to 0.5 gal of 0.5% solution/animal

(equivalent to a maximum rate of 9.5 g ai/animal)	Apply as a low
pressure coarse spray and apply only to point before runoff.  Repeat in
2 weeks if necessary.  There is no withholding period from last
application to slaughter.  

Feed through (oral)	7.76% G

[61438-48]	22.7 mg/1000 lb BW;

0.077 g ai/750 kg BW	For use as an oral larvicide in swine feeds to
prevent the development of flies in the manure of treated cattle. 
Concentrate must be mixed with feed.

Direct dusting of animal 	3% D

[61483-45]	2.6-3.4 g ai/animal 	Apply by conventional hand or power
duster to each animal with special attention given to the neck and
around the ear.  

Horses

Feed through (animal supplement)	7.76% G

[61438-48]	5.4 mg ai/100 lb BW/day	For use as an oral larvicide in horse
feeds to prevent the development of flies in the manure of treated
cattle.  Concentrate must be mixed with feed.  The product is not to be
used for horses designed for slaughter.

1Note:  Application rates for backrubber and premise treatments are not
included in this table as they are likely to lead to lower exposure than
the direct application via sprays and dusts.  Only the use directions
from products registered by the technical registrant, KMG-Bernuth, are
included.

Table 3C.   Calculation of Application Rates for Direct Animal Spray
(EPA Reg. No. 61483-43)1

Pounds

Product	Percent of ai in Product	Volume Water, Gallons	Solution
Percentage	Volume Applied to Animal, Gallons	Application Rate, lb
ai/animal2 	Application Rate, g ai/animal 3

0.5	50	9	0.35	1	0.03	13.6

0.5	50	6	0.5	1	0.0417	18.9

0.5	50	6	0.5	0.5	0.021	9.5

2	50	36	0.35	1	0.0278	12.6

2	50	25	0.5	1	0.04	18.2

4	50	75	0.35	1	0.0267	12.1

4	50	50	0.5	1	0.04	18.2

8	50	150	0.35	1	0.0267	12.1

8	50	100	0.5	1	0.04	18.2

1   The lb product, % ai, volume values were obtained directly from the
label.

2   Calculated by the following formula:  (lb product x % ai in product
x volume applied to animal)/volume water in spray solution.

3  Calculated by the following formula:  lb ai/animal x 454 g/lb.

Conclusions.  The end-use product labels of KMG Bernuth, Inc. were
examined and are deemed adequate to allow evaluation of the residue data
relative to the registered animal use patterns.  Based on the magnitude
of the residue study on cattle, the product labels with direct animal
spray uses on cattle (EPA Reg. Nos. 61483-43 and 61483-50) should be
amended to specify a maximum of three applications, with two-week
retreatment intervals, at 19 g ai/animal/dose.  The product label for
Ravap (EPA Reg. No. 61483-50) should also be amended to provide
conversion factors to allow calculation of direct animal spray treatment
rate in terms of g ai/animal.  

Based on the magnitude of the residue study on poultry, the product
labels with direct animal spray uses on poultry (EPA Reg. Nos. 61483-43
and 61483-50) should be amended to specify a maximum of seven
applications (with two-week retreatment intervals) at 0.18 g
ai/hen/application.  Note that the labels should state the amount of
product (weight or volume) to be applied to the animal so the applicator
will not have to calculate the amount of product equivalent to 0.18 g
ai/animal.

860.1300 Nature of the Residue - Plants

There are no registrations or tolerances for plant commodities, so these
studies are not required for tetrachlorvinphos.

860.1300 Nature of the Residue - Livestock

Residue Chemistry Memo:  DP# 243528, 3/11/98, D. Miller

Residue Chemistry Memo:  DP# 206721, 9/21/94, D. Miller (Addendum to
RED)

Residue Chemistry Chapter to Tetrachlorvinphos RED (DP# 199644, 7/6/94,
F. Suhre)

Residue Chemistry Memo:  J. Abbotts, No DP#, 4/93, Results of Metabolism
Committee Meeting

The qualitative nature of the residue in ruminants following oral or
dermal dosing, and in poultry following dermal application is adequately
understood based on previously submitted studies.  The Agency has
determined that the residues of concern are tetrachlorvinphos,
des-O-methyl tetrachlorvinphos, 1-(2,4,5-trichlorophenyl)ethanol (free
and conjugated forms), 2,4,5-trichloroacetophenone, and
1-(2,4,5-trichlorophenyl)ethanediol.

The metabolism of tetrachlorvinphos in ruminants and poultry differs
somewhat.  The metabolites des-O-methyl tetrachlorvinphos and
1-(2,4,5-trichlorophenyl)ethanediol are found only in hens, and the
metabolite 1-(2,4,5-trichlorophenyl)ethanol is found only in goats
(following both oral and dermal administration).  The difference in
metabolic profiles between goats and swine, both mammals, would be
expected to be less significant than the difference between goat and
hens.  Therefore, the requirements for swine metabolism studies have
been waived, provided that a magnitude of the residue study with swine
is conducted including analysis of all residues of concern.

The HED Metabolism Committee has determined that the residues of concern
are tetrachlorvinphos, des-O-methyl tetrachlorvinphos,
1-(2,4,5-trichlorophenyl)ethanol (free and conjugated forms),
2,4,5-trichloroacetophenone, and 1-(2,4,5-trichlorophenyl)ethanediol. 
Time-limited tolerances for livestock commodities, based on feed-through
and direct dermal uses on livestock, were estimated by the Agency from
the acceptable metabolism data.  Permanent tolerances are to be
established when adequate magnitude of the residue data for ruminants,
swine and poultry are available.

860.1340 Residue Analytical Methods

Residue Chemistry Chapter to Tetrachlorvinphos RED (DP# 199644, 7/6/94,
F. Suhre)

DER Reference List:  47369201.der.doc

Tolerance Enforcement Methods

Analytical methods for plant commodities are not required because there
are no tetrachlorvinphos end-use products registered for use on any
plant commodity.

The registrant has submitted a method for tolerance enforcement of
livestock commodities (MRID 47369201, 2007).  This method involves the
extraction of TCVP and its four major metabolites from tissues, milk and
cream using acetonitrile and the removal of lipid interferences using
partition with hexane and a C18 solid phase extraction (SPE) cartridge. 
TCVP, TCVPdeme and TCPEdiol are isolated on the C18 cartridge and are
quantified using liquid chromatography with mass spectrometric detection
(LC-MS).  TCPEone and TCPEol are further cleaned up with an ENVI-CARB
cartridge before quantitation using gas chromatography with electron
capture detection (GC-ECD).  Conjugated TCPEol and TCPEdiol are
extracted from the initial acetonitrile extract using saturated sodium
chloride solution and liberated by hydrolyzing overnight under acidic
conditions.  Further clean up is performed using an ENVI-CARB cartridge
prior to quantitation by GC-ECD (TCPEol) or LC-MS (TCPEdiol).  

The method was validated by SRA International using quintuplet sets of
control samples of bovine muscle, bovine liver, bovine kidney, bovine
fat, milk and cream fortified with TCVP, TCVPdeme, TCPEol, TCPEone and
TCPEdiol at 10 and 100 ppb.  Individual recoveries from fortified
samples ranged from 70% to 110%.  Standard deviations for each
crop/spiking level were no higher than 15%.  

An independent laboratory validation (ILV) trial has not been submitted
to HED for review and radiovalidation data were not provided with this
method validation trial.  Since the extraction scheme is similar to
those employed in the metabolism study, and the tissues from the
metabolism study are not likely still available, the requirement for
radiovalidation data is waived.

Data Collection Methods

Egg, milk and tissue samples from the cattle and poultry magnitude of
the residue studies were analyzed for residues of tetrachlorvinphos,
(TCVP), des-O-methyl tetrachlorvinphos (TCVPdeme),
1-(2,4,5-trichlorophenyl)ethanol (TCPEol; free and conjugated),
2,4,5-trichloroacetophenone (TCPEone), and
1-(2,4,5-trichlorophenyl)ethanediol (TCPEdiol; free and conjugated)
using LC/MS, LC/MS/MS, GC/ECD, or GC/MS methods.  Briefly, samples were
initially extracted with acetonitrile (ACN), and lipid interferences
were removed by partitioning with hexane and C18 solid phase extraction
(SPE) cartridge.

TCVP, TCVPdeme, and TCPEdiol were isolated on a C18 cartridge and
quantified using LC/MS or LC/MS/MS.  Separate LC conditions were used
for each analyte.  Quantitation of TCVP residues was performed using an
electrospray interface in the positive ion mode.  Quantitation of
TCVPdeme residues was performed using an electrospray interface in the
negative or positive ion mode.  Quantitation of TCPEdiol residues was
performed using LC/MS with an electrospray interface in the negative ion
mode.

TCPEone and TCPEol were further cleaned up by Envicarb cartridge before
quantitation using GC/ECD or GC/MS.  Conjugated TCPEol and TCPEdiol were
extracted from the initial acetonitrile extract using a saturated sodium
chloride solution and liberated by hydrolyzing overnight under acidic
conditions.  Further clean-up is performed by Envicarb cartridge prior
to quantitation by GC/ECD or GC/MS (TCPEol) or LC/MS (TCPEdiol).

The LOQ was 0.01 ppm for each analyte and was defined as the lowest
fortification level at which acceptable recovery data are obtained.  The
estimated limit of detection (LOD) was 0.002 ppm for TCVP (and TCVPdeme
in poultry matrices), 0.005 ppm for TCPEdiol, and 0.0025 ppm for all
other analytes.  Concurrent method recoveries were within the acceptable
range of 70-120%.

Conclusions.  A tolerance enforcement method has been submitted, but the
requirement for an ILV remains outstanding.  Samples collected from the
animal studies were analyzed for all tetrachlorvinphos residues of
concern using LC/MS/MS, LC/MS, GC/ECD, or GC/MS methods.  The limit of
quantitation was 0.01 ppm for each analyte and was defined as the lowest
fortification level at which acceptable recovery data are obtained.  The
methods used for analysis of cattle matrices were adequately validated
by fortifying control matrices with each analyte at 0.01-0.6 ppm. 
However, the poultry methods were only verified at fortification levels
of 0.01 and 0.1 ppm.  Adequate dilutions were used, so no further
validation data are required.

860.1360 Multiresidue Methods

Residue Chemistry Chapter to Tetrachlorvinphos RED (DP# 199644, 7/6/94,
F. Suhre)

The FDA PESTDATA database dated 8/93 (PAM Vol. I, Appendix II) indicates
that tetrachlorvinphos is completely recovered (>80%) using FDA
multiresidue method protocol D (section 232.4) but is not recovered
using protocol E (Sections 211.1/231.1 and 212.1/232.1, fatty and
nonfatty matrices).  No data pertaining to the behavior of regulated
tetrachlorvinphos metabolites using FDA's multiresidue protocols have
been submitted.  As requested in the 1994 Residue Chemistry Chapter, the
regulated metabolites of tetrachlorvinphos should be analyzed by the FDA
multiresidue protocols as appropriate to ascertain if the methods are
capable of accurately quantifying all residues of concern.  See Decision
Tree for MRM in Appendix II-2 of PAM Vol. I for more information.

860.1380 Storage Stability

Sample Storage Conditions and Intervals

The integrity of samples collected from the animal studies was
maintained by appropriate handling and freezer storage.  Sample storage
conditions and durations are summarized in Table 4.

Table 4.   Summary of Storage Conditions.

Matrix	Storage Temperature

 (°C)	Actual Storage Duration	Interval of Demonstrated Storage
Stability

Cattle Study (MRID 47193001)

Milk	 -20	<30-50 days	None.

Cream

<30-50 days

	Liver

<30-54 days

	Kidney

<30-54 days

	Muscle

<30-64 days

	Fat, Subcutaneous

<30-54 days

	Fat, Peritoneal

<30-54 days

	Poultry Study (MRID 47589301)

Egg	-20	144 days	None.

Tissues

59 days

	

Storage Stability Data

Residue Chemistry Chapter to Tetrachlorvinphos RED (DP# 199644, 7/6/94,
F. Suhre)

DER Reference List:  47193001.de2.doc

The 1994 Residue Chemistry Chapter reported that storage stability
studies have been conducted for the parent compound using fortified
samples of milk and animal tissues.  Residues of the tetrachlorvinphos
per se are stable for 25 days at 0 °C in milk, for 31 days at 0 °C in
milk fat, for 3 days at room temperature in muscle, for 4 days at room
temperature in kidney, for 5 days at room temperature in liver, and for
11 days at room temperature in fat.

The registrant submitted additional storage stability data for the
parent and all residues of concern along with the cow feeding study
(MRID 47193001).  HED has reviewed the companion study, and the
Executive Summary of the Data Evaluation Records is reproduced below.

SRA International, Inc., on behalf of KMG Bernuth, Inc., has included
supporting storage stability data in the amended final report of a dairy
cattle feeding study with tetrachlorvinphos.  To generate data on the
stability of weathered tetrachlorvinphos residues of concern in milk,
cream, liver, kidney, muscle, and fat, selected samples of these
matrices were re-assayed after the initial analysis.  Initial residue
analyses of samples from the cattle feeding study were made after the
collected samples were stored frozen for up to 50 days for milk and
cream, 54 days for liver, fat, and kidney, and 63 days for muscle; the
registrant reported that the majority of samples were stored for less
than 30 days.  Samples were re-analyzed at the following intervals after
the initial analysis:  74 and 112 days for milk, 70 and 84 days for
cream, 57 days for liver, 60 days for kidney, 68 days for muscle, and 63
and 65 days for fat.

Milk and tissue samples were analyzed for residues of tetrachlorvinphos,
TCVPdeme, TCPEol, TCPEone, and TCPEdiol using LC/MS, LC/MS/MS, or GC/ECD
methods.  The validated LOQ was 0.01 ppm for each analyte.  The adequacy
of the method for data collection was verified by fortifying untreated
samples of milk and tissues with TCVP and its metabolites at 0.01 and
0.1 ppm.  Additional untreated samples of muscle were fortified with
TCVP at 0.5 ppm and peritoneal fat were fortified with TCVP and TCPEol
each at 0.6 ppm.  Concurrent method recoveries were within the
acceptable range of 70-120%. 

Considerable variability in the sample results was observed.  Initial
analysis for some analytes showed nondetectable residues, but residues
were quantifiable at later intervals (TCPEol -conjugated).  For some
matrices extensive degradation was observed, but extensive increases
were observed for other matrices (e.g., free TCPEol). The registrant
concluded that overall results for total TCVP-derived residues did not
indicate any consistent or significant losses outside the expected
limits of analytical variation.  HED does not concur with the
registrant’s conclusion.  The samples were stored for at least 50 days
prior to the initial assay.  Considerable degradation may have occurred
prior to the initial analysis.  Many of the matrices did not have
quantifiable residues of one or more of the analytes at the time of
initial analysis, so potential degradation upon storage cannot be
accurately assessed.

Conclusions.  Storage durations of cattle and hen samples collected from
the magnitude of the residue studies are not supported by adequate
storage stability data.  Although a companion storage stability study
was submitted in support of the cattle study, the data were deemed
inadequate because considerable degradation may have occurred prior to
the initial analysis of storage stability samples.  New storage
stability studies should be conducted with quantifiable (i.e.,
fortified) residues of all analytes in cattle and poultry matrices
according to 860.1380.  In addition, the registrant needs to submit
information pertaining to dates of treatment, collection, extraction,
and analysis to verify the maximum storage intervals from collection to
extraction and analysis of all samples from both the cattle and poultry
studies.

860.1400 Water, Fish, and Irrigated Crops

This guideline is not applicable to tetrachlorvinphos as the only use is
on livestock.

860.1460 Food Handling

This guideline is not applicable to tetrachlorvinphos as the only use is
on livestock.

860.1480 Meat, Milk, Poultry, and Eggs

Residue Chemistry Chapter to Tetrachlorvinphos RED (DP# 199644, 7/6/94,
F. Suhre)

New ruminant, swine, and poultry magnitude of the residue studies were
requested in the 1994 Residue Chemistry Chapter.  The Chapter concluded
that no residue data are required for horses provided that all
applicable labels prohibit treatment of horses destined for slaughter. 
Examination of the 7.76% G oral larvacide label (EPA. Reg. No.
56493-35), a product registered to the technical registrant, shows that
it has been amended to prohibit treatment of horses intended for
slaughter.  It is possible that other registrants may have uses on
horses; the product labels of these other registrants need to be
examined to ensure that such restrictions are established.

Protocols for the conduct of the required animal studies were reviewed
by HED in memos dated 06/01/99 (DP# 246716, S. Hummel) and 8/27/01 (DP#
277227, M. Metzger).  The results of the new ruminant and poultry
magnitude of the residue studies have now been submitted.  HED has
reviewed these studies, and the Executive Summaries of the Data
Evaluation Records are reproduced below.  The requirements for a swine
study remain outstanding.

Cattle Oral/Dermal Study

DER Reference List:  47193001.de1.doc

SRA International, Inc., on behalf of KMG Bernuth, Inc., has submitted
the amended final report of a dairy cattle feeding study with
tetrachlorvinphos.  The study was designed to quantify the residues of
tetrachlorvinphos and its four significant metabolites in the milk and
tissues of dairy cows following oral administration of tetrachlorvinphos
for 29-31 days and concurrent topical (spray) application of
tetrachlorvinphos on three occasions at two-week intervals.  A summary
of the five treatment groups is presented in Table 5.  Groups of
lactating dairy cows received tetrachlorvinphos incorporated twice daily
into the concentrate feed in oil suspensions at target levels equivalent
to 1.155 or 3.465 g ai/750 kg body weight per day for 29-31 days.  In
addition, doses of tetrachlorvinphos were administered by the dermal
route on three occasions, at ~14 day intervals, as a solution in water
at target levels equivalent to 6.055 and 12.11 g ai per animal per dose.
 An untreated animal was also included to provide control data.

Table 5.  Treatment Parameters Used in the Cattle Study.

Group	Treatment	Target and (Actual) Exposure Level 1	Cow numbers



Oral	Dermal

	1	Control	--	--	1

2	Oral 	1.155 (1.553)	--	2, 3, 4/16

3	Oral + Dermal 	1.155 (1.512)	6.055 (10.111)	5, 6, 7

4	Oral + Dermal 	1.155 (1.555)	12.11 (19.166)	8, 9, 10

5	Oral + Dermal 	3.465 (4.630)	12.11 (19.493)	11, 12, 13, 14, 15

1  Dose levels are in g ai/750 kg body wt/day for oral doses and g
ai/animal/dose for dermal doses.

Milk was collected twice daily.  A portion of the milk collected on days
14 and 28/29 were separated into skim milk and cream.  One cow from each
group was sacrificed after 29, 30, or 31 consecutive days of treatment. 
The following tissues were collected at sacrifice for analysis:
subcutaneous fat, muscle, peritoneal fat, liver, and kidney.

Two cows from treatment group 5 were used in a depuration study to
determine how quickly residues in tissues dissipate.  Milk was collected
from both animals on days 30, 34, 36, and from the remaining cow on days
38 and 43 after the first dose.  On study day 37 and 44, (7 and 14 days
without treatment), the depuration animals were sacrificed, and samples
of liver, kidney, muscle, subcutaneous fat, and peritoneal fat were
collected for analysis.

Milk and tissue samples were analyzed for residues of tetrachlorvinphos,
TCVPdeme, TCPEol, TCPEone, and TCPEdiol using LC/MS, LC/MS/MS, or GC/ECD
methods.  The validated method LOQ was 0.01 ppm for each analyte.  The
adequacy of the method for data collection was verified by fortifying
untreated samples of milk and tissues with TCVP and its metabolites at
0.01 and 0.1 ppm.  Additional untreated samples of muscle were fortified
with TCVP at 0.5 ppm and peritoneal fat were fortified with TCVP and
TCPEol each at 0.6 ppm.  Concurrent method recoveries were within the
acceptable range of 70-120%.

Prior to residue analysis, samples of milk and cream were stored frozen
for up to 50 days; liver, fat, and kidney samples for up to 54 days; and
muscle samples for up to 64 days.  It is noted that only the storage
intervals exceeding 30 days were documented in the report.  The storage
stability data (refer to 47193001.de2) submitted in conjunction with
this study are inadequate.  Additional data are required to support the
study.

The results show that in milk, quantifiable residues occurred as TCVP
and TCPEol.  TCVP was not present in any samples from Group 2 (oral
treatment only), but was found in all groups treated both orally and
dermally (Groups 3, 4, and 5) on Days 1 and 2, with the highest
concentrations occurring in Group 5.  No other quantifiable residues of
TCVP occurred except on Day 30 in the two animals maintained for
depuration.  No residues were generally detectable in any groups on Days
7-14 and Days 24-28.

In cream, quantifiable residues occurred mainly as free TCPEol, with
some low quantifiable residues for TCPEone in Group 5 only.  Residues of
TCVP and other metabolites were below the LOQ in all treatment groups.

In tissues, TCVP-derived residues were overall highest in subcutaneous
and peritoneal fat  Lower residues occurred in kidney and muscle, and
the lowest residue concentrations were found in liver.  Residues
generally showed some correlation with exposure levels.  In the two
depuration animals, tissue residues declined after cessation of dosing,
reaching levels below the LOQ by 14 days of withdrawal in all tissues
except subcutaneous fat, in which a low quantifiable residue of TCVP
only was measured.

The maximum individual residues of TCVP, TCVPdeme, TCPEone, TCPEol (free
and conjugated), and TCPEdiol (free and conjugated) as well as the
maximum total residues in milk and tissues from the dairy cattle feeding
study are presented in Table 6 below.

Table 6.   Maximum Individual/Combined Residues in Milk and Tissues of
Dairy Cattle.



Matrix	Residues (ppm) 1

	TCVP	TCVP-deme	TCPEone	TCPEol 

(free)	TCPEol

 (conj.)	TCPEdiol

 (free)	TCPEdiol

(conj.)	Total 2

(TCVP equiv.)

Group 2

Milk	<0.01	<0.01	<0.01	0.014	<0.01	<0.01	<0.01	0.014

Cream	<0.01	<0.01	<0.01	0.020	<0.01	<0.01	<0.01	0.034

Liver	<0.01	0.012	<0.01	<0.01	<0.01	<0.01	<0.01	0.032

Kidney	<0.01	<0.01	<0.01	<0.01	0.044	<0.01	<0.01	0.081

Muscle	<0.01	<0.01	<0.01	<0.01	<0.01	<0.01	<0.01	ND

Fat, subcutaneous 	<0.01	<0.01	<0.01	0.012	<0.01	<0.01	<0.01	0.020

Fat, peritoneal	<0.01	<0.01	<0.01	0.024	<0.01	<0.01	<0.01	0.044

Group 3

Milk 	0.032	<0.01	<0.01	0.015	<0.01	<0.01	<0.01	0.063

Cream	<0.01	<0.01	<0.01	0.035	<0.01	<0.01	<0.01	0.077

Liver	<0.01	0.031	<0.01	0.017	<0.01	<0.01	<0.01	0.070

Kidney	<0.01	0.012	<0.01	0.052	0.039	<0.01	<0.01	0.168

Muscle	0.128	0.021	<0.01	<0.01 	<0.01	<0.01	<0.01	0.158

Fat, subcutaneous	0.343	0.072	<0.01	0.115	<0.01	<0.01	<0.01	0.485

Fat, peritoneal	0.203	0.024	0.028 	0.139	<0.01	<0.01	<0.01	0.485

Group 4

Milk	0.036	<0.01	<0.01	0.022	<0.01	<0.01	<0.01	0.072

Cream	<0.01	<0.01	<0.01	0.036	<0.01	<0.01	<0.01	0.078

Liver	<0.01	<0.01	0.010	0.056	<0.01	<0.01	<0.01	0.158

Kidney	0.015	<0.01	<0.01	0.075	0.069	<0.01	<0.01	0.278

Muscle	0.212	0.034	<0.01	0.015	<0.01	<0.01	<0.01	0.272

Fat, subcutaneous	0.558	0.111	<0.01	0.098	<0.01	<0.01	<0.01	0.842

Fat, peritoneal	0.340	0.040	0.027	0.198	<0.01	<0.01	<0.01	0.747

Group 5

Milk	0.040	<0.01	<0.01	0.018	<0.01	<0.01	<0.01	0.080

Cream	<0.01	<0.01	0.016	0.217	<0.01	<0.01	<0.01	0.380

Liver	<0.01	0.070	0.011	0.035	<0.01	<0.01	<0.01	0.122

Kidney	0.019	0.018	0.023	0.085	0.131	<0.01	<0.01	0.419

Muscle	0.474	0.112	<0.01	0.021	<0.01	<0.01	<0.01	0.625

Fat, subcutaneous 	0.534	0.144	0.011	0.153	<0.01	<0.01	<0.01	0.859

Fat, peritoneal	0.318	0.032	0.028	0.246	<0.01	<0.01	<0.01	0.725

1    LOQ = 0.01 ppm for each analyte. 

2   Total residues, in TCVP equivalents, were calculated by the
registrant.  To convert to TCVP equivalents, assay results were
multiplied by the following factors:  TCVPdeme = 1.04; TCPEone = 1.64;
TCPEol = 1.62.

Conclusions.  The submitted magnitude of the residue study on cattle is
inadequate but upgradeable pending submission of supporting storage
stability data.  The residue data reflect a combination of two
treatments:  oral administration of tetrachlorvinphos for 29-31 days at
actual rates of 1.512-1.555 and 4.630 g ai/750 kg BW per day (6.3-6.5x
and 19.3x, respectively, the maximum registered rate of 0.24 g ai/750 kg
BW for feed-through treatment) and dermal spray treatments on three
occasions, at ~14 day intervals, at actual rates of 10.111 and
19.166-19.493 g ai per animal per dose (~0.5 and 1.0x, respectively, the
maximum registered rate of 18.9 g ai/animal for direct animal spray
treatment).  Among the combination of treatment regimes used in the
study, the oral treatment at 1.555 g ai/750 kg BW per day (6.5x) plus
dermal spray treatments at 19.166 g ai per animal (~1.0x) may be used to
estimate residue exposure for the purpose of tolerance reassessment (see
Table 9).  At this treatment regime (labeled as Group 4 in the study),
the maximum total residues of concern (with the maximum residues of the
parent in parentheses) were:  0.072 (0.036) ppm for milk, 0.078 (<0.01)
ppm for cream, 0.158 (<0.01) ppm for liver, 0.278 (0.015) ppm for
kidney, 0.272 (0.212) ppm for muscle, 0.842 (0.558) ppm for subcutaneous
fat, and 0.747 (0.340) ppm for peritoneal fat.  These data will support
the registered feed-through (oral) and direct animal spray uses of
tetrachlorvinphos on cattle.

No data were submitted reflecting application of tetrachlorvinphos as a
backrubber treatment, direct animal dusting and/or premise spray
treatment; also no data were submitted directly reflecting the use of
cattle ear tag uses which may still be registered to other companies. 
The OPPTS 860.1480 Guideline states that when a pesticide may be applied
by more than one mode of treatment, separate studies are required;
however, only oral and dermal spray studies were required in the TCVP
RED.  Because the oral and dermal treatments are expected to result in
the highest residue levels, no additional data will be required to
support backrubber or premise spray treatments.  Data from wetting
sprays may be accepted in lieu of data from dust treatments.

Poultry Dermal Study

DER Reference List:  47589301.der.doc

SRA International, Inc. has submitted the results of a magnitude of the
residue study with tetrachlorvinphos.  Groups of 12 hens were topically
(dermally) treated with an aqueous solution of a 23% EC formulation of
tetrachlorvinphos.  A total of 6-7 applications were made at two-week
intervals at 0.0908, 0.1816, or 0.5448 g ai/hen/application (0.5x, 1x,
or 3x the nominal rate).  Another group was treated with water only as
the control group.  A fifth group of hens was treated at 1.816 g
ai/hen/application (10x nominal rate), but because of moderate to severe
signs of toxicity/intolerance indicative of acute cholinergic effects
attributed to the test substance, this treatment level was discontinued
and excluded from the study.

Eggs were collected daily on a group basis.  Hens were sacrificed
following the last application (0-day) from all groups.  Subgroups of
four hens from a second group of 12 hens, treated at the nominal 3x
rate, were sacrificed 7, 14, or 21 days following the last application,
for residue depuration.  The following tissues were collected at
sacrifice for analysis:  abdominal fat, liver, kidneys, muscle
(breast/leg composite), and skin with underlying subcutaneous fat. 
Group application rates and sacrifice times are summarized below in
Table 7.

Table 7.  Treatment Parameters Used in the Poultry Study.

Group	Treatment	Number of Doses	Exposure Level

(g ai/hen/dose)	Sacrifice

(DALA)1	Hen #

1	Control	7

(water only)	--	0	201-205, 208, 211-216 (n=12)

2	Dermal (Nx1)	7	0.1816	0	218-220, 222-228, 230, 231 (n=12)

3	Dermal (Nx3)	7	0.5448	0	233, 235, 236, 238-245, 248 (n=12)

3R	Dermal

(Nx3)	7	0.5448	7	246, 247, 252, 253 (n=4)





14	251, 256, 259, 262 (n=4)





21	257, 261, 263, 264 (n=4)

4	Dermal (Nx0.5)	6	0.0908	0	267-274, 277-280 (n=12)

1  Days after last treatment (DALA).

Egg and tissue samples were analyzed for residues of tetrachlorvinphos,
TCVPdeme, TCPEol, TCPEone, and TCPEdiol using LC/MS, LC/MS/MS, or GC/MS
methods.  The validated method LOQ was 0.01 ppm for each analyte.  The
adequacy of the method for data collection was verified by fortifying
untreated samples of eggs and tissues with TCVP and its metabolites at
0.01 and 0.1 ppm.  Concurrent method recoveries were within the
acceptable range of 70-120%.  The fortification levels encompassed most
residues found in hen eggs and tissues; however, residues exceeding an
order of magnitude of the highest fortification level in the concurrent
method validation, were observed for TCVP, TCVPdeme, and TCPEol (free)
in skin with fat and abdominal fat.

The registrant did not provide study dates, but based on the start,
sacrifice and experimental end dates, samples may have been stored for
up to 144 days (4.7 months) for eggs and 59 days (1.9 months) for
tissues.  The registrant did not address storage issues, and no
supporting storage stability data were provided.

TCVP-derived residues showed a linear dose response with the dosing
level.  Conjugated residues of TCPEol and TCPEdiol were each below the
method LOQ (<0.01 ppm) in all samples of egg and hen tissues (muscle,
kidney, liver, skin with fat, and abdominal fat) from all treatment
rates.

TCVP-derived residues occurred in eggs from all treatment groups in a
cyclical pattern of accumulation and depletion after each application. 
Residues of TCVP and the metabolites TCVPdeme, TCPEone, TCPEol (free)
and TCPEdiol (free) were detected, with TCPEdiol accounting for the
highest levels in eggs.  With comparison of the high and low values
observed after successive applications to the hens, residues appear to
plateau in eggs after the third or fourth treatment.  Residues in eggs
appear to decline after the final application, but quantifiable residues
(free TCPEol and TCPEdiol) were still present in eggs following 21 days
of withdrawal.

TCVP-derived residues occurred in tissues from all treatment groups, and
TCVP and the metabolites TCVPdeme, TCPEone, TCPEol (free) and TCPEdiol
(free) were detected in all matrices, except for TCPEone which was not
quantifiable in liver.  Residues were highest in skin with subcutaneous
fat by a significant margin (~30x higher) than those observed in
abdominal fat, which bore the next highest levels of residues.  Similar
lower levels were observed in liver and muscle, and the lowest residue
levels were found in kidney.  The principal residues in hen tissues were
free TCPEol and free TCPEdiol in liver and kidney; TCVP and TCVPdeme in
muscle and skin with fat; and free TCPEol in abdominal fat.   The
registrant states that since similar levels of the parent and TCVPdeme
were found in skin with fat, the results represent incurred residues and
not simply residual contamination with the test substance.  Overall
residues of TCVP, TCVPdeme, TCPEone, TCPEol (free) and TCPEdiol (free)
declined in hen tissues collected following longer withdrawal periods;
however, quantifiable residues were still present in all tissues
following 21 days of withdrawal.

The maximum individual residues of TCVP, TCVPdeme, TCPEone, TCPEol (free
and conjugated), and TCPEdiol (free and conjugated) as well as the
maximum total residues in eggs and tissues from the laying hen dermal
dosing study are presented below in Table 8.

Table 8.   Maximum Individual/Combined Residues in Poultry Eggs and
Tissues.



Matrix	Residues (ppm) 1

	TCVP	TCVP-deme	TCPEone	TCPEol 

(free)	TCPEol

 (conj.)	TCPEdiol

(free)	TCPEdiol

(conj.)	Total 2

(TCVP equiv.)

Group 4 (0.5x)

Egg	<0.01	0.019	<0.01	0.021	<0.01	0.066	<0.01	0.154

Liver	<0.01	0.018	<0.01	0.031	<0.01	0.145	<0.01	0.284

Kidney	<0.01	0.020	<0.01	0.083	<0.01	0.077	<0.01	0.292

Muscle	0.029	0.077	<0.01	0.014	<0.01	0.025	<0.01	0.165

Skin with fat 	4.393	13.314	0.401	0.940	<0.01	0.038	<0.01	20.462

Fat, abdominal	0.039	0.021	0.069	0.247	<0.01	0.083	<0.01	0.699

Group 2 (1x)

Egg	0.026	0.034	0.010	0.037	<0.01	0.114	<0.01	0.288

Liver	0.016	0.024	<0.01	0.076	<0.01	0.238	<0.01	0.517

Kidney	0.022	0.051	0.015	0.150	<0.01	0.175	<0.01	0.583

Muscle	0.082	0.169	0.011	0.030	<0.01	0.047	<0.01	0.396

Skin with fat 	6.030	9.857	0.668	1.489	<0.01	0.094	<0.01	19.405

Fat, abdominal	0.099	0.028	0.139	0.474	<0.01	0.149	<0.01	1.298

Group 3 (3x)

Egg	0.065	0.089	0.014	0.097	<0.01	0.230	<0.01	0.584

Liver	0.131	0.120	<0.01	0.184	<0.01	0.882	<0.01	1.865

Kidney	0.056	0.047	0.020	0.227	<0.01	0.238	<0.01	0.848

Muscle	1.017	0.726	0.020	0.068	<0.01	0.090	<0.01	2.045

Skin with fat 	44.761	42.477	0.971	2.398	<0.01	0.191	<0.01	94.099

Fat, abdominal	0.753	0.101	0.296	1.158	<0.01	0.250	<0.01	3.265

1    LOQ = 0.01 ppm for each analyte. 

2   Total residues, in TCVP equivalents, were calculated by the
registrant.  To convert to TCVP equivalents, assay results were
multiplied by the following factors:  TCVPdeme = 1.04; TCPEone = 1.64;
TCPEol = 1.62; TCPEdiol = 1.516.

Conclusions:  The submitted magnitude of the residue study on poultry is
inadequate but upgradeable pending submission of additional method
validation data, storage stability data/information, and label revisions
to specify appropriate retreatment intervals.  The residue data reflect
6-7 dermal spray treatments of laying hens with an EC formulation, made
at two-week retreatment intervals, at 0.0908, 0.1816, or 0.5448 g
ai/hen/application.  These application rates, respectively, correspond
to ~0.5x, 1.0x, or 2.9x the maximum registered direct spray treatment
rate of 0.19 g ai/bird daily.  At ~1.0x, the maximum total residues of
concern (with the maximum residues of the parent in parentheses) were: 
0.288 (0.026) ppm for egg, 0.517 (0.016) ppm for liver, 0.583 (0.022)
ppm for kidney, 0.396 (0.082) ppm for muscle, 19.405 (6.030) ppm for
skin with fat, and 1.298 (0.099) ppm for abdominal fat.  These data will
support the registered direct animal spray use of tetrachlorvinphos on
poultry and may be used to estimate residue exposure for the purpose of
tolerance reassessment (see Table 9).  

No data are available to support the remainder of poultry uses
registered to KMG Bernuth such as direct animal dusting and premise
spray treatment.  However, because the dermal treatments are expected to
result in the highest residue levels, no additional data will be
required to support premise spray treatments.  Data from wetting sprays
on poultry may be accepted in lieu of data from dust treatments. 

860.1500 Crop Field Trials

860.1520 Processed Food and Feed

860.1850 Confined Accumulation in Rotational Crops

860.1900 Field Accumulation in Rotational Crops

No tetrachlorvinphos end-use products are currently registered for use
on any plant commodity.  Therefore, no field residue data, processing
data, or confined/field rotational crop studies are required.  Previous
tolerances on crops have been revoked.

860.1650 Submittal of Analytical Reference Standards

An analytical standard for tetrachlorvinphos is currently available in
the EPA National Pesticide Standards Repository (personal communication
with Theresa Cole, ACB, 8/31/10) with an expiration date of 2/01/2011. 
No reference standards are available for the metabolites which are also
regulated (TCVPdeme, TCPEone, TCPEol, and TCPEdiol).  Analytical
reference standards of the TCVPdeme, TCPEone, TCPEol, and TCPEdiol must
be supplied and supplies replenished as requested by the Repository. 
The reference standards should be sent to the Analytical Chemistry Lab,
which is located at Fort Meade, to the attention of either Theresa Cole
or Thuy Nguyen at the following address:

	USEPA

	National Pesticide Standards Repository/Analytical Chemistry Branch/OPP

	701 Mapes Road

	Fort George G. Meade, MD  20755-5350

(Note that the mail will be returned if the extended zip code is not
used.)

860.1550 Tolerance Reassessment

Residue Chemistry Memo:  DP# 243528, 3/11/98, D. Miller

The HED Metabolism Committee has determined that the residues of concern
are tetrachlorvinphos, des-O-methyl tetrachlorvinphos,
1-(2,4,5-trichlorophenyl)ethanol (free and conjugated forms),
2,4,5-trichloroacetophenone, and 1-(2,4,5-trichlorophenyl)ethanediol. 
The current tolerance expression under 40 CFR §180.252 includes all of
these residues except des-O-methyl tetrachlorvinphos. To allow separate
risk assessments for cholinesterase inhibition (involving parent only),
the tolerances for each animal commodity also specify the maximum
residues of tetrachlorvinphos per se from the total residues.  The
revised tolerance definition should be modified as follows, to be
consistent with the Tolerance Expression Guidance issued 5/27/09 (S.
Knizner).

Tolerances are established for residues of the insecticide
tetrachlorvinphos, 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 the sum of
tetrachlorvinphos [(Z)-2-chloro-1-(2,4,5-trichlorophenyl)vinyl dimethyl
phosphate) and its metabolites chloro- 1
-(2,4,5-trichlorophenyl)-vinylmonomethyl phosphate,
1-(2,4,5-trichlorophenyl)-ethanol (free and conjugated forms),
2,4,5-trichloroacetophenone, and 1-(2,4,5-trichlorophenyl)-ethanediol,
calculated as the stoichiometric equivalent of tetrachlorvinphos, in or
on the commodity.

The time-limited tolerances for livestock commodities under
§180.252(a), based on feed-through and/or direct dermal uses on
livestock, were estimated by the Agency from the acceptable metabolism
data.  A tolerance for poultry skin could not be estimated at that time
because this matrix was not included in the hen metabolism study.  HED
recommended time-limited tolerances to allow time for the registrant to
submit new feeding/dermal studies to determine permanent tolerances.

The submitted magnitude of the residue study on cattle is inadequate but
upgradeable pending submission of supporting storage stability data and
label revisions.  The reviewed data will support the registered
feed-through (oral) and direct dermal uses.  HED has concluded that the
oral and dermal data represent the worst-case and no additional data
will be required to support other uses such as backrubber treatment and
premise spray treatment.

The submitted magnitude of the residue study on poultry is inadequate
but upgradeable pending submission of additional method validation data,
storage stability data/information, and label revisions.  The reviewed
data will support the registered direct animal uses.  HED has concluded
that the dermal data represent the worst-case and no additional data
will be required to support premise spray treatments.

The established/needed tolerances for hog commodities cannot be
reassessed at this time as a magnitude of the residue study on swine is
outstanding.

A summary of tolerance reassessment is detailed in Table 9.  



Table 9. 	Tolerance Reassessment Summary for Tetrachlorvinphos.

Commodity	Established

Tolerance 1

(ppm)	Maximum Residues 2

(ppm)	Reassessed Tolerance 3

(ppm)	Comments; 

Correct Commodity Definition

Cattle, fat (of which no more than 0.1 ppm is tetrachlorvinphos per se)
0.2	0.84 (0.56) subcutaneous fat;

0.75 (0.34) peritoneal fat	1.0	Cattle, fat (of which no more than 0.6
ppm is tetrachlorvinphos per se)

Cattle, kidney (of which no more than 0.05 ppm is tetrachlorvinphos per
se)	1.0	--	Remove

	Cattle, liver (of which no more than 0.05 ppm is tetrachlorvinphos per
se)	0.5	--	Remove

	Cattle, meat (of which no more than 2.0 ppm is tetrachlorvinphos per
se)	2.0	0.27 (0.21) muscle	0.3	Cattle, meat (of which no more than 0.2
ppm is tetrachlorvinphos per se)

Cattle, meat by products, except kidney and liver	1.0	--	Remove	See
cattle, meat byproducts

Cattle, meat by products	None	0.16 (<0.01) liver;

0.28 (0.015) kidney;

0.84 (0.56) subcutaneous fat;

0.75 (0.34) peritoneal fat;

0.27 (0.21) muscle	1.0	Cattle, meat byproducts (of which no more than
0.6 ppm is tetrachlorvinphos per se) 4



Egg (of which no more than 0.05 ppm is tetrachlorvinphos per se)	0.2
0.288 (0.026)	0.3	Egg (of which no more than 0.03 ppm is
tetrachlorvinphos per se)

Hog, fat (of which no more than 0.1 ppm is tetrachlorvinphos per se)	0.2
TBD 5	TBD	Magnitude of the residue data in hog remains outstanding.

Hog, kidney (of which no more than 0.05 ppm is tetrachlorvinphos per se)
1.0	TBD	TBD

	Hog, liver (of which no more than 0.05 ppm is tetrachlorvinphos per se)
0.5	TBD	TBD

	Hog, meat (of which no more than 2.0 ppm is tetrachlorvinphos per se)
2.0	TBD	TBD

	Hog, meat byproducts, except kidney and liver	1.0	TBD	TBD

	Milk, fat (reflecting negligible residues in whole milk and of which no
more than 0.05 ppm is tetrachlorvinphos per se)	0.05	0.072 (0.036) for
milk;

0.078 (<0.01) for cream	0.1	Milk (of which no more than 0.04 ppm is
tetrachlorvinphos per se)

Poultry, fat (of which no more than 7.0 ppm is tetrachlorvinphos per se)
7.0	1.298 (0.099) abdominal fat	1.4	Poultry, fat (of which no more than
0.1 ppm is tetrachlorvinphos per se)

Poultry, liver (of which no more than 0.05 ppm is tetrachlorvinphos per
se)	2.0

Remove	See poultry, meat byproducts

Poultry, meat (of which no more than 3.0 ppm is tetrachlorvinphos per
se)	3.0	0.40 (0.082) muscle	0.4	Poultry, meat (of which no more than 0.1
ppm is tetrachlorvinphos per se)

Poultry, meat byproducts, except liver	2.0	--	Remove	See poultry, meat
byproducts

Poultry, meat byproducts	None	0.52 (0.016) liver;

0.58 (0.022)

kidney;

0.40 (0.082) muscle;

19.41 (6.03) skin with fat;

1.30 (0.099) abdominal fat	20	Poultry, meat byproducts (of which no more
than 6.0 ppm is tetrachlorvinphos per se) 4



1   Time-limited tolerances; current tolerance expression is for the
combined residues of tetrachlorvinphos
[(Z)-2-chloro-1-(2,4,5-trichlorophenyl)vinyl dimethyl phosphate] and its
metabolites, 1-(2,4,5-trichlorophenyl)-ethanol (free and conjugated
forms), 2,4,5-trichloroacetophenone, and
1-(2,4,5-trichlorophenyl)-ethanediol; should also include des-O-methyl
tetrachlorvinphos.

2   Total residues of tetrachlorvinphos and its metabolites, TCVP-deme,
TCPEone, TCPEol (free and conjugated forms), and TCPEdiol (free and
conjugated), expressed in terms of parent equivalents; the value in
parentheses represents the maximum residues of the parent
tetrachlorvinphos.

3   Reassessed tolerance is based on the maximum residue from the
respective magnitude of the residue study; the maximum residues of the
parent tetrachlorvinphos are reported in the corrected commodity
definition.

4  According to the 18 July 2007 Minutes of the HED ChemSAC meeting, the
guidance document will be revised to include language detailing the use
of the highest residue data for any tissue (liver, kidney, fat, skin or
muscle) to determine the tolerance for meat byproducts.  A single
tolerance on “meat byproducts” will be recommended based on that
highest residue, and individual tolerances will no longer be set on
liver, kidney, or meat byproducts (except liver and kidney).

5   TBD = to be determined.  

Codex and Canadian MRL Harmonization

There are no Codex maximum residue limits (MRLs) established or proposed
for residues of tetrachlorvinphos.  Canada has established MRLs for
plant and animal commodities.  Canada’s residue definition is
2-chloro-1-(2,4,5-trichlorophenyl) vinyl dimethyl phosphate and its low
melting isomer.  A summary of U.S. and international tolerances and
maximum residue limits is presented in Table 10.  At this time the
Agency cannot harmonize with the Canadian MRL since the new magnitude of
residue data support the different tolerances.  HED has not examined the
Canadian registrations; different use patterns may account for the
different residue levels.  

Table 10.  Summary of U.S. and International Tolerances and Maximum
Residue Limits.

Commodity	U.S. Tolerances, 40 CFR §180.252 1	Codex MRL	Canada’s MRL 2

	Established U.S. Tolerance, ppm	Reassessed U.S. Tolerance, ppm 



Milk, fat (reflecting negligible residues in whole milk)	0.5 (of which
not more than 0.05 ppm is tetrachlorvinphos per se) 	milk:  0.1 (of
which not more than 0.04 ppm is tetrachlorvinphos per se)	None	None

Fat, cattle	0.2 (of which not more than 0.1 ppm is tetrachlorvinphos per
se)	1.0 (of which not more than 0.8 ppm is tetrachlorvinphos per se)
None	1.5 3

Muscle	meat of cattle and hog:  2.0 (of which not more than 2.0 ppm is
tetrachlorvinphos per se)	meat of cattle:  0.3 (of which not more than
0.2 ppm is tetrachlorvinphos per se)	None	1.5 3

Kidney	kidney of cattle and hog:  1.0 (of which no more than 0.05 ppm is
tetrachlorvinphos per se)	meat byproducts of cattle:  1.0 (of which no
more than 0.6 ppm is tetrachlorvinphos per se) 	None	1.5 3

Liver	liver of cattle and hog:  0.5 (of which no more than 0.05 ppm is
tetrachlorvinphos per se)

None	1.5 3

Meat byproducts	meat byproducts, except kidney and liver of cattle and
hog: 1.0

None	1.5 3

Poultry	0.75	poultry fat:  1.4 (of which not more than 0.1 ppm is
tetrachlorvinphos per se)	None	0.75 4

Eggs	0.2 (of which not more than 0.05 ppm is tetrachlorvinphos per se)
0.3 (of which not more than 0.03 ppm is tetrachlorvinphos per se)	None
None

Poultry, muscle	meat of poultry:  3.0 (of which not more than 3.0 ppm is
tetrachlorvinphos per se)	meat of poultry:  0.4 (of which not more than
0.1 ppm is tetrachlorvinphos per se)	None	0.75 4

Poultry, liver	2.0 (of which not more than 0.05 ppm is tetrachlorvinphos
per se)	meat byproducts of poultry:  20 (of which not more than 6.0 ppm
is tetrachlorvinphos per se)	None	0.75 4

Poultry, meat byproducts	meat byproducts, except liver, of poultry:  2.0

None	0.75 4

Poultry, fat	7.0 (of which not more than 7.0 ppm is tetrachlorvinphos
per se)	1.4 (of which not more than 0.1 ppm is tetrachlorvinphos per se)
None	0.75 4

Apples	None	None	None	10

Grapes	None	None	None	10

1   Current US residue definition is tetrachlorvinphos, des-O-methyl
tetrachlorvinphos, 1-(2,4,5-trichlorophenyl)ethanol (free and conjugated
forms), 2,4,5-trichloroacetophenone, and
1-(2,4,5-trichlorophenyl)ethanediol.  

Hog U.S. tolerances cannot be reassessed at this time (the magnitude of
the residue in hogs study is outstanding); because the current
tolerances for hog are time limited, hog tissues were not included in
the tolerance and MRL comparison summary.

2   Canada residue definition is 2-chloro-1-(2,4,5-trichlorophenyl)
vinyl dimethyl phosphate and its low melting isomer.

3   Meat, meat byproducts and fat of cattle and hogs, calculated on the
fat content.

4   Meat, meat byproducts and fat of poultry, calculated on the fat
content.

References

DP#:	199644

Subject:	Tetrachlorvinphos (Case 0321, Chemical 083701).  Product
Chemistry Chapter and Residue Chemistry Chapter for the Reregistration
Eligibility Decision Document  SEQ CHAPTER \h \r 1 

From:	F. Suhre

To:	L. Propst

Dated:	07/6/94

MRIDs:	None

DP#:	206721

Subject:	Tetrachlorvinphos.  Addendum to RED.  PTRL Response to EPA
Review of Nature of Residue Study (MRID Nos. 42828801-03).  Request
Dated August 11, 1994.  CBRS No. 14227; Case No. 0321.  SEQ CHAPTER \h
\r 1 

From:	D. Miller

To:	D. McNeilly

Dated:	09/21/94

MRIDs:	None

DP#:	243528

Subject:	Tetrachlorvinphos (083701).  Development of Tolerance Estimates
for Revised HED Chapter.  SEQ CHAPTER \h \r 1 

From:	D. Miller

To:	K. Boyle

Dated:	03/11/98

MRIDs:	None

DP#:	246716

Subject:	Tetrachlorvinphos (Case 0321, Chemical 083701).  Protocol for
Combined Oral/Dermal Livestock Studies  SEQ CHAPTER \h \r 1 

From:	S. Hummel

To:	D. Fuller and C. Swartz

Dated:	06/01/99

MRIDs:	None

DP#:	277227

Subject:	Tetrachlorvinphos.  Livestock Feeding Study Protocols. 
Response to Questions from Boehringer Ingelheim  SEQ CHAPTER \h \r 1 

From:	M. Metzger

To:	D. Fuller

Dated:	08/27/01

MRIDs:	None

Template Version September 2005

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Tetrachlorvinphos	Summary of Analytical Chemistry and Residue Data	DP#s:
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