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HPV 2 TEST RULE DATA ADEQUACY REVIEW ( REVISED FINAL ):

MICRONUCLEUS TEST

Phosphorochloridothioic acid, O,O

- diethyl ester, CASRN 2524

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Prepared by:

Amy Nguyen, William L. Richards, and Teresa Manyin

Defense and Environmental Solutions Division

SRC, Inc. 7502 Round Pond Road North Syracuse, NY 13212

Contract No. EP

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- 027 Task FG007.4 .009.00 1

Submitted to:

OCSPP/OPPT/RAD (7403M) U.S. Environmental Protection Agency 1200 Pennsylvania Avenue Washington, D.C. 20460

Bryan Lobar, Project Officer David Brooks, Work Assignment Manager Amy Benson, Alternate Work Assignment Manager

March 4
, 201 5Final HPV 2 Test Rule Data Adequacy Review ( March 2015) CAS RN 2524

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i TABLE OF CONTENTS

A. SOURCE MATERIAL USED FOR ASSESSMENT

................................ .............................. 1 B. EVALUATING DATA ADEQUACY

................................ ................................ ..................... 1 C. SUMMARY OF DATA ADEQUACY FOR TESTING REQUIRED BY TEST RULE

........ 2
D. DATA FOR SIDS ENDPOINTS

................................ ................................ .............................. 3

D

- 1. Genetic Toxicity

– Chromosomal Aberrations

................................ ................................ .. 3Final HPV 2 Test Rule Data Adequacy Review ( March 2015) CAS RN 2524

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1 A. SOURCE MATERIAL USED FOR ASSESSMENT

This document evaluates a micronucleus test for CASRN 2524

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- 1 (p hosphorochloridothioic acid, O,O

- diethyl ester ; O,O

- diethyl phosphorochloridothioate [DEPCT]) submitted by Dow AgroSciences to EPA in Decem ber 2014 in response to the final test rule, “Testing of Certain High Production Volume Chemicals; Second Group of Chemicals” (76 FR 1067, January 7, 2011; referred to herein as HPV2; available online at http://www.regulations.gov/#!document Detail;D=EPA

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- 0579 as of March 4, 2015 ).

The HPV2 test rule requires the following toxicological testing f or CASRN 2524

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- 1: C1 ( aquatic toxicity, consisting of Test Group 1 [acute toxicity to fish, acute toxicity to Daphnia
, and toxicity to algae test s ] if log K ow < 4.2 or Test Group 2 [chronic toxicity to Daphnia and toxicity to algae tests] if log Kow ≥ 4.2)
, E1 (bacterial reverse mutation test), E2 (chromosomal aberration s or micronucleus test), and F2 (reproduction/developmental toxicity screening test). Based on an estimated log K ow of 2.37 1 , Test Group 1 testing is required to determine the toxicity of CASRN 2524

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- 1 to aquatic organisms.

The December 2014 submission from Dow AgroSciences contained the following study report :

 Schisler, M.R., and McFadden, L.G. 2014

. Evaluation of phosphorochloridothi oic acid, O,O

- diethyl ester (DEPCT) in the mouse peripheral blood micronucleus test. Performing Laboratory: The Dow Chemical Company (Toxicology and Environmental Research and Consulting), Midland, MI. Sponsor: Dow AgroSciences LLC

. Study report availab le online at http://www.regulations.gov/#!documentDetail;D=EPA

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. These newly submitted data are evaluated for adequacy herein. No other toxicity data are evaluated in this report.

B. EVALUATING DATA ADEQUACY

The submitted data are evaluated for adequacy in Section D. The study was summarized according to a standa rd format and assigned a Klimisch reliability code based on its scientific merit and conduct, using professional judgment. To determine whether data were adequate to satisfy the E 2 testing requirement for CASRN 2524

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- 1, study details were compared to OE CD TG 47 4 2

. In addition, the study was evaluated to determine whether recommendations provided

1 U.S. EPA. 2012. Estimation Programs Interface SuiteTM (EPI Suite) for Microsoft ® Windows, v4.11. U.S. Environmental Protection Agency, Washington, DC, USA. Available online at http://www.epa.gov/opptintr/ exposure/pubs/episuitedl.htm as of March 4, 2015

. 2 Al though the HPV2 test rule specifies that chromosomal aberrations testing should be conducted according to TSCA guideline 40 CFR 799.9537, 40 CFR 799.9538, or 40 CFR 799.9539, EPA previously granted a request from Dow AgroSciences to follow OECD TG 474 inst ead (request granted in EPA’s study plan review of CASRN 2524

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- 1, “HPV2 Review of Toxicity Study Plan Dated February 25, 2014: Phosphorochloridothioic acid, O,O

- diethyl ester, CASRN 2524

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- 1”, SRC Technical Report #14

- 008, dated April 3, 2014; available online at http://www. regulations.gov/#!documentDetail;D=EPA

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2 in EPA’s study plan review 1 were followed. B ecause CASRN 2524

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- 1 has physicochemical properties (i.e., potential for hydrolysis 2 and volatili zation 3 ) that necessitate special considerations in the chromosomal aberrations testing process , EPA had previously provided recommendations aimed to minimize loss of the test substance during toxicity testing

. C. SUMMARY OF DATA ADEQUACY FOR TESTING REQUIRED BY TEST RULE

Evaluation of Data Submitted for the Chromosomal Aberrations Endpoint: Data submitted by Dow Agro S ciences and reviewed in this document are considered adequate to satisfy the chromosomal aberrations (E2) testing requirement for CASRN 2524

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. Remaining HPV2 Test Rule Toxicity Testing Requirements: Dow AgroSciences submitted a study report of a bacterial reverse mutation test of CASRN 2524

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- 1 4 , which was reviewed by EPA in a separate report 5 and determined to be not adequate to satisfy the gene mutation (E1) testing requirement for CASRN 2524

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- 1 promulgated in the HPV2 test rule.

Dow AgroSciences has not yet submitted d ata f or the following toxicity testing requirements for CASRN 2524

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- 1: a cute toxicity to fish (component of C1) , acute toxicity to Daphnia (component of C1) , toxicity to algae (component of C1), reproductive toxicity (component of F2), and developmental toxicity (component of F2 ).

Summary of Data Adequacy for Toxi cological Endpoints: Adequate data have been submitted for the chromosomal aberrations endpoint. The acute toxicity to fish, acute toxicity to Daphnia , toxicity to algae, gene muta tion, reproductive toxicity, and developmental toxicity endpoints are considered data gaps and testing is still required for these endpoints.

1 “ HPV2 Review of Toxicity Study Plan Dated February 25, 2014: Phosphorochloridothioic acid, O,O

- diethyl ester, CASRN 2524

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- 1 ” , SRC Technical Report #14

- 008, dated April 3, 2014; available online at http://www. regulations.gov/#!documentDetail;D=EPA

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. 2 West, R.J., and Hu, J. 2014. Phosphorochloridothioic acid, O,O

- diethyl ester: Determination of hydrolysis as a function of pH according to OECD Guideline 111. Performin g Laboratory: The Dow Chemical Company (Toxicology and Environmental Research and Consulting), Midland, MI. Sponsor: Dow AgroSciences LLC.
3 CASRN 2524

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- 1 is considered volatile based on an estimated Henry’s Law Constant of 6.72 x 10

- 4 atm

- m 3 /mole at 25°C (U.S. EPA. 2012. Estimation Programs Interface SuiteTM [EPI Suite] for Microsoft ® Windows, v4.11. U.S. Environmental Protection Agency, Washington, DC, USA. Available online at http://www.epa.gov/opptintr/ exposure/pubs/episuitedl.htm as of March 4, 2015 ).
4 Tendulkar, K.E. 2014. Phosphorochloridothioic acid, O,O

- diethyl ester : Salmonella

- Escherichia coli mammalian

microsome reverse mutation assay pre

- incubation method with a confirmatory assay. Performing Laboratory: JAI Research Foundation, Gujarat, India. Sponsor: Dow AgroSciences LLC.
5 “ HPV2 Test Rule Data Adequacy Review: Bacterial Reverse Mutation Test
, Phosphorochloridothioic acid, O,O

diethyl ester, CASRN 2524

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- 1 ”, SRC Technical Report #15

- 023 , dated March 4, 2015.Final HPV 2 Test Rule Data Adequacy Review ( March 2015) CAS RN 2524

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3 D . DATA FOR SIDS ENDPOINTS

D

- 1 . Genetic Toxicity

– Chromosomal Aberrations

Summary of endpoint: Adequate

Study 1: In vivo mouse micronucleus assay ( Schisler and McFadden , 201 4 )

Title : Evaluation of phosphorochloridothioic acid, O,O

- diethyl ester (DEPCT) in the mouse peripheral blood micronucleus test

Th is study is: Adequate Not Adequate

TEST SUBSTANCE

Identity: Phosphorochloridothioic acid, O,O

- diethyl ester (DEPCT) , CASRN 2524

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Remarks: Purity: 99.3%; Lot No. C032013081501

METHOD

Method/guideline followed: OECD TG 474 (1997; “Mammalian Erythrocyte Micronucleus Test”), Method B

. 12 of Commission Regulation (EC) No. 440/2008 (2008 ; “Mutagenicity

– In vivo Mammalian Erythrocyte Micronucleus Test” ), and OPPTS 870.5395 (1998; “ Mammalian Erythrocyte Micronucleus Test ”)

Test type: In vivo Mouse Micronucleus Assay

GLP compliant?: Yes , with the following exception: “ A concentration check or stability for the positive control substance (cyclophosphamide monohydrate) used in this study were not performed; however, the responsiveness of the animals to the control substance met expectations, therefore this exception had n o impact on the study.” [Schisler and McFadden 2014, p. 2]

Year study performed: 201 4

Test species: Crl : CD1(ICR) male mice; obtained from Charles River
, Kingston, NY ; at initiation
, the animals were approximately 8 to 10 weeks old and weighed 31.6 to 35. 5 grams (body weights of animals on day 1 of the micronucleus test)

.
Metabolic activation: Not applicable

Number of animals/sex/dose: 6 males/dose (0, 75, and 150 mg/kg

- bw/day); 8 males/dose (300 mg/kg

- bw/day)

Route of administration: O ral (gavage)Final HPV 2 Test Rule Data Adequacy Review ( March 2015) CAS RN 2524

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4 Vehicle: Corn oil (non

- anhydrous) 1

Doses/concentrations tested: 0 (vehicle only), 75
, 150 , and 3 00 mg/kg

- bw /day

Statistical methods used: Micronucleated reticulocytes (MN

- RET) and percent reticulocytes (RET) were tested for equality of variance with Bartlett’s test ( alpha = 0.01 ). MN

- RET data were log transformed for comparison of the positive control to the negative control.

“ Based on the similarity of the response between sexes in the RFT [ range

- finding test ] , the MN

RET data and t he data on percent RET were analyzed by a one

- way analysis of variance (only males were used )

... The alpha level at which all tests were conducted was 0.05.” [ Schisler and McFadden 2014 , p. 16]

“ The MN

- NCE [ micronucleated normochromatic erythrocyte s] w as not analyzed statistically and

w as only used as an adjunct end point to evaluate the biological significance of the MN

- RET results.” [ Schisler and McFadden 2014 , p. 16]

Test method/conditions remarks: Dosing formulations of the test substance in corn oil were prepared fresh for each consecutive day of dosing

. Concentration and Homogeneity of Dosing Formulations in the Micronucleus Test: Test c oncentration s and homogeneity were determined in the micronucleus test for dos ing formulations prepared on the first of two consecutive days of dosing using gas chromatography with electron capture detection (GC/ECD)

. Test concentrations were determined in each dosing formulation ( i.e., control, low

- , intermediate

- , and high

- dose levels ) based on two or three samples collected from each dosing formulation container . Homogeneity was evaluated for the low

- and high

- dose levels based on samples collected from three different positions (top, middle, and bottom) of each dosing formulat ion container. S amples for concentration and homogeneity determination were collected with a wide

- orifice pipet tip while the dosing formulation s were being stirred

.
Animal Housing and Environmental Conditions : Prior to the start of the study, the animals were acclimated to the laboratory conditions for at least one week. During the study, animals were housed one per cage in stainless steel cages

. The animal room was maintained at 22 ± 1°C and 40

- 70% humidity, with 12

- 15 air changes per hour (aver age) and a 12

- hour light/dark photoperiod.

Range

- Finding Test Procedure: A dose range

- finding test was conducted in male and female mice to determine suitable dose level s for the micronucleus test. On the first day of dosing, males weighed 29.1 to 36.5 grams and females weighed 22.9 to 30

. 2 grams. G roups of mice were administered the test item as either a single dose (1/sex /dose at 1000 and 2000 mg/kg

- bw) or a single dose on each of two

1 Although the corn oil vehicle was not fully described in the study report, Dow AgroSciences indicated in a submission to EPA on F ebruary 16, 2015 (email from Dr. George Oliver of Dow AgroSciences to Mr. John Schaeffer of EPA ) that the corn oil used as a vehicle was non

- anhydrous

.Final HPV 2 Test Rule Data Adequacy Review ( March 2015) CAS RN 2524

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5 consecutive days (3/sex /dose at 250 and 375 mg/kg

- bw/day; 3 males and 1 female at 500 mg/kg

bw/day). Doses were administered at a constant dosing volume of 10 mL/kg

- bw

.
All treated animals were observed for mortalities. Surviving animals were observed daily for signs of toxicity until the day of scheduled sacrifice (day 4)

. Body weights were determined on the day of dosing and on the day of scheduled sacrifice. “The relative body temperatures of the treated animals were monitored during the RFT [range

- finding test] using programmable transponders

... The temperatures were generally collected by scanning the microchip prior to each dosing, and approximately 2, 5, and 24 hours after dosing as well as prior to sacrifice. ” [ Schisler and McFadden 2014, p. 1 4 ]

“ All mortalities a nd/or moribund animals were necropsied to ascertain whether the condition was related to a dosing mishap. ” [ Schisler and McFadden 2014, p. 11 ]

Micronucleus Test Procedure: Male mice received a single dose of the test item on each of two consecutive days via gavage at 75
, 150 , or 300 mg/kg

- bw /day at a constant dos ing volume of 10 mL/kg

- bw . Groups of 6 animals were dosed at 75 and 150 mg/kg

- bw /day and 8 animals were dosed at 300 mg/kg

bw /day

. 1 A negative control group of 6 animals was similarly administered a single dose of the vehicle (corn oil) on two consecutive days

. A positive control group of 6 animals was administered a single dose of cyclophosphamide monohydrate at 40 mg/kg

- bw by gavage. Mortalities were recorded and the mice were observed daily for other signs of toxicity. Animal body weights were recorded prior to dosing and on the day of scheduled sacrifice (day 4). Peripheral blood samples were collected from all animals approximately 48 hours after the second dose o f the test item (and 48 hours after the single dose of the positive control substance).

“ Temperatures were monitored during the main study since a decrease of at least 3 ° C for more than 5 hours was observed during the RFT [range

- finding test]

. Body temperature changes outside this range have been previously reported to cause an increase in micronucleus formation .” [Schisler and McFadden 2014, p. 14]

Evaluation of Micronuclei Formation: Approximately 5000 reticulocytes per animal (6/dose) 2 were analy zed by flow cytometry for micronuclei formation

. “ Samples were prepared and analyzed per instructions in the Mouse MicroFlow Micronucleus Analysis Kit Manual

... At the end of the specified interval following treatment, a peripheral blood sample was collect ed from the orbital sinus of all surviving animals into anticoagulant solution following anesthesia with isoflurane. Briefly, the blood samples were fixed in ultracold (

- 70 to

- 80°C) methanol within five hours of collection. All fixed blood samples were stored at

- 80°C. Fixed blood samples of the first six mice of each group were washed with a cold, buffered salt solution and isolated by centrifugation. The resulting cell pellets were stored at approximately 4°C until staining. Blood samples were ultimately incubated with RNase to degrade the high levels of RNA present in the reticulocytes (RET) and a fluorescently labeled antibody to the transferrin receptor (anti

- CD71

- FITC) to specifically

1 Two additional mice were dosed at 300 mg/kg

- bw/day to provide possible replacements in the event of mortality in this group.
2 Reticulocytes from only 6 (out of 8 total) mice dosed at 300 mg/kg

- bw/day were analyzed.Final HPV 2 Test Rule Data Adequacy Review ( March 2015) CAS RN 2524

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6 identify the RET. A propidium iodide solution was added to each sample immediately before flow cytometry (FCM)

... analysis to stain the DNA, including that of micronuclei. Blood samples were analyzed by high

- speed FCM. In this system, the sample was moved at a high velocity past a laser set to provide 488 nm ex citation. The fluorescent wavelengths emitted by each cell were collected by photomultiplier tubes. Using the previously described staining procedure, the propidium iodide

- stained DNA of the micronuclei emitted a red fluorescence and the anti

- CD71

- FITC a ntibody emitted a high green fluorescent signal permitting differentiation between cells with and without micronuclei. In addition to obtaining fluorescent profiles, FCM simultaneously provided cell size information by determining the light scatter proper ties of each cell or combination of cells. ” [Schisler and McFadden 2014, pp. 14

- 15]

“ The number of normochromatic erythrocytes (NCE), MN [micronucleated]

- NCE, RET, and MN

- RET were recorded for each sample and the frequency of MN

- RET was determined to provide an indication of genotoxic potential. The frequency of RETs relative to total erythrocytes [results reported as “% RET” in Tables 12 and 13 of the study report] was determined to provide an indication of perturbations in hematopoietic activity ind icative of cell toxicity. For each of the treatment groups, a mean and standard deviation was calculated to describe the frequency of RET, MN

- NCE, and MN

- RET observed. ” [Schisler and McFadden 2014, p. 15]

Slide Preparation:

“ Duplicate cell smears were p repared and stored to serve as backups in the event that the flow cytometric analysis was not possible. Blood was collected into a microtainer tube coated with EDTA. Wedge smears were prepared, fixed in methanol, and stored at room temperature. ” [Schisl er and McFadden 2014, p. 15]

Criteria for Determin ation of a Response: The t est material was considered positive in this assay if the following criterion was met:

“ Statistically significant increase in MN

- RET frequency at one or more dose levels accompanied by a dose response. ” [Schisler and McFadden 2014, p. 1 6 ]

The test material was considered negative in this assay if the following criterion was met:

“ No statistically significant dose

- related increase in MN

- RET when compared to the negative control.” [Schisler and McFadden 2014, p. 16]

“ A test result not meeting the criteria for either the positive or the negative response was considered to be equivocal.” [Schisler and McFadden 2014, p. 16]

Criteria for a Valid Test : The test was considered valid if the following conditions were met:

 “The range of MN

- RET values in the negative controls were within reasonable limits of the recent laboratory background range.

 There was a significant increase in the incidence of MN

- RET in th e positive control treatment as compared to the concurrent negative controls.Final HPV 2 Test Rule Data Adequacy Review ( March 2015) CAS RN 2524

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7  The mean for percent RET value in one or more of the test material treated groups was ≥ 20% of the control value indicating no undue effect on erythropoiesis (toxicity).” [Schisl er and McFadden 2014, pp. 15

- 16]

RESULTS
Genotoxicity result : Negative

T oxic concentration (if applicable): ≥ 300 mg/kg

- bw/day ( based on cli nical signs of toxicity observed in 6/8 animals )

Results remarks: The analytically determined mean measured concentrations of test item in the dosing formulations prepared on the first day of dosing in the micronucleus test ranged from 90.7% to 92.4% of nominal concentrations 1

. The dosing formulations prepared on the first day of dosing in the mic ronucleus test were homogenous
, based on a relative standard deviation (RSD) of 1.8% and 4.8% for the low

- and high

- dose formulations, respectively

. Range

- Finding Test Results: Mortalities occurred in the male administered a single dose of the test item at 1000 mg/kg

- bw and in both animals (1/sex) administered a single dose of the test item at 2000 mg/kg

- bw. These 3 animals died within 5 hours following dosing. The female dosed with 1000 mg/kg

- bw was found in a moribund condition at the 5

- hour observation and was sacrificed . Clinical signs of toxicity observed in one or more animals at 1000 or 2000 mg/kg

- bw included labored respiration with mouth breathing, incoordinated gait, no or decreased activity, no reactivity, reduced body tempera ture, bluish skin and mucous membranes, cold to the touch
, clear perioral soiling, fecal perineal soiling, and soft feces

. Examination of animals dosed with 2000 mg/kg

- bw by a pathologist revealed “ watery contents in the intestines and hemolyzed blood in the stomach with no evidence of a dosing error. ” [Schisler and McFadden 2014, p. 1 7 ] The study report did not indicate whether similar abnormalities were observed at necropsy in the intestines and stomach of animals dosed with 1000 mg/kg

- bw.

A lthough no spontaneous mortalities occurred in the animals administered a dose of 500 mg/kg

bw/day on two consecutive days
, the female and two of the three males administered 500 mg/kg

bw/day were found in a moribund condition on the second day of dosing ( after the second dose was administered) and were sacrificed

. Although no evidence of gavage error was found at necropsy in any of the se animals sacrificed prior to scheduled sacrifice , one male ha d small

1 Given that the test item is susceptible to hydrolysis and volatilization , EPA recommended in its review of the protocol submitted for the proposed micronucleus test of CASRN 2524

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- 1 that the vehicle be anhydrous and that precautions (e.g., airtight seals, minimal headspace, and min imal exposure to air) be taken to minimize volatilization during preparation and handling of dosing formulations. Althou gh the corn oil vehicle was non

- anhydrous , and the study report does not specify whether or not precautions were taken to minimize vola tilization, EPA considers concerns regarding hydrolysis and volatilization of the test substance in corn oil during the test to be negligible for the following reasons: (a) The mean measured concentrations of the dosing formulations in this micronucleus test were within an acceptable range ( measured concentrations on the first day of dosing were 90.7 to 92.4% of nominal concentrations) ; and (b) T wo stability tests (Perala and McFadden, 2014; Andrus et al., 2014 ) submitted to EPA by Do w AgroSciences on February 23, 2015 ( as attachments in an email from Dr. George Oliver of Dow AgroSciences to Mr. John Schaeffer of EPA ) demonstrated that CASRN 2524

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- 1 wa s stable in non

- anhydrous corn oil for up to 24 days

.Final HPV 2 Test Rule Data Adequacy Review ( March 2015) CAS RN 2524

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8 ulcers in the glandular mucosa and hemolyzed blood in the lumen of the stomach. Clinical signs of toxicity observed at 500 mg/kg

- bw/day included continuous muscle tremor, muscle tremor associated with movement or stimuli, reduced body temperature, cold to the touch, urine perineal soiling, fecal perineal soiling, watery and/or soft feces, decreased quantity of feces, decreased activity, and partially closed eyelids (bilateral).

Of the animals (3/sex/dose) administered 375 mg/kg

- bw/day on two consecutive days, one female was found dead on the day following the second dose. Examination of this animal by a pathologist revealed no evidence of a gavage error. No other animals died or were sacrificed moribund at this dose level. C linical signs of toxicity observed at 375 mg/kg

- bw/day included slight muscle tr emor, muscle tremor associated with movement or stimuli, decreased activity, reduced body temperature, cold to the touch, fecal perineal soiling, watery and/or soft feces, and decreased quantity of feces or absent feces

. No mortalities occurred in animals administered 250 mg/kg

- bw/day on two consecutive days. Clinical signs of toxicity observed at 250 mg/kg

- bw/day were limited to perineal fecal soiling and watery feces in one female.

Since there were no appreciable dif ferences in toxicity between males and females during the range

- finding test , the micronucleus test was performed in male mice only.

Micronucleus Test Results: No mortalities occurred in the micronucleus test. No treatment

- related changes in body weight or body temperature were observed. One of six negative control animals exhibited urine perineal soiling and decreased feces. No clinical signs of toxicity were observed in animals dosed with 75 mg/kg

- bw/day. At 150 mg/kg

- bw/day, clinical signs were limited to soft feces in 1/6 animal s

. Clinical signs of toxicity were observed in 6 /8 animals at 300 mg/kg

- bw/day and included soft feces, decreased quantity of feces, urine perineal soiling, and fecal perineal soiling.

“ There were no significant differences in MN

- RET frequencies between the groups treated with the test material and the negative controls. The adequacy of the experimental conditions for the detection of induced micronuclei was ascertained from t he observation of a [statistically] significant [p < 0.05] increase in the frequencies of micronucleated RET in the positive control group

... ” [Schisler and McFadden 2014, p. 21 ]

“ The percent RET values observed in the test material

- treated animals were not significantly different f rom the negative control values

... The percent RET values of the positive control animals were found to be [statistically] significantly [p < 0.05] lower than those of the negative control animals. ” [Schisler and McFadden 2014, p. 21 ]

CONCLUSIONS

The test item did not induce micronuclei in peripheral blood reticulocytes in male mice administered the test item on two consecutive days at dose levels of 75, 150, and 300 mg/kg

bw/day.Final HPV 2 Test Rule Data Adequacy Review ( March 2015) CAS RN 2524

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9 STUDY RELIABILITY

[ 1 ] Reliable with out restrictions.

REFERENCE S

Andrus, A.K., Zablotny, C.L., Hannas, B.R., and Sura, R. 2014. Phosphorochloridothioic acid, O,O

- diethyl ester: 14

- day oral gavage range

- finding study in Crl:CD(SD) rats. Performing Laboratory: The Dow Chemical Company (Toxicology and Environmental Research and Consulting), Midland, MI. Sponsor: Dow AgroSciences LLC

. Perala, A.W., and McFadden, J.R. 2014. Phosphorochloridothioic acid, O,O

- diethyl ester: Method validatio n and stability in rodent feed, corn oil, and toluene. Performing Laboratory: The Dow Chemical Company (Toxicology and Environmental Research and Consulting), Midland, MI. Sponsor: Dow AgroSciences LLC

.
Schisler
, M

. R., and McFadden, L.G. 201 4

. Evaluation of p hosphorochloridothioic acid, O,O

diethyl ester (DEPCT) in the m ouse p eripheral b lood m icronucleus t est

. Performing Laboratory: The Dow Chemical Company (Toxicology and Environmental Research and Consulting), Midland, MI. Sponsor: Dow AgroSciences LLC

. Study report available online at http://www. regulations.gov/#!documentDetail;D=EPA

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. Text in quotes is taken directly from Schisler and McFadden (201 4 ).