SRC TR-10-057

HPV1 TEST RULE STUDY – DATA ADEQUACY ASSESSMENT

Methyl Heptanone, CAS No. 409-02-9

Acute Toxicity

Prepared by:

Kendra Moran, Ashlee Aldridge, and Joan D. Garey

Environmental Science Center
SRC, Inc.

7502 Round Pond Road North Syracuse, NY 13212

Contract No. EP-W-09-027

Task FG007.0.009.004

Submitted to:

OPPT/RAD/HPVCB (7403M) U.S. Environmental Protection Agency 1200 Pennsylvania Avenue

Washington, D.C. 20460

Elizabeth Margosches, Project Officer Meena Sonawane, Work Assignment Manager David Brooks, Alternate Wo rk Assignment Manager

March 5, 2010HPV1 Test Rule – Data Adequacy Assessment

Methyl Heptanone, CAS No. 409-02-9

Acute Toxicity

March 2010

Submitted to: High Production Volume Chemicals Branch

Risk Assessment Division

Office of Pollution Prevention and Toxics Environmental Protection Agency

WAM: Meena Sonawane

Alternate WAM: David Brooks 1200 Pennsylvania Avenue, NW

Washington, DC 20460-0001

Prepared By:

SRC, Inc.

Environmental Science Center 2451 Crystal Drive, Suite 804 Arlington, VA 22202Draft HPV1 Test Rule – Data Adequacy – Acute Toxicity CAS No. 409-02-9

PREPARATION OF THE DAT A ADEQUACY ASSESSMENT

This document contains the review of a toxi city study conducted in response to the first

HPV TSCA Section 4 Test Rule (71 FR 13708, March 16, 2006). Using the applicable test guideline and professional judgment as guide s, the study was reviewed for adequacy and evaluated for compliance with the test guideline. (T he applicable test guid eline is not always the test guideline required by the test rule, becau se some test sponsors requested and received approval from EPA to use a different guideline .) The study was summarized according to a standard format, assessed for adequacy, and assi gned a Klimisch reliability code. If the study was determined to be inadequate, a basis for th at conclusion is supplie d. For studies already assigned Klimisch codes, an explanation is prov ided if the reviewer’s assessment of data adequacy differed from the pre-assigned Klimisch code.

A detailed evaluation of the test report a nd study conduct is provided at the end of the summary document in a section entitled “Revie w of TSCA Section 4 Final Study Report”. Any deviations from the applicable test guideline are described. The study is also evaluated for compliance with Standard Operating Procedur es, Good Laboratory Prac tice Standards, and Quality Assurance procedures, as well as the use of appropriate controls and test substances. Any deficiencies in the descri ptions of the study method, test system, animals studied, physical conditions, dosage information, indi vidual animal data, calculations, and statistical analyses are described, and internal inconsistencies within the study report are identified. An overall assessment is provided for each of the following: study conduct, data reliability, and data utility.

1Draft HPV1 Test Rule – Data Adequacy – Acute Toxicity CAS No. 409-02-9

ACUTE TOXICITY

Title: Acute Oral Toxicity To The Rat (Up-And-Down Procedure)

The study is: Adequate Not Adequate

TEST SUBSTANCE

Identity: Methyl Heptanone, CAS No. 409-02-9

Remarks: The test substance, Baton Rouge MEK Hea vy Ketone Heart Cut C8 Ketone Fraction, was characterized as a complex mixture.

METHOD

Method/guideline followed: OECD TG 425 (2001); EPA Health Effects Test Guidelines OPPTS 870.1100 (2002).

Test type: Acute Oral Toxicity – Limit Test

GLP compliant?: Yes

Year study performed: 2007

Test species: Female Crl:CD SD rats were obtained from Charles River (UK) Ltd, Magate, Kent, England. Animals selected for the study had body weights between 200 and 231 g and were between 8 and 12 weeks of age.

Number of animals/sex/dose: 5 females/dose

Route of administration: Oral Gavage

Vehicle: Corn Oil

Doses/concentrations tested: Single dose, 2000 mg/kg bodyweight

Statistical methods used: Not stated

Test method/conditions remarks: Animals were dosed in sequentia l order, one at a time, at a

minimum of 48 hour intervals. Animals were obser ved at approximately 30 and 60 minutes postdosing, followed by approximately hourly interv als throughout Day 1. Subsequently, animals were observed twice daily for 15 days post-dosing. All animals were killed and necropsied on Day 15.

2Draft HPV1 Test Rule – Data Adequacy – Acute Toxicity CAS No. 409-02-9

RESULTS

Endpoint value(s): LD 50 > 2000 mg/kg.

Results remarks: All animals survived to the scheduled study termination. Clinical signs included strong odored urine and pilo erection observed in all female s; an unsteady gait in four females; partially closed eyelids, underactivity and salivation in two fema les; and urine staining of the perigenital area, hunched posture, deep breathing, brown staining on the muzzle and head and pale light brown feces in individual female s. All animals exhibited a satisfactory bodyweight gain throughout the study. M acroscopic examination at study termination revealed no

abnormalities.

CONCLUSIONS

The acute oral LD 50 for methyl heptenone is > 2000 mg/kg.

STUDY RELIABILITY [1] Reliable without restrictions.

REFERENCE Huntingdon Life Sciences, Ltd. 2008. Methyl Hepte none Acute Oral Toxicity to the Rat (Upand-Down Procedure). Study #EXN/0093.

3Review of TSCA Section 4 Final Study Report

CITB Project Manager: Catherine Roman

Chemical Name: Methyl Heptanone

CAS Registry Number: 409-02-9

Report Title: Acute Oral Toxicity To The Rat

Test Sponsor: Exxon Mobil Chemical Company

Testing Lab: Huntingdon Life Sciences Ltd.

Test Standard: OECD TG 425

Date Study Received by EPA: 6/23/09 (date posted to http://www.regulations.gov )

Date Study Due to EPA: 5/17/07

Special Instructions (e.g., regarding approved protocol modifications, etc.):

Part I. Test Report and Study Conduct

Enter one of the following codes into each of the checkboxes 1 through 13: Agree [ A ], Disagree [ D ], Not Applicable [ NA ], or Cannot Determine [ C ], and add comment, below, as needed

[D] 1. The final study report indicates evidence of gross, unauthorized or undocumented deviation from the EPA test standard requirements, including “shall,” “must,” or “will” violations. List significant test standard deviations and “shall,” “must,” or “will” violations in comments below.

[D] 2. The final study report indicates evidence of deviations from the “should” statements in the study protocol that may have a bearing on the study conclusions. List these in comments below.

[D] 3. Approved modifications of test standard or testing protocol (CITB PM describe or attach) were not followed or are inadequately documented.

[D] 4. There is evidence that laboratory Standard Operating Procedures (SOPs) were inadequately followed.

[D] 5. The Statement of Quality Assurance (QA) inspect ions, their dates, and findings were missing or not signed. There is evidence that QA pr ocedures may be inadequate.

[D] 6. There is evidence that Good Laboratory Practice Standards (GLPS) were inadequately followed.

[D] 7. The test, control, or reference substances are di fferent from that specified in the section 4 test rule or

Enforceable Consent Agreement (ECA).

[D] 8. Animal identification is inadequate or unclear; use of unhealthy animals or other factors (e.g., deviations from temperature, lighting, dosing) are apparent.

[D] 9. The final study report inadequately describes the study method.

[D] 10. The final study report inadequately describes the test system.[D] 11. The final study report inadequately describes the dosage information.

[D] 12. The final study report does not accurately reflect the individual animal data (or that of other discrete observations pertinent to the type of study conducted), or individual data were not provided.

[D] 13. The final study report inadequately describes the calculations, interpolations, data transformations, statistical analyses, or modeling parameters used.

Part II. Conclusions

Place a check mark beside the summar y statement(s) that apply to this review and add comments below as appropriate

Part A. To be filled out by Reviewer

Study Conduct 1. The study was well-conducted. [x] 2. The study was generally well-conducted, with some minor [ ] deficiencies (list in notes below). 3. The study conduct was significantly deficient or questionable, (give [ ] reasons in notes below).

Data Reliability 4. The study results are precise and accurate. [x] 5. Appropriate methods were used to determine [x] statistical significance. 6. If repeated, the test results would be expected to be the [x]

same.

Data Utility 7. The data are useful for risk assessment for the endpoint tested. [x] 8. The data are useful for some other purpose (e.g., dose-setting). [ ] 9. The data are not useful for any purpose (describe in notes below). [ ]

Reviewer Comments (continue on separate page, if needed):

Reviewer Name/Title/Bran ch/Division/Office: Kendra Moran / SRC, Inc.

Reviewer Signature: David Brooks/HPVCB/RAD/OPPTS

Part B. To be filled out by CITB PM

Tiered Testing Decision 1. The tiered testing trigger was me t, additional testing is indicated. [ ] (when applicable) 2. The trigger for additional (tiered) testing was not met. [ ]

Study Acceptability 3. The study is acceptable. [ ] 4. The study may not be acceptable [ ] (provide rationale in memo to CITB chief).