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 Work Assignment Manager 

March 5, 2010 

 
HPV1 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 22202
Draft HPV1 Test Rule – Data Adequacy – Acute Toxicity CAS No. 409-02-9

PREPARATION OF THE DATA ADEQUACY ASSESSMENT

This document contains the review of a toxicity 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 guides, the study was reviewed for adequacy and 

evaluated for compliance with the test guideline. (The applicable test guideline is not always the 

test guideline required by the test rule, because 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 assigned a Klimisch reliability code. If the study 

was determined to be inadequate, a basis for that conclusion is supplied. For studies already 

assigned Klimisch codes, an explanation is provided if the reviewer’s assessment of data 

adequacy differed from the pre-assigned Klimisch code. 

A detailed evaluation of the test report and study conduct is provided at the end of the 

summary document in a section entitled “Review 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 Procedures, Good Laboratory Practice Standards, and 

Quality Assurance procedures, as well as the use of appropriate controls and test substances. 

Any deficiencies in the descriptions of the study method, test system, animals studied, physical 

conditions, dosage information, individual 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. 

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Draft 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 Heavy 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 sequential order, one at a time, at a 

minimum of 48 hour intervals. Animals were observed at approximately 30 and 60 minutes postdosing, followed by approximately hourly intervals throughout Day 1. Subsequently, animals 

were observed twice daily for 15 days post-dosing. All animals were killed and necropsied on 

Day 15. 

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

RESULTS

Endpoint value(s): LD50 > 2000 mg/kg. 

Results remarks: All animals survived to the scheduled study termination. Clinical signs 

included strong odored urine and piloerection observed in all females; an unsteady gait in four 

females; partially closed eyelids, underactivity and salivation in two females; 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 females. All animals exhibited a satisfactory bodyweight 

gain throughout the study. Macroscopic examination at study termination revealed no 

abnormalities.

CONCLUSIONS

The acute oral LD50 for methyl heptenone is > 2000 mg/kg. 

STUDY RELIABILITY

[1] Reliable without restrictions. 

REFERENCE

Huntingdon Life Sciences, Ltd. 2008. Methyl Heptenone Acute Oral Toxicity to the Rat (Upand-Down Procedure). Study #EXN/0093. 

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Review 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) inspections, their dates, and findings were missing or not signed. 

There is evidence that QA procedures 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 different 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 summary 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/Branch/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 met, 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).