SRC TR-10-047

HPV1 TEST RULE STUDY – DATA ADEQUACY ASSESSMENT

1-Chlorododecane, CAS No. 112-52-7

Acute Toxicity

Prepared by:

Ashlee Aldridge, Justine Von Runnen and Joan D. Garey

Environmental Science Center
SRC, Inc.

7502 Round Pond Road North Syracuse, NY 13212

Contract No. EP-W-09-027

Task FG007.0.009.002

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

1-Chlorododecane, CAS No. 112-52-7

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. 112-52-7

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. 112-52-7

ACUTE TOXICITY

Title: Acute Oral Toxicity with 1-Chlorododeca ne: Up And Down Procedure In Rats

The study is: Adequate Not Adequate

TEST SUBSTANCE

Identity: 1-Chlorododecane, CAS No. 112-52-7

Remarks: The test substance was a colorless to pale yellow liquid, stored at room temperature and was stable for the duration of testing. Batch #N6227945. Purity 97.42%; specific gravity = 0.883 g/mL.

METHOD

Method/guideline followed: 40 CFR 799.9110 TSCA Acute Oral Toxicity (1997), OECD Guidelines for Testing Chemicals, Test N o. 425 (2006) U.S. EPA Health Effects Test Guidelines, OPPTS 9870.110 (2002).

Test type: Acute oral toxicity – limit test

GLP compliant: Yes

Year study performed: 2008

Test species: Sprague-Dawley derived albino rats (rece ived from Ace Animals Inc., Boyertown PA; 9 – 11 weeks; 180-241g)

Number of animals/sex/dose: 8 female (nulliparous and non-pregnant)

Route of administration: Gavage

Vehicle: None

Doses/concentrations tested: 2000 mg/kg

Statistical methods used: Not applicable

Test method/conditions remarks: All animals were fasted overnight prior to dosin g. A preliminary toxicity test was performed

with undiluted 1-Chlorododecane administered via gavage to one healthy female rat at a limit dose of 2000 mg/kg body weight. Due to the absence of mortality in this animal, four additional

female rats were administered undiluted 1-Chlorododecane at 2000 mg/kg body weight. Because food was not withheld from these animals immediately post-dosing, an additional three female

rats were administered undiluted 1-Chlorodode cane at 2000 mg/kg body weight in order to meet

2Draft HPV1 Test Rule – Data Adequacy –Acute Toxicity CAS No. 112-52-7

the guideline requirements for a limit test. All animals were observed for clinical signs of toxicity and mortality fo r 14 days following dosing.

RESULTS

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

Results remarks: All animals survived, gained body weight, and appeared active and healthy during the study. There were no signs of gross toxicity, adverse pharmacologic effects, or abnormal behavior. No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.

CONCLUSIONS

Under conditions of this study, the acute oral LD 50 of 1-Chlorododecane in the female rat is greater than 2000 mg/kg -bw.

STUDY RELIABILITY

[1] – Reliable without restrictions

REFERENCE

EPA-HQ-OPPT-2005-0033-0314.1; Durando, J. 2008. Acute Oral Toxicity with 1- Chlorododecane: Up and Down Procedure in Rats . Eurofins/Product Safety Laboratories for Lonza Inc. Study No. 22019 (unpublished report).

3Review of TSCA Section 4 Final Study Report

CITB Project Manager: Catherine Roman

Chemical Name: 1-Chlorododecane

CAS Registry Number: 112-52-7

Report Title: Acute Oral Toxicity with 1-Chlo rododecane: Up and Down Procedure in Rats

Test Sponsor: Lonza, Inc.

Testing Lab: Eurofins Product Safety Laboratories

Test Standard: OECD 425

Date Study Received by EPA: September 19, 2008 Date Study Due to EPA: May 17, 2007

Special Instructions (e.g., regarding approved protocol modifications, etc.): As required for compliance with the "Testing of certain High Production Volume Chemicals; Final Rule" (Federal Register; 40 CFR Parts 9 and 799; Thursday, March 16, 2006 pp 13708-13730), the guideline reference, 40 CFR 799.91 10 TSCA Acute Oral Toxicity, was added to the Test Procedure Guidelines section of the protocol.

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.

[NA] 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 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 ri sk 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): As required for compliance with the "Testing of certain High Production Volume Chemicals; Final Rule" (Federal Register; 40 CFR Parts 9 and 799; Thursday, March 16, 2006 pp 13708-13730), the guideline reference, 40 CFR 799.91 10 TSCA Acute Oral Toxicity, was added to the Test Procedure Guidelines section of the protocol. This had no negative impact on this study as the 40 CFR 799.91 10 TSCA Acute Oral Toxicity guideline refere nces the OECD Guideline No. 425 also included in the protocol.

Reviewer Name/Title/Bran ch/Division/Office: Ashlee Aldridge/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).