An equal opportunity employer 

1220 L Street, Northwest Russell White

Washington, DC 20005-4070 Health Sciences Manager 

Tel 202-682-8344 

Fax 202-682-8270 

whiter@api.org

January 10, 2011 

Karl Simon 

Division Director, Office of Transportation and Air Quality Compliance and Innovative Strategies 

Division 

USEPA 1200 Pennsylvania Avenue, N.W. (6406J) 

Washington, D.C. 20460 

RE: Interim Report # 20 – Fuels and Fuel Additives Health Effects Testing Regulation; 

Pursuant to Section 211(b)(2) and 211(e) of the Clean Air Act. 

Dear Mr. Simon: 

The American Petroleum Institute (API), on behalf of the Section 211(b) Research Group (RG) 

is submitting this interim report on the progress and status between 01 July 2010 and 01 

January 2011 of the testing program set forth in the Alternative Tier 2 provisions of the testing 

regulation. 

I would like to call two issues to your attention. First, the RG received a report amendment on 

September 21st from the performing laboratory for the chronic study on Gasoline/MTBE Vapor 

Condensate. This is after EPA had accepted the final report for this study. The RG had an 

independent quality assurance review of the proposed amendment done and the performing 

laboratory is now preparing an amended report. The RG will send the amended report to EPA 

upon completion. 

Second, the protocol and study schedule for pharmacokinetic studies on DIPE will be available 

soon. The RG will be asking EPA for an expedited review of the protocol so the performing 

laboratories can keep to the study schedule. 

1. Toxicology Testing1

Baseline Gasoline Vapor Condensate: 

• Subchronic study (with GFAP, genotoxicity, immunotoxicity, and neurotoxicity assays) – 

The final report was submitted to EPA 05 July 2007. 

• Two-generation reproductive study – The final report was submitted to EPA 23 January 

2009. 

• Rat and mouse developmental toxicity studies – The rat final report was submitted to 

EPA 11 August 2008. The mouse final report was revised and resubmitted to EPA 23 

November 2009. 

• Chronic study – The final report was submitted to EPA 16 June 2010. 

 

1

 All studies were conducted in rats, unless otherwise noted 
July 6, 2010 

Page 2 of 3 

Gasoline/MTBE Vapor Condensate: 

• Subchronic study (with GFAP, genotoxicity, immunotoxicity, and neurotoxicity assays) 

– The final report was submitted to EPA 14 September 2007. 

• Two-generation reproductive study – The second draft report was accepted by EPA 

on 17 December 2010. Preparation of the final report was in progress.

• Rat and mouse developmental toxicity studies – The final report of the rat study was 

submitted to EPA 07 July 2009. The mouse final report was submitted to EPA 04 June 

2009. The final report of the repeat mouse study was submitted to EPA 06 May 2010.

• Chronic study – The final report was submitted to EPA 16 June 2010. An amended 

report was being prepared by the performing laboratory. 

Gasoline/Ethanol Vapor Condensate: 

• Subchronic study (with GFAP, genotoxicity, immunotoxicity, and neurotoxicity assays) 

–The final report was submitted to EPA on 24 February 2010. 

• One-generation reproductive toxicity study – The final report was submitted to EPA 29 

May 2009. 

• Developmental toxicity study -The final report was submitted to EPA 10 December 

2008. 

Gasoline/TAME Vapor Condensate: 

• Subchronic study (with GFAP, genotoxicity, immunotoxicity, and neurotoxicity assays) 

– The second draft report was accepted by EPA 09 December 2010. Preparation 

of the final report was in progress. 

• One-generation reproductive study - The final report was submitted to EPA 29 May 

2009. 

• Developmental toxicity study – The final report was submitted to EPA 17 December 

2008. 

Gasoline/ETBE Vapor Condensate: 

• Subchronic study (with GFAP, genotoxicity, immunotoxicity, and neurotoxicity assays) 

– Preparation of the final report, in response to EPA comments, was in progress. 

• One-generation reproductive study – The second draft report was accepted by EPA 

on 17 December 2010. Preparation of the final report was in progress.

• Developmental toxicity study – The final report was submitted to EPA 17 December 

2008.

Gasoline/DIPE Vapor Condensate: 

• Subchronic study (with GFAP, genotoxicity, immunotoxicity, and neurotoxicity assays) 

– EPA comments on the first draft report and responses to peer-reviewers 

comments were received 09 December 2010. Preparation of the second draft 

report was in progress. 

• One-generation reproductive study - The second draft report was submitted to EPA 

on 28 July 2010. The second draft report was accepted by EPA on 17 December 

2010. Preparation of the final report was in progress. 

• Developmental toxicity study – EPA comments on the first draft report and 

responses to peer-reviewers comments were received 17 December 2010. 

Preparation of the second draft report was in progress. 
July 6, 2010 

Page 3 of 3 

Gasoline/TBA Vapor Condensate: 

• Subchronic study (with GFAP, genotoxicity, immunotoxicity, and neurotoxicity assays) 

– EPA comments on the first draft report and responses to peer-reviewers 

comments were received on 09 December 2010. Preparation of the second draft 

report was in progress. 

• One-generation reproductive study - The second draft report was accepted by EPA 

on 17 December 2010. Preparation of the final report was in progress.

• Developmental toxicity study - The final report was submitted to EPA 16 October 2009. 

Pharmacokinetic Studies on DIPE, ETBE, and TBA:

• ETBE – Preparation of the first draft report was in progress. 

• DIPE – Preparation of the first draft report for pilot studies was in progress. 

Preparation of the definitive study protocol was in progress. 

• TBA – Preparation of the final report for the pilot study was in progress. 

2. Exposure Screening Studies

The report entitled “Section 211(B) Tier 2 High End Exposure Study of Conventional and 

Oxygenated Gasoline” and previously submitted associated materials were accepted by EPA on 

19 May 2010. 

Sincerely, 

Russell White, Ph.D. 

Health Sciences Manager 

cc: Joe Sopata, EPA (via email)