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1220 L Street, Northwest Russell White

Washington, DC 20005-4070 Health Sciences Manager

Tel 202-682-8344

Fax 202-682-8270

whiter@api.org

July 18, 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 # 21 – 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 January 2011 and 01 

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

regulation.

API would like to thank EPA staff for the expedited review of the draft protocol for the definitive 

pharmacokinetic studies on DIPE. The contract laboratory is making the requested changes 

and we should have a final protocol by August 1. 

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. 

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.

 

1 All studies were conducted in rats, unless otherwise noted
July 18, 2011

Page 2 of 3

 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. A report 

amendment was submitted to EPA on 21 April 2011.

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) 

– The final report was submitted to EPA on 23 March 2011.

 One-generation reproductive study – The final report was submitted to EPA 06 May 

2010

 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 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. 

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.
July 18, 2011

Page 3 of 3

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. A compiled version of the final report was submitted to EPA on 10 June 

2011, completing the Section 211(B) Tier 2 exposure screening study requirements.

Sincerely,

Russell White, Ph.D.

Health Sciences Manager

cc: Joe Sopata, EPA (via email)