An equal opportunity employer 1220 L Street, Northwest Russell White Washington, DC 20005

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J uly 18 , 201 1

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 Secti on 211(b) Research Group (RG) is submitting this interim report on the progress and status between 0 1 J anuary 2011 and 01 J uly 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 proto c ol 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 Testing 1

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 20 10

. 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 notedJuly 18 , 201 1 Page 2 of 3

 Rat and mouse developmental toxicity studies

– The final report of the rat study wa s 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 amendm ent 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 2 0 10.

 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 accepte d 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 stud y

– 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 D e cember 2008.

Gasoline/DIPE Vapor Condensate:

 Subchronic study (with GFAP, genotoxicity, immunotoxi city , 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 t he second draft report was in progress.

Gasoline/TBA Vapor Condensate:

 Subchronic study (with GFAP, genotoxicity, immunotoxic ity, 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 stud y

- The final report was submitted to EPA 16 October 2009.July 18 , 201 1 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

T he 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 1 9 May 2010

. A compiled version of the final r eport was submitted to EPA on 10 June 2011 , completing the Section 211(B) Tier 2 e x p o s u r e s c r e e n i n g s t u d y requir e ments.

Sincerely,

Russell White, Ph.D. Health Sciences Manager

cc: Joe Sopata, EPA (via email)