March 23 , 2011 Page 1

211(b) Research Group (RG) Response to EPA ’s Comments on the Second Draft Report dated April 27, 2010

Final Report: Gasoline ETBE Vapor Condensate: A 13

- Week Whole

- Body Inhalation Toxicity Study in Rats with Neurotoxicity Assessments and 4

- Week

In Vivo Genotoxicity and Immunotoxicity Assessments (HLS 00

- 6129 )

GENERAL COMMENT S BY ORD

Summation of EPA MEMO RANDUM (Hauchman to Oge, April 27, 2010 ) It is the ORD’s position that 10,000 mg/m 3 should be considered an adverse effect level based on immunotoxicity results and that this information should be included in the summary and conclusions section of the main body o f the report.

RG Response to EPA Memo dated April 27, 2010

: The RG appreciates the EPA comments on this issue. Several revisions have been made to this report to clarify the presentation and significance of various NOAEL and LOAEL

values.

This report covers several distinct toxicology endpoints required for the 211(b)

Alternative Tier 2 health effects testing program. The sub

- chronic and neurotoxicity results are described in the main body of the report while GFAP, genotoxicity, and immunotoxicity re sults are described in their respective Appendices

. A table listing the

NOAEL and LOAEL for each toxicology endpoint was included in the Summary section in

the main body of this report ( page 9)

. Language has been added in several parts of the
report to clarify the scope of the particular NOAEL or LOAEL being discussed.

Because of the distinct nature of the toxicity endpoints covered in this report, a single

NOAEL and /or LOAEL value for the entire set of stud ies will not be determined.

SPECIFIC COMMENTS BY ORD

April 27, 2010 Comment 1 and Comment 2 :

We believe that the overall conclusion as stated in Volume I of the report is incorrect and misleading. Specifically:

2 nd Draft Final Report, Volume I of IV, S ummary section, page 8: The report concludes that “the 10000 mg/m 3 exposure level...was considered a no observable adverse effect level (NOAEL)”.March 23 , 2011 Page 2

2 nd Draft Final Report, Volume I of IV, Conclusion section, page 57: The report repeats

the conclusion that “the 10000 mg/m 3 exposure level...was considered a no observable adverse effect level (NOAEL)”.

RG Response to EPA

April 27, 2010 Comment 1 :

C larifying language was added to the first and last paragraphs in the Summary section of the report as follows;

Revised first paragraph This study was designed to assess the potential inhalation toxicity of Gasoline ETBE Vapor Condensate when administered via whole

- body exposures to Sprague Dawley rats for 13 weeks followed by a 4 week recovery period. This summary covers only the

routine sub

- chroni c toxicology parameters as well as detailed evaluations of neurotoxicity parameters (with the exception of the glial fibrillary acidic protein (GFAP) evaluations)

. The GFAP, genotoxicity and immunotoxicity reports, which include endpoint specific NOAELs, are appended to this report.

Revised last paragra ph Therefore, the 10000 mg/m 3 exposure level (excluding male rat nephropathy) was considered a no observable adverse effect level (NOAEL) for the routine sub

- chronic and neurotoxicity parameters discussed here . The NOAEL for other satellite study endpoints

are included in the Table below.

RG Response to EPA

April 27, 2010 Comment 2 :

C larifying language was added to the Conclusion section of the report.

Revised last sentence Therefore, the 10000 mg/m 3 exposure level (excluding male rat nephropathy) was considered a no observable adverse effect level (NOAEL) for the routine sub

- chronic and neurotoxicity parameters discussed here

.