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 COMMENTS BY ORD

Summation of EPA MEMORANDUM (Hauchman to Oge, April 27, 2010)

It is the ORD’s position that 10,000 mg/m3should 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 of 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 results 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 studies 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, Summary section, page 8: The report concludes 

that “the 10000 mg/m3exposure 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/m3exposure level...was considered a no observable 

adverse effect level (NOAEL)”.

RG Response to EPA April 27, 2010 Comment 1:

Clarifying 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-chronic 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 paragraph

Therefore, the 10000 mg/m3exposure 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:

Clarifying language was added to the Conclusion section of the report.

Revised last sentence

Therefore, the 10000 mg/m3exposure level (excluding male rat nephropathy) was 

considered a no observable adverse effect level (NOAEL) for the routine sub-chronic and 

neurotoxicity parameters discussed here.