Final Report: Whole-Body Inhalation Developmental Toxicity Study in Rats

With Gasoline with Ethanol Vapor Condensate (MRD-00-714)

211(b) Research Group (RG) Response to EPA Second Draft Report

Comments dated July 31, 2008

EPA July 31, 2008 Comment #1:

Although the inferential statistics now used to analyze the fetal
examination data are valid, the report tables still inappropriately show
fetal incidences.  As currently presented, these data are still
difficult to properly evaluate.  The fetal incidences in Appendices H
and K should be modified to show means + SD values for the percentage
affected per litter.  

On a related note, the text of the report (page 4-3, first paragraph)
continues to inappropriately refer to fetal-based inferential statistics
rather than the revised statistical analyses.  The text should be
modified to refer to the revised analyses.

RG Response to EPA July 31, 2008 Comment:

The RG concurs that the present format of data presentation is
scientifically valid, and considers this to be a valuable comment. 
However, it would be a lengthy procedure for the laboratory to revise
report tables as EPA has suggested, as such revisions would require
programming changes.  Programming changes require computer validation
and subsequently also require additional Quality Assurance review. 
These tasks would need to be completed before the report could be
resubmitted for QA review as required under GLP. For those reasons, the
work group has not requested that the lab revise the report as described
in this comment.  However, the results can be presented in the suggested
format at later stages of data utilization, such as publication/risk
assessment, where the change would not delay completion of the 211(b)
testing requirement.

The work group requested the change noted by EPA for page 4-3, first
paragraph.

EPA July 31, 2008 Comment #2:  

Page 4-3, paragraph 3, line 2.  The passage listing visceral
observations appears to be missing a comma between “raised
subcutaneous area on the head” and “umbilical artery arises from
left side of urinary bladder.”

RG Response to EPA July 31, 2008 Comment #2:

The API work group has requested this change.

EPA July 31, 2008 Comment 3:  

Page 4-3, paragraph 3, last sentence.  The statement that
“observations that were not variations or malformations were
considered to be artifacts” appears to describe converse logic.  That
is, it sounds as if the determination that an observation was an
artifact was based on its failure to be classified as a malformation or
variation.  A suggested revision:  “All other visceral observations
were considered to be artifacts…”

RG Response to EPA July 31, 2008 Comment:

The API work group has requested this change.

