Final Report: Whole Body Inhalation Developmental Toxicity Study in Rats

With Gasoline with ETBE Vapor Condensate (MRD-00-716: 171634)

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.  

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.

EPA July 31, 2008 Comment #2:  

Page K-4, Table 1:  Item 39, the combined analysis of “supernumerary
ribs” lists items 13, 14, and 17.  This appears to be incorrect as
item 14 describes fused ribs and item 17 describes misshapen ribs.  Is
this a typographical error?  Was the actual analysis a combination of
items 12, 13, and 16 (cervical rib, well-formed lumbar rib, and
rudimentary ribs)?

RG Response to EPA July 31, 2008 Comment:

This was, in fact, a typographical error.  The report was corrected on
the noted page.

EPA July 31, 2008 Comment #3:  

Although the combined analysis of supernumerary ribs as described above
(items 12, 13, and 16: cervical, well-formed lumbar, rudimentary lumbar)
is warranted, an additional analysis combining only items 13 and 16
(supernumerary lumbar ribs) is also warranted.  The two manifestations
of lumbar ribs (rather common in rats) are very closely related;
cervical ribs (rare in rats) are less closely related.  A combined
analysis of supernumerary lumbar ribs is unlikely to alter
interpretation of the data; however, such an analysis reflects a highly
appropriate grouping of observations.

RG Response to EPA July 31, 2008 Comment:

Only one cervical rib was observed in this study, thus we concur with
EPA’s assessment that an analysis of supernumerary lumbar-only ribs is
unlikely to alter interpretation of the data.   Although a new
statistical analysis as suggested above was not performed for this
report in the interest of report completion, we agree that this is
another appropriate observational grouping and may conduct the analysis
for a later stage of data usage.

EPA July 31, 2008 Comment #4:  

Page 4-3, paragraph 2.  The final sentence listing single incidences of
visceral observations lacks a verb.

RG Response to EPA July 31, 2008 Comment:

Verb added.

