211(b) Toxicology Research Group Gasoline TBA VC:
In Vivo Micronucleus Assay

Reviewer Checklist

1 Comments Action/Response Page

EPA

No comments Agreed.

Peer Reviewer

– Goldsworthy This study was properly conducted and scientifically sound. Positive and negative controls performed as expected and within historical range. G

- TBA did not

caus e any significant increases in the incidence of micronucleated mature erythrocytes and did not cause any decreases in the proportion of immature erythrocytes. No evidence of bone marrow toxicity was observed. I concur with the report conclusions. Agre ed.

Peer Reviewer

– Schlesinger The data presented support the conclusion. Agreed. p.ll. Replace "?" in first paragraph with appropriate

dates. The term "negative control"is used interchangeably with "air control." The investigators should use just one term forthis group. Dates for inclusion entered as provided overleaf (7/26 and 8/21/01). Terminology unchanged in line with previous reports.

OK p.1096

p.13. The material presented under the "Deviations

from Protocol" banner are not

deviations f

rom protocol, unless they really do represent changes from the originally submitted study design. Deviations entered as they are not present within the final protocol. Validity statement

entered.

OK p. 1098

211(b) Research Group Reviewer

Please a dd a table of male and female data separately

as was done for the second draft of the Gasoline study. This was not a pre

- requisite for previous API studies.

OK Table 1, p. 19: Is the % ie/ie+me calculated from the ratio of total values within each gro up or as a mean of the summed % for individual animals? The method makes a slight difference in the 20000mg/m 3 value since the ratio calculated from

total values is 45.6 rounded to 46 as stated in the table or the average of summed % from individual

anima ls is 45.4, rounded to 45. Please check (Also cited by QA). Data unchanged as 46, once

rounded from 45.55.

Calculated from total values using more accurate values.

OK

Conclusions: Suggest the addition of “of either sex” to the conclusion that no sig nificant increases ...were

observed in rats of either sex treated with Gasoline TBA vapor condensate. Entered, as requested.

OK p. 1100211(b) Toxicology Research Group Gasoline TBA VC:
In Vivo Micronucleus Assay

Reviewer Checklist

2 Comments Action/Response Page

211(b) Research Group QA/QC Reviewer

1. Satellite Procedure Report

– Rat Micronucleus Test. The ERC Quality

Assurance Statement for this report does not indicate a date on which the report was sent to the Study Director and Test Facility Management. Per GLPs, QA inspection and audit reports are to be given to the Study Director and Management. Dates of this reporting n eed to be included. Not entered, as per previous studies. This does not require reporting, only to be performed

, and confirmation that Management and the required personnel are informed. Ok

2. Satellite Procedure Report

– Rat Micronucleus Test. Page 11: Dates need to be filled in for the first sentence. (7/26 and 8/21/01). Dates entered. Ok

3. Satellite Procedure Report

– Rat Micronucleus Test. Page 10: The last sentence indicates the experimental start and completion dates for the slide evaluation phas e of the test. Since the GLPs have specific definitions for “experimental start date” and it does not mean slide evaluation, maybe another term

would be better. Report clearly states the dates

for actual timelines for the in

life phases and the slide

an alysis phase. No change

necessary. OK

4. Satellite Procedure Report

– Rat Micronucleus Test. Page 13: The deviations to protocol are listed but give no potential affect on the study. This should

be indicated. Validity statement entered for clarity of s tudy conduct. Ok

5. Satellite Procedure Report

– Rat Micronucleus Test. Page 19, Table 1, 20,000 mg/m3 Proportion of ie, please verify this mean to be 46. Means may be calculated with more significant figures that are present in this report. Left as 46, thus using more significant figures in

calculation. Ok