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EC number: 200-889-7
CAS number: 75-65-0
In Vitro data
The in vitro genotoxicity of tertiary butyl alcohol has been
investigated in four Ames tests, a mammalian cell gene mutation assay
(mouse lymphoma assay), a chromosome aberration study, a sister
chromatid exchange study and a comet assay. The majority of studies were
non-guideline, but were conducted using methods considered equivalent to
The majority of the Ames tests were negative. A positive result was
reported in strain TA 102 in the presence of metabolic activation in the
published Williams-Hill et al (1999) study. In this study, the number of
revertants increased in a dose dependent manner up to approximately 2.75
mg/plate. At this dose level, the number of revertants had almost
doubled. At higher doses the number of revertants decreased dose
dependently. Although the authors concluded tertiary butyl alcohol was
mutagenic, no criteria as to what constituted a positive result were
included in the paper and no information on toxicity was provided, which
is imperative given the very high dose level employed. In follow up,
the mutagenic potential of tertiary butyl alcohol in strain TA102 was
investigated in a study conducted at two independent laboratories
(McGregor et al (2005)). The first laboratory used a pre-incubation
method to restrict evaporation, whereas the second used the plate
incorporation procedure (as was used in the Williams-Hill study). Both
studies were conducted in accordance with OECD 471 in GLP-accredited
laboratories. No significant increase in the numbers of mutations per
plate was observed in either laboratory. Given the increase reported in
the Williams-Hill study was less than 2-fold and the results of the
follow-up studies showed no significant increase in mutations, tertiary
butyl alcohol is not considered mutagenic in bacteria.
The mutagenic potential of tertiary butyl alcohol was investigated in
mammalian cells in a mouse lymphoma assay (McGregor et al (1988)). In
this study, a small dose-related increase was observed in one study
conducted in the absence of S9; however, the increase was only 1.6-fold
at the top dose (5000 ug/plate) and, as such, is not considered to
constitute a positive result. The results of both trials conducted in
the presence of metabolic activation were clearly negative. Overall,
tertiary butyl alcohol does not appear to be mutagenic in mammalian
The results of a chromosome aberration study (non-guideline) and a
sister chromatid exchange study have been included in NTP summary of
tertiary butyl alcohol. A weak positive result was observed in one test
of the SCE assay; however, as this result was not reproducible, the
overall result of the study is considered negative (in accordance with
the criteria outlined in OECD guideline 476). There were a number of
deficiencies in the in vitro chromosome aberration study; however, a
statistically significant increase in the number of cells with
aberrations was observed at the top dose in one trial of the chromosome
aberration study (6 % of cells had aberrations compared to none in the
controls) in the presence of S9. The increase is small compared to the
positive control, was not dose-related, and may have been exacerbated by
the absence of aberrations in control cells. On this basis the
biological significance of this increase is doubtful. This conclusion is
supported by the negative response observed in the in vivo micronucleus
study (see discussion below). Severe toxicity in the repeat trial meant
that only 13 metaphases could be scored at the top dose.
A dose-related positive response was reported in an in vitro comet assay
following incubation of tertiary butyl alcohol with HL-60 cells for one
hour (Tang, 1997). No OECD guideline is available for the in vitro comet
assay and at the time the methodology is unlikely to have been well
developed. There are a number of issues with the reporting and
interpretation of the data that reduce confidence in the result.
Firstly, the results are presented as % DNA damage; however, it is not
clear what this relates to. No information on the % DNA present in the
tail or tail length or the number of cells undergoing apoptosis has been
reported (a minimum requirement for acceptance of an in vivo comet assay
by EFSA: http://www.efsa.europa.eu/en/efsajournal/doc/ 2977.pdf).
Furthermore, the results of three separate experiments have been grouped
together and no information on the variability of the data is available
to determine whether this approach was justified. Finally, there are
concerns with the assessment of cytotoxicity (estimated by measuring %
LDH released). The authors concluded that tertiary butyl alcohol was not
cytotoxic based on a similar % of LDH released in treated cells (3.62 –
4.49 %) and controls (3.29 %). However, similar levels of LDH release
were also reported for other substances in the same paper, but in these
cases (due to a comparison to the internal control) the extent (2.79 -
4.15 %) was considered indicative of cytotoxicity, raising doubts over
the use of LDH as a measure of cytotoxicity. Overall, the results of
this study are not considered reliable.
In Vivo Data
One study investigating the potential for tertiary butyl alcohol to
cause cytogenetic damage to peripheral blood cells of mice following 13
week exposure is available. No increase in micronucleus formation was
observed following oral administration of very high doses of tertiary
butyl alcohol. No change in the P/N ratio was observed; however,
detection of tertiary butyl alcohol in the blood (see section 5.1)
suggests the bone marrow will have been exposed. In addition, deaths in
the high dose group suggest the maximum tolerated dose was exceeded.
There are a number of studies available investigating the mutagenic
potential of tertiary butyl alcohol in vitro and in vivo. Although a
positive response was reported in the Ames test for strain TA102, this
result was not replicated in two tests conducted in two independent
GLP-accredited laboratories and, therefore, tertiary butyl alcohol is
not considered mutagenic in bacteria. The results of the other in vitro
studies did not provide any convincing evidence that tertiary butyl
alcohol was mutagenic. The results of an in vivo micronucleus study
indicate tertiary butyl alcohol is not clastogenic or aneugenic.
Overall, tertiary butyl alcohol is not considered genotoxic.
Short description of key information:
Several in vitro and in vivo tests are available and the total weight of evidence available indicates that tertiary butyl alcohol is not expected to induce heritable mutations in the germ cells of humans.
Endpoint Conclusion: No adverse effect observed (negative)
The mutagenic profile of tertiary butyl alcohol has been investigated in
vitro and in vivo. Although a positive response was reported in the Ames
test strain for TA102, the result was not replicated in tests conducted
in two independent GLP accredited laboratories. Tertiary butyl alcohol
is not considered mutagenic in bacteria. The results of the other in
vitro studies and the in vivo study did not provide any convincing
evidence that tertiary butyl alcohol is genotoxic. Overall, the
genotoxic potential of tertiary butyl alcohol has been adequately
investigated and tertiary butyl alcohol is not considered genotoxic. No
classification is warranted.
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