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EC number: 203-051-9
CAS number: 102-76-1
Justification for grouping of substances and read-across
There are no data available on the genetic toxicity (mutagenicity
in mammalian cells in-vitro) of Triacetin (CAS 102-76-1). In order to
fulfil the standard information requirements set out in Annex VIII,
8.4.3, in accordance with Annex XI, 1.5, of Regulation (EC) No
1907/2006, read-across from a structurally related substance is
In accordance with Article 13 (1) of Regulation (EC) No 1907/2006,
"information on intrinsic properties of substances may be generated by
means other than tests, provided that the conditions set out in Annex XI
are met.” In particular for human toxicity, information shall be
generated whenever possible by means other than vertebrate animal tests,
which includes the use of information from structurally related
substances (grouping or read-across).
Having regard to the general rules for grouping of substances and
read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC)
No 1907/2006 whereby substances may be predicted as similar provided
that their physicochemical and toxicological properties are likely to be
similar or follow a regular pattern as a result of structural
Overview of Genetic toxicity
Reaction mixture of glycerol-1,3-di(acetate), glycerol acetate and triacetin
134.13 - 218.20 g/mol
Genetic toxicity (mutagenicity) in bacteria in-vitro
Experimental result:not mutagenic
Genetic toxicity (cytogenicity) in mammalian cells in-vitro
Experimental result:not clastogenic
Genetic toxicity (mutagenicity) in mammalian cells in-vitro
RA EC 905-964-4
(a) The target substance is indicated in bold font.
(b) Reference (read-across) substance is indicated in normal font.
Lack of data for a given endpoint is indicated by “--“.
The above mentioned substances are considered to be similar on the
basis of the structural similarity resulting in similar properties
and/or activities. The available endpoint information is used to predict
the same endpoints for Triacetin (CAS 102-76-1). A detailed analogue
approach justification is provided in the technical dossier (see IUCLID
In vitro gene mutation in bacteria
Two reliable studies are available investigating the mutagenic
potential of Triacetin (CAS 102-76-12) in bacteria.
A bacterial reverse mutation assay (Ames test) with the substance
was performed similarly to OECD guideline 471 and under GLP conditions
(Mulky, 1988). Salmonella typhimurium strains TA1535, TA1537, TA98 and
TA100 were treated with Triacetin diluted in DMSO using the plate
incorporation method with one hour pre-incubation. Five concentrations
in triplicate, both with and without the addition of a rat liver
homogenate metabolising system (S9) were used. The concentration range
was determined in a preliminary toxicity assay and was 50, 150, 500,
1500 and 5000 µg/plate for both of two consecutive experiments. The
included positive and negative controls in the experiments showed the
expected results and were therefore considered as valid. No cytotoxicity
was observed as the test material caused no reduction of number in
revertant colonies at any concentration. No significant increases in the
frequency of revertant colonies were recorded for any of the bacterial
strains, at any test material concentration, either with or without
Furthermore, a bacterial reverse gene mutation assay (Ames test)
with the substance was conducted using the pre-incubation method
similarly to OECD guideline 471/472 and under GLP conditions (MHLW,
1998). Salmonella typhimurium strains TA100, TA98, TA1535 and TA1537 and
E. coli WP2 uvrA strain were treated with 313, 625, 1250, 2500, 5000
µg/plate Triacetin in water with and without metabolic activation. Two
independent experiments were carried out in triplicate. The included
positive and negative controls in the experiments showed the expected
results and were therefore considered as valid. No cytotoxicity was
observed up to the limit concentration. Triacetin was not mutagenic in
Salmonella typhimurium TA100, TA1535, TA98, TA1537 and Escherichia coli
WP2 uvrA at concentrations up to 5000 ug /plate, with or without an
exogenous metabolic activation system.
A further Ames test with the substance performed similar to OECD
guideline 471 is available (Wallat, 1982), in which Salmonella
typhimurium strains TA 1535, TA 1537, TA 1538, TA 98 and TA 100 were
treated with Triacetin concentrations of 0, 4, 20, 100, 500 and 2500
µg/plate diluted in Tween 80 with and without rat liver S9 mix using the
plate incorporation method. No mutagenicity was reported at any
concentration in any of the used bacteria strains. However, since only a
short abstract of the study was available, it was not further taken into
account for hazard assessment of the substance.
In conclusion, the available data on genetic toxicity in the
selected strains of bacteria demonstrate that the substance is not
considered to be mutagenic in vitro.
In vitro cytogenicity in mammalian cells
An in vitro mammalian chromosome aberration test was performed
with Triacetin (CAS 102-76-1) in Chinese hamster lung (CHL/IU) cells
similarly to OECD Guideline 473 and under GLP conditions (MHLW, 1998).
The occurrence of chromosome aberrations was investigated in the
presence and absence of metabolic activation (S9-mix from rats treated
with phenobarbital and 5,6-benzoflavone). Test substance concentrations
of 0.55, 1.1 and 2.2 mg/mL were used. Cells were treated continuously
for 24 or 48 h without metabolic activation. For short term treatment,
cells were treated for 6 h with and without S9 mix and cultivated with
fresh media for 18 h. Positive controls significantly increased the rate
of chromosome aberrations indicating the sensitivity of the assay. In
the absence of metabolic activation, no chromosomal aberrations were
observed at any test substance concentration up to 48 h of continuous
exposure. Structural chromosomal aberrations (including gaps) were found
following short-term treatment with an exogenous metabolic activation
system at the highest dose of 2.2 mg/L in the second experiment.
However, at the highest test substance concentration the culture
conditions were considered to be not physiological due to a decrease of
the pH value which was visible in a change in medium colour.
Concomitantly, an increase in cytotoxicity was found at this test
concentration. These confounding factors do not allow an interpretation
of the observed chromosomal damages as test-substance specific. Cifone
et al. (1987) showed that the mutant frequency in L5178Y cells increased
sharply for pH values below pH 6.8 and the colonies were found to be of
the small-colony phenotype, indicating possible clastogenic activity.
Similar pH effects are expected for other mammalian cell culture
systems. In addition, in the current study, polyploidy was not induced
under any conditions. Without metabolic activation no relevant cytotoxic
effects of the test substance were observed.
A further study in Chinese hamster lung (CHL/IU) cells studying
the clastogenic potential of Triacetin is available (Kusakabe, 2002),
which, however, was not taken into account for hazard assessment due to
insufficient documentation of experimental conditions and results.
In summary, the substance was not considered to induce
clastogenicity in Chinese hamster lung (CHL/IU) cells in the presence
and absence of metabolic activation under the conditions of this assay.
In vitro gene mutation in mammalian cells
No studies are available investigating the in vitro mutagenicity
in mammalian cells of Triacetin (CAS 102-76-1). In order to fulfil the
standard information requirements set out in Annex VIII, 8.4.3, in
accordance with Regulation (EC) No 1907/2006 Annex XI, 1.5 read-across
from the structurally related substance Reaction mixture of
glycerol-1,3-di(acetate), glycerol acetate and triacetin (EC 905-964-4)
Two in vitro Mammalian Cell Gene Mutation Assays according to OECD
Guideline 476 and GLP are available for Reaction mixture of
glycerol-1,3-di(acetate), glycerol acetate and triacetin (EC 905-964-4)
in mouse lymphoma L5178Y cells (Adams,1996 a,b). In both assay, cells
were treated for 3 h with 300, 625, 1250, 2500, 3750 and 5000 µg/mL with
and without metabolic activation (Phenobarbital/β-naphtoflavone-induced
rat liver S9-mix). The vehicle and positive controls in both studies
showed the expected results and were in the range of historical control
data. As no cytotoxicity was observed, the highest concentrations
ranging from 1250 to 5000 µg/mL were evaluated for mutagenic effects in
the absence and presence of S9-mix. A decrease in the pH value was
observed from the physiological pH value of 7.4 in controls to a pH
value of 6 at the limit concentration of 5000 µg/mL. No significant
increase in the mutation frequency at the TK locus was observed after
treatment with Reaction mixture of glycerol-1,3 -di(acetate), glycerol
acetate and triacetin, neither in the absence nor in the presence of
metabolic activation. Based on these results, it was concluded that
Reaction mixture of glycerol-1,3 -di(acetate), glycerol acetate and
triacetin is not mutagenic in the mouse lymphoma L5178Y test system
under the experimental conditions of both studies.
Conclusion for genetic toxicity in vitro
In summary, several bacterial reverse mutation assays are
available for Triacetin (CAS 102 -76 -1), which consistently showed
negative results. Furthermore, the in vitro mammalian chromosome
aberration test with Triacetin was evaluated to be negative. However, at
the highest test substance concentration the culture conditions were not
considered to be physiological due to a decrease of the pH value which
was visible in a change in medium colour. Concomitantly, an increase in
chromosomal aberrations and cytotoxicity was found at this test
concentration. In addition, two mouse lymphoma assays conducted with the
structurally related substance Reaction mixture of glycerol-1,3
-di(acetate), glycerol acetate and triacetin (EC 905-964-4) were found
to be negative. Again, the pH value of the treatment culture medium was
found to be reduced from pH 7.5 to pH 6.0 at the highest dose of 5000
Ambiguous results in vitro observed at the highest test
concentrations were evaluated as negative results as the effects were
observed at nonphysiologic pH values. Therefore, the available data do
not provide any indications for a potential genetic toxicity, and thus
all available in vitro genotoxicity studies with the substance and the
structurally related analogue Reaction mixture of glycerol-1,3
-di(acetate), glycerol acetate and triacetin (EC 905-964-4) were judged
to be negative.
Cifone, M.A. et al. (1987). Effect of pH shifts on the mutant frequency
at the thymidine kinase locus in mouse lymphoma L5178Y TK+/- cells.
Mutat Res. 189(1):39-46.
The available data on in vitro genetic toxicity of the substance do not
meet the criteria for classification according to Regulation (EC)
1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not
sufficient for classification.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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