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EC number: 249-044-4
CAS number: 28472-97-1
Justification for grouping of substances and read-across
There are only limited data available on the genetic toxicity of
diisodecyl azelate (CAS 28472-97-1). In order to fulfil the standard
information requirements set out in Annex VII and VIII, 8.4, in
accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006,
read-across from structurally related substances was conducted.
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, toxicological and ecotoxicological
properties are likely to be similar or follow a regular pattern as a
result of structural similarity.
Overview of genetic toxicity
Molecular weight (range)
Genetic toxicity (mutagenicity) in vitro, bacteria
Genetic toxicity (cytogenicity) in vitro, mammalian cells
Genetic toxicity (mutagenicity) in vitro, mammalian cells
RA: CAS 103-24-2
Experimental result:not mutagenic
Experimental result:not clastogenic
(a) The substance subject to registration is indicated in bold font.
(b) Reference (read-across) substances are 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 similar properties and/or activities. The available
endpoint information is used to predict the same endpoints for
diisodecyl azelate (CAS 28472-97-1). A detailed analogue approach
justification is provided in the technical dossier (see IUCLID Section
Gene mutation in bacteria in vitro
Diester of azelaic acid
The potential mutagenicity of bis(2-ethylhexyl) azelate (CAS 103-24-2)
was tested in a bacterial gene mutation assay (Ames test) according to
OECD 471 and in compliance with GLP (Miwa, 2004). Based on the results
of a preliminary cytotoxicity experiment, the Salmonella typhimurium
strains TA 98, TA 100, TA 1535 and TA 1537 and Escherichia coli WP2 uvrA
were treated with the test substance at concentrations of 312.5, 625,
1250, 2500 and 5000 µg/plate using the plate incorporation assay. The
test was performed in two independent experiments, both with and without
metabolic activation system (S9-mix). No cytotoxicity was observed in
the two experiments up to the limit concentration of 5000 µg/plate.
Colourless oil drop-like and oil membrane-like precipitations were
observed on the surface of agar at all test concentrations. The mean
number of revertant colonies was not increased at any test concentration
compared to control. The positive controls included showed the expected
Under the conditions of this experiment, bis(2-ethylhexyl) azelate did
not induce mutations in the bacterial gene mutation assay in the
selected strains of S. typhimurium (TA 98, TA 100, TA 1535 and TA 1537)
and in E. coli WP2 uvrA in the presence and absence of metabolic
Cytogenicity in vitro
The clastogenic potential of bis(2-ethylhexyl) azelate (CAS 103-24-2)
was assessed in an in vitro mammalian chromosome aberration test in
Chinese hamster lung (CHL/IU) cells according to OECD guideline 473 and
under GLP conditions (Miwa, 2004). In a preliminary cytotoxicity test,
50% growth inhibition was observed after 6 h short-term treatment with
the test substance at concentrations of 1859.0 µg/mL with S9 mix and at
1555.5 µg/mL without S9 mix. After continuous treatment for 24 h, cell
growth was inhibited by 50% at 534.2 µg/mL without S9 mix. Based on
these results, concentrations ranging from 150 to 2400 µg/mL (with and
without S9 mix) and 37.5 to 600 µg/mL (without S9 mix) were selected for
chromosome analysis after 6 and 24 h treatment in the main study,
respectively. No increase in the number of cells with chromosomal
aberrations was observed compared to controls in any of the experiments
performed. The test substance was cytotoxic at ≥ 600
µg/mL after 6 h short-term treatment and at ≥ 300 µg/mL after 24 h
continuous treatment. Visible precipitation of the test substance was
observed at concentrations ≥ 1200 µg/mL, but did not interfere with
chromosomal analysis. The positive controls included during short-term
and continuous exposure showed the expected results and thus verified
the sensitivity of the assay.
Under the conditions of this experiment, bis(2-ethylhexyl) azelate was
considered not to be clastogenic in Chinese hamster lung (CHL/IU) cells
in the presence or absence of metabolic activation.
Gene mutation in mammalian cells in vitro
An in vitro mammalian cell gene mutation assay was performed with
diisodecyl azelate (CAS No. 28472-97-1) according to OECD guideline 476
(Verspeek, 2010). Mouse lymphoma L5178Y were treated with the test
substance diluted in ethanol at concentrations of 0.03, 0.1, 0.3, 1, 3,
10, 33 and 100 µg/mL in cell culture medium with and without S9 mix. Due
to solubility of the test substance no higher concentrations had been
tested. After treatment the cells were incubated in selective medium
with 5 µg/mL trifluorothymidine (TFT) to determine the mutation
frequency. No cytotoxicity was observed in range finding tests or the
main mutation experiment. The mutation frequency of the treated cultures
was in range of historical control data and did not increase at the
various concentrations compared to the negative control. Therefore
diisodecyl azelate (CAS No. 28472-97-1) did not induce gene mutations in
the mouse lymphoma cell line L5178Y at the given test conditions.
Conclusions for genetic toxicity
The available data on diisodecyl azelate (CAS 28472-97-1) and the
structurally related substance bis(2-ethylhexyl) azelate (CAS 103-24-2)
showed that the results of all in vitro genetic toxicity studies
performed in bacteria and mammalian cells with and without metabolic
activation were negative.
Based on substance-specific data and read-across from the structurally
similar substance, the available data on genetic toxicity do not meet
the classification criteria according to Regulation (EC) 1272/2008 or
Directive 67/548/EEC, and are therefore conclusive but not sufficient
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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