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EC number: 947-899-4
CAS number: -
Ames test: negative with and without metabolic activation in S.
typhimurium TA 1535, TA 1537, TA 100, TA 98, E. coli WP2 uvrA
Chromosome aberration: negative in Chinese hamster ovary cells
with and without metabolic activation.
Read-across from structural source substance fatty acids C8-10,
mixed esters with dipentaerythritol, isooctanoic acid, pentaerythritol
and tripentaerythritol (CAS 189200-42-8)
Gene mutation in mammalian cells: negative in mouse lymphoma
L5178Y cells with and without metabolic activation
Read-across from structural source substance 2,2-bis[[(1-oxoisopentyl)oxy]methyl]propane-1,3-diyl
divalerate (PE C5 tetraester) (CAS 15834-04-5)
Table 2: Summar of Results of Experiment I
Table 3: Summary of results of Experiment II
Justification for read-across
Data on mutagenicity in bacterial cells with fatty acids C18-C22
(even numbered), tetraesters with pentaerythritol are
available, whereas in vitro studies in mammalian cells of fatty acids
C18-C22 (even numbered), tetraesters with pentaerythritol are missing.
The assessment was therefore based on studies conducted with
analogue substances as part of a read-across approach, which is in
accordance with Regulation (EC) No. 1907/2006, Annex XI, 1.5. For each
specific endpoint the source substance(s) structurally closest to the
target substance is/are chosen for read-across, with due regard to the
requirements of adequacy and reliability of the available data.
Structural similarities and similarities in properties and/or activities
of the source and target substance are the basis of read-across. A
detailed justification for the analogue read-across approach is provided
in the technical dossier (see IUCLID Section 13).
Genetic toxicity (mutagenicity) in bacteria in vitro
The mutagenic potential of fatty acids C18-C22 (even numbered),
tetraesters with pentaerythritol was tested in a reverse mutation assay
according to OECD 471 under GLP conditions (Safepharm Laboratories,
2000). Salmonella typhimurium strains TA1535, TA1537, TA98, TA100 and E.
coli WP2 uvrA were used. Tester strains were incubated with test
material at concentrations of 0, 50, 150, 500, 1500, and 5000 µg/plate
with and without the addition of a metabolic activation system
(phenobarbitone and β-naphthoflavone induced rat liver S9 mix).
Precipitation occurred at doses ≥ 500 µg/plate. Vehicle and appropriate
positive controls were included into the study design. Positive control
materials induced statistically significant increases in the frequency
of revertant colonies indicating the satisfactory performance of the
test and the activity of the metabolizing system. No increase in the
frequency of revertant colonies compared to concurrent negative controls
was observed in all strains treated with the test material, neither in
the presence nor in the absence of metabolic activation. Thus, Fatty
acids C18-C22 (even numbered), tetraesters with Pentaerythritol (CAS
61682-73-3) did not induce point mutations by base-pair changes or
frame-shifts in the genome of the strains tested, and thus, was not
mutagenic in bacteria.
Genetic toxicity (cytogenicity) in mammalian cells in vitro
A study investigating the in vitro mammalian chromosome aberration
was performed with fatty acids C8-10, mixed esters with
dipentaerythritol, isooctanoic acid, pentaerythritol and
tripentaerythritol (CAS 189200-42-8) in Chinese hamster ovary cells (CHO
cells) comparable to OECD 473 and under GLP conditions (ExxonMobil,
1995). Duplicate cultures of CHO cells were evaluated for chromosome
aberrations in the presence and absence of metabolic activation (rat
liver S9-mix). In the first experiment, cells were exposed to the test
substance for 3 h and for 16 h followed by 16 h expression time with and
without metabolic activation, respectively. The test substance was
dissolved in acetone and used at concentrations of 40, 80 and 160 µg/mL.
In the second experiment cells were again exposed for 3 h and for 16 h
followed by 16 h expression time with and without metabolic activation,
respectively. Additionally, cells were exposed for 3 and 16 h followed
by 40 h expression time with and without metabolic activation,
respectively. The same substance concentrations as in first experiment
were used. The test substance did not induce cytotoxicity but a
precipitate was visible in the second experiment at 160 µg/mL after 16 h
incubation without metabolic activation. Vehicle (solvent) controls
induced aberration frequencies within the range expected for normal
human lymphocytes. N-Methyl-N-Nitro-N-Nitrosoguanidine and
7,12-Dimethylbenz[a]anthracene were used as positive control materials
inducing statistically significant increases in aberration frequencies
indicating the satisfactory performance of the test and of the activity
of the metabolizing system. Evaluation of 100 well-spread metaphase
cells from each culture for structural chromosomal aberrations revealed
no increase in the frequency of chromosome aberrations and polyploid
cells at any dose level tested in comparison to the negative controls.
The test material was therefore considered to be non-clastogenic to CHO
cells in vitro.
Genetic toxicity (mutagenicity) in mammalian cells in vitro
An in vitro mammalian cell gene mutation assay according to OECD
476 and under GLP conditions was performed with 2,2-bis[[(1-oxoisopentyl)oxy]methyl]propane-1,3-diyl
divalerate (PE C5 tetraester) (CAS 15834-04-5) in mouse lymphoma
L5178Y cells (Notox, 2010). In the first experiment, the cells were
treated for 3 h with 0.03, 0.1, 0.3, 1, 3, 10, 33, 100 µg/mL in the
presence or absence of S9-mix (8% (v/v)). In the second experiment,
concentrations of 0.03, 0.1, 0.3, 1, 3, 10, 33, 100 µg/mL were applied
with metabolic activation (12%, v/v) for 3 h and 0.1, 1, 3, 10, 33, 100,
200, 250 µg/mL without metabolic activation for 24 h. The test substance
was tested up to precipitating concentration (100 µg/mL and above).
Cyclophosphamide and methylmethanesulfonate were used as positive
controls with and without S9 mix, respectively. No toxicity was observed
and all dose levels were evaluated in the absence and presence of
S9-mix. Positive and negative controls were valid and in range of
historical control data. No significant increase in the mutation
frequency at the TK locus was observed after treatment with the test
substance either in the absence or in the presence of S9-mix. It was
concluded that the test substance is not mutagenic in the mouse lymphoma
L5178Y test system under the experimental conditions described.
Overall conclusion for genetic toxicity
There are no available studies on the genetic toxicity of the
target substance fatty acids C18-C22 (even numbered), tetraesters with
pentaerythritol. Therefore analogue read-across from source substances
was applied for in vitro studies on cytogenicity and in vitro studies on
gene mutation in mammalian cells. The results of the available studies
were consistently negative. Based on the available data and following
the analogue approach, no hazard regarding genotoxicity is identified
for the target substance fatty acids C18-C22 (even numbered),
tetraesters with pentaerythritol.
According to Article 13 of Regulation (EC) No. 1907/2006 "General
Requirements for Generation of Information on Intrinsic Properties of
substances", information on intrinsic properties of substances may be
generated by means other than tests e.g. from information from
structurally related substances (grouping or read-across), provided that
conditions set out in Annex XI are met. Annex XI, "General rules for
adaptation of this standard testing regime set out in Annexes VII to X”
states that “substances whose physicochemical, toxicological and
ecotoxicological properties are likely to be similar or follow a regular
pattern as a result of structural similarity may be considered as a
group, or ‘category’ of substances. This avoids the need to test every
substance for every endpoint". Since the analogue concept is applied to
fatty acids C18-C22 (even numbered), tetraesters with pentaerythritol,
data will be generated from data for reference source substance(s) to
avoid unnecessary animal testing. Additionally, once the analogue
read-across concept is applied, substances will be classified and
labelled on this basis.
Therefore, based on the analogue read-across approach, the
available data on genetic toxicity do not meet the classification
criteria according to Regulation (EC) No 1272/2008 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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