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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

In vitro gene mutation:

Bacterial reverse mutation assay (Ames test / OECD 471): negative with and without metabolic activation (RA from CAS 147256-33-5)

In vitro chromosome aberration test in human lymphocytes (CA / OECD 473): negative with and without metabolic activation (RA from CAS 147256-33-5)

In vitro gene mutation assay in Chinese hamster cells (HPRT / OECD 476): negative with and without metabolic activation (RA from CAS 77-99-6)

In vitro gene mutation assay in mouse lymphoma cells (MLA / OECD 476): negative with and without metabolic activation (RA from CAS 61788-89-4)

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for grouping of substances and read-across

There are only limited data available on genetic toxicity of Fatty acids, C18-unsatd., dimers, reaction products with fatty acids, C14-18 and C16-18-unsatd. and propylidynemethanol (CAS 162353-70-0). 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

CAS

Chemical name

Molecular weight [g/mol]

Gene mutation in vitro (Ames)

Chromosome aberration in vitro

Gene mutation in vitro (MLA/HPRT)

 

 162353-70-0 (a)

Fatty acids, C18-unsatd., dimers, reaction products with fatty acids, C14-18 and C16-18-unsatd. and propylidynemethanol

 

 610.99 - 1209.97

 

 RA: CAS 147256-33-5

 

RA: CAS

147256-33-5

 

RA: CAS 77-99-6

RA: CAS 61788-89-4

 

147256-33-5 (b)

Fatty acids, C18-unsatd., dimers, mixed esters with oleic acid and trimethylol-propane

 

624.97 - 1762.80

 

Experimental result:

negative

 

Experimental result:

negative

 

--

 77-99-6 (b)

 Propylidynemethanol

 134.18

 --

 --

Experimental result:

negative

 61788-89-4 (b)

Fatty acids, C18-unsaturated, dimers

 564.93

 --

--

Experimental result:

negative

(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 either similar on the basis of the structural similar properties and/or activities or the possible hydrolysis products of Fatty acids, C18-unsatd., dimers, reaction products with fatty acids, C14-18 and C16-18-unsatd. and propylidynemethanol (CAS 162353-70-0).The available endpoint information is used to predict the same endpoints for Fatty acids, C18-unsatd., dimers, reaction products with fatty acids, C14-18 and C16-18-unsatd. and propylidynemethanol (CAS 162353-70-0). A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

Discussion

No data on genetic toxicity are available with Fatty acids, C18-unsatd., dimers, reaction products with fatty acids, C14-18 and C16-18-unsatd. and propylidynemethanol (CAS 162353-70-0). Therefore, read across from the structurally analogue substance Fatty acids, C18-unsatd., dimers, mixed esters with oleic acid and trimethylolpropane (CAS 147256-33-5) and the possible hydrolysis products Propylidynemethanol (CAS 77-99-6) and Fatty acids, C18-unsaturated, dimers (CAS 61788-89-4) was applied.

Genetic toxicity (mutagenicity) in bacteria in vitro

CAS 147256-33-5

A reliable bacterial gene mutation study (Ames test) performed according to OECD TG 471 and in compliance with GLP with Fatty acids, C18-unsatd., dimers, mixed esters with oleic acid and trimethylolpropane (CAS 147256-33-5) is available (Harlan CCR, 2012a). The strains Salmonella typhimurium TA 1535, TA 1537, TA 98, TA 100 and E.coli WP2 uvr A were tested according to the plate incorporation (experiment I) and pre-incubation (experiment II) procedure in the absence and presence of a metabolic activation system (phenobarbitone/β-naphthoflavone-induced rat liver S9-mix). Two independent experiments were conducted in three repetitions at concentrations from 3 to 5000 µg/plate. The test material did not induce cytotoxicity in any of the tested strains at any tested concentration.In the first experiment, precipitation was observed at concentrations ≥333 µg/plate or ≥1000 µg/plate with or without metabolic activation, respectively. In the second experiment precipitation was evident at ≥1000 µg/plate in the presence or absence of S9-mix.Appropriate solvent (acetone) and positive controls were included and gave the expected results. No significant increase in the number of revertants was observed in any of the tester strains with and without metabolic activation. Based on the results of the study the test material was considered to be not mutagenic to bacteria under the conditions of the test.

 

Genetic toxicity (cytogenicity) in mammalian cells in vitro

CAS 147256-33-5

Two studies addressing genetic toxicity in mammalian cells in vitro are available with Fatty acids, C18-unsatd., dimers, mixed esters with oleic acid and trimethylolpropane (CAS 147256-33-5).

An in vitro chromosome aberration test in human lymphocytes was performed with Fatty acids, C18-unsatd., dimers, mixed esters with oleic acid and trimethylolpropane (CAS 147256-33-5) according to OECD TG 473 and in compliance with GLP (Harlan CCR, 2012b). Human peripheral lymphocytes were cultured and treated with the test material or vehicle (acetone) in the absence or presence of a metabolic activation system (phenobarbitone/β-naphthoflavone-induced rat liver S9-mix) in duplicates at concentrations of 0.01, 0.02, 0.03, 0.06, 0.10, 0.17, 0.30, 0.53, 0.93, 1.63, 2.86 and 5.00 µL/mL for 4 or 22 hours (with and without S9-mix, experiment I and without S9-mix, experiment II) and 0.01, 0.02, 0.03, 1.68, 2.86 and 5.00 µL/mL for 4 hours (with S9-mix, experiment II). Fixation and staining of the cells were performed 22 hours after start of exposure with the test material. Cytotoxicity was assessed by determination of the mitotic index. Appropriate solvent and positive controls were included in the test and gave the expected results. The test substance did not cause a statistically significant, dose-related increase in chromosome aberrations under the tested conditions. Neither cytotoxicity nor precipitation of the test material was recorded at any concentration during the course of the study.

A supporting in vitro chromosome aberration test in Chinese hamster lung fibroblasts (V79) was performed with Fatty acids, C18-unsatd., dimers, mixed esters with oleic acid and trimethylolpropane (CAS 147256-33-5) according to OECD TG 473 and in compliance with GLP (LPT, 2009). Chinese hamster cells were cultured and treated with the test material or vehicle (DMSO) in the absence or presence of a metabolic activation system (Arochlor 1254-induced rat liver S9-mix) in duplicates at concentrations of 312.5, 625, 1250, 2500 and 5000 µg/mL for 4 (with and without S9-mix, experiment I) or 20 hours (without S9-mix, experiment II). Fixation and staining of the cells were performed 20 hours after start of exposure with the test material. Cytotoxicity was assessed by determination of the mitotic index. Appropriate solvent and positive controls were included in the test and gave the expected results. The test substance did not cause a statistically significant, dose-related increase in chromosome aberrations under the tested conditions. No cytotoxicity of the test material was recorded at any concentration during the course of the study.

Based on the above study results the test material is considered not to be clastogenic in these chromosome aberration tests in vitro.

 

Genetic toxicity (mutagenicity) in mammalian cells in vitro

CAS 77-99-6

An in vitro gene mutation test (hypoxanthine-guanine phosphoribosyl transferase (HPRT)) in Chinese hamster lung fibroblasts (V79) was performed with Propylidynemethanol (CAS 77-99-6) according to OECD TG 476 and in compliance with GLP (Harlan CCR, 2010). Chinese hamster cells were treated with the test material or vehicle (deionized water) in the absence or presence of a metabolic activation system (phenobarbitone/β-naphthoflavone-induced rat liver S9-mix) at concentrations from 43.8 to 1400 µg/mL for 4 (with and without S9-mix, experiment I and with S9-mix, experiment II) or 24 hours (without S9-mix, experiment II). Appropriate solvent and positive controls were included in the test and gave the expected result. No evidence of marked toxicity following exposure to the test item in either the absence or presence of metabolic activation was recorded in both experiments. The test substance did not cause a statistically significant, dose-related increase in mutant frequency under the tested conditions. Based on the results of the study the test material is considered not to be mutagenic in this HPRT test in vitro.

 

CAS 61788-89-4

An in vitro gene mutation test in mouse lymphoma L5178Y cells was performed with Fatty acids, C18-unsaturated, dimers (CAS 61788-89-4) according to OECD TG 476 and in compliance with GLP (Huntingdon Research Centre, 1993). Mouse lymphoma cells were treated with the test material or vehicle (DMSO) in the absence or presence of a metabolic activation system (Arochlor 1254-induced rat liver S9-mix) in duplicates at concentrations from 25 to 300 µg/mL for 3 hours (with and without S9-mix, experiment I + II). After exposure with the test material mouse lymphoma cells were cultured in microtiter plates containing trifluorothymidine selective medium for additional 12 days. Appropriate solvent and positive controls were included in the test and gave the expected result. Cytotoxicity following exposure to the test item was recorded in both the absence and presence of metabolic activation (at 300 and 150 µg/mL, respectively).The test substance did cause a statistically significant increase in mutant frequency at 250 µg/mL in one of the two experiments without metabolic activation. However, this increase was small and not considered to be biologically relevant (no dose-response relationship, within historical control data, less than 2 -fold increase compared to concurrent negative control). No statistically significant increase in mutant frequency was observed in the presence of metabolic activation in any experiment at any concentration. Based on the results of the study the test material is considered not to be mutagenic in this mouse lymphoma test in vitro.

Conclusion for genetic toxicity

Based on the above results from the structurally analogue substance Fatty acids, C18-unsatd., dimers, mixed esters with oleic acid and trimethylolpropane (CAS 147256-33-5) and the possible hydrolysis products Propylidynemethanol (CAS 77-99-6) and Fatty acids, C18-unsaturated, dimers (CAS 61788-89-4) no genetic toxicity is expected for Fatty acids, C18-unsatd., dimers, reaction products with fatty acids, C14-18 and C16-18-unsatd. and propylidynemethanol (CAS 162353-70-0).


Justification for classification or non-classification

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-unsatd., dimers, reaction products with fatty acids, C14-18 and C16-18-unsatd. and propylidynemethanol (CAS 162353-70-0), 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) 1272/2008, and are therefore conclusive but not sufficient for classification.

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