Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

Justification for grouping of substances and read-across

The category covers fatty acid polyesters of polyols (Trimethylolpropane (TMP) or Pentaerythritol (PE)) mixed with adipic acid. The category contains UVCB substances with fatty acid carbon chain lengths from C8-C18 (even-numbered, including linear saturated and unsaturated chains) building mono-, di-,tri- or higher esters with TMP or PE respectively in variable proportions.

The available data allows for an accurate hazard and risk assessment of the category and the category concept is applied for the assessment of environmental fate, environmental and human health hazards. Thus where applicable, environmental and human health effects are predicted from adequate and reliable read across data within the group applying the group concept in accordance with Annex XI, Item 1.5, of Regulation (EC) No 1907/2006.

A detailed justification for the grouping of chemicals and read-across is provided in the technical dossier

(see IUCLID Sections 7.1 and 13) and within Chapter 5.1 of the CSR.

Endpoint specific data matrix:

ID#

Identifier

Genetic Toxicity in vitro: Gene mutation in bacteria

Genetic Toxicity in vitro: cytogenicity in mammalian cells

Genetic Toxicity in vitro: gene mutation in mammalian cells

1

CAS 95912-89-3 (a)

Experimental result:
Negative

Experimental result:
Negative

Experimental result:
Negative

2

CAS 91001-61-5

RA: CAS 95912-89-3

RA: CAS 95912-89-3

RA: CAS 95912-89-3

3

EC 921-836-0

RA: CAS 95912-89-3

RA: CAS 95912-89-3

RA: CAS 95912-89-3

 (a) Category members subject to the REACh Phase-in registration deadline of 31 May 2013 are indicated in bold font.

Only for these substances a full set of experimental results and/or read-across is given.

Discussion

Genetic toxicity

Mutagenicity in bacteria in vitro

CAS 95912-89-3

The potential mutagenicity of Fatty acids, C8-10, mixed esters with adipic acid and trimethylolpropane (CAS 95912-89-3) was investigated in an Ames test (bacterial gene mutation assay) according to OECD 471 and in compliance with GLP (Garcia, 2010). The study was performed in two independent experiments in Salmonella typhimurium strains TA 98, TA 100, TA 1535 and TA 1537 and the Escherichia coli strain WP2 uvrA pKM 101 at concentrations of 0.06, 0.19, 0.56, 1.67 and 5 µL/plate, both in the absence and in the presence of liver microsomal activation system (S9 mix). In the first experiment, bacteria were incubated with the test substance concentrations for a period of 48 h using the plate incorporation method. In the second experiment, the same exposure duration was applied, but an additional preincubation period of 20 min was included in the assay. In both experiments, no cytotoxicity was observed up to the maximum concentration and the mean number of revertant colonies per plate was not increased at any test concentration. The positive controls included in both experiments showed the expected results.

Based on these results, Fatty acids, C8-10, mixed esters with adipic acid and trimethylolpropane was not mutagenic in the presence and absence of metabolic activation in the selected strains of S. typhimurium (TA 98, TA 100, TA 1535 and TA 1537) and E. coli WP2 uvrA pKM 101 under the conditions of this bacterial mutation assay.

Cytogenicity in mammalian cells in vitro

CAS 95912-89-3

The potential of Fatty acids, C8-10, mixed esters with adipic acid and trimethylolpropane (CAS 95912-89-3) to induce chromosomal aberrations was investigated in a GLP-conform in vitro mammalian chromosome aberration test according to OECD guideline 473 (Flügge, 2012). Based on a preliminary cytotoxicity test, duplicate cultures of human peripheral lymphocytes were incubated with the test substance at concentrations of 312.5, 625, 1250, 2500 and 5000 µg/mL in two independent experiments. In the first experiment, cells were exposed to the test substance for a period of 4 h in the presence and absence of metabolic activation, while the duration of treatment in the second experiment was 4 h with S9 activation and 24 h without S9 activation, respectively. No signs of cytotoxicity were noted in both experiments each carried out without and with metabolic activation up to the maximum concentration of 5000 µg/mL. Based on these results, chromosome analyse was performed at concentrations of 625, 1250, 2500 and 5000 µg/mL. No increase in the number of cells with chromosomal aberrations was observed compared to controls at any concentration in the presence and absence of metabolic activation. In addition, no polyploidy and no endoreduplication was noted in any of the treated cells. The positive controls included in both experiments showed the expected results and thus verified the sensitivity of the assay

Based on the negative results obtained in this chromosome aberration assay, it was concluded that Fatty acids, C8-10, mixed esters with adipic acid and trimethylolpropane did not induce structural and numerical chromosomal aberrations in cultured peripheral human lymphocytes in the presence or absence of metabolic activation.

Mutagenicity in mammalian cells in vitro

CAS 95912-89-3

To assess the potential mutagenicity of Fatty acids, C8-10, mixed esters with adipic acid and trimethylolpropane (CAS 95912-89-3) in mammalian cells, a GLP-conform Mouse Lymphoma Assay was performed according to OECD guideline 474 (Flügge, 2012). Based on the results of a preliminary cytoxicity test, mutations at the TK locus of mouse-lymphoma L5178Y cells were investigated at test substance concentrations ranging from 312.5 to 5000 µg/mL in two independent experiments. In the first experiment, cells were treated for a period of 3 h both in the presence and absence of metabolic activation (S9 mix). In the second experiment, the same treatment duration was used in the presence of S9 mix, whereas exposure to the test substance was extended to 24 h in the absence of S9 mix. After an expression period of 48 h in the presence of 5-trifluorothymidine (TFT) selective medium, the test substance did not induce an increase in the mutant frequency at any test substance concentration in the presence and absence of metabolic activation compared to controls. No cytotoxicity and no alterations in the ratio of small to large mutant colonies were observed at any concentrations with and without S9 activation between treated and control cultures. The positive controls significantly increased mutant frequency, demonstrating the sensitivity of the test system and the efficacy of the metabolic activation system.

In conclusion, Fatty acids, C8-10, mixed esters with adipic acid and trimethylolpropane did not increase the mutant frequency in mouse-lymphoma L5178Y cells in the absence and presence of metabolic activation.

 

Conclusion for genetic toxicity

In summary, three in vitro studies investigating the genetic mutation in bacteria, cytogenicity in mammalian cells and mutagenicity in mammalian cells are available for the PFAE mixed and branched category member Fatty acids, C8-10, mixed esters with adipic acid and trimethylolpropane (CAS 95912-89-3), all providing negative results.

Therefore, no genetic toxicity is expected for any member of the PFAE mixed and branched category.

 

A detailed reference list is provided in the technical dossier (see IUCLID, section 13) and within CSR.

 


Short description of key information:
No properties for genetic toxicity were observed within the PFAE mixed and branched group.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

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 group concept is applied to the members of the PFAE mixed and branched category, data will be generated from data for reference source substance(s) to avoid unnecessary animal testing. Additionally, once the group concept is applied, substances will be classified and labelled on this basis.

Therefore, based on the group concept, all 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 for classification.