Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

Justification for grouping of substances and read-across

There are only limited data available on the genetic toxicity of 1,2 benzenedicarboxylic acid, di-C16-C18-alkyl esters (CAS 90193-76-3). 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

Genetic toxicity (mutagenicity) in vitro, bacteria

Genetic toxicity (cytogenicity) in vitro, mammalian cells

Genetic toxicity (mutagenicity) in vitro, mammalian cells

Genetic toxicity

in vivo

90193-76-3 (a)

1,2 benzenedicarboxylic acid, di-C16-C18-alkyl esters

RA: CAS 68442-70-6

 

Experimental result:
not clastogenic

Experimental result:
not mutagenic

--

68442-70-6 (b)

1,2-Benzenedicarboxylic acid, mixed cetyl and stearyl esters

Experimental result:
not mutagenic

--

--

--

(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 substance is 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 1,2 benzenedicarboxylic acid, di-C16-C18-alkyl esters (CAS 90193-76-3). A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

 

Discussion

Gene mutation in bacteria in vitro

CAS 68442-70-6

A Bacterial Reverse Mutation Assay was performed with 1,2-Benzenedicarboxylic acid, mixed cetyl and stearyl esters (CAS No. 68442-70-6) equivalent to OECD Guideline 471 (Wallat, 1981). Salmonella typhimurium strains TA 1535, TA 1537, TA 1538, TA 98 and TA 100 were treated with 1,2-Benzenedicarboxylic acid, mixed cetyl and stearyl esters diluted in Tween 80 using the plate incorporation method with dose levels of 0, 4, 20, 100, 500 and 2500 µg/plate. The experiment was performed in quadruplicates with and without the addition of a rat liver homogenate metabolising system (S9-mix). No influence on bacterial background lawn or bacterial growth reduction was reported. No increase in the frequency of revertant colonies compared to concurrent negative controls were observed in all tested strains, neither in the presence nor in the absence of metabolic activation. Positive control substances, sodium azide, 4-Nitro-o-phenylendiamine and 2-Aminoanthracene significantly increased the frequency of revertant colonies. Thus, 1,2-Benzenedicarboxylic acid, mixed cetyl and stearyl esters did not induce gene mutations in Salmonella typhimurium under the given test conditions.

 

Cytogenicity in vitro

CAS 90193-76-3

An in vitro mammalian chromosome aberration test was performed with 1,2-Benzene-dicarboxylic acid, di-C16-18-alkyl esters (CAS No. 90193-76-3) in cultured human lymphocytes (Buskens, 2010). The occurrence of chromosome aberrations was investigated in the presence and absence of metabolic activation (rat liver S9-mix) with test substance concentrations of 0 (solvent control), 10, 33 and 100 µg/mL diluted with ethanol. At higher concentrations the test substance precipitated in culture medium. The test substance did not induce a significant increase in the number of phases with aberrations at any preparation time and dose level. No relevant cytotoxic effects were reported up to precipitating concentrations. Positive controls significantly increased the rate of chromosome aberrations indicating the sensitivity of the assay.

In conclusion, 1,2-Benzene-dicarboxylic acid, di-C16-18-alkyl esters did not induce chromosome aberrations in human lymphocytes, neither in the presence nor in the absence of a metabolic activation system, under these experimental conditions.

 

Gene mutation in mammalian cells in vitro

CAS 90193-76-3

An in vitro mouse lymphoma assay was performed with 1,2-Benzene-dicarboxylic acid, di-C16-18-alkyl esters (CAS No. 90193-76-3) according to the OECD guideline 476 (Verspeek-Rip, 2010). Two experiments were performed. In the first experiment, the test substance was tested up to concentrations of 33 µg/mL in the absence and presence of 12% (v/v) S9 -mix. The incubation time was 3 hours. The test item precipitated in the culture medium at this dose level. In the second experiment the test item was tested again up to concentrations of 33 µg/mL, but in the absence and presence of 12% (v/v) S9 -mix. The incubation times were 24 and 3 hours for incubations in the absence and presence of S9 -mix, respectively. In the mutations assay, no severe toxicity was observed. The spontaneous mutation frequencies in the solvent-treated control cultures were between the minimum and maximum value of the historical control data range and within the acceptability criteria of this assay. Positive controls significantly increased the rate of mutations with and without metabolic activation indicating the sensitivity of the assay.

Thus, 1,2-Benzene-dicarboxylic acid, di-C16-18-alkyl esters was not mutagenic in the mouse lymphoma L5178Y test system under the experimental conditions

 

Conclusions for genetic toxicity

The available data on 1,2-Benzene-dicarboxylic acid, di-C16-18-alkyl esters (CAS No. 90193-76-3) and the structurally related substance with 1,2-Benzenedicarboxylic acid, mixed cetyl and stearyl esters (CAS No. 68442-70-6) showed that the results of all in vitro genetic toxicity studies performed in bacteria and mammalian cells with and without metabolic activation were negative.


Justification for selection of genetic toxicity endpoint
Hazard assessment is conducted by means of read-across from structural analogues. No study was selected, since all available in vitro genetic toxicity studies were negative. All available studies are adequate and reliable based on the identified similarities in structure and intrinsic properties between source and target substances and overall quality assessment (refer to the endpoint discussion for further details).

Short description of key information:
In vitro chromosome aberration assay: negative
In vitro mammalian gene mutation assay: negative
Read Across substance 1,2-Benzenedicarboxylic acid, mixed cetyl and stearyl esters (CAS No. 68442-70-6): Mutagenicity in bacteria: negative

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

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 for classification.