Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

Justification for grouping of substances and read-across

There are no data available on the genetic toxicity of 1,3-Butylene diacetate (CAS 1117-31-3). In order to fulfil the standard information requirements set out in Annex VIII, 8.4, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from a structurally related substance is 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 physicochemical, toxicological and ecotoxicological properties may be predicted from data for reference substance(s) by interpolation to other substances on the basis of structural similarity, Ethylene diacetate (CAS 111-55-7) and Propane-1,2-diyl diacetate (CAS 623-84-7) are selected as reference substances for assessment of genetic toxicity in vitro.

The read-across is based on the structural similarity between the source and target substances which are all esters of similar di-functional alcohols with the carboxylic acid acetic acid. A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

Overview of Genetic toxicity

CAS#

1117-31-3 (a)

111-55-7 (b)

623-84-7

Chemical name

1,3-Butylene diacetate

Ethylene diacetate

Propane-1,2-diyl diacetate

Molecular weight

174.20 g/mol

146.14 g/mol

160.17 g/mol

Genetic toxicity (mutagenicity) in bacteria in-vitro

RA: CAS 111-55-7

Experimental result: Negative

--

Genetic toxicity (cytogenicity) in mammalian cells in-vitro

RA: CAS 111-55-7

Experimental result: Negative

--

Genetic toxicity (mutagenicity) in mammalian cells in-vitro

RA: CAS 623-84-7

--

Experimental result: Negative

(a) The substance subject to the REACh Phase-in registration deadline of 31 May 2013 is indicated in bold font. Only for this substance a full set of experimental results and/or read-across is given.

(b) Reference (read-across) substances are indicated in normal font. Lack of data for a given endpoint is indicated by “--“.

 

Gene mutation in bacteria

CAS 111-55-7

One study investigating the induction of gene mutation in bacteria by Ethylene diacetate is available (Lawlor, 2000). The study was conducted according to OECD guideline 471 under GLP conditions. The tester strains, Salmonella typhimurium TA 1535, TA 1537, TA 98 and TA 100 and the E. coli strain WP2 uvr A pKM 101 were used.

The experiments were performed according to the plate incorporation procedure at concentrations from 10-5000 µg/plate in the first experiment and from 33.3-5000 µg/plate in the second experiment with and without a metabolic activation system (S9-mix from rats treated with Aroclor 1245). The included positive and negative controls in the experiments showed the expected results and were therefore considered as valid. No increase in the number of revertant colonies was observed in any of the bacterial strains, with and without metabolic activation system. No cytotoxicity was observed in the main study up to the limit concentration of 5000 µg/plate. Under the conditions of this study, Ethylene diacetate did not induce mutations in the bacterial mutation tests in the absence and presence of a metabolic activation system in any of the strains tested.

In vitro cytogenicity in mammalian cells

CAS 111-55-7

A study investigating the cytogenicity in mammalian cells in-vitro with Ethylene diacetate was performed in accordance with OECD guideline 473 under GLP conditions (Murli, 2000). The induction of structural chromosome aberrations was evaluated in vitro in Chinese hamster ovary (CHO) cells, incubated for 3 h with and without and for 18 h without a metabolic activation system (S9-mix from rats treated with Aroclor 1245). Concentrations of 515-1500 µg/mL (3 h incubation, Experiment I) and 500-1500 µg/mL (18 h and 3 h incubation, Experiment II) of the test substance in the vehicle water were applied. The negative as well as the positive controls showed the expected results and were within the range of historical control data. The frequency of polyploidy cells with and without metabolic activation was within the expected range. In the experiments without metabolic activation and 18 h incubation, an influence of the test substance was observed which led to a reduction in the mitotic index. No statistically or biologically significant increase in the incidence of chromosome aberrations was observed. Therefore, under the conditions of the study, the test substance did not show clastogenic activity in the chromosomal aberration test with and without metabolic activation performed in CHO cells in vitro.

In vitro gene mutation in mammalian cells

CAS 623-84-7

The in vitro mammalian cell gene mutation study of Propane-1,2-diyl diacetate was carried out according to OECD guideline 476 under GLP conditions (Indrani, 2011). Gene mutations in the HPRT locus were investigated in Chinese hamster ovary (CHO) cells in the presence and absence of a metabolic activation system (S9-mix from rats treated with Aroclor 1245).

In the first experiment, cells were exposed for 4 h to test substance at concentrations of 13-1602 µg/mL (in sterile water) with and without metabolic activation. Concentrations of the second experiment without metabolic activation for an exposure time of 4 h ranged from 20-1602 µg/mL with and without metabolic activation. The vehicle and positive controls in the study showed the expected results and were within the range of historical control data. No cytotoxicity was observed up to the highest tested concentration of 1602 µg/mL. There was no significant increase in the number of forward mutations at the HPRT locus of CHO cells treated with the test material, neither in the presence nor in the absence of a metabolic activation system. Under the conditions of the study, Propane-1,2-diyl diacetate did not show gene mutation activity in this test performed in CHO cells in vitro.

Conclusion for genetic toxicity

The studies with Ethylene diacetate (CAS 111-55-7) investigating genetic mutations in bacteria in-vitro and cytogenicity in mammalian cells in-vitro provided negative results. In addition, no mutagenicity in mammalian cells in-vitro was observed with the structurally related analogue substance Propane-1,2-diyl diacetate (CAS 623-84-7).

Therefore, based on read-across the available data do not provide any indications for a potential genetic toxicity of 1,3-Butylene diacetate (CAS 1117-31-3).


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 substance and overall quality assessment (refer to the endpoint discussion for further details).

Short description of key information:
Based on read-across from Ethylene diacetate (CAS 111-55-7) and Propane-1,2-diyl diacetate (CAS 623-84-7):
In vitro gene mutation in bacteria: negative with and without metabolic activation
In vitro cytogenicity in mammalian cells: negative with and without metabolic activation
In vitro gene mutation in mammalian cells: negative with and without metabolic activation

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on read-across from the source substances Ethylene diacetate (CAS 111-55-7) and Propane-1,2-diyl diacetate (CAS 623-84-7) following an analogue approach, all available data on genetic toxicity do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and the data are therefore conclusive but not sufficient for classification.