Dioctyltin dilaurate

Endpoint summary

Additional information

In vitro Bacterial Gene Mutation:

Two studies have been provided to address the potential for the registered substance to cause gene mutation in bacterial cells, on the basis of read across to analogue substances. Krul (2002) determined the genotoxic potential of the structural analogue dioctyltin oxide, in a bacterial reverse mutation test. Under the conditions of the test, the test material was found to be non-mutagenic in S. typhimurium strains TA 1535, TA 1537, TA 98 and TA 100 and in the E. coli strain WP2 uvrA, up to the precipitating concentration both in the absence and presence of metabolic activation (S9-mix). Aldekoa (2008) also determined the genotoxic potential of the structural analogue dioctyltin diacetylacetonate, in a bacterial reverse mutation test. Under the conditions of the study, no concentration of the test material showed a biologically significant increase in the number of revertant colonies either with or without metabolic activation. No dose-response was observed in any of the bacterial strains tested and no cytotoxic effects were observed. Subsequently, the test material was determined to be non-mutagenic in S. typhimurium strains TA 1535, TA 1537, TA 98 and TA 100 and in the E. coli strain WP2.

 

In vitro Mammalian Cytogenicity:

A chromosome aberration test conducted by Braun (2011) on the analogue tin, dioctylbis(pentane-2,4-dionato-O,O’), has been provided to address in vitro cytogenicity in mammalian cells. Under the conditions of the test, the test material was found to produce a negative effect in V79 Chinese hamster cells both in the presence and absence of metabolic activation, when tested up to precipitating concentration.

 

In vitro Mammalian Cell Gene Mutation:

Two studies have been provided to address in vitro mammalian cell gene mutation on a read across basis. Czich (2011) determined gene mutation using the analogue substance tin, dioctylbis(pentane-2,4-dionato-O,O’), in a Chinese hamster V79 HPRT assay. Under the conditions of the study, the test material was found to produce a negative effect both in the presence and absence of metabolic activation up to concentrations exhibiting test material precipitation. Additionally no cytotoxic effects were observed. Flanders (2012) determined gene mutation in a mouse lymphoma assay, using the analogue substance dioctyltin oxide. Under the conditions of the test, the test material did not induce any toxicologically significant dose-related increases in the mutant frequency at any dose level, either with or without metabolic activation. The test material is therefore considered to be non-mutagenic to L5178Y cells under the conditions of this assay.

 

In vivo Mammalian Cell Genotoxicity:

An in vivo genotoxicity study (de Vogel, 2004) has been also been provided on the analogue substance dioctyltin oxide. Under the conditions of the mammalian erythrocyte micronucleus test, the test material was found to be non-genotoxic and non-clastogenic up to 2000 mg/kg bw (limit concentration).

 

All studies provided to address in vitro and in vivo genetic toxicity were conducted under GLP conditions and line with standardised guidelines. All studies were performed using following the supporting substances, dioctyltin oxide, dioctyltin diacetylacetonate and tin, dioctylbis(pentane-2,4-dionato-O,O’). Accordingly they have all been assigned a reliability score of 2 in line with the principles for assessing data quality as defined in Klimisch (1997).

Justification for selection of genetic toxicity endpoint
No study was selected as key, since both the in vitro and in vivo studies assess different types of genetic toxicity and are all important in addressing this endpoint (see Discussion below). The gentoxicity studies provided were performed on structural analogues of the substance to be registered, and were performed in line with standardised guidelines and GLP. Accordingly they were all assigned a reliability score on 2, in accordance with the principles for assessing data quality as defined in Klimisch (1997).

Short description of key information:
In vitro Bacterial Gene Mutation:
- Krul (2002), OECD 471 and EPA OPPTS 870.5100 (bacterial reverse mutation test), dioctyltin oxide (DOTO); Negative up to the precipitating concentrations with and without metabolic activation.
- Aldekoa (2008) OECD 471 and EU Method B.13/14 (bacterial reverse mutation test), dioctyltin diacetylacetonate (DOT); Negative with and without metabolic activation.

In vitro Mammalian Cytogenicity:
- Braun (2011), OECD 473 and EU Method B.10 (chromosome aberration test), tin, dioctylbis(pentane-2,4-dionato-O,O’); Negative up to precipitating concentrations with and without metabolic activation.

In vitro Mammalian Cell Gene Mutation:
- Czich (2011), OECD 476, EU Method B.17 (Chinese hamster V79 HPRT assay), tin, dioctylbis(pentane-2,4-dionato-O,O’); Negative up to precipitating concentrations with and without metabolic activation.
- Flanders (2012), OECD 476, EU Method B.17, EPA OPPTS 870.5300 (mouse lymphoma assay), dioctyltin oxide (DOTO); Negative up to precipitating concentrations with and without metabolic activation.

In vivo Mammalian Cell Genotoxicity:
- de Vogel (2004), OECD 474 (mammalian erythrocyte micronucleus test), dioctyltin oxide (DOTO): Negative up to 2000 mg/kg bw (limit concentration).

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

In accordance with criteria for classification and labelling as defined in Regulation (EC) No. 1272/2008 (CLP) and Directive 67/548/EEC (DSD), the substance does not require classification for genetic toxicity.