Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vivo

Description of key information
Available data from both in vitro and in vivo studies indicate that mixed xylene has no significant genotoxicity.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vivo:

Mixed xylene (CAS 1330-20-7) comprises individual xylene isomers (m-xylene, o-xylene, p-xylene) and <10% ethylbenzene. The following information is available to characterise the genotoxic potential of this substance.

In vitro data

Mixed xylene has been examined for activity on both gene mutation and cytogenetic endpoints. A sample comprising 52% m-xylene, 11% o-xylene, 36% ethyl benzene was not mutagenic in bacterial mutagenicity assays using Salmonella typhimurium (Litton Bionetics, 1978). In assays examining for chromosomal effects in mammalian cells, mixed xylene (composition unspecified) did not induce either sister chromatid exchanges or chromosomal aberrations in Chinese hamster ovary cells (Anderson, 1990) or gene mutation in mouse lymphoma L5178Y cells (Litton Bionetics, 1978). Litton Bionetics (1979) also reported negative results for gene mutation from the evaluation of mitotic recombination in Saccharomyces cerevisiae. A recent assay examining for DNA damage, the comet assay (Chen, 2008), reported increases in fragmentation when isolated human peripheral blood lymphocytes were exposed to levels of m-, o- or p-xylene. Their investigations suggested that reactive oxygen species may play a role in the damage observed. The relevance of the small changes possibly due to active oxygen species observed in isolated lymphocytes is considered limited. In particular, no evidence to support a consequence of any radical-induced damage was seen in a cytogenetic assay (Anderson, 1990). In view of the available studies including the key endpoints of gene mutation and chromosomal damage, additional in vitro assays of the genotoxicity potential of mixed xylene are considered unnecessary, as also concluded by the recent ATSDR (2007) review.

In vivo data

Non-human information

Mixed xylene (comprising 52% m-xylene, 11% o-xylene, 36% ethyl benzene) did not induce chromosome aberrations in the bone marrow of treated rats (0.044, 0.147 and 0.441 cc/kg by intraperitoneal injection), Litton Bionetics (1978). A negative result was obtained for mixed xylene in dominant lethal assays conducted in rats and mice (Hine Laboratories Inc., for API, 1973). In view of the lack of significant genotoxicity observed in the in vitro studies, and the available negative results examining for chromosomal damage in vivo, mixed xylene is considered not to have genotoxic potential.

Human information

Limited data is available demonstrating a lack of genotoxicity of mixed xylene following inhalation in humans (ATSDR, 2007).

The genotoxicity of ethyl benzene is reviewed in the recent RAR (2008) and it was concluded from various in vitro and in vivo mutagenicity tests that there is no relevant indication that ethyl benzene is genotoxic. The same conclusion has been drawn for xylene isomers in the recent comprehensive review of ATSDR (2007). Neither ethyl benzene or any of the xylene isomers are classified for mutagenicity under the DSD (Dir. 67/548/EEC).

Justification for selection of genetic toxicity endpoint
Negative results were obtained for mixed xylene when tested in a dominant lethal assay in rats, and also in a complementary assay assay conducted in mice (Hine Laboratories Inc., 1973). Results from an in vivo rat bone marrow chromosome aberration assay on mixed xylene were also negative (Litton Bionetics, 1978). In vitro genetic toxicity data for xylene isomers are also consistently negative.

Justification for classification or non-classification

No classification is warranted under DSD or CLP since all xylene isomers, ethylbenzene and mixed xylene show no evidence of genotoxicity in vitro or in vivo.