3,4-dichlorobut-1-ene

Endpoint summary

Additional information

Genotoxicity (in vitro)

3,4-dichlorobut-1-ene has been tested for bacterial reverse mutation in Salmonella typhimurium and Escherichia coli with and without an exogenous metabolic activation by OECD TG 471 test. This chemical shows mutagenicity only in TA1535 at 1000 µg/plate, but not in other Salmonella typhimurium strains or Escherichia coli strain. In the case of TA1535, the number of induced colonies/plate, 20- 30/mg-dose, indicates that this chemical is weakly mutagenic [MHW, Japan (1996)]. This study was identified to be a key study because it was well conducted and reported. The in vitro mammalian cell gene mutation test (HPRT assay) was conducted using Chinese Hamster Ovary cells with and without metabolic activation (OECD TG 476). The positive result was observed only without metabolic activation. [Du Pont, Haskell Laboratory, USA (1980)]. In the chromosomal aberration test (OECD TG 473), this chemical induced structural chromosome aberrations and polyploidy in Chinese hamster lung cells (CHL/IU) with and without metabolic activation at the 50% growth inhibition - concentrations of 0.01 and 0.2 mg/mL, respectively [MHW, Japan (1996)]. Among these studies MHW study was identified to be a key study because it was well conducted and reported. On the basis of these data, it can be concluded that 3,4-dichlorobut-1-ene is mutagenic in bacterial and mammalian cells and induced chromosomal aberrations in mammalian cells in vitro assays.

Genotoxicity (in vivo)

There are not studies available which have been performed according to the OECD test guidelines but there studies which give sufficient information to evaluate this endpoint.

3,4-dichlorobut-1-ene induced chromosomal aberrations in rat bone marrow cells after inhalation exposure for 30 and 120 days (4 hours/day, 5 days/week). The concentration of 13.7 and 81.3 mg/m³ caused chromosome damages, mainly of the chromatid type. [Nalbandyan, T. I. et al. (1985)] Another positive cytogenetic study is reported at the concentration of 13.9 and 107.8 mg/m³ in the bone marrow. [Gizhalaryan, M. S. et al. (1984)].

At concentration of 0.01 or 0.1 mg/kg 3,4 -dichlorobut-1-ene was found positive in an in vivo chromosome aberration test.

[Gizhalaryan, M. S. et al. (1984)]

On the basis of these data, it can be concluded that 3,4-dichlorobut-1-ene is clastogenic in rat bone marrow in vivo assays.

Short description of key information:
-Bacterial Test (gene mutation; S. typhimurium and E.coli; OECD 471 and Japanese guide line): + with and without metabolic activation;
-Non-Bacterial In Vitro Test (Chromosomal aberrations; CHL cells, OECD 473 and Japanese guideline): + with and without metabolic activation;
- In vitro cell gene mutation test (HPRT, CHO cells, OECD TG 406): positive result was observed only with metabolic activation;
-3 Cytogenetic (chromosome aberration assay in rat bone marrow: after inhalation and oral exposure.

Endpoint Conclusion: Adverse effect observed (positive)

Justification for classification or non-classification

On the basis of these results 3,4 -dichlorobut-1 -ene is to be classified as Xn, R68 according to DSD classification criteria and Muta. 2 (H341), according to the CLP classification criteria.