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Administrative data

Key value for chemical safety assessment

Additional information

In vitro:

Mutagenicity in bacteria:

1-chlorobutane was tested in a preincubation assay and due to its high volatility in a vapour desiccator method equivalent to OECD guideline 471 for its mutagenicity in bacteria (Zeiger, 1990). In this bacterial reverse mutation assay according to Ames the test substance showed negative results in Salmonella typhimurium strains TA 100, TA 1535, TA 98 and TA 97 with and without metabolic activation. The negative test result was confirmed by several other authors using sealed containers or the common preincubation method for genotoxicity testing in the mentioned strains and in Salmonella typhimurium TA 1537 (OECD, Japan. Berichte, 1995; 89-0642-FGM; Barber et al., 1981). However, in a publication provided as short summary information (Simmon, 1981), it was reported, that when the cells were exposed to vapours in a desiccator 1-chlorobutane was mutagenic in strain TA 100 in the absence of S9. The experiment was not performed with metabolic activation system. Negative mutagenic results in a bacteria strain with a A/T base pair as primary mutation site (E. coli WP2 uvr A) were also observed in a preincubation assay (OECD, Japan. Berichte, 1995) with and without S9-mix. Data on cytotoxicity were inconsistent. Zeiger (1990) and Barber et al. (1981) examined cytotoxicty from approx. 3000 µg/plate, whereas no bacteriotoxic effects up to 10000 µg/plate were reported in the study record 89-0642-FGM. OECD, Japan. Berichte (1995) described inhibitions of growth against bacteria using 78.12 µg/plate 1-chlorobutane.

Mutagenicity in mammalian cells:

A mouse lymphoma assay was conducted in mouse lymphoma L5178Y cells (Myhr et al., 1990).In the absence and in the presence of a metabolic activation system, no mutagenic potential of the test substance was observed. Cytotoxicity was observed at the highest test concentrations, either with or without addition of metabolic activation. At first glance, the mutant frequency was increased in one out of the seven trials without metabolic activation. However, the supposed positive result was due to cytotoxicity which was seen at high test concentrations, and is considered not to be related to genotoxicity. Therefore, under the experimental conditions chosen, the mouse lymphoma assay provided negative results for genotoxicity in mammalian cells.

Cytogenicity:

A chromosomal abberation test according to OECD Test guideline 473 was conducted using cultured Chinese hamster lung cells (CHL/IU).The highest concentration of 1-chlorobutane was used within no apparent cytotoxic effects in continuous treatment (24 and 48 h). In short time treatment (6 h) it was set to 3.5 mg/mL. No structural chromosomal aberrations or polyploidie were detected up to a maximum concentration of 0.93 mg/mL under conditions of both continuous treatment and short-term treatment with or without S9-mix. (OECD, Japan. Berichte, 1993). The negative result was confirmed by Anderson et al. (1990) performing another chromosomal abberation test using Chinese hamster ovary cells (CHO) with and without metabolic activation system up to 5.0 mg/mL. In addtion, Anderson et al. (1990) examined the cytogenetic potential of 1-chlorobutane in a sister chromatid exchange assay. No reciprocal exchanges of DNA between two sister chromatids of a duplicating chromosome could be detected in CHO-cells in concentrations up to 5000 µg/mL.

 

In vivo:

In a GLP-report according to guideline 474, 1-chlorobutane was administered once intraperitoneally at one dose level of 2000 mg/kg bw to NMRI-mice. Samples of the bone marrow were taken after 24, 48 and 72 hours from 5 males and 5 females each. Results from the data analysis show, that there was no significant difference in the number of micronucleated polychromatic erythrocytes (PCE) (per 1000 polychromatic erythrocytes) compared to the control values at any time.The number of polychromatic and normochromatic erythrocytes (NCE) and the ratio PCE/NCE was not significantly different to the controls. 

In summary, the available studies demonstrate that 1-chlorobutane is not genotoxic in in vitro and in in vivo systems.The positive test result in the bacterial strain TA 100 by Simmon (1981) was refuted by several other bacterial gene mutation tests and the negative genotoxic results in all other test results in vitro and in vivo.    

 


Short description of key information:
in vitro:
- mutagenicity in bacteria:
Ames, S. typhimurium TA 97, TA 98, TA 100, TA 1535, +/- S9, preincubation and vapour desiccator method: negative (Zeiger, 1990)
Ames, S. typhimurium TA 98, TA 100, TA 1535, TA 1537, E. coli WP2 uvr A, +/- S9, plate incorporation assay: negative (OECD, Japan.Berichte, 1995)
Ames, S. typhimurium TA 98, TA 100, TA 1535, TA 1537, +/- S9, plate incorporation assay: negative (89-0642-FGM)
- mutagenicity in mammalian cells: mouse lymphoma assay in L5178Y cells, +/- S9: negative (Myhr et al., 1990)
- cytogenicity:
chromosome aberration: Chinese hamster CHL/IU cells, +/- S9: negative (OECD, Japan. Berichte, 1995)
sister chromatid exchange: Chinese hamster ovary (CHO), +/- S9: negative (Anderson et al., 1990)

in vivo:
-cytogenicity:
micronucleus assay: mouse, 2000 mg/kg bw i.p.: negative (89-0640-FGM)

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The data is conclusive but not sufficient for classification according to DSD (67/548/EEC) and CLP (1272/2008/EC).