1-chlorobutane

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

publication

Title:

Mutagenicity of 42 Chemicals in Salmonella

Author:

Zeiger, E.

Year:

1990

Bibliographic source:

Environmental and Molecular Mutagenesis 16 (18): 32-54

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

strain with A/T base pair as primary mutation site missing

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

1-chlorobutane

EC Number:

203-696-6

EC Name:

1-chlorobutane

Cas Number:

109-69-3

Molecular formula:

C4H9Cl

IUPAC Name:

1-chlorobutane

Details on test material:

- Name of test material (as cited in study report): n-butyl chloride

Method

Target gene:

His Operon

Species / strain

Species / strain / cell type:

other: S. typhimurium TA 100, TA 1535, TA 97, TA 98

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

two metabolic activation systems were used separately: 1.) Aroclor induced Sprague Dawley rat liver S9-mix; 2.) Aroclor induced Syrian hamster liver S9-mix; 30 % and 10% S9 in the S9 mixture)

Test concentrations with justification for top dose:

preincubation method: 100, 333, 1000, 3333, 6666 and 10000 μg/plate
vapour desiccator method: 0.1, 0.5, 1, 2, 3 and 4 mL/chamber

Vehicle / solvent:

preincubation method: DMSO

Controls

Untreated negative controls:

yes

Remarks:

vapour desiccator method

Negative solvent / vehicle controls:

yes

Remarks:

preincubation method

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: with metabolic activation: 2-aminoanthracene for all strains; without metabolic activation: sodium azide for TA 100 and TA1535, 9-aminoacridine for TA 97 and 4-nitro-o-phenylenediamine for TA 98.

Details on test system and experimental conditions:

METHOD OF APPLICATION:
Preincubation method: Cells and test compound or DMSO were incubated for 20 minutes at 37 °C in the presence of either S9-mix or buffer. After the addition of soft agar, the contents of each tube was poured onto minimal medium, and the plates were incubated at 37°C for 48 hours [Haworth et al. 1983]
Vapour desiccator method: S9 or buffer was incorporated into the top agar and poured onto the plate. The lids of the plates were removed and the plates were stacked on a perfoated porcelain plate in a 9 L glass desiccator jug containing a magnetic stirring bar. A measured volume of test chemical, in liquid form, was introduced into a watch glass suspended below the porcelain plate, and the desiccator was sealed and placed on a magnetic stirrer in a 37 °C incubator. After 24 h the plates were removed from the desiccator and incubated at 37°C in air for an additional 24 h.


NUMBER OF REPLICATIONS:
vapour desiccator method: 2
preincubation method: 1

Evaluation criteria:

A chemical was judged mutagenic or weakly mutagenic if it gave a reproducible dose-related response over the solvent control in replicate trials, and judged questionable if the results of individual trials were not reproducible or if only single doses produced increase in his+ revertants in repeat trials. Chemicals were judged nonmutagenic, if they do not meet the criteria for mutagenic or questionable response.

Results and discussion

Test results

Metabolic activation:

with and without

Genotoxicity:

negative

Remarks:

in preincubation and vapour desiccator method

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

from 3333 µg/plate and at 4 mL/chamber

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Preincubation method	number of revertants: mean value of negative control	number of revertants: mean value of positive control	max. number of revertants: mean value of test material [µg/plate]
without S9-mix
TA 1535	14 ± 0.9	958 ± 34.3	17 ± 1.5 [100]
TA 100	119 ± 7.4	955 ± 37.8	135 ± 9.9 [100]
TA 97	206 ± 9.5	742 ± 42.2	213 ± 4.6 [100]
TA 98	36 ± 4.0	677 ± 20	36 ± 1.8 [100]
with S9-mix (30% HLI)
TA 1535	10 ± 1.9	607 ± 16.8	13 ± 0.9 [1000]
TA 100	163 ± 12.0	837 ± 39.5	176 ± 5.8 [1000]
TA 97	212 ± 8.1	436 ± 2.2	230 ± 2.9 [100]
TA 98	45 ± 3.3	770 ± 11.3	43 ± 5.2 [1000]
with S9-mix (30% RLI)
TA 1535	18 ± 3.0	105 ± 3.6	18 ± 0.7 [1000]
TA 100	175 ± 0.9	440 ± 26.1	170 ± 7.9 [1000]
TA 97	230 ± 5.8	442 ± 3.5	233 ± 1.7 [333]
TA 98	42 ± 6.5	168 ± 3.5	49 ± 3.2 [100]
Vapour desiccator method	number of revertants: mean value of negative control	number of revertants: mean value of positive control	number of revertants: mean value of test material [ml/chamber]
without S9-mix
TA 1535	14 ± 1.2	1671 ± 41.8	16 ± 2.7 [0.1]
TA 100	144 ± 8.6	1569 ± 21.7	147 ± 28.3 [0.1]
TA 97	208 ± 17.2	978 ± 54.7	198 ± 15.3 [0.5]
TA 98	34 ± 2.8	557 ± 17.4	43 ± 3.8 [1.0]
with S9-mix (30% HLI)
TA 1535	11 ± 4.2	459 ± 21.2	20 ± 0.9 [0.5]
TA 100	165 ± 6.0	843 ± 24.8	158 ± 9.7 [1.0]
TA 97	140 ± 6.8	564 ± 15.9	172 ± 8.5 [1.0]
TA 98	22 ± 3.3	657 ± 47.6	42 ± 4.7[1.0]
with S9-mix (30% RLI)
TA 1535	19 ± 3.2	90 ± 6.4	20 ± 2.5 [1.0]
TA 100	142 ± 9.5	463 ± 58	145 ± 10.5 [0.5]
TA 97	166 ± 20.1	461 ± 10.7	186 ± 9.7 [0.5]
TA 98	33 ± 4.8	120 ± 7.5	39 ± 4.1 [1.0]

HLI: aroclor 1254-induced hamster liver S9

RLI: aroclor 1254-induced rat liver S9

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative