Propyl chloroformate

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:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

Only 4 test strains, S. typhimurium TA102/ E. coli WP2 uvrA are missing. However chloroformates are neither cross linking nor oxidizing agents.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

Principles of method if other than guideline:

Only 4 test strains, S. typhimurium TA102/ E. coli WP2 uvrA are missing.

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Propyl chloroformate

EC Number:

203-687-7

EC Name:

Propyl chloroformate

Cas Number:

109-61-5

Molecular formula:

C4H7ClO2

IUPAC Name:

propyl carbonochloridate

Details on test material:

- Name of test material (as cited in study report): chloroformic acid propylester
- Physical state: colorless liquid
- Purity: > 99%
- Batch No.: Versuch 29/1
- Expiration date of the lot/batch: not reported
- Stability under test conditions: lt is known, that chloroformic acid propylester hydrolysates very rapidly. Therefore, the stability of the test substance in the solvent ethanol and in aqua dest. was not determined analytically.
- Storage condition of test material: 4°C; solvent: ethanol

Method

Target gene:

Salmonella typhimurium: (his-)

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Metabolic activation:

with and without

Metabolic activation system:

S-9 mix from Aroclor 1254 induced rat liver

Test concentrations with justification for top dose:

0.0005 - 5.0 µl/plate (= approx. 5 to 5000 mg/plate)

Vehicle / solvent:

ethanol

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

other: see free text

Remarks:

Dimethylcarbamoyl chloride was used as positive reference substance of the chemical class of the chloroformic acid ester

Details on test system and experimental conditions:

Preincubation assay
0.1 ml test solution, 0.1 ml bacterial suspension and 0.5 ml S-9 mix are incubated at 37°C for the duration of 20 minutes. Subsequently, 2 ml of soft agar is added and, after mixing, the samples are poured onto the Vogel-Bonner agar plates within approx. 30 seconds.
In each experiment 3 test plates per dose or per control used; after fter incubation at 37°C for 48 hours in the dark, the bacterial colonies (his revertants) are counted.

Positive control
with metabolic activation: 10 μg/plate 2-aminoanthracene for each strain;
without metabolic activation: 5 μg/plate N-methyl-N'-nitro-N-nitrosoguanidine for TA 100 and TA 1535, 10 μg/plate 4-nitro-o-phenylendiamine
for TA 98 and 100 μg 9-aminoacridine chloride monohydrate for TA 1537, all substances were dissolved in DMSO.
The titer was determined and in regularly measurements the strain characteristics were checked. Sterility control performed.

Evaluation criteria:

Positive results
- doubling of the spontaneous mutation rate (control)
- dose-response relationship
- reproducibility of the result

Statistics:

Mean and standard deviation calculated in result tables. No further data.

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

A bacteriotoxic effect was observed at doses of about >0.002 - 0.005 µl/plate (without S-9 mix) and from about 0.3 µl - 0.5 µl/plate onward (with S-9 mix).

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 2

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

A bacteriotoxic effect was observed at doses of about >0.002 - 0.005 µl/plate (without S-9 mix) and from about 0.3 µl - 0.5 µl/plate onward (with S-9 mix).

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 3

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

A bacteriotoxic effect was observed at doses of about >0.002 - 0.005 µl/plate (without S-9 mix) and from about 0.3 µl - 0.5 µl/plate onward (with S-9 mix).

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 4

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

A bacteriotoxic effect was observed at doses of about >0.002 - 0.005 µl/plate (without S-9 mix) and from about 0.3 µl - 0.5 µl/plate onward (with S-9 mix).

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 5

Species / strain:

E. coli WP2

Remarks:

S. typhimurium TA102/ E. coli WP2 uvrA are missing.

Metabolic activation:

not applicable

Genotoxicity:

not determined

Cytotoxicity / choice of top concentrations:

not determined

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'. Remarks: Salmonella typhimurium; TA98 TA100 TA1535 TA1537

Any other information on results incl. tables

Preincubation test
Strain	Metabolic activation system	concentr. range (µl/plate)	Replicates	maximum revertant factor	dose dependency	Assessment
TA 98	no	.0005-.004	3	1.0	no	negative
	yes	.05-.5	3	1.0	no	negative
TA 100	no	.0005-.004	3	0.7	no	negative
	yes	.05-.5	3	0.9	no	negative
TA 1535	no	.02-5.0	3	0.0	no	negative
	yes	.02-5.0	3	1.5	no	negative
	no	.0005-.02	3	0.9	no	negative
	yes	.05-.5	3	0.9	no	negative
	yes	.05-.5	3	0.9	no	negative
TA 1537	no	.0005-.004	3	0.7	no	negative
	yes	.05-.5	3	0.9	no	negative

Applicant's summary and conclusion

Conclusions:

According to the results of the present study, the test substance Propyl chlorformate is not mutagenic in the Salmonella typhimurium reverse mutation assay under the experimental conditions chosen here.

Executive summary:

The study is conducted according to the OECD Guideline 471and is reliable with acceptable restrictions. TA102/ E. coli WP2 uvrA arr missing. However chloroformates are neither cross linking nor oxidizing agents.

Propy chlorformate was tested in the preincubation assay with and without metabolic activation in S. typhimurium TA98, TA100, TA1535 and TA1537 at dose levels of 5 -5000 µg/plate. No increase in the number of revertants was detected in any strain with and without MA. Vehicle controls and positive controls were valid. Cytotoxicity was found depending on the strain and metabolic activation. No precipitation was reported.

According to the results of the present study, the test substance Propyl chlorformate is not mutagenic in the Salmonella typhimurium reverse mutation assay under the experimental conditions chosen here.