Reaction product of 1-chloro-2,3-expoxypropane, sodium hydroxide, sodium carbonate and water

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in mammalian cells

Remarks:

Type of genotoxicity: gene mutation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Study period:

Not stated

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to guideline and/or standard method but was non-GLP.

Data source

Reference

Reference Type:

publication

Title:

The genotoxic activity of glycerol in an in vitro test battery

Author:

Doolittle, D., Lee, D.A. and Lee, C.K.

Year:

1988

Bibliographic source:

Fd Chem Toxic 26(7): 631-635

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)

Deviations:

yes

Remarks:

No cytotoxicity was observed at 1000 ug/ml, the highest concentration tested.

GLP compliance:

not specified

Type of assay:

mammalian cell gene mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Glycerol

EC Number:

200-289-5

EC Name:

Glycerol

Cas Number:

56-81-5

Molecular formula:

C3H8O3

IUPAC Name:

glycerol

Test material form:

not specified

Details on test material:

purity >99.5%

Method

Target gene:

HGPRT gene

Species / strain

Species / strain / cell type:

Chinese hamster Ovary (CHO)

Metabolic activation:

with and without

Metabolic activation system:

rat S-9

Test concentrations with justification for top dose:

100, 200, 400, 600, 800 and 1000 ug/mL

Vehicle / solvent:

water

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Remarks:

without S-9 ethyl methanesulphonate; with S-9 dimethylbenzanthracene

Details on test system and experimental conditions:

SYSTEM OF TESTING
- Cell type: CHO-K1-BH4
- Proficiences: HGPRT gene
- Metabolic activation system: rat S-9

ADMINISTRATION:
- Dosing: 100, 200, 400, 600, 800 and 1000 ug/mL
- Number of replicates: not indicated
- Negative control: water (solvent)
- Positive control groups: without S-9 ethyl methanesulphonate; with S-9 dimethylbenzanthracene
- Treatment: 5 hours

Evaluation criteria:

CRITERIA FOR EVALUATING RESULTS:
At least a three-fold increase in mutation frequency above controls in a dose dependent manner.

Statistics:

No additional information available.

Results and discussion

Test results

Species / strain:

Chinese hamster Ovary (CHO)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Remarks:

no evidence of cytotoxicity at 1000 ug/ml, the highest concentration tested

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

- With metabolic activation: negative
- Without metabolic activation: negative

At 800 and 1000 ug/mL the mutation frequency was increased >= 3 fold (24E-06 and 6E-06, respectively) compared to controls (2E-06).

PRECIPITATION CONCENTRATION: not indiated

CYTOTOXIC CONCENTRATION: Not observed

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

The increased mutation frequency seen at the two highest concentrations (800 and 1000 ug/mL) in absence of a concentration response relationship are not considered biologically significant and do not fulfil the criteria for a positive response due to the absence of a dose-response relationship.

Table 1

Treatment and Concentration (ug/ml)	Cloning efficiency (%)	No. of mutants	Mutation Frequency (x10(-6))
	Activation assay
Negative control	96	2	2
Solvent control (H2O)	76	6	7
Positive control	77	178	200*
Glycerol
100	65	6	7
200	66	0	0
400	77	2	3
600	63	3	4
800	72	7	9
1000	80	12	15
	Non-activation assay
Negative control	75	4	5
Solvent control (H2O)	84	2	2
Positive control	79	122	153*
Glycerol
100	87	0	0
200	85	1	1
400	85	1	1
600	79	4	5
800	83	20	24*
1000	83	5	6*

* Values are at least three times that for the solvent control.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

The test material did not meet the criteria set for a positive response set by the author of the report and was considered to be negative by the author.

Executive summary:

The test material was evaluated in the Chinese hamster ovary assay with and without metabolic activation. The test material did not meet the criteria set for a positive response set by the author of the report and was considered to be negative by the author.