4-hydroxymethyl-1,3-dioxolan-2-one

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

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

Adequacy of study:

key study

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

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 473 (In Vitro Mammalian Chromosome Aberration Test)

Deviations:

yes

Remarks:

highest dose tested was 1000 ug/ml with no evidence of cytotoxicity or precipitate formation

GLP compliance:

not specified

Type of assay:

in vitro mammalian chromosome aberration test

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:

propan-1,2,3-triol

Details on test material:

purity >99.5%

Method

Target gene:

chromosomal aberrations

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:

no

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Remarks:

triethylenemelamine(-S9); cyclophosphamide (+S9)

Details on test system and experimental conditions:

SYSTEM OF TESTING
- Species/cell type: CHO-cells WBL
- Metabolic activation system: rat S-9
- No. of cells scored: 100/concentration (50 for positive controls)

ADMINISTRATION:
- Dosing: 100, 200, 400, 600, 800 and 1000 ug/mL
- Treatment: 10 and 14 hours (with S-9) without recovery; 2 hours (without S-9) with 10 and 14 hr recovery
- Negative control: water (solvent)
- Positive control groups: triethylenemelamine(-S9); cyclophosphamide (+S9)

Evaluation criteria:

CRITERIA FOR EVALUATING RESULTS:
A statistically significant, reproducible and dose-dependent increase in frequency of cells with aberrations compared to solvent control.

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

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Additional information on results:

GENOTOXIC EFFECTS:
- With metabolic activation: negative
- Without metabolic activation: negative

In the initial assay with metabolic activation a statistically significant increase in the number of aberrations compared to controls was seen only at 200 ug/mL (recovery period 10 hr)

PRECIPITATION CONCENTRATION: not indicated

MITOTIC INDEX:
without S-9 (10 hr): 84-97% of control
without S-9 (14 hr): 78-101% of control
with S-9 (10 hr rec.): 59-92% of control (no relationship with concentration)
with S-9 (14 hr rec): no decrease observed

CYTOTOXIC CONCENTRATION:
No cytotoxicity observed with concentrations tested.

Any other information on results incl. tables

Table 1 Chromosome aberration assay

Treatment and concentration (ug/ml)	Duration of treatment or recovery (h)	Mitotic index (%)	No. of cells scored	No. of aberrations/cell	Cells with aberrations (%)
			Non-activation assay
Solvent control (H2O)	10	8.6	100	0.02	1.0
Positive control	10	3.4	50	0.44	36.0*
Glycerol
100	10	7.3	100	0.07	6.0
200	10	7.4	100	0.01	1.0
400	10	8.0	100	0.06	5.0
600	10	8.0	100	0.02	2.0
800	10	8.3	100	0.01	1.0
Solvent control (H2O)	14	12.1	100	0.02	2.0
Positive control	14	3.8	50	1.04	68.0*
Glycerol
100	14	11.1	100	0.02	2.0
200	14	9.4	100	0.03	2.0
400	14	10.1	100	0.04	3.0
600	14	11.3	100	0.01	1.0
800	14	12.2	100	0.00	0.0
1000	14	11.7	100	0.00	0.0
		Activation assay
Solvent control (H2O)	10	5.1	100	0.03	3.0
Positive control	10	6.3	50	1.98	78.0*
Glycerol
100	10	4.7	100	0.01	1.0
200	10	3.0	100	0.18	9.0*
400	10	3.7	100	0.02	2.0
600	10	3.7	100	0.04	3.0
800	10	3.3	100	0.04	4.0
1000	10	3.2	100	0.02	2.0
100	14	11.0	100	0.00	0.0
200	14	11.4	100	0.00	0.0
400	14	12.3	100	0.02	2.0
600	14	11.3	100	0.01	1.0
800	14	11.7	100	0.00	0.0
1000	14	12.3	100	0.02	2.0

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

The test material did not induce a mutagenic response in the Chinese Hamster Ovary assay with and without metabolic activation.

Executive summary:

The test material was evaluated in the Chinese hamster ovary Chromosomal Aberration assay. The test material did not induce a mutagenic response in the Chinese hamster ovary CA assay with and without metabolic activation.