Triglycerides, C16-C18 (even numbered) and C18 (unsaturated), maleated

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well documented publicationt which meets basic scientific principles. As the substance is a breakdown product of the target substance, this study is considered valid for read-across.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

The genotoxic activity of glycerol in an in vitro test battery

Author:

Doolittle, D.J. et al.

Year:

1988

Bibliographic source:

Fd Chem. Tox., 26(7): 631-35

Reference 2

Reference Type:

secondary source

Title:

OECD SIDS Initial Assessment Report For SIAM 14 - Glycerol

Author:

OECD

Year:

2002

Bibliographic source:

http://www.inchem.org/documents/sids/sids/56815.pdf

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)

GLP compliance:

no

Type of assay:

in vitro mammalian chromosome aberration test

Test material

Test material information

Constituent 1

Reference substance name:

Glycerine

IUPAC Name:

Glycerine

Constituent 2

Reference substance name:

Glycerol

EC Number:

200-289-5

EC Name:

Glycerol

Cas Number:

56-81-5

IUPAC Name:

glycerol

Details on test material:

- Analytical purity: >99.5%
- Supplier: Fisher Scientific (Springfield, NJ)

Method

Target gene:

Not applicable

Species / strain

Species / strain / cell type:

Chinese hamster Ovary (CHO)

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

rat S-9 (40mg protein/mL; Hazleton Laboratories America, Inc., Vienna, VA)

Test concentrations with justification for top dose:

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

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: water

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

triethylenemelamine

cyclophosphamide

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium

DURATION
- Exposure duration: 10 h and 14 h(non-activation); 2 h (with activation)
- Expression time (cells in growth medium): 10 h and 14 h (with activation)

NUMBER OF CELLS EVALUATED: 100; 50 for positive control

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index

OTHER:
- Positive control: Triethylenemelamine, 0.5 µg/gmL (non-activated); Cyclophosphamide. 35 µg/mL (activated)

Evaluation criteria:

A test result was considered positive if there was a reproducible dose-dependent increase (P < 0.01) in the frequency of cells with structural chromosomal aberrations compared with the solvent control cells.

Statistics:

Fisher's exact test

Results and discussion

Test results

Species / strain:

Chinese hamster Ovary (CHO)

Metabolic activation:

with and without

Genotoxicity:

negative

Remarks:

An isolated, statistically significant increase was seen at 200 µg/mL with a 10-hr recovery time in the presence of S-9. Since there was no dose response this isolated result was considered to be spurious and biologically insignificant.

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

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

Results:

Treatment and concentration (µg/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	10	8.6	100	0.02	1
Positive control	10	3.4	50	0.44	36.0*
Glycerol
100	10	7.3	100	0.07	6
200	10	7.4	100	0.01	1
400	10	8	100	0.06	5
600	10	8	100	0.02	2
800	10	8.3	100	0.01	1
Solvent control (H2O)	14	12.1	100	0.02	2
Positive control	14	3.8	50	1.04	68.0*
Glycerol
100	14	11.1	100	0.02	2
200	14	9.4	100	0.03	2
400	14	10.1	100	0.04	3
600	14	11.3	100	0.01	1
800	14	12.2	100	0	0
1000	14	11.7	100	0	0
	Activation assay
Solvent control	10	5.1	100	0.03	3
Positive control	10	6.3	50	1.98	78.0*
Glycerol
100	10	4.7	100	0.01	1
200	10	3	100	0.18	9.0*
400	10	3.7	100	0.02	2
600	10	3.7	100	0.04	3
800	10	3.3	100	0.04	4
1000	10	3.2	100	0.02	2
100	14	11	100	0	0
200	14	11.4	100	0	0
400	14	12.3	100	0.02	2
600	14	11.3	100	0.01	1
800	14	11.7	100	0	0
1000	14	12.3	100	0.02	2

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

Glycerol was not found to induce chromosomal aberrations in Chinese hamster Ovary Cells when tested with concentrations up to 1000 mg/mL with and without metabolic activation.

Executive summary:

Glycerol was assessed in a chromosomal aberration assay conducted comparable to OECD guideline 473 where it was tested in Chinese hamster Ovary Cells with concentrations up to 1000 mg/mL with and without metabolic activation. As a result, no mutagenic response was noted.