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The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Study period:
26 Mar to 09 May 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.10 (Mutagenicity - In Vitro Mammalian Chromosome Aberration Test)
Deviations:
no
GLP compliance:
yes
Type of assay:
in vitro mammalian chromosome aberration test

Test material

Constituent 1
Reference substance name:
Sorbitan laurate
EC Number:
215-663-3
EC Name:
Sorbitan laurate
Cas Number:
1338-39-2
IUPAC Name:
1,4-anhydro-6-O-dodecanoyl-D-glucitol
Details on test material:
- Name of test material (as cited in study report): sorbitan laurate
- Physical state: yellow turbid viscous liquid
- Analytical purity: >80%
- Lot/batch No.: 0000357933
- Expiration date of the lot/batch: 27 October 2011
- Storage condition of test material: stable at room temperature in the dark

Method

Target gene:
not applicable
Species / strain
Species / strain / cell type:
lymphocytes: cultured peripheral human lymphocytes
Details on mammalian cell type (if applicable):
- Type and identity of media: RPMI 1640 medium supplemented with 20% (v/v) FCS, 2 mM L-glutamine, penicillin/streptomycin (50 U/mL and 50 mG/mL respectively) and 30 U/mL heparin
- Properly maintained: yes
Metabolic activation:
with and without
Metabolic activation system:
cofactor supplemented post-mitochondrial fraction (S9 mix), prepared from the livers of rats treated with a combination of phenobarbital and beta-naphtoflavone
Test concentrations with justification for top dose:
3 h exposure time: 33, 100 and 333 µg/mL
24 h exposure time: 50, 100 and 600 µg/mL
48 h exposure time: 100, 450 and 500 µg/mL
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
Controlsopen allclose all
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
no
Positive controls:
yes
Positive control substance:
cyclophosphamide
Remarks:
with rat liver S9-mix

Migrated to IUCLID6: 10 µg/mL for a 3 h exposure period (24 h fixation time)
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
no
Positive controls:
yes
Positive control substance:
mitomycin C
Remarks:
without rat liver S9-mix

Migrated to IUCLID6: 0.5 µg/mL for a 3 h exposure period, 0.2 µg/mL for a 24 h exposure period and 0.1 µg/mL for a 48 h exposure period
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium

DURATION
- Exposure duration: 3, 24 and 48 h
- Fixation time (start of exposure up to fixation or harvest of cells): 3 h treatment: 24 and 48 h; 24 h treatment: 24 h; 48 h treatment: 48 h

SPINDLE INHIBITOR (cytogenetic assays): colchicine 0.5 µL/mL medium
STAIN (for cytogenetic assays): Giemsa 5% (v/v) in tap water

NUMBER OF REPLICATIONS: 2

NUMBER OF CELLS EVALUATED: 100 per culture

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index of 1000 cells

OTHER EXAMINATIONS:
- Determination of polyploidy: yes
Evaluation criteria:
A test substance was considered positive (clastogenic) in the chromosome aberration test if: a) It induced a dose-related statistically significant (Chi-square test, one-sided, p < 0.05) increase in the number of cells with chromosome aberrations. b) A statistically significant and biologically relevant increase in the frequencies of the number of cells with chromosome aberrations was observed in the absence of a clear dose-response relationship.
A test substance was considered negative (not clastogenic) in the chromosome aberration test if none of the tested concentrations induced a statistically significant (Chi-square test, one-sided, p < 0.05) increase in the number of cells with chromosome aberrations. The preceding criteria are not absolute and other modifying factors might enter into the final evaluation decision.
Statistics:
Chi-square test, one-sided, p < 0.05

Results and discussion

Test results
Species / strain:
lymphocytes: cultured human peripheral lymphocytes
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity, but tested up to precipitating concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: At a concentration of 333 µg/mL and higher sorbitan laurate precipitated in the culture medium

RANGE-FINDING/SCREENING STUDIES: The highest concentration analysed was selected based on the solubility of the test substance in the culture medium (3 h and 24 h continuous exposure) or on toxicity inhibition of the mitotic index of about 50% or greater (48 h continuous exposure).

Any other information on results incl. tables

  Table 1: Maximum number of cells with aberrations (with gaps)

 

Maximum number of cells with aberrations [%](with gaps)

solvent control

positive control

treatment (conc. µg/mL)

treatment [exposure time/fixation time]

with S9-mix

without S9-mix

with S9-mix

without S9-mix

with S9-mix

without S9-mix

3h/24h

2

7

31

24

3 (100)

5 (100)

3h/48h

3

-

29

-

2 (33)

-

24h/24h

-

1

-

32

-

3 (600)

48h/48h

-

1

-

26

-

4 (450)

Table 2: Maximum number of cells with aberrations without gaps

 

Maximum number of cells with aberrations [%](without gaps)

solvent control

positive control

treatment (conc. µg/mL)

treatment [exposure time/fixation time]

with S9-mix

without S9-mix

with S9-mix

without S9-mix

with S9-mix

without S9-mix

3h/24h

1

5

30

24

2 (333)

4 (333)

3h/48h

3

-

28

-

1 (33)

-

24h/24h

-

1

-

32

-

2 (100)

48h/48h

-

1

-

26

-

4 (450)

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative