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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:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
2001
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to an appropriate OECD test guideline. It was not compliant with GLP.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2001

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
GLP compliance:
not specified
Type of assay:
in vitro mammalian chromosome aberration test

Test material

Constituent 1
Reference substance name:
Phytosterol ester
IUPAC Name:
Phytosterol ester
Details on test material:
- Name of test material (as cited in study report): phytosterol esters
Composition as presented in report.

Sterol profile Composition of sample (%, w/w)

Cholesterol 0.2
Brassicasterol 2.9
Campesterol 26.7
Stigmasterol 17.7
β-Sitosterol 51.0
'Others' 1.5

Phytosterols (ex-Roche) were sourced from a variety of common edible vegetable oil distillates (mainly soya bean) and were dissolved in acetone. The phytosterols were then re-esterified with fatty acids from sunflower oils to form phytosterol esters, which were dissolved in acetone.

Method

Species / strain
Species / strain / cell type:
other: human peripheral blood lymphocytes
Metabolic activation:
with and without
Metabolic activation system:
Aroclor induced rat liver S9
Test concentrations with justification for top dose:
1st and 2nd tests - 50, 100 and 200 µg/ml
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: Acetone
- Justification for choice of solvent/vehicle: The solvent was determined by the solubility of the substance in question and its suitability in the assay.
Controlsopen allclose all
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
mitomycin C
Remarks:
without metabolic activation 3 hr and 21 hr treatment respectively

Migrated to IUCLID6: 0.8 µg/ml and 0.4 µg/ml
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
cyclophosphamide
Remarks:
with metabolic activation

Migrated to IUCLID6: 20.0 µg/ml
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium; in suspension

ACTIVATION: Co-factor mix consisted of magnesium chloride, potassium chloride, buffer, glucose-6-phosphate and NADP giving a total of 10% S9 mix.

DURATION
- Exposure duration: 1st test +/-S9 3hr treatment and 18 hr recovery; 2nd test -S9 21 hr treatment, +S9 3 hr treatment and 18 hr recovery
Evaluation criteria:
Evidence of mutagenic potential by a statistically and biological significant, dose-related increase in the percentage of cells with aberrations
Statistics:
Fishers exact test

Results and discussion

Test results
Species / strain:
other: human peripheral blood lymphocytes
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Remarks:
limited by solubility in the solvent
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid

Any other information on results incl. tables

In vitro chromosome aberration assay in human peripheral blood lymphocytes

Concentration µg/ml

Without S9 (Mean %)

With S9 (Mean %)

Excluding gaps

Including gaps

Relative MI (%)

Excluding gaps

Including gaps

Relative MI (%)

1sttest

3h treatment and 18h recovery

 

Solvent control

1.0

1.0

100

0.5

1.5

100

50

1.0

1.0

91

2.0

2.5

88

100

0.5

0.5

80

0.0

0.0

87

200

0.0

0.0

68

2.5

3.5

88

Positive control

20.0***

20.0***

-

33.0

34.0***

-

 

 

 

 

 

 

 

2ndtest

21 h continuous treatment

3h treatment and 18h recovery

Solvent control

1.5

3.5

100

0.0

0.5

100

50

0.0

1.0

111

0.0

1.0

95

100

0.0

0.5

109

0.0

0.0

73

200

0.0

0.5

77

0.5

2.0

91

Positive control

21.0***

21.0***

-

21.0***

21.0***

-

 

 

 

 

 

 

 

*** P<0.001

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative with and without metabolic activation

Phytosterol ester has been tested for clastogenicity in human peripheral blood lymphocytes, in a study which was conducted according to OECD 473, but not compliant with GLP. No evidence of a test-substance related increase in the number of chromosomal aberrations was observed with or without activation in the initial or repeat experiments. Appropriate solvent and positive controls were concluded and gave expected results. It is concluded that the test-substance is negative for mutagenicity to lymphocytes under the conditions of the test.