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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
key study
Study period:
no data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
no cross linking strain was used
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
The toxicity of behenyl alcohol: I. Genotoxicity and subchronic toxicity in rats and dogs
Author:
Iglesias G, J J Hlywka, J E Berg, M H Khalil, L E Pope and D Tamarkin
Year:
2002
Bibliographic source:
Regulatory Tox. and Pharm. 36, 69-79, 2002

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
(no TA102 or E. coli WP2 uvrA; 2-aminoanthracene only positive control with metabolic activation)
Principles of method if other than guideline:
Well-conducted study according to a protocol very similar to OECD guideline 471
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: Waxy Solid

Method

Target gene:
histidine
Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Species / strain / cell type:
S. typhimurium TA 1538
Metabolic activation:
with and without
Metabolic activation system:
liver microsomal fractions from male rats prepared by "established methods"
Test concentrations with justification for top dose:
10, 100, 333, 667, and 1000 µg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: ethanol
- Justification for choice of solvent/vehicle: solubility
Controlsopen allclose all
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
sodium azide
Remarks:
TA100, TA1535 without metabolic activation
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 4-nitro-O-phenylenediamine
Remarks:
TA98, TA1537, TA1538 without metabolic activation
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: aminoanthracene
Remarks:
all strains with metabolic activation
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Preincubation period: none
- Exposure duration: no data

NUMBER OF REPLICATES:
- two independent experiments, both with and without metabolic activation
- each concentration (including controls) tested in triplicate

DETERMINATION OF CYTOTOXICITY
- Method: no data
Evaluation criteria:
To be considered positive in TA100, >=2x increase in revertants over spontaneous rate; in TA98, TA1535, TA1537 and TA1538, >=3x increase; alternatively a concentration-dependent increase irrespective of 2- or 3-fold increase
Statistics:
none

Results and discussion

Test resultsopen allclose all
Key result
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
other: not determined, but number of revertants reduced in TA 98 at 1000 µg/plate
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
other: not determined, but number of revertants not reduced at 1000 µg/plate
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: no data
- Effects of osmolality: no data
- Evaporation from medium: no data
- Water solubility: insoluble
- Precipitation: no data
- Other confounding effects: no data

RANGE-FINDING/SCREENING STUDIES: yes, no data presented

COMPARISON WITH HISTORICAL CONTROL DATA: no

ADDITIONAL INFORMATION ON CYTOTOXICITY: none
Remarks on result:
other: No mutagenic potential

Any other information on results incl. tables

Table 1 Revertants per plate (mean of 3 plates)

Concentration µg/plate

TA 98

TA100

TA1535

TA1537

TA1538

- S9

+ S9

- S9

+ S9

- S9

+ S9

- S9

+ S9

- S9

+ S9

Negative control

15.3

17.0

82.3

833.7

5.7

8.0

5.0

4.0

14.3

16.7

0*

15.3

15.7

83.3

77.3

8.3

8.3

7.0

5.0

14.7

15.0

10.0

14.0

19.0

70.7

80.3

10.7

9.7

3.0

5.0

14.3

14.0

100.0

9.3

15.3

85.0

82.0

7.7

9.0

4.0

4.3

14.7

15.7

333.3

11.7

15.7

80.0

79.7

8.0

12.3

4.7

5.0

15.0

15.3

666.6

12.0

12.7

74.0

82.3

8.3

6.3

4.3

5.3

14.0

15.3

1000

6.7

8.0

76.0

86.3

4.7

3.3

3.7

5.0

13.7

14.7

Positive control

1573

2337.7

1158

2414

601.7

345

109.7

85.3

1980

495.7

* Solvent control with

Applicant's summary and conclusion

Conclusions:
In a valid and reliable study, behenyl alcohol (C22) did not increase the reverse mutation rate in histidine dependent bacterial strains of Salmonella typhimurium in the presence or absence of metabolic activation at concentrations up to and including 1000 µg/plate. It is concluded that the test substance is negative for mutagenicity in bacteria under the conditions of the test.
Executive summary:

In the bacterial mutagenicity study, S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 1538 bacteria were incubated with 10, 100, 333, 667, and 1000 µg/plate of test material, with and without metabolic activation. The test material did not increase the reverse mutation rate in histidine dependent bacterial strains of Salmonella typhimurium in the presence or absence of metabolic activation up to limit concentration. The study concludes that the test substance is negative for mutagenicity in bacteria under the conditions of the test. The study was conducted according to a test protocol that is comparable to the appropriate OECD test guideline, with the exception that no cross linking strain was used. Read across to the registered substance is considered scientifically justified.