Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

The genotoxic potential of the substance has been investigated in 3 in vitro tests, i.e. an Ames test, an HPRT test in V79 cells and an in vitro MNT test in V79 cells. All tests have been performed according to OECD guidelines and under vGLP regulation.

In the Ames test, an increase in the number of revertants was observed with metabolic activation only with 30% S9, not with 10% S9. This effect, however, occured in the precipitated concentration range only. No increase was observed without metabolic activation.

No mutagenicity was observed in an HPRT test with and without metabolic activation, when tested up to the limit of toxicity and precipitation.

Moreover, the substance was not mutagenic in an in vitro micronucleus assay.

Link to relevant study records

Referenceopen allclose all

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2011-08-25 to 2011-11-17
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Version / remarks:
adopted 21 July 1997
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of assay:
bacterial reverse mutation assay
Specific details on test material used for the study:
Designation: Art. 132720
Synonym: Avodiol
Chem. Name: 1-(4-tert-Butyl-phenyl)-3-(4-methoxy-phenyl)-propane-1,3-diol
CAS-No.: 955359-35-0
Batch: 11/LE/016 K1
Purity: 95.1% (w/w)
Appearance: White, solid
Released until: May 18, 2012
Storage: Tightly closed, dark at room temperature (15 to 25°C)
Target gene:
HIS operon (S. thyphimurium), TRP operon (E. coli)
Species / strain / cell type:
S. typhimurium TA 1535
Species / strain / cell type:
S. typhimurium TA 1537
Species / strain / cell type:
S. typhimurium TA 98
Species / strain / cell type:
S. typhimurium TA 100
Species / strain / cell type:
S. typhimurium TA 102
Species / strain / cell type:
E. coli WP2 uvr A
Metabolic activation:
with and without
Metabolic activation system:
liver S9 mix from Aroclor 1254-pretreated rats with standard co-factors
Test concentrations with justification for top dose:
The test material concentrations were used selected according to the EC and OECD guidelines for this test system:
1st series: 5.00, 15.8, 50.0, 158, 500, 1580 and 5000 µg per plate
2nd series: 5.00, 15.8, 158, 500, 889 and 1580 µg per plate
3rd series: 250, 500, 750, 1000, 1250, 1500, 2000, and 2500 µg/plate
Vehicle / solvent:
DMSO
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
4-nitroquinoline-N-oxide
9-aminoacridine
sodium azide
benzo(a)pyrene
cumene hydroperoxide
other: Daunomycin, 2-Aminoanthracene
Details on test system and experimental conditions:
according to guideline
Rationale for test conditions:
The test conditions were chosen as described in OECD 471.
Evaluation criteria:
Definitions:
The assessment of test material-induced effects is dependent on the number of spontaneous revertants of each bacterial strain (solvent controls) and the in-crease in the number of revertants at the test material concentration which shows the highest number of colonies. The following criteria, based upon the historical controls of the laboratory and statistical considerations, are established:


Mean Number of Colonies Maximal Mean Number of Colonies over the Actual
(Solvent Control) Solvent Control
(Test Material)
<=10 <=9 >=30
<=30 <=19 >= 40
<=80 <=29 >=80
<=200 <=49 >=120
<=500 <=79 >=200

Assessment: "No Increase" "Clear Increase"

All further results, ranging between "no" and "clear", are assessed as "weak in-creases".
Interpretations:
A test material is defined as non-mutagenic in this assay if
• "no" or "weak increases" occur in the first and second series of the main ex¬periment. ("Weak increases" randomly occur due to experimental variation.)

A test material is defined as mutagenic in this assay if
• a dose-related (over at least two test material concentrations) increase in the number of revertants is induced, the maximal effect is a "clear increase", and the effects are reproduced at similar concentration levels in the same test system;
• "clear increases" occur at least at one test material concentration, higher concentrations show strong precipitation or cytotoxicity, and the effects are reproduced at the same concentration level in the same test system.

In all further cases, a third test series with the bacterial strain in question should be performed. If the criteria for a positive test result are not fulfilled in at least two out of the three series, the test material is defined as being non-mutagenic in this test system.

Statistics:
Dunnett's test
Species / strain:
S. typhimurium TA 98
Metabolic activation:
without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 100
Metabolic activation:
without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 102
Metabolic activation:
without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1537
Metabolic activation:
without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with
Genotoxicity:
positive
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 102
Metabolic activation:
with
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
with
Genotoxicity:
positive
Cytotoxicity / choice of top concentrations:
no cytotoxicity, but tested up to precipitating concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1537
Metabolic activation:
with
Genotoxicity:
positive
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
with
Genotoxicity:
positive
Cytotoxicity / choice of top concentrations:
no cytotoxicity, but tested up to precipitating concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Remarks on result:
other: 10% S9: negative; 30% S9: positive

The investigations for the mutagenic potential of the test item were performed using Salmonella typhimurium tester strains TA 98, TA 100, TA 102, TA 1535 and TA 1537, and Escherichia coli WP2 uvrA. The plate incorporation test with and without addition of liver S9 mix from Aroclor 1254-pretreated rats was used. Thwo independent series were performed without metabolic activation. Three independent experimental series were performed with S9 mix as the metabolic activation system. In the three series with S9 mix, 10 % S9 in the S9 mix were used in the 1st and 30 % in the 2nd and 3rd series, respectively.

The test item was dissolved in dimethyl sulfoxide (DMSO) and tested at concentrations ranging from 5.00 to 5000 µg/plate. Precipitation of the test material on the agar plates occurred at con-centrations ≥ 500 µg/plate. Toxicity to the bacteria was observed at concentrations ≥ 889 µg/plate.

Daunomycin, sodium azide, 9-aminoacridine, 4-nitroquinolin-N-oxide and cumene hydroperoxide served as strain specific positive control test materials in the absence of S9 mix. 2-Aminoanthracene and benzo[a]pyrene were used for testing the bacteria and the activity of the S9 mix. Each treatment with the test materials used as positive controls led to a clear increase in revertant colonies, thus, showing the expected reversion properties of all strains and good meta-bolic activity of the S9 mix used.

Without addition of S9 mix and with addition of S9 mix containing 10% S9 as the external metabolizing system,the test item was not mutagenic under the conditions described. After addition of S9 mix containing 30% S9 in the 2nd and 3rd series as the external metabolizing system, Art. 132720 induced an increase in the number of revertants at concentrations ≥ 1500 µg per plate, i.e. in the precipitated concentration range only.

It can be concluded that after metabolic activation, the test item was mutagenic to bacteria under the experimental conditions described. These effects, however, occurred in the precipitated concentration range only.

Conclusions:
Based on all this data, the test item was positive in this bacterial mutagenicity assay.
The test item was negative in the Ames test without metabolic activation and with metabolic activation when S9 mix containing 10% S9 was used as the metabolic activation system. However, the test item was mutagenic to bacteria in case S9 mix containing 30% S9 was used as the metabolic activation system.
Executive summary:

The test item was negative in the Ames test without metabolic activation and with metabolic activation when S9 mix containing 10% S9 was used as the metabolic activation system. However, the test item was mutagenic to bacteria in case S9 mix containing 30% S9 was used as the metabolic activation system.

Taking together, the test item was positive in this bacterial mutagenicity assay.

Endpoint:
in vitro gene mutation study in mammalian cells
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2012-05-31 to 2012-10-12
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
Version / remarks:
adopted 21 July 1997
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.17 (Mutagenicity - In Vitro Mammalian Cell Gene Mutation Test)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of assay:
other: In vitro mammalian cell gene mutation assay (HPRT)
Specific details on test material used for the study:
Designation: Art. 132720
Synonym: Avodiol
CAS-No.: 955359-35-0
Batch: 11/LE/016K1
Purity: 94.7% (w/w)
Appearance: white solid
Released until: 2013-04-04
Species / strain / cell type:
Chinese hamster lung fibroblasts (V79)
Additional strain / cell type characteristics:
not applicable
Metabolic activation:
with and without
Metabolic activation system:
S9 mix from Aroclor 1254 treated male Wistar rats
Test concentrations with justification for top dose:
V79 cells were exposed to concentrations of the test item ranging from 5.00 to 500 µg/mL (without and with S9 mix). Concentrations ≥ 158 µg/mL exhibited a macroscopically visible precipitation in the culture medium. Test material related cytotoxic effects, i.e. a clear decrease in the number of cells at days 5 or 8 of the experiments (cf. Table 1), were seen at concentrations ≥ 50 µg/mL in the absence of S9 mix. Hence, solubility and toxicity of the test material were the limiting factors for dose selection in the current study. Thus, concentrations from 5.00 up to 50.0 µg/mL in the absence and from 15.8 to 500 µg/mL in the presence of S9 mix were evaluated.

Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO, Acetone
- Justification for choice of solvent/vehicle:
DMSO (0.1% final concentration) and Acetone (0.1% final concentration) were used as solvents. Analysis of the historical data of the laboratory and experience of other research groups showed that such amounts of the selected solvents have no influence on the mutation frequency in this test system. For this reason the respective solvent control is the only negative control used in the present study.
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
7,12-dimethylbenzanthracene
other: N-Methyl-N'-nitro-N-nitrosoguanidine
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium
- Cell density at seeding: 1.5 x 10^6 cells in 30 mL culture medium

DURATION
- Preincubation period:
- Exposure duration: without S9 mix: 24 hours (1st series) and 3 hours (2nd series);
with S9 mix: 3 hours each series
- Expression time (cells in growth medium): 72 hours
- Selection time (if incubation with a selection agent):
- Fixation time (start of exposure up to fixation or harvest of cells):

SELECTION AGENT (mutation assays): 6-Thioguanine

NUMBER OF REPLICATIONS: Two parallel cultures per concentration were treated with the test item and the positive controls. Three parallel cultures were established for the solvent control.

NUMBER OF CELLS EVALUATED:

DETERMINATION OF CYTOTOXICITY
- Method: cloning efficiency; relative total growth; other:
- Any supplementary information relevant to cytotoxicity:

- OTHER:
Rationale for test conditions:
Test conditions were selected according to Guideline
Evaluation criteria:
Positive controls:
MNNG and DMBA at the selected concentrations should cause a 4-fold or greater increase in the mean mutation frequency of the current experimental series.

Criteria for negative and positive results
The effects of the test item upon the mutation frequency is defined as
• "No increase" in the mutation frequency if the mean frequency of the two parallel incubations of a given test material concentration is less than 2.0-fold above the mean of the actual negative controls or the mean mutation frequency is < 20.0 x 10-6.
• "Clear increase" in the mutation frequency if the test material induces at least a 4.0-fold increase above the mean of the actual negative controls and the mean mutation frequency for a given test material concentration is > 40.0 x 10-6.
• All other results are defined as a "weak increase" of the mutation frequency.
A test item is assessed as negative or non-mutagenic in this test system if
• no effect (no increase in the mutation frequency) occurs in the two independent experimental series performed or
• a weak effect (weak increase) occurs in one series and no effect (no increase) in the other series of experiments.
Confirmation of negative results is not considered necessary if these criteria are fulfilled.
A test item is assessed as positive or mutagenic in this test system if
• a clear effect (clear increase in the mutation frequency) occurs at similar concentrations of the test material in the two independent experiments performed,
• a clear effect (clear increase) occurs in one series and a weak effect (weak increase) in the other series of experiments at identical concentrations, or
• weak effects (increases) occur dose-dependently (over at least two test material concentrations) and reproducibly at identical concentrations in the two experimental series performed.
Key result
Species / strain:
Chinese hamster lung fibroblasts (V79)
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: Concentrations ≥ 158 µg/mL exhibited a macroscopically visible precipitation in the culture medium

RANGE-FINDING/SCREENING STUDIES: The concentrations of the 1st test series were selected based on the results of two studies conducted earlier (Simon, 2012, study numbers T18318 and T18193).

HISTORICAL CONTROL DATA (with ranges, means and standard deviation and confidence interval (e.g. 95%)
- Positive historical control data: MNNG (1.00 µg/mL; without S9 mix): 1458 +/- 1181
DMBA (5.00 to 20.0 µg/mL; with S9 mix): 649 +/- 665
- Negative (solvent/vehicle) historical control data: without S9 mix: 7.26 +/- 5.08
with S9 mix: 5.80 +/- 4.35

The test item was investigated for induction of gene mutations at the HPRT locus in V79 Chinese hamster cells in vitro. The test item was dissolved in dimethyl sulfoxide (DMSO) and was tested in two independent experimental series in both the presence and absence of an exogenous metabolizing system (S9 mix from livers of rats pretreated with Aroclor 1254). Cells were exposed to the test item, the respective positive control or the solvent (as negative control) for 24 hours (first series) and 3 hours (second series) in the absence and 3 hours (both series) in the presence of S9 mix. Two parallel cultures per concentration were treated with the test item and the positive controls. Three parallel cultures were established for the negative/solvent control.

V79 cells were exposed to concentrations of the test item ranging from 5.00 to 500 µg/mL (in the absence or presence of S9 mix). Test item related cytotoxic effects, i.e. a clear decrease in the number of cells at days 5 or 8 of the experiments, were seen at concentrations ≥ 50 µg/mL in the absence of S9 mix (3 and 24 hours exposure time). No relevant change was observed for the cloning efficiency.

Concentrations ≥ 158 µg/mL exhibited a macroscopically visible precipitation in the culture medium. Hence, solubility and toxicity of the test item were the determinant factors for selection of test concentrations for evaluation in the current study.

N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG, 1 µg/mL) and 7,12-dimethylbenz[a]anthracene (DMBA, 10 µg/mL) served as positive controls in the absence and presence of S9 mix, respectively. The positive controls induced the expected clear increase in the mutation frequency.

In the absence and presence of S9 mix, the test item did not significantly increase the mutation frequency of V79 cells as compared to the current solvent controls. According to the predetermined criteria for the evaluation of results, the test item was clearly negative in this test system.

In conclusion, the test item was not mutagenic in the V79 mammalian cell gene mutation test up to the limit of toxicity and precipitation under conditions where the positive controls exerted potent mutagenic effects.

Conclusions:
In conclusion, the test item was not mutagenic in the V79 mammalian cell gene mutation test up to the limit of toxicity and precipitation under conditions where the positive controls exerted potent mutagenic effects.
Executive summary:

In conclusion, the test item was not mutagenic in the V79 mammalian cell gene mutation test up to the limit of toxicity and precipitation under conditions where the positive controls exerted potent mutagenic effects.

Endpoint:
in vitro cytogenicity / micronucleus study
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2012-04-26 to 2012-09-04
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 487 (In vitro Mammalian Cell Micronucleus Test)
Version / remarks:
adopted: 22 July 2010
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of assay:
in vitro mammalian cell micronucleus test
Specific details on test material used for the study:
Designation: Art. 132720
Synonym: Avodiol
CAS-No.: 955359-35-0
Batch: 11/LE/016K1
Purity: 94.7% (w/w)
Appearance: white solid
Released until: 2013-04-04
Target gene:
not relevant
Species / strain / cell type:
Chinese hamster lung fibroblasts (V79)
Additional strain / cell type characteristics:
not applicable
Metabolic activation:
with and without
Metabolic activation system:
S9 mix from Aroclor 1254 treated male Wistar rats
Test concentrations with justification for top dose:
Without S9 mix, [µg/mL]: 0.050; 0.158; 0.50; 1.58; 5.00; 8.89; 15.8; 28.1; 50.0; 88.9 and 158 µg/mL
With S9 mix [µg/mL]: 25.0; 50.0; 60.0; 70.0; 80.0 and 90.0 µg/mL

For the experiment with metabolic activation, concentrations were selected based on the results of a dose-range finding study.
For experiments without metabolic activation, no screening data were available. Therefore, initial concentrations were applied according to OECD 487. The test item was soluble up to a concentration of 5000 µg/mL in DMSO. The final solvent concentration in cell culture medium was 1.0%.
According to these criteria, the concentrations outlined in the tables section were selected for the main study in the presence and absence of S9 mix.
Vehicle / solvent:
- Vehicle/solvent used: DMSO
- Justification for choice of solvent/vehicle:Solubility of the test item
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Positive control substance:
7,12-dimethylbenzanthracene
mitomycin C
other: Griseovulvin
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium
- Cell density at seeding (if applicable): 5 x 10^4 cells in 5 mL culture medium

DURATION
- Exposure duration: 3 hours and 24 hours in the absence and 3 hours in the presence of S9 mix
- Fixation time (start of exposure up to fixation or harvest of cells): 24 hours

STAIN (for cytogenetic assays): May-Grünwald and Giemsa solutions

NUMBER OF REPLICATIONS:

METHODS OF SLIDE PREPARATION AND STAINING TECHNIQUE USED:

NUMBER OF CELLS EVALUATED:

NUMBER OF METAPHASE SPREADS ANALYSED PER DOSE (if in vitro cytogenicity study in mammalian cells):

CRITERIA FOR MICRONUCLEUS IDENTIFICATION:

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; cloning efficiency; relative total growth; other:
- Any supplementary information relevant to cytotoxicity:

OTHER EXAMINATIONS:
- Determination of polyploidy:
- Determination of endoreplication:
- Methods, such as kinetochore antibody binding, to characterize whether micronuclei contain whole or fragmented chromosomes (if applicable):

- OTHER:
Rationale for test conditions:
According to OECD TG 487
Evaluation criteria:
Test materials are assessed as negative or non-mutagenic in this test system if
• the assay is considered valid and
• no relevant increase in the mutation frequency (at least a 2-fold) occurs.
Test materials are assessed as positive or mutagenic in this test system if
• the assay is considered valid and
• clear increase in the micronucleus frequency (at least a 3-fold) occurs dose-dependently (over at least two test material concentrations) or reproducibly at identical concentrations in two independent experimental series performed and
• the maximal test material-induced value is above the highest value of the historical negative control value
Statistics:
not applicable
Key result
Species / strain:
Chinese hamster lung fibroblasts (V79)
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid

The test item was dissolved in dimethyl sulfoxide (DMSO) and screened for its ability to induce micronuclei in V79 Chinese hamster cells. The study was conducted in the absence and presence of an exogenous metabolizing system (S9 mix from livers of rats pretreated with Aroclor 1254). The exposure time was 3 hours and 24 hours in the absence and 3 hours in the presence of S9 mix.

The concentrations tested were selected on the basis of solubility and cytotoxicity characteristics of the test material. The test item precipitated in the culture medium at concentrations ≥ 500 µg/mL and was cytotoxic to the V79 cells at concentrations ≥ 50.0 µg/mL in the absence and at concentrations ≥ 80.0 µg/mL in the presence of S9 mix. Concentrations ranging from 0.50 to 70.0 µg/mL were evaluated for micronuclei.

Negative (solvent) and positive control treatments were included in each experiment in the absence and presence of S9 mix. Micronucleus frequencies in negative control cultures fell within normal ranges, and clear increases were induced by the positive control chemicals Griseofulvin and Mitomycin C (without S9 mix) and 7,12-dimethylbenz[a]anthracene (with S9 mix). Therefore the study was accepted as valid.

No relevant increase in micronucleus frequency was observed following treatment with the test item in neither the absence nor presence of S9 mix. It is therefore concluded that the test item was non-mutagenic in this test system under conditions where the positive controls exerted potent mutagenic effects.

Conclusions:
It is concluded that the test item was non-mutagenic in this test system under conditions where the positive controls exerted potent mutagenic effects.
Executive summary:

No relevant increase in micronucleus frequency was observed following treatment with the test item in neither the absence nor presence of S9 mix. It is therefore concluded that the test item was non-mutagenic in this test system under conditions where the positive controls exerted potent mutagenic effects.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

No in vivo tests have been performed.

Mode of Action Analysis / Human Relevance Framework

Avodiol was negative in the Ames test without metabolic activation and with metabolic activation when 10% S9 mix was used, up to the highest test item concentration tested. However, an increase of the S9 mix concentration to 30% resulted in an increase in the number of revertants. The analysis of the chemical structure of Avodiol with different (Q)SAR/in silico tools, i.e. DEREK Nexus v.5.0.1 and Sarah Nexus v.2.0.1 does not result in any alert for genotoxicity. Moreover, butyl methoxydibenzoylmethane (BMDBM), a common used UV filter with a close analogue structure as Avodiol (2 keto groups in BMDBM instead of 2 alcohol groups for Avodiol) is negative in the Ames test.

The positive result of Avodiol in the Ames test at high S9 mix concentrations might be explained by redox processes which occur at high concentrations only and which are not relevant for the in vivo situation.

Additional information

Justification for classification or non-classification

The substance must not be classified with regard to genetic toxicity.