Biphenyl-2-ol

Genetic toxicity: in vitro

Administrative data

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:

1989

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP study, procedure similar to current guideline but without additional strain for the detection of crosslinking agents. No test article purity is given in the study report.

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report Date:

1989

Reference 2

Reference Type:

secondary source

Title:

O-Phenylphenol and its Sodium and Potassium Salts: A Toxicological Assessment

Author:

Bomhard, E. M. et al.

Year:

2002

Bibliographic source:

Crit. Rev. Toxicol. 32(6):551-626

Reference 3

Reference Type:

secondary source

Title:

Analysis of Genotoxicity and the Carcinogenic Mode of Action for Ortho-Phenylphenol

Author:

Brusick, D.

Year:

2005

Bibliographic source:

Environ Mol Mutagen 45:460-481

Materials and methods

Test guideline

Qualifier:

equivalent or similar to

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

(1997)

Deviations:

yes

Remarks:

no additional strain for the detection of crosslinking agents was included into this study and no test substance purity is given

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Reference

Name:

Unnamed

Type:

Constituent

Test material form:

solid: crystalline

Details on test material:

- Name of test material (as cited in study report): test article ID 02290
- Physical state: white crystalline solid
- Analytical purity: no data
- Storage condition of test material: room temperature

Method

Target gene:

his operon

Species / strain

Species / strain / cell type:

S. typhimurium, other: TA98, TA100, TA1535, TA1537, TA1538

Metabolic activation:

with and without

Metabolic activation system:

CO-factor supplemented liver S9 homogenate from Aroclor 1254 induced male Sprague Dawley rats and male Golden Syrian hamsters

Test concentrations with justification for top dose:

33, 67, 100, 333 and 667 (-S-9) or 1000 µg/plate (+S-9)

Vehicle / solvent:

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

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

2-nitrofluorene

sodium azide

other: 2-aminoanthracene

Remarks:

+S9: 2-Aminoanthracene 0.5 µg/plate (all strains); -S9: 2-nitrofluorene 1 µg/plate (TA98, TA1538), sodium azide 1 µg/plate (TA100, TA1535), 9-aminocacridine 75 µg/plate (TA1537)

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Exposure duration: 48 h

NUMBER OF REPLICATIONS: 3 plates in one experiment

DETERMINATION OF CYTOTOXICITY
- Method: evaluation of bacterial background lawn

Evaluation criteria:

For a test article to be evaluated as positive, it must cause at least a doubling in the mean revertants per plate of at least one tester strain. This increase in the mean number of revertants per plate must be accomponied by a dose response to increasing concentrations of the test article. If the study is to be judged positive solely on the basis of a dose-responsive, less than 3-fold increase in TA1537 or TA1538, the response must be confirmed in a repeat experiment.

Results and discussion

Test results

Species / strain:

S. typhimurium, other: TA98, TA100, TA1535, TA1537, TA1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

other: TA98: at 667 µg/plate (-S9) and 100 µg/plate (+S9); TA100: at 667 µg/plate (-S9/+S9),

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS:
None stated in the study report.

RANGE-FINDING/SCREENING STUDIES:
In a range-finding study with TA100 (+S9 and -S9) concentrations of 10-10,000 µg/plate in half-log steps were tested. The test revealed cytotoxicity at concentrations of 1000 µg/plate and above with metabolic activation and at 667 µg/plate and above without metabolic activation.

ADDITIONAL INFORMATION ON CYTOTOXICITY:
No positive responses were seen with tester strains TA100 and TA98 in the presence or absence of microsomal enzymes. Due to excessive cytotoxicity, the complete assay was repeated with a different dose range, but no positive reactions were noted. The test was also negative in TA1535, TA1537, and TA1538, with or without metabolic activation. The respective positive controls caused a strong increase in the number of revertants.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Table 1: Results of the definite assay with tester strains TA98 and TA100 with and without metabolic activation

Dose [µg/plate]	TA98	TA100
Metabolic activation: none
Vehicle control*	17±4	117±13
3.3	14±2	108±14
10	14±4	111±17
33	16±3	125±21
100	11±3	122±18
200	14±2	102±8
Positive control**	196±15	836±79
Metabolic activation: rat liver S9
Vehicle control*	19±7	148±17
3.3	-	136±1
10	21±3	137±10
33	20±2	129±1
100	19±5	146±11
333	15±3	108±12
500	12±2	-
Positive control**	644±43	846±18
Metabolic activation: hamster liver S9
Vehicle control*	20±3	128±5
10	20±2	145±16
33	18±6	148±6
100	24±3	155±2
333	14±2	138±14
500	20±9	95±10
Positive control**	1052±96	995±70

*Vehicle control: acetone (all strains +S9 and -S9)

**Positive controls: +S9: 2-aminoanthracene 0.5 µg/plate (TA98, TA100); -S9: 2-nitrofluorene 1 µg/plate (TA98) and sodium azide 1 µg/plate (TA100)

Table 2: Results of the definite assay with tester strains TA1535, TA1537 and TA1538 with and without metabolic activation

Dose [µg/plate]	TA1535	TA1537	TA1538
Metabolic activation: none
Vehicle control*	15±3	6±2	10±4
10	10±1	7±3	7±3
33	12±3	7±3	7±2
100	9±1	7±3	7±1
250	9±3	4±3	9±2
500	3±1	0±0	0±1
Positive control**	417±25	243±41	447±38
Metabolic activation: rat liver S9
Vehicle control*	13±8	13±4	13±4
10	11±2	9±0	13±2
33	15±5	12±3	12±4
100	12±2	10±2	14±5
333	11±3	7±3	12±1
667	2±1	0±1	3±1
Positive control**	44±6	40±16	532±42
Metabolic activation: hamster liver S9
Vehicle control*	12±3	7±1	13±2
10	13±7	11±1	12±4
33	13±2	10±3	13±6
100	12±3	6±1	10±2
333	12±4	8±1	11±2
667	4±2	1±1	4±3
Positive control**	77±1	92±10	1212±62

*Vehicle control: acetone (all strains +S9 and -S9)

**Positive controls: +S9: 2-aminoanthracene 0.5 µg/plate (TA1535, TA11537, TA1538); -S9: sodium azide 1 µg/plate (TA1535), 9-aminoacridine 75 µg/plate (TA1537) and 2-nitrofluorene 1 µg/plate (TA1538)

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative