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Toxicological information

Genetic toxicity: in vitro

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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

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989
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 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