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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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
neither TA102 or WP2uvrA strains were used
GLP compliance:
yes
Remarks:
(ICI Central Toxicology Laboratory)
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 4,4'-dihydroxydiphenylsulphone
- Physical state: white powder
- Analytical purity: > 99% w/w
- Sample Reference: PMLRF013.03
- Stability under test conditions: stable under normal storage and test conditions

Method

Target gene:
Salmonella typhimurium: histidine operon
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:
Aroclor 1254 induced liver S9 mix
Test concentrations with justification for top dose:
Main experiment (Expt I): 0.32, 1.6, 8, 40, 200, 1000 µg/plate with and without S9 mix in all 5 tester strains.
Repeat experiment (Expt II): 1.6, 8, 40, 200, 1000, 5000 µg/plate with S9 mix in TA1535 and TA1537.
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
Controlsopen allclose all
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Positive control substance:
other: 2-Aminoanthracene for all strains
Remarks:
with S9 mix
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Positive control substance:
other: N-ethyl-N-nitro-N-nitrosoguanidine for TA100 and TA1535
Remarks:
without S9
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Positive control substance:
other: Acridine mutagen ICR191 for TA1537
Remarks:
without S9
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Positive control substance:
other: 4-Nitro-O-Phenylenediamine for TA1538
Remarks:
without S9
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Positive control substance:
other: Daunorubicin HCl for TA98
Remarks:
without S9
Details on test system and experimental conditions:
The Salmonella mutagenicity assay was conducted using the plate incorporation assay as described by Maron and Ames (Mutation Res. 113: 173-215, 1983).
Evaluation criteria:
A positive response in a individual experiment is achieved when one or both of the following criteria are met:
- a statistically significant dose-related increase in the number of revertant colonies is obtained,
- a two-fold or greater increase in the mean number of revertant colonies (over that observed for the concurrent solvent control plates) which is statistically significant, is observed at at least one dose level.

Results and discussion

Test resultsopen allclose all
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:
cytotoxicity
Remarks:
at 1000 and 5000 ug/plate
Vehicle controls validity:
valid
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
at 1000 ug/plate
Vehicle controls validity:
valid
Positive controls validity:
valid
Additional information on results:
RANGE-FINDING/SCREENING STUDIES: The dose range was selected following a dose-ranging study, where only TA100 strain was exposed to the test substance at concentrations of 5000-1.6 ug/plate in both the presence and absence of liver S9 mix. The test compound showed significant toxicity in strain TA100, both in the presence and absence of S9 at both 5000 and 1000 µg/plate. The dose range for the main experimental work was therefore set at 1000-0.32 ug/plate. In view of the lack of toxicity in the main experiment (+S9) with strains TA1535 and TA1537, the repeat experiment with these strains (+S9) was carried out over the dose range of 5000-1.6 µg/plate.

Applicant's summary and conclusion

Conclusions:
Interpretation of results:
negative

Under the conditions of this Ames test, 4,4'-dihydroxydiphenylsulphone was not mutagenic with and without metabolic activation in bacterial systems.
Executive summary:

This study was conducted according to OECD guideline 471 with deviations (neither TA102 or WP2uvrA strains were used) and is therefore reliable with restrictions. Five strains of Salmonella typhimurium (TA1535, TA1537, TA1538, TA98 and TA100) were exposed to the test substance at concentrations ranging from 0.16-1000 µg/plate with or/and without S9 mix. The test was repeated in strains TA1535 and TA1537 at concentrations ranging from 0.16-5000 µg/plate with S9 mix. The test substance did not induce any significant reproducible increases in the observed numbers of revertant colonies. The positive and solvent controls were valid. Under the conditions of this assay, 4,4'-dihydroxydiphenylsulphone gave an non-mutagenic response in both the presence and absence of S9 mix, in all five strains of Salmonella used.