Registration Dossier

Toxicological information

Genetic toxicity: in vitro

Currently viewing:

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions. (tester strains which were able to detect crosslinking/oxidising agents were not used)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979
Report Date:
1979

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
tester strains which were able to detect crosslinking/oxidising agents were not used
GLP compliance:
no
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): Tri-phenyl-phosphinoxid
- Physical state: solid
- Purity: not reported

Method

Target gene:
his-
Species / strain
Species / strain / cell type:
other: S. typhimurium TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Metabolic activation system:
S-9 mix from Aroclor 1254 induced rat livers
Test concentrations with justification for top dose:
4 - 2500 ug/plate
Vehicle / solvent:
acetone
Controls
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: without S-9 mix: N-Methyl-N'-nitro-N-nitroso-guanidine for all strains; with S-9 mix: cyclophosphamide for TA 100; 2-aminoanthracene for TA 100, TA 98, TA 1537
Details on test system and experimental conditions:
METHOD OF APPLICATION: plate incorporation, two independent trials

NUMBER OF REPLICATIONS: 3
Evaluation criteria:
substances were considered as positive in the Ames test if following criteria are fulfilled:
- doubling the spontaneous mutation rate
- dose-effect-relationship observed
- reproducibility of the results

Results and discussion

Test results
Species / strain:
other: S. typhimurium TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
2000 µg/plate
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

The TS was neither mutagenic in the Ames-test with metabolic activation by S-9 mix, nor without.
The amount of revertants was in the range of the negative controls
 (differences not significant):

Negative control groups (means ± SD):
              with S-9            without S-9
TA98
    test1: 33.25 ± 9.36      28.5  ± 5.8
             test2: 27    ± 4.08      34.75 ± 14.27   
TA100
  test1: 141.25 ± 15.97     107   ± 7.96
             test2: 97.75 ± 14.73     153.25 ± 9.03
TA1537 test1:
 8.25  ± 2.75      6.5   ± 3.42
             test2: 5.75  ± 1.71      4.5   ± 1.73

The TS demonstrated to be toxic for the Salmonella strains employed upon
 concentrations > 2000 µg/plate.

Positive controls showed a distinct increase in revertants in all experimental approaches.

 

Applicant's summary and conclusion