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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:
January 3 - February 21, 1992
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions (E. coli strain is missing)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
E. coli strain is missing
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Purity: 99%
- Physical state: clear, colorless liquid
- Storage Conditions: -20+/-5°C; protected from exposure to light
- Expiration date: 1992-06-30

Method

Species / strain
Species / strain / cell type:
other: S. typhimurium TA98, TA100, TA1535, TA1537, TA1538
Metabolic activation:
with and without
Metabolic activation system:
Aroclor 1254-induced rat liver S-9
Test concentrations with justification for top dose:
0.3, 1.0, 3.3, 10, 33, 100, 33, 1000, 3333, 5000 µg/plate
Vehicle / solvent:
- Vehicle/solvent used: water (CAS# 7732-18-5)
Controls
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Remarks:
With S9: 1 µg/plate 2-aminoanthracene (all strains); without S9: 1 µg/plate 2-nitrofluorene (TA98, TA1538), 1 µg/plate sodium azide (TA100, TA1535), 75 µg/plate 9-aminoacridine (TA1537)
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation)
NUMBER OF REPLICATIONS: 3 plates
NUMBER OF EXPERIMENTS: 3 individual experiments were conducted (dose range-finding study, mutagenicity study, and confirmatory study)
DETERMINATION OF CYTOTOXICITY: condition of the bacterial background lawn
Evaluation criteria:
To be evaluated positive, there must be an increase of revertants by factor >= 2 (TA 98, TA 100) or factor >= 3 (TA 1535, TA 1537, TA 1538) at the peak of the dose response.

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:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Vehicle controls validity:
valid
Positive controls validity:
valid

Any other information on results incl. tables

Frequency of mutants (confirmatory assay):

 

TA98

TA100

TA1535

TA1537

TA1538

 

- S-9

+ S-9

- S-9

+ S-9

- S-9

+ S-9

- S-9

+ S-9

- S-9

+ S-9

Vehicle control

13

(16)

28

(27)

134

(153)

208

(187)

12

(13)

14

(17)

6

(5)

9

(9)

8

(6)

12

(12)

Treatments

12-19

(16-18)

26-33

(28-33)

124-144

(141-158)

180-212

(171-196)

10-13

(9-14)

11-14

(11-15)

5-8

(5-6)

6-9

(6-12)

5-8

(6-9)

11-14

(10-13)

Positive control

169

(191)

717

(1513)

596

(699)

754

(1779)

377

(431)

76

(99)

434

(474)

96

(79)

388

(364)

1082

(831)

Result

negative

negative

negative

negative

negative

negative

negative

negative

negative

negative

 

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative in all strains with and without metabolic activation

Under the conditions of this study, the test substance has no mutagenic potential in Salmonella typhimurium strains TA98, TA100, TA1535. TA1537 and TA1538 tested with and without metabolic activation at dose levels up to 5000 μg/plate.
Executive summary:

The study is comparable to OECD Guideline 471 with acceptable restrictions (E. coli strain is missing), and GLP standards were fulfilled.

Salmonella typhimurium TA98, TA100, TA1535, TA1537 and TA1538 were tested in the plate incorporation assay with and without metabolic activation at dose levels of 0.3, 1.0, 3.3, 10, 33, 100, 33, 1000, 3333, 5000 µg/plate in 3 independent experiments. Water was used as the vehicle (CAS# 7732-18-5). No increase in the number of revertants was found in comparison to the concurrent vehicle control at any concentration in any strain. Neither precipitate nor appreciable toxicity was observed (but tested up to the recommended limit dose level of 5000 µg/plate). The vehicle control and the positive control values were valid.

Conclusion: Under the conditions of this study, the test substance has no mutagenic potential in Salmonella typhimurium strains TA98, TA100, TA1535. TA1537 and TA1538 tested with and without metabolic activation at dose levels up to 5000 μg/plate.