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Toxicological information

Genetic toxicity: in vitro

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in vitro gene mutation study in bacteria
Type of genotoxicity: gene mutation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: comparable to guidelines: the comprehensive validation programme provided unequivocally identical results among the institutes

Data source

Reference Type:

Materials and methods

Principles of method if other than guideline:
largely acc. to OECD Guideline 471
GLP compliance:
testing lab.
Type of assay:
bacterial reverse mutation assay

Test material

Details on test material:
Na3.NTA.H20, commercial


Species / strain
Species / strain / cell type:
other: TA 98, 100, 1535, 1537, 1537, 1538; E. coli WP2 uvrA (trp+ reversion)
Metabolic activation:
with and without
Metabolic activation system:
rat liver S-9 mix
Test concentrations with justification for top dose:
3 - 3333 ug/plate (series of 7 sequential doses)
Details on test system and experimental conditions:
Liver S-9's were prepared from male Fischer 344 rats, B6C3F1 [C57B16 X C3H(He)] mice, and Syrian hamsters. The rats and mice were supplied to all laboratories by the NCI Carcinogenesis Testing Program and the hamsters were obtained by each laboratory from different suppliers. Livers were used from animals either without treatment or following treatment with Aroclor 1254 as described by Ames et al [1975]. The S-9 activation mixes were prepared daily, as needed.
The chernicals were from the Same batch used for the in vivo carcinogenicity bioassays conducted by the NCI/NTP. Each chemical was acquired by the NC.I Repository from the laboratory that had performed the in vivo bioassay and was reanalyzed for chemical purity (Midwest Research Institute, Kansas City, MO or Radian Corp., Austin, TX). Chemicals were not selected on the basis of the in vivo carcinogenicity test results because these results were not available, at that time, for all chemicals. Rather, an attempt was made to select those chemicals for which the experimental design (50 animalslgroup) was expected to provide conclusive carcinogenesis results.
The majority of chemicals were tested by the plate-incorporation procedure.
Each laboratory was asked to make its independent assessment of the dose ranges to be tested based on the solubility and toxicity of the test chemicals, but not to exceed 10.0 mg/plate. The doses were to be ordered in half-log increments. Chemicals were tested without activation, and with uninduced and Aroclor 1254-induced S-9's from rats, mice, and hamsters. All plates were prepared in triplicate, and concurrent positive and negative controls were run at all times.

Results and discussion

Test results
Species / strain:
other: TA 98, 100, 1535, 1537, 1537, 1538; E. coli WP2 uvrA (trp+ reversion)
Metabolic activation:
with and without
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
not specified
Untreated negative controls validity:
not specified
Positive controls validity:
not specified
Remarks on result:
other: all strains/cell types tested
Migrated from field 'Test system'.

Applicant's summary and conclusion

Interpretation of results (migrated information):