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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:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions (only single plating, dissimilar positive control substances), read-across

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1978
Report Date:
1978

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
; only single plating, dissimilar positive control substances
Principles of method if other than guideline:
Pre-guideline study; but the method used is similar to OECD test guideline 471
GLP compliance:
no
Remarks:
pre-GLP study
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): MCTR-25-78
- Physical state: slightly viscous yellowish liquid
- no further information on test substance

Method

Target gene:
his¯ (S. thyphimurium)
Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium, other: TA1535, TA1537, TA1538, TA98, and TA100
Species / strain / cell type:
Saccharomyces cerevisiae
Metabolic activation:
with and without
Metabolic activation system:
S9-mix from livers of Aroclor 1254 induced male Sprague-Dawley rats
Test concentrations with justification for top dose:
0.01, 0.1, 1.0, 5.0, and 10.0 µL/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: no data
Controls
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
50 µL solvent/plate
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: without S9-mix : ethylmethansulfonate (TA1535, TA100, D4 ), QM (TA1537), nitrofluoren (TA98, TA1538); with S9-mix: anthracene (TA1535, TA1537, TA1538, TA98, TA100, D4)
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Exposure duration: S. thyphimurium 48 h at 37°C ; S. cerevisiae 3 - 5 days at 30°C (nonactivation) or at 37°C (activation)
- Expression time (cells in growth medium): 48 h or 3-5 days

NUMBER OF REPLICATIONS: single plating

DETERMINATION OF CYTOTOXICITY
- Method: no data
Evaluation criteria:
Strains TA1535, TA1537, and TA 1538
If the solvent control value is within the normal range, a chemical that produces a positive dose response over three concentrations with the lowest increase equal to twice the solvent control value is considered to be mutagenic.
Strains TA98, TA100, and D4
If the solvent control value is within the normal range a chemical that produces a positive dose response over three concentrations with the highest increase equal to twice the solvent control value for TA100 and 2-3 times the solvent control value for strains TA98 and D4 is considered to be mutagenic. For these strains, the dose-response increase should start at approximately the solvent control value.
Reproducibility
If a chemical produces a response in a single test that cannot be reproduced in one or more additional runs, the initial positive test data lose significance.

Results and discussion

Test resultsopen allclose all
Species / strain:
S. typhimurium, other: TA1535, TA1537, TA1538, TA98, and TA100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
; at the highest doses some cytotoxicity was observed
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Species / strain:
Saccharomyces cerevisiae
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
; at the highest doses some cytotoxicity was observed
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
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

For detailed results, see Attached background material.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

Diisotridecyl adipate was not mutagenic as it did not increase the number of revertants in five strains of Salmonella typhimurium or in Saccharomyces cerevisiae strain D4 with or without metabolic activation in an Ames test performed similar to OECD TG 471.
Executive summary:

In a gene mutation assay according to Ames (1975), strains of Salmonella typhimurium (strains TA 98, TA 100, TA 1535, TA 1537, TA 1538) and Saccharomyces cerevisiae (strain D4) were exposed to diisotridecyl adipate at concentrations of 0.01, 0.1, 1.0, 5.0, and 10 µL/plate in the presence and absence of mammalian metabolic activation. Exposure was in agar (plate incorporation method) and only single plates were used per test concentration.

 

Diisotridecyl adipate was tested up to the limit concentration of 10 µL/plate, which exhibited slight toxicity. The positive controls induced the appropriate responses in the corresponding strains. Diisotridecyl adipate did not increase the number of revertants in the test strains used. There was no evidence of induced mutant colonies over background.

 

This study is classified as acceptable with restrictions due to some deviations from OECD test guideline 471 (only single plating, dissimilar positive control substances).