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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:
April to July 2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study, performed in conformity with GLP-principles
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report Date:
2002

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
GLP compliance:
yes (incl. certificate)
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): LZ1780 (identical with L-Carnitine-L-Tartrate)
- Physical state: white, crystalline solid
- Lot/batch No.: 00202
- Stability under test conditions: stable
- Storage condition of test material: ambient temperature

Method

Target gene:
not applicable
Species / strain
Species / strain:
other: the following five strains were used: Salmonella typhimurium strains TA98, TA100, TA102, TA1535 and TA 1537
Additional strain characteristics:
not applicable
Metabolic activation:
with and without
Metabolic activation system:
S9-liver fractions of Sprague-Dawley rats, induced with Aroclor 1254
Test concentrations with justification for top dose:
Concentration range in the main test (with metabolic activation): 100 - 5000 µg/plate
Concentration range in the main test (without metabolic activation): 100 - 5000 µg/plate
Vehicle:
Solvent: aqua ad iniectabilia
Controls
Negative controls:
yes
Solvent controls:
yes
Remarks:
(aqua ad iniectabilia)
True negative controls:
no
Positive controls:
yes
Positive control substance:
sodium azide
Remarks:
further positive control substances were used: 9-Aminoacridine, 2-Nitrofluorene, Methyl methanesulfonate without metabolic activation and 2-Anthracene amide, Cyclosphosphamide with metabolic activation.
Details on test system and conditions:
The first experiment was performed by the standard plate incorportaion method, whereas the second one was carried out by the preincubation method.
Evaluation criteria:
A mutagenic effect is significant when, at least in one strain, the number of revertants histidine+ is twice higher than that found in the control.
Statistics:
According to the OECD guideline 471, a statistical analysis of the data is not mandatory.

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:
no
Vehicle controls valid:
yes
Negative controls valid:
yes
Positive controls valid:
yes
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.
Species / strain:
S. typhimurium TA 102
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity:
no
Vehicle controls valid:
yes
Negative controls valid:
yes
Positive controls valid:
yes
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.
Additional information on results:
No signs of cytotoxicity were noted up to the highest tested concentration of 5000 µg/plate.

No mutagenic effect (no increase in revertant colony numbers as compared with controls) was observed up to the maximum concentration of 5000 µg/plate in any of the 5 test strains in two independent experiments without and with metabolic activation (plate incorporation or preincubation test).

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
ambiguous with metabolic activation
negative without metabolic activation

It can be stated that during the described mutagenicity test and under the experimental conditions reported, the test item did not induce gene mutations in the five strains tested.
Executive summary:

The assay was performed 2002 in compliance with GLP and in accordance with OECD 471/EU-method B.13/14. The test was performed with and without liver microsomal activation and used strains TA 1535, TA 1537, TA 1538, TA 98 and TA 100. Each concentration and the controls were tested in duplicate.

The test item was tested at five concentrations from100 up to 5000 µg/plate (main test).The plates incubated with the test item showed normal back­ground growth up to 5000 µg/plate with and without S9 mix in all strains used. No toxic effects, evident as a reduction in the number of revertants occurred in the test groups with and without metabolic activation. Cytotoxicity and precipitation was not observed.

The test item was found to be non-mutagenic in this test system.