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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Primary mutagenicity screening of food additives currently used in Japan
Author:
Ishidate Jr M, Sofuni T, Yoshikawa K, Hayashi M, Nohmi T, Sawada M and Matsuoka A
Year:
1984
Bibliographic source:
Fd Chem Toxic 22, 623-636
Reference Type:
review article or handbook
Title:
Final Report on the Safety Assessment of Malic Acid and Sodium Malate
Author:
Fiume MZ, Bergfeld WF, Belsito DV, Klaassen CD, Schroeter AL, Shank RC, Slaga TJ, Snyder PW, and Andersen FA
Year:
2001
Bibliographic source:
Int J Toxicol 20 (Suppl 1): 47-55

Materials and methods

Principles of method if other than guideline:
Cells cultured overnight were pre-incubated with both the test sample and the S-9 mix for 20 min at 37°C before plating. Duplicate plates were used for each of six different concentrations of the sample. The number of revertant (his +) colonies was scored after incubation at 37°C for 2 days.
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Specific details on test material used for the study:
dl-malic acid
99.7%

Method

Species / strainopen allclose all
Species / strain / cell type:
other: TA92
Species / strain / cell type:
other: TA94
Species / strain / cell type:
S. typhimurium TA 98
Species / strain / cell type:
S. typhimurium TA 100
Species / strain / cell type:
S. typhimurium TA 1535
Species / strain / cell type:
S. typhimurium TA 1537
Metabolic activation:
with and without
Metabolic activation system:
The liver microsome fraction (S-9) was prepared from the liver of Fischer rats (Charles River Japan Co.) pretreated 5 days before with polychlorinated biphenyls (500 mg/kg body weight of Kanechlor KC-400 in olive oil, ip).
Test concentrations with justification for top dose:
max dose 10 mg/plate (equivalent to 5 mg/plate L-malic acid)
Vehicle / solvent:
phosphate buffer
Evaluation criteria:
The result was considered positive if the number of colonies found was twice the number in the control (exposed to the appropriate solvent or untreated). If no reasonable dose response was detected, additional experiments using different doses or induced mutation frequency assays (Yoshikawa, Nakadate, Watabe et al. 1980) were performed.

Results and discussion

Test resultsopen allclose all
Species / strain:
other: TA92
Metabolic activation:
with and without
Genotoxicity:
negative
Species / strain:
other: TA94
Metabolic activation:
with and without
Genotoxicity:
negative
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with and without
Genotoxicity:
negative
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
with and without
Genotoxicity:
negative
Species / strain:
S. typhimurium TA 1537
Metabolic activation:
with and without
Genotoxicity:
negative

Applicant's summary and conclusion

Conclusions:
Malic Acid was not mutagenic.