L-malic acid

Genetic toxicity: in vitro

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

Reference

Reference 1

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 2

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

Test material information

Constituent 1

Reference substance name:

L-malic acid

EC Number:

202-601-5

EC Name:

L-malic acid

Cas Number:

97-67-6

Molecular formula:

C4H6O5

IUPAC Name:

malic acid

Test material form:

solid

Specific details on test material used for the study:

dl-malic acid
99.7%

Method

Species / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium, other: TA92

Species / strain 2

Species / strain / cell type:

S. typhimurium, other: TA94

Species / strain 3

Species / strain / cell type:

S. typhimurium TA 98

Species / strain 4

Species / strain / cell type:

S. typhimurium TA 100

Species / strain 5

Species / strain / cell type:

S. typhimurium TA 1535

Species / strain 6

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 results

Test results 1

Species / strain:

S. typhimurium, other: TA92

Metabolic activation:

with and without

Genotoxicity:

negative

Test results 2

Species / strain:

S. typhimurium, other: TA94

Metabolic activation:

with and without

Genotoxicity:

negative

Test results 3

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Test results 4

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Test results 5

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Test results 6

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Applicant's summary and conclusion

Conclusions:

Malic Acid was not mutagenic.