Registration Dossier

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: well documented study, a reliability of 2 is assigned

Data source

Reference
Reference Type:
publication
Title:
Nonmutagenicity of maleic acid and its sodium salts in Salmonella assays
Author:
Lake RS, DeVito GL, Szot RJ, Schwartz E
Year:
1988
Bibliographic source:
Mutation Research 207: 1-5

Materials and methods

Principles of method if other than guideline:
According to Ames et al. (1975, revised 1981) and Maron et al. (1983).
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Maleic acid, from EM Sciences, Darmstadt, no data on purity

Method

Target gene:
his-
Species / strain
Species / strain:
other: Salmonella typhimurium TA98, TA100, TA1535, TA1537, TA1538
Metabolic activation:
with and without
Metabolic activation system:
Aroclor-1254-induced male rat liver S9 mix
Test concentrations with justification for top dose:
0 - 7500 µg/plate (4 dose groups)
Vehicle:
nutrient broth
Controls
Solvent controls:
yes
Positive controls:
yes
Positive control substance:
other: see below
Details on test system and conditions:
METHOD OF APPLICATION: in agar (plate incorporation)

NUMBER OF REPLICATIONS: 3

POSITIVE CONTROLS:
TA 1535 NaAz 5.00 µg/p1ate - S9, 2-AA 2.5 µg/plate + S9;
TAI00 NaAz 5.00 µg/plate - S9, 2-AA 2.5 µg/pIate +S9;
TA 1537 NaAz 75.00 µg/plate -S9, 2-AA 2.5 µg/plate +S9;
TA1538 2-NF 5.00 µg/plate -S9, 2-AA 2.5 µg/plate +S9;
TA98 2-NF 5.00 µg/plate - S9, 2-AA 2.5 µg/pIate + S9


Statistics:
Treatment-related effects and dose-response trends were calculated using the statistical model of Snee and Irr (1984).

Results and discussion

Test results
Species / strain:
other: Salmonella typhimurium TA98, TA100, TA1535, TA1537, TA1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity:
other: > 7500 µg/plate
Vehicle controls valid:
yes
Positive controls valid:
yes
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

Maleic acid dose levels above 7.5 mg/plate were highly cytotoxic; at doses as high as 7.5 mg/plate, initial pH was as low as 2.4; according to  the authors, no dose-related or statistically significant changes were observed.

Applicant's summary and conclusion