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
Study period:
1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report Date:
1990

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): N-heptylamine
- Physical state: colorless liquid
- Analytical purity: 99.04%
- Purity test date: 1989-09-07
- Lot/batch No.: 8905P0172

Method

Target gene:
Histidine operon
Species / strain
Species / strain:
other: S. typhimurium TA 1535, TA 1537, TA 1538, TA 98 and TA 100
Metabolic activation:
with and without
Metabolic activation system:
Aroclor 1254 induced rat liver S9
Test concentrations with justification for top dose:
50, 100, 500, 1000, 2500, 5000 and 10000 µg/plate
Vehicle:
- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: no data
Controls
Negative controls:
no
Solvent controls:
yes
Remarks:
DMSO, solvent
True negative controls:
no
Positive controls:
yes
Positive control substance:
9-aminoacridine
2-nitrofluorene
sodium azide
other: 2-aminoanthracene
Details on test system and conditions:
METHOD OF APPLICATION: preincubation

DURATION
- Preincubation period: 20 minutes
- Exposure duration: 48 hours

DETERMINATION OF CYTOTOXICITY
- Method: decrease in the number of colonies per plate/control groups
Evaluation criteria:
Evaluation criteria:
- Number of the revertant His+ colonies per plate increased at least two fold compared to the negative/vehicle control
- Dose-response relationhip
- Reproductibility
Statistics:
No data

Results and discussion

Test results
Species / strain:
other: S. typhimurium TA 1535, TA 1537, TA 1538, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity:
yes
Remarks:
Cytotoxicity from 1000 µg/plate
Vehicle controls valid:
yes
Negative controls valid:
not examined
Positive controls valid:
yes
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.
Additional information on results:
RANGE-FINDING/SCREENING STUDIES:
-Two strains studied: 1000, 5000 and 10000 µg/plate for TA98; 100, 500, 1000 and 5000 µg/plate for TA100.
-Triplicate assays

COMPARISON WITH HISTORICAL CONTROL DATA: no

ADDITIONAL INFORMATION ON CYTOTOXICITY: Without metabolic activation, concentrations up to 1000 µg/plate caused an important cytotoxicity on TA98 and TA100 strains. With metabolic activation, only concentrations of 5000 and 10000 µg/plate were toxic on TA98 and concentration of 5000µg/plate on TA100.

Applicant's summary and conclusion

Conclusions:
Results of the two studies confirm the absence of genotoxicity for the test item N-heptylamine at the higher concentration of 2500 µg/plate and at the lesser concentrations, with and without metabolic activation.
Executive summary:

The potential of the test item N-heptylamine to induce reverse mutation in Salmonella typhimurium (strains: TA 1535, TA 1537, TA 1538, TA 98 and TA 100) was evaluated in accordance with the international guidelines (OECD 471, Commission Directive No. B13/14) in compliance with the Principles of Good Laboratory Practice.

The test item was tested in two independent experiments, with and without a metabolic activation system, both performed according to preincubation method. Bacterias were exposed to the test item at five dose-levels (three plates/dose-level) selected from a preliminary toxicity test: 50, 100, 500, 1000 and 5000µg/plate. After 48 of incubation at 37°C, the revertant colonies were scored.

 

The test item did not induce any noteworthy increase in the number of revertants, both with and without S9 mix, in any of the five strains.

Under our experimental conditions, N-heptylamine did not show any mutagenic activity in the bacterial reverse mutation test with Salmonella typhimurium.