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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1990-11-02 - 1991-02-28
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
Version / remarks:
(1983)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.10 (Mutagenicity - In Vitro Mammalian Chromosome Aberration Test)
GLP compliance:
yes
Type of assay:
in vitro mammalian chromosome aberration test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
Dodecane-12-lactam of Atochem SA, batch no. 9611, purity determined by NMR: no impurities > 0.5 % detectable

Method

Target gene:
not applicable
Species / strain
Species / strain / cell type:
lymphocytes: Human
Details on mammalian cell type (if applicable):
Human lymphocyte cultures from a single male donor, duplicate cultures
Metabolic activation:
with and without
Metabolic activation system:
male Sprague-Dawley rat liver post-mitochondrial fraction (S-9) from Aroclor 1254 induced animals
Test concentrations with justification for top dose:
30.06; 37.58; 46.98; 58.72; 73.40; 91.75; 114.7; 143.4; 179.2; 224.0; 280.0; 350.0 mg/l
Vehicle / solvent:
Solvent: dimethyl sulfoxide (DMSO)
Controls
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Remarks:
solvent
True negative controls:
yes
Positive controls:
yes
Positive control substance:
cyclophosphamide
methylmethanesulfonate
Details on test system and experimental conditions:
- No. of metaphases analyzed: 100 from each culture if possible, i.e. 200 metaphases / dose group
- Number of replicates: 2
- Application:
with S-9: 3 hours treatment + 17 or 41 h recovery period
without S-9: 20 or 44 h treatment
Chromosome aberrations were analysed in cells sampled 20 hours after the start of treatment at 3 consecutive dose levels. The highest concentrations chosen for analysis at this time, 280 and 350 ug/ml, induced approximately 61% and 46% mitotic inhibition in the absence and presence of S-9, respectively.
Evaluation criteria:
The proportions of cells with structural aberrations excluding gaps for each treatment condition were compared with the proportion in negative controls using Fisher's exact test, p <= 0.05; binominal dispersion test demonstrated acceptable homogenity between replicate cultures; proportion of cells with strucural aberrations without gaps in negative controls fell within the normal range; at least 160 cells out of an intended 200 were analysable at each treatment level; positive control chemicals both induced clear increases in number of cells with structural aberrations; test chemical is considered to be positive if: statistically significant increases in the proportion of structurally aberrant cells without gap ocurred at one or more concentrations and the proportion of aberrant cells at such data points exceeded the normal range; increases in numbers of cells with gaps or increases in numbers of cells with structural aberrrations not exceeding the normal range or occuring only at very high or toxic concentrations were likely to be concluded as "equivocal" or "probably of no biological importance". Cells with exchange aberrations or cells with greater than one aberration were to be considered of greater biological significance
Statistics:
Fisher's exact test, p <= 0.05

Results and discussion

Test results
Key result
Species / strain:
lymphocytes: Human
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
- With metabolic activation: 46 % mitotic inhibition at 350 mg/l - Without metabolic activation: 61 % mitotic inhibition at 280 mg/l
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
Treatment of cultures with lauryl lactam in both the absence and presence of S-9 resulted in frequencies of aberrant cells which were similar to and not significantly different from those observed in concurrent negative controls. Proportions of aberrant cells in all treated cultures fell within historical negative control ranges.
Remarks on result:
other:
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

no further remarks

Applicant's summary and conclusion

Conclusions:
It is concluded that lauryl lactam was unable to induce chromosome aberrations in human lymphocytes when tested to its solubility limit in either the absence or presence of S-9.
Executive summary:

The test item lauryl lactam was tested in an in vitro cytogenetics assay using duplicate human lymphocyte cultures from a single male donor. The highest dose level used, 350 µg/ml was close to the solubility limit of lauryl lactam in culture medium. Treatments were performed both in the absence and presence of metabolic activation by a rat liver post-mitocondrial fraction (S-9). Appropriate negative (solvent) controls and positive controls (methylmethanesulphonate; cyclophosphamide) were included in the test system. Treatment of cultures with lauryl lactam in both the absence and presence of S-9 resulted in frequencies of aberrant cells which were similar to and not significantly different from those observed in concurrent negative controls. Proportions of aberrant cells in all treated cultures fell within historical negative control ranges. It is concluded that lauryl lactam was unable to induce chromosome aberrations in human lymphocytes when tested to its solubility limit in either the absence or presence of S-9.