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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (GLP)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report Date:
1987

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 473 (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

Method

Target gene:
his-
Species / strain
Species / strain / cell type:
lymphocytes: human
Metabolic activation:
with and without
Test concentrations with justification for top dose:
1250, 2500 und 3500 µg/ml (without S9-Mix), 2500, 5000 und 6000 µg/ml (with S9-Mix)
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: water
Controls
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Positive control substance:
other: without S-9 mix (0.2 µg mitomycin C/mL culture medium); with metabolic activation (6 µg cyclophosphamide/mL culture medium)
Details on test system and experimental conditions:
NUMBER OF REPLICATIONS: 2


NUMBER OF CELLS EVALUATED: 100 (positive controls: 50) per replicate
Statistics:
The Fisher exact test was applied to determine significant differences between the relative frequencies of a characteristic of two groups.

Results and discussion

Test results
Species / strain:
lymphocytes: human
Metabolic activation:
with and without
Genotoxicity:
negative
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

Without metabolic activation

Treatm. 
 % aber. + gaps 
 % aber. - gaps 
 % exchanges 
negative
      5         
      1         
     0
solvent 
      6         
      2.5       
     0
1250 ug 
      8.5       
      1         
     0.5
2500 ug 
      7         
      3         
     0
3500 ug 
      4         
      1         
     0
positive
     44**       
     37**       
     5*

Multiple abberation metaphases were detected in the 1250 ug treatment  (0.5%) and the positive control (2%).
Aneuploid metaphases were detected in the solvent control (1%) and the  2500 ug treatment (1%).
Polyploid metaphases were detected in the negative control (1%), the 1250  ug and the 2500 ug treatment (0.5% each).

With metabolic activation
Treatm. 
 % aber. + gaps 
 % aber. - gaps 
 % exchanges 
negative
      2         
      0         
     0
solvent 
      7.5       
      2         
     0
2500 ug 
      6.5       
      0.5       
     0
5000 ug 
      8#        
      0.5       
     0
6000 ug 
      8.5#      
      1         
     0
Multiple aberration metaphases were not detected in any treatment or control.
Aneuploid metaphases were detected in the 5000 ug treatment (0.5%).
Polyploid metaphases were detected in the solvent control (1%), the 5000 ug and the 6000 ug treatment (0.5% each).

**/* = statistically different from both the negative and solvent control (significance level 99/95%)
# = statistically different from the negative control (significance level  95%)

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

2-pyrrolidone is not genotoxic in human lymphocyte chromosome abberation assay.
Executive summary:
2 -pyrrolidone was tested in the Human Lymphocytes Cromosome Aberation Assay in the present and absent of metabolic activation. There were statistically significant differences between both negative and solvent control in the two high dose groups without and with metabolic activation. However, there were also aberration observable in the negative control. Therefore, these significant differences are considered to be of no importance for genotoxicity of the test material. 2 -pyrrolidone does not induce clastogenic effects and chromosomal aberrations in this assay.