Reaction mass of 2-ethyl-2-[[3-(2-methylaziridin-1-yl)propionyl]methyl]propane-1,3-diyl bis(2-methylaziridine-1-propionate) and 2,2-bis({[3-(2-methylaziridin-1-yl)propanoyl]oxy}methyl)butyl 3-[2,2-bis({[3-(2-methylaziridin-1-yl)propanoyl]oxy}methyl)butoxy]propanoate

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

January 1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Performed before test guidelines and GLP principles were in place, but performed according to the published method of Ames: only two strains were used to proof earlier positive results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Principles of method if other than guideline:

Procedures followed in the present study, mimic as closely as possible those described by Ames and coworkers in Mutation Research 31, 1975, 347-365. Only S. typhimurium TA1535 and TA100 have been tested, based on findings in another performed study.

GLP compliance:

no

Remarks:

before GLP came into force

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

2-({3-[2,2-bis({[3-(2-methylaziridin-1-yl)propanoyl]oxy}methyl)butoxy]-3-oxopropoxy}methyl)-2-({[3-(2-methylaziridin-1-yl)propanoyl]oxy}methyl)butyl 3-(2-methylaziridin-1-yl)propanoate; 2-ethyl-6-(2-methylaziridin-1-yl)-2-({[3-(2-methylaziridin-1-yl)propanoyl]oxy}methyl)-4-oxohexyl 3-(2-methylaziridin-1-yl)propanoate

EC Number:

939-180-9

Molecular formula:

Not relevant - Multiconstituent substance

IUPAC Name:

2-({3-[2,2-bis({[3-(2-methylaziridin-1-yl)propanoyl]oxy}methyl)butoxy]-3-oxopropoxy}methyl)-2-({[3-(2-methylaziridin-1-yl)propanoyl]oxy}methyl)butyl 3-(2-methylaziridin-1-yl)propanoate; 2-ethyl-6-(2-methylaziridin-1-yl)-2-({[3-(2-methylaziridin-1-yl)propanoyl]oxy}methyl)-4-oxohexyl 3-(2-methylaziridin-1-yl)propanoate

Details on test material:

- Name of test material (as cited in study report): CX-100
- Substance type: polyfunctional aziridene crosslinkers
- Physical state: yellow liquid
- Lot/batch No.: Three batches were used for testing, CX-100 PCH Lot 36.942, CX-100 PCH lot 36110 and CX-100 PCI.
- Other: Received material January 30, 1980

Method

Species / strain

Species / strain / cell type:

S. typhimurium, other: TA100 and TA1535

Details on mammalian cell type (if applicable):

approx. 10E9 bacteria/ml were used

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254 induced livers of male wistar rats

Test concentrations with justification for top dose:

0, 0.06, 0.18, 0.56, 1.67, 5, 10 mg/plate (+/- S9 mix)

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO

Controls

Controls 1

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

1.3 µg/plate

Migrated to IUCLID6: without S9 mix

Controls 2

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene (with S9 mix)

Remarks:

0.5 µg/plate

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation); test concentrations were prepared immediately before use.

DURATION
- Exposure duration: 3 days

NUMBER OF REPLICATIONS: triplicate, positive controls in duplicate

DETERMINATION OF CYTOTOXICITY
Less dense background lawn of bacterial growth.

Results and discussion

Test results

Species / strain:

S. typhimurium, other: TA100 and TA1535

Metabolic activation:

with and without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at 10 mg/plate the substance was toxic for the bacteria

Vehicle controls validity:

valid

Positive controls validity:

valid

Additional information on results:

The positive effect, was more pronounced in the presence than in the absence of the liver microsome activation system.

COMPARISON WITH HISTORICAL CONTROL DATA: historical positive control data are included in the report for 2-aminoanthracene (not for sodium azide)

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
positive with and without metabolic activation

CX-100 showed to be positive in two strains, TA100 and TA1535, in an Ames test with and without metabolic activation.