3-hydroxypropiononitrile

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:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study well documented, meets generally scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Report date:

1979

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

Version / remarks:

Ames Test according to old guideline

Deviations:

not specified

Principles of method if other than guideline:

Method: other: in accordance with "Ames, B.N. et al., Mutat. Res. 31, 347-364"

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

3-hydroxypropiononitrile

EC Number:

203-704-8

EC Name:

3-hydroxypropiononitrile

Cas Number:

109-78-4

Molecular formula:

C3H5NO

IUPAC Name:

3-hydroxypropanenitrile

Details on test material:

- Name of test material (as cited in study report): Ethylencyanhydrin
- Substance type: Aliphatic Nitrile
- Physical state: liquid
- Analytical purity: as supplied by producer: purity in the test report not mentioned, but probably > 98,5%
- Impurities (identity & concentrations): no data availible by the study report, but according to the current product information sheet the
impurities are: glykol <1%, formic acid: max 0.06%, HCN: max 0.0010% , water: max 0.10%.
- Stability under test conditions: no data
- Storage condition of test material: no data

Method

Species / strain

Species / strain / cell type:

other: Salmonella typhimuriumTA 98, TA 100, TA 1535, TA 1537, TA 1538

Metabolic activation:

with and without

Metabolic activation system:

S9 Homogenate (prepared from Aroclor1254-induced Sprague-Dawley adult male rat liver)

Test concentrations with justification for top dose:

0.005; 0.01; 0.1; 1.0; 5.0; 10.0 µL/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: Dimethyl sulfoxide (DMSO)
- Justification for choice of solvent/vehicle: no data
- Vehicle controls tested: solvent control (test system with solvent alone)

Controls

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

Positive controls:

yes

Remarks:

2-nitrofluorene; 9-aminoacridine; 2-anthramine; sodium azide - Justification for choice of positive control(s): no data

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation) no preincubation

DURATION
- Exposure duration: 48h at 37°C: plates were incubated with the test substance (with and without metabolic system)
- Expression time (cells in growth medium): "overnight culture"=> 24h expression time
- Selection time (if incubation with a selection agent):
- Fixation time (start of exposure up to fixation or harvest of cells): no data

SELECTION AGENT (mutation assays): (selective) agar (with biotin and a trace of histidin)


NUMBER OF REPLICATIONS: no data
NUMBER OF CELLS EVALUATED: approximately 10 exp 8 (amount of cells at the beginning)

Evaluation criteria:

Evaluation criteria described in the study report are given as an attechment(see: atteched background materials)

Statistics:

no data

Results and discussion

Test results

Key result

Species / strain:

S. typhimurium, other: TA-1535, TA-1537, TA-1538, TA-98, TA-100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

RANGE-FINDING/SCREENING STUDIES: no data
COMPARISON WITH HISTORICAL CONTROL DATA: criteria used to determine positive effects are based primarily on a historical data
ADDITIONAL INFORMATION ON CYTOTOXICITY: no data

Any other information on results incl. tables

I. Table of Test Results:                                                                                                       Revertants per plate:          Nonactivation  Species  Tissue  TA-1535  TA-1537  TA-1538  TA-98  TA-100  Solvent Contrtol  -  -  17  10  15  33  133  Positive Control**  -  -  813  733  872  1509  1948  Test Compund (µl/plate):                0.0050  -  -  14  9  10  33  120  0.0100  -  -  22  9  6  30  104  0.1000  -  -  15  8  3  30  111  1.0000  -  -  16  7  7  32  129  5.0000  -  -  19  5  7  31  128  10.0000  -  -  16  9  6  34  125                  Activation                Solvent Control  rat  liver  17  16  16  64  106  Positive Control***  rat  liver  445  499  1563  2159  1561  Test Compound (µl/plate):                0.0050  rat  liver  15  6  16  57  105  0.0100  rat  liver  10  15  15  43  110  0.1000  rat  liver  10  13  7  41  95  1.0000  rat  liver  12  14  12  46  105  5.0000  rat  liver  14  6  8  44  84  10.0000  rat  liver  10  10  17  45  83  ** positive control: substances/concentration see: "information on materials and methods: 3.a" ***positive control: substances/concentration see: "information on materials and methods: 3.b"

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

Ethylene cyanohydrin has to be judged as nonmutagenic according to the test results.

Executive summary:

In a reverse gene mutation assay in bacteria (Ames test), strains TA1535, TA1537, TA1538, TA98 and TA100 of S. typhimurium were exposed to Ethylene cyanohydrin probably > 98% at concentrations of 0.005, 0.01, 0.1, 1.0, 5.0 and 10.0 µL/plate in the presence and absence of mammalian metabolic activation . 

 

Ethylene cyanohydrin was tested to limit concentrations 10.0 µL/plate. The positive controls induced the appropriate responses in the corresponding strains. There was no evidence of induced mutant colonies over background.

 

This study is classified as acceptable. This study satisfies the requirement for tests for in vitro mutagenicity (bacterial reverse gene mutation) data.