Formamide, N-[[(4-methylphenyl)sulfonyl]methyl]-

Genetic toxicity: in vitro

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)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

in vitro mammalian chromosome aberration test

Test material

Test material information

Constituent 1

Reference substance name:

N-[[(4-methylphenyl)sulfonyl]methyl]formamide

EC Number:

700-490-2

Cas Number:

36635-56-0

Molecular formula:

C9H11NO3S

IUPAC Name:

N-[[(4-methylphenyl)sulfonyl]methyl]formamide

Details on test material:

- Name of test material (as cited in study report): CGA 224433
- Physical state: solid
- Analytical purity: ca 100%
- Lot/batch No.: P. 709027

Method

Species / strain

Species / strain / cell type:

Chinese hamster Ovary (CHO)

Metabolic activation:

with and without

Test concentrations with justification for top dose:

Toxicity test:
9.77 - 5000.0µg/ml range

Without activation:
125.0 - 1000.0µg/ml range

With microsomal activation:
200.0 - 1600.0µg/ml range

Vehicle / solvent:

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

Controls

Controls 1

Untreated negative controls:

yes

Remarks:

DMSO

Positive controls:

yes

Positive control substance:

cyclophosphamide

Remarks:

harvesting time 21hrs only

Migrated to IUCLID6: 40.0µg/ml

Controls 2

Untreated negative controls:

yes

Remarks:

DMSO

Positive controls:

yes

Positive control substance:

mitomycin C

Remarks:

harvesting time 21hrs only

Migrated to IUCLID6: 1.0µg/ml

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium; in agar (plate incorporation); preincubation; in suspension; as impregnation on paper disk

DURATION
- Preincubation period: 22hrs
- Exposure duration: 3hrs
- Expression time (cells in growth medium): 4hrs and 21hrs

DETERMINATION OF CYTOTOXICITY
- Method: mitotic suppression

Evaluation criteria:

Criteria for positive response:
- a test substance is considered to be active if, in comparison to the negative control, a marked increase in the number of specific chromosomal aberrations appear or if an increased number of exchange figures appear together with a high number of other specific chromosomal aberrations such as breaks or fragments
- a concentration-related response in the number of aberrations should be demonstrable

Results and discussion

Test results

Species / strain:

Chinese hamster Ovary (CHO)

Metabolic activation:

with and without

Genotoxicity:

positive

Remarks:

with and without activation

Cytotoxicity / choice of top concentrations:

cytotoxicity

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'.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
positive with metabolic activation 21hrs only
positive without metabolic activation both 4hrs and 21hrs

In the experiment with a harvesting time of 4 hours performed without microsomal activation, at concentrations of 1000µg/ml an increase in specific chromosomal aberrations was registered.
In the experiment with a harvesting time of 21 hours performed without microsomal activation, at concentrations of 1000µg/ml a marked increase in specific chromosomal aberrations was detected (23%).
In the experiment with a harvesting time of 21 hours performed with microsomal activation, at concentrations of 1600µg/ml 19% of metaphases with specific chromosomal aberrations was detected, thereof 9% containing exchange figures.

Thus the results indicate that under the given experimental conditions CGA 224433, in 21hrs with and without activation and 4hrs without activation, exerted a mutagenic effect in Chinese hamster ovary cells in vitro.

Executive summary:

CGA 224433 under test conditions was seen to exert a mutagenic effect on the tested cells and thus suggests this substance is a cause of concern for man owing to possible carcinogenic effects and should be assign the appropriate hazard phrases

EU classification R40 limited evidence of carcenogenic effect

GHS classifiaction Category 2 suspected human carcinogen.