3,3'-sulphonyldianiline

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

performed according to GLP and OECD guideline 474. The read-across of toxicological data is considered justified because 4,4’-DDS (dapsone) and 3,3’-DDS are structural isomers with identical mol mass, identical elemental composition and identical functional groups. To the best of our knowledge, only Dapsone is used as a pharmaceutical. It is not known whether 3,3’-DDS acts as 4,4’-DDS as a folate synthesis inhibitor in microorganisms.The main toxicological hazard of 4,4’-DDS is the methemoglobin formation. This is due to the aromatic amine substituent of the molecule, which is present in both isomers. It is concluded that the main toxicological hazard of 3.3’-DDS is also methemoglobin formation. Both isomers do not show a structural alert for mutagenicity. The toxicological and ecotoxicological hazard profiles of both isomers are considered to be identical. A read-across 1:1 is considered reasonable and justified due to the very small structural difference of both substances.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Dapsone

EC Number:

201-248-4

EC Name:

Dapsone

Cas Number:

80-08-0

Molecular formula:

C12H12N2O2S

IUPAC Name:

4,4'-sulfonyldianiline

Details on test material:

Dapsone, batch no. 70522014, white powder, purity 99.69%, stored at 1-10 degrees C in the dark.

Test animals

Species:

mouse

Strain:

CD-1

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River-UK Ltd
- Age at study initiation: 7 weeks
- Weight at study initiation: 26-33g
- Diet (e.g. ad libitum): availabe ad-libitum
- Water (e.g. ad libitum): availabe ad-libitum
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-23 deg C
- Humidity (%): 52-61%
- Photoperiod (hrs dark / hrs light): 12-hour light/12-hour dark cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

1% methylcellulose in water

Details on exposure:

Groups of 8 males mice (as there was no evidence of sex-related differences in toxicity in the range finding test) were used for each dose groups and one control group. Dose levels were 0, 43.75, 87.5, 175 mg/kg bw/day in the main experiment. A positive control group of 8 male mice received 40 mg/kg cyclophosphamide once on day 2 of the experiment.

Duration of treatment / exposure:

2 consecutive days

Frequency of treatment:

daily once

Post exposure period:

none

No. of animals per sex per dose:

8 males per dose (as no evidence of sex-related differences in toxicity was revealed in the range finding test)

Control animals:

yes, concurrent no treatment

Positive control(s):

cyclophosphamide, 40 mg/kg bw once on day 2

Examinations

Tissues and cell types examined:

Bone marrow were analysed for numbers of micronucleated polychromatic erythrocytes.

Details of tissue and slide preparation:

femours were excised and the content washed out with a syringe into 1% fetal bovine serum in RPMI medium

Evaluation criteria:

Slides had to have at least 1000 scorable cells (PCE and NCE).
A statistical increase in CE is necessary,
the frequency of PCE is higher than the historical control range.

Statistics:

Statistics was applied

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

yes

Vehicle controls validity:

valid

Positive controls validity:

valid

Additional information on results:

A significant increase in PCE was found with Dapsone as compared to the control group, but a significant increase with the positive control was observed, thus validating the study.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
Based on the available Mouse micronucleus test (bone-marrow) it can be concluded that Dapsone is not mutagenic in-vivo.

Executive summary:

In the present mouse micronucleus study, no increase in PCE was observed with Dapsone, while the positive control Cyclophosphamide showed a significant increase in PCE. With Dapsone the mice were treated up to the highest dose not causing mortality as shown in the pre-experiment.

Based on the absence of any increase of PCE with Dapsone at any dose level tested, it is concluded that Dapsone has no mutagenic potential in-vivo.