3,3'-sulphonyldianiline

Dermal absorption

Administrative data

Endpoint:

dermal absorption

Type of information:

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

Adequacy of study:

supporting study

Study period:

2000

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

This study was performed in a single male to determine dermal absorption. 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:

publication

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

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

Administration / exposure

Duration of exposure:

Rats and rabbits: 28 days
Humans: 1 day

Doses:

50 mg/kg/day for rats and rabbits (28 days), 1.67 mg/kg (single application) for humans

Details on study design:

Dapsone and N-acetyl dapsone concentrations in nonclinical samples were analyzed with HPLC and mass spectroscopy. The method was adequately validated and had acceptable limit of quantitation.

Results and discussion

Conversion factor human vs. animal skin:

Rat and rabbit skin absorption is about 20x higher than human skin

Applicant's summary and conclusion

Conclusions:

In the FDA review of non-disclosed studies on the safety pharmacology of a dapson gel it is summarised that topically applied dapsone is bioavailable at 10-20% in rats and rabbits. In humans, less than 1% of a topically applied dose is bioavailable.

Executive summary:

In the FDA review of non-disclosed studies on the safety pharmacology of a dapson gel it is summarised that topically applied dapsone is bioavailable at 10-20% in rats and rabbits. In humans, less than 1% of a topically applied dose is bioavailable.

Rat male (topical)       Dose: 50 mg/kg       Cmax: 2613 ng/ml       AUC: 32587 ng hr/mL

Rat female (topical)      Dose: 50 mg/kg       Cmax: 10909 ng/ml       AUC: 159928 ng hr/mL

Rabbit male (topical)       Dose: 50 mg/kg       Cmax: 1469 ng/ml       AUC: 14916 ng hr/mL

Rabbit female (topical)      Dose: 50 mg/kg       Cmax: 1864 ng/ml       AUC: 13427 ng hr/mL

Human male (topical)       Dose: 1.37 mg/kg       Cmax: 17.1 ng/ml       AUC: 349 ng hr/mL

Human female (topical)      Dose: 1.37 mg/kg       Cmax: 22.3 ng/ml       AUC: 481 ng hr/mL

Human male (oral)       Dose: 1.67 mg/kg       Cmax: 1375 ng/ml       AUC: 52641 ng hr/mL