3,3'-sulphonyldianiline

Toxicity to reproduction

Administrative data

Endpoint:

one-generation reproductive toxicity

Remarks:

based on generations indicated in Effect levels (migrated information)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Information is available from the pre-approval review of Aczote (a cream containing 5% dapsone for use against acne) by U.S. FDA.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Principles of method if other than guideline:

Combined oral (gavage) female fertility and teratogenicity study. Fertility effects on males have been evaluated in a separate study.

GLP compliance:

yes (incl. QA statement)

Limit test:

no

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

Test material form:

solid - liquid: suspension

Details on test material:

Dapsone plus 180 mg/kg/day diethylene glycol monoethylether

Test animals

Species:

rat

Strain:

other: Rat/Crl:CD(SD)IGS BR VAF/Plus

Sex:

female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

0.5%

Details on exposure:

The study was conducted with dosages of 0, 12, 30 and 75 mg/kg/day. A satellite group received 180 mg/kg/day of diethylene glycol monoethylether.

Details on mating procedure:

- M/F ratio per cage: 1/1
- Proof of pregnancy: vaginal plug or sperm in vaginal smear referred to as day 0 of pregnancy

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

The test substance was administered 15 days prior mating and for 17 days thereafter.

Frequency of treatment:

daily

Details on study schedule:

Virgin females were treated from day 15 prior mating until day 17 post mating. Males were untreated (male effects investigated in a separate study)
Sacrifice of F0 females: Day 21 of pregnancy

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
0 mg/kg bw
Basis:
actual ingested

Doses / concentrations 2

Remarks:

Doses / Concentrations:
12 mg/kg bw
Basis:
actual ingested

Doses / concentrations 3

Remarks:

Doses / Concentrations:
30 mg/kg bw
Basis:
actual ingested

Doses / concentrations 4

Remarks:

Doses / Concentrations:
75 mg/kg bw
Basis:
actual ingested

No. of animals per sex per dose:

25 females / dose plus untreated males for mating

Control animals:

yes, concurrent vehicle

Positive control:

none

Examinations

Parental animals: Observations and examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
- Cage side observations: Yes
DETAILED CLINICAL OBSERVATIONS: Yes
BODY WEIGHT: Yes
FOOD CONSUMPTION Yes
WATER CONSUMPTION No data

Sperm parameters (parental animals):

Studied in separate study Male fertility.01

Litter observations:

yes

Postmortem examinations (parental animals):

yes

Postmortem examinations (offspring):

yes

Statistics:

yes

Reproductive indices:

yes

Offspring viability indices:

yes

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

effects observed, treatment-related

Results: P1 (second parental generation)

Effect levels (P1)

Remarks on result:

not measured/tested

Results: F1 generation

Effect levels (F1)

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

>= 12 - <= 75 mg/kg bw/day (actual dose received)

Based on:

act. ingr.

Sex:

female

Basis for effect level:

other: Reduced number of implantations, increase of the early resorption rate, reduced mean litter size. Effects probably secondary to maternal toxicity. No effects on the incidence of external, visceral or skeletal malformations or variations observed.

Overall reproductive toxicity

Reproductive effects observed:

not specified