Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
3 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
The whole database is excellent, because dapsone has a dual use as an industrial chemical and a pharmaceutical.

Additional information

In the 90d gavage study in the rat treatment-related findings were observed at 30 mg/kg/day or above. The main effects were cyanosis of the skin, hyperactivity, increased WBC count, decreased RBC count, hemoglobin concentration and hematocrit., increased prothrombin time, spleenomegaly (especially in males), mild spleenic congestion, and mild pigmentation of the spleen. These effects are typical for methemoglobinaemia. Human experience (due to the dual use of dapsone as a pharmaceutical) shows the same effect at doses above the usual therapeutic dose of 100 mg/person/day.


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
The selected study is a 90d study with most parameters evaluated. No data are on neurotoxicity (this endpoint is covered by human experience due to dapsone use in leprosy treatment for 60 years)

Repeated dose toxicity: via oral route - systemic effects (target organ) cardiovascular / hematological: spleen; cardiovascular / hematological: other; digestive: liver

Justification for classification or non-classification

According to Guidance to Regulation (EC) No 1272/2008 on classification, labelling and packaging

(CLP) of substances and mixtures, the substance should be classified for Specific Target Organ Toxicity after repeated exposure Category 2 with effects on blood (methemoglobinaemia), Spleen and liver.