Registration Dossier

Administrative data

short-term repeated dose toxicity: dermal
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
Justification for type of information:
According to column 2 of Annex VIII "Testing by the dermal route is appropriate if: (1) inhalation of the substance is unlikely; and (2) skin contact in production and/or use is likely; and (3) the physicochemical and toxicological properties suggest potential for a significant rate of absorption through the skin."

The skin contact in production and/or use is not likely. It is prevented by technical measures. No consumer contact is intended or possible.
The physicochemical and toxicological properties do not suggest potential for a significant rate of absorption through the skin that is higher than the absorption at oral exposure. Based on the Section R. of the 'Guidance on information requirements and chemical safety assessment' an even lesser dermal absorption, compared to the oral absorption, is predicted, mainly because the n-octanol/water partition coefficient of the test item is very low. A molecular weight of less than 100 would favour a dermal absorption. The test substance has a molecular weight of 333.8. For substances with log P values <0, the poor lipophilicity will limit penetration into the stratum corneum and hence dermal absorption. Values <–1 suggest that a substance is not likely to be sufficiently lipophilic to cross the stratum corneum, therefore dermal absorption is likely to be low.
It is generally accepted that the dermal absorption is usually lower than the oral one, leading to a lower toxicity after dermal exposure than after the oral one. Also local effects are not expected for the substance as no skin irritation was observed in an in vivo study.
No new information are therefore expected from a dermal experiment compared to the otherwise similar oral study.
A risk assessment do not need the results from a dermal toxicity study but can be performed with results of a study with oral dosing.
The oral toxicity studies are performed more routinely than the dermal or inhalation experiments, and they cause less complications and more reliable results. In the ECHA Guidance on Info Requirements and CSA, Part 7.a of July 2017, p. 436 and 450 it is stated " Concerning repeated dose toxicity testing, the oral route is the default one because it is assumed to maximise systemic availability (internal dose) of most substances."

Data source

Materials and methods

Results and discussion

Applicant's summary and conclusion