Registration Dossier

Administrative data

short-term repeated dose toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
Justification for type of information:
According to column 2 of Annex IX "Testing by the inhalation route is appropriate if: — exposure of humans via inhalation is likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size."

Inhalation by workers in production and/or use is not likely. It is prevented by technical measures. No consumer contact is intended or possible. Toxic effects in humans by inhalation of the substance are unlikely because the substance has a low vapour pressure of 2.3E-14 Pa at 25 °C and the median particle size was between 500 and 1000 µm, with no particles <100 µm. Particles will therefore not be inhaled by nose and mouth to a relevant extent, and will not reach thoracic and alveolar regions, and will not be 'respirable'.
An acute inhalation toxicity study in rats with a MMAD of 2.56 µm did not indicate systemic toxic effects at the limit concentration of 5 mg/L. Only dyspnoe during and shortly after the exposure period were observed, which is likely a sign of discomfort of the rats sitting in the inhalation tubes. The test item is not classified as irritant to eyes or skin and no other relevant indications were obtained that the test item might cause local lesions to the mucosa of the respiratory tract.

The relevant parameters for estimating absorption at inhalation exposure are not very different to those for oral absorption, as described in the Section R. of the 'Guidance on information requirements and chemical safety assessment'. The NOEC for the inhalation route can be derived from the NOELoral, taking into account a higher (2-fold) absorption at inhalation compared to oral, as is described in the Guidance Document on Information Requirements Chapter R.8.4.2. It is considered that this approach is sufficient for a risk assessment.
An inhalation animal experiment is therefore considered not to be justified.
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