Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

The initial key study was a mouse Local Lymph Node Assay. Under the conditions of the study, Stimulation Indices (SI) of 3.36, 4.00, and 3.24 were calculated for 25%, 50%, and 100% Phosflex 71B, respectively. Considering the SI threshold value of 3 as stated in Annex I of 1272/2008/EC and Annex VI of 67/548/EEC, the substance needs to be classified as a sensitizer.

 

In the LLNA test performed with tBuTPP, the SI was >3 in all concentrations tested, however, no dose-response relationship was observed. The LLNA test is designed to study the induction phase of skin sensitization and usually provides quantitative data suitable for dose-response assessment. Furthermore, according to OECD guideline 429, the decision process with regard to a positive response includes a stimulation index ≥ 3, together with consideration of dose-response and, where appropriate, statistical significance.

 

It is not clear why no dose-response was observed in the study with tBuTPP. A cause may be that the substance has reached a maximum saturation in the skin, which is supported by the expectation based on the log Kow (4.68) that uptake into the stratum corneum will be high, but the rate of penetration may be limited by the value of transfer between the stratum corneum and the epidermis. Therefore, a new study should be performed with lower concentrations to be able to calculate an EC3 value.

 

With the currently available information, no DNEL can be derived and the risk of sensitization should be assessed using a qualitative approach.

To verify the potenttial sensitizig effects in humans, a Human Patch test was performed. This test was initiated because there was a doubt about the validity of the test in relation to humans, as no major incidences have been recorded at the production site nor from downtream users regarding sensitization. The substance is being produced over 40 years in US production facilities.

The result of the Patch test was clearly negative, and this result in combination with the fact that there is no human epidemiological data that shows that the substance causes sensitization, it was concluded that it does not need to be classified for sensitization classification of the substance under CLP.


Migrated from Short description of key information:
Mouse Local Lymph Node Assay (LLNA) (according to OECD 429): sensitising , Patch test on humans, non-sensitizing, case study production facility, no incidences of sensitization known.

Justification for classification or non-classification

Based on the outcome of the Humand Patch test in combination with worker information from the production facility, it has been decided not to classify the substance for sensitization.