Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

A local dermal DNEL can be derived from the results of the LLNA:

The general approach for assessing and controlling risks and setting DNELs for skin sensitizers is outlined in the ECHA Guidance Chapter R.8. The first step should always be a qualitative approach by using potency categorization to define risk management measures (RMMs) and operational conditions (OCs). Data derived from the LLNA can serve for the potency categorization and is based on EC3 value. The second step is setting a DNEL to judge the remaining/residual likelihood of risks after the appropriate RMMs and OCs are implemented.

It is suggested that the LLNA EC3 value correlates relatively well with the NOEL from human sensitization tests designed to confirm lack of induction (Gerberick et al., 2001; Griem et al., 2003; Basketter et al., 2005). Therefore, a threshold for skin sensitization can be defined as EC3 concentration (%), which is converted into dose per skin area (in µg/cm2):

EC3 [%] x ρ x 250 [µg/cm²/%] = EC3 [µg/cm²] = NOEL

where ρ is density of the liquid, 250 factor is calculated by converting 25 µL (applied to the mouse ear in a standard LLNA protocol) into µg/cm².

LLNA descriptor:

EC3 [%] x ρ x 250 [µg/cm²/%] = 7 x 0.99 x 250 = 1732.5 [µg/cm²]

Dermal sensitization DNEL:

In order to calculate a DNEL for sensitization, sensitization uncertainty (assessment) factors must be applied to the NOEL (in this case the EC3 value).

¾    Interspecies variation = 1.

Skin sensitization is considered as local immunological effect. Mechanistically, the biological sequelae that take place for the immune system to mount a response are the same across mammalian species, so, toxicokinetic and toxicodynamic Assessment Factors are not applicable (Api, 2006; Basketter, 2000)

¾    Intraspecies (human-human inter-individual variation) = 5

¾    Dose response = 3.

Linear relationship was observed in the study (r2= 0.9932), and the test material is shown to be moderate skin sensitizer.

 

The final assessment factor is 15.

DNEL = 1732.5 µg/cm² ÷15 =115.5 [µg/cm²]


Migrated from Short description of key information:
The Key study (Durando 2012) was performed according to OECD 429, EU Method B42 and US EPA OPPTS 870.2600, Local Lymph Node Assay.
Three concentrations of the test substance in acetone/olive oil (AOO 4:1 v/v) or the vehicle alone were topically applied to twenty healthy mice (5/dose) for three consecutive days. Treatment of mice with 1, 5 or 10% of the test material resulted in stimulation index values of 0.95, 2.07 and 3.96, respectively, relative to vehicle control mice. The substance was considered positive for a dermal sensitisation potential with a score > 3 at a test concentration at 10%. The positive control elicited a response of 4.66 relative to the vehicle control. The test substance is considered to be a contact dermal sensitiser at concentrations of greater than or equal to 7% (EC3 value)

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

In accordance with EU CLP Regulation (EC) No. 1272/2008, classification of this substance is required for skin sensitisation:

Category 1B, H317 may cause an allergic skin reaction.