4-amino-m-cresol

Endpoint summary

Description of key information

According the result of the key study (Klimisch 1, GLP, OECD guideline 429 method followed), the registered substance 4 -amino-m-cresol induced delayed contact hypersensibility on LLNA Local Lymph Node Assay and EC3 values were calculated for DMSO vehicle, as 1.45% and for aqua/acetone/oil vehicle as 2.15%. According to the CLP regulation and criteria, the registered substance was classified as Category 1A for sensitizing effect.

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

The key study was performed to assess the skin sensitization potential of 4-amino-m-cresol by following the OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)(GLP compliant study, Klimisch 1). A total of 55 Female CBA/J mice of 10 week age. 25 μL of 0 (vehicle only), 0.5, 1.5, 5 and 10 % of 4-amino-m-cresol in DMSO and 0.5, 1.5, 3 and 5 % in a mixture of aqua/acetone (1:1) with olive oil (3:1) (equal to the maximum solubility) were applied to the surface of the ear to each of five female CBA/J mice per group for three consecutive days.. p-Phenylenediamine (PPD) at 1 % in DMSO was used as the positive control in parallel under identical test conditions. Animals were checked for morbidity/mortality at least once daily. Observation for clinical signs was done daily before and at least once after dosing. Body weight was determined on Day -2 and on Day 5.On Day 5, the mice received an intravenous injection of 250 μL phosphate buffered saline containing 23.6 μCi of [H3] methyl thymidine. Approximately 5 hours later, the mice were and the draining auricular lymph nodes were removed and weighed. After preparing a single cell suspension for each mouse, cells were precipitated by TCA and the radioactivity was determined (incorporation of [H3] methyl thymidine in the pellets) by means of liquid scintillation counting as disintegration per minute (dpm).

Lymph node weights were increased after treatment with 4-amino-m-cresol as compared to the vehicle controls indicating an immune response in both vehicles. The mean stimulation indices were affected in a dose-dependent manner by the treatment with 4-amino-m-cresol. With the test substance in DMSO, mean stimulation indices of 0.9, 3.1, 6.5 and 6.7 were obtained for the 4 test concentrations of 0.5, 1.5, 5 and 10 %, respectively. An EC3 value (equal to the concentration inducing a stimulation index of 3) of 1.45 % was calculated. In the second vehicle (aqua/acetone/olive oil), the indices were 1.5, 1.7, 4.7 and 6.9 for the 4 test concentrations of 0.5, 1.5, 3 and 5 %, respectively. An EC3 value of 2.15 % was calculated from these findings.

4-amino-m-cresol induced a biologically relevant immune response in local lymph nodes after dermal application to the mouse ear with either vehicle (DMSO or aqua/acetone/olive oil ) used. EC3 values of 1.45 % and 2.15 % were calculated for DMSO and aqua/acetone/olive oil, respectively. The concurrent positive control demonstrated the sensitivity of the assay.

Justification for classification or non-classification

According to the result of the key study (Klimisch 1, GLP, OECD guideline 429 method followed), the registered substance 4 -amino-m-cresol induced delayed contact hypersensibility on LLNA Local Lymph Node Assay and EC3 values were calculated for DMSO vehicle, as 1.45% and for aqua/acetone/oil vehicle as 2.15%. According to the CLP regulation and criteria, the registered substance was classified as Category 1A for sensitizing effect.