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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

According to the results of the key studies, the registered substance induced delayed contact hypersensibility on LLNA Local Lymph Node Assay and an EC3 of 0.4% in the first LLNA and 3.4 in the second. Hence, the registered substance was classified as strong sensitizer Category 1A according to CLP regulation.

Key value for chemical safety assessment

Skin sensitisation

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

- Two in vivo studies were available to evaluate the potential sensitizer effect of the registered substance 4-amino-2-hydroxytoluene. These studies were Local Lymph Node Assays (Klimisch 1, GLP compliant, OECD Guideline 429 method). In the two studies, CBA mice were used. 25 μL of 0 (vehicle only), 0.5, 1.5, 3 and 5 % of 5-Amino-2-methyl-phenol in a mixture of aqua/acetone (1:1) with olive oil (4:1) (First study) or DMSO (second study) was applied to the surface of the ear to each of five female mice per group for three consecutive days. On the day 5, intravenous injection of 250 µL solution of tritiated methyl thymidine was performed. Approximately five hours later, the mice were killed, and the draining auricular lymph nodes were removed and collected in order to be analysed. Mean stimulation indices for the test substance at the concentrations of 0.5, 1.5, 3 and 5% were 3.2, 5.9, 5.3 and 9.4 respectively. An EC3 was estimated by extrapolation to be 0.44% when tested in mixture of aqua/acetone (1:1) with olive oil (4:1). Mean stimulation indices for test substance at the concentrations of 0.5, 1.5, 3 and 5% were 2.6, 2.4, 2.8 and 3.9 respectively when tested in DMSO. An EC3 calculated by linear interpolation was 3,4%.

-Two in vitro studies were performed (Acceptable study report, follows basic scientific principles/standards, Klimisch 2). Peripheral Blood Monocyte Derived Dendritic Cells were used. PBMDCs were exposed in three independent experiments for 24 h to the following non cytotoxic range of concentrations of test material. The activation of immaturedendritic cells(DC) pooled from four different human donors was evaluated by flow cytometric analysis of CD86 positive cells and quantitative measurement of interleukin-1ß, interleukin-8 and Aquaporin P3 gene expression by real time PCR. Dose level used in the first study was 600 and 500 mg/mL and 812, 1624, 3248, 4100 and 4872 µM was used in the second study. No clear dose response curves were observed with any of the four markers for the in vitro DC activation assay. However, the test substance clearly modulated three out of the four markers (i.e. CD86, IL-1β andIL-8) (at 4872 µM for the second study).  In conclusion,4-Amino-2-Hydroxytoluene was considered as an in-vitro sensitizer in the Peripheral Blood Monocyte Derived Dendritic Cell Activation assay.

Justification for classification or non-classification

In regard with the results of the two in vivo key studies,the registered substance 4 -amino-2 -hydroxytoluene induced delayed contact hypersensibility on LLNA Local Lymph Node Assay and an EC3 of 0.4% in the first LLNA and 3.4% in the second. Furthermore, test item induced expression of interleukines on Peripheral Blood Monocyte Derived Dendritic Cell and it was considered as sensitizer. .Hence, the registered substance was classified as strong sensitizer Category 1A according to CLP regulation and EC3 value.