Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

Sensitizing in mouse LLNA (multiple studies similar to OECD 429); EC3 = 0.11%
Reports of sensitisation reactions in humans have been reported in the literature (refer to IUCLID 5 for additional details).

Key value for chemical safety assessment

Skin sensitisation

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

LLNA assay

The test substance induced a positive response in the local lymph node assay, as there was at least a 3-fold increase in isotope incorporation in the draining auricular lymph node relative to the vehicle, with a calculated value of 0.06%. The mean stimulation indices were 2.6, 10.4, and 16.1 at concentrations of 0.05, 0.25, and 1.25%, respectively. Numerous reports of sensitisation reactions in humans have been reported in the literature (refer to IUCLID 5 for additional details).

Weight of Evidence approach

From the available publications(Goebel et al., 2012; Warbrick et al., 1999; White et al., 2006) and the LLNA results (MDS Pharma, 2003) it is evident that there is a steep dose-response in SI between 0.05 and 0.25%. Therefore, it is considered more appropriate to use the available studies in a weight of evidence approach, thus increasing the statistical power.

Basketter and colleagues have reviewed thecollation of EC3 data from repeat testing in multiple laboratories the utility and validity of these relative potency measurements including the LLNA(Basketter et al., 2007). A total of 10 EC3 values for the substance were collected from the literature, 8 of which collected once a month over a 4 month period in 1998 and two collected in 2005.The concerning studies were conducted similar to OECD TG 429 without obvious deviations.The EC3 values ranged from 0.06 to 0.18, and the authors calculated a mean EC3 of 0.11± 0.014 %.Considering the statistical power resulting from the large number of available EC3 values (10) and the relatively small range of the reported EC3 values (0.06-0.18) (despite the steep dose-response), the averaged EC3 of 0.11% is regarded the most appropriate value reflecting the relative skin sensitizing potency of the substance.


Basketter DA, Gerberick F, Kimber I. The local lymph node assay and the assessment of relative potency: status of validation. Contact Dermatitis. 2007 Aug;57(2):70-5.

Goebel C, Diepgen TL, Krasteva M, Schlatter H, Nicolas JF, Blömeke B, Coenraads PJ, Schnuch A, Taylor JS, Pungier J, Fautz R, Fuchs A, Schuh W, Gerberick GF, Kimber I. Quantitative risk assessment for skin sensitisation: consideration of a simplified approach for hair dye ingredients. Regul Toxicol Pharmacol. 2012 Dec;64(3):459-65. doi: 10.1016/j.yrtph.2012.10.004. Epub 2012 Oct 13.

Warbrick EV, Dearman RJ, Basketter DA, Kimber I. Local lymph node assay responses to paraphenylenediamine: intra- and inter-laboratory evaluations. J Appl Toxicol. 1999 Jul-Aug;19(4):255-60.

White, J.M., Kullavanijaya, P., Duangdeeden, I., Zazzeroni, R., Gilmour, N.J., Basketter, D.A., McFadden, J.P., 2006. p-Phenylenediamine allergy: the role of Bandrowski’s base. Clin. Exp. Allergy 36, 1289–1293.

Respiratory sensitisation

Endpoint conclusion
Additional information:

There was no evidence of respiratory sensitisation during inhalation exposure.

Justification for classification or non-classification

The test substance produced skin sensitisation in laboratory animals, but there was no evidence of respiratory sensitisation during inhalation exposures. The substance should be classified as R43: May cause sensitisation by skin contact according the EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.