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:
Discussion

Annex VII of the REACH regulation requires that before new tests are carried out, all available data including valid QSARs shall be assessed first. Therefore we have undertaken a comprehensive literature search on the potential of phenolphthalein to induce hypersensitivity in humans and in animal experiments. In addition a QSAR prediction was performed.

In the public literature there are reports on case studies showing that allergy to phenolphthalein is often manifested as cutaneous inflammatory reaction or fixed drug eruption, i.e. solitary or multiple, well-defined, erythematous macules that may progress to vesicles and/or bullae. These lesions characteristically recur in the same location with each subsequent dose of phenolphthalein and generally leave residual hyperpigmentation that increases in intensity with each exposure; numerous melanincontaining dermal macrophages have been found in pigmented areas. [1-5]

Further we have undertaken a QSAR prediction using the knowledge based Derek for Windows. From the prediction as shown in the report it is considered plausible that phenolphthalein is a skin sensitizer.

Phenolphthalein is used as a laboratory reagent and acid-base indicator and, in the past, in over-the-counter laxative preparations. For such wide dispersive use one would assume much more reports on potential hypersensitivity induced by Phenolphthalein. Both, the few number of reports and the low reliability of the published data lead to the overall conclusion that all available data are not sufficient for a reliable hazard assessment on skin sensitization according to REACH.

Therefore in vivo testing was performed using a Local Lymph Node assay as required according to Annex VII of the REACH regulation. This GLP study has shown that Phenolphthalein was not a skin sensitizer in this assay and must thus not be classified as skin sensitizer.

References

1.    Wyatt, E., M. Greaves, and J. Sondergaard, Fixed Drug Eruption (Phenolphthalein) Evidence for a Blood-Borne Mediator. Arch Dermatol, 1972. 106(5): p. 671-673.
2.    Davies, D.M., Textbook of Adverse Drug Reactions. 3rd ed, ed. D.M. Davies. 1985, New York, Oxford: University Press.
3.    Stroud, M.B. and T.J. Rosio, A Case of Recurring Painful Red Macules. Arch Dermatol, 1987. 123(9): p. 1230A-.
4.    Zanolli, M.D., J. McAlvany, and D.P. Krowchuk, Phenolphthalein-induced fixed drug eruption: a cutaneous complication of laxative use in a child. Pediatrics, 1993. 91(6): p. 1199-201.
5.    Ellenhorn, M.J., et al., Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2 ed. 1997, Baltimore.




Migrated from Short description of key information:
As REACH requires using all available data, we have undertaken following activities before in vivo testing:

- Literature search on Phenolphthalein induced hypersensitivity
- QSAR prediction on hypersensitivity using Derek for Windows

The data obtained are not sufficient for hazard prediction further for classification and labeling as outlined according to REACH. Therefore a GLP study (Local Lymphnode Assay) was performed, showing that Phenolphthalein is not a skin sensitizer in this assay.

Justification for classification or non-classification

According to the EU Regulation (EC) No 1272/2008 on Classification, Labelling and Packaging of Substances and Mixtures,

Phenolphthalein does need to classified for skin sensitization based on the key and supporting information provided in this dossier.