Skin sensitization and possible groupings for 'read across' for rosin based substances.

A series of chemically modified rosin resins have been tested for their potential to cause skin sensitization using the mouse LLNA. Where direct comparative evidence is available, the results of the mouse LLNA are consistent with previously obtained data using the GPMT. Reactions with sufficient fumaric acid or maleic anhydride lead to maleopimaric acid anhydride (an acid anhydride), and give a clear response of a strong sensitizer that definitely requires classification. This sensitization is probably immunologically distinct from that claimed for oxidized rosin. Esterification will deactivate acid anhydrides formed from reacting rosin with maleic anhydride or fumaric acid. However, with maleic anhydride, there remains material capable of inducing a marginal (but classifiable under current criteria) immune response after the rosin had been maleinated and esterified. If proposed potency criteria are used these substances would not be considered 'strong sensitizers'. This response may be a function of a greater solubility in vehicle of the esterified maleinated (or fumarated) rosin over directly esterified material. Solubility limitations in the case of gum rosin directly esterified with pentaerythritol mean that it is not classifiable. Decarboxylated rosin and the glycerol ester of tall oil rosin are adequately soluble, and are not classifiable according to EU criteria. Polymers formed from rosin are also not classifiable as sensitizers. These studies confirm the value of grouping substances for 'read across' and the groupings chosen under the US EPA High Production Volume (HPV) Challenge Program. They also confirm the difficulties involved in dealing scientifically when examining the problem of skin sensitization associated with rosin related substances whilst still meeting current EU regulatory criteria.

On the skin sensitisation potential of rosin and oxidised rosin.

In the EU rosin is classified as a skin sensitiser, apparently on the basis of its oxidation to sensitising agents. Rosin (gum, tall oil or wood) is not a skin sensitiser when examined in the guinea pig maximisation test (GPMT). Oxidised rosins are sensitisers in the GPMT. Oxidised gum rosin was further tested in the mouse local lymph node assay (LLNA) and the Buehler test, but is not a sensitiser in either of these tests. Further, the outcome of the LLNA can be used to assess the potency of oxidised rosin as an inducing agent in humans, and oxidised rosin is, at most, a weak sensitiser in this test. Thus, oxidised rosin is not a potent inducing agent for skin sensitisation unless the dermal barrier is bypassed and/or there is deliberate use of Freund's Complete Adjuvant to induce greater susceptibility. The material used for human patch testing ('colophony') is in oxidised form. A re-examination of epidemiological studies suggests that patients in dermatological clinics show higher response rates than do the general population or those occupationally exposed to presumably oxidised rosin. Thus, the differences seen in susceptibility in the regulatory tests may be reflected in the human population. These results are discussed in terms of possible testing and classification strategies for dealing with existing chemicals, with particular reference to the new European Union legislation.