Regulatory classification of substances oxidized to skin sensitizers on exposure to air

Abstract

Regulatory classification of substances in the European Union (EU) is intended to identify their hazardous toxicological properties in a formal and harmonized manner. In the regulatory work, a specific chemical with its molecular structure is classified as a skin sensitizer. This implies that the compound is stable throughout its lifetime. The purpose of the present paper is to discuss the problem of skin sensitizing oxidation/degradation products formed by air exposure of various materials or substances with very low allergenic activity. In regulatory classification work on skin sensitizers, the intrinsic suspectibility of a chemical to air oxidation (autoxidation) should be taken into consideration. We give examples of natural terpenoid materials, but the concept of allergens formed by air oxidation can apply to other materials widely used in industrial products. If a positive classification is made for a substance with a known chemical structure, a note should indicate that the primary chemical structure of the notified substance is not a skin sensitizer, but that (some of) its oxidation products are. Complex mixtures which inevitably contain sensitizing oxidation products should (on the basis of sufficient evidence) be classified as skin sensitizing.

Oxidative transformation processes and products of para-phenylenediamine (PPD) and para-toluenediamine (PTD)—a review

“…The European Economic Community Cosmetics Directive has set limit values for the maximal concentration of phenylenediamines in hair dyes to 6 % (PPD) and 10 % (PTD), provided that the active dye formulation contains an excess of coupling compounds [18]. The toxicological potential of technical and commercial formulations of aryldiamines is not only coined by the pure compounds themselves but also by side products of their technical synthesis and by chemical (aut)oxidation products formed during post production handling, product formulation, storage, application, or environmental exposure [19]. In contact with air or oxidizing agents like peroxides, phenylenediamines are easily transformed into complex mixtures of monomeric, dimeric, oligomeric, and polymeric oxidation products.…”

Preclinical evaluation of repeated dose toxicity and anxiolytic activity of monoterpene R - (+) limonene via inhalation

“…Sunil et al (2007) have shown that young and old mice when exposed to the product of the reaction between limonene and ozone for 3 h show an inflammatory response induction, increasing TNFa, cyclooxygenase-2 and superoxide dismutase in alveolar macrophages. This monoterpene is a potentially sensitizer compound, probably due to the presence of limonene-1,2-epoxide, a product of its oxidation (Karlberg et al, 1999). In contrast, Rolseth et al (2002) showed that limonene-1,2-epoxide was not responsible for the limonene toxicity when investigated in culture of human pulmonary cells.…”

Scientific Opinion on the safety of glycerol esters of gum rosin for the proposed uses as a food additive

“…As reviewed by Karlberg et al (1999) and Downs and Sansom (1999) abietic type acids are easily oxidised when in contact with air, and the oxidation products are thought to be contact sensitisers. Apart from resin acids and esters of resin acids, the non-acidic part of a rosin has provoked positive reactions in human patch testing (Hausen and Mohnert, 1989).…”