374 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS remainder reacts with the QDI already formed to give.Bandrowski's base and other products. When resorcinol was co-oxidized with PPD, the ammonia evolved dropped to insignificant levels, showing that free QDI was not present for any time measurable by hydrolysis. It may not have formed at all, and one may envisage other reaction paths not involving QDI. Or, if formed, it reacted rapidly with resorcinol before it could undergo hy- drolysis. That QDI can react with dye intermediates is apparent from Table II which shows that addition of PPD or resorcinol to QDI gives a marked decrease of ammonia evolved. The QDI reacts faster with these intermediates than with water to give ammonia and faster with resorcinol than with PPD. In oxidation reactions involving PPD with m-aminophenol (Table III), some ammonia is evolved but this is less than for PPD alone and very much less than for QDI. In this case, the ammonia may arise from the oxidative hydrolysis of m-aminophenol itself as well as from Just how rapidly QDI reacts is indicated by the second method of detection, which is a spectrophotometric one. QDI was subjected to three different reaction conditions (Fig. $). In one case, it was placed in a buffer at pH 9.6. An ether extract taken three minutes later showed QDI still present but reduced to 25% of its initial amount. In another case, a small amount of resorcinol was added to the QDI in the buffer. An ether extract made one minute later showed no recognizable QDI. Finally, when a large amount of resorcinol was added, the spectrum after one minute showed only resorcinol to have been extracted into the ether layer. Accordingly, it seems unlikely that QDI, as a discrete entity, is present for any length of time in oxidation mixtures prepared for commer- cial use as hair coloring agents. If formed at all, QDI would be destroyed by the aqueous environment, or would react rapidly with other inter- mediates present in these formulations. Since QDI was not detectable in chemical systems designed to represent current hair coloring mixtures, it seems improper to consider observations of the toxic effects of QDI alone (8) as relevant to present day hair coloring formulations. This work has implications for patch testing to detect individuals hypersensitive to hair coloring formulations. Patch testing should be carried out with the combination of oxidation dye intermediates to be used, freshly mixed with peroxide. The patch test should not be based on PPD without the other hair color reactants.

REACTIONS OF OXIDATION DYE INTERMEDIATES OH 375 Structure C: Polyoxazine Figure d. Possible structures of oxidation pigment, PPD: resorcinol, 1:1 Oxidation Pigment The co-oxidation of PPD and resorcinol, 1: 1, yielded a final pigment almost at once. Attempts to isolate an early oxidation stage were un- successful, even when the reaction was carried out under the mildest conditions by bubbling air through an alkaline solution of the two components. After 30 seconds, the chromatographic pattern was the same as it was after 72 hours, namely, brown immobile pigment accompanied by seven bands of colored impurities. The yield of pigment increased with time without build-up of the impurities apparently these contained the early oxidation stages which were con- tinuously converted to the pigment. Because of the absence of a stable intermediate stage, attention was focused on the final pigment. The pigment was a high-melting material, insoluble in most solvents, and resistant to chromatographic develop- ment. The best chromatogram showed six bands of identical yellow- brown shade, poorly separated, just beyond the origin. These properties suggested that the pigment is a polymeric mixture of at least six components, all having the same unit structure but differ- ing only in molecular weight. When a p-phenylenediamine compound