TESTING FOIl INHALATION TOXICITY g89 (6). In 1962, Bergmann published a second paper (7) in •vhich he offered 19. further cases which he had diagnosed as pulmonary thesaurosis resulting from inhalation of hair spray. As with his previous paper, however, his case was built around the presence of PAS-positive granules in the lung and lymph tissue •vhich he took to be evidence of polyvinylpyrrolidone resin from the hair spray. In the meantime, several reports •vere published on the efforts to induce thesaurosis-like changes in the lungs of animals (2, 8-11). It was found that, indeed, PAS-positive granules could be demonstrated in the lung tissue after exposure to hair spray by inhalation, but that they were present to an equal extent in both treated and control animals. In addition, an in vitro procedure for staining the PVP resin •vith PAS yielded a negative restdt (9). As for the tissue changes, a study •vas performed in which rats •vere exposed to aero- solized PVP for 8 hours a day, 5 days a •veek, for one month (11). The con- centration used, 146 mg/m a, is equivalent to discharging a typical 13-ounce can of hair spray continuously for about 11/z minutes in a room measuring 8 x 8 x 8 feet, and then maintaining that level for the duration of the test. Histological examination of the lungs was carried out immediately following the study, and at 1, 3, 4, and 6 months after completion. Lung tissue from the animals sacrificed immediately and at one month showed no structural changes. At 3 months, mild peribronchial lymphold hyperplasia or fibroplasia was seen. In none of these sections was PAS-positive material found. At 4 months, ho•vever, PAS-positive particles •vere seen in the peribronchial lymphatics, and also at 6 months. At no time were any inflammatory changes seen in the lungs, nor did the authors feel that the PAS-positive reaction was due to the staining of PVP itself, but was probably some material coating the particles. The fact that PVP could be identified in the lung tissue by chemical analysis follo•ving this extremely high level of inhaled resin, but that nothing suggesting granulomatous lung disease was seen at autopsy up to 6 months after completion of the study, is perhaps the most important finding here. At this point, then, the state of knowledge on this problem •vas that the diagnosis of pulmonary thesaurosis in humans hinged on the demonstration of PAS-positive granules (•vhich, incidentally, were found in lung tissue taken from persons •vho had never been exposed to hair spray) (12). In addition, the signs seen in humans could not be reproduced in animals, even by heroic means. Since animal studies alone, ho•vever, could not really exclude the possibility that this might be a phenomenon unique to humans, several in- vestigators decided to undertake surveys involving human subjects. It was anticipated that if such a thing as hair spray thesaurosis could be produced in humans, it would certainly be seen to a much greater extent in a group that had been subjected to high concentrations of the suspected agent for long periods of time professional hairdressers seemed ideally suited to this purpose. During the period 1963-72, over 2200 such hairdressers, the ma-

290 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS jority of whom •verc female, were examined by 10 different investigators utilizing chest X-ray (13-22) the reports came from England, France, Ger- many, and the U.S., and conclude unequivocally that no symptoms such as were seen by Bergmann et al., and which could be diagnosed as pulmonary thesaurosis, had been seen in any of the subjects. Notably, however, one ease of a lung disorder called sareoidosis was uncovered in a group of 114 in the U.S. (19), and a second diagnosis of sareoidosis made from a group of 596 in France (20). Because of many diagnostic similarities between sareoidosis and the proposed thesaurosis, many investigators began to have doubts as to whether the two were distinct clinical entities. During the same period that the hairdressers were being surveyed, solitary eases diagnosed as hair spray thesauresis continued to be reported (15, 22- 24). More care appears to have been taken in the diagnosis of some of these later eases (9 in number), sareoidosis having been specifically eliminated in a few of them. So while there is no real evidence to date to link the use of hair sprays to harmful effects on the lungs, the possibility continues to be suggest- ed. It therefore remains the responsibility of industry to continue a program of investigation to settle the issue for once and all. The ultimate question will not be whether thesaurosis or sarcoidosis is the proper diagnosis, but whether these are real, pathological effects on lung tissue as a result of the inhalation of hair sprays. Spray Powders Another cosmetic prodnet which has received attention as a potential inha- lation hazard is tale. The most common toxicological consequence of misuse of this material seems to be accidental aspiration of large quantities which choke off the airways and overwhelm clearance mechanisms (25-27) this occurs most h-equently in young children. Recently, there was a brief uproar surrounding asbestos contamination of the tales being used in cosmetics. The concern which followed the original report arose because certain forms of asbestos have been implicated in the production of cancer in man and animals the insidious nature of the carcino- genesis, in that it takes up to 20 years to manifest itself, xvas the main motiva- tion for the initial reaction. However, upon closer investigation of the prob- lem, it was found that the asbestos forms that are implicated in carcinogene- sis (ehrysotile, amositc, eroeidolite, and anthophylite) were not present in the tales used for cosmetics. Another variety, tremolite, for which there is no evi- dence of carcinogenic hazard, was identified as being present at concentra- tions of less than 5%. Even though carcinogenicity does not seem to be a potential problem, then, as far as the tales are concerned, they should still be subjected to rigorous in- halation testing the same as other aerosolized products.