g88 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS loading of the system-that is, too much foreign material entering the alveoli for the septal cells to handle effleiently. In such eases, foreign particles may penetrate the alveolar membrane or otherwise enter the interstitium. In this ease, the particle is transported to a satellite lymph node whose purpose it is to drain the lung tissue. From there, it may then enter the blood stream. Another alternative is that the particle or group of particles may not be cleared by the lung at all, but rather be sequestered in the lung tissue and walled of[ by reactive fibrous tissue formation this is referred to as pneumo- eoniosis. This pathological condition may be entirely benign and have no real long-term adverse effect on the individual, or, on the other hand, it may lead to a slowly developing, steady deterioration of lung function. A third system in the lungs which may suffer toxicological effects of aerosol inhalation is the pulmonary surfaetant. It is this biochemical substance (thought to be a mixture of lipid, protein, and possibly carbohydrate) which is responsible for evening out large differences in alveolar surface forces due to differences in their size during respiration. If it were not for the presence of this substance, the alveoli would tend to collapse, and each breath would become increasingly more diffleult. Impairment of the pulmonary surfaetant, through inhalation toxicity, then, would have obvious consequences. The sur- factant is also related to the alveolar clearance mechanisms in that move- ment of the septal cell out of the alveolus and up into the airways actually occurs in the surfaetant bathing these surfaces. Measurements of the sur- face tension of puhnonary washings has been used to study this parameter. PROBLEMS IN COSMETIC AEROSOL TOXtCOLOGY Inhalation Toxicity of Hair Sprays The first area for this discussion of some of the problems that have arisen in the field of cosmetic aerosol toxicology will be the allegations concerning the use of hair sprays. These questions have been around for almost as long as aerosolized hair sprays have been in existence, but, as will be seen, extensive animal testing and human clinical observations have failed thus far to prove any of the charges. In 1958, Bergmann published a paper (4) in which he described certain findings in X-rays of the lungs of two fenrole patients. In addition to darkened areas of the lungs (indicating fibrous tissue formation), he biopsied the lymph nodes associated with drainage from the lung and found a large nmnber of granules which reacted positively with the Periodic Acid-Schiff histologieal stain. As a result of his findings, Bergmann concluded that he had uncovered a new elinieopathologic entity, which he called "puhnonary thesaurosis." Within a year, a second paper appeared (5) describing another young woman with similar findings the diagnosis of thesaurosis was also made here. And again, 2 years later, a fourth case was reported and similarly diagnosed

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-