TESTING FOIl INHALATION TOXICITY 287 tions at autopsy, and to the blood data, to get a picture of the effect of the test material. Special Measurements Besides histological examination of tissue sections, another parameter which may be of interest to the inhalation toxicologist is the observation of the muco- ciliary activity .of the respiratory system. This activity is one of the ways that the lungs are protected from the deposition of foreign material. Basi- cally, the cells lining the trachea, larynx, and upper airways have special modifications called cilia which are microfine, whisker-like projections from the free surfaces of these cells. These cilia have an inherent, rhythmic beat, whose total activity produces a wave-like motion directed towards the pharynx. In addition to the ciliated cells, interspersed among the latter are the so-called goblet cells which secrete a mucous substance. This mucous forms a blanket overlying the cilia so that fine inhaled particles may become entrapped in the mucous and removed from the respiratory system by move- ment of the blanket layer via the underlying cilia. It is known that certain inhaled materials impede this mucociliary stream- ing, and some actually paralyze it. To determine whether it is still operating effectively, a fresh tracheal preparation taken from an animal that has been exposed to the suspect material can be examined. Usually, pollen grains or synthetic microspheres are placed on the tracheal membrane, and their pro- gress between two fixed points is observed under a microscope. Another meth- o,d for monitoring mucociliary function involves administration of an aerosol containing radiolabelled particles to an animal (usually of large size). The tnovement of these particles back up the airways is then monitored by scintil- lation detectors and their rate of clearance is deternfined. If the inhaled particle escapes the mueoeiliary system and actually gains access to the alveoli of the lungs, it is confronted with a second system which is concerned with entrapment and removal of foreign matter. There is pres- ent in the interalveolar walls a specialized cell called the septal cell whose job it is to act like the policeman for the alveolus. In performing this func- tion, termed phagoeytosis, projections of the septal eytoplasm sun'ound the particle, and then join, enclosing it within a vacuole. Soon after this, such a cell becomes detached from the alveolar wall. In this free state it is commonly referred to as an alveolar maerophage it still participates in phagoeytie activ- ity, and it also appears to. be capable of ameboid movement. It is by way of this movement that the maerophage reaches the ciliated lining of the air- ways through which it is carried toward the nasopharynx, where it enters and is swallowed. The possibility exists that the septaI cells too may be adversely affected by aerosol inhalation. The most common derangement might be a simple over-

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