J'. Soc. Cosmet. Chem., 25, 283-296 (May 1974) Testing for Inhalation Toxicity WILLIAM R. TROY, M.S.* Presented March 7, 1973, before the New York Chapter, Clifton, N.I. Synopsis-The purpose of this review is to outline some of the fundamental considerations involved in testing for INHALATION SAFETY of COSMETIC PRODUCTS. Apart from design of the exposure system and selection of test animals, factors such as environmental controls, proper dose levels, and signs of TOXICITY to watch for are of prime importance when conducting such studies. A discussion of three areas of concern with regard to the inhalation safety of cosmetic AEROSOLS is also included. The questions of hair spray "storage disease," possible aspi- ration of spray talc, and allegations of cardiotoxicity of aerosol propellants are treated with regard to experimental activity in these areas and what, if anything, has been proven to date by these investigations. INTRODUCTION Investigations in inhalation toxicity present some rather unique problems. Unlike most other cosmetic products, aerosols are afforded practically immedi- ate access to the systemic circulation by virtue of their being inhaled into the highly vascular lungs. For this reason, the potential for toxicity for such prod- ucts is greater than for formulations that are routinely applied to the skin such as flowing make-ups or body lotions. In addition to the possibility of sys- temic toxicity, there may also be localized adverse effects on the organs of the respiratory system by inhaled toxicants. Naturally, not even the slightest hint of either type of adverse effect would be acceptable for any cosmetic aerosol. The following review has a twofold intention: first, to outline some of the equipment used in inhalation toxicology, parameters measured, and conditions necessary for proper investigation and second, a discussion of the recent literature in the area of cosmetic aerosol toxicology. *Avon Products, Inc., Suffern, N.Y. 10901. 283

284 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS INHALATION METHODOLOGY Systems The first factor to be considered with regard to the design of an inhalation experiment is the design of the exposure system. Many considerations, includ- ing the number and species of animals to be used, space available, nature of the sample, etc., are involved in the selection of equipment for this type of toxicity testing. There are two basic types of inhalation exposure (and sev- eral variables of these): head-only and whole-body exposure. In the former type of experiment, the animal may be in an enclosure which is external to the actual chamber only its head protrudes into the chamber and is exposed to the test material. This approach finds frequent use in noncosmetic areas where the possibility of oral ingestion of the test material should be separated from the inhalation route of entry oral intake of the material can occur quite easily if the whole animal is exposed and goes through the normal routine of preening its fur which has been saturated with an aerosolized prod- uct. A modification of the head-only type of exposure is one in xvhich the aerosol is delivered through a face-mask which has been fitted to the animal an antiasthma preparation was recently reported as having been tested in this manner ( 1 ). The whole-body method of exposure probably best approximates the types of contact with which we must deal in the use of cosmetic aerosols. In expos- ing the entire animal to an aerosolized material, of course, it must be under- stood that in addition to conducting an experiment in inhalation toxicology, we are also performing qualitative tests in eye irritation, oral toxicity, and derreal toxicity since all of these organ systems are being exposed to the aerosol in addition to the lungs. It makes good sense, then, to fully investigate the potential for toxicity on these other organ systems before investing time and effort in an inhalation study. Many differcnt chamber designs have been suggested since the original plexiglass box used by Draize (2). In one type, the axis of orientation is hori- zontal and the test material is introduced on one side, while the chamber is evacuated on the other side. In a second type, the axis is vertical and sample movement is from top to bottom. The latter seems to be more popular and is generally used in conjunction with a chamber whose body is basically cubical and tapers towards the top and bottom. Allusion was made to the introduction and distribution of sample. Again, there are two basic approaches available. In the so-called "static chamber" system, the dose of material is introduced into the chamber atmosphere, the system is sealed, and the animals breathe only thb air which is present in the chamber. In the "dynamic" system, the gas or suspended liquid is introduced into a stream of air which is continuously sweeping through the chamber at a constant rate. With proper chamber design, good distribution of the aerosol is almost assured if the airflow is rapid enough.