J. Soc. Cosmet. Chem., 25, 645-654 (December 1974) The Uptake, Distribution, and Excretion of a Commercial Aerosol Antiperspirant by the Monkey PAUL FINKELSTEIN, Ph.D.,* and RONALD J. WULF, Ph.D.t Presented December 11, 1973, New York City Synopsis-Four monkeys were exposed to the spray of an AEROSOL ANTIPERSPIBANT in a head-only exposure chamber by directing the stream directly at the face for 5 seconds. One ingredient of the formulation, ISOPRQPYL MYRISTATE, was RADIOLABELED with carbon-14. Following exposure, two animals were sacrificed immediately and two others were allowed to live for 24 hours before necropsy. The distribution of carbon-14 in several tissues, as well as in the exhaled breath, was determined. The results indicate that only about 0.025% of the dose sprayed at the animals reached the lower respiratory tract. In 24 hours about 85% of the carbon-14 had been eliminated. INTRODUCTION For many years the most widely used active ingredients in commercial an- tiperspirant products have been aluminum salts. They have been formulated and sold in a variety of vehicles and applicators, including simple aqueous solutions, lotions, creams, and sticks. More recently, the aerosol sprays have been introduced and have assumed a leading role in the marketplace. These formulations usually contain a suspension of an aluminum salt in a nonaque- ous vehicle which is propelled by fiuorocarbons. With the introduction of these aerosol spray products, the possibility of inhalation hazards had to be considered. The usual procedures for testing for such hazards include acute inhalation exposures of rats and 30- or 90-day exposures of rabbits or rats and, more recently, monkeys. These tests are con- ducted under exaggerated conditions of exposure compared to the normal use of the product. Examination of toxicologic symptoms, as well as physio- logic, histologic, and chemical alterations, is made in the animals. However, no attempt is made to determine what fraction of the spray is actually ab- *Present address: Johnson & Johnson, New Brunswick, N.J. '•Carter Products Research, Div. Carter-Wallace, Inc., Cranbury, N.J. 08512. 645

646 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS sorbed by the animals. This is governed by several factors, among which is the particle or droplet size when the sprays contain partially volatile or sus- pended materials. The studies reported here were an attempt to estimate the amount of anti- perspirant spray inhaled by monkeys exposed to an exaggerated dose of the test product (5 sec of spray) directed at the face. This was done by labeling the major ingredient of the nonaqueous vehicle, isopropyl myris- tate (IPM), with carbon-14. No beta-emitting isotope of aluminum was con- venient or practical to use as a label, although this might have been desirable. The only other ingredients in the formulation were perfume and the anti- caking agent Bentone©-34.* The monkeys were sacrificed immediately after exposure to minimize meta- bolic uptake and translocation. Since it was also desirable to look at the pat- tern of distribution of the absorbed spray, some of the monkeys were allowed to live for 24 hours before being sacrificed. EXPERIMENTAL METHODS The antiperspirant spray formulation was radiolabeled by adding a very small quantity of carboxyl x4C-IPM? with a high specific activity to a sample of concentrate in a spray can. Propellants were then added and the can was sealed. The formulation was shaken overnight to insure uniform distribution. Approximately i millicurie of x4C was thus dispersed in 90 g of formulation. Adult male rhesus monkeys weighing about 2.5 kg were used. The animals were allowed to accommodate to the laboratory environment for four weeks or longer. All received a general physical examination with special attention to the respiratory system. Only animals in good health were placed on the study. A special chamber was constructed to permit a head-only exposure of the animals to the spray. Each animal was placed in a standard primate restrain- ing chair with his head in the chamber. The system is shown in Fig. 1. The acrylic chamber measured 6 in. x 6 in. x 18 in. One end of the box had an opening for admitting the spray, while air was drawn out from a port at the other end. A membrane filter (0.45-/• pore size) was positioned in front of this exit port to trap any airborne particles. Air was pulled through the cham- ber at 4 1./min. A 5-sec burst of the aerosol spray was directed at the face of each animal. This released a mean of 53.05/•c of activity into the chamber. The animal was allowed to take 30 breaths, which took i to 2 min. Two animals were sacri- ficed immediately and two others were fitted with a face mask covering the nose and mouth to collect the exhaled breath for 24 hours. *Bentone©-34, a magnesium aluminum silicate proprietary composition from National Lead Corp., Hightstown, N.J. ?Carboxyl '•C-IMP, synthesized by New England Nuclear Corp., Boston, Mass.