THE PHARMACOLOGY OF CHEMICAL IRRITATION* By LLOYD 'W. HAZLETON Research Consultant, Falls Church, Va. CHEMICALS used as irritants comprise one of the older forms of medication, and still enjoy a rather wide popularity. Originally plant and animal drugs such as mustard, volatile oils, tars, and cantharides were most commonly used, but more recently many pure chemicals such as methyl salicylate, salicylic acid, alcohol, and phenol have been ex• tensively employed. In very recent years the progress of chemotherapy and physiotherapy has greatly re- duced the clinical popularity of the chemical irritants although they maintain a significant place in self- medication. Almost simultaneously with this change in therapeutic im- portance there has arisen a wide- spread interest in the control of chemical irritation which appears as a side reaction following the contact of chemicals with the body in such varied roles as medication, cosmetic effect, industrial hazards, clothing, and food processing. When it is realized that the undesirable reac- tion may arise from the pure chemi- cal or impurities, from chemicals used in processing, from solvent * Presented at the May 13, 1947, Meet- ing, New York City. action on containers and other sources, the importance of the prob- lem may be readily appreciated. Currently two types of irritation are recognized, primary irritation and allergic or sensitizing irritation, either of which may cause the symp- toms of contact dermatitis. The following discussion is concerned with primary irritation although occasional reference to sensitization will be made. The essential dif- ference lies in whether irritation arises from single or repeated ex- posure, although a chemical may exhibit both properties. As has so frequently befallen our older scientific terms, the words "irritant" and "irritation" have had apended to them new meanings or donnotations. These words originate from "irritare," to excite, and the original meaning of irritation was a condition of undue excitement, the stimulus necessary to the perform- ance of a function, or the act of stimulating. An irritant, then, was any agent which caused or induced irritation. Such an agent might be chemical, mechanical, or electrical. From an academic point of view this remains the meaning of the terms, 161

162 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS and it is also the sense in which' a modern physiologist uses the term when he refers to the irritability of a cell, a tissue, or an organ. Thus he may study the irritability of a muscle under different conditions, using induced current as the stimu- lus or the irritant. Unfortunately the term has come to be applied to almost anything that affects the living cell, particularly if the effect is deleterious. It becomes apparent then, that to discuss the practical problem of chemical irritation it is necessary to first describe the term in more detail. Certain fundamental biological principles form the basis for a con- sideration of irritation. First, the function of a cell or more complex biological unit may be changed quantitatively but not qualita- tively that is, we may increase, decrease, or stop the performance of a biological unit, but we can- not change the effect of that per- formance. Second, if the quantita- tive change is not sufficiently great to interfere with the nutrition or metabolism of the cell, the effect is reversible that is, the function re- turns to normal when the irritant is removed. Finally, excessive irrita- tion results in permanent, irreversi- ble damage to the cell. In pharmacological terminology, Which in this case is the one com- monly used by industry and the laity, a "stimulant" is an agent which increases function, a "de- pressant" is one which decreases function, and an "irritant" is an agent which reproduces the symp- toms of inflammation. Even so, there is room for confusion and often heated academic debate because stimulants frequently cause depres- sion after the stimulation, or in some cases even before, depression is often preceded briefly by stimula- tion, and small quantities of irritants may produce only stimulation or de- pression. Rarely could there be a topic more conducive to confusion. These conceptions do assist, how- ever, in delineating the topic of chemical irritation to more narrow bounds for the purpose of discussion. Technical criticism excepted, it may be pointed out that since the terms stimulation and depression refer to functional levels which may be altered, they apply to the sys- temic actions of highly specialized tissues or organs, while irritation might occur in less specialized tissue and applies to local actions re- sulting from direct contact. In general this is the case and we asso- ciate irritation with the less special- ized and more accessible tissues such as the skin and mucous membrane. The symptoms of irritation are easily recognized in the visible tis- sues. As classically described through the ages under the term of inflammation they consist of red- ness, heat, swelling, and pain. These are the cardinal symptoms of irrita- tion and are often described under the impressive terms of rubor, calor, turgot, and dolor, respectively. Be- tween these extremes of terminology are the more commonly used clinical terms such as hyperemia, erythema, thermal elevation, edema, conges-