mfety tip/
edited by MIRIAMC. NAGEL Avon High School
Awn. CT 06001
Toxicology and Chemical Safety Stephen K. Hall American Industrial Health Services, Wood River, IL 62095 Toxicology is the study of the adverse effects of chemicals on living organisms. In the modern-day world with our constant exposure to foreign chemicals, i t is important to have some knowledge of toxicology and chemical safety. Toxicity is defined as the capacity of a chemical to produce injury. In practical situations, the critical factor is the hazard or risk associated with chemical use. Hazard is defined as the practical certainty that injury will occur when a chemical is used in a stated auantitv under specific conditions. Safetv is the reciprocal oi hazard; it is the practical certainty that injury will not occur when a chemical is used in a stated quantity under specified conditions. Depending on the quantity and conditions under which a chemical is used, a verv toxic chemical may be less hazardous than a relatively nbntoxic chemical. Hazard assessment takes into account possible toxic effecb from the use of a material in the quantity and in the manner oronosed. In evaluatine hazard. toiicitv is hut one factor. Two chemicals may possess the same degree of toxicity hut present different degrees of hazard. Carbon monoxide, for example, is odorless, colorless, and nonirritating to the eye, nose and throat while ammonia has a pungent odor and is an eye, nose, and throat irritant. By comparison, ammonia, with the warning properties, presents a lesser degree of hazard. Many chemicals are nonselective in their action on tissues or cells. For example, strong acids and bases exert corrosive effects on all living matter. Other chemicals may act only on specific tissues or target organs. For example, heavv metals A
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and trichloroethene affect the hepatic system. Although the toxic effects of many chemicals are well known, there are many other commonly used chemicals, the toxic effects of which are not as well defined. The toxicity of a chemical is not a physical constant, such as melting point or vapor pressure, and usually only a general statement can be made concerning the toxic nature of some of the chemicals. Route of Exposure In discussing toxicity, it is necessary to describe how a chemical gains entrance into the bodv and then into the blooddrt.1111.O i i ~ilh,tdit.d ~t~ i t i t . ) t hr l h d ~ ~ r ~ .rl~( il ~ i ie .i t:il ~ t111:~~ ~ t i c i l xt.it1 r.11 tirc.t. or. I I I , ~thim likt-I).. 1111 1%~ i c . t ~ t e ,\\.ill ti be localized in specific tissues or target organs. The major routes by which chemicals gain access to the hody are through the lungs (inhalation),the skin (topical absorption), and the gastrointestinal tract (ingestion). Inhalation is by far the most important route of entry for chemicals. Any chemical that is airborne can be inhaled. The Editor's Note Readers concerned about the toxicology properties of many important classes of organic and inorganic compounds used in the iaboratory will find additional valuable information in two Resource Papers on Chemical TOxiCObgy published in THIS J o u n ~ aVoi. ~ , 56.Number 5 (May 1979) and Number 8 (August 1979).
total amount of chemical absorbed via the respiratory tract depends upon its concentration in the air, the duration and frequency of exposure, and the rate of breathing. The solubility of the gases and vapors in water is generally the major characteristic determining the relative toxicities of chemicals. The second important route of entry is absorption through the intact or abraded skin. The absorption of liquid organic compounds may follow surface contamination or the skin or of clothes, or it may occur directly from the vapor phase. Temperature elevation may increase skin absorption by increasing vasodilation. If the skin is damaged by scratching or other abrasion. the normal nrotective barrier to absorntion is lessened andenhanced penetration may occur. The problem of ingesting chemicals is not widespread hut accidental swallowing does occur. Ingestion of inhaled chemicals can also occur because chemicals deposited in the respiratory tract can he carried out to the throat by the action of the ciliated lining of the respiratorv tract. These chemicals are then swallowedand significant absorption from the gastrointestinal tract may occur. Dose Response Relationship
All toxicological considerations are based on the dose-response relationship. The toxic potency of a chemical is ultimately defined by the relationship between the dose (the amount) of the chemical and the response that is produced in a biological system. In toxicity testing, death of the experimental animal is the response must commonly chosen. Given a compound with no known toxicity data, the initial step is one of range finding. A dose is administered and, depending on the outcome, is increased or decreased until a critical range is prepare a dose-response curve relating percent mortality to dose administered. If the only variable being considered is the number of deaths, then it is possible to use the concept of the lethal dose (LD). The dose that will produce death in 50% of the experimental animals is commonly abbreviated as LDal, and the dose is expressed as amount per unit of hody weight such as mglkg. The LD5o is the concentration that kills half of the exposed animals. but it does not mean that the other half are inkood health. The LDso values should also be accompanied by an indication of the species of exnerimental animal used, the route of administradion for the'chemical, and the time period over which the animals were observed. If the experiment has involved inhalation as the route of exposure, the dose to the animal will he expressed as the concentration of the chemical in the air such as mglm". In this case, the term LCm is used to designate the concentration in air that may he expected to kill 50% of the animals exposed for the specified length of time. Action of Toxic Substances The toxic action of a chemical can he arhitrarilv divided into acute and chronic effects. Acute exposure and acute effects involve short-term high concentrations and immediate results Volume 60
Number 2
February 1983
145
of sotn@nd resulting in illness, irritation, or death. Acute expo'su%es,typically, are sudden and severe and are characterized by rapid absorption of the offending chemical. For examnle. inhaling high concentrations of carbon monoxide or swalloking a large quantity of sodium cyanide will produce acute poisoning very rapidly. The critical period for death or survival of a victim occurs suddenly. Such incidents generally involve a single exposure in which the chemical is rapidly absorbed and damages one or more of the vital organs. The effect of a chemical hazard is considered acute when it appears with little time lag, such as within hours or minutes. In contrast to acute effec,?, chronic effects are characterized by symptoms or disease 01 iong duration or frequent recurrence that often develop slowly. The term chronic also relates to continued exoosure to substances throuahout a working lifetime. chronic effects can also he produce2 by exposure to a harmful material which produces irreversible damage such that the injury accumulates, rather than the poison itself. The symptoms in chronic ooisoning are usually different from those seen in acute poisoning caused by the Same toxic agent. For example, acute benzene poisoning affects the central nervous system or may even result in death, h u t chronic benzene poisoning affects the hlood cell production capability of the bone marrow. Effects of Exposure to Chemicals The spectrum of undesired effects of chemicals is broad. Some are deleterious and others are not. One distinction between types of effects is made on the general location of action. Local effects refer to those that occur a t the site of first contact between the chemical and the biologic system. Examples of local effects are demonstrated hy the corrosive actions of acids and bases. Systemic effects require absorption and distribution of the chemical to a site distant from its entry point. Most chemicals produce systemic effects. For some chemicals, however, both local and systemic effects can he observed. For example, tetraethyl lead produces local effects on the skin a t the site of absorption and then is transported in the hlood system to produce its typical effects on the central nervous system and other systems. Asphyxiation is a common effect caused by some gases and vapors. Asphyxiants exert their effects hy interfering with the supply of oxygen. Simple asphyxiants are physiologically inert gases that act by diluting atmospheric oxygen below that required to maintain hlood levels sufficient for normal tissue respiration. Some common examples are the inert gases, hydrogen, nitrogen, and low-molecular-weight alkanes. Chemical asphyxiants, on the other hand, through their direct chemical action, either prevent the uptake of oxygen by the hlood, interfere with the transportation of oxygen from lungs to the tissues, or prevent normal oxygenation of tissues even though the hlood is well oxygenated. Carbon monoxide prevents oxygen dissociation by preferentially combining with hemogluhin, while hydrogen .yanide inhibits enzyme systems to utilize molecular oxyge~t. Irritation is another toxic effect caused bviases . " and vaoors. Irritation involves some sort of aggravation of whatever tissue the chemical comes in contact with. Direct contact of some chemicals with the face and upper respiratory tract affects the eyes, the tissues lining the nose, and the throat. Ammonia and chlorine are classic examples of irritant gases. Bronchoconstrictmn or the feeling of an inahility to breathe occurs immrdiately on inhalation. Both gases are well tolerated in that, unless the concentration is sufficient to cause death, the acute effects do not result in chronic poisoning. A variety of chemicals produce damage to the cells of the "Safety Tips" is planned to be a source of safety information and practical suggestions to meet the special needs of high school chemistry teachers. It is also intended to be a forum for teachers to share their experiences and seek solutions to safety related problems.
146
Journal of Chemical Education
airways and alveoli. The resulting increase in permeability mav lead to the release of fluids into the lunes oroducine an edema. Ozone and nitrogen dioxide are examples of t k c chemicals that produce cellular damage. The water solubility of these chemicals is sufficiently low that the main site of action is in the lower respiratory tract. Phosrene is another irritant capable of prodicing delayed pulmonary edema. The
and the development of symptoms. Individuals exposid to phosgene should he under medical surveillance for a t least 48 hours. Inhalation of solid particles or chemical dusts may have some health effects. There is a certain amount of filtration hv crometersk diameter can he &haled and reach the deep lung readily. Once they get there, the simplest effect is to he deposited in t h e lung without causing any damage. Inert dusts such as calcium carbonate and barium sulfate are considered relatively harmless unless the exposure is long-term and severe. Inert dusts are sometimes called nuisance dusts. They may cause radiopaque deposits in the lung that are visible on X-ray films, but they produce little or no tissue reactions unless the exposure is overwhelming. Pneumoconiosis is the term applied to a class of diseases caused by the accumulation of dusts in the lungs. Pneumoconiosis associated with inert dusts are potentially reversible and sometimes called benign pneumoconiosis. Far more serious is the effect of insoluble particles which cause fibrotic changes in the lung. Fibrotic changes are produced by materials such as free silica which produce the typical silicotic nodule or small area of scar-like tissue. Asbestos fibers also produce typical fibrotic damage to lung tissue and, in addition, cancerous lung changes. Chronic pulmonary disease can result from inhalation of a variety of materials that appear to act wholly or partly through an allergic response. This underlying mechanism is demonstrated by the presence of antibodies to specific components of the inhaled materials. In some inst,ances, these reactions are caused by spores of molds or by bacterial contaminants. In other instances. as in the case of cotton dusts. they appear to he related to components of the material itself. An examnle of an organic dust that can nroduce allerric-like symptonk on inhalation is toluene diisocyanate, which is widely used in the manufacture of polyurethane plastics. It is well established that exposure to some chemicals can produce cancer in laboratory animals and humans. A carcinogen can he defined as a substance that will induce a malignant tumor in an animal following a reasonable exposure. Benzene exposure has been associated with hlood dyscrasias which may progress to leukemia. Coal tar and various petroleum products have been identified as skin and subcutaneous carcinogens. Vinyl chloride monomer has been identified to cause cancer of the lining of the liver among some workers. Inorganic salts of metals such as beryllium and chromium are associated with cancer of the resoiratorv tract. t is impossible to discuss all Within the scope of this space, Y the specific toxic actions of various classes of chemicals, although wherever possible, specific examples have been used to illustrate the principles involved. Prudence is the most important factor in the safe and careful handling of chemicals whether or not their specific toxicity is known. Desoite the potential hazards of hundreds of new chemicals each year, most injuries from chemicals are due to those which are in daily and general use.
Excerpts from a paper presented at the Kansas City Conference on Chemical Education, September. 1982.
