Toxicology and Industrial Hygiene The chemical engineers must be knowledgeable about • The way toxicants enter biological organisms (T); • The ways toxicants are eliminated from biological organisms (T); • The effects of toxicants on biological organisms (T); • Methods to prevent or reduce the entry of toxicants into biological organisms (H). Poison “All substances are poisons; there is none which is not a poison. The right dose differentiates a poison and a remedy.” by Paracesus “There are no harmless substances, only harmless ways of using substances.” More Definitions • Toxicant: A toxicant can be a chemical or physical agent, including dusts, fibers, noises and radiation. • Toxicity: Toxicity is the a property of the toxicant describing its effects on biological organisms. • Toxicology: The qualitative and quantitative study of the adverse effects of toxicants on biological organisms. How toxicants enter biological organisms? • • • • Ingestion – via mouth into stomach; Inhalation – via mouth or nose into lungs; Injection – via cuts into skin; Dermal Absorption – through skin membrane. Methods for Control • Ingestion: enforcement of rules on eating, drinking and smoking. • Inhalation: ventilation, respirators, hoods and other personal protection equipment. • Injection: proper protective clothing. • Dermal absorption: proper protective clothing. How toxicants are eliminated from biological organisms? • Excretion: through the kidney, liver, lungs or others. Kidneys are the dominant means. • Detoxification: by changing the chemical into something less harmful by biotransformation. Liver is the dominant organ. • Storage: in the fatty tissue. Toxic effects that are irreversible • Carcinogen causes cancer. • Mutagen causes chromosome damage. • Reproductive hazard causes damage to reproductive system. • Teratogen causes birth defects. Effects may or may not be reversible • Dermatotoxic affects skin. • Hemotoxic affects blood. • Hepatotoxic affects liver. • Nephrotoxic affects kidneys. • Neurotoxic affects nervous system. • Pulmonotoxic affects lungs. Toxicological Studies A major objective is to quantify the effects of the suspected toxicant on a targeted organism. For most studies, small animals (mice, rabbits or guinea pigs) are used. The following items must be identified in advance: (1) the toxicant, (2) the target or test organ, (3) the effect or response to be monitored, (4) the dose range and (5) the test period. The Dose Units • For substance delivered directly into the organism by ingestion or injection, the dose is measured in mg of agent per kg of body weight. • For gaseous airborne substances, the dose is measured in either ppm or mg of agent per cubic meter of air (mg/m^3). • For air borne particulates, the dose is measured in mg of agent per cubic meter of air (mg/m^3) or millions of particles per cubic foot (MPPCF). Dose Versus Response The lethal dose curve in Figure 2-3 is a curve of probability of lethality (P) vs. logarithm of the dose (V). This curve is usually sigmoidal. For comparison purposes, the dose that result in 50% lethality is often reported. This is called the LD50 dose. The Probit Variable Probit is the abbreviation of Probability Unit. The probit variable Y is chosen as a normally distributed random variable with mean 5 and variance 1. Thus, a given lethality probability can be expressed with Y according to 1 P(Y ) 2 Y 5 e u2 2 du (See Table 2-1, Figure 2-4). Note that a Y can be determined from a given P. The Probit Transformation The probit relationship transforms the sigmoid shape of the normal response vs dose curve into a straight line when plotted using a linear probit scale (Figure 2-5). Standard curve fitting techniques are used to determine the best fit straight line, i.e. Y a b ln V The Causative Factor (Dose) • Continuous Discharge: V C nt, where C is concentration in ppm, t is the exposure timein minutes, a, b and n are regression constants (listed in Table 2-2). m • Instantaneous Discharge: V Citi , where the i 1 subscript i is used to indicate the i-th time interval. • Other (see Table 2-3)