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 bio- transformation. 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 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 (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.

The Causative Factor (Dose) Continuous Discharge:, where C is concentration in ppm, t is the exposure timein minutes, a, b and n are regression constants (listed in Table 2-2). Instantaneous Discharge:, where the subscript i is used to indicate the i-th time interval. Other (see Table 2-3)