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.50LD

The Probit VariableProbit is the abbreviation of Probability Unit. The probit variable Y is chosen as a normally distributed randomvariable with mean 5 and variance 1. Thus, a given lethalityprobability can be expressed with Y according to

dueYPY

u

52

2

2

1)(

(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.

lnY a b V

The Causative Factor (Dose)• Continuous Discharge: , where C is conc

entration 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)

i

m

iitCV

1

nV C t