toxicology

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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)
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