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Chapter 2 –Toxicology
Definitions, Entry to Biological organism and
elimination, Effects of toxicants on biological
organisms, Dose versus response, Models for
dose and response curves, Threshold limit values
Definitions
Toxicology: - entry of toxicants into organism
•elimination from organism
•effects on organism
Toxicology is the qualitative and quantitative study of the adverse effects
of toxicants on biological organisms
Industrial hygiene: prevention or reduction of entry (Chapter 3)
Toxicant
• chemical agents
• physical agents: particulates < 5 μm, noise, radiation
Toxicity: property related to effect on organism
Problem: organisms respond via a distribution of effects
Toxic hazard: likelihood of damage to biological organisms
based on exposure
“All substances are poisons; there is none which is not poison. The right dose
differentiates a poison and a remedy” (Paracelsus, 1500s)
How Toxicants Enter Biological Organisms?

Toxicant enters the organisms → moves into the bloodstream → elimination or
organ
transportation to target
Table 2.1: Entry Routes for Toxicants and Methods for control
Entry Route
Entry Organ
Method for Control
Ingestion
Mouth or
stomach
Enforcement of rules on eating, drinking and
smoking
Inhalation
Mouth or nose
Ventilation, respirators, hoods and other personal
protection equipment
Injection
Cuts in skin
Proper protective clothing
Dermal absorption
Skin
Proper protective clothing
Source: Crowl and Louvar (2002)
Toxic blood levels
Routes and elimination
Toxicological Studies
Objective: To quantify the effects of the suspect toxicants on target organism.
Biological organisms respond differently to the same dose of a toxicant as a result
of age, sex, weight, general health and other factors. The following items must be
identified:
• Toxicant: chemical composition and physical state.
Example: Benzene (vap or liq ??) different routs of entry
• Target or test organism: from single cell to higher animal. (cost and availability)
• Dose unit. ( milligrams of agent per kilogram of body weight)
• Period of the test. Acute toxicity is the effect of a single exposure or a series of
exposures close together in a short period of time. Chronic toxicity is the effect of multiple
exposures occurring over a long period of time. Chronic toxicity studies are difficult to
perform because of the time involved; most toxicological studies are based on acute
exposures
Tests are carried out on animals such as mice and
rabbits. very poor animal indeed!
Dose versus Response
Now, it’s the time to refresh our skills in statistics!
Gaussian chart plot or
Normal distribution
µ is the arithmetic mean
n

 x f (x )
i 1
n
i
i
 f (x )
i 1

i
f ( x ) = probability (or fraction) of individuals
experiencing a specific response
x = response
σ = the standard deviation
1 21( x )2
f ( x) 
e
 2
•Standard deviation measures how
the data are spread out with respect
to the mean
Standard deviation
•The bigger σ, the more spread the data are
•Area under the curve represents the percentage
of individuals affected for a specific response
interval
Example 2.1
Seventy-five people are tested for skin
irritation of a specific dose of a substance.
The responses are recorded on a scale from 0
to 10, with 0 indicating no response and 10
indicating a high response. The number of
individuals exhibiting a specific response is
given in the following table :
i.Plot a histogram of the number of individuals
affected versus the response.
ii.Determine the mean and the standard
Deviation.
iii.Plot the normal distribution curve on the
histogram of the original data.
Solution:
σ = 2.24
Dose versus Response
When you injected 100 rabbits with a substance, you
will find that they respond differently. Some of them
will suffer even at small dose, while other need bigger
doses to feel the same pain!.
Dose
Response category
D1 (for example 1ppm)
1 (to denote for example
“not being felt”)
D2
2
D3
3 to denote for example
(“severe impact’)
D4 (for example 100 ppm)
4 (to denote for example
“death”)
Convert this
table to
figure
This plot is not very useful, especially
at low doses. So we produce the log
curve which takes the S-shape
Dose versus Response
•
•
•
•
Dose → 50% lethality (LD50) used for comparison. (LD10 and LD90) sometimes also
used.
For gases → LC (Lethal Concentration) curve
For minor and reversible responses → ED (Effective Dose) curve
Toxics (not lethal, but irreversible response) → TD (Toxic Dose) curve
Models for Dose and Response Curves
•Response vs. dose curves can be drawn for a wide variety of exposures, including
exposure to heat, pressure, radiation, impact, and sound. For computational
purposes such curve is not convenient; an analytical equation is preferred
•Change S-shape into straight line using a mathematical transformation called a probit.
(probit= probability unit)
•In mathematical terms probit is a straight line probability relationship
developed to measure, for example, killing a certain proportion of the
population, expressed as a standard deviation and related to a mean of 5.
It has the advantage of being easily used without deep understanding of
the underlying theory, provided suitable data is available.
•Using probits, most response vs. dose curves can be represented in the form:
Y = k1+ k2 ln ( V )
where Y = Probit
variable
k1, k2 are constants
V = causative variable (the magnitude of the exposure such as
heat, pressure, radiation, impact, and sound in their rightfull units)
Models for Dose and Response Curves
Probit (probability unit) Method provides straight-line equivalent to response-dose curve
1
P
(2 )1/ 2
Y 5
 u2 
 exp   2  du
more pratical to use
 Y 5
 Y  5 

P  50 1 
erf 

Y

5

 2 
Y  k1  k 2 ln V
Transformations from Percentages to Probit
Relative Toxicity
Toxicity might differ with the amount of dose
Two toxicants with differing relative toxicities at different doses.
Toxicant A is more toxic at high doses, whereas toxicant B is more
toxic at low doses.
Threshold Limit Values
Threshold dose: The lowest value in the response vs. dose curve below which
the body is able to detoxify the agent without any detectable effects
Threshold Limit Value - TLV: airborne concentrations that correspond to
conditions under which no adverse effects are normally expected during worker’s
life time Often called maximum allowable concentration (MAC)
TLV values are Published by ACGIH: American Conference of Governmental
Industrial Hygienists (ACGIH), a professional organization without legal
authority
Some materials have zero threshold
IDLH: Immediately Dangerous to Life and cause Death , thus Exposure should be
avoided.
Values in Table are tabulated. For vapors, mg/m3 is converted to ppm
using the equation
Examples for TLV
TLVs are reported using ppm (parts per million by volume), mg/m3
(milligrams of vapor per cubic meter of air), or, for dusts, mg/m3 or mppcf
(millions of particles per cubic foot of air).
PEL - Permissible Exposure Level (another system) versus TLV
•Published by OSHA, and have legal authority.
•Defined in the same way as TLV.
•Most PELs are same as TLVs.
•Not updated as regularly as TLVs.
•Most companies use lowest of the two values .
•TLV estimates assume that workers are only exposed during the normal
eight-hour workday.
•Companies use the lowest values of both. In all cases, every effort must be
done to reduce worker exposures to toxicants to below the PEL and lower if
possible.