TOXICOLOGY

CH153
Q3 AY2021

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 Toxicological Studies
A major objective is to quantify the effects of the suspect toxicant on a target organism.

• must be identified with respect to its chemical composition and

Toxicant
its physical state
Target or Test • can range from a simple single cell up through the higher
Organism animals (based on cost and availability of test organism)
Effect or Response to
• depends on the toxicant and target organism
be Monitored

Dose Range • depends on the method of delivery

• depends on whether long- or short-term effects are of interest

Test Period
(acute vs. chronic exposure)
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 Toxicological Studies
A major objective is to quantify the effects of the suspect toxicant on a target organism.

• must be identified with respect to its chemical composition and

Toxicant
its physical state
Target or Test • can range from a simple single cell up through the higher
Organism animals (based on cost and availability of test organism)
Effect or Response to
• depends on the toxicant and target organism
be Monitored

Dose Range • depends on the method of delivery

• depends on whether long- or short-term effects are of interest

Test Period
(acute vs. chronic exposure)
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 Toxicological Studies
A major objective is to quantify the effects of the suspect toxicant on a target organism.

• must be identified with respect to its chemical composition and

Toxicant
its physical state
Target or Test • can range from a simple single cell up through the higher
Organism animals (based on cost and availability of test organism)
Effect or Response to
• depends on the toxicant and target organism
be Monitored

Dose Range • depends on the method of delivery

• depends on whether long- or short-term effects are of interest

Test Period
(acute vs. chronic exposure)
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 Toxicological Studies
A major objective is to quantify the effects of the suspect toxicant on a target organism.

• must be identified with respect to its chemical composition and

Toxicant
its physical state
Target or Test • can range from a simple single cell up through the higher
Organism animals (based on cost and availability of test organism)
Effect or Response to
• depends on the toxicant and target organism
be Monitored

Dose Range • depends on the method of delivery

• depends on whether long- or short-term effects are of interest

Test Period
(acute vs. chronic exposure)
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 Dose vs Response
Biological organisms respond differently to the same dose of a toxicant
depending on
Dose • actual amount of a chemical that enters the body

• Age Dose-Response
• suggests that a dose, or a time of exposure will cause an effect on
the exposed organism

• Sex • suggests that there should be a dose or exposure level below

Threshold Dose
which harmful or adverse effects are not seen in a population

• Weight

• Diet

• General health

• Other factors

Response of human eye due to exposure to irritant vapor

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 Dose vs Response Mean
(location of curve)

Consider a
toxicological test run
on a large number of
individuals.
Standard
Each individual is deviation
exposed to the same (determines the shape)
dose and the response
is recorded.
The fraction (f(x))of
individuals
experiencing a specific
response (x) is plotted.

1 æ x-m ö
2 Low Average High
1 - ç ÷ response response response
2è s ø
f (x) = e
s 2p
A Gaussian distribution representing the biological response to exposure to a toxicant
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 Dose vs Response Mean
(location of curve)

Consider a
toxicological test run
on a large number of
individuals.
Standard
Each individual is deviation
exposed to the same (determines the shape) Percentage of
dose and the response individuals affected for
a specific response
is recorded.
The fraction (f(x))of
individuals
experiencing a specific
response (x) is plotted.

1 æ x-m ö
2 Low Average High
1 - ç ÷ response response response
2è s ø
f (x) = e
s 2p
A Gaussian distribution representing the biological response to exposure to a toxicant
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Dose vs Response

Effect of standard deviation on percentage of individuals affected

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Dose vs Response

Curve becomes more

pronounced as σ
decreases

Effect of standard deviation on normal distribution shape

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 Dose vs Response
Seventy five people are tested for skin irritation because of a specific dose of a substance. The
responses are recorded on a scale of 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.
(a) Plot a histogram of the number of individuals affected vs. the response; (b) Determine the mean
and the standard deviation; (c) Plot the normal distribution on the histogram of the original data.
No. of Individuals No. of Individuals
Response Response
Affected Affected
0 0 6 9
1 5 7 6
2 10 8 3
3 13 9 3
4 13 10 2
5 11
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 Dose vs Response
Response Individuals 14
0 0
12
1 5
2 10 No of individuals affected 10
3 13
4 13 8

5 11
6
6 9
7 6 4
8 3
2
9 3
10 2 0
sum 75 1 2 3 4 5 6 7 8 9 10

Response

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 Dose vs Response
Response Individuals 14
0 0
12
1 5
2 10 No of individuals affected 10
3 13
4 13 8

5 11
6
6 9
7 6 4
8 3
2
9 3
10 2 0
sum 75 1 2 3 4 5 6 7 8 9 10

Response

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 Dose vs Response
1 æ x-4.51 ö
2
x f(x) 75 f(x) 1 - ç ÷
f (x) = e 2 è 2.24 ø
0 0.02328 1.74631 2.24 2p
1 0.05192 3.89427
16.00000
2 0.09480 7.11003
14.00000
3 0.14171 10.62815

No of individuals affected
4 0.17343 13.00724 12.00000

4.51 0.17800 13.35000 10.00000

5 0.17378 13.03328 8.00000

6 0.14256 10.69211 6.00000

7 0.09575 7.18149 4.00000

8 0.05266 3.94917
2.00000
9 0.02371 1.77803
10 0.00874 0.65541 0.00000
0 2 4 6 8 10
Response
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 Dose vs Response
Dose-Response Curves

Cumulative mean response at each dose Cumulative mean response vs

Error bars at + around the mean logarithm of dose

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 Dose vs Response
Dose-Response Curves

Effective • used when the response is

Dose minor and reversible

Toxic • used when the response is not

Dose lethal but irreversible

Lethal • used when the response is

Dose death or fatality

ED50, • dose that results to 50% of the

TD50, LD50 response

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 Dose vs Response
For several toxicants, interactions may be:

Additive Synergistic Potentiate Antagonistic

• the combined • the combined • the presence of • both counteract
effect is the effect is more one increases each other
sum of the than the the effect of
individual individual another
effects effects

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 Models for Dose vs Response
For single exposures: Probit (probability unit) method

Probability variable
æ u2 ö
ò
1 Y -5
Y= exp ç - ÷du
è 2ø
1 -¥
( 2p ) 2

Y – probability variable
P – probability
See table 2-4 (Transformations from Percentages to Probits

Y = k1 + k2 lnV
V – dose
See table 2-4 (Probit correlations for a number of different types of exposures)

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 Models for Dose vs Response

The probit transformation converts the sigmoidal

response vs. log dose curve into a straight line when
plotted on a linear probit scale

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 Models for Dose vs Response
Table 2-5. Probit correlations for a number of different types of exposures

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 Relative Toxicity
Hodge-Sterner Table for Toxicity Degree

Experimental LD50 per kg Degree of Toxicity Probable LD for a 70-kg

of body weight Person
< 1.0 mg Dangerously toxic A taste
1.0 – 50 mg Seriously toxic A teaspoonful
50 – 500 mg Highly toxic An ounce
0.5 – 5 g Moderately toxic A pint
5 – 15 g Slightly toxic A quart
> 15 g Extremely low toxicity More than a quart

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 Relative Toxicity

TD50

The given curves represent dose-response by Two toxicants with differing relative toxicities at different doses:
toxicants, the values were TD50. A is more toxic at high doses;
A is most toxic, followed by B, C and D. B is more toxic at low doses
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 Threshold Limit Values
• Threshold Limit Value – Time-Weighted Average
TLV- • Time-weighted average for a normal 8-hour workday or 40-hour work week, to which nearly all
TWA workers can be exposed, day after day, without adverse effects
• Excursions above the limit are allowed if compensated by excursions below the limit
• Threshold Limit Value – Short-Term Exposure Limit
• Maximum concentration to which workers can be exposed for a period of up to 15 minutes continuously
TLV- without suffering (1) intolerable irritation; (2) chronic or irreversible tissue change; (3) narcosis of sufficient
STEL degree to increase accident proneness, impair self-rescue or materially reduce worker efficiency, provided
that no more than 4 excursions per day are permitted, with at least 60 minutes between exposure periods
and provided that the daily TLV-TWA is not exceeded

• Threshold Limit Value – Ceiling

TLV-C
• The concentration that should not be exceeded, even instantaneously
PEL • Permissible Exposure Level

IDLH • Immediately Dangerous to Life and Health

*TLVs are reported using ppm (parts per million by volume) or mppcf (millions of particles per cubic foot of air)
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TOXICOLOGY

END

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