24-Mar-21

Toxicology
Chapter 2 in C&L

Definitions
"All substances are poisons; there is none which is not a poison. The right
dose differentiates a poison and a remedy " Paracelsus (1493 - 1541)
Toxicology The study of poison (Old Definition)
Quantitative Toxicology: Entry of toxicants into organism;
Elimination from organism; Effects on organism
A fundamental principle of toxicology is “There are no harmless
substances, only harmless ways of using substances”.
Toxin A poisonous substance produced by living cells or organisms
Toxicant A toxicant is any toxic substance. The term is often used to denote
substances made by humans or introduced into the environment
by human activity, in contrast to toxins, which are toxicants
produced naturally by a living organism.
- Chemical agents
- Physical agents: particulates < 5 µm, noise, radiation
Toxic It is the likelihood of damage to biological organisms based on
hazard: Exposure. The toxic hazard of a substance can be reduced by the
application of appropriate industrial hygiene techniques. The
toxicity, however, cannot be changed. 2

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Entry Routes for Toxicants

Industrially most significant

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Toxic Blood Level: Route of Exposure

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Food Chain Exposure

Elimination of Toxicants

Volatiles → lungs: e.g. chloroform and Massive exposure

alcohols to chemical agents
can damage
kidneys, liver or
lungs

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Effects of Toxicants
Effect of toxicants

Types of Toxic Effects Caused by Industrial Chemicals

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Quantitative Toxicology
Types of Exposure with Time

Acute exposure: A single exposure to a toxic substance which

may result in severe biological harm or death; acute exposures
are usually characterized as lasting no longer than a day.

Chronic exposure: Continuous exposure to a toxic substance over

an extended period of time, often measured in months or years;
it can cause irreversible side effects.

Quantitative Toxicology
Toxicology Dose-Response Experiments with Lab Animals

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Quantitative Toxicology
Toxicology Dose-Response Experiments with Lab Animals, Cont’d (1)

Get S-shaped curve

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Quantitative Toxicology
Toxicology Dose-Response Experiments with Lab Animals, Cont’d (2)

Probit: a unit of probability based on deviation

from the mean of a standard distribution. See
Table 2-4 in text for numerical conversion.

Along row From 0-9%

Along row From 10-19%

Along row From 90-99%

Along row From 99.0-99.9% 12

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Quantitative Toxicology
Toxicology Dose-Response Experiments with Lab Animals, Cont’d (3)

Using probits, most

response vs. dose
curves can be
represented in the
form (Table 2-5):

Where:
Y = Probit variable
k1, k2 are constants
V = Causitive variable

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Example 1
A blast produces a peak overpressure of 47,000 N/m2. What fraction of
structures will be damaged by exposure to this overpressure? What fraction of
people exposed will die as a result of lung hemorrhage? What fraction will have
eardrums ruptured? What conclusions about the effects of this blast can be
drawn?

Solution
From Table 2-5

Y = Probit variable
k1, k2 are constants
V = Causitive variable

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Example 1, cont’d (1)

Overpressure (Po) = 47,000 N/m2
From Table 2-5:

Structural damage: Y = -23.8 + 2.92 ln (Po) Structural damage: Y = 7.61

Death (lung hemorrhage): Y = -77.1 + 6.91 ln (Po) Death (lung hemorrhage): Y = -2.76

Ear Drums: Y = -15.6 + 1.93 ln (Po) Ear Drums: Y = 5.163

Convert from Y to percentage from Table 2-4

Structural damage: 99.54%

Death (lung hemorrhage):

0 (-ve)

Ear Drums: 56.3%

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Example 1, cont’d (2)

Comment:
The explosion is not serious enough to expect fatalities, but is series to cause
extensive damage to surrounding structures and to rupture ear drums for
about 56% of the people exposed (Take care that additional injuries from debris
might be expected)

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Example 2 – In-class Exercise

Determine the concentration of ethylene oxide that will cause a 50% fatality rate if
the exposure occurs for 30 min.

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Example 3
The peak overpressure expected as a result of the explosion of a tank in a plant
facility is approximated by the equation log P = 4.2 – 1.8 log r where P is the
overpressure in psi and r is the distance from the blast in feet. The plant
employs 500 people who work in an area from 10 to 500 ft from the potential
blast site.
Estimate the number of fatalities expected as a result of lung hemorrhage and
the number of eardrums ruptured as a result of this blast. Be sure to state any
additional assumptions.

Solution r

Explosion overpressure is given by

log P = 4.2 – 1.8 log r where P in psi and r in feet
500 people who work in an area
from 10 to 500 ft
Assume that the 500 people are evenly distributed throughout the area

Total Area: π [(500)2-(10)2]=7.85×105 ft2

500
People Density: 7.85×105 ft2 = 6.37 × 10−4 𝑝𝑒𝑟𝑠𝑜𝑛/𝑓𝑡 2
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Example 3, cont’d (1)

From Table 2-5:
Death (lung hemorrhage): Y = -77.1 + 6.9 ln (Po)
Ear Drums: Y = -15.6 + 1.93 ln (Po)
Po in N/m2
Determine the maximum distance that does not cause fatality:
when Y = 0 (the percentage is zero )
By substitution
Death (lung hemorrhage): Po = 7.01 × 104 N/m2 (10.17 psi)

From explosion overpressure eq.: log P = 4.2 – 1.8 log r where P in psi and r in feet

For death (lung hemorrhage), the zero percentage will occur at:
r = 59.4 ft

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Example 3, cont’d (2)

People in the area until zero probability are exposed to different probability to die
by lung hemorrhage. This probability is function of r.

The right procedure is to divide the area to shells. Determine average radius in this
area, overpressure, no. of people in each shell, probability (or probit and hence
percentage) and the actual no. affected in this shell. Finally, add the number of
people affected in all shells

However, since the radius for death by lung hemorrhage is small, we will consider
one shell only

Calculation for Death (lung hemorrhage):

Assuming a single shell with 59.4 ft in radius
Area of shell: π [(59.4)2-(10)2]=10,771 ft2

Total people in shell:

Area × People Density = 10,771 ft2 × 6.37 × 10−4 𝑝𝑒𝑟𝑠𝑜𝑛/𝑓𝑡 2 = 6.86 person
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Example 3, cont’d (3)

10+59.4
Average r in the area = = 34.7 𝑓𝑡
2

By substitution in log P = 4.2 – 1.8 log r (P in psi and r in feet)

Average overpressure = 28.1 psi (1.94 × 105 N/m2)
By substitution in the probit equation for Death (lung hemorrhage):
Y = -77.1 + 6.9 lnPo (Po in N/m2)
Y = 7.033
Convert from Y to percentage from Table 2-4, which is approx. 98%
Therefore, about 6.68 persons are in the area with percentage 98% of them
will die due to lung hemorrhage (about 6.5 person)

It is recommended that people should not be allowed within 50 ft of the

source instead of 10 ft

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Example 3, cont’d (4)

Calculation for eardrum rupture:

The zero probability for Ear Drums gives: Po = 3.24 × 103 N/m2 (0.47 psi)
This will occur at r = 328 ft, which is too extreme (very far away)

Instead, we will assume 1% percentage → Y=2.67 from Table 2-4

∴2.67 = -15.6 + 1.93 lnPo →Po =1.292×104 N/m2 or 1.87 psi
From explosion overpressure eq.: log P = 4.2 – 1.8 log r where P in psi and r in feet

The 1% will occur at: r = 152 ft

Area of shell: π [(152)2-(10)2]=7.24 × 104 ft2

Total people in the area:

Area × People Density = 7.24 × 104 ft2 × 6.37 × 10−4 𝑝𝑒𝑟𝑠𝑜𝑛/𝑓𝑡 2 = 46.1 person

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Example 3, cont’d (5)

If we assume one shell (not accurate because of the large radius):

10+152
Average r in the area = 2
= 81 𝑓𝑡

By substitution in log P = 4.2 – 1.8 log r (P in psi and r in feet)

Average overpressure = 5.82 psi (40128 N/m2)
By substitution in the probit equation for eardrum rupture:
Y = -15.6 + 1.93 lnPo (Po in N/m2)
Y = 4.86
Convert from Y to percentage from Table 2-4, which is approx 44.5%

Therefore, about 46.1 persons are in the area with percentage 44.5% of
them will have eardrum rupture = 20.5 person

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Example 3, cont’d (6)

The assumption of one shell actually is not accurate because of the large radius and
overestimate the results

We can divide the area to 5 shells with fixed number of people per shell (also we
can divide it to shells with equal radius increments instead)

Divide into 5 shells with 46.1/5 = 9.22 person in each shell. Each shell will have 7.24
× 104 ft2 / 5 = 1.45 × 104 ft2
𝐴𝑟𝑒𝑎
To compute radius, 𝑅2 = 4
+ 𝑅12

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Example 3, cont’d (7)

Shell no. R1 R2 Rav Pav (psia) Pav (N/m2)
1 10 68.7 39.3 21.4 1.47×105
2 68.7 96.6 82.6 5.62 3.87×104
3 96.6 118.2 107.4 3.5 2.41×104
4 118.2 136.3 127.3 2.58 1.78×104
5 136.3 152.3 144.3 2.06 1.42×104

Shell no. Pav (N/m2) Y % No. of People If we did it using Excel from 10 ft
to 500 ft with increment of 5 ft
1 1.47×105 7.36 99.1 9.1
2 3.87×104 4.79 42 3.9 Death by lung hemorrhage = 3
Eardrum rupture = 13.7
3 2.41×104 3.87 13 1.2
4 1.78×104 3.29 4.2 0.4
5 1.42×104 2.85 1.7 0.2
Total 14.8 ≈ 15 persons
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