Faculty of Chemical

Engineering
Universiti Teknologi MARA

Process Safety - CPE615

 Allsubstances are poison; there is none which is
not a poison.
 The right dose differentiate between a poison
and a remedy.
 Harmless substances, such as water, can
become fatal if delivered to the biological
organism in large enough doses.
 A fundamental principle of toxicology is:
there are no harmless substances, only harmless
ways of using substances.

Process Safety - CPE615

 Toxicant: Can be a chemical, physical or
biological agent that may have an adverse effect
on biological organisms.
 Toxicology: Qualitative and quantitative study
of the adverse effects of toxicants on a
biological organisms.
 Toxicity: Property of the agent describing its effect
on biological organisms.
 Industrial Hygiene: Technique to reduce toxic
hazard of a substance.

Process Safety - CPE615

 Chemical Toxicants: include inorganic substances
(e.g. lead, mercury, asbestos, hydrofluoric acid, and
chlorine gas) organic compounds (e.g. methyl
alcohol), most medications, and poisons from living
things (e.g. snake’s venom).
 Biological Toxicants: include those bacteria and
viruses that are able to induce disease in living
organisms.
 Physical Toxicants: include things not usually thought
of under the heading of "toxic" by many people: dust,
fiber, direct blows, concussion, sound and vibration,
heat and cold, non-ionizing electromagnetic radiation
such as infrared and visible light, and ionizing radiation
such as X-rays and alpha, beta, and gamma radiation.
Process Safety - CPE615
 You have to know about:
 The way toxicants enter biological
organisms
 The way toxicants are eliminated Toxicology
from biological organisms
 The effects of toxicants on a
biological organisms
 Methods to prevent or reduce the
Industrial
entry of toxicants into biological Hygiene
organisms

Process Safety - CPE615

Route Entry Control

Ingestion Through mouth into Rules on eating, drinking and

stomach smoking
Inhalation* Through mouth or nose Ventilation, respirators, hood
into the lungs. and other personal
protections.
Injection Through cuts into the Proper protective clothing
skin
Dermal Through skin Proper protective clothing
Absorption membrane
*

* The most significant to industrial facilities

Process Safety - CPE615
Process Safety - CPE615
 Excretion: through the kidneys, lungs, liver and
other organs.
 Detoxification: by changing the chemical into
something that is less harmful by
biotransformation.
 Storage: in the fatty tissue.

Process Safety - CPE615

DIGESTIVE
TRACK BLOOD TARGET ORGAN

LIVER KIDNEYS/LUNGS
Elimination

Process Safety - CPE615

Effects that are irreversible
Carcinogen causes cancer
Mutagen causes chromosome damage
Reproductive hazard causes damage to reproductive system
Teratogen causes birth defects

Effects that may or may not be reversible

Dermatoxic affects skin
Hematoxic affects blood
Hepatoxic affects liver
Nephrotoxic affects kidneys
Neurotoxic affects nervous system
Pulmonotoxic affects lungs
Process Safety - CPE615
 The main objective: to quantify the effects of the
suspect toxicant on a target organism.
 Animals are normally used, usually with the
hope that the results can be extrapolated to
humans.
 Before a study, the following items must be
identified:
 The toxicant (as well as its chemical composition and
physical state)
 The target organism
 The effect or response to be monitored
 The dose range
Process Safety - CPE615
 The period of test
 The dose units depend on the method of
delivery.
 For substances delivered directly (ingestion or
injection), the dose is measured in milligrams of
agent per kilogram of body weight.
 For gaseous airborne substances the dose is
measured in ppm or milligrams of agent per
cubic meter of air (mg/m3).
 For airborne particulates, the dose is measured
in milligrams of agent per cubic meter of air
(mg/m3) or millions of particles per cubic foot
(mppcf). Process Safety - CPE615
 The period of the test depends on whether long
or short term effects are of interest.
 Acute toxicity = effect of a single exposure or a
series of exposures close together in a short
period of time.
 Chronic toxicity = effect of multiple exposures
occurring over along period of time.
 Chronic toxicity studies are difficult to perform;
most toxicological studies are based on acute
exposures.
Process Safety - CPE615
 Biologicalorganisms respond differently to the
same dose of toxicant.
 These differences are a result of:
 Age
 Sex
 Weight
 Diet
 General Health
 Other factors

Process Safety - CPE615

 Start with 50 rabits

Expose each to a fixed concentration

Get variety of responses

p/s: Read page 46 in your text book

Process Safety - CPE615
Response (xi) Number (f(xi)) Fraction
Least 1 2 0.04

2 14 0.28

3 18 0.36

4 15 0.3

Worst 5 1 0.02

TOTAL 50 1.00

= 2.98
Process Safety - CPE615
Process Safety - CPE615
Dose Average
Response
D1 R1 = 2.98
D2 R2
D3 R3
D4 R4

Process Safety - CPE615

Process Safety - CPE615
Process Safety - CPE615
 Ifthe response of interest is death or lethality,
the response versus log dose curve is called a
lethal dose curve.
 The dose that results in 50% lethality of the
subjects is frequently reported.
 This is called the LD50 (lethal dose for 50% of the
subject).
 Other values such as LD10 and LD90 are
sometimes also used.
 For gases, LC (lethal concentration) are used.

Process Safety - CPE615

ED = Effective Dose; TD = Toxic Dose; LD = Lethal
Dose
Process Safety - CPE615
 Many methods exist for representing the
response-dose curve.
 For single exposures, the probit (probit =
probability unit) method is particularly suited,
providing a straight-line equivalent to the
response-dose curve.
 The probit variable, Y, is related to the
probability P by:
1 Y 5  u2 
P
2 
1/ 2 

exp 
 2
du …………………

 .(1.1)
Process Safety - CPE615
Process Safety - CPE615
 What about 6.82?

Process Safety - CPE615

 Equation 1.1 transforms the sigmoid shape of
the normal response versus log-dose curve into
a straight line when plotted using a liner probit
scale.

Process Safety - CPE615

• Using probits, most response versus dose curve
can be represented by:
Y  k1  k2 lnV ……………..…(1.2)

Where:
Y = Probit Variable
k1 and k2 = constants
V = Causitive Variable
Note: can also be used for the case of fire &
explosion
Process Safety - CPE615
Process Safety - CPE615
 Write
the relationship between
percentage and probit for
• Burn deaths from pool burning
• Injuries from the impact of explosion

Process Safety - CPE615

A blast produces a peak overpressure of 47,000
N/m2.

a) What fraction of structures will be damaged

by exposure to this overpressure?
b) What fraction of people exposed will die as a
result of lung hemorrhage?
c) What fraction will have eardrums ruptured?
d) What conclusions about the effects of this
blast can be drawn?

Process Safety - CPE615

 Probit Equation
Y  k1  k2 lnV

Structural damage:
Y  23.8  2.92 lnPo
Death from lung hemorrhage:
Y  77.1  6.91lnPo
Eardrum ruptures:
Y  15.6  1.93 lnPo
Process Safety - CPE615
 For Po  47,000 N/m 2
Structural damage:
Y  7.61
Death from lung hemorrhage:
Y  2.76
Eardrum ruptures:
Y  5.163
Process Safety - CPE615
Process Safety - CPE615
 From probit-percentage conversion
table

Percent Affected (%)

Structural Damage 99.6

Death (Lung Hem) 0 (Y is negative)

Eardrum ruptures 56

Process Safety - CPE615

The blast is not serious enough to expect
fatalities, but serious enough to cause
extensive damage to surrounding structures
and to rupture eardrums of more than half of
the people exposed.

Process Safety - CPE615

 Threshold dose: the lowest value on the response versus
dose curve. Below this dose, the body is able to detoxify
and eliminate the agent without any detectable effects.

Process Safety - CPE615

 The American Conference of Governmental
Industrial Hygienists (ACGHIH) has established
threshold doses, called TLV, for a large number
of chemical agents.
 TLV= airborne concentrations that correspond
to conditions under which no adverse effects are
normally expected during a worker’s lifetime.
 The exposure occurs only during normal
working hours – 8 hrs/day, 5 days/week (not
continuous exposure).
 TLV was formerly called MAC (maximum
allowable concentration).
Process Safety - CPE615
TLV Type Definition

TLV-TWA Time-weighted average for a normal 8-hr workday or

40-hr workweek, to which nearly all workers can be
exposed, day after day, without adverse effects.
Excursions above the limit are allowed if compensated
by excursions below the limit.
TLV-STEL Short-term exposure limit. Spot exposure for a duration
of 15 minutes, that cannot be repeated more than 4 times
per day.
TLV-C Absolute exposure limit that should not be exceeded at
any time, even instantaneously.

Process Safety - CPE615

 TLV are reported using ppm (parts per million
by volume), mg/m3 (miligram of vapour per
cubic meter of air), or for dust, mg/m3 or mppcf
(millions of particles per cubic foot of air).
 For vapours, mg/m3 is converted to ppm using:

22.4  T  1 
Cppm  Concentrat ion in ppm     (mg/m 3 )
M  273  P 
 T 
 0.08205   (mg/m )
3

 PM 
Where: T = Temp in K; P = absolute pressure in atm and M= molecular
weight in g/gmol
Process Safety - CPE615
 OSHA has defined its own threshold dose, called
a permissible exposure level (PEL).
 PEL values are not as numerous and are not
updated as frequently.
 Another quantity frequently reported: Amount
immediately dangerous to life and health
(IDLH).
 Exposures to this quantity and above should be
avoided under any circumstances.

Process Safety - CPE615