Toxicology

Chapter 2

1 Apr 6, 2020 Chemical process safety

 Toxicology

 Definitions
 Toxicological studies
 Dose-response correlations
 Threshold limit values
 Examples

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 Definitions
 Toxicology is the quantitative and qualitative study of
the adverse effects of toxicants on biological organisms

 Toxicant is a chemical or physical agent that produces

adverse effects on biological organisms including
dusts, fibers, noise and radiation
 Toxicity is a property of the agent describing its effect
on biological organisms.

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 Three Types of Toxic Hazardous
Materials

 Chemical Agents (poisons)

 Physical Agents (dusts, fibers, heat, noise,

corrosive)

 Biological Agents (pathogens)

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 Toxicology

Paracelsus, an early investigator of toxicology during the

1500s stated that “all substances are poisons; there is none
which is not a poison. The right dose differentiate a poison and
a remedy. ” Harmless substances such as water, can become
fatal if delivered to the biological organism in large amounts.

There are no harmless substances , only harmless ways of

using substances

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 Environmental Health Paradigm

Exposure Assessment
Emission Sources  Environmental
Concentrations
Effects Assessment 

Internal Dose  Human Exposure


Health Effects

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 Hazardous

 Industrial Hazards
– Toxicity
– Explosivity
– Ignitability
– Reactivity

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 Toxic Substance

 Capacity of a substance to produce injury or

illness
 Acute(‫ ( فوري‬Effects
– Short term, appear shortly after exposure. Can be
from single exposure
 Chronic ‫ن‬
( ‫مزم‬ (Effects
– There is a latency, long period of time before you
see effect

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 So Toxicology is the study of:
 How toxicants enter the organism

 How toxicants effect the organism

 How toxicants are eliminated from the organism

Remember that , all substances are toxic if taken in the

wrong quantities

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 2.1 How toxicants enter organism

 Inhalation (mouth or nose to lungs) then into

blood(+*)
 Ingestion (mouth to stomach) then into
blood(+)
 Injection (cuts, punctures in skin) into blood
 Dermal absorption (through skin) into blood(+*)
+ Involve membrane transport
* Greatest threats in industry

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 2.3 Effects of Toxicants

Irreversible Effects
 Carcinogen - causes cancer
 Mutagen - causes chromosome damage
 Reproductive hazard - damage to reproductive
system
 Teratogen - causes birth defects

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 Effects of Toxicants

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

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 Definitions

 Pharmacokinetics – the absorption, distribution,

metabolism and excretion of chemicals through the
(human) system.

 Bioaccumulation – things such as lead, mercury,

PCBs  (polychlorinated biphenyl) , carbon
tetrachloride that build up in organs and have low
excretion rate. Low exposure over a long time leads
to response

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 2.2 Elimination of toxins

 Excretion through kidneys, liver and lungs

 Detoxification (liver) is the biotransformation of

chemicals into something less harmful.

 Storage in fatty tissue

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 2.4 Toxicological Studies

 A major objective of toxicological study is to

quantify the effect of toxicants on specified
physical state.
For most toxicological studies
animals are used.

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 Difficulties in Toxicological studies
 Response not necessarily numerical.
 Specificity of individual response
– Allergy or immunity (‫) المناعة والحساسية‬
– Statistical study required
– Organism specific response, not applicable to humans
– Dosage response
– Response time, latency, acute versus chronic
– Difficulty in measuring intended variable (lead in liver
measured by lead in blood)

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 Difficulties in Toxicological Studies

 Major Problem
– No ethical way to get human volunteers, hence
need to use “model” systems of rats, cats, dogs,
rabbits, etc.

 Hinders production of a new chemical, almost

as stringent as a new drug.

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 2.5 Dose versus Response
 Run test on “large”
population
 Given same dose
(usually in dose/body
mass)
 Determine the number
or fraction of individuals
that have a response
Low High
* Read example 2-1 response response
Figure 2-5 Percentage of individuals affected based on response.

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 Dose versus Response (cont)
 Repeat tests using
different doses
 Find average response
to each dose
 Plot Response versus
logarithm of dose
 Forms Sigmoid shaped
curve

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 Dose Limit Values; Dose curves

 EDf – (minor) Effective dose

for f percent of population.
Reversible response
 TDf – Toxic dose for f percent
of population. Undesirable
response that is irreversible
 LDf or LC – Lethal dose for f
percent of population.

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 Dose/Response Models

 Use Probits to Linearize Dose-Response Curve

 Use Table 2.4

 Some calculators calculate the erfc
(complimentary error function)
erfc = 1 – erf(x)

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 Probit Correlations

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 Probit Correlations

 Table 2-5 gives values of a linear interpolation

of Dose/Response data that has been
linearized using Probits.

 Y = k1 + k2*Ln(V)
Y – Probit
V – Causative variable

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 Chemical Vapors

 When dealing with exposures of a chemical

vapor (toxic cloud) then the probit constants
are correlated by:
– Y = a + b ln Cnt
– a, b and n are experimentally determined constants
– C is concentration in ppm
– t is the exposure time in minutes

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 Chemical Vapors
 When the exposed subjects receive different doses
as a function of time

t2

C t   C dt   C ti
n n
i
n

t1 i

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 2.7 Relative Toxicity Classification

Classification Lethal Dose for a 70 KG person

Dangerously Toxic A taste ,
Highly Toxic a teaspoon
Moderately Toxic 1 oz = ~ 28.3 g
Slightly Toxic 1 pint = ~ 473 g
Practically nontoxic 1 qt = ~ 946 g
Relatively harmless > 1 qt
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 2.8 Threshold Limit Values
 Lowest value on the response versus dose curve is
called the threshold dose.
 American Conference of Governmental Industrial
Hygienists (ACGIH) has established “Threshold Limit
Values” (TLV)
 United States Occupational Safety and Health
Administration (OSHA) has established “Permissible
Exposure Limits” (PEL)
 Table 2-8 gives the TLVs and PELs for many
substances
For some toxicants (particularly carcinogens) exposures at any level are not permitted.
These toxicants have zero thresholds.

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 Threshold Limit Values

 TLVTWA Time weighted average for a normal 8

hour workday or 40 hour workweek.
 TLVSTEL Short-term exposure limit. The
maximum concentration can be exposed to for
up to 15 minutes. Four excursions per day with
at least 60 minutes between.
 TLVC Ceiling limit. This concentration should
not be exceeded

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 Converting from mg/m3 to ppm(v/v)

22.4  T   1 
C ppm  
3
   (mg / m )
M  273   P 

 M is molecular weight
 T is temperature in Kelvin
 P is pressure in atm

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 Threshold Limit Values

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