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Toxicology
An introduction for
chemical engineers
Toxicology
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Definitions
Toxicological studies
Dose-response correlations
Threshold limit values
Examples
Environmental Health Paradigm
Exposure Assessment
Emission Sources
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Effects Assessment
Internal Dose
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Health Effects
Environmental
Concentrations
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Human Exposure
Hazardous
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Denotes the probability of injury or illness from
contact or use
Industrial Hazards
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Toxicity
Explosivity
Ignitability
Reactivity
Toxic Substance
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Capacity of a substance to produce injury or
illness
Acute Effects
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Short term, appear shortly after exposure. Can be
from single exposure
Chronic Effects
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There is a latency, long period of time before you
see effect
Three Types of Toxic Hazardous
Materials
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Chemical Agents (poisons)
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Physical Agents (dusts, fibers, heat, noise,
corrosive)
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Biological Agents (pathogens)
Definitions
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Toxicology is the quantitative and qualitative
study of the adverse effects of toxicants on
biological organisms
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Toxicant is a chemical or physical agent that
produces adverse effects on biological
organisms.
So Toxicology is the study of:
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How toxicants enter the organism
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How toxicants effect the organism
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How toxicants are eliminated from (leave) the organism
All substances are toxic if taken in the wrong quantities
How toxicants enter organism
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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
Effects of Toxicants
Irreversible Effects
 Carcinogen - causes cancer
 Mutagen - causes chromosome damage
 Reproductive hazard - damage to reproductive
system
 Teratogen - causes birth defects
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
Definitions
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Pharmacokinetics – the absorption,
distribution, metabolism and excretion of
chemicals through the (human) system.
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Bioaccumulation – things such as lead,
mercury, PCBs, carbon tetrachloride that build
up in organs and have low excretion rate. Low
exposure over a long time leads to response
Elimination of toxins
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Excretion through kidneys, liver and lungs
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Detoxification is the biotransformation of
chemicals into something less harmful
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Storage in fatty tissue
Toxicological Studies
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Baseline study with no toxicant
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Toxicology study to quantify response to
toxicants in specified physical state
Difficulties in Toxicological studies
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Baseline study required (control group)
Response not necessarily numerical
Specificity of individual response
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Allergy or immunity
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)
Difficulties in Toxicological Studies
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Major Problem
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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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Currently averages 17 years and 1 million pages
Dose versus Response
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Run test on “large”
population
Given same dose
(usually in dose/body
mass)
Determine the number
or fraction of individuals
that have a response
Dose versus Response (cont)
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Repeat tests using
different doses
Find average response
to each dose
Plot Response versus
logarithm of dose
Forms Sigmoid shaped
curve
Dose Limit Values
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EDf – Effective dose for f
percent of population.
Reversible response
TDf – Toxic dose for f
percent of population.
Undesirable response
that is irreversible
LDf – Lethal dose for f
percent of population.
Definitions
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Therapeutic Margin
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Margin of Safety
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MOS = LD5% - ED95%
Safety Index
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TM = LD50% - ED50%
SI = LD5%/ED95%
Therapeutic Index
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TI = LD50%/ED50%
Relative Toxicity Classification
Classification
Human Oral LD50
Extremely Toxic
Taste (1 grain)
Highly Toxic
1 tsp
Moderately Toxic
1 oz
Slightly Toxic
1 pt
Practically nontoxic
1 qt
Relatively harmless
> 1 qt
Dose/Response Models
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Use Probits to Linearize Dose-Response
Curve
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P(Y) = ½[erf(Y-5/2) + 1]
Use Table 2.4
Some calculators calculate the erfc
(complimentary error function)
erfc = 1 – erf(x)
Probit Correlations
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Table 2-5 gives values of a linear interpolation
of Dose/Response data that has been
linearized using Probits.
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Y = k1 + k2*Ln(V)
Y – Probit
V – Causative variable
Chemical Vapors
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When dealing with exposures of a chemical
vapor (toxic cloud) then the probit constants
are correlated by:
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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
Chemical Vapors
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When the exposed subjects receive different doses
as a function of time
t2
C t   C dt   C ti
n
n
t1
n
i
i
Received handout with constants, ought to place in your
book
Threshold Limit Values
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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
Threshold Limit Values
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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
Converting from mg/m3 to ppm
C ppm
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22.4  T   1 
3
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   (mg / m )
M  273   P 
M is molecular weight
T is temperature in Kelvin
P is pressure in atm