Toxicology

An introduction for
chemical engineers
Toxicology

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

Exposure Assessment
Emission Sources  Environmental
Concentrations
Effects Assessment 

Internal Dose  Human Exposure


Health Effects
Hazardous

 Denotes the probability of injury or illness from

contact or use
 Industrial Hazards
– Toxicity
– Explosivity
– Ignitability
– Reactivity
Toxic Substance

 Capacity of a substance to produce injury or

illness
 Acute Effects
– Short term, appear shortly after exposure. Can be
from single exposure
 Chronic Effects
– There is a latency, long period of time before you
see effect
Three Types of Toxic Hazardous
Materials

 Chemical Agents (poisons)

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

corrosive)

 Biological Agents (pathogens)

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.
So Toxicology is the study of:

 How toxicants enter the organism

 How toxicants effect the organism

 How toxicants are eliminated from (leave) the organism

All substances are toxic if taken in the wrong quantities

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
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

 Pharmacokinetics – the absorption,

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

 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

 Excretion through kidneys, liver and lungs

 Detoxification is the biotransformation of

chemicals into something less harmful

 Storage in fatty tissue

Toxicological Studies

 Baseline study with no toxicant

 Toxicology study to quantify response to

toxicants in specified physical state
Difficulties in Toxicological studies
 Baseline study required (control group)
 Response not necessarily numerical
 Specificity of individual response
– 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

 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
– Currently averages 17 years and 1 million pages
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
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
Dose Limit Values

 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

 Therapeutic Margin
– TM = LD50% - ED50%
 Margin of Safety
– MOS = LD5% - ED95%
 Safety Index
– SI = LD5%/ED95%
 Therapeutic Index
– 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

 Use Probits to Linearize Dose-Response

Curve
– 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

 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
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
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

Received handout with constants, ought to place in your

book
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
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
Converting from mg/m3 to ppm

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