Toxicology

An introduction for
chemical engineers

Toxicology
Definitions
Toxicological

studies
Dose-response correlations
Threshold limit values
Examples

Environmental Health Paradigm

Exposure Assessment
Emission Sources

Effects Assessment
Internal Dose

Health Effects

Environmental
Concentrations

Human Exposure

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

TM = LD50% - ED50%

Margin

of Safety

MOS = LD5% - ED95%

Safety

Index

SI = LD5%/ED95%

Therapeutic

Margin

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) = [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.

= 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

t1

n
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

C ppm
M

22.4 T 1
3

(mg / m )
M 273 P

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