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Lethal Dose LD50

APES Chapter 8
Toxicology

Toxicology is the
study of the adverse
physico-chemical
effects of chemical,
physical or biological
agents on living
organisms and the
ecosystem.
Includes the
prevention and
treatment of disease.
Toxicology, ancient in
practice, came to be
known simplistically as
the science of poisons.


The dose makes the poison. almost everything is toxic at some level.
(According to Swiss scientist Paracelsus 500 years ago.)

How do you determine if a drug or chemical is safe to uselab testing!


Laboratory Investigations to
Measure Toxicity

Animal Studies
Populations of lab animals usually rodents
Measured doses under controlled conditions
Takes two to five years
Costs $200,000 to $2,000,000 per substance
Newer methods
Laboratory Investigations
Newer methods
Bacteria (Transgenic experiments)
Cell and tissue culture
Appropriate tissue
Stem cells
Chicken egg membrane
Laboratory Investigations
Love Canal Part I

Love Canal Part 2
Biohazards / Superfund
Site
Epidemiology is the study of distribution and
determinants of health problems in specified
populations.
a) applying the learned information to control
the health problems.
It is the scientific method of problem solving
diseaseepidemiologists, laboratory scientists,
statisticians,
physicians and other health care providers, and
public health.
Epidemiology
Determine severity of health concernis it an
epidemic or an outbreak?
Identify the cause.
Identify if it is a small cluster or larger
population
Geographic location(s)



Criteria used to measure
concerns
Epidemic--refers to a
contagious, infectious
or viral illness that
spreads to many
people in one
geographic region that
occurs in excess of the
numbers of cases that
would usually be
expected.
Pandemic refers to a
contagious, infectious
or viral illness that
spreads, and may
include millions of
people in many areas
across the globe,
according to the World
Health Organization's
description.

Laboratory testing on different drugs or
chemicals are done by looking at a dose
response curve.
To determine the toxicity of a chemical, look at
dose to which 50% of the test population is
sensitive.
Which dose is right?
Fig. 8.16, p. 171
100
75
50
25
0
2 4
6
8 10
12 14
16
P
e
r
c
e
n
t
a
g
e

o
f

p
o
p
u
l
a
t
i
o
n

k
i
l
l
e
d

b
y

a

g
i
v
e
n

d
o
s
e

Dose (hypothetical units)
LD
50
In case of lethal
dose (LD), this is
called LD50.
LD-50 Dose Response
LD50 =individual dose
required to kill 50% of test
population (e.g., rats, fish,
mice, cockroaches).
Standard to compare relative
toxicities of chemicals.

The lower the LD50 dose, the
more toxic the pesticide.
A pesticide with an LD50
value of 10 mg/kg is 10 times
more toxic than a pesticide
with an LD50 of 100 mg/kg

Fig. 8.15, p. 171
Very
Sensitive
Majority
of Average
Population
low
Sensitivity
0 20 40 60 80
Dose (hypothetical units)
N
u
m
b
e
r

o
f

i
n
d
i
v
i
d
u
a
l
s

a
f
f
e
c
t
e
d

Different sensitivities
to toxin to specific
populations.
Low
Sensitivity
Validity Challenged
Human physiology is different
Different species react different to same toxins
Mice die with aspirin
Species can be selected depending on physiological area
Pigs circulatory very similar to humans
Laboratory Investigations
Toxicity
Toxicity LD50 Lethal Dose Examples
Super < 0.01 less than 1 drop dioxin, botulism
mushrooms
Extreme <5 less than 7 drops heroin, nicotine
Very 5-50 7 drops to 1 tsp. morphine, codeine
Toxic 50-500 1 tsp. DDT, H
2
SO
4
, Caffeine
Moderate 500-5K 1 oz.-1 pt. aspirin, wood alcohol
Slightly 5K-15K 1 pt. ethyl alcohol, soaps
Non-Toxic >15K >1qt. water, table sugar

(LD50 measured in mg/kg of body weight)

Why so little is known of toxicity
Only 10% of at least 75,000 commercial chemicals have been screened

~
2% determined to be carcinogen, teratogen or mutagen
>1000 new synthetic chemicals added per year
>99.5% of US commercial chemicals are NOT regulated
Dose-Response Curves
Nonlinear
dose-response
Linear
dose-response
Threshold
level
E
f
f
e
c
t

Dose
Nonlinear
dose-response
Linear
dose-response
No threshold
E
f
f
e
c
t

Threshold
Dose
Fig. 16.6, p. 401