{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 use…lab 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 methodsLaboratory Investigations
Newer methods Bacteria (Transgenic experiments) Cell and tissue culture
Appropriate tissue Stem cells
Chicken egg membraneLaboratory 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 disease—epidemiologists, laboratory scientists, statisticians, physicians and other health care providers, and public health.
Epidemiology
Determine severity of health concern…is 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
02 4 6 8 10 12 14 16
Perc
enta
ge o
f pop
ulat
ion
kille
d by
a g
iven
dos
e
Dose (hypothetical units)
LD50
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
Majorityof Average Population
lowSensitivity
0 20 40 60 80
Dose (hypothetical units)
Num
ber o
f ind
ivid
uals
affe
cted
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 humansLaboratory Investigations
ToxicityToxicity LD50 Lethal Dose ExamplesSuper < 0.01 less than 1 drop dioxin, botulism
mushroomsExtreme <5 less than 7 drops heroin, nicotineVery 5-50 7 drops to 1 tsp. morphine, codeineToxic 50-500 1 tsp. DDT, H2SO4, Caffeine
Moderate 500-5K 1 oz.-1 pt. aspirin, wood alcoholSlightly 5K-15K 1 pt. ethyl alcohol, soapsNon-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
Nonlineardose-responseLineardose-response
Thresholdlevel
Effe
ct
Dose
Nonlineardose-response
Lineardose-response
No threshold
Effe
ct
Threshold
Dose
Fig. 16.6, p. 401