{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