“Study the effects of chemical contaminants on various ecological systems.”
• Harvey Wiley and his “Poison squad”.
• Federal laws:-
– Pure food and drug act.1906.
– Food, drug & cosmetic act, 1938.
– EPA, 1970.
• 6,000,000 chemicals are know known & 50,000 are in common use. But
only a few hundred are detailed studied.
• Safety is involves not simply the degree of toxicity of a substance but
rather the degree of risk under given condition.
EXPOSURE AND DOSE
• Exposure concentration :- Amount of a substance present in the
medium with which an organism has contact.
• Dose:- Amount of the chemical that is received by the target (organ).
The exposure conc. May differ from the dose owing to biochemical transformations in
the living organism.
• Critical things:-
• Body size and dose ratio.
• Medium of exposure .(total dose received).
• Absorption or absorbed dose.
• Absorption rate depends on medium and species.
Ideally, an estimation of a systemic dose should consider absorption rates.
• Extrapolation or drawing inferences.
• Administration of chemical to the subject.
• Injection- subcutaneous, intravenous, intra-peritoneal.
• When experimental routes ,differ from human routs ,safety factor must
Evaluating of Toxicity:
• Understanding toxic properties of substance.
• Exposed dose.
• Clinical studies.
• Identification of the nature of the health damage.
• LD50 values.
• Calculate doses that will not be lethal.
• Used for long duration studies.
• Provide comparative toxicity and organ indications.
Sub chronic toxicity:
• After Acute toxicity confirmation.
• Tab.1- sub chronic toxicity
• Tab.2- chronic toxicity.
Here :- Rodent rat for oral and inhalation studies, Rabbits for dermal studies and non rodents
(dogs) as 2nd
species for oral tests. Recommended.
Species Rodents, non rodent
No. of animals 20 of each sex for rodent,
4 of each sex for non
Dosage 3 dose level, include a
toxic dose level
observation 12- 24 months
species Rodents, non rodent
No. of animal 10 of each sex for
rodent, 4 of each sex
for non rodent
Dosage 3 dose level + 1
observation 90 days
• Definition – Lethal dose for 50% exposed population.
• Estimates lethal properties of a substance.
• Principle – “Not all individuals exposed to the same dose of a substance will
respond in the same way.”
• It is also explains evolutionary relationship between species.
• Pharmeco -kinetics and ADMET studies.
– Tab. Some chemical’s LD50 oral for rat :
chemical LD50 values (mg/KG)
Vit. A 2000
Manifestation of Toxicity
• Some Dose related important Factors:
– Severity and Incidence.
– Degree of reversibility.
– Site at which substance acts.
• Choice of organism depends on :
- Time, Budget, occurrence in environment or some Artificially
contained communities- macrocosms.
• Tab. Organisms commonly used in toxicity studies.
Type of Organism Organism
Invertebrates Daphnia magna, Crayfish, Mayfish, Midges, Plandria
Rainbow Trout, Goldfish, Fathead minnow, Catfish
Algae Microcystis aeruginosa, Chlarnydomonas reinhardi
mammals Rats , Mice
Avian Species Bobwhite, Ring-neck pheasant
• Table. Choice of animal depends on system being used
• Toxicity tests for Carcinogenicity :
– Carcinogenicity bioassay.
– Higher doses of chemical tested (MTD50).
– Teratoma and genetic level markers.
Choice of animal System being study
Monkey and baboons Reproductive studies
Rats & mice physiological
• Descriptive epidemiological study
– Self reported symptoms in exposed person.
– Case report by medicinal person.
– Correlation studies.( difference of disease rate in different environment)
• Non descriptive
– Compares the health of a group of person who have been exposed to
a suspected agent with tat of a non exposed control group.
Types of epidemiological studies:-
– Case control studies.
– Cohort studies.
Problems with these kind of studies:-
• Difficulties in obtaining & interpreting the results.
• Control groups are difficult to identify.
• Controlling the risk factors that have strong effect on health
• Data may be incomplete.
• The data on the degree of hazardous substance are only rarely
• Establishing dose – response relation is difficult.
• Independent confirmatory evidence is necessary.
• Negative findings interruptions.
Short term tests for toxicity:-
• Correlate with specific toxic effects.
• Benefits over lifetime animal effects.
Ex. Enzymatic measurement for finding toxicity of heavy metals in the soil.
Table. Some tests and their uses
Test Organism applications
Ames test Salmonella typhimurium Mutagen, carcinogen &
Toxicity of industrial