ENVIRONMENTAL TOXICOLOGY

Vinars Dawane

ENVIRONMENTAL TOXICOLOGY

“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.

Experimental routes

• 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 apply.

Evaluating of Toxicity:• Understanding toxic properties of substance.• Exposed dose.• Clinical studies.• Identification of the nature of the health damage.• LD50 values.

Acute toxicity:• 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

Age young

No. of animals 20 of each sex for rodent, 4 of each sex for non rodent

Dosage 3 dose level, include a toxic dose level

observation 12- 24 months

species Rodents, non rodent

age young

No. of animal 10 of each sex for rodent, 4 of each sex for non rodent

Dosage 3 dose level + 1 control

observation 90 days

LD50 values

• 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)

Chloroform 800

DDT 85

Strychnine 2.5

NaCN 6.4

Vit. A 2000

Nicotine 53

NaCl 300

Manifestation of Toxicity

• Immediate/Delayed/Local/Systemic.

• Some Dose related important Factors:

– Severity and Incidence.

– Seriousness.

– Degree of reversibility.

– Site at which substance acts.

Toxicity Testing

• 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

Aquatic vertebrates

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

Rabbits Dermal

Rats & mice physiological

Epidemiological studies

• 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 is difficult.• Data may be incomplete.• The data on the degree of hazardous substance

are only rarely available.• 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 & teratogen detection

Bioluminescent bioassay

Photobacterium phosphoreum

Toxicity of industrial wastes, sediment extracts, hazardous waste leachates.

Response to toxic substances:-

• Absorption.

• Distribution.

• Excretion.

• Metabolism.

• Biotransformation - Phase 1 and Phase 2.

Thank you ……….!