4 th stage Assistant lecturer Shahad Saldeen Department of pharmacology and toxicology April2021 introduction Toxicology is the study of the adverse effects of chemicals on living organisms ID: 1011675
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1. General principles of toxicology4th stage Assistant lecturer: Shahad S.aldeen Department of pharmacology and toxicology April-2021
2. introductionToxicology is the study of the adverse effects of chemicals on living organisms.Xenobiotic is a chemical that interacts with an organism and not found in the normal metabolic pathway of that organism. Toxicologist is a trained person to examine the nature of those adverse effects (including their cellular, biochemical, and molecular mechanisms of action) and assess the probability of their occurrence
3. Cont..Toxicant is a substance that produce adverse biological effect. It can be chemical or physical in nature.Toxin is a specific protein produced by living organism ex: mushroom toxin , tetanus toxin. Most of them exhibit immediate effect.Poisons is a toxicant that produced immediate death or illness when experienced in very small amount. It can be produced by plants, animals and bacteria ex: phytotoxin , bacteriotoxin, zootoxin
4. Phytotoxin Bacteriotoxin zootoxin
5. Measures of ToxicityThe normal procedure is to expose test animals by Ingestion Application to the skin inhalation or By placing the test material in the water or air of the test animals’ environment
6. Cont.…Rats, mice, dogs, monkeys etcSafety in experimental animals does not necessarily indicate the same in humans. Ex: Thalidomide a human teratogen shows toxicity(caused shortening or complete absence of limbs) at doses as low as 0.5-1 mg/kg and has little or no effect in mice or rats at doses as high as 4000 mg/kg.
7. Cont.…Toxicity tests are routinely performed by pharmaceutical manufacturers in the investigation of a new drug. These test measureMortality (death)Teratogenicity (ability to cause birth defects)Carcinogenicity (ability to cause cancer), and,Mutagenicity (ability to cause heritable change in the DNA)
8. Cont...Median lethal dose ( LD50) The amount (dose) of a chemical which produces death in 50% of a population of test animals. Normally expressed as milligrams of substance per kilogram of animal body weight( mg/kg).
9. Cont..The Median Lethal Concentration (LC50) The concentration of a chemical in an environment (generally air or water) which produces death in 50% of an exposed population of test animals in a specified time frame .Normally expressed as milligrams of substance per liter (mg/l) of air or water (or as ppm).
10. The ExposureRoute and site of exposureFrequency of exposureDuration of exposure
11. Rout and site of exposure1) Oral ⇒ GI tract2) Inhalation ⇒ Lungs3) Topical, percutaneous, or dermal ⇒ Skin4) Ocular, conjunctiva, cornea ⇒ Eyes5) Other routes ⇒ IP, SC, IM, ID, IV…..
12. Duration and Frequency of ExposureToxicologists usually divide the exposure of experimental animals to chemicals into four categories: Acute exposure is defined as exposure to a chemical for less than 24 h Subacute exposure refers to repeated exposure to a chemical for 1 month or lessSubchronic for 1 to 3 monthsChronic for more than 3 months
13. Immediate versus Delayed ToxicityImmediate toxic effects occur or develop rapidly after a single administration of a substance, whereas delayed toxic effects occur after a period of time.Carcinogenic effects of chemicals usually have long latency periods, often 20 to 30 years after the initial exposure, before tumors are observed in humans.
14. Reversible versus Irreversible Toxic EffectsIf a chemical produces pathological injury to a tissue, the ability of that tissue to regenerate largely determines whether the effect is reversible or irreversible.
15. Local versus Systemic ToxicityLocal effectsOccur at the site of first contact between the biological system and the toxicantTarget organs: hepatotoxicitySystemic effectsRequire absorption and distribution of a toxicant from its entry point to a distant site at which deleterious effects are producedEx: multiple organic toxicities
16. Dose responseThe characteristics of exposure and the spectrum of effects come together in a correlative relationship referred to dose-response relationshipTwo typesIndividual to varying doses of a chemical, response of an individual organism to varying doses of a chemicalPopulation of individuals
17. Dose –response relationship
18. What Can Be Learned From A Dose-Response Curve?LD50 – Median Lethal Dose, quantity of the chemical that is estimated to be fatal to 50% of the organisms LD50 values are the standard for comparison of acute toxicity between chemical compounds and between speciesTD50 – Median Toxic DoseED50 – Median Effective DoseLC50 – Median Lethal Concentration
19. Cont..NOAEL Value – No Observed Adverse Effect Level, The highest dose of a chemical that, in a given toxicity test, causes no observable effect in test animals. LOAEL Value – Lowest Observed Adverse Effect Level, The lowest dose of a chemical that, in a given toxicity test, does cause an observable effect in test animals These two values are used in risk assessment and research
20. Cont…
21. Toxicity rating for humans (70-74 kg) body weight)
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