Basic of toxicology and regulatory guidelines for toxicity.pptx

Basic of toxicology and regulatory guidelines for toxicity.
MPHRAM, 2ND SEM, UNIT 1

1. Basic of toxicology and regulatory guidelines for toxicity studies(OECD, ICH) INSTITUTE OF PHARMACEUTICAL SCIENCES KURUKSHETRA UNIVERSITY, HARYANA Submitted to- Prabjeet ma’am Submitted by – Arshi khanam M.Pharm pharmacology(2 nd sem )

2. What is toxicology the study of the of the adverse effects of chemical or physical agents on living organisms. Toxicology is a field of science that helps us understand the harmful effects that chemicals, substances, or situations, can have on people, animals, and the environment. Some refer to toxicology as the “Science of Safety” because as a field it has evolved from a science focused on studying poisons and adverse effects of chemical exposures, to a science devoted to studying safety.

3. Why toxicology is important? It provides protection to human and environment from toxic effects of toxicants. Toxicity study will ultimately lead towards the development of newer, innovative and more safe selective drug therapies to treat different disease such as cancer drugs with reduced side effects. Safest drug in trails Animals are also protected somehow.

4. Basic terms in toxicology Toxin :   A harmful substance produced within living cells or organisms. Toxicants : any chemical that can injure or kill human, animals or plants. Poison : substance that can cause immediate death or illness when introduced in small quantity.

5. History of toxicology Humans have long history of using poisons. Some of the well known toxicants were hemlock used for punishment, aconite used for the arrow poisons. Paracelsus(1500AD) stated that “ all substances are poisons ”, it is the dose that make them poison. O rfila (1800AD) referred as the founder of the toxicology, Because it was the one who created a systemic correlation between the chemical and biological properties of poison.

6. Types of toxicants Systemic toxin : it is the one that affect the entire body or many organs rather than a specific site. Organ toxin: it is the one that affects only specific tissues or organ. Toxicants could be – Chemical( e.g. Cyanide) Biological(e.g. Snake venom) Physical (e.g. Radiation)

7. Routes of exposure to toxicity Ocular Ingestion Lung S kin Parenteral Mucous membrane Environmental circumstances

8. Types of toxicology General type toxicology Mechanistic type toxicology Descriptive type toxicology Regulatory type toxicology

9. Other types of toxicities Acute toxicity : It refers to those adverse effects occurring following oral or dermal administration of a single dose of a substance, or multiple doses given within 24 hours, or an inhalation exposure of 4 hours. Sub acute Toxicity : It resembles acute toxicity except that the exposure duration is greater, from several days to one month. Sub chronic toxicity : It is the toxic exposures repeated or spread over an intermediate time range (1 – 3 months) Chronic Toxicity : It is the exposures (either repeated or continuous) over a long (greater than 3 months) period of time.

10. 1. General types of toxicity Analytical toxicology Applied toxicology Clinical toxicology Forensic toxicology Environment toxicology Industrial toxicology Reproductive and developmental toxicology Immune toxicology

11. Analytical toxicology: The branch of toxicology which deals with the study of detection and assay of poisonous chemicals including their metabolites that could affect the biological system. Applied toxicology: It is the application of new and modern methods or technologies for early detection of toxicants in the field setting or practice area.

12. Clinical toxicology : It is mainly involved in the study of diagnosis and treatment of poisoning that can occur in humans Veterinary toxicology : The study of diagnosis and treatment of animal poisoning including the transmission of toxin from animals to humans via milk, meat, fish, food stuff and etc .

13. Environmental toxicology: The study of presence of different toxicants including their metabolites and degradation products in the environment and their effects on humans and animals Industrial toxicology : It is the study of selective and specific are of environmental toxicology.

14. Immuno toxicology: It deals with the effect of toxicant on immune system. Reproductive and developmental toxicology: It focus on the effect of chemicals or toxins on the reproductive system and the developing embryo .

15. 2.Mechanistic toxicology   T he study of how chemical or physical agents interact with living organisms to cause toxicity . Aim of mechanistic toxicology is to identify that how xenobiotic enter an organism and how these are distributed metabolize in the body. Knowledge of the mechanism of toxicity of a substance enhances the ability to prevent toxicity and design more desirable chemical .

16. Mechanistic understanding helps the governmental regulator to establish legally binding safe limits for human exposure . It is also useful in forming the basis for therapy and the design of new drugs for treatment of human disease .

17. Two important concept of mechanistic toxicology- Toxicodynamics refers to the molecular, biochemical, and physiological effects of toxicants or their metabolites in biological systems . Toxicokinetics is the quantitation of the time course of toxicants in the body during the processes of absorption, distribution, biotransformation, and excretion or clearance of toxicants.

18. Mechanism of toxicity

19. Understanding of this mechanism will help investigator in- Extrapolate data better Improve risk assessment of potentially toxic chemicals for human safety, and also for pollutants, chemicals in the workplace. Improve risk assessment for synthetic and naturally occurring hazardous compounds in food and water.

20. 3. Descriptive toxicology  It is concerned directly with toxicity testing, which provides information for safety evaluation and regulatory requirements . • Focuses on toxicity testing of chemicals, usually on animals and then correlated to human conditions. • It provides dose-response information upon exposure to a harmful toxic agent. • The results from the toxicity testing are typically applied to approval of product use and regulating allowable concentrations in the environment.

21. The toxicity assessment commonly involves following steps- Hazard identification Dose response assessment Exposure assessment Risk characterization

22. 4. Regulatory toxicity It deals with the relationship between the discipline of toxicology and regulatory institutions . The regulatory authorities have to protect the health of humans which relies on toxicological principal and toxicity evaluation data to formulate a decision. The authority has to take a decision on Acceptable Daily Intake (ADI) of a chemical so that quantity of that chemical exposure is adjusted safe in terms of health. The authority also have the power to formulate some law or regulatory roles and to implement them rigidly .

23. Principle of toxicology says no chemical is safe all chemicals are potentially toxic depending upon their exposure, concentration , time, frequency and nature. Regulators formulate the threshold doses to reduce exposure concentration so that risks can be minimized to highest level .

24. Regulatory authorities WHO - World heath organization ICH - international conference on harmonization EPA -  Environmental Protection Agency OECD - Organization for Economic Co-operation and Development  FDA -   The Food and Drug Administration

25. Importance of toxicology study The data on acute toxicity test for various chemicals against various organisms may be valuable in following ways: To have an idea of toxic doses of xenobiotic for certain organisms. Fixation of sub lethal doses for long term toxicity test. Evolution of safe doses of those toxicants for certain organisms. Recommendation of maximum permissible limits of those substances in the ambient air and drinking water.