PRINCIPLES OF TOXICOLOGY BY PUROHIT TEJENDRA J M.V.Sc. First Semester Major Advisor: Dr. A. M. Thaker Minor Advisor: Dr. C.G. Joshi
Scope The main goals of toxicology include: to elucidate the toxic properties of chemicals to evaluate the hazards of chemicals to organisms in relation to the concentration of these substances in the environment (risk estimation) to advise society on measures to control or prevent the harmful effects of chemicals (hazard control)
Introduction DEFINITIONS Toxicology science which studies adverse chemicobiological interactions and assesses the probability of their occurrence. Toxicologists examine the nature of these interactions including: Molecular,Cellular,Systemic Toxic agent - anything that can produce an adverse biological effect. It may be chemical, physical, or biological in form. Toxin refers to toxic substances produced naturally Toxicant toxic substances that are anthrapogenic
Areas of Toxicology Descriptive Toxicology toxicity testing, information for safety evaluation and regulatory requirements Mechanistic Toxicology identify and characterize the mechanisms by which chemicals exert their toxic effects on living organisms Regulatory Toxicology determine potential hazards based on descriptive and mechanistic data Forensic Toxicology concerned with the medico legal aspects Clinical Toxicology medical/veterinary science dealing with disease processes caused by toxic substances Environmental Toxicology effects of toxic agents on environment and the ecosystem EcoToxicology branch of environmental toxicology focuses more on impact of toxic substances on population dynamics and ecosystem
SPECTRUM OF TOXIC DOSE Poison: Any agent capable of producing deleterious effect on biological system, seriously injuring functions or death. LD50 : Dosage of chemicals needed to produce death in 50% of treated animals. "All substances are poisons; there is none which is not a poison. The right dose differentiates a poison and a remedy." -Paracelsus
Classification of Toxic Agents What are general ways to classify toxic agents? I. Physical state (gas, solid, liquid) II. Labeling requirements (explosive, flammable, oxidizer) III. Chemistry (aromatic amine, halogenated hydrocarbon, etc.) IV. Poisoning potential (extremely toxic, very toxic, slightly toxic, etc.) V. Biochemical mechanisms (sulphydryl inhibitor, methb producer etc.) VI. Target organs (liver, kidney etc.) VII. Use ( pesticide, solvent, food additives etc.) VIII. Source ( animal or plant) IX. Effects (cancer, mutation, hepatotoxicity etc.)
Characteristics of Exposure Toxic agent requires breakdown of biotransformation or biotransformation to reach suitable site in appropriate time in proper concentration. ROUTE AND SITE OF EXPOSURE DURATION & FREQUENCY OF EXPOSURE Lungs (inhalation) Acute < 24 h Gastrointestinal tract (ingestion) Skin (topical, percutaneous, or dermal) Parenteral Sub acute 1 month (I/V.S/C) Sub chronic 1-3 months (any) Chronic > 3 months (any)
Spectrum of undesired effects it is an immunologically mediated adverse reaction to a chemical resulting from previous sensitization to that chemical or to a structurally similar one. Not true toxic reaction ( curve may be different) Haptens puls endogenus protein = Ag Symptoms: dermatitis, urticaria, itching, bronchiolar constriction
genetically determined abnormal reactivity to chemical Extreme sensitivity to low dose Extreme insensitivity to high dose ( Pseudocholinesterase Succinylcholine, NADH Methemoglobin reductase - Nitrate )
Immediate: cyanide Delayed: organophosphates Reversible: liver Irreversible: CNS Local: lung damage by chlorine Systemic: potassium cyanide
Systemic toxicity CNS Circulatory Blood & haemopoetic Viscera and skin Bone and muscles
Interaction of chemicals Indicator Effect Example 1+1=2 Additive Organophosphates insecticides 1+1=11 Synergistic Carbon tetrachloride & Ethanol Carbon tetrachloride & Isopropanol 1+1=0 Antagonism Functional barbiturate X norepinephrin Chemical dimercaprol(bal)x As-Hg-Pb Dispositional osmotic diuretic, charcoal X toxicant Receptor- organophosphate X atropine
Tolerance A state of decreased responsiveness to a toxic effect of a chemical resulting from prior exposure to that chemical or a structurally related chemical. Dispositional : decreased amount of toxicant reaching to site Eg. CCl4, Cd Decrease responsiveness of the tissue
Summary, Basic Toxicology Principles Toxicology is the study of poisons (drugs, pollutants, occupational chemicals) Whether a chemical will cause toxicity is dependent on its physical/chemical structure as well as susceptibility of the organism Route and duration of exposure may affect the toxicity observed. Toxic responses are often seen systemically. Target tissue/organ/cell describes where the toxic response is observed
Chapter 2, Casarett & Doull s Toxicology, 5th Ed http://www.sci.tamucc.edu/pals/moslen/toxlec.html