Chemistry of Toxicology Lecture 1 PDF

Definition Toxicology Toxicology is "the study of the adverse effects of chemicals or physical agents on living organisms. A toxicologist is a scientist that determines the harmful effects of agents and the cellular, biochemical, and molecular mechanisms responsible for the effects. All substances...

Definition Toxicology Toxicology is "the study of the adverse effects of chemicals or physical agents on living organisms. A toxicologist is a scientist that determines the harmful effects of agents and the cellular, biochemical, and molecular mechanisms responsible for the effects. All substances are poisons; it is the dose that makes the poison  What is Toxicology? It is the study of the adverse effects of chemical or physical agents on living organisms. It is one of the multidisciplinary fields of science which encompasses many sciences such as basic biochemical, chemical, pathological and physiological knowledge along with experimental observation to gain an understanding of why certain substances cause the disruption in a biological system which may lead to toxic effects  The traditional definition of toxicology is "the science of poisons." As our understanding of how various agents can cause harm to humans and other organisms, a more descriptive definition of toxicology is : 1. "The study of the adverse effects of chemicals or physical agents on living organisms". 2. All substances are poisons; it is the dose that makes the poison  Toxicant, toxin, and poison are often used interchangeably in the literature Toxic substances may be systemic toxins or organ toxins. A systemic toxin is one that affects the entire body or many organs rather than a specific site.  Toxicology is divided into several sections Introduction to Toxicology. Dose and Dose Response, Toxic Effects, Interactions, Toxicity Testing Methods, Risk Assessment, Exposure Standards and Guidelines, Basic Physiology, Introduction to Toxicokinetics, Absorption, Distribution, Biotransformation, Excretion, Cellular Toxicology, Intuitive Toxicology and Risk Communication, Environmental Toxicology, Environmental Health, and One Health 1.  Scope of Toxicology Descriptive toxicology It evaluates the toxicity of chemicals exposed to human beings and environment as a whole via gathering information from animal experimentation Mechanistic toxicology It focuses on the study of mechanisms by which chemicals or physical agents exert their toxicity on living organisms Clinical toxicology It is concerned with the diagnosis & management of poisoned patients  Scope of Toxicology ENVIROMENTAL TOXICOLOGY It focuses on the effects of chemical or physical pollutants in the environment on living organisms. It deals with pollution & industrial hygiene. Genetic toxicology It is a branch of the field of toxicology that assesses the effects of chemical and physical agents on the hereditary material (DNA) of living cells. Forensic toxicology It is concerned with identification of the cause of death and determining its circumstances in a postmortem investigation  Toxicologic Terms Toxin: These are naturally produced toxic substances such as snake venom. Toxicant: Human-made toxic substance such as industrial wastes. Xenobiotic A chemical which is foreign to the normal physiology of the body. It includes drugs and other chemicals such as pesticides Toxicology Terminology  What is a Poison? All substances are poisons; there is none that is not a poison. The right dose differentiates a poison and a remedy. "The dose makes the poison.“ Paracelsus (1493- 1541) Types of toxic agents: Source Drug toxicity can be due to over doses, frequent administrations of 1) Therapeutic agents : therapeutic doses & drug interactions (Digoxin & Paracetamol). These chemicals may contribute to environmental pollution & 2) Industrial Chemicals : they may be a direct hazard in the work place they are used (Heavy metals). The top household products ingested are cleaning 3) House-hold chemicals : agents, cosmetics & personal products Compound Lethal dose Ethanol 700 g Salt 300 g Acetyl salicylic acid 100 g DDT 8g Strycnine 150 mg Nicotine 100 mg Arsenic (III) oxide 100 mg Tetrodotoxin 10 mg Dimethyl mercury 0,1 mg 2,3,7,8-tetrachlorodibenzodioxine 0,1 mg Botulinum toxin 0,001 mg Routes of Toxic Exposure Classification of toxicity  Toxicological concepts a) Acute or chronic effects: example: Benzene acute effect: narcotic chronic effect: leukemia  Toxicological effects - IMMEDIATE TOXIC EFFECTS: can be defined as those that occur or develop rapidly after a single administration of a substance. - DELAYE TOXIC EFFECTS are those that occur after the lapse of some time. Ex: Carcinogenic effects of chemicals usually have a long latency period, often 20 to 30 years after the initial exposure, before tumors are observed in humans. For example, daughters of mothers who took diethylstilbestrol (DES) during pregnancy have a greatly increased risk of developing vaginal cancer  Reversible versus Irreversible Toxic Effects Some toxic effects of chemicals are reversible, and others are irreversible. If a chemical produces pathological injury to a tissue, the ability of that tissue to regenerate largely determines whether the effect is reversible or irreversible. - Thus, for a tissue such as liver, which has a high ability to regenerate, most injuries are reversible, whereas injury to the CNS is largely irreversible because differentiated cells of the CNS cannot divide and be replaced. Carcinogenic and teratogenic effects of chemicals, once they occur, are usually considered irreversible toxic effects  Local Versus Systemic effects - Local effects are those that occur at the site of first contact between the biological system and the toxicant. Such effects are produced by the ingestion of caustic substances or the inhalation of irritant materials. EX: chlorine gas reacts with lung tissue at the site of contact, causing damage and swelling of the tissue. Systemic effects require absorption and distribution of a toxicant from its entry point to a distant site, at which deleterious effects are produced. - For some materials, both effects can be demonstrated. For example, tetraethyl lead produces effects on skin at the site of absorption and then is transported systemically to produce its effects on the CNS and other organs. Interactions of Toxicants Toxicokinetic (TK) processes I) Absorption : GIT  I) Absorption : Skin Uptake of chemicals by the skin depends on: The general condition (abrasions, cuts, etc) The thickness (arms thin, palms thick) Application of corrosive acids or alkalis organic solvents & which increase the skin`s permeability  I) Absorption : Lung Uptake of chemicals by the lung depends on: - Small particles (< 1μm) goes down in the alveoli and can cause e.g. silicosis or asbestosisthe thickness - Gas reactivity: very reactive gases (HCl, NH3, SO2) are irritating and blocks respiration and can therefore not be inhaled in larger quantities. While Chemicals with intermediate reactivity and lipophilicity(phosgene, ozone, isocyanates) can be inhaled and give injuries at all levels in the lungs  II) Distribution Volume of distribution (Vd) is defined as the apparent volume into which asubstance is distributed. Vd = dose /plasma concentration The blood concentration of a toxicant depends on its volume of distribution (Vd) - Small Vd = High concentration in plasma. - Large Vd = low concentration in plasma The importance of volume of distribution in toxicology is : Predicting peak blood concentration of the chemical taken Deciding whether to apply systemic toxin elimination technique II) Distribution  II) Distribution If used near term during pregnancy or in neonates, these drugs increase blood levels of unconjugated bilirubin and increase risk of kernicterus in the fetus or neonate. Sulfonamides enter breast milk.  II) Distribution Affinity of chemicals to certain tissues Liver and kidney - They concentrate more amount of toxicant other than organs because they are very important in the elimination of toxicants Adipose tissue - Toxicant with high lipid solubility may stored in body fat and become harmful when the toxicant is liberated from the adipose tissue to the circulation. E.g. DDT thus (starvation) can rapidly increase blood conc & toxicity Bone - Some toxicant such as fluoride, lead & tetracycline are stored in the bone II) Distribution  Thank you