MEV 018: Unit 13 – Response to Toxin Exposures

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 UNIT 13: RESPONSE TO TOXIN EXPOSURES

13.0 Introduction

Toxins and toxicants are harmful substances that enter the body through various routes and produce a wide range of biological effects. The study of how organisms respond to different doses of toxicants is central to toxicology. Understanding the body’s absorption, distribution, metabolism, and storage of these substances is crucial for risk assessment, clinical treatment, and environmental safety. This unit covers the dose-response relationship, lethal and sub-lethal doses, and the physiological responses of different body systems to toxic exposure.

13.1 Objectives

After studying this unit, learners will be able to:

  • Understand the concepts of dose, dose-response, and cumulative response.
  • Differentiate between lethal and sub-lethal doses.
  • Analyze toxicological indicators like LD₅₀, LC₅₀, and MLD.
  • Describe how toxicants are absorbed, distributed, and stored in the human body.
  • Recognize factors influencing toxicity and bioavailability.

13.2 Dose Response, Frequency Response and Cumulative Response

13.2.1 Dose

  • Refers to the amount of a substance an organism is exposed to.
  • Can be expressed in mg/kg body weight.
  • Categories: acute (single exposure), chronic (long-term exposure).

13.2.2 Dose-Response Relationship

  • Illustrates the correlation between dose and the magnitude of toxic effect.
  • Threshold Dose: Minimum dose below which no effect is observed.
  • No Observed Effect Level (NOEL) and Lowest Observed Effect Level (LOEL) are important regulatory benchmarks.
  • Sigmoid Curve: Commonly used to show dose-response.

13.2.3 Frequency and Cumulative Response

  • Frequency Response: Number of individuals showing a response at each dose level.
  • Cumulative Response: Total percentage of subjects affected up to a given dose.

13.3 Lethal and Sub-Lethal Doses

  • Lethal Dose: Quantity sufficient to cause death. Usually expressed as LD₅₀.
  • Sub-Lethal Dose: Causes physiological or biochemical changes but not death.
  • Important for assessing chronic exposure risks and long-term effects.

13.4 Analysis of LD₅₀, LC₅₀, and MLD

  • LD₅₀ (Lethal Dose 50%): Dose that kills 50% of test organisms.
  • LC₅₀ (Lethal Concentration 50%): Concentration in air or water that kills 50%.
  • MLD (Minimum Lethal Dose): Smallest dose causing death.
  • Purpose: Comparative toxicity, risk assessment, regulatory limits.

13.5 Toxic Response of Body System

Different systems respond variably to toxic exposure:

  • Nervous System: Neurotoxins can cause tremors, paralysis (e.g., mercury, lead).
  • Respiratory System: Inhalation of irritants (e.g., SO₂, NOx) leads to asthma, bronchitis.
  • Digestive System: Ingestion of toxins may cause nausea, liver damage.
  • Renal System: Kidneys filter toxins; damage may lead to renal failure.
  • Cardiovascular System: Toxins may affect blood pressure and heart rhythm.

13.6 Absorption of Toxicants

13.6.1 Factors Affecting Absorption

  • Molecular size, lipid solubility, concentration gradient, and pH.
  • Exposure duration and surface area.

13.6.2 Mechanism of Transmembrane Transport

  • Passive Diffusion: Movement from high to low concentration.
  • Facilitated Diffusion: Carrier protein-assisted.
  • Active Transport: Requires energy (ATP).
  • Endocytosis: Engulfing particles into cells.

13.6.3 Sites of Absorption

  • Skin, lungs, gastrointestinal tract depending on exposure route.

13.6.4 Absorption through Digestive Tract

  • Most common for pesticides, heavy metals.
  • Stomach and small intestine are key absorption sites.

13.6.5 Absorption through Skin (Dermal Absorption)

  • Important in industrial and agricultural exposure.
  • Lipid-soluble substances absorb faster.

13.6.6 Absorption through Respiratory Organs

  • Gases and vapors quickly absorbed via alveoli into bloodstream.

13.6.7 Kinetics of Absorption

  • Follows zero-order or first-order kinetics.
  • Determines how quickly toxins enter systemic circulation.

13.7 Distribution of Toxicants

After absorption, toxicants are distributed via the bloodstream.

13.7.1 Factors Affecting Distribution

  • Blood flow rate to organs
  • Affinity of toxicant to tissues
  • Binding to plasma proteins

13.7.2 Kinetics of Distribution

13.7.2.1 Body Water and Volume of Distribution

  • Water-soluble toxins are diluted in body fluids.
  • Volume of distribution (Vd) helps in calculating toxin spread.

13.7.2.2 Plasma Binding, Blood Flow, and Barriers

  • Toxins bound to plasma proteins cannot leave the bloodstream easily.
  • Blood-brain barrier and placental barrier may restrict toxin access.

13.7.3 Storage of Toxicants

Toxins are stored in tissues which can prolong their effects:

13.7.3.1 Plasma Proteins

  • Albumin acts as a temporary reservoir.

13.7.3.2 Liver and Kidney

  • Major detoxification and excretion organs; also store metals.

13.7.3.3 Fat

  • Lipophilic toxins like DDT are stored in adipose tissues.

13.7.3.4 Bone

  • Heavy metals like lead, strontium accumulate in bone matrix.

13.7.3.5 Effects of Storage on Toxicity

  • Delayed release from storage can cause chronic toxicity.
  • Mobilization during stress or fasting may increase toxicity.

13.8 Let Us Sum Up

Toxicological responses depend on the dose, route, and duration of exposure. Understanding dose-response relationships, absorption pathways, distribution mechanisms, and storage sites is essential for predicting health outcomes and managing toxin exposure. Concepts like LD₅₀ and MLD help quantify toxicity, while knowledge of body responses supports effective intervention and prevention strategies.

13.9 Key Words

  • Toxicant: A harmful chemical substance.
  • Dose-Response Curve: Graphical representation of toxin effect at different doses.
  • LD₅₀/LC₅₀: Measures of lethal dosage or concentration.
  • Transmembrane Transport: Movement of substances across cell membranes.
  • Bioavailability: Fraction of the toxin that enters systemic circulation.
  • Volume of Distribution: Hypothetical volume in which a toxin is distributed.
  • Tissue Depots: Sites where toxins accumulate in the body.

 

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