Heavy Metal Toxicity PDF

Here is a summary of the information from the sources, organised by topic: Heavy Metal Toxicity General Toxicity Mechanism: Heavy metal poisoning primarily works by inhibiting enzymes that contain SH groups. Stomach tube washing can be used to treat most heavy metal poisonings...

Here is a summary of the information from the sources, organised by topic: Heavy Metal Toxicity General Toxicity Mechanism: Heavy metal poisoning primarily works by inhibiting enzymes that contain SH groups. Stomach tube washing can be used to treat most heavy metal poisonings except for barium chloride and antimony trichloride. Arsenic Toxicity Absorption and Excretion: Arsenic is absorbed through the descending colon and then re-excreted into the gastrointestinal tract. Uses: Inorganic salts of arsenic are used in weed killers and wood preservatives. Arsenical dips should not be used on stallions, boars, or rams during mating season. Storage: Arsenic is stored in bone and keratinized tissues and can be detected in these tissues even in decomposed remains. Withdrawal Time: ○ It takes 2 weeks for arsenic to be eliminated from the body after treating a poisoned animal. ○ The withdrawal time for arsenic from the body is 6 weeks after stopping the administration of arsenic drugs. Acute Toxicity: Acute arsenic toxicity is characterized by rice-watery diarrhea and bloody dysentery. Antidotes: ○ Freshly prepared ferric hydroxide solution is the classic antidote for arsenic poisoning. ○ BAL (British Anti-Lewisite), an oily solution, is a chelating agent used to treat arsenic poisoning. Mercury Toxicity Excretion: Mercury is re-excreted through the cecum after being absorbed. Toxicity Mechanism: Mercury permanently inhibits selenoenzymes such as thioredoxin reductase, which prevents antioxidants from being restored to their reduced form. Symptoms: Mercury poisoning can cause aphthous patches (small ulcers) to appear on the mucous membrane of the buccal cavity (mouth). Antidotes: ○ BAL, an oily solution, is a chelating agent used to treat mercury poisoning. ○ Albumin is the physical and chemical antidote. ○ Leishica solution is another treatment option. It contains 500 ml skimmed milk, 50 g glucose, 20 g sodium bicarbonate, 3 egg white, and barley water. Antimony Toxicity Toxicity Symptoms: Antimony poisoning can cause loss of smell in dogs and aphthous patches on the mucous membrane of the mouth.  Types: Organic salts of antimony include antimony barium tartarate and antimony trisulphide. Lead Toxicity Excretion: Lead is not easily excreted in urine. Chronic Toxicity: Chronic lead poisoning is called plumbism. Toxicity Mechanism: ○ Lead inhibits δ-ALAD and ferrochelatase enzymes, which are needed to make haem. ○ Lead prevents haem from being formed from protoporphyrin by inhibiting the enzyme ferrochelatase. Symptoms: Lead poisoning can cause: ○ Microcytic hypochromic anemia. ○ Erythrocytic basophilic stippling, which appears as granules in the red blood cells. ○ Acid-fast inclusion bodies, which can be seen in the renal cortex under a microscope. Types: Organic salts of lead include lead alkyl and lead acetate. Antidotes: CaNa2EDTA and D-penicillamine can be used to treat lead poisoning. Cadmium Toxicity Toxicity Mechanism: Cadmium interferes with metabolic processes that involve zinc and can cause prostate cancer by increasing the activity of the prostatic acid phosphatase enzyme. Chronic Toxicity: Chronic exposure to cadmium causes a bone disease called Itai-Itai (Ouch-Ouch) disease. Itai-Itai disease is characterized by osteomalacia (softening of the bones) and osteoporosis (weakening of the bones). Fluorine Toxicity Toxicity Mechanism: Fluorine binds to enzymes that contain SH groups, such as aconitase and AChE. Symptoms: Fluorine poisoning can cause hyperesthesia (increased sensitivity to stimuli) and mottling of the teeth. Chronic Toxicity: Chronic exposure to fluorine, like chronic exposure to cadmium, can cause osteomalacia and osteoporosis. Treatment: Aluminium sulphate can be used to precipitate leftover fluorine in the stomach. Postmortem Detection: It is not possible to detect fluoride in decomposed remains through chemical analysis. Other Metals Nickel: Nickel poisoning can cause white patches on the skin of fish.  Selenium: Selenium poisoning can cause a variety of symptoms in fish, including nephrocalcinosis, ascites, localized haemorrhage of the eye and the base of the fine, cataracts, exophthalmia, lordosis, and kyphosis. TBT (tributyltin): TBT can cause localised haemorrhage of the eye and the base of the fine and cataracts in fish. Copper: Copper poisoning can cause kyphosis in fish. Zinc: Zinc can cause a fuzzy appearance of the gills. Reproductive Toxicity The sources provide information about the effects of toxicity on the male and female reproductive systems. Female Reproductive Toxicity Hormonal Control: Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) stimulate the production of oestrogen by the theca and granulosa cells of the ovarian follicles. Developmental Stages: ○ Preimplantation period: This period includes fertilization and the beginning of the erosion of the uterine wall. ○ Organogenesis: This is the stage of organ formation. In rabbits, it lasts from day 6 to day 18 of gestation. ○ Fetal period: This period starts with the formation of the organs and ends with birth. Toxicity Effects: ○ Exposure to toxic substances during the fetal period can cause growth retardation. ○ Exposure of pregnant mothers to certain substances can lead to neonatal jaundice (yellowing of the skin and whites of the eyes) in their offspring. ○ Exposure to toxins before puberty can cause the complete destruction of oocytes, leading to infertility. Male Reproductive Toxicity Testicular Cells: ○ Sertoli cells are essential cells in the seminiferous tubules of the testes. They provide mechanical support for spermatogenic cells, form the blood-testis barrier (which protects developing sperm cells from the immune system), and help with sperm maturation. ○ Leydig cells, also found in the testes, produce testosterone. ○ Spermatogenic cells are the cells that develop into sperm cells. Sperm Maturation and Transport: ○ Androgen-binding protein (ABP) carries testosterone through efferent ducts to the epididymis, where it supports sperm maturation. ○ Spermatogenesis (sperm cell development) takes about 50-54 days in rats. ○ Spermiation is the release of immature spermatozoa from Sertoli cells into the lumen of the seminiferous tubules.  Seminal Plasma: The various accessory sex glands produce seminal plasma, the fluid that carries sperm. Toxicity Effects: Damage to Leydig cells, Sertoli cells, or spermatogenic cells can lead to reduced testosterone production and impaired sperm production. Genotoxicity Genotoxicity refers to the ability of a substance to damage DNA. Types of Mutations: ○ Reverse phenotype mutation: This type of mutation restores the usual phenotype. ○ Transition mutation: This occurs when a purine base (adenine or guanine) is replaced by another purine base or when a pyrimidine base (cytosine or thymine) is replaced by another pyrimidine base. For example, substituting four thymine bases with four cytosine bases would be a transition mutation. ○ Transversion mutation: This occurs when a purine base is replaced by a pyrimidine base or vice versa. ○ Missense mutation: This occurs in the coding regions of DNA and results in a change in the amino acid sequence of the protein that is being produced. ○ Frameshift mutation: This occurs when nucleotides are added to or deleted from a DNA sequence, shifting the reading frame and altering the amino acid sequence of the protein produced. For example, adding four nucleotides to a DNA sequence would result in a frameshift mutation. ○ Small addition mutation: This occurs when one or two nucleotides are added to a DNA sequence. Chromosomal Abnormalities: ○ Monosomy: This is the condition where a cell has 2n-1 chromosomes (one chromosome is missing). Turner syndrome is an example of monosomy, where individuals have only one X chromosome (47, X). ○ Trisomy: This is the condition where a cell has an extra chromosome (2n+1). Down syndrome, also called trisomy 21, is a condition where there are three copies of chromosome 21. Klinefelter syndrome (47, XXY) and Trisomy X syndrome (47, XXX) are sex chromosome trisomies. Oncogenes and Tumor Suppressor Genes: ○ Proto-oncogenes are genes involved in normal cell growth and division. When mutated, they can become oncogenes, contributing to the development of cancer. These mutations can be expressed when a single copy of the gene is affected (heterozygote). ○ Tumor suppressor genes help to prevent uncontrolled cell growth. Mutations in these genes can increase the risk of cancer. Mechanisms of Genotoxicity: ○ Some substances, such as aflatoxins, cosmetics, bromouracil, and mitomycin, can generate reactive radicals that react with DNA, forming adducts (covalent bonds).  ○ Intercalating agents, like ethidium bromide, insert themselves between adjacent base pairs of DNA, disrupting DNA replication and transcription. ○ Ultraviolet (UV) radiation can cause pyrimidine dimers, which are usually formed between adjacent thymine bases. Carcinogenesis: ○ Pro-carcinogen: A pro-carcinogen is a substance that is not carcinogenic itself but can be converted into a carcinogen in the body. ○ Ultimate carcinogen: This is the form of a carcinogen that actually interacts with DNA and causes damage. ○ Proximate carcinogen: This is an intermediate metabolite of a carcinogen that requires further metabolism to become an ultimate carcinogen. ○ Co-carcinogen: A co-carcinogen is a substance that is not carcinogenic on its own but can enhance the activity of a carcinogen. Latency period: The latency period for a carcinogen is the time between exposure to the carcinogen and the development of cancer. It can range from a few months to many years. Mitogenic carcinogens: These agents stimulate cell division, which can increase the chances of mutations and cancer development. ○ Endogenous mitogens: These are substances produced by the body that can stimulate cell division. Initiated cells: These are cells that have been exposed to a carcinogen and have undergone genetic changes that make them more likely to develop into cancer cells. Initiated cells may be more resistant to cell death and have a higher rate of cell division than normal cells. Immunodeficiency: Neoplasms (tumours) can suppress the immune system, making the body more susceptible to infections. Neurotoxicity Neurotoxicity refers to the ability of a substance to damage the nervous system. Cells of the Nervous System: ○ Oligodendrocytes and Schwann cells are myelinating cells that produce myelin, a fatty substance that insulates nerve fibers and speeds up nerve impulse transmission. ○ Astrocytes (pericytes) and endothelial cells (cells that line blood vessels) form the blood-brain barrier, which restricts the passage of certain substances from the bloodstream into the brain. Transport Across the Blood-Brain Barrier: Lipophilic (fat-soluble) toxins can cross the blood-brain barrier relatively easily by passive diffusion. Axonal Transport: ○ Anterograde axonal transport: This involves the movement of substances from the cell body of a neuron down the axon to the nerve terminal. It includes fast transport (for transporting organelles and vesicles) and slow transport (for transporting cytoskeletal components). ○ Retrograde axonal transport: This involves the movement of substances from the nerve terminal back to the cell body.  For example, tetanus toxin uses retrograde axonal transport to travel from peripheral nerve endings to the central nervous system (CNS). Types of Neurotoxicity: ○ Neuropathy: This refers to damage to peripheral nerves, which can cause symptoms such as numbness, tingling, weakness, and pain. ○ Functional neurotoxicity: This involves changes in the function of the nervous system without any observable structural damage. Examples of Neurotoxic Substances and Their Effects: ○ Nitrogen trichloride: This substance can cause senile dementia, a decline in cognitive function. ○ Aluminium: Exposure to high levels of aluminium has been linked to neurodegenerative diseases, but the exact mechanisms are not fully understood. ○ Organophosphates: Organophosphate insecticides can cause delayed neuropathy by inhibiting neuropathy target esterase (NTE). ○ Agent that causes dog hysteria: This unknown agent inhibits the synthesis of glutathione, a crucial antioxidant, and disrupts the balance of redox ions, leading to dog hysteria (a condition characterized by abnormal behavior, seizures, and other neurological symptoms). Mechanisms of Neurotoxicity: ○ Dying-back process: This refers to the degeneration of an axon starting from the distal end (farthest from the cell body) and progressing towards the cell body. ○ Glial scar formation: When an axon is damaged, glial cells (support cells in the nervous system) can form a glial scar, which can prevent regeneration of the axon. ○ Microtubule disruption: Some substances, like cisplatin and colchicine, can bind to tubulin (the protein that makes up microtubules) and prevent the formation of microtubules. Microtubules are important for transporting substances within neurons, so disrupting them can lead to axonal swelling and impaired nerve impulse conduction. ○ Ephatic transmission: This is a phenomenon where nerve impulses can "jump" from one neuron to another without passing through a synapse (the junction between two neurons). It can occur when myelin is damaged, allowing nerve impulses to spread to adjacent neurons. ○ Minamata disease: This is a neurological disorder caused by mercury poisoning. Neurotransmitters and Their Disruption: ○ GABA (gamma-aminobutyric acid) and glycine: These are inhibitory neurotransmitters. ○ Acetylcholine: This is a neurotransmitter involved in muscle contraction, memory, and other functions. Triethylcholine can inhibit acetylcholine synthesis. ○ Monoamines: Monoamines are a class of neurotransmitters that include dopamine, norepinephrine, and serotonin. Heroin and morphine can inhibit monoamine degradation, leading to an increase in their levels in the brain. Other Neurotoxic Effects:  ○ Type I pyrethroids: These insecticides inhibit Ca2+/Mg2+ ATPase, an enzyme involved in calcium and magnesium transport. ○ Secondary messengers: These are molecules that relay signals within cells. Some neurotoxins can interfere with secondary messenger systems. ○ Ion channels: Some neurotoxins can block ion channels, such as Na+ and Ca2+ channels, disrupting nerve impulse transmission. Prolonged opening of Na+ channels can lead to hyperexcitability, while blocking Ca2+ channels can prevent the release of neurotransmitters. Insecticides The sources provide information on various types of insecticides and their mechanisms of action. Anticholinesterase Insecticides: Organophosphates and carbamates are examples of anticholinesterase insecticides, meaning they inhibit the enzyme acetylcholinesterase (AChE). ○ Organophosphates: Diazinon is an organophosphate insecticide. Organophosphates are not biodegradable. They can cause delayed neuropathy by inhibiting neuropathy target esterase (NTE), also known as neurotoxic esterase (NIE). ○ Carbamates: Carbamates are not biodegradable. AChE and its Inhibition: ○ True AChE: True AChE is found in red blood cells (RBCs). It takes several months for new true AChE to be generated. ○ Active Sites: AChE has an anionic site and an esteratic site. ○ Mechanism of Inhibition: Organophosphates bind to the esteratic site of AChE. ○ Aging: Aging of the phosphorylated AChE occurs due to the loss of an alkyl group. This makes the bond between the organophosphate and AChE irreversible. Treatment of Organophosphate Poisoning: ○ Atropine: Atropine blocks muscarinic receptors but not nicotinic receptors. ○ Oximes: Oximes, such as pralidoxime and obidoxime, are antidotes for organophosphate poisoning. They work by directly reacting with the organophosphate molecule and reactivating AChE. They also have anti-muscarinic effects like atropine. Pralidoxime and obidoxime can cross the blood-brain barrier. Organochlorine Insecticides: ○ Biodegradability: Organochlorine insecticides, such as DDT, are non-biodegradable, meaning they persist in the environment for long periods.  ○ Toxicity in Birds: Organochlorines can disrupt estrogen metabolism and calcium mobilization to eggshells in birds by inhibiting the enzyme carbonic anhydrase. ○ DDI and Chlorinated Cyclodienes: Both DDI (a metabolite of DDT) and chlorinated cyclodienes bind to calmodulin and inhibit its ability to transport calcium. Pyrethroid Insecticides: Pyrethrins are natural insecticides derived from plants. ○ Types: Pyrethrin I: Esters of chrysanthemic acid. Pyrethrin II: Esters of pyrethric acid. ○ Mechanism of Action: Type I pyrethroids: Induce the T-syndrome, a set of toxic effects including tremors and hyperexcitability. They do not inhibit Ca2+/Mg2+ ATPase. Type II pyrethroids: Induce the CS-syndrome, characterized by choreoathetosis (involuntary writhing movements) and salivation. They block GABA receptors and may also inhibit Ca2+/Mg2+ ATPase. DDI and Type I Pyrethroids: Both DDI and type I pyrethroids can induce the T-syndrome. Rodenticides Zinc Phosphide: ○ Zinc phosphide is an inorganic rodenticide that is black in color and has a rotten fish odor. Sodium Fluoroacetate and Fluoroacetamide: ○ These rodenticides inhibit the citric acid cycle, a crucial metabolic pathway. ○ Fluorocitrate, formed from fluoroacetate, inhibits the enzyme aconitase, preventing citrate from being converted to isocitrate. ANTU (α-Naphthylthiourea): ○ ANTU is a rodenticide that reacts with sulfhydryl (SH) groups in the body. Mycotoxins General Characteristics: Mycotoxins have low lipid/water partition coefficients and large molecular weights, making it difficult for them to pass through all body barriers. Fusarium Mycotoxins: ○ Aflatoxins: Fusarium fungi produce various aflatoxins, including aflatoxin B1 (the most potent type), aflatoxin B2, aflatoxin G1, aflatoxin G2, and aflatoxin epoxide. Toxicity Mechanism: Aflatoxin B1 is metabolized by the cytochrome P450 enzyme system, which can convert it into a reactive epoxide that can bind to DNA and cause liver damage. It is broken down into aflatoxin P1 through O-demethylation. Effects: Aflatoxins are known to cause liver damage and cancer. Vaccination failure in broiler chickens can occur in cases of aflatoxicosis.  Permissible Levels: The permissible level of aflatoxin B1 in food for humans, immature animals, poultry, and dairy animals is 20 ppb (parts per billion). Treatment: HSCAS (hydrated sodium calcium aluminosilicate), a clay mineral toxin binder, is an effective treatment for aflatoxicosis. ○ Zearalenone: Zearalenone is an estrogenic mycotoxin that can cause reproductive problems in animals. It is considered a "field mycotoxin" because it can contaminate crops before harvest. ○ T2 Toxin: Fusarium fungi also produce T2 toxin. Other Mycotoxins: ○ Ochratoxin: Ochratoxin is a nephrotoxic mycotoxin that can damage the kidneys. It is a field mycotoxin. ○ Citrinin: Citrinin is another nephrotoxic mycotoxin. Degradation of Mycotoxins: Some enzymes, such as esterase and epoxidase, can degrade certain mycotoxins. Natural Organic Adsorbents: Glucomannan, a natural organic adsorbent derived from the cell wall of the yeast Saccharomyces cerevisiae, can be used to bind mycotoxins and prevent their absorption. is a region in the stratosphere with a high concentration of ozone that protects life on Earth by absorbing harmful ultraviolet (UV) radiation from the sun. ○ Thickness Measurement: The thickness of the ozone layer is measured in Dobson units (DU). ○ Ozone Hole: An ozone hole is an area of the stratosphere with significantly depleted ozone levels (less than 220 DU). Ozone Depletion: ○ Nitrous Oxide: The main source of nitrous oxide (N2O) pollution is the microbial oxidation of artificial fertilizers. N2O can contribute to ozone depletion. ○ Chlorine and Bromine Compounds: Human-made chemicals containing chlorine and bromine, such as chlorofluorocarbons (CFCs), can reach the stratosphere and break down ozone. Temporary Inactivation: In the stratosphere, chlorine monoxide (ClO) is temporarily inactivated by reacting with nitrogen dioxide (NO2) to form chlorine nitrate (ClONO2). Chlorine radicals (Cl) are temporarily inactivated by reacting with methane (CH4) to form hydrochloric acid (HCl). Reactivation in Polar Spring: During the polar spring, sunlight breaks down ClONO2 and HCl, releasing ClO and Cl, which can then react with ozone and deplete it. HOCl + UV → Cl + OH Other Toxic Substances Carbon Monoxide (CO): CO is a colorless, odorless gas that is highly toxic because it binds to haemoglobin in red blood cells with an affinity about 200-250 times greater than that of oxygen. This prevents oxygen from being transported throughout the body. Poisonous Plants Examples of Poisonous Plants and Their Toxic Parts: ○ Strychnos nux-vomica: The seeds are toxic. ○ Ricinus communis (Castor bean): The seeds are toxic. They contain ricin, a highly toxic protein. ○ Croton tiglium (Croton seeds): The seeds are toxic. ○ Gossypium barbadense (Cotton seeds): The seeds are toxic. ○ Citrullus colocynthis (Bitter apple): The seeds and fruit are toxic. ○ Datura species (Thorn apple): The seeds and fruit are toxic. They contain atropine, which can cause dilated pupils (mydriasis). ○ Solanum species: Solanum capsicum (Chilli pepper): The seeds are toxic. Solanum melongena (Eggplant): The seeds are toxic. Solanum lycopersicum (Tomato): The seeds are toxic. Unripe potatoes contain solanine and can cause poisoning. ○ Sesamum indicum (Sesame): The seeds are toxic. ○ Allium cepa (Onion): The seeds are toxic. ○ Atropa belladonna (Deadly nightshade): The seeds are toxic. The fruit contains atropine. ○ Papaver somniferum (Opium poppy): The seeds and fruit are toxic. Opium Alkaloids: Opium contains several alkaloids, including narcotine, morphine, and narceine. Narcotine is the main convulsant alkaloid in opium. Morphine is a powerful analgesic. Toxicology Principles The sources cover fundamental principles of toxicology, including dose-response relationships, absorption, distribution, metabolism, and excretion of toxic substances. LD50 (Median Lethal Dose): The LD50 of a substance is the dose that is lethal to 50% of a population of test animals. It is used to assess the toxicity of a substance. ○ A poison with an LD50 of 5 mg/kg body weight is considered extremely toxic. Factors Affecting Toxicity: ○ Species: Different species can have different sensitivities to the same toxic substance. For example, atropine causes mydriasis (pupil dilation) in both cats and rabbits. ○ Individual Variation: Individuals within the same species can also vary in their susceptibility to toxins. Unexpected toxicity can occur even with small amounts of a substance. ○ Presence of Other Substances: The presence of fatty foods in the stomach can hinder the absorption of some toxins and accelerate the absorption of others. ○ Health Status: Animals with heart disease may be less affected by large doses of certain toxins. Absorption: Absorption is the process by which a toxic substance enters the bloodstream.  ○ Routes of Absorption: Ingestion: Many toxins are absorbed through the gastrointestinal tract. Inhalation: Toxins in the form of gases, vapors, or particles can be absorbed through the lungs. The rate of absorption from the lungs depends on the substance's solubility in blood and the ventilation rate. Increasing the respiration rate or blood flow rate increases the absorption of highly blood-soluble volatiles. Increasing the ventilation rate does not affect the absorption of low blood-soluble volatiles. Dermal Absorption: Some toxins can be absorbed through the skin. Other Routes: Toxins can also be absorbed through other routes, such as injection (e.g., intravenous, intramuscular) or mucous membranes (e.g., eyes, nose). Distribution: Distribution refers to the process by which a toxin is transported throughout the body. ○ Accumulation: Some toxins can accumulate in certain tissues. For example, chlorinated hydrocarbons tend to accumulate in fat, while lead accumulates in bone. Metabolism (Biotransformation): Metabolism is the process by which the body transforms a toxin into a more water-soluble form that can be more easily excreted. ○ Phase I Reactions: These reactions involve oxidation, reduction, and hydrolysis. Oxidation: Oxidation reactions often involve adding oxygen to a molecule. For example, alcohols are oxidized to aldehydes and then to ketones. Epoxidation: Epoxidation is a specific type of oxidation reaction that converts alkenes and aromatic compounds into epoxides. Hydrolysis: Hydrolysis reactions involve breaking a bond by adding water. Reduction: Reduction reactions involve removing oxygen or adding hydrogen to a molecule. ○ Phase II Reactions: These reactions involve conjugation, where a molecule is attached to a larger, more water-soluble molecule. Types of Conjugation: Examples of conjugation reactions include glucuronidation, sulfation, acetylation, and methylation. Glutathione Conjugation: Glutathione is an endogenous tripeptide compound that plays a crucial role in detoxifying various toxic substances. Toxins conjugated with glutathione are converted into mercapturic acids. Excretion: Excretion is the process by which the body eliminates toxins. ○ Routes of Excretion: Urine: The kidneys filter toxins from the blood and excrete them in urine. Feces: Toxins can be excreted in feces, either unchanged or as metabolites.  Other Routes: Toxins can also be excreted through sweat, saliva, tears, breast milk, and exhaled air. Toxicodynamics: Toxicodynamics refers to the effects of a toxin on the body. ○ Mechanisms of Toxicity: Enzyme Inhibition: Many toxins work by inhibiting enzymes. Receptor Binding: Some toxins bind to receptors, either mimicking or blocking the effects of endogenous substances. Cell Membrane Damage: Some toxins can damage cell membranes, leading to cell death.