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1.

Define absorption of toxicants. Briefly discuss the routs of exposure of toxicants in human body.

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Toxicant: A toxic substance is simply a material which has toxic properties. It may be a discrete toxic chemical, or a variety of composition or a mixture of toxic chemicals. For example: Lead chromate discrete toxic chemical. Asbestos Toxic Material a variety of fibers and minerals. Gasoline Toxic substance mixture of many chemicals. Absorption: The process whereby a substance moves from outside the body into the body. Routs of exposure in human body: The skin (dermal absorption) The respiratory tract ( inhalation) The digestive tract (ingestion) The injection (IM, IV, ID, IP, SC) Dermal absorption: Layers Epidermis (outer layer) Stratum corneum (carnified layer) Outmost later determines the rate of absorption of substances through the epidermis; for example, a pesticide such as malathion, which easily penetrates the stratum corneium, makes quickly through the other layers of the skin and is rapidly absorbed into the bloodstream. But DDT does not easily penetrate the stratum corneium so the rate of absorption is much slower. Dermis (inner layer): True skin. Source of oxygen and of nutrients for the epidermis. Hair follicles, sweet glands, and sebaceous (oil) glands are found is the layer. These structures play a limited role in the absorption of substances across the skin. Inhalation: Factors affect inhalation of toxic substances: Concentration of toxic substance in the air Solubility of substance in the blood & tissue Respiration rate Length of exposure Condition of respiratory tract and Size of toxic particle Ingestion: Occurs accidentally or unknowingly. Parts of GI tract Mouth, esophagus, stomach and intestine, and other associate organ. HBS Liver, pancreas & spleen. Major function of GI Tract digest and absorb the food we eat. Factors affected absorption Concentration of target orgasm Chemical & physical form What happens to it after it is absorbed. How long it remains in the tissue or organs of choice. Translocation and Biotransformation. Injection: Doctors, nurse medical or chemical persons are in risk. It can control by awareness. Mainly used in laboratory studies on experimental animals. Types of injections are IV (intravenous) into a vein IM (Intramuscular) into the muscle IP (intra peritoneal) into the abdominal cavity ID (intra dermal) into the skin SC (subcutaneous) under the skin Differentiate among antagonism, potentiation and synergism. State how the factors influencing during the toxic chemical distribution. Antagonism refers to an interaction in which: a) There is an increase in chemicals toxicity due to the presence of another chemical. b) A reduction in chemicals toxicity due to the presence of another chemical. c) Toxicity resulting from exposure to two or more chemicals equals the sum of the toxicities of the individual substance. Potentiation: When a chemical that does not have a specific toxic effect make another chemical more toxic. Example: The hepatotoxicity of carbon tetrachloride is greatly enhanced by the presence of isopropanol. Such exposure may occur in the workplace. Synergism: Exposure to a chemical may drastically increase the effect of other chemical can have serious health effect with synergism. Example: Exposure to both cigarette smoker and radon results in a significantly greater risk for lung cancer than the sum of the risks of each. Factors influencing TOXICITY in distribution 2.

Exposure Route: e.g. Ingested chemicals, when absorbed from the intestine, distribute first to the liver and may be detoxified. Species: Rats cannot vomit and expel toxicants before they are absorbed or cause severe irritation. Antibiotic are selectively toxic to microorganism while virtually nontoxic to humans. Age: Parathion is more toxic to young animals. Sex: Male rats are 10 times more sensitive than females to liver damage from DDT. Ability to be absorbed: Ethanol is readily absorbed from the gastrointestinal tract but poorly absorbed through the skin. Matabolism: (Biotransformation) Detoxification xenobiotic is converted to a less toxic form.

10) Distribution: Blood servers as the main avenue for distribution. 11) Excretion: Kidney (liquid), GI tract (solid), and the Lung
(gases).

12) Presence of other chemicals: Alcohol may enhance the effect


of many antihistamines and sedatives.

3.

What do you mean by target organ toxicity? Explain shortly on hepatotoxicity and gonadotoxicity.

An organ that stores/ damaged/ absorbed by the xenobitic or its metabolic. Many xenobitics distribute in the body and often affect only specific target organs. The target organs that are affected may vary depending on dosage and route of exposure. For example: the target for a chemical after acute exposure may be the nervous system, but after chronic exposure that liver. Toxicity can result from adverse cellular, biochemical, or macromolecular change. Toxic substance may be systematic, organ, tissue or cell toxins. Toxicants may also affects only specific tissues or organs while not producing damage to the body as a whole. These specific sites are known as the target organs or target tissues. Benzene is a specific organ toxin in that it is primarily toxic to the blood-forming tissues. Lead is also a specific organ toxin; It has three targets organs: 1) Central nervous system, 2) kidney and 3) hematopoietic system. Liver is an organ involved in Biotransformation, cell involve is called parenchymal cells (hepatocytes). Major of function of liver or Hepatocytes are as bellow: 1) Biotransformation of xenobiotics, endogenous compounds, including hormones 2) Carbohydrate metabolism and storage 3) Synthesis of blood proteins (albumin, lipoproteins) 4) Urea formation 5) Fat metabolism 6) Bile formation Type of injury/damage Representative Toxins Fatty liver (Steatosis) CCI4, ethanol, Valproic acid Hepatocyte Necrosis (Cell death) Acetaminophen,ethanol, chloroform Canalicular choiestasis Estrogens, chlorpromazine Bile duct damage amoxicillin Sinusoidal damage Anabolic steroids Fibrosis & cirrhosis Ethanol, Vitamin A Tumors Aflatoxin, vinyle chloride Biomarkers of Hepatotoxicity: Symtoms: Nausea, vomiting, fatigue, hepatomegaly, jaundice Histopathology: Fatty liver, cirrhosis, necrosis, fibrosis Hepatocellular tumors Blood test: Serum hepatic enzymes ALT, AST, GGT Drug clearance Clotting times Billirubin Response to xenobiotics and Repair of Hepatotoxicity: Hypertrophy (increased cell size) Hyperplasia (increased cell number) Liver has enormous regenerative capacity. Gonadotoxic in Human (Drug) Male Female Bi sulfan Bi sulfan Chlorambucil Chlorambucil Cyclophosphamide Cyclophosphamide Nitrogen mustard Vincristine Vinblastine Reproductive Toxicity/Gonadotoxicity endpoints Reproductive dysfunction Decreased libido, Impotence Sperm abnormalities decrease numbers/ motility: Morphology Decrease Motility Subfecundity -- Abnormal gonads -- Abnormal pubertal development -- Amanorhoea -- Anovulatory cycles -- Delay in conception Endpoints of Gonadotoxicity

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FORM for metallic elements. The toxicity of mercury vapor differs greatly from methyl mercury. The innate chemical activity: e.g. Hydrogen cyanide binds to Cytochrome oxidase resulting in cellular hypoxia and rapid death. The DOSAGE: e.g. a) excess of 650 mg Tylenol as a single dose. b) Excess of 10 mg DDT/ day for 90 days.

- Illness during pregnancy/ partum: Toxemia/ Hemorrhage - Early fetal loss (<28 weeks) - Late fetal loss (>28 weeks) - Intrapartum death - Death in first week - Decrease birth weight - Pre maturity/ post maturity - Altered sex ratio - Multiple birth; birth defects - Infant death - Childhood morbidity - Childhood - malignancis. Differentiate between excretion and depuration. Discuss briefly the process pf kidney excretion. Excretion Depuration Excretion is the process of Elimination of a chemical from an elimination of metabolic wastes organism by desorption diffusion, and other toxic substances from excretion, egestion, the body. biotransformation or another route. This is primarily carried out by The act or process of depurating the lungs, kidneys and skin. or freeing from foreign or impure matter, as a liquid or wound Excretion is an essential process Depuration will only remove light in all forms of life. waste products to moderate levels of microbial are discharged directly through contaminants and cannot be used the surface of the cell for heavily contaminated Process of kidney excretion: Excretion is a function of the kidney which can eliminate significant amounts of soluble materials through urine formation. Accumulation of toxins in the urine can damage this vital system. Main function of the kidney: Excretion of body wastes and harmful chemicals. Process of urinary excretion: Three processes for urinary excretion: 1) Filtration 2) Secretion 3) Re absorption 1) Filtration: Filtration takes place in glomerulus of the nephron. One fourth of the cardiac output circulates through the kidney. About 99% of the water like filtrate, small molecules, and lipid soluble substances, are reabsorbed downstream in the nephron tubule. 2) Secretion: Secretion occurs in the proximal tubule section of the nephron. It is responsible for the transport of certain out of the blood and into the urine. Secreted substances include potassium ions, and some xenobiotics. 3) Reabsorption: Re absorption take place mainly in the proximal convoluted tubule of the nephron. And occurs primarily by passive transfer based on concentration gradient, moving from a high concentration in the proximal tubule to the lower concentration in the capillaries surrounding the tubule. 4.

-- Counteraction of removal of effects it is, in some cases done by administration of physiological antidotes as for example: injection of atropine in opium poisoning -- Symptomatic treatment: For gastric pain Administration of anodynes. -- Shock and collapse v- to be prevented, as far as positive. -- Maintenance of body heat by friction, Hot water bags or bottles and massage. -- Nutrition and correction of shock IV fluid -- Pulselessness rectal, subcutaneous or IV saline. -- Asphyxia inhalation of O2 -- Failure of respiration Artificial respiration -- Cardiac failure respiratory stimulant -- Secondary infection Antibiotic. -- Catherization with urobag to measure the urine volume. Complication of poisoned patients -- Aspiration pneumonia. -- Retention of urine -- Tachycardia -- Heart failure -- Pyrexia -- Atropine toxicity Immediate management of poisoned patient: -- Hospitalization -- Complete bed rest -- Remove the contaminated cloths and wash the body surface and nails thoroughly. -- Induce vomiting or stomach with water or pharyngeal section of the drug ingested. -- Maintain clear airway. Oxygen inhalation Immediate treatment. Infuse 5% DA 2000cc + DNS 1000cc IV drip 24 hours + Atropine (1amp = 0.6mg). 10 amp IV start and 10 amp in the IV drip and 2 amp in every 1015 minutes interval till the pupil is widely dilated and then reduce gradually and this is maintained for at least 2-3 days, Inj. Pralidoxime 30 mg / kg IV, Inj. Obidoxime 3 mg /kg in recently. What are the lead (pb) and mercury (Hg)? What are the health effects caused by lead and mercury, how? Lead (Pb) Lead symbol Pb is an abbreviation of its latin name plumbum for soft metal. Atomic number 82 First smelled is approx. 4000Bc as a byproduct of silver processing as golena (lead sulfide). Lead is a heavy, soft, toxic, gray-blue metal present in some insecticides, auto exhaust, industrial emissions and a variety of products. E.g. lead is found automotive and storage batteries and is used in the manufacture of paint, enamel, ink, glass, rubber, ceramics, chemicals and other items. Lead is a poisonous substance to animals, including humans. It damages the nervous system and causes brain disorder. Excessive lead also causes blood disorder in mammals. Mercury: Chemical element, Symbol Hg, Scientific Name: Hydrargyrum (Greek Hydro water, and argros silver). Atomic number 80. Freezing point = 388*c, Boiling point = 356.73*c. Mercury occurs deposits throughout the world mostly as Cinnabar (mercuric sulfide) Mercury is used in thermometer, barometer, Monometers, sphgmomanometers, flat valves, mercury switches, alalgam, fluresent lamp, ultraviolet light, Cinnarber is highly toxic by ingestion or inhalation at the dust. Mercury poisioning can also result from exposure to water solubic from of mercury . Chemical froms 3 oxidation states: Hgo, Hg+1, Hg+2 Metalic /Element: Hgo Inorganic salts: Mercuric Hgcl2, or mercurous Organic: Alkyl Hg: dimethyl or methyl Hg. Lead poisoning/ Health effect of lead. Pathway by which lead can enter the human body 1. Ingestion & 2. Inhalation. Lead is a natural element in the ecosystem. Through human activity, concentration of lead if enter the human body in large amount, is detrimental to health. Lead can effect hematologic (blood), neuromuscular, gastrointestinal, CNS an reproductive system. At lower levels of exposure- Hyperirritability, poor memory, & sluggish. In high levels mental retardation, epileptic, convention, coma, and even death may occur. Children are of special concern regarding lead poisoning for three major reason 1). Higher based metabolic rate which affects the absorption and metabolism of toxicants 2). Different breathing zone they are closer to the ground or flood where lead is deposited. 3). Rapid growth and differentiation at cell Because the nervous systems at children are still developing and their body masses are relatively small. Health effect at Mercury; Mercury accumulates in the liver, kidney, brain, blood. Health effect Acute & Chronic Severe acute effects: -- Gastrointestinal damage -- Cardiovascular collapse -- Kidney failure Chronic effect: CNS effects e.g. mental instability tendency to weep. Fine tremors of the hands and feet, personality changes mad as Hatter. Kidney effects increase protein in the urine, kidney failure. Birth defect: -- Neurological damage from Mythyl mercury. -- Altered muscle tone and tendon reflexer. -- Depressed intelligence. Effect of Inhalation: 6.

5. Write an essay on poisoned patient management. Introduction: Any substance that cause severe injury or death as a result of physiochemical interaction with living tissue issue is called poison The English word management come from the Latin word Maneggiare that means To train up the horses. Literally means the operation of human power. The word: management into 3 word as manage + men + T (tactfully). Management of poisoned patient to save the life and control the complication of poison. Management of poison patient depend on -- Elimination of poison -- Prevention of action or absorption -- Counteraction of removal of effects -- Symptomatic treatment, Elimination of poison: - elimination of the poison vary according to the mode of its administration e.g. If injected suction of the poison or excision of the affected part is indicated. If ingested stomach to be washed out. If inhaled fresh air O2 or artificial respiration is to be given according to the need of the patient. If applied locally the part is to be washed out with water, antidotes or emollients ore to be painted on the affected area. Prevention of action or absorption: Antidotes neutralize or render the poison harmless by formation of an insoluble salt. Universal antidote may use it signs and symptom are too vague and employed. Corrosives causing destruction of tissues should be rendered. Irritants In these, one or the other of the following methods one usually employed according to the mode of action of the poison. Machanical such substances as powdered glass or diamod dust which are linely to cause injuries to the mucous measure.

1-3 mg/m3 for 2-5 hour may case. -- Headache, salivation, Metallic test, Chills, cough, fever, tremors, abdominal cramps, diarrhea, nausea, vomiting, tightness in the chest difficult breathing, fatigue etc. Effect of children: Severe poisoning Acrodynia -- Irritability -- Sweating -- Rapid heart beat Loss of mobility.