Toxicology Chapter 6.docx

ENDOTOXINS: - mostly from gram (-) bacteria; lipoidal - low toxicity - high dose to become lethal > Typhoid – MS: Salmonella typhosa - causes typhoid fever > Proteus – MS: Proteus spp - causes UTI infections. ii. MINERALS a. Acids > HCl – aka muriatic acid - found in bathroom disinfectants - causes whitish burns > H2SO4 - aka sulfuric acid, oil of vitriol - causes brown-black burns and ground coffee vomit > HNO3 – aka aqua fortis - causes yellow burns > Phenol – aka carbolic acid - causes bleaching (whitish) burns b. Bases > NaOH – aka lye, sosa - found in detergent, hard soaps > KOH – aka caustic potash - found in detergent, soft soaps c. Salts > NaOCl – aka Dakin’s solution - bleaching and deodorizing agent > Lead chromate – used as yellow food coloring as seen in icing iii. SYNTHETIC 1. Aluminum chlorohydrate – Al2Cl(OH)5 - found in deodorants 2. Eosin – found in lipstick - also used in histology (study of tissues) for staining 3. Methanol – CH3OH - aka wood alcohol - denaturant, paint solvent and varnish - causes blindness 4. Formaldehyde – H2CO or CH2O - aka formalin - found in embalming fluid - colorless, flammable, strong-smelling chemical - also used 5. Isopropyl alcohol – C3H8O - aka crude oil alcohol

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- ingredient of rubbing alcohol - very toxic (limit of 120 ml) Phencyclidine – C17H25N - aka angel dust - psychedelic (drugs that cause unusually strong experiences of color, smell, taste and touch and other mental effects like hallucination to pxs) Asbestos – Mg3Si2O5(OH)4 - used as a fire retardant - used in fire proof clothing of firemen - causes silicosis and lung cancer Carbon tetrachloride – CCl4 - ingredient of non-flammable cleaning fluids and fire extinguishers Naphthalene – C10H8 - moth balls - also used as toilet bowl deodorant Hydrogen sulfide - H2S - aka “stink damp” - causes ‘gas eye’ for workers in tunnels - sewer gas Aniline – C6H5NH2 - aka blue oil - found in crayons - has the odor of a rotten fish Ethylene oxide – C2H4O - antifreeze liquid (used in aeronautics and in automobile cooling systems Chloral hydrate – C2H3Cl3O2 - knock-out drops (sedative) - date-rape drug - used as short-term treatment of insomnia and sedative before a minor or dental treatment - has a very narrow therapeutic window, thus, complicated to use - higher doses can depress respiration and blood pressure Barbiturate – C4H3N2O3 - found in sleeping pills - suppress REM sleep and is typically used to treat anxiety, headaches and insomnia Chloramine – NH2Cl - found in milk Amphetamine – C9H13N - “PEP Pill” - CNS stimulant - used to treat ADHD - helps increase ability of the brain to pay attention, stay focused on an activity and control behavior problems Carbon disulfide – CS2

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- colorless, volatile liquid - used in textile industry - causes red blood hemolysis Picric acid – (O2N)3C6H2OH - aka trinitropheniol - one of the most acidic phenol - used as an explosive and colorant in textile industries Acetone – (CH3)2O - found in nail polish removers and model airplane glues or cements - colorless, volatile, flammable liquid and is the simplest and smallest ketone Nitrobenzene – C6H5NO2 - found in shoe polish - water-insoluble pale yellow oil with an almond-like odor - prepared by nitration of benzene with a mixture of conc. sulfuric acid, water and nitric acid - aka ‘essence of mirbane’ Lysergic acid diethylamide (LSD) – C20H25N3O - psychedelic and hallucinogenic - aka ‘morning glory’ - clear or white crystalline and can produce an effect as little as 20 mcg - ssxs: dilated pupils, increased BP and body temp, dry mouth, profuse sweating, muscular numbness->weakness->tremors Saponated cresol – C7H8O - aka ‘Lysol’ - originally marketed as ‘feminine hygiene’, claiming that vaginal douching with diluted Lysol solution prevented infections and vaginal odor - m-cresol (similar cresol derivative) is used in making explosives

B. Based on properties:  Chemical composition i. INORGANIC 1. Pb – causes plumbism - sources: canned goods, automobile exhaust (as tetraethyl lead), wine, glasses, old pipes, cables and paints - exposure to high levels may cause anemia, weakness and kidney and brain damage - very high exposure can cause death - damages a developing baby’s nervous system

- usually repeated lead exposure is needed to manifest symptoms - ssxs: aggressive behavior, abdominal behavior, constipation, sleep problems, irritability 2. Au (Gold) - source: gold salts used as an anitinflammatory agent (for tx of rheumatoid arthritis) and tx for lupus erythematosus - ssxs: headache, jaundice (eyes), chrysiasis (eyes), pneuominitis (lungs), vomiting (GIT), bleeding (GIT), proteinuria (kidney), dermatitis (skin), decreased bone marrow function, impaired biliary tract flow 3. Li – used as tx of mania (LiCO3) - metals used as heat exchanger in air conditioners - a mood-stabilizing medication used to treat bipolar disorder and major depressive disorder - ssxs (mild to moderate): diarrhea, vomiting, stomach pains, fatigue, tremors, muscle weakness, drowsiness - ssxs (severe – serum levels above 2.0 mEq/L): heightened reflexes, seizures, agitation, slurred speech, kidney failure, rapid heartbeat, hyperthermia, uncontrollable eye movements, low BP, confusion, coma, delirium, death 4. Co – metal found in Vit. B12 - used in manufacture of permanent magnet - also used in beer for foam stability (causes alcoholic cardiomyopathy in heavy beer drinkers) - is also used in metal-on-metal hip implants together with chromium (excessive movement can cause wear and tear of the implant, thus poisoning) - ssxs (for large amount over longer periods of time): cardiomyopathy (heart becomes big and floppy and has problems pumping blood), deafness, nerve problems, tinnitus (ringing of the ears), thickening of the blood, thyroid problems 5. Os – used in fingerprint detection and pacemakers

- densest and rarest metal of all natural elements - also used in preparation of slides for electron microscopy - osmium tetroxide is used as a component for terrorists’ “dirty bomb” - ssxs: pulmonary edema and subsequent death - symptoms are noticeable hours after exposure 6. Mn – causes manganism - Ssxs (initial stages of exposure): reduced response speed, irritability, mood changes, compulsive behavior - Ssxs (protracted stages of exposure): symptoms resemble those of Parkinson’s disease (CM: shaking, rigidity, slowness of movement, difficulty walking, anxiety, dementia), Lou Gehrig’s disease (CM: stiff muscles, muscle twitching, gradually worsening and weakened) and multiple sclerosis (CM: double vision, blindness in one eye, muscle weakness, problems with coordination) - used as cofactor in enzyme reactions - also used in dry cell batteries, drying agent in black paints - also added in soda cans to improve resistance and corrosion 7. As – aka Lewisite metal - ssxs (for brief exposures): vomiting, abdominal pain, watery diarrhea that contains blood - ssxs (for long time exposure): thickening of the sin, darker skin, abdominal pain, diarrhea, heart disease, numbness and cancer - most common reason for long-term exposure is contaminated drinking water - used in manufacture of insecticides (Paris green, Fowler’s solution, Donovan’s solution) - metal present in Salvarsan/Arsphenamine (first effective treatment for symphilis and was also used to treat trypanosomiasis)

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possesses anti-leukemic properties (as trioxide salt) protoplasmic poison (substance that damages or kills living cells)

8. Cd – component of electric batteries - found in anti-dandruff shampoos and smoke/stink bombs and solder - released into the rivers of Japan around 1912, thus known as one of the Four Big Pollution Diseases of Japan - metal responsible for Itai-itai poisoning (CM: softening of the bones and kidney failure) - ssxs: weak and brittle bones, spinal and leg pain - Itai-itai is Japanese for “it hurts-it hurts” 9. Be – found in fluorescent and neon laps - Usual exposure is through inhalation - Causes berylliosis (chronic beryllium disease - ssxs: shortness of breath (SOB), weakness, loss of appetite, fatigue, cough - targets the lungs by developing granulomas that may cause scarring of the lungs and eventually reduces the lungs’ ability to function 10. B – used in vulcanizing of rubber - Increases thermal coefficient of expansion of glass - Ssxs: skin inflammation and peeling, irritability, tremors, convulsions, weakness, headaches, depression, diarrhea, vomiting 11. Sn – found in canned milk and canned products - Ssxs (after ingesting canned food containing 200 mg/kg Tin): nausea, vomiting, diarrhea 12. I – causes iodism - Sources: over-ingestion of iodized salt - Ssxs (mild exposure): diarrhea, burning sensation in the mouth, nausea and vomiting - Ssxs (severe exposure): swelling of airways, cyanosis (turning blue), weak pulse, coma

13. Cu – causes Wilson’s disease aka copperiedus - Ssxs (acute): vomiting, hematemesis (vomiting of blood), hypotension, melena (black “tarry” feces), coma, jaundice and GI distress - Ssxs (chronic): liver and kidney damage - Used in water purification by killing algae (as copper sulfate) 14. Mg – natural Calcium channel blocker - Second most abundant intracellular fluid cation - Possesses cathartic action and anticonvulsive properties - Causes hypermagnesemia - Ssxs: impaired breathing, abnormal heart rhythms and low heart rate, decreased respirations and impaired breathing, asystole (absence of ventricular contractions of the heart) 15. Fe – hematinic - Poisoning may lead to liver failure - Usually due to over-ingestion of iron pills - Ssxs occurs in 5 stages: o Stage 1 (within 6 hours after exposure): vomiting blood, diarrhea, abdominal pain, irritability, drowsiness o Stage 2 (6-8 hours after): pxs condition appears to improve o Stage 3 (12-48 hours after): very low blood pressure (shock), fever, bleeding, jaundice, liver failure, seizures o Stage 4 (2-5 days after): bleeding, blood-clotting abnormalities, pxs may die from shock, low blood sugar levels, confusion, sluggishness (lethargy), coma o Stage 5 (2-5 weeks after): stomach or intestines are blocked by scars causing abdominal pain and vomiting, cirrhosis (severe scarring of the liver 16. Ni – found in fancy jewelry - Produced in fossil fuel combustion - Causes contact dermatitis - Most powerful inorganic carcinogen

17. Mo – used in bacterial fixation of atmospheric nitrogen 18. Ce – used as a catalyst in resin forming materials 19. Cr – found in brown sugar and butter - Toxicity resembles diabetes mellitus - component of glucose tolerance factor that potentiates the effects of insulin - ssxs: increased blood and tissue acidity, inadequate blood supply to tissues that result in shock and kidney diseases, “chrome holes” (persistent ulcers due to skin contact) 20. Al – causes Shaver’s disease - Ssxs: dry cough, expectoration, anorexia, cyanosis, rales (abnormal rattling sound heard when examining unhealthy lungs with a stethoscope), enlarge lymph nodes - Third’s most abundant element in earth; most abundant metal - Constipating and astringent effects - Used as abrasive in industries - Used for the healing of burns 21. Zr – causes granulomas - used as an ingredient of deodorant and anti-perspirant 22. Zn – deficiency causes parakeratosis - Toxicity causes “metal fume fever” - Used in galvanizing iron and container for battery cells - Ssxs: chest soreness, muscle aches, thirst, fatigue, tiredness, GI pain 23. Ag – causes Argyria - Turns skin, eyes, internal organs, nails and gums a blue-gray color, especially in areas of the body exposed to sunlight. This change in skin color is permanent - Symptoms usually start in the mouth/gums - The whites of the eyes and nail beds may also turn blue-gray 24. Bi – aka “beautiful meadow” - Used in silvering mirrors 25. Ga - used in the manufacture of arc lamps

26. Hg – aka ‘quick silver’ - Causes Minamata’s disease - Ssxs: ataxia (lack of voluntary coordination of muscle movements), numbness in the hands and feet, general muscle weakness, loss of peripheral vision, and damage to hearing and speech - Found in thermometers, cosmetics (calomel), merthiolate - May cause insanity in extreme cases 27. Ba – found in depilatories and green-colored fireworks - Causes baritosis (CM: muscular twitching and hoarseness) 28. F – causes fluorosis in children - Found in drinking water supplies and in toothpaste - Used as a rat and roach poison 29. Br – dark brownish volatile liquid with a suffocating odor - Causes brominism (CM: psychosis and ataxia) 30. Sb – found in tartar emetic - Protoplasmic poison 31. P – aka “lucifer’s jaw”; “St. Elmo’s fire” - Found in matches and firecrackers - Used as a rat and roach poison 32. W – used in manufacture of lamps and ballpoint in pens 33. Cl – usual component for tear gas - used in water disinfection 34. Tl – most toxic metal - Used as a rat, roach and ant poison ii. ORGANIC 1. Potassium bromate – KBrO3 - dough improver - Found in cold wave neutralizers 2. Tartrazine – food colorant (lemon yellow azo dye) 3. Monosodium glutamate – causes Chinese restaurant syndrome or MSG symptom complex

Ssxs: headache, sweating, skin flushing, numbness or burning sensation in the mouth and throat, nausea, fatigue

4. Monomethyl hydrazine – produced by a poisonous mushroom, Gyrometra esculenta - Ssxs: nausea, stomach cramps, diarrhea 5. Tannic acid – carcinogen found in iced tea - Prolonged exposure may cause liver damage - If inhaled, may cause respiratory tract irritation 6. Nitrite – food preservative/colorant - Overexposure may lead to methemoglobinemia (body is deprived of oxygen causing a blue-gray discoloration of the skin) 7. BHA and BHT – carcinogenic antioxidant - butylated hydroxytoluene and butylated hydroxyanisole - widely used as food preservatives 8. Saccharin and Aspartame – artificial sweeteners - Ssxs of overdose: weight gain, anxiety attacks, muscle spasm and heart palpitation 9. Boric acid – used in astringent preparations - Causes “boiled lobster” appearance - Aka borax poisoning - Ssxs: blisters, twitching of facial muscles, arms, hands, leg and feet, convulsions, decreased or no urine output 

Volatility

i. VOLATILE 1. Hyaluronic acid – obtained from prussic acid 2. Carbon monoxide – formed as a by-product of incomplete combustion in automobiles, furnaces and cigarettes 3. Alcohols, phenols and formaldehyde ii. NON-VOLATILE 1. Alkaloids and alkaloid-based products