Environmental/toxicology cram Flashcards
Phase 1 and 2
Phase II biotransformation- In general, ingested chemicals are modified by the body to increase excretion and thereby limit toxic action. Chemicals modified by phase I reactions can be further metabolized by a variety of phase II reactions. Phase I metabolism includes oxidation, reduction and hydrolysis. Phase II reactions act to further increase hydrophilicity of the chemical, hastening its excretion. Phase II principally involves conjugation or synthesis reactions.
An alkaline toxin is excreted faster in acid urine.
An alkaline toxin is excreted faster in acid urine. Things are excreted better in an ionized state. An alkaline substance will be able to ionize when in acidic solution. When you suspect a child of having aspirin (acetylsalicylic acid) toxicity, you alkalinize the urine.
Toxins eliminated – protein bound/non-protein bound excreted the same?
Toxins eliminated – protein bound/non-protein bound excreted the same? No, lipid soluble toxins are passively reabsorbed. Only free compounds unbound by plasma proteins are filtered by the glomerulus. Tubular reabsorption-ionized and polar compounds are poorly reabsorbed they remain in the urine and are excreted.
IV administration of drugs is the quickest route of absorbtion, followed by:
IV administration of drugs is the quickest route of absorbtion, followed by:
IP, inhalation, IM, oral, SQ, ID and topical.
toxicant, toxin, toxicity, toxicosis/poisoning/intoxication
Toxicant- synonym for poison
Toxin- toxicant produced by living organism
Toxicity- amount of toxicant it takes to produce poisoning usually dose ie mg/kg
Toxicosis, poisoning, intoxication- disease state induced by toxicant
hazard, dose reponse, LC50, effectiveC50
Hazard- Likelihood of poisoning under conditions of use
Dose-response- any increase in dose will cause graded increase in response
LC50: dosage lethal concentration in 50% of animals,
LC50/EffectiveC50: Therapeutic Index
acute, subhronic, chronic
Acute toxicity- first 24 hrs (subacute 7-30 days)
Subchronic- <90 days (generally 30-90 days)
Chronic >90 days
half life, first order kinetics, zero order, lethal synthesis
Half life: time needed for ½ of a chemical to be eliminated. 20 ½ life periods will virtually eliminate chemical residues from the body.
First order kinetics: constant fraction per unit of time eliminated
Zero order kinetics: constant amount per unit of time eliminated
Lethal Synthesis: metabolized product may be more toxic than original compound
cat toxins
Cats lack gluconyl transferase therefore cannot metabolize phenols (aspirin, Tylenol)
atropine
Atropine- a sympathetic cholinergic blocking (antichloinergic) agent, a naturally occurring belladonna alkaloid, a parasympatholytic
2 PAM-
2 PAM- is a reactivator of acetylcholinerase.
GI toxins
GI: Blister Beetle, Mustard seeds, Corn, Cockle, Nightshade, Oleander, Castor bean (from which the very toxic RICIN comes from), chinaberry, tung, pokeweed, sesbania (coffee weed, bladder pod, rattlebox), azalea (rhododendron), baccaris (salt bush), Black locust, Hairy Vetch, Slaframine from fungus of Red Clove
Hematopoietic toxins
Hematopoietic system: Anemia &Hemoglobinuria, Bracken fern, Sweet clover (Meliotus), Cynanide, Cherry, Johnson Grass, Rye, Rape, Kale, Red Maple leaves, fresh onions
hepatic toxins
Hepatic: Aflatoxin, Lantana, Kleingrass, Zamia, Cotton, St Johnswort, Lupine, Cocklebur
Pyrrolizidine Alkaloids ragwort (Senecia jacobea), woolly groundsel (Senecia), Rattleweed (Crotalaria). Plants eaten in drought. Cattle, horses, pigs most susceptible Goats and sheep require 20 x more plant material
renal toxins
Renal: Black Locust, Quercus-oakbud, acorn poisoning, Oxalate-(beet, halogeton, greasewood, rhubarb, pigweed)
cardiovascular toxins
Cardiovascular: Cardiac glycoside containing: Milkweed, Laurel, Oleander, Dogbane, Lily of the Valley, Azalea, Foxglove. Japanese Yew, Jessamine, Halogeton, Pigweed, Oak, Digitalis, Jimsonweed, Gossypol (Cottonseed). Fungi: Ergot (Claviceps), Tall Fescue. White snakeroot; Rayless Goldenrod; Rhododendron
neuro toxins
Neurological: Seizure/tremors Bracken fern; Locoweed; Tremorgenic mycotoxins; Dallis grass; Ryegrass staggers, Centaurea spp- Yellow star Thistle & Russian Knap-weed, Poison Hemlock, water hemlock, nightshades, cycads, milkweeds
repro toxins
Reproductive Failure: Fescue forage prolonged feeding or grazing on endophyte-infected fescue during late pregnancy. Remove mares from fescue pastures or hay 6-8 weeks prior to foaling.
pulmonary toxins
Pulmonary: Locoweed, rumen microbes converting Tryptophan to 3 methylindole-“green grass sickness/Fog Fever”. Perilla mint, moldy sweet potatoes
Tetratogenic toxins
Tetratogenic:Lupine, poison hemlock, locoweed (astragalus) tobacco, lead tree, false hellbore
Mycotoxins that are teratogenic, cause abortion, infertility: rubratoxin, ochratoxin, slaframine, zearalenone, aflatoxin
Viruses that are teratogenic BVD, Blue tongue, akabane, and Ibaraki
Paspalitrems (ergot of Dallis Grass – Paspalum dilatatum) Cattle, Horses
Indol alkaloids are derivatives of LSD; inhibit GABA with signs of excitement, ataxia, tremors,
Slaframine (Red Clover or some other legumes infected with Rhizoctonia leguminicola) Cattle, Horses
Horses, Cattle
Slaframine has parasympathetic effects with production Called slobber factor, blackpatch. Signs: SLUD
T-2 Toxin
swine, Cattle, Sheep
Severe toxicosis characterized by leukopenia, petechiae, lymphoid and thymic depletion
Aflatoxins- Aspergillus flavus and parasiticus on peanuts, corn, soybeans
Primarily B1 most toxic seen in drought years,
Poultry, Ducklings most affected.
Baby pigs, calves, dogs. Signs- ADR, hepatitis, Chronic-wt loss, anorexic
Contaminated feed can be mixed with good feed to dilute. Can be fed to less affected animals.
Should not be fed to dairy cows. Residue in milk (M1) toxic at >300 ppb
Only aflatoxin is potentially detected by direct fluorescence, a yellow-green glow that results from a coincidental metabolite of Aspergillus flavus known as kojic acid.
Aflatoxin in corn- 40 ppm- action level is 20 ppm. What can farmer do to dispose of 50K bushels of corn? Ans: dilute to half with clean feed; feed to any livestock dairy no? mix with some chemical to reduce aflatoxin? No. FDA considers aflatoxins adulterants.
Algae Poisoning
Blue-green algae (cyanobacteria)
Anabeana, microcystis
Ruminants and birds more sensitive than monogastrics
Signs- dead w/ algae in mouth; in gut
ANTU Toxicity
alpha-napthlythiourea
Pets/livestock.
Signs- vomiting, HYPERSALIVATION, cough: PULMONARY EDEMA
Arsenic Poisoning
Trivalent (arsenite) 5-10 x more toxic
Pentavalent (arsenate) ant baits
activated charcoal; BAL (dimercaprol), sodium thiosulfate
Source: lead arsenate (pink powder) in storage areas, leaking herbicide containers, burned wood dumped in pasture, sweet ant baits
Botulism Toxin one of the most lethal toxins
Clostridium botulinum- anaerobic in hay
Types C, D most common in animals
Horse, Waterfowl very susceptible- ascending paralysis; incoordination
Decreased tongue tone, hard to withdraw tongue, colic. Vaccinate other horses on farm.
Bracken Fern Poisoning
Pteridium aquilirum: found throughout world
Ruminants – aplastic anemia
Nonruminants- thiaminase causing Vit B1 deficiency
Horse- very susceptible Pigs- rare
Horses- STAGGERS, death, convulsions
Cattle- acute hemorrhage/sudden death
Sheep- retinal atrophy (bright blindness)
Tx- Thiamine :Vit B1
Mortality in cattle > 90%
Coal Tar poisoning
Phenol most important toxicant (clay pigeons, tar paper, creosote)
Many animals- pigs common
CATS very susceptible
Cantharidin Poisoning
Blister beetle: 1st and last cut hay generally safe
Epicauta sp. Cantharidin is the toxin
Horses susceptible - mild depression to death, hematuria,
Severe hypocalcemia
Chocolate Poisoning-Theobromine
Dogs most susceptible
Signs-excitement, agitation, nervousness, vomiting
Copper Poisoning “gun metal blue kidneys”
Sheep mostly affected, dog: (Bedlington Terrier)
Source- Cu in feed, especially Cu to Molyb ratio ideal sheep 6:1
Usually chronic-GI, intravascular hemolysis-anemia/jaundice, hemoglobinuria
Citrinin or Ochratoxin (corn, wheat, barley, rye, oats, peanuts)
swine, Poultry
Renal effects. Chronic signs are anorexia, weight loss, polyuria and polydipsia.
Ochratoxin - A. ochraceus, Penicillium also has caused fetal death and resorption in cattle.
Carbamate Insecticide Carbamate, carbaryl
Same mechanism of action as Organophosphates; persistent parasympathetic stimulation but reversible inhibition of ACHase: ½ life 45 min. Will come off on their own. Tx: atropine
Chronic ergotism
Chronic ergotism - causes gangrene in cattle. Alkaloids of ergot, especially ergotamine, cause arteriolar spasm with restriction of circulation, gangrene of extremities in cattle. Acute ergotism convulsive episodes or nervous depression when alkaloids consumed in large amounts
Cyanide Poisoning Prussic acid
Cyanide Poisoning Prussic acid mm- bright red. Ruminants more sensitive than monogastrics; cattle and sheep are more susceptible than swine. Stagger, labored breathing. Severe drought is the most common cause of prussic acid poisoning. Mostly from plants; Arrowgrass, velvet grass, sorghum, Johnson grass, Sudan grass, Prunus sp. (apricot, peachpits, chokeberry), Prunus, wild black cherry trees (P. serotina). Signs- dyspnea, excitability, mm BRIGHT RED “almond smell”Tx- Sodium nitrite followed by sodium thiosulfate
Deoxynivalenol: DON, Vomitoxin (corn, barley, wheat, small grains), Swine, dairy cattle
Deoxynivalenol: DON, Vomitoxin (corn, barley, wheat, small grains), Swine, dairy cattle. Fusarium graninearum. In WET seasons, “scabby grain”. Cytotoxic, rapid feed refusal. GI signs. Dilute with clean feed. Swine: most sensitive.
Dicoumarol (sweet clover – Melilotus spp)
Cattle, Sheep, Swine
Dicoumarol (sweet clover – Melilotus spp)
Cattle, Sheep, Swine
Mold infestation of forage coumarin goes to dicoumarol, which is a Vitamin K antagonist.
Ethylene Glycol Poisoning
Ethylene Glycol Poisoning Antifreeze, dogs/cats most likely First stage CNS: drunk third stage Renal /seizure stage Vomiting, PD/PU, renal failure Ca Oxalate in urine 4-methylpyrozole (4-MP), 20% alcohol,
Fescue Toxicosis 4
Fescue Toxicosis – a) summer syndrome - Cattle grazing tall fescue in the summer: general unthriftiness. Infection of fescue grass with an endophyte fungus which is associated with presence of pyrrolizidine alkaloids (loline etc) b) fescue foot (gangrene) c) fat necrosis in cattle grazing fescue fertilized with poultry manure. d) agalactia in mares
Fog Fever/ Green grass sickness-
Fog Fever/ Green grass sickness- acute pulmonary edema in cattle.
Rumen microbes converting Tryptophan to 3 methylindole when cows transfer to a lush pasture.
Fumonisin moniliforme on corn B1
Fumonisin moniliforme on corn B1
Leukoencephalomalacia of horses and donkeys.
Muscle tremors, stagger, circle, can’t swallow, liver disease.
Death in 48-72 hours.
Pigs show pulmonary edema and massive hydrothorax.
Gen CNS stimulants-
Gen CNS stimulants-
neuromuscular, trembling, convulsions, death, head pressing
Muscle tremor/increase sensitivity nerves, eyes dilated.
Cats very susceptible when dog products used on them.
Gossypol Poisoning; Cottonseed w/excess gossypol
Gossypol Poisoning
Cottonseed w/excess gossypol
Monogastrics (pigs), immature ruminants and poultry most affected
Holstein most affected cow, weight loss, anorexia, violent “thumping in pigs”
Public Health Aspects- tissue residue, only eat animals surviving 1 month
Halogenated Cyclic Hydrocarbons
PCB, PBB, Dioxin
Halogenated Cyclic Hydrocarbons
PCB, PBB, Dioxin
Livestock most common affected
Signs- multi system, non-specific, stored in fat, long excretion, meat/milk may be contaminated.
PBB very fat soluble/ dispose of animals, ex. Firemaster in Michigan dairy feed
Syndromes: chicken edema disease, wildlife endocrine disruption w/estrogen/repro/immune
Human-chloracne, possible sperm count disease
Herbicide Toxicosis paraquat.
Herbicide Toxicosis paraquat.
Cause specific inhibition of enzymes
2,4-D; phenoxyacetic acid herbicide, linked with myotonia (stiff rear muscle) dogs, possibly assoc. w/ lymphoma in dogs
Horsetail, Equisetum ravens
Horsetail, Equisetum ravens
Causes thiamine deficiency as does Bracken fern in horses and aplastic anemia in cows.
Farmer with brood mares, pasture is bad because of drought, has sorghum field, and wants advice on pasturing mares on sorghum. Not during the drought, that’s for sure and not near foaling time.
Ionophores Toxicosis
Ionophores Toxicosis
Source Ionophores growth stimulants cattle, coccidiostats sheep/poultry
Monensin (Rumensin), lasalocid
Horses EXTREMELY susceptible LD50 2-3 mg/kg Never feed horse poultry feed
Horse: colic, sweat, tachycardic
Sheep: less cardiac, myoglobinuria, ataxia, reluctant to walk
Dog: skeletal muscle pain rear leg paresis
Lead grease, oils, batteries, paint, caulk
Lead grease, oils, batteries, paint, caulk
Most cattle/dogs CNS/GI Dx: basophilic stippling
No FDA approved agent for food animals
Ca EDTA, MgSO4, Thiamine (Vit B1) cattle
Mesquite in cattle
Mesquite in cattle-ruminal atony; tongue paralysis, emaciation.
Metaldehyde Poisoning
Metaldehyde Poisoning
Snail poison: salivation, vomiting, and muscle tremor, incoordination
Nitrate/nitrite Poisoning
Nitrate/nitrite Poisoning
Ruminants reduce Nitrate to Nitrite (10X more toxic) Ammonia
Cattle most frequent problem. Nitrite combines with hemoglobin to form methemoglobin.
CYANOTIC Membranes. Blood-CHOCOLATE BROWN
IV 1% methylene blue SLOWLY reduces MetHb ferric to Hb ferrous
Pigweed, lambsquarters, thistle, jimson weed, smartweed, dock, Johnson grass. Sorghum, oats, millet, rye, corn, sunflower,sudan grass.
Associated with drought.
Non-Protein Nitrogen Poisoning
Non-Protein Nitrogen Poisoning
Ammonia toxicosis, “bovine bonkers”
NPN -> NH4 (ammonia in gut)
Horse most affected monogastric
Ruminants most total affected, acidosis and hyperkalemia
NPN should be no more than 1% total and no more than 1/3 of total N source
Organochlorine Insecticides (chlorinated hydrocarbons)
Organochlorine Insecticides (chlorinated hydrocarbons) DDT, dieldrin, aldrin, chlordane, toxaphene, mirex, lindane, absorbed in fat-causes residues
Organophosphates (parathion, Dursban, fenthion, malathion, chlorpyrifos, Dichlorvos, Coumaphos)
Organophosphates (parathion, Dursban, fenthion, malathion, chlorpyrifos, Dichlorvos, Coumaphos) irreversible inhibition of acetylcholinesterase, thus preventing the degradation of acetylcholine & results in persistent parasympathetic stimulation. Muscarinic receptors: SLUD miotic pinpoint pupils, bradycardia. Nicotinic effects include skeletal muscle fasciculations. Ataxia, convulsions, and respiratory distress. Treatment: atropine, a parasympatholytic. Pralidoxime chloride (2-PAM) regenerates acetylcholinesterase. Cause of death pulmonary edema.
Oxalate poisoning-
Oxalate poisoning- beet, halogeton, greasewood, rhubard, pigwee
Rodenticide Poisoning:
Rodenticide Poisoning: Anticoagulant: get soft, impartial blood clots
Warfarin less popular, 2nd generation more toxic: brodifacoum; bromodialone; diphacinone
Signs-hemorrhage, epistaxis, anemia, weakness
Tx- Vit K1 for 3-4 weeks!
Rubratoxin
Rubratoxins - hepatic and hemorrhagic disease. May add to signs of aflatoxin, etc. in moldy corn.
Rye-grass staggers –
Rye-grass staggers –
caused by tremorgenic mycotoxins (lolitrems) produced by endophyte
Acremonium loli. S
heep, cattle, horses affected.
P. cyclopium - one cause of Rye Grass Staggers.
Soil-borne fungus outbreaks associated with litter on pasture. Moldy walnuts have poisoned dogs.
Strychnine Poisoning
Strychnine Poisoning
Indol alkaloid, Ingestion gopher bait.
rigid clonic seizures, sawhorse stance (extensor muscles)
Tx- emesis, lavage, seizures-diazepam, pentobarbital
Ace contraindicated
Selenium Toxicity
Selenium Toxicity
Selenium is both toxic and essential element, Selenium in soil, feed, plants, “garlicky breath”
Chronic- alkali poisoning- joint disease, hoof disease, thin
Acute: BLIND STAGGERS
Selenium deficiency causes white muscle disease in cattle/sheep
Selenium accumulating plants Astragalus, Astriplex sp., prince’s plume, woody asters
The secondary selenium accumulators include some native range plants, and crop plants such as western wheatgrass, barley, wheat, and alfalfa.
Salt Toxicity
Salt Toxicity
Or water deprivation: sodium ion toxicosis.
Most common in swine, cattle, poultry. Sheep resistant.
Swine- lack of h2O. Cattle: excess salt intake
Pigs: Blind, deaf, circling, pivot on hindfoot, stargasing
Cattle: GI/CNS signs, circling.
Eosinophilic vascular cuffing pathognomic
Urea toxicity
Urea toxicity- is the horse more susceptible? No, cattle are most susceptible. Rumen bacteria contain urease, which breaks urea down into ammonia and non-protein nitrogen. Give acetic acid into rumen but bicarb in iv fluids.
Vitamin D3 (Cholecalciferol)
Vitamin D3 (Cholecalciferol)
Rodenticides and feed additives- formulation error
Primary dogs, Increase Ca absorption
Affects: GI, Cardiac, Renal PD/PU, calcification kidneys etc
White snakeroot
White snakeroot-cs trembles, weakness “milk sickness” shed in milk, toxic to young & humans. Tremertol, an alcohol, is toxic compound.
Yellowstar thistle
Yellowstar thistle-affects horses-alkaloid invol chewing, eventually liquefactive necrosis of brain.
Zearalenone Toxicosis
Zearalenone Toxicosis Fusarium graminearum in corn and other small grains
Note: same organism as Vomitoxin, may be co-contaminant WET season,
Primarily swine problem F2, Estrogenic
