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toxicity
- the quantity of a toxicant, which under specified conditions, will result in detrimental changes to an organism
- mg/kg, dose
- not equal to hazard
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hazard
- the likelihood or chance that a toxicant will produce a dz state under the conditions of use
- or
- the likelihood or chance of exposure to a particular toxicant under the conditions of use
- no equal to toxicity
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toxicologist
a health professional interested in and knowledgable of the properties of toxicants and the tx of dz conditions
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veterinary toxicologist
a veterinarian who is an expert in the toxic dz of animals as well as one who is expert in extrapolating from animals to humans and is a diplomate of the American Board of Veterinary Toxicology (ABVT)
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toxicosis
the dz state which may result from exposure to a toxicant or poison
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dose
- mg of chemical/ kg of body wt
- no equal to ppm
-
parts per million
- ppm not equal to dose
- concentration
- 1ppm= 0.0001%
- 10,000ppm= 1%
- 1 inch in 16 mi
- 1g needle in a ton of hay
- 1 drop in 80 fifths
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LD50
- quantity of toxicant required to kill 50% of animals
- single oral dose
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LC50
conc of toxicant in water or feed that will kill 50% animals
-
acute vs subacute vs chronic toxicity
- A: single exposure, 7d
- S: daily exposure for 90d
- C: daily exposure >90d
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toxicity rating chart
- highly 1mg/kg
- non-toxic 15gm/kg
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margin of safety
- ratio btw LD50 and ED50 normally
- in tox we want therapeutic index so LD01 over ED99
- want MS 20-40 but anesthetic agents are 1
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NOEL or NOAEL
- no observed (adverse) effect level in the most sensitive species
- mg/kg/d
- max dose that does not did not produce any adverse effect
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ADI
- acceptable daily intake
- mg/kg/d
- max amt ingested and not expect adverse effect after lifetime of use
- =NOEL/safety factor
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tolerance
- max quantity that can appear legally in food for human consumption or in animal feeds
- =(ADI x 60kg)/(food factor x 1.5kg/d)
- =residue
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action level
- similar to tolerance
- a guide line and not legally established
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delany clause
n amendment to the federal food drug and cosmetic act whhich states that a carcinogen may not appear in food for human consumption
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TLV
- threshold limit value
- upper limit of toxicant conc in which an avg healthy person can work an 8hr day, 40hr week, for a lifetime and not be adversely affected
- ex- breathing limit of iso for anesthesia techs
- can either be a time weighted avg or ceiling vlue
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zero order kinetics
a fixed quantity is excreted during a given time
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first order kinetics
a constant fraction is excreted per unit time
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specific diagnosis of intoxication
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phases of biotransformation of toxicants
- phase I- non synthetic chemical rxns (oxidation, reduction, hydrolysis)
- phase II- synthetic rxns (amino acids, sugars, fatty acids, sulfates, acetates)
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if owner insists tx animal with intoxication
- only if time delay and animal not depressed
- wash with soap and water
- 5ml hydrogen peroxide
- 1tbs ipecac
- milk with egg white
- activated charcoal
- water
- transport animal, bring suspect materials, bring vomitus
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delay absorption
- remove external contaminants
- induce emesis
- gastric lavage
- absorbants
- cathartics
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induce emesis
- syrup of ipecac
- table salt
- hydrogen peroxide
- apomorphine
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contraindications for induction of emesis
- unconscious or CNS depression
- intox with petroleum
- caustic materials
- >2-4 hr post ingestion
-
gastric lavage
- light anesthesia
- cuffed ET tube
- lower head and thorax
- measure oral-gastric tube nose to xiphoid cartilage
- flush with water and aspirate, repeat
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activated charcoal
- absorbent
- ex- toxiban, superchar
- then give cathartic
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cathartic
saline, sodium sulfate, Mg sulfate, mineral oil
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pKa
- high is strong base
- low is strong acid
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ion trapping
- used in GIT and kidney
- compounds non-ionized at physiologic pH
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chelating agent
- donor molecule that forms a bond with a metal or metalloid
- higher Km means tighter bond in vitro
- organic material donate both electrons and contain N, O, or S
- induce histamine release with toxic amts
- tox has low incidence of adverse effects
- only BAL causes neuro dz in toxic amts
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metals
- MOA: bind with active site of enzymes
- bind sulf-hydrial groups
- mealleable when pure
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metalloid
- not malleable when pure
- bind sulf-hydrial groups on enzyme
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arsenic forms
- arsenite (As+3) more toxic than arsenate (As+5)
- once there, always there
-
arsenic uses
- hematinics
- fowlers solution
- wood preservative
- syphilis and HW tx
- growth promotant
- tx swine dysentery
- fever tick dip
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inorganic arsenicals and trivalent organics
- effect GIT and capillaries
- ex- arsenic trioxide, sodium arsenite/arsenate, chromated copper arsenate, lead arsenate, paris green, smelters
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pentavalent organic arsenical
- effect neuro
- ex- MSMA, DMSA
-
phenylarsenic
- demyelination
- arsenic should not be found
- no tx
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growth promotant arsenic source
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medicinal arsenic sources
- arsenamide
- fowlers solution- K arsenite
- sodium cacodylate
- tryparsamide
- melarsoprol
- neoarsphenamine
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MOA arsenic (AS+3)
- react with -SH of proteins and inhibit enzymes by blocking active groups
- inhibits alpha-keto oxidases which contain dithiol groups and are involved in oxidation of pyruvate
- inhibit lipoic acid, an essential co-enzyme for pyruvic acid oxidase
- BAL will reverse
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MOA arsenic (AS+5)
- uncouple oxidative phosphorylation
- may interfere with B6 and B1= demyelination
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arsenic absorption
- small amt via skin
- best via GIT
- accumulates in liver
- cros placenta
- stored in bones, skin, hair, hooves
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-
arsenic toxicity
inorganic As3 (arsenite)> inorganic As5 (arsenate)> trivalent organics (As+3)> pentavalent organics (As+5)
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arsenic causes of poisoning
- soil around old dipping vats
- improper disposal of containers
- around smelters
- human carelessness
- feeding gin trash instead of cotton seed hulls
- HUMAN MISTAKES!
-
acute arsenic tox
- abdominal pain
- staggering gait
- incoordination
- diarrhea
- sudden death
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sub-acute arsenic tox
- depression
- anorexia
- convulsions
- fluid, dark feces
- hematuria
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chronic arsenic tox
- easily fatigued
- intense thirst
- dry hair coat
- brick red MM
- looks like vit A def
-
phenylarsonic clinical signs
- neuro
- blind
- erythema
- BAL will not help
-
arsenic tox lesions
- soft, yellow liver
- hemorrhagic gastroenteritis
- rumen mucosal necrosis
- intestinal ulcers
-
phenylarsonic lesions
- downer pig
- demyelination of optic nerve
-
arsenic tx
- early- emetics, gastric lavage, milk, cathartic, Na thiosulfate
- late- BAL (will reverse lipoic acid inhibition)
- no tx for phenyllarsenic
-
arsine (AH3) intox
- hot acid interacts with metal
- most toxic arsenical
- causes hemolysis
- abnormal ECG and pulm edema
- BAL is tx if chronic
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sources of lead tox
- old paint
- glazed pottery
- lined feed troughs, buckets, pipes
- batteries
- smelters
- vegetation sprayed with lead arsenate
- white lotion
- leaded gas on forages
- lead shot
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lead absorption
GI or resp
-
lead distribution
- bound to RBC
- soft tissue
- bone, teeth, hair
-
lead excretion
- urine- adults
- feces- infants, animals
- milk
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organ systems affected by lead
- nervous
- GI
- blood and bone marrow
- renal
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MOA lead tox
- inhibits -SH groups on enzymes
- interfere with hemoglobin synthesis
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chronic lead tox
- roaring in equine
- lead line in gums
- lead lines in metaphysis of long bones of immature dog
- inhibit hematopoiesis
-
lead tox lesion
- agonal hemorrhages
- pale muscles
- hemorrhagic thymus
-
lead tox diagnosis
- renal cortex
- blood- high in acute and chronic
- liver
- feces - high if 2 to 4 wk, normal if more than 4 wks
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lead tox tx
- CaNa EDTA
- thiamine (combo with EDTA to reduce neuro)
- BAL+EDTA if severe neuro
- succimer
- must tx for 3-5 days
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copper:molybdenum in ruminants
- 6:1
- if adequate SO4 then will excrete opposite
-
copper tox in ruminants
- mostly sheep
- 10:1
- never feed cattle feed to sheep bc high in Cu
- chronic accumulation in liver- hepatic necrosis, hemolysis
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molybdenum tox in ruminants
- mostly cattle
- 2:1, excess sulfate
- chronic dz- poor doers, hypoproteinemia, repro prob, jt prob
- achromotrichia- hair color black to grey or red to tan
- sheep- wool slipping, swayback lamb
-
copper tox lesion in ruminants
- icterus
- gun metal kidney
- yellow friable liver
- blackberry jam spleen
- hemoglobinuria
-
copper tox tx in ruminants
penicillamine
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Cu and Mo in non-ruminants
- interactions not as marked
- dec Cu tx with Zn
- no hemolysis with Cu tox
- achromotrichia, aortic rupture with Mo tox
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-
elemental vapor Hg
- inhalation
- oxidized to Hg++
- in blood- renal prob
- in CNS- neuro (primary)
- BAL to tx renal
- no tx for CNS
-
mercuric (Hg++)
- ingestion
- charged so does not cross BBB
- GI, renal (primary)
- CNS
- tx with BAL
- most toxic
-
mercurous (Hg+)
- ingestion
- not metabolized to Hg++
- BAL gor renal prob
-
alkyl Hg++(CH3)2
- ingestion
- dealkylated to HG++
- in blood- renal prob
- in CNS- neuro (primary)
- BAL to tx renal
- no tx for CNS
-
aryl Hg++
- ingestion
- does not enter CNS as readily as alkyl
- renal prob (primary)
- BAL to tx
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Fluoride
- in tap water, supplements, soil
- max water level= 2ppm
-
fluoride MOA
- affects enamel
- damages ameloblasts, ondontoblasts, and osteoblasts
- faulty calcification
-
-
chronic fluoride tox
- brown mottled teeth
- no cavities
- excess wear and crumbling of teeth
- bones affected
- mature animals- no teeth color change, hyperostosis, economic loss from exostosis
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iron tx sources
- inj (piglets)
- cast iron skillet
- oral prep (vit)
-
iron MOA
- PO- injure GI
- hepatic necrosis
- no means of excretion
-
acute iron tox
- CV collapse
- death in 1-3hr
- anaphylactic syndrome
-
chronic iron tox
hemosiderosis in heart, liver, bone marrow
-
iron tox lesions
- yellow-brown discoloration of tissues
- hepatic necrosis
- renal lesions
- GI ulcers
-
iron tox tx
- MgO
- Deferoxamine- chelating agent
-
cadmium sources
- galvenized metals
- smelters
- NiCad batteries
-
cadmium tox
- stored as metallothionine in kidney
- renal dz like Hg with secondary hypertension
-
acute cadmium tox
- GI irritant
- fume fever when inhaled- pulm edema, resp prob
-
chronic cadmium tox
- renal prob
- stunted growth
- chronic pain- itah, itah
-
cadmium tox tx
- chelating agents may inc tox (Cd-BAL)
- vit D and Ca
- EDTA
-
cobalt tox
- old foaming agent in beer
- bone marrow stimulant
- beer drinkers cardiomyopathy
-
chromium tox
- hexavalent toxic
- chronic ulcers in nasal septum
- ddx: snorting cocaine
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barium tox
- barium carbonate used as rodenticide
- do not confuse with barium sulfate used as radiopaque dye
- stimulates all mm
- tx by giving Na or Mg to form barium sulfate
-
Magnesium tox
- cathartic and equine euth
- acts at NMJ and competes with Ca
- CNS dep
-
iodine general
- used to tx foot rot in cattle
- iodized salt to prevent goiter
- excess may mimic hyperthyroidism
-
iodism
- mimic vit A def
- crusty skin around eyes
- ddx: arsenic
- scruffy hair coat
- bug-eyed (exopthalmus)
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silver general
- disinfectant
- used in babies eyes to tx syphillus
-
silver tox
- gastroenteritis
- chronic- agyria (slate black discoloration of skin)
- not usually a problem
-
selenium general
- deficiency= white mm dz
- only FDA regulated nutrient
- accumulates in plants
-
selenium tox
- >5ppm
- substitute for S in amino acids
- peri acute- CV collapse, GIT
- acute- misformulated feed or eat Se accumulating plant
- chronic- hair loss, liver prob, hoof sloughing
- calves with garlic odor breath
- porcine focal symmetrical poliomyelomalacia- posterior ataxia
- looks like arsenic tox
-
selenium tox tx
arsanilic acid to promote excretion
-
-
sulfate tox
- cause polioencephalomalacia in ruminant
- GI irritation
- sulfate to sulfide gas in rumen, smells like rotten egg
-
zinc general
- industrial pollution
- galvanized material
- relatively nontoxic
- nuts, bolts, pennies
-
zinc tox
- puppies- poor growth, renal prob, bouts of syncope
- horses- arthritis due to cartilage erosion
-
zinc tox tx
- dog- EDTA
- foals- EDTA, Ca, Cu
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