Tox 1a

• the quantity of a toxicant, which under specified conditions, will result in detrimental changes to an organism
• mg/kg, dose
• not equal to 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

a health professional interested in and knowledgable of the properties of toxicants and the tx of dz conditions

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)

the dz state which may result from exposure to a toxicant or poison

• mg of chemical/ kg of body wt
• no equal to ppm

• 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

• quantity of toxicant required to kill 50% of animals
• single oral dose

conc of toxicant in water or feed that will kill 50% animals

• A: single exposure, 7d
• S: daily exposure for 90d
• C: daily exposure >90d

• highly 1mg/kg
• non-toxic 15gm/kg

• 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

• no observed (adverse) effect level in the most sensitive species
• mg/kg/d
• max dose that does not did not produce any adverse effect

• acceptable daily intake
• mg/kg/d
• max amt ingested and not expect adverse effect after lifetime of use
• =NOEL/safety factor

• 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

• similar to tolerance
• a guide line and not legally established

n amendment to the federal food drug and cosmetic act whhich states that a carcinogen may not appear in food for human consumption

• 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

• FDA-CVM term
• definition?

a fixed quantity is excreted during a given time

a constant fraction is excreted per unit time

• clinical signs
• history

• phase I- non synthetic chemical rxns (oxidation, reduction, hydrolysis)
• phase II- synthetic rxns (amino acids, sugars, fatty acids, sulfates, acetates)

• 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

• remove external contaminants
• induce emesis
• gastric lavage
• absorbants
• cathartics

• syrup of ipecac
• table salt
• hydrogen peroxide
• apomorphine

• unconscious or CNS depression
• intox with petroleum
• caustic materials
• >2-4 hr post ingestion

• light anesthesia
• cuffed ET tube
• lower head and thorax
• measure oral-gastric tube nose to xiphoid cartilage
• flush with water and aspirate, repeat

• absorbent
• ex- toxiban, superchar
• then give cathartic

saline, sodium sulfate, Mg sulfate, mineral oil

• high is strong base
• low is strong acid

• used in GIT and kidney
• compounds non-ionized at physiologic pH

• 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

• MOA: bind with active site of enzymes
• bind sulf-hydrial groups
• mealleable when pure

• not malleable when pure
• bind sulf-hydrial groups on enzyme

• arsenite (As+3) more toxic than arsenate (As+5)
• once there, always there

• hematinics
• fowlers solution
• wood preservative
• syphilis and HW tx
• growth promotant
• tx swine dysentery
• fever tick dip

• effect GIT and capillaries
• ex- arsenic trioxide, sodium arsenite/arsenate, chromated copper arsenate, lead arsenate, paris green, smelters

• effect neuro
• ex- MSMA, DMSA

• demyelination
• arsenic should not be found
• no tx

• arsanilic acid
• roxarsone

• arsenamide
• fowlers solution- K arsenite
• sodium cacodylate
• tryparsamide
• melarsoprol
• neoarsphenamine

• 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

• uncouple oxidative phosphorylation
• may interfere with B6 and B1= demyelination

• small amt via skin
• best via GIT
• accumulates in liver
• cros placenta
• stored in bones, skin, hair, hooves

• urine
• feces
• sweat

inorganic As3 (arsenite)> inorganic As5 (arsenate)> trivalent organics (As+3)> pentavalent organics (As+5)

• soil around old dipping vats
• improper disposal of containers
• around smelters
• human carelessness
• feeding gin trash instead of cotton seed hulls
• HUMAN MISTAKES!

• abdominal pain
• staggering gait
• incoordination
• diarrhea
• sudden death

• depression
• anorexia
• convulsions
• fluid, dark feces
• hematuria

• easily fatigued
• intense thirst
• dry hair coat
• brick red MM
• looks like vit A def

• neuro
• blind
• erythema
• BAL will not help

• soft, yellow liver
• hemorrhagic gastroenteritis
• rumen mucosal necrosis
• intestinal ulcers

• downer pig
• demyelination of optic nerve

• early- emetics, gastric lavage, milk, cathartic, Na thiosulfate
• late- BAL (will reverse lipoic acid inhibition)
• no tx for phenyllarsenic

• hot acid interacts with metal
• most toxic arsenical
• causes hemolysis
• abnormal ECG and pulm edema
• BAL is tx if chronic

• old paint
• glazed pottery
• lined feed troughs, buckets, pipes
• batteries
• smelters
• vegetation sprayed with lead arsenate
• white lotion
• leaded gas on forages
• lead shot

GI or resp

• bound to RBC
• soft tissue
• bone, teeth, hair

• urine- adults
• feces- infants, animals
• milk

• nervous
• GI
• blood and bone marrow
• renal

• inhibits -SH groups on enzymes
• interfere with hemoglobin synthesis

• death
• GI signs
• CNS

• roaring in equine
• lead line in gums
• lead lines in metaphysis of long bones of immature dog
• inhibit hematopoiesis

• agonal hemorrhages
• pale muscles
• hemorrhagic thymus

• renal cortex
• blood- high in acute and chronic
• liver
• feces - high if 2 to 4 wk, normal if more than 4 wks

• CaNa EDTA
• thiamine (combo with EDTA to reduce neuro)
• BAL+EDTA if severe neuro
• succimer
• must tx for 3-5 days

• 6:1
• if adequate SO4 then will excrete opposite

• mostly sheep
• 10:1
• never feed cattle feed to sheep bc high in Cu
• chronic accumulation in liver- hepatic necrosis, hemolysis

• 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

• icterus
• gun metal kidney
• yellow friable liver
• blackberry jam spleen
• hemoglobinuria

penicillamine

• interactions not as marked
• dec Cu tx with Zn
• no hemolysis with Cu tox
• achromotrichia, aortic rupture with Mo tox

• ingestion
• nontoxic

• inhalation
• oxidized to Hg++
• in blood- renal prob
• in CNS- neuro (primary)
• BAL to tx renal
• no tx for CNS

• ingestion
• charged so does not cross BBB
• GI, renal (primary)
• CNS
• tx with BAL
• most toxic

• ingestion
• not metabolized to Hg++
• BAL gor renal prob

• ingestion
• dealkylated to HG++
• in blood- renal prob
• in CNS- neuro (primary)
• BAL to tx renal
• no tx for CNS

• ingestion
• does not enter CNS as readily as alkyl
• renal prob (primary)
• BAL to tx

• in tap water, supplements, soil
• max water level= 2ppm

• affects enamel
• damages ameloblasts, ondontoblasts, and osteoblasts
• faulty calcification

• GI irritation
• neuro

• brown mottled teeth
• no cavities
• excess wear and crumbling of teeth
• bones affected
• mature animals- no teeth color change, hyperostosis, economic loss from exostosis

Al salts

• inj (piglets)
• cast iron skillet
• oral prep (vit)

• PO- injure GI
• hepatic necrosis
• no means of excretion

• CV collapse
• death in 1-3hr
• anaphylactic syndrome

hemosiderosis in heart, liver, bone marrow

• yellow-brown discoloration of tissues
• hepatic necrosis
• renal lesions
• GI ulcers

• MgO
• Deferoxamine- chelating agent

• galvenized metals
• smelters
• NiCad batteries

• stored as metallothionine in kidney
• renal dz like Hg with secondary hypertension

• GI irritant
• fume fever when inhaled- pulm edema, resp prob

• renal prob
• stunted growth
• chronic pain- itah, itah

• chelating agents may inc tox (Cd-BAL)
• vit D and Ca
• EDTA

• old foaming agent in beer
• bone marrow stimulant
• beer drinkers cardiomyopathy

• hexavalent toxic
• chronic ulcers in nasal septum
• ddx: snorting cocaine

• 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

• cathartic and equine euth
• acts at NMJ and competes with Ca
• CNS dep

• used to tx foot rot in cattle
• iodized salt to prevent goiter
• excess may mimic hyperthyroidism

• mimic vit A def
• crusty skin around eyes
• ddx: arsenic
• scruffy hair coat
• bug-eyed (exopthalmus)

• disinfectant
• used in babies eyes to tx syphillus

• gastroenteritis
• chronic- agyria (slate black discoloration of skin)
• not usually a problem

• deficiency= white mm dz
• only FDA regulated nutrient
• accumulates in plants

• >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

arsanilic acid to promote excretion

• purgative
• >2500 ppm tox

• cause polioencephalomalacia in ruminant
• GI irritation
• sulfate to sulfide gas in rumen, smells like rotten egg

• industrial pollution
• galvanized material
• relatively nontoxic
• nuts, bolts, pennies

• puppies- poor growth, renal prob, bouts of syncope
• horses- arthritis due to cartilage erosion

• dog- EDTA
• foals- EDTA, Ca, Cu