Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
199 Cards in this Set
- Front
- Back
|
Toxicology
|
The study or knowledge of toxicants including their chemical and physical properties, indentification, biologic effects and treatment of the disease conditions produced by them.
|
|
|
Toxicant (poison)
|
any solid, liquid gas or energy which when introduced into a biologic system or applied to it, can interefere with the life processes of the organisms or its subparts without actin mechanically and irrespective of temperature. includes bacterial toxins, particulate and non -particulate radiation
|
|
|
Hazard
|
The likelihood or chance that a toxicant will produce a disease state under the conditions of use, or the likelihood or chance of exposure to a particular toxicant under the conditions of use.
|
|
|
Toxicosis
|
Disease state which may result from exposure to a toxicant or poison
|
|
|
Roles of a toxicologist
|
Defines the limits of safety of chemical agents
Demostration of safety or hazard of chemicals prior to their entry on the market |
|
|
Branches of Toxicology
|
Environmental
Economic Forensic |
|
|
Economic branch of toxicology
|
develpment of drugs, food/feed additives and pesticides as well as the study of toxicants on economic and non-economic species
|
|
|
Evironmental branch of toxicology
|
Pollution, Residues, Industrial
|
|
|
LD50
|
Dose of toxicant required to kill 50 % of a group of animals.
|
|
|
LC 50
|
Concentration of a toxicant in water or feed that will be lethal to 50% of the animals ingesting the material or living in the material
|
|
|
Units of toxicology dose
|
mg/kg
|
|
|
PPM units
|
Parts per Million - concentration
|
|
|
1 PPM =
|
.0001%
|
|
|
1 % = ? PPM
|
10,000 PPM
|
|
|
Exposure is always expressed as
|
mg/kg or mg/lb.
|
|
|
What information can be obtained from a LD50?
|
Comparative toxicity date
Descriptive information about the acute toxicosis caused by the toxicant Information on how to treat the toxicosis |
|
|
margin of safety equals
|
LD50/ED 50
|
|
|
To be a drug or chemical hypersensitivity reaction the reaction must be
|
truly an antigen- antibody reaction
|
|
|
NOEL
|
no observed adverse effect - mg/kg/day
|
|
|
ADI
|
acceptable daily intake - mg/kg/day
|
|
|
Tolerance
|
quantity of a chemical or drug which is the maximum level which can legally appear in food for human consumption or in animal feeds. Et by regulatory agencies
|
|
|
Action level
|
similar to a tolerance, except it is a guide-line and not legally established.
|
|
|
Delaney Clause
|
amendment to the Food Drug and Cosmetic act which states that a carcinogen may not appear in food for human consumption
|
|
|
Safety factor if good human data exists
|
10
|
|
|
Safety factor if good animal data exists
|
100
|
|
|
Zero order kinetics in toxicokinetics
|
a fixed quantity is excreted - 10 mg/kg/day
|
|
|
Frist order Kinetics in toxicokinetics
|
a constant fraction is excreted per unit time - most commone
|
|
|
Phase 1 Active biotransformations of toxicants
|
Inactive compound to active compound
Active compound to more active compound Active compound to inactive compound |
|
|
Phase 1 Chemical reactions
|
oxidation
Reduction Hydrolysis |
|
|
Phase 2 biosynthetic or conjugation reactions
|
amino acids
sugars - glucuronic acid - cats cant fatty acids sulfates acetates |
|
|
Phase II lethal synthesis
|
sodium fluoroacetate
Warfarin Antimetabolite compounds - 5 FU, methotrexate |
|
|
Goals of treatment of toxic injestion
|
delay absorption
induce excretion |
|
|
Induce emesis with
|
Syrup of Ipecac
Hydrogen peroxide Apomorphine Table salt - dangerous Copper sulfate - dangerous |
|
|
syrup of ipecac protocol
|
1 - 2 ml/kg
50 % effective not with activated charcol |
|
|
Apomorphine protocol
|
.04 mg/kg IV
.08 mg/kg IM |
|
|
Apomorphine contraindications
|
respiration depression
CNS depression |
|
|
Contraindications for induction of emesis
|
unconsciousness or CNS depression
Intoxication of Petroleum distillates - pneumonia aspirate > 2 - 4 hrs since ingestion Ingestion of acids or alkalis - weakens stomach wall and may rupture with wretching |
|
|
Adsorbents
|
activated charcoal from vegetable or petroleum origin
activated by increasing surface area and heating |
|
|
Intravenous lipid emulsion therapy can be used with toxicosis from
|
local anesthetics - bupivacaine, lidocaine
Clomipramine, tricyclic antidepressants Propranolog Buproprion Muscle relaxants Macrocyclic lactones |
|
|
Urinary acidifying agents
|
ammonium chloride
Ethylenediamine dihydrochloride Physiological saline |
|
|
Urinary alkalinizing agents
|
sodium bicarbonate
|
|
|
chelating agent
|
When tow or more ligands in a molecule simultaneously or nearly simultaneiously form bonds with a metal or metalloid, the donor molecule i
|
|
|
Factors influencing chelate behavior
|
nature of donor groups
size of ring - 5 or 6 member number of chelate rings formed molecular configuration |
|
|
Lead is held more strongly by
|
brain and nervous tissue
|
|
|
Hg and Cd is held more strongly by the
|
kidney
|
|
|
3 destinations of chelating agents
|
rapidly excreted
rapidly biotransformed rapidly distributed throughout the ECF |
|
|
Therapeutic role of chelating agents
|
seek out, bind toxic metals to allow for excretion,
deliver essential trace metals to tissues inactivate bacteria and viruses by sequestering esesntial metals |
|
|
What chelating agents are used in lead poisoing
|
Calcium disoldium EDTA
Ca Na2 EDTA + BAL (CNS) Penicillamine, Succimer |
|
|
Chelating agents used in iron poisoning
|
Deferoxamine
|
|
|
BAL side effects
|
Neuro convulsions
|
|
|
BAL is an antidote for
|
Arsenic, antimony bismuth, cadmium, mercury, zinc, gold and lead (but not alone with lead)
|
|
|
BAL binds metals by
|
displacing the metal from the sulfhydryl group of enzymes
|
|
|
BAL is not ____ so it must be administered _____
|
absorbed through the GI tract
must be given IM. |
|
|
Arsenic is a
|
metalloid - it is not maleable in pure form
|
|
|
Arsenics have been used as
|
insecticides, medicinals, wood preservatives and hematinics.
|
|
|
What are the 2 main types of arsenicals
|
trivalent
pentavalent |
|
|
Trivalent arsenicals cause
|
syndrome of GI tract and capillaries
|
|
|
Pentavalent arsenicals cause
|
neurological syndorme
|
|
|
In Texas ________ is the second leading cause of intoxication
|
arsenic
|
|
|
More toxic arsenic
|
+3 arsenite
|
|
|
+5 arsenic
|
less toxic
Arsenate |
|
|
Arsenics are
|
persistent
Once there always there |
|
|
Hemotinic
|
stimulate erythropoeisis
|
|
|
Fowler's solution
|
Potassium aresenite - tonic, conditioner
|
|
|
Sodium caparsolate
|
old treatment for heartworms - arsenamide
|
|
|
Immiticide
|
melarsomine dihydrochloride
|
|
|
Arsenic feed additives
|
Arsanilic Acid and Roxarsone
pentavalent increased feed efficiency, swine dysentery |
|
|
Other sources of arsenic
|
paints
smelters - Arsenic trioxide Lewisite gas - war gas |
|
|
Arsenate method of action
|
uncouple axidative phosphorylation
|
|
|
Arsenite metod of action
|
reacts wtih sylfhydryl groups of proteins and inhibits enzymes
inhibits lipoic acid - an essential coenzyme for both pyruvic acid oxidase and oxyglutaric acid oxidase - BAL will reverse this action |
|
|
BAL will reverse what arsenic action
|
inhibition of lipoic acid
|
|
|
Arsenic induces what vascular effects
|
vasodialtion and capillary damage
|
|
|
Low doses of arsenic can produce
|
tolerance to arsenicals
|
|
|
Absorption of arsenic can occur through
|
intact skin
petavalent absorbed better then trivalents |
|
|
Chronic doses of arsenic are stored in
|
bones, skin, and keratinized tissues - hair
|
|
|
Trivalent arsenicals are excreted via
|
the feces
|
|
|
Pentavalent arsenicals are excreted via the
|
urine.
|
|
|
Sources of arsenic poisoning
|
contamination by smelters
feeding gin trash instead of cottonseed hulls Contamination of herbage from spraying cotton with improper concentrations |
|
|
Clinical signs of peracute arsenic poisoning
|
abdominal pain, staggering, collapse, death - may die before getting lesions - hyperemia of abomassum
|
|
|
Clinical signs of acute arsenic poisoning
|
Salivation, thirst, grinding of teeth, vomiting, moaning, weakness, muscular incoordiation, trembling, abdominal pain, thready pulse, diarrhea, rear limb paralysis, hematuria, prostration, death, skin lesions
|
|
|
Clinical signs of subacute arsenic poisoning
|
depressed, anorexic, difficult movement, convulsions, dark feces with mucous and blood, hematuria
|
|
|
Clinical signs of chronic arsenic poisoning
|
Easily fatigued, violent breathing, thirst, unthrifty, dry rough hair coat, brick read coloration, to mucous membranes, Joints may be enlarged
|
|
|
Clinical signs of phenylarsonic intoxication
|
3 days after high exposure of chornic exp.
Neurological involvement - incoordinations, BAR, will eat may be blind, and signs reversible |
|
|
Lesions of typical arsenic poisoning
|
depends on dose
GI irritation - hemorrhage, hyperemia of abomasum Capillary damage Soft yellow liver |
|
|
Phenylsarsonic poisoning
|
"Downer" pig - with severe abrasion with muscle atrophy
microscopic lesions in the nerves |
|
|
Early carnivore treatment of Arsenic poisoning.
|
emetics, gastric lavage, milk, egg white, sodium thiosulfate
|
|
|
Early herbivore treatment of arsenic poisoning
|
Large oral dose of saline purgative, demulcents, sodium thiosulfate
|
|
|
Late treatment of of arsenic poisoning
|
Demercaprol ( BAL )
sodium thiosulfate Supportive measures |
|
|
Phenylarsonic compound treatment
|
NO effective treatment
|
|
|
Arsenic poisoning diagnosis
|
History, signs, and lesions
Kidney, liver, urine, feces |
|
|
Is arsenic found in phenylarsonic intoxications
|
NO
|
|
|
ARsenic is stored where
|
hair, fingernails, hooves,
|
|
|
Arsine is ________ toxic arsenical and is of what form?
|
Toxic
Gas |
|
|
Arsine sources
|
industry from refining of tin, lead and zinc
|
|
|
Arsine intoxication clinical signs
|
GI
intravascular hemoysis pulmonary edema, cyanosis ECg abnormalities Hemoglobinuria Liver dysfunction Delirium, coma, deah |
|
|
Arsine treatment
|
None
|
|
|
What are the qualitative tests for arsenic?
|
Reinsch Test
Gutzeit test |
|
|
Reinsch equation
|
6Cu + 2 AsCl3 = 3 CuCl2 + Cu3 As2 (gray)
|
|
|
During the Reinsch test the copper can be coated with what metals
|
mercury, antimony, silver, bismuth and organic sulfur.
|
|
|
The Gutzeit test mechanism
|
arsine gas reacts with silver nitrate forming a yellow powder which then turns black
|
|
|
To determine the quantitative amount off arsenic use
|
atomic absorption spectroscopy.
|
|
|
Lead is usually absorbed via
|
GI - primarily - young >> adults
Respiratory - minor Skin - insignificant |
|
|
Lead distribution
|
Bound to RBC;s
deposited in soft tissues renal cortex >> than medulla Liver redistributed to bone, teeth and hair |
|
|
With lead poisoning you can see ___
|
Lead line on bone
|
|
|
Inorganic lead biotransformation
|
Is not biotransformed
|
|
|
Lead excretion
|
76% via urine - adults
Feces - infants, |
|
|
Lead clearance can take a
|
long time
|
|
|
Lead intoxication clinical signs
|
GI, Neuro, erythrocytic, and renal
|
|
|
Lead intoxication progression in calves
|
Neuro first, then GI, then Hb production, they hypochromic anemia
|
|
|
Lead pathogenesis
|
interferes with SH groups on enzymes.
|
|
|
Lead acute poisoning lesions
|
GI - hemorrhage
Liver - pale - lobular degeneration, putty like consistency Kidney - congested wtih areas of hemorrhage Heart - petechiation ecchymoisis Lungs - diffuesely congested |
|
|
Lead chronic poisoning lesions
|
Anemia
Basophilic stippling Lead line on gigival larygneal paralysis in horses |
|
|
Lead diagnosis
|
Metaphysis of long bones develop lead line on rads
|
|
|
Lead hemogram
|
neutrophilic leucocytosis with left shift
PVC normal Nucleated RBC |
|
|
Lead detection
|
Blood - EDTA or heparinized
Feces - Liver Kidney |
|
|
Lead poisoning treatment
|
GI - saline purgatives, emetics, gastric lavage
Antidote - CaNa2EDTA BAL Succimer Thyiamine - adjunct therapy - doesn't chelate |
|
|
Copper - Molybdenum relationship
|
Toxicity of one means deficiency of the other.
|
|
|
Copper toxicoses occurs primarily in
|
sheep
|
|
|
Molybdenum toxicoses occurs primarily in _____ but also causes ____
|
cattle
Swayback in young lambs production loss in adult sheep. |
|
|
Molybdenum toxicoses pathogenesis in young
|
Myelin doesn't form
|
|
|
Ideal ration of Cu : Mo
|
6: 1 in the diet.
2: 1 causes molybdenosis 10:1 causes copper toxicity |
|
|
Copper toxicoses acute signs
|
typical heavy metal signs along with intravascular hemolysis
|
|
|
Chronic copper accumulation occurs in what organ
|
liver
|
|
|
Stress can cause the ___ to release copper and cause copper to accumulate in the _______
|
liver
kidney/urine |
|
|
Common sign of chronic accumulation with stress relief
|
hemolytic crisis leading to anemia and jaundice
|
|
|
Course of Cu toxicity lasts
|
24 - 48 hours
|
|
|
Cu toxicity lesions
|
gun metal colored kidneys, yellow friable liver, black berry jam spleen
|
|
|
Copper toxicity treatment
|
Blood transfusion
Penicillamine S- Adenyosyl methionine Molybdenized licks Zinc |
|
|
Molybdenum toxicoses signs
|
poor doer
chronic diarrhea, hypoproteinemic achromotrichia - hair color change wool problems, |
|
|
Molybdenum toxicoses treatment
|
Copper glycinate
change diet |
|
|
Copper toxicoses in non-ruminants
|
No hemolytic crisis
Jaundice may be present in pigs Liver and kidney degeneration Treat with Penicilliamine |
|
|
Molybdenum toxicosis in non-ruminants
|
anemia
bone deformation/decalcification Cerebral edema and necrosis Achromotrichia fetal resorption aortic rupture reduced ceruloplastin |
|
|
Elemental mercury toxic forms
|
Mercury solid/liquid is almost non-toxic, Vapors are very toxic.
|
|
|
Mercury distribution
|
Brain levels are higher than after ingestion
Accumulates in kidneys |
|
|
Alkyl Muercury characteristics
|
Highly lipid soluble
Dealkylated and converted to Hg +2 Molecules of alkyl mercury in the CNS are dealkylated and cannot escape the brain. |
|
|
Elemental solid/liquid Hg0 pathogenesis
|
Oral exposure, not readily absorbed
|
|
|
Elemental Vapor Hg0 pathogenesis
|
inhalation, lipid soluble - Hg++ in blood harms renal, some crosses BBB before oxidation - CNS Neuronyl degeneration - mucous membranes
|
|
|
Mercuric Hg++ pathogenesis
|
Ingestion, GI irritation, renal toxicity, minimal CNS
Hg0 = Hg++ in body |
|
|
Alkyl Hg ++ pathogenesis
|
ingestion, lipid soluble
dealkylated in blood = renal otxicity in CNS - neuro disease |
|
|
Aryl Hg++
|
ingestion lipid soluble but dearylated and does not enter CNS as readily as alkyl form - primary renal disease
|
|
|
Elemental solid liquid Hg diseses/organ affected
|
no toxicological consequence
|
|
|
Elemental Vapor Hg0 diseases/organ affected
|
Some renal but primarily CNS
|
|
|
Mercuric Hg++ diseases/organs affected
|
GI, renal minimal CNS
|
|
|
Mercurous HG + disease/organs affected
|
mild GI irritation, minimal renal toxicity
|
|
|
Alkyl Hg++ disease/organs affected
|
CNS some renal
|
|
|
Aryl Hg++ disease/organs affected
|
GI irritation, Renal disease
|
|
|
Treatment for elemental solid/liquid mercury
|
none
|
|
|
Treatment for Elemental Vapor Hg0
|
BAL for renal, nothing for CNS
|
|
|
Treatment for Elemental Mercuric Hg++
|
BAL
|
|
|
Treatment for Mercurous Hg+
|
BAL if necessary
|
|
|
Alkyl Hg++ treatment
|
BAL for renal, nothing for CNS
|
|
|
Aryl Hg++ treatment
|
BAL
|
|
|
Mercury is mostly excreted via
|
urine, with saliva, feces and hair of less importance.
|
|
|
Mercury toxicity normally harms
|
the kidneys
|
|
|
Mercury toxicosis clinical signs - acute
|
violent gastoreneteritis, bloody diarrhea,
Arrhythmias and fibrillation |
|
|
Clinical signs of chronic mercury exposure
|
hemorrhage, renal, GI effects
|
|
|
Mercury vapors exposure clinical signs
|
psychic and emotional distrubances, motor disturbances, GI renal lungs
|
|
|
Mercury intoxication diagnosis
|
confirmation of chemical in tissues
|
|
|
Mercury intoxication treatment
|
Give protein such as egg white or milk and empty stomach
BAL - but will not reverse any neuronal damage |
|
|
Fluoride sources
|
forages from industrial contamination
feed and mineral supplements vegetation on high fluoride soils |
|
|
Fluoride toxicity MOA
|
ameloblastic and odontoblastic damage
faulty calcification of teeth Osteoblastic damage dental and bone lesions |
|
|
Fluoride toxicosis may resemble
|
chronic debilitating disease
|
|
|
Tissue affected by fluoride
|
bone and teeth
|
|
|
First sign of bone lesion due to fluoride toxicosis
|
bilateral, medial surfaces of proximal 1/3 of metatarsals
|
|
|
Fluoride toxicosis joint problems
|
pain where bone encroaches on the joint, but the joint is not affected.
|
|
|
Production loses of fluoride toxicosis due to
|
pain, animals don't move to eat and drink
|
|
|
Iron toxicosis ultimate cause
|
no excretion means in the body
|
|
|
High iron doses cause
|
damage to GI wall,
cardiovascular collapse, capillary permeability, decreased plasma volume, inactivation of oxidative enzymes, eatbolic acidosis |
|
|
Iron clinical signs acute
|
shock, CV collapse, vomiting, edema at site of injection,
|
|
|
Cadmium uses/sources
|
byproduct of Cu, Pb and Zn - used for rust-proofing, niCad batteries, galvanized troughs
|
|
|
Cadmium is stored in the body as
|
metallothionin
|
|
|
Cd methallothionine is
|
nephrotixic - activates renin system causing hypertension
|
|
|
Cd toxicity clinical signs
|
hyperchromic anemia
bone marrow hyperplasia stunted growth cardiac hypertrophy pulmanry fibrosis |
|
|
Cd toxicity treatment
|
chelating agents increase tissue damage - expecially BAL-Cd increases renal damage
Vitamin D and Ca EDTA |
|
|
Cobalt toxicosis characteristics
|
Cobalt is an essential element
Used as beer foaming agent Causes beer drinkers cardiomyopathy |
|
|
Chromium toxicosis
|
TRivalents - essential nutrient
hexavalent is toxic - nephritis, pulmonary congestion, dermatitis Lung cancer, chronic ulcers in nasal setpum, chronic enteropathy |
|
|
Barium toxicosis
|
Barium carbonate used as rodenticide
stimulates all muscle |
|
|
magnesium toxicosis signs
|
purgation
CNS depression Curare like action on myoneural junction - death from respiratory depression |
|
|
Mg toxicosis treatment
|
Ca++
|
|
|
Iodine toxicosis clinical signs
|
increased secretions of respiratory tract
exopthalmus intermittent non-productive cough sloughing of superficial epidermis |
|
|
Iodine toxicosis resembles
|
Vitamin A deficiency in mammals
|
|
|
Iodine lesions
|
scattered areas of scaly skin
seromucous accumulation in the upper respiratory tract |
|
|
Silver toxicosis antidote
|
NaCl - forms AgCl which is insoluble
|
|
|
Chronic silver toxicosis can cause
|
slate-black discoloration of the skin due to deposition of silver - Blue man
|
|
|
Selenium normally functions as
|
component of glutathione peroxidase prevent damage to cell membranes
|
|
|
Selenium toxicosis clinical signs - acute
|
swine - emesis, diarrhea, weakness, fever, colic, depression,
|
|
|
Selenium toxicosis chronic clinical signs
|
blind staggers and alkali disease
hair loss, deformation and sloughing of hooves in cattle, sheep and horses |
|
|
Selenium toxicosis treatment
|
arsanilic acid
|
|
|
Sulfur toxic forms
|
elemental - non toxic
H2S - as toxic as cyanide |
|
|
Common source of H2S gas
|
anaerobic bacterial decomposition in sewage - animal production plants
|
|
|
Sulfates may cause ____ in cattle
|
polioencephalomalacia
|
|
|
H2S causes what lesions
|
cyanosis, pulmonary edema, congestion, and emphysems
|
|
|
Sulfites
|
generally non-toxic
cause some human hypersensitivity reactions |
|
|
Zinc toxicosis sources
|
nuts, bolts, pennies,
|
|
|
Zinc toxicosis clinical signs
|
Acute signs - emesis, decreased feed consumption, pica, reduced growth, Heinze body, hemolytic anema, poor bone merialization, damage to pancreas
|
|
|
Young puppies with zinc toxicosis symptoms
|
vomiting, icterus from hemolytic anemia, renal tubular necrosis,
|
|
|
Adult dogs with zinc toxicosis clinical signs
|
periodic bouts of syncope
|
|
|
Chornic Zn poisoning lesions
|
growth plates
epiphysis becomes enlarged stiff gait |
|
|
Zinc poisoning treatment
|
EDTA
blood transfusions reduce zinc in diet and increase Cu |
