Exam 3: Lecture 11, Toxicity of Specific Chemicals Flashcards
5 Major substances of air pollution?
Co = 52% Sulfur Oxides = 14% Hydrocarbons = 14% Nitrogen Oxides = 14% Particulate matter = 4%
air pollution implicated as contributing factor for….
Bronchitis Obstructive Ventilatory disease Pulmonary emphysema Bronchial Asthma Lung Cancer
Carbon monoxide info
combines reversibly with oxygen binding sites of hemoglobin and has affinity for hemoglobin that is 220 times that of 02
brain and heart most effected
Sulfur Dioxide info
approx 90% inhaled is absorbed in upper respiratory tract = site of principle effect
Carbon tetrachloride and trichloroethylene have….
largely bene removed from workplace due to carcinogenic potential
Tetrachloroethylene and trichloroethane are…
still used for dry cleaning and solvent degreasing, but likely limited use in future
Fluorinated Aliphatics
use limited by agreements due to severe environmental damage
Halogenated aliphatic solvents can cause….
depressant of CNS (chloroform = most potent)
Impaired memory and peripheral neuropathy
Hepatotoxicity in humans after acute/chronic exposure (Carbon tetrachloride most potent)
Nephrotoxicity in humans
Benzene info
important composent of gasoline
Acute toxic event = CNS depression
Fatal dose: 7500ppm/30 min
chronic exposure = toxic, bone marrow injury, associated leukemia
most organizations classify as known human carcinogen
toluene
CNS depressant, skin/eye irritant
exposure to 800ppm can lead to severe fatigue
doesn’t possess myelotoxic properties of benzene/associated with leukemia
Xylene
CNS depressant and skin irritant
doesn’t possess myelotoxic properties of benzene/associated with leukemia
Organochlorine Pesticides major effect is…
impact on CNS stimulation
interfere with inactivation of Na channel in excitable membranes, inhibit Ca ion transport
affect depolarization and enhance excitability
DDT manifestations
tremor 1st, possibly convulsions
no Treatment
Organophosphorus Pesticides
Major effect is inhibition of acetylcholinesterase
absorbed by skin, respiratory and GI tract
causes altered neurologic and cognitive functions,
Carbamate Pesticides
inhibit acetylcholinesterase
clinical effects are shorter duration than those observed with organophosphorus compound
Chlorophenoxy Herbicides
2,4-D ad 2,4,5-T
Toxicity rating of 4/3
can cause coma and generalized muscle hypotonia
Most important Chlorophenoxy Herbicide
Dioxin
Likely human carcinogen
Glyphosate Herbicide
most injuries minor, some can be lethal
eye/skin irritant
less potent than bipyridyl herbicides
Bipyridyl herbicides
Paraquat is most important
Toxicity rating of 4 (50-500mg/kg)
Lethal intoxication been reported
paraquat accumulates in lungs, causes lung edema, alveolitis and progressive fibrosis
Polychlorinated biphenyls
most important is TCDD
food major source of contamination
Endocrine Disruptors
DDT and PCBs
concerns: increasing contamination of enviornment, appearance of bioaccumulation and potential for toxicity
Asbestos
widely used in industry for over 100 yrs
all forms shown to cause progressive lung disease
Toxic heavy metals interfere with…
function of essential cations
cause enzyme inhibition, oxidative stress and alter gene expression
Soluble arsenic compounds well absorbed through
respiratory and GI tract
Most absorbed form of arsenic is…
inorganic
Trivalent vs pentavalent arsenic?
trivalent = 2-10 times more toxic
Actue inorganic arsenic poisoning
can be confirmed by demonstration of elevated amounts of inorganic arsenic/its metabolites in urine
arsenic disappears rapidly from blood, except in anuric patients, blood arsenic levels should not be used as diagnostic
Acute arsenic treatment
unithiol, 3-5 mg/kg IV every 4-6hrs
or
dimercaprol, 3-5 mg/kg IM every 4-6hr
Arsine gas poisoning
currently available chelating agents haven’t shown clinical value
after latent period 2/24 hr, massive IV hemolysis may occur
Adult % lead absorbed?
10-15%
Children % lead absorbed?
up to 50%
Lead Half-life in blood/soft tissues
1-2 months
Lead Half-life in skeleton
years to decades
systems lead can effect
Nervous
Reproductive
GI
Cardiovascular
Acute inorganic lead poisoning
uncommon today
Chronic inorganic lead poisoning
diagnosis of lead intoxication is best confirmed by measuring lead in whole blood
pt presents with multi systemic findings, difficulty concentrating, irritability, depressed mood
treatment of Lead poisoning
IV EDTA admin 30-50 mg/kg/d continuous infusion up to 5 day
organolead poisoning
very rare
initial treatment = decontaminating, treat seizures and chelation if high blood/lead conc
primary source of occupational exposure mercury?
inhaled
Mercury distribution
excreted through urine and feces
highest conc in kidney
most excreted within weeks/months but fraction retained in kidney/brain for years
blood and whole body half-life of mercury is…
50 days
Acute mercury poisoning
potentially life threatening
chronic mercury poisoning
symptoms; change in mood, withdrawal, depression, explosive anger or blushing
Dimethylmercury is
rarely encountered by extremely neurotoxic form of organomercury that maybe lethal in small quantities
Acute exposure treatment mercury
prompt chelation with oral and IV unithiol, IM dimercaprol, or oral succimer
Chronic Exposure treatment mercury
Dimercaprol not recommended, distributes metal to CNS
Unithiol and Succimer for chronic exposure
Chelators
contain one of more coordinating atom, usually Oxygen/sulfer/nitrogen
used to prevent or reverse toxic effects of heavy metals
Dimercaprol
known as British Anti-lewisite (BAL) has to be given in peanut oil
water soluble analogs (unithiol and succimer) have higher therapeutics
Unithiol given…
IV
Succimer is given..
Oraly
to Prevent potentially life-threatening Ca depletion, Eda should be admin as
calcium disodium salt
Chelator of choice for iron poisoning?
Deferoxamine
Prussian Blue
approved for treatment of contamination with radioactive cesium and intoxication with thallium salts
