NON-METALLIC ENVIRONMENTAL TOXICANTS
SIDNEY GREEN Ph.D
DEPARTMENT OF PHARMACOLOGY
ABSORPTION AND DEPOSITION IN THE LUNGS
Size of particle >5µm 1-5µm <1µm
site upper airways terminal airways or alveoli suspended in inhaled air
REMOVAL OF PARTICLES
SITE
HOW REMOVED
Unciliated anterior portion of nose posterior portion of nose
wiping, blowing, sneezing
insoluble; pharynx and swallowed soluble; pharynx or absorbed cleared by upward movement of mucus by cilia
Tracheobronchial tree
alveolus
-mucociliary escalator -phagocytosis -absorbed into lymphatic system
CHEMICAL CONSTITUTION OF AIR POLLUTION
Carbon monoxide Sulfur oxides Hydrocarbons Particulate matter
52% 18% 12% 10%
Nitrogen oxides
6%
TYPES OF POLLUTANTS
Reducing type; sulfur dioxide and smoke and by fog and cool temperatures Oxidizing or photochemical type; hydrocarbons, oxides of nitrogen and photochemical oxidants
MAJOR SOURCES OF POLLUTANTS
5 sources account for 90%
Automobiles Industry Electric power generation Space heating Refuse disposal
HEALTH EFFECTS
Reducing type; acute effects Oxidizing or photochemical type; allergic disorders, inflammatory eye disease, acute upper respiratory infections, influenza and bronchitis
TOXICOLOGY OF AIR POLLUTANTS
Sulfur dioxide acute toxicity low; slight bronchial constriction chronic (10 ppm for 1-2 months) -thickening of mucus layer of trachea -bronchial constriction -asthmatics more sensitive
TOXICOLOGY OF AIR POLLUTANTS CONT’D
Sulfuric acid sulfur dioxide produces sulfuric acid increases airway resistance asthmatics more sensitive
Nitrogen dioxide lung irritant -pulmonary edema -farmers at risk -LC50 for 4 hour=90ppm -2-3 ppm can damage pulmonary function; lower concentrations may affect asthmatics
OZONE
Oxidant found at highest concentration in atmosphere Irritant; death from pulmonary edema Nitrogen dioxide yields ozone Mice; 2ppm- gross pulmonary edema Chronic exposure to 1ppm causes; chronic bronchitis, fibrosis and emphysematous changes 0.25- 0.75ppm causes shallow rapid breathing, decrease in pulmonary compliance Sensitivity of lungs to histamine, ACh and allergens Concentration in urban air similar to that causing decline in respiratory function Free radical intermediates responsible
CARBON MONOXIDE
Colorless,odorless, tasteless and nonirritating Most abundant pollutant in lower atmosphere Average concentration is 0.1 ppm Natural sources account for 90% -atmospheric oxidation of methane -forest fires -terpene oxidation -ocean (microorganisms) Other source is smoking -carboxyhemoglobin levels reach 5.9% (heavy smokers)
CARBON MONIXIDE CONT’D
Automobile greatest source of man-made CO Natural means of removing CO -sinks are: reaction of CO with hydroxyl radicals to form CO2 -upper atmosphere -soil
TOXICITY OF CO
Due to combination with hemoglobin yielding COHb COHb cannot carry oxygen (first problem) Affinity of Hb for CO is 220 x affinity for O2 Ability of unaltered oxyHb to release O2 decreases (second problem) Also due to direct toxic effect by binding to cellular cytochromes of respiratory enzymes and myoglobin Anemic persons more susceptible and those with high metabolic rate
PATHOLOGY OF ACUTE CO POISONING
Primarily hemorrhagic; subendocardial infarctions, and in brain, cerebral edema Posthypoxic unconsciousness>21 hrs and <48 years old, no complete neurological recovery Posthypoxic unconsciousness >11 hours, and >48 years old, complete neurological recovery Skin lesions
DIAGNOSIS OF ACUTE CO POISONING
Carboxyhemoglobin is cherry-red and gives a red color to skin, mucus membrane and finger nails In living patient, cherry-red cyanosis is not seen; usually cyanotic and pale Final diagnosis is concentration of carboxyhemoglobin if blood
TREATMENT OF ACUTE CO POISONING
Fresh air Artificial respiration Rapid administration of 100 % oxygen Recovery determined by return of neurological function
TOXICITY OF PROLONGED AND LOW LEVEL EXPOSURE OF CO
Cardiovascular system; heart Atherosclerosis Behavior; vigilance tests Teratogenicity; neurological and gross brain damage
polycythemia
ORGANOCHORINE INSECTICIDES
DDT -readily absorbed when dissolved I oils, fats,etc. -concentrates in adipose tissue -crosses placenta -bioaccumulates up food chain -signs and symptoms of poisoning -paresthesias of tongue,lips and face -apprehension, hyper susceptibility to stimuli, irritability, tremors, tonic and clonic convulsion -stimulates MFOs -weak evidence of carcinogenicity
CHLORDECONE (KEPONE)
Extremely persistent, concentrated in food chain Stimulates CNS, causes hepatic injury and stimulates MFOs Causes testicular atrophy and decreased sperm count
Carcinogenic in animals
Hopewell incident; tremors, hepatomegaly, reduced sperm counts and motility
ACUTE TOXICITY OF ORGANOPHOSPHORUS INSECTICIDES
Muscurinic and nicotinic signs Inhalation; immediate,orally; delayed and percutaneously; delayed Symptoms -bronchoconstriction, ocular pain, reduced vision -GI exposure; anorexia, nausea, vomiting, cramps -time of death may be less than 5 minutes to 24 hours depending on dose, route cause of death; respiratory failure
ORGANOPHOSPHORUS INSECTICIDES; DIAGNOSIS AND TREATMENT (ACUTE)
If suspect; determine CHE in erythrocytes and plasma Atropine in sufficient dose to cross BBB Moderate or sever intoxication, pralidoxime recommended- 1-2 gms IV Supportive measures; patent airway, artificial respiration, oxygen treatment of shock
CHRONIC TOXICITY OF ORGANOPHOSPHORUS CMPDS
Fluorine-containing alkyl phosphates produce a delayed type of neurotoxicity -not mediated by Ache inhibition -it is due to axonal swelling, segmentation and breakdown into granular debris -demyelination due to axonal changes -neurotoxic esterase is involved
FUMIGANTS
Cyanide -one of most rapidly-acting poisons -Used to fumigate ships, buildings, soil -Found in silver polish, insecticides, rodenticides -Found in plants, cassava and in seeds of apple, apricot, almond - Affinity for iron in ferric state -Reacts with trivalent iron of cytochromes oxidase inhibiting respiration In cells -Causes transient stage of CNS stimulation with hyperpnea -Hypoxic convulsions result and usually dies from respiratory failure
TREATMENT OF CYANIDE POISONING
Treatment should be rapid Aimed at preventing binding of cytochromes oxidase -large pool of ferric iron Nitrite used to oxidize hemoglobin to methemoglobin (amyl nitrate)
HERBICIDES
CHLOROPHENOXY COMPOUNDS -2,4,D and 2,4,5 T -control broadleaf weeds -no accumulation In animal -growth hormone for plants -death from ventricular fibrillation -produces chloracne -2,3,7,8 TCDD
PARAQUAT
Several hundred accidental or suicidal fatalities over last 10 years Target organs, liver,lungs and kidneys -toxic action via superoxide anion radical -delayed toxicity in lungs -death due to respiratory failure