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CHEMICAL FACTORS AS CAUSES OF DISEASE
LECTURES FROM GENERAL
PATHOLOGICAL PHYSIOLOGY
OLIVER RÁCZ
CLASSIFICATION OF TOXIC SUBSTANCES
AND INTOXICATIONS
• ANORGANIC (metals, gases, cyanide, nitrites, etc.)
• ORGANIC (almost everything)
• BIOLOGICAL (animal, plants, mycotoxins, bacteria)
• NATURALLY OCCURING & SYNTHETIC
• ACUTE & CHRONIC (CUMULATIVE)
• ACCIDENTAL & VOLUNTARY
• POLLUTION, TERRORISM

Cadmium ( 48 Cd 112 )
• Itai-itai; Japan, 1940 - 1960
– 1 mg Cd/day from rice contaminated by mining waste
– Deficit of vitamin D, Ca, Zn
• Postmenopausal & multiparous women
– Bone deformities, pain in the joints
– Chronic renal disease - hypercalcuria, proteinuria &
glycosuria
(max. permitted 50µg/d; avg ≅ 5 µg; smokers ≅ 10 µg)
Cadmium ( 48 Cd 112 )
• Binding to metallothionein (Cd-Mt)
– 8.5 - 10 kD; rich in Cys; binds 4 - 12 atoms of metalls
• Mechanism of toxicity
– antagonism with Zn
– covalent binding to DNA
– interference with the transport of other Me 2+
– interaction with SH groups
• Nutritional protection
– Zinc

Mercury ( 80 Hg 201 )
• WIDESPREAD USE IN A VARIETY OF PRODUCTS
❊ 5-6*10 6 kg released to the environment every year
❊ accumulation in marine sediment → fish
• HIGHLY TOXIC COMPOUND (lipohilic, volatile)
• Hg 0 vapors - inhalation, lung damage
• Hg salts (sublimate, HgCl 2 - GIT, kidney damage
• Hg in medicine (syfilis, calomel, dermatology,)
• MethylHg - CNS, teratogen
• amalgames used in dentistry ?
❊ Affinity for SH groups & Fenton reaction catalyst → oxidative
stress
❊ inactivation of enzymes, membrane & transport system damage
etc.
Mercury ( 80 Hg 201 )
• MINAMATA BAY, JAPAN
Metallic Hg released from a factory into the sea
transformed to organic mercury compounds.
Consumption of contaminated fish and shellfish →
staggering cats, CNS injury & deaths in fishermen, birth
defects in newborns
• IRAQ, 3 epidemics (50‘s - 70‘s)
Bread made from grain treated with organomercurial
antifungal agents

Lead ( 82 Pb 207 )
• Used throughout modern history of mankind
• XXth Century - gasoline additive
• Current production - 3.8*10 6 tons/year
contribution to history
❋ Nero‘s madness (wine in pewter vases)
❋ The fall of Roman Empire (lead water pipes*)
❋ „Franklin“ expedition to the Northwest Passage, 1845 (lead
seals of tin cans)
❋ Vincent van Gogh‘s illness & madness (paints)
*EPA & WHO standard < 0.05 mg/l
YEAR Pb, µg/m 3
1970 0.91
1978 0.84
1982 0.32
Lead - toxicity
• Lethal dose ≅ 0.5 g
• Harmful > 10 µg/l blood
• accumulation in bones,
replaces Ca
• t 1/2 ≅ 15 - 20 years
• children more sensitive
• organic compounds are
more dangerous
DAMAGE OF
• Brain and nerves
• Liver
• Kidney
• Blood
– synthesis of porphyrins
• Reproductive system
• Digestive system
• Immune system

Cyanide and related compounds
• HCN, KCN - electron transport in mitochondria
(Cytochrome A)
• Increase in respiration, paralysis of all cells (BP fall,
convulsions, coma)
• Sources
– Industry
– Cassava & manioca roots (glycosides)
– stones of bitter almonds, apricots (glycosides)

*and heavy metals!
Baia Mare (RO), 30 th January 2000
Gold reprocessing facility,
leak of a tailing pond
378 500 liters toxic
sludge (8g KCN /l)*
River Lapus Somes
Tisza (February 3, 12 mg/l;
590 km of very sensitive
ecosystem)
Danube (end of February
till higher than 0.1 mg/l )
• More than 100 tons of dead fish,
some of them rare and
endangered species.
• Other water animals killed too -
frogs, crabs, insects, etc.
• Secondary intoxication &
perishing of otters, beavers,
birds, dogs
• Cyanides are unstable
• Danger of ecological
catastrophe
• Monitoring & prevention in the
future
Purvis A.: Deadly Discharge. Time 155, 2000, No 6; February 28, p.26
Bombová E., Kupcová M.: V zápase s kyanidom v riekach život azda celkom neprehrá. SME 22.2.2000
Further examples
• Contergan, thalidomid, 1957 - 1961
– 2625 cases of birth defects (phocomelia)
• Seveso, Italy, 1976 (& in Vietnam war)
– DIOXIN ➡ SKIN, LIVER, BRAIN (CUMULATIVE)
• Bhopal, India, 1984, Union Carbide
– CH 3 -N=C=O (methyl isocyanate)
– 7000 residents died within days, 500 000 affected,
many survivors remain ill or disabled after 15 years
• Asbestos - Lung Ca, bankruptcy of Lloyd‘s

CHERNOBYL, 1986
6 tons of radioactive fuel released = 10 EBq* in two
phases (during the explosion and a week later)
143 cases of acute radiation illness, 28 ✟
(unsuccessful attempts of bone marrow transplantation)
Radioactive fallout and exposition:
600 000 person*sievert
40 % Soviet Union; 50 % Europe
Exa = 10 18

CHERNOBYL 1986 - RELEASE OF SOME
RADIONUCLIDES
NUCLIDE HALF-LIFE ACTIVITY, PBq RELEASE
Xenon 133 5.3 d 6500 6500
Iodine 131 8 d 3200 1760
Cesium 134 2 y 180 54
Cesium 137 30 y 280 85
Tellurium 132 78 h 2700 1150
THYROID CANCER IN CHILDREN BEFORE AND
AFTER CHERNOBYL
AREA 1981-1985 1986-1994
GOMEL 1 164
BELARUS 3 333
NORTHERN
1 118
UKRAINE
UKRAINE 25 209
PREVENTION BY KI DELIBERATELY NEGLECTED

POPULATION DOSE, mSv + DEATHS
200 000
emergency workers
135 000
evacuees (30 km)
270 000
control zone residents
6 800 000
whole area residents
100 2200
10 160
50 1600
7 5000
GREECE: 2.6* Increase of leukemia in children ?!
MAYAK RIVER, PLUTONIUM PLANT
1949 - 1956; 65*10 6 m 3 radioactive waste
1700 times the permitted exposition
28 000 affected people in 28 villages
The effects of alcohol
• Acute alcohol intoxication (Noe)
• Alcoholism (addiction)
– Alcoholic is who drinks more than his doctor
• Withdrawal syndrome (delirium, white mice)
• Diseases associated to alcohol consumption
• Beneficial health effects of moderate drinking
– The French paradox

Alcohol and the western populations
• Absolute abstainers 10 %
• Consistent consumers 20 %
• Nonconsistent consumers 20 %
• Occasional heavy drinkers 27 %
• Regular heavy drinkers 20 %
• Addictive alcoholics 3 %
Alcohol and diseases
• Direct effect (brain, liver)
• Energy content (beer ⇒ obesity)
• Deficient nutrition (B vitamins ⇒neuropathy)
• Toxic compounds (Methanol, Glycols, Cobalt, Thujone
from absynth
♥ The French paradox (CHD in France vs Scotland
♥ ⇑ HDL cholesterol, ⇑ fibrinolysis, ⇓coagulation,
⇑insulin sensitivity
♥ Decreased risk of MI
♥ Antioxidants ? Life style ?