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Институт теоретической и экспериментальной биофизики Российской академии наук.

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199406, Санкт-Петербург, ул.Гаванская, д. 49, корп.2

ISSN 1999-6314

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VOL. 2, Art. 50 (p. 298) // Мay, 2001

LEAD INTOXICATION: PATHOGENESIS AND PREVENTIVE MEASURES

Tatiana G. Fedorova
Saint-Petersburg State Medical Academy, Russia


Heavy metals are widespread adopted in a great number of mothern industries: in metallurgy, engineering industry,printing plants, electrotechnical works, etc.
One of the most common heavy metal is lead. It is a polytropos poison, because it produces a great ecological problem and can damage various organs in a human body. Lead is especially dangerous in combination with other unfavorable industrial factors.
In connection with rising of expenditures for energy resources it is necessary to increase production of repeating electric accumulators for different technical arragements. Undoubtedly they have possess an advantage over disposable electric batteries. They are long-lived, economical and ecologically safer than other ones owing to small content of heavy metal salts (and lead,too) and other toxicants.
There are many scientific reports dealt with biological effects of lead. Most of them are concerned to blood levels of this metal (1, 2, 7, 8, 15, 22, 24, 27, 31, 32). Becides, there is an interesting information about urinary content of lead (6, 25, 29), urinary ALA (24). Some scientists investigates different aspects of clinical effects of the metal on human body : gastrointestinal manifestations (13, 14, 30), neurotoxic aspects (5, 9, 12, 14, 23), vibratory sensitivity (16) and visual reactions (3), damaging of kidneys (4) and skeleton (11, 17, 21).
Great interest of scientists is shown about biochemical indicators of saturnism: urinary ALA, delta-ALA Dehydrataze, porphyrines and pyrimidine 5`-nucleotidase (19,20,24,28).
But there are only a little information about so basical biochemical aspects of toxic effect as lipid peroxidation and mainy about experiments made on animals. Also I couldn`t find much information on complex investigations about clinico- biochemical effects of low levels of lead on industrial workers (23).
The succession of biochemical and clinical changes in human body depends on time of contact with small concentrations of lead and unfavorable microclimate had not been investigated completely. Meanwhile knowledge about pecularities of stages of that influence would help for exposure of risk group and to ensure the efficiency of prophylaxis.
In this work hygenical, medico-sociological, clinical, functional and biochemical methods of investigation was used. A modern factory producing small electric accumulators and soldering sections of two radio-electronic enterprises was selected as objects for scientific research.
The study of work conditions was made. They included fixing concentrations of toxins in the working place air and in washes from surfaces, measuring of sound lewels and degree of illumination, taking temperature of the room air, speed of moving and relative humidity of air. Time-study of the work process was also made.
Detailed hygienic description and investigation of the industrial works allowed me to apprise the basic factors which influenced on health of the personnel. They include influence of low lead aerosol concentrations, infavorable microclimate parameters (low room temperature, heightened speed of moving and relative humidity of air), forced working posture, necessity for prolonged attention concentration.
All workers in these works were divided into two groups in accordance with the lead concentration in the air. The first group included personnel from a small accumulator factory . The level of lead aerosol in the air of the work zone was higher than maximum permissible concentration limit (Toxic Level Value) in 5.7 times. That is why all preventive measures were ordered. They included isolation for working zones, using all-room and local drawing ventilation. Workers had shorter working day and longer annual leave of absence. They used measures for individual defence and prophylaxis: respirators, rubber gloves, overalls. They also had a shower and gargled their mouths after shifts, use pectines and medicinal-preventive diet and every year they were examined by medical specialists.
The second group included workers from soldering sections of radioelectronic enterprises, where lead concentrations were more than maximum permissible concentration limit (Toxic Level Value) in 2.2 times only in 12-40% of measurements. That is why the main prophylactic measures there were: isolation of the work zones, all-room and local drawing ventilation, regulated technological breaks. Workers had longer annual holidays, wore overalls, took medicinal-preventive diet. Medical examinations were once in a two-year period.
All workers of these objects (417 persons) were clinically examined including the most important laboratory methods. They were examined therapeutically and neurologically. The external breathing function and tepping-test were also studied. Urine was analysed on delta aminolevulinic acid, coproporphyrin and lead excretion. Capillary peripherial blood was checked for erythrocytes,reticulocytes, basophilic-grainy erythrocytes, leucocytes and leycocytes formula account. Venous blood was examined on cholesterol, betalipoproteides, diene conjugates, malonic dial, medium molecules, index of endogene intoxication and superoxid dismutasa`s activity.
In the program there were also 27 patients with chronic professional lead intoxication and 44 healthy persons who had never contacted with lead.
After questioning it was established that all workers from the basic group had known that they had contacts with unhealthy conditions at their work places. But more than half of them (53.4%) had come to these conditions because of high levels of wages (for accumulator productors that cause was the most important in 75.0%). 28.2% of respondents worked at their places because of custom for these plants and collectives. One quarter of persons were complied with their work conditions, and nearly the same part (23.3%) of personnel had not other speciality. For 16.5% of persons very important factors were their houses lockation near to the factory, suitable work schedule and a possibility for appartments renting.
Analysis of social and private life, anamnesis of life had shown equality between the basic and control groups. That is why the general evidenses of pathology development were the result of the infavorable industrial factors influence .
There was no one case of lead intoxication in the gruop of persons who had contacts with low lead concentrations. But during medical examination some workers (10,9-25,0%) were complaining of general weakness,efficiency decreasing, low spirits, narrowing of interests circle. Digestion problems had 8.1-21.1% of persons, 21.1% of clients complained of their bone and articulation pains. These indications are early symptoms of lead poisoning. Profound study allowed to exclude influence of non-toxic factors and to determine that such phenomena were the most typical for persons who had contacted with lead during 6-9 years. The objective study also showed a weak reaction of nervous and cardiovascular systems (decreasing of pain sensitivity in the upper extremities, deterioration of audio-visual perceptivity and motor coordination, bradicardia).
Blood clinical analysis of 14.9% workers from the first and 12.3% workers from the second group showed insignificant decreasing of erythrocytes number and in 9.2% courses - decreasing of haemoglobin level. These data didn`t give reasons for determination for anemia, which was characteristic for lead intoxication, but it showed the tendency for it.
Break of porphyrine metabolism as some increasing of delta aminolevulinic acid and coproporphyrin urine excretion (but without heightened lead excretion) was exposed in every fourth worker. This phenomenon was shown only in persons with 3-5 years contacts with lead and then it disappeared in the other groups.
Besides, it was founded a very concrete change of trombocytes content in blood under the influence of small lead concentrations. The number of trombocytes had close relationship with lead excreation value and the length of the contact with lead. Fluctuation of the trombocyte`s number has undulating character.
There was a considerable number of clients with trombocytopenia (42%). It was a great surprise that in the second group this phenomena was shown for a half of patients. A deep mathematical analysis showed that the number of trombocytes in blood was closely related with lead excretion, the number of erythrocytes and also with the duration of work in contact with lead. It was shown that there was the relationship between the number of trombocytes in blood and the degree of intoxication.
Lead as a metal with variable valency is capable to disturb functions of some ferments and initiate lipid peroxidization process. Owing to this, cellular membrane composition may be changed, some enzymes may be activated and other ones may be inhibited, phagocytosis and pinocytosis may be distorted. That is why I had studied blood concentration of the primary and final products of lipid peroxidization - diene conjugates and malonic dial, and activity of the most important enzyme of antioxidant system - superoxid dismutasa.
It was discovered that workers who had contacted with low levels of lead had considerably more concentrations of the primary products of lipid peroxidization - diene conjugates - in their serum than persons from the control group and patients with lead intoxication. These changes depended on the work period longivity and related to urine excretion of lead. Besides, it was also shown negative average relationship (r=-0.47, t=-4.78, p=0) between the number of trombocytes and concentration of primary products of lipid peroxidization - diene conjugates. So, I decided that the number of trombocytes, as one of the components of antioxidant system, was able to change in compensation for developing of lipid peroxidatoin under the influence of lead. Probably, change of trombocytes` quantity under the pressure of lead has compensatory, adaptive character as a reaction on variation of lipid peroxidization. The concentration of the last product of lipid peroxidization - malonic dial - was the same in all groups. Superoxid dismutasa`s activity and number of trombocytes in blood went down and depended on the longivity of the work period. In the first group superoxid dismutasa`s activity was less than in the second group.
Then I tried to apprize efficiency of some preventive methods. The reliable decreasing of diene conjugates in blood of workers who had taken precautions was discovered in comparison with the group where persons neglected these measures (Table 1).
Thus, if a person has a long contact with little doses of lead and unfavorable microclimatic parameters there will be successive changes of adaptation. They manifest themselves in consecutive fluctuation of parameters of a human body. The first stage, when the system (alive organism) is in search for new stationary condition, usually lasts during first 5 years contact with lead. This is not evident outwardly and it requires some additional laboratory tests from medical staff. This period is characterized by maximum delta aminolevulinic acid and coproporphyrin urine excretion; number of trombocytes in blood is reducing and then rising, activity of superoxid dismutasa is rising, diene conjugates concentration is coming down.
The second stage shows changing of laboratory parameters to the opposite direction. And also frequency of specific complaints is rising as particular changes in blood creating system and in nervous system are developing.
The third stage begins after 10 years of work in contact with lead. Laboratory parameters are becaming stable. But pathological affection is increasing.
As a result of the scientific research several preventive measures are elaborated for health defence in the case of contact with small lead concentrations. It was shown that if a person who had contacts with lead uses those measures even during a year, laboratory tests would become better. Clinical manifestation of the poisoning displays later and so need to have longer period for rehabilitation. Besides, it was established that risk factors for poisoning reinforce lipid peroxidization and decrease antioxidant system activity, as inclination to trombocytopenia and also work with lead more than during 5 years.

Table 1. The main laboratory indices of workers before and after the experiment, meanvalues.

Indices of blood content First investigation Repeated investigation
Erythrocytes  x 1012/l 4.08 +(-) 0.11 4.12 +(-) 0.08
Haemoglobin, gr/l 143.0 +(-) 2.1 137.0 +(-) 2.8
Trombocytes  x 109/l 219.1 +(-) 16.5 205.0 +(-) 13.6
Leycocytes  x 109/l 6.15 +(-) 0.39 5.56 +(-) 0.28
Reticulocytes %0 5.83 +(-) 0.98 4.58 +(-) 0.28
Diene Conjugates, mcmol/l 0.89 +(-) 0.18 0.51 +(-) 0.04
Malonic Dial, mcmol/l 3.33 +(-) 0.47 3.54 +(-) 0.16
Urinary excretion:    
Delta aminolevulinic acid, mcmol/gr creat. 9.37 +(-) 0.65 9.75 +(-) 1.85
Coproporphyrin, mcmol/gr creat. 78.0 +(-) 9.1 51.7 +(-) 8.2


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