INTOXICATION BY BENZOL.

INTOXICATION BY NITROCOMPOUNDS AND OILSPERSES OF BENZOL, CARBON OXIDE

INTOXICATION BY LEAD.

I. INTOXICATION BY BENZOL

(benzene properties, industrial uses, pathogenesis of benzene poisoning, clinical picture, diagnosis, preventive measures, management of benzene poisoning).

Among the various substances which are used in industry, there are compounds which mainly influence on a bloody pigment - haemoglobin and transform it into methaemoglobin. Such substances are derivatives of benzene, which molecules include amino (NH2) and nitro (NO2) groups. Amino- and nitrogroups of benzene are wide-spread in industry and used for making of organic dyes, pharmaceutical preparations, artificial resins, insecticides, blasting matters and other.

Electron micrograph of benzene particles. Individual particles are about 25nm in diameter.

Among amino- and nitrogroups of benzene aniline, benzidin, nitrobenzene, dinitrobenzene, nitrotoluol, nitrofenol are frequently used in industry and have the practical value.

In the production terms these substances get into an organism through the organs of breathing and skin, rarely through a gastrointestinal tract.

Amino- and nitro compounds of benzene, getting to the organism, accumulate in a cerebrum, kidneys, heart, liver. Then their redistribution occurs and most of matter stay too long in a temporal depot - subcutaneous-fatty cellulose and liver, that causes relapses of intoxication, particular after hot procedures and use of alcohol.

In organism amino- and nitrocompounds of benzene unite with sulphuric and glucuronic acids, form connections and are excreted with urine. Little amount of amino- and nitrocompounds are excreted by lungs.

Sources of exposure to benzene

Outdoor air – Low levels of benzene can be in the atmosphere because it's commonly found in gasoline. The area around gas stations and motor vehicle exhaust will therefore probably have slightly higher levels of benzene. Factories sometimes emit the chemical, and the air around hazardous waste sites tend to contain higher levels of benzene than in other areas.

Indoor air – Levels of benzene indoors is usually slightly higher than outdoor levels. That's because everyday household items such as paints, detergents, furniture wax, and glues have benzene in them.

Smoking – A major source of benzene exposure is tobacco smoke. A smoker puts himself at risk of the carcinogenic effects of benzene. Additionally, anyone in the vicinity of the smoker can be at risk through second-hand smoke.

Water – Occasionally, benzene from underground storage tanks or hazardous waste sites can contaminate drinking water sources. This is very rare, but has very serious health effects on the people who drink the water.

Benzene workers – People who work in factories that produce or use benzene are generally exposed to the highest levels of the chemical. Proper protection should always be worn, and safety protocols should be outlined, reviewed, and practiced regularly.

Long term exposure to benzene causes harmful effects on the bone marrow. This can result in anemia and possibly even leukemia. Additionally, low birth weights, delayed bone formation, and bone marrow damage have been shown in studies that observed the health of newborn animals. These birth effects are suspected, but unconfirmed, in humans as well. It's therefore very important to protect yourself as much as possible from benzene exposure.

Industrial processes

As benzene occurs naturally in crude petroleum at levels up to 4 g/l, human activities using petroleum lead to exposure. These activities include processing of petroleum products, coking of coal, production of toluene, xylene and other aromatic compounds, and use in industrial and consumer products, as a chemical intermediate and as a component of petrol (gasoline) and heating oils. The presence of benzene in petrol and as a widely used industrial solvent can result in significant occupational exposure and widespread emissions to the environment. Automobile exhaust accounts for the largest source of benzene in the general environment. Off-gassing from building materials and structural fires lead to increased atmospheric benzene levels. Industrial discharge, landfill leachate and disposal of benzenecontaining waste are also sources of exposure.

Indoor residential air

Benzene has been detected at high levels in indoor air. Although some of this exposure might be from building materials (paints, adhesives, etc.), most is from cigarette smoke in both homes and public spaces. Levels of benzene are higher in homes with attached garages than in those with detached garages. Levels are increased in homes close to petrol filling stations.

Benzene may be released to indoor air from unflued oil heating and from the use of benzenecontaining consumer products in residences. People spending more time indoors, such as children, are likely to have higher exposure to benzene.

Potential Industrial Exposures to Benzene

1. Detergent Producers and Users.

2. Pesticide Producers and Users.

3. Gasoline Producers and Users.

4. Solvent Producers and Users.

5. Paint and Varnish Producers and Users.

6. Adhesive Producers.

7. Rubber Industry Processors.

8. Petroleum Industry Processors.

9. Chemical Workers.

10. Waste Management.

11. Laboratory Technicians.

12. Auto Mechanics, Painters, Printers, Degreasing Operations.

13. Extraction & Sampling (Industrial Labs).

14. Hauling, Loading, Unloading & Tank Cleaning Operations.

15. Burning of Organically Originated Materials - Wood Burning, Garbage Burning, Insulation Materials, Hydraulic Fluids (Fire-Fighters, Law Enforcement, Technicians, Laborers).

16. Rubber & Rubber Coating, Adhesives, Sealants.

17. Engine Emissions.

18. Parts Washing in Solvents.

19. Cigarette Smoking.

Many epidemiological studies have been carried out on benzene-exposed workers in shoemaking, rotogravure (printing), petroleum, petrochemical and rubber industries. A number of these studies followed up on case reports. The relationship between benzene and leukaemia has also been investigated in several hospital-based case-control studies. As in much epidemiology, many of these studies suffer from lack of good exposure data, losses of former workers to follow-up, incomplete or possibly faulty diagnoses on death certificates, potentially confounding exposures, and other problems. Several studies used general population incidence rates for comparison, and neglected to take into account the healthy worker effect in analysis of results. Despite these shortcomings, an impressive amount of evidence has been amassed to support the benzene-leukaemia connection.

Girard and Revol (1970) - in a hospital-based case-control study, investigated patients with leukaemia in two Lyon Hospitals between 1966 and 1969. 17 cases (12%) of patients with acute leukaemia, 9 cases (15%) with chronic lymphocytic leukaemia, 4 cases (7%) with myeloid leukaemia and 2 cases (15.3%) of myelofibrosis had evidence of previous exposure to benzene and toluene compared to five (4%) controls, for relative risks of 3.3 (1.2-8.9), 4.1 (1.4-12.0), 1.8 (0.5-6.6) and 4.3 respectively. (It is assumed that haematologic effects are likely to be due to benzene present as a contaminant in toluene.)

Ishimaru et al (1971) -- analyzed 303 leukaemia cases and 303 matched controls in Nagasaki and Hiroshima and assessed occupational exposures to benzene and to medical x-rays (on the basis of occupations). The benzene-associated relative risk of leukaemia was 2.5 (1.3-5.0) in 42 exposure-discordant pairs. Reviewers noted that the small numbers involved considerable uncertainty and that the risk may have been influenced by other chemical exposures as well. (Austin, 1988; IARC, 1982).

Thorpe(1974) - found 18 leukaemia cases among 38,000 active workers and pensioners from 8 European affiliates of a large U.S. oil company during the years 1962-1971. Workers who had quit before retirement were not included. Workers were classified as exposed (for five years minimum to products containing at least 1 percent benzene) or not (no or occasional exposure). The SMR for leukaemia in exposed workers was 121 (37-205) when compared to the general populations in the countries where the affiliates were located. (Exposed workers accounted for 8 cases.) Reviewers commented on problems of ascertainment, validity of diagnoses, deficit of deaths in unexposed workers, exposure assessment and the healthy worker effect in calculating the SMR. The type of leukaemia was not specified in 12 cases.

Aksoy and coworkers (1974, 1976, 1977, 1985) -- identified 34 cases of acute leukaemia or preleukaemia, including 4 cases of acute lymphoblastic leukaemia, among 28,500 Turkish shoe workers exposed to benzene between 1967 and 1973. Eight of 34 had previous pancytopenia. He estimated a crude annual incidence rate of 13.5 per 100,000 among these workers, compared to an estimated annual incidence of 6 per 100,000 in the general population. (Case ascertainment was based only on diagnoses made at the Internal Clinic of Istanbul Medical School, and was incomplete. It is also unlikely that the whole study population was exposed.) Average exposures were estimated to range between 150-210 ppm when adhesives were in use and 15-30 ppm at other times. Mean duration of exposure for leukaemia cases was 9.7 years. In the 1977 report, Aksoy also compared types of leukaemia in 40 individuals with chronic benzene poisoning and in 50 leukaemic individuals without benzene exposure. Of exposed cases, 65% had acute non-lymphocytic leukaemias, compared to 26% of non-exposed cases. Non-exposed cases had higher rates of acute lymphocytic, chronic myelocytic and chronic lymphocytic leukaemias. Aksoy updated this study in 1985, reporting a total of 51 cases of leukaemia.

Infante et al and Rinsky et al(1977, 1981, 1987) -- a series of studies and follow-ups have been carried out on workers employed in the manufacture of rubber hydrochloride (trade name Pliofilm) at three Ohio plants. The 1987 study included 1165 men exposed to benzene at least one day during 1940-1965, and extended follow-up through 1981. Estimates were made of cumulative benzene exposure of men in the study. Fifteen deaths were observed from lymphatic and haematopoietic cancers versus 6.6 expected. Nine leukaemias were observed versus 2.7 expected for an SMR of 337 (154-641), in comparison to the general population of U.S. white men. A tenth death due to leukaemia was not included because it occurred shortly after the date set for the end of follow-up for the study. Four cases of multiple myeloma were also observed compared to one expected for an SMR of 409 (110-1047). Increases in cumulative exposure were associated with marked progressive increases in the SMR for leukaemia. All leukaemias were myelocytic or monocytic. The estimated exposure levels of the Pliofilm workers sparked considerable controversy, especially during the U.S. debate on the proposed benzene PEL. Infante et al suggested exposures were mainly below 100 ppm. Other analysts have suggested that exposure excursions up to several hundred parts per million may have occurred. Each of these alternate exposure analyses was used to prepare a quantitative risk assessment for benzene-induced leukaemia. (Tabershaw and Lamm, 1987; Kipen et al, 1988; Paustenbach, 1993).

Ott et al, Fishbeck et al and Bond et al(1978, 1978, 1986) -- Ott and colleagues followed 594 Dow Chemical Company employees exposed to benzene in the production of alkyl benzene, chlorobenzene and alkyl cellulose. Exposures occurred during 1938-1970 and the workers were initially followed through 1973. Bond extended the study through 1982 and included an additional 362 exposed employees. Four deaths occurred due to myelogenous leukaemia where 0.9 were expected. Another case of myelomonocytic leukaemia was not included. The incidence rate ratio was 4.4 (1.2-11) relative to the general population of white US males. Cumulative benzene exposure of three leukaemia cases was below the average cumulative exposure of the cohort. One death attributed by Ott to aplastic anaemia, another due to myelofibrosis and a third due to multiple myeloma also occurred among workers. The latter two cases occurred to workers from the same area of the plant where four out of five leukaemia cases were located.

Linos et al(1980) -- carried out a case-control study of 138 leukaemia cases and 276 controls. The criterion for benzene exposure was any mention in the medical records. A relative risk of 3.3 (0.6-28) was based on four exposed cases and three controls. Three of the exposed cases were identified as having chronic lymphocytic leukaemia.

Rushton and Alderson(1981) -- conducted a case-control mortality study of workers in 8 oil refineries in the United Kingdom, nested in an earlier, retrospective cohort study. An earlier retrospective follow-up study reported an SMR of 94. The case-control study included 30 leukaemia deaths among men employed between 1950 and 1975 (and 6 deaths with leukaemia cited as an underlying cause) and 216 controls from refineries during same period. Exposures were classified as low, medium or high based on work histories. The relative risk for medium or high exposures compared with low exposures was 2.0 (1.0-4.0). Leukaemia cases were identified as: 10 lymphatic leukaemias (3 acute, 5 chronic, 2 unspecified); 15 myeloid leukaemias (6 acute, 4 chronic and 5 unspecified); and 5 others, including 4 acute monocytic and 1 "other" acute. Relative risks for different types of leukaemia were not presented. The study is supportive of a leukaemogenic effect of benzene and/or related solvents, but is limited by lack of data on exposure and inconsistent criteria for matching cases and controls. (Austin, 1988).

Schottenfield et al(1981) -- in a preliminary study of the morbidity and mortality of U.S. petroleum workers cited by OSHA, observed statistically significant increases in the incidence of acute and chronic lymphocytic leukaemias among refinery workers and multiple myeloma in petrochemical workers, compared to U.S., age-specific cancer incidence rates. Seven leukaemias were observed compared to 2.8 expected, for a standardized incidence ratio (SIR) of 274. For nonlymphocytic leukaemias the SIR was elevated to 113, but was not significant. Multiple myeloma had a significant SIR of 552 among petrochemical workers. These rates may have been underestimates, according to the authors, because the period of observation was quite short, the number of older workers included in the analysis was limited, and the degree of under-reporting of mortality was unknown.

Decoufle et al(1983) -- Studied 259 males employed during 1947-1960 at a chemical plant where benzene was used in large quantities. Workers were followed to 1977. Investigators found 4 deaths from lymphoreticular cancers, compared to 1.1 expected for an SMR of 364 (RR 3.7). Three deaths were due to leukaemia compared to 0.4 expected (RR 6.8), including one case of chronic lymphocytic, one acute monocytic and one acute myelomonocytic leukaemia. One leukaemia case had previously been treated for multiple myeloma. One death was due to multiple myeloma. No exposure information was available.

Wong and colleagues(1980, 1983) -- conducted a mortality study of 4602 male chemical workers occupationally exposed to benzene at 7 plants for least 6 months between 1946 and 1975. The controls were 3074 workers from the same plants with no known exposure to benzene. Workers were followed through 1977. Exposed workers were identified as having continuous (with some intermittent), intermittent/casual exposures or no exposures. The exposed groups were further subdivided into low, medium, and high. Wong found 7 deaths due to leukaemia in all exposed workers compared to none in the nonexposed group. Continuously exposed workers had an excess of lymphopoietic cancer. Two of 3 deaths from multiple myeloma were from the intermittent exposure group. Wong found a significant dose-response relationship by cumulative exposure (not duration). Wong concluded that there was a significant association between occupational exposure to benzene and leukaemia, and all lymphopoietic cancers including non-Hodgkin's lymphoma. (Described in ACGIH, 1991).

Arp et al, Checkoway et al(1983, 1984) -- conducted one of several case-control studies investigating the relationship between leukaemia and solvent exposures in the rubber industry. Benzene exposures were defined as "primary" for those workers whose jobs entailed direct handling of benzene or benzene-containing solutions, or "secondary" for workers located in areas where benzene was used, but direct contact did not occur. Relative risks for lymphocytic leukaemia were 4.5 for workers with primary exposure and 1.5 for workers with secondary exposure. Relative risks for workers exposed to other solvents were almost identical. Checkoway et al studied 11 of the lymphocytic cases (no distinction between primary and secondary exposure) and 1350 controls. Relative risk of lymphocytic leukaemia was 2.5 in benzene exposed workers, but was also elevated for workers exposed to other solvents. Most workers had exposures to several solvents.

Yin et al. (1987, 1989) -- reported studies of 508,818 Chinese workers exposed to benzene, in which aplastic anaemia occurred at a 5.8 fold increase over the general population. The authors went on to design a study involving a cohort of 28,460 exposed workers and 28,257 controls. Thirty cases of leukaemia were found in the exposed group compared to 4 among the controls. The excess risk was calculated at 5.7. The average latency was 11.4 years. The risk of leukaemia rose as duration of exposure to benzene increased up to 15 years, and then declined with additional years of exposure. Leukaemia occurred among some workers with as little as 6 to 10 ppm average exposure and 50 ppm-years (or possibly less) cumulative lifetime exposure. Among the 30 benzene-exposed leukaemia cases, acute non-lymphocytic cancers occurred at a much higher frequency and acute lymphocytic leukaemia at a lower frequency than in the general population. (Twenty cases were acute non-lymphocytic; 5 cases chronic myelogenous; 2 cases acute lymphocytic, 1 acute unspecified; 1 case "lymphocytoid"; and 1 case lymphosarcomatous.) Reviewers have noted possible confounding exposures to other solvents and high rates of cigarette smoking among Chinese workers. (Snyder and Kalf, 1994).

PATHOGENESIS.

General toxicity

Benzene is not generally regarded as an acutely toxic material and there are correspondingly few reports pertaining to the (human) health effects of a single exposure. In general, acute exposure to concentrations of benzene in excess of 500 ppm may illicit signs and symptoms consistent with solvent intoxication (Table 2). Overt signs of exposure have previously been referred to as “benzol jag”, characterised by euphoria, unsteady gait and confusion.

Recovery from an acute exposure is dose-dependent, with breathlessness, nervous irritability and unsteadiness in gait persisting in severe cases for two to three weeks.

Inhalation

The commonly quoted “lethal dose” of benzene (20,000 ppm) is an estimate based on a review of a single case report following 5 – 10 minutes’ exposure. Fatal exposures have been associated with asphyxiation, respiratory arrest, central nervous system depression and possibly cardiac arrhythmias. Death may be due to CNS depression, asphyxiation or respiratory or circulatory arrest. It has been observed that aspiration of benzene directly onto the lungs causes “immediate pulmonary oedema and haemorrhage at the site of contact with the pulmonary tissue”. Benzene is irritating to the nose and respiratory tract at “high” concentrations.

Ingestion

The single, acute lethal dose of benzene in humans is estimated to be 125 mg kg^-1, equivalent to 10 ml per 70 kg man^-1. Signs of intoxication following ingestion include staggered gait, vomiting, shallow and rapid pulse, somnolence, delirium, pnuemonitis, central nervous system depression, coma and death.

Dermal / ocular exposure

Whilst benzene is poorly absorbed through the skin, prolonged or excessive contact may cause signs consistent with the defatting (delipidising) effects of organic solvents, viz., erythema, vesiculation and dermatitis.

Benzene vapour may cause a smarting effect on the eyes at high concentrations. Eye contamination with droplets of benzene may cause a moderate burning sensation with only slight, transient injury to the epithelial cells. From http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1194947391801

With acute poisoning, the action of benzol is mostly obvious in the central nervous system and it progresses according to the type of poisoning with narcotic poisoning. Mostly, pathogenesis of chronic poisoning is in the inhibition of haemopoiesis – affection of proliferation of progenitor cells on haemopoiesis. Obviously, from the intensiveness (concentration of benzol vapors in the air of production territories) and the duration (number of work years in contact with benzol) impact, as well as from individual properties of the organism and its haematogenous organs (inherited inclination and previous diseases, which influence the blood system) depends the depth and the stage of affection of the marrow.

With the great intensiveness of toxic impact, the deepest affection of haematogenous organs is possible. In such cases, total inhibition of haemapoesis, disorder in proliferation of stem haematogenous cells and partially – predecessor of haemapoesis take place. Also, ability of these cells to differentiate can be affected. The result of such deep disorder of haemapoesis is progressing pancytopenia.

Less intensive toxic impact onto the marrow is accompanied by the inhibition of proliferation of differentiated blood cells (myeloblasts, erythroblasts and megacaryoblasts). Prevalent affection of granulocytopoiesis is possible here (progressing leukopenia) or thrombopoiesis (thrombocytopenia or hemorrhagic syndrome). Affection of germ of haemapoiesis can be assisted by pathologic changes or the impact ontpo a corresponding germ of haemapoisesis (fibromyoma, prolonged and excessive menses, gastric achylia, toxic impact onto the leucopoiesis of some medicinal drugs). It has been stated that the toxic impact onto haematogenous cells are caused by not only benzol, as its transformations (phenols), which are created in the marrow, where benzol is accumulated. Thus, mutation in the chromosomal apparatus of haematogenous cells and the disorder of mitosis are conditioned by toxic impact of phenols.

Amino- and nitrocompounds of benzene influence on the organism politopically. During acute intoxication central nervous system and peripheral blood are mainly affected, formation of methaemoglobin and development of hemolysis of erythrocytes occur. During chronic intoxication – mainly liver, urinary tracts, vision organ and nervous system are affected.

In the human organism haemoglobin oxidizes to oxyhaemoglobin, and its small part - to methaemoglobin. In a norm the quantity of methaemoglobin in erythrocytes forms 1-2,5 % from the common quantity of haemoglobin. Methaemoglobin - it is steady compound which is not able to transport oxygen to tissues. Formation of a large amount of methaemoglobin is a main pathogenic link in the origin of most symptoms of intoxication of amino- and nitrocompounds of benzene, that results in the origin of hypoxemia. As a result of accumulation in a blood of methaemoglobin and soulfhaemoglobin, skin and mucus are painted in a grey-dark-blue colour.

Intoxication by compounds of methaemoglobin causes development of irreversible degenerative changes in erythrocytes with formation of the rounded dark-blue inclusions on periphery - Gaints corpuscles.

Erythrocytes with Gaints corpuscles

In the severe case the amount of methaemoglobin is increased to 60-70 %, Gaints corpuscles - to 8 %. Amino- and nitrocompounds of benzene have toxic influence on the nervous system and affect pyramid ways, striped body, cerebral cortex, fibres of the peripheral nervous system.

Erythroid dysplasia and dyserythropoiesis in benzene-induced dysplasia. Abnormal erythroid cells exhibit megaloblastic abnormalities and abnormal nuclear morphology including nuclear bridging. BM aspirate slides stained with Wright-Giemsa (original magnification 1000×).

From http://www.sciencedirect.com/science/article/pii/S014521260500322X

The long-term contact with amino- and nitrocompounds of benzene at the promoted individual sensitivity of organism cause neoplasm process in urinary tracts. Acute renal insufficiency during haemolysis occurs in first three days.

CLINICAL PICTURE.

Acute intoxication by amino- and nitrocompounds of benzene cause considerable changes in the central nervous system.

The cerebral manifestations are: acute headache, severe fatigue, nausea, vomiting, disorders of equilibrium (balance). Patients are disposed to syncope, depression. Cramps occur, tendon reflexes disappear, the loss of consciousness and comma appear. Patients may die from the paralysis of respiratory centre, heart failure. In the first days after the comma patient complains on intensive headache, weakness, dizziness.

One of the most characteristic signs of acute intoxication of amino- and nitrocompounds is discoloration of skin. During examination grey-dark blue colouring of mucus and skin, cyanosis are revealed, dyspnoea is absent. Blood is of chocolate-brown colour; its colour depends on the quantity of formed methaemoglobin and sulfhaemoglobin.

Results of blood investigations: increasing of methaemoglobin, conjugated bilirubin, little Geynts bodies, anizocytosis, poycilocytosis, erythrocytes with a basophilic stippling, reticulocytosis, blood viscosity rises, ESR decreases.

Amino- and nitrocompounds of benzene cause the irritation of mucus of respiratory tract that is accompanied by the sneeze, cough. Burns of nose mucus, nose-bleeding may occur.

Urinary tracts are affected. Dysuric changes occur. In some cases ,,haemolitic kidney” and acute renal failure.

Acute toxic damage of liver by amino- and nitro compounds of benzene is caused by inflammatory and necrotic processes in liver tissues and leads to acute toxic hepatitis. In some cases acute or subacute atrophy of liver occur and it is accompanied by the severe haemorrhagic syndrome and hepatic comma.

Clinical picture of acute intoxication by amino- and nitrocompounds of benzene is divided into three stages of severity of disease.

During MILD STAGE of intoxication patients complain on the headache, dizziness, weakness, sleepiness. At the objective examination cyanosis of mucus and skin of fingers, auricles, and uncertain step, rise of tendon reflexes, tachycardia are revealed. Pathological changes of internal organs are absent.

Results of blood investigations: content of methaemoglobin in blood does not exceed 15-20 %, single Geynts bodies. In a few hours after intoxication all these complaints pass, methaemoglobin level decreases, a work capacity recovers. Duration of intoxication does not exceed 2-4 days.

MODERATE STAGE is characterised by neurological symptoms: acute headache, dizziness, nausea, vomiting, severe muscles weakness, clouded consciousness. The patient orientation is broken, there is uncertain step. In these stage syncope may occur.

At the objective examination: more expressed cyanosis of skin and mucus with a grey-asp tint, pulse is labile, rise of tendon reflexes, insignificant dyspnoea, poor reaction on light, insignificant expansion of heart, quit heart sounds, tachycardia. Sometimes liver is enlarged. Neurological status: nervous trunks are painful.

Results of blood investigations: increasing of methaemoglobin level to 30-40%, little Geynts bodies - to 15%. Blood viscosity rises; ESR decreases, sometimes moderate leucocytosis. The content of oxygen in an arterial blood falls. The clinical-laboratory symptoms of intoxication are observed during 5-7 days, although reverse development of basic manifestations of illness begins in 1-2 days.

At SEVERE STAGE of intoxications there are severe changes of the central nervous system. Consciousness is cloded, often absent, there can be cramps, dilation of pupils, disappearance of reaction on light, absence of tendon reflexes.

In a acute period prostration is determined, it changes by acute excitement, involuntary urination and act of defecation.

At the objective examination: severe cyanosis of skin and mucus, which sometimes acquires a dark blue-black tint and is caused by considerable met- and sulfhaemoglobinemia and vein congestion. Skin hemorrhages, ulcer of mucus are revealed. Heart is delatated, heart sounds are decreased, tachycardia, decreasing of arterial pressure. Liver is enlarged and painful.

Results of blood investigations: conjugated bilirubin in blood is increased. A blood is thick, elm, chocolate-brown coloured, contains 60-70% methaemoglobin, a lot of Geynts corpuscles, anizocytosis, reticulocytosis, a lot of normoblasts and megaloblasts, leucocytosis can appear, ESR slows down.

On 5-7 day haemolytic anaemia may appear. In case of intravessel hemolysis haemoglobinuria occurs, it stimulates development of renal syndrome.

Duration of main symptoms at severe stage of intoxication lasts 12-14 days.

CHRONIC BENZENE POISONING develops as a result of the protracted influence of small doses of poison that have cumulative action. Hot bath action, alcohol, the carried infection may cause exacerbation of chronic intoxication. The patients complain on general weakness, headache, dizziness, disturbance of sleep, rapid fatigue, dyspeptic symptoms, pain in right hypohondrium. Skin is pale, with cyanosis, colour of the eyes is icteric, pulse is labile, arterial pressure has a tendency to hypotonic. Heart sounds are decreased, chronic gastritis (frequently with decreased secretion), toxic hepatitis with moderate disturbance of liver function occur. The function of pancreas is affected.

Disturbance of the urinary system occurs: chronic inflammation of mucus of urinary bladder, appearance of pappiloms of urinary bladder, malignant formations.

Some benzene compounds cause occupational cataract.

Оccupational cataract

DIAGNOSIS.

Diagnosis of acute intoxication is made in case of contact of the patient with high concentrations of aromatic amino- and nitrocompounds (occupational anamnesis), characteristic clinical-laboratory symptoms: grey-dark-blue colour of skin and mucus, increased level of blood methaemoglobin and sulfhaemoglobin, appearance of Geynts corpuscles, erythrocytes with a basophilic stippling, reticulocytosis.

Diagnosis of chronic intoxication of amino- and nitrocompounds of benzene is based on a presence of complex of the exposed violations of blood, liver, nervous system, protracted contact with the indicated compounds.

TREATMENT.

At acute intoxications patient should be taken out of the gassed atmosphere. At the getting of poison to skin it is necessary to wash soil area by water. Hot baths or showers are contraindicated. According to indications cardiac medicines are prescribed: camphora, coffein, cordiamin, corglycon. Desintoxication, vitamin and symptomatic therapy is recommended.

At deppression of the central nervous system cytiton, lobelin are given. Oxygen therapy is the basic method of medical treatment.

For reduction of blood viscosity intravenous 20-30 ml 40 % solution of glucose, with 5 % solution of Vit. C are prescribed. Glucose is a good demethaemoglobinisation mean. Use of vitamin B12 is also recommended. In case of renal failure hemodialysis is conducted.

During chronic intoxication medical treatment is conducted taking into account the clinical picture of disease.

Verification of the ability to work.

At mild poisoning, patients are not able to work for a short period of time (for several days). At acute intoxication of mean and severe degrees, temporary inability to work is 3 to 4 days. Then with the purpose to ensure the results of the treatment of patients, they are transferred to lighter work beyond the impact of toxic matters with the provision of a sick leave on occupational inability to work for 1 to 2 months. Further, they are considered capable to work according to their speciality.

In cases of mild chronic intoxication to ensure the treatment effect, patients are recommended to be transferred to another temporary position outside the impact of toxic matters for the period of 2 months with the additional payment if needed to provide average monthly payment according to the sick leave on the occupational inability to work. Further, they are permitted to work according to their occupation, but only under condition of keeping to sanitary and hygienic norms of labor.

If the disease is a relapse, patients should be reemployed rationally (without the loss of qualification) at another place, which is more favorable in industrial meaning. In case of impossibility of such employment, a decision is made on temporary provision of invalidism group (for 1 to 2 years) due to the occupational disease until a new profession is not acquired. At the moderately marked form of intoxication, further working contact with toxic matters is not recommended, and patients are subjects to rational employment; and in case of the reduction of the qualification – they should be sent to the Expert Commission to acquire an invalidism group.

Preventive measures. The basis of preventive measures is further limitation of the contact with toxic matters. It can be achieved due to mechanization of production processes, sealing-in the equipment and reconstruction of ventilation. Wet cleaning should be done in premises. All those who work in possible contact with these matters, should use individual protection and should have an opportunity to take a shower at work. Those, who are being employed or employees who contact with oilspereses and nitrocompounds of benzol, should go through preliminary and periodical medical examinations.

II. CARBON MONOXIDE POISONING

(sources of carbon monoxide, pathophysiology, clinical picture, diagnosis, treatment, prevention of carbon monoxide poisoning)

CARBON MONOXIDE intoxication continues to be one of the most common causes of morbidity due to poisoning in the United States. It may be intentional or accidental, and exposure may be lethal. Approximately 600 accidental deaths due to carbon monoxide poisoning are reported annually in the United States, and the number of intentional carbon monoxide–related deaths is 5 to 10 times higher.

The rate of accidental death caused by carbon monoxide from motor vehicles is higher in the northern United States and peaks during the winter months. The intentional deaths occur yearround without significant peaks. The severe winter of 1995–1996 was associated with increased numbers of reported injuries from carbon monoxide exposure. In the winter of 1997–1998, the unusually high number of deaths from carbon monoxide was related to the use of poorly ventilated gasoline-powered generators during a severe ice storm in the northeastern United States.

SOURCES OF CARBON MONOXIDE

Carbon monoxide is a product of the incomplete combustion of hydrocarbons. The concentration of carbon monoxide in the atmosphere is usually less than 0.001 percent. The levels are higher in urban areas than in rural areas. Endogenous carbon monoxide production from the catabolism of hemoglobin is a component of normal biochemical processes. A low base-line level of carboxyhemoglobin is detectable in every person. Tobacco smoke is an important source of carbon monoxide. Blood carboxyhemoglobin commonly reaches a level of 10 percent in smokers and may even exceed 15 percent, as compared with 1 to 3 percent in nonsmokers.

The sources of exogenous carbon monoxide that cause poisoning include motor vehicle exhaust fumes, poorly functioning heating systems, and inhaled smoke. Propane-operated forklifts have been implicated as a cause of headache in warehouse workers. “Cleaner” fuels such as propane and methane undergo more complete combustion but have also been reported to be sources of carbon monoxide poisoning. The carbon monoxide in motor vehicle exhaust fumes accounts for the majority of deaths from carbon monoxide poisoning in the United States. Of the 11,547 accidental carbon monoxide deaths reported between 1979 and 1988, motor vehicle exhaust accounted for 57 percent. In a series of 56 motor vehicle– associated deaths reported from 1980 to 1995, 43 percent were due to faulty exhaust systems, 39 percent to operation in an improperly ventilated structure, and 18 percent to the use of a fuel-burning heating device in the passenger compartment.

One or the sourses of СО

Lethal concentrations of carboxyhemoglobin can be achieved within 10 minutes in the confines of a closed garage. Carbon monoxide from motor vehicles can also cause death in semienclosed spaces or in working or living quarters adjacent to garages. An often overlooked source of carbon monoxide poisoning is methylene chloride, a common component of paint remover and other solvents. Methylene chloride is readily absorbed through the skin and lungs as a vapor and circulates to the liver, where its metabolism results in the generation of carbon monoxide.

Risks for exposure to carbon monoxide include

· Children riding in the back of enclosed pickup trucks (particularly high risk)

· Industrial workers at pulp mills, steel foundries, and plants producing formaldehyde or coke (a hard grey fuel)

· Personnel at fire scenes

· Using heating sources or electric generators during power outages

· Those working indoors with combustion engines or combustible gases

· Swimming near or under the stern or swim-step of a boat with the boat engine running

· Back drafting when a boat is operated at a high bow angle

· Mooring next to a boat that is running a generator or engine

· Improper boat ventilation

PATHOPHYSIOLOGY

Carbon monoxide is a colorless, odorless, and nonirritant toxic gas that is easily absorbed through the lungs. The amount of gas absorbed is dependent on the minute ventilation, the duration of exposure, and the relative concentrations of carbon monoxide and oxygen in the environment. Carbon monoxide is principally eliminated by the lungs as an unchanged gas. Less than 1 percent is oxidized to carbon dioxide. Ten to 15 percent of carbon monoxide is bound to proteins, including myoglobin and cytochromec oxidase. Less than 1 percent of the absorbed gas exists in solution. Carbon monoxide toxicity appears to result from a combination of tissue hypoxia and direct carbon monoxide–mediated damage at the cellular level. Carbon monoxide competes with oxygen for binding to hemoglobin. The affinity of hemoglobin for carbon monoxide is 200 to 250 times as great as its affinity for oxygen. The consequences of this competitive binding are a shift of the oxygen–hemoglobin dissociation curve to the left and its alteration to a more hyperbolic shape (Fig.3).

Figure 3.

Oxygen–Hemoglobin Dissociation Curve. The presence of carboxyhemoglobin shifts the curve to the left and changes it to a more hyperbolic shape. This results in a decrease in oxygen-carrying capacity and impaired release of oxygen at the tissue level.

These alterations result in impaired release of oxygen at the tissue level and cellular hypoxia. The binding of carbon monoxide to hemoglobin alone does not account for all of the pathophysiologic consequences observed. In studies in animals, transfusion of blood with highly saturated carboxyhemoglobin but minimal free carbon monoxide does not reproducibly result in clinical symptoms. This observation suggests that the small fraction of free carbon monoxide dissolved in plasma has an important role. Recent investigations suggest other mechanisms of carbon monoxide–mediated toxicity. One hypothesis is that carbon monoxide–induced tissue hypoxia may be followed by reoxygenation injury to the central nervous system. Hyperoxygenation facilitates the production of partially reduced oxygen species, which in turn can oxidize essential proteins and nucleic acids, resulting in typical reperfusion injury. In addition, carbon monoxide exposure has been shown to cause lipid peroxygenation (degradation of unsaturated fatty acids), leading to reversible demyelinization of central nervous system lipids.

Carbon monoxide exposure also creates substantial oxidative stress on cells, with production of oxygen radicals resulting from the conversion of xanthine dehydrogenase to xanthine oxidase. Carbon monoxide exposure has an especially deleterious effect on pregnant women, because of the greater sensitivity of the fetus to the harmful effects of the gas. Data from studies in animals suggest a significant lag time in carbon monoxide uptake between mother and fetus. Fetal steady states can occur up to 40 hours after maternal steady states are achieved. The final carboxyhemoglobin levels in the fetus may significantly exceed the levels in the mother. The exaggerated leftward shift of fetal carboxyhemoglobin makes tissue hypoxia more severe by causing less oxygen to be released to fetal tissues. Although the teratogenicity of carbon monoxide is controversial, the risk of fetal injury seems to be increased by carbon monoxide.

CLINICAL SIGNS AND SYMPTOMS

The clinical symptoms of carbon monoxide poisoning are nonspecific and can suggest a broad range of diagnostic possibilities.

The signs and symptoms of nonlethal carbon monoxide exposure may mimic those of a nonspecific viral illness. Since viral illnesses and carbon monoxide exposure both peak during the winter, a substantial number of initial misdiagnoses may occur. Carbon monoxide poisoning often occurs in concert with other medical emergencies, such as smoke inhalation, and may affect many people at the same time. Table 1 shows the variety of acute symptoms reported by patients after exposure to carbon monoxide in a number of clinical series. Patients often present with tachycardia and tachypnea, which are compensatory mechanisms for cellular hypoxia. Headache, nausea, and vomiting are common symptoms. Presyncope, syncope, and seizures may result from cellular hypoxia and cerebral vasodilatation, which can also lead to cerebral edema. Angina, pulmonary edema, and arrhythmias may result from increased cardiac output caused by cellular hypoxia, carbon monoxide– myoglobin binding, and diminished oxygen release. In patients with underlying pulmonary or cardiac disease, the symptoms of their disease may be worsened by impaired oxygen release. The classic findings of cherry-red lips, cyanosis, and retinal hemorrhages occur rarely. Erythematous lesions with bullae over bony prominences have been described but are not specific for carbon monoxide poisoning. Necrosis of the sweat glands is a characteristic histologic feature.The severity of symptoms ranges from mild (constitutional symptoms) to severe (coma, respiratory depression, and hypotension). It is important to recognize that carboxyhemoglobin levels do not correlate well with the severity of symptoms in a substantial number of cases. The duration of exposure appears to be an important factor mediating toxicity. Being in a carbon monoxide–containing environment for one hour or more may increase morbidity. If no dissolved carbon monoxide is present in the plasma, the symptoms can be minimal even with extremely high levels of carboxyhemoglobin, as experiments in animals show. Therefore, the decision whether to administer hyperbaric oxygen therapy cannot be made only on the basis of carboxyhemoglobin levels.

DELAYED NEUROPSYCHIATRIC SYNDROME

Many patients with carbon monoxide poisoning do not have acute signs of cerebral impairment. Delayed onset of neuropsychiatric symptoms after apparent recovery from the acute intoxication has been described 3 to 240 days after exposure. The syndrome is estimated to occur in 10 to 30 percent of victims, but the reported incidence varies widely. Symptoms such as cognitive and personality changes, parkinsonism, incontinence, dementia, and psychosis have been described. No clinical or laboratory results predict which patients are at risk for this complication, but advanced age appears to be a risk factor. Recovery from delayed neuropsychiatric syndrome occurs in 50 to 75 percent of affected persons within one year. Different abnormalities have been shown by computed tomography, molecular resonance imaging, and single-photon-emission computed tomography. The regions most commonly involved include the globus pallidus and the deep white matter. Delayed neuropsychiatric sequelae after exposure to carbon monoxide have been the subject of several reports.

The mechanisms are uncertain, but hypoxia alone is not sufficient to explain the observed clinical manifestations. Postischemic reperfusion injury as well as the effects of carbon monoxide on vascular endothelium and oxygen-radical–mediated brain lipid peroxygenation may also have a role. In addition, nitric oxide liberated from platelets at the time of carbon monoxide exposure has been linked to central nervous system damage.

The possibility of c h r o n i c p o i s o n i n g with carbon oxide are denied by some researchers, but others consider them the result of numerous mild acute poisonings. Patients complain to have a headache, buzzing in the head, dizziness, increased fatigability, irritability, poor sleep, worsening of memory, short-term disorder of orientation, heart beating, dyspnea, states of unconsciousness, disorders of skin sensitivity, hearing and sight. Functional disorders of the central nervous system can be observed, like asthenia, vegetative dysfunction with angiodystonic syndrome, inclination to vessel spasms, and hypertension with further development of a hypertonic disease.

Chronic poisoning causes the development of arteriosclerosis. Possible disorders of a menstrual cycle, generative function among women, as well as unfavorable progress of pregnancy, and weakening of male sex functions. The amount of hemoglobin and erythrocytes increase in the blood, and moderate anemia and reticulocytosis can be observed.

DIAGNOSIS

Because carbon monoxide poisoning has no pathognomonic signs or symptoms, a high level of suspicion, particularly among primary care clinicians and emergency medicine specialists, is essential for making the diagnosis. The measurement of carbon monoxide levels alone may be insufficient to rule out the diagnosis, but in the majority of cases, increased levels of carboxyhemoglobin will be diagnostic. Serum levels of carboxyhemoglobin may already have fallen substantially at the time of presentation to the emergency department. Therefore, elevated carbon monoxide values in the exhaled air of the patients or in the ambient air at the scene of exposure can help confirm the diagnosis. This latter test can be performed by fire departments and should be encouraged. Blood obtained on the scene by emergency medical technicians may also be helpful for confirming the diagnosis. Venous blood samples are adequate for measurements of carboxyhemoglobin, although arterial samples allow for the additional determination of coexisting acidosis. Carboxyhemoglobin has to be measured directly with a spectrophotometer. Pulse oximetry cannot distinguish carboxyhemoglobin from oxyhemoglobin at the wavelengths that are commonly employed by most oximeters (pulse-oximetry gap). When the diagnosis of carbon monoxide poisoning has been established, a detailed neurologic examination and neuropsychological testing should be performed to document neurologic and neuropsychiatric abnormalities, which may be subtle. The Carbon Monoxide Neuropsychological Screening Battery is a frequently used tool that takes 30 minutes to administer and provides a base line for assessing subsequent changes in mental status. Computed tomographic imaging of the head is not helpful in establishing the diagnosis of carbon monoxide intoxication, but it may be used to rule out other conditions that might result in changes in mental status or loss of consciousness in patients presenting to an acute care facility.

TREATMENT

The carbon monoxide–intoxicated patient must first be removed from the source of carbon monoxide production without endangering the health of the rescuing personnel. Firefighters must use breathing apparatus not only to supply oxygen but also to protect against carbon monoxide poisoning. High-flow oxygen, preferably 100 percent as normobaric oxygen, should be administered to the patient immediately. Oxygen shortens the half-life of carboxyhemoglobin by competing at the binding sites of hemoglobin and improves tissue oxygenation. Oxygen should be administered until the carboxyhemoglobin level has become normal. In patients with carbon monoxide poisoning who have been rescued from a fire, special consideration should be given to the respiratory status and the airway, since urgent or prophylactic intubation may be necessary. Most patients can be evaluated and treated in an ambulatory setting. Hospitalization should be considered for patients with severe poisoning, serious underlying medical problems, or accompanying injuries. Patients often have concomitant problems, including smoke inhalation and burns, that require specialized treatment and may necessitate transfer to specialized facilities. Since carbon monoxide may affect others who have been exposed to the same source, appropriate local agencies, usually the fire department, should be alerted to investigate the source of the intoxication and arrange for all other possible victims to be screened.

NORMOBARIC VERSUS HYPERBARIC OXYGEN

Carbon monoxide elimination is related to minute ventilation, the duration of exposure, and the fraction of inspired oxygen (FiO2). The half-life of carboxyhemoglobin is 4 to 6 hours when the patient is breathing room air, 40 to 80 minutes when the patient is breathing 100 percent oxygen, and only 15 to 30 minutes when the patient is breathing hyperbaric oxygen. In 1895 Haldane showed that hyperbaric oxygen prevented carbon monoxide poisoning in mice, and since 1962 hyperbaric oxygen has been used to treat carbon monoxide poisoning. The indications for hyperbaric-oxygen therapy have recently been reviewed. Hyperbaricoxygen therapy hastens the resolution of symptoms. It is unclear whether hyperbaric-oxygen therapy influences the rate of late sequelae or mortality in non–life-threatening carbon monoxide poisoning, since different studies have led to conflicting conclusions. Coma is an undisputed indication for hyperbaricoxygen therapy. Outcome studies of hyperbaricoxygen therapy have not yet identified other circumstances in which this therapy is clearly indicated. The indications for this therapy in patients with mild-to-moderate cerebral dysfunction are particularly disputed. Nonetheless, suggestions are available to help physicians decide whether to administer hyperbaricoxygen therapy (Table 2).

Once the diagnosis of carbon monoxide poisoning has been established, the physician must decide whether hyperbaric-oxygen therapy is indicated, and if so, make appropriate arrangements for a safe transfer to the nearest facility. More than 340 single-occupant chambers are available in the United States. Information on the location and use of decompression chambers is available by telephone from the Divers Alert Network at Duke University at 919-684-8111.Callers should request the Divers Alert Network oncall staff.

PREVENTION

Awareness of the dangers of carbon monoxide and public education are the keys to decreasing morbidity and mortality from carbon monoxide poisoning. Primary prevention is aimed at decreasing production of and exposure to carbon monoxide. The Environmental Protection Agency and the Occupational Safety and Health Administration provide regulations and suggestions, and general information is easily available from sources such as the American Gas Association. In particular, the current regulations of the Occupational Safety and Health Administration prohibit the exposure of workers to carbon monoxide levels exceeding 35 ppm, averaged over an 8-hour workday, with an upper limit of 200 ppm over a 15-minute period. Fuel-burning heating systems require regular professional maintenance and appropriate ventilation. Motor vehicles should not remain in enclosed spaces with the engine running, and the exhaust pipe must be free of obstructions (particularly snow and leaves). Outdoor gas grills should not be operated indoors. Media campaigns should warn the public about the dangers of carbon monoxide at times of increased risk, such as anticipated cold spells and snowstorms. Members of minority groups and non–English-speakers are at greate risk, and public education must be tailored to reach these parts of the population. Secondary prevention efforts should be aimed at warning people about potentially harmful carbon monoxide concentrations in the environment. Although carbon monoxide detectors are inexpensive and widely available, they should not be considered a substitute for proper maintenance of appliances. There are currently no standard recommendations regarding their use in the home or the workplace.

Verification of work ability. After treating of patients with acute poisoning of mean form in hospital, they are provided with an occupational sick leave and they stay under observation. Depending on the presence of severity of complications, their work ability can be limited, what conditions the invalidism of the occupational character. Patients with initial signs of chronic intoxication are promoted to another job with the provision of an occupational sick leave for two months. In case of little effectiveness of the conducted treatment and preventive measures or marked symptoms, it is recommended to promote the patient to another job permanently with possible invalidism group on the occupational disease.

III. INTOXICATION BY LEAD

(lead properties, industrial uses, pathogenesis of lead poisoning, clinical picture, diagnosis, preventive measures, management of lead poisoning)

Lead poisoning existed and was already known in Antiquity but was forgotten, at least in the literature, until the end of the Middle Ages, where it was mentioned sporadically. In the 19th century this disease, which reached epidemic dimensions during the period of industrialization, was ``rediscovered.'' Several comprehensive clinical articles appeared in the literature. The clinical picture deepened during the beginning of the 20th century, and preventive efforts were started. However, the concept of poisoning remained strictly clinical. During the latter half of the 20th century a new concept emerged: subclinical and early forms became recognized as undesirable effects. This led to a substantial lowering of hygienic standards. Pediatric poisoning has also been a serious problem during the 20th century. After the 1920s, environmental pollution by lead caused by the introduction of tetraethyl lead in gasoline became an alarming public health problem. The use became restricted in the 1980s; its effects on blood lead levels are now evident. Today's research focuses on the effects of low exposure, often with the aim of de®ning noneffect levels for different types of effects

Physical Properties

— Lead (Pb) has been used by humans for at least 7000 years, because it is widespread, easy to extract, and easy to work with. It is highly malleable and ductile as well as easy to smelt.

— Lead’s elemental symbol Pb, is an abbreviation

of its Latin name plumbum .

— Metallic lead (Pb0) is resistant to corrosion and can combine other metals to form various alloys(Lead alloys are used in batteries, shields from radiation, water pipes, and ammunition)

— Inorganic Lead

— Organic Lead

Lead has no known biological function.

More industrial workers are exposed to lead than to any other toxic metal. Lead is used widely in a variety of industries because of its properties : (1) low boiling point (2) mixes with other metals easily to form alloys (3) easily oxidised and (4) anticorrosive. All lead compounds are toxic - lead arsenate, lead oxide and lead carbonate are the most dangerous; lead sulphide is the least toxic.

Short hystory

— 6200 BC. - Lead discovered in Turkey, first mine.

— 500 BC-300 AD.- Roman lead smelting produces dangerous emissions.

— 100 BC. - Greek physicians give clinical description of lead poisoning. "Lead makes the mind give way."

— 1904 - Child lead poisoning linked to lead-based paints.

— 1922 - League of Nations bans white-lead interior paint; U.S. declines to adopt

— 1923 - Leaded gasoline goes on sale in selected markets

— 1971- U.S. Lead-Based Paint Poisoning Prevention Act passed

— 1986 - Primary phase out of leaded gas in US completed

INDUSTRIAL USES

Over 200 industries are counted where lead is used - manufacture of storage batteries; glass manufacture; ship building; printing and potteries; rubber industry and several others.

Rubber workers in mill room

Foundry workers may be exposed to a complex mixture of carcinogenic agents in fumes

Smokestack industry - global relocation to the poorest countries

NON-OCCUPATIONAL SOURCES

The greatest source of environmental (non-occupational) lead is gasoline. Thousands of tons of lead every year is exhausted from automobiles. Lead is one of the few trace metals that is abundantly present in the environment. Lead exposure may also occur through drinking water from lead pipes; chewing lead paint on window sills or toys in case of children.

Lead has multiple toxic health effects—haematological, renal, and neurological—although at typical levels of exposure in the environment, neuropsychological impacts are the main concern, especially for developing children. Aside from local contamination or pollution, exposure to lead has been quite widespread from dissolution into drinking water from lead piping, use of lead in paint in old houses, and airborne exposure from leaded petrol. In addition, people have been exposed via their food from the use of lead solder for sealing cans, although this has now been completely phased out. However, the other sources still lead to exposure. Although the use of lead additive in petrol has virtually ceased, there is still much dust on roadsides from past use and this is resuspended or picked up by children; lead present in paint in older houses remains an important source as it is chipped off through normal wear and tear; again in older dwellings, lead pipes in the home or connecting with the main water supply can be a source, with solubility depending on the chemistry and pH of the water supply. Research into the effects of lead exposure on children’s neurological development measures their intelligence quotient and emotional and behavioural development.

Children are more vulnerable to occupational disease—they are smaller, have the potential to be exposed for many years, and their tissues are more sensitive. They are also more likely to be exploited and, being less aware, more accident prone.

IN CHILDREN, A DOUBLING OF BODY LEAD BURDEN 10–20 MCG/DL IS ASSOCIATED WITH A DEFICIT OF 1–2 FULL SCALE IQ POINTS

Lead smelter—the starting point of dissemination of a toxic metal

MODE OF ABSORBTION

Lead poisoning may occur in three ways :

(1) INHALATION : Most cases of industrial lead poisoning is due to inhalation of fumes and dust of lead or its compounds.

(2) INGESTION : Poisoning by ingestion is of less common occurrence. Small quantities of lead trapped in the upper respiratory tract may be ingested. Lead may also be ingested in food or drink through contaminated hands

(3) SKIN : Absorption through skin occurs only in respect of the organic compounds of lead, especially tetraethyl lead Inorganic compounds are not absorbed through the skin.

BODY STORES

The body store of lead in the average adult population is about 150 to 400 mg and blood levels average about 25 μg /100 ml. An increase to 70μg/100 ml blood is generally associated with clinical symptoms. Normal adults ingest about 0.2 to 0.3 mg of lead per day largely from food and beverages.

DISTRIBUTION IN THE BODY

Ninety per cent of the ingested lead is excreted in the faeces. Lead absorbed from the gut enters the circulation, and 95 per cent enters the erythrocytes. It is then transported to the liver and kidneys and finally transported to the bones where it is laid down with other minerals. Although bone lead is thought to be 'metabolically inactive', it may be released to the soft tissues again under conditions of bone resorption. Lead probably exerts its toxic action by combining with essential SH-groups of certair enzymes, for example some of those involved in prophyrin synthesis and carbohydrate metabolism. Lead has an effect on membrane permeability and potassium leakage has been demonstrated from erythrocytes exposed to lead. Inorganic lead is toxic to the testis in animal experiments. A wide spectrum of adverse effects has been reported on the reproductive function in male experimental animals, including suppression of spermatogenesis, changes in hormone levels and changes in testicular morphology. Most of these studies have been performed following chronic lead exposure, at levels comparable to those in the occupational environment. In studies where lead is given in doses close to the tolerable maximum, some of the results may be explained by non-specific toxic effects due to the general stress response. Based mainly on animal models, the biologic rationale for the adverse effects is that lead (and some other toxic metals, such as cadmium or mercury) may partially replace zinc, which is an important component of semen and is needed for sperm head stabilization. Lead has induced changes in the stability of mouse sperm chromatin. Because of the genotoxic potential of lead, the possibility that reproductive capacity may be influenced also by direct changes in the genetic material, e.g. by induction of chromosomal aberrations - particularly in heavy paternal exposure - cannot be ruled out. Some of the alterations in the reproductive function at low lead levels are presumed to result from the lowering of the serum and intratesticular testosterone levels. The adverse effects of occupational lead exposure on human sperm have been documented in several studies. Semen ana lysis of workers whose exposure level has been monitored with blood lead concentrations (B-Pb) has shown dose-dependent reductions in the motility, morphology, viability and sperm count. Some functional hormonal and other biochemical effects influencing the production of sperm and semen - such as decreased libido, reduced testosterone, defects in thyroid function and testicular dysfunction - have also been reported. The adverse effects are well manifest in exposure, corresponding roughly to B-Pb levels from 2.0 to 2.4 umol/1 upwards. There is no systematic information available as to the critical exposure level. A study of storage battery workers in Romania reported significantly increased frequencies of asthenospermia, hypospermia and teratospermia when B-Pb levels ranged from 2.0 umol/1 to 3.6 umol/1. Non-significanlly increased frequencies of asthenospermia and hypospermia were seen in a group of workers whose lead exposure stemmed from the polluted environment (current mean B-Pb 1.0 umol/1). Further studies are warranted for the low exposure level. On the other hand, it has been documented that at very low exposure levels (say, B-Pb < 0.5 umol/1) seminal plasma lead does not correlate with the concentration of lead in the blood, and that the concentrations of lead in the seminal plasma are much lower than in the blood. This suggests that there probably are no major direct genetic effects through semen at very low concentrations of lead. The lead concentrations in the seminal plasma are higher than those in the blood at higher exposure levels, as seen in heavy occupational exposure. Only a limited number of epidemiological studies have been performed on the associations between paternal exposure to lead and adverse reproductive outcome. Three studies have reported an increase in the risk of spontaneous abortion following paternal exposure to lead. Although there is suggestive evidence for a positive association, at least at high exposure levels (B-Pb 2.0-2.4 umol/1 or more), firm conclusions cannot be drawn, due to the small number of exposed cases and difficulties in controlling the potential confounders or effect modifiers. Two of the studies have suggested effects for B-Pb 1.0 or 1.2 umol/1. Two epidemiological studies have reported that paternal exposure to lead increases the risk of deaths in the perinatal period - late abortion, stillbirth and early neonatal death. There is also some weak evidence that paternal lead may increase the risk of congenital malformations in the offspring. Studies on cancer in the offspring have also implicated effects for exposure to heavy metals including lead. Due to the poor information on specific exposures, the available data do not, however, allow reliable identification of the specific aetiological agents. Most of the studies on lead have been performed among lead smelters or battery manufacturers. Elevated concentrations of lead (whether metallic lead or lead compounds) which could be potentially harmful for the male reproductive function have been documented in several other industries or jobs as well, such as in founding, casting, scrapping, welding, and torch-cutting of leaded metals; car repair and service; glass and pottery manufacture; indoor shooting ranges and stevedoring work; spray painting; and in the use and disposal of various other chemicals. Historical descriptions of the reproductive outcome of women exposed to high levels of lead include high rates of miscarriage, neonatal mortality, premature babies and low birth weight. Recent studies among women occupationally exposed to lead have indicated no decrease in fecundability in terms of time to pregnancy, nor an increased risk of spontaneous abortions. The level of the exposure, as measured by blood lead concentrations, is low at present; therefore, the results do not disagree with the reported harmful effects at earlier high exposure levels – lead compounds were formerly used as an abordifacient. Lead is transferred across the placenta during the 12th to 14th weeks of pregnancy. At birth the blood lead concentration (B-Pb) in the umbilical cord of the child is close to that of the mother. The fact that placental transfer of lead takes place after organogenesis gives biological plausibility to the findings: lead does not cause major birth defects, but an increased risk of minor anomalies has been reported. There is also evidence of outcomes such as low birth weight, prematurity and impaired cognitive development in children exposed to lead during gestation. The risk of worsened postnatal mental development and intrauterine growth retardation may increase when the B-Pb prenatally is 15 ug/dl or more (0.7 umol/1); the risk of lowered birth weight may occur at prenatal B-Pb level of 25 ug/dl (1.2 umol/1). These levels are rather low and do not exceed the work environment limit values. Lead may be mobilized from bones to blood during pregnancy and lactation, and female workers should also avoid heavy exposure before pregnancy. In Finland, it is recommended that the blood lead level of pregnant women should not exceed 0.3 umol/1 (6.2 ug/dl), which is the reference value of the non-occupationally exposed female population.

CLINICAL PICTURE :

Cardinal used to be characteristic for chronic intoxication with lead – lead border (dark gray, and sometimes, violet-flaky narrow line along the end of jaws) and the lead coloration (sallow gray color of a face) – now due to the improvement of the environment at the production, connected with lead; they lost their diagnostic meaning. Chronic intoxication with lead can be characterized with mostly affection in the blood system, affection of the nervous system and gastrointestinal tract. Changes of biochemical indications in the blood, caused by the intoxication with lead, comprise disorders of porphyrinic exchange; first of all aminolevulate- dehydrase reacts when an increased amount of lead gets into the organism, the activity of which in erythrocytes decreases; the content of aminolevulinic acid, protoporphyrin and coproporphyrin increase in erythrocytes, which are considered the most reliable and specific sings of poisoning. The detected dependence of the expression of changes of porphyrinic exchange from the degree of the impact of lead. its content in blood and the severity of poisoning. Changes in the morphological pattern of blood – reticulocytosis, increase of the amount of basophile-grainy erythrocytes – refer to non-specific signs of saturnism, their diagnostic value is insignificant. Anemia at saturnism belongs to the group of hypochromic anemia, as its characteristic sign is hypochromia of erythrocytes at the increased content of iron in the blood serum (the so-called sideroachrestic anemia). In its development, a significant part is played by the direct impact of lead to erythrocytes, what leads to the reduction of the long term of their life. In the clinical pattern of the chronic lead intoxication, three stages can be distinguished:

Initial form of the chronic lead intoxication can be characterized by the absence of clinical signs and is determined based on the so-called laboratory symptoms of the intoxication. The content of aminolevulinic acid in the urine achieves 15 mg per one gram of creatine and coproporphyrin- 300 mkg per one gram of creatine. The level of lead in blood does not usually exceed 500 mkg/l, and in the urine – 100 mkg/l; reticulocytosis – up to 20 – 25 %, the amount of basophile-grainy erythrocytes increases up to 35 %.

Mild form of chronic lead intoxication is characterized by the joining of clinical symptoms. At this form of intoxication, the initial form of polyneuropathy can be diagnosed. Here, vegetative-trophic disorders can be diagnosed: pain, parasthesia, the feeling of numbness in limbs, especially at night at rest. Objectively at the neurological examination, the change of coloration of the skin on fingers can be observed (light cyanosis or paleness of the skin), hyperhydrosis, hypothermia, symmetrical distant disorders of the sensibility, first in the form of hyperstesia, and then – hyperstesia, muscular hypotonia, dormancy of dermatographism, labiality of arterial pressure, and tendency to bradycardia. The decrease of the excitement of olfactory, gustatory and visual analyzers can be observed. Changes in gastrointestinal tract at the mild form of chronic lead intoxication are expressed through the affection of stomach secretion (increase or decrease), processes of adsorption into the intestines, intestinal mobility with the development of dyskinetic syndrome. Functional disorders of the liver are possible.

Disorders of biochemical indicators at this form of intoxication of the lead are more marked: the content of aminolevulinic acid and coproporphyrin in urine can increase up to 25 mg and up to 500 mkg per 1 g of creatine correspondingly, the content of lead in blood, as a rule, does not increase 800 mkg/l, and in urine it reaches up to 150 mkg/l; reticulocytoosis – up to 40 %0, and the number of erythrocytes with basophile grains – up to 60 %0. Some decrease of the content of hemoglobin is possible.

Marked form of chronic intoxication with lead is characterized by the development of marked polyneuropathy, at this with sensitive disorders, movement disorders can be observed, and asthenovegetative disorders can develop.

The classical form of polyneuritis at the lead impact onto the body of a worker is the so-called antebrachial type of the paralysis. The syndrome is characterized by the major affection of extensors of hands and fingers (Fig. 4). The process starts with the affection of bending extensor of fingers, and later it is accompanied by paresis of other finger extensors and hands, which stays in the position at right angle in a semi prone position. Fingers are bent; a thumb bends towards the palm (the so-called “hanging hand”).

Sensitive and movement forms of polyneuritis at lead intoxication.

At the marked form of chromic intoxication with lead, the following can be observed very often: the so-called lead colic, which is expressed with fit-like pain in the abdomen, persistent constipation (the duration can be up to 10 – 14 days), which cannot be cued by laxative preparations; increase of arterial blood pressure, often with bradycardia, increase of the body temperature, as well as moderate leukocitosis and dark red color of the urine (due to the excretion of a big number of porphyrin). Sometimes, lead colic is accompanied by the affection of urinary tracts, and it develops as kidney colic. It is necessary to take into the consideration the possibility of the development of atypical vague forms of lead colic, progressing of which takes place during a long period of time in a wave-like form (from 3 to 4 months) and which are characterized by less marked clinic pattern and laboratory symptoms. Recently, new data have been collected as to the mechanism of the development and progressing of lead colic. It is considered that at the action of lead onto the organism, autoantibodies are created, which, even before the appearance of clinical indications of the lead intoxication assist to the development of immune complexes. Autoantibodies appear in the result of changes of antigenicproperties of erythrocytes due to metabolic disorders at the formation of heme or at the expense of creation of metal protein. These immune complexes, as well as erythrocytes with antigenic properties circulate in the peripheral blood, and first they affect normal blood provision in organs (at the expense of “plugging in” capillaries). It is caused by the disorder of microcirculation of organs and conditions a pain syndrome.

Nowadays under production conditions, lead colic starts gradually, with prodrome: increased fatigability in the end of a work day; general indisposition; pain in cortical bones, muscles and in the waist zone; loss of appetite, inclination to delaying of bladder emptying, irritability and sleep disorder. Sometimes, these phenomena appear together with pain in the stomach, which increase much and get cutting character. For the marked form of chronic lead intoxication, the development of the anemic syndrome with the decrease of the level of hemoglobin lower than 130 g/l in men and 120 g/l in women is characteristic.

At the prologuned contact with lead, affection of the determined portions of bones and limbs can be noted: appearance of homogeneous levelly darkened intensive shadows in the metaphases in long cortical bones, which are much separated from the diaphyses of bones. Changes in the bone tissue at the intoxication with lead are not accompanied by the destructive processes, changes in periosteum are absent. Mostly, large and small cannon-bones, hip, shoulder, elbow and spoke bones, as well as ribs are affected.

Biochemical disorders at the marked intoxication with lead are the most expressed. The content of the aminolevulinic acid and coproporphyrin in the urine is over 25 mg and over 500 mkg per 1 g of creatinine correspondingly. The concentration of lead in blood achieves 800 mkg/ and higher, and in the urine 0 over 150 mkg/l; reticulocytosis is higher than 40 ‰; and the number of basophile-grain erythrocytes is over 60 ‰.

Positive patch tests to acrylates in a worker who glued lead flashing onto window units. She had developed an allergic contact dermatitis affecting the hands. In such a situation, two way communication can be beneficial to the patient - a patient may see their general practitioner for hand dermatitis, and liaison with the occupational health department may help identify the cause.

DIAGNOSIS

Diagnosis of lead poisoning is based on :

(1) HISTORY: as history of lead exposure

(2) CLINICAL FEATURES : such as loss of appetite, intestinal colic, persistent headache, weakness. abdominal cramps and constipation, joint and muscular pains, blue line on gums, anaemia, etc.

(3) LABORATORY TESTS : (a) Coproporphyrin in urine (CPU) : Measurement of CPU is a useful screening test. In non-exposed persons, it is less than 150 microgram/litre. (b) Amino levulinic acid in wine (ALAU): If it exceeds 5 mg/litre, it indicates clearly lead absorption. (c) Lead in blood and urine : Measurement of lead in blood or urine requires refined laboratory techniques. They provide quantitative indicators of exposure. Lead in urine over 0.8 mg/litre (normal is 0.2 to 0.8 mg) indicates lead exposure and lead absorption. A blood level of 70 μg/ 100 ml is assosiated with clinical symptoms, (d) Basophilic stiplng of RBC : is a sensitive parameter of the heamatological response.

PREVENTIVE MEASURES :

(1) Substitution : That is, where possible lead compounds should be substituted by less toxic materials.

(2) Isolation : All processes which give rise to harmful concentration of lead dust or fumes should be enclosed and segregated.

(3) Local exhaust ventilation: There should be adequate local exhaust ventilation system to remove fumes and dust promptly

(4) Personal protection : Workers should be protected by approved respirators.

(5) Good housekeeping : Good housekeeping is essential where lead dust is present. Floors, benches, machines should be kept clean by wet sweeping.

(6) Working atmosphere : Lead concentration in the working atmosphere should be kept below 2.0 mg per 10 cu. metres of air, which is usually the permissible limit or threshold value.

(7) Periodic examination of workers : All workers must be given periodical medical examination. Laboratory determination of urinary lead, blood lead, red cell count, haemoglobin estimation and coproporphyrin test of urine should be done periodically. Estimation of basophylic stippling may also be done. An Expert Committee of the WHO states that in the case of exposure to lead, it is not only the average level of lead in the blood that is important, but also the number of subjects whose blood level exceeds a certain value (e.g., 70μg/ml or whose ALA in the urine exceeds 10 mg/litre)

(8) Personal hygiene : Hand-washing before eating is an important measure of personal hygiene. There should be adequate washing facilities in industry. Prohibition on taking food in work places is essential.

(9) Health education : Workers should be educated on the risks involved and personal protection measures.

MANAGEMENT

Oral Chelation Therapy

2,3 Dimercaptosuccinic Acid (DMSA, Succimer)

Succimer is an orally chelating agent that is commonly used for the treatment of blood lead concentrations above 45 mcg/dL in the United States. It is a water soluble analog of dimercaprol. However, it has a wider therapeutic index and has advantages over dimercaprol and CaNa₂ EDTA.

Pharmacology and pharmacokinetics: Succimer is a four carbon molecule with two carboxyl groups and two sulfur groups. Lead and cadmium bind to adjoining sulfur and oxygen atoms whereas arsenic and mercury bind to both sulfur atoms resulting in a pH dependent water-soluble compound.

The pharmacokinetics of succimer have been assessed in primates and humans. In primates, the absorption has been shown to be rapid with the time to peak concentration occurring within 1-2 hours. In adult human volunteers, the peak concentration occurred in 3.0 + 0.45 hours after 10 mg/kg dosing orally. DMSA has been found to be, primarily, albumin-bound in plasma through a disulfide bond with cysteine with very little remaining unbound. It is unknown if protein bound DMSA is able to bind lead.

While DMSA is primarily distributed in the extravascular space, nonhuman primate models have shown that the volume of distribution is greater than plasma volume and estimated to be 0.4 L/kg.

DMSA is metabolized in humans to mixed disulfides of cysteine. Only 20% of the administered dose was eliminated unchanged in the urine after oral dosing compared to 80% after intravenous dosing. However, fecal elimination (nonabsorbed drug and biliary elimination) was not assessed.

In addition, enterohepatic recirculation of the parent compound and its metabolites are suspected to occur. The majority of the elimination occurs within 24 hours and as DMSA-cysteine disulfide conjugates. Renal clearance is greater in healthy adults than in children or adults with lead poisoning. The elimination half-life in nonhuman primates is 35 and 70 minutes for the parent and parent plus metabolites, respectively.

Dosing: While few studies have been performed to determine appropriate dosing in humans, only one pediatric study is available. Oral DMSA at 30 mg/kg/day (1050 mg/m²/day) was used and based on previous adult studies. This dose in children produced significantly (p<0.0001) greater lead excretion than 10 mg/kg/day (350 mg/m²/day) or 20 mg/kg/day (700 mg/m²/day). The current recommended dose for DMSA in the United States for children is 30 mg/kg/day for 5 days followed by a 14-day course of 20 mg/kg/day to prevent or blunt the rebound of the blood lead concentration. However, the duration of dosing has been controversial. In a study of 19 lead poisoned children, the DMSA dosing was randomized to include 30 mg/kg/day for 5 days followed either by no chelation, DMSA 10 mg/kg/day for 14 days or DMSA 20 mg/kg/day for 14 days. Rebound blood lead concentrations were noted in all groups, but was less for the 20 mg/kg/day group. However, there was no difference in the mean blood lead concentration between any groups at 2 weeks implying that there may not a benefit for an extended course of therapy. A second study (n=11) compared the effect of the traditional 19-day DMSA course and two 5-day courses (30 mg/kg/day) separated by a week. Blood lead concentrations were obtained at the time of chelation and 4 weeks after treatment. No difference between groups was noted showing that two 5-day courses of DMSA (30 mg/kg/day) may be comparable to the 19-day course. Limitations to both studies exist including the small sample sizes and failure to obtain urine lead excretion tests to assess for efficacy.

Efficacy: The precise nature of the lead-chelating moiety is not known. Thus, the assessment of the efficacy of a chelating agent is difficult to determine. The blood lead concentration is the most widely used “biomarker” to assess for efficacy of DMSA. It assesses the concentration of lead in the vascular compartment and may be considered a continuum to the soft tissues. As the blood lead concentration is what treatment is based, it aids the practitioner on the “success” of the chelation therapy. However, this laboratory value does not measure total body burden (e.g. deep tissue stores and bone).

Racemic-2,3-dimercapto-1-propanesulfonic acid (DMPS, Unithiol, Dimaval)

DMPS is a chelating agent that is related to dimercaprol and DMSA. It is water soluble and is reported to be less toxic than dimercaprol. It is available for oral, intravenous and intramuscular use for the treatment of mercury, arsenic, lead, chromium and copper (Wilson’s Disease) poisoning. Currently, it is not FDA approved in the United States, but is used more commonly in the Soviet Union and Europe.

Dosing: Different dosing is required depending on the heavy metal toxicity. As DMPS is primarily used for the treatment of arsenic and/or mercury poisoning, more information is available with different dosing parameters. Oral doses of 200 to 400 mg in 2-3 divided doses increase the mercury excretion and reduce the body burden in adults.

DMPS has been shown to be effective when copper levels are elevated and has been dosed as single oral dose of 300 mg daily or 100 mg three times daily for up to 15 days in adults. Little data is available regarding its use in children. However, for the treatment of lead poisoning in children, the oral daily dose of 200 to 400 mg per meter squared BSA has been used safely.

Efficacy: Few studies are available comparing the efficacy of DMPS to other chelating agents. One animal study found that administration of CaNa2EDTA or DMSA was more effective than that of DMPS. In addition, the combination of CaNa2EDTA and DMSA was more efficient than that of CaNa2EDTA and DMPS or the individual chelators in enhancing urinary/fecal excretion of lead. The brain lead was depleted by DMSA only. In addition, DMPS has been found to be an equally effective chelator for other heavy metals such as arsenic and bismuth.

Penicillamine:

Penicillamine is a D-B, B-dimethylcysteine, a penicillin degradation product. It is a potent gold, lead, mercury, zinc and copper chelator and is the drug of choice for treating Wilson’s disease. It has been used since 1957 for the treatment of lead poisoning and was the only oral chelator for lead until the availability of DMSA. However, it is not FDA approved in the United States. Its sulfhydryl group combines with lead to form ring compounds increasing elimination. In addition, it has been used to treat cystinuria and rheumatic disorders.

Dosing: The dose for penicillamine was, largely, established during the treatment of toxicity from other heavy metals such as arsenic and copper. An early case report documented the effectiveness of D-penicillamine in three children with arsenic poisoning treated with 4 daily doses of 25 mg/kg/dose. The standard dose for the treatment of lead poisoning used similar daily dosing at 25 to 30 mg/kg/dose for several months. However, a further study by Shannon and Townsend showed similar effectiveness at a lower daily dose of 15 mg/kg/dose with decreased adverse reactions. Currently, the most commonly used dose in the United States is 30 to 40 milligrams/kilogram/day or 600 to 750 milligrams/square meter/day for 1 to 6 months, given 2 hours before or 3 hours after meals.

Efficacy: In an early study of occupational exposed workers, the efficacy between IV CaNa₂EDTA was compared to oral penicillamine and oral CaNaEDTA. While all three agents increased the urinary excretion of lead in the workers, the greatest elimination of lead occurred with the IV formulation. As penicillamine was the only oral chelation therapy available for a number of years, early studies assessed exposed patients and the efficacy of penicillamine compared to placebo. In a retrospective cohort study, penicillamine was found to decrease the blood lead concentration by 33% compared to no significant change in the placebo group. Studies have not been performed to compare the efficacy between penicillamine and DMSA or DMPS. However, it has been found to be at least as effective as dimercaprol and EDTA

From http://www.who.int/selection_medicines/committees/expert/18/applications/4_2_LeadOralChelators.pdf

Verification of the ability to work. The issue on verification of the ability to work at saturnism is solved depending on the expression of poisoning. At the initial form of intoxication, it is necessary to promote a person to another temporary workplace beyond the contact with lead for 1 to 2 months. In future, such patients can return to the same workplace (under condition of complete normalization of indicators of porphyrin exchange). In case of relapses of the intoxication, the worker has to terminate the contact with lead completely. At the expressed form of intoxication, patients should be released from work with lead completely, even when complete disappearing of signs of saturnism can be observed in the result of treatment.

Preventive measures. The most effective preventive measure is, certainly, replacing lead and its compounds with other non-toxic matters at corresponding productions. Maximum mechanization of operations of processing of materials which contain lead; sealing-in of sources of dust discharge; equipping of production zones with rational ventilation, mechanical purification of work premises from dust. In premises with much dust, people should work in respirators or industrial filtering gas masks. When working with lead and its compounds, it is necessary to keep closely to the rules of personal hygiene, prohibit eating at work places; smoking should be permitted only on specially equipped rooms. Significant role in prevention of intoxication with lead is on preventive eating products with pectin matters (fruit non-clarified juices and apples), as well as preliminary and periodic medical examinations.

Case report

Appendectomy due to lead poisoning: a case-report

S Mohammadi, AH Mehrparvar and M Aghilinejad

(Source: Journal of Occupational Medicine and Toxicology 2008, 3:23 doi:10.1186/1745-6673-3-23)

Patient is a 41 year-old married male (with 3 children, the eldest being 7) living in Tehran. His medical history did not show any other disease or hospitalization. He is a heavy smoker (about 30 pack-year). He has been working as an operator of a machine used to cut and finish lead plates for 14 years in a battery-manufacturing plant. He used to work in a lead smelting plant for 2 years before his current job. He has had severe abdominal colic since 4 months ago. He was admitted in a hospital with the diagnosis of appendicitis and underwent an appendectomy operation (pathology revealed normal tissue of appendix) without any improvement in symptoms. He has also had other symptoms including headache, lethargy, fatigue, irritability, insomnia, muscle pain (especially in the legs), consti pation, decreased libido, nausea, vomiting, tremor, loss of appetite, and weight loss. After discharge from hospital without any improvement, he was referred to occupational medicine clinic of Tehran University of Medical Sciences with suspicion of lead intoxication by an occupational medicine specialist who was in charge of medical examinations of the workers inthat plant.

When we visited him, he had the aforementioned abdominal pain. Upon physical examination he was afebrile (37.2°C oral) with respiratory rate of 14/min and pulse rate of 82/min. His blood pressure was 145/90 mmHg. His conjunctivae were pale; he had a mild tenderness in deep abdominal palpation and a surgery scar on his right lower quadrant. Blood test revealed a blood lead level of 118 μg/dl. However, he didn't have any other symptoms such as lead lines or symptoms related to neuropathy. The results of other laboratory tests are as follows:

Three months after appearance of symptoms: WBC 6.8 × 10³, RBC 4.3 × 10⁶, Hb 10.9, Hct 35.1, MCV 80.1, MCH 24.9, MCHC 31.1, PLT 255 × 103. One month later (after admission): Hb 9.7, Hct 29.8, MCV 81, MCH 26.4, MCHC 32.5. He was treated with continuous IV infusion of CaNa2-EDTA 1 g Bid for 5 days. During treatment his renal function was evaluated on a daily basis. After starting the treatment his symptoms improved and he was discharged from hospital. After 2 weeks his blood lead level was 38.3 μg/dl. Upon complete recovery he returned to his job at his former workplace.

REFERENCES

1. 1. Davidson’s Principles and practice of medicine (21^st revised ed.) / by Colledge N.R., Walker B.R., and Ralston S.H., eds. – Churchill Livingstone, 2010. – 1376 p.

2. Harrison’s principles of internal medicine (18^th edition) / by Longo D.L., Kasper D.L., Jameson J.L. et al. (eds.). – McGraw-Hill Professional, 2012. – 4012 p.

3. The Merck Manual of Diagnosis and Therapy / Edited by Robert S. Porter., 19th Revised edition. - London: Elsevier Health Sciences, 2011. – 3754 p.

4. Kostyuk I. and Kapustnyk V. Translated from the Ukrainian by Occupational Diseases: Manual. – Kharkiv: Osnova, 2005. – 400 p.

5. Second national report on human exposure to environmental chemicals. Atlanta: Centers for Disease Control and Prevention, 2003. (Accessed October 6, 2003, at http:// www.cdc.gov/exposurereport/.

6. ABC of occupational and environmental medicine. Second edition / edited by David Snashall. – 2003. – p. 177-223.

7. Kuziv P.P., Bodnar L. P., Pokynchereda V.V. Professional diseases. - Ternopil, 2003. – 296 p.

8. K. Park. Park’s textbook of preventive and social medicine. – India. – 2005. – 711p.

9. Kostyuk I. and Kapustnyk V. Translated from Ukrainian. Occupational Diseases: Manual.- Kharkiv: Osnova, 2004.- 400 p.

10. Web -sites:

a) http://emedicine.medscape.com/

b) http://meded.ucsd.edu/clinicalmed/introduction.htm

c) http://www.cdc.gov