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[100 years of lead poisoning studies from a reading of articles published in La Medicina del Lavoro].

In preparing this paper we considered the articles published in La Medicina del Lavoro from 1901, its first year of publication. This scientific journal was founded in Milan, when an animated debate arose in Italy on the necessity of treating and, above all, preventing occupational diseases. In the same city, the "Clinica del Lavoro" (i.e. Institute of Occupational Medicine) was inaugurated in 1910. Its founder, Professor Luigi Devoto, had to overcome numerous obstacles caused by the hostility of the Rector of the University of Pavia--the future Nobel prize winner Camillo Golgi--and the clinicians of the main hospital of Milan, founded by Francesco Sforza in the XV century. From reading a century of articles which appeared in La Medicina del Lavoro, it is clear that for occupational physicians lead is an exemplary topic by which to evaluate the evolution of research in the field of occupational diseases. The numerous pathological features of lead poisoning, the successive therapeutic responses of physicians, and the gradual development of preventive techniques constitute a paradigm that has subsequently been applied to all other fields of industrial toxicology. Reading the papers of 100 years gives a clear picture of the evolution of clinical syndromes over the decades. The pathological picture of lead poisoning gradually became less serious and progressively changed into aspecific, subclinical manifestations. The categories of workers in which lead poisoning had a high incidence changed over the years: painters, printers and munition makers had the highest incidence in the first three decades of this century; afterwards, those engaged in lead smelting, alloy production, painters, and in the last few decades those employed in battery, ceramic and PVC production. Prevention consisted mainly of early diagnosis of lead poisoning and instruction in proper hygiene measures. Later, in 1929, insurance of occupational diseases was made compulsory in Italy, and among the few risk factors covered by law were lead and its compounds. This law was a great advance not only in the diagnostic and insurance fields but also for prevention. Two aspects of occupational lead poisoning are particularly instructive: treatment on the one hand and the use of laboratory analysis on the other. In treatment, the initial approach was mainly empirical and physicians insisted on evacuation of the bowel. Laboratory analysis started in the 20's with analysis of erythrocytes with basophilic stippling and continued with the study of urinary porphyrins. This was followed by the determination of lead in blood and urine. These tests were used initially as diagnostic tools, and only since the 60's they have been used for biological monitoring of workers for preventive purposes. The identification of indicators of dose, of critical/subcritical effect, and of critical organ started with studies on lead poisoning. Since then, following this model, biological monitoring has been applied to numerous other metals, solvents, and pesticides. The evaluation of the Italian scientific literature on lead over one hundred years in La Medicina del Lavoro has been a very exciting experience. It suggests that knowledge of the evaluation of lead poisoning and lead exposure should be taught to medical students and young physicians, thereby stimulating them to put into practice the maxim that was engraved on the foundation stone of the Clinica del Lavoro: in aliis vivimus, movemur et sumus.

History, 20th Century↗

[Earthenware and lead poisoning. Description of a case].

A case of acute lead poisoning caused by drinking wine that had been kept in a decorative amphora is reported. Chomico-physical analysis of the internal surface of the recipient evidenced a layer of lead paint very soluble in wine. It is hoped that this report will draw the attention of the practising physician and Preventive Medicine Departments to this unusual cause of saturnism. The craft production of earthenware recipients that have been inadequately glazed and their improper use as containers of drings of foods could be commoner than might be thought on the basis of the sporadic reporting of such cases of lead poisoning.

Adult↗

Lead poisoning in cattle and its implications for food safety.

The lead poisoning incidents in cattle investigated by the Veterinary Laboratories Agency between 1990 and 2003 are reviewed. Lead poisoning was most commonly encountered in young calves, but cattle of all ages were affected. The lead was derived mainly from lead paint, lead accumulator batteries and lead in soil from old mine workings. Paint was responsible for the majority of cases of poisoning in young calves; yearling animals were most at risk from discarded batteries, and adult cows were most commonly poisoned by geochemical sources of lead. There was a marked seasonal incidence, with most cases occurring after turnout in the spring and early summer.

Animals↗

Lead poisoning associated with use of traditional ethnic remedies--California, 1991-1992.

Exposure to lead-based paint is the leading cause of high-dose lead exposure among children in the United States. However, previous reports have documented childhood lead poisoning related to the use of traditional ethnic remedies (1-4), and such exposures may not be considered routinely. This article describes a case report of lead poisoning resulting from use of a traditional ethnic remedy and summarizes the identification of this problem as a result of lead poisoning surveillance in California from December 1991 through December 1992.

California↗

Prevalence of lead poisoning in an urban cohort of infants with high socioeconomic status.

The purpose of this study was to assess the prevalence of lead poisoning in an urban cohort of infants with high socioeconomic status and to determine the usefulness of the Centers for Disease Control (CDC) questionnaire in predicting lead poisoning. The CDC questionnaire was administered to consecutive parents of infants, beginning with their 6-month well-child visit. All infants had a venous lead level by 12 months of age. The 165 infants were between 5.9 and 12 months (mean = 9.4 months). The majority (67%) lived in a major city, had parents who were college graduates (67%), and had private medical insurance (85%). The overall prevalence of lead poisoning (Pb > or = 10 micrograms/dL [0.483 mumol/L]) was 29%. The relative risk of lead poisoning, given exposure as defined by the CDC instrument, was 0.99 (95% CI = .81 to 1.21). The sensitivity and specificity of the questionnaire were 40% and 60%, respectively. We conclude that the prevalence of lead toxicity and the poor sensitivity of the CDC questionnaire in this cohort of urban infants with high socioeconomic status support the 1991 CDC recommendation for universal lead screening in this region.

Centers for Disease Control and Prevention, U.S.↗

Lead poisoning in pregnancy: a case study with implications for midwives.

Lead poisoning remains a significant problem in the United States affecting the health of women and children. Although the damage is greatest at higher levels of accumulation, no level of lead has been found to be safe. Over the last 25 years, the blood level of lead thought to be associated with toxicity has dropped dramatically, from to 60 mcg/dL in 1960 to 10 mcg/dL today. Studies confirm that exposure to lead causes kidney damage, encephalopathy, and impaired cognitive function in children and in adults. Recent evidence indicates children with levels less than 10 mcg/dL may suffer from compromised development and intellectual performance later in life. This article discusses the case of a woman found to have lead poisoning during pregnancy. Environmental sources of lead, implications for the immediate and future health of the fetus and mother, and techniques clinicians can use in their practice to minimize the adverse effect of lead on their clients are reviewed.

Adult↗

Lead poisoning--Part I. Incidence, etiology, and toxicokinetics.

In summary, we review the recent and not so recent but lesser known information on lead poisoning. We review the incidence of lead poisoning and find that no one is really safe from its effects. We have also examined the many and varied sources of lead poisoning, and critically review the ubiquitous ways in which lead enters the body and is eventually dealt with in the body.

Absorption↗

An outbreak of lead poisoning in dogs.

An outbreak of lead toxicosis in working dogs on a sheep farm is described. The affected dogs exhibited neurological signs which appeared to be initiated by strenuous physical activity. Radiological examination and estimation of urinary delta aminolevulinic acid (U-ALA) was not found to be useful for clinical diagnosis but blood lead estimation was helpful in detecting and confirming dogs that were exposed to lead. Gross pathological lesions were absent in a lead poisoned dog. However, histopathological lesions were seen in brain and bone. Acid-fast lead inclusion were not detected in liver and kidney epithelial cells but were present in osteoclasts.

Aminolevulinic Acid↗

Lead's legacy? Early and late mortality of 454 lead-poisoned children.

A series of 454 pediatric hospital patients who were diagnosed with lead poisoning between 1923 and 1966 were traced through 1991 to examine possible mortality effects. Numbers of observed deaths were compared with those expected, based on the rates of the U.S. population. Eighty-six deaths were observed (O/E = 1.7, 95% confidence interval (95% CI) = 1.4-2.2), of which 17 were attributed to lead poisoning. Mortality from all cardiovascular disease was elevated (O/E = 2.1, 95% CI = 1.3-3.2), and cerebrovascular deaths were particularly common among women (O/E = 5.5, 95% CI = 1.1-15.9). Among men, 2 deaths resulted from pancreatic cancer (O/E = 10.2, 95% CI = 1.1-36.2), and 2 deaths resulted from non-Hodgkin's lymphoma (O/E = 13.0, 95% CI = 1.5-46.9). Chronic nephritis was not a significant cause of death. Despite limitations in the data, the pattern of mortality suggests that effects of lead poisoning in childhood may persist throughout life and may be experienced differently by men and women.

Cause of Death↗

Lead poisoning among young children in Russia: concurrent evaluation of childhood lead exposure in Ekaterinburg, Krasnouralsk, and Volgograd.

The Gore-Chernomyrdin Commission encouraged a binational collaboration to evaluate pediatric lead poisoning in Russia. The study evaluated children in three Russian cities: Krasnouralsk, a small city with minimal traffic centered around a copper smelter; and Ekaterinburg and Volgograd, both of which are large cities with multiple factories and heavy vehicular traffic. This project was the first international use of portable blood lead analysis instruments. In each city, at least 90% of children attending selected neighborhood kindergartens participated. We selected kindergartens on the basis of their proximity to industrial areas and major traffic corridors. We obtained capillary blood samples and analyzed for lead content and hemoglobin (Hgb) levels in the field, and collected environmental samples (i.e., indoor dust, tap water, play area soil, and interior and exterior paint) and analyzed for each participating school and in the homes of about 10% of the children who had elevated blood lead levels (BLLs; greater than or equal to 10 microg/dL). We calculated all age-, sex-, and city-specific geometric means using generalized estimating equations to account for covariance within kindergartens, and used multivariate logistic regression models to identify variables predictive of elevated BLLs. Overall, 23% of study children had elevated BLLs and 2% were anemic, defined as Hgb < 11 g/dL. Krasnouralsk had the highest geometric mean BLL (10.7 microg/dL), the highest percentage of children (60%) with elevated BLLs, and the highest percentage of anemic children (4%). All soil samples in Krasnouralsk had detectable lead levels. Volgograd was the only city that had paint samples with elevated lead levels. We found apparent city-specific differences in the percentages of children with elevated BLLs. Lead-contaminated soil and dust, which can result from lead-based automotive fuel and from lead-related industrial emissions, appear to be the most important routes of lead exposure of those evaluated in this study. Elevated lead levels found in paint samples from Volgograd may indicate old undercoats of lead-based paint that could represent a regionally rather than nationally important source of exposure.

Anemia↗

Alterations in the activity of enzymes of haem biosynthesis in lead poisoning and acute hepatic prophyria.

1. The activities of six of the enzymes of haem biosynthesis have been assayed in peripheral blood from patients with lead poisoning, acute intermittent porphyria or hereditary coproprophyria. 2. Compared with normal subjects the lead-poisoned subjects had highly significant depression of delta-aminolaevulinate dehydratase, coproporphyrinogen oxidase and ferrochelatase. 3. Lead-poisoned subjects had highly significant elevation of delta-aminolaevulinate synthase activity. 4. delta-Aminolaevulinate synthase activity was inversely related to the haemoglobin concentration. 5. Increased delta-aminolaevulinate synthase and decreased delta-aminolaevulinate dehydratase activity are also found in acute intermittent porphyria. 6. Increased delta-aminolaevulinate synthase, normal prophobilinogen deaminase and uroporphyrinogen decarboxylase and decreased coproporphyrinogen oxidase are found in both lead poisoning and hereditary coproporphyria. 7. These enzyme changes explain the recognized patterns of porphyrins and prophyrin precurosrs in blood and urine in these conditions.

5-Aminolevulinate Synthetase↗

Acute lead poisoning of the pigeon induced by single, intraperitoneal administration of lead acetate.

A single dose of lead acetate (either 30 mg/kg or 150 mg/kg) was intraperitoneally (i.p.) administered to adult feral pigeons, Columba livia var and the effects of calcium disodium ethylenediamine tetraacetate (CaNa2EDTA), (0, 150, 300, 600 mg/kg), administered i.p. twice a week in the ensuing period were observed. Lead acetate caused dose related mortality and decreases in weight, hematocrit and delta-aminolevulinic acid dehydratase activity (ALA-D). Acute toxicity of lead acetate in the pigeon, when given intraperitoneally, appeared approximately equivalent to that in the rat and mouse in terms of LD50. Blood lead (blood Pb) levels observed during the lethal stage were five to ten times less than those reported for chronic oral lead poisoning in the pigeon. Biological implications of elevated levels of blood Pb observed in the feral pigeon in the urban Tokyo area are discussed. CaNa2EDTA induced dose related recovery in ALA-D in 30 mg/kg group, and reduction of blood Pb levels in the group dosed with 150 mg/kg of lead acetate.

Animals↗

Childhood lead poisoning in China.

In China, comprehensive epidemiological data relating to the prevalence of childhood lead poisoning are not available. However, existing data suggest that this disease may be widely pervasive as a result of rapid industrialization and the use of leaded gasoline. Seventeen publications have reported elevated blood lead levels in children from different areas of the country. Children residing in industrial and busy traffic areas had average blood lead levels(BPb) of 21.8-67.9 mu g/dl. The percentages of BPb values above 10 mu g/dl, which is the definition of lead poisoning in children, ranged from 64.9% to 99.5%. Even for 'unexposed' children, about 50% of them had BPb values above 10 mu g/dl. Furthermore, several retrospective pilot studies were conducted in Shanghai, Shenyang, Fuzhou and Beijing to evaluate the health effects of lead at current degree of exposure. The link between low-level lead exposure and deficits in IQ, neurobehavioral development and physical growth is remarkably consistent without exception. In summary, the harmful health effects of childhood lead poisoning in limited studies of exposed and 'unexposed' children demonstrate that this totally preventable disease warrants considerable public health attention in China.

Child↗

Erythrocyte ALA-d activity in experimentally lead-poisoned ducks and its change during treatment with disodium calcium EDTA.

To determine useful procedures for the diagnosis and prognosis of lead poisoning in waterfowl caused by ingestion of lead pellets, erythrocyte delta-aminolevulinic acid dehydratase (ALA-d) was investigated in experimentally lead-poisoned ducks. A highly positive correlation was observed between the concentration of blood lead and the ALA-d activity ratio (the ratio of activated:non-activated enzyme activity) in those birds given seven lead pellets (3 mm diameter). The ALA-d activity ratio rapidly increased after the administration of lead pellets, but began to fall immediately after the initiation of disodium calcium ethylenediamine tetra-acetate (CaEDTA) therapy which resulted in a rapid decrease in the concentration of lead in the blood of these birds. In contrast, the ALA-d activity remained inhibited even after blood lead levels began to decrease following treatment. These results demonstrated that the ALA-d activity ratio is a very useful and sensitive indicator for the diagnosis and evaluation of therapeutic effects after lead poisoning in waterfowl.

Animals↗

[Magnesium metabolism in chronic lead poisoning: influence of chelating treatment].

Thirteen patients with chronic lead poisoning were compared to 13 healthy subjects for magnesium in blood (plasma and erythrocytes) and in 24-hour urine, and serum and urinary Ca and P. Determinations were made before an infusion of 1 g Ca EDTA and on the following day. In the basic state, all the parameters were identical in both groups. Ca EDTA elicits a significant drop in plasma Mg only in the patients with lead poisoning, without modifications of erythrocytic or urinary Mg. Consequently, the drop in plasma Mg might be due to a shift from an extracellular to a tissue pool. This shift might be cause by the action of EDTA itself, or might be the consequence of removal of lead from cellular sites of fixation, where it could be replaced by Mg ions.

Calcium↗

Residual cognitive deficits 50 years after lead poisoning during childhood.

The long term neurobehavioural consequences of childhood lead poisoning are not known. In this study adult subjects with a documented history of lead poisoning before age 4 and matched controls were examined with an abbreviated battery of neuropsychological tests including measures of attention, reasoning, memory, motor speed, and current mood. The subjects exposed to lead were inferior to controls on almost all of the cognitive tasks. This pattern of widespread deficits resembles that found in children evaluated at the time of acute exposure to lead rather than the more circumscribed pattern typically seen in adults exposed to lead. Despite having completed as many years of schooling as controls, the subjects exposed to lead were lower in lifetime occupational status. Within the exposed group, performance on the neuropsychological battery and occupational status were related, consistent with the presumed impact of limitations in neuropsychological functioning on everyday life. The results suggest that many subjects exposed to lead suffered acute encephalopathy in childhood which resolved into a chronic subclinical encephalopathy with associated cognitive dysfunction still evident in adulthood. These findings lend support to efforts to limit exposure to lead in childhood.

Cognition Disorders↗

[Late sequelae of recurrent occupational lead poisoning--the status of the nervous system].

In 44 men with a history of repeated occupational lead poisoning multidisciplinary clinical and laboratory investigations were carried out. The number of lead poisoning episodes was from 2 to 7. Apart from peripheral hypalgesia on the extremities (in 6 cases) no other neurological abnormalities were found. The motor nerve conduction velocity in the median, ulnar, radial, peroneal and tibial nerves was slightly slower in 27 cases and considerably slower in one case. Slowed down conduction velocity was most often observed in 2 nerves (12 cases) and in one nerve (9 cases), less frequently in three (4 cases) and four (2 cases) nerves. In one case this slowing down was found in all five studied nerves. Conduction changes were found in 21 peroneal nerves, 15 ulnar nerves, 12 median nerves, 7 tibial nerves and 2 radial nerves. The authors think that for the evaluation of the condition of the peripheral neuron in cases of past lead poisoning it would be sufficient to determine the conduction velocity in the ulnar and peroneal nerves. Plumbism neuropathy have the character of subclinical lesions not impairing motor skill.

Humans↗

Occupational and environmental lead poisoning: case study of a battery recycling smelter in Taiwan.

The rapid industrialization in Taiwan has caused both prosperity and environmental pollution. The purpose of this study is to demonstrate a case of both occupational and environmental lead poisoning. A patient of lead poisoning initiated a survey of the battery recycling factory, which revealed that 31 of 64 workers suffered from lead poisoning. Children who attended a nearby kindergarten showed a significant increase of blood lead up to 15-25 micrograms/dl and a mild but significant decrease of IQ (intelligent quotient, by Binet-Simon scale) if compared with children of a nonexposed but socioeconomically comparable kindergarten. Outdoor workers of the nearby forging factory also showed a significant increase of blood lead if compared with indoor workers or workers of another nonexposed forging factory 20 Km away. Air sampling showed an average of more than 10 micrograms/m3 in the kindergarten. Soil sampling and analysis also revealed 400 folds increase of lead content, which decreased if the sample was taken deep down to 15-30 cm or 350 meters away from the battery recycling smelter. Moreover, after children were moved away from the pollution source, follow-up examination performed 2.5 years later showed a significant decrease of blood lead and partial recovery of IQ among them.

Adolescent↗