Heavy metals are naturally occurring elements that have a high atomic weight and a density at least five times greater than that of water. Their multiple industrial, domestic, agricultural, medical, and technological applications have led to their wide distribution in the environment, raising concerns over their potential effects on human health and the environment. Their toxicity depends on several factors including the dose, route of exposure, and chemical species, as well as the age, gender, genetics, and nutritional status of exposed individuals. Because of their high degree of toxicity, arsenic, cadmium, chromium, lead, and mercury rank among the priority metals that are of public health significance. These metallic elements are considered systemic toxicants that are known to induce multiple organ damage, even at lower levels of exposure. They are also classified as human carcinogens (known or probable) according to the US Environmental Protection Agency and the International Agency for Research on Cancer. This review provides an analysis of their environmental occurrence, production and use, potential for human exposure, and molecular mechanisms of toxicity, genotoxicity, and carcinogenicity.

/pdf/heavy-metal-toxicity-and-the-environment-32mfkxp6nb.pdf

Heavy metal toxicity and the environment.

https://stacks.cdc.gov/view/cdc/37676/cdc_37676_DS1.pdf

Toxicological Profile for Lead

Lead toxicity is an important environmental disease and its effects on the human body are devastating. There is almost no function in the human body which is not affected by lead toxicity. Though in countries like US and Canada the use of lead has been controlled up to a certain extent, it is still used vehemently in the developing countries. This is primarily because lead bears unique physical and chemical properties that make it suitable for a large number of applications for which humans have exploited its benefits from historical times and thus it has become a common environmental pollutant. Lead is highly persistent in the environment and because of its continuous use its levels rise in almost every country, posing serious threats. This article reviews the works listed in the literature with recent updates regarding the toxicity of lead. Focus is also on toxic effects of lead on the renal, reproductive and nervous system. Finally the techniques available for treating lead toxicity are presented with some recent updates.

/pdf/lead-toxicity-a-review-487tgdz2g1.pdf

Lead toxicity: a review.

Lack of bias in the estimation of relative effect in epidemiologic studies depends on the internal validity of the study. This paper conveys in graphic and tabular form the direction and magnitude of bias due to misclassification of study subjects. A series of computer-generated graphs shows that the departure of the estimate of effect (relative risk or odds ratio) from its true value is a function of sensitivity and specificity (measures of classification validity), disease frequency, and exposure frequency. The discussion of bias emphasizes misclassification of the "outcome" variable; i.e., disease occurrence in a cohort study and exposure rate in a case-control study. Examples are used to illustrate that the magnitude of the bias can be large under circumstances which occur readily in epidemiologic research. When misclassification is equal for the two compared groups, the estimate is biased toward the null value, and in some instances beyond; when differential misclassification occurs (as in selective recall in case-control studies) the bias can be in either direction, and may be great. Formulas are derived to estimate the underlying true value of the relative risk or odds ratio using the investigator's observations together with the estimated sensitivity and specificity of the classification procedure.

Bias due to misclassification in the estimation of relative risk.

Preventing lead poisoning in young children

The use of chelating agents in the treatment of acute and chronic lead intoxication in childhood.

A study of some environmental, behavioral and social factors in the production of lead poisoning in children in an urban community has been reported. Most significant among the environmental data presented were the magnitude of the exposure to lead from repetitive ingestion of small quantities of leaded-paint flakes, and the role of the seasonal factor (summer) in the precipitation of acute lead encephalopathy. The predominance of these two factors may explain the absence of any significant correlation between severity of disease and increments (beyond a minimum of 3 months) in the probable duration of exposure. It was concluded that a child without symptoms but having increased absorption of lead, recognized during the summer months, may progress to severe encephalopathy within a few weeks if the sources of lead are not promptly identified and eliminated. The present studies demonstrate that exposure to lead may be intense in children over 1 year of age living in dilapidated dwellings in which flaking leaded paint is readily accessible. The amounts of lead found in the feces of the poisoned children in the present study exceeded that found by others in the feces of exposed industrial workers. This suggests that the higher incidence of lead encephalopathy among children as compared with adults may, in part, result from their relatively greater exposure. The importance of continued environmental exposure to lead in increasing the incidence of severe permanent damage to the brain among survivors of an initial attack of acute lead encephalopathy was demonstrated. The correlation between the occurrence of such sequellae and re-exposure to lead in patients recovering from mild acute encephalopathy was statistically highly significant. It was concluded that removal of lead from the child9s environment is the only adequate protective measure in such cases. The high proportion of children aged 12 to 35 months with average intellectual capacity found among cases of lead intoxication, and the high incidence of unsuspected cases found among 12- to 35- month-old housemates of the index cases demonstrate the importance of the environmental aspect of the problem in urban slum areas. This high incidence of "secondary cases" emphasizes the physician9s obligation to examine carefully and promptly all environmental contacts under 3 years of age whenever an index case is found. The developmental factors in the child and the social situations in the home which may intensify the ingestion of lead-containing materials were discussed. While the responsibility of parents to protect their children from environmental hazards is not denied, no mother can reasonably be expected to prevent the repetitive ingestion of a few paint chips when these are readily accessible. As lead is widely used as a paint drier, continued good maintenance of painted surfaces would appear to be more pertinent to the long-range prevention of childhood plumbism than specific limitations on the content of nonpigment lead in fresh paint. The various environmental data all point to the conclusion that, where housing has been permitted to deteriorate, exposure to lead may be of such intensity as to outweigh such individual variables as mental retardation and emotional maladjustments in the child. Such intense exposure is a preventable hazard to normal small children, and, as such, constitutes a public health problem which may be more extensive than has heretofore been thought to exist. Pending the wider availability of better housing, preventive measures will have to be adapted to individual home situations and to the available facilities within a given community. Basic to any preventive program are facilities for the prompt identification and removal of environmental sources of lead, as has been emphasized by others, Equally important is a comprehensive social investigation of the home in order to evaluate the circumstances under which the child obtained toxic quantities of lead and to determine whether the identified sources of lead can be adequately removed, or whether a change of dwelling is required to prevent further dangerous exposure to lead.

The exposure of children to lead.

Micro-Scale Photofluorometric Determination of "Free Erythrocyte Porphyrin" (Protoporphyrin IX)

SUMMARY

The serious sequelae of lead intoxication during early childhood are mental retardation, behavior disturbances, convulsive disorders and nephropathy. The protean symptoms of this chronic disease and the paucity of specific abnormal physical signs make a biochemical approach essential for accurate diagnosis. Fundamentally, the diagnosis of plumbism requires the demonstration of an excessive body burden of lead together with some metabolic evidence of lead's toxic effects in the soft tissues. In children serial determinations of the concentration of lead in whole blood provide the best means for following trends in total body lead burden and its distribution. Minimal elevations in blood lead concentration are often difficult to evaluate, and the edathamil calcium disodium (edta) mobilization test can then be most useful in revealing an increased body lead burden.



The cornerstone of therapy is prompt interruption of abnormal lead exposure. Even so, the excessive body lead burden may persist for months or years after the excessive intake is halted. In the long-term management of such patients chelating agents might be used more effectively than they are at present. They are now given mainly for the treatment of obvious acute symptomatic episodes. It is more logical to use these agents to reduce and maintain soft tissue lead concentrations as close to normal as is consistent with safety.



RESUME

Intoxication saturnine chronique chez les enfants



Les sequelles graves de l'intoxication saturnine au cours de la petite enfance sont: retard mental, troubles du comportement, desordres convulsifs et nevropathie. Les symptomes changeants de cette maladie chronique et la pauvrete des signes anormaux specifiques rendent essentielle l'utilisation de la voie biochimique pour un diagnostic precis. En principe le diagnostic du saturnisme demande la mise en evidence d'une charge excessive de plomb dans l'organisme en meme temps que quelque evidence metabolique des effets toxiques du plomb sur les tissus mous. Chez les enfants des dosages en serie de la concentration du plomb dans le sang complet constituent le meilleur moyen de suivre l'evolution de la charge en plomb dans la totalite de l'organisme et sa distribution. Des augmentations minimes de la concentration sanguine du plomb sont souvent difficiles aevaluer et le test de mobilisation de l'edathamil calcium disodium (edta) devient alors tres utile pour mettre en evidence une charge accrue du plomb dans l'organisme.



La pierre angulaire de la therapie est la prompte interruption de l'exposition anormale au plomb. Meme alors l'excessive charge en plomb de l'organisme peut persister pendant des mois et meme des annees apres l'interruption de l'absorption excessive. Pour le traitement a long terme de ces patients des agents chelateurs pourraient etre utilises de facon plus efficaces qu'ils ne le sont a present. Ils sont administres maintenant surtout pour le traitement d'episodes symptomatiques aigus evidents. Il est logique d'utiliser ces agents pour reduire et maintenir les concentrations en plomb des tissus mous aussi pres de la normalite qu'il est possible de le faire sans danger.



ZUSAMMENFASSUNG

Chronische Bleivergiftung bei Kindern



Die ernsthaften Folgen einer Bleivergiftung wahrend der friihen Kindheit sind geistige Zuruckgebliebenheit, Benehmensstorungen, konvulsive Storungen und Nephropathie. Die proteischen Symptome dieser chronischen Krankheit und die Geringheit spezifischer abnormer physischer Anzeichen machen eine biochemische Einstellung notwendig fur eine genaue Diagnose. Fundamental erfordert die Diagnose des Plumbismus die Demonstration einer ekzessiven Korperlast an Blei, mit zugleich auftretenden Beweisen der vergiftenden Auswirkungen des Bleis in dem weichen Gewebe. Bei Kindern sind serielle Determinationen der Blei-Konzentration im unverdunnten Blut die beste Moglichkeit, Tendenzen der totalen Korper-Blei-Last und deren Verteilung zu verfolgen. Minimale Erhohungen der Blei-Konzentration im Blut sind oft schwierig auszuwerten, und der Edathamil-Kalzium-Disodium (edta)-Mobilisations-Test kann in dem Falle ausserst nutzlich sein, zur Feststellung einer erhohten Korperlast an Blei.



Der Grundstein der Therapie ist sofortige Unterbrechung der abnormen Blei-Einnahme. Selbst dann kann die ekzessive Korper-Blei-Last Monate oder Jahre lang anhalten, nachdem die ekzessive Einnahme abgestoppt worden ist. Bei der Behandlung solcher Patienten auf lange Sicht konnten narbenbildende Wirkstoffe effektiver angewendet werden als dieses heute der Fall ist. Sie werden heute meistens zur Behandlung offensichtlich akuter symptomatischer Episoden verschrieben. Es ware logischer, diese Wirkstoffe zur Verminderung und Aufrechterhaltung der Bleikonzentrationen im Weichgewebe auf einem der Sicherheit entsprechend moglichst normalen Niveau zu verwenden.



RESUMEN

La intoxicacion cronica por el plomo en los ninos



Los resultados serios de la intoxicacion por el plomo durante los primeros anos son atraso mental, disturbios de comportamiento, trastornos convulsivos, y nefropatia. Los sintomas de esta enfermedad cronica son proteiformes, y los signos anormales especificos son pocos, por eso no es posible diagnosticarla exactamente sin hacer una investigation bioquimica. Al fondo, la diagnosis del plumbismo exige la demostracion de una cantidad excesiva de plomo en el cuerpo, ademas de evidencia metabolica de los efectos toxicos del plomo en los tejidos no oseos. En los ninos, unas mediciones en serie de la concentracion del plomo en sangre entera son el mejor metodo de coleccionar informes sobre los cambios en la cantidad total de plomo en el cuerpo, y su distribution. Muchas veces es dificil averiguar aumentos muy pequenos en la concentracion de plomo en la sangre, y entonces la prueba de movilizacion edatamil calcio disodio (edta) puede ser muy util en el descubrimiento de una carga aumentada de plomo en el cuerpo.



En la terapia, lo mas importante es que el paciente cese inmediatamente de exponerse a cantidades anormales de plomo. Sin embargo, una carga excesiva de plomo en el cuerpo puede persistir meses o anos despues de que se haya cesado toda aportacion excesiva. En el tratamiento de larga duracion de taies pacientes, los quelatores podrfan emplearse mas eficazmente que ahora. Ahora se dan principalmente en el tratamiento de fases agudas con sintomas claros. Seria mas logico usar de los quelatores para reducir la concentracion de plomo en los tejidos no oseos, y mantenerla tan proxima como posible a lo normal, con tal que se tome en cuenta la seguridad.

J. Julian Chisolm

Papers

The use of chelating agents in the treatment of acute and chronic lead intoxication in childhood.

The exposure of children to lead.

Micro-Scale Photofluorometric Determination of "Free Erythrocyte Porphyrin" (Protoporphyrin IX)

Chronic Lead Intoxication in Children

Disturbances in the biosynthesis of heme in lead intoxication.