Lead Poisoning
Lead 2

Author: Aurelio Bard
Date: 16/07/2012


Lead is a heavy metal, naturally found in nature, often associated with Zn, Ag and S and other minerals.
For years it was used in paint industries, metal foundries, batteries for vehicles, bullets for guns.
People exposed the most to lead are metal workers, painters, families (in particular children) who live near factories that make lead dust. In these places, in fact, the soil and the groundwater are highly polluted.

People get lead poisoning from breathing its dust (from the soil, filings, paint and so on), swallowing polluted water (from leadpipes) or with the simple contact with skin and mucosa.
In the bloodstream lead spread to every organs, in particular in bones (with a half-life of about 30 years), hair follicles, hepatocytes, which contain several target enzymes. Lead in fact bonds with sulfuric group, mimicking the action of other metal cofactors, such as Fe, Ca, Zn
Lead interacts with ALAD the enzyme that takes part in the synthesis of Protoporphirine IX and acts by inhibiting Ferrochetalase that allows the bond between Fe and Protoporphirine IX. This cause a severe hypocromic anemia and the formation of ZPP.
On neurons lead interacts with NMDA receptor, blocking glutamate release.

In kidneys lead interacts with 25(OH)D-1α hydroxylase, essential for the vitamin D synthesis. A decrease of calcemia lead a loss of Calcium in skeletal muscle (that causes fatigue), cardiac failure, loss of those metabolic processes that require Calcium as second messenger.
In hepatocytes lead accumulates for the high affinity with CYP450, e.g. the 3A4, 2C9, 2C19. Because of its saturation, xenobiotic and the major medicines are less metabolized by the liver, this cause severe complications.
In CNS lead interacts with TPH, an enzyme that requires Fe as cofactor, involved in synthesis of the serotonin. Lead replace the iron, decreasing 5-HT levels. Severe depression can occur, more over many studies demonstrated the link between depression and immune system failure.

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Often patients complain general weakness, anorexia, skeletal muscle fatigue, depression.
Haematic levels of lead are considered dangerous and harmful above 10 μg/dL in children and 25 μg/dL in adults. An easy blood test can be done to detect poisoning, as an alternative a hair follicle can be tested.
In case of acute or severe chronic poisoning a strong chelating agent is given (like an EDTA). A diet full of Fe, Ca, Zn and vitamin C is highly recommended.
To prevent lead poisoning is helpful replace old painting, leaded plumbing and clean down the house with HEPA vacuum.


Screening test for lead poisoning

Toxicokinetics of Bone Lead

Lead in the Home Garden and Urban Soil Environment

2013-03-19T08:30:51 - Costanza Pira

Lead poisoning from wine and other non professional sources


1.a Lead: physical and chemical properties.
Lead (atomic number 82; relative atomic mass 207.19; specific gravity 11.34) is a chemical element represented by the symbol Pb, which belongs to the heavy metal chemical series. It is a bluish or silvery grey soft metal. The melting point is 327.5° C and the boiling point at atmospheric pressure is 1740°C. It has four naturally occurring isotopes (208, 206, 207 and 204 in order of frequency).
It has several characteristic properties: high density, softness, ductility and malleability, poor electrical conductivity compared to other metals, high resistance to corrosion, and ability to react with organic chemicals.
World Health Organization, Environmental Health Criteria 165 Inorganic Lead; Geneva, 1995

1.b Sources
Lead can derive from:
natural sources: erosion of the earth's crust, volcanic emissions;
anthropogenic sources: exhaust gas of motor vehicles powered by gasoline containing Pb.
Lead is a ubiquitous element: we introduce up to 250 -500 micrograms with our daily diet.
Nowadays the main sources of occupational lead exposure are represented by:
the manufacture and demolition of batteries;
the fusion of lead and its alloys;
the operations of filing of the automotive body;
the ceramics industry.
In the industrial environment, the occupational lead intoxication has reached levels so high that, in 1991, Italian state has received the European directives n. 80/1107/CEE, n. 82/605/CEE, n. 83/477/CEE, n. 86/188/CEE e n. 88/642/CEE concerning the risk prevention for workers exposed to chemical, physical and biological agents during their working activity. The D. Lgs n. 212 of july 30th 1990, active from September 11th, 1991 describes safety measures against risks deriving from asbestos, lead and noise exposure.
DECRETO LEGISLATIVO 15 agosto 1991, n. 277 Attuazione delle direttive n. 80/1107/CEE, n. 82/605/CEE, n. 83/477/CEE, n. 86/188/CEE e n. 88/642/CEE, in materia di protezione dei lavoratori contro i rischi derivanti da esposizione ad agenti chimici, fisici e biologici durante il lavoro, a norma dell'art. 7 della legge 30 luglio 1990, n. 212
Health surveillance of exposed workers has been integrated in the 9th title of Legislative Decree 81/2008 where the Exposure limit values for inorganic lead is 0.15 mg/mc and the biological limit values are 60 mcg/100 ml (female and male adult) and 40 mcg/100ml (menacme).
D. Lgs n. 81 del 9 aprile 2008, Testo Unico sulla Salute e Sicurezza sul Lavoro

2.a Metabolism
The main adsorption ways are through the upper airways and the digestive systems. There is also a lower transdermic adsorption rate. Through the respiratory system lead penetrates as fine dust, fumes and vapors, which are absorbed almost totally because they reach the alveolar compartment easily. Another proportion is absorbed as lead chloride.
Lead is distribuited to both soft tissues (blood, liver, kidney, etc.) and mineralizing systems (bone and teeth). Bone may be affected adversely by lead but also serves as the body’s major storage site. Bone accumulates lead over much of the human life span, and a study of the kinetics of distribuition is important since bone can, under appropriate conditions, pose a risk as a potential endogenous source of lead.
In adults, approximately 94% of the body burden of lead is in the bones, whereas only 73% of the body burden in children is located in this compartment.

Elimination and excretion.
In both humans and experimental animals lead is eliminated from the body in both urine and faeces. Any dietary (including waterborne) lead not absorbed in the gastrointestinal tract is excreted in faeces.

2.b Toxicology
The lead toxic effects are given by the circulating lead in the ionic state through body fluids.
The lead toxicity is related to the spasmodic effect on smooth muscle, lytic action on circulating red blood cells, neurotoxic effect and to the inhibition of enzymatic activity (thiol-dependent).

One of the lead effects is the inhibition of some stages of heme synthesis due to the interference with certain enzymes. This effect has no great importance on what concerns the health status matter. The effect is not directly responsible for the forms of anemia that primarily depend on the lytic action on the red blood cells but it is of great importance for the diagnostic implications based on the growing levels of products involving impaired synthesis or inhibition of enzymes function. It is actually known that the half-life of the free-lead circulating in the blood is very short and that the fraction not excreted lodges in the bone as lead triphosphate. The lead deposited in the bone tissue represents a stable pool with slow-release.
It is possible to evidentiate a state of chronic impregnation through the research of various “no synthesis” products that can be evaluated in the urine, the blood or the faeces.

As shown in fig. 1, lead inhibits the activity of three enzymes of the biosynthetic pathway, 5-aminolaevulinate dehydratase (ALA-D), coproporphynogen oxidase (COPRO-O) and ferro-chelatase (FERRO-C). This depletes heme synthesis and depresses the synthesis of the initial and rate- limiting enzyme 5-aminolaevulinate (ALA) synthase. As a consequence there is increased production and excretion of the precursors ALA and coproporphyrin (COPRO) with increased circulatory protoporphyrin (PROTO) usually bound to zinc. In the red cell, diminished synthesis of monooxygenases (cytochromes P450) compromises drug oxidation and lead is bound to haemoglobin.
Downey D. C., Porphyria and Chemicals, Medical Hypotheses, 1999; 53 (2), 166-171

2.c Clinic
There are various clinical forms of lead intoxication.
The first form can be characterized by an abnormal absorption with the retention of the toxic, without clinical manifestations. Rarely we can see bluish gums, due to lead sulfide deposition. (Figure 2)

The second clinical form is represented by acute forms of intoxication and it is characterized by the presence of signs and symptoms as abdominal pain, normochromic anemia, radial paralysis, increased blood pressure and acute encephalopathy. This stage is the most severe stage of the disease and it is also called the “flourishing lead poisoning”. The enteric and cardiovascular symptoms are due to the lead spasmodic action on the digestive system smooth muscle and on the circulatory system smooth muscle.
The neuropathy is mainly a peripheric motor neuropathy (initial radial localization with “horn hands” as pathognomonic sign) and sometimes asymmetrical; the prognosis depends on the cessation of the exposure (prompt exposure removal allows fast recovery).

The adult acute encephalopathy is a rare disease and it has an occupational origin in 90% of all the cases. It is characterized by an initial stage also called prodromal with confusion, memory loss, decreased orientation and perception. In the advanced stages we can see severe impairment of consciousness and seizures. The serum lead levels are generally 120 mg / dL or more. The acute encephalopathy in children represents the most severe form of lead intoxication in children. It has a prodromal phase with memory loss and decreased concentration capacity, tremors, agitation, headache. During advanced stages the symptoms can be vomiting, lethargy, stupor, convulsions and finally coma. Serum lead levels are generally higher than 100 mcg / dL. The prognosis is always poor.
Behavioral neurotoxicity:
Especially during childhood. There is a close dose-effect relationship between the cognitive deficit and exposure levels. There is evidence of progressive alterations in certain neuropsychological functions also for values next to 10 mcg / dL of PbB.
Last but not least the chronical forms of lead poisoning slowly evolving. Digestive forms of intoxication are described as gastroduodenitis, dyspeptic disorders and colitis with abnormal intestinal transit.
Hematopoietic effects are characterized by hypo-regenerative anemia. The cardiovascular and renal system forms present symptoms and signs like arterial hypertension and renal insufficiency due to the increased vascular peripheral resistance, especially in the renal district.Dermic effects are desquamation, ulceration and trophic nail alteration.

Lead and cancer.
The carcinogenic effect of lead is described by the International Agency on Research on Cancer (IARC Monographs on the Evaluation of Carcinogenic Risks to Humans – Vol 87 2006 1 ). IARC classifies Inorganic Lead as a 2A group compound (Limited evidence in humans, Sufficient evidence in experimental animals for Pb acetate, subacetate, chromate, phosphate but inadequate for Pb oxide and arsenate) and Organic compounds of Lead as a 3rd compound (Inadequate evidence for humans and for the experimental animal).

There are specific biomarkers that indicate presence of the toxic in the body as blood lead levels, urinary lead levels and urinary lead levels after chelation (Ca-NaEDTA).
The blood lead level is not strictly correlated with the presence of toxic manifestations. Blood lead level and piomburia may be normal in patients with chronic poisoning no actually exposed. In the clinical practice it can also be used the porphyrin metabolism test (Decrease of Ala-d, Increase of Ala-u, Increase of ZnPP).
The metabolites related to the presence of lead in the human body are indicators of the effect of heme synthesis inhibition. These are ALA-U (delta aminolevulinic acid in urine) and ZnPP (zinc protoporfirin in blood).

A therapeutic strategy is based on chelation with Ca-NaEDTA 25mg/kg/day for 5 days. It can be administrated either intravenous (5% dilution in dextro¬sio or 0.9% dilution in saline solution; it should be administrated in slow infusion in order to prevent flebitic processes) either intramuscular that allows a good adsorption rate (pain in the administration site is possible; in such cases is it advisable administrate local anesthetic).

Nonprofessional lead poisoning goes as far back as Ancient Greece. In most cases the poisoning is due to accidental pollution of foodstuffs or alcoholic drinks when the vessels used for storage or drinking cause the lead contamination. Drinking water was, for a long time, another important source, as one pure lead or lead-treated pipes were used to carry the water (Bacon et al, 1967; Beattie et al, 1972; Crawford, 1983)
Bacon APC et al, Lead poisoning from drinking soft water, Lancet 1967; 2: 264-266
Beattie AD et al, Environmental lead pollution in an urban soft-water area, Br Med J. 1972; 2: 491-493
Crawford MD, Lead in bones and drinking water in towns with hard and soft water, Br Med J, 1973; 2:21 .
Lead contamination has also been found in drinking water carried by PVC pipes in which lead stearate was used as a stabilizer (Griffin and Knelson, 1975). Another practice of long duration, first used by the Romans, is that of adding lead sugar to stop wine fermentation without changing either its color or taste. Therefore ancient Romans, not knowing of the danger, were among the first victims of the use of lead sugar that resulted in serious cases of toxicity, both acute and chronic (Gilfillan, 1965) Gilfillan SC, Lead poisoning and the fall of Rome, JOM, 1965; 7: 53- 60 .

Later this custom was adopted by Germans, about the end of the 15th century, when it was no longer possible to treat wine with sulphur. This custom was also used in England, Denmark, Scandinavia and other European countries, with consequent poisoning. Accidental or international poisoning is also reported from beer, apple cider, and fruit juice. (Griffin and Knelson, 1975). Another source of intoxication, reported mainly in the United States, is the consumption of illegal, "moonshine" whisky produced in home-made stills (for example, an old car radiator), which may release lead into the whisky. In such cases the lead intake was reported to be greater than 1 mg/liter (Zenz, 1975).
Lead intoxication due to ceramic vessel is a recognized problem, especially when they are hand-made ands the craftsmen or artists have paid less attention to toxic problems than to esthetics (Browder, 1972; Dufour et al, 1972; Klein et al, 1970; Zenz, 1975)
Browder AA, Lead poisoning from glazes, Ann Intern Med, 1972; 76: 665 .
Dufour M et al, Saturnisme et poterie vernisés, Nouv Press Led, 1972 ;1 : 1018. .
In this case the source of food or drink poisoning is the glaze that lines cooking ware to which lead was added for technical or esthetic reasons (either to produce a lower melting point or a greater luster) (Dickinson et al, 1972; Klein et al, 1970; Scansetti et al, 1980)
Dickinson L et al, Lead poisoning in a family due to cocktail glasses, Ann J Med, 1972; 52: 391-396.
Low-pH solutions (e. g., wine) cause release of lead that varies with the lead content in the glaze and other items such as pigment additions and kiln temperature at firing. Poisoning caused by release of lead has been reported by Beritic et al (1961), Whitehead and Prior (1960) Whitehead TP et al, Lead poisoning from home- made wine, Lancet, 1960; 2: 1343-1344 , Harris and Elsea (1962) Harris RW et al, Ceramic glaze as a source of lead poisoning, JAMA, 1967; 202: 544-646 , and Klein et al (1970) Klein M et al, Earthenware containers as a source of fatal lead poisoning, N Engl J Med, 1970; 283: 669-672 .
In all these cases ceramic vessels were involved. Of 264 sample cases of vessels examined by Klein et al (1970), 35% were found to contain more than 110 ppm of lead. In England the practice of reinforcing the wine with lead continued over the centuries, to the point that the epidemic of gout among the English aristocracy in the eighteenth and nineteenth centuries was also attributed to the high consumption of Portuguese and Spanish wines with a high lead content. There were also described behavioral sources of lead poisoning as the ingestion of flakes of walls painted with paints containing lead (CDC 1991: lead based paint is the most common high dose source of lead exposure for children) the use of traditional topical drugs, the combustion of battery cases for the purpose of domestic heating.
In western countries the professional lead intoxication is nowadays a rare condition and the environmental pollution is also well controlled after the introduction of rules regarding the use of unleaded gasoline. For instance the Turin airborne lead concentration has dropped from 4.7 µg/mc in 1973 to 0.53 µg/mc in 1993.
Consequently the lead blood concentration in a representative sample of adult men in Turin ( 2 ) has similar patterns; where the mean value of lead blood level has dropped from 25 µg/dl in 1977 to 10 µg/dl in 1993/1994.
The risk of lead intoxication is still important in the general population due to the exposure/ intake at home by food and drinks contaminated and by handling objects (mainly toys for children) made or painted with lead containing materials. This aspect is not well- known and the environmental protection agency publishes periodically warnings on this topic.
Lead Poisoning in Children, 2010
(figure n. 4)


The intoxication at home is mainly due to the consumption of wine contaminated by lead and for children to the fruit juices stored in handcrafted ceramics vessels. The clinical patterns could be very important and in my work I would analyze the ways of wine lead contamination and the biological effect as described in some case reports published from the Occupational Health Clinic of Turin University.


We could find lead on grapes (from some pesticides used in the past as lead arseniate or for the deposit on grapes of inorganic lead released in the environment from cars. This condition was characteristic of vineyards along with the motorways.) The contamination could occur also during the wine harvesting where containers painted with varnish lead containing have been used.
In this phase levels of 13,1- 21,2 mg/l have been observed during the 1998 harvest when grapes remained for 24 hours inside the painted containers.
In 1999 after harvest the grapes remained inside the container for only few hours and we were able to see a decrease in the red wine lead levels: 0.693 mg/L. One year after the containers have been replaced with plastic containers and the measurements showed an important decrease of the red wine lead levels: 0.034 mg/l have been documented .
The pressing process could represent a risk for the presence of lead containing materials in the press. Typical condition has been described due to the handcrafted repair of the press using a lead containing barrier or heavy lead blocks facilitating the pressing operation.
The fermentation process could be dangerous if lead contaminated earthenware containers are used as well as during the conservation in vats made with similar materials.
Also the preservation in bottles could be dangerous for the presence of lead in some cork used for champagne.
Lead poisoning cases caused by acid beverages (for example fresh fruit juice) are also described. The sources are generally represented by the lead contained in the glaze of the pottery and the contact with an acid drink ( e. g. orange juice) could cause the release of the lead from the glaze.
This specific topic is stressed in the EPA warnings and some broadcasting advices in the USA remind that the use of handcrafted pottery could be dangerous mainly for children.
In the following chapter 3 case reports of lead poisoning from wine are summarized, stressing the key importance of biochemical investigations in the diagnosis and follow up of the patients.
Perrelli G. et al, Further Cases of Lead Poisoning from Wine, American Journal of Industrial Medicine, 1984; 5: 377- 381

Wine and lead. CASE REPORTS

Case 1

C. D., a 44 year-old man, has always worked as motor mechanic. There is no evidence of lead exposure from his occupational history. He has been hospitalized several times in the last few years suffering from abdominal pain: dolicomegacolon and gallbladder dyskinesia were diagnosed. On admission to the Institute of Occupational Health, results of clinical examination were negative. The blood cell count showed mild anemia (RBC 3710000/ mm3; Hb 10 g/dL; Hct 30.2%) with marked anisocytosis and poikilocytosis. Biological indicators of lead poisoning were all abnormal on admission: blood lead level 81 μg%, ZPP 468 μg%, Ala-D 61 IU/ml, Ala-U 75 mg/liter, CPU 945 μg/liter, lead urine level 304 μg/liter. Calcium disodium EDTA (1 g/day intravenously) was continuously administrated for 30 days, all values resulting within normal range 50 days after institution of therapy. Excretion of urinary lad reached a peak of 4 mg/day during therapy.

Case 2

V. R., a 40 years-old woman, is the wife of the patient of Case 1. She was admitted 15 days after the Case 1 hospitalization. Abdominal pain, fatigue, nausea, and anorexia had been reported in previous years. Laboratory findings including mild anemia ( RBC 3940000/ mm3; Hb 35%) and increased levels of ZnPP (400 μg%) and Ala-U (24 mg/L). Blood lead level was close to the limit value (56.2 μg%). Two other members of the family underwent laboratory examination : the sister of Patient 2 ( V. A.) showed increased ZnPP (319/ μg%) and Ala-U ( 60 mg/L) values, but her blood lead levels was within normal limits ( 49.1 μg%). C. A. the 12-year-old son of V. A., who did not drink wine, showed all values within normal limits.
In the case reports 1 and 2 the individuated source was a lead plate (120 × 120 × 0.5 cm) placed at the base of the press squeezing to remedy the breaking of the stone base (the plate is the reservoir for collecting the liquid coming from the pressing of the grape stalks).

Case 3

A 58 year-old male complained abdominal colic, fatigue, anemia and progressive motor neuropathy borne by the radial since 5 years. His lead blood level was 103.2 mcg/dL and urinary ZnPP level was ++. He was treated with 4 cycles of chelation therapy (CaNa2EDTA 1 g / day for 5 days)The lead source was the cement vat covered with ceramic tiles which released 202 μg of lead per cm2 in one day and, consequently, the lead wine level was 19,5 mg/L.


Lead poisoning is a risk often underestimated or not considered at all by medical practitioners. In front of suspect cases the physician has to consider also the possibility of lead poisoning because it has a great clinical impact, especially among young subjects.
The problem, especially in children, could be very important, and the perception of risk is not so strog. I believe that information campaign could be organized based on “easy” channel of communication. Under this aspect it’s interesting the history written by a well- known “best seller author” in his recent novel (figure n. 5). John Grisham (American narrative author) describes the case of a young child who died for a lead intoxication due to vampire teeth made in China.
Grisham J, The Litigators, Doubleday, 0ctober 25th, 2011

I have chosen the following paragraphs from the original novel to represent the dramatic history of a child poisoning from lead.

"The housekeeper has a nephew who is in the hospital right now because his suffered a brain damage. He is in coma, attached to a respirator, and the situation is desperate. Doctors suspected a case of lead poisoning and asked the housekeeper to look for the lead throughout. It is possible to find a source among the child toys.”
"The source of the ingested lead is a toy made in China ... it is a Halloween gadget called 'vampire teeth'. According to the toxicologist toy teeth are covered with brightly colored lead paint saturated " (figure n. 6 nfa)

"The levels of lead in the paint used for the teeth staining are toxic. Any child, or adult, who use this product in the manner intended by the manufacturer, namely by inserting it in the oral cavity and superimposing the real teeth, he runs serious risks to ingest significant quantities of lead-based paint.”
"Thuya had a series of violent convulsions and died three days after Christmas."

This dramatic history described in this book confirm the opportunity of a strong action against the risk of lead poisoning in non professional conditions.

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