Lead
The toxic effects of (inorganic) lead have been known since ancient times, but this metal still presents significant health problems (Tong et al. 2000). Lead compounds have been used as cosmetics and components of medicines (Bayly et al. 1995; Hardy et al. 1998; Fisher and Le Couteur 2000; Moor and Adler 2000). Acute lead poisoning is relatively uncommon, however, and most symptomatic cases result from chronic ingestion, or inhalation of lead fumes or dusts during occupational exposure, or use of lead containing ‘traditional’ medicines and ingestion of paint (pica) in children (Carton et al. 1987; Braithwaite and Brown 1988). Recognition of exposure to lead from leaded fuels has led to the withdrawal of these products in most developed countries. In adults, barely 10% of ingested lead is absorbed from the gastrointestinal tract but in children this proportion may be much higher. However, the bioavailability of ingested lead may be influenced substantially by the individual’s diet and nutritional status (e.g. iron and calcium deficiency). Lead absorbed by inhalation has a much greater bioavailability, but this may depend on factors such as respiratory rate, particle size, the atmospheric concentration of lead and the duration of exposure. The clinical diagnosis of lead poisoning can be difficult when there is no clear history of exposure, since many of the signs and symptoms of lead poisoning are relatively nonspecific, e.g. tiredness, abdominal pain, anorexia. Laboratory investigations, therefore, play an essential part in the diagnosis and management of lead poisoning and also in the assessment of occupational and environmental lead exposure. By measuring lead isotope ratios in biological specimens it is possible to correlate these with the likely sources of exposure that might be found in a chemical incident or poisoning from an unusual source of lead (Delves and Campbell 1988, 1993).
The best-understood toxic effect of lead is its influence on haemoglobin synthesis leading to anaemia. Lead inhibits the enzyme ferro chelatase, which is involved in iron transport in the bone marrow and catalyses the introduction of ferrous iron (Fe2+) into the porphyrin ring to form haem (Sakai 2000). (This is the last stage of haemoglobin synthesis.) Chronic lead exposure leads to the incorporation of zinc (rather than iron) into the porphyrin ring to produce erythrocyte zinc protoporphyrin (ZPP). The assay of ZPP is relatively simple and is used as an inexpensive screening test for chronic lead exposure (Solé et al. 2000). Monitoring the reduction in blood haemoglobin and the elevation in erythrocyte ZPP helps to assess chronic lead poisoning (Braithwaite and Brown 1988).
About 95% of the lead in blood is associated with the erythrocytes and has a half-life of a few months. Constant exposure results in the accumulation of lead in blood and tissues until a ‘steady-state’ is reached. Provided the degree and type of exposure are relatively constant, blood lead concentrations in environmentally, as well as in some occupationally, exposed individuals maybe stable over long periods of time. Although lead can be found in most tissues of the body, over 90% of the body burden is deposited in the skeleton as insoluble lead phosphate. Following chronic exposure over many years, as occurs in some industrial workers, tissue stores such as bone become saturated. This effectively causes a much slower apparent elimination of lead from the circulation, so that, on cessation of exposure, the blood lead concentration may decline relatively slowly, with an elimination half-life of up to 1 year. Lead is poorly excreted from the body, the most important route being via the kidney. Normal urinary output of lead is less than 10 lg/day (50 nmol/day), but this can be increased greatly by chelation therapy.
Extensive studies have demonstrated the harmful effect of lead exposure on child devel opment, behaviour and intelligence (Needle mann and Gatsonis 1990) and many countries have adopted occupational restrictions for blood lead concentrations to protect workers including young children and the developing fetus in pregnant women.
Normal urinary output of lead is 10 lg/day. A maximum blood lead concentration of 100 lg/L has been recommended in adults and children (Bellinger et al. 1992) but recent evidence suggests that there may be intellectual impair ment in children with blood lead concentrations below this value (Canfield et al. 2003). Somewhat higher levels may be acceptable in adults who are occupationally exposed to lead, but careful monitoring of exposure is essential.
