DefinePK

Abstract

INTRODUCTION


There is no evidence that lead is involved in any of the physiological or biochemical functions of the organism and, therefore, it is a purely toxic element. Thus, in theory, the normal lead level in any body fluid should be zero although it has become customary to accept the normal blood levels observed in industrialised society as “nor­mal”. The main aim among clinical biochemists has been to establish “safe values”, “safety limits” or “maximum allowable concentrations”, if, in­deed, such exist at all. Lead has been known for about 5000 years. During the Roman Empire, production was about 80,000 tons per year and has risen, very much more rapidly this century, to about three million tons annually. Half a million tons of this ends up in the atmosphere, 70% of which originates from the combustion of petrol which contains tetraethyl­lead, an additive which is used to improve its anti-knock characteristics.1 The average Ameri­can absorbs about 21 ug/day of lead from food1 and between 1976 and 1980 there has been a drop of 36.7% in blood lead levels in U.S.A. due mainly to the introduction of unleaded petrol. 2 Lead inspired as small particulate matter is absorbed through the lungs and a proportion of that in the diet, about 10% in adults3 and up to 53% in young children,4 is absorbed by the gas-trointes­tinal tract and taken up predominantly by the red blood cells. Over 94% in adults but only about 64% in children is deposited in the bones, 5 where it accumulates. The toxic effects of lead are given by that in the soft tissues of which the brain is the main target organ. 5 Excretion is principally by the liver into the bile, part of which is lost in the faeces and part is reabsorbed into the general circulation and excreted by the kidneys. Blood levels rise rapidly after an exposure to lead but as the half life in blood is only about 18 days, blood levels are a measure of recent ex­posure only whereas lead is retained in the brain for far longer. 6 However, a blood lead estimation is the most convenient biochemical method for the determination of lead status although urinary y-aminolaevulinic acid is often estimated, as the activity of y-aminolaevulinic acid dehydratase, involved in the biosynthesis of baem, is inhibited by lead. Unfortunately the latter estimation some­times fails to indicate the presence of toxic levels of lead, 7 especially in children. 8 Lead poisoning was known to the ancient Greeks, was common among the Romans who used lead water pipes and stored their wine in lead-glazed containers, caused the insanity of some of the Roman emperors and was a con­tributory factor towards the downfall of their empire. In the modern literature, the neurotoxic effects were first reported in 1839, 9 with en­cephalopathy noted in 1910. 10 A massive single dose of lead may cause death or severe brain damage but a lesser not necessarily toxic dose over a long period may cause minimal brain damage and one or more of many subtle effects on the central nervous system, less easily linked by the clinician to lead exposure. These are now the focus of recent research and will be discussed later.