Placental transfer of lead occurs in humans as early as the 12th week of gestation and
continues throughout development. Young children absorb 4–5 times as much lead
as adults, and the biological half-life may be considerably longer in children than in
adults. Lead is a general toxicant that accumulates in the skeleton. Infants, children
up to 6 years of age and pregnant women are most susceptible to its adverse health
effects. Inhibition of the activity of d-aminolaevulinic dehydratase (porphobilinogen
synthase; one of the major enzymes involved in the biosynthesis of haem) in children
has been observed at blood lead levels as low as 5mg/dl, although adverse effects are
not associated with its inhibition at this level. Lead also interferes with calcium metabolism,
both directly and by interfering with vitamin D metabolism. These effects have
been observed in children at blood lead levels ranging from 12 to 120mg/dl, with no
evidence of a threshold. Lead is toxic to both the central and peripheral nervous
systems, inducing subencephalopathic neurological and behavioural effects. There is
electrophysiological evidence of effects on the nervous system in children with blood
lead levels well below 30mg/dl. The balance of evidence from cross-sectional epidemiological
studies indicates that there are statistically significant associations
between blood lead levels of 30mg/dl and more and intelligence quotient deficits of
about four points in children. Results from prospective (longitudinal) epidemiological
studies suggest that prenatal exposure to lead may have early effects on mental
development that do not persist to the age of 4 years. Research on primates has supported
the results of the epidemiological studies, in that significant behavioural and
cognitive effects have been observed following postnatal exposure resulting in blood
lead levels ranging from 11 to 33mg/dl. Renal tumours have been induced in experimental
animals exposed to high concentrations of lead compounds in the diet, and
IARC has classified lead and inorganic lead compounds in Group 2B (possible human
carcinogen). However, there is evidence from studies in humans that adverse neurotoxic
effects other than cancer may occur at very low concentrations of lead and that
a guideline value derived on this basis would also be protective for carcinogenic effects.