35
1960s (CDC 2005, 2012, Green and Pain 2012).
The removal of lead additives fromvehicle fuel across Europe has
resulted in a substantial decrease in lead absorbed through the
lungs from the atmosphere. Today, themajority of lead exposure
in the general population across the EU, including the UK, is
from the diet (EFSA 2010). For decades, the principal approach
of public health authorities to assessing health impacts of lead
in the diet has been to identify a tolerable rate of dietary intake.
This sought tomaintain exposure belowa no-observed-adverse-
effect-level (NOAEL) that was assumed to exist. In 1982, the Joint
Food and Agriculture Organisation/World Health Organisation
Expert Committee on Food Additives (JECFA) set a Provisional
Tolerable Weekly Intake (PTWI) of dietary lead of 25 μg/kg bw
for infants and children This was extended to all age groups in
1993 and confirmed by JECFA in 1999. The PTWI was endorsed
in 1992 by the European Commission’s Scientific Committee
for Food (SCF 1994). The European Commission carried out an
updated lead exposure assessment in 2004 (SCOOP 2004) and
together with the SCF opinion this formed the basis of setting
Maximum Levels of lead in foodstuffs in the EU (Regulation (EC)
No 1881/2006). However, today it is considered that there is no
blood lead concentration below which negative physiological
effects of lead are known tobe absent (EFSA2010, ACCLPP 2012).
Hence, the concept of a tolerable intake level has been called
into question. In 2007, the European Commission requested the
European Food Safety Authority (EFSA) to produce a scientific
opinion on the risks to human health related to the presence of
lead in foodstuffs. In particular, EFSA was asked to consider new
developments regarding the toxicity of lead, and to consider
whether the PTWI of 25 μg/kg bw was still appropriate.
Following a detailed analysis of the toxicological information,
the EFSA CONTAM Panel based their dose-response modelling
on chronic effects in humans, and identified developmental
neurotoxicity in young children and cardiovascular effects
and nephrotoxicity in adults as the critical effects for the risk
assessment. Several key findings are briefly summarised below
with numerous individual studies fully referenced in EFSA (2010).
NEUROTOXICITY
A large number of studies have examined the relationship
between B-Pb and measures of nervous system function in
childrenandadults.Toxiceffectsof leadupon thenervous system
in adults include impairment of central information processing,
especially for visuospatial organisation and short-term verbal
memory, psychiatric symptoms and impaired manual dexterity.
There is also evidence that the developing brains of children are
especially susceptible to the effects of lead exposure, even at
low concentrations of lead.
A meta-analysis of the results of seven studies published
between 1989 and 2003 of the IQ of 1,333 children in relation
to B-Pb (Lanphear et al. 2005), and a refinement/reanalysis of
the same data (Budtz-Jørgensen 2010) found marked decreases
in IQ with increasing B-Pb, even at low B-Pb values. The effects
of lead on the developing nervous system appear to persist, at
least until late teenage years.
CARDIOVASCULAR EFFECTS
Long-term low-level exposure to lead is associatedwith increased
blood pressure in humans. Meta-analyses support a relatively
weak, but statistically significant, association between B-Pb levels
and systolic blood pressure, amounting to an increase in systolic
blood pressure of approximately 1mmHg with each doubling of
B-Pb (Nawrot et al. 2002, Staessen et al. 1994), without any clearly
identifiable B-Pb threshold for this effect.
NEPHROTOXICITY
A range of cross-sectional and prospective longitudinal studies
have been conducted to examine the relationship between
serum creatinine levels, which rise when kidney filtration is
deficient, and B-Pb. Studies suggest an increased likelihood of
chronic kidney disease as B-Pb levels rise, and the EFSA CONTAM
Panel concluded that nephrotoxic effects are real, that they may
be greater inmen thanwomen and that they are exacerbated by
concurrent diabetes or hypertension.
The EFSA CONTAM Panel’s analysis led to the conclusion that
there is no evidence for a minimum B-Pb threshold belowwhich
effects on IQ, systolic blood pressure and chronic kidney disease
do not occur. Hence, the NOAEL and PTWI approaches were
not supported by evidence. Instead, the EFSA CONTAM Panel
proposed the use of the Benchmark Dose (BMD) approach. The
BMD is the B-Pb concentration associated with a pre-specified
change in response (i.e. a specified loss of IQ, increase in systolic
blood pressure, increased incidence of chronic kidney disease),
the Benchmark Response (BMR).
The EFSA CONTAM Panel proposed BMRs that could have
significant consequences for human health on a population basis
(Table1).Thesewere: a 1%reduction in IQ (aonepoint reduction in
UK human health risks from ammunition-derived lead