Table 1.

Evidence-based changes in the approach to the evaluation of risks from chronic low-level exposure to lead

Event	References
Public health authorities formerly identified a tolerable rate of dietary intake of lead intended to maintain exposure below an assumed no-observed-adverse-effect-level (NOAEL). An example is the Provisional Tolerable Weekly Intake (PTWI) of lead for infants and children set by the World Health Organization Joint Expert Committee on Food Additives and Contaminants (JECFA) in 1982. The PTWI approach was endorsed by the EU Commission’s Scientific Committee on Food. In the EU, this approach, together with data on lead exposure, resulted in the setting of Maximum Levels of lead in many foodstuffs in the EU Regulation (EC) No 1881/2006	SCF (1994), SCOOP (2004)
The U.S. Environmental Protection Agency, California EPA and World Health Organization concluded that lead is a substance for which a threshold level for negative effects on human health cannot currently be determined. This rendered the NOAEL and PTWI approaches suspect	USEPA (2006), CalEPA (1997, 2009), WHO (2009)
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 including to consider whether the PTWI of 25 μg/kg b.w. was still appropriate	EFSA (2010)
The EFSA CONTAM Panel identified developmental neurotoxicity in young children and cardiovascular effects and nephrotoxicity in adults as the critical effects for the risk assessment	EFSA (2010)
A meta-analysis of the results of seven studies published between 1989 and 2003 of the IQ of 1333 children in relation to B-Pb, and a refinement/reanalysis of the same data found marked decreases in IQ with increasing B-Pb, even at low B-Pb values.	Lanphear et al. (2005), Budtz-Jørgensen (2010), EFSA (2010)
Meta-analyses supported 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 1 mmHg with each doubling of B-Pb without any clearly identifiable B-Pb threshold for this effect	Staessen et al. (1994), Nawrot et al. (2002) EFSA (2010)
A range of cross-sectional and prospective longitudinal studies were 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. EFSA CONTAM Panel concluded that nephrotoxic effects are real, that they may be greater in men than women and that they are exacerbated by concurrent diabetes or hypertension	EFSA (2010)
EFSA (2010) concluded that there is no evidence for a minimum B-Pb threshold below which effects on IQ, systolic blood pressure and chronic kidney disease do not occur. Hence, they considered that the NOAEL and PTWI approaches were not supported by evidence	EFSA (2010)
Abandonment of NOAEL and PTWI approaches by EFSA was followed by similar conclusions by the WHO/FAO JECFA, Health Canada, and the Centers for Disease Control and Prevention in the United States	JECFA (2011), Health Canada (2012), ACCLPP (2012)