NEHA December 2022 Journal of Environmental Health

18 Volume 85 • Number 5 A D VANC EME N T O F T H E SCIENCE  S P E C I A L R E P O R T Michelle Del Rio, MPH, PhD Department of Environmental and Occupational Health, Indiana University–Bloomington Christina Sobin, PhD Department of Public Health Sciences, University of Texas at El Paso Ganga Hettiarachchi, PhD Department of Agronomy, Kansas State University Introduction Lead poisoning in U.S. children continues at staggering rates in selected sectors, particularly among those living in under-resourced communities where older unrenovated housing and lead paint are still major sources of exposure. In over 3,000 U.S. cities, child lead poisoning rates exceed those found in Flint, Michigan, at the height of the crisis (Pell & Schneyer, 2016, 2017). Solving the problem of lead poisoning in U.S. children will require accurate detection of exposed children. In many states, child BLL testing practices rely on single tests among only the youngest children (i.e., 0–5 years) to rule out lead exposure, implicitly assuming that one or two tests in early childhood can accurately reflect a child’s ongoing exposure risk. Lead exposure occurs via inhalation or ingestion. Among children, when exposure is chronic, 99% of absorbed lead is taken up by red blood cells (RBCs) (Agency for Toxic Substances and Disease Registry [ATSDR], 2017; deSilva, 1981) and child lead exposure is most commonly determined from whole blood samples. BLLs reflect circulating lead and, in many cases, exposure occurring in the preceding 28 to 40 days (Griœn et al., 1975; Rabinowitz et al., 1973). The potent toxicity of lead during development has been attributed to many factors but in particular, lead structurally mimics calcium and causes multitiered damage in calcium-channel dependent pathways, systems, and organ mechanisms (Lidsky & Schneider, 2003). More specifically, Pb2+ readily enters RBCs because its radius is slightly smaller than that of Ca2+ (Kirberger & Yang, 2008; Simons, 1986a, 1986b). Lead also gains entry to RBCs when the permeability of cell walls shift the processes that are dependent on developmental and individual di¤erences as well as exigencies in the child’s environment (Hasan et al., 1967; Riordan & Passow, 1971; Vincent, 1958). Once absorbed, Pb2+ binds to delta-aminolaevulinic acid dehydratase enzyme (ALAD), specifically the three-cysteine site of ALAD, replacing Zn2+ and interrupting the second step in heme synthesis (Gonick, 2011; Sakai et al., 1983). The binding aœnity of Pb2+ is, in fact, greater than that of Zn2+ (Boudene et al., 1984; Gonick, 2011). With regard to individual variability in these processes, there are three ALAD common genetic variants (ALAD-1, ALAD-1-2, and ALAD-2-2) that vary in their binding properties and thus their aœnity for lead. ALAD-2-2 has the highest aœnity for lead (Gonick, 2011; Pérez-Bravo et al., 2004; Scinicariello et al., 2007) and is associated with higher BLLs in children (Kim et al., 2004; Pérez-Bravo et al., 2004; Scinicariello et al., 2007; Sobin et al., 2009, 2011, 2015; Wetmur et al., 1991). It is logical to suggest that the stability of BLLs over time in children with each of these genetic variants would be expected to di¤er. Some key absorption mechanisms and their development throughout childhood suggest additional sources of variability and Abs t r ac t Childhood lead poisoning in the U.S. continues to be a major unresolved child public health issue. One barrier to solving the problem of lead poisoning concerns current child blood lead level (BLL) monitoring practices. In most states, one or two BLL tests administered in early childhood are used to rule out lead exposure. Current knowledge, however, regarding the multiple, complex biological mechanisms that underlie lead absorption and distribution during development suggests that child BLLs should be assumed to be an informative but necessarily fluctuating metric of current child lead exposure. We review some key mechanisms and pathways that influence lead absorption, lead distribution, and the stability of lead in red blood cells. We also consider how each of these factors and their development are likely to drive fluctuations in child BLLs over time. The goal of this special report is to provide a starting point for change in current child BLL testing practices. Solving the problem of child lead exposure will require new approaches to child BLL testing that take into account likely fluctuations in child BLLs. Biological Factors That Impact Variability of Lead Absorption and Blood Lead Level Estimation in Children: Implications for Child Blood Lead Level Testing Practices