and function image clinical disease is often not possible, because of the lack of specificity and persistence of the response.

Conclusions from the 2012 Environmental Protection Agency and 2012 National Toxicology Program Lead Documents

Environmental Protection Agency 2012 Integrated Science Assessment for Lead (Second External Review Draft)

Because of few data on the immunologic effects of lead in exposed adults, EPA’s draft assessment relied heavily on animal data and epidemiologic studies in children to support its overall conclusion of a causal relationship between lead exposures and immune system effects in adults. EPA’s draft assessment concluded that lead exposure is associated with a broad spectrum of changes in both cell-mediated and humoral immunity that cumulatively promote a TH2 phenotype and a hyperinflammatory state. The principal conclusions were that lead, at BLLs of 30 μg/dL or under, induced an increased production of TH2 cytokines, suppressed production of TH1 cytokines, increased neutrophil infiltration (a marker of inflammation), and increased circulating IgE. In the studies of adults (mostly males) who had occupational lead exposures, the most consistent finding was decreased neutrophil function in workers who had BLLs of 21-71 μg/dL (Valentino et al. 1991). Studies reviewed by EPA also reported a shift toward TH2 cytokines in workers who had a BLL of 5 μg/dL. Uncertainty exists regarding the contributions of current lead exposures and cumulative lead stores in bone, but recent evidence on adults who had no occupational exposure has demonstrated altered concentrations of allergic IgE and specific cytokines in populations of adults who had BLLs of 1.9-7.0 μg/dL. On the basis of the consistency and coherence of findings across the continuum of related immune measures that demonstrated a stimulation of TH2 responses, combined with the supporting epidemiologic evidence on children, EPA concluded that there is a causal relationship between lead exposure and immune system effects. No BLLs were noted as part of that conclusion although decreased neutrophil function, increased concentrations of autoantibodies, increased inflammation, and a shift to TH2 cytokines were observed at BLLs of 30 μg/dL or lower and for some end points as low as 5 μg/dL. Some conclusions drawn by EPA differ from those of the NTP. That probably reflects the fact that data from studies of children and rodent models were used to provide the weight of evidence for EPA’s conclusions.

National Toxicology Program 2012 Monograph on Health Effects of Low-Level Lead

The NTP concluded that there was inadequate evidence on adults to support a causal relationship between a BLL under 10 μg/dL and any immune end points, including IgE, allergy, and other hypersensitivity reactions. That conclusion was



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