International Agency for Research on Cancer 2006 Monograph
On the basis of sufficient evidence from experimental animal studies and limited evidence on humans, IARC (2006) classified inorganic lead compounds as “probably carcinogenic to humans” (Group 2A). The evidence presented in the IARC report consisted of results of human studies of exposed workers and environmentally exposed groups, results of experimental animal studies, and other relevant data. Except for two studies of the second National Health and Nutrition Examination Survey (NHANES II), human studies have relied primarily on comparisons of exposed workers who had blood lead levels (BLLs) mostly over 40 μg/dL. Those studies provided evidence of “no or a slight excess of lung cancer”, a 30-50% excess risk of stomach cancer, a two-fold increase in renal cancer, and a risk of glioma. One concern regarding the stomach-cancer findings was the use of external referent populations and the potential differences in dietary habits and Helicobacter pylori prevalence (see also Ward et al. 2010). Because of the crude exposure classification used in the studies and because effects of confounding could not be ruled out, IARC did not conclude the epidemiologic evidence sufficient to support a causal association. Instead, IARC found that “there is limited evidence in humans for the carcinogenicity of inorganic lead compounds” (IARC 2006, p. 377). However, IARC found the evidence from animal studies sufficient for lead acetate, lead subacetate, lead chromate, and lead phosphate and noted that “extensive experimental evidence shows that various water-soluble and insoluble lead compounds can induce kidney tumours in rodents” and that a study showed they “can occur in the absence of lead-induced nephropathy” (p. 374). It further highlighted the ability of lead to be an effective promoter of organic renal carcinogens.
National Toxicology Program 2011 Report on Carcinogens
The 2004 and 2011 editions of the NTP Report on Carcinogens list lead and lead compounds as “reasonably anticipated to be human carcinogens” (NTP 2011, p. 251). The document supporting the NTP deliberation is the Report on Carcinogens Background Document for Lead and Lead Compounds (NTP 2003). NTP concluded that the epidemiologic evidence linking cancer with lead was strongest for lung and stomach cancer. It noted, however, that evidence