Collated by Elizabeth O’Brien, Lead Scientist and Lead Advisor, The LEAD Group Inc, Australia, Nov 2021
From the Reference:
United States Environment Protection Agency (US EPA) Integrated Science Assessment for Lead – [published June 26, 2013, with Errata Sheet Created May 12, 2014], https://cfpub.epa.gov/ncea/isa/recordisplay.cfm?deid=255721
PREAMBLE – EPA Framework for Causal Determination: Evaluating Evidence for Inferring Causation page lii [page 54/1886 in whole pdf]
Many of the health and environmental outcomes reported in these studies have complex etiologies. Diseases such as asthma, coronary heart disease (CHD) or cancer are typically initiated by multiple agents.
PREAMBLE – Quantitative Relationships: Effects on Human Populations page lxiii-lxiv [pages 65-66/1886]
…the available human data at ambient concentrations for some environmental pollutants [cont’d next page] (e.g., particulate matter [PM], O3, lead [Pb], environmental tobacco smoke [ETS], radiation) do not exhibit thresholds for cancer or noncancer health effects, even though likely mechanisms include nonlinear processes for some key events.
EXECUTIVE SUMMARY – Health Effects of Pb page lxxxvii [page 89/1886]
CHAPTER 1 – INTEGRATIVE SUMMARY – 1.6 Health Effects page 1-19 [page 117/1886]
Table 1-2 (Continued): Summary of causal determinations for the relationship between exposure to Pb and health effects.
CHAPTER 1 – INTEGRATIVE SUMMARY – 1.6 Health Effects: 1.6.7 Cancer pages 1-37 – 1-38 [page 135-136/1886]
The toxicological literature provides the strong evidence for the effect of long-term exposure (i.e., 18 months or 2 years) to high concentrations of Pb (> 2,600 ppm) on cancer. The consistent evidence indicating Pb-induced carcinogenicity in animal models is substantiated by the mode of action findings from multiple high-quality toxicological [cont’d next page] studies in animal and in vitro models from different laboratories. Based on such evidence, IARC has classified inorganic Pb compounds as a probable human carcinogen and the National Toxicology Program has listed Pb and Pb compounds as “reasonably anticipated to be human carcinogens.” Strong evidence from animal toxicological studies demonstrates an association between Pb and cancer, genotoxicity or epigenetic modification. Carcinogenicity in animal toxicology studies with relevant routes of Pb exposure has been reported in the kidneys, testes, brain, adrenals, prostate, pituitary, and mammary gland, albeit at high doses of Pb. Epidemiologic studies of cancer incidence and mortality reported inconsistent results; one strong epidemiologic study demonstrated an association between blood Pb and increased cancer mortality, but the other studies reported weak or no associations. In the 2006 Pb AQCD, various indicators of Pb exposure were found to be associated with stomach cancer, and a recent study on stomach cancer and occupational Pb exposure reported mixed findings depending on the type of Pb exposure (organic Pb, inorganic Pb, or Pb from gasoline emissions). Similarly, some studies in the 2006 Pb AQCD reported associations between Pb exposure indicators and lung cancer. Recent epidemiologic studies of lung cancer focused on occupational exposures and reported inconsistent associations. The majority of epidemiologic studies of brain cancer had null results overall, but positive associations between Pb exposure indicators and brain cancer were observed among individuals with certain genotypes. Overall, the consistent and strong body of evidence from toxicological studies on carcinogenicity and potential modes of action but inconsistent epidemiologic evidence is sufficient to conclude that a causal relationship is likely to exist between Pb exposure and cancer.
CHAPTER 1 – INTEGRATIVE SUMMARY – 1.8 Integration of Health and Ecological Effects page 1-61 [page 159/1886]
Table 1-4 Summary of causal determinations for health and ecological effects.
CHAPTER 1 – INTEGRATIVE SUMMARY – 1.8.1 Modes of Action Relevant to Downstream Health and Ecological Effects page 1-64 [page 162/1886]
Table 1-5 Modes of action, their related health effects, and information on concentrations eliciting the MOAs.
Table 1-8 (Continued): Summary of evidence from epidemiologic, animal toxicological and ecological studies on the effects associated with exposure to Pb.
CHAPTER 1 – INTEGRATIVE SUMMARY – References for Chapter 1 page 1-101 [page 199/1886]
Weisskopf, MG; Jain, N; Nie, HL; Sparrow, D; Vokonas, P; Schwartz, J; Hu, H. (2009). A prospective study of bone lead concentration and death from all causes, cardiovascular diseases, and cancer in the department of veterans affairs normative aging study. Circulation 120: 1056-1064. http://dx.doi.org/10.1161/circulationaha.108.827121
CHAPTER 3 – EXPOSURE, TOXICOKINETICS, AND BIOMARKERS – 3.3 Pb Biomarkers page 3-55 [page 518/1886]
Numerous mechanistic models of Pb biokinetics in humans have been proposed, and these are described in the 2006 Pb AQCD (U.S. EPA, 2006b) and in the supporting literature cited in that report. In this section, for simplicity and for internal consistency, discussion is limited to predictions from a single model, the ICRP Pb biokinetics model (Pounds and Leggett, 1998; ICRP, 1994; Leggett, 1993). The ICRP model consists of a systemic biokinetics model (Leggett, 1993) and a human respiratory tract model (ICRP, 1994). The Leggett model simulates age-dependent kinetics of tissue distribution and excretion of Pb ingestion and inhalation intakes. This model was originally developed for the purpose of supporting radiation dosimetry predictions and it has been used to develop cancer risk coefficients for internal radiation exposures to Pb and other alkaline earth elements that have biokinetics similar to those of calcium (ICRP, 1993).
CHAPTER 3 – EXPOSURE, TOXICOKINETICS, AND BIOMARKERS – References for Chapter 3 page 3-179 [page 642/1886]
Weisskopf, MG; Jain, N; Nie, HL; Sparrow, D; Vokonas, P; Schwartz, J; Hu, H. (2009). A prospective study of bone lead concentration and death from all causes, cardiovascular diseases, and cancer in the department of veterans affairs normative aging study. Circulation 120: 1056-1064. http://dx.doi.org/10.1161/circulationaha.108.827121
CHAPTER 4 – INTEGRATED HEALTH EFFECTS OF LEAD EXPOSURE – 4.1 Introduction page 4-1 [page 645/1886]
Chapter 4 concludes with a discussion of the evidence for the cancer effects of Pb (Section 4.10).
CHAPTER 4 – INTEGRATED HEALTH EFFECTS OF LEAD EXPOSURE – 4.2.8 Summary page 4-52 [page 696/1886]
Table 4-2 MOAs, their related health effects, and information on concentrations eliciting the MOAs.
CHAPTER 4 – INTEGRATED HEALTH EFFECTS OF LEAD EXPOSURE – 4.4.5 Mortality page 4-389 [page 1033/1886]
Using NHANES II (1976-1980) data, Lustberg and Silbergeld (2002) found significant increases in all-cause mortality, circulatory mortality, and cancer mortality, comparing adults with blood Pb levels of 20-29 μg/dL to those with blood Pb levels less than 10 μg/dL (measured 12-16 years before ascertainment of vital status). Using NHANES III data, Schober et al. (2006) found significant increased all-cause, cardiovascular, and cancer mortality comparing adults with blood Pb levels from 5-9 μg/dL and above 10 μg/dL to those with blood Pb levels less than 5 μg/dL (measured a median of 8.8 years before ascertainment of vital status).