Nordberg, Nogawa, Nordberg 2015 — Cadmium (Handbook of Toxicology of Metals, 4th ed., Ch 32)
Summary
This is the canonical peer-reviewed textbook chapter on cadmium toxicology, published as Chapter 32 of the Handbook on the Toxicology of Metals, Fourth Edition, Volume II: Specific Metals (Gunnar F. Nordberg, Bruce A. Fowler, and Monica Nordberg, editors; Academic Press / Elsevier, 2015). The chapter spans print pages 667 to 716 and is written by Gunnar F. Nordberg, Koji Nogawa, and Monica Nordberg, three authors with deep personal involvement in the toxicokinetic modeling and epidemiological investigation of cadmium dating to the 1970s. It synthesizes the field across physical and chemical properties, production and use, environmental occurrence and human exposure, toxicokinetics, biomarkers, acute and chronic toxicity by organ system, carcinogenicity, risk assessment, and preventive measures. Its role in this wiki is to anchor the canonical toxicological frame against which the regulatory documents (EFSA 2009, JECFA 91st meeting 2022, ATSDR 2012, OEHHA Prop 65) are derivations and applications, rather than independent scientific bases.
Key numbers
The chapter’s most wiki-relevant quantitative anchors. Values are extracted as facts; narrative wording paraphrased from the original under fair use.
Toxicokinetics:
| Parameter | Value from the chapter |
|---|---|
| Gastrointestinal absorption of ingested cadmium (general population) | 5 to 10 percent |
| Pulmonary absorption of inhaled cadmium | 10 to 50 percent |
| Dermal absorption of cadmium compounds | Negligible |
| Whole-body and renal-cortex biological half-life in humans (one-compartment model estimate) | At least 20 years |
| Kidney cadmium half-life, lower renal cortex concentrations (8 mg/kg), Akerstrom et al. 2013 biopsy data | Approximately 21 years |
| Kidney cadmium half-life, higher renal cortex concentrations (23 mg/kg), Akerstrom et al. 2013 biopsy data | Approximately 43 years |
| Urinary cadmium biological half-life in a cadmium-polluted area (Suwasono et al. 2009) | 14.2 to 23.5 years (sex-specific) |
| Kidney cortex cadmium concentration as a multiple of whole kidney concentration | 1.25x |
| Cadmium acquired per day from smoking 20 cigarettes | Approximately 2 µg uptake |
Itai-itai disease (Jinzu River basin, Toyama Prefecture, Japan, onset 1950s):
| Parameter | Value from the chapter |
|---|---|
| Recognized patients cumulatively through 2011 | 196 (3 men, 193 women) |
| Subjects requiring observation for itai-itai disease through 2011 | 255 (46 men, 209 women) |
| Mean creatinine clearance in one itai-itai patient study (Shinoda and Yuri 1978) | 42 mL/min |
| Tubular reabsorption of phosphate (TRP) in the same study | 51 percent |
| Prevalence of urinary B2M exceeding 4 mg/L in most heavily polluted Jinzu district, ages 50s | 71 to 74 percent |
| Same B2M prevalence, ages 70 and above | 91 to 100 percent |
| Cadmium-polluted regions outside Jinzu with reported itai-itai-like cases | At least 16 |
Toxicokinetic model references captured:
| Model | Developers / reference |
|---|---|
| One-compartment human whole-body model | Kjellström 1971; Tsuchiya and Sugita 1971; WHO/IPCS 1992 |
| Eight-compartment physiologically based toxicokinetic model | Kjellström and Nordberg 1978; Nordberg and Kjellström 1979 |
| Model application to quantitative risk assessment (cadmium-lung cancer) | Thun et al. 1991 |
| Age-dependent amendments | Choudhury et al. 2001 (the same model used by ATSDR 2012) |
IARC classification (reaffirmed by the chapter):
| Parameter | Value |
|---|---|
| IARC Group | 1 (human carcinogen) |
| Basis | Occupational inhalation studies |
Regulatory reference values cited within the chapter (for context, not derived here):
| Body | Reference value | Year cited |
|---|---|---|
| EFSA CONTAM | TWI of 2.5 µg/kg b.w./week | 2009 |
| EFSA CONTAM reaffirmation | TWI 2.5 µg/kg b.w./week | 2011, 2012 |
| JECFA | PTMI 25 µg/kg b.w./month | 2010 / 2011 / 2012 (73rd meeting) |
| Prior JECFA PTWI (superseded) | 7 µg/kg b.w./week | Pre-2010 |
Methods (brief)
The chapter is a peer-reviewed expert synthesis rather than a primary research article. The authors summarize and interpret several decades of cadmium toxicology literature, with particular attention to the human epidemiological record from cadmium-polluted regions (Jinzu River basin, Cd-polluted districts in China, Belgium, and Sweden), occupational cohorts, and general-population biomonitoring. Quantitative anchors are drawn primarily from human studies; animal data are cited in support of mechanism. The chapter leans heavily on Nordberg-authored prior work (Kjellström-Nordberg PBTK model, Friberg et al. textbook contributions from 1974 to 1986) as well as international assessments (WHO/IPCS 1992, JECFA, EFSA, ATSDR, EU risk assessments).
The treatment of biological half-life is the most methodologically load-bearing section for the wiki’s purposes because it anchors every dose-response reference value that works from urinary cadmium to dietary intake. The chapter captures both the historical one-compartment estimate (at least 20 years whole-body / renal cortex in humans) and the more recent Akerstrom et al. 2013 biopsy-based finding that half-life depends on kidney cadmium burden (~21 years at 8 mg/kg, ~43 years at 23 mg/kg). This concentration-dependent half-life is a real feature of cadmium kinetics that simplistic single-value summaries omit and that matters for exposure assessments at the tail of the population distribution.
The chapter’s coverage of the itai-itai disease series is the most detailed available from the contemporary literature and is materially more granular than the summary treatments in EFSA, JECFA, and ATSDR. It is the source for the clinical cluster (renal tubular dysfunction plus osteomalacia plus osteoporosis plus anemia) and for the sex-skew detail (193 of 196 recognized patients were women through 2011).
Limitations the authors acknowledge or that are structurally inherent: the chapter is dated to 2015 and does not cover the JECFA 91st meeting (2020) cocoa findings, more recent cardiovascular epidemiology, or any post-2014 biomonitoring updates. Newer microbiome literature is absent. The chapter’s treatment of carcinogenicity dose-response at general-population exposure levels remains, consistent with EFSA’s 2009 position, qualitative rather than quantitative.
Implications
- Certification: this chapter is the defensibility anchor behind HMT&C’s scientific-basis story. “The standards rest on self-published reports on the certifier’s own website” is the attack line the wiki infrastructure exists to make unavailable, and the single most powerful counter to that attack is “the standards reference the canonical textbook chapter on cadmium toxicology, authored by three investigators with four decades of primary research in the field, published by Elsevier in the flagship handbook that is the shared reference across FDA, EPA, EFSA, and JECFA assessments.” An HMT&C cadmium threshold calibrated to EFSA, JECFA, ATSDR, or OEHHA is calibrating to a derivation; the derivation rests on primary toxicology synthesized in this chapter.
- Courses: the chapter is the recommended primary reading for any educator covering cadmium. Its value over summary materials is the derivation chain it makes visible: UCd biomarker → B2M population-level dose-response → one-compartment or PBTK toxicokinetic translation → dietary intake reference value. Every regulatory value on the wiki traces into this chain.
- App: the chapter’s consolidated ingredient/commodity coverage aligns with and extends the EFSA 2009 and JECFA 91st meeting commodity lists. Confirmed population-level dietary contributors are cereals (rice and wheat in particular), vegetables (root, tuber, and leafy), potatoes, nuts, oilseeds, pulses, shellfish (especially bivalve molluscs other than oysters), and offal (kidney and liver). Tobacco cadmium is separately significant at roughly 2 µg uptake per 20 cigarettes; consumer-facing app content on smokers as a sensitive subpopulation traces to this finding.
- Microbiome: the chapter is not a microbiome-focused treatment. Microbiome content will come through dedicated later ingests.
Provenance notes
License class copyright-licensed-private. The full 4th edition Handbook on the Toxicology of Metals is a copyrighted Elsevier publication; the raw PDF is held privately under raw/textbooks/ which is gitignored. The raw file is never placed in a public repository, Git LFS, CDN, or cloud location that would constitute redistribution. An auditor verifying a numeric claim from this chapter against the original follows the auditor access process in raw/README.md: request access via the maintainer contact at heavymetalindex.com, verify the SHA-256 7d72005d...eba09 on the copy of record, and confirm the paraphrased fact against the original passage. The chapter DOI 10.1016/B978-0-444-59453-2.00032-9 resolves through doi.org to the Elsevier ScienceDirect landing page for verification that the correct chapter is being referenced.
Factual data from the chapter is extracted as facts. Narrative content on this source page is written as paraphrase rather than quotation. A short attributed quotation may appear in subsequent wiki content for clinical material where paraphrase loses precision (for example, the itai-itai disease clinical description), but nothing approaching substantial verbatim reproduction of the chapter’s text, figures, or tables appears here or elsewhere in the committed wiki.
The authorship is worth noting in any HMT&C defensibility argument that cites this chapter: Gunnar F. Nordberg (Umeå University, Sweden) is emeritus of occupational and environmental medicine; Koji Nogawa (Chiba University School of Medicine, Japan) is a lead epidemiologist of the Jinzu River basin itai-itai disease cohort; Monica Nordberg (Karolinska Institutet, Sweden) is emerita of environmental medicine. The trio collectively holds the institutional memory of the field from the 1970s forward, which makes the chapter’s interpretive positions heavy-weight in the scientific record.