Clinical Pharmacist and Master’s student in Clinical Pharmacy with research interests in pharmacovigilance, behavioral interventions in mental health, and AI applications in clinical decision support. Experience includes digital health research with Bloomsbury Health (London) and pharmacovigilance practice in patient support programs. Published work covers drug awareness among healthcare providers, postpartum depression management, and patient safety reporting. 
Clinical Pharmacist and Master’s student in Clinical Pharmacy with research interests in pharmacovigilance, behavioral interventions in mental health, and AI applications in clinical decision support. Experience includes digital health research with Bloomsbury Health (London) and pharmacovigilance practice in patient support programs. Published work covers drug awareness among healthcare providers, postpartum depression management, and patient safety reporting. What was reviewed?
This commentary systematically critiques the cadmium risk assessment paradigm, with special focus on how urinary cadmium (U-Cd) is used as a proxy for cumulative dose and how that choice shapes regulatory limits for food and occupational exposure. Centering the cadmium risk assessment paradigm, the author synthesizes epidemiologic and toxicokinetic evidence showing that low-level U-Cd is strongly affected by renal physiology, recent exposure, and essential-element status, rather than long-term body burden alone conditions that can mislead certification and regulatory decisions. The review also contrasts European and international risk managers’ decisions, explaining why differing points of departure and uncertainty factors produced conflicting intake limits and product standards relevant to HTMC.
Who was reviewed?
Evidence spans industrial workers with high historical exposures, environmentally exposed general populations across Europe, Asia, and the United States, smokers and former smokers, children and adolescents, and healthy adult kidney donors. Biomonitoring and follow-up cohorts are highlighted where U-Cd covaries with protein excretion and glomerular filtration, and where nutritional status (iron, zinc, calcium) modulates absorption. Regulatory analyses by EFSA, JECFA, and SCOEL are dissected to show how method choices shift “safe” intakes, with practical implications for setting product limits in foods like cereals, vegetables, chocolate, and infant products under ALARA constraints.
Most important findings
| Critical point for HTMC | Details for certification and regulation |
|---|---|
| U-Cd is not a pure body-burden marker at low levels | Low-level U-Cd varies widely within and between individuals with urinary flow, creatinine adjustment artifacts, and recent exposure; adolescents can show U-Cd similar to adults despite 5–10× lower burden. This undermines using fixed U-Cd cutoffs for certification screening. |
| Renal physiology confounds associations | Co-excretion of cadmium with low-molecular-weight proteins and albumin creates spurious links between U-Cd and “renal effects,” risking false attribution of toxicity in compliance investigations. |
| Essential-element status modifies absorption | Iron deficiency and zinc/calcium requirements up-regulate shared transporters, increasing Cd uptake; dietary habits thus influence both exposure and outcomes, complicating residue-based pass/fail criteria. |
| Recent exposure signal is strong | U-Cd declines 20–40% within a year after smoking cessation or smoke-free legislation, indicating sensitivity to short-term changes rather than lifetime dose—critical for interpreting retests and corrective-action timelines. |
| Historical PoDs vs. modern thresholds diverge | Worker-based critical kidney Cd (~200 ppm) corresponds to U-Cd ≈10 µg/g creatinine; later population-based approaches selected lower U-Cd thresholds (e.g., 2–4 µg/g) and applied large variability factors, driving stricter food limits. |
| EFSA vs. JECFA inconsistency | Using the same model but different adjustment factors produced TWI ≈2.5 µg/kg/week (EFSA) versus PTMI 25 µg/kg/month (≈6 µg/kg/week, JECFA), yielding conflicting compliance implications for commodity categories. |
| ALARA and selective product limits | The EU targeted cocoa/infant foods because broad limits on cereals/vegetables are infeasible given soil backgrounds; certification programs must anticipate such selective tightening and communicate risk-tradeoffs. |
| Non-renal outcomes at very low U-Cd are likely confounded | Reported links to bone, cardiovascular, developmental and other endpoints at U-Cd <0.5 µg/g may reflect reverse causation via proteinuria or nutritional deficits, cautioning against equating correlation with causation in audits. |
Key implications
For HTMC, the cadmium risk assessment paradigm demands recalibration: regulatory impacts center on avoiding sole reliance on U-Cd at low exposure; certification requirements should prioritize exposure source characterization, matrix-specific bioavailability, and nutritional-status context; industry applications should integrate transporter-linked modifiers and recent-exposure sensitivity; research gaps include validated alternatives to U-Cd and robust confounder control; practical recommendations are to couple residue testing with iron and zinc indices, specify standardized urine collection, and use conservative yet feasible limits tied to commodity-specific bioavailability.
Citation
Bernard A. Confusion about cadmium risks: the unrecognized limitations of an extrapolated paradigm. Environmental Health Perspectives. 2016;124(1):1-5. doi:10.1289/ehp.1509691
Cadmium is a persistent heavy metal that accumulates in kidneys and bones. Dietary sources include cereals, cocoa, shellfish and vegetables, while smokers and industrial workers receive higher exposures. Studies link cadmium to kidney dysfunction, bone fractures and cancer.
