JECFA 73rd Meeting (2010) — Cadmium Addendum (WHO FAS 64)
Summary
This is the primary published cadmium addendum from the Joint FAO/WHO Expert Committee on Food Additives 73rd meeting (Geneva, June 2010), prepared as part of WHO Food Additives Series No. 64 (Safety Evaluation of Certain Food Additives and Contaminants), published in 2011. The addendum is the document of record for JECFA’s establishment of the cadmium provisional tolerable monthly intake (PTMI) of 25 µg per kilogram body weight per month, which replaced the prior provisional tolerable weekly intake of 7 µg/kg b.w./week that had been in force since the 33rd meeting (1988). The PTMI is the operative international cadmium dietary reference value that Codex Alimentarius matrix-specific maximum levels are aligned to, and is the international counterpart to the European Union’s EFSA TWI of 2.5 µg/kg b.w./week.
This source page replaces an earlier secondary-citation-only version that recorded the PTMI value from references in JECFA 91st 2022 and Codex CXS 193-1995. The primary document is now in the corpus with full SHA-256 provenance.
Key numbers
Derivation of the PTMI:
| Parameter | Value |
|---|---|
| Critical endpoint | Renal tubular dysfunction biomarkered by urinary β2-microglobulin (B2M) |
| Cohort basis | Meta-analysis of dose-response studies relating urinary cadmium to B2M excretion in environmentally exposed populations |
| Critical age cohort | Persons 50 years of age and older (steady-state body burden) |
| Apparent half-life of cadmium in human kidneys | Approximately 15 years (steady-state achieved after 45 to 60 years of exposure) |
| Critical urinary cadmium concentration (breakpoint) | 5.24 µg Cd/g creatinine (5th to 95th percentile range 4.94 to 5.57) |
| Toxicokinetic model | One-compartment model |
| Dietary intake corresponding to breakpoint | 0.8 µg Cd/kg b.w./day at the lower-bound 5th population percentile, approximately 25 µg/kg b.w./month |
| PTMI | 25 µg Cd/kg b.w./month |
| Prior PTWI (withdrawn) | 7 µg Cd/kg b.w./week (in force from 33rd meeting, 1988) |
| Rationale for monthly window | Long biological half-life makes monthly averaging more biologically appropriate than weekly |
JECFA’s previous review history for cadmium (16th, 33rd, 41st, 55th, 61st, 64th meetings):
| Meeting | Year | Key conclusion |
|---|---|---|
| 16th | 1972 | First evaluation |
| 33rd | 1988 | PTWI 7 µg/kg b.w./week established (from critical kidney concentration 200 mg/kg tissue and toxicokinetic model linking cadmium bioaccumulation to dietary exposure) |
| 41st | 1993 | Reaffirmed PTWI; noted small margin of safety between dietary exposure and effect levels |
| 55th | 2000 | Reaffirmed; noted that prevalence of renal tubular dysfunction would be negligible below urinary cadmium of 2.5 µg/g creatinine |
| 61st | 2003 | Reaffirmed PTWI; considered CadmiBel (Belgium) and Japanese cohort studies |
| 64th | 2005 | Evaluated impact of different Codex MLs; concluded total dietary exposure was 40-60 percent of PTWI |
| 73rd | 2010 | Withdrew PTWI; established PTMI 25 µg/kg b.w./month |
US dietary cadmium exposure data captured in this addendum (FDA Total Diet Study 2004-2008 with 2003-2006 NHANES consumption):
| Population | Mean exposure (µg/kg b.w./month) | 90th percentile (µg/kg b.w./month) |
|---|---|---|
| M+F 6-11 months | 9.4 | 17.6 |
| M+F 2 years | 12.9 | 21.5 |
| M+F 6 years | 10.9 | 17.1 |
| M+F 10 years | 7.2 | 12.7 |
| M 14-16 years | 5.5 | 10.1 |
| F 14-16 years | 5.3 | 8.9 |
| M 25-30 years | 5.3 | 9.5 |
| F 25-30 years | 4.6 | 8.6 |
| M 40-45 years | 4.7 | 7.2 |
| F 40-45 years | 4.5 | 8.4 |
| M 60-65 years | 4.7 | 8.9 |
| F 60-65 years | 4.3 | 7.2 |
European dietary cadmium exposure (median consumption × mean occurrence by food category, adults):
| Food category | Cadmium exposure (µg/day, consumers only) |
|---|---|
| Cereals/grains | 4.2 |
| Vegetables, nuts, pulses | 3.7 |
| Offal only | 3.0 |
| Starchy vegetables/roots | 2.7 |
| Meat + offal combined | 2.5 |
| Alcoholic beverages | 1.7 |
| Fish and seafood | 1.7 |
| Sugars | 1.1 |
| Milk and dairy products | 1.1 |
| Coffee, tea, cocoa | 1.1 |
| Meat | 1.0 |
Toxicokinetic anchors:
| Parameter | Value |
|---|---|
| GI absorption (humans) | 1 to 10 percent |
| GI absorption (experimental animals) | 0.5 to 3.0 percent |
| Long-term tissue distribution | 50 to 75 percent of total body burden in liver and kidneys at autopsy; additional 20 percent in muscle; small fraction in bone |
| Renal vs hepatic ratio | After short-term exposure, comparable; after prolonged exposure, kidney exceeds liver |
Methods (brief)
The 73rd meeting’s reassessment was driven by the request from the Codex Committee on Contaminants in Food and the availability of new epidemiological evidence using urinary biomarkers (urinary cadmium and B2M) to estimate risk through statistical modeling. The Committee considered whether recent modeled risk estimates would support the previously-established PTWI.
The pivotal methodological choice was a meta-analysis of dose-response studies relating urinary cadmium excretion to urinary B2M excretion in environmentally exposed populations 50 years of age and older. Restriction to this age cohort captured steady-state body burden conditions (cadmium half-life in kidneys ~15 years; steady state at 45-60 years of exposure). The breakpoint analysis identified 5.24 µg Cd/g creatinine as the urinary concentration below which no increased B2M excretion was detectable, with a 5th-to-95th percentile range of 4.94 to 5.57.
Translation from urinary cadmium to dietary intake used a one-compartment toxicokinetic model to estimate the dietary intake that, sustained over a lifetime, would produce the breakpoint urinary concentration in the 5th population percentile. The result was 0.8 µg Cd/kg b.w./day, expressed monthly as approximately 25 µg/kg b.w./month. The Committee chose the monthly averaging window over the prior weekly window because cadmium’s exceptionally long biological half-life makes a monthly time scale more biologically appropriate.
Implications
- Certification: this is the operative international PTMI of record. HMT&C calibration-rationale documentation should cite this primary document for the PTMI value, not the secondary citation in the JECFA 91st meeting monograph.
- Courses: the FAS 64 addendum is the primary teachable derivation document for the PTMI. The shift from PTWI to PTMI (averaging window change) and the meta-analytic approach to the urinary B2M dose-response are the two methodologically novel features of the 73rd meeting compared to prior JECFA cadmium evaluations.
- App: the PTMI of 25 µg/kg b.w./month already operative in app reference-value benchmarking is now backed by full primary-document SHA-256 provenance. The 5.24 µg/g creatinine urinary cadmium breakpoint is a useful biomarker target for app users with biomonitoring data.
Provenance notes
License CC-BY-NC-SA-3.0-IGO per WHO standard publication terms. The PDF (9789241660648_eng.pdf, ISBN 978 924 166064 8) is the official WHO publication and is now in raw/reports/ with SHA-256 verification. The companion document is WHO Technical Report Series 960 (the 73rd meeting Report), which contains the high-level summary of the same conclusions; FAS 64 is the detailed safety evaluation monograph carrying the cadmium addendum.
This source page supersedes an earlier secondary-citation-only version of the same cite key. The values previously recorded from JECFA 91st secondary citations are confirmed against the primary document.