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JECFA 67th Meeting (2006) — Aluminium PTWI Revision and Methylmercury PTWI Confirmation (WHO TRS 940)

The sixty-seventh meeting of the Joint FAO/WHO Expert Committee on Food Additives (Rome, 20-29 June 2006) addressed five food additives and three contaminants, of which two are within scope for Heavy Metal Index: aluminium from all sources including food additives (Section 4.1, a full re-evaluation that revised the provisional tolerable weekly intake downward from 7 mg/kg b.w./week to 1 mg/kg b.w./week expressed as Al) and methylmercury (Section 4.3, a clarification meeting that confirmed the 1.6 µg/kg b.w./week PTWI set at the 61st meeting in 2003 and formally withdrew the prior 3.3 µg/kg b.w./week PTWI). The chloropropanols section (Section 4.2, covering 3-chloro-1,2-propanediol and 1,3-dichloro-2-propanol) and the food-additive sections (annatto, lycopene, natamycin, propyl paraben, and seven specifications-only items) are out of scope and are not summarized below.

Key numbers

Aluminium — new provisional tolerable weekly intake (this meeting)

ParameterValueSource page
New PTWI for aluminium (this meeting)1 mg/kg b.w./week, expressed as Alp. 43
Previously established PTWI (withdrawn at this meeting)7 mg/kg b.w./weekp. 33, p. 37 (originally JECFA 33rd, 1988)
Range of lowest LOELs from dietary studies in mice, rats, and dogs50-75 mg/kg b.w./day, expressed as Alp. 43
Lower end of the LOEL range used as point of departure50 mg/kg b.w./day, expressed as Alp. 43
Uncertainty factor for inter- and intraspecies differences100p. 43
Additional uncertainty factor for database deficiencies (no NOELs, no long-term studies on relevant endpoints)3p. 43
Composite uncertainty factor300p. 43 (50 ÷ 300 ≈ 0.17 mg/kg b.w./day ≈ 1 mg/kg b.w./week)
Critical endpoints driving the revisionReproductive and developmental effects (LOELs 13-200 mg/kg b.w./day, soluble Al), histopathological changes in kidney/brain at 17-20 mg/kg b.w./day, neurobehavioural effects at 50-200 mg/kg b.w./dayp. 35-37
Form basisPTWI applies to all aluminium compounds in food, including additivesp. 43
All previously established Al ADIs and PTWIsWithdrawnp. 43

Aluminium — Table 6: estimated ranges of mean adult dietary exposure (this meeting)

Sourcemg/week (as Al)% PTWI (60 kg adult)
Natural dietary sources7-702-120
Water (typical untreated)<0.71-20 (entire water column)
Water (treated with aluminium salts)1.4-2.8
Water (acidic untreated)14
Food-contact materials (theoretical, conservative assumption)0-49<80
Overall diet, including additives14-28020-500

Aluminium — exposure in young children and infants (this meeting)

PopulationMean exposureSource
UK children, 1.5-4.5 years (measured body weight)0.16 mg/kg b.w./dayp. 41
UK children, 1.5-4.5 years, high-consumption0.33 mg/kg b.w./dayp. 41
USA children, ~age 2 (assuming 12 kg body weight)~0.5 mg/kg b.w./dayp. 41
China children, ages 2-7 (assuming 16.5 kg body weight)~1 mg/kg b.w./dayp. 41
China children, ages 8-12 (assuming 29.4 kg body weight)~1 mg/kg b.w./dayp. 41
Infant (3 months, 6 kg, 1 L/day at 95th-percentile consumption) fed soya-based formulaup to 1 mg/kg b.w./dayp. 42
Same infant fed milk-based formulaup to 0.06 mg/kg b.w./dayp. 42
Same infant fed human or cow’s milk<0.01 mg/kg b.w./dayp. 42

Aluminium — total adult dietary exposure ranges (this meeting)

Survey or modelled valueValueGeography
Duplicate-diet study mean (range across countries)3-13 mg/daymultinational (p. 41)
Highest single reported value100 mg/daymultinational (p. 41)
75th-percentile multicentre exposure3-26 mg/dayby country (p. 41)
Most recent French survey, mean adult exposure2 mg/dayFrance (p. 41)
Modelled or market-basket high estimate>40 mg/dayChina (p. 41)
Germany — change in dietary Al, 1988 vs 1996Decreased by about halfGermany (p. 41)
Cereal-products mean Al concentration50 mg/kg (highest food-group mean)China 1992-1993 TDS (p. 41)
Miscellaneous-cereals mean Al concentration19 mg/kg (highest food-group mean)UK 2000 TDS (p. 41)
French model-diet exposure (general population)0.03 mg/kg b.w./dayFrance (p. 38, from 2 L water/day at 1 mg/L)

Aluminium — concentrations in source foods (this meeting)

Source / matrixAl concentration (mg/kg unless noted)Geography or note
Most foods (typical content)<5 mg/kggeneral (p. 38)
Dissolved Al in untreated water near pH 71-50 µg/Lgeneral (p. 38)
Dissolved Al in acidic waterup to 1000 µg/Lgeneral (p. 38)
Finished drinking-water Alusually <0.2 mg/Lgeneral (p. 38)
Treated drinking-water dietary contributionup to 0.4 mg/day = 0.007 mg/kg b.w./day2 L/day (p. 38)
Processed cheese300 mg/kgUSA (p. 41)
Home-made corn bread400 mg/kgUSA (p. 41)
Muffins130 mg/kgUSA (p. 41)
Baking powder2300 mg/kgUSA (p. 41)
Table salt164 mg/kgUSA (p. 41)
Biscuits22 mg/kgGermany (p. 41)
Soft cheese8-16 mg/kgGermany (p. 41)
Reconstituted soya-based formula (range)0.4-6 mg/L (ready-to-drink)(p. 42)
Reconstituted cow’s-milk-based formula (range)0.01-0.4 mg/L (ready-to-drink)(p. 42)
Human milk and cow’s milk Al<0.05 mg/L(p. 42)
Antiperspirant absorption (single use, both underarms)~4 µg Al absorbed(p. 42)
Aluminium-buffered aspirin daily contributionup to 0.7 g Al/dayrheumatoid arthritis use case (p. 42)
Aluminium antacid daily intakeup to 5 g Al/dayas directed (p. 42)

Aluminium — Codex GSFA-listed aluminium compounds reviewed (Table 5, this meeting)

CompoundINS No.Function (abbreviated)Levels of use (mg/kg as Al)Prior JECFA evaluation
Sodium aluminium phosphate (SALP), acidic and basic541(i), 541(ii)Acidity regulator, emulsifier, raising agentup to 35 000 in processed cheese; 45 000 in floursPTWI for Al powder (GSFA Tables 1 and 2)
Aluminium ammonium sulfate523Firming/raising agentup to 10 000 in bakery products; GMP in starch and soya-bean productsPTWI for Al powder (GSFA Tables 1 and 2)
Sodium aluminium silicate554Anti-caking agentup to 20 000 in salt; GMP in grain, food in generalADI “not specified” (GSFA Tables 1, 2 and 3)
Calcium aluminium silicate556Anti-caking agentup to 20 000 in salt; GMP in grain, grape wines, generalADI “not specified” (GSFA Tables 1, 2 and 3)
Aluminium silicate559Anti-caking agentup to 10 000 in salt; GMP in grain, herbs/spices, generalADI “not specified” (GSFA Tables 1, 2 and 3)

Aluminium — specifications status

StatusCompounds (INS)Source
Existing specifications monographs not reviewed at this meetingAluminium ammonium sulfate (523), Aluminium lakes of colouring matters, Aluminium potassium sulfate (522), Aluminium powder (173), Aluminium silicate (559), Aluminium sulfate (anhydrous) (520), Calcium aluminium silicate (556), Sodium aluminium phosphate, acidic (541(i)), Sodium aluminium phosphate, basic (541(ii)), Sodium aluminosilicate (554)p. 44
Compounds with specifications but no GSFA provision (as of meeting)Aluminium lakes of colouring matters; aluminium sulfate; aluminium powder; potassium aluminium sulfatep. 40
Compounds used internationally but in neither Codex GSFA nor JECFA Combined CompendiumAluminium oxide; potassium aluminium silicatep. 40

Methylmercury — re-evaluation outcome (this meeting)

ParameterValueSource
Confirmed PTWI for methylmercury1.6 µg/kg b.w./weekp. 53, p. 58
Previously established PTWI formally withdrawn at this meeting3.3 µg/kg b.w./weekp. 54 (had been replaced at JECFA 61st in 2003)
Critical endpointDevelopmental neurotoxicity (in utero exposure through maternal seafood)p. 53
Most sensitive subgroupEmbryo and fetusp. 53-54
Susceptible-species referenceHumansp. 58
Maternal-hair BMDL/NOEL used in 2003 PTWI derivation14 mg/kg (= 14 µg/g)p. 53
Corresponding maternal-blood methylmercury concentration0.056 mg/L (= 56 µg/L)p. 54
Corresponding maternal daily intake1.5 µg/kg b.w./dayp. 54
Composite uncertainty factor applied6.4p. 54
Cohort basisFaroe Islands and Seychelles childrenp. 53
Intake level considered to pose no neurotoxicity risk in adults (excluding women of childbearing age)up to ~2 × PTWI (i.e. ~3.2 µg/kg b.w./week)p. 58

Methylmercury — Codex guideline-level impact analysis (this meeting)

Codex guideline levelApplicationSource
Predatory fish1.0 mg/kgp. 56
Non-predatory fish0.5 mg/kgp. 56
Mean concentration reduction in species exceeding the guideline levels, if such samples removed from market30-100%France/UK/USA submissions (p. 57)
French analysis — threshold below which women’s PTWI exceedance becomes significantly reduced0.5 mg/kg in all predatory species (= one-half the current guideline)p. 57
Impact on children aged 3-10 years from removing fish > Codex guidelineNot significantly reducedFrance (p. 57)
Japan — data submitted permitted percentage-by-species exceedance estimationNot possible to determinep. 57
Conclusion on Codex guideline levels as a risk-management tool for the general population”Not an effective way of reducing exposure”p. 58
Conclusion on targeted advice to at-risk subgroups”May provide an effective method for lowering the number of individuals with exposures greater than the PTWI”p. 59

Methylmercury — life-stage applicability framework (this meeting)

Life-stageVulnerability conclusionSource
Embryo and fetusConfirmed as most vulnerable life-stage; new data do not suggest the 1.6 µg/kg b.w. PTWI needs revision for maternal intakesp. 54
Infants (postnatal exposure via human milk or formula)Postnatal exposure is considerably lower than in utero exposure; the data did not enable firm conclusions on whether infants/children are more or less vulnerable than adultsp. 55-56
Children up to ~17 yearsInsufficient data to draw firm conclusions; Committee could not identify an intake higher than the existing PTWI that would pose no risk of developmental neurotoxicityp. 58
Adults (excluding women of childbearing age)Intakes up to ~2× PTWI would not pose risk of neurotoxicity in adultsp. 58
Adults (cardiovascular endpoint)Weight of evidence at this time did not indicate an increased risk of adverse cardiovascular events; fish consumption is associated with cardiovascular benefitsp. 56

Methods (brief)

For aluminium, the Committee carried out a full toxicological and exposure re-evaluation as requested by CCFAC at its Thirty-seventh Session (Annex 1 reference 4). Two prior assessments were used as starting points: the IPCS Environmental Health Criteria document on aluminium (1997, EHC 194) and the UK Committee on Toxicity report on the 1988 Lowermoor water-pollution incident; other peer-reviewed literature was also reviewed. No original toxicological data on aluminium-containing food additives were submitted to JECFA for this meeting. The Committee judged dietary-administration studies (rather than gavage) most appropriate for the point of departure because gavage toxicokinetics were expected to differ from dietary toxicokinetics, and the gavage studies generally did not report total dietary Al exposure. The lower end of the LOEL range from dietary studies in mice, rats, and dogs (50-75 mg/kg b.w./day) was taken as the point of departure; an uncertainty factor of 100 was applied for inter- and intraspecies differences, and an additional factor of 3 for database deficiencies (absence of NOELs in most evaluated studies and absence of long-term studies on the relevant endpoints), partly counterbalanced by the probable lower bioavailability of less-soluble Al species in food. The PTWI was set at 1 mg Al/kg b.w./week because of the potential for bioaccumulation. Exposure was estimated from duplicate-diet, market-basket, model-diet, and Total Diet Study data in adults, and from infant-formula concentration data combined with a 95th-percentile-consumption infant model (1 L/day, 6 kg body weight, age 3 months).

For methylmercury, the Committee re-examined the PTWI of 1.6 µg/kg b.w./week that had been established at the 61st meeting in 2003 based on developmental neurotoxicity in the Faroe Islands and Seychelles cohorts; the prior PTWI of 3.3 µg/kg b.w./week, which had effectively been replaced in 2003, was formally withdrawn at this meeting. CCFAC had asked the Committee at its Thirty-seventh Session to clarify whether the PTWI applies equally to all life-stages and whether Codex guideline levels for methylmercury in fish (1.0 mg/kg predatory, 0.5 mg/kg non-predatory) effectively reduce population exposure. The Committee reviewed new toxicokinetic, toxicological, and epidemiological studies on the embryo/fetus, infant/child, and adult life-stages; reviewed submissions from France, Japan, UK, and USA on methylmercury distributions in fish; and considered impact analyses showing that excluding fish samples exceeding the Codex guideline levels would reduce mean methylmercury concentration in those species by 30-100% but would not significantly reduce the proportion of the general population exceeding the PTWI in most countries, because the total seafood market is dominated by species that do not accumulate methylmercury to high levels.

Implications

  • Certification: For aluminium, this monograph is the source of record for the international 1 mg/kg b.w./week PTWI and is the document on which Codex GSFA provisions for Al-containing additives are expected to be aligned (Recommendation 2 of Section 6). HMTc threshold-setting on Al-containing categories (particularly bakery products, processed cheese, salt, and infant formulas with soya-protein basis) should anchor on the JECFA PTWI established here, not on the prior 7 mg/kg b.w./week value or on the earlier compound-specific ADIs, which were all withdrawn at this meeting. The Committee’s explicit finding that the new PTWI “is likely to be exceeded to a large extent by some population groups, particularly children, who regularly consume foods that include aluminium-containing additives” is the documentary basis for treating Al exposure in the infant-and-child-foods master category as a calibration concern rather than as comfortably below the tolerable intake. For methylmercury, this monograph is the JECFA confirmation of the 1.6 µg/kg b.w./week PTWI documented in jecfa-methylmercury-ptwi and is the document of record for the formal withdrawal of the prior 3.3 µg/kg b.w./week PTWI; HMTc calibration documentation referencing the methylmercury tolerable intake should cite the 61st-meeting derivation for the value and this 67th-meeting report for the life-stage applicability and the Committee’s finding that Codex guideline levels are not an effective general-population risk-management tool.
  • Courses: A clean teaching example of how a tolerable intake gets revised when new data are reviewed — the prior Al PTWI rested on a single beagle-dog study with sodium aluminium phosphate (acidic), and the seven-fold reduction came from combining new reproductive and developmental-effects data with bioaccumulation concerns rather than from a single decisive study. Also useful for teaching the distinction between a population-level risk-management tool (Codex guideline levels for methylmercury in fish, found here to be largely ineffective for the general population) and subgroup-targeted dietary advice (found here to be the more effective approach for reducing exceedance in vulnerable populations).
  • App: Provides the international tolerable-intake anchors for aluminum (1 mg/kg b.w./week) and methylmercury (1.6 µg/kg b.w./week), the order-of-magnitude difference between soya-based formula Al (up to 6 mg/L reconstituted) and milk-based formula Al (up to 0.4 mg/L reconstituted), and the comparative scale of Al exposure from aluminium-containing additives versus drinking water (additives dominate; treated water contributes ≤0.4 mg/day).

Provenance notes

License CC-BY-NC-SA-3.0-IGO per WHO standard publication terms. Redistribution permitted non-commercially with attribution and under the same or equivalent license. Heavy Metal Index extracts numerical findings and Committee conclusions as facts and paraphrases narrative content; no verbatim passages of substantial length are reproduced.

The PDF as held in raw/ (SHA-256 782f8a3326e26b4aada1c3837fa90f83f54ba77e1159f6c7e5e0653068a84195) is the official WHO publication (ISBN 92 4 120940 2, ISBN 978 92 4 120940 3, ISSN 0512-3054), published by WHO Geneva in 2007, typeset in Hong Kong and printed in Singapore. Cover and title-page typography identify “WHO Technical Report Series 940” and the meeting as “Sixty-seventh report of the Joint FAO/WHO Expert Committee on Food Additives.” The Contents lists five food-additive items (annatto extracts, lycopene synthetic, lycopene from Blakeslea trispora, natamycin, propyl paraben), seven specifications-only revisions (acetylated oxidized starch, carob bean gum, guar gum, DL-malic acid and salts, maltitol, titanium dioxide, zeaxanthin synthetic), and three contaminant items (aluminium, chloropropanols, methylmercury). Only aluminium and methylmercury are summarized on this page.

The 67th-meeting report (TRS 940) is the high-level summary document. The detailed toxicological monographs for each agenda compound are published as the companion volume, WHO Food Additive Series 58 (Safety evaluation of certain food additives and contaminants), which is in preparation at the time of TRS 940 publication and is a separate primary document not included in this source page. Where TRS 940 cites “Annex 1” reference numbers for prior JECFA meetings, those refer to the Annex 1 reports/documents list rather than to underlying primary literature.

Verification notes

  • Aluminium PTWI regulation page proposal (Karen review): The 1 mg Al/kg b.w./week PTWI established at this meeting would, in the regulation taxonomy, justify a new regulations/jecfa-aluminium-ptwi.md page parallel to the existing regulations/jecfa-methylmercury-ptwi.md. The ingest layer should not create regulation pages on its own (Part 10, regulation slugs have hard agency identifiers). Surfacing here so Karen can decide whether to scaffold the regulation page; ATSDR Al MRLs (atsdr-aluminum-mrls) and the EFSA Al TWI (efsa-aluminium-twi) exist as siblings, but the JECFA Al PTWI rule itself is missing.
  • Access URL left null: WHO IRIS handle for TRS 940 was not verified against a primary lookup at ingest time; rather than invent a URL, this field is left null and can be added by access_url patch after Karen confirms the IRIS handle (the 64th-meeting page uses https://iris.who.int/handle/10665/43258 for TRS 930, and the 940 handle would follow the same domain pattern).
  • Year field set to 2007 (publication year): Following the JECFA 64th convention (meeting Feb 2005, year frontmatter 2006 = TRS publication year), the meeting was held June 2006 but the cite-key and year: field follow the TRS 940 publication year 2007.

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