Quantifiable risk–benefit assessment of micronutrients: From theory to practice

Figures & data

Figure 1. Design of the proposed risk–benefit approach for micronutrients for use in risk management decision-making.

Table 1. Overview of health effects on which the ED₅₀ is based with their proposed reasonable incidence.

Health effect	Proposed reasonable incidence
Biochemical changes within or outside the homeostatic range and without known sequelae	< 1:10
Biochemical changes outside homeostatic range which represent a biomarker of potential beneficial or adverse effects	< 1:100
Clinical symptoms indicative of a minor but reversible change	< 1:1,000
Clinical symptoms of significant but reversible effects	< 1:10,000
Clinical signs indicative of significant but reversible organ damage	< 1:100,000
Clinical signs indicative of irreversible organ damage	< 1:1,000,000

Table 2. Uncertainty factors as published by EFSA (2012).

Uncertainty factors	Default value proposed
Interspecies extrapolation	No data on kinetics and/or dynamics available: 10 If relevant chemical-specific data on either kinetics or dynamics available, use for the remaining: Variability in toxicokinetics: 4.0 Variability in toxicodynamics: 2.5
Intrahuman extrapolation	No data on kinetics and/or dynamics available: 10 If relevant chemical-specific data on either kinetics or dynamics available, use for the remaining: variability in toxicokinetics: 3.16 variability in toxicodynamics: 3.16
Duration of exposure extrapolation	Subchronic to chronic: 2

Figure 2. Schematic depiction of processes and factors relevant to bioavailability of micronutrients. Note: conversion factors and interaction factors can be integrated if known, otherwise an uncertainty factor can be used instead.

Figure 3. Schematic depiction of assessment of validity of bioavailability data. Green lines indicate positive answers, red lines negative answers.

Table 3. Folate intake calculations (in dietary folate equivalents) at predefined incidences for benefit and risk.

Benefit ED50:	250	µg/day
Risk ED50:	8,300	µg/day
Incidence	Intake at predefined incidences of benefit[15%CV](µg/day)	Intake at predefined incidences of risk[45% CV](µg/day)
1:10	303	4,800
1:20	320	4,100
1:50	340	3,400
1:100	354	3,100
1:500	384	2,400
1:10E3	396	2,200
1:10E4	435	1,700
1:10E5	472	1,300
1:10E6	508	1,100

Table 4. Overview of ED₅₀s, intake at the decision benefit/risk incidences and intake of folate (in dietary folate equivalents) via the diet.

Population	BenefitED50(µg/day)	Intake at decision benefit incidence 1:100(µg/day)	RiskED50(µg/day)	Intake at decision risk incidence (µg/day)	P5intake via diet (µg/day)	P50 intake via diet (µg/day)	P95Intake via diet (µg/day)
Adults	250	354	8300	4100^2	125^4	242^5	492^6
Pregnant women	600	850	Equal to adults on body-weight basis	—	125^4	216^4	355^4
Lactating women	380	540	Equal to adults on body-weight basis	—
B12-deficient population^1	250	354	8300	1100^3	155^7	309^7	492^7

¹ B₁₂ deficient population is considered to be part of the adult population.

² a decision risk incidence of 1:20 is considered.

³ a decision risk incidence of 1:10E6 is considered.

⁴ P5/50/95 values for females 19–30 years; no specific intake figures for pregnant women are reported. It is assumed that the intake for pregnant women via normal diet equals the intake in de female 19–30 year group. Note that the female 31–50 year group has a slightly higher intake, for which it is considered that the females in the 19–30 years group have the most profit from supplement intake.

⁵ median of adult female intakes at the P50.

⁶ P95 value for males 51–69 years as highest value.

⁷ P5 value for females 51–69 years; P50/95 value for males 51–69 years.

Intake levels used were retrieved from the Dutch Food Consumption Survey (RIVM, 2011).

Table 5. Iron intake calculations at predefined incidences for benefit and risk.

	General population ED50 = 6 mg/d	Iron bisglycinate ED50 = 120 mg/d	Iron sulphate ED50 = 50 mg/d
Incidence	Intake at predefined incidences of benefit [15%CV] (mg/day)	Intake at predefined incidences of risk [45% CV] (mg/day)	Intake at predefined incidences of risk [45% CV] (mg/day)
1:10	7.3	69.2	28.8
1:20	7.7	59.2	24.7
1:50	8.2	49.7	20.7
1:100	8.5	44.2	18.4
1:500	9.2	34.9	14.5
1:10E3	9.5	31.8	13.3
1:2 × 10E3			13.1^1
1:10E4	10.5	24.3	10.1
1:10E5	11.3	19.2	8.0
1:10E6	12.2	15.6	6.5

¹ when applying a scaling factor of 2, a 1:2000 decision incidence intake for iron is calculated of 13.1 mg/day.

Table 6. Overview of ED₅₀s, intake at the decision benefit/risk incidences and intake of iron via the diet.

Population	Benefit ED50	Intake at decision benefit incidence 1:100(mg/d)	Risk ED50 (mg/d)	Intake at the decision risk incidence (mg/d)	P5intake via diet (mg/d)	P50 intake via diet (mg/d)	P95Intake via diet(mg/d)
General population	6	8.5	120^150^2	69.2^113.3^2	7.2^3	10.7^3	15^3

¹ iron bisglycinate, a decision risk incidence of 1:10 is considered.

² iron sulphate, a decision risk incidence of 1:2000 is considered.

³ mean value for intake of males and females in the age groups of 19-50 years; Dutch Food Consumption Survey (RIVM, 2011).

EFSA. (2012). Guidance on selected default values to be used by the EFSA scientific committee, scientific panels and units in the absence of actual measured data. EFSA J. 10(3):2579.

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