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ARSENIC IN FOOD FOR INFANTS AND YOUNG CHILDREN

NOVEMBER 2018SHC № 9252

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ADVISORY REPORT OF THE SUPERIOR HEALTH COUNCIL no. 9252

Arsenic in food for infants and young children

In this scientific policy advisory report the Superior Health Council of Belgium provides a

risk assessment of Arsenic (As) in food for infants and young children.

This report aims at providing health professionals and parents of infants and young

children with specific recommendations on As in food

This version was validated by the Board on

November - 20181

SUMMARY

An assessment to estimate the exposure of infants and young children to Arsenic (As) was

performed. The focus was principally on rice products and inorganic As (iAs), the most toxic

species of this metalloid.

To do this, a whole series of scenarios have been designed for children from the age of 3

months to the age of 36 months, taking as a reference a normal diet to which different

alternatives based on rice (solid products and drinks) have been compared. For each of these

scenarios, inorganic As exposure was estimated. It was found that children's exposure to

inorganic arsenic (expressed in µg iAs/kg bw per day) was higher than that of adults and

strongly influenced by the inclusion of rice products in the diet.

It is therefore recommended to avoid the use of rice-based products for the feeding of young

children and, in case of intolerance or allergies to the classic constituents of the diet, to consult

health professionals in order to choose the most appropriate alternatives.

1 The Council reserves the right to make minor typographical amendments to this document at any time. On the other hand, amendments that alter its content are automatically included in an erratum. In this case, a new version of the advisory report is issued.


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Keywords and MeSH descriptor terms2

MeSH (Medical Subject Headings) is the NLM (National Library of Medicine) controlled vocabulary thesaurus used for indexing

articles for PubMed http://www.ncbi.nlm.nih.gov/mesh.

2 The Council wishes to clarify that the MeSH terms and keywords are used for referencing purposes as well as to provide an easy definition of the scope of the advisory report. For more information, see the section entitled "methodology".

MeSH terms*

Keywords Sleutelwoorden Mots clés Schlüsselwörter

Legislation, Food

Food legislation Voedingswetgeving Législation, nutrition

Gesetzgebung

Food Safety Food safety Voedselveiligheid Sécurité alimentaire

Lebensmittelsicherheit

Risk assessment

Risk assessment Risicoanalyse Evaluation des risques

Risikobewertung

Arsenic Arsenic Arseen Arsenic Arsen

http://www.ncbi.nlm.nih.gov/mesh


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TABLE OF CONTENT

I Introduction and issue .................................................................................................... 5

II Conclusion and recommendations (including research) ................................................. 7

III Methodology .................................................................................................................. 7

IV Elaboration and argumentation ...................................................................................... 8

1 General context .......................................................................................................... 8

2 Scope ......................................................................................................................... 8

3 Hazard identification and characterization .................................................................. 8

Identification of exposure groups ......................................................................... 9

As content in rice, rice-based products and other relevant food matrices for young children .......................................................................................................................... 9

Toxicokinetics and toxicodynamics .................................................................... 12

Placental transfer and reproductive and developmental toxicity ......................... 14

4 Overview of Health-Based Guidance Values for risk characterization ....................... 16

5 Exposure assessment .............................................................................................. 17

Contamination data: As content in infant food products ..................................... 17

Consumption data ............................................................................................. 18

Arsenic exposure values ................................................................................... 20

6 Discussion of the results ........................................................................................... 28

Exposure levels and toxicological concern for adults and children ..................... 28

Comparison of exposure between infants and adults ........................................ 29

7 Recommendations ................................................................................................... 30

8 Uncertainties ............................................................................................................ 31

Analytical methods used and chemical species considered ............................... 31

8.2 Toxicological concerns .............................................................................................. 31

V References .................................................................................................................. 32

VI Acknowledgments ........................................................................................................ 36

VII Composition of the working group ............................................................................ 37

VIII Appendices .............................................................................................................. 38


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ABBREVIATIONS AND SYMBOLS

ADME Absorption, Distribution, Metabolism and Excretion

As Arsenic

AsIII Arsenite AsV Arsenate ATSDR Agency for Toxic Substances and Disease Registry BMDL Lower confidence limit (95 %) of the benchmark dose BMDL01 BMDL corresponding to 1 % extra risk

BW Body weight

DW Dry weight

DMA Dimethylarsenic

DMAIII Dimethylarsonous acid

DMAV Dimethylarsinic acid

EFSA European Food Safety Authority

EPA United States Environmental Protection Agency

FASFC Federal Agency for the Safety of the Food Chain (Belgium)

IARC International Agency for Research on Cancer

iAs Inorganic arsenic

JECFA Joint FAO/WHO Expert Committee on Food Additives

LD50 Median lethal dose

LOAEL Lowest observed adverse effect level

LOQ Limit of quantification

MMA (Mono)methylarsenic

MMAIII (Mono)methylarsonous acid

MMAV (Mono)methylarsonic acid

MPFE Meat, poultry, fish, eggs

MRL Minimal Risk Level

NHFS Nutrition, Health and Food Safety

PTWI Provisional Tolerable Weekly Intake

SHC Superior Health Council (Belgium) TDI Tolerable Daily Intake


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I INTRODUCTION AND ISSUE

Arsenic is one of the most predominant metalloids that can cause significant adverse human

health effects, both after acute and chronic exposure. While acute arsenic exposure primarily

results from anthropogenic activities (such as mining), chronic arsenic exposure is primarily

derived from naturally contaminated drinking water (aquifers in Bangladesh, Nepal, etc.) and

dietary sources.

There are two forms of arsenic in food, inorganic [i.e. arsenic acid (AsV) and arsenous acid

(AsIII)] and organic [i.e. methylated arsenic compounds, arsenobetain, arsenocholine,

arsenosugars and arsenolipids]. Several foodstuffs (fish, crustaceans and seaweed) are

known to contain quite substantial levels of arsenic. While in many cases, foodstuffs can

contain high levels of non-toxic arsenic species (such as arsenobetain, arsenocholine and

arsenosugars in fish), several other foodstuffs may contain considerable levels of toxic arsenic

species (like inorganic arsenic and organic methylated arsenic compounds such as

monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA)).

Previous studies carried out in Belgium (SPECAs and BIOTRAs projects) have demonstrated

that:

i. Several arsenic species, both toxic and non-toxic, are identified in foodstuffs present

on the Belgian consumer market;

ii. Rice can be a substantial source of dietary arsenic exposure for the Belgian consumer;

iii. Specific foodstuffs like hijiki seaweed can lead to significant exposure to toxic arsenic

species (AsIII and AsV) when prepared, stored and digested by the human

gastrointestinal tract.

These projects have pointed out that arsenic exposure from dietary intake is inevitable, yet

must be limited as much as possible. While the results from both of these projects are primarily

based on dietary exposure of the healthy adult Belgian population to arsenic, no data are

available on the dietary arsenic exposure for children, particularly for infants and young

children that are still in full development in terms of physiology, diet and microbiome.

Furthermore, there are several specific scenarios - lactose intolerance, milk protein allergy or

vegan diets - where parents sometimes opt for dietary constituents that are based on rice.

While specific products as Novarice (an infant formula drink) can only be sold in pharmacy

stores and under medical supervision, several rice-based food products for children exist and

are freely available including rice-based stews, rice drinks, rice porridge and rice crackers.

Due to nutritional concerns, several EU member states (Ireland, United Kingdom, Sweden,

Denmark) have published a report to limit and even avoid the consumption of certain rice

products like rice drinks, rice crackers and rice stew. In Belgium, the consumption of rice based

drinks is discouraged by ”Kind en Gezin” because of these nutritional concerns.


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However, given the important contribution of rice to dietary arsenic exposure, it needs to be

investigated to what extent there are also toxicological arguments for discouraging rice-based

food product consumption by young children. Moreover, as risk factors for arsenic intake are

based on daily intake per unit body weight, young children may more easily reach or exceed

acceptable exposure levels. Given the high degree of uncertainty concerning the toxic effects

of arsenic towards children and the oral exposure of children to arsenic, several aspects need

to be addressed:

i. Dietary arsenic exposure in infants and young children and contribution of rice-based

food products to this exposure;

ii. Specific advice regarding consumption of rice-based food products by young children

(till the age of 3), based on nutritional as well as on toxicological data;

iii. Specific consumption advice for other exposure groups of the population like pregnant

and lactating women.


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II CONCLUSION AND RECOMMENDATIONS (INCLUDING RESEARCH)

In this report, focus was put on infants’ and young children’s exposure to inorganic arsenic as most of the risk assessment studies have been performed for this arsenic species and benchmark dose limit (BMDL) values have been calculated. According to the different scenarios investigated (with the exception of the breastfed 3-month-old infants), young children’s and infants’ estimated inorganic As exposure always exceeds the exposure of adults as estimated in the SPECAs project (i.e. 0.11 µg iAs/kg bw per day) (SPECAs, 2013). Hence, the margin of exposure relative to the BMDL01 values of 0.3-8 µg/kg bw per day for lung and bladder cancer and for dermal lesions, that is already small for adults, seems to be further reduced or even absent for young children and infants. Children’s exposure to contaminants expressed in µg/kg bw per day is generally higher than that of adults due to the higher food intake of young children relative to their body weight. In addition, the developing child is characterized by a high degree of anatomical, physiological and microbial dynamics. For all of these reasons it is not possible to accurately characterize health risks for children by comparing their (rapidly changing) exposure to toxicological endpoints that are linked to chronic health effects. However, as a precautionary measure, exposure to contaminants in general, including arsenic, should be as low as possible. As arsenic is a natural contaminant in foodstuffs, dietary exposure cannot be avoided. Yet, since rice and rice-based products are important sources of inorganic arsenic in the diet, the consumption of rice by young children should be limited. Therefore, it is recommended to parents and health professionals i) to provide infants with a healthy, balanced and varied diet and to not substitute starch sources with rice-based solid foods alone, ii) to boil rice in enough water (water to rice ratio of 6) and pour away boiling water prior to consuming the rice iii) to avoid rice biscuits as regular snacks and iv) to not substitute breast milk, infant formula or cows’ milk with rice drinks.

III METHODOLOGY

After analysing the request, the Board and the Chair of the domain « Nutrition and Health, including Food Safety » (NHFS) and the working group identified the necessary fields of expertise. An ad hoc working group was then set up which included experts in areas of expertise as listed in the table in Section VI. The experts of this working group provided a general and an ad hoc declaration of interests and the Committee on Deontology assessed the potential risk of conflicts of interest. This advisory report is based on:

i. A review of the scientific literature published in both scientific journals and reports from national and international organisations competent in this field (peer-reviewed);

ii. Information on arsenic content in several dietary matrices and food sources that are relevant for oral consumption by children;

iii. An exposure assessment calculation for children of four different age groups based on respective dietary recommendations and for four different exposure scenarios; and

iv. On the opinion of the experts. Once the advisory report was endorsed by the ad hoc working group and by the standing working group tasked with NHFS, it was ultimately validated by the board.


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IV ELABORATION AND ARGUMENTATION

1 General context

Arsenic (As) is a toxic substance for which detailed risk assessment has been conducted in the last couple of decades. This includes risk assessment from dietary As exposure, either to inorganic As from drinking water or to inorganic and organic As species from solid foods. Previous advisory reports from the SHC have highlighted possible risks from As in dietary supplements (SHC 6976, 2000) or from As in edible algae or food supplements (SHC 9149, 2015). These reports resulted in maximum set levels of 1 mg As per kg product of food supplement or a recommendation of restricted use of specific algae-based food supplements. However, there are concerns over particular exposure groups (e.g. infants), namely the lack of exposure data based on the actual consumed foodstuffs and the lack of a proper risk assessment process for a young age group. In this context, it is noteworthy that dietary profiles of children significantly differ from those of adults. Despite the available dietary recommendations for children of different age, dietary preferences or sensitivities like lactose intolerance, gluten intolerance or digestive issues may result in deviated dietary profiles. For example, parents may give rice-based products (e.g. rice drinks) to their lactose intolerant children. Moreover, given the existence of specific foodstuffs for infants and young children that are prone to a higher As content (e.g. rice drinks, rice crackers, etc.), it is possible that daily As exposure expressed as µg As per kg of body weight may approach or even exceed the normal adult As exposure. In view of these uncertainties, a separate risk assessment procedure is required.

2 Scope

An assessment to estimate the exposure of infants and young children to As was performed. When selecting the different exposure scenarios, specific attention was paid to include foodstuffs with a high inorganic As content that are relevant for consumption by infants and young children. Therefore, focus has been put on rice-based products. Given the highly dynamic anatomical, physiological and microbial evolution of the developing child, different age groups were defined as well as different exposure scenarios in which common dietary substances – like starch-based products – were not or completely replaced by rice-based products. In addition, complementary information was given for the hazard identification and characterization of As.

3 Hazard identification and characterization

For the general toxicokinetics and dynamics of ingested As one can refer to the SHC’s advisory report 9149 where the risks concerning As exposure from ingestion of algae-based food supplements were assessed. In the framework of the current advisory report, additional data is provided on:

i. The identification of exposure groups that undergo different exposure scenarios to dietary As;

ii. Specific adaptations to toxicokinetic and dynamic models for children; iii. Placental transfer of As and reproductive and developmental toxicity of As.


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Identification of exposure groups

The developing child is characterized by a high degree of dynamics on different levels: general physiology and anatomy, gut physiology, immune development, organ function, etc. These processes are all modulated by a diverse set of determinants such as maternal dietary habits and exposure during gestation, way of delivery, feeding type (breastfeeding vs. formula), dietary evolution, microbiome development, childhood infections, antibiotic use, genetic predisposition, ethnicity, age, etc. Considering the huge degree of dynamics the developing child experiences, there is a need to specify different age groups. For each of these age groups, scenarios were identified in which infants/young children may consume additional rice-based products, as these are an important source of (inorganic) arsenic. Therefore, the following age groups were considered:

- 3-month-old infants: this exposure group has only partly or not yet entered the stage of weaning. Energy intake primarily occurs through breastfeeding or formula feeding. Nevertheless, medicinal use of rice-based products may already occur under specific scenarios of allergy or intolerance;

- 6-month-old infants: this exposure group will start to be exposed to a more diverse profile of dietary substances, making a more permanent transition from liquid to solid-based foods. For a normal exposure scenario, rice-based stews may enter the list of food products contributing to oral As exposure;

- 12-month-old infants: the dietary profile of this exposure group further diversifies. Next to the common carbohydrate/protein/lipid intake, coming from similar conventional food products as for 6-month-old infants (yet at higher energy intake), other rice-based products such as rice crackers, rice biscuits etc. may enter the diet;

- 36-month-old young children: dietary profile of this exposure group is fully diversified, akin to adults. This also results in a microbiome that is quite representative of that of adults. Yet, specific exposure scenarios may still apply.

As content in rice, rice-based products and other relevant food matrices for young children

This paragraph provides a summary of knowledge regarding As content in rice and rice based products, with particular reference to products for young children. Information was extracted from the article ‘As speciation in food in Belgium. Part 2: Cereals and cereal products’ (Ruttens et al., 2018).

3.2.1 Rice arsenic

The high contribution of rice to inorganic As exposure in European countries, as reported by the European Food Safety Authority (EFSA, 2014), results from its high inorganic As concentration in combination with the dose consumed. Rice has higher grain As contents than other cereals grain (e.g. wheat and barley), as it is much more efficient in accumulating soil As (Williams et al., 2007b; Su et al., 2010; Zhao et al., 2010). Moreover, the flooded soil conditions in paddy rice fields enhance As bioavailability (Xu et al., 2008; Li et al., 2009). Inorganic arsenic always represents an important fraction of As in rice (Williams et al., 2007a; Fontcuberta et al., 2011).


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Since January 2016, maximum levels for inorganic As apply at the European level for rice and various rice based products (Commission Regulation 1006/2015 of June 25, 2015). The specified levels range from 100 µg/kg in rice destined for feeding infants and young children to 300 µg/kg in rice waffles, rice wafers, rice crackers and rice cakes. In non-parboiled milled rice (polished or white) the allowed maximum level is 200 µg/kg; in parboiled rice and husked rice it is 250 µg/kg.

3.2.2 Total As in rice and rice products

Variations in total As concentrations in rice are known to be determined by genetic differences on the one hand and soil characteristics on the other hand (Norton et al., 2009; Zhao et al., 2009). A wide geographic variation in rice arsenic concentrations has been reported previously, with concentrations being low in Indian Basmati, and high in EU and US rice (Williams et al., 2005; Zavala and Dubury, 2008). In a survey on market rice Williams et al. (2005) have reported a range of 110 to 400 µg kg-1 in US long grain rice (average 260), a range from 130-220 in European rice (average 180) and a range from 30-80 in Basmati rice (average 50). Similar ranges were reported by Heitkemper et al. (2001) for US market rice (110-340). In various types of rice sampled on the Swedish retail market a mean level of 200 µg kg-1 was found (Jorhem et al., 2008), and, in rice cultivated in Northern Italy, D’Illio et al. (2002) reported As levels ranging from 80 to 280 µg kg-1. According to Zavala and Dubury (2008), Asian rice types show in general a lower total As concentration compared to US and European rice types. In contrast to the results reported above, Bangladeshi rice surveys show in general a larger variability among studies (Meharg and Rahman, 2003; Das et al., 2004; Williams et al., 2005) reflecting the large variability of soil arsenic and water arsenic levels in paddy fields in Bangladesh. In rice based products such as breakfast cereals, rice crackers and Japanese rice condiments As concentrations were found to be similar to the ones in rice (Sun et al.; 2009). In commercial rice drinks, Meharg et al. (2008c) reported total arsenic levels in the range of 10.2–33.3 µg l-1, with a median value of 22 µg l-1. These total arsenic levels were all above the EU total arsenic standard of 10 µg l-1 for drinking water. The median value was 7-fold higher than total arsenic levels in soy and oat drink samples.

3.2.3 As speciation in rice and rice products

Regarding As speciation in rice, AsIII, AsV, DMA, and MMA are generally detected (Heitkemper et al., 2001; Zhu et al., 2008b; Huang et al., 2012). Exceptionally also the presence of tetramethylarsonium has been reported in rice with elevated As content (Hansen et al., 2011). The fraction of inorganic As can vary widely among samples. Zavala et al. (2008) have categorised rice into ‘inorganic As types’ (inorganic As > DMA concentrations) on the one hand, and DMA rice types (DMA > inorganic As concentrations) on the other hand. In the first group increases in total As were mostly associated with increasing inorganic As, while in the second group they were mostly associated with increasing DMA. Rice from the southern states of the U.S. was predominantly the DMA type, as were single samples from Australia and China, whereas rice from Asia and Europe generally was of the inorganic As type (Zavala et al., 2008b).


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Williams et al. (2005) also reported a dominance of DMA in US grown rice, while in Chinese rice iAsIII dominated (Zhu et al., 2008). While it was proposed first that differences in both rice types reflect genotypic variation in As methylation in planta (Williams et al., 2005; Zavala et al., 2008), Lomax et al. (2011) have suggested, based on results of rice cultivation under axenic conditions, that plants are unable to methylate iAs, but take up methylated As produced by microorganisms. The high DMA fraction present in US rice grains (produced in the southern states of the USA) is most likely a consequence of specific soil conditions that promote microbial methylation or may be linked to the past use of arsenical pesticides (Meharg and Zhao, 2012; Williams et al. 2007a). In general, genotypic as well as geographical variations and management practices seem to determine As speciation in rice (Meharg et al., 2009; Norton et al., 2009; Pillai et al., 2010, Zavala et al., 2008). Williams et al. (2005) reported that respectively, 64 ± 1 % (n = 7), 80 ± 3 % (n = 11), and 81 ± 4 % (n = 15), of the recovered arsenic was found to be inorganic in European, Bangladeshi, and Indian rice. In contrast, in rice from the USA only 42 ± 5 % (n = 12) of arsenic was inorganic. In a study of Heitkemper et al. (2001) the percentage of inorganic As from US market rice was shown to vary from 10 to 61 %. Several authors have reported quantitative data on inorganic As in market rice samples. Jorhem et al. (2008) for example found 110 µg kg/kg inorganic As as mean value in rice bought on the Swedish market. In rice on the Spanish market, inorganic As was on average 114 μg kg/kg dry weight (Torres-Escribano et al., 2011). The mean baseline concentrations for inorganic As in Chinese market rice was estimated to be 96 µg/kg in a study of Zhu et al. (2008b). Zavala et al. (2008b) reported that 75 % of the samples showed <0.138 mg/kg with average and median values of 0.103 (±0.045) and 0.110 mg kg/kg respectively. While total As concentrations tend to be higher in US rice compared to Asian samples, this difference is not linearly reflected in the inorganic As concentrations, because DMA dominates the high As US samples (Zavala et al 2008b). Meharg et al. (2008b) have shown that inorganic arsenic is elevated in the bran layer of rice, resulting in brown rice having a higher inorganic As fraction than corresponding white rice. In many studies on As speciation in rice, dilute acids (often nitric acid or trifluoroacetic acid) are used to extract As species (Zhao and Meharg, 2012). Because these methods alter the oxidation status of As (Abedin et al., 2002; D’Amato et al., 2011), the sum of inorganic arsenic is reported in these cases, without reporting AsIII and AsV separately. As both arsenite and arsenate are readily assimilated in mammalian systems, where they interconvert (Juhasz et al., 2006), this lack of discrimination is therefore not considered problematic (Meharg and Zhao, 2012; De la Calle, 2011). In studies where AsIII and AsV were analysed separately, AsIII was highly predominant in the inorganic fraction with only very few exceptions (Huang et al., 2012). In rice-based products As species and their concentrations are similar to the ones observed in rice. Sun et al. (2009) reported iAs fractions of 75.2–90.1 % in a series of rice products under investigation. In the commercial rice drinks, inorganic arsenic ranged from 7.1–20.7 µg/l, with a median value of 13.4 µg/l. Inorganic As was the dominant As species present (55-86 %) (Meharg et al. 2008a).


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3.2.4 Total As and As speciation in rice based food for infants and young children

Some studies have focused specifically on inorganic As and As speciation in food for infants and young children. In baby rice (this is rice sold in small portions intended for infant use which are available in some countries), Meharg et al. (2008c) reported total As concentrations in the range 120-470 µg/kg, with a median value of 220 µg/kg. The median inorganic As concentration was 110 µg/kg. In US rice cereals for infants Juskelis et al. (2013) reported average total arsenic and inorganic As concentrations of 174.4 and 101.4 μg/kg, respectively. Mixed-grain rice cereals contained lower total arsenic (105 μg/kg) and lower inorganic arsenic (63 μg/kg). Reported total and inorganic As concentrations in mixed-grain cereals in some European studies (Rintale et al. 2014; Llorente-Minrandes, 2014) were slightly lower on average, but the inorganic fraction was generally higher compared to the US data. A particular concern is the As content in rice biscuits and rice crackers. This seems to be quite high with reported values ranging between 83 and 354 µg As/kg. As mentioned earlier, regulatory levels for arsenic in rice matrices and, more in particular, rice matrices for infant food production have been specified. It is noteworthy to observe that several food matrices as found back in literature exceed these regulatory values.

Toxicokinetics and toxicodynamics

This advisory report focuses on the consumption of rice-based products by young children. While rice can display a diverse As speciation profile, the SPECAs project has revealed that it consist of 70-80 % inorganic As, the remainder primarily consisting of pentavalent dimethylarsinic acid (SPECAs, 2012). Organic arsenic species like arsenobetain, arsenosugars or arsenolipids are irrelevant species in rice and will not be considered further.

3.3.1 In the general population

Inorganic arsenic compounds are readily absorbed after oral exposure, although absorption can be influenced by:

i. the solubility of the arsenical compound; ii. the presence of other food constituents and nutrients in the gastrointestinal tract; iii. the food matrix itself.

Once absorbed, inorganic arsenic is widely distributed to almost all organs and extensively transformed. Biotransformation of inorganic arsenic in mammals includes reduction of pentavalent arsenic to trivalent arsenic and methylation of trivalent arsenic (DMAIII, MMAIII) with formation of MMAV and DMAV. Most of the inorganic arsenic is excreted via urine as DMAV (EFSA, 2009). Inorganic arsenic does not only display high acute toxicity, it is also classified as a human carcinogen, both via ingestion and inhalation routes (IARC, 1987, 2012). Although both forms of inorganic arsenic are potentially harmful, trivalent arsenic is considered more harmful than the pentavalent forms (FAO/WHO, 2011).


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Interestingly, data from in vitro and in vivo studies indicate that organic arsenic species (e.g. mono- and dimethylated trivalent and pentavalent arsenicals) formed during metabolism contribute to inorganic arsenic induced toxicity (FAO/WHO, 2011; EFSA, 2009a; Rehman & Naranmandura, 2012). MMAIII and DMAIII were even more cytotoxic in cell cultures than their parent compounds AsIII and AsV (Petrick et al., 2000; Mass et al., 2001). Based on these results, the order of toxicity is expected to be MMAIII > DMAIII = AsIII > AsV > MMAV > DMAV (FAO/WHO, 2011). Based on the evidence of cancer caused by DMA in experimental animals and the extensive metabolism of MMA to DMA, IARC has classified both DMA and MMA as “possibly carcinogenic to humans” (Group 2B)(IARC, 2012).

3.3.2 In population groups at high risk

While specific data on the toxicokinetics of As in children is missing, some general remarks need to be made with respect to possible modulation of the different ADME processes (absorption, distribution, metabolism and excretion). Firstly, the intestinal barrier in infants can be variable depending on different determinants. While the development of barrier function already occurs in utero, there is ongoing postnatal maturation. The gut barrier in neonates is more permeable, in part to allow movement of colostrum-derived antibodies into the infant's circulation (Halpern and Denning, 2015). Multiple factors induce postnatal intestinal barrier maturation including growth factors, hormones, nutrients and, importantly, microbes. Encouraging growth of the appropriate complement of commensal bacteria may be of particular benefit in premature neonates who are deprived of the benefits of an in utero environment. An immature epithelial barrier causes increased intestinal permeability. This, in turn, predisposes the gut to invasion of toxins and bacteria located within the gut lumen resulting in both inflammation and injury (Bjarnasson, 1994). It is clear that a compromised gut barrier can significantly alter the translocation of ingested dietary arsenic and thus modulates As bioavailability. A second factor concerns the maturation state of the liver. The liver is the most important biotransformation organ in the human body and will drive As methylation processes, intending to detoxify bioavailable inorganic arsenic species. While the first hours after birth are characterized by a dramatic shift in portal blood flow, it is the infant’s first feed that will more consistently affect portal blood flow (Beath, 2003). In addition, within hours and for the consecutive days, weeks and months, a dynamic microbial colonization process takes place in the gut affecting vitamin K production and gradually establishing an interplay with liver biotransformation processes. The liver’s central role in biotransformation requires the induction of enzymes from the cytochrome P450 group and peroxisomal enzymes. While synthetic and conjugation reactions fully occur directly at birth or within 2 weeks, full transferase activity can often take several months, evidently impacting biotransformation potency towards bioavailable toxicants such as arsenic. While above-mentioned physiological processes affect the absorption and metabolism of ingested arsenic, the distribution of the toxicant is significantly affected by the ratio of adipose vs. lean tissue and the general body water content. To exemplify, the newborn child has a body water content of around 80 % compared to a 70 % water content in children and 55-65 % water content in adults. This will also affect the distribution of As or As metabolites in the body and its excretion.


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A final modulating factor affecting arsenic ADME processes concerns the commensal microbiota in the gastrointestinal tract. While composition and functionality of commensal gut microbiota will affect gut barrier integrity and immune development, the gut microbiota will also be involved in the release process of As out of its food matrix, resulting in a bioaccessible fraction (soluble As fraction that is available for intestinal transport). Besides, gut microbes can perform presystemic metabolism of As in the gut. This does not only entail deconjugation reactions of phase II liver metabolites from biliary secretion into the intestine, but also direct metabolism of As species that have reached or are released from the food matrix in the colon. From the BIOTRAs project, it was previously described that gut microbiota are actively contributing to methylation and thiolation of inorganic arsenic with strongly reducing conditions (anaerobiosis) often resulting in the trivalent, more toxic, arsenic species (BIOTRAs, 2015). It is noteworthy that the high degree of dynamics in microbiome colonization of the infant gut also comes with high variability in the potency of As metabolism by gut microbiota. From the same BIOTRAs project, it was observed that methylation capability experiences a dramatic increase from 10 months to 18 months, despite the high degree of interindividual variability. Finally, gut microbiota can also interfere with the food matrix in which a toxicant is embedded. In this sense, it was observed that fiber-bound arsenic in brown rice was completely released from the rice matrix due to fiber fermentation by colon microbiota. No such colon microbial contribution to arsenic release was observed for white rice, which does not contain any fiber-bound As. It is clear that all of these elements regarding gut physiology, biotransformation potency and microbiome dynamics are highly variable in the developing child. Each of these will impact As toxicokinetics. However, knowledge on the impact on As bioavailability and toxicity is completely lacking.

Placental transfer and reproductive and developmental toxicity

3.4.1 Placental transfer of As

Inorganic arsenic and its methylated metabolites, MMA and DMA, readily cross the human and animal (e.g. mice and monkeys) placenta and may adversely affect fetal development (Chattopadhyay et al., 2002; Concha et al., 1998a, Vahter, 2008). Furthermore, both inorganic As and DMA have also been reported to cross the immature blood-brain barrier in mice (Jin et al., 2006). Importantly, methylation of arsenic is induced during pregnancy, and consequently, almost all arsenic in the blood plasma and urine of new born babies is present as DMA (Concha et al., 1998a). The improved methylation efficiency, including a marked decrease of the toxic metabolite MMA and a marked increase in the less toxic metabolite DMA, has been observed early in gestation. Furthermore, the urinary excretion of arsenic relative to blood arsenic concentrations was increased, indicating that up-regulation of arsenic metabolism may provide protection to the fetus already in early pregnancy (Gardner et al., 2011). A more recent study showed that placental arsenic concentrations were positively associated with arsenic levels in maternal urine, maternal and infant toenails and household drinking water. Lower ratios of maternal-to-infant toenail arsenic concentrations, which indicate greater placental transfer, were observed at high placental arsenic concentrations (Punshon et al., 2015). These data suggest that placental arsenic concentrations reflect both maternal and infant exposures.


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In contrast to the free passage of arsenic through the placenta to the fetus, the passage to the mammary gland is limited. Only AsIII will be transported by the aquaglyceroporins in the mammary glands during lactation as the other arsenic forms are not protonated at the physiologic pH. Due to the efficient maternal methylation of inorganic arsenic, little arsenic will thus be excreted in breast milk (Rebelo & Caldas, 2016). For this reason, the infant may be protected against arsenic exposure during the breastfeeding period, compared to infants fed with formula prepared from drinking water contaminated with arsenic (Concha et al., 1998b; Vahter, 2008). This hypothesis is supported by a recent study examining the exposure to arsenic in breastfed and formula-fed infants in a United States cohort (Carignan et al., 2015).

3.4.2 Reproductive and developmental toxicity

Inorganic arsenic has long been identified as an embryotoxic and teratogenic compound in experimental animals. However, most of these studies have used high parental arsenic dosing, which might have been associated with maternal toxicity (EFSA, 2009). Over the last years, growing evidence from human and animal studies has become available suggesting that early life exposure to arsenic may increase the risk of adverse health effects and risk of impaired development in infancy and childhood and later in life (NRC, 2013). Since most of these studies were not yet available for the assessments of inorganic arsenic by ATSDR (2007) or EFSA (2009), the US FDA recently performed a literature review to evaluate whether pregnancy, infancy, and/or early childhood are periods of greater susceptibility to the toxic effects of oral inorganic arsenic exposure (US FDA, 2016). For this review, only published literature studies conducted in humans were considered since interpretation of animal data is complicated by the important differences between species (Vahter, 1999). The major conclusions of this review are summarized below (US FDA, 2016):

- Effects of arsenic on fetal development during pregnancy: Literature data indicate that low-to-moderate levels (50 – 100 μg/L) of maternal intake of inorganic arsenic during pregnancy may be associated with adverse health effects for the fetus (stillbirths, spontaneous abortion, low birth weight and size, pre-term birth and infectious-disease susceptibility). However, the uncertainty in the measurement of exposure to inorganic arsenic in the pregnant women studied along with other weaknesses and confounders in the studies complicate the determination of a point of departure for adverse pregnancy outcome.

- Effects of arsenic during infancy and childhood: Literature data indicate that low-to-moderate levels of inorganic arsenic appear to be associated with adverse health effects during childhood. However, there are uncertainties in the data including:

(1) the measurement of exposure to inorganic arsenic in the children studied, (2) the small number of children studied, (3) the use of IQ testing not standardized for the population studied, in many cases.

Studies should also assess the long-term consequences in cognitive function (permanent or transitory). US FDA and EPA are currently collaborating in order to consider any new findings or refined methodological approaches to address these issues.


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4 Overview of Health-Based Guidance Values for risk characterization

Acute effects Reports on the acute and subacute exposure in humans show that almost all physiological systems of the body can be affected including the gastro-intestinal, cardiovascular, renal and nervous systems and to a lesser extent, the respiratory system, liver, skin and hematologic system. ATSDR (2007) reported a lethal dose in humans after acute ingestion of 100-300 mg (1-5 mg As/kg bw) and derived a minimal risk level (MRL) of 0.005 mg As/kg bw per day for acute duration (14 days or less) oral exposure to inorganic arsenic, based on the results of a Japanese study (Mizuta et al., 1956). Within this study; arsenic exposure through the intake of contaminated soy sauce was estimated to be 3 mg/day during 2-3 weeks. For derivation of the acute oral MRL, facial edema and gastrointestinal symptoms (nausea, vomiting, diarrhea), which were characteristic of the initial poisoning and then subsided, were considered to be the critical effects. The MRL of 0.005 mg As/kg bw per day was calculated by applying an uncertainty factor of 10 (10 for use of a LOAEL and 1 for human variability) to the LOAEL of 0.05 mg As/kg bw per day (ATSDR, 2007). Chronic effects Specific dermal effects (hyperpigmentation and hyperkeratosis) are one of the first signs of chronic exposure to arsenic . Exposure to inorganic arsenic is associated with many adverse health effects including peripheral vascular effects, cardiovascular disease, diabetes, peripheral neuropathy, diseases of the respiratory system, neurodevelopmental toxicity, immunologic effects and cancers (ATSDR, 2007; EFSA, 2009, IARC, 2012 and NRC, 2013). In 2004, IARC concluded that arsenic in drinking water causes cancers of the urinary bladder, lung and skin and that the evidence was “limited” for cancers of the kidney, liver and prostate. In 2012, IARC confirmed that arsenic and inorganic arsenic compounds are carcinogenic to humans (Group 1). Up to now, the underlying molecular mechanisms of iAs-induced carcinogenicity are not completely identified. Evidence from a wide range of studies has led to the conclusion that arsenic compounds do not react directly with DNA. However, inorganic arsenic has been shown in vitro and in vivo to induce chromosome breaks and cause DNA damage in a variety of human tissues (FDA, 2016). Established mechanistic events are oxidative DNA damage, genomic instability, aneuploidy, gene amplification, epigenetic effects and DNA-repair inhibition leading to mutagenesis. Some studies suggest that bladder cancers may result from urothelial cytotoxicity and regenerative proliferation (FDA, 2016). In 1989, the Joint FAO/WHO Expert Committee on Food Additives (JECFA) established a provisional tolerable weekly intake (PTWI) of 15 μg/kg bw for inorganic arsenic (FAO/WHO, 1989). The PTWI was however withdrawn by JECFA in 2010 as more recent studies indicated that inorganic arsenic caused cancer of the lung and urinary tract in addition to skin cancer, at exposure levels lower than the PTWI. Based on epidemiological studies, JECFA identified a benchmark dose lower confidence limit for 0.5 % increased incidence of lung cancer (BMDL0.5) of 3.0 µg/kg bw per day (FAO/WHO, 2011).


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EFSA noted that the association between inorganic arsenic exposure and the incidence of lung cancer was much stronger in smokers. This observation is consistent with inorganic As being a co-carcinogen. However, EFSA could not determine whether there would be residual confounding after adjustment for smoking. In contrast, the data for skin lesions were from larger populations and showed a high degree of consistency between studies. EFSA has thus concluded that the overall range of BMDL01 values of 0.3 to 8 μg/kg bw per day should be used instead of a single reference point in the risk characterisation for inorganic arsenic (EFSA, 2009a).

5 Exposure assessment

Contamination data: As content in infant food products

Assessing the As content in food products that are representative for young children in the above-mentioned four different age categories is a challenging exercise. As stated, dietary profiles shift dramatically over time and may substantially differ between children of the same age group as well. Therefore, this advisory report is based on different data sources. First, data on As content in rice-based food products for children have been collected both from literature and from the FAVV-AFSCA survey on arsenic content in consumer foods. In addition, data on the As content in other food sources consumed by children were obtained from the SPECAs project and other literature sources. Additional analyses of the As content in several batches of Novarice, a rice-based infant food that is used in specific medical conditions, were performed by CODA/CERVA. Table 1: Overview of the As data sources in the infant food products selected for exposure assessment (The complete database is shown in attachment 1)

Infant food products As data sources

Rice, white rice, brown rice, basmati rice, Thai rice and wild rice

FASFC, SPECAs

Pasta with rice, rice noodles FASFC, Munera-Picazo et al. 2014, Sun et al. 2009

Bread SPECAs, Munera-Picazo et al. 2014

Rice biscuits* Sciensano (ex CODA/CERVA)

Rice cereals (e.g. crispies, coco pops) SPECAs

Stew with rice FASFC

Rice based drinks* FASFC, Sciensano (ex CODA/CERVA

Infant rice cereal Llorente-Mirandes et al. (2014), Carbonell-Barachina et al. (2012), Juskelis et al. (2013)

Infant multicereals and rice-based baby foods

Llorente-Mirandes et al. (2014), Juskelis et al. (2013), Rintala et al. (2014), Ljung et al. (2011)

* Rice biscuits and rice drinks were analyzed by CODA-CERVA, in the context of the control program of The Grand Duchy of Luxemburg.

As the As content may differ substantially depending on geographical locations, inconsistent data are sometimes encountered in the database. In such case, available data from the Belgian consumer market have primarily been taken into account to fill in some gaps in the database. To make a relevant selection, a 2013-2014 FASFC survey of the As content in food products was used. In the absence of data, information from the SPECAs project was used. By combining all the data, an overview of the As content in representative food products that are used for infant nutrition can be obtained (see attachment 1) which allows to calculate the daily arsenic intake under different exposure scenarios (see below).


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In addition, given the fact that current risk assessment practice is primarily based on the exposure to inorganic arsenic, this variable was included in the exposure assessment.

- From the SPECAs project, a thorough analysis of As speciation in different foodstuffs was conducted.

- From the BIOTRAs project it was observed that As speciation does not change during food preservation and preparation.

For those foodstuffs relevant for the dietary exposure scenarios for infants and young children, the SPECAs and BIOTRAs projects were used to make the following assumptions on iAs content:

- Water: 100 % - Plant based foodstuffs other than rice: 100 % - Drinks / Novarice: 78 % - Rice: 70 % - Meat, fish, eggs: 10 %

Consumption data

As mentioned above, 4 different age groups were considered based on the important shifts in dietary profile diversification. For each of these age groups, several assumptions had to be made with respect to the consumption of different food products. While food consumption surveys for the Belgian population are available (2004 and 2014), they both lack specific data for children and certainly for infants and young children. Therefore, dietary recommendations from Kind & Gezin for the different age groups were used. An appropriate energy intake, as recommended from a previous SHC advisory report (SHC, 2009 & 2016), was also taken into account. This information was then combined with ideal food consumption data from week menus at the pediatric department of the ULB University Children’s Hospital Queen Fabiola (ULB) in Brussels. For each of the 4 age groups, three scenarios characterized by a different consumption of rice-based products were considered (see attachment 2-5 for more details on the rice-based products taken into account). An additional scenario was included for the 36-month-old infants (see below). For all 13 scenarios, the range of As exposure was calculated using the lowest, median and highest available As concentrations for the different food products. In addition, a scenario in which all water used as drinking water or for food preparation contained the maximally allowed concentration of 10 µg As/L was taken up. This resulted in 52 different exposure scenarios. An overview of the detailed dietary patterns for the different age groups, the As content in the food products and the eventual calculation of daily As exposure per unit of body weight can be consulted in attachment 2-5 for each exposure scenario.

5.2.1 ’Infants 3-month-old’

For the 3 month old infants, three consumption scenarios were considered:

- Infants receiving breastfeeding only: Three month-old infants may still completely rely on breastfeeding. Within this scenario, the As content in mother’s milk was based on Carignan et al. (2015) where a range of 0 to 0.62 µg As/L was reported. For the lower risk calculation, the LOQ of 0.22 µg As/L was used as lower limit.


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- Infants receiving formula milk only: Infants fed with formula milk will be exposed to drinking water. Bottled water as well as tap water were considered as possible scenarios. Publications from Sullivan et al. (2011) and the FAVV/AFSCA file mention a range between 0.07 to 5.3 µg As/L with a low average content of 1.67 µg As/L. However, data on the As content in milk powder is lacking in the FAVV/AFSCA survey. The reported concentration of 2.2 µg As/kg milk powder by Jackson et al. (2012) was therefore used.

- Infants receiving Novarice only: Use of rice-based products is sometimes medically advised, with Novarice being the most important product. No data on As content were available. CODA/CERVA has therefore performed analysis of several Novarice batches and found a range of 17.6 to 20.8 µg As/kg powder. Obviously, once dissolved in water to make the actual milk, this translates to substantially lower As concentrations in the milk ranging between 2.7-7.6 µg As/L.

5.2.2 Infants 6-month-old

Infants 6-month-old experience a more diversified dietary profile. The ideal dietary composition was based on available week menus from the ULB children’s hospital. However, a correction factor was taken into account for the energy intake as recommended by SHC (SHC, 2009 & 2016) and Kind & Gezin. Importantly, consumption of rice based crackers and biscuit was not considered yet for this age group. Three exposure scenarios were considered:

- Infants receiving a normal diet: the normal exposure scenario consisted of the normal recommended diets, corrected for recommended energy intake, and assuming one rice meal per week;

- Infants receiving a rice-based diet: In this scenario, all starch sources for hot meals (potatoes, pasta, rice) were replaced with rice only;

- Infants receiving Novarice: This exposure scenario took into account the normal dietary pattern, but the milk source was completely replaced by Novarice drink.

As content in the milk source was again based on Jackson et al. (2012). The concentrations on inorganic arsenic were calculated based on the assumptions discussed under 5.1.

5.2.3 Infants 12-month-old

Similar to the 6-month-age group, ideal dietary composition was based on available week menus from the ULB children’s hospital. A correction factor was taken into account for the energy intake as recommended by SHC (SHC, 2009 & 2016) and Kind & Gezin. For this age group, the consumption of rice crackers and rice biscuits was taken into account. One piece of fruit replaced by a rice biscuit was assumed.


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The following three exposure scenarios were considered: - Infants receiving a normal diet:

One rice meal per week. - Infants receiving a rice-based diet:

Seven rice meals per week. In addition, a rice-based breakfast meal was considered and a rice waffle was considered as starch source for the dinner.

- Infants receiving Novarice: Milk source completely replaced by Novarice drink.

5.2.4 Young children 36-month-old

The dietary profile of 3-year-old children is further diversified but the most important difference compared to 1-year-old children is the total energy intake. The same three exposure scenarios were considered:

- Young children receiving a normal diet: One rice meal per week.

- Young children receiving a rice-based diet: Seven rice meals per week. In addition, a rice-based breakfast meal was included and a rice waffle was considered as starch source for the dinner.

- Young children receiving Novarice: Milk source was completely replaced by Novarice drink.

As children in this age group sometimes also consume rice drinks, a separate exposure scenario was included:

- Young children receiving rice drink: Milk source completely replaced by rice drink. Data on As content are derived from the FAVV/AFSCA survey and range from 5-37 µg As/L with a median value of 21. Arsenic exposure values

Taking into account the 4 different age groups, 3 different exposure scenarios per age group, estimates for minimum, median and maximal As exposure were made based on the following calculations.

• Minimum estimated exposure, μg/kg per day = (IR × minC) ÷ mean bw • Median estimated exposure, μg/kg per day = (IR x medianC) ÷ mean bw • Maximum estimated exposure, μg/kg per day = (IR × maxC) ÷ mean bw

With IR indicating the food product ingestion rate (g/d), C the As concentration in the food (µg/g food) and bw the body weight (kg). As indicated above, an additional exposure scenario was considered in which all water used for drinking and food preparation was containing the threshold value of 10 µg As/L. For the 36-month-age group, a scenario where milk consumption solely consisted of rice drink was included as well. All data regarding total As exposure and inorganic As exposure are presented in tables 2-5. For the discussion of the estimated exposure values, values for inorganic arsenic are primarily considered since this is the As species on which most of the risk assessment studies have been performed and for which benchmark dose limit (BMDL) values are available.


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Some interesting observations can be made:

- From all exposure scenarios, breastfed infants display the lowest estimates for total As exposure, 0.03-0.08 µg As/kg bw per day, and inorganic As exposure, 0.01-0.04 µg iAs/kg bw per day. Replacing breast milk with formula milk in this age group results in a substantial increase in inorganic As exposure values, 0.05-1.00 µg iAs/kg bw per day. The As content in Novarice contributes to a further increase in estimated iAs exposure values, 0.31-1.53 µg iAs/kg bw per day.

- For the other age groups (6, 12 and 36 months) iAs exposure ranges from 0.20-1.32

µg iAs/kg bw per day for a normal dietary exposure scenario. The replacement of milk with Novarice results in an iAs exposure range of 0.27-0.99 µg iAs/kg bw per day. It must be noted that the minimum estimated exposure values increase with the Novarice scenario while this is not the case for the median and high estimated exposures. This can be attributed to the lower variability in As levels for Novarice while As levels in other foodstuffs are much more variable and thus lead to higher increases in the median and high exposure values.

- An important contributor to increased iAs exposure is the rice-based dietary scenario:

all age groups experience a sharp increase with more than a doubling and sometimes almost tripling of iAs exposure values. Values go from 0.64 µg iAs/kg bw per day for minimum exposure levels to 1.57 µg iAs/kg bw per day and even 3.29 µg iAs/kg bw per day for median and high exposure levels, respectively. Particularly predictions for 6-month-old infants are affected by high exposure scenarios, probably due to their lower body weight compared to their food intake.

These values are quite consistent with what is reported in previous EFSA studies. A 2009 report indicated that children under the age of three years are the most vulnerable group regarding iAs exposure. Estimates from two different studies show an inorganic arsenic intake ranging from 0.50 to 2.66 µg iAs/kg bw per day. These studies did not yet take into account exposure scenarios where lactose intolerant children substitute formula and cow’s milk with rice drinks. The same holds true for children that consume rice on a much more frequent basis. An updated EFSA report from 2014 finds dietary iAs exposure to be highest for the younger population and provides estimates of a mean consumption of 0.47-1.37 µg iAs/kg bw per day for infants and young children, which is quite close to the 0.35-0.55 µg iAs/kg bw per day range provided in table 3.


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Table 2. Minimum estimated As exposure values (µg As/kg bw per day) in function of age for different exposure scenarios

age (months)

As exposure (µg/kg bw/d) 3 6 12 36

Breast milk 0.03 - - - normal 0.06 0.23 0.23 0.31 Novarice 0.39 0.34 0.32 0.33 rice-based solid food - 0.33 0.86 0.89

Inorganic As exposure (µg/kg bw/d)


Table 3. Median estimated As exposure values (µg As/kg bw per day) in function of age for different exposure scenarios

age (months)






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Table 4. Maximum estimated As exposure values (µg As/kg bw per day) in function of age for different exposure scenarios

age (months)





Finally, Table 5 illustrates the scenario in which all water, used for drinking or food preparation, would contain the threshold value of 10 µg As/L. Taking into account the median As content values in foodstuffs, it is clear that contaminated waters would still be a predominant contributor to As exposure. Primarily younger age groups (3- and 6-months-old infants) would experience a substantial additional As exposure from contaminated drinking water. Table 5. Median estimated As exposure values (µg As/kg bw per day) in function of age for different exposure scenarios in case all water contains the threshold value of 10 µg As/L

age (months)


Breast milk - - - - normal 1.56 1.01 0.87 0.88 Novarice 1.56 1.10 0.91 0.85 rice-based solid food - 2.19 2.20 2.40

Inorganic As exposure (µg/kg bw/d) Breast milk - - - -

normal 1.54 0.93 0.78 0.76 Novarice 1.53 1.00 0.79 0.75 rice-based solid food - 1.73 1.63 1.84

Given the fact that the current exposure assessment makes use of 52 different scenarios, a visual representation of age-dependent iAs exposure was made to easily capture the dynamics (Figures 1 and 2).


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Figures 1-2 clearly illustrate the low exposure of 3-month-old breastfed infants. Other dietary exposure scenarios display higher exposure values with rice-based solid foods resulting in substantially high As exposure. Interestingly, compared to the normal dietary exposure, uptake of Novarice does not bring about higher exposure values. This indicates that its rigorous quality assurance prevents putative health risks from additional toxicant exposure. With respect to exposure evolution, it is interesting to note that 3-year-old children do not necessarily experience higher As exposure values, despite their higher total intake values. This can be explained by their proportionally higher weight gain compared to the increase in consumption rate. Particularly younger infants (3- and 6-month-old) would be more sensitive to high As exposure under worst case scenarios (high exposure, contaminated drinking water).

Low exposure

Median exposure

High exposure

10 µg/L water exposure

Figure 1. Evolution of total As exposure over time for different exposure levels and exposure scenarios


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Low exposure

Median exposure

High exposure

10 µg/L water exposure

Figure 2. Evolution of inorganic As exposure over time for different exposure levels and exposure scenarios An additional post-processing of the exposure assessment was done by calculating the contribution of the different dietary ingredients to the total As exposure. These calculations no longer focused on iAs, but on the exposure to total As. Additionally, to keep the overview, only the scenario of normal dietary exposure was considered. Figure 3 depicts the values for the 4 different age groups. The graph for 3-month-old infants illustrates the limited contribution of breastfeeding to As exposure compared to other dietary patterns. Arsenic present in drinking water (median concentration levels) is the most important contributor when infants are formula fed, while As from rice-drink powder results in a substantially higher contribution to total As exposure for the Novarice scenario.


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Infants 6 months of age display a diversified dietary profile resulting in more potential sources of As exposure. Under normal dietary conditions, water and milk are only minor contributors while rice and non-rice plant foods are contributing for almost 60 % to total As exposure. As exposure from animal derived foods is ignorable. For the Novarice scenario the “milk” source – in this case the Novarice drink – contributes for 15 % to the total As intake. This is a little increase compared to normal diet, but still fairly moderate compared to the substantial contribution from rice and non-rice-based food products. Finally, in the case of a diet where rice is the most important starch source and rice biscuits and crackers have been introduced, a dramatic increase in As intake is observed. Rice-based ingredients account for almost 90 % of the total daily As intake. This is a highly important observation in view of risk mitigation. Estimates of As exposure for 12-months-old children are more dominated by the milk component, particularly because milk contains higher amounts of arsenic than regular drinking water and even more than Novarice. Again, children frequently consuming rice-based nutrition would experience a dramatic increase in As exposure with values exceeding 2 µg As/kg bw per day. The diet from a 3-year-old child is characterized by a further diversification and lower dependence on milk. Corrected for body weight, As exposure is lower than for 1-year-old infants and the contribution from other food ingredients than milk become bigger. Yet again, frequent consumption of rice-based ingredients would result in a highly significant increase in As exposure exceeding 2 µg As/kg bw per day.

3-month-old infants

6-month-old infants

12-month-old infants

36-month-old young children

Figure 3. Contribution of different dietary ingredients to total As exposure for different infant age groups. Take notice of the difference in scale for the Y-axis.


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For 3-year-old children, a fourth scenario was considered in which rice drinks are introduced into the diet by the parents due to the occurrence and/or persistence of dietary intolerance problems. In figure 4, the “Novarice” and “rice drink’ exposure scenarios for 3-year-old children are compared. For the median exposure levels, the contribution from the different dietary ingredients to the total As content is also provided. It immediately becomes clear that the choice for rice drink has a profound impact on As exposure, maybe not for exposure at the low range As levels, but certainly for the median and high range As levels with a 60 % increase due to consumption of rice drink instead of e.g. Novarice. The increasing effect from rice drink to As contribution is a bit less pronounced for the exposure scenario with contaminated drinking water, yet it remains clearly visible. When considering the median range As levels and calculating the contribution from the different dietary ingredients it is clear that rice drinks has a major role in terms of As intake. While rice drink is a minor contributor to As exposure in the Novarice scenario, it contributes for more than 50 % to the total As intake in the rice milk scenario.

Figure 4. Contribution of rice drinks to total As exposure in 3-year-old children (on the left, comparison of several scenarios for low to high intake assumptions; on the right, contribution of the various foodstuffs (median uptake) for the Novarice and rice milk scenarios, respectively). A final post-processing step was performed to be able to inform the consumer, or rather their parents, on how much the choice for a dietary ingredient would affect a child’s exposure to arsenic. In this exercise, only age groups of 6, 12 and 36 months with a normal diet (see attachment 2-5) were considered. Given the higher As content of some specific rice-based products (biscuits, rice drinks, etc.), some extra food items were selected and added to the diet to provide examples of scenarios with a higher As intake. The results are presented in Table 6. Scenarios are provided for the inclusion of 1 or 2 additional rice biscuits per day, the choice for an extra rice meal per week and the consumption of one or 2 glasses of rice drinks per day. An additional consumption of Novarice was not included as previous figures indicate Novarice as a minor contributor to As exposure. These values should provide more tangible data for parents when making choices for their children’s diet.


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Table 6. Intake of inorganic As according to several scenarios for children aged 6,12 and 36 months

6 months

12 months

36 months

Normal diet (1 rice meal per week)

As exposure (µg As/kg bw per day)

0.45 0.70 0.55

1 rice biscuit/day

Extra As exposure (µg As/kg bw per day) Contribution to new total exposure (%)

0.12 21

0.10 13

0.07 11

2 rice biscuits/day Extra As exposure (µg As/kg bw per day) Contribution (%)

0.24 35

0.20 23

0.14 20

1 additional rice meal per week

Extra As exposure (µg As/kg bw per day) Contribution (%)

0.17 27

0.05 7

0.04 7

1 glass rice drink/day Extra As exposure (µg As/kg bw per day) Contribution (%) - -

0.12 18

2 glasses rice drink/day

Extra As exposure (µg As/kg bw per day) Contribution (%) - -

0.37 40

6 Discussion of the results

Exposure levels and toxicological concern for adults and children

The PTWI of 15 μg/kg bw for inorganic As was withdrawn as studies indicated that inorganic As caused cancer of the lung and urinary tract in addition to skin cancer, at exposure levels lower than the PTWI. Hence, EFSA has identified a range of values for the 95 % lower confidence limit of the benchmark dose of 1 % extra risk (BMDL01) for several endpoints. The lowest BMDL01 values were found for lung cancer (0.34 – 0.69 µg/kg.bw per day) (EFSA, 2009a; SHC, 2015). According to the SPECAs project, the Belgian adult population is estimated to be exposed to 0.11 µg iAs/kg bw per day (SPECAs, 2013), with only a small margin (3.1 to 6.3) between adult exposure and BMDLs corresponding to lung cancer. As to the children, it is important to note that, apart from the breastfed 3-month-old infants, the estimated inorganic As exposure always exceeds the values for adults, meaning that the margin of exposure is further reduced or even absent. Breastfed children appear to be less exposed to inorganic As since the passage to the mammary gland is limited and the actual As concentrations in maternal milk are relatively low. In contrast, placental arsenic concentrations do reflect both maternal and infant exposures. Therefore, it is recommended for pregnant women to lower their inorganic arsenic exposure as much as possible during pregnancy. Children’s exposure to contaminants expressed in µg/kg bw per day is generally higher than that of adults due to the higher food intake of young children relative to their body weight. In addition, the developing child is characterized by a high degree of dynamics on different levels. For all these reasons it is not possible to accurately characterize health risks for children by comparing their (rapidly changing) exposure to toxicological endpoints that are linked to chronic health effects. However, as a precautionary measure, the exposure of young children to As, and in particular to inorganic As, should be as low as possible. To illustrate, switching to one rice meal per month instead of one rice meal per week in the normal diet scenario would result in a drop in As exposure with 37 %, 7,5 % and 23 % for 6 month old, 12 month old and 36 month old children, respectively.


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Completely eliminating rice from the infant’s normal diet would reduce the As exposure with 50 %, 10 % and 30 % for 6 month old, 12 month old and 36 month old children.

Comparison of exposure between infants and adults

For children aged 12 months, the normal diet (ND) scenario is characterized by an inorganic As intake of 0.70 µg/kg bw per day, which is 6 times higher than the estimated dietary exposure of the adult population (SPECAs project report: 0.11 µg iAs/kg bw per day). When rice based solid food or rice drinks are added to the diet, the iAs intake can rise to even higher levels up to 1.57 µg/kg bw per day, which is 14 times the intake estimated for adults (Table 7). Table 7: Summary table showing the differences in inorganic As intake according to several scenarios for children aged 12 months.

Scenario iAs intake at the age of 12 months (µg/kg

bw per day)

Increase (in % as opposed to

normal diet)

Children (12 months) vs Adult population ratio

Normal diet (ND) 0.70 100 6

ND + 1 rice biscuit/day 0.80 14 % 7

ND + 2 rice biscuits/day 0.90 29 % 8

ND + 1 glass rice drink/day

1.00

31 % 9

ND + 2 glasses rice drink/day

1.21 73 % 11

Rice-based solid food 1.57 124 % 14

Novarice diet 0.42 - 40 % 4

Thus, daily consumption of rice drinks in quantities similar to the average consumption of cows’ milk (one glass, approximately 200 ml by adults or half a pint, approximately 280 ml by a young child) would lead to an additional daily dietary exposure to inorganic arsenic. This increase is minor for adults and young persons and they do not need to change their diet. For young children (ages 1- 4.5 years), consuming rice drinks instead of breast milk, infant formula or cows’ milk could increase the intake of inorganic arsenic with more than 70 %. A moderate increase in iAs intake is also noticeable when rice biscuits are added to a normal diet. The most dramatic increase (more than twofold) is obtained when all starch sources are replaced by rice (i.e. the rice-based solid foods scenario). This results in a 14-fold higher exposure per kg body weight than for adults. In most cases, the use of Novarice (infant formula) does not lead to a higher increase in inorganic As intake by children and can actually be linked to a reduction of the intake compared to the normal diet of a 1 year old child.


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7 Recommendations

The analysis of various scenarios with rice products in the diet of infants and young children lead to the conclusion that the intake of inorganic As could be relatively high for this group of the population. Hence, the following recommendations were drawn: It is recommended to parents of infants and young children and to health professionals

i) to provide infants with a balanced and varied diet and thus not substitute starch sources with rice-based solid foods alone;

ii) to boil rice in enough water (water to rice ratio of 6) and pour away boiling water prior to consuming the rice;

iii) to avoid rice biscuits as regular snacks; iv) to not substitute breast milk, infant formula or cows’ milk with rice drinks.

To parents of infants and young children who are currently consuming rice drinks because they are allergic to or intolerant of cows’ milk,

i) it is recommended to consult their health professional or dietician about suitable alternatives to cows’ milk.

To pregnant women and young mothers, it is recommended

i) to lower their exposure to inorganic As during pregnancy in order to avoid placental transfer to the fetus. This can be done by limiting the consumption of rice, rice-based foodstuffs and other foodstuffs with high inorganic As concentrations such as algae and some algae derived food supplements (see SHC advisory report n°9149);

ii) to breastfeed their children in order to limit as much as possible the intake of inorganic As during the first months of their life.

For research It is recommended:

i) to increase our knowledge of health effects linked to inorganic As intake and to further investigate on the potential toxicity of some organic As species (methylated As species, arsenosugars, arsenolipids, etc.);

ii) to develop biomarkers of As exposure in order to gain more insight in the children exposure according to their diet and to be able to perform epidemiological studies;

iii) to have better epidemiological data on adverse health effects of inorganic arsenic in certain susceptible life stages (e.g. infancy and childhood);

iv) to develop agricultural and processing practices that would reduce arsenic content of rice by limiting the plant’s uptake of arsenic.


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8 Uncertainties

Analytical methods used and chemical species considered

As the As content may differ substantially depending on geographical locations, inconsistent data are sometimes encountered in the database. In such case, available data from the Belgian consumer market have primarily been taken into account to fill in some gaps in the database. It should also be indicated that only inorganic As was considered in the exposure assessment. Some foods may however also contain high amounts of organic As compounds. Arsenobetaine for example (mainly present in marine samples) was not included because it is a non-toxic compound. Other organic As compounds could however not be included due to the lack of precise analytical methods and toxicological information (e.g. arsenolipids and arsenosugars). Finally, it should be noted that the sampling procedure prior to analysis is also a point of attention. To fully preserve the speciation of arsenic compounds in a sample, it is advised to flash freeze the sample in liquid nitrogen and subsequently store it at -20°C. A slow freezing process may convert some As species, leading to an inaccurate assessment of As speciation in some types of samples.

8.2 Toxicological concerns

Many elements regarding gut physiology, biotransformation potency and microbiome dynamics are highly variable in the developing child. Each of these will impact As toxicokinetics. However, knowledge on the impact on As bioavailability and toxicity is completely lacking.


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V REFERENCES

ATSDR - Agency for Toxic Substances and Disease Registry. Toxicological profile for arsenic (update). U.S. Department of Health and Human Services. Public Health Service. Atlanta; 2007. Carignan CC, Cottingham KL, Jackson BP, Farzan SF, Gandolfi AJ, Punshon T et al. Estimated exposure to arsenic in breastfed and formula-fed infants in a United States cohort. Environ Health Perspect 2015;123:500-6. Chattopadhyay S, Bhaumik S, NagChaudhury A, Das Gupta S. Arsenic induced changes in growth development and apoptosis in neonatal and adult brain cells in vivo and in tissue culture. Toxicol Lett 2002;128:73–84. Concha G, Vogler G, Lezcano D, Nermell B, Vahter M. Exposure to inorganic arsenic metabolites during early human development. Toxicol Sci 1998a;44:185-90. Concha G, Vogler G, Nermell B, Vahter M. Low-level arsenic excretion in breast milk of native Andean women exposed to high levels of arsenic in the drinking water. Int Arch Occup Environ Health 1998b;71:42–6. Das HK, Mitra AK, Sengupta PK, Islam F, Rabban GH. Arsenic concentrations in rice, vegetables and fish in Bangladesh: a preliminary study. Environment International 2004;30:383-87. D’Amato M, Aureli F, Ciardullo S, Raggi A,Cubadda F. Arsenic speciation in wheat and wheat products using ultrasound- and microwave-assisted extraction and anion exchange chromatography-inductively coupled plasma mass spectrometry. J Anal At Spectrom 2011;26:207. de la Calle MB, Emteborg H, Linsinger TP, Montoro R, Sloth JJ, Rubio R et al. Does the determination of inorganic arsenic in rice depend on the method? Trends in Analytical Chemistry 2011;30:641–51. D’Ilio S, Alessandrelli M, Cresti R, Forte G, Caroli S. Arsenic content of various rice types and determined by plasma based techniques. Microchemical Journal 2002;73:195-201. EFSA - European Food Safety Authority. Dietary exposure to inorganic arsenic in the European population. EFSA Journal 2014;12:1-68. EFSA - European Food Safety Authority. Scientific opinion on arsenic in food. EFSA Journal 2009;7:1351–1550. Fontcuberta M, Calderon J, Villalbí JR, Centrich F, Porta AS, Espelt A et al. Total and inorganic arsenic in marketed food and associated health risks for the Catalan (Spain) population. J of Agricultural and Food Chemistry 2011;59:10013–22. Gardner RM, Nermell B, Kippler M, Grandér M, Li L, Ekström EC et al. Arsenic methylation efficiency increases during the first trimester of pregnancy independent of folate status. Reprod Toxicol 2011;31:210-8. Hansen HR, Raab A, Price AH, Duan GL, Zhu YG, Northon GJ et al. Journal of Environmental Monitoring 2011;13:32-4.


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NRC - National Research Council of the National Academies. Critical aspects of EPA’s IRIS assessment of inorganic arsenic: interim report. 2013. Available from: URL:< http://www.nap.edu> Norton GJ, Duan G, Dasgupta T, Islam MR, Lei M, Z hu YG et al. Environmental and Genetic Control of Arsenic Accumulation and Speciation in Rice Grain: Comparing a Range of Common Cultivars Grown in Contaminated Sites Across Bangladesh, China, and India. Environmental Science and Technology 2009;43:8381–6. Pillai TR, Yan WG, Agrama HA, James WD, Ibrahim AM, McClung AM et al. 2010. Total grain-arsenic and arsenic-species concentrations in diverse rice cultivars under flooded conditions. Crop Science 2010;50:2065-75. Punshon T, Davis MA, Marsit CJ, Theiler SK, Baker ER, Jackson BP et al. Placental arsenic concentrations in relation to both maternal and infant biomarkers of exposure in a US cohort. J Expo Sci Environ Epidemiol 2015;25:599-603. Rebelo FM & Caldas ED. Arsenic, lead, mercury and cadmium: Toxicity, levels in breast milk and the risks for breastfed infants. Environ Res. 2016 Nov;151:671-688. doi:10.1016/j.envres.2016.08.027. Epub 2016 Sep 10. Review. Rintala EM, Ekholm P, Koivisto P, Peltonen K, Venäläinen ER. The intake of inorganic arsenic from long grain rice and rice-based baby foods in Finland-Low saety margin warrants follow up. Food Chemistry 2014;150:199-205. Ruttens A, Cheyns K, Blanpain AC, De Temmerman L, Waegeneers N. Arsenic speciation in food in Belgium. Part 2: Cereals and cereal products. Food and Chemical Toxicology 2018;118:32–41 SHC - Superior Health Council. Arsenic and other elements in algae and dietary supplements based on algae. Brussels: SHC; 2015. Advice n° 9149. SHC - Superior Health Council. Recommandations nutritionnelles pour la Belgique/Voedingsaanbevelingen voor België. Brussels: SHC; 2009. Advice n° 8309. SHC - Superior Health Council. Recommandations nutritionnelles pour la Belgique/Voedingsaanbevelingen voor België. Brussels: SHC; 2016. Advice n° 9285. SPECAS. Project RF 6205. Speciatie van arseen in vis en andere voedingswaren - Eindverslag Contractueel onderzoek 2009-2010. Su Y H, McGrath SP, Zhao FJ. Rice is more efficient in arsenite uptake and translocation than wheat and barley. Plant and Soil 2010;328:27–34. Sun GX, Williams PN, Zhu YG, Deacon C, Carey AM, Raab A et al. Survey of arsenic and its speciation in rice products such as breakfast cereals, rice crackers and Japanese rice condiments. Environment International 2009;35:473-5. Torres-Escribano S, Leal M, Vélez D, Montoro R. Total and inorganic arsenic concentrations in rice sold in Spain, effect of cooking, and risk assessment. Environmental Science and Technology 2008;42:3867-72. U.S. FDA - U.S. Food and Drug Administration. Arsenic in Rice and Rice Products Risk Assessment Report. 2016. Available from: URL :<http://www.fda.gov/Food/FoodScienceResearch/RiskSafetyAssessment/default.htm>

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VI ACKNOWLEDGMENTS

Useful information on As content of some foodstuffs and water could be extracted from the FASFC control survey database. FASFC is acknowledged for agreeing the use of these data to complete the As content database used in the framework of this advisory report. The rice-based biscuits and rice drinks analysed by CODA-CERVA were provided in the context of the control program of the Grand Duchy of Luxemburg. The ‘Ministère de la Santé de Luxembourg’ is acknowledged for agreeing the use of the obtained data in the framework of this advisory report.


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VII COMPOSITION OF THE WORKING GROUP

The composition of the Committee and that of the Board as well as the list of experts appointed by Royal Decree are available on the following website: composition and mode of operation.

All experts joined the working group in a private capacity. Their general declarations of interests as well as those of the members of the Committee and the Board can be viewed on the SHC website (site: conflicts of interest). The following experts were involved in drawing up and endorsing this advisory report. The working group was chaired by Luc PUSSEMIER and Tom VAN DE WIELE; the scientific secretaries were Anouck WITTERS, Michèle ULENS and Florence BERNARDY. GOYENS Philippe Paediatrics, metabolism ULB

MERTENS Birgit Toxicology, food contaminants Sciensano

PUSSEMIER Luc Residues and contaminants, chemical risks

CODA-CERVA

RIGO Jacques Pediatric nutrition ULiège

RUTTENS Ann Chemical analysis Sciensano

VAN DE WIELE Tom Microbial technology, contaminants UGent

VLEMINCKX Christiane Toxicology Sciensano

The standing working group NHFS (Nutrition and Health, including Food Safety) has endorsed the advisory report. The standing working group was chaired by Stefaan DE HENAUW, the scientific secretaries were Florence BERNARDY and Michèle ULENS. BRASSEUR Daniel Pediatric nutrition ULB DE BACKER Guy Preventive medicine, public health,

epidemiology UGent

DE HENAUW Stefaan Public health nutrition UGent DELZENNE Nathalie Nutrition, toxicology UCLouvain HUYGHEBAERT André Chemistry, food technology UGent NEVE Jean Therapeutic Chemistry and Nutritional

Sciences ULB

PENNINCKX Michel Endocrinology, toxicology, biotechnology

ULB

VANDEVIJVERE Stefanie Epidemiology and public health Sciensano VANHAUWAERT Erika Dietetics, food and health UC Leuven-Limburg

The following administrations and/or ministerial cabinets were heard: FIOLET Thibault EFSA Scientific Cooperation FPS HFCSAE, DG 4 POTTIER Jean Nutrition and Health Claims, Food for

Specific Groups, Novel Food FPS HFCSAE, DG 4

http://www.health.belgium.be/eportal/Aboutus/relatedinstitutions/SuperiorHealthCouncil/about-us/composition/index.htm?fodnlang=en

http://www.health.belgium.be/eportal/Aboutus/relatedinstitutions/SuperiorHealthCouncil/conflictsofinterests/index.htm?fodnlang=en

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ice

0

,07

1 0

,06

3 0

,89

Bel

giu

m-S

PEC

AS

(CO

DA

-CER

VA

) SP

ECA

S H

PLC

-IC

P-M

S 0

,1 M

HN

O3

+ 3

%H

21

6 1

Th

ai r

ice

0

,14

5 0

,07

6 0

,52

Bel

giu

m-S

PEC

AS

(CO

DA

-CER

VA

) SP

ECA

S H

PLC

-IC

P-M

S 0

,1 M

HN

O3

+ 3

%H

21

7 1

Th

ai r

ice

0

,13

2 0

,06

3 0

,48

Bel

giu

m-S

PEC

AS

(CO

DA

-CER

VA

) SP

ECA

S H

PLC

-IC

P-M

S 0

,1 M

HN

O3

+ 3

%H

21

8 1

W

ild r

ice

0

,18

9 0

,14

1 0

,75

Bel

giu

m-S

PEC

AS

(CO

DA

-CER

VA

) SP

ECA

S H

PLC

-IC

P-M

S 0

,1 M

HN

O3

+ 3

%H

21

9 1

W

ild r

ice

0

,10

2 0

,08

4 0

,82

Bel

giu

m-S

PEC

AS

(CO

DA

-CER

VA

) SP

ECA

S H

PLC

-IC

P-M

S 0

,1 M

HN

O3

+ 3

%H

22

0 1

W

ild r

ice

0

,04

3 0

,04

0 0

,93

Bel

giu

m-S

PEC

AS

(CO

DA

-CER

VA

) SP

ECA

S H

PLC

-IC

P-M

S 0

,1 M

HN

O3

+ 3

%H

22

1 1

Typ

e o

f fo

od

TOTA

L A

s IN

OR

GA

NIC

A

s R

ATI

O

Re

fere

nce

or

sam

ple

n°

An

alys

is m

eth

od

n

Co

mm

en

t Fo

od

Cat

ego

ry

tota

l A

s (m

g/kg

as

sold

) i

As

(mg/

kg

as s

old

) %

i A

s o

f to

tal

Ori

gin

of

dat

a e

xtra

ctio

n

liqu

id

PA

STA

wit

h r

ice

rice

no

od

les

0

,19

Bel

giu

m-F

ASF

C

40

40

-14

-01

68

1

ri

ce n

oo

dle

s 0

,07

4

B

elgi

um

-FA

SFC

4

04

0-1

4-0

25

2

1

ri

ce n

oo

dle

s 0

,08

0

B

elgi

um

-FA

SFC

4

04

0-1

4-0

26

3

1

ri

ce n

oo

dle

s 0

,07

3

B

elgi

um

-FA

SFC

4

04

0-1

4-0

29

2

1

ri

ce n

oo

dle

s 0

,19

0,1

2 0

,63

UK

Su

n e

t al

. 20

09

H

PLC

-IC

P-M

S 1

% H

NO

3 1

ri

ce b

ased

pas

ta

0,0

46

0,0

31

67

,39

Spai

n

Mu

ner

a-P

icaz

o e

t al

., 2

01

4

AA

S-H

G +

HP

LC

1

gl

ute

n f

ree

ri

ce b

ased

pas

ta

0,2

56

0,1

28

50

,00

Spai

n

Mu

ner

a-P

icaz

o e

t al

., 2

01

4

AA

S-H

G +

HP

LC

1

gl

ute

n f

ree

ri

ce b

ased

pas

ta

0,1

28

0,0

75

58

,59

Spai

n

Mu

ner

a-P

icaz

o e

t al

., 2

01

4

AA

S-H

G +

HP

LC

1

gl

ute

n f

ree

ri

ce b

ased

pas

ta

0,2

02

0,1

35

66

,83

Spai

n

Mu

ner

a-P

icaz

o e

t al

., 2

01

4

AA

S-H

G +

HP

LC

1

gl

ute

n f

ree

RIC

E B

REA

D

bre

ad

0,0

72

0,0

34

47

,22

Spai

n

Mu

ner

a-P

icaz

o e

t al

., 2

01

4

AA

S-H

G +

HP

LC

1

gl

ute

n f

ree

b

read

0

,06

2 0

,03

4 5

4,8

4 Sp

ain

M

un

era-

Pic

azo

et

al.,

20

14

A

AS-

HG

+ H

PLC

1

glu

ten

fre

e

RIC

E B

ISC

UIT

S ri

ce b

iscu

its

0

,16

Lu

xem

bo

urg

co

ntr

ol p

rogr

am (

CO

DA

-CER

VA

) 2

01

3.1

063

LU

X

HP

LC-I

CP

-MS

des

tille

d w

ater

1

ri

ce b

iscu

its

0

,17

Lu

xem

bo

urg

co

ntr

ol p

rogr

am (

CO

DA

-CER

VA

) 2

01

3.1

062

LU

X

HP

LC-I

CP

-MS

des

tille

d w

ater

1

ri

ce b

iscu

its

0

,33

Lu

xem

bo

urg

co

ntr

ol p

rogr

am (

CO

DA

-CER

VA

) 2

01

3.1

061

LU

X

HP

LC-I

CP

-MS

des

tille

d w

ater

1

ri

ce b

iscu

its

0

,34

9

Luxe

mb

ou

rg c

on

tro

l pro

gram

(C

OD

A-C

ERV

A)

20

13

.106

0 L

UX

H

PLC

-IC

P-M

S d

esti

lled

wat

er

1

ri

ce b

iscu

its

0

,27

2

Luxe

mb

ou

rg c

on

tro

l pro

gram

(C

OD

A-C

ERV

A)

20

13

.105

9 L

UX

H

PLC

-IC

P-M

S d

esti

lled

wat

er

1

ri

ce b

iscu

its

0

,19

3

Luxe

mb

ou

rg c

on

tro

l pro

gram

(C

OD

A-C

ERV

A)

20

13

.105

8 L

UX

H

PLC

-IC

P-M

S d

esti

lled

wat

er

1

ri

ce b

iscu

its

0

,08

3

Luxe

mb

ou

rg c

on

tro

l pro

gram

(C

OD

A-C

ERV

A)

20

13

.105

7 L

UX

H

PLC

-IC

P-M

S d

esti

lled

wat

er

1

ri

ce b

iscu

its

0

,22

4

Luxe

mb

ou

rg c

on

tro

l pro

gram

(C

OD

A-C

ERV

A)

20

13

.105

6 L

UX

H

PLC

-IC

P-M

S d

esti

lled

wat

er

1

ri

ce b

iscu

its

0

,26

8

Luxe

mb

ou

rg c

on

tro

l pro

gram

(C

OD

A-C

ERV

A)

20

13

.105

5 L

UX

H

PLC

-IC

P-M

S d

esti

lled

wat

er

1

ri

ce b

iscu

its

0

,28

Lu

xem

bo

urg

co

ntr

ol p

rogr

am (

CO

DA

-CER

VA

) 2

01

3.1

054

LU

X

HP

LC-I

CP

-MS

des

tille

d w

ater

1

ri

ce b

iscu

its

0

,11

3

Luxe

mb

ou

rg c

on

tro

l pro

gram

(C

OD

A-C

ERV

A)

20

13

.105

3 L

UX

H

PLC

-IC

P-M

S d

esti

lled

wat

er

1

ri

ce b

iscu

its

0

,35

9

Luxe

mb

ou

rg c

on

tro

l pro

gram

(C

OD

A-C

ERV

A)

20

13

.105

2 L

UX

H

PLC

-IC

P-M

S d

esti

lled

wat

er

1

ri

ce b

iscu

its

0

,21

8

Luxe

mb

ou

rg c

on

tro

l pro

gram

(C

OD

A-C

ERV

A)

20

13

.105

1 L

UX

H

PLC

-IC

P-M

S d

esti

lled

wat

er

1

ri

ce b

iscu

its

0

,27

3

Luxe

mb

ou

rg c

on

tro

l pro

gram

(C

OD

A-C

ERV

A)

20

13

.105

0 L

UX

H

PLC

-IC

P-M

S d

esti

lled

wat

er

1

ri

ce b

iscu

its

0

,1

Lu

xem

bo

urg

co

ntr

ol p

rogr

am (

CO

DA

-CER

VA

) 2

01

3.1

049

LU

X

HP

LC-I

CP

-MS

des

tille

d w

ater

1

ri

ce b

iscu

its

0

,24

6

Luxe

mb

ou

rg c

on

tro

l pro

gram

(C

OD

A-C

ERV

A)

20

13

.104

8 L

UX

H

PLC

-IC

P-M

S d

esti

lled

wat

er

1

ri

ce b

iscu

its

0

,11

Lu

xem

bo

urg

co

ntr

ol p

rogr

am (

CO

DA

-CER

VA

) 2

01

3.1

047

LU

X

HP

LC-I

CP

-MS

des

tille

d w

ater

1

ri

ce b

iscu

its

0

,29

8

Luxe

mb

ou

rg c

on

tro

l pro

gram

(C

OD

A-C

ERV

A)

20

13

.104

6 L

UX

H

PLC

-IC

P-M

S d

esti

lled

wat

er

1

ri

ce b

iscu

its

0

,21

7

Luxe

mb

ou

rg c

on

tro

l pro

gram

(C

OD

A-C

ERV

A)

20

13

.104

5 L

UX

H

PLC

-IC

P-M

S d

esti

lled

wat

er

1

ri

ce b

iscu

its

0

,20

8

Luxe

mb

ou

rg c

on

tro

l pro

gram

(C

OD

A-C

ERV

A)

20

13

.833

LU

X

HP

LC-I

CP

-MS

des

tille

d w

ater

1

ri

ce c

rack

ers

0,3

9 0

,21

0,5

4 U

K

Sun

et

al. 2

00

9

HP

LC-I

CP

-MS

1%

HN

O3

1

ri

ce c

rack

ers

0,3

7 0

,20

0,5

4 U

K

Sun

et

al. 2

00

9

HP

LC-I

CP

-MS

1%

HN

O3

1

Ty

pe

of

foo

d

TOTA

L A

s IN

OR

GA

NIC

As

RA

TIO

Re

fere

nce

or

sam

ple

n°

An

alys

is m

eth

od

n

Foo

d C

ate

gory

to

tal A

s (m

g/kg

as

sold

) i A

s (m

g/kg

as

sold

) %

i A

s o

f to

tal

Ori

gin

of

dat

a

ext

ract

ion

liq

uid

R

ICE

(BR

EAK

FAST

) C

EREA

LS

rice

cri

spie

s 0

,23

3 0

,16

6 0

,71

Bel

giu

m-S

PEC

AS

(CO

DA

-CER

VA

)

HP

LC-I

CP

-MS

des

tille

d w

ater

ch

oco

po

ps

0,1

01

0,0

76

0,7

5 B

elgi

um

-SP

ECA

S (C

OD

A-C

ERV

A)

H

PLC

-IC

P-M

S d

esti

lled

wat

er

IN

FAN

T ST

EW W

ITH

R

ICE

bab

yfo

od

(st

ew w

ith

ric

e)

0,4

6 0

,00

43

0,0

09

Bel

giu

m-F

ASF

C (

CO

DA

-CER

VA

) 1

48

8-1

3-0

55

6 H

PLC

-IC

P-M

S 0

,1 M

HN

O3

+ 3

%H

20

2 1

b

abyf

oo

d (

stew

wit

h r

ice)

0

,02

6 0

,00

92

0,3

54

Bel

giu

m-F

ASF

C (

CO

DA

-CER

VA

) 1

48

8-1

3-0

55

7 H

PLC

-IC

P-M

S 0

,1 M

HN

O3

+ 3

%H

20

3 1

b

abyf

oo

d (

stew

wit

h r

ice)

0

,01

1 0

,00

75

0,6

82

Bel

giu

m-F

ASF

C (

CO

DA

-CER

VA

)

14

88

-13

-05

63

HP

LC-I

CP

-MS

0,1

M H

NO

3+

3%

H2

04

1

b

abyf

oo

d (

stew

wit

h r

ice)

0

,31

0,0

05

9 0

,01

9 B

elgi

um

-FA

SFC

(C

OD

A-C

ERV

A)

14

88

-13

-05

92

HP

LC-I

CP

-MS

0,1

M H

NO

3+

3%

H2

05

1

b

abyf

oo

d (

stew

wit

h r

ice)

0

,06

3 0

,01

0,1

59

Bel

giu

m-F

ASF

C (

CO

DA

-CER

VA

) 1

48

8-1

3-0

60

2 H

PLC

-IC

P-M

S 0

,1 M

HN

O3

+ 3

%H

20

6 1

b

abyf

oo

d (

stew

wit

h r

ice)

0

,11

0,0

12

0,1

09

Bel

giu

m-F

ASF

C (

CO

DA

-CER

VA

) 2

46

3-1

3-0

05

5 H

PLC

-IC

P-M

S 0

,1 M

HN

O3

+ 3

%H

20

7 1

b

abyf

oo

d (

stew

wit

h r

ice)

0

,01

6 0

,01

3 0

,81

3 B

elgi

um

-FA

SFC

(C

OD

A-C

ERV

A)

24

63

-13

-00

56

HP

LC-I

CP

-MS

0,1

M H

NO

3+

3%

H2

08

1

b

abyf

oo

d (

stew

wit

h r

ice)

0

,03

0,0

13

0,4

33

Bel

giu

m-F

ASF

C (

CO

DA

-CER

VA

) 2

59

5-1

3-0

04

1 H

PLC

-IC

P-M

S 0

,1 M

HN

O3

+ 3

%H

20

9 1

b

abyf

oo

d (

stew

wit

h r

ice)

0

,11

Bel

giu

m-F

ASF

C

25

73

-14

-00

04

HP

LC-I

CP

-MS

0,1

M H

NO

3+

3%

H2

10

1

b

abyf

oo

d (

stew

wit

h r

ice)

0

,19

Bel

giu

m-F

ASF

C

32

89

-14

-00

68

HP

LC-I

CP

-MS

0,1

M H

NO

3+

3%

H2

11

1

b

abyf

oo

d (

stew

wit

h r

ice)

0

,10

Bel

giu

m-F

ASF

C

33

39

-14

-00

34

HP

LC-I

CP

-MS

0,1

M H

NO

3+

3%

H2

12

1

b

abyf

oo

d (

stew

wit

h r

ice)

0

,12

Bel

giu

m-F

ASF

C

33

39

-14

-00

36

HP

LC-I

CP

-MS

0,1

M H

NO

3+

3%

H2

13

1

RIC

E B

ASE

D D

RIN

KS

rice

bas

ed d

rin

k (l

iqu

id)

0

,02

32

Lu

xem

bo

urg

co

ntr

ol p

rogr

am (C

OD

A-C

ERV

A)

20

13

.832

LU

X

HP

LC-I

CP

-MS

wat

er

1

ri

ce b

ased

dri

nk

(liq

uid

)

0,0

24

5

Luxe

mb

ou

rg c

on

tro

l pro

gram

(CO

DA

-CER

VA

) 2

01

3.8

38 L

UX

H

PLC

-IC

P-M

S w

ater

1

ri

ce b

ased

dri

nk

(liq

uid

)

0,0

14

8

Luxe

mb

ou

rg c

on

tro

l pro

gram

(CO

DA

-CER

VA

) 2

01

3.8

40 L

UX

H

PLC

-IC

P-M

S w

ater

1

ri

ce b

ased

dri

nk

(liq

uid

)

0,0

18

6

Luxe

mb

ou

rg c

on

tro

l pro

gram

(CO

DA

-CER

VA

) 2

01

3.8

41 L

UX

H

PLC

-IC

P-M

S w

ater

1

ri

ce b

ased

dri

nk

0,0

2 0

,01

3 0

,65

Bel

giu

m-F

ASF

C

14

88

-13

-06

67

1

ri

ce b

ased

dri

nk

0,0

21

0,0

14

0,6

7 B

elgi

um

-FA

SFC

1

48

8-1

3-0

67

4

1

ri

ce b

ased

dri

nk

0,0

22

0,0

18

0,8

2 B

elgi

um

-FA

SFC

1

48

8-1

3-0

69

3

1

ri

ce b

ased

dri

nk

0,0

19

0,0

07

1 0

,37

Bel

giu

m-F

ASF

C

14

88

-13

-06

94

1

ri

ce b

ased

dri

nk

0,0

18

0,0

15

0,8

3 B

elgi

um

-FA

SFC

1

48

8-1

3-0

69

5

1

ri

ce b

ased

dri

nk

0,0

15

0,0

12

0,8

0 B

elgi

um

-FA

SFC

2

48

7-1

3-0

10

7

1

ri

ce b

ased

dri

nk

0,0

05

2 0

,00

45

0,8

7 B

elgi

um

-FA

SFC

2

57

4-1

3-0

08

3

1

ri

ce b

ased

dri

nk

0,0

37

0,0

36

0,9

7 B

elgi

um

-FA

SFC

2

61

9-1

3-0

09

1

1

ri

ce b

ased

dri

nk

0,0

26

0,0

14

0,5

4 B

elgi

um

-FA

SFC

2

62

8-1

3-0

09

3

1

ri

ce b

ased

dri

nk

0,0

25

0,0

23

0,9

2 B

elgi

um

-FA

SFC

2

63

2-1

3-0

04

3

Typ

e o

f fo

od

TOTA

L A

s IN

OR

GA

NIC

A

s R

ATI

O

Re

fere

nce

or

sam

ple

n°

An

alys

is m

eth

od

n

Co

mm

en

t Fo

od

Cat

ego

ry

tota

l A

s (m

g/kg

as

so

ld)

i A

s (m

g/kg

as

so

ld)

% i

As

of

tota

l O

rigi

n o

f d

ata

ext

ract

ion

liq

uid

INFA

NT

RIC

E C

EREA

LS

infa

nt

rice

ce

real

s 0

,26

7 0

,07

4 0

,28

Spai

n

Llo

ren

te-M

iran

des

et

al.,

20

14

HP

LC-I

CP

-MS

0,2

% H

NO

3 +

2

%H

2O

2 1

in

fan

t ri

ce (

pre

p u

sin

g in

fan

t fo

rmu

la)

0,1

26

0,0

69

0,5

5 Sp

ain

C

arb

on

ell-

Bar

ach

ina

et

al.,

20

12

H

PLC

-IC

PM

S 1

% H

NO

3 1

3

glu

ten

fre

e

in

fan

t ri

ce c

ere

als

0,2

72

0,1

05

0,3

9 U

SA

Jusk

elis

et

al.,

20

13

H

PLC

-IC

PM

S 0

,28

M H

NO

3 1

o

rgan

ic

in

fan

t ri

ce c

ere

als

0,1

46

0,0

91

0,6

2 U

SA

Jusk

elis

et

al.,

20

13

H

PLC

-IC

PM

S 0

,28

M H

NO

3 1

o

rgan

ic

in

fan

t ri

ce c

ere

als

0,2

3 0

,13

7 0

,60

USA

Ju

skel

is e

t al

., 2

01

3

HP

LC-I

CP

MS

0,2

8M

HN

O3

1

rice

sin

gle

grai

n c

erea

l

in

fan

t ri

ce c

ere

als

0,2

12

0,1

18

0,5

6 U

SA

Jusk

elis

et

al.,

20

13

H

PLC

-IC

PM

S 0

,28

M H

NO

3 1

ri

ce s

ingl

e gr

ain

cer

eal

in

fan

t ri

ce c

ere

als

0,2

56

0,1

32

0,5

2 U

SA

Jusk

elis

et

al.,

20

13

H

PLC

-IC

PM

S 0

,28

M H

NO

3 1

ri

ce s

ingl

e gr

ain

cer

eal

in

fan

t ri

ce c

ere

als

0,1

08

0,0

73

0,6

8 U

SA

Jusk

elis

et

al.,

20

13

H

PLC

-IC

PM

S 0

,28

M H

NO

3 1

ri

ce s

ingl

e gr

ain

cer

eal

in

fan

t ri

ce c

ere

als

0,1

01

0,0

68

0,6

7 U

SA

Jusk

elis

et

al.,

20

13

H

PLC

-IC

PM

S 0

,28

M H

NO

3 1

ri

ce s

ingl

e gr

ain

cer

eal

in

fan

t ri

ce c

ere

als

0,0

93

0,0

58

0,6

2 U

SA

Jusk

elis

et

al.,

20

13

H

PLC

-IC

PM

S 0

,28

M H

NO

3 1

ri

ce s

ingl

e gr

ain

cer

eal

in

fan

t ri

ce c

ere

als

0,2

27

0,1

25

0,5

5 U

SA

Jusk

elis

et

al.,

20

13

H

PLC

-IC

PM

S 0

,28

M H

NO

3 1

ri

ce s

ingl

e gr

ain

cer

eal

in

fan

t ri

ce c

ere

als

0,1

27

0,0

9 0

,71

USA

Ju

skel

is e

t al

., 2

01

3

HP

LC-I

CP

MS

0,2

8M

HN

O3

1

rice

sin

gle

grai

n c

erea

l

in

fan

t ri

ce c

ere

als

0,2

41

0,1

07

0,4

4 U

SA

Jusk

elis

et

al.,

20

13

H

PLC

-IC

PM

S 0

,28

M H

NO

3 1

ri

ce s

ingl

e gr

ain

cer

eal

in

fan

t ri

ce c

ere

als

0,2

37

0,0

98

0,4

1 U

SA

Jusk

elis

et

al.,

20

13

H

PLC

-IC

PM

S 0

,28

M H

NO

3 1

ri

ce s

ingl

e gr

ain

cer

eal

in

fan

t ri

ce c

ere

als

0,0

85

0,0

68

0,8

0 U

SA

Jusk

elis

et

al.,

20

13

H

PLC

-IC

PM

S 0

,28

M H

NO

3 1

o

rgan

ic w

ho

le g

rain

ric

e ce

real

in

fan

t ri

ce c

ere

als

0,1

78

0,1

33

0,7

5 U

SA

Jusk

elis

et

al.,

20

13

H

PLC

-IC

PM

S 0

,28

M H

NO

3 1

o

rgan

ic b

row

n r

ice

cere

al

in

fan

t ri

ce c

ere

als

0,0

84

0,0

56

0,6

7 U

SA

Jusk

elis

et

al.,

20

13

H

PLC

-IC

PM

S 0

,28

M H

NO

3 1

o

rgan

ic b

row

n r

ice

cere

al

in

fan

t ri

ce c

ere

als

0,2

61

0,0

64

0,2

5 U

SA

Jusk

elis

et

al.,

20

13

H

PLC

-IC

PM

S 0

,28

M H

NO

3 1

o

rgan

ic b

row

n r

ice

cere

al

in

fan

t ri

ce c

ere

als

0,1

65

0,1

28

0,7

8 U

SA

Jusk

elis

et

al.,

20

13

H

PLC

-IC

PM

S 0

,28

M H

NO

3 1

o

rgan

ic b

row

n r

ice

cere

al

in

fan

t ri

ce c

ere

als

0,2

06

0,0

89

0,4

3 U

SA

Jusk

elis

et

al.,

20

13

H

PLC

-IC

PM

S 0

,28

M H

NO

3 1

o

rgan

ic b

row

n r

ice

cere

al

in

fan

t ri

ce c

ere

als

0,1

27

0,0

87

0,6

9 U

SA

Jusk

elis

et

al.,

20

13

H

PLC

-IC

PM

S 0

,28

M H

NO

3 1

o

rgan

ic b

row

n r

ice

cere

al

in

fan

t ri

ce c

ere

als

0,1

33

0,0

96

0,7

2 U

SA

Jusk

elis

et

al.,

20

13

H

PLC

-IC

PM

S 0

,28

M H

NO

3 1

o

rgan

ic b

row

n r

ice

cere

al

in

fan

t ri

ce c

ere

als

0,1

6 0

,10

5 0

,66

USA

Ju

skel

is e

t al

., 2

01

3

HP

LC-I

CP

MS

0,2

8M

HN

O3

1

org

anic

wh

ole

gra

in r

ice

cere

al

wit

h a

pp

les

in

fan

t ri

ce c

ere

als

0,2

42

0,1

41

0,5

8 U

SA

Jusk

elis

et

al.,

20

13

H

PLC

-IC

PM

S 0

,28

M H

NO

3 1

o

rgan

ic w

ho

le g

rain

ric

e ce

real

in

fan

t ri

ce c

ere

als

0,2

44

0,1

58

0,6

5 U

SA

Jusk

elis

et

al.,

20

13

H

PLC

-IC

PM

S 0

,28

M H

NO

3 1

o

rgan

ic w

ho

le g

rain

ric

e ce

real

Typ

e o

f fo

od

TOTA

L A

s IN

OR

GA

NIC

A

s R

ATI

O

Re

fere

nce

or

sam

ple

n°

An

alys

is

me

tho

d

n

Co

mm

en

t Fo

od

Cat

ego

ry

tota

l A

s (m

g/kg

as

so

ld)

i A

s (m

g/kg

as

so

ld)

% i

As

of

tota

l O

rigi

n o

f d

ata

ext

ract

ion

liq

uid

INFA

NT

MU

LTI G

RA

IN C

EREA

LS

infa

nt

cere

als

(mu

ltic

erea

ls)

0,0

14

0,0

14

1,0

0 Sp

ain

Ll

ore

nte

-Mir

and

es e

t al

., 2

01

4 H

PLC

-IC

P-M

S 0

,2%

HN

O3

+ 2

%H

2O

2 1

in

fan

t ce

real

s (m

ult

icer

eals

) 0

,01

6 0

,01

6 1

,00

Spai

n

Llo

ren

te-M

iran

des

et

al.,

20

14

HP

LC-I

CP

-MS

0,2

% H

NO

3 +

2%

H2

O2

1

in

fan

t ce

real

s (m

ult

icer

eals

) 0

,02

2 0

,02

2 1

,00

Spai

n

Llo

ren

te-M

iran

des

et

al.,

20

14

HP

LC-I

CP

-MS

0,2

% H

NO

3 +

2%

H2

O2

1

in

fan

t ce

real

s (m

ult

icer

eals

) 0

,01

0,0

11

1,1

0 Sp

ain

Ll

ore

nte

-Mir

and

es e

t al

., 2

01

4 H

PLC

-IC

P-M

S 0

,2%

HN

O3

+ 2

%H

2O

2 1

in

fan

t ce

real

s (m

ult

icer

eals

) 0

,01

4 0

,01

4 1

,00

Spai

n

Llo

ren

te-M

iran

des

et

al.,

20

14

HP

LC-I

CP

-MS

0,2

% H

NO

3 +

2%

H2

O2

1

in

fan

t ce

real

s (m

ult

icer

eals

) 0

,02

4 0

,02

3 0

,96

Spai

n

Llo

ren

te-M

iran

des

et

al.,

20

14

HP

LC-I

CP

-MS

0,2

% H

NO

3 +

2%

H2

O2

1

in

fan

t ce

real

s (m

ult

icer

eals

) 0

,03

6 0

,02

6 0

,72

Spai

n

Llo

ren

te-M

iran

des

et

al.,

20

14

HP

LC-I

CP

-MS

0,2

% H

NO

3 +

2%

H2

O2

1

in

fan

t ri

ce c

ere

als

(mix

ed g

rain

) 0

,08

8 0

,05

7 0

,65

USA

Ju

skel

is e

t al

., 2

01

3

HP

LC-I

CP

MS

0,2

8M

HN

O3

1

in

fan

t ri

ce c

ere

als

(mix

ed g

rain

) 0

,11

2 0

,06

3 0

,56

USA

Ju

skel

is e

t al

., 2

01

3

HP

LC-I

CP

MS

0,2

8M

HN

O3

1

in

fan

t ri

ce c

ere

als

(mix

ed g

rain

) 0

,08

8 0

,05

6 0

,64

USA

Ju

skel

is e

t al

., 2

01

3

HP

LC-I

CP

MS

0,2

8M

HN

O3

1

in

fan

t ri

ce c

ere

als

(mix

ed g

rain

) 0

,12

4 0

,06

4 0

,52

USA

Ju

skel

is e

t al

., 2

01

3

HP

LC-I

CP

MS

0,2

8M

HN

O3

1

in

fan

t ri

ce c

ere

als

(mix

ed g

rain

) 0

,12

6 0

,07

2 0

,57

USA

Ju

skel

is e

t al

., 2

01

3

HP

LC-I

CP

MS

0,2

8M

HN

O3

1

in

fan

t ri

ce c

ere

als

(mix

ed g

rain

) 0

,13

1 0

,06

9 0

,53

USA

Ju

skel

is e

t al

., 2

01

3

HP

LC-I

CP

MS

0,2

8M

HN

O3

1

in

fan

t ri

ce c

ere

als

(mix

ed g

rain

) 0

,12

8 0

,06

5 0

,51

USA

Ju

skel

is e

t al

., 2

01

3

HP

LC-I

CP

MS

0,2

8M

HN

O3

1

in

fan

t ri

ce c

ere

als

(mix

ed g

rain

) 0

,10

9 0

,05

7 0

,52

USA

Ju

skel

is e

t al

., 2

01

3

HP

LC-I

CP

MS

0,2

8M

HN

O3

1

ri

ce b

ased

bab

y fo

od

s

<lo

q

Fi

nla

nd

R

inta

la e

t al

., 2

01

4

HP

LC-I

CP

-MS

HN

O3

+ H

2O

2 1

ri

ce b

ased

bab

y fo

od

s

<lo

d

Fi

nla

nd

R

inta

la e

t al

., 2

01

4

HP

LC-I

CP

-MS

HN

O3

+ H

2O

2 1

ri

ce b

ased

bab

y fo

od

s

<lo

d

Fi

nla

nd

R

inta

la e

t al

., 2

01

4

HP

LC-I

CP

-MS

HN

O3

+ H

2O

2 1

ri

ce b

ased

bab

y fo

od

s

0,0

7 1

,00

Fin

lan

d

Rin

tala

et

al.,

20

14

H

PLC

-IC

P-M

S H

NO

3 +

H2

O2

1

ri

ce b

ased

bab

y fo

od

s

0,2

1 0

,72

Fin

lan

d

Rin

tala

et

al.,

20

14

H

PLC

-IC

P-M

S H

NO

3 +

H2

O2

1

ri

ce b

ased

bab

y fo

od

s

<lo

d

Fi

nla

nd

R

inta

la e

t al

., 2

01

4

HP

LC-I

CP

-MS

HN

O3

+ H

2O

2 1

ri

ce b

ased

bab

y fo

od

s

0,0

9 0

,82

Fin

lan

d

Rin

tala

et

al.,

20

14

H

PLC

-IC

P-M

S H

NO

3 +

H2

O2

1

ri

ce b

ased

bab

y fo

od

s

0,0

8 0

,80

Fin

lan

d

Rin

tala

et

al.,

20

14

H

PLC

-IC

P-M

S H

NO

3 +

H2

O2

1

ri

ce b

ased

bab

y fo

od

s

<lo

d

Fi

nla

nd

R

inta

la e

t al

., 2

01

4

HP

LC-I

CP

-MS

HN

O3

+ H

2O

2 1

ri

ce b

ased

bab

y fo

od

s

<lo

d

Fi

nla

nd

R

inta

la e

t al

., 2

01

4

HP

LC-I

CP

-MS

HN

O3

+ H

2O

2 1

fo

od

bas

ed o

n w

ho

legr

ain

ric

e

0,0

33

Swed

en

Lju

ng

et a

l., 2

01

1 IC

PM

S (t

ota

l)

HN

O3

1

o

rgan

ic

fo

od

bas

ed o

n w

ho

legr

ain

ric

e

0,0

3

Sw

eden

Lj

un

g et

al.,

20

11

ICP

MS

(to

tal)

H

NO

3

1

org

anic

fo

od

bas

ed o

n r

ice

+ b

anan

a 0

,01

7

Sw

eden

Lj

un

g et

al.,

20

11

ICP

MS

(to

tal)

H

NO

3

1

org

anic

fo

od

bas

ed o

n r

ice

+ b

anan

a 0

,01

8

Sw

eden

Lj

un

g et

al.,

20

11

ICP

MS

(to

tal)

H

NO

3

1

fo

od

bas

ed o

n r

ice

+ lo

cust

bea

n

0,0

32

Swed

en

Lju

ng

et a

l., 2

01

1 IC

PM

S (t

ota

l)

HN

O3

1

h

ypo

alle

rgen

ic

form

ula

Att

achm

ent 2

– D

ieta

ry p

rofile

As e

xp

osu

re c

hild

ren a

ge

d 3

mo

nth

Infa

nt

3m

B

od

y w

eig

ht

(kg)

6

,28

B

reas

t m

ilk

In

fan

t fo

rmu

la

N

ova

rice

lo

w

hig

h

lo

w

med

ian

h

igh

w

ater

10

µg/

L

low

m

edia

n

hig

h

wat

er 1

0µ

g/L

Solid

up

take

spo

on

s /

po

rtio

n

n.a

.

6

6

6

6

6

6

6

6

mas

s /

spo

on

(g)

n

.a.

4,5

4

,5

4,5

4

,5

4

,5

4,5

4

,5

4,5

po

rtio

n f

req

uen

cy (

/d)

n.a

.

5

5

5

5

5

5

5

5

mas

s /

po

rtio

n (

g)

n.a

.

2

7

27

2

7

27

27

2

7

27

2

7

dai

ly s

olid

inta

ke (

g)

n.a

.

1

35

13

5 1

35

13

5

13

5 1

35

13

5 1

35

A

s co

nte

nt

(µg/

kg)

2

,20

5,7

6 1

2,6

0 5

,76

1

7,6

0 1

9,2

0 2

0,8

0 5

,76

As

inta

ke v

ia s

olid

(µ

g/d

)

0,3

0 0

,78

1,7

0 0

,78

2

,38

2,5

9 2

,81

0,7

8

%iA

s

90

9

0

90

9

0

7

8

78

7

8

78

iAs

inta

ke v

ia s

olid

(µ

g iA

s/d

)

0,2

7 0

,70

1,5

3 0

,70

1

,85

2,0

2 2

,19

0,6

1

Liq

uid

up

take

(b

reas

t m

ilk o

r w

ate

r)

Po

rtio

n v

olu

me

(mL)

1

40

14

0

18

0 1

80

18

0 1

80

1

80

18

0 1

80

18

0

po

rtio

n f

req

uen

cy (

/d)

6

6

5

5

5

5

5

5

5

5

dai

ly li

qu

id in

take

(m

L)

84

0 8

40

9

00

90

0 9

00

90

0

90

0 9

00

90

0 9

00

A

s co

nte

nt

(µg/

L)

0,2

2 0

,62

0

,07

1,6

7 5

,30

10

,00

0

,07

1,6

7 5

,30

10

,00

As

inta

ke v

ia li

qu

id (

µg/

d)

0,1

8 0

,52

0

,06

1,5

0 4

,77

9,0

0

0,0

6 1

,50

4,7

7 9

,00

%

iAs

50

5

0

1

00

10

0 1

00

10

0

10

0 1

00

10

0 1

00

iAs

inta

ke v

ia li

qu

id (

µg

iAs/

d)

0,0

9 0

,26

0

,06

1,5

0 4

,77

9,0

0

0,0

6 1

,50

4,7

7 9

,00

fi

nal

As

con

cen

trat

ion

in m

ilk (

µg/

L)

0,2

2 0

,62

0

,40

2,5

3 7

,19

10

,86

2

,71

4,5

5 8

,42

10

,86

e

stim

ate

d e

xpo

sure

(IR

*C)

(µg/

d)

0,1

8 0

,52

0

,36

2,2

8 6

,47

9,7

8

2,4

4 4

,10

7,5

8 9

,78

exp

osu

re (

µg/

d/k

g B

W)

0,0

3

0,0

8

0

,06

0

,36

1

,03

1

,56

0,3

9

0,6

5

1,2

1

1,5

6

iA

s e

xpo

sure

(µ

g iA

s/d

) 0

,09

0,2

6

0,3

3 2

,20

6,3

0 9

,70

1

,92

3,5

2 6

,96

9,6

1

iAs

exp

osu

re (

µg

iAs/

d/k

g B

W)

0,0

1 0

,04

0

,05

0,3

5 1

,00

1,5

4

0,3

1 0

,56

1,1

1 1

,53

%

iAs

up

take

5

0,0

0 5

0,0

0

91

,75

96

,59

97

,37

99

,20

7

8,5

7 8

6,0

7 9

1,8

5 9

8,2

5

Att

achm

ent 3

– D

ieta

ry p

rofile

As e

xp

osu

re c

hild

ren a

ge

d 6

mo

nth

MEN

U

exp

osu

re g

rou

p

infa

nt

age

6

mo

nth

s

Re

com

me

nd

ed

:

en

erg

y u

pta

ke

va

lue

bas

al m

eta

bo

lic r

ate

6

0W

-31

7

,93

kg

44

9

kcal

age

6

mo

nth

s

en

erg

y co

nsu

mp

tio

n

7

6

kcal

/kg/

d

we

igh

t

7,9

3

kg

en

erg

y re

qu

ire

d f

or

mai

nte

nan

ce

60

3

kcal

/d

en

erg

y re

com

me

nd

ed

81

kc

al/k

g/d

en

erg

y re

qu

ire

d f

or

gro

wth

64

2

kcal

/d

pro

tein

inta

ke

1

,14

g/

kg/d

9,0

4

g/d

lipid

s

40

%

dai

ly e

ner

gy

25

7

kcal

30

g/

d

carb

oh

ydra

tes

5

0

% d

aily

en

ergy

pro

tein

10

%

dai

ly e

ner

gy

CO

MM

EN

TS

-

En

erg

y in

take d

erive

d fro

m S

HC

(S

HC

, 2

00

9 &

201

6)

- d

ieta

ry in

take

fro

m U

LB

se

em

ed to

be o

ve

restim

ate

d fo

r 6

mo

nth

s o

ld infa

nts

. C

orr

ecte

d b

ase

d o

n e

ne

rgy in

take K

ind &

Ge

zin

-

As c

onte

nt fr

om

CO

DA

an

d fro

m S

PE

CA

S

- M

ilk c

onsum

ption

(4

50

mL

) a

lso

co

rre

spo

nd

s w

ith

re

com

me

nd

atio

n K

ind &

Ge

zin

(5

00

mL

) -

Assu

min

g M

PF

E (

me

at, p

ou

ltry

, fish,

eg

gs)

do n

ot

co

nta

in s

ign

ific

ant am

ou

nts

of

iAs.

NO

RM

AL

SCEN

AR

IO

Q

e

ne

rgy

Q

As

A

s in

take

So

urc

e

assu

min

g 1

tim

e r

ice

pe

r w

ee

k

kcal

co

rre

cte

d

for

6m

an

d

1ri

ce/w

ee

k

µg/

kg

µ

g/kg

Low

m

ed

ian

h

igh

w

ate

r 1

0

low

m

ed

ian

h

igh

w

ate

r 1

0

bre

akfa

st

wat

er

wat

er

Spa

Re

ine

18

0 0

1

32

,64

0,0

7 1

,67

5,3

1

0

0

,01

0,2

2 0

,70

1,3

3 ta

ble

SH

C

BB

nu

trilo

n 2

Nu

tric

ia

29

,2

13

4 2

1,5

2 2

,2

5,7

6 1

2,6

5

,76

0

,05

0,1

2 0

,27

0,1

2 ta

ble

SH

C

st

arch

sa

lte

d w

hit

e b

read

1

5

40

,2

11

,05

10

1

0

10

1

0

0

,11

0,1

1 0

,11

0,1

1 sp

ecas

fa

t b

utt

er

5

36

,2

3,6

8

ex.

jam

6

1

5,4

4

,42

22

5,8

0

,00

din

ne

r st

arch

n

atu

re p

ota

to

10

0 6

8,2

7

3,6

9 3

3

3

3

0,1

9 0

,19

0,1

9 0

,19

spec

as

din

ne

r st

arch

b

aby

foo

d -

ste

w w

ith

ric

e 1

00

68

,2

16

9,4

8 1

1

70

1

90

70

0,2

7 1

,69

4,6

0 1

,69

FAV

V

ve

g.

coo

ked

ve

g. a

vera

ge

10

0 2

3,5

7

3,6

9 5

5

5

5

0,3

2 0

,32

0,3

2 0

,32

spec

as

M

PFE

M

PFE

ave

rage

2

0

30

,5

14

,74

4

4

4

4

0

,05

0,0

5 0

,05

0,0

5

fa

t co

lza

oil

10

9

0

7,3

7

w

ate

r w

ate

r Ev

ian

5

0

0

36

,84

0,0

7 1

,67

5,3

1

0

0

,00

0,0

6 0

,20

0,3

7 ta

ble

SH

C

21

2,2

0

,00

snac

k fr

uit

s fr

uit

s -

app

le

10

0 5

2,3

7

3,6

9 2

2

2

2

0,1

5 0

,15

0,1

5 0

,15

fr

uit

s fr

uit

s -

ban

ana

10

0 8

6,3

7

3,6

9 2

2

2

2

0,1

5 0

,15

0,1

5 0

,15

w

ate

r w

ate

r ev

ian

5

0

0

36

,84

0,0

7 1

,67

5,3

1

0

0

,00

0,0

6 0

,20

0,3

7 ta

ble

SH

C

13

8,6

0

,00

bab

y b

ott

le

(fo

llow

on

fo

rmu

lae

wat

er

wat

er

spa

rein

e 9

0

0

66

,32

0,0

7 1

,67

5,3

1

0

0

,00

0,1

1 0

,35

0,6

6 ta

ble

SH

C

BB

nu

trilo

n 2

Nu

tric

ia

14

,6

67

1

0,7

6 2

,2

5,7

6 1

2,6

5

,76

0

,02

0,0

6 0

,14

0,0

6 ta

ble

SH

C

67

0

,00

sup

pe

r ve

g.

veg.

so

up

w/o

po

tato

1

00

17

,7

73

,69

5

5

5

5

0

,37

0,3

7 0

,37

0,3

7 sp

ecas

wat

er

for

sou

p

49

,12

0,0

7 1

,67

5,3

1

0

0

,00

0,0

8 0

,26

0,4

9

st

arch

sa

lte

d w

hit

e b

read

1

5

40

,2

11

,05

10

1

0

10

1

0

0

,11

0,1

1 0

,11

0,1

1 sp

ecas

fa

t b

utt

er

5

36

,2

3,6

8

94

,1

0,0

0

b

aby

bo

ttle

(f

ollo

w o

n

form

ula

e)

wat

er

wat

er

spa

rein

e 1

80

0

13

2,6

4 0

,07

1,6

7 5

,3

10

0,0

1 0

,22

0,7

0 1

,33

tab

le S

HC

BB

nu

trilo

n 2

Nu

tric

ia

29

,2

13

4 2

1,5

2 2

,2

5,7

6 1

2,6

5

,76

0

,05

0,1

2 0

,27

0,1

2 ta

ble

SH

C

13

4 0

tota

l

87

1,7

0

TO

TAL

1

,86

4

,20

9

,13

7

,99

µ

g/d

in

take

0,2

3

0,5

3

1,1

5

1,0

1

µg/

kg B

W/d

NO

VA

RIC

E SC

ENA

RIO

Q

e

ne

rgy

Q

As

A

s in

take

So

urc

e

assu

min

g m

ilk c

om

es f

rom

No

vari

ce

kc

al

corr

ect

ed

fo

r 6

m

µg/

kg

µ

g/kg

low

m

ed

ian

h

igh

w

ate

r 1

0

low

m

ed

ian

h

igh

w

ate

r 1

0

bre

akfa

st

wat

er

wat

er

Spa

Re

ine

18

0 0

1

32

,64

0,0

7 1

,67

5,3

1

0

0

,01

0,2

2 0

,70

1,3

3 ta

ble

SH

C

NO

VA

RIC

E 2

9,2

1

34

21

,52

17

,6

19

,2

20

,8

19

,2

0

,38

0,4

1 0

,45

0,4

1 ta

ble

SH

C

st

arch

sa

lte

d w

hit

e b

read

1

5

40

,2

11

,05

10

1

0

10

1

0

0

,11

0,1

1 0

,11

0,1

1 sp

ecas

fa

t b

utt

er

5

36

,2

3,6

8

ex.

jam

6

1

5,4

4

,42

22

5,8

din

ne

r st

arch

n

atu

re p

ota

to

10

0 6

8,2

7

3,6

9 3

3

3

3

0,1

9 0

,19

0,1

9 0

,19

spec

as

din

ne

r st

arch

b

aby

foo

d -

ste

w w

ith

ric

e 1

00

68

,2

16

9,4

8 1

1

70

1

90

70

0,2

7 1

,69

4,6

0 1

,69

FAV

V

ve

g.

coo

ked

ve

g. a

vera

ge

10

0 2

3,5

7

3,6

9 5

5

5

5

0,3

2 0

,32

0,3

2 0

,32

spec

as

M

PFE

M

PFE

ave

rage

2

0

30

,5

14

,74

4

4

4

4

0

,05

0,0

5 0

,05

0,0

5

fa

t co

lza

oil

10

9

0

7,3

7

w

ate

r w

ate

r Ev

ian

5

0

0

36

,84

0,0

7 1

,67

5,3

1

0

0

,00

0,0

6 0

,20

0,3

7 ta

ble

SH

C

21

2,2

snac

k fr

uit

s fr

uit

s -

app

le

10

0 5

2,3

7

3,6

9 2

2

2

2

0,1

5 0

,15

0,1

5 0

,15

fr

uit

s fr

uit

s -

ban

ana

10

0 8

6,3

7

3,6

9 2

2

2

2

0,1

5 0

,15

0,1

5 0

,15

w

ate

r w

ate

r ev

ian

5

0

0

36

,84

0,0

7 1

,67

5,3

1

0

0

,00

0,0

6 0

,20

0,3

7 ta

ble

SH

C

13

8,6

bab

y b

ott

le

(fo

llow

on

fo

rmu

lae)

w

ate

r w

ate

r sp

a re

ine

90

0

6

6,3

2 0

,07

1,6

7 5

,3

10

0,0

0 0

,11

0,3

5 0

,66

tab

le S

HC

NO

VA

RIC

E 1

4,6

6

7

10

,76

17

,6

19

,2

20

,8

19

,2

0

,19

0,2

1 0

,22

0,2

1 ta

ble

SH

C

67

sup

pe

r ve

g.

veg.

so

up

w/o

po

tato

1

00

17

,7

73

,69

5

5

5

5

0

,37

0,3

7 0

,37

0,3

7 sp

ecas

wat

er

for

sou

p

49

,12

0,0

7 1

,67

5,3

1

0

0

,00

0,0

8 0

,26

0,4

9

st

arch

sa

lte

d w

hit

e b

read

1

5

40

,2

11

,05

10

1

0

10

1

0

0

,11

0,1

1 0

,11

0,1

1 sp

ecas

fa

t b

utt

er

5

36

,2

3,6

8

94

,1

b

aby

bo

ttle

(f

ollo

w-o

n

form

ula

e)

wat

er

wat

er

spa

rein

e 1

80

0

13

2,6

4 0

,07

1,6

7 5

,3

10

0,0

1 0

,22

0,7

0 1

,33

tab

le S

HC

NO

VA

RIC

E 2

9,2

1

34

21

,52

17

,6

19

,2

20

,8

19

,2

0

,38

0,4

1 0

,45

0,4

1 ta

ble

SH

C

13

4 0

tota

l

87

1,7

0

TOTA

L

2

,68

4

,93

9

,57

8

,71

µ

g/d

in

take

0,3

4

0,6

2

1,2

1

1,1

0

µg/

kg B

W/d

RIC

E B

ASE

D S

CEN

AR

IO

Q

en

erg

y Q

A

s

As

inta

ke

Sou

rce

assu

min

g lu

nch

is r

ead

y to

eat

ric

e b

ase

d f

oo

d

kc

al

corr

ect

ed

fo

r 6

m

µg/

kg

µ

g/kg

assu

min

g n

o b

iscu

its

yets

low

m

ed

ian

h

igh

w

ate

r 1

0

low

m

ed

ian

h

igh

w

ate

r 1

0

bre

akfa

st

wat

er

wat

er

Spa

Re

ine

18

0 0

1

32

,64

0,0

7 1

,67

5,3

1

0

0

,01

0,2

2 0

,70

1,3

3 ta

ble

SH

C

BB

nu

trilo

n 2

Nu

tric

ia

29

,2

13

4 2

1,5

2 2

,2

5,7

6 1

2,6

5

,76

0

,05

0,1

2 0

,27

0,1

2 ta

ble

SH

C

st

arch

sa

lte

d w

hit

e b

read

1

5

40

1

1,0

5 1

0

10

1

0

10

0,1

1 0

,11

0,1

1 0

,11

spec

as

fa

t b

utt

er

5

36

3

,68

ex.

jam

6

1

5

4,4

2

22

6

din

ne

r st

arch

b

aby

foo

d -

ste

w w

ith

ric

e 1

00

68

1

69

,48

11

7

0

19

0 7

0

1

,86

11

,86

32

,20

11

,86

FAV

V

FAV

V t

able

ran

ges

fro

m 1

1-86

,5-

44

0 !

44

0 c

on

sid

ere

d a

s O

L

w

ate

r w

ate

r Ev

ian

5

0

0

36

,84

0,0

7 1

,67

5,3

1

0

0

,00

0,0

6 0

,20

0,3

7 ta

ble

SH

C

21

2 1

69

,48

snac

k fr

uit

s fr

uit

s -

app

le

10

0 5

2

73

,69

2

2

2

2

0

,15

0,1

5 0

,15

0,1

5

fr

uit

s fr

uit

s -

ban

ana

10

0 8

6

73

,69

2

2

2

2

0

,15

0,1

5 0

,15

0,1

5

w

ate

r w

ate

r ev

ian

5

0

0

36

,84

0,0

7 1

,67

5,3

1

0

0

,00

0,0

6 0

,20

0,3

7 ta

ble

SH

C

13

9

bab

y b

ott

le (

follo

w

on

fo

rmu

lae)

w

ate

r w

ate

r sp

a re

ine

90

0

6

6,3

2 0

,07

1,6

7 5

,3

10

0,0

0 0

,11

0,3

5 0

,66

tab

le S

HC

BB

nu

trilo

n 2

Nu

tric

ia

14

,6

67

1

0,7

6 2

,2

5,7

6 1

2,6

5

,76

0

,02

0,0

6 0

,14

0,0

6 ta

ble

SH

C

67

sup

pe

r ve

g.

veg.

so

up

w/o

po

tato

1

00

18

2

4,5

6 5

5

5

5

0,1

2 0

,12

0,1

2 0

,12

spec

as

wat

er

for

sou

p

49

,12

0,0

7 1

,67

5,3

1

0

0

,00

0,0

8 0

,26

0,4

9

st

arch

sa

lte

d w

hit

e b

read

1

5

40

1

1,0

5 1

0

10

1

0

10

0,1

1 0

,11

0,1

1 0

,11

spec

as

fa

t b

utt

er

5

36

3

,68

94

bab

y b

ott

le (

follo

w

on

fo

rmu

lae)

w

ate

r w

ate

r sp

a re

ine

18

0 0

1

32

,64

0,0

7 1

,67

5,3

1

0

0

,01

0,2

2 0

,70

1,3

3 ta

ble

SH

C

BB

nu

trilo

n 2

Nu

tric

ia

29

,2

13

4 2

1,5

2 2

,2

5,7

6 1

2,6

5

,76

0

,05

0,1

2 0

,27

0,1

2 ta

ble

SH

C

13

4

tota

l

87

2

TOTA

L

2,6

5

13

,57

35

,93

17

,36

µg/

d

in

take

0,3

3

1,7

1

4,5

3

2,1

9

µg/

kg B

W/d

Att

achm

ent 4

– D

ieta

ry p

rofile

As e

xp

osure

ch

ildre

n a

ge

d 1

2 m

onth

MEN

U

exp

osu

re g

rou

p

infa

nt

age

12

m

on

ths

Re

com

me

nd

ed

:

e

ne

rgy

up

take

valu

e

b

asal

me

tab

olic

rat

e

60

W-3

1

age

12

m

on

ths

en

erg

y co

nsu

mp

tio

n

7

8

kcal

/kg/

d

we

igh

t

9,6

2

kg

en

erg

y re

qu

ire

d f

or

mai

nte

nan

ce

75

0

kcal

/d

en

erg

y re

com

me

nd

ed

81

kc

al/k

g/d

en

erg

y re

qu

ire

d f

or

gro

wth

77

9

kcal

/d

pro

tein

inta

ke

1

,14

g/

kg/d

10

,97

g/

d

lipid

s

40

%

dai

ly e

ner

gy

31

2

kcal

30

g/

d

carb

oh

ydra

tes

5

0

% d

aily

en

ergy

pro

tein

10

%

dai

ly e

ner

gy

CO

MM

EN

TS

-

En

erg

y in

take d

erive

d f

rom

SH

C (

SH

C,

200

9 &

201

6)

- d

ieta

ry in

take

fro

m U

LB

-

As c

onte

nt fr

om

CO

DA

an

d fro

m S

PE

CA

S

- a

ssum

ing

milk

co

nsum

ptio

n is t

hro

ug

h N

ova

Ric

e

- A

ssu

min

g M

PF

E (

me

at, p

ou

ltry

, fish,

eg

gs)

do n

ot

co

nta

in s

ign

ific

ant am

ou

nts

of

iAs

NO

RM

AL

SCEN

AR

IO

Q

e

ne

rgy

As

A

s in

take

So

urc

e

kcal

µg/

kg

µ

g/kg

low

m

ed

ian

h

igh

w

ate

r 1

0

low

m

ed

ian

h

igh

w

ate

r 1

0

bre

akfa

st

star

ch

salt

ed

wh

ite

bre

ad

15

4

0

10

1

0

10

1

0

0

,15

0,1

5 0

,15

0,1

5 sp

ecas

fa

t b

utt

er

5

36

0

0

0

0

0,0

0 0

,00

0,0

0 0

,00

ex.

jam

6

1

5

0

0

0

0

0

,00

0,0

0 0

,00

0,0

0 sp

ecas

gro

wth

milk

Ne

stlé

1+

20

0 1

40

1

10

,08

20

1

0,0

8

0,2

0 2

,02

4,0

0 2

,02

23

2

d

inn

er

star

ch

nat

ure

po

tato

1

00

68

3

3

3

3

0,2

6 0

,26

0,2

6 0

,26

rice

1

00

1

1,7

5

0,7

1

40

,4

50

,7

0

,17

0,7

2 2

,01

0,7

2

ve

g.

coo

ked

ve

g. a

vera

ge

10

0 2

4

5

5

5

5

0

,43

0,3

6 0

,43

0,4

3 sp

ecas

M

PFE

M

PFE

ave

rage

2

0

31

4

4

4

4

0,0

7 0

,07

0,0

7 0

,07

spec

as

fa

t co

lza

oil

10

9

0

0

,00

0,0

0 0

,00

0,0

0

w

ate

r w

ate

r Ev

ian

5

0

0

0,0

7 1

,67

5,3

1

0

0

,00

0,0

8 0

,27

0,5

0

21

2

tab

le S

HC

snac

k fr

uit

s fr

uit

s -

app

le

10

0 5

2

2

2

2

2

0

,20

0,2

0 0

,20

0,2

0

fr

uit

s fr

uit

s -

ban

ana

10

0 8

6

2

2

2

2

0

,20

0,2

0 0

,20

0,2

0

w

ate

r w

ate

r Ev

ian

5

0

0

0,0

7 1

,67

5,3

1

0

0

,00

0,0

8 0

,27

0,5

0

gro

wth

milk

Ne

stlé

1+

10

0 7

0

1

10

,08

20

1

0,0

8

0,1

0 1

,01

2,0

0 1

,01

tab

le S

HC

20

8

su

pp

er

veg.

ve

g. s

ou

p w

/o p

ota

to

10

0 1

8

0,6

5 0

,76

1,0

0 1

,32

0

,07

0,0

8 0

,10

0,1

3 ta

ble

SH

C

st

arch

sa

lte

d w

hit

e b

read

1

5

40

1

0

10

1

0

10

0,1

5 0

,15

0,1

5 0

,15

tab

le S

HC

bu

tte

r 5

3

6

0

,00

0,0

0 0

,00

0,0

0

94

b

aby

bo

ttle

(g

row

ing

up

m

ilk /

dri

nk

for

you

ng

child

ren

)

gro

wth

milk

Ne

stlé

1+

20

0 1

40

1

10

,08

20

1

0,0

8

0,2

0 2

,02

4,0

0 2

,02

tab

le S

HC

14

0

tota

l

88

6

TOTA

L

2

,19

7

,39

1

4,0

9 8

,35

µ

g/d

inta

ke

0

,23

0

,77

1

,46

0

,87

µ

g/kg

BW

/d

NO

VA

RIC

E SC

ENA

RIO

Q

e

ne

rgy

As

A

s in

take

So

urc

e

kcal

µg/

kg

µ

g/kg

low

m

ed

ian

h

igh

w

ate

r 1

0

low

m

ed

ian

h

igh

w

ate

r 1

0

bre

akfa

st

star

ch

salt

ed

wh

ite

bre

ad

15

4

0

10

1

0

10

1

0

0

,15

0,1

5 0

,15

0,1

5 sp

ecas

fa

t B

utt

er

5

36

0

0

0

0

0,0

0 0

,00

0,0

0 0

,00

ex.

jam

6

1

5

0

0

0

0

0

,00

0,0

0 0

,00

0,0

0 sp

ecas

NO

VA

RIC

E 2

00

14

0 2

,71

4,5

5 8

,42

10

,86

4

0,5

4 0

,91

1,6

8 2

,17

23

2

d

inn

er

star

ch

nat

ure

po

tato

1

00

68

3

3

3

3

0,2

6 0

,26

0,2

6 0

,26

rice

1

00

1

1,7

5

0,7

1

40

,4

50

,7

0

,17

0,7

2 2

,01

0,7

2

ve

g.

coo

ked

ve

g. a

vera

ge

10

0 2

4

5

5

5

5

0

,43

0,4

3 0

,43

0,4

3 sp

ecas

M

PFE

M

PFE

ave

rage

2

0

31

4

4

4

4

0,0

7 0

,07

0,0

7 0

,07

spec

as

fa

t C

olz

a o

il 1

0

90

0,0

0 0

,00

0,0

0 0

,00

w

ate

r w

ate

r Ev

ian

5

0

0

0,0

7 1

,67

5,3

1

0

0

,00

0,0

8 0

,27

0,5

0

21

2

tab

le S

HC

snac

k fr

uit

s fr

uit

s -

app

le

10

0 5

2

2

2

2

2

0

,20

0,2

0 0

,20

0,2

0

fr

uit

s fr

uit

s -

ban

ana

10

0 8

6

2

2

2

2

0

,20

0,2

0 0

,20

0,2

0

w

ate

r w

ate

r Ev

ian

5

0

0

0,0

7 1

,67

5,3

1

0

0

,00

0,0

8 0

,27

0,5

0

NO

VA

RIC

E 1

00

70

2

,71

4,5

5 8

,42

10

,86

0

,27

0,4

6 0

,84

1,0

9 ta

ble

SH

C

20

8

su

pp

er

veg.

ve

g. s

ou

p w

/o p

ota

to

10

0 1

8

0,6

5 0

,76

1,0

0 1

,32

0

,07

0,0

8 0

,10

0,1

3 ta

ble

SH

C

st

arch

sa

lte

d w

hit

e b

read

1

5

40

1

0

10

1

0

10

0,1

5 0

,15

0,1

5 0

,15

tab

le S

HC

bu

tte

r 5

3

6

0

,00

0,0

0 0

,00

0,0

0

94

b

aby

bo

ttle

(f

ollo

w o

n

form

ula

e)

N

OV

AR

ICE

20

0 1

40

2,7

1 4

,55

8,4

2 1

0,8

6

0,5

4 0

,91

1,6

8 2

,17

tab

le S

HC

14

0

TOTA

L

3

,05

4

,70

8

,30

8

,74

µ

g/d

inta

ke

0

,32

0

,49

0

,86

0

,91

µ

g/kg

BW

/d

RIC

E B

ASE

D IN

FAN

T FO

OD

SC

ENA

RIO

Q

e

ne

rgy

As

A

s in

take

So

urc

e

assu

min

g b

iscu

it in

ste

ad o

f 1

fru

it p

iece

kcal

µg/

kg

µ

g/kg

assu

min

g ri

ce a

s st

arch

so

urc

e, a

ssu

min

g ri

ce c

ere

als

as

bre

akfa

st a

nd

din

ner

lo

w

me

dia

n

hig

h

wat

er

10

low

m

ed

ian

h

igh

w

ate

r 1

0

bre

akfa

st

star

ch

rice

ce

real

s (k

risp

ies,

po

ps)

(7

1%

iAs)

1

5

40

1

01

16

7 2

33

16

7

1,5

2 2

,51

3,5

0 2

,51

spec

as

fa

t B

utt

er

5

36

0

0

0

0

0,0

0 0

,00

0,0

0 0

,00

ex.

jam

6

1

5

0

0

0

0

0

,00

0,0

0 0

,00

0,0

0 sp

ecas

gro

wth

milk

Ne

stlé

1+

20

0 1

40

1

10

,08

20

1

0,0

8

0,2

0 2

,02

4,0

0 2

,02

23

2

d

inn

er

star

ch

rice

(6

8%

iAs)

1

00

68

1

1,7

5

0,7

1

40

,4

50

,7

1

,00

4,3

5 1

2,0

3 4

,35

rice

(6

8%

iAs)

1

00

1

1,7

5

0,7

1

40

,4

50

,7

0

,17

0,7

2 2

,01

0,7

2

ve

g.

coo

ked

ve

g. a

vera

ge

10

0 2

4

5

5

5

5

0

,43

0,4

3 0

,43

0,4

3 sp

ecas

M

PFE

M

PFE

ave

rage

2

0

31

4

4

4

4

0,0

7 0

,07

0,0

7 0

,07

spec

as

fa

t C

olz

a o

il 1

0

90

0,0

0 0

,00

0,0

0 0

,00

w

ate

r w

ate

r Ev

ian

5

0

0

0,0

7 1

,67

5,3

1

0

0

,00

0,0

8 0

,27

0,5

0

21

2

0,0

0 0

,00

0,0

0 0

,00

tab

le S

HC

snac

k fr

uit

s fr

uit

s -

app

le

10

0 5

2

2

2

2

2

0

,20

0,2

0 0

,20

0,2

0

b

iscu

it

rice

waf

fle

15

7

0

83

2

24

35

9 2

24

1

,25

3,3

6 5

,39

3,3

6

w

ate

r w

ate

r Ev

ian

5

0

0

0,0

7 1

,67

5,3

1

0

0

,00

0,0

8 0

,27

0,5

0

gro

wth

milk

Ne

stlé

1+

10

0 7

0

1

10

,08

20

,00

10

,08

0

,10

1,0

1 2

,00

1,0

1 ta

ble

SH

C

20

8

su

pp

er

veg.

ve

g. s

ou

p w

/o p

ota

to

10

0 1

8

0,6

5 0

,76

1,0

0 1

,32

0

,07

0,0

8 0

,10

0,1

3 ta

ble

SH

C

st

arch

ri

ce w

affl

e 1

5

40

8

3

22

4 3

59

22

4

1,2

5 3

,36

5,3

9 3

,36

tab

le S

HC

bu

tte

r 5

3

6

0

,00

0,0

0 0

,00

0,0

0

94

b

aby

bo

ttle

(y

ou

ng

child

d

rin

k)

gr

ow

th m

ilk N

est

lé 1

+ 2

00

14

0 1

0,0

8 1

0,0

8 1

0,0

8 1

0,0

8

2,0

2 2

,02

2,0

2 2

,02

tab

le S

HC

14

0

tota

l

88

6

TOTA

L

8

,26

2

0,2

8 3

7,6

5 2

1,1

6 µ

g/d

inta

ke

0

,86

2

,11

3

,91

2

,20

µ

g/kg

BW

/d

Att

achm

ent 5

– D

ieta

ry p

rofile

As e

xp

osu

re c

hild

ren a

ge

d 3

6 m

onth

M

ENU

exp

osu

re g

rou

p

infa

nt

Age

3

6

mo

nth

s

Re

com

me

nd

ed

en

erg

y u

pta

ke

va

lue

bas

al m

eta

bo

lic r

ate

6

0W

-31

Age

36

m

on

ths

en

erg

y co

nsu

mp

tio

n

8

4

kcal

/kg/

d

We

igh

t

13

,52

kg

en

erg

y re

qu

ire

d

1

13

5,6

8

kcal

/d

pro

tein

inta

ke

0

,9

g/kg

/d

pro

tein

dai

ly

3

2,4

g/

d

Wat

er

8

29

m

L

CO

MM

EN

TS

-

En

erg

y in

take d

erive

d fro

m S

HC

(S

HC

, 2

00

9 &

201

6)

- d

ieta

ry in

take

fro

m U

LB

-

As c

onte

nt fr

om

CO

DA

an

d fro

m S

PE

CA

S

- a

ssum

ing

milk

co

nsum

ptio

n is t

hro

ug

h N

ova

Ric

e

- A

ssu

min

g M

PF

E (

me

at, p

ou

ltry

, fish,

eg

gs)

do n

ot

co

nta

in s

ign

ific

ant am

ou

nts

of

iAs.

REC

OM

MEN

DED

In

take

U

nit

A

s

As

inta

ke

Sou

rce

assu

min

g sn

acks

are

ric

e-b

ase

d c

oo

kie

s

µ

g/kg

µg/

kg

lo

w

me

dia

n

hig

h

wat

er

10

lo

w

me

dia

n

hig

h

wat

er

10

bre

akfa

st

wh

ole

milk

(co

w)

20

0 m

L 1

1

0,0

8 2

0,0

0 1

0,0

8

0,2

2

,02

4

2,0

2 ta

ble

SH

C

star

ch -

sal

ted

wh

ite

bre

ad

15

g

10

1

0

10

,00

10

0,1

5 0

,15

0,1

5 0

,15

spec

as

star

ch -

sal

ted

bro

wn

bre

ad

15

g

10

1

0

10

,00

10

0,1

5 0

,15

0,1

5 0

,15

b

utt

er

5

g

0

0

0

0

ex

. jam

6

g

0

0

0

0

ex. N

ute

lla s

pre

ad

7,5

g

0

0

0

0

sn

ack

raw

fru

its

10

0 g

2

2

2,0

0 2

0,2

0

,2

0,2

0

,2

spec

as (

vege

tab

les)

d

inn

er

star

ch -

sal

ted

wh

ite

bre

ad

39

g

10

1

0

10

,00

10

0,3

9 0

,39

0,3

9 0

,39

spec

as

star

ch -

sal

ted

bro

wn

bre

ad

39

g

10

1

0

10

,00

10

0,3

9 0

,39

0,3

9 0

,39

spec

as

bu

tter

1

0

g

0

0

0

0

m

elte

d f

at c

he

ese

2

0

g 1

0

10

1

0,0

0 1

0

0

,2

0,2

0

,2

0,2

veg.

so

up

6

6,6

7 m

L 5

5

5

,00

5

0

,33

0,3

3 0

,33

0,3

3 sp

ecas

wat

er in

so

up

1

33

,33

0

,07

1,6

7 5

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About the Superior Health Council (SHC) The Superior Health Council is a federal advisory body. Its secretariat is provided by the Federal Public Service Health, Food Chain Safety and Environment. It was founded in 1849 and provides scientific advisory reports on public health issues to the Ministers of Public Health and the Environment, their administration, and a few agencies. These advisory reports are drawn up on request or on the SHC's own initiative. The SHC aims at giving guidance to political decision-makers on public health matters. It does this on the basis of the most recent scientific knowledge. Apart from its 25-member internal secretariat, the Council draws upon a vast network of over 500 experts (university professors, staff members of scientific institutions, stakeholders in the field, etc.), 300 of whom are appointed experts of the Council by Royal Decree. These experts meet in multidisciplinary working groups in order to write the advisory reports. As an official body, the Superior Health Council takes the view that it is of key importance to guarantee that the scientific advisory reports it issues are neutral and impartial. In order to do so, it has provided itself with a structure, rules and procedures with which these requirements can be met efficiently at each stage of the coming into being of the advisory reports. The key stages in the latter process are: 1) the preliminary analysis of the request, 2) the appointing of the experts within the working groups, 3) the implementation of the procedures for managing potential conflicts of interest (based on the declaration of interest, the analysis of possible conflicts of interest, and a Committee on Professional Conduct) as well as the final endorsement of the advisory reports by the Board (ultimate decision-making body of the SHC, which consists of 30 members from the pool of appointed experts). This coherent set of procedures aims at allowing the SHC to issue advisory reports that are based on the highest level of scientific expertise available whilst maintaining all possible impartiality. Once they have been endorsed by the Board, the advisory reports are sent to those who requested them as well as to the Minister of Public Health and are subsequently published on the SHC website (www.shc-belgium.be). Some of them are also communicated to the press and to specific target groups (healthcare professionals, universities, politicians, consumer organisations, etc.). In order to receive notification about the activities and publications of the SHC, please contact: [email protected].

http://www.shc-belgium.be/

mailto:[email protected]

mailto:[email protected]

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HEALTH, FOOD CHAIN SAFETYAND ENVIRONMENT

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