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Application of the BRAFO tiered approach for benefit–risk assessment to casestudies on heat processing contaminants

Katrin Schütte a, Heiner Boeing b, Andy Hart c, Walther Heeschen d, Ernst H. Reimerdes e, Dace Santare f,Kerstin Skog g, Alessandro Chiodini h,⇑a Procter & Gamble Eurocor, Temselaan 100 Box 43, 1853 Strombeek-Bever, Belgiumb German Institute of Human Nutrition (DIFE), Department of Epidemiology Potsdam, Rehbrücke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germanyc The Food and Environment Research Agency (FERA), Risk Analysis Team YO41 1LZ York, UKd Federal Dairy Research Centre, Dielsweg 9, 24105 Kiel, Gemranye FoodInfoTec (FIT), 1096 Bourg-en-Lavaux, Switzerlandf Food and Veterinary Service of Latvia 30 Pelds Str., 1050 Riga, Latviag University of Lund, Centre for Chemistry and Chemical, Engineering Box 124, 22100 Lund, Swedenh ILSI Europe, Avenue E. Mounier 83, Box 6, 1200 Brussels, Belgium

a r t i c l e i n f o

Article history:Available online 7 February 2012

Keywords:Benefit–risk assessmentTiered approachHeat processingAcrylamidePAHMilk

a b s t r a c t

The aim of the European Funded Project BRAFO (benefit–risk analysis of foods) project was to develop aframework that allows quantitative comparison of human health risks and benefits of foods based on acommon scale of measurement. This publication describes the application of the BRAFO methodologyto three different case studies: the formation of acrylamide in potato and cereal based products, the for-mation of benzo(a)pyrene through smoking and grilling of meat and fish and the heat-treatment of milk.Reference, alternative scenario and target population represented the basic structure to test the tiers ofthe framework.

Various intervention methods intended to reduce acrylamide in potato and cereal products were eval-uated against the historical production methods. In conclusion the benefits of the acrylamide-reducingmeasures were considered prevailing.

For benzo(a)pyrene, three illustrated alternative scenarios were evaluated against the most commonsmoking practice. The alternative scenarios were assessed as delivering benefits, introducing only mini-mal potential risks.

Similar considerations were made for heat treatment of milk where the comparison of the microbiolog-ical effects of heat treatment, physico-chemical changes of milk constituents with positive and negativehealth effects was assessed. In general, based on data available, benefits of the heat treatment were out-weighing any risks.

� 2012 ILSI Europe. Published by Elsevier Ltd. All rights reserved.

1. Introduction and methodology

Food matrices are highly complex systems of proteins, carbohy-drates, lipids, minerals and other nutrients. Due to the compo-nents’ individual reactivity substantial interactions and changesoccur during heat processing. That processing can induce desiredand positive changes to a food product, but on the other side also

leads to formation of heat-formed contaminants that are poten-tially hazardous to human health.

Hence, the risk–benefit assessment methodology proposed byHoekstra in context of the European Funded Project BRAFO (bene-fit–risk analysis of foods) (Hoekstra et al., 2010) appears to beworthwhile to test on different heat-processing situations for differ-ent foods. Benefit–risk analysis is supposed to give a clear picture ofquality profiles of food systems and allow their optimization viapositive balancing of the benefit–risk ratio for suitable nutrition(Fig. 1).

2. Case study: Acrylamide

One example of a heat-processing contaminant evaluated inthis BRAFO work package is acrylamide formed in potato and

0278-6915/$ - see front matter � 2012 ILSI Europe. Published by Elsevier Ltd. All rights reserved.doi:10.1016/j.fct.2012.01.044

Abbreviations: AA, acrylamide; BRAFO, benefit–risk assessment of foods; BaP,benzo(a)pyrene; BMDL, benchmark dose (lower confidence limit); GA, glycidamide;IARC, International Agency for Research on Cancer; MOE, margin of exposure;NIEHS, National Institute of Environmental Health Sciences; PAH, polycyclicaromatic hydrocarbon; PTDI, provisional tolerable daily intake; UHT, ultra hightreatment; USL, upper safe level.⇑ Corresponding author. Address: ILSI Europe a.i.s.b.l., Avenue E. Mounier 83,

Box 6 1200 Brussels, Belgium. Tel.: +32 (0) 27710014; fax: +32 (0) 27620044.E-mail address: [email protected].

Food and Chemical Toxicology 50 (2012) S724–S735

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cereal based products. Acrylamide has been selected as a casestudy because it is one of the best characterized heat-processingcontaminants known in food. It is an animal carcinogen and whilehuman epidemiological data is not fully conclusive, results fromanimal studies suggest this contaminant could impair health(Shipp et al., 2006; Klaunig, 2008).

Since 2002, industry efforts have far advanced to identify poten-tial mitigation options to reduce the level of acrylamide formationin the concerned foods. However, little investigations have beendone so far on whether these mitigating interventions come withany undesired side effects. Other parameters of the food might bechanged which might impact the benefit–risk equation of consum-ing potato-based and cereal-based products together with a certainintake of acrylamide.

This work looked at the problem of acrylamide formation infoods and potential changes in the benefit–risk equation if foodprocessing is changed such as to reduce acrylamide formation.The working group did not look at the beneficial effects of heat pro-cessing of foods generally – this is dealt with in a comprehensiveILSI review on the same topic (van Boekel et al., 2010). The mainpurpose of this case study is to evaluate how well the BRAFO tieredmethodology can be applied to the evaluation of reduced intake ofheat-processing contaminants like acrylamide.

Acrylamide (AA) is an industrial chemical and a food contami-nant which may be formed in foods, particularly carbohydrate-richand protein-low plant commodities, during cooking, frying, bakingor roasting at temperatures of 120 �C or higher. Most foods madefrom cereals, potatoes and also coffee, and some other foods havebeen shown to contain AA.

The health effects of acrylamide have been extensively re-viewed (Exon, 2006; Klaunig, 2008; Shipp et al., 2006; LoPachinet al., 2008; JECFA, 2010). The critical effects of AA are neurotox-icity (mostly relevant in occupational industrial exposure only)and carcinogenicity. The compound has been recognized as beinggenotoxic and carcinogenic in laboratory animals and is catego-rized as probable human carcinogen (IARC, 1995). The margin ofexposure (MOE) calculated for acrylamide in food is low and thismay indicate a human health concern (EFSA, 2005).

Animal studies showed that AA is metabolized to glycidamideby CYP2E1. Glycidamide (GA) forms DNA-adducts, which are as-sumed being responsible for the carcinogenic effects. The latestbioassays conducted in rats and mice by the US National Toxicol-ogy Program (NTP) program have confirmed acrylamide as a car-cinogen acting via its metabolite glycidamide and a genotoxicmechanism (NTP, 2011). In the human body, hemoglobin adductsof AA and GA have been established as biomarkers of exposure tothese compounds (Dybing et al., 2005; Ogawa et al., 2006). A re-cent bio-monitoring survey of a representative subset of the USpopulation conducted by National Institute of EnvironmentalHealth Sciences (NIEHS) showed a large variability in AA and GAadduct levels between individuals. This variability was consideredto be mostly due to different individual intakes of AA from foodrather than from other exposure sources like smoke or industrialcontact. Due to different consumption patterns of the high riskfoods for AA in the different European countries (e.g. high coffeeconsumption in the Nordic countries/high bread consumption inGerman-speaking countries/high consumption of fried potatoproducts in the UK and Benelux) exposure may vary between amean intake of 0.001 mg/kg body weight (bw) per day and a highintake of 0.004 mg/kg bw per day (JECFA, 2010). Mean acrylamideexposure in Europe is estimated to range between 0.31 and1.1 lg/kg bw per day for adults (>18 years), between 0.43 and1.4 lg/kg bw per day for adolescents (11–17 years), between0.70 and 2.05 lg/kg bw per day for children (3–10 years) andbetween 1.2 and 2.4 lg/kg bw per day for toddlers (1–3 years)(EFSA, 2011).

Formation of AA during food processing can be controlled tosome extent, but it will never be possible to completely eliminateAA from our diets.

All AA-reduction interventions that have been tried and are fora good part being commercially applied by industry today are sum-marized in a guidance document called the European Food andDrink Manufacturers’ Association (CIAA) Toolbox, published bythe members of the (CIAA). (http://www.ciaa.eu/asp/documents/brochures_form.asp?doc_id=65, last update February 2009, nextupdate September 2011).

Pre-assessment and problem formulation

Tier 1Individual assessment of risks and benefits

Tier 2Qualitativeintegration of risks and benefits

Tier 3Deterministic computationof common health metric----------------------------------worst/bad case analysisSensitivity analysisIncreasingly assessing more and more parametersprobabilistically----------------------------------Tier 4Probabilistic computation

Reference scenarioAlternative scenario

both risks and benefits

no risk

risks clearly dominates benefits

benefits clearly dominates risks

no clear dominance

Stop: advise reference

Stop: advise alternative

relativelysmall uncertainties Net benefit < 0 advise reference

Net benefit > 0 advise alternative

large uncertainties Health units

Stop: advise reference

Stop: advise alternative

no benefit

Fig. 1. A flow chart of the BRAFO tiered approach for health risk–benefit assessment of different dietary scenarios (reference and alternative). The formulation of the risk–benefit question may be iteratively refined in consultation with the risk manager/policymaker as the assessment progresses, as indicated by the dashed arrows at the left sideof the figure. (from Hoekstra, J., et al. BRAFO tiered approach for benefit–risk assessment of foods. Food Chem. Toxicol. (2010))

K. Schütte et al. / Food and Chemical Toxicology 50 (2012) S724–S735 S725


Depending on the consumption pattern of AA-containing foodsthe outcome of the benefit–risk assessment will likely vary.

2.1. Pre assessment and problem formulation

The BRAFO methodology, describes in its first step the benefitsand risks potentially involved in a particular exposure situation. Inthis case study, focus has been on the comparison of the situationregarding AA intake as it was prior to 2003 where little to no AA-control was applied (reference scenario) with an alternative sce-nario describing an AA intake via the same foods to which AA-reduction measures have been applied in production (alternativescenarios). For a complete set of information all scenarios are listedbelow:

Referencescenario:

Cooking practices before AA-mitigationmeasures were introduced(AA exposure estimated: 0.004 mg/kg bw/day)

Alternativescenarios:

AA-mitigation methods

(AA exposure estimated: 30% reduction =0.0028 mg/kg bw/day)– Lower frying temp– NaCl addition– Ca-salt addition– Na-bicarbonate use instead of ammonium-bicarbonate as raising agent– pH-reduction– Use of asparaginase

Acrylamide exposure occurs mainly through the diet and themargin of exposure (MOE) is smaller than desirable. Comparingtypical intake levels for the average adult from all dietary sources(prior to mitigation options being applied) reported by competentinternational bodies of 60–70 lg/day or 1 lg/kg bw/day with theBenchmark Dose (BMDL) 10 for mammary tumours in rats, theMOE values are 310 for mean exposure and 78 for high exposure,much smaller than 10,000 which has been described as of no hu-man health concern and risk management actions. Compared withthe BMDL10 for Harderian gland tumours in mice, the MOE valuesare 180 and 45 for mean and high exposures, respectively (JECFA,2010). For details on the general approach how these MOE valueswere derived also in the JECFA assessment please see Benfordet al. (2010) and Bolger et al. (2010). While there is some questionmark around the relevance of Harderian gland tumours to humans(who do not have this organ), the occurrence of Harderian glandtumours in mice are almost exclusively associated with genotoxiccarcinogens that are active at multiple sites. In addition to the lim-ited relevance of Harderian gland tumours for humans, also theconsiderably higher metabolic activation rate of the mouse, ascompared to humans, deserves mentioning (Sumner et al., 1999).Hence regulators, risk assessors and industry view strategies thatreduce the AA content in foods as a health benefit. However, effectsbrought about by these AA-reduction interventions could lead toundesired effects or potential health risks, which are attemptedto be evaluated here.

The postulated benefit of acrylamide reduction in foods is:

� Reduction of acrylamide exposure = human health benefit dueto reduced potential cancer risk.

This assumption makes a simplification for the purpose of testingthis BRAFO benefit–risk assessment methodology. The assumption

is that AA is indeed a human carcinogen and that the most relevantcancer types are renal cell, endometrial and ovarian cancer based onthe two epidemiological studies known thus far which have showna positive correlation (Hogervorst et al., 2007, 2008). However, thetotality of the epidemiological evidence does not allow clear-cutconclusions on these or any other cancer types yet. An epidemiologyexpert group concluded at the EFSA Scientific Colloquium in 2008that the epidemiological evidence to date probably rules out a verystrong effect on risk of most cancers from dietary intake, but advisedthat also the low relative risk ratios observed in some studies couldbe of importance in public health terms given the widespread expo-sure through the diet.

The potential risks from use of different acrylamide reductiontools are:

� Increased Ca-intake (Ca-salt addition in potato products)� Increased Na-intake (raising agent replacement in bakery ware,

NaCl addition in potato products)� Increased 3-MCPD intake (pH reduction in bakery ware)� Increased fat intake (lowered frying temperature in potato

products)� Some loss of asparagine (use of enzyme asparaginase in potato

and cereal products)

The different alternative scenarios all constitute food prepara-tion methods that lead to a lower AA content of the respectivefoods. However, other factors of the diet are altered to a varying ex-tent due to the AA mitigation effort and these side effects are beinglooked at with the BRAFO methodology to analyse if they representa risk or a benefit in comparison to the benefit of reduced AA up-take. The alternative scenarios do not cover all possible mitigationscenarios, but the main ones.

� Lower frying temperature (which mostly means longer fryingtime) have been shown to limit AA formation but also to leadto an increased fat content of chips and fries or other friedpotato and/or cereal based products.� pH reduction in bread and bakery ware has been shown to limit

AA formation but can bring about two side effects: the increasein Na-content of the baked good if pH changes is achievedthrough exchange of ammonium bicarbonate with sodiumbicarbonate and/or the formation of another process contami-nant, 3-MCPD, which is described to form in doughs at a higherrate if the pH is lowered. 3-MCPD is described as a non-geno-toxic carcinogen (EC-SCF, 2001).� The addition of salt (NaCl) has been shown to limit AA forma-

tion in bread or other dough-based products. However, thisreduction tool would lead to an increased Na-intake.� Also the addition of Calcium salts was shown effective in reduc-

ing AA levels in snacks products. Consequently, the Ca-intakemight be increased.� The enzyme asparaginase has been described as a tool to elim-

inate the amino acid asparagine, one of the starting materials inAA formation. The effect of this reaction is a decreased aspara-gine-content of the foods where the enzyme was used duringproduction.

2.2. Acrylamide intake considerations

Mean and high acrylamide intake values are taken from theassessments of JECFA (2010) which had also been considered rele-vant by EFSA (2008a,b).

Monitoring data collected by the EU member states and sum-marized by EFSA show that while not for all product types mitiga-tion tools were developed successfully, significant reductions havebeen achieved in some critical product groups:

S726 K. Schütte et al. / Food and Chemical Toxicology 50 (2012) S724–S735


‘French fries’ and ‘fried potato products for home cooking’, ‘softbread’, ‘bread not specified’, ‘infant biscuit’, ‘biscuit not specified’,‘muesli and porridge’ and ‘other products not specified’ showedstatistically significantly lower levels of acrylamide in 2008 datacompared to 2007 data (Table 1). No statistical difference wasshown for the remaining (50%) of the food sub-groups in the meanacrylamide content between the sampling years 2007 and 2008.

Based on the above, a maximum intake reduction of 30% foracrylamide through the total diet is assumed for the alternativescenario in this evaluation.

2.2.1. BRAFO tier 1 level(a) Acrylamide reduction through single or combined mitiga-

tion tools/reduction of potential cancer riskAll alternative scenarios describe a technological intervention

to reduce AA levels of certain foods. Based on currently known data(which reports successful AA reduction in some foods but less so inothers) the overall dietary AA intake could be decreased by an esti-mated 30%, potentially also more in future. Although difficult toquantify, the reduced exposure to AA must be considered as a de-crease in potential incidence of cancers, hence an overall benefit attier 1 (Hoekstra et al., 2010).

(b) Increased Calcium intake and adverse effects (e.g. kidney ef-fects/hypercalciuria)

The addition of certain divalent metal ions like calcium hasbeen reported (CIAA toolbox 2009) to reduce acrylamide formationin several food categories. It is assumed that these ions interactwith the asparagine in the foods and make it less available forthe reaction with reducing sugars to form acrylamide.

Addition of up to 0.3% CaCl2 or other Ca-salt to a dough-basedproduct (e.g. bread, bakery products, formed potato crisps, otherdough-based snacks or pommes croquettes) can reduce acrylamidelevels by ca. 30%, with limited negative impact on product charac-teristics and organoleptic properties. In dough-based snacks up to1% CaCl2 can be used which can reduce AA by 20–80% (CIAA tool-box 2009).

The 0.3% addition is equivalent to an addition of ca. 1100 mg Caper kg of product. When other calcium salts are used (e.g. calciumlactate) the amount of added calcium is reduced, in the case of cal-cium lactate to ca. 600 mg Ca/kg of product, with a similar acryl-amide reduction seen. The levels of addition considered here arecomparable to the calcium levels naturally found in a wide rangeof foods: the most important dietary calcium source, milk, containstypically 1200 mg Ca/L.

The following evaluation assesses the potential increase inexposure to Calcium under estimated maximum addition and in-take conditions.

Exposure assessment increased Ca-intake:Consumption of potato

productsMedian: 116 g/day

(boys 15–18 years, DGE, 2008) Mean + 2 SD: 302 g/dayMedian calcium intake

(baseline)1518 mg/day

(Boys 15–18 years, DGE, 2008) (P10/P90: 871–2603 mg/day)

Added calcium in thoseproducts

1100 mg/kg

All consumption figures are taken from the German NutritionReport (Max Rubner Institute, 2008), which provides the mostrecent food consumption data currently available; the data are con-sistent with consumption data published earlier for other countries.

The group of 15–18 year old boys is the population with thehighest consumption of fried potato products; based on the

published data, it is assumed that using their intake figures for po-tato products provides for a worst-case exposure assessment inthis alternative scenario.

- 116 g � 1100 mg/1000 g = 127.6 mg/day- 302 g � 1100 mg/1000 g = 332.2 mg/day

Added exposure through consumption of potato products with0.3% CaCl2 (1100 mg/kg):

- Mean potato products consumer: 128 mg/day = 1.8 mg/kg bw/day

- High potato products consumer: 332 mg/day = 4.7 mg/kg bw/day

The addition of calcium to the products would lead to an addi-tional intake of 128 mg of Ca/day; for the high end consumptionthe intake would be 332 mg additional Ca/day.

The mean calcium intake reported for this group is 1518 mg/day; the figures for the 10th and 90th percentile are 871 and2603 mg/day.

The Upper Safe Level for calcium has been proposed at2500 mg/day. It is recommended in the general medicinal litera-ture not to exceed this value including foods, drinks and supple-ments. This Upper Safe Level (USL) for daily calcium intake inadults is the highest level that likely will not pose risks of un-wanted side effects in the general population. This means that evenfor individuals with a high end intake of Ca from treated products,the additional 332 mg would raise the overall intake for this grouponly to 1850 mg/day, a level still below the USL. The combinationof both high end consumption of treated potato products and ofhigh end background intake of calcium would be inappropriate,since boys eating large amounts of fried potato products are usu-ally low consumers of milk/dairy products and calcium-rich min-eral waters, which today provide more than 77% of the dietarycalcium for teenage boys (Mensink et al., 2007).

Thus, even for the group with the highest dietary calcium intake,there is no indication that the USL for calcium would be exceededdue to the addition of calcium salts to the selected food groups.

2.3. Calcium intake and kidney stones

First adverse effects like hypercalciuria and stone formation areobserved in healthy people only at much higher intake levels(>5000 mg/day) and usually only when some medical conditionsoccur, which are very rare for young people (Nordin, 1988). Itshould be noted that for elderly men, where side effects are morelikely to occur, both the actual intakes (median: 634 mg/day) andthe likelihood of high intake from treated foods are much lowerthan those for teenage boys (Max Rubner Institute, 2008). Thesame applies for elderly women.

At intakes not exceeding the USL of 2500 mg/day, no risk is tobe expected. The largest prospective epidemiological study pub-lished on calcium and kidney stones concluded that high calcium

Table 1Adaptation from scientific report of EFSA: results on acrylamide levels in food frommonitoring year 2008 (EFSA 2010).

Mean values in lg/kg 2007 2008 % Reduction

Crackers 284 204 28Infant biscuits 204 110 46Soft bread 70 49 30Bread not specified 190 23 88French fries 357 280 22Home-cook potato product (oven) 385 235 39Home-cook potato product (deep-fry) 354 228 36



intake is associated with a decreased risk of symptomatic kidneystones (Curhan et al., 1993). Perhaps just as importantly, the study,conducted among over 45,000 men, found that those individualswho consumed less than 850 mg of Ca/day were at an increasedrisk for a higher incidence of kidney stones. The authors concludedthat calcium might actually have a protective effect by binding tooxalate in the gut and preventing its absorption in a form thatleads to kidney stones. This conclusion was supported by a subse-quent study on long-term calcium supplementation in pre-meno-pausal women, which found no increase in stone formation(Sakhaee et al., 1994). Calcium supplementation lowered both uri-nary oxalate and urinary phosphorous (also thought to contributeto the formation of stones) by binding both agents in the intestine.

It seems demonstrated that the addition of calcium for the ben-efit of AA mitigation is not likely to lead to exceeding the UpperSafe Level, even under worst case assumptions. Thus, the potentialhealth impact of this alternative scenario b is assessed as none andevaluation of this scenario hence stopped at tier 1.

(c) Increased calcium intake and bone healthFor evaluation of the effects on bone health, the same exposure

assumptions as in scenario (b) are being used as maximum intakechanges. The consideration of calcium intake for bone health ismost relevant in women where osteoporosis is more frequent thanin men.

The background calcium intake in teenage girls (12–18 years) isnot favorable. The median intake is around the DACH-recommen-dations (DGE, 2000), thus nearly half the girls (similar to the adultwomen) would actually benefit from an increased calcium intake.The intake for the 10th percentile was as low as 665 mg/day. Anappropriate calcium intake would decrease their risk to developosteoporosis later in life: in a 14-year prospective study by Hol-brook et al. (1988), below the group cut-off intake of 765 mg Ca/day the risk for osteoporotic fractures had increased by 60%. Othermore recent studies have confirmed this benefit although the riskreduction has been less pronounced. It is important to note thatit is calcium intake over the whole lifetime, especially also duringyoung age, which determines the risk for osteoporosis later in life.

The actual dietary calcium intake is even lower in adult andespecially in elderly women (65–95 years) with a median intakeat only around 60% of the Division of Adult and Community Health(DACH) recommendations (DGE, 2008). For them, next to potatoproducts, bread and other bakery products would be the mainsources of acrylamide, thus categories where addition of calciumcould also be a potential mitigation step.

If one includes the potential benefit of an increased calcium in-take on bone health, i.e. bone formation at young age and reducedbone loss later in life, there seems to be a potentially significantreduction in the risk of osteoporotic fractures. Based on the Ca-in-take data available for women and the positive effects described onbone health through an adequate or increased Ca-intake, the over-all health impact of this alternative scenario (c) is judged asbeneficial.

(d) NaCl addition for AA mitigation/increased Na-intakeTwo mitigation options achieving a reduction of AA levels associ-

ated with an increase in sodium content of the respective productshave been identified, i.e. a change in raising agents from ammoniumto sodium bicarbonate in some fine bakery products, and the addi-tion of table salt to the dough in a much wider range of foods, includ-ing bread and dough based potato products. While considered aneffective tool initially, the addition of salt does not seem to be widelyapplied in industry today, however is considered in this risk–benefitassessment exercise as an illustration of the methodology.

The replacement of the raising agent ammonium bicarbonateby sodium bicarbonate in ginger bread and certain biscuits hasbeen recently assessed in detail for its impact on dietary sodiumintake and related risks (Seal et al., 2008). As expected, the increase

in sodium intake turned out to be limited due to the low consump-tion figures for the small number of foods involved. Only 1.3% ofthe population would be expected to shift from a Na intake below40 mg/kg/day to above this figure, and the net increase through AAmitigation in fine bakery ware remains small.

2.4. Exposure estimation for replacing NH4CO3 with NaHCO3

� In biscuits and gingerbread, the replacement of NH4 with Naleads to an increase in sodium content of the products, from140 mg/kg product to 500 mg/kg product.� Intake data cookies: German National Food Consumption Sur-

vey 2008 (Max Rubner institute, 2008)� Men 46 g/day, women 33 g/day, average both sexes = 40 g/day

(likely a high estimate, as intake is for bakery wares in total)� Additional Na-intake through this reference scenario:� 40 g/day at Na-level 140 mg/kg = 5.6 mg/day� 40 g/day at Na-level 500 mg/kg = 20 mg/day

Additional Na-intake of 15 mg/day through replacement of theraising agent.

Starting from the findings by Seal et al. (2008), the direct addi-tion of sodium as sodium chloride to a wider range of foods to re-duce acrylamide may lead to a significantly higher net increase inNa intake and thus warrants a more detailed evaluation.

Kolek et al. observed in simple food model systems that theaddition of NaCl favours the further polymerization of acrylamideduring heating and can hence lead to a decrease in AA content (Ko-lek and Simon, 2006, 2007).

Early observations had shown that the addition of an additionalca. 1% of NaCl to dough based products like bread or some potatoproducts or the soaking of French fries in salt solution prior to fry-ing can be associated with a reduction of acrylamide formation by20–30% (Seal et al. 2008).

Especially in the case of bread, such an additional intake in saltlevels would run counter to current EU attempts to limit the totalsalt addition as a step against the rising incidence of hypertensionin Europe.

The ingoing assumption, based on the technical informationavailable from industry, is that an addition of 1% salt to doughbased products, especially bread and some other non-sweet bakeryproducts can reduce acrylamide levels by 30%.

The following assumptions are used:

� Intake data based on latest German figures (DGE, 2008).� Actual consumption of bread in young men:

Mean: 234 gHigh end (Mean + 2 SD): 494 g1% Extra salt = 1 g extra salt/100 g bread = 0.4 g

extra sodium/100 g bread (salt = 40% sodium byweight)

0.4 g � 2.34 = 0.936 g extra sodium (meanconsumer)

0.4 g � 4.94 = 1.980 g extra sodium (highconsumer)� Current background Na intake in young men:

Mean: 4.1 g/day10th centile: 2.5 g/day90th centile: 6.2 g/day

The use of German consumption figures appears right not onlybecause they present a recent set of data (published in December2008) but German consumption of bread and sodium intake seemto be at the high end of Europe. Figures for Denmark are compara-ble to Germany, data for The Netherlands (Zo eet Nederland, 1998),Austria (Elmadfa, 1998) and UK show lower consumption. For



countries like Poland or Italy, where also high bread consumptionhas been reported by Elmadfa (1998), no specific Na-content dataare currently available.

Based on these assumptions, we find an incremental Na intakefrom mean bread consumption of 0.94 g/day and even 1.98 g/dayfor individuals with high-end bread consumption.

It can be assumed that an increase in Na intake is closely mir-rored in urinary Na excretion. In this context, a meta-analysis of40 intervention studies on sodium intake and blood pressure (Gel-eijnse et al., 2003) can be useful. In this study, a significant reduc-tion of systolic blood pressure was observed between a decrease inurinary Na excretion above and below 77 mmol (1.8 g) sodium perday.

Based on the figures presented above on incremental Na intakefrom the added salt, one can assume that the intake/excretion ofthe average population of young males – and likely parts of othersubpopulations – would be pushed above the excretion limit deter-mined in this review. For high end bread consumption, the incre-mental Na intake of 1.98 g/day alone would be comparable to thecut-off level in the Geleijnse-Study.

It is important to note that already during childhood and ado-lescence an increased salt/sodium intake is associated with an in-creased blood pressure (He et al., 2008). In addition, it is beingcriticized that early consumption of high salt foods conditions peo-ple towards an overall high salt consumption over their lifetime(DGE, 2008).

The review by Geleijnse et al. (2003) also indicates that withincreasing age the sensitivity of blood pressure to increased Na in-take increases. Based on data from Max Rubner Institute 2008 (ad-justed from their energy intake), elderly men (mean age 70 years)in Germany are consuming 2.7 g of Na per day. Their bread con-sumption is comparable to the mean of young adults, since theoverall lower energy intake is not reflected in a reduction of breadconsumption: bread remains a key part of their traditional diet.With this background, the use of salt/sodium to reduce acrylamideformation would lead to an increase of their daily Na intake ofnearly 1 g, i.e. by about one third of their current average.

The data suggest that such a significant increase in the salt con-tent of bread must be assumed to have a noticeable undesired ef-fect on the blood pressure of consumers in general. Clearly, thisprobable influence on blood pressure changes must be consideredtogether with the – so far not fully conclusive – evidence of a caus-ative effect of increased blood pressure on cardiovascular diseaseslike stroke or infarction.

Overall, for this alternative scenario an increased incidence ofthe health impact has to be assumed which leads to describingthe health impact at tier 1 level as adverse.

(e) Lowered dough pH/increased potential for 3-MCPDformation

Increased 3-monochloropropane-1,2-diol (3-MCPD) formationat lowered pH values in bread and bakery ware was shown (Sealet al., 2008). 3-MCPD was recently reviewed by the InternationalAgency For Research on Cancer (IARC) (Grosse et al., 2011). In rats,it produced benign renal tumours in both sexes and Leydig-cell andmammary tumours in males. 3-MCPD is genotoxic in vitro, butthere is no evidence of genotoxicity in vivo. The potential health ef-fect of increased intake of an animal carcinogen is considered rel-evant. However, 3-MCPD is currently regulated by a maximumlevel in products where its formation occurs the most and a provi-sional maximum tolerable intake (PMTDI) (2 lg/kg bw/day) hasbeen published (WHO, 2007). For this assessment, the group con-cluded that a health effect should be excluded unless the exposurewould be estimated to exceed the PMTDI.

Data on 3-MCPD formation in bread and bakery dough at low-ered pH is still limited. Based on the analytical values available,the following exposure estimation was conducted:

Exposure:3-MCPD levels in continental breads (normal

pH): 40–50 [lg/kg] 400% increase observed asa maximum from addition of acids:50 � 4 = 200 = lg/kg bread

Bread consumption (DGE, 2008):Mean: 234 g/dayHigh end (Mean + 2 SD): 494 g/day234 g � 200 lg/kg/1000 g = 47 lg/day494 g � 200 lg/kg/1000 g = 98 lg/dayExposure at 400% increased 3-MCPD production:Mean bread consumer: 47 lg/d = 0.7 lg/kg bw/

dayHigh bread consumer: 98 lg/d = 1.4 lg/kg bw/

day

The exposure to 3-MCPD through increased formation in lowpH dough is even under worst-case assumption (400% 3-MCPDformation increase and high bread consumption) still below thePTDI.

Consequently, the health impact of this alternative scenario d isassessed as none and evaluation of this scenario hence stopped attier 1.

The authors would like to point out that only 3-MCPD exposurefrom bread consumption was considered for this assessment, asthese were the only data available of a scenario where acrylamidemitigation has impacted 3-MCPD levels in foods. There are not suf-ficient data available currently to allow conclusions on whetheracrylamide mitigation tools applied to other food categories likee.g. cereals or coffee could also increase the uptake of 3-MCPD inthe population.

(f) Lower frying temperature/increased fat contentCompany-owned unpublished data from various snacks and

French fries producers from the years 2002–2004 show that a fry-ing temperature reduction from e.g. 200 to 175 �C leads to � 30%decrease in AA and can lead to a 10% increase of fat content ofthe fried product.

A potential health effect of increased fat uptake would be anincreased risk of hyperlipoproteinaemia and cardiovasculardiseases.

Today, based on increased industry learning, these estimated10% increased fat content are not considered to be occurring inpractice to the total population as products that are commerciallyfried can undergo other formulation adaptations to avoid such anincreased fat content. The increased fat uptake through reducedfrying temperature would then remain relevant only for home-cooked freshly fried goods, which is likely to be a negligible changein overall fat uptake through the diet.

The health impact of this alternative scenario c is assessed asnone and evaluation of this scenario hence stopped at tier 1.

(g) Enzyme Asparaginase/loss of asparagineFor completeness it is mentioned here that also the use of

asparaginase is a possible AA reduction tool, effective in some foodproducts. The enzyme is commercially available as product fromtwo different production organisms, and both have received safetyapproval (US FDA GRAS status for their intended use). The enzymereduces asparagine (transforming it to aspartate) and hence willreduce the level of asparagine in the foods on which the enzymeis used during production. However, given that asparagine is anon-essential amino acid and given the positive safety evaluationof the enzyme for use in food production there is no relevant healthimpact to be expected.

This alternative scenario is stopped for evaluation at tier 1.



2.4.1. BRAFO tier 2 levelIn tier 2, both benefits and risks should be characterized based

on the severity of the effects and on the potential number of indi-viduals affected (Hoekstra et al., 2010). For the AA case study,health effects of high severity included cancer risk (reduced here)and hypertension and associated CVDs (increased risk), while amedium to low rank was attributed to the effect improved bonehealth/reduced fractures (Table 3).

However, the authors found the precise health significance of anacrylamide reduction of 30% in some food products difficult to as-sess. The same holds true for the actual effect of the increased Ca-intake for bone health. Dose response curves for dietary acrylamideexposure and adverse effects in humans are not available. Somedata exist in experimental animals (at exposures different to thosethrough the human diet). However, no standard methodology iscurrently developed to extrapolate human dose–response fromanimal data in the context of the BRAFO benefit–risk assessmentmethodology.

2.5. Conclusion

In tier 1, as the overall evaluation in Table 2 outlines, a resolu-tion of the benefit–risk assessment for acrylamide and mitigationefforts could not be found at that level as a potential beneficialand a potential adverse effect contrast each other.

However, some risks or benefits could be ruled out from occur-ring based on available realistic data; based on low quality of evi-dence or small change in incidence based on practical industryexperience: increased fat uptake, increased 3-MCPD intake, Ca-in-take above USL, and enzyme influence on asparagine intake havebeen ruled out.

In tier 2, as the overall evaluation in Table 3 outlines, a resolu-tion of the benefit–risk assessment for acrylamide and mitigationefforts could not be found at tier 2 yet either, as a potential de-crease in mortality (through reduced AA exposure, and throughadditional Ca-intake considered beneficial for bone health) is tobe evaluated against a potential increase in mortality from anothereffect (potentially increased Na-uptake). Hence the next stepsaccording to the methodology would be to estimate the corre-sponding DALY changes of both effects. This could theoreticallybe tried out using the QALIBRA tool, however, the authors con-cluded that not sufficient data of satisfactory quality necessary toundertake this modelling were available.

Overall, it can be concluded though that the beneficial effect ofreducing acrylamide in processed foods through various interven-tion methods in the food production is desirable. These acrylam-ide-reducing actions should hence be applied as long as theadverse side effects are recognized and minimized to the extentpossible.

3. Case study: Benzo(a)pyrene

3.1. Background

Benzo(a)pyrene (BaP) is a chemical contaminant found in food.BaP belongs to the group of polycyclic aromatic hydrocarbons(PAHs), which generally occur in complex mixtures. The contami-nation of food with PAHs can occur both by environmental path-way and during heat treatment applications in food processing,e.g. roasting, grilling, smoking, drying. PAHs are primarily formedby incomplete combustion or pyrolysis of organic matter, duringvarious heat processing.

There are several food categories that can be affected by PAHs,such as cereals, vegetable oils, coffee, home-cooked foods, usuallywhen smoking, heating and drying processes are involved, or

seafood from polluted waters. Home cooking, such as grilling,roasting and smoking, particularly charcoal grilled/barbecuedfoods, can lead to high concentrations of PAHs. One the most pop-ular and oldest food processing technology relevant to the issue issmoking. The technology is widely used not only for special orga-noleptic properties of smoked products, but also for the inactivat-ing effect of smoke and heat on enzymes and microorganisms(Stolyhwo and Sikorski, 2005).

It has to be stated that, the toxicity of PAH is not well character-ized. The toxic equivalency factors (TEF) approach to the risk char-acterization for PAHs in food is not considered to be scientificallyvalid because of the lack of data from oral carcinogenicity studieson different PAHs, their different modes of action and the evidenceof poor predictability of the carcinogenic potency of PAH mixturesbased on the currently proposed TEF values (EFSA, 2008a). PAHsdiffer in carcinogenic potency or may function in living organismsas synergists increasing carcinogenic activity of other PAHs. Thehealth effects of PAHs have been extensively reviewed (EFSA,2007, 2008a).

In the EFSA Scientific Opinion on Contaminants in the FoodChain (EFSA, 2008a) it is also concluded that BaP may be used asa marker of occurrence and effect of the carcinogenic PAHs in food.However, it is stressed the fact that data collection on the wholePAH profile should continue in order to be able to evaluate the con-tamination of food commodities and any future change in the PAHprofile.

3.2. Exposure to BaP and PAHs via the diet

According to EFSA (2007, 2008b)) the median dietary exposureacross European countries, calculated both for mean and high die-tary consumers and varied between 235 ng/day (3.9 ng/kg bw perday) and 389 ng/day (6.5 ng/kg bw per day) respectively for BaPalone, 641 ng/day (10.7 ng/kg bw per day) and 1077 ng/day(18.0 ng/kg bw per day) respectively for PAH2 (BaP and chrysene),1168 ng/day (19.5 ng/kg bw per day) and 2068 ng/day (34.5 ng/kgbw per day) respectively for PAH4 (BaP, chrysene, benzo[a]anthra-cene & benzo[b]fluoranthene) and 1729 ng/day (28.8 ng/kg bw perday) and 3078 ng/day (51.3 ng/kg bw per day) respectively forPAH8.

The two highest contributors to the dietary exposure were cere-als and cereal products, and sea food and sea food products (EFSA,2007, 2008a). The indicated margins of exposure (MOE) for averageconsumers were 17,900 for BaP, 15,900 for PAH2, 17,500 for PAH4and 17,000 for PAH8. For high level consumers, the respectiveMOEs were 10,800, 9500, 9900 and 9600. These MOEs indicate alow concern for consumer health at the average estimated dietaryexposures. This applies to the full range of estimates of averageexposures across EU Member States (3.1–4.3 ng/kg bw perday, MOEs: 16,300–22,600 for benzo[a]pyrene alone and23.6–35.6 ng/kg bw per day, MOEs: 13,800–20,800 for PAH8).However, for high level consumers the MOEs are close to or lessthan 10,000, which as proposed by the EFSA Scientific Committeeindicates a potential concern for consumer health and a possibleneed for risk management action (EFSA, 2008a,b).

3.3. Pre-assessment and problem formulation

BaP is a genotoxic carcinogen and human exposure to this com-pound via the diet should be kept to as low as can be reasonablyachieved (Scientific Committee of Foods, 2002). Whilst an MOE ap-proach indicates that for average consumers exposure is of lowconcern, for high consumers the MOE is not sufficient. In formulat-ing the reference scenario consideration of BaP present in food dueto smoking and grilling of fish and meat is considered. Potentialenvironmental contamination is excluded.



In order to reduce exposure to BaP from smoking or grilling offoodstuffs several alternative approaches could be used. Theseare presented below, taking into consideration the European pop-ulation as target.

Referencescenario:

– Smoking and grilling of fish and meat asper current practice in home, which may giverise to product contamination with PAHs

Alternativescenarios:

– Addition of artificial smoke flavours (fromEFSA positive list) instead of smoking– Industrial controlled smoking– Consumer advice: to discourage home-smoking, to recommend using of aluminiumfoil for grilling, or vertical grilling

The potential benefits are:

� The reduction of BaP and PAHs uptake is stressed as single, mostimportant benefit due to potential impact on human healthfrom a potential reduction in cancer risk.

The potential risks are:

� As the alternative scenarios proposed lead to slightly changedfood processing methods with the aim to achieve reduction ofPAHs in the food matrices, other possible effects relevant to par-ticular methods, substances or process may be introduced, andappear as benefit–risk neutral or may raise cause to another riskor an additional benefit. For example incomplete cooking due toreducing grilling time (alternative scenario 3).

3.3.1. BRAFO tier 1 level3.3.1.1. Alternative scenario 1: addition of artificial smoke flavoursinstead of smoking. Smoked fish and meat forms a significant partof the human diet, important because of their specific, desirableorganoleptic profile, and the high nutritional value and abundance,in fatty species, of lipids rich in unsaturated fatty acids.

One alternative food processing method to avoid formation ofPAHs completely is the heat processing of meat or fish, avoidingany smoking or grilling. In order to give products the expectedtaste profile, smoke flavours would be added. Smoke flavourswhich will in future be allowed for use, based on the new FIAP reg-ulation have all undergone a recent evaluation by EFSA and areconsidered safe for consumption at a defined level (EFSA positivelist of smoke flavours). Based on the fact that smoke flavours havebeen evaluated and are considered as safe this alternative scenarioof increasing their intake will not deliver any potential benefit orrisk.

3.3.1.2. Alternative scenario 2: industrial controlled smoking. Smok-ing is an ancient and popular food heat processing method tradi-tionally used by industry and in local communities. Formation ofPAHs depends on numerous processing parameters like, time, tem-perature, source of heat, type of heat treatment and technologicalsolutions used.

Next to the very traditional, uncontrolled processing methodshome grilling or home smoking, the fish and meat industry hasestablished very well controlled smoking processes which guaran-tee an adequate level of preservation of the food but at the sametime limit the formation of PAHs. Maximum tolerated levels ofbenzo[a]pyrene have been set in Regulation (EC) 1881/2006 andindustrially controlled processes are supposed to monitor and re-spect these. We hence assume that exposure to the contaminantsis reduced in this alternative scenario and are not aware of anydata suggesting that other risks (e.g. through other heat-formedTa

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3.3.1.3. Alternative scenario 3: consumer advice: discourage home-smoking, recommend using of aluminium foil for grilling, or verticalgrilling. To increase effectiveness of consumer health protection itis crucial to support benefit–risk analysis with guidelines or riskcommunication message promoting safe food processing practicesto support the reduction of BaP and PAHs in food.

A significant amount of dietary exposure to PAHs and particu-larly BaP is believed to occur through uncontrolled combustionprocesses when home grilling or home-smoking. Detailed con-sumer advice as to how and why to avoid these processes or im-prove them through e.g. vertical grills or use of aluminium foilduring grilling of meat or fish will help reduce exposure.

These recommended changes could however in some consum-ers who are less expert lead to insufficient cooking of meat or fishwhich in turn can again increase exposure to food-borne microbi-ological pathogens such as Escherichia coli spp, salmonella spp andothers. However, the health impact of such contamination onlyfrom these food sources is considered overall a minor effect buthas the potential to introduce some risk whilst the extent of thebenefits (reduced BaP levels) is unknown and may vary. Overallthere is the potential for an increase in risk which would have tobe considered adverse.

3.4. Conclusions

A tier 1 assessment using the BRAFO methodology indicatedthat the three alternative scenarios in the case study have the po-

tential to deliver a benefit whilst the potential adverse risks areminimal for scenarios 1 and 2. Consequently, the case study onBaP is stopped at tier 1. For alternative scenario 3 more data wouldbe required on the effects of changes in cooking practice on micro-biological load and BaP levels in grilled and smoked meat and fish.The assessment was stopped as such data from a home-cookingscenario are not available.

4. Case study: Heat treatment of milk

4.1. Pre assessment and problem formulation

Today heat treatment is standard for most of consumer milkand milk products and has the primary objective to inactivatepathogenic and spoilage microorganisms in order to have safeproducts and increase shelf life of liquid drinking milk and the suit-ability for different manufacturing purposes. Besides the microbio-logical (microbiocidal and microbiostatic) effects physico-chemicalchanges of milk constituents with positive and negative health ef-fects (potential benefits and/or risks) occur.

These directly depend on the heat load, i.e. temperature � timeregimes resulting in different quality profiles of the related con-sumer products. Today the following processing technologies areapplied:

� Pasteurization: minimum 72 �C/15 s. (phosphatase negative)� High temperature pasteurization more than 85 �C (peroxidase

negative).� UHT treatment 135 �C/few s.� Sterilized milk 121 �C/30 min.

Table 3Case study on acrylamide benefit–risk assessment for a change from the reference scenario to different alternative scenarios at tier 2.

Effect severity⁄ (w = 0–1) Years lived with disease, peraffected person (YLD)

Change in mortality Years of life lost permortality (YLL)

Cancers through AA 0.09–0.1 (cancers pre-metastasis) Average 5–10 years (5 yr survivalrates 50–60%)

Decrease 0–30 years

Ca – kidney issues: not considered at tier 2 – – –Bone health – Ca 0.077–0.37 (fractures) <1 years Decrease? 0Hypertension/stroke through Na 0.25 (hypertensive heart

disease) – 0.90 (stroke)5–6 years (stroke) Increase RR = 1.3–1.4 (disease)

RR = 1.4–1.9 (mortality)0–30 years

3MCPD cancer risk: not considered at tier 2 – – –Increased fat/CVDs: not considered at tier 2 – – –Loss of ASN: not considered at tier 2 – – –Not considered at tier 2Overall ⁄ WHO disability weights 2004 ?

1www.nationaalkompas.nl.2Global burden of disease. (WHO 2004).

Table 4Case study on benzo[a]pyrene benefit–risk assessment for a change from the reference scenario to different alternative scenarios at tier 1.

Health effect Change Quality ofevidence based onWHO criteria

Magnitude of theeffect

Populationaffected

Health impact(beneficial/adverse/none)

References

Tier 1Mutagenicity/genotoxicity Reduced benzo[a]-pyrene and PAHs

uptakeHigh Decrease EU population B EFSA

(2007,2008a,b)None (EFSA positive list) Increased Smoke flavours intake – – EU population N EFSA (2007,

2008a,bMutagenicity/genotoxicity Reduced uptake of benzo[a]-pyrene

and PAHs through industrial,controlled smoking

High Decrease EU population B EFSA (2007,2008a,b

Diarrhoea enteritis Increased uptake of microbialpathogens through insufficientgrilling/smoking

Low Increase EU population R EFSA (2007,2008a,b

Overall change B



� Microfiltration plus heat treatment.

Microbiological and physico-chemical changes depend on therelated processing conditions (temperature � time). Pasteurizationinactivates pathogenic and relevant spoilage microorganisms.With further increasing heat load sterilization is achieved.

Physico-chemical changes are concerned with practically allmilk components as well as with their interactions and again de-pend on heat load during processing. Typical examples are:

� Denaturation of proteins and structural changes.� Increase of digestibility, formation of bioactive peptides and

improvement of amino acid bioavailability.� Reduction of bioactivities: imunoglobulines, enzymes, vitamins,

etc.� Formation of dehydro-alanine, lanthionine and lysino-alanine

with reduced availability of amino acids, especially of lysine.� Carbohydrates: Maillard-reactions, formation of the prebiotic

lactulose.� Carbohydrates and proteins: e.g. formation of furosine.� Minerals: Calcium phosphate morphology: better Calcium

absorption, etc.

As example for the BRAFO tiered approach and benefit–riskanalysis of heat treatment of milk with respect to microbiologicaland physico-chemical changes the scenarios are:

Reference scenario: Raw cow’s milk (natural unchanged biolog-ical matrix) with the presence of pathogenic microorganisms suchas Salmonella spp., Listeria monocytogenes, Campylobacter sp.,Mycobacterium spp., Brucella spp., pathogenic E. coli, enterotoxinforming Staphylococcus aureus and some others. Some of thesepathogenic microorganisms are included as food safety criteria inRegulation (EEC) No. 2073/2005 on microbiological criteria.

Alternative scenario: UHT milk has been chosen as alternativescenario because this is a safe (sterile) commercial product withlong shelf life at ambient temperature and no detectable pathogenicor saprophytic (spoilage) microorganisms if manufactured accord-ing to the process parameters as given above and packaged underaseptic conditions. Due to the relatively high heat load substantialphysico-chemical changes take place during UHT-treatment. Themost relevant results have been included for benefit–risk analysis.

4.2. Parameters for benefit–risk analysis

Microbial benefits:

� Elimination or inactivation of pathogenic microorganisms(safety).� Reduction/elimination of spoilage microorganisms (shelf-life,

suitability) – no health aspect.

The potential physico-chemical benefits:

� Formation of the prebiotic lactulose.� Denaturation of proteins and improved digestibility and forma-

tion of bioactive peptides.

The potential physico-chemical risks are:

� Formation of Maillard reactions products.� Reduction of bioavailability of lysine due to the formation of

lysino-alanine.� Inactivation of bioactives such as immunoglobulines, enzymes.

The limitation to the German population is necessary due tosubstantial differences in milk consumption within the Europeanpopulation.

In tier 1, the predominant health effect of heat treatment of milk(UHT) is the elimination of pathogenic and spoilage microorgan-isms. In Table 5 all the potential health effects related to this casestudy are listed. According to the literature research the quality ofevidence for the listed benefits is overall high; however the magni-tude of the effects for the potential risks is considered to be low ornegligible. Consequently the overall change has a net benefit im-pact for the target population.

4.3. Conclusions

The development of heat treatment of milk is one of the mile-stones in food processing to ensure hygienic conditions which in-clude the safety (for the consumer) and the suitability for theintended purpose (manufacturing of safe products of high quality).The Regulation (EEC) No 853/2004 with specific hygiene rules forfood of animal origin and the Codex Alimentarius Code of Hygienic

Table 5Case study on heat treatment of milk benefit–risk assessment for a change from the reference scenario to different alternative scenarios at tier 1.

Health effect Change Quality of evidencebased on the WHOcriteria

Magnitude of theeffect

Populationaffected

Health impact(beneficial/adverse/none)

References to key studies

Tier 1Milk borne

infections andintoxications

Elimination orinactivation ofpathogenicmicroorganisms

High Low incidenceeliminated

Germanpopulation

B IDF (1980a,b,1981,1983,1984)

Better intestinalflora

Formation of Lactulose Medium Negligible lack ofclinical data

Germanpopulation

N Geier and Klostermeyer (1983),Strohmaier (1996), Clausen andMortensen (1997)

Improveddigestibility

Denaturation ofproteins

Medium Negligible lack ofphysiological data

Germanpopulation

N Klostermeyer et al. (1981), Kleberand Hinrichs (2007)

Variety of potentialpositive andnegative effects

Formation of Maillardreactions products

Low Negligible(concentration toolow)

Germanpopulation

N Nangpal and Reuter (1990),Montella et al. (1997)

Developmentaleffects

Formation of lysino-alanine

Low Negligible (highprotein intake)

Germanpopulation

N Fritsch et al. (1983), Klostermeyerand Reimerdes (1976)

Loss of immuno-protection

Denaturation ofImmunoglobulins,

Low Negligible (lowconcentration inreference scenario)

Germanpopulation

N Chandra (1978), Kessler (1981),Schroten and Koletzko (1991)

Loss of enzymeactivity

Inactivation of enzymes Low Negligible (lowcontribution inreference scenario)

Germanpopulation

N Griffiths (1986)

Overall change B



Practice for Milk and Milk Products specify the respective processparameters for pasteurization and UHT treatment (Codex, 2004).

For the BRAFO tiered approach UHT milk was chosen due to theextremely high bactericidal efficacy of this technology on the onehand, resulting in a commercially sterile product, and the poten-tially occurring chemical changes as a result of a relative high ther-mal impact in comparison to pasteurization conditions on theother hand.

Pasteurization and UHT treatment of milk have been appliedworldwide already for many decades and have shown to be safeand effective. The International Dairy Federation (IDF) has ex-pressed several times the opinion that after correct heat treatmentof milk no cases of any milk borne infections have been detected,provided that the equipment works properly and recontaminationsare avoided.

Besides physico-chemical changes have been investigatedintensively mainly for the characterization of the products andfor better control of processing and are well documented (EFSA,2008a; EFSA 2008b). The results indicate for most of the milk com-ponents typical changes due to heat treatments, e.g. denaturationof proteins or formation of new molecules.

During the follow up of the BRAFO tiered approach especiallythe changes in proteins (e.g. more than 100-fold increase of stom-ach digestion), loss of lysine via lysino-alanine or Maillard-products (relevant especially at low protein intake) or the forma-tion of lactulose in sufficient concentrations for prebiotic effectsin the intestine could be useful parameters for benefit–riskanalysis.

Unfortunately the lack of physiological data with relevantdose-/response-relationships allows only assumptions, which limitthe demands for exact risk-/benefit-results and answers. An addi-tional important gap is given with the influence of food matriceson the physiological data and related nutrition kinetics.

To fulfil these requirements guidelines for the investigation ofsufficient data for benefit–risk analysis are essential and have tobe developed and harmonized.

Therefore, it has to be stated that heat treatment of milk in termsof pasteurization or UHT treatment has strong benefits. In compar-ison to these benefits potentially occurring physico-chemicalchanges and substances after heat treatment are negligible for ben-efits and risks, mainly due to lack of suitable physiological data.

Consequently, the case study on UHT-treatment of milk wasstopped at tier 1.

4.4. Conclusions on all three case studies

The exercise showed that the BRAFO methodology in principleis suitable also to evaluate benefits and risks of changes in differentfood matrices brought about by different heat-processing methodsor adaptations to them (Table 4). Comparison of reference andalternative scenario at tier 1 level led to useful conclusions. How-ever, evaluation of some scenarios at higher tiers where a quanti-tative comparison of benefits and risk would be interesting wasunfortunately not possible to execute for the given case studiesbased on unavailability of reliable human data.

Conflict of interest

For those experts affiliated with academic institutions, theEuropean Commission through ILSI Europe covered the expensesrelated to their participation in the BRAFO project. H.B., W.H.,E.R. and D.S. received an honorarium. None of the authors declaredany interest that may conflict with the provision of their solely sci-entific input to this manuscript.

Acknowledgements

This study has been carried out with financial support of theCommission of the European Communities, Priority 5 Food Qualityand Safety, within the Sixth Framework Programme (Contract No:031731 BRAFO: Benefit Risk Analysis of Foods). This manuscriptdoes not necessarily reflect the views of the Commission and inno way anticipates the future policy in this area. The preparationof this manuscript was coordinated by ILSI Europe.

ILSI Europe would like to thank all the contributors to the BRA-FO Scientific Supported Action. Overall, we would like to thank theILSI Europe Risk Assessment of Chemicals in Food Task Force mem-bers and the BRAFO Steering Committee members for their supportand guidance. Finally we would like to thank the European Com-mission for the financial support. As a co-ordinator of the ScientificSupport Action, ILSI Europe would like to express its profoundgratefulness to all of them.

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