UNCORRECTED PROOF 1 2 Comparison of human health risks resulting from exposure to fungicides 3 and mycotoxins via food 4 Stefan D. Muri a, * , Hilko van der Voet b , Polly E. Boon c , Jacob D. van Klaveren c , Beat J. Brüschweiler a 5 a Federal Office of Public Health, Nutritional and Toxicological Risks Section, Stauffacherstrasse 101, CH-8004 Zurich, Switzerland 6 b Biometris, Wageningen University and Research Centre, P.O. Box 100, NL 6700 AC Wageningen, The Netherlands 7 c RIKILT – Institute of Food Safety, Wageningen University and Research Centre, P.O. Box 230, NL 6700 AE Wageningen, The Netherlands 8 10 article info 11 Article history: 12 Received 14 July 2008 13 Accepted 26 March 2009 14 Available online xxxx 15 Keywords: 16 Deoxynivalenol 17 Margin of exposure 18 Risk perception 19 Spiroxamine 20 Tebuconazole 21 Zearalenone 22 23 abstract 24 The interest in holistic considerations in the area of food safety is increasing. Risk managers may face the 25 problem that reducing the risk of one compound may increase the risk of another compound. An example 26 is the potential increase in mycotoxin levels due to a reduced use of fungicides in crop production. The 27 Integrated Probabilistic Risk Assessment (IPRA) model was used to compare the estimated health impacts 28 on humans caused by crops contaminated with the fungicides spiroxamine (SPI) and tebuconazole (TEB) 29 or with the mycotoxins deoxynivalenol (DON) and zearalenone (ZEA). The IPRA model integrates a dis- 30 tribution characterising the exposure of individuals with a distribution characterising the susceptibility 31 of individuals towards toxic effects. Its outcome, a distribution of Individual Margins of Exposure (IMoE), 32 served as basis to perform comparisons of compounds, effects, countries, and population groups. Based 33 on the available data and the assumptions made, none of the four compounds was found to have impact 34 on human health in the addressed scenarios. The IMoE distributions were located as follows: DON < 35 TEB = ZEA < SPI, showing DON to be the compound with the highest potential for negative health impacts. 36 The presented approach can help risk managers to prioritise risk-reduction measures. 37 Ó 2009 Published by Elsevier Ltd. 38 39 40 41 1. Introduction 42 Until now, risk managers have mainly dealt with health risks re- 43 lated to one compound by comparing the outcome of an exposure 44 assessment with a health based guidance value like the Acceptable 45 Daily Intake (ADI) or the Acute Reference Dose (ARfD). It has be- 46 come clear in the last few years that – apart from traditional risk 47 assessment – more holistic considerations are desirable with many 48 foods, like in a risk-benefit analysis (EFSA, 2006). An example is 49 eating fish containing important nutrients such as polyunsaturated 50 fatty acids, but also contaminants such as dioxins. Another exam- 51 ple is the potential increase in mycotoxin levels due to a reduced 52 use of fungicides in crop production (risk–risk comparison). To 53 come to a balanced decision in these cases, risk managers need 54 to weigh all potential consequences of a certain policy or advice. 55 In order to compare risks when dealing with two compounds 56 with different toxicological adverse effects (as in the example of 57 fungicides and mycotoxins), the Integrated Probabilistic Risk 58 Assessment (IPRA) model may be a useful tool (van der Voet and 59 Slob, 2007). This model integrates a distribution characterising 60 the diverse exposure between individuals with a distribution char- 61 acterising the variable susceptibility between individuals towards 62 toxic effects. Its outcome is a distribution of Individual Margins 63 of Exposure (IMoE). Calculating the IMoE distribution for each 64 compound may help risk managers to weigh risk and benefit of a 65 certain policy and to prioritise risk-reduction measures. 66 In this paper, we will demonstrate the use of the IPRA model as 67 a case study to compare human health risks resulting from expo- 68 sure to fungicides and mycotoxins via food. These compounds 69 may be regarded as counteracting agents since fungicides are ap- 70 plied to protect crops from being infected by fungi and thus pre- 71 vent the growth of mycotoxin producing organisms, but 72 potentially lead to residues of the applied fungicides on or in the 73 crop. Fungicides are a type of pesticides which are thoroughly 74 studied concerning their toxic potential. For each pesticide a full 75 toxicological data package produced according to regulatory 0278-6915/$ - see front matter Ó 2009 Published by Elsevier Ltd. doi:10.1016/j.fct.2009.03.035 Abbreviations: ADI, Acceptable Daily Intake; AGH, adrenal gland hypertrophy; ARfD, Acute Reference Dose; BW, body weight; CES, critical effect size; CED, critical effect dose; CZ, Czech Republic; DK, Denmark; DON, deoxynivalenol; FBW, foetal body weight; FOPH, Federal Office of Public Health; HIC, health impact criterion; ICED, individual critical effect dose; IMoE, individual margin of exposure; IPRA, integrated probabilistic risk assessment; JECFA, FAO/WHO Joint Expert Committee on Food Additives; JMPR, FAO/WHO Joint Meeting on Pesticide Residues; LOR, limit of reporting; MRL, maximum residue level; NL, The Netherlands; NOAEL, no- observed-adverse-effect-level; OCL, oestrous cycle length; PMTDI, provisional maximum tolerable daily intake; RAC, raw agricultural commodity; RBC, red blood cell; SCF, Scientific Committee on Food; SPI, spiroxamine; TDI, tolerable daily intake; TEB, tebuconazole; ZEA, zearalenone. * Corresponding author. Tel.: +41 43 322 21 18; fax: +41 43 322 21 99. E-mail addresses: stefan.muri@bag.admin.ch, etr.tox@bag.admin.ch, stefanmuri@ hotmail.com (S.D. Muri). Food and Chemical Toxicology xxx (2009) xxx–xxx Contents lists available at ScienceDirect Food and Chemical Toxicology journal homepage: www.elsevier.com/locate/foodchemtox FCT 4847 No. of Pages 12, Model 5G 15 April 2009 Disk Used ARTICLE IN PRESS Please cite this article in press as: Muri, S.D., et al. Comparison of human health risks resulting from exposure to fungicides and mycotoxins via food. Food Chem. Toxicol. (2009), doi:10.1016/j.fct.2009.03.035