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doi:10.1016/j.toxlet.2009.06.455

240 Abstracts / Toxicology L

11dvanced international training courses in health risk assess-ent

ohanna Zilliacus 1,∗, Annika Hanberg 2, Helen Håkansson 2

Karolinska Institutet, Biosciences and Nutrition, Huddinge, Sweden,Karolinska Institutet, Institute of Environmental Medicine,tockholm, Sweden

mplementation of reliable and efficient risk assessment proce-ures for the exposure to various types of chemicals is of highoncern in Europe today. To meet these needs and interests theres an increasing need for well-educated experts in risk assessmentrocedures.

The EU-funded projects CASCADE and RA-COURSES have devel-ped and offer a coherent European course programme in healthisk assessment that includes 1-week-long courses. The courses,hich are given as independent modules, are open for MSc, PhD

nd post doc students, senior scientists and other professionals.he courses are organised by a network of European universities.

Eleven courses have been given in the programme during005–2009. Some of the courses are basic courses on principles

n health risk assessment including methodologies and theoreti-al approaches and some are specialized courses on for exampleuantitative analysis of toxicological effect data and state-of-thert understanding of the special difficulties involved with hazardnd exposure assessment due to early life-stage exposure to chem-cals and other toxic agents. The courses are highly over subscribed

ith more than 3 applicants for each course place. The course par-icipants come from all over Europe. The courses have receivedxcellent evaluations from the participants.

Based on the experience from the CASCADE/RA-COURSES train-ng programme as well as experience from education in toxicologyt several other universities DG SANCO at the European Com-ission is now discussing a future permanent training in risk

ssessment resulting in a certification system for European riskssessors.

oi:10.1016/j.toxlet.2009.06.453

12mproving the assessment of risks from dietary exposuresy modeling variation and uncertainty in exposure and doseesponse using linked exposure and PBPK/PD models

aul Price 1,∗, Karl Schnelle 2, Torka Poet 3, Paul Hinderliter 3

Dow Europe GmbH, EH&S/TERC, Horgen, United States, 2 DowgroSciences, GLOBAL AG MATH MODELING, INDIANAPOLIS, Unitedtates, 3 Pacific Northwest National Laboratory, Biological Monitoringnd Modeling, Richland, United States

ietary risk assessments are typically conducted based on the ratiof exposure to a No-Observed Adverse Effect Level in test ani-als and require the use of assessment or uncertainty factors to

ddress interspecies extrapolation and human variation. An alter-ative approach is to use physiologically based, pharmacokineticnd pharmacodynamic (PBPK/PD) models coupled with models ofariation in human physiology and longitudinal models of dietary

xposures. A case study in the use of such models is presentedor chlorpyrifos, a model compound exhibiting extensive low-doserst pass metabolism by gut, liver, and blood. Publicly availableietary residue data and publicly available dietary software mod-

189S (2009) S57–S273

ls are used to estimate longitudinal exposures for 1000 adultsnd 1000 children for the years 2002–2007. The combined modelirectly predicts the interindividual variation in exposure, intesti-al and hepatic bioactivation and detoxification, circulating blood

evels, and pharmacodynamic endpoints based on body mass index.he results of the analysis for chlorpyrifos confirmed that currentietary exposures have negligible effects in adults and children.ariation in kinetics and level of activity were investigated but

ound to have minimal impact on the variation in response at theoses currently received from dietary exposures. Assessment fac-ors are not required in this analysis since effects are predicted inumans and variability in humans is modeled directly. This exam-le of source-to-effect modeling demonstrates the feasibility of

inking multiple models and data on food residues to directly pre-ict the risk of adverse effects.

oi:10.1016/j.toxlet.2009.06.454

13uidance documents on submissions for the technical and tox-

cological evaluation of substances proposed for use as food

dditives or nutrient sources in the EU�

ederica Lodi ∗, Joanne Gartlon, Majlinda Lahaniatis, Huguesenigswald

European Food Safety Authority (EFSA), Food Additives and Nutrientources added to Food, Parma, Italy

substance shall only be authorised for use as a food additive (FA)r nutrient source (NS) on the European market if it is demonstratedhat it does not represent a risk to human health at the proposed useevel. The Scientific Panel on Food Additives and Nutrient Sourcesdded to Food (ANS) of the European Food Safety Authority (EFSA)eals with questions of safety in the use of FAs, NSs and otherubstances deliberately added to food, excluding flavourings andnzymes.

For new FAs and NSs applications, the ANS Panel evaluation isased on a supporting dossier submitted by an applicant, whichhould follow the Guidance on Submissions for Food Additive eval-ations by the Scientific Committee on Food or the Guidance onubmissions for safety evaluation of sources of nutrients or of otherngredients proposed for use in the manufacture of foods (2001).

These documents outline the technical (chemistry and expo-ure) and toxicological (core studies: metabolism, toxicokinetics,ubchronic toxicity, genotoxicity, chronic toxicity and carcinogenic-ty, reproduction and developmental toxicity) data that are requiredn the dossier in order to allow a comprehensive evaluation of theubstance. For NSs, bioavailability information of the nutrient fromhe source is required. Based on the data provided by the applicantnd other information, the ANS Panel issues an independent Sci-ntific Opinion on whether the substance will be of safety concernor human health for the proposed uses, taking into account theelevant toxicological results in animal studies or from human data