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26 Abstracts / Toxicology

other–child cohorts from four European regions with differ-nt food contaminant exposure patterns; (2) to relate perinatalxposure to EDCs with health effect data related to obesity inhildren; (3) to perform hazard characterization of perinatal expo-ure to EDCs for the development of obesity later in life, usingrodent model; (4) to determine mechanisms of action of obe-

ogenic EDCs on developmental programming with epigeneticnalysis; and (5) to perform risk assessment of perinatal expo-ure to obesogenic EDCs. First results of this project indicateidespread prenatal exposure to PCBs and organochlorine pesti-

ides throughout Europe, as well as a negative correlation betweenCB 153 levels in cord blood and birth weight (Govarts et al, EHP,011). Animal studies have revealed effects of perinatal exposureo BPA on elevated bodyweight in male mice (Van Esterik et al,rg. Comp, 2011). In vitro studies have shown that a variety ofDCs promote differentiation of adipocyte cells, which is accom-anied by changes in DNA methylation (Bastos et al., Org. Comp.,011).

This project has received funding from the European Com-unity’s Seventh Framework Programme [FP7/2007-2013] under

rant agreement OBELIX n◦ 227391.

oi:10.1016/j.toxlet.2012.03.113

02-4one as a target for persistent organic pollutants

onica Lind

Uppsala University, Sweden

Since World War II there has been an increase in age-tandardized incidence rates of osteoporotic fractures in industri-lized countries. The reason for this is unknown, but the idea thatxposure to anthropogenic chemicals could be involved has beenut forward. Many persistent organic pollutants (POPs) possessndocrine-disrupting properties, and as bone is an endocrine-egulated tissue it is a possible target.

From results published within the last decade, it is apparenthat the bone tissue of experimental, as well as wild animalss negatively affected when exposed EDCs in the environment.n addition, epidemiological studies on humans also support theypothesis, since they show a relationship between exposure toOPs and a poor bone mineral density or increased risk of boneractures.

This review will summarize the evidences that POPs could playrole in bone disorders in experimental, as well as wild animals

nd humans. It will also discuss evidences for a possible role forome other kinds of environmental contaminants, such as the plas-ic associated compounds bisphenol A and phthalates, on boneealth.

oi:10.1016/j.toxlet.2012.03.114

3: Mixture Toxicity: Current Approaches and Futuretrategies

03-1efic MIAT decision tree: Applications to real world mixtures

aul Price, Xianglu Han

The Dow Chemical Company, United States

211S (2012) S24–S34

Purpose: A decision tree for the assessment of cumulative chem-ical risks has been developed by Cefic based on WHO and EUguidance and industry-sponsored research. The tree allows riskassessors to identify cumulative exposures that pose a concern forhuman and ecological effects that would not have been detectedusing traditional chemical-by-chemical approaches. The goal of thispaper is to present the results of the application of the tree to real-world examples of cumulative exposures. Methods: The tree wasapplied to cumulative exposures to chemicals measured in samplesof surface water and effluents. A screening exposure assessmentwas performed to determine cumulative exposures to human andenvironmental receptors. Toxicity data were taken from publishedstandards or conservatively estimated using the Threshold of Toxi-cological Concern. The tree divides cumulative exposures into fourgroups, Group I, where one or more individual compounds area concern; Group II, where there is low concern for cumulativeeffects; Group IIIA, where cumulative exposures are a concern butone chemical is the clear driver; and Group IIIB, where informationon mode of action is needed for refining the assessment. Results:The decision tree demonstrated that cumulative exposures wereunlikely to pose significant risks to humans but had the poten-tial to cause ecological effects. However, most of the mixturespredicted to pose an ecological risk and mixtures predicted topose the largest risks would have been identified by chemical-by-chemical approaches. The mixtures where chemical-by-chemicalapproaches would have missed cumulative ecotoxicity were iden-tified.

doi:10.1016/j.toxlet.2012.03.116

W03-2Risk assessment of mixtures of pesticides

Trine Klein Reffstrup

Technical University of Denmark, Denmark

Humans are simultaneously exposed to several pesticides viafood. These chemicals may have a combined action that causes alower or higher toxic effect than would be expected from knowl-edge about the single compounds. Therefore, combined actionsneed to be addressed in the risk assessment.

Some of the methods for risk assessment of combined actions ofchemicals are based on knowledge on whole mixtures and otherson single compounds in the mixture. The data needed for the wholemixture approaches are rarely available for pesticides and thereforethe single compound approaches are more realistic.

When the individual compounds in a mixture have beengrouped in cumulative assessment group(s) or common mech-anism groups the risk assessment will be performed assumingsimple similar action (dose addition) using e.g. hazard index basedon, e.g. ADIs or the point of departure index based on NOAELs.

If more than one common mechanism group are identified,they should be assessed separately. Simple dissimilar action canbe anticipated if no interactions are identified, and the effect of themixture should be assessed by response addition.

A crucial point in the assessment is whether the compounds inthe mixture interact or not. Interactions among chemicals at highdoses are well-known, but no single simple approach is currentlyavailable to judge upon potential interactions at low doses. Physio-logically based toxicokinetic/toxicodynamic (PBTK/TD) modelling

could be a useful tool to assess combined tissue doses and helppredict potential interactions including thresholds for such effects.

doi:10.1016/j.toxlet.2012.03.117