Abstracts / Toxicology Letters 221S (2013) S4–S30 S19

S11-3Analysis of developmental neurotoxicity

Sandra L. Allen

Regulatory Science Associates, Dunoon, Argyll, UK

The assessment of developmental neurotoxicity requires theuse of a variety of methods from a number of different scien-tific fields. Regulatory guideline studies require offspring fromcontrol and treated litters to be evaluated for gross neurologicaland behavioural abnormalities during postnatal development andadulthood. These include assessments of physical development,behavioural ontogeny, motor activity, motor and sensory func-tion, learning and memory, and post-mortem evaluation of brainweights and neuropathology. The studies are complicated in termsof design, conduct and interpretation and great care is needed inthe practical aspects of study design in order to ensure robust inter-pretable data and avoid potential confounders.

The presentation will discuss selection of appropriate methodsand their strengths and weaknesses. It will also cover replicateddesigns, technical challenges of directly dosing pups and otheraspects of study management. Interpretational issues include: (i)the challenges to the maternal animal in terms of degree of toxi-city expected; (ii) impact of maternal toxicity on pup behaviour;(iii) impact of pup body weight on test results; (iv) differentiatingacute effects from developmental effects; (v) relative sensitivityand what constitutes increased sensitivity. Data will be presentedgiving some examples of the above.

http://dx.doi.org/10.1016/j.toxlet.2013.06.066

S11-4Developmental toxicity in reproductive organs

Geertje Lewin

Fraunhofer Institute for Toxicology and Experimental Medicine,Hannover, Germany

Within the design of the EOGRTS the cohort 1A+B encompassesthe largest number of offspring, serving the assessment of repro-ductive and general toxicity effects. Parameter assessment ondevelopment and maturation of the reproductive organ systemscontains several new parameters compared to other guidelines.The examinations start with postnatal external examinations(abnormalities of genital organs, retentions of male nipples andareolae), measurement of the ano-genital distance, organ weightand macroscopic examinations from F1 weanlings, achievementof sexual maturity, testing of sperm parameters, oestrus cyclicityand thyroid hormones as indicators of hormonal balance andterminate in a detailed histopathology of the reproductive systemin adult offspring. In the case, when no mating of F1 to producea second generation is triggered, this list is sufficient to detectweather adverse effects on reproductive organ development haveoccurred. The challenge in interpreting an EOGRT study will be tounderstand the interplay of maternal effects, hormonal influencesand pre- and postnatal maturational processes.

While the indifferent bipotential embryonic gonad differenti-ates based on genetic determination and hormonal influences, thedevelopment of other structures such as the reproductive tract withits accessory sex organs majorly depends on the delicate interplayof hormonal interactions. Therefore, multiple targets for interfer-ence are present.

An emphasis will be laid upon several practical examples on howthe assessed parameters are affected by different modes of action

influencing genesis, maturation and functionality of the reproduc-tive organs.

http://dx.doi.org/10.1016/j.toxlet.2013.06.067

S11-5Epigenetics: how genes and environmentinteract

Randy L. Jirtle

McArdle Laboratory for Cancer Research, University of Wisconsin,Madison, USA

Human epidemiological and animal experimental data indicatethat the risk of developing adult onset diseases and neurologi-cal disorders is influenced by persistent adaptations to prenataland early postnatal environmental exposures. One group of epi-genetically regulated genes that potentially links environmentalexposures early in development to adult diseases are those withmetastable epialleles. These genes have highly variable expressionbecause of stochastic allelic changes in the epigenome rather thanmutations in the genome. The viable yellow agouti (Avy) mouseharbors a metastable Agouti gene because of an upstream inser-tion of a transposable element. We have used the Avy mouse toinvestigate the importance of epigenetic alterations in determin-ing adult disease risk in response to early developmental exposureto both chemical agents and ionizing radiation. The importance ofthese studies with regard to human health and disease risk will bediscussed.

http://dx.doi.org/10.1016/j.toxlet.2013.06.068

Symposium 12: Integration of human and environmental riskassessment – is it the future?

S12-1HEROIC – an integrated European approach tothe coordination of human and environmentalrisk assessment

M.F. Wilks 1,∗, D. Barcelò 2, E. Capri 3, P. Ciffroy 4, M. Faust 5, C.R.Glass 6, K. Machera 7, A.R. Péry 8, G. Schüürmann 9

1 SCAHT, University of Basel, Switzerland, 2 Consejo Superior deInvestigaciones Cientificas, Spain, 3 Università Cattolica del SacroCuore, Italy, 4 EDF Research & Development, France, 5 Faust undBackhaus Environmental Consulting GbR, Germany, 6 Food andEnvironment Research Agency, UK, 7 Benaki PhytopathologicalInstitute, Greece, 8 Institut National de l’EnvironmentIndustriel et desRisques, France, 9 UFZ Helmholtz Centre for Environmental Research,Leipzig and Technical University Bergakademie Freiberg, Germany

While the integration of human and environmental risk assess-ment (RA) has been discussed and promoted for more than adecade, existing European regulations of chemical substances suchas REACH, the Plant Protection Products and Biocide Regulationscontinue to ask for sector-specific RAs, each of which have theirspecific information requirements and use different methodologiesfor the ultimate risk quantification. In response to this gap betweenthe vision for integration and current scientific and regulatorypractice, the EU FP7 project HEROIC aims to contribute to the devel-opment of harmonised approaches which meet the challenges ofRA. A comprehensive landscaping exercise has identified commonmethodological and data needs and opportunities in current humanand environmental RA practices (Péry et al., 2013). Existing in vivo,