the opentox predictive toxicology framework

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tlevel (NOAEL) for both F0 systemic toxicity and F1 neonatal anddevelopmental neurotoxicity of DeBDPO was considered to be1000 mg/kg/day.

doi:10.1016/j.toxlet.2009.06.382

260 Abstracts / Toxicology L

11ew structural alerts for carcinogenicity derived from a pesti-ide data set

usanne Stalford ∗, Carol Marchant, Richard Williams

Lhasa Limited, Knowledge Base, Leeds, United Kingdom

data set of 310 chemicals published as part of the U.S. Environ-ental Protection Agency’s ToxCast program has been analysed to

dentify new structural alerts for carcinogenicity. The chemicals inhis data set are mostly active ingredients in food-use pesticidesnd may represent different regions of chemical space to the phar-aceutical and industrial chemicals typically used in mammalian

oxicology (Q)SAR development.The data set was compared with a collection of existing struc-

ural alerts for carcinogenicity and analysed using clusteringoftware and visual analysis. The common structural classes iden-ified during analysis were reviewed to determine those associatedith tumour induction at the same site(s). Further research for

hese classes was conducted using the published literature to iden-ify additional supporting toxicity data and a mechanistic rationalehere possible.

It was found that existing structural alerts predicted activityor 41% of rodent carcinogens in the data set. Subsequent analysisielded eight classes which may form the basis of new structurallerts for carcinogenicity. These include triazoles (e.g. cyprocona-ole) and pyrethroids (e.g. permethrin). In addition to new alerts,he analysis also identified the potential for improvements to somexisting structural alerts.

In conclusion, this work has shown the feasibility of derivingew structural alerts for carcinogenicity from a data set of pesti-ides. This indicates that the data set describes somewhat differentegions of chemical space to those used to derive existing structurallerts.

oi:10.1016/j.toxlet.2009.06.380

12he OpenTox predictive toxicology framework

arry Hardy

Douglas Connect GmbH, HQ, Zeiningen, Switzerland

he EC-funded FP7 project OpenTox is developing an open source-ased integrating predictive toxicology framework that provides anified access to toxicological data and (Q)SAR models.

OpenTox provides tools for the integration of data, for the gen-ration and validation of (Q)SAR models for toxic effects, librariesor the development and integration of (Q)SAR algorithms, andcientifically sound validation routines. OpenTox supports theevelopment of applications for non-computational specialists inddition to interfaces for risk assessors, toxicological experts andodel and algorithm developers.OpenTox is relevant for the implementation of REACH as it

llows risk assessors to access experimental data, (Q)SAR modelsnd toxicological information from a unified interface that adhereso European and international regulatory requirements includingECD Guidelines for validation and reporting. The OpenTox frame-

enotoxic and carcinogenic effects. These are the endpoints whereomputational methods promise the greatest potential reductionn animal testing required under REACH.

189S (2009) S57–S273

Initial research defined the essential components of theramework architecture, approach to data access, schema and man-gement, use of controlled vocabularies and ontologies, web servicend communications protocols, and selection and integration oflgorithms for predictive modeling. Analyses of use cases were per-ormed and included cases for REACH-relevant risk assessment,hemical categorization and prioritisation, drug development, andood safety evaluation, with the resulting requirements guidingramework design and initial application development. The initialesults of these applications and next steps in development, testingnd validation will be discussed.

oi:10.1016/j.toxlet.2009.06.381

13n oral (gavage) developmental neurotoxicity study of decabro-odiphenyl oxide (DeBDPO) in rats

ylvia Jacobi 1,∗, Hanna Silberberg 2, Todd Stedeford 3, Johniesemeier 4, John Adriano 4, Melissa Beck 5

Albemarle Europe SPRL, Health and Environment,ouvain-La-Neuve, Belgium, 2 ICL-IP America, St. Louis, United States,Albemarle Corporation, Baton Rouge, United States, 4 Chemturaorporation, Middlebury, United States, 5 WIL Research LaboratoriesLC, Ashland, United States

ecabromodiphenyl oxide (DeBDPO; CASRN 1163-19-5) (alsonown as decabromodiphenyl ether (DecaBDE)) is a flame retar-ant used in electrical and electronic equipment and upholsteryextiles. DeBDPO underwent extensive toxicity testing and riskssessments. The current GLP study provides the needed data forssessing developmental neurotoxicity effects. It was designed inonsultation with the EU Competent Authorities and combined theequirements of both US EPA OPPTS 870.6300 and OECD 426 guide-ines. It also included a 6-month assessment period of F1 offspringnd an increased offspring neuropathology sample size.

The scope was to investigate potential functional and morpho-ogical insult to the nervous system in offspring of dams exposed toeBDPO during pregnancy and lactation. Female Sprague–Dawley

ats were administered DeBDPO in corn oil daily by oral gavage,rom gestation day 6 through lactation day 21, at dosage levels of 0,, 10, 100 and 1000 mg/kg body weight/day.

The examination of F0 animals included regular clinical obser-ations, detailed off cage assessments, body weight and foodonsumption during gestation and lactation.

Observations in F1 pups included clinical observations, bodyeights and gender identities, detailed clinical observations (PND, 11, 21, 35, 45, 60), acoustic startle response (PND 20, 60), locomo-or activity (PND 13, 17, 21 61, 120, 180), learning and memory (PND2, 62), brain weight and neuropathological evaluations (PND 21,2).

Under the conditions of this study, no evidence of developmen-al neurotoxicity was observed and the no-observed-adverse-effect