Benchmark dose modelling (BMDL) - Bibra | Toxicology ...
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Benchmark dose modelling (BMDL) ... Traditionally, the hazard and risk assessor has attempted to identify the critical no-observed-adverse-effect level (NOAEL) ... Benchmarkdosemodelling(BMDL)Home»Benchmarkdosemodelling(BMDL)Traditionally,thehazardandriskassessorhasattemptedtoidentifythecriticalno-observed-adverse-effectlevel(NOAEL)fromtheavailabledatasetfromwhichanacceptableortolerablehumandose(e.g.ADI/TDI)canbeextrapolated(forsubstanceswhicharenotgenotoxiccarcinogens).Whereadverseeffectswereobservedatalltestdoses,alowest-observed-adverse-effectlevel(LOAEL)issometimesusedastheReferencePoint(RP)/point-of-departure(POD)forriskassessmentpurposes.Bothapproacheshavelimitations(particularlyextrapolatingfromaLOAEL),notablythatthecriticaleffectlevel(NOAEL/LOAEL)isrestrictedtooneofthepredefineddoselevelsusedinthestudy.Inaddition,theseapproachesfailtotakeintoaccountdirectlytheshapeofthedose-responsecurve,thusallavailableinformationisnotutilised.Sincestudieswithlowpower(e.g.smallgroupsizes)and/orinsensitivemethodsareabletodetectonlyrelativelylargeeffects,thesetendtoresultinhigherNOAELsthanwouldperhapshavebeenreportedinbetterqualitystudies.However,theBenchmarkDose(BMD)approachaimsatestimatingthedosethatcorrespondstoalow,butmeasurablechangeinresponse(BMDR;e.g.5%increaseinrelativekidneyweight(continuousdata)ora10%increaseintheincidenceoflivertumours(quantaldata)fromthemodelledbackgroundresponse).Thechoiceof10or5%fortheBMDRisdependentontoxiceffectandconservatismofevaluatorandiscalculatedbyfittingmathematicalmodelstothedose-responsedata.Anumberofmodelsarerun,andalower95%confidencelimitcalculated(BMDL;totakeaccountofthequalityofthestudy).Fromthosemodelsconsideredcompatiblewiththedata(i.e.thatpassthegoodness-of-fittest)thelowestBMDListypicallyusedastheRP/POD.Atleast2testgroupsandacontrol,togetherwithadose-responserelationship,areneededinordertousethisapproach.ThetwomainmodelsaretheUSEPABMDsoftwareandTheNationalInstituteforPublicHealthandtheEnvironmentoftheNetherlands(RIVM)softwarefordose-responsemodellingandbenchmarkdoseanalysis(PROAST).Overall,theBMDapproachisconsideredamoresophisticatedandpowerfulapproachfordeterminingaRP/PODasitmakesuseofagreaternumberofcharacteristicsofthestudyunderexamination.Critically,theBMDapproachcanbeusedforgenotoxiccarcinogens.Indeed,anEFSAScientificCommitteerecommendedin2011thatEFSAScientificPanelsandUnitsadopttheBMDapproachfortheriskassessmentofchemicalsinfood.Wecanrunthemodels,providetheoutputsandhelpinterprettheresults. OurteamofexperiencedtoxicologistshasusedBMDanalysisinhazardandriskassessmentsforaUKgovernmentagencyandinassessmentsforindustryacrossmultiplesectors EnvironmentAgencyChemical (e.g.forREACHregistrations,petrochemicalindustry;phthalates)Pharmaceuticalproducts(e.g.manufacturingimpurities,excipientsandactives)Medicaldevices(e.g.heavymetalcontamination)Foodandfood-contactmaterials(e.g.contaminantininfantfood)BiocidalproductsPlantprotectionproducts(e.g.agenotoxiccarcinogenimpurityinapesticideapplicationforauthorisation,followingevaluationbytheChemicalsRegulationDirectorate(CRD)oftheUKHealthandSafetyExecutive) RecentworkinthisfieldBenchmarkdoseforaveterinaryproductAnimalfeedandVeterinaryproducts,...ClientAnanimal-healthproduct-developmentconsultancy.BackgroundTheclientwasinterested...detailspreviewRecommendationofatolerabledailyintakeforacontaminatingpesticideBenchmarkDoseModelling,Food&...ClientAnindustrialfoodmanufacturer.BackgroundThepotentialforcontamination...detailspreviewUKEnvironmentAgency(EA)BenchmarkDoseModelling,HealthCriteria...ContaminatedlandDevelopmentoftoxicitycollationsusingtheprinciplesoutlined...detailspreviewMoreaboutusHowwecanhelpOurrecentworkADDRESSBibratoxicologyadvice&consultingCantiumHouseRailwayApproachWallingtonSurreySM60DZUKTel:+44(0)2086190770E-mail:[email protected]linkedinRecentNewsTGAsafetyassessmentoflowdosecannabidiolNTPfinalisestoxicologyandcarcinogenicityreportonperfluorooctanoicacid(PFOA)COCfinalisesguidancestatementonepigeneticsNewWHOEnvironmentalHealthCriteriadocumentontheimmunotoxicityofnanomaterialsToxicologyandRegulatoryNews–ContentsArchiveJune2020PUBLICATIONSToxicityProfilesToxicologyandRegulatoryNewsBlogSearchbibraSearchfor:Copyright(c)2014Bibratoxicologyadvice&consultingLtd.Allrightsreserved.CompanyRegNumber:4612011CookiePolicyTerms&Conditions
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