DR SUSAN MICHAELIS, PHD, MSC, ATPL UNIVERSITY OF STIRLING ppt_EC_EASA... · DR SUSAN MICHAELIS,...
Transcript of DR SUSAN MICHAELIS, PHD, MSC, ATPL UNIVERSITY OF STIRLING ppt_EC_EASA... · DR SUSAN MICHAELIS,...
DRSUSANMICHAELIS,PHD,MSC,ATPLUNIVERSITYOFSTIRLING
EUROPEANCOMMISSIONFACTSCAQSCIENTIFICCOMMITTEEMEETINGCOLOGNE,29NOVEMBER,2017
IntroducAon
• ThereisadifferenceinthediseasepaIernbetweenaircrewandthegeneralpopulaAon.
• Aircrewarerepeatedlyexposedtolow-levelsofengineoilsviathebleedairsupplyinnormalflight.+hydraulicandotherfluids
• Findings:publishedinthepeerreviewliteratureovermanyyearsincludingMichaelisetal,Howardetal.2017
ProblemswithcurrentEASA/ECstudies
• NothoughtexperimenttoensuresuitabledesignofstudiestoanswernecessaryquesAons– Ignoreschroniclowlevelexposures(belowLOD)–normaloperaAonsdespite• IntermiIent,conAnualwithcumulaAveexposure• Complexmixture/UFPs(monitoring+127substances/634peaks)
– Focusonshort-termexposures/higherlevels/OELs…./OPIDN(TOCP)– Gapsinknowledge–Mixtures,OELs,variability– Primary&secondaryTCASisflawed(e.g.:primaryrelatedtosealfailure/oiloverfilling)
– IncompleteLiteraturereview– Frequencybasedonhigherlevelfailureevents
ProblemswithcurrentEASA/ECstudies
• Findings:Inappropriatetosay:– Qualityofairisverygood/beIerthanoffices/housing– InfrequentOPexposures–Tracesofmeta/paraisomersin‘nearlyallsamples’(~261bleedairoilleakagesamples)
– Levelsaretoolowtocauseeffects– PsychosomaAcfeatures/personalitystressors– Futurestudiesshoulddismiss‘misguided’aerotoxicity
• Focusonindividualacute/higherdoseexposuresignoresincreasedtoxicmechanismsrelatedtoUFPandchemicalexposures,repeatlowlevelbackgroundexposures.
• Airmonitoring,invitro/invivostudiesdonotprovideanyinsightintowhyaircrewareavulnerablepopulaAon(Michaelisetal,Howardetal…..)
Frequency/Mechanismofoilleakage–SMichaelisMSc(CranfieldUniversity,2016)
• FugiAveemissionsofoiloccurasafuncAonofnormalflight:Changingsealingpressures/balances/mechanicalandthermalenginestructures– BelowpermissibleoilconsumpAonrate– FrequencyesAmatesareincorrect(Shehadi,2015…)asfocusonofficialreporAngdatabases,notdesign
• CannotassessusingengineeringfailureesAmatesaswillnottakeintoaccountthelow-doseleakageofoilsinnormalflight:Ignoresengineeringjudgment/experience
• Lower-levelleakageisregardedbyindustryasnormal“permissibleconsumpAonrate”andregardedasanonfailure/safecondiAon
OilBearingsump
ExxonMobil.JetEngineOilSystem-PartOneAndTwo.ExxonMobilAvia-onTechTopics.ExxonMobil:2016hIps://www.exxonmobil.com/en/aviaAon/knowledge-library/resources/categories/tech-topics
Design• Airmonitoringhasfocusonhigherlevelsofleakage–limitedbytechnologyLOD(EASACAQstudy)
• OilemissionsoccurinALLflights=>10-5/eq• ‘Major’failurecondiDons:– cannotoccur>10-5/eqor1x10-5/q– =Impairedcrewefficiency,discomforttopilots,physicaldistress/injuriestootheroccupants–includingbleedair(oil)contaminaAon
– mustberemoteorless-UnlikelytooccurtoeachaeroplanebutmayoccurseveralAmesduringtotallifeoffleet
THESEREQUIREMENTSARENOTBEINGMET
EASAFACTSStudy
• SimulaAngleakageatpermissibleconsumpAonrate&failurerateto:– Determinetoxicity(ECHA:2016-TCPinhalaAontoxnotdone/complexmixture)–Notpossibleasproposed
• IgnoringFugiAveemissionsthatareafeatureofthedesignusingthepressurisedsecondaryairsysteminenginesto:1)sealbearingchambers2)providebleedairtocabinvenAlaAonsystem
OccupaDonalexposurelimits(OEL)
• NotsuitablefortheaviaAonserng(Michaelis2016)
• Shouldnotbeusedforcomplexmixtures:e.g.:thermaldecomposiAonproducts
• Donotprotectallorapplytothepublic• NoOELformanysubstancesincludingTCP• Notfinelinebetweensafeanddangerous• Notindicatoroftoxicity/disease/adverseeffects• Someindividualsmayexperiencediscomfort,moreseriousadverseeffectsat/belowtheTLV
UseofTLVs-ACGIH
ACGIH(2008)AmericanConferenceofGovernmentalIndustrialHygienists.TLVsandBEIs,AppendixF-MinimalOxygenContent.2
OELs
• Nophysiologicaleffectsofoxygendeficiency(healthyadults)atoxygenparAalpressures(pp)>132torrorbelow5000feet.
• AtelevaAonsof~7000t.Maybelessthan120torr–symptomsincompaAblewithsafeperformanceofduAes
• AddiAonalworkpracAcesrequiredatOxygenpp<132torr/5000t.Similarargumentsshouldapplyforotherlimit
values,suchasindoorairguidlines.
Otherkeyissues• AcuteonchronicpaIernofeffectsbeingseeninaircrew(Michaelis
etal,Howardetal2017)• ConAnuallow-levelemissions• DamagebeingseenwellbelowOELs• ToxicityofOPs&mixtures-repeatlow-level–Terry2012:Non
cholinesterasemechanisms• LowlevelchronicexposuretoOPs–Axelrad2003:Mayreduce
thresholdoftoxicity• UFPs:providesmechanismforOPs&VOCsto‘piggyback’across
BBB• Completereviewoftheliteraturenotundertaken• Noresearchrequired–EnoughdatatotakeacDonnow• SciencewillhelpmakecurrentesAmatesmoreprecise.• EC:Conflictofinterest:SCindependence?
Michaelisetal(2017)BAe146pilotsstudy
• 70%+responserate(274pilots)• Workenvironmentconfirmedto
leakoilbymanufacturer-BAeSyst.• Mostreportedlowerlevelnormal
fumeevents/notfailures• 63%reportsymptomsconsistent
withexposuretooils/fluids• 13%-chronicillhealth/reDredwith
illhealth….
15Incidentsreview• 80%-fumesonly• 100%-transientengineops• 80%-climbordescent• 93%-impairment–incapacitaDon• 33%-full/parAalincapac’of2pilots• 53%-LTadverseeffects• 47%-10-23symptoms• 87%-posiDveoilfindings(93%)• 66%-fumesreportedbefore/ajer• ST<medicalfindings/diagnoses
• ConsistentpaIern• Cause&effectidenAfiedlinkingenvironmenttoadverseeffects
• OccupaAonaldisease:AerotoxicSyndrome• Supportedbyliterature(notjustOPIDN/TOCP)
Epidemiologicalstudy1/2
Fromtheorytoprac-ceinenvironmentalepidemiology:developing,conduc-nganddissemina-nghealthresearch.C.L.Soskolne,J.E.Andruchow,F.RacioppihIp://www.euro.who.int/__data/assets/pdf_file/0006/91095/E91890.pdf
ReferhIps://www.ijpc-se.org/,ProfessorCSoskolne,UniversityofAlberta,CollegiumRamazzini
Epidemiologicalstudy2/2QUESTIONTOBEADDRESSED:WhatisthePrevalenceofAerotoxicSyndromesymptomsamongworkersinEuropewhohaveworkedonaircratknownorsuspectedtoexperiencecontaminatedairproblems?1) ADescrip-ve(Retrospec-ve)EpidemiologyStudyofAerotoxic
Syndrome2) AProspecAveEpidemiologicalstudyofAerotoxicSyndrome
– RequiresSUITABLEmedicalprotocol(developedbyindependentexpertswithrelevantclinicalexperAse)
– Undertakenwithfocusonreportedcontaminatedairexposures
PrioriAesofResearchRelatedtoFumeEventsinAircratCabinsFurlongLaboratory,UniversityofWashington
1. DevelopprotocolsforcharacterizingbiomarkersofexposurefrombloodsamplesFivepotenAalcandidatebiomarkersidenAfied,oneextensivelycharacterized–resultspublished,asecondwithalongerhalf-lifeparAallycharacterized.Protocolforcharacterizingathirddeveloped.AgenerichighsensiAvitymassspectrometricprotocolhasbeendevelopedforanalysisoftriarylphosphateadductstobiomarkerproteins.
2. DeterminebasisforgeneDcdifferencesinsensiDvitytoexposuresPathwaysofmetabolismexaminedforthecommercialaddiAves,crucialbioacAvaAngenzymesidenAfied.Heavyisotopestandardsformassspecsynthesized.
3. ExamineapproachesformiDgaDngtheconsequencesofexposureOneeffecAveinhibitorofbioacAvaAonoftriarylphosphatesidenAfiedtodate.ValidaAonoftheusefulnessoftheinhibitorneedstobecarriedoutinananimalmodelsystem.
4. AssistindustryindevelopingsaferanD-wearaddiDvesforenginelubricantsInvitroandinvivoprotocolsdevelopedforexaminingthepotenAaltoxicityofdifferenttriarylphosphates.
Bloodbiomarkers
• ProfessorMAbou-Donia-DukeUniversity• AutoanAbodiesagainstneuronalandglialproteinsasbloodbiomarkersforoccupaAonalrelatedneurodegeneraAvedisordersamongstaircrew
• CaseControlstudy
SUMMARY
• ThecurrentresearchundertakenisaskingthewrongquesAonstogetaccurateanswertoexposuretocontaminatedairsupplysubstances
• FocussAllonacutefailurescenario&exposurelimits/highdosetoxicity
• Cannotsaynopoisoning/toxicity-justimpairment–ContrarytoFLIGHTSAFETYandpublichealth
NOCEBO?X• Lossof:
– flyingcareer– Income– Health
• Nocebo/hypervenAlaAon/personalityfactorsorjetoilemissions…?– Healthy
workereffect
EASAstudyalteraAveconclusions• CAQstudy:Lowlevelsofavarietyofsubstancesincluding
thoselinkedtooilsourcedbleedaircontamina-onwerefrequentlyiden-fiedbelowexposurelimitsandotherguidelines.Theuseofsuchlimitsandguidelinesandlevelsiden-fiedcannotbeusedtosuggestthatexposuretooilsourcedbleedaircontamina-onissafeorcannotcauseadversehealtheffects.
• AVOILstudy:Awiderangeofpyrolysedsubstanceswereiden-fieduponhea-ngtheoilstohightemperatures,someatrela-velyhighconcentra-ons.Exposuretopyrolysedengineoilscannotbesaidtocausenoharmtoneuronalfunc-onorotheradverseeffects.