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

Sealsandbearings

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&LTmedicalfindings/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.