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CollaborativeonHealthandtheEnvironmentPioneersUnder40inEnvironmentalPublicHealth
October24,2017
CourtneyCarignan,Ph.D.AssistantProfessor
MichiganStateUniversity
1
Replacement Flame Retardants
2
Flameretardants
3
Infants&ChildrenHighlyExposed
Polybrominated diphenylethers(PBDEs)
• ThyroidHormone– ReducedTSHandT4
• Neurodevelopment
– Behavior,cognitionandmotorskillsinbirthcohorts
• Reproductive– Increasedtimetopregnancyandfailedimplantation,
decreasedbirthweight,alteredgrowthtrajectory4
ReplacementsinFoam
5
PentaBDE
EH-TBB TPHP
TDCIPP Firemaster550®Phased-Out
(2005)
BEH-TBPH ITPs
6
NursingMothers
OfficeWorkers
Gymnasts
CharacterizingHumanExposure
DataAnalysis
Data&Sample
Processing&Storage
Data&Sample
Collection
Normalize
S
eβ
Biomonitoring StudyFramework
7
Carignanetal.ES&T(2012)
Motherswith7ormoreelectronicitemshadaverageHBCDconcentrationsthatwere153%higherthanthosewhohad4orfewer(95%CI=34-375%).
8
HBCDinBreastMilk
• AlternativesAssessment• SignificantNewUseRule
9
EPA’sIntervention
Carignanetal.EnvironInt (2013)
10
UrinaryTDCIPPMetabolite
100%DetectionFrequency
ParentCompound UrinaryMetabolite
Linearregression:Evaluateassociationswithdemographic,dietary,andbehavioralcharacteristics
29Officeworkers
Carignanetal.EnvironInt (2013)
11
PredictedbyOfficeBuilding
GMconcentration26%loweramongworkersinBuildingA(p=0.01)
Officeenvironmentasourceofexposure
12
Carignanetal.EnvironInt (2013)
PredictedbyHandwashing
(≥6x/day)
13
PublicHealthInterventions
2.ChangeinBostonFireCodesnegatingrequirementforflameretardantsinupholsteredfurnitureforpublicspaces
1. Hand-washing
14
FoaminGymnasticsSafetyEquipment
15
LooseFoamPit
16
Carignanetal.ES&T(2013)
ElevatedinGymAirandDust
Dust:200xhigheringymcomparedtoresidences(371vs1.69ug/g)
Air:400xhigheringymcomparedtoresidences(120vs0.29ng/m3)
Consistentwithfirstgymandwithasecondstudy(Laguardia etal.2014)
17
LightDegradesFoamintoDust
ElevatedinGymnastSerum
18
1
10
100
BDE-47
1
10
100
BDE‐153
1
10
100
PCB‐153
0
1
2
3
4
5
6
7
8
9
10
0 0.2 0.4 0.6 0.8 1 1.2
Foamrecyclersandcarpetinstallers
(2006)(Stapletonetal.2008)
NHANES,Californians(2003‐04)
(Zotaetal.2008)
NHANES,Ages12‐19(2003‐04)
(Sjödinetal.2008)
NHANES,FullDataset(2003‐04)
(Sjödinetal.2008)
PregnantWomen(2008−2010)
(Stapletonetal.2011)
OfOiceWorkers(2009)
(Watkinsetal.2011)
0
1
2
3
4
5
6
7
8
9
10
0 0.2 0.4 0.6 0.8 1 1.2
Foamrecyclersandcarpetinstallers
(2006)(Stapletonetal.2008)
NHANES,Californians(2003‐04)
(Zotaetal.2008)
NHANES,Ages12‐19(2003‐04)
(Sjödinetal.2008)
NHANES,FullDataset(2003‐04)
(Sjödinetal.2008)
PregnantWomen(2008−2010)
(Stapletonetal.2011)
OfOiceWorkers(2009)
(Watkinsetal.2011)
*" *" *"
*" *"
*" *"*"
*"
*"
0
1
2
3
4
5
6
7
8
9
10
0 0.2 0.4 0.6 0.8 1 1.2
*Signi'icantlydifferentfromgymnast
GMattheα=0.05level
NHANES,Californians(2003‐04)
(Zotaetal.2008)
NHANES,Ages12‐19(2003‐04)
(Sjödinetal.2008)
NHANES,FullDataset(2003‐04)
(Sjödinetal.2008)
PregnantWomen(2008−2010)
(Stapletonetal.2011)
Of'iceWorkers(2009)
(Watkinsetal.2011)
0
1
2
3
4
5
6
7
8
9
10
0 0.2 0.4 0.6 0.8 1 1.2
*Signi'icantlydifferentfromgymnast
GMattheα=0.05level
NHANES,Californians(2003‐04)
(Zotaetal.2008)
NHANES,Ages12‐19(2003‐04)
(Sjödinetal.2008)
NHANES,FullDataset(2003‐04)
(Sjödinetal.2008)
PregnantWomen(2008−2010)
(Stapletonetal.2011)
Of'iceWorkers(2009)
(Watkinsetal.2011)
0
1
2
3
4
5
6
7
8
9
10
0 0.2 0.4 0.6 0.8 1 1.2
Gymnasts(2012)(OurSample)
NHANES,Californians(2003‐04)
(Zotaetal.2008)
NHANES,Ages12‐19(2003‐04)
(Sjödinetal.2008)
NHANES,FullDataset(2003‐04)
(Sjödinetal.2008)
PregnantWomen(2008−2010)
(Stapletonetal.2011)
OfNiceWorkers(2009)
(Watkinsetal.2011)
ng/g
-lipi
d
Carignan et al. ES&T (2013)
19Carignanetal.EnvironInt (2016)
PitCubesandReplacementFRs89% contained flame retardants
20
www.gymnastcollaborative.org
FlameRetardantsActontheHypothalamicPituitaryThyroidAxis
21
triphenyl Phosphate(TPHP)
isopropyltriphenyl phosphate(mono-ITP)
tris(1,3-dichloro-2-propyl)phosphate(TDCIPP)
polybrominated diphenyl ethers(PBDEs)
hexabromocyclododecane(HBCD)
tetrabromobisphenol-A(TBBP-A)
HealthEffectsofReplacements
• Potentialcarcinogen(TDCIPP)
• Neurologic– Neurotoxicity:invitroeffectssimilartochlorpyrifos (TDCIPP)
– Neurodevelopment:Increasedanxiety(FM550)
• Reproductive– Reducedeggquality,spermiation,andfecundityinzebrafish
(TDCIPP,TPHP)
– Decreasedsemenqualityinadultmen(TDCIPP)22
Pre-conception
23
Pregnancy EarlyLife Childhood Adolescence
Benefits:• Measureexposurepreconception(sensitive)• Includeinfertilecouples(susceptible)• Includemalepartner(important)• Measureearlydevelopmentalendpoints
PreconceptionCohortStudyDesign
Infertilityclinicpopulation
24
HigherAmongWomen
BDCIPP DPHP ip-PPP
Carignanetal.EHP2017
25
PredictorsandTrends
• DecreasedwithAge
• IncreasedwithBMI
• Variedwithtime(yearandseason)
• WeaktoModeratelyCorrelated(rs=0.19to0.25;p<0.05)
• ICCmonths=0.34to0.37;ICCweek=0.44to0.53
Carignanetal.EHP2017 26
31%
41%
38%
Carignanetal.EHP2017 27
ClinicallyRelevant
28
18%Declineintheproportionoflivebirths
Fertilization LiveBirthPregnancyImplantationOocyteCount
ƩPFRs ƩPFRs ƩPFRsƩPFRs
Negativeassociation,p<0.20Positiveassociation(p<0.05)
Negativeassociation(p<0.05)
Consistentwithotherstudies
• Promotionofoocytematurationbutreductionineggquality,reducedspermiation,anddecreasedfecundityinzebrafish(Wangetal.2015)
• Decreasedspermmotilityinadultmen(Meekeretal.2010)
30
• SupportprogramslikeEPA’sSaferChoice
• OptforFR-freeproducts(www.greensciencepolicy.org)
• Limitelectronicitems(AV)
• Avoidinstallingcarpetpaddingthatusesrecycledfoam
• Washhandsbeforeeating31
TipsforReducingExposure
32
Poly- andPerfluoroalkyl Substances
Hu et al. 2016 Environ Sci Technol Lett
TomWebsterMikeMcCleanWendyHeiger-BernaysAliciaFraserDebWatkinsNerissaWu
HeatherStapletonEllenCooperSimonRobertsMingliangFangCraigButt
T32ES014562,R01ES015829,R01ES016088
Andreas SjödinMohamedAbdallahStuartHarrad
AcknowledgementsExposureStudies
33
StudyParticipants
HeatherStapletonCraigButt
T32ES007069,R01ES009718,R01ES022955,R01ES000002
JohnMeekerRussHauserPaigeWilliamsLidiaMinguezAlarconJenniferFord&Staff
AcknowledgementsFertilityStudy
ThomasToth&Clinicians
