Replacement Flame Retardants

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

ThankYou!

carignan@anr.msu.edu