associaon of phthalates, parabens and phenols in personal care … · 2021. 1. 28. · hu 2013,...
TRANSCRIPT
KimHarley,PhDUniversityofCalifornia,Berkeley
Collabora:veonHealthandtheEnvironment
Genera:onChemicalWebinarJan28,2021
Associa:onofphthalates,parabensandphenolsinpersonalcareproductswithpubertal:ming
ingirlsandboys
v
PersonalCareProducts:What’stheConcern?• Theaveragewomanuses12personalcareproductsaday• Theaverageteenagegirluses17• Morethan12,500chemicalsareusedincosme:csandpersonalcareproducts
Soap&Shampoo Deodorant
Source: Environmental Working Group
Cosme:cs Fragrance
Lo:on
Sunscreen
Toothpaste
TheseChemicalsCanEnterourBodies
Inhala:on
Inges:on DermalAbsorp:on
Phthalates• Diethylphthalate(DEP)• Di-n-butylphthalate(DBP)• Di-isobutylphthalate(DiBP)
SuspectedEndocrineDisruptorsinPersonalCareProducts
Parabens• MethylParaben(MP)• PropylParaben(PP)
Sunscreens• Benzophenone-3(BP-3)
An:bacterials• Triclosan(TCS)
0
100
200
300
400
500
No Yes
Geo
metric
MeanBP
3Levels(n
g/ml)
PersonalCareProductsaretheMainSourceofExposure
UsedSunscreenPast24hours?
P-value<0.01
Bergeretal,2018
UrinaryBP-3
Geo
metric
MeanProp
ylParab
en(n
g/ml)
0
10
20
30
40
50
No Yes No Yes No YesFoundaIon
Past24hours?Blush
Past24hours?Mascara
Past24hours?
P-value<0.01 P-value=0.05P-value<0.01
UrinaryPropylParaben
TimingofPubertyinGirlsisGe_ngEarlier
EvidenceSuggeststhisisaGlobalPhenomenon
Eckert-Lindetal,JAMAPediatrics,2020
Ageatonsetofbreastdevelopmenthasdecreasedbyoneyearoverpast40
years
p-value=0.02
Age of First Breast Development
HowDoWeMeasurePubertalTiming?
Girls:• Breastdevelopment(thelarche)• Pubichairdevelopment(pubarche)• Menarche
EdvardMunch,Na:onalGallery,Oslo
Boys:• Tes:cularvolume>3ml• Genitaldevelopment• Pubichairdevelopment
Trendtowardsearlierpubertyingirlsisquitewell-established.Trendinboysislessclear.
Associa:onswithPuberty:AnimalStudies
• LMWphthalates:• Earlierpubertyinfemalerats• Laterpubertyinmalerats
• Parabens:• Earlierpubertyinfemalerats• Laterpubertyinmalerats
• Triclosan:• Earlierpubertyinfemalerats
Hu2013,Sallenfait2008,Vo2010,Kang2001,Zhang2014,Stoker2012,Zorilla2009
Mean age of onset of vaginal opening following an oral exposure to triclosan from PND 21 to 42 in the female pubertal assay (From: Stoker et al, Tox Sci, 2010)
ResearchQues:on
Is:mingofpubertyinchildrenassociatedwithpersonalcareproductchemicalexposureattwocri:cal:mepoints:
• Inutero(biomarkersinmaternalurineduringpregnancy)
• Pre-puberty(biomarkerschildurineatage9)
Pregnancy(twovisits)
6mo
Birth 1yr
12yr2yr
10½yr
9yr
7yr
5yr
3½yr 14yr
16yr9¾
11¼
12¾
N=538
N=338
18yr
N=338
CHAMACOSLongitudinalBirthCohortStudy
Findings:Associa:onswithTimingofPuberty
Associa:onofPrenatalUrinaryMetabolites(con:nuous)andPubertyinGirls
-3
-2
-1
0
1
2
3
MEP MBP MiBP TCS BP3 MP PP
MeanShio(m
onths)
PubicHairDevelopment
-3
-2
-1
0
1
2
3
MEP MBP MiBP TCS BP3 MP PP
MeanShio(m
onths)
BreastDevelopment
-3
-2
-1
0
1
2
3
MEP MBP MiBP TCS BP3 MP PP
MeanShio(m
onths)
Menarche
Harleyetal,HumanRepro,2019
Adjus:ngfor:• Familyincome• Mother’seduca:on• Mother’syearsofresidenceinUS• Mother’spre-pregnancyBMI
Quar:lesofPrenatalMEPandPubertyinGirls
-15
-10
-5
0
5
10
Q1 Q2 Q3 Q4
MeanShio(m
onths)
PrenatalMEPandpubarche
-15
-10
-5
0
5
10
Q1 Q2 Q3 Q4
MeanShio(m
onths)
PrenatalMEPandthelarche
• Highestquar:leofprenatalMEPassociatedwith5-6monthsearlierpubertalonset
(Ref) (Ref)
MEP=metaboliteofdiethylphthalate
Adjus:ngfor:• Familyincome• Mother’seduca:on• Mother’syearsof
residenceinUS• Mother’spre-
pregnancyBMI
Harleyetal,HumanRepro,2019
• Highestquar:leofprenatalTriclosanassociatedwith4monthsearliermenarche
-15
-10
-5
0
5
10
Q1 Q2 Q3 Q4
MeanShio(m
onths)
PrenatalTriclosanandmenarche
(Ref)
Quar:lesofPrenatalTriclosanandMenarcheinGirls
Triclosan=An:bacterialagent
Harleyetal,HumanRepro,2019
Adjus:ngfor:• Familyincome• Mother’seduca:on• Mother’syearsof
residenceinUS• Mother’spre-
pregnancyBMI
-3
-2
-1
0
1
2
3
MEP MiBP MnBP TCS BP3 MP PP
MeanShiP(m
onths)
PubicHairDevelopment
Phthalatesnotmeasured
-3
-2
-1
0
1
2
3
MEP MiBP MnBP TCS BP3 MP PP
MeanShiP(m
onths)
Menarche
Phthalatesnotmeasured
-3
-2
-1
0
1
2
3
MEP MiBP MnBP TCS BP3 MP PP
MeanShiP(m
onths)
BreastDevelopment
Harleyetal,HumanRepro,2019
Associa:onofChildhood(age9)UrinaryMetabolites(con:nuous)andPubertyinGirls
Adjus:ngfor:• Familyincome• Mother’seduca:on• Mother’syearsofresidenceinUS• Mother’spre-pregnancyBMI
Phthalatesnotmeasured
-15
-10
-5
0
5
10
Q1 Q2 Q3 Q4
MeanShio(m
onths)
ChildhoodMPandthelarche
-15
-10
-5
0
5
10
Q1 Q2 Q3 Q4
MeanShio(m
onths)
ChildhoodMPandpubarche
-15
-10
-5
0
5
10
Q1 Q2 Q3 Q4
MeanShio(m
onths)
ChildhoodMPandmenarche
• Highestquar:leofchildhoodmethylparabenconcentra:onsassociatedwith6monthsearlierpubarcheandmenarche
(Ref) (Ref) (Ref)
Quar:lesofChildhood(age9)MethylParabenandPubertalMilestonesinGirls
Methylparaben=preserva:ve
Adjus:ngfor:• Familyincome• Mother’seduca:on• Mother’syearsofresidenceinUS• Mother’spre-pregnancyBMI
Associa:onofUrinaryMetabolites(con:nuous)andPubertyinBoys
Harleyetal,HumanRepro,2019
-4
-2
0
2
4
MEP MBP MiBP TCS BP3 MP PP
MeanShio(M
onths)
GenitalDevelopment
-4
-2
0
2
4
MEP MBP MiBP TCS BP3 MP PP
MeanShio(M
onths)
PubicHairDevelopmentPrenatalExposure
ChildhoodExposure(9years)
-4
-2
0
2
4
MEP MBP MiBP TCS BP3 MP PP
MeanShio(M
onths)
GenitalDevelopment
-4
-2
0
2
4
MEP MBP MiBP TCS BP3 MP PP
MeanShio(M
onths)
PubicHairDevelopment
Phthalatesnotmeasured
Phthalatesnotmeasured
InSummary…
• Severalchemicalsinpersonalcareproductswereassociatedwithearlierpubertyingirls…butnotboys
• Associa:onswithbothprenatalandperipubertalexposures
Prenatal:• Highestmaternalexposuretodiethylphthalateà6monthsearlierpubarche• Highestmaternalexposuretotriclosanà4monthsearliermenarche
Peripubertal:• Highestchildhoodexposuretomethylandpropylparabensà6monthsearlier
ReasonsforCau:on
• Firststudytoexamineprenatalexposurestosomeofthesepersonalcareproductchemicals
• Veryspecificpopula:on(low-income,ruralLa:nasinCalifornia)
• Urinarybiomarkersreflectshort-termexposures(24-48hours)
• Associa:onswithchildhoodexposuresmightreflectreversecausa:on.
PolicyImplica:ons
• Weknowthatthechemicalsinpersonalcareproductsarege_ngintoourbodies.
• Evidencethatendocrinedisrup:ngchemicalsmaybeimpac:ngpubertal:ming
• TheFDAhasverylimitedauthorityoverthecosme:csandpersonalcareproductsindustry
• Regula:onofcosme:csisslowingstar:ngtochange(e.g.CaliforniaToxic-FreeCosme:csAct)
SwitchingyourProductscanReduceExposure!
• Enrolled100teengirls• Collectedpre-interven:onurinesample• Stopusingregularpersonalcareproductsfor3
days.Lowchemicalproductsinstead.• Collectedpost-interven:onurinesample
Chemicalsinthebodydecreasedin3daysSG
-Cor
rect
ed U
rinar
y Co
ncen
tra1
on (n
g/m
l)
Harleyetal,EHP,2016 Allp-values<0.01
35% 36% 44%28%
Thanks to:
Grants:R82670901,RD83171001,RD83451301
Grants:R21ES024909,P01ES009605,R01ES017054,RC2ES018792,R01ES021369,R24ES028529
UCBerkeleyBrendaEskenaziKimberlyP.BergerKatherineKogutKimberlyParraUCSanFranciscoRobertH.Lus:g
KaiserPermanenteLouiseC.Greenspan
CenterforDiseaseControlandPreven:onAntoniaM.Calafat,XiaoyunYe
OurFundersOurResearchTeam
Grant:18BB-1800
AndaveryspecialthankstotheCHAMACOSfamilies!
CHAMACOSStudyPhoto