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