Associa:on of phthalates, parabens and phenols in personal care products with pubertal :ming in girls and boys
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Associa:on of phthalates, parabens and phenols in
personal care products with pubertal :ming
in girls and boys
v
Kim Harley, PhD
University of California, Berkeley
Collabora:ve on Health and the Environment
Genera:on Chemical Webinar
Jan 28, 2021
Personal Care Products: What’s the Concern?
• The average woman uses 12 personal care products a day
• The average teenage girl uses 17
• More than 12,500 chemicals are used in cosme:cs and personal care products
Cosme:cs Fragrance
Lo:on
Soap & Shampoo Deodorant
Toothpaste
Sunscreen
Source: Environmental Working Group
These Chemicals Can Enter our Bodies
Inhala:on
Inges:on
Dermal Absorp:on
Suspected Endocrine Disruptors in
Personal Care Products
Phthalates
• Diethyl phthalate (DEP)
• Di-n-butyl phthalate (DBP) Parabens
• Di-isobutyl phthalate (DiBP) • Methyl Paraben (MP)
• Propyl Paraben (PP)
An:bacterials
• Triclosan (TCS)
Sunscreens
• Benzophenone-3 (BP-3)
Personal Care Products are the Main
Source of Exposure
Urinary BP-3 Urinary Propyl Paraben
500 50
Geometric Mean Propyl Paraben (ng/ml)
P-value < 0.01 P-value < 0.01 P-value = 0.05
Geometric Mean BP3 Levels (ng/ml)
P-value < 0.01
400 40
300 30
200 20
100
10
0
0
No Yes
No Yes No Yes No Yes
Used Sunscreen FoundaIon Blush Mascara
Past 24 hours? Past 24 hours? Past 24 hours? Past 24 hours?
Berger et al, 2018
Timing of Puberty in Girls is Ge_ng Earlier
Evidence Suggests this is a Global Phenomenon
Age of First Breast Development
Age at onset of breast
p-value = 0.02
development has decreased
by one year over past 40
years
Eckert-Lind et al, JAMA Pediatrics, 2020
How Do We Measure Pubertal Timing?
Girls:
• Breast development (thelarche)
• Pubic hair development (pubarche)
• Menarche
Boys:
• Tes:cular volume >3 ml
• Genital development
• Pubic hair development
Trend towards earlier puberty in girls is quite well-established.
Trend in boys is less clear.
Edvard Munch, Na:onal Gallery, Oslo
Associa:ons with Puberty: Animal Studies
• LMW phthalates:
• Earlier puberty in female rats
• Later puberty in male rats
• Parabens:
• Earlier puberty in female rats
• Later puberty in male rats
Mean age of onset of vaginal opening following an oral exposure
• Triclosan: to triclosan from PND 21 to 42 in the female pubertal assay
(From: Stoker et al, Tox Sci, 2010)
• Earlier puberty in female rats
Hu 2013, Sallenfait 2008, Vo 2010, Kang 2001, Zhang 2014, Stoker 2012, Zorilla 2009
Research Ques:on Is :ming of puberty in children associated with personal care product chemical exposure at two cri:cal :me points: • In utero (biomarkers in maternal urine during pregnancy) • Pre-puberty (biomarkers child urine at age 9)
CHAMACOS
Longitudinal Birth Cohort
N = 338 Study
Birth 1 yr 3 ½ yr 7 yr 10 ½ yr 14 yr 18 yr
11 ¼
N = 538 N = 338
9¾ 12 ¾
Pregnancy 6 mo 2 yr 5 yr 9 yr 12 yr 16 yr
(two visits)Findings: Associa:ons with Timing of Puberty
Associa:on of Prenatal Urinary Metabolites (con:nuous)
and Puberty in Girls
Breast Development Pubic Hair Development
3 3
Mean Shio (months)
2 2
Mean Shio (months)
1 1
0 0
-1 -1
-2 -2
-3 -3
MEP MBP MiBP TCS BP3 MP PP MEP MBP MiBP TCS BP3 MP PP
Menarche
3 Adjus:ng for:
• Family income
Mean Shio (months)
2
1 • Mother’s educa:on
0
• Mother’s years of residence in US
• Mother’s pre-pregnancy BMI
-1
-2
-3
Harley et al, Human Repro, 2019 MEP MBP MiBP TCS BP3 MP PPQuar:les of Prenatal MEP and Puberty in Girls
Prenatal MEP and thelarche Prenatal MEP and pubarche
10 10
5 5
Mean Shio (months)
Mean Shio (months)
MEP = metabolite of 0 0
diethyl phthalate
-5 -5
Adjus:ng for:
-10 -10 • Family income
• Mother’s educa:on
• Mother’s years of
residence in US
-15 -15 • Mother’s pre-
Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 pregnancy BMI
(Ref) (Ref)
• Highest quar:le of prenatal MEP associated with 5-6 months earlier pubertal onset
Harley et al, Human Repro, 2019Quar:les of Prenatal Triclosan and Menarche in Girls
Prenatal Triclosan and menarche
10
5
Mean Shio (months)
0
Triclosan =
An:bacterial agent -5
Adjus:ng for:
• Family income
-10 • Mother’s educa:on
• Mother’s years of
residence in US
-15 • Mother’s pre-
Q1 Q2 Q3 Q4 pregnancy BMI
(Ref)
• Highest quar:le of prenatal Triclosan associated with 4 months earlier menarche
Harley et al, Human Repro, 2019Associa:on of Childhood (age 9) Urinary Metabolites
(con:nuous) and Puberty in Girls
Breast Development Pubic Hair Development
3 3
2 2
Mean ShiP (months)
Mean ShiP (months)
1 1
0 0
Phthalates not Phthalates not
-1 -1
measured measured
-2 -2
-3 -3
MEP MiBP MnBP TCS BP3 MP PP MEP MiBP MnBP TCS BP3 MP PP
Menarche
3 Adjus:ng for:
2 • Family income
Mean ShiP (months)
1 • Mother’s educa:on
0
• Mother’s years of residence in US
Phthalates not
• Mother’s pre-pregnancy BMI
-1
measured
-2
-3
MEP MiBP MnBP TCS BP3 MP PP
Harley et al, Human Repro, 2019Quar:les of Childhood (age 9) Methyl Paraben and
Pubertal Milestones in Girls
Methyl paraben =
preserva:ve
Childhood MP and thelarche Childhood MP and pubarche Childhood MP and menarche
10 10 10
5 5 5
Mean Shio (months)
Mean Shio (months)
Mean Shio (months)
0 0 0
-5 -5 -5
-10 -10 -10
-15 -15 -15
Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4
(Ref) (Ref) (Ref)
• Highest quar:le of childhood methyl paraben concentra:ons associated
with 6 months earlier pubarche and menarcheAssocia:on of Urinary Metabolites (con:nuous) and
Puberty in Boys
Genital Development Pubic Hair Development
Prenatal 4 4
Mean Shio (Months)
Mean Shio (Months)
Exposure
2 2
0 0
-2 -2
-4 -4
MEP MBP MiBP TCS BP3 MP PP MEP MBP MiBP TCS BP3 MP PP
Genital Development Pubic Hair Development
Childhood 4 4
Mean Shio (Months)
Exposure
Mean Shio (Months)
2 Phthalates not 2
Adjus:ng for:
Phthalates not
(9 years) measured • Family income
measured
0 0 • Mother’s educa:on
-2 -2 • Mother’s years of residence in US
-4 • Mother’s pre-pregnancy BMI
-4
MEP MBP MiBP TCS BP3 MP PP MEP MBP MiBP TCS BP3 MP PP
Harley et al, Human Repro, 2019In Summary… • Several chemicals in personal care products were associated with earlier puberty in girls … but not boys • Associa:ons with both prenatal and peripubertal exposures Prenatal: • Highest maternal exposure to diethyl phthalate à 6 months earlier pubarche • Highest maternal exposure to triclosan à 4 months earlier menarche Peripubertal: • Highest childhood exposure to methyl and propyl parabens à 6 months earlier
Reasons for Cau:on • First study to examine prenatal exposures to some of these personal care product chemicals • Very specific popula:on (low-income, rural La:nas in California) • Urinary biomarkers reflect short-term exposures (24-48 hours) • Associa:ons with childhood exposures might reflect reverse causa:on.
Policy Implica:ons • We know that the chemicals in personal care products are ge_ng into our bodies. • Evidence that endocrine disrup:ng chemicals may be impac:ng pubertal :ming • The FDA has very limited authority over the cosme:cs and personal care products industry • Regula:on of cosme:cs is slowing star:ng to change (e.g. California Toxic-Free Cosme:cs Act)
Switching your Products can Reduce Exposure!
• Enrolled 100 teen girls
• Collected pre-interven:on urine sample
• Stop using regular personal care products for 3
days. Low chemical products instead.
• Collected post-interven:on urine sampleChemicals in the body decreased in 3 days
28% 35% 36% 44%
SG-Corrected Urinary Concentra1on (ng/ml)
Harley et al, EHP, 2016 All p-valuesThanks to:
Our Research Team
Our Funders
UC Berkeley
Brenda Eskenazi
Kimberly P. Berger
Katherine Kogut
Grants: R21 ES024909, P01 ES009605, R01 ES017054, Kimberly Parra
RC2 ES018792, R01 ES021369, R24 ES028529
UC San Francisco
Robert H. Lus:g
Grants: R82670901, RD83171001,
RD83451301 Kaiser Permanente
Louise C. Greenspan
Grant: 18BB-1800
Center for Disease Control and Preven:on
Antonia M. Calafat, Xiaoyun YeAnd a very special
thanks to the
CHAMACOS families!
CHAMACOS Study PhotoYou can also read
