International Journal of Hygiene and Environmental Health 221 (2018) 632–641

Contents lists available at ScienceDirect

International Journal of Hygiene and

Environmental Health
journal homepage: www.elsevier.com/locate/ijheh

Urinary parabens and triclosan concentrations and associated exposure T

characteristics in a Korean population—A comparison between night-time
and first-morning urine
Sujin Kima, Seonyeong Leea, Chorong Shina, Jangwoo Leea, Sunmi Kima,b, Aram Leec,
Jeongim Parkc, Younglim Khod, Rebecca K. Moose, Holger M. Koche, Sungkyoon Kima,b,
⁎
Kyungho Choia,b,
a
School of Public Health, Seoul National University, Seoul, 08826, Republic of Korea
b
Institute of Health and Environment, Seoul National University, Seoul, 08826, Republic of Korea
c
College of Natural Sciences, Soonchunhyang University, Asan, 31538, Republic of Korea
d
Department of Health, Environment and Safety, Eulji University, Seongnam, 13135, Republic of Korea
e
Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-University Bochum (IPA), Bürkle-de-la-Camp-Platz 1,
Bochum, 44789, Germany

A R T I C LE I N FO A B S T R A C T

Keywords: Parabens and triclosan have been widely used in many personal care products and cosmetics. The endocrine
Endocrine disruptor disrupting potential of these compounds is of increasing public health concern. The aim of this study is to
Biomonitoring understand the current exposure profile of these chemicals in last void before bedtime (night-time) and first-
Spot urine morning void (first-morning) urines among a Korean population and to characterize their exposure sources and
Diurnal variability
pathways.
A total of 261 people, including infants (0–2 years), toddlers (3–6 years), children (7–12 years), adolescents
(13–18 years), and adults (≥19 years), were recruited, and sampled for night-time urine and first-morning urine
of the following day. Methyl (MeP), ethyl (EtP), propyl (PrP) and butyl paraben (BuP), and triclosan were
measured in urine. The demographic characteristics, use of personal care products, and food consumption were
obtained through a questionnaire.
Among the target compounds, EtP and MeP were most frequently detected at the highest concentrations. The
median concentration of EtP in night-time urine was 32.4 μg/L (interquartile range: 8.37–82.8 μg/L), which is
higher than previously reported worldwide. Unlike other test compounds, compared to those measured from
first-morning urine, the EtP concentrations were significantly higher in night-time urine, suggesting the presence
of different exposure sources. Among adults, the MeP and PrP concentrations in night-time urine were associated
with frequent use of skin care products, colored cosmetics, bath products, toothpaste, vinyl food packaging, or
consumption of canned food. The MeP and PrP concentrations were higher in females than in males, especially in
night-time urine. The results of this study also show that multiple urine samples are necessary to capture the
diurnal variation of non-occupational exposure to environmental chemicals, such as parabens.

1. Introduction
Parabens (alkyl esters of p-hydroxybenzoic acid) and triclosan (5-
chloro-2-(2,4-dichlorophenoxy)phenol) have been widely used as anti-
microbial agents in many consumer and personal care products. Among
parabens, methyl paraben (MeP), ethyl paraben (EtP), and propyl
paraben (PrP) are commonly added to pharmaceuticals, cosmetics, lo-
tions, and hair products. Additionally, some parabens are used as anti-
spoiling agents in foods, beverages, and food packaging materials (Soni
et al., 2005). Triclosan has been used in soaps, body wash, shampoo,
toothpastes, mouthwash, and other household products (Dann and
Hontela, 2011).
Reflecting the widespread use of these compounds in consumer
products, parabens and triclosan have been frequently reported in hu-
mans worldwide. MeP and PrP have been detected in the urine
of > 94% of the population in the United States (U.S.) who participated

⁎
Corresponding author at: Department of Environmental Health Sciences, School of Public Health, Seoul National University, 1, Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of
Korea.
E-mail address: kyungho@snu.ac.kr (K. Choi).

https://doi.org/10.1016/j.ijheh.2018.03.009
Received 23 November 2017; Received in revised form 16 March 2018; Accepted 17 March 2018
1438-4639/ © 2018 Elsevier GmbH. All rights reserved.
S. Kim et al.
in the National Health and Nutrition Examination Survey (NHANES)
2011–2012 (n = 2489; calculated from datasets provided by CDC,
2015). Of 660 urine samples collected in Germany between 1995–2012,
MeP, EtP and PrP were detected in 79–99% of samples, followed by
butyl paraben (BuP) in only 40% of samples (Moos et al., 2017; Moos
et al., 2015). Among 143 Danish children, 79% of urine samples con-
tained triclosan (Frederiksen et al., 2013), which was also detected in
the urine of 93% of Korean adults (Kim et al., 2011).
Several in vivo and in vitro studies have reported endocrine and re-
production related effects of parabens (Oishi, 2002; Routledge et al.,
1998; Taxvig et al., 2008) and triclosan (Lan et al., 2015; Zorrilla et al.,
2009). Epidemiological studies also support their associations with
decreased sperm quality (Meeker et al., 2011) and serum thyroid hor-
mones (Koeppe et al., 2013). Because of increasing concerns regarding
the potentially adverse health consequences of exposure to parabens
and triclosan, these chemicals have been regulated in many products
worldwide. According to the European Commission Regulation (EU) No
358/2014, the maximum level of parabens was restricted to 0.4% for
one ester, 0.8% for a mixture, and 0.3% for triclosan in cosmetics (EC,
2009). In 2014, the maximum permitted concentration of the total
amount of PrP and BuP in cosmetics was set at 0.14%, and other
parabens (e.g., iso-PrP and iso-BuP) were banned (EC, 2014). In the
European Union, only MeP and EtP are permitted as food additives
(EFSA, 2004). Triclosan was not included in the list of food additives,
and its use in food contact materials is banned according to a March
2010 Commission Decision. In Korea, the Ministry of Food and Drug
Safety has restricted the use of certain parabens and triclosan in
mouthwashes since 2016 (Korean MFDS Notification No. 2016-113).
This study was conducted to determine the current occurrence of
major parabens and triclosan in the urine of a Korean population and to
identify their major exposure sources and pathways. Since these che-
micals have relatively short biological half-lives in humans (Janjua
et al., 2008; Moos et al., 2016; Sandborgh-Englund et al., 2006) and
may have various exposure sources and pathways, the urinary con-
centrations of these chemicals could vary significantly by time (Koch
et al., 2014). Therefore, by collecting both last void before bedtime
(night-time) and first-morning void (first-morning) urines and by
comparing the differences in the paraben and triclosan concentrations,
more representative exposure profiles of these chemicals were ob-
tained. The results of this study will help understand the characteristics
of exposure to parabens and triclosan and develop exposure mitigation
measures for major parabens and triclosan among the Korean popula-
tion.
2. Materials and methods
2.1. Study population, sample collection, and questionnaire
A total of 261 subjects were recruited mostly during autumn be-
tween the end of July and mid-November, 2015 in Seoul, Korea and its
vicinity. Participating subjects were recruited through convenience
sampling, e.g., advertisements in online communities and personal
networks. The subjects included different age groups, i.e., ‘infant’ (up to
2 years old, n = 31), ‘toddler’ (between 3 and 6 years of age, n = 45),
‘child’ (between 7 and 12 years of age, n = 48), ‘adolescent’ (between
13 and 18 years of age, n = 46), and ‘adult’ (≥19 years of age, n = 91),
with 108 males and 153 females. When the mother of a participating
infant, toddler, or child wished to participate, she was also included in
our study population as an adult woman. As a result, a total of 78
mother-offspring pairs were recruited. All participants were instructed
to collect two urine samples at home in sterilized polypropylene tubes,
one at night before bedtime (hereafter ‘night-time urine’) and the other,
first in the next morning (‘first-morning urine’). A detailed guide
booklet explaining the sampling, storing, and delivery procedures with
photos was provided. For infants, organic cotton cloth diapers were
used for urine collection following a protocol employed previously for
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International Journal of Hygiene and Environmental Health 221 (2018) 632–641
the measurement of phthalate metabolites, with some modifications
(Kim et al., 2017). Briefly, cloth diapers were purchased and pre-wa-
shed/dried at least four times without detergents in the laboratory.
Mothers were instructed to wash their hands before squeezing the wet
diapers to prevent potential contamination, and to collect urine in a
sterilized collection cup. A detailed instructional video with a demon-
stration was also prepared and provided. For toddlers, the urine were
collected using sterilized collection cups, as all the participating tod-
dlers were toilet-trained. For this sampling, the same protocol as the
sampling for children, adolescents, and adults was used. Immediately
after the collection, urine samples were moved into the tubes, and
stored in a home freezer (−20 °C). Later, the samples were shipped in a
cooler with ice packs to keep them cold (< −4 °C) during the delivery
to the laboratory. Most of the samples were delivered within 24 h (all
within three working days). Upon delivery to the laboratory, urine
samples were stored at −40 °C until analysis. Since stability of the
urinary phenolics under −20 °C has not been guaranteed and potential
degradation could be an issue, the storage duration in the home freezer
was limited as short as possible (average 4.6 d, SD 7.4 d). A self-ad-
ministered questionnaire was filled out and provided information on
the demographic parameters, average frequency of personal care pro-
duct use within the previous 1–2 months, and average frequency of
food consumption within a year. For infants, toddlers, and children,
their parents or guardians were instructed to answer the questionnaire
on their behalf. The Institutional Review Board of Seoul National Uni-
versity approved the study (Approval No. 1506-002-004), and informed
consent was obtained from each of the participants or their parents/
guardians.
2.2. Chemical analysis
Four major parabens, including MeP, EtP, PrP, and BuP, and tri-
closan were measured in both night-time and first-morning urine.
Target chemicals, internal standards, i.e., 13C6-MeP, 13C6-EtP, 13C6-PrP,
13
C6-BuP, and 13C12-triclosan, and β-glucuronidase (Helix pomatia, H1)
were purchased from Sigma-Aldrich (St. Louis, MO, U.S.A.). The urine
samples were treated and analyzed following the methods of Ye et al.
(2005, 2006) with some modifications. Briefly, 500 μL of urine sample
was mixed with 10 μL of 2 μg/mL internal standard solution, 20 μL of a
β-glucuronidase/sulfatase solution (10,000 units/mL), and 100 μL of
1 M ammonium acetate buffer (pH 6.5). After a 4 h incubation at 37 °C
and a 10 min sonication, 100 μL of 0.1 M formic acid was added.
Samples were then centrifuged at 10,000 rpm for 10 min, and the su-
pernatant was analyzed by an online solid-phase extraction-liquid
chromatography–tandem mass spectrometry (SPE–HPLC–MS/MS)
system. HPLC analysis was performed on a Nexera system (Shimadzu,
Kyoto, Japan) equipped with an autosampler, dual pump, column oven,
vacuum degasser and switching valve. An SPE column in gradient mode
was employed. The target compounds were detected by an API 4000
triple quadrupole mass spectrometer (Applied Biosystems, Foster City,
CA, U.S.A.). The detailed HPLC and mass spectrometer conditions are
described in Tables S1 and S2 of the Supplementary material, respec-
tively.
For quality assurance, procedure blanks were included for each in-
strumental run. Five field blanks, including four for polypropylene
tubes and one for cloth diapers, and two trip blanks were analyzed, and
no target chemicals were detected above quantifiable concentrations.
Accuracy was considered to be acceptable when deviations from the
nominal spiked value were within 20%. Precision was considered to be
acceptable when the intra- and inter-day coefficients of variation were
within 20%. Both the accuracy and precision of analysis for each
compound in this study were within the acceptable range (Table S3).
The limits of detection (LODs) were 0.2 μg/L for MeP, 0.5 μg/L for EtP,
0.1 μg/L for PrP, 0.2 μg/L for BuP, and 0.3 μg/L for triclosan.
Additionally, for external quality assurance, we performed a cross-
validation of the analytical procedure with a subset of the samples
S. Kim et al. International Journal of Hygiene and Environmental Health 221 (2018) 632–641

representing the full bandwidth of the urinary paraben concentrations Table 1

(6–9% of the total samples, blinded) among Seoul National University Socio-demographic and behavioral characteristics of the study population.
(Seoul, Republic of Korea), Eulji University (Seongnam, Republic of Characteristic N (%) or Mean ± SD
Korea) (Kang et al., 2013), or Institute of the Ruhr-University (Bochum,
Germany) (Moos et al., 2014). We obtained excellent agreement of the Gender
results with correlation coefficients R2 > 99 and slopes between 0.88 Male 108 (41)
Female 153 (59)
and 1.27. The results of one exemplary comparison for EtP are depicted Age (years)
in Supplementary Fig. S1. 0–2 31 (12)
Furthermore, in a subset of urine samples (n = 32), we also tested 3–6 45 (17)
the conjugation status of the metabolites by performing analyses with 7–12 48 (18)
13–18 46 (18)
and without enzymatic deconjugation. In most of the samples, we could
19–29 8 (3.1)
not detect any free parabens, with their maximum free concentrations 30–39 58 (22)
at the 95th percentile representing 3.5% of the total MeP and 1.3% of 40–49 23 (8.8)
the total EtP. For triclosan, we could not detect any free form next to ≥50 2 (0.8)
the conjugates. Via these conjugation analyses, we were able to exclude Missing 1 (0.4)
Smoking status in the family
any significant influence of external contamination on the results. Never 111 (43)
For the specific gravity (SG) and creatinine measurements, aliquots Former 55 (21)
of urine samples were transferred to a commercial laboratory (Green Current 44 (17)
Cross LabCell, Yongin, Gyeonggi, Korea) and measured using the ki- Missinga 51 (20)
Monthly household incomeb (KRW)
netic colometry assay and reflection refractometry, respectively. The
≤990,000 5 (1.9)
urinary concentrations of parabens and triclosan were adjusted by the 1,000,000–2,990,000 33 (13)
specific gravity of the urine using the following formula (Meeker et al., 3,000,000–5,990,000 114 (44)
2011) > 6,000,000 81 (31)
Missinga 28 (11)
CSG = C [(SGagegroup − 1)/SG−1] Highest education levelc
≤High school 6 (2.3)
where CSG is the SG-adjusted concentration (μg/L), C is the measured University 118 (45)
concentration of parabens or triclosan in urine (μg/L), SGagegroup is the Graduate school 69 (26)
median specific gravity value of a given age group (no unit), and SG is Missinga 68 (26)

the measured value of the urine sample (no unit). For adolescents and
adults, SGagegroup by gender was employed to adjust the urinary mea-
surements. Because of the high variation in the creatinine concentra-
tions by age and gender, we used SG adjustment in the statistical
analyses. The creatinine-adjusted values are also reported in the
Supplementary material for comparison purposes with other published
data. For the SG or creatinine adjustment, missing values for specific
gravity (n = 3 in night-time urine; n = 25 in first-morning urine) and
the creatinine concentration (n = 23 in first-morning urine) were re-
placed with age-specific (for infants to children) or age/gender-specific
(for adolescents and adults) median values (Table S4).
2.3. Statistical analysis
Statistical analyses were performed for the SG-adjusted urinary
concentrations, but only for analytes with a detection frequency >
50%. Non-detects were assigned with LODs divided by the square root
of 2 (Hornung and Reed, 1990). The normality of the distribution was
confirmed using the Shapiro-Wilk test, and data analyses were con-
ducted accordingly. Spearman’s correlation coefficients were used to
determine the correlations among parabens and triclosan. To assess
differences in the urinary chemical concentrations by gender and age,
the Mann–Whitney U test and Jonckheere-Terpstra were used, respec-
tively. For paired comparisons between night-time and first-morning
urine measurements, the Wilcoxon signed rank test was conducted.
To explore the exposure sources of parabens in urine, multivariate
linear regression analyses were conducted by age group. Adolescents
were excluded from the regression analysis because of their low re-
sponse rate to the questionnaire (56%). The response rates for the other
age groups were 100%. Covariates that had been reported to be po-
tential confounding variables in previous studies were added to the
regression models. These variables included gender (dichotomous), age
(continuous), smoking in the family (categorical), body weight (con-
tinuous), household income (categorical), and education level (cate-
gorical). For the education variable in the young population, the edu-
cation level of the parents was used. Missing values for body weight
(n = 10) were replaced with age-specific (for infants to children), or
a
Missing values are mostly due to the low response rate (56%) among
adolescents.
b
Average monthly income during the immediate past 6 months.
c
For subjects ≤ 18 years old, parents’ education levels were employed.
age/gender-specific (for adults) median values (Table S5). Different
covariates, depending on the age group and respective target com-
pound, were determined using a stepwise selection method and were
included in the final statistical models. Because the urinary con-
centration of triclosan did not meet the normality assumption, Mann-
Whitney or Kruskal-Wallis nonparametric tests were conducted to
compare the categorized sub-groups.
All data analyses were performed using SAS version 9.4 (SAS
Institute Inc., Cary, NC, U.S.A.). Box-plots were generated with
SigmaPlot version 10.0 (Systat Software Inc., San Jose, CA, U.S.A.).
3. Results
3.1. Parabens and triclosan concentrations in urine
The demographic and behavior-related characteristics of the parti-
cipating subjects are summarized in Table 1. Specific gravity and the
creatinine-adjusted concentrations along with the unadjusted con-
centrations of the four parabens and triclosan can be found in Tables S6
(night-time urine) and S7 (first-morning urine).
MeP and EtP were detected most frequently, i.e., in 91–98% of the
samples, followed by PrP and triclosan, which were detected in 55–66%
of the samples (Table 2). BuP was detected in only 27–28% of the urine
samples; therefore, subsequent statistical analysis was not performed
for this compound.
In both night-time and first-morning urine, EtP was detected at the
highest concentrations, followed by MeP, PrP, and triclosan. EtP was
detected at higher concentration in night-time urine (median 32.4 μg/L)
compared to first-morning voids (median 19.2 μg/L). However, this
diurnal difference was not observed for MeP, PrP and triclosan.
Between the urinary MeP and PrP concentrations, a significant po-
sitive correlation was detected for night-time urine samples (Fig. 1,

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Table 2
Parabens and triclosan in night-time and first-morning urine samples by gender and age group (unadjusted; μg/L).
Night-time urine

MeP EtP PrP BuP Triclosan

N (M/F) DF Median (IQR) DF Median (IQR) DF Median (IQR) DF Median (IQR) DF Median (IQR)

All 261 (108/ 91.2 9.9 (3.5, 98.1 32.4 (8.4, 82.8) 58.2 0.6 (< LOD, 6.2) 28.4 < LOD (< LOD, < LOD) 55.2 0.4 (< LOD, 1.4)
153) 39.8)
Age group
0−2 31 (14/17) 90.3 7.0 (3.2, 96.8 23.6 (2.7, 41.4) 61.3 0.7 (< LOD, 4.1) 45.2 < LOD (< LOD, 0.345) 41.9 < LOD (< LOD, 0.9)
39.8)
3–6 45 (23/22) 95.6 10.8 (4.4, 97.8 32.6 (6.9, 63.2) 62.2 0.5 (< LOD, 3.3) 22.2 < LOD (< LOD, < LOD) 71.7 0.5 (< LOD, 2.1)
32.0)
7–12 48 (25/23) 83.3 7.8 (1.0, 93.8 24.6 (3.9, 64.9) 41.7 < LOD (< LOD, 2.7) 22.9 < LOD (< LOD, < LOD) 45.8 < LOD (< LOD, 1.6)
30.9)
13–18 46 (24/22) 84.8 5.4 (2.0, 100 32.9 (7.7, 101) 45.7 < LOD (< LOD, 2.3) 30.4 < LOD (< LOD, < LOD) 58.7 0.4 (< LOD, 1.1)
25.9)
≥19 91 (22/69) 96.7 19.5 (5.0, 100 48.9 (16.0, 182) 70.3 3.1 (< LOD, 27.5 < LOD (< LOD, 0.3) 55.0 0.4 (< LOD, 1.7)
59.7) 12.6)
Gender
Male 108 89.8 9.10 (2.8, 99.1 32.6 (8.2, 80.0) 49.1 < LOD (< LOD, 2.7) 20.4 < LOD (< LOD, < LOD) 58.9 0.3 (< LOD, 1.4)
31.6)
Female 153 92.2 11.6 (3.9, 97.4 31.4 (8.4, 90.1) 64.7 0.9 (< LOD, 34.0 < LOD (< LOD, 1.4) 58.2 0.5 (< LOD, 1.4)
52.1) 10.7)

First-morning urine

MeP EtP PrP BuP Triclosan

N (M/F) DF Median (IQR) DF Median (IQR) DF Median (IQR) DF Median (IQR) DF Median (IQR)

All 261 (108/153) 93.1 15.8 (4.0, 62.0) 95.8 19.2 (5.81, 62.5) 66.3 1.5 (< LOD, 8.8) 27.2 < LOD (< LOD, < LOD) 60.2 0.5 (< LOD, 2.0)
Age group
0–2 31 (14/17) 96.8 14.2 (5.0, 46.2) 83.9 3.97 (0.9, 17.1) 71.0 1.2 (< LOD, 3.1) 35.5 < LOD (< LOD, 0.4) 61.3 0.4 (< LOD, 1.4)
3–6 45 (23/22) 91.1 12.5 (3.2, 94.5) 95.6 16.8 (6.3, 43.7) 68.9 1.1 (< LOD, 4.2) 26.7 < LOD (< LOD, < LOD) 71.1 1.0 (< LOD, 3.0)
7–12 48 (25/23) 89.6 8.55 (2.8, 42.3) 100 13.0 (3.4, 53.0) 56.3 0.7 (< LOD, 8.4) 10.4 < LOD (< LOD, < LOD) 50.0 0.3 (< LOD, 2.8)
13–18 46 (24/22) 91.3 15.8 (2.9, 42.4) 95.7 40.9 (9.2, 123) 60.9 1.7 (< LOD, 11.8) 39.1 < LOD (< LOD, 0.3) 60.9 0.4 (< LOD, 1.1)
≥19 91 (22/69) 95.6 25.5 (7.7, 93.2) 97.8 30.2 (9.1, 75.3) 71.4 2.5 (< LOD, 12.4) 27.5 < LOD (< LOD, < LOD) 59.3 0.5 (< LOD, 1.9)
Gender
Male 108 90.7 11.1 (3.7, 48.2) 98.2 19.4 (5.9, 67.1) 59.3 0.8 (< LOD, 5.9) 20.4 < LOD (< LOD, < LOD) 62.0 0.5 (< LOD, 2.1)
Female 153 94.8 19.2 (4.2, 69.5) 94.1 19.2 (5.2, 56.8) 71.2 1.8 (< LOD, 11.0) 32.0 < LOD (< LOD, < LOD) 58.8 0.5 (< LOD, 2.0)

DF, detection frequency (%); IQR, interquartile range; LOD, limit of detection. The LODs were 0.2 μg/L for MeP, 0.5 μg/L for EtP, 0.1 μg/L for PrP, 0.2 μg/L for BuP,
and 0.3 μg/L for triclosan.

rho = 0.61, p < 0.05). Even after stratifying by gender or age group,
the significant correlations between the two compounds remained (Fig.
S2). The correlation observed in night-time urine became weaker the
next morning, but was still significant (Fig. 1).
3.2. Parabens and triclosan concentrations by gender and age
Compared to males, the urinary concentrations of MeP and PrP were
higher among females, but only in night-time urine (Fig. 2).
For EtP, the concentration measured in first-morning urine was
significantly lower than that measured in night-time urine (Fig. 3). The
concentrations of MeP and PrP appeared to be higher in first morning
voids, but differences did not reach statistical significance.
Significant age-dependent increasing trends were observed for MeP,
EtP, and PrP in both night-time and first-void urine (Fig. 4, p < 0.05;
based on non-parametric Jonckheere-Terpstra test). Especially in first-
morning voids, adolescents (13–18 years) and adults (≥19 years)
showed > 7-fold (median: 48.0 μg/L) and > 5-fold (median: 33.0 μg/L)
higher concentrations of EtP, respectively, compared to those measured
in infants (median: 6.48 μg/L), based on the SG-adjusted concentrations

Fig. 1. Spearman’s correlation coefficients between the specific gravity-adjusted concentrations of parabens and triclosan in (A) night-time and (B) first-morning
urine among a Korean population (n = 261). All of the urinary concentrations were log-transformed prior to the analysis. Asterisks (p* < 0.05) indicate a significant
correlation.

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Fig. 2. Comparison of the urinary paraben and triclosan

concentrations in night-time and first-morning urine by
gender. The solid lines of the box represent, from the bottom
upward, the Q1 (25th percentile), Q2 (median or 50th per-
centile), and Q3 (75th percentile) values. Whisker caps denote
the 10th and 90th percentiles, and dots show outliers.
Asterisks (p* < 0.05; Mann–Whitney U test) indicate a sig-
nificant difference between genders.

Fig. 3. Comparison of the urinary paraben and triclosan concentrations by sample collection time. Asterisks (p* < 0.05; Wilcoxon signed-rank test) indicate a
significant difference by sampling time. N: night-time urine, F: first-morning urine.

Fig. 4. Comparison of the urinary paraben and

triclosan concentrations in night-time and first-
morning urine by age group. The solid lines of
the box represent, from the bottom upwards,
the Q1 (25th percentile), Q2 (median or 50th
percentile), and Q3 (75th percentile) values.
Whisker caps denote the 10th and 90th per-
centiles, and dots show outliers.

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Table 3
Associations between urinary methyl paraben, ethyl paraben, and propyl paraben concentrations (μg/L) and potential exposure sources among the participating
adults (n = 91).
Variables Category N MeP EtP PrP

Night-time First-morning Night-time First-morning Night-time First-morning

Median βa Median βa Median βb Median βb Median βc Median βc

Skin care products Less than daily/ 16 5.1 0.65* 23.3 0.25 50.0 0.03 31.0 0.16 0.7 0.37 1.2 0.26
never
Daily or more 71 31.0 28.3 65.6 33.5 4.1 3.2
Body lotion Less than daily/ 62 28.9 −0.02 24.4 −0.11 48.9 0.10 33.3 −0.03 2.1 0.27 1.7 0.31
never
Daily or more 22 26.1 32.7 73.0 30.7 6.8 6.6
Fragrance No 58 16.7 0.28 17.0 0.41 45.7 0.21 19.8 0.17 1.9 0.15 1.7 0.15
Yes 17 63.6 65.6 91.1 49.0 12.4 6.6
Nail polish No 52 20.3 0.17 18.1 0.07 45.3 0.12 30.9 0.00 1.3 0.17 1.6 0.03
Yes 21 32.2 34.1 53.2 19.9 6.9 4.6
Colored cosmetics (facial makeup, eye Seldom/never 49 20.0 0.39# 18.2 0.19 50.7 −0.10 35.8 −0.33# 1.2 0.46* 1.6 0.32
makeup, lipsticks, etc.) Every second day 27 73.8 48.5 38.0 17.1 11.9 6.6
or more
Sunscreen Seldom/never 43 20.0 0.16 18.2 0.16 61.2 −0.02 36.1 −0.02 0.8 0.40# 1.5 0.39#
Every second day 37 32.2 35.9 51.5 27.3 8.4 5.3
or more
Hand cream Less than daily/ 58 18.1 0.14 19.8 −0.03 48.9 −0.00 30.1 −0.03 1.2 0.55* 1.6 0.23
never
Daily or more 20 47.7 32.7 59.4 30.7 9.2 5.8
Bath products (shampoo, hair Less than daily/ 23 4.9 0.48* 13.42 0.20 23.0 0.53* 13.4 0.53* 0.7 0.50* 1.0 0.44*
conditioner or body wash) never
Daily or more 60 31.6 33.9 64.1 35.9 5.1 4.6
Liquid soap Less than daily/ 43 28.4 −0.16 25.9 −0.26 43.9 0.05 33.5 −0.06 2.0 0.06 2.3 −0.02
never
Daily or more 35 16.3 20.5 53.2 18.9 3.20 2.4
Hair spray or hair gel No 51 12.1 0.37 18.2 0.27 47.6 0.14 18.9 0.22 1.2 0.20 1.6 0.19
Yes 23 47.6 48.5 70.0 33.5 6.6 2.5
Toothpaste Twice a day or less 44 9.07 0.56* 18.2 0.40* 43.9 0.27# 17.1 0.36* 0.8 0.41* 1.4 0.43*
More than three 44 33.1 38.5 70.5 40.0 5.3 4.6
times a day
Mouthwash No 44 19.0 0.21 18.1 0.45* 67.8 0.02 33.2 0.05 1.9 0.10 2.1 0.32
Yes 45 41.1 73.3 49.3 33.0 6.6 4.7
Drinking water Tap water 12 17.6 0.075 13.9 0.15 63.4 0.02 28.4 −0.04 1.6 0.20 0.8 0.00
Water purifier 56 28.1 41.1 58.2 35.9 1.9 4.6
Bottled water 21 31.5 34.1 47.6 20.6 6.9 2.4
Vinyl food packaging Once a month or 48 16.7 0.46* 20.5 0.24 51.1 0.13 33.3 −0.02 1.9 0.24 2.8 −0.03
less
Several times per 37 51.0 48.5 73.8 34.1 4.6 2.4
month
Canned food Once a month or 64 11.3 0.39* 15.8 0.28 53.5 0.07 27.3 0.11 3.1 0.05 2.6 −0.03
less
Several times per 25 30.1 37.5 61.2 35.8 3.2 2.5
month
Paste source Once a week or 37 30.3 −0.03 33.9 −0.11 68.1 0.15 39.1 0.11 3.9 −0.02 3.6 −0.04
less
Several times per 49 28.9 21.2 51.1 33.3 2.8 2.2
week
Jam Once a month or 34 16.7 0.11 27.3 0.05 57.1 0.00 35.1 −0.10 1.2 0.09 2.8 −0.05
less
　 Several times per 55 30.1 　 28.3 　 53.8 　 32.9 　 4.6 　 2.5 　
month

Sign * indicates statistical significance at p = 0.05. For p > 0.05 but < 0.1, # sign was shown.
a
Urinary concentrations were log–transformed. The results of the association were adjusted for gender, household income, and education level.
b
Urinary concentrations were log–transformed. The results of the association were adjusted for household income and smoking in family.
c
Urinary concentrations were log–transformed. The results of the association were adjusted for age and education level.

(Table S7). who used mouthwash and those with more frequent contact with vinyl
food packaging and canned food. Frequent use of colored cosmetics was
positively associated with higher concentrations of PrP. Unlike MeP and
3.3. Potential sources of exposure
PrP, the urinary EtP concentrations were not significantly associated
with a frequent use of personal care products, except bath products and
Among adults (n = 91, for the socio-demographic and behavioral
toothpaste.
characteristics, refer to Table S8), the urinary MeP, EtP, and PrP con-
The triclosan concentrations in both night-time and first-morning
centrations were significantly associated with frequent use of bath
voids were also higher among people who frequently used bath pro-
products (including shampoo, hair conditioner, and body wash) or the
ducts (p < 0.1; Table S9). In addition, the concentrations of triclosan
use of toothpaste in night-time and/or first-morning void (Table 3). The
in night-time urine were significantly associated with the source of
urinary concentrations of MeP were significantly higher among adults

637
S. Kim et al. International Journal of Hygiene and Environmental Health 221 (2018) 632–641

Table 4
Urinary concentrations of parabens and triclosan (μg/L) reported in the present study and elsewhere.
Country Sampling year N Population (years of age) Urine type Median urinary concentrations (μg/L) Reference

MeP EtP PrP BuP Triclosan

Population in different age groups

Korea 2015 261 Population (0–72) Spota 9.87 32.4 0.614 < LOD 0.374 This study
Korea 2009–2010 2541 Population (3–69) Spot 166 32.8 15.5 0.51 – Kang et al. (2016)
Belgium 2013 261 Population (1–85) Spot 16.1 1.7 1.2 < LOD – Dewalque et al. (2014)
Belgium 2011 131 Population (1–75) First-morning – – – – 2.24 Pirard et al. (2012)
Greece 2012 100 Population (2.5–87) Spot 11.6 2.0 5.3 0.9 5.8 Asimakopoulos et al. (2014)
U.S.A. 2011–2012 2489 Population (6–80) Spot 45.6 < LOD 5.6 < LOD 6.8 CDC (2015)d
U.S.A. 2009–2010 2749 Population (6–80) Spot 60.3 < LOD 6.6 < LOD 9.7 CDC (2015)d
Infants, toddlers, children, and adolescents
Korea 2015 31 Infants (0–2) Spota 7.03 23.6 0.719 < LOD < LOD This study
　 　 45 Toddlers (3–6) Spota 10.8 32.6 0.511 < LOD 0.543 This study
　 　 48 Children (7–12) Spota 7.81 24.6 < LOD < LOD < LOD This study
　 　 46 Adolescents (13–18) Spota 5.43 32.9 < LOD < LOD 0.436 This study
Korea 2011 46 Newborn infants Spot 79.6 2.4 3.4 < LOD – Kang et al. (2013)
Korea 2009–2010 659 Children (3–12) Spot 71.6 8.82 3.61 0.33 – Kang et al. (2016)
Korea 2009–2010 359 Adolescents (13–18) Spot 135 21.7 6.54 0.33 – Kang et al. (2016)
China 2012 70 Children (9–10) Spot 3.66 0.62 1.49 0.03 – Wang et al. (2013)
Belgium 2013 48 Infants, toddlers, and children (1–11) Spot 18.6 1.1 1.1 0.5 – Dewalque et al. (2014)
Belgium 2011 23 Infants and toddlers (1–6) First-morning 34.8 2.3 2.1 0.8 – Pirard et al. (2012)
25 Children (7–11) First-morning 9.1 0.7 0.8 < LOD – Pirard et al. (2012)
30 Adolescents (12–19) First-morning 18 1.1 4.2 < LOD – Pirard et al. (2012)
Denmark 2011 143 Children (6–11) Spot 3 0.4 < LODb < LODc 0.46 Frederiksen et al. (2013)
Sweden – 80 Children (6–11) First-morning 5.3 0.66 1.9 < LOD < LOD Larsson et al. (2014)
U.S.A. 2012 40 Toddlers and children (3–10) Spot 51.8 0.15 0.99 < LOQ – Wang et al. (2013)
U.S.A. 2009–2010 415 Children (6–11) Spot 31.6 < LOD 3.6 < LOD 9.5 CDC (2015)d
420 Adolescents (12–19) Spot 72.2 < LOD 9.4 < LOD 8.7 CDC (2015)d
U.S.A. 2011–2012 396 Children (6–11) Spot 20.2 < LOD 2.2 < LOD 5.4 CDC (2015)d
388 Adolescents (12–19) Spot 40.65 < LOD 5.2 < LOD 6.8 CDC (2015)d
Adults
Korea 2015 91 Adults (≥19) Spota 19.5 48.9 3.12 < LOD 0.433 This study
Korea 2009–2010 1523 Adults (≥19) Spot 254 53.4 24.0 1.97 – Kang et al. (2016)
Korea 2009 1870 Adults (18–69) Spot – – – – 1.53 Kim et al. (2011)
China 2010 26 Young adults (mostly 22–30) Spot 19.5 0.09 4.33 < LOQ – Wang et al. (2013)
Germany 2012 60 Young adults (20–30) 24 h 42.6 1.0 2.2b < LOQc – Moos et al. (2015)
U.S.A. 2011–2012 1705 Adults (20–80) Spot 58.3 < LOD 7.4 < LOD 7.2 CDC (2015)d
U.S.A. 2009–2010 1914 Adults (20–80) Spot 69.6 1.2 7.7 < LOD 10.25 CDC (2015)d
Adult women
Korea 2011 46 Pregnant women Spot 134 38 6.6 < LOD – Kang et al. (2013)
Japan 2007–2010 111 Pregnant women Spot 75.8 7.53 20.2b 0.59c – Shirai et al. (2013)
Puerto Rico 2010–2012 105 Pregnant women Spot 153 – 36.7 0.4 26.2 Meeker et al. (2013)
Denmark 2011 145 Mothers Spot 14 0.89 1.7b < LODc 0.64 Frederiksen et al. (2013)
Sweden – 76 Mothers First-morning 40 2.4 18 < LOD < LOD Larsson et al. (2014)
Adult men
U.S.A. 2004–2015 400 Men (23.9–66.6) Repeated spot 23.2 – 2.30 < LOD – Nassan et al. (2017)

LOD, limit of detection; LOQ, limit of quantification.

a
Night-time urine.
b
n-PrP.
c
n-BuP.
d
NHANES, National Health and Nutrition Survey conducted by the U.S. Centers for Disease Control and Prevention (CDC).

drinking water.
The correlation between mothers and their offspring regarding the
urinary concentrations of parabens and triclosan was negligible in our
study population (Fig. S3). Thus, we did not consider the influence of
potential exposure sources shared within a family in the analysis. In this
study, significant associations with potential exposure sources were less
obvious in younger age groups, including infants, toddlers, and children
(data not shown).
4. Discussion
The concentrations of urinary EtP in a Korean population were
higher than those reported elsewhere, but the concentrations of the
other parabens and triclosan were generally lower or comparable
(Table 4). The urinary EtP concentrations observed in the present po-
pulation were notably higher than those previously reported from other
countries, including Belgium, Greece, China, Denmark, Sweden,
Germany, Japan (Asimakopoulos et al., 2014; Dewalque et al., 2014;
Frederiksen et al., 2013; Larsson et al., 2014; Moos et al., 2015; Wang
et al., 2013), and the United States (calculated from datasets of
NHANES 2009–2010, 2011–2012 provided by CDC, 2015), regardless
of the age of the subjects. Among Koreans, relatively high concentra-
tions of urinary EtP have also been reported previously (Table 4, Kang
et al., 2013; Kang et al., 2016). The median urinary concentration of
EtP among the Korean general population (n = 2541), recruited from
2009 to 2010, was 32.8 μg/L (interquartile range: 6.61–113 μg/L)
(Kang et al., 2016), which is very similar to that detected in the present
study (32.4 μg/L; 8.37-82.8 μg/L). Our previous study on the urinary
paraben concentrations of pregnant women (n = 46) in Korea (Kang
et al., 2013) also reported similar concentrations of urinary EtP.
In contrast, the median MeP concentration observed among adults
in the present study was similar to that of a Chinese population (Wang
et al., 2013), but lower than those reported for the German and United
States’ populations (Moos et al., 2015; CDC, 2015). The urinary

638
S. Kim et al.
detection frequency and concentration of triclosan among the present
population were also lower compared to those reported elsewhere
(Frederiksen et al., 2013; Kim et al., 2011; Meeker et al., 2013). BuP
was least frequently detected among the present population, which is in
accordance with previous studies (Dewalque et al., 2014; Frederiksen
et al., 2013; Larsson et al., 2014).
Among the present population, the use of bath products, such as
shampoo, hair conditioner, or body wash, was associated with higher
urinary concentrations of EtP (Table 3). It should be noted that the use
of bath products was also associated with higher concentrations of
other parabens measured (Table 3), suggesting a possibility that bath
products may serve as a common exposure source for major parabens.
There were no gender-related differences in the EtP concentrations in
the present population (Fig. 2), while among Belgian and German
adults, females showed significantly higher urinary concentrations of
all four parabens, including EtP (Dewalque et al., 2014; Moos et al.,
2015). These observations suggest the presence of exposure sources of
EtP that are not related to gender in Korea. One potential exposure
source of EtP among Koreans might be diet, as EtP is permitted as a food
preservative in jam (1.0 g/kg), pastes (0.25 g/kg), sauces (0.2 g/kg),
and beverages (0.1 g/L) by the Ministry of Food and Drug Safety of
Korea. EtP was detected at higher concentrations than MeP in bev-
erages in the United States (Liao et al., 2013b) and in condiments in
China (Liao et al., 2013a). The observation of higher EtP concentrations
in night-time urine compared to first-morning urine, unlike other
measured compounds (Fig. 3), may provide another hint regarding the
possible sources of EtP exposure among Koreans. Further efforts to
identify possible sources of exposure in the Korean population are
warranted.
Many studies have associated urinary paraben concentrations with
the use of personal care products (Braun et al., 2014; Fisher et al., 2017;
Koch et al., 2014; Larsson et al., 2014; Nassan et al., 2017; Meeker
et al., 2013; Philippat et al., 2015). In the present study, we also ob-
served that urinary MeP and PrP concentrations were significantly as-
sociated with the frequent use of skin care products, cosmetics, hand
cream, and fragrance, especially in night-time urine (Table 3). The
observation of higher MeP and PrP concentrations among females in
night-time urine (Fig. 2) may outline the importance of these exposure
sources compared to males, because females use more of these personal
care products during the daytime (Biesterbos et al., 2013).
The strong and significant correlation between the urinary MeP and
PrP concentrations found in our present study (Fig. 1) is comparable to
those reported in several other studies on the populations of China,
Germany, Greece, and the United States (Asimakopoulos et al., 2014;
Calafat et al., 2009; Ma et al., 2013; Moos et al., 2015; Philippat et al.,
2015; Wang et al., 2013). This correlation indicates overlapping source
characteristics for both parabens among our study populations from
Korea. In fact, MeP and PrP have been used in combination in many
consumer products, e.g., cosmetics, and toothpastes, to generate a
stronger antimicrobial activity. As usage patterns might differ by
country, correlations among parabens may also vary. In agreement with
our data, no significant correlations were observed between EtP and
MeP in the urine of Japanese women and Chinese young adults (Ma
et al., 2013; Shirai et al., 2013). However, significant correlations be-
tween urinary EtP and MeP were observed among German adults
(r = 0.553, p < 0.0001) and Swedish mothers (r = 0.38, p < 0.0001)
(Larsson et al., 2014; Moos et al., 2015). The apparent inconsistency
between European and Asian studies might represent different patterns
of paraben use in consumer products from one country to another.
Significant increases in urinary MeP, EtP, and PrP concentrations by
age in both night-time and first-morning urine samples (Fig. 4) possibly
suggest the presence of age-dependent exposure sources for these major
parabens among the study population. Increased urinary MeP and PrP
concentrations by age have been reported from NHANES 2009–2012
(CDC, 2015), but have not been observed among a smaller sized Belgian
population (n = 131, Pirard et al., 2012).
639
International Journal of Hygiene and Environmental Health 221 (2018) 632–641
As for the triclosan concentrations in urine, the use of bath products
was determined to be associated with both night-time and first-morning
urine at marginal significance (Table S9). Similarly, in Puerto Rico, the
urinary triclosan concentrations were higher among those using liquid
soap and hairspray compared to those who did not (Meeker et al.,
2013). In addition, those drinking bottled water showed higher urinary
triclosan concentrations compared to those drinking tap water in our
present study. The source of drinking water has been considered to be
one of the important routes of human exposure to triclosan. In China,
18 out of 21 bottled water samples contained triclosan, ranging from
0.6 to 9.7 ng/L, while no triclosan was detected in tap water (Li et al.,
2010). The possibility of additional triclosan exposure through drinking
bottled water warrants further confirmation in other populations. Koch
et al. (2014) reported urinary triclosan concentrations in individuals
using triclosan-containing toothpaste (in the range of 1000–3000 μg/L)
to be 100–1000-fold higher than in non-users. Apparently, the urinary
triclosan concentrations in this study indicate that triclosan is seldom
used in toothpaste in Korea. Consistent with previous studies (Kim
et al., 2011; Pirard et al., 2012), no significant differences were ob-
served for the triclosan concentrations between genders.
The urinary concentrations of parabens and triclosan vary sig-
nificantly, not only day-to-day but also during the day, because of their
short biological half-lives and rapid changes in exposure amount ac-
cording to the use of personal care products, activity patterns, or other
environmental or biological factors (Fisher et al., 2017). Several studies
that reported repeated measurements of those compounds in urine over
time (Braun et al., 2014; Engel et al., 2014; Fisher et al., 2017; Philippat
et al., 2015) have indicated a relatively moderate reproducibility of the
urinary paraben or triclosan concentrations over weeks to months’
periods of time (Engel et al., 2014; Koch et al., 2014; Meeker et al.,
2011; Smith et al., 2012; Teitelbaum et al., 2008). It should be noted
that the concentrations of the study chemicals reported in environ-
mental media such as wastewater and sewage showed seasonal varia-
tions (Chen et al., 2017; Loraine and Pettigrove 2006), and the present
population was recruited only during the late summer and autumn
seasons. Since the usage patterns of certain personal care products vary
by season, seasonal variation in exposure levels to these chemicals
should be considered in future studies.
One strength of this study is that we analyzed exposure to parabens
and triclosan in various age groups in Korea. While a number of studies
have focused only on adolescents or adults, we also examined urine
collected from younger groups, including infants and toddlers.
Additionally, we compared night-time and first-morning urine mea-
surements and the results clearly show that a one-time spot urine
sample may not represent exposure profiles to these chemicals that
occur during the day. However, our study also has some limitations.
Because of a relatively small sample size (n = 261) and the use of
convenience sampling, a simple generalization of the study results is
not possible, and further confirmation in other populations is war-
ranted. The correlations of urinary paraben or triclosan concentrations
between mother-child pairs (n = 78, Fig. S3) or between siblings
(n = 9, data not shown) were generally weak or insignificant in our
present population, but the potential influence of common exposure
sources within a family should not be ignored. Moreover, our analysis
did not fully characterize the exposure sources of target chemicals,
especially EtP. Further studies that are specifically designed to study
this chemical and its possible exposure sources and pathways should be
followed.
5. Conclusions
In both night-time and first-morning urine samples, EtP and MeP
were detected in > 90% of the samples of the Korean population. The
urinary EtP concentrations measured in the study population were
among the highest worldwide, outlining the importance of identifying
sources and exposure pathways among Koreans. For an exposure
S. Kim et al.
assessment of parabens that have various exposure sources and short
biological half-lives, multiple urine samples are required to reflect re-
presentative exposure profiles.
Acknowledgements
This research was supported by a grant (15172MFDS219) from
Ministry of Food and Drug Safety in 2015. This study was also sup-
ported by the Ministry of Environment (MoE) of Korea through the
“Integrated Risk Assessment Method for EDCs (IRAMe;
#2015001940003)”.
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in the
online version, at https://doi.org/10.1016/j.ijheh.2018.03.009.
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