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Box 24885, Safat, 13109, Kuwait e Environmental and Chemistry Group, Sede San Pablo, University of Cartagena, Cartagena, Bolívar 130015, Colombia f Faculty of Chemistry, Hanoi University

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Full length article

A comparative assessment of human exposure to tetrabromobisphenol A

and eight bisphenols including bisphenol A via indoor dust ingestion in

twelve countries

Wei Wanga, Khalid O Abualnajab, Alexandros G Asimakopoulosa, Adrian Covacic, Bondi Gevaod,

Haruhiko Nakatah, Ravindra K Sinhai, Kurunthachalam Kannana,b,⁎

a Wadsworth Center, New York State Department of Health, Department of Environmental Health Sciences, School of Public Health, State University of New York at Albany, Empire State Plaza, P.O Box 509, Albany, NY 12201-0509, United States

b

Biochemistry Department, Faculty of Science, Experimental Biochemistry Unit, King Fahd Medical Research Center, Bioactive Natural Products Research Group, King Abdulaziz University, Jeddah, Saudi Arabia

c

Toxicological Center, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk-Antwerp, Belgium

d Environmental Management Program, Environment and Life Sciences Center, Kuwait Institute for Scientific Research, P.O Box 24885, Safat, 13109, Kuwait

e Environmental and Chemistry Group, Sede San Pablo, University of Cartagena, Cartagena, Bolívar 130015, Colombia

f

Faculty of Chemistry, Hanoi University of Science, Vietnam National University, Hanoi, 19 Le Thanh Tong, Hoan Kiem, Hanoi, Viet Nam

g

Department of Marine Sciences and Convergent Technology, College of Science and Technology, Hanyang University, Ansan, South Korea

h

Graduate School of Science and Technology, Kumamoto University, 2-39-1 Kurokami, Kumamoto 860-8555, Japan

i

Department of Zoology, Patna University, Patna 800 005, India

a b s t r a c t

a r t i c l e i n f o

Article history:

Received 20 April 2015

Received in revised form 22 June 2015

Accepted 25 June 2015

Available online xxxx

Keywords:

TBBPA

BPA

Human exposure

Indoor dust

Microenvironment

Tetrabromobisphenol A (TBBPA) and eight bisphenol analogues (BPs) including bisphenol A (BPA) were deter-mined in 388 indoor (including homes and microenvironments) dust samples collected from 12 countries (China, Colombia, Greece, India, Japan, Kuwait, Pakistan, Romania, Saudi Arabia, South Korea, U.S., and Vietnam) The concentrations of TBBPA and sum of eight bisphenols (ƩBPs) in dust samples ranged from b1 to

3600 and from 13 to 110,000 ng/g, respectively The highest TBBPA concentrations in house dust were found

in samples from Japan (median: 140 ng/g), followed by South Korea (84 ng/g) and China (23 ng/g) The highest

∑BPs concentrations were found in Greece (median: 3900 ng/g), Japan (2600 ng/g) and the U.S (2200 ng/g) Significant variations in BPA concentrations were found in dust samples collected from various microenviron-ments in offices and homes Concentrations of TBBPA in house dust were significantly correlated with BPA and

∑BPs Among the nine target chemicals analyzed, BPA was the predominant compound in dust from all coun-tries The proportion of TBBPA in sum concentrations of nine phenolic compounds analyzed in this study was the highest in dust samples from China (27%) and the lowest in Greece (0.41%) The median estimated daily in-take (EDI) of∑BPs through dust ingestion was the highest in Greece (1.6–17 ng/kg bw/day), Japan (1.3–16) and the U.S (0.89–9.6) for various age groups Nevertheless, in comparison with the reported BPA exposure doses through diet, dust ingestion accounted for less than 10% of the total exposure doses in China and the U.S For TBBPA, the EDI for infants and toddlers ranged from 0.01 to 3.4 ng/kg bw/day, and dust ingestion is an important pathway for exposure accounting for 3.8–35% (median) of exposure doses in China

© 2015 Elsevier Ltd All rights reserved

1 Introduction

Chemical concentrations in residential dust have been used as

surro-gates for indoor chemical exposures in many studies (Whitehead et al.,

2011; Wang et al., 2013a; Ma et al., 2014) Indoor dust is a source of

human exposure to pesticides, polychlorinated biphenyls (PCBs),

polybrominated diphenyl ethers (PBDEs), phthalates, and bisphenols (BPs) (Liao et al., 2012a; Besis and Samara, 2012; Wang et al., 2013b, 2013c, 2013d) Indoor dust is an important source of human exposure

to brominatedflame retardant (BFR) such as PBDEs in North America (Besis and Samara, 2012)

Tetrabromobisphenol A (TBBPA) is the largest production volume BFR, with an annual global production of more than 170,000 t in 2004 and is applied as a reactive or additive FR in polymers, resins, adhesives, and in the manufacture of printed circuit boards and electric equipment (ECB, 2006; Ni and Zeng, 2013) TBBPA released from these products

⁎ Corresponding author at: Wadsworth Center, Empire State Plaza, P.O Box 509, Albany,

NY 12201-0509, United States.

E-mail address: Kurunthachalam.kannan@health.ny.gov (K Kannan).

http://dx.doi.org/10.1016/j.envint.2015.06.015

Contents lists available atScienceDirect Environment International

j o u r n a l h o m e p a g e :w w w e l s e v i e r c o m / l o c a t e / e n v i n t

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can adhere to suspended particulate matter, due to its low vapor

pres-sure (6.24 × 10−6Pa) and high affinity for organic surfaces (log Kow:

7.20) (European Union, 2006) TBBPA has been reported to occur in

in-door dust from Belgium (0.85–1480 ng/g), Japan (490–520 ng/g), and

the UK (b1–382 ng/g) (Geens et al., 2009; Takigami et al., 2009;

Abdallah et al., 2008); Little is known on the occurrence of TBBPA in

in-door dust from other countries and on the relationship of TBBPA with

other bisphenols including BPA (Ma et al., 2014)

With the structural resemblance to the thyroid hormone, thyroxin,

TBBPA can bind to human transthyretin and disrupt thyroid hormone

functions (Covaci et al., 2009) TBBPA's potential as an endocrine

disruptor (EDC) is of concern and several studies have indicated the

thy-roid hormone-like and estrogen receptor-mediated effects of this

com-pound (Kitamura et al., 2002; Ghisari and Bonefeld-Jorgensen, 2005;

Grasselli et al., 2014) TBBPA was reported as a reproductive toxicant

(Van der Ven et al., 2008) Additionally, immunotoxicity, neurotoxicity

and interference of cellular signal pathways have been reported for

TBBPA (Mariussen and Fonnuma, 2003; Pullen et al., 2003; Strack

et al., 2007) In a recent study, TBBPA-mediated uterine cancer has

been shown in rodents exposed under laboratory conditions (Dunnick

et al., 2015)

Bisphenols (BPs) are a group of chemicals with two hydroxyphenyl

functionalities and are used as additives and/or reactive raw materials

in polycarbonate plastics, plastic linings for food containers, dental

seal-ants, and thermo-sensitive coatings for paper products among others

(Song et al., 2014) Among BPs, BPA is widely used in numerous

com-mercial applications and has been produced at over 3,600,000 t annually

worldwide (Liao et al., 2012b) Human exposure to BPA is of concern

be-cause animal and human studies have identified potential health effects

(Liao et al., 2012a; Song et al., 2014) The Canadian Government, the

European Union and the U.S Food and Drug Administration (FDA)

have prohibited BPA-based baby bottles/packaging in 2010, 2011 and

2012, respectively (Government of Canada, 2010; The European

Com-mission, 2011; FDA, 2012) Owing to adverse health effects associated

with exposure to BPA and other BPs, including bisphenol S (BPS, 4,4

′-sulfonyldiphenol) and bisphenol F (BPF, 4,4

′-dihydroxydiphenyl-methane), these chemicals are under scrutiny by various global health

organizations (Zhou et al., 2014; Liao et al., 2012c)

Although diet is an important source of human exposure to

contam-inants such as PCBs and BPA, indoor dust contributes to a considerable

proportion of exposure to certain contaminants, especially in toddlers

(Liao et al., 2012a; Besis and Samara, 2012; Wang et al., 2013d)

Contri-bution of dust to TBBPA exposure in humans is not well known In light

of the above gaps in knowledge, this study was conducted to (1) report

the occurrence and profiles of TBBPA and BPs in indoor dust (home and

other microenvironments) collected from 12 countries, and (2) estimate

human exposure to TBBPA and BPs via dust ingestion

2 Materials and methods

2.1 Sample collection

In total, 388 indoor dust samples were collected from 12 countries,

with 284 samples from homes and 104 from other microenvironments

(laboratories, offices, cars, air conditioner, and e-waste workshop)

(Table S1; Supporting Information) House dust samples (5–50 g) were

collected from select cities in China (CN, number of samples: n = 34),

U.S (US, 22), India (IN, 35), Japan (JP, 14), Greece (GR, 28), Colombia

(CO, 42), Pakistan (PK, 22), Saudi Arabia (SA, 19), South Korea (KR, 16),

Kuwait (KW, 17), Romania (RO, 23), and Vietnam (VN, 12) from 2012

to 2014 Dust samples from laboratories, offices, cars, and public areas

were collected from South Korea (lab, n = 11; office, 14), Kuwait (car,

15), Pakistan (car, 6; office 24), Saudi Arabia (air conditioners in homes,

12; car, 10), and Vietnam (e-waste work shop, 4; public area, 8) We

employed volunteers to collect samples in each country, and these

volun-teers sampled sites for which they had access This approach of

opportunistic sampling is not expected to be representative of the coun-try, but it can obtain a sufficient sample size in the variety of different types of sites (homes, offices, cars, etc.) desired for the study Floor dust samples were obtained from vacuum cleaner bags in each of the sampling sites following the same sampling protocol, with the exception of samples from China and India, which were obtained by sweeping thefloor Only bedrooms and living rooms of homes and apartments (all countries) were selected for sampling All samples were transported to the

laborato-ry at Wadsworth Center, sieved through a 150μm sieve to represent the indoor settled dust, homogenized, packed in clean aluminum foil, and stored at 4 °C until analysis

2.2 Chemicals and reagents BPA, BPS, BPF, bisphenol Z (BPZ), bisphenol AP (BPAP), and bisphenol

AF (BPAF) were obtained from Sigma-Aldrich (St Louis, MO) Bisphenol B (BPB) and TBBPA were purchased from TCI America (Portland, OR) and BOC Sciences (Shirley, NY), respectively Mass-labeled13C-BPA (RING-13C12, 99%) and13C-TBBPA (RING-13C12, 99%) were obtained from Cambridge Isotope Laboratories (Andover, MA) and Wellington Laboratories (Guelph, Ontario, Canada), respectively HPLC grade metha-nol and tetrahydrofuran were supplied by J.T Baker (Phillipsburg, NJ) Ultra-pure water (18.2 Ω) was generated using a Milli-Q system (Millipore, Billerica, MA) Sep-Pak® C18 (1 g, 6 mL) solid-phase extraction cartridges were obtained from Waters (Milford, MA)

2.3 Sample preparation Dust samples were extracted and analyzed by following the method described elsewhere (Liao et al., 2012a; Song et al., 2014), with some modifications Briefly, 0.1 g of sample was weighed and transferred into a 15 mL polypropylene (PP) conical tube After spiking with 20 ng

13

C12-BPA and13C12-TBBPA (internal standards, IS), sample was

extract-ed with a 5 mL solvent mixture of methanol and water (5:3, v/v) by shaking for 60 min The mixture was centrifuged at 4500 g for 5 min (Eppendorf Centrifuge 5804, Hamburg, Germany), and the supernatant was transferred into a glass tube The extraction step was repeated three times with same amount of solvent, and the extracts were combined and concentrated to∼4 mL under a gentle nitrogen stream The solution was diluted to 10 mL with 0.2% formic acid (pH 2.5), and the extracts were loaded onto a Sep-Pak C18 cartridge preconditioned with 5 mL

of methanol and 5 mL of water After loading, the cartridge was washed with 5 mL of water and the analytes were eluted with 4 mL of methanol,

3 mL of tetrahydrofuran/methanol (4:6) and 3 mL of tetrahydrofuran, andfinally concentrated to 1 mL prior to high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) analysis 2.4 Instrumental analysis

The concentrations of BPs were determined with a Shimadzu Prom-inence LC-20 AD HPLC (Shimadzu, Kyoto, Japan) interfaced with an Applied Biosystems API 3200 electrospray triple quadrupole mass spec-trometer (ESI-MS/MS; Applied Biosystems, Foster City, CA) An analyti-cal column (Betasil® C18, 100 × 2.1 mm column; Thermo Electron Corporation, Waltham, MA), connected to a Javelin guard column (Betasil® C18, 20 × 2.1 mm) was used for LC separation TBBPA was de-termined with an Agilent 1260 HPLC (Agilent Technologies Inc., Santa Clara, CA) interfaced with an Applied Biosystems QTRAP 4500 mass spectrometer (ESI-MS/MS; Applied Biosystems, Foster City, CA) An an-alytical column (Ultra Biphenyl USP L11 5μm, 100 × 2.1 mm column; Restek Corporation, Bellefonte, PA), connected to a Javelin guard column (Betasil® C18, 20 × 2.1 mm), was used for LC separation The negative ion multiple reaction monitoring (MRM) mode was used The MS/MS parameters were optimized by infusion of individual com-pounds into the MS through aflow injection system (Table S2) The

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MRM transitions of ions monitored are listed in Table S3 Nitrogen was

used as both a curtain and a collision gas

2.5 Quality assurance and quality control (QA/QC)

With each set of 20 samples analyzed, a procedural blank, a spiked

blank (containing water instead of dust), a pair of matrix spike samples

(20 ng), and duplicate samples were analyzed Trace levels of BPA and

BPF (approximately 0.25 and 0.34 ng/g, respectively) were found in

pro-cedural blanks, and background subtraction was performed for these

compounds in the quantification of concentrations Recoveries of BPs

in spiked matrices ranged from 78.3 ± 24.0% for BPB to 105 ± 29.5%

for BPAF (Table S3) Duplicate analysis of randomly selected samples

showed a coefficient variation of b20% for BPs and TBBPA The limits

of quantification (LOQs) were 0.1 ng/g for BPAF, 0.5 ng/g for BPA,

BPAP and BPZ, 1 ng/g for BPF, BPB and TBBPA, and 2.0 ng/g for BPS

and BPP (Table S3), which were calculated from the lowest acceptable

calibration standard and a nominal sample weight of 0.1 g A midpoint

calibration standard (in methanol) was injected as a check for

instru-mental drift in sensitivity after every 20 samples, and a pure solvent

(methanol) was injected as a check for carry-over from sample to

sam-ple Instrumental calibration was verified by injection of 10 calibration

standards (ranging from 0.02 to 100 ng/g), and the linearity of the

cali-bration curve (r) wasN0.99 Concentrations of TBBPA and BPs in the

fourth extraction with a mixture of methanol and water (5:3, v/v) for

15 randomly selected dust samples wereb1% of the concentrations

found in thefirst three extractions, which indicated that the three

ex-traction cycles completely extracted the target chemicals For ease of

discussion and exposure assessment, dust from homes and other

micro-environments were segregated

2.6 Calculation of exposure doses

The median and 95th percentile concentrations of the target

analytes measured in home dust were applied for the estimation of

median and high scenarios for daily intakes (EDI; ng/kg bw/day),

re-spectively, through dust ingestion, as shown in Eq.(1)

where C is the TBBPA/BPs concentration in measured house dust (ng/g),

DIR is the dust ingestion rate (g/day), and BW is the body weight (kg) In

this study, only a limited number of samples were analyzed from offices,

cars and other public places Therefore, only residential dust exposures

were taken into account, with median and high exposure profiles, based

on the median and the 95th percentile concentrations of the

contami-nants in house dust The dust intake rate was applied as 0.03, 0.06,

0.06, 0.06, 0.03 g/d for infants (b1 year), toddlers (1–5 year), children

(6–10 year), teenagers (11–20 year) and adults (N20 year),

respective-ly, by following the data reported elsewhere (US EPA, 2011) The

respective average body weights for infants, toddlers, children,

teen-agers and adults in Asian countries were 5, 19, 29, 53, and 63 kg, as

re-ported for China (Guo and Kannan, 2011; Liao et al., 2012a), while the

values for U.S., Colombia, and European countries were 7, 15, 32, 64, and

80 kg as reported for the U.S (US EPA, 2011) Considering the low

concen-trations of other bisphenol analogues, such as BPB, only the exposure

doses for BPA, BPS, BPF,∑BPs and TBBPA were calculated in this study

Details of the parameters used in EDI calculation are shown in Table S4

2.7 Statistical analysis

Statistical analyses were performed with Origin ver 8 (for profile

analyses and box plot) and SPSS 16.0 software (for correlation analyses,

test for normality and ANOVA) Normality of the data was checked by

Shapiro–Wilk test The 95% upper confidence limit (UCL) was calculated

using ProUCL 4.0 Concentrations below the LOQ were substituted with

a value equal to LOQ divided by the square root of 2 for the calculation of geometric mean (GM) Differences between groups were compared using a one-way ANOVA followed by a Tukey test Prior to one-way ANOVA, the data were log-transformed to meet the normality assump-tions Spearman correlation was used to investigate the relationship be-tween BPs and TBBPA concentrations The probability value of p≤ 0.05 was set for statistical significance

3 Results and discussion 3.1 TBBPA in house dust

In spite of the limited sample size for individual countries, this study describes the widespread occurrence of TBBPA in indoor dust TBBPA was found in 80% of house dust samples at a concentration that ranged fromb1 to 2300 ng/g (Table 1) High concentrations of TBBPA were found in house dust from Japan (range: 12–1400 ng/g), South Korea (43–370 ng/g) and China (b1–2300 ng/g) and the concentrations found in these three countries were 10 to 100 times higher than the concentrations found in the other countries studied Relatively lower concentrations of TBBPA were found in dust from Colombia (b1–280 ng/g), Romania (b1–380), Kuwait (b1–36) and Greece (b1–630)

In 2001, the highest TBBPA consumption was registered in Asia (89,400 t/year) (Covaci et al., 2009) Considering the high market de-mand for thisflame retardant in eastern Asian countries, high concen-trations of TBBPA found in dust from Japan, South Korea, and China can be related to the emission from commercial products The median concentrations of TBBPA in house dust were in the following decreasing order: Japan (140 ng/g)N South Korea (84) N China (23) N the U.S (20) N Saudi Arabia (18) N Greece (11) N India (9.0) N Kuwait (8.4)N Pakistan (7.2) N Romania (6.0) N Colombia (3.3) N Vietnam (1.6) (Fig 1) In comparison with the reported median concentra-tions of PBDEs in indoor dust from China (median: 739–1940 ng/g) (Kang et al., 2011), the U.S (1910–21,000) (Johnson-Restrepo and Kannan, 2009; Batterman et al., 2009), Kuwait (90) (Gevao et al., 2006) and Japan (485–700) (Suzuki et al., 2006; Takigami et al., 2009), TBBPA concentrations were significantly (one to three orders of magnitude) lower, possibly attributing to the limited proportion (20–30%) of this compound applied as an additive BFR in products However, TBBPA con-centrations as high as 2300 ng/g were found in dust from Chinese homes 3.2 BPs in house dust

BPA was found in all house dust samples at concentrations that ranged from 9.6 to 32,000 ng/g, with a global median concentration of 440 ng/g, which was 10 to 100 times higher than that of TBBPA concentration The highest BPA concentration was found in dust from Japan (median: 1700 ng/g), followed by Greece (1500), the U.S (1500) and South Korea (720) (Fig 1) Besides BPA, BPS and BPF were also found widely in dust samples, collectively accounting for, on average, 45% of∑BPs concentra-tions This profile was similar to those reported previously for indoor dust from the U.S., Japan, South Korea and China (Liao et al., 2012a) High con-centrations of BPF found in dust from South Korea (median: 1000 ng/g), Greece (780), Japan (230), and the U.S (200) indicated high usage of this BP analogue in these countries BPF has been reported as a major al-ternative to BPA in industrial applications in South Korea (Lee et al.,

2015) BPP (detection frequency: 0.34%), BPAF (73%), and BPAP (0.68%) were also found in some dust samples, but their concentrations were very low The concentrations of∑BPs in house dust from the 12 coun-tries investigated, were in the following decreasing order: Greece (range

510–110,000; median 3900 ng/g), Japan (360–12,000; 2600), the U.S (550–89,000; 2200), South Korea (540–6100, 1600), Saudi Arabia (130–3200, 1200), Romania (37–6000, 870), Vietnam (66–1600, 400), Kuwait (61–1400, 380), China (43–4400, 350), India (40–6200, 180), Colombia (42–2300, 180) and Pakistan (23–860, 150)

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3.3 TBBPA and BPA in various microenvironments and comparison of

results with other studies

The concentrations and profiles of TBBPA and BPs in dust from

vari-ous microenvironments are shown in Table S5 andFig 2, respectively

The concentrations of TBBPA in dust from laboratories and offices from South Korea (65–660 ng/g) were significantly (p b 0.05) higher than those in homes (43–370 ng/g) Similarly, significantly (p b 0.05) higher BPA concentrations were found in dust from offices (510–

6600 ng/g) and laboratories (980–27,000 ng/g) than homes

Table 1

TBBPA and BP concentrations in house dust (ng/g) from 12 countries.

a

DR = detection rate.

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(270–3600 ng/g) in South Korea Our results are similar to those found for house and office dust from Belgium, with the concentra-tions in office dust (median: BPA 6530, TBBPA 75 ng/g) 5–10 times higher than those in house dust (median: BPA 1460, TBBPA 10 ng/g) (Geens et al., 2009) The use of TBBPA and BPA in electrical and electronic equipment in offices is an explanation for the elevated concentrations of these chemicals in offices However, dust samples from Pakistan did not show a significant difference in TBBPA and BPA concentrations between

offices and homes Harrad et al found significantly higher concentrations

of TBBPA in dust from classrooms (n = 43) and homes (n = 45) than in

offices (n = 28) and cars (n = 20) (Abdallah et al., 2008) The nature and magnitude of indoor products, ventilation, and residential settings can contribute to variations in emissions of TBBPA and BPA No significant difference was found for BPA and TBBPA concentrations between dust samples collected from homes and air conditioners in Saudi Arabia No significant difference was found for TBBPA concentrations in dust

collect-ed from cars and homes in Pakistan (mcollect-edian: car dust 28, house dust 7.2 ng/g) and Kuwait (median: car dust 6.7, house dust 8.4 ng/g) BPA concentrations in house dust from rural homes (range:b0.5–29 ng/g)

in Pakistan were significantly lower than those in urban (b0.5–800 ng/g) homes, which can be attributed to lifestyles including consumer products usage However, TBBPA concentrations in dust collected in urban homes were not significantly different from those in rural homes in Pakistan These results suggest differences in the sources of BPA and TBBPA in dust The highest TBBPA concentrations were found in dust from e-waste workshops in Vietnam, with TBBPA concentrations that ranged from 23 to 3600 ng/g; these values were significantly (p b 0.05) higher than those found for dust from homes and public areas in Vietnam

A summary of median and range of concentrations for TBBPA and BPA in indoor dust analyzed in this study and those reported in earlier studies is shown in Fig S1 The concentrations of TBBPA measured in house dust for various countries in this study were similar to those reported in earlier studies: the U.S (b10–3400 ng/g, sampling year: 2006/2011) (Dodson et al., 2012), Japan (495–520 ng/g, 2006) (Takigami et al., 2009), the UK (bMQL-382 ng/g, 2007) (Abdallah

et al., 2008) and Belgium (0.85–1481 ng/g, 2008) (Geens et al., 2009) The concentrations of TBBPA determined in office dust in this study were higher than those reported in the UK (bMQL-140 ng/g, 2007)

Fig 1 Worldwide distribution of TBBPA and BPA (median values) in house dust from 12 countries.

Fig 2 Comparison of TBBPA (A) and BPA (B) concentrations in indoor dust from various

microenvironments (KRH, KRL, KRO-Home, laboratory and office dust from South

Korea; KWC and KWH-Car and home dust from Kuwait; PKC, PKR, PKU and PKO-Car,

rural home, urban home and office dust from Pakistan; SAA, SAC and SAH-Air conditioner,

car and home dust from Saudi Arabia; VNE, VNH and VNP-E-waste work shop, home and

public area dust from Vietnam The box represented 25–75 percentiles, the whiskers were

10th and 90th percentiles, the lowest and highest circles were the minimum and

maxi-mum, and line inside the box showed the median).

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(Abdallah et al., 2008) and Belgium (45–100 ng/g, 2008) (Geens et al.,

2009) For BPA, the concentrations determined in house dust from

Japan were similar to those reported previously (496–12,300 ng/g,

2010) (Liao et al., 2012a) BPA concentrations found in dust from

office and laboratories were within the ranges reported from Belgium

(4685–8380 ng/g, 2008), China (117–3490, 2010), Japan (11,400–

21,800, 2010), South Korea (2310–39,100, 2010) and the U.S

(445–2950, 2006/2010) (Geens et al., 2009; Loganathan and Kannan,

2011; Liao et al., 2012a)

3.4 Correlations and profiles

A significant (p b 0.05), but weak correlation (r = 0.27) was found

between TBBPA and BPA concentrations in 284 house dust samples

(only house dust samples were compared here) (Table S6), indicating

the existence of multiple sources An earlier study reported that

TBBPA concentrations in dust samples were not correlated with BPA

concentrations (Geens et al., 2009) No significant correlation was

found between TBBPA and BPF/BPS concentrations, which suggests

dif-ferences in sources and emissions of these compounds A significant

correlation was found between BPA and BPS (pb 0.05, r = 0.21), and

between BPA and BPF (pb 0.05, r = 0.17)

The contribution of each of the target compounds to the sum

concen-trations of all nine target chemicals analyzed in dust is presented inFig 3

BPA accounted for 64 ± 22% of the total concentrations TBBPA accounted

for 27% of the total concentrations in dust from China, followed by

Pakistan (22%)N Vietnam (15%) N India (10%) N Japan (8.4%) N South

Korea (5.2%) N Saudi Arabia (4.4%) N Colombia (4.0%) N Romania

(2.4%)N Kuwait (2.3%) N the U.S (1.1%) N Greece (0.41%) The proportion

of BPF and BPS to the total concentrations in house dust from the U.S.,

South Korea, and Greece was higher than in other countries, indicating

a greater usage of BPF and BPS in resin coatings and polycarbonate plastics

in these countries (Lee et al., 2015) and hence the market shift from BPA

to its alternatives The contribution of BPF was elevated in office dust in South Korea than in home dust These results agree with elevated concen-trations of BPF found in sewage sludge from South Korea (Lee et al., 2015), which suggested high usage of BPF in that country The proportion of TBBPA was elevated in dust from e-waste workshop in Vietnam, which can explain that electronic products are the sources of this chemical in dust TBBPA/BPA ratios in home dust from Asian countries (0.12–0.48) were considerably higher than those found for Greece and the U.S (0.02), which suggests differences in contamination profiles among various countries Principal Component Analysis (PCA) was carried out

on house dust samples from each country to identify patterns in their con-centrations (Table S7) Two principal components were identified based

on the component matrix (except for Kuwait), and TBBPA and BPA were identified with similar potential origin in China, Columbia, India and Greece, while with varied sources in Japan, Pakistan and Romania Furthermore, BPF and BPAF explained the predominance of total variance for samples from Korea

3.5 Exposure assessment The sources and pathways of human exposure to TBBPA are not well known (Covaci et al., 2009) We estimated daily intake (EDI) dose for TBBPA and BPs via dust ingestion for different age groups Since the number of samples collected from offices, cars and other microenviron-ments is small, data collected only for residential homes were taken into account for exposure calculation Median and high exposure scenarios were assessed for BPA, BPS, BPF,∑BPs and TBBPA based on median and 95th percentile concentrations of the target contaminants deter-mined in home dust Because of the low frequency of detection of other BPs, they were not included in the calculation

The median EDIs of TBBPA and BPA through dust ingestion have been summarized inFig 4 Further details (median and 95UCL) of EDIs for BPS, BPF, and∑BPs are shown in Fig S2 and Table S8 The highest exposure dose was found for toddlers, which can be explained

by the high dust ingestion rate and the low body weight The highest EDI was found for BPA in all 12 countries, except for South Korea and Greece where BPS and BPF showed highest EDIs The highest exposure doses of∑BPs were found for the U.S (median, high: 0.89–9.6, 6.2–

66 ng/kg bw/day) and Greece (1.6–17, 6.2–67), whereas the lowest in-takes were found for Pakistan (0.07–0.88, 0.12–1.5), Kuwait (0.19–2.3, 0.34–4.1), Romania (0.35–3.8, 0.57–6.2), and India (0.09–1.1, 0.35– 4.2) The overall median EDI of BPA was estimated to be 0.4–10, 0.21– 5.3, 0.14–3.6, 0.07–1.9, and 0.03–0.85 ng/kg bw/day for infants, tod-dlers, children, teenagers, and adults, respectively

The daily dietary intakes of BPA and BPs in the U.S (calculated from the mean concentration of foods from the U.S.) were reported to be 195, 243; 114, 142; 91.2, 117; 48.6, 63.6; and 44.6, 58.6 ng/kg bw/day for toddlers, infants, children, teenagers, and adults, respectively (Liao and Kannan, 2013).Lorber et al (2015)reported the dietary BPA intake

at 12.6 ng/kg/day for the U.S population, with canned food accounting for a majority of the exposure dose Based on the 2005–2006 U.S NHANES data for the urinary levels of BPA, the total daily intake of BPA was estimated at 35.1 ng/kg/day (Lakind and Naiman, 2011) Similarly, the daily dietary intakes of BPs in China were 646 and

664 ng/kg bw/day for adult men and women, respectively (Liao and Kannan, 2014) In comparison with the median intake doses for BPs es-timated via dust ingestion in the U.S and China, diet contributesN90% of the daily intake of BPs Our results suggest that dust ingestion is a minor contributor to total BPA exposure in the U.S., and the EDI values are much lower than the oral reference dose for BPA (50μg/kg bw/day) (US EPA, 2008) Thisfinding agrees well with the report that diet accounted forN90% of the total daily BPA intake in human populations (Geens et al., 2012), potentially from the usage of BPA in epoxy can

Fig 3 Composition profiles of TBBPA and BPs in house dust from 12 countries (A) and

in-door dust from various microenviroments (B) (KRL, KRO-Laboratory and office dust from

South Korea; KWC-Car dust from Kuwait; PKC, PKO-Car and office dust from Pakistan;

SAC-Car dust from Saudi Arabia; VNE, VNP-E-waste work shop, and public area dust

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linings for foods (Guo and Kannan, 2011) In this study, a high exposure

dose for BPS via dust ingestion was found for Greece (median 0.34–3.7;

high 1.1–12 ng/kg bw/day) and Japan (median 0.08–0.96; high 0.35–

4.3 ng/kg bw/day).Liao et al (2012b)also found high BPS

concentra-tions in urine from Japanese populaconcentra-tions (0.10–15.3, with a mean of

3.47μg/day) Japan banned the use of BPA in certain products (such as

thermal receipt papers) in 2001 and BPS was used as a replacement

since then (Liao et al., 2012b)

Dust is an important source of chemical exposures for young

children because of frequent hand-to-mouth contact For TBBPA, the

highest EDI was found for infants and toddlers in Japan (median: 0.82,

0.43 ng/kg bw/day), South Korea (0.50, 0.26), and China (0.14, 0.07),

and the estimated values for these three countries were 10 times higher

than those found for other countries At high exposure scenario (95th

percentile), the EDIs of TBBPA were the highest for infants and toddlers

in China (2.5, 1.3 ng/kg bw/day), Japan (3.4, 1.8) and South Korea (1.1,

0.56), which were up to 100 times higher than those estimated for

other countries In general, the overall EDIs of TBBPA ranged from 0.01

to 3.4; 0.01 to 1.8; 0.01 to 1.2; 0.003 to 0.61; 0.001 to 0.28 ng/kg bw/

day for infants, toddlers, children, teenagers, and adults, respectively,

in this study

The reported TBBPA exposure via dust ingestion for adults in

Belgium was 0.0128 to 0.0286 ng/kg bw/day from home dust and

0.0417 ng/kg/day from office dust (Geens et al., 2009) The median

ex-posure dose of TBBPA for UK adults via the dust ingestion was

0.002 ng/kg bw/day (Abdallah et al., 2008) In China, the average

expo-sure dose to TBBPA via PM2.5and PM10inhalation was 0.0462 ng/kg bw/

day for adults (Ni and Zeng, 2013) Assuming that TBBPA concentrations

in indoor dust from China were similar to those in airborne particulate

matter, the contributions of dust ingestion, inhalation, and diet to

TBBPA intake were estimated to be ~76%, ~4%, and ~20% for adults (Ni

and Zeng, 2013) TBBPA exposure via dietary intake in China was reported

to range from 0.032 to 1.3 ng/kg bw/day, with a mean value of 0.256 ng/kg bw/day (Shi et al., 2009) In our study, the median exposure doses for TBBPA via dust ingestion in China ranged from 0.01 to 0.14 ng/kg bw/day for thefive age groups, which were 3.8–35% of the total TBBPA exposures In Japan, the daily exposure dose for TBBPA via dust ingestion was estimated to range from 2.0 to 4.0 ng/kg bw/day for children and 0.035 to 0.46 ng/kg bw/day for adults (Takigami et al.,

2009).Takigami et al (2009)concluded that dust ingestion was an im-portant contributor to TBBPA exposure in Japan In our study, the TBBPA exposure doses calculated for Japanese children and adults ranged in 0.29–1.2 and 0.07–0.28 ng/kg bw/day, respectively TBBPA exposure doses calculated via dust ingestion for Greece (median EDI: 0.004– 0.05 ng/kg bw/day; high EDI: 0.055–0.59 ng/kg bw/day) were higher than the reported dietary intake estimates for the Netherlands (0.04 ng/kg bw/day) (Abdallah et al., 2008).Abdallah et al (2008)

reported that dust ingestion accounted for 34% and 90% of the total TBBPA exposures for adults and toddlers in the UK, respectively.Geens

et al (2009)reported that 7% of the total daily intakes of TBBPA for adults and 56% of the intake for toddlers in Belgium originated from dust inges-tion Thus, dust ingestion is an important pathway for human exposure to TBBPA whereas diet is the major source of BPs exposures Considering the limited data available for the assessment of exposure to TBBPA, future work should focus dietary and inhalation sources of exposures

To compare exposures from various microenvironments (Table S9, Fig S3), the exposure estimates were calculated based on a typical activity pattern as described previously, i.e., 63.8% home, 22.3% office, and 4.1% car for adults (Klepeis et al., 2001; U.S EPA, 2002) Exposure doses of TBBPA, BPA and BPF from offices were higher than those in houses, and laboratories, based on data for samples from Korea The exposure doses for BPA, BPF, BPS and TBBPA were lower based on data obtained for dust from cars, compared to households in Pakistan, Saudi Arabia and Kuwait, which can be explained by low exposure Fig 4 Median levels of Estimated Daily Intakes (EDI, ng/kg bw/day) of TBBPA and BPA from house dust ingestion for different age groups in 12 countries.

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fraction A significantly higher exposure dose for TBBPA was found in

e-waste workshop than homes in Vietnam, which can be attributed to

the elevated contamination levels

4 Conclusions

In summary, TBBPA and BPA were detected inN80% of the 388

indoor dust samples collected from 12 countries, indicating widespread

occurrence of these phenolic compounds in the indoor environment

The highest TBBPA exposures were found in house dust collected

from China, Japan, and South Korea which can be explained by high

consumption/production in Asian countries; whereas the highest BPA

exposures were found in the U.S., Greece, and Japan The ratios of

TBBPA/BPA were higher in house dust from China (0.37), Pakistan

(0.48), Vietnam (0.30), India (0.12) and Japan (0.13), than in Greece

(0.02) and the U.S (0.02), which suggested differences in

contamina-tion profiles and sources for these two chemicals among countries

Con-centration profiles of TBBPA and BPs varied among several indoor

microenvironments The contribution of dust to daily intakes of TBBPA

and BPA varied For BPA, dust ingestion accounted for a minor (b10%)

proportion of EDI in countries such as China and the U.S., in comparison

with the dietary sources However, dust ingestion is an important

pathway for TBBPA exposure, accounting for 3.8–35% (median intake

scenario) of exposure in China However, the number of samples

collected from each country was limited and comprehensive sampling

strategies are needed in the future

Acknowledgments

Pierina Maza-Anaya, a youth research follow, supported by

Colciencias, helped in the collection of dust samples from Colombia; Dr

Dilip Kumar Kedia, Patna University, helped in the collection of dust

sam-ples from India This study was funded by a grant (1U38EH000464-01)

from the Centers for Disease Control and Prevention (CDC, Atlanta, GA)

to Wadsworth Center, New York State Department of Health Its contents

are solely the responsibility of the authors and do not necessarily

repre-sent the official views of the CDC

Appendix A Supplementary data

Supporting information for this article includes additional details

of methods as well as samples (Table S1), instrument parameters

(Table S2), summary statistics for LOQs (Table S3), exposure analyses

parameters (Table S4), correlation analyses (Table S6) and compound

specific exposure estimates (Table S8) Plots of worldwide data for

TBBPA and BPA and EDI estimates for compound specific exposure

are contained therein

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