Occurrence and human health risks of phthalates in indoor air of laboratories

Journal Pre-proof Occurrence and human health risks of phthalates in indoor air of laboratories

Yu-Xi Feng, Nai-Xian Feng, Li-Juan Zeng, Xin Chen, Lei Xiang, Yan-Wen Li, Quan-Ying Cai, Ce-Hui Mo PII:

S0048-9697(19)35604-9

DOI:

https://doi.org/10.1016/j.scitotenv.2019.135609

Reference:

STOTEN 135609

To appear in:

Science of the Total Environment

Received date:

26 September 2019

Revised date:

14 November 2019

Accepted date:

17 November 2019

Please cite this article as: Y.-X. Feng, N.-X. Feng, L.-J. Zeng, et al., Occurrence and human health risks of phthalates in indoor air of laboratories, Science of the Total Environment (2019), https://doi.org/10.1016/j.scitotenv.2019.135609

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© 2019 Published by Elsevier.

Journal Pre-proof

Occurrence and human health risks of phthalates in indoor air of laboratories

Yu-Xi Feng1, Nai-Xian Feng1, Li-Juan Zeng, Xin Chen, Lei Xiang, Yan-Wen Li, Quan-Ying Cai, Ce-Hui Mo*

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Guangdong Provincial Research Center for Environment Pollution Control and Remediation

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Materials, College of Life Science and Technology, Jinan University, Guangzhou 510632, China

*Corresponding author

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Yu-Xi Feng and Nai-Xian Feng contributed equally to this work.

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1

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Ce-Hui Mo. E-mail: [email protected]. Phone: +86 20 85223405.

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Abstract Phthalate acid esters (PAEs) are of serious concern as a human health risk due to their ubiquitous presence in indoor air. In the present study, fifteen PAEs in the indoor air samples from physical, chemical, and biological laboratories in Guangzhou, southern China were analysed using gas chromatography mass spectrometry. Extremely high levels of PAEs of up to 6.39×104 ng/m3 were detected in some laboratories. Diisobutyl phthalate (DiBP), di(methoxyethyl) phthalate (DMEP), and di-n-butyl phthalate (DBP) were the dominant PAEs with median levels

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of 0.48×103, 0.44×103, and 0.39×103 ng/m3, respectively, followed by di-(2-propylheptyl)

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phthalate (DPHP) and di(2-ethylhexyl) phthlate (DEHP) (median levels: 0.16×103 and 0.13×103

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ng/m3, respectively). DMEP and DPHP were found for the first time in indoor air. Principal component analysis indicated that profiles of PAEs varied greatly among laboratory types,

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suggesting notable variations in sources. The results of independent samples t-tests showed that

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levels of PAEs were significantly influenced by various environmental conditions. Both the non-carcinogenic and carcinogenic health risks from human exposure to PAEs based on the daily

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exposure dose in laboratory air were acceptable. Further research should be conducted to

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investigate the long-term health effects of exposure to PAEs in laboratories. Keywords: Phthalate esters, Indoor atmosphere, Labs, Human exposure, Health risk assessment

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Journal Pre-proof 1. Introduction Phthalate acid esters (PAEs) are a group of semi-volatile organic compounds (SVOCs) that are widely used as plasticizers in a range of household and industrial products. More than 200,000 tonnes of PAEs are produced globally each year (Gong et al., 2014). PAEs can be found in numerous products including polyvinyl chloride (PVC) flooring, building materials, personal care products, food packaging, solvents, and detergents due to their unique physicochemical properties

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(Gómez-Hens and Aguilar-Caballos, 2003; Fromme et al., 2004). Low molecular weight PAEs

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(e.g. dimethyl phthalate [DMP] and diethyl phthalate [DEP]) are mainly found in cosmetics,

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personal care products, and surface coating materials, whereas those of high molecular weight

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(e.g. di(2-ethylhexyl) phthalate [DEHP] and butyl benzyl phthalate [BBP]) are generally used in

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PVC production (Gong et al., 2014). As additives that are not covalently bound to the materials, PAEs are readily released through volatilization during manufacturing, storage, use, and disposal

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(Liang et al., 2014). Widespread production and use of PAEs has resulted in their ubiquitous

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presence in various environmental media, including residential and occupational settings, air, water, and soil (Kamrin et al., 2009; Net et al., 2015; Albar et al., 2017). The occurrence of PAEs in the indoor air of various microenvironments, including homes, day care centres, offices, schools, and even hospitals have been investigated, with concentrations generally measured in the hundreds to thousands of ng/m3 ( Song et al., 2015;Li et al., 2016). For example, the total concentrations of PAEs in office and residential buildings in China were reported to be approximately 3.80×103 ng/m3 (Wang et al., 2014). Relatively low PAE concentrations were found in homes in France (0.32×103 ng/m3) and North America (0.54×103 ng/m3) (Rudel et al., 2010; Blanchard et al., 2014). Statistically, DEHP in indoor air was found to be the major PAE, making up 40.6% of total PAEs, followed by DMP, DEP, di-n-butyl phthalate 3

Journal Pre-proof (DBP), BBP, and di-n-octyl phthalate (DnOP), each of which ranged in proportion from 9% to 15% (Kashyap et al., 2018). Indoor sources of PAEs include building and furnishing materials as well as personal products, which provide a major fraction of the total PAEs exposed to humans (Dodson et al., 2017). These results indicate that indoor air pollution by PAEs should be investigated further. However, very few reports are currently available on PAEs in the indoor air of laboratories. Laboratories are important workplaces for conducting scientific research. They

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usually contain a variety of analytical instruments and chemical regents, all of which are potential

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sources of indoor PAE pollution. Meanwhile, the indoor environment of laboratories is generally

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enclosed and overcrowded (Jin et al., 2018). In China, more than 4 million researchers work in

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laboratories, accounting for over 25.3% of all laboratory workers worldwide (MOSTC, 2012;

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RCTI, 2014). Most researchers, including undergraduate students, graduate students, and other technicians are of childbearing age. As environmental endocrine disruptors, PAEs have effects on

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human health that may last for several years, possibly affecting the next generation's health

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(Zhang et al., 2013; Li et al., 2016). The specific indoor environment of laboratories may result in varying degrees of human exposure to PAEs, leading to potential risks and serious concerns for human health.

PAEs can enter the human body via inhalation, ingestion, and dermal absorption, exhibiting potential for bioaccumulation and common occurrence in human hair, blood, serum, urine, and even breast milk (Högberg et al., 2008; Hines et al., 2009; Wittassek et al., 2011; He et al., 2018; Lehmann et al., 2018). PAEs in the human body may pose serious risks to health. Some PAEs (e.g. DBP, DEHP, and BBP) and their metabolites are suspected to have oestrogenic effects (Heudorf et al., 2007; Lyche et al., 2009; Tran and Kannan, 2015). Increased PAE exposure in humans may have harmful effects on human reproductive and developmental systems, such as causing DNA 4

Journal Pre-proof damage in sperm or affecting semen parameters (Li et al., 2016; Zhu et al., 2019). Additionally, asthma, allergic symptoms, and the intelligence of elementary school students have been shown to be associated with indoor PAE exposure (Bornehag et al., 2004; Cho et al., 2010). Consequently, six PAEs, namely DMP, DEP, DBP, DnOP, DEHP, and BBP, have been classified as priority pollutants by the United States Environmental Protection Agency (US EPA) and the European Union (EU). Therefore, investigation on the occurrence and human health risk of PAEs in the

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indoor air of laboratories is urgently needed.

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In the present study, 40 indoor air samples were collected from physical, chemical, and

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biological laboratories in Guangzhou, southern China, to 1) analyse the concentrations and

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profiles of PAEs; 2) identify the sources of PAEs; 3) determine the factors affecting the levels of

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PAEs; and 4) estimate the risk associated with human exposure to PAEs. For comparison, three indoor air samples from offices were also collected and analysed as controls. To our knowledge,

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laboratories in China.

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this is the first report on the occurrence and human health risks of PAEs in the indoor air of

2. Materials and methods

2.1. Chemicals and materials

Mixed standard solution of 15 PAEs was purchased from TCI America (Portland, OR, USA), containing the six priority PAEs (DMP, DEP, DBP, DEHP, DnOP, BBP) and nine other common PAEs: diisobutyl phthalate (DiBP), dimethoxyethyl phthalate (DMEP), bis(4-methyl-2-pentyl) phthalate (BMPP), di(2-ethoxyethyl) phthalate (DEEP), dipentyl phthalate (DPP), di-n-hexyl phthalate (DHXP) di(2-n-butoxyethyl) phthalate (DBEP), dicyclohexyl phthalate (DCHP), and diphenyl phthalate (DPHP). The concentration of each PAE compound in the mixture standard solution was 1000 mg/L. Four d4 (deuterated) standards including d4-DMP, d4-DBP, d4-DiBP, and 5

Journal Pre-proof d4-DEHP were used as internal (surrogate) standards. When deuterated standards were used as surrogates, they were spiked into samples, and run through the entire analytical procedure to determine the recoveries. When deuterated standards were used as internal standards, they were used to quantify the PAE compounds by reducing detection interference from instrument fluctuation. All chemicals and solvents used for pre-treatment and gas chromatography-mass spectrometry (GC-MS) analysis were of HPLC grade.

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2.2. Description of the study sites

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A calibration study was conducted to determine uptake rates of polyurethane foam (PUF)

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disk passive air samplers (PUF-PAS) in a 160-m3 laboratory located in a 10-year-old laboratory

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building from July to August of 2018. Windows, doors, and airing chambers were kept closed

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throughout the sampling period to restrict ventilation. The room temperature ranged from 24.5 to 30.4 °C. Potential sources of PAEs in the selected laboratories included workbenches, tables with

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vinyl covering, instruments, and chemical reagents. The basis for selecting the laboratories

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included (a) at least 2 years elapsed since the last renovation; and (b) occupied with relatively higher population density. Active air samplers (AAS) and passive air samplers (PAS) were co-deployed for the entire 28-d period of the calibration study. A total of 43 indoor air samples were collected from laboratories in Guangzhou, southern China from July to August 2018, including biological (n = 11), chemical (n = 15), and physical (n = 14) laboratories, as well as offices (n = 3) near the laboratories as controls. In each laboratory sampled, humidity and temperature were also monitored throughout the sampling period. Detailed information about the selected laboratories is provided in Supporting Information M1 and Table S1. 2.3. Sampling 6

Journal Pre-proof 2.3.1. Calibration study Passive air samples were collected every 7 days for 28 days using PUF-PAS. Each disk was 14 cm in diameter and 1.2 cm in thickness, with a surface area of 360 cm 2 and density of 0.021 g/cm3 (Fig. S1). Each PUF disk was pre-cleaned via ultrasonic extraction with n-hexane and dichloromethane (1:1, v/v) and dried in a vacuum desiccator. All PUF disks were deployed in fully sheltered (double bowl) housings, with the top bowl larger than the bottom bowl (Saini et al.,

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2015; Okeme et al., 2018). Triplicate passive air samples were also collected on day 7 to verify

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the reproducibility of the results.

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Active air samples were collected at 7-d intervals using a low-volume active air pump

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(LV-AAS) that ran throughout the 28-d deployment period at a flow rate of 15 L/min.

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Particle-phase PAEs were collected through a sampling system consisting of a glass fibre filter (GFF), and gas-phase PAEs were collected with a PUF plug (Φ 38 × 76 mm) from the same air

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samples. The GFF and PUF plug were extracted to determine the concentrations of PAEs in the

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particle and gas phases, and gas-phase sorption to filters was considered negligible (Okeme et al., 2018). PAEs in the air could exist in both gas phase and particle phase. However, PAS could not distinguish between gas- and particle-phase compounds. Therefore, data provided by PAS should be calibrated when mathematically estimating PAE compounds in air (Okeme et al., 2018). Uptake rates of PAS were obtained by comparison with AAS that were used to measure PAE concentrations in both gas- and particle- phase laboratory air. Triplicate active air samples were collected on day 7 to verify the reproducibility of the results. The uptake rate of a PAS could be determined from bulk air concentrations derived from time- integrated active sampling and the mass accumulated on a co-deployed PAS. The equivalent air volume (Veq, m3) was calculated using the following equation (Saini et al., 2015): 7

Journal Pre-proof Veq 

M CA

(1)

where M is the mass of PAE compounds accumulated in the PUF (ng), CA is the environmental bulk air concentration (ng/m3) determined from AAS, and Veq is the equivalent air volume (m3). The uptake rates of PAS could be calculated using the following equation:

Veq  Rt

(2)

where Δt is the sampling time interval (d). Linear fitted curves between Veq and deployment time

was obtained:

M Rt

(3)

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Cp 

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provide the uptake rate (R, m3/day). Thus, the following calibration equation for AAS and PAS

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where Cp is the environmental bulk air concentration (ng/m3) obtained with the PAS and t is the sampling time (21 d). Based on Shoeib and Harner (2002), PAS uptake occurred in three

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phases-the linear, curvilinear, and equilibrium phases. Sampling rates (R, m3/d) were derived from

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the linear uptake phase of the chemicals, as the loss rate of chemicals from the passive sampler was insignificant relative to the R value during the linear stage (Shoeib et al., 2002; Wania et al., 2003). In this study, the uptake rates of PAS could be described in linear phase during 21 days (Fig. S2). Moreover, the half-live time of PAEs varies from mouths to possibly years (Stales et al., 1997). Therefore the loss of PAEs from the PAS could be ignored. Detailed information about the calibration study used for evaluating laboratory air concentrations of PAEs is presented in Fig. S2 and Tables S2, S3, and S4. Fifteen PAEs in indoor air samples from laboratories and offices were measured using GC-MS. Six PAEs including DBP, DEP, DiBP, DMEP, DPHP, and DEHP were detected in >97% of AAS and PAS samples. The other nine PAEs were not analyzed further because they were detected in <80% of AAS and PAS 8

Journal Pre-proof samples that could not meet the requirements of statistics and analysis (Tables S3 and S4). The masses of six individual PAEs in fully sheltered PUF disks increased linearly over the 28-d sampling period (Fig. S2). Positive correlations (R2 = 0.833–0.949) were observed between sampling time (T) and equivalent volume (Veq). The uptake rate of DMEP was the smallest, followed by those of DBP, DPHP, DiBP, DEHP, and DEP in ascending order, with values ranging from 0.124 to 10.565 m3/d (Table S2). Thus, indoor air concentrations of six PAEs could be

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estimated using results of PAS vs. AAS due to their clear linear sorption patterns.

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2.3.2. Laboratory deployment

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Passive air samplers were deployed in laboratories for 21 days (Okeme et al., 2018). The

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height of PUF disk placement was set based on the human respiratory height at 1.5 m above the

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floor. The average temperature and humidity of these laboratories were 26.8 ± 3.5°C and 53.7 ± 7.2%, respectively. All samples in the calibration and laboratory deployment studies were

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retrieved into air tight glass jars and stored at -20℃ until extraction and analysis.

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2.4. Extraction and analysis of PAEs

Each sample was extracted using a 100 mL mixed solution of n-hexane and dichloromethane (1:1, v/v) through a Soxhlet extractor at 6 cycles per hour for 24 h (Orecchio et al., 2013; Tran et al., 2017). The extracts were concentrated into a volume of 2 mL with a rotary evaporator at 40°C. The concentrations of 15 PAE compounds were measured using GC-MS with splitless injection on a 30-m Agilent HP-5MS chromatographic column (length 30 m × diameter 0.25 mm × film thickness 0.25 μm) with helium gas as a carrier. The chromatographic temperature program included a 60 °C hold for 1 min, a 20 °C/min increase to 200 °C, another increase at 10 °C/min to 280 °C, hold for 4 min. The injector and ion source temperatures were 260 and 230 °C, respectively. The auto injection volume was 1 μL. 9

Journal Pre-proof 2.5. Quality assurance/quality control (QA/QC) QA/QC was conducted throughout the sampling, pre-treatment, and analytical measurement procedures. All glassware used in the experiment was steeped in alkaline liquor for 12 h, rinsed with double-distilled water, and then baked in a muffle at 450 °C furnace for 4 h. The GFFs were baked in a muffle at 400 °C furnace for 4 h to remove possible residual PAEs. This process was repeated three times. Procedural blanks were analysed with every batch of air samples. Surrogate

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standards (100 ng, d4-phthalate) were spiked into blank PUF, PUF-plug and GFF, and run through

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the entire analytical procedure. Good recoveries of 86.55–101.45% were obtained for surrogate

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standards in methodological blanks. The recoveries of the PUF, PUF-plug, and GFF ranged from

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67.9 to 98.5%, 65.4 to 101.4%, and 76.6 to 104.3% with relative standard deviations (RSD) less

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than 9.3%, 7.5%, and 4.8%, respectively. The limit of detection (LOD) based on a signal to-noise ratio of three ranged from 0.20 to 5.76 ng/m3.

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2.6. Human health risk assessment

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Indoor air concentrations of PAEs were used to evaluate the daily exposure dose (DED) via dermal absorption (DEDdermal) based on the following equation (Wang et al., 2014):

DEDdermal 

Cair  k  SA f  t BW

(4)

where Cair (ng/m3) is the concentration of PAEs in laboratory air; k (m/h) is the transdermal permeability coefficient of PAEs in the air according to Xu et al. (2009) (Table S5); SA is the body surface area; f is the exposed dermal fraction, assumed to be 30%; t (h) is the exposure time, with uptake of PAEs via dermal absorption assessed over an exposure period of 8 h; and BW is the body weight of a male (62.7 kg) or female (54.4 kg) individual (Wang et al., 2009). DED via inhalation (DEDinhalation) of PAEs in indoor air was estimated with the following 10

Journal Pre-proof equation:

DEDinhalation

Cair  IR  t BW

(5)

where Cair (ng/m3) is the concentration of PAEs in laboratory air, IR is the inhalation rate of air (m3/d) estimated according to Wang et al. (2009), and t (h) is the exposure time (8 h). Hence, the total DED (ΣDED) of air PAEs was calculated as the sum of DEDdermal and DEDinhalation.

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The hazard index (HI) was used to assess non-carcinogenic risk. A value of HI >1 indicates a

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potentially significant health risk from chronic exposure to specific chemicals (OEHHA, 2003). The HI is the sum of hazard quotients (HQ) that were calculated as the ratios of DEDinhalation

DED d e r ma D l ED i n h a l a t i o n Rf D

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HQ 

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estimated using equations (6) and (7) as follows:

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values of various PAEs to a reference dose. The HQ and HI of indoor air PAEs were separately

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HI   HQ i  

DEDi RfDi

(6)

(7)

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where RfD is the reference dose (μg·day-1·kg-1). The cumulative risks of DEP, DBP, and DEHP were estimated in accordance with the reference doses recommended by the US EPA (1990, 1997), and the cumulative risks of DiBP and DMEP were assessed according to reference doses described elsewhere (Benson et al., 2009; Yang et al., 2014; Bui et al., 2016). Reference dose information for DPHP was not available. In addition, the carcinogenic risk of DEHP exposure was assessed by multiplying DED with the carcinogenic slope factor (SF) of DEHP (Chai et al., 2017). 2.7. Statistical analyses Statistical analyses were performed using SPSS 12.0 software. The mean, median, standard 11

Journal Pre-proof deviation, and ranges were determined. The independent-samples t-test was conducted to identify significant differences between PAE levels and influencing factors. Principal component analysis (PCA) was used to explore the associations and origins of PAEs in various types of laboratories. 3. Results 3.1 Concentrations and profiles of PAEs in the indoor air of laboratories The concentrations of PAEs in the indoor air of laboratories varied greatly, with

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concentrations of total PAEs (ΣPAEs) in various laboratories ranging from 0.80×103 to 6.4×103

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ng/m3 (median: 1.68×103 ng/m3; mean: 6.04×103 ng/m3) (Table 1). The ΣPAE levels in physical,

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chemical, and biological laboratories ranged from 8.48×103 to 6.4×103 ng/m3 (median: 1.66×103

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ng/m3; mean: 1.16×103 ng/m3), 8.95×103 to 1.79×103 ng/m3 (median: 1.71×103 ng/m3; mean:

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5.03×103 ng/m3), and 0.80×103 to 2.61×103 ng/m3 (median: 1.72×103 ng/m3; mean: 1.64×103 ng/m3), respectively. Based on mean values physical laboratories contained the most ΣPAEs,

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followed by chemical laboratories and then biological laboratories. However, median ΣPAE levels

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were roughly equivalent (ca. 1.70×103 ng/m3) among laboratory types, as extremely high ΣPAE levels were observed in some chemical and physical laboratories (Table S1). In contrast to laboratories, levels of ΣPAEs in the indoor air of offices were generally much lower, ranging from 0.93×103 to 1.64×103 ng/m3 (mean: 1.29×103 ng/m3; median: 1.30×103 ng/m3). Although the median levels of various PAEs, in particular DEHP and DPHP, did not vary greatly among types of laboratories, the highest median levels of DEP, DBP, and DMEP were recorded in physical laboratories and the lowest medians in chemical laboratories, whereas the highest median level of DiBP was recorded in chemical laboratories and the lowest median level in physical laboratories. In terms of mean values, DiBP levels generally decreased in the order of physical laboratories > chemical laboratories > biological laboratories. The mean levels of four 12

Journal Pre-proof PAEs (DEP, DBP, DiBP, and DMEP) were much higher than their median levels in physical laboratories, as some extremely high concentrations were observed. A similar result was obtained for DMEP in chemical laboratories. As noted above, the median levels of ΣPAEs in laboratories were much higher than those in offices, and DBP and DiBP levels were also much higher in laboratories than in offices. However, PAEs in the indoor air of different laboratories and offices exhibited similar

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distribution patterns. DBP, DiBP, and DMEP were the dominant PAE compounds, accounting for

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ca. 80% of ΣPAEs (Fig. 1). The remaining 20% of ΣPAEs were primarily composed of DPHP and

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DEHP, with the former slightly more abundant than the latter. Nevertheless, some specific

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variations were noted in the distribution patterns of DBP, DiBP, and DMEP in various laboratories

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and offices. Specifically, in chemical and biological laboratories, DiBP had the highest concentrations, followed by DBP and DMEP at roughly equivalent levels. In physical laboratories,

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DiBP had the lowest concentration, and DBP and DMEP were present at similar levels. In office

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samples, DMEP was much more abundant than DBP or DiBP, and the DBP level was slightly higher than that of DiBP. Generally, DiBP was the most abundant PAE in laboratories, whereas DMEP was the most common compound in offices. Notably, this is the first report of DMEP and DPHP in indoor air.

3.2 PCA of PAEs in the indoor air of laboratories Relationships between concentrations of different PAEs in laboratory air were determined using a correlation matrix map (Fig. 2). Based on Pearson correlation coefficients, DBP exhibited moderate but significant positive correlations with DEP (r = 0.566, p <0.05) and DiBP (r = 0.657, p <0.05), and a strong positive correlation with DMEP (r = 0.932, p <0.05). DEP exhibited moderate but significant positive correlations with DiBP (r = 0.715, p <0.05) and DMEP (r = 13

Journal Pre-proof 0.582, p <0.05); DiBP exhibited a moderate positive correlation with DMEP (r = 0.636, p <0.05), and a weak positive correlation with DPHP (r = 0.329, p <0.05); and DPHP exhibited a strong positive correlation with DEHP (r = 0.994, p <0.05). Significant correlations among concentrations of PAE congeners indicate similarities in their sources or behaviours. PCA was used to identify the sources of PAEs in the indoor air of laboratories. The concentrations of PAE compounds in 40 air samples were used as active variables, and the

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correlation matrix was rotated for use in PCA (Feng et al., 2017). The results of PCA yielded two

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principal components with eigenvalues >1. The first principal component (PC1) explained

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55.03% of the total variation (eigenvalue = 3.302), and the second principal component (PC2)

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explained 30.62% of total variation (eigenvalue = 1.837) (Fig. 3a). We identified two groups

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(Group 1 and Group 2) according to the loading scores of various PAEs that corresponded to PC1 and PC2, respectively. PC1 had strong positive correlations with four variablesDiBP (0.833),

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DEP (0.846), DBP (0.887), and DMEP (0.898). PC2 was positively correlated with DPHP and

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DEHP. The results of PCA were consistent with those of Pearson correlation analysis (Fig. 2). PCA of PAEs in the three types of laboratories was also conducted individually. The results showed that PC1 explained 63.54%, 37.46%, and 61.19% of the total variation (eigenvalues = 3.813, 2.248, and 3.672, respectively) in chemical, biological, and physical laboratories, respectively, and PC2 explained 20.83%, 28.75%, and 31.50%, respectively (eigenvalues = 1.250, 1.725, and 1.890, respectively) (Fig. 3b–d). In physical laboratories, we identified two groups of PAEs according to their loading scores. Group 1, which corresponded to PC1, had strong positive correlations with DiBP, DEP, DBP, and DMEP, whereas Group 2, which corresponded to PC2, was positively correlated with DPHP and DEHP (Fig. 3d). In chemical laboratories, four groups of PAE compounds were identified according to the loading scores of various PAEs. Groups 1, 3, 14

Journal Pre-proof and 4, which corresponded to PC1, had strong positive correlations with DEHP and DPHP, whereas Group 2, which corresponded to PC2, was strongly correlated with DBP and DMEP (Fig. 3b). In biological laboratories, three groups of PAEs were identified based on the loading scores of various PAEs. Group 1, which corresponded to PC1, had strong positive correlations with DiBP, DPHP, and DEHP, whereas Groups 2 and 3, which corresponded to PC2, were positively correlated with DEP, DBP, and DMEP (Fig. 3c). These results from PCA were consistent with

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those from Pearson correlation analysis (Table S6). Overall, more groups were identified in

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chemical laboratories than in biological or physical laboratories, suggesting that there was a

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difference in the compositions or concentrations of PAEs among laboratory types. Additionally,

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the loading scores of various PAEs in physical laboratories were similar to those in all laboratories,

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indicating that PAEs in physical laboratories contributed much more to total laboratory loading scores, because extremely high concentrations occurred more frequently in physical laboratories.

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3.3. Factors affecting the levels of PAEs in the indoor air of laboratories

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The levels of PAEs in the indoor air of laboratories depended on environmental factors such as whether conditions were wet or dry, air exchange, and radiation from sunlight, which were tested using the independent samples t-test (Fig. 4). The average concentrations of PAEs (DEP, DBP, and DMEP) were significantly (p <0.05) higher in dry and closed laboratories than in wet laboratories or those with open windows. Additionally, the average concentrations of PAEs (DEP, DBP, DiBP, and DMEP) in laboratories without sunlight radiation were 11-fold higher (p <0.01) than in those receiving sunlight radiation. On the other hand, the ventilation system had no significant (p >0.05) effect on the concentrations of PAEs in these laboratories aside from DEHP and DPHP (p <0.05). No significant (p >0.05) correlations were found between concentrations of PAEs and laboratory size (Fig. S3). 15

Journal Pre-proof 3.4. Human health risk assessment To estimate the human health risk of PAEs in the indoor air of laboratories, DEDs of PAEs via dermal absorption and inhalation were calculated (excluding DPHP due to lack of a reference dose). DEDinhalation values of PAEs (median: 153.55 and 130.86 ng/kg·d for males and females, respectively) were much higher than DEDdermal values (median: 38.12 and 39.75 ng/kg·d for males and females, respectively) (Table 2). The ΣDED value of PAEs for dermal absorption and

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inhalation for males (median: 191.67 ng/kg·d) was higher than that for females (median: 170.61

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ng/kg·d). The ΣDED values of various PAEs followed the order DiBP > DMEP > DBP > DEHP >

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DEP for both males and females (Table 2). The ΣDED values of PAEs were greatest in physical

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laboratories (92.31–8379 and 82.64–7564 ng/kg·d for males and females, respectively), followed

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by chemical laboratories (98.09–2334 and 87.7–2107 ng/kg·d for males and females, respectively). The lowest ΣDED values were measured in biological laboratories (88.95–300.0

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and 79.46–269.1 ng/kg·d for males and females, respectively), but these were still much higher

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than the values measured in offices (98.23–182.8 and 88.10–163.9 ng/kg·d for males and females, respectively) (Table 3). Overall, the DED values of DBP, DEP, DEHP, DiBP, and DMEP in all laboratories were far below recommended levels (100, 800, 20, 800, and 1000 μg/kg·d, respectively) (US EPA, 1990, 1997; Benson et al., 2009; Yang et al., 2014; Bui et al., 2016). To estimate the non-carcinogenic risks of PAEs, the HQ and HI of PAEs were calculated (Tables S7 and S8). The median HQ values of the tested PAEs decreased according to the following order: DEHP > DBP > DMEP > DiBP > DEP, for both males and females. The HI values for males (2.08 × 10-4–2.94 × 10-2; median: 1.51 × 10-3) were slightly higher than those for females (7.78 × 10-4–1.13 × 10-2; median: 1.33 × 10-3), and all values were much lower than 1, indicating acceptable human health risk levels. In addition, the carcinogenic risks of DEHP for 16

Journal Pre-proof both males (1.23–4.91 × 10-7; median: 2.33 × 10-7) and females (1.10–4.42 × 10-7; median: 2.09 × 10-7) were also well below the threshold value (1 × 10-5) (Li et al., 2016). 4. Discussion 4.1 Occurrence and profiles of PAEs in the indoor air of laboratories Laboratories represent a microenvironment that has received little attention to date. Information on the concentrations of PAEs in laboratory air is currently scarce (Kanazawa et al.,

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2010; Tran and Kannan, 2015; Tran et al., 2017;). To our knowledge, the present study is the first

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report on the occurrence of PAEs in the indoor air of laboratories in China. Here, three types of

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laboratories were selected for investigating PAEs in indoor air, with much higher ΣPAE levels

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(0.80×103–6.34×103 ng/m3; median: 1.68×103 ng/m3) (Table 1) detected than in similar studies in

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other environments (0.05×103–1.50×103 ng/m3) (Kanazawa et al., 2010; Tran and Kannan, 2015; Tran et al., 2017). In particular, the extremely high concentrations of PAEs observed in some

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physical and chemical laboratories were generally much higher than those reported previously in

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other microenvironments, comparable to those observed in a public transport carrier and mixed industrial-residential building (Table 4). For example, the concentrations of PAEs ranged 223-6176 ng/m3 in homes (Rudel et al., 2010; Pei et al., 2013; Blanchard et al., 2014; Takeuchi et al., 2014; Zhang et al., 2014; Takeuchi et al., 2015), and ranged 3590-4748 ng/m3 in offices and apartments (Wang et al., 2014; Song et al., 2015; Bu et al., 2016). These results suggest that some concerns is warranted and further investigation is imperative on indoor air of laboratories. Based on concentrations of PAEs reported previously (Table 4), we calculated the contributions of individual PAEs to ΣPAEs (Table S9). DBP, DEHP, and DEP were the dominant PAEs in various microenvironments, accounting for 30.73%, 26.48%, and 26.12% of ΣPAEs, respectively, followed by DMP, BBP, and DnOP, which accounted for 13.48%, 8.63%, and 7.30%, 17

Journal Pre-proof respectively. Large-scale production and widespread consumption of PAEs, especially DBP, DEHP, and DEP in plastic products, combined with their volatility have resulted in the ubiquitous presence of these compounds in indoor air environments (Albar et al., 2017; Kashyap et al., 2018). Notably, in the present study, DMEP, DiBP, and DBP were found to be the dominant PAEs in laboratories, accounting for up to 93.52%, 49.14%, and 40.28% of ΣPAEs, respectively (Fig. 1). Moreover, we report here the first observations of DMEP and DPHP in indoor air, and the

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extremely high levels of DMEP detected in some laboratories imply that it is a PAE compound

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specifically associated with laboratories. Overall, detailed information on PAE concentrations and

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profiles in the indoor air of laboratories may help with linking these PAEs to their specific

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sources.

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4.2 Possible sources of PAEs in the indoor air of laboratories To illustrate the possible sources of PAEs in laboratory air, the applications of some common

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PAEs are included in Table S10. High-molecular-weight PAEs such as BBP, DEHP, and DnOP are

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primarily used as plasticizers in PVC flooring, toys, furniture, and food packaging, whereas low-molecular-weight PAEs such as DMP, DEP, and DBP are generally used in plastic bottles, fragrances, cosmetics, and medications (Li et al., 2016). These items are commonly used in homes and offices, indicating that PAEs in the indoor air of homes and offices are derived from stationary sources. However, the sources of PAEs in indoor air of laboratories may be more complicated due to the diverse scientific instruments and materials present. In the present study, the sources of PAEs in three types of laboratories were identified separately through PCA (Fig. 3b–d). In chemical laboratories, high-molecular-weight PAEs (e.g. DPHP and DEHP) contributed the highest loading scores to PC1. These PAEs likely originated from experimental benches, culturing equipment, instrumentation, and laboratory consumables (Reid et al., 2007; Nguyen et 18

Journal Pre-proof al., 2008). By contrast, low-molecular-weight PAEs (e.g. DBP) contributed mainly to the loading of PC2, and these PAEs are thought to be derived from chemical reagents (Reid et al., 2007; Nguyen et al., 2008; Kwong et al., 2019). A similar pattern occurred in biological laboratories. Interestingly, the opposite result was found in physical laboratories, with low- and high-molecular-weight PAEs exhibiting strong positive correlations to PC1 and PC2, respectively, indicating that the PAEs at these locations were derived from different sources, such as

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experimental benches, instrumentation, plastic fittings, plastic-coated electrical wires, and

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computers (Jin et al., 2018). In particular, DMEP and DPHP are commonly used as plasticizer in

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cellulosic resins, vinyl ester resins, adhesives, wires, cables, and building materials commonly

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used in laboratories (NICNAS, 2003; CPSC, 2011). These results indicate that the PAEs in the

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indoor air of physical laboratories are derived from different sources compared to those found in other types of laboratories. Few chemical regents are used in the physical laboratories sampled.

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Additionally, our results suggested that low- and high-molecular-weight PAEs in the indoor air of

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laboratories might be derived from the same sources (Fig. 3). However, the exact sources of PAEs in the indoor air of laboratories should be investigated further. 4.3 Factors affecting PAEs in the indoor air of laboratories PAEs are in a state of dynamic flux in the indoor air environment due to the processes of emission, transportation, degradation, deposition, and exchange. The concentrations and profiles of PAEs depend not only on intrinsic factors (e.g. source intensity and emission rate of PAEs) but also on extrinsic factors (e.g. humidity, room size, air exchange rate, and sunlight radiation) (Orecchio et al., 2013; Kashyap et al., 2018). In the present study, levels of low-molecular-weight PAEs such as DEP, DBP, and DMEP were significantly (p <0.05) affected by whether conditions were wet or dry, whether windows were open or closed, and sunlight radiation, whereas those of 19

Journal Pre-proof high molecular weight such as DEHP and DPHP were significantly affected by ventilation installation (p <0.05) (Fig. 4), suggesting that the occurrence of PAEs in indoor air is affected by both their physicochemical properties and environmental conditions. Radiation from sunlight was the most important environmental factor that significantly (p <0.01) affected the concentrations of PAEs in laboratory air (Fig. 4). Extremely high concentrations of DEP, DBP, DiBP, and DMEP were observed in laboratories that received little

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sunlight radiation (Table S1), implying that low-molecular-weight PAEs are efficiently degraded

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by sunlight (Orecchio et al., 2013; Vela et al., 2018). Ultraviolet rays could catalyse the

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degradation of PAEs, thereby exerting strong effects on the concentrations of PAEs in indoor air

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(Xu et al., 2007; Chen et al., 2010). Humidity is an important factor affecting PAE concentrations

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in the indoor air of laboratories. High levels of DEP, DBP, and DMEP were found in laboratories with low humidity. By contrast, low levels of PAEs were detected in laboratories equipped with

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water supply and drainage systems. Higher humidity was conducive to the degradation of PAEs in

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indoor air, which resulted in gradual decreases in the concentrations of PAEs in both source and sink areas over time (Kashyap et al., 2018). Air exchange was also a crucial factor affecting PAE concentrations in the indoor air of laboratories. High concentrations of PAEs were found in laboratories where windows were normally closed (Fig. 4), suggesting that natural ventilation contributes strongly to the dilution and diffusion of PAEs in indoor air. Previous research showed that increasing the air change rate (from 0.5/h to 1.5/h) reduced total concentrations of SVOCs in the indoor environment (Xu and Zhang. 2011). However, typical ventilation systems were not efficient enough to control PAE levels (i.e. those of DEP, DBP, DiBP, and DMEP) due to their limited contribution to air exchange throughout the laboratory. Parthasarathy et al. (2012) also found that typical ventilation systems in commercial buildings were ineffective for controlling 20

Journal Pre-proof levels of SVOCs with high Koa (>12), as they remained adsorbed on particles. 4.4 Human health risk assessment In the present study, the ΣDED values of PAEs in all laboratories were below the reference doses suggested by the US EPA (800, 100, 800, 20, and 1000 μg/kg·d for DEP, DBP, DiBP, DEHP, and DMEP, respectively), and both the non-carcinogenic and carcinogenic risks were also below threshold values, suggesting that human health risks were at acceptable levels. However, the

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ΣDED values of PAEs in laboratories reached a maximum of 8379 ng/kg·d (Table 2), which

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greatly exceeded the levels observed in homes and offices (Table 4). This finding suggests that the

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specific indoor environment of laboratories might result in increased exposure to PAEs. The DED

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values of PAEs for inhalation were approximately 4-fold higher than those for dermal absorption,

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suggesting that the inhalation pathway was the main contributor to health risk. However, this result does not mean that the dermal absorption pathway is negligible. Previous studies have

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showed that dermal absorption of gas-phase PAEs is the dominant route of exposure for children

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(Gaspar et al., 2014; Weschler and Nazaroff, 2014). The transdermal permeability coefficient (Pskin/air) is a mass-transfer parameter describing the ability of organic compounds to be transferred from the air to dermal capillaries (Weschler et al., 2014). Here, estimated values of Pskin/air were in the range of 0.49–4.3 m/h for PAEs (Table S5), indicating non-negligible dermal absorption of PAEs (Lao et al., 2018). Thus, control techniques and management methods should be enacted to decrease PAE concentrations in the indoor air of laboratories. Personal protective measures, such as the use of respirators and laboratory coats, should be strictly observed. Dietary intake is generally considered the major pathway of human exposure to PAEs, and therefore little attention has been paid to human exposure through inhalation and dermal absorption (Otake et al., 2004; Yu et al., 2010). In fact, high concentrations of PAEs in indoor air 21

Journal Pre-proof led to greatly increased values of DEDinhalation and DEDdermal (Table 2). In the present study, ΣDED values of PAEs for inhalation and dermal absorption were extremely high in some laboratories (Tables 2 and 3), surpassing most previous reports based on dietary intake, which ranged from 114–2463 ng/kg·day for adults across China (Guo et al., 2012; Ji et al., 2014; Sui et al., 2014; He et al., 2015; Zhang et al., 2018). These findings strongly indicate that PAEs in the indoor air of laboratories contribute significantly to total exposure. Moreover, a comprehensive assessment of

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human exposure to PAEs from environmental media and food is lacking (Ji et al., 2014), and

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therefore most studies underestimate overall exposure.

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Our evaluation based on current knowledge indicates that an appreciable adverse human

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health impact directly related to PAE exposure in the indoor air of laboratories is unlikely. Despite

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the absence of any direct risk, indoor air will always be a major focus of attention, as it is an essential element for human health and acts a carrier of contaminants into the body. As hormones

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and endocrine-disrupting chemicals, the impacts of PAEs on human health cannot be ignored.

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Previous research has indicated that long-term and low-level exposure to environmental endocrine disruptors has specific damaging effects on the health of animals and humans (Hayes et al., 2002; Miyawaki et al., 2007; Botelho et al., 2009). The effects of low doses cannot be predicted from the effects observed at high doses (Vandenberg et al., 2012). With in-depth research into environmental endocrine disruptors such as PAEs and PFOA, their health risks are becoming clear. For example, the reference dose of pentadecafluorooctanoic acid (PFOA) was 3000 ng/kg·d in 2006 (UK COT, 2006) but was reduced to 0.8 ng/kg·d in 2018 (EFSA, 2018). Therefore, investigating patterns of long-term and low-level exposure to PAEs is essential for the early detection of harmful effects in exposed populations over time (Yang et al., 2010). 5. Conclusion 22

Journal Pre-proof This is the first report on the occurrence of PAEs in the indoor air of laboratories in China. Significantly elevated (p <0.05) concentrations of PAEs were observed in some physical and chemical laboratories. DMEP, DBP, and DiBP were the dominant PAEs measured. We report here the first observations of DMEP and DPHP in indoor air. The PCA results indicated that the PAEs in physical laboratories were derived from different sources than those in other types of laboratories. The overall patterns of occurrence of PAEs in indoor air were determined by both

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their physicochemical properties and environmental conditions. The ΣDEDs of PAEs for

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inhalation and dermal absorption in the indoor air of laboratories were generally higher than those

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via dietary intake for adults across China. Therefore, further research should be conducted to

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investigate the long-term effects of exposure to PAEs in laboratories.

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Acknowledgement

This work was funded by the Research Team Project of the Natural Science Foundation of

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Guangdong Province (2016A030312009), the Project of the Guangzhou Science and Technology

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(201704020074), and the NSFC-Guangdong Joint Fund (U1501233). The authors would like to thank the anonymous reviewers for their helpful comments and suggestions. Notes

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Journal Pre-proof Conflict of Interest Statement

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The authors declare that there is no conflict of interest.

29

Journal Pre-proof

Figures Fig. 1 Individual PAE contributions to ΣPAEs in laboratories air. Fig. 2 Correlation matrix map of PAEs in laboratories air (**p < 0.05; *p < 0.1). Fig. 3 Principal component analysis of PAEs in laboratories air. Loading scores for PAE congeners in all laboratories (a); laoding scores for PAE congeners in chemical (b), biological (c), and physical laboratories (d).

of

Fig. 4 Effects of environment factors on PAE concentrations (ng/m3) in laboratories air.

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Fig. 5 The levels of six priority PAEs in indoor air collected from several regions in the world.

30

Journal Pre-proof

Tables

DiBP 100

DMEP 100

DEHP 100

DPHP 100

ΣPAEs 100

0.003

0.437

0.528

3.756

0.140

0.167

5.031

SD

0.003

0.174

0.168

6.084

0.049

0.058

6.210

Min

0

0.216

0.205

0.137

0.073

0.083

0.895

Median

0.002

0.394

0.515

0.380

0.129

0.160

1.707

Max

0.012

0.772

0.815

16.528

0.273

0.319

17.861

100

100

100

100

100

100

100

0.003

0.468

0.437

0.446

0.133

0.157

1.644

SD

0.002

0.159

0.164

0.210

0.044

0.054

0.522

Min

0.001

0.293

0.199

0.131

0.068

0.079

0.800

Median

0.002

0.412

0.495

0.428

0.133

0.153

1.721

Max

0.005

0.738

0.644

0.956

0.192

0.224

2.609

DF（%）

100

100

100

100

100

100

100

Mean

0.011

0.794

0.506

9.960

0.139

0.169

11.579

SD

0.022

0.798

0.348

20.151

0.035

0.044

21.255

Min

0

0.197

0.205

0.174

0.091

0.112

0.884

Median

0.004

0.441

0.411

0.453

0.128

0.157

1.662

Max DF（%）

0.084

2.783

1.519

59.754

0.201

0.247

63.893

100

100

100

100

100

100

Mean

0.006

0.571

0.495

5.017

0.138

0.165

6.391

SD

0.013

0.507

0.243

12.804

0.042

0.051

13.462

0

0.196

0.199

0.131

0.068

0.079

0.800

Median

0.003

0.406

0.483

0.434

0.130

0.157

1.697

Max

0.084

2.783

1.519

59.754

0.273

0.319

63.893

DF（%）

100

100

100

100

100

100

100

Mean

0.003

0.290

0.293

0.429

0.125

0.153

1.293

SD

0.002

0.069

0.151

0.118

0.029

0.036

0.353

Min

0.001

0.211

0.143

0.296

0.095

0.115

0.934

Median

0.003

0.330

0.292

0.469

0.127

0.157

1.303

Max

0.005

0.330

0.445

0.521

0.152

0.188

1.641

Total (n=40)

Min

Offices (n = 3)

100

ro

-p

re

Physical labs (n = 14)

Jo ur

Biological labs DF（%） (n = 11) Mean

of

DBP 100

Chemical labs DF（%） (n = 15) Mean

na

DEP 100

lP

Table 1 Statistical summary of PAE concentrations (×103 ng/m3) in the laboratories and offices.

31

Journal Pre-proof Table 2 The daily exposure dose (ng/kg·d) of PAEs via dermal absorption and inhalation. DEP

DBP

DiBP

DMEP

DEHP

ΣPAEs

0.12

10.48

10.74

151.52

3.88

176.75

0.29

9.41

5.40

399.85

1.18

412.48

Median 0.07

7.5

10.72

14.05

3.67

38.12

Range

0.01-1.87

3.74-52.95 3.19-33.91 4.22-927.6 1.94-7.5

0.56

55.16

48.19

470.17

13.70

599.88

1.29

49.5

24.21

1240.74

4.16

1317.51

Median 0.32

39.46

48.09

43.61

12.96

153.55

Range

0.02-8.38

19.67-278.6 14.2952.09 13.09-591.6 6.83-27.3 72.20-6372.26

Mean

0.7

65.6

58.9

SD

1.6

58.9

29.6

Median 0.4

47

58.8

Range

0.0-10.3

23.4-331.6 17.5-186.0 17.3-7909.4 8.8-35.1

Mean

0.13

10.93

SD

0.3

9.81

SD

ΣDED

Female

DEDDermal

Median 0.07

SD

1640.6

5.3

1716.6

57.7

16.6

190.9 88.9-8379.0

11.20

157.99

4.05

184.30

5.63

416.91

1.23

430.09

11.18

14.65

3.83

39.75

0.48

47.36

41.38

403.73

11.76

504.70

42.51

20.79

1065.39

3.57

1119.84

33.88

41.30

37.45

11.13

130.86

1.11

4.40-2009.9 2.02-8.08 17.46-2092.41

0.02 -7.2

16.89-239.2 12.27-130.6 11.24-5136 5.87-23.5 62.00-5471.69

Mean

0.6

58.3

52.6

561.7

15.8

689.0

SD

1.4

52.3

26.4

1482.3

4.8

1549.9

Median 0.3

41.7

52.5

52.1

15.0

170.6

Range

20.8-294.4 15.6-15.9

na

Range

Jo ur

Note:

764.5

3.90-55.21 3.32-3.36

Median 0.27 ΣDED

17.6

0.01-1.95

lP

Range DEDInhalation Mean

7.82

16.75-2006.77

621.7

of

DEDInhalation Mean

ro

SD

-p

Exposure pathway DEDDermal Mean

re

Gender Male

0.0-9.1

ΣDED = DEDDermal+DEDInhalation

32

15.6-7146.3 7.9-31.5

79.5-7564.1

Journal Pre-proof Table 3 The daily exposure dose (ng/kg·d) of PAEs in different types of laboratories.

ro

re 33

DMEP 59.00 27.85 56.69 17.31-126.5 669.42 805.36 50.29 18.14-2187 1318.36 2667.28 60.02 23.05-7909 56.75 15.56 62.12 39.22-68.93 53.31 25.16 51.22 15.64-114.3 604.83 727.66 45.44 16.39-1976 1191.16 2409.94 54.23 20.82-7146 51.28 14.06 56.12 35.43-62.28

of

DiBP 53.55 20.04 60.58 24.31-78.8 16.05 20.62 63.01 25.13-99.78 61.96 42.65 50.29 25.14-185.9 35.88 18.48 35.72 17.48-54.44 47.78 17.88 54.05 21.69-70.33 14.32 18.40 56.22 22.42-89.03 55.28 38.05 44.87 22.43-165.9 32.01 16.49 31.87 15.60-48.57

-p

DBP 55.81 18.89 49.12 34.96-87.9 17.15 20.72 46.95 25.73-91.98 94.57 95.12 52.53 23.41-331.5 34.56 8.17 39.28 25.13-39.28 49.56 16.78 43.62 31.05-78.09 15.23 18.4 41.7 22.85-81.68 83.98 84.48 46.65 20.79-294.4 30.69 7.26 34.88 22.32-34.88

lP

DEP 0.36 0.2 0.27 0.11-0.67 0.24 0.36 0.25 0.06-1.5 1.33 2.68 0.44 0.03-10.25 0.37 0.27 0.32 0.14-0.67 0.32 0.18 0.24 0.10-0.6 0.22 0.32 0.22 0.05-1.33 1.18 2.39 0.39 0.03-9.15 0.33 0.24 0.28 0.12-0.59

na

Female

Labs Biological Mean labs SD Median Range Chemical Mean labs SD Median Range Physical Mean labs SD Median Range Offices Mean SD Median Range Biological Mean labs SD Median Range Chemical Mean labs SD Median Range Physical Mean labs SD Median Range Offices Mean SD Median Range

Jo ur

Gender Male

DEHP 17.06 5.69 17.02 8.77-24.61 4.43 6.32 16.61 9.33-35.07 17.90 4.56 16.38 11.69-25.84 16.00 3.72 16.26 12.15-19.58 15.34 5.12 15.31 7.89-22.13 3.98 5.68 14.93 8.39-31.54 16.10 4.10 14.73 10.52-23.24 14.39 3.35 14.62 10.93-17.61

ΣPAEs 185.78 59.77 193.23 88.95-300.0 681.75 819.54 190.86 98.09-2334 1494.10 2797.90 193.66 92.31-8379 143.57 42.65 149.59 98.23-182.8 166.31 53.58 172.97 79.46-269.1 615.79 740.25 170.62 87.70-2107 1347.70 2526.11 173.74 82.64-7564 128.71 38.21 134.09 88.10-163.9

Journal Pre-proof Table 4 3

Median concentrations (ng/m ) of six priority phthalates in indoor air reported in different countries. n

DMP

DEP

DBP

BBP

DEHP

DnOP

ΣPAEs

References

Apartment

28

1770

340

740

10

730

-

3590

Bu et al., 2016

Bus, subway, taxi, car

235 6348.7

4627.65

2689.97

3401.55

5289.48

2332.96

24690.31

Chi et al., 2017

University campus

77

1.82

0.9

39.67

1.87

318.7

-

362.96

Ma et al., 2014

Office, residential building

28

610

-

1650

-

1510

3770

Wang et al., 2014

Homes

13

368.36

54.52

573.47

0.59

71.7

0.12

1068.76

Zhang et al., 2014

Homes

10

1455

2290.2

1938.6

3975

2438

-

12096.8

Pei et al., 2013

Office

10

815.55

1042.75

1099.2

665.33

f o

-

1125.4

-

4748.23

Song et al., 2015

India

Industrial cum residential building

40

18311

12368

13909

11927

14995

11833

83343

Das et al., 2014

Japan

Homes

21

19

33

67

22

86

5.5

232.5

Takeuchi et al., 2015

Homes,cars,kindergartens,laboratories,office, and 40 hair salons

40

47.9

60.7

200

-

147

495.6

Kanazawa et al., 2010

Homes

181.17

408.33

3611.67

45.83

1928.3

0.83

6176.13

Takeuchi et al., 2014

376

133

16.4

187

10.9

762.8

Tran et al., 2017

158

99.99

3.7

51.5

-

321.39

Blanchard et al., 2014

163

208

283

-

276

-

930

Fromme et al., 2013

14

-

-

149

21

24

-

194

Rakkestad et al., 2007

30

9.6

1170.33

735.33

21

197.67

-

2133.93

Bergh et al., 2011

10

0.39

2.14

-

0.04

5.91

0.11

8.59

Aragón et al., 2012

America Child care facility

40

-

210

520

100

100

-

930

Gaspar et al., 2014

Homes

50

-

330

140

6.8

68

-

544.8

Rudel et al., 2010

15.9

445

112

9.25

85.3

-

667.45

Tran and Kannan, 2015

Countries China

Sampling location

6

Vietnam Homes, cars, kindergartens, laboratories, offices, 97 and hair salons France

Homes

30

u o

Germany Day care centre

63

J

Norway

University, school, kindergarten, dwelling

Sweden

Home, day care, work

Spain

Harbour

Home, office, lab, schools, salons, public places 60

l a

rn 39.5 8.2

p e

r P

“n” indicates the number of samples; “-” indicates no detected or below the detection line 34

ro

Journal Pre-proof

Jo ur

na

lP

re

-p

ro

of

Graphic Abstract

35

Journal Pre-proof Highlights: 1. This is the first report on the occurrence and health risks of PAEs in labs of China. 2. We report here the first observations of DMEP and DPHP in indoor air. 3. Extremely high levels of PAEs were observed in labs.

Jo ur

na

lP

re

-p

ro

of

4. PAEs levels varied significantly in different types of labs.

36

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5