Decreased Human Respiratory Absorption Factors of Aromatic...

Subscriber access provided by University of Florida | Smathers Libraries

Environmental Science & Technology Letters is published by the American ChemicalSociety. 1155 Sixteenth Street N.W., Washington, DC 20036Published by American Chemical Society. Copyright © American Chemical Society.However, no copyright claim is made to original U.S. Government works, or worksproduced by employees of any Commonwealth realm Crown government in the courseof their duties.

Letter

Decreased Human Respiratory Absorption Factors of Aromatic Hydrocarbonsat Lower Exposure Levels: The Dual Effect in Reducing Ambient Air Toxics

Zhonghui Huang, Yanli Zhang, Qiong Yan, Zhaoyi Wang, Zhou Zhang, and Xinming WangEnviron. Sci. Technol. Lett., Just Accepted Manuscript • DOI: 10.1021/acs.estlett.7b00443 • Publication Date (Web): 23 Oct 2017

Downloaded from http://pubs.acs.org on October 24, 2017

Just Accepted

“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are postedonline prior to technical editing, formatting for publication and author proofing. The American ChemicalSociety provides “Just Accepted” as a free service to the research community to expedite thedissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscriptsappear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have beenfully peer reviewed, but should not be considered the official version of record. They are accessible to allreaders and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offeredto authors. Therefore, the “Just Accepted” Web site may not include all articles that will be publishedin the journal. After a manuscript is technically edited and formatted, it will be removed from the “JustAccepted” Web site and published as an ASAP article. Note that technical editing may introduce minorchanges to the manuscript text and/or graphics which could affect content, and all legal disclaimersand ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errorsor consequences arising from the use of information contained in these “Just Accepted” manuscripts.

1

Decreased Human Respiratory Absorption Factors of Aromatic Hydrocarbons 1

at Lower Exposure Levels: The Dual Effect in Reducing Ambient Air Toxics 2

Zhong-Hui Huang,†,‡

Yan-Li Zhang,†,§

Qiong Yan,‖

Zhao-Yi Wang,†,‡

Zhou 3 Zhang,

† and Xin-Ming Wang*,†,§

4

†State Key Laboratory of Organic Geochemistry and Guangdong Key Laboratory of 5

Environmental Protection and Resources Utilization, Guangzhou Institute of Geochemistry, 6 Chinese Academy of Sciences, Guangzhou 510640, China 7

‡University of Chinese Academy of Sciences, Beijing 100049, China 8

§Center for Excellence in Urban Atmospheric Environment, Institute of Urban Environment, 9

Chinese Academy of Sciences, Xiamen 361021, China 10

ǁDepartment of Respiratory Diseases, Guangzhou No.12 People’s Hospital, Guangzhou 11 510620, China 12

13

14

15 16

17

18

19

20

*Corresponding author: 21

Dr. Xinming Wang 22

State Key Laboratory of Organic Geochemistry 23

Guangzhou Institute of Geochemistry, Chinese Academy of Sciences 24

Guangzhou 510640, China 25

Tel.: +86-20-85290180; fax: +86-20-85290706. 26

E-mail: [email protected] 27

Page 1 of 22

ACS Paragon Plus Environment

Environmental Science & Technology Letters

2

ABSTRACT 28

Respiratory absorption factors (AFs) are important parameters for assessing human health 29

risks of long-term inhalation exposure to low-level hazardous air pollutants. However, it is 30

uncertain whether previously measured respiratory AFs for high-level exposures could be 31

directly applied. Here we measured real-time respiratory AFs using proton transfer reaction 32

time-of-flight mass spectrometry (PTR-TOF-MS) for 50 fifty subjects (aged 20-30; 24 33

females and 26 males) exposed in a normal office room with aromatic hydrocarbons (AHs) at 34

concentration levels of several part per billion by volume (ppbv). The mean respiratory AFs 35

of benzene, toluene, and C8-aromatics (ethylbenzene and xylenes) from all subjects were 36

28.2%, 63.3%, and 66.6%, respectively. No gender difference in the respiratory AFs of AHs 37

was observed. Correlation analysis revealed that exposure concentration, rather than 38

physiological parameters like body mass index (BMI) or body fat ratio (BFR), was the 39

dominant factor influencing the AFs of AHs. The results also demonstrated that respiratory 40

AFs decreased in a logarithmic way when lowering exposure levels of AHs. The decreased 41

respiratory AFs at lowered exposure levels suggest the dual effect of reducing ambient air 42

toxics like AHs on lowing human inhalation intake. 43

44

Keywords: Inhalation exposure; respiratory absorption factors; volatile organic compounds 45

(VOCs); hazardous air pollutants; PTR-TOF-MS 46

47

48

49

50

51

52

53

54

Page 2 of 22



3

� INTRODUCTION 55

There has been an increasing attention about volatile organic compounds (VOCs) in ambient 56

air, not only for their roles in forming tropospheric ozone and secondary organic aerosols 57

(SOA),1-4 but also for their potential carcinogenic and non-carcinogenic health effects on the 58

human population. Exposure to hazardous VOCs might be associated with respiratory, 59

cardiovascular, and neurological diseases including asthma, chronic obstructive pulmonary 60

disease (COPD), and leukemia.5-12 The inhalation intake of toxic VOCs, however, depends 61

not merely on the ambient levels of VOCs. Respiratory absorption factors (AFs), which 62

denote the percentages of inhaled toxicants retained authentically inside the human body, are 63

considered to be indispensable parameters in assessing daily intakes and health risks due to 64

exposure to toxic VOCs.13-18 65

The air we breathe contains a diverse range of low-level VOCs that can be taken up by the 66

body, and health endpoints related to long-term low-level exposure of air toxics is a 67

challenging issue in environmental health. Yet very little is known about the respiratory AFs 68

of low-level VOCs in indoor or outdoor environments. Results from the Total Exposure 69

Assessment Methodology (TEAM) studies conducted in the 1980’s indicated that higher 70

fractions of inhaled benzene concentrations are absorbed at very low doses.19, 20 Based on a 71

wide range of earlier studies concerning respiratory AFs of VOCs in very high levels (tens of 72

ppmv or even higher),21 AFs were assumed to be 90%,14-17, 22-25 100%18, 26-38 or most recently 73

to be 50-60%39, 40 when assessing health risks of inhalation exposure to toxic VOCs. It is 74

questionable whether these AFs can be applied to low-level exposure situations. Moreover, 75

AFs are regarded as constant to simplify the inputs in pharmacokinetic models studying the 76

fate of exogenous VOCs within the human body.41-44 In essence, these AFs are more likely to 77

be variable as they are affected by a multitude of factors including exposure concentrations, 78

physicochemical behaviors of VOCs and individual human physiological conditions.45 Hence 79

it is necessary to determine respiratory AFs of toxic VOCs particularly in the low-level 80

exposure environments. 81

Page 3 of 22



4

The most common aromatic hydrocarbons (AHs), namely benzene, toluene, ethylbenzene, 82

and xylenes (BTEX), were chosen as typical toxic VOCs in the present study. BTEX are a 83

major class of hazardous air pollutants: benzene is a well-known carcinogen causing leukemia, 84

and TEX may deteriorate developmental, nervous, and heart and blood vessel systems.13, 46 85

Additionally, BTEX are ubiquitous in both indoor and outdoor environments, particularly in 86

developing countries.47-53 Even at background sites in China ambient benzene levels might 87

exceed the limit set by European Union (EU).54 In this study, fifty volunteers were asked to 88

stay in a normal office room, and by using a homemade online breath sampling device 89

coupled to a proton transfer reaction time-of-flight mass spectrometry (PTR-TOF-MS), 90

real-time respiratory AFs were measured for all subjects exposed to indoor AHs at several 91

part per billion by volume (ppbv). The purposes of this study are: 1) to check if there is a 92

gender difference in the respiratory AFs of AHs; 2) to explore the relationship between AFs 93

and exposure levels under low-level exposure situations; and 3) to investigate if physiological 94

factors, such as body mass index (BMI) and body fat rate (BFR), influence the respiratory 95

AFs. 96

� MATERIALS AND METHODS 97

Subjects. First phase test: a total of fifty young volunteers, who were then all graduate 98

students studying in the Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, 99

participated in this study. Every test subject was required to stay in a well-ventilated normal 100

office room for about half an hour during the test with PTR-TOF-MS. It should be noted that 101

this was not a human toxicity test because none of the BTEX were injected into the office 102

room. All subjects gave written informed consent prior to participation in the study. Subjects 103

completed a brief questionnaire concerning needed information regarding their gender, age, 104

height, weight, BMI, BFR, smoking/drinking status, and personal/familial past medical 105

history. These fifty subjects included 26 males and 24 females, aged 20-30 years old. They 106

were all non-smokers and non-drinkers. Demographic data of the subjects represented in the 107

study are summarized in Table S1 (Supporting Information). 108

Second phase test: in order to further verify the relationships between exposure 109

Page 4 of 22



5

concentrations and AFs of BTEX, one male and one female subjects were randomly selected 110

from volunteers participating the first phase test. They were asked to stay 4 h per day in the 111

same office room over 3 days for more tests of AFs with the variation of BTEX largely due to 112

ventilation. 113

Online Breath Sampling and Measurement. A homemade online breath sampling 114

device was used for sampling air inhaled and exhaled by subjects. Detailed description of the 115

sampling device can be found in our previous study.21 There is, however, an improvement 116

that a Swagelok plug valve was added between the left end of the tube and the nose interface 117

in the current study. 118

A commercial high-sensitivity PTR-TOF-MS (model 2000; Ionicon Analytik GmbH, 119

Innsbruck, Austria) was deployed to measure BTEX levels in the breath samples. The 120

measurement principle of PTR-TOF-MS has been described elsewhere in detail.55-57 The 121

PTR-TOF-MS acquired data at a 0.5 Hz time resolution with H3O+ reagent ion. The drift tube 122

of the instrument was operated at a voltage of 610 V, pressure of 2.20 mbar, and temperature 123

of 60°C, with an E/N ratio of about 139 Townsend (Td) (where E is the electric field strength 124

and N is the number density of a neutral gas; 1 Td = 10−17 V cm2). 125

Detailed online breath sampling and measurement steps were described in our 126

previous study.21 Briefly, indoor air, which was the air inhaled by subjects, was firstly 127

sampled and measured through the online breath sampling device. During the ensuing exhaled 128

air measurements, the subject steadily exhaled alveolar air into the sampling device, and then 129

closed the plug valve right after a complete expiration. The plug valve was blocked until the 130

exhaled air in the buffer tube was exhausted and hereafter the indoor air was extracted and 131

measured for several minutes. According to the above operating steps, the inhaled and 132

exhaled air for each subject was continuously measured to determine their respiratory AFs as: 133

�� =��

��×100% (1) 134

where Ci and Ce (ppbv) were the concentrations of the target compound in the inhaled and 135

exhaled air, respectively. Isoprene was used as a breath tracer for identifying the expiratory 136

Page 5 of 22



6

and inspiratory phases in this study.21 137

Quality Assurance and Quality Control. Target VOCs were identified based on their 138

exact mass to charge ratio (m/z) and quantified by external calibration methods. Mass 139

calibration was performed using two ion peaks with known exact masses: hydronium ion 140

isotope (H318O+; m/z 21.022) and protonated 1, 2, 4-trichlorobenzene ((C6H3Cl3)H

+, m/z 141

180.937). The isomeric ethylbenzene and xylenes, all with a molecular mass of 106 amu, 142

cannot be distinguished by PTR-TOF-MS, and thus these C8-aromatics were reported as their 143

sum. 144

Background levels for target compounds were determined by introducing zero air into the 145

instrument. Multi-point calibration of the PTR-TOF-MS was carried out before the breath air 146

measurement using VOC standard mixtures (including isoprene, benzene, toluene, o-xylene) 147

that were dynamically diluted to five levels (2, 5, 10, 15, and 20 ppbv) from a certified 148

standard gas mixture (Ionicon Analytik GmbH; ~1 ppmv). The linear correlation coefficients 149

(R2) of calibration curves were 0.996–0.999 for BTEX compounds. Their sensitivities, 150

indicated by the ratio of normalized counts per second (ncps) to the levels of BTEX in ppbv, 151

were 27, 35, and 40 ncps/ppbv for benzene, toluene and C8-aromatics, respectively. The 152

method detection limits (MDL) for benzene, toluene, and C8-aromatics in 2 s integration time 153

were 0.055, 0.044, and 0.039 ppbv, respectively. The measurement precisions and accuracies 154

were determined by repeated analysis of a standard mixture (1 ppbv) seven times. The relative 155

standard derivations for BTEX were all < 5%, and the accuracies of BTEX were all within ± 156

10%. BTEX will accept a proton from H3O+, but their reaction with (H2O)2H

+ is 157

thermodynamically unavailable. Previous studies have shown no significant humidity 158

dependence on their sensitivities.58-61 To re-confirm this, three levels of standard mixtures in 159

the range of 0-10 ppbv were prepared at relative humidity (RH) of 20% and 95%, respectively. 160

RH was controlled as per the details provided in Kumar and Sinha.62 As shown in Figure S1, 161

no significant differences in the BTX sensitivities (ncps/ppbv) were observed between the 162

standard mixtures at RH of 20% and 95% probably due to a high proportion of H3O+ ion in 163

the drift tube with a high E/N ratio. Thus humidity effects in breath samples can be ignored 164

Page 6 of 22



7

when measuring BTEX by PTR-TOF-MS in the present study. 165

Statistical analysis. The Student’s t-test in the statistical software package SPSS (Version 166

19) was used to examine statistical differences in measured concentration levels. Two-tailed 167

tests of significance were used, and p < 0.05 indicated statistical significance. It was also used 168

as critical value for significant correlation. 169

� RESULTS AND DISCUSSION 170

Real-time AFs of BTEX. The measured BTEX exposure levels ranged from 0.19–3.26 171

ppbv for benzene, 0.35–8.72 ppbv for toluene, and 0.31–6.84 ppbv for C8-aromatics in the 172

first phase test. Five sets of inhaled and exhaled air for each subject were successively 173

measured to acquire the respiratory AFs of BTEX. The average respiratory AFs and their 174

standard deviations (SD) of benzene, toluene, and C8-aromatics from all 50 subjects were 175

28.2% (SD = 10.9%), 63.3% (SD = 12.7%), and 66.6% (SD = 10.6%), respectively (Figure 176

S2). The mean respiratory AFs of benzene was much lower than previously assumed or 177

measured 90%,14-17, 22-25 100%18, 26-38 or 50-60%21, 39, 40; for toluene and C8-aromatics, the 178

mean values were near that measured in our previous study,21 but still much lower than 179

previously assumed values of 90%14-17, 22-25 or 100%18, 26-38 when assessing inhalation health 180

risks. 181

The mean respiratory AFs of benzene, toluene and C8-aromatics were 28.0%, 57.6% and 182

63.4% for the female subjects; and 28.5%, 69.1% and 69.7% for the male subjects, 183

respectively. No significant difference (p > 0.05) was observed in the respiratory AFs between 184

the female and male subjects, implying no gender difference in the respiratory AFs. In our 185

previous preliminary tests with 7 subjects,21 the 3 female subjects had significantly higher 186

respiratory AFs of BTEX than the 4 male ones (p < 0.05). Probably the small numbers of 187

subjects for the test in our previous study statistically bias the gender difference discussion. 188

Influencing Factors of AFs. Three aspects of factors, i.e., physicochemical properties of 189

VOCs, individual human physiology, and environmental factors, govern the respiratory 190

AFs.45 In this study we only focused on BTEX and their mean respiratory AFs appeared to 191

increase with molecular weight, reflecting the influence of physicochemical properties of 192

Page 7 of 22



8

these compounds such as lipophilicity, solubility in blood, and blood/air partition 193

coefficients.41, 63, 64 194

Humans are incredibly diverse, and common individual physiological parameters such as 195

gender, age, health state, BMI, and BFR needed to be seriously considered for discerning the 196

crucial influencing factors of AFs.41, 65, 66 As mentioned above, gender was not a key factor 197

affecting the AFs. Regarding age and health state, all volunteers were healthy young people 198

aged 20-30 without any past personal or familial medical history (Table S1). BMI, defined as 199

a person’s weight in kilograms divided by the square of one’s height in meters (kg/m2), is a 200

universal standard introduced by the World Health Organization for assessing the body fat 201

levels and health state. BFR is another parameter of reflecting the percentage of body fat 202

content to the body weight (Table S1). Figure 1 shows scatter plots of the respiratory AFs 203

versus BMI and BFR. No significant correlations between AFs and BMI/BFR were observed, 204

either for all subjects or for female and male subjects individually. 205

Environmental factors including pre-exposure concentration, exposure concentration and 206

duration, also influence the absorbed dose of toxic VOCs.65, 67 Because all subjects were then 207

graduate students working and living in the same institute campus, they should have quite 208

similar pre-exposure experience. During our test, subjects were exposed to different levels of 209

BTEX in the normal office room due diurnal variations. The correlations between the AFs 210

and exposed BTEX concentrations for all volunteers are shown in Figure 2a-c. The highly 211

significant log-based (p < 0.001) correlations between the AFs and exposure levels of BTEX 212

suggested that exposure levels rather than individual physiological factors were responsible 213

for the AFs, consistent with the conclusions in some previous studies.65, 68-70 214

Relationship between Exposure Levels and AF. The second phase test with just one male 215

subject and one female subject for extensive measurements would eliminate the effects of 216

inter-individual physiological variations. The relationships between exposure levels and AFs 217

for the two subjects are illustrated in Figure 2d-i, confirming the highly significant 218

logarithmic correlations for all subjects as discussed above. 219

The mechanism for the logarithmic relationship remains unexplained so far. But the 220

Page 8 of 22



9

phenomenon is reasonable because at low-exposure levels the inhalation absorption process 221

of BTEX might be similar to the Langmuir isothermal adsorption process of VOCs on the 222

surface of adsorbents, in which the adsorption efficiencies would increase with the elevated 223

concentrations of VOCs until reaching a relatively stable value when concentrations of VOCs 224

exceed a certain level.71 As showed in Figure S3, the relationships between exposure levels 225

and AFs could be well fitted with Langmuir adsorption isotherms. 226

Our results, as showed in Figure 2, demonstrated that if BTEX concentrations go down to 227

about 2 ppb or even lower, respiratory AFs decrease rapidly, implying the dual effect in 228

lowering human inhalation dose by reducing BTEX concentration in ambient air: inhalation 229

uptake would further reduced by lower AFs at lower exposure levels. This is very important 230

for some air pollutants, such as benzene, that are carcinogenic to humans and no safe level of 231

exposure can be recommended, although the inhalation minimal risk level (MRL) of 3 ppbv 232

was recommended by the United States Environmental Protection Agency (USEPA) for 233

benzene,72 and an annual limit of 5 µg/m3 (or 1.6 ppbv at 25°C and 1 atm) was established by 234

the EU for benzene in ambient air.73 From our study, as showed in Figure 2a, if benzene 235

levels decrease from 1.0 ppbv to 0.5 ppbv, its AFs would decrease from ~70% to ~40%, 236

consequently the internal intakes would decrease by ~70%, more than the 50% expected due 237

to a decrease in exposure levels alone. 238

We observed that the AFs decreased in a logarithmic way with decreasing the exposure 239

levels of BTEX. The finding is valuable for rationally assessing human health risks of 240

long-term inhalation exposure and for evaluating the effects of control measures for BTEX. 241

Nonetheless, since in this study all subjects shared similar demographic characteristics (age, 242

weight, height, and etc.) and lived in the same area, it is of concern whether our conclusions 243

can be applied to the general population and this needs to be verified with more extensive 244

study in the future. 245

246

� ASSOCIATED CONTENT 247

Page 9 of 22



10

Supporting Information 248

Demographic data of subjects in this study (Table S1); Normalized sensitivities at 249

different relative humidity of 20% and 95% for benzene, toluene and o-xylene. Slopes 250

(i.e. sensitivities) are indicated by mean values ± standard errors (Figure S1); 251

Respiratory AFs of benzene, toluene, and C8-aromatics from fifty test subjects. The 252

columns and their error bars represent the mean values and standard deviations of the 253

respiratory AFs of BTEX, respectively (Figure S2); Extended Langmuir isotherms 254

between respiratory AFs and exposure concentrations of benzene (open squares), 255

toluene (open cycles), and C8-aromatics (open triangles) collected from all (blue, a-c), a 256

male (cyan, d-f) and a female (green, g-i) subjects, respectively. Curve-fitting equations 257

and their correlation coefficient (R2) and significance levels (p) were also presented 258

(Figure S3). 259

260

� AUTHOR INFORMATION 261

Corresponding Author 262

*Phone: +86-20-85290180. Fax: +86-20-85290706. E-mail: [email protected]. 263

ORCID 264

Zhong-Hui Huang: 0000-0003-0144-0852 265

Yan-Li Zhang: 0000-0003-0614-2096 266

Xin-Ming Wang: 0000-0002-1982-0928 267

Notes 268

The authors declare no competing financial interest. 269

270

� ACKNOWLEDGMENTS 271

This work was financially supported by the Natural Science Foundation of Guangdong (Grant 272

No. 2016A030313164), the Health and Family Planning Commission of Guangzhou 273

Municipality (Grant No. 20161A010050), and the Natural Science Foundation of China 274

(Grant No. 41530641/41571130031). The authors would like to express their sincere thanks 275

Page 10 of 22



11

to volunteers in Guangzhou Institute of Geochemistry, Chinese Academy of Sciences for their 276

supports. 277

278

� REFERENCES 279

(1) O'Dowd, C. D.; Aalto, P.; Hameri, K.; Kulmala, M.; Hoffmann, T. Aerosol formation: 280

atmospheric particles from organic vapours. Nature 2002, 416, 497-498. 281

(2) Russell, A.; Milford, J.; Bergin, M. S.; McBride, S.; McNair, L.; Yang, Y.; Stockwell, 282

W. R.; Croes, B. Urban ozone control and atmospheric reactivity of organic gases. Science 283

1995, 269, 491-495. 284

(3) Ding, X.; Wang, X. M.; Gao, B.; Fu, X. X.; He, Q. F.; Zhao, X. Y.; Yu, J. Z.; Zheng, M. 285

Tracer-based estimation of secondary organic carbon in the Pearl River Delta, south China. J. 286

Geophys. Res. Atmos. 2012, 117, D05313. 287

(4) Zhang, Y. L.; Wang, X. M.; Blake, D. R.; Li, L. F.; Zhang, Z.; Wang, S. Y.; Guo, H.; 288

Lee, S. C.; Gao, B.; Chan, L. Y.; Wu, D.; Rowland, F. S. Aromatic hydrocarbons as ozone 289

precursors before and after outbreak of the 2008 financial crisis in the Pearl River Delta 290

region, south China. J. Geophys. Res. Atmos. 2012, 117, D15306. 291

(5) Lewtas, J. Air pollution combustion emissions: characterization of causative agents and 292

mechanisms associated with cancer, reproductive, and cardiovascular effects. Mutat. Res. Rev. 293

Mutat. Res. 2007, 636, 95-133. 294

(6) Elliott, L.; Longnecker, M. P.; Kissling, G. E.; London, S. J. Volatile organic compounds 295

and pulmonary function in the third national health and nutrition examination survey, 296

1988-1994. Environ. Health Perspect. 2006, 114, 1210-1214. 297

(7) Ramirez, N.; Cuadras, A.; Rovira, E.; Borrull, F.; Marce, R. M. Chronic risk assessment 298

of exposure to volatile organic compounds in the atmosphere near the largest Mediterranean 299

industrial site. Environ. Int. 2012, 39, 200-209. 300

(8) IARC (International Agency for Research Cancer). Agents Classified by the IARC 301

Monographs: List of Classifications by Cancer Sites, volumes 1-114. International Agency for 302

Research Cancer, Lyon. Available at: 303

Page 11 of 22



12

http://monographs.iarc.fr/ENG/Classification/Table4.pdf (last access: 20 July 2017). 2015. 304

(9) Boeglin, M. L.; Wessels, D.; Henshel, D. An investigation of the relationship between air 305

emissions of volatile organic compounds and the incidence of cancer in Indiana counties. 306

Environ. Res. 2006, 100, 242-254. 307

(10) Leikauf, G. D. Hazardous air pollutants and asthma. Environ. Health Perspect. 2002, 308

110, 505-526. 309

(11) Viegi, G.; Maio, S.; Pistelli, F.; Baldacci, S.; Carrozzi, L. Epidemiology of chronic 310

obstructive pulmonary disease: health effects of air pollution. Respirology 2006, 11, 523-532. 311

(12) WHO (World Health Organization). WHO Guidelines for Indoor Air Quality: Selected 312

Pollutants. In: The WHO European Centre for Environment Health B.O, editor. World Health 313

Organization, Copenhagen. Available at: 314

http://www.euro.who.int/__data/assets/pdf_file/0009/128169/e94535.pdf?ua=1 (last access: 315

20 July 2017). 2010. 316

(13) USEPA (United States Environmental Protection Agency), Integrated Risk Information 317

System (IRIS). United States Environmental Protection Agency, Washington, DC. Available 318

at: https://www.epa.gov/iris (last access: 20 July 2017). 1998. 319

(14) Guo, H.; Lee, S. C.; Chan, L. Y.; Li, W. M. Risk assessment of exposure to volatile 320

organic compounds in different indoor environments. Environ. Res. 2004, 94, 57-66. 321

(15) Du, Z. J.; Mo, J. H.; Zhang, Y. P. Risk assessment of population inhalation exposure to 322

volatile organic compounds and carbonyls in urban China. Environ. Int. 2014, 73, 33-45. 323

(16) Lerner, J. E. C.; Sanchez, E. Y.; Sambeth, J. E.; Porta, A. A. Characterization and health 324

risk assessment of VOCs in occupational environments in Buenos Aires, Argentina. Atmos. 325

Environ. 2012, 55, 440-447. 326

(17) Li, S.; Chen, S. G.; Zhu, L. Z.; Chen, X. S.; Yao, C. Y.; Shen, X. Y. Concentrations and 327

risk assessment of selected monoaromatic hydrocarbons in buses and bus stations of 328

Hangzhou, China. Sci. Total Environ. 2009, 407, 2004-2011. 329

(18) Liu, Y. J.; Liu, Y. T.; Li, H.; Fu, X. D.; Guo, H. W.; Meng, R. H.; Lu, W. J.; Zhao, M.; 330

Wang, H. T. Health risk impacts analysis of fugitive aromatic compounds emissions from the 331

Page 12 of 22



13

working face of a municipal solid waste landfill in China. Environ. Int. 2016, 97, 15-27. 332

(19) USEPA (United States Environmental Protection Agency). Extrapolation of the benzene 333

inhalation unit risk estimate to the oral route of exposure. United States Environmental 334

Protection Agency, Washington, DC. Available at: 335

https://cfpub.epa.gov/ncea/iris/iris_documents/documents/supdocs/benzsup.pdf (last access: 336

20 July 2017). 1999. 337

(20) Wallace, L. A.; Pellizzari, E. D.; Hartwell, T. D.; Whitmore, R.; Zelon, H.; Perritt, R.; 338

Sheldon, L. The California TEAM study: breath concentrations and personal exposures to 26 339

volatile compounds in air and drinking water of 188 residents of Los Angeles, Antioch, and 340

Pittsburg, CA. Atmos. Environ. 1988, 22, 2141-2163. 341

(21) Huang, Z. H.; Zhang, Y. L.; Yan, Q.; Zhang, Z.; Wang, X. M. Real-time monitoring of 342

respiratory absorption factors of volatile organic compounds in ambient air by proton transfer 343

reaction time-of-flight mass spectrometry. J. Hazard. Mater. 2016, 320, 547-555. 344

(22) Lee, C. W.; Dai, Y. T.; Chien, C. H.; Hsu, D. J. Characteristics and health impacts of 345

volatile organic compounds in photocopy centers. Environ. Res. 2006, 100, 139-149. 346

(23) Chandra, B. P.; Sinha, V. Contribution of post-harvest agricultural paddy residue fires in 347

the NW Indo-Gangetic Plain to ambient carcinogenic benzenoids, toxic isocyanic acid and 348

carbon monoxide. Environ. Int. 2016, 88, 187-197. 349

(24) Huang, Y.; Ho, S. S. H.; Ho, K. F.; Lee, S. C.; Yu, J. Z.; Louie, P. K. K. Characteristics 350

and health impacts of VOCs and carbonyls associated with residential cooking activities in 351

Hong Kong. J. Hazard. Mater. 2011, 186, 344-351. 352

(25) Lerner, J. E. C.; Kohajda, T.; Aguilar, M. E.; Massolo, L. A.; Sanchez, E. Y.; Porta, A. 353

A.; Opitz, P.; Wichmann, G.; Herbarth, O.; Mueller, A. Improvement of health risk factors 354

after reduction of VOC concentrations in industrial and urban areas. Environ. Sci. Pollut. Res. 355

2014, 21, 9676-9688. 356

(26) Demirel, G.; Özden, Ö.; Döğeroğlu, T.; Gaga, E. O. Personal exposure of primary school 357

children to BTEX, NO2 and ozone in Eskişehir, Turkey: relationship with indoor/outdoor 358

concentrations and risk assessment. Sci. Total Environ. 2014, 473–474, 537-548. 359

Page 13 of 22



14

(27) Durmusoglu, E.; Taspinar, F.; Karademir, A. Health risk assessment of BTEX emissions 360

in the landfill environment. J. Hazard. Mater. 2010, 176, 870-877. 361

(28) Hazrati, S.; Rostami, R.; Farjaminezhad, M.; Fazlzadeh, M. Preliminary assessment of 362

BTEX concentrations in indoor air of residential buildings and atmospheric ambient air in 363

Ardabil, Iran. Atmos. Environ. 2016, 132, 91-97. 364

(29) Hazrati, S.; Rostami, R.; Fazlzadeh, M. BTEX in indoor air of waterpipe cafés: levels 365

and factors influencing their concentrations. Sci. Total Environ. 2015, 524–525, 347-353. 366

(30) He, Z. G.; Li, G. Y.; Chen, J. Y.; Huang, Y.; An, T. C.; Zhang, C. S. Pollution 367

characteristics and health risk assessment of volatile organic compounds emitted from 368

different plastic solid waste recycling workshops. Environ. Int. 2015, 77, 85-94. 369

(31) Hoddinott, K. B.; Lee, A. P. The use of environmental risk assessment methodologies for 370

an indoor air quality investigation. Chemosphere 2000, 41, 77-84. 371

(32) Kumar, A.; Singh, B. P.; Punia, M.; Singh, D.; Kumar, K.; Jain, V. K. Determination of 372

volatile organic compounds and associated health risk assessment in residential homes and 373

hostels within an academic institute, New Delhi. Indoor Air 2014, 24, 474-483. 374

(33) Muller, E.; Diab, R. D.; Binedell, M.; Hounsome, R. Health risk assessment of kerosene 375

usage in an informal settlement in Durban, South Africa. Atmos. Environ. 2003, 37, 376

2015-2022. 377

(34) Sofuoglu, S. C.; Aslan, G.; Inal, F.; Sofuoglu, A. An assessment of indoor air 378

concentrations and health risks of volatile organic compounds in three primary schools. Int. J. 379

Hyg. Environ. Health. 2011, 214, 38-46. 380

(35) Chen, W. H.; Chen, Z. B.; Yuan, C. S.; Hung, C. H.; Ning, S. K. Investigating the 381

differences between receptor and dispersion modeling for concentration prediction and health 382

risk assessment of volatile organic compounds from petrochemical industrial complexes. J. 383

Environ. Manage. 2016, 166, 440-449. 384

(36) Singh, D.; Kumar, A.; Kumar, K.; Singh, B.; Mina, U.; Singh, B. B.; Jain, V. K. 385

Statistical modeling of O3, NOx, CO, PM2.5, VOCs and noise levels in commercial complex 386

and associated health risk assessment in an academic institution. Sci. Total Environ. 2016, 387

Page 14 of 22



15

572, 586-594. 388

(37) Kularatne, R. K. A. Occurrence of selected volatile organic compounds in a bra cup 389

manufacturing facility. Int. J. Environ. Sci. Technol. 2017, 14, 315-322. 390

(38) Kanjanasiranont, N.; Prueksasit, T.; Morknoy, D. Inhalation exposure and health risk 391

levels to BTEX and carbonyl compounds of traffic policeman working in the inner city of 392

Bangkok, Thailand. Atmos. Environ. 2017, 152, 111-120. 393

(39) Du, Z. J.; Mo, J. H.; Zhang, Y. P.; Xu, Q. J. Benzene, toluene and xylenes in newly 394

renovated homes and associated health risk in Guangzhou, China. Build. Environ. 2014, 72, 395

75-81. 396

(40) Lim, S. K.; Shin, H. S.; Yoon, K. S.; Kwack, S. J.; Um, Y. M.; Hyeon, J. H.; Kwak, H. 397

M.; Kim, J. Y.; Kim, T. Y.; Kim, Y. J.; Roh, T. H.; Lim, D. S.; Shin, M. K.; Choi, S. M.; 398

Kim, H. S.; Lee, B. M. Risk assessment of volatile organic compounds benzene, toluene, 399

ethylbenzene, and xylene (BTEX) in consumer products. J. Toxicol. Environ. Health Part A 400

2014, 77, 1502-1521. 401

(41) Pleil, J. D.; Stiegel, M. A.; Risby, T. H. Clinical breath analysis: discriminating between 402

human endogenous compounds and exogenous (environmental) chemical confounders. J. 403

Breath Res. 2013, 7, 017107. 404

(42) Cao, W. Q.; Duan, Y. X. Breath analysis: potential for clinical diagnosis and exposure 405

assessment. Clin. Chem. 2006, 52, 800-811. 406

(43) Wallace, L. A.; Pellizzari, E. D. Recent advances in measuring exhaled breath and 407

estimating exposure and body burden for volatile organic compounds (VOCs). Environ. 408

Health Perspect. 1995, 103, 95-98. 409

(44) Sato, A.; Nakajima, T. Pharmacokinetics of organic solvent vapors in relation to their 410

toxicity. Scand. J. Work Environ. Health 1987, 13, 81-93. 411

(45) Beauchamp, J. Inhaled today, not gone tomorrow: pharmacokinetics and environmental 412

exposure of volatiles in exhaled breath. J. Breath Res. 2011, 5, 037103. 413

(46) USEPA (United States Environmental Protection Agency), Agency for Toxic Substances 414

and Diseases Registry (ATSDR): Substances A-Z. United States Environmental Protection 415

Page 15 of 22



16

Agency, Washington, DC. Available at: http://www.atsdr.cdc.gov/substances/indexAZ.asp 416

(last access: 20 July 2017). 2015. 417

(47) Chan, L. Y.; Lau, W. L.; Wang, X. M.; Tang, J. H. Preliminary measurements of 418

aromatic VOCs in public transportation modes in Guangzhou, China. Environ. Int. 2003, 29, 419

429-435. 420

(48) Tang, J. H.; Chan, C. Y.; Wang, X. M.; Chan, L. Y.; Sheng, G. Y.; Fu, J. M. Volatile 421

organic compounds in a multi-storey shopping mall in guangzhou, South China. Atmos. 422

Environ. 2005, 39, 7374-7383. 423

(49) Wang, X. M.; Sheng, G. Y.; Fu, J. M.; Chan, C. Y.; Lee, S. C.; Chan, L. Y.; Wang, Z. S. 424

Urban roadside aromatic hydrocarbons in three cities of the Pearl River Delta, People's 425

Republic of China. Atmos. Environ. 2002, 36, 5141-5148. 426

(50) Zhang, Y. J.; Mu, Y. J.; Liang, P.; Xu, Z.; Liu, J. F.; Zhang, H. X.; Wang, X. K.; Gao, J.; 427

Wang, S. L.; Chai, F. H.; Mellouki, A. Atmospheric BTEX and carbonyls during summer 428

seasons of 2008-2010 in Beijing. Atmos. Environ. 2012, 59, 186-191. 429

(51) Zhang, Y. L.; Li, C. L.; Wang, X. M.; Guo, H.; Feng, Y. L.; Chen, J. M., Rush-hour 430

aromatic and chlorinated hydrocarbons in selected subway stations of Shanghai, China. J. 431

Environ. Sci. 2012, 24, 131-141. 432

(52) Zhang, Y. L.; Wang, X. M.; Barletta, B.; Simpson, I. J.; Blake, D. R.; Fu, X. X.; Zhang, 433

Z.; He, Q. F.; Liu, T. Y.; Zhao, X. Y.; Ding, X. Source attributions of hazardous aromatic 434

hydrocarbons in urban, suburban and rural areas in the Pearl River Delta (PRD) region. J. 435

Hazard. Mater. 2013, 250, 403-411. 436

(53) Zhao, L. R.; Wang, X. M.; He, Q. S.; Wang, H.; Sheng, G. Y.; Chan, L. Y.; Fu, J. M.; 437

Blake, D. R. Exposure to hazardous volatile organic compounds, PM10 and CO while walking 438

along streets in urban Guangzhou, China. Atmos. Environ. 2004, 38, 6177-6184. 439

(54) Zhang, Z.; Wang, X. M.; Zhang, Y. L.; Lu, S. J.; Huang, Z. H.; Huang, X. Y.; Wang, Y. 440

S. Ambient air benzene at background sites in China's most developed coastal regions: 441

exposure levels, source implications and health risks. Sci. Total Environ. 2015, 511, 792-800. 442

(55) Cappellin, L.; Karl, T.; Probst, M.; Ismailova, O.; Winkler, P. M.; Soukoulis, C.; Aprea, 443

Page 16 of 22



17

E.; Mark, T. D.; Gasperi, F.; Biasioli, F. On quantitative determination of volatile organic 444

compound concentrations using proton transfer reaction time-of-flight mass spectrometry. 445

Environ. Sci. Technol. 2012, 46, 2283-2290. 446

(56) Graus, M.; Mueller, M.; Hansel, A. High resolution PTR-TOF: quantification and 447

formula confirmation of VOC in real time. J. Am. Soc. Mass. Spectrom. 2010, 21, 1037-1044. 448

(57) Jordan, A.; Haidacher, S.; Hanel, G.; Hartungen, E.; Mark, L.; Seehauser, H.; 449

Schottkowsky, R.; Sulzer, P.; Mark, T. D. A high resolution and high sensitivity 450

proton-transfer-reaction time-of-flight mass spectrometer (PTR-TOF-MS). Int. J. Mass 451

Spectrom. 2009, 286, 122-128. 452

(58) Inomata, S.; Tanimoto, H.; Kato, S.; Suthawaree, J.; Kanaya, Y.; Pochanart, P.; Liu, Y.; 453

Wang, Z., PTR-MS measurements of non-methane volatile organic compounds during an 454

intensive field campaign at the summit of Mount Tai, China, in June 2006. Atmos. Chem. 455

Phys. 2010, 10, 7085-7099. 456

(59) Jobson, B. T.; McCoskey, J. K., Sample drying to improve HCHO measurements by 457

PTR-MS instruments: laboratory and field measurements. Atmos. Chem. Phys. 2010, 10, 458

1821-1835. 459

(60) Sarkar, C.; Sinha, V.; Kumar, V.; Rupakheti, M.; Panday, A.; Mahata, K. S.; Rupakheti, 460

D.; Kathayat, B.; Lawrence, M. G., Overview of VOC emissions and chemistry from 461

PTR-TOF-MS measurements during the SusKat-ABC campaign: high acetaldehyde, isoprene 462

and isocyanic acid in wintertime air of the Kathmandu Valley. Atmos. Chem. Phys. 2016, 16, 463

3979-4003. 464

(61) Vlasenko, A.; Macdonald, A. M.; Sjostedt, S. J.; Abbatt, J. P. D., Formaldehyde 465

measurements by proton transfer reaction-mass spectrometry (PTR-MS): correction for 466

humidity effects. Atmos. Meas. Tech. 2010, 3, 1055-1062. 467

(62) Kumar, V.; Sinha, V., VOC-OHM: A new technique for rapid measurements of ambient 468

total OH reactivity and volatile organic compounds using a single proton transfer reaction 469

mass spectrometer. Int. J. Mass Spectrom. 2014, 374, 55-63. 470

(63) Jakubowski, M.; Czerczak, S. Calculating the retention of volatile organic compounds in 471

Page 17 of 22



18

the lung on the basis of their physicochemical properties. Environ. Toxicol. Pharmacol. 2009, 472

28, 311-315. 473

(64) Gargas, M. L.; Burgess, R. J.; Voisard, D. E.; Cason, G. H.; Andersen, M. E. Partition 474

coefficients of low-molecular-weight volatile chemicals in various liquids and tissues. 475

Toxicol. Appl. Pharmacol. 1989, 98, 87-99. 476

(65) Egeghy, P. P.; Tornero-Velez, R.; Rappaport, S. M. Environmental and biological 477

monitoring of benzene during self-service automobile refueling. Environ. Health Perspect. 478

2000, 108, 1195-1202. 479

(66) Sato, A.; Nakajima, T.; Fujiwara, Y.; Murayama, N. Kinetic studies on sex difference in 480

susceptibility to chronic benzene intoxication-with special reference to body fat content. Br. J. 481

Ind. Med. 1975, 32, 321-328. 482

(67) USEPA (United States Environmental Protection Agency), Integrated Risk Information 483

System (IRIS) Assessments. United States Environmental Protection Agency, Washington, 484

DC. Available at: http://cfpub.epa.gov/ncea/iris2/atoz.cfm (last access: 20 July 2017). 2011. 485

(68) Chen, M. L.; Chen, S. H.; Guo, B. R.; Mao, I. F. Relationship between environmental 486

exposure to toluene, xylene and ethylbenzene and the expired breath concentrations for 487

gasoline service workers. J. Environ. Monit. 2002, 4, 562-566. 488

(69) Egeghy, P. P.; Nylander-French, L.; Gwin, K. K.; Hertz-Picciotto, I.; Rappaport, S. M. 489

Self-collected breath sampling for monitoring low-level benzene exposures among 490

automobile mechanics. Ann. Occup. Hyg. 2002, 46, 489-500. 491

(70) Egeghy, P. P.; Hauf-Cabalo, L.; Gibson, R.; Rappaport, S. M. Benzene and naphthalene 492

in air and breath as indicators of exposure to jet fuel. Occup. Environ. Med. 2003, 60, 493

969-976. 494

(71) Chuang, C. L.; Chiang, P. C.; Chang, E. E. Modeling VOCs adsorption onto activated 495

carbon. Chemosphere 2003, 53, 17-27. 496

(72) USEPA (United States Environmental Protection Agency), Agency for Toxic Substances 497

and Diseases Registry (ATSDR): Minimal Risk Levels (MRLs) for Hazardous Substances. 498

United States Environmental Protection Agency, Washington, DC. Available at: 499

Page 18 of 22



19

http://www.atsdr.cdc.gov/mrls/mrllist.asp#14tag (last access: 25 September 2017). 2016. 500

(73) EU (European Union), Directive 2008/50/EC of the European Parliament and of the 501

Council of 21 May 2008 on ambient air quality and cleaner air for Europe. Official Journal of 502

the European Union. Available at: http://eur-lex.europa.eu/ (last access: 25 September 2017). 503

2008. 504

Page 19 of 22



20

505

Figure 1. Scatter plots of respiratory AFs of benzene, toluene, and C8-aromatics versus BMI 506

and BFR, respectively. 507

508

509

510

Page 20 of 22



21

511

Figure 2. Regression analysis between respiratory AFs and exposure concentrations of 512

benzene (open squares), toluene (open cycles), and C8-aromatics (open triangles) collected 513

from all (blue, a-c), a male (cyan, d-f) and a female (green, g-i) subjects, respectively. 514

Curve-fitting equations and their correlation coefficient (R2) and significance levels (p) were 515

also presented. R2 > 0.5 and p < 0.05 were used as critical values for significant correlations. 516

517 518 519 520 521 522 523 524 525 526 527 528 529 530 531 532

Page 21 of 22



22

For Table of Content Use Only 533

Decreased Human Respiratory Absorption Factors of Aromatic Hydrocarbons 534

at Lower Exposure Levels: The Dual Effect in Reducing Ambient Air Toxics 535

Zhong-Hui Huang,†,‡

Yan-Li Zhang,†,§

Qiong Yan,‖

Zhao-Yi Wang,†,‡

Zhou 536 Zhang,

† and Xin-Ming Wang*,†,§

537 538

539 540

Page 22 of 22



Decreased Human Respiratory Absorption Factors of Aromatic...

Documents

Transcript of Decreased Human Respiratory Absorption Factors of Aromatic...