Health Effects of Exposure to Indoor Semi-Volatile Organic Compounds in Chinese Building Environment: A Systematic Review

People spend a considerable portion of their lives indoors; thus, the quality of the indoor environment is crucial. Semi-volatile organic compounds (SVOCs) are among the primary indoor pollutants responsible for various health risks. This paper systematically reviews the impact of SVOC exposure on human health in Chinese built environments. Based on a set of criteria, we judged 12 publications as providing sufficient information on both SVOC exposure and health effects to inform the relationship. Out of six studies on polycyclic aromatic hydrocarbons (PAHs), three observed a positive association between PAH exposure and lung cancer. Out of six studies of phthalate exposure, two studies reported a significant positive association between DEP and DiBP and asthma, between DEP and DEHP and dry cough among children, and between DBP and rhinitis among younger adults. The results of this review suggest that there might be a link between phthalate exposure and asthma and allergies, as well as a link between PAH exposure and lung cancer. However, due to the limited number of studies conducted, more evidence is necessary to definitively guide the establishment of standards for SVOC control in China.


Introduction
People's lives are affected by the indoor air quality, or IAQ, described as the air quality inside constructions and structures. IAQ is essential to provide healthy and comfortable conditions for residents in buildings [1,2]. Around 90% of people's time is spent inside buildings in today's modern societies [3]. Therefore, an increased attention to safety is observed in residential places [2, [4][5][6][7]. Indoor air pollution can be considered a significant source of risk for some residents because of insufficient ventilation, along with low-quality construction materials, diffusing toxic or dangerous gases together with dust [8,9].
Thus, issues associated with human health make the environmental conditions of buildings extremely important [4]. One type of indoor pollutant associated with considerable health concerns is the group of semi-volatile organic compounds (SVOCs) [10,11], classified by the World Health Organization (WHO, Geneva, Switzerland) as indoor organic substances with boiling points ranging from 240/260 to 380/400 • C [12]. Different pathways contribute to the entrance of these pollutants into buildings, among which infiltrating outdoor air, indoor combustion, spray products, as well as material additives, can be mentioned. Due to the low vapor pressures of SVOCs at a temperature of 25 • C (77 • F) (10 −9 to 10 Pa) in comparison with volatile organic compounds (VOCs) (10 to 104 Pa), the gas or condensed phases of these compounds can typically be observed, leading to their redistribution from the primary source to the buildings' interior and surfaces inside them, such as airborne particles, dust, and skin [11].
A total of 5477 papers were obtained in the literature search. Papers which provided information on indoor SVOC exposure and their impact on human health were selected; the rest were eliminated. Screening and evaluation of the papers occurred in two steps: First, we determined relevance based on the title and abstract of each article. Second, we read the full texts of the remaining papers. Papers were excluded if (1) studies had not been performed in China; (2) studies had been carried out on animals; (3) in vitro or in vivo studies had been performed on cells; (4) studies showed no data on health outcomes; (5) health risks were estimated with the use of models or equations; and (6) the studies investigated the health effects of pollutants on rivers, soil, vegetables, biomarkers, or ambient air. The screening process yielded 58 papers for further examination by the review panel. Prior to the workshop, the panel studied these 58 publications, and at the workshop, they discussed the papers and created a consensus statement based on the available evidence.

Literature Review
The review panel consisted of 5 people, with backgrounds in Environmental Science, Environmental Engineering, Public Health, and Built Environment. The full texts of the chosen papers were reviewed by two independent review panel members to avoid bias.
Reviewers retrieved data from each article, specifically the type of study, setting/location, investigated population, indoor pollution and health outcomes, potential sources of bias, research results, and conclusions. A primary reviewer verbally summarized each of the 58 papers during the workshop. A second reviewer provided further feedback. The review panel's broad discussion of each article resulted in its ultimate categorization into one of the following categories: • Relevant and (partially) conclusive-giving sufficient information regarding exposure to indoor SVOCs and its health outcomes, and relationship between indoor SVOC exposure and its health outcomes. • Relevant and suggestive (background)-although not conclusive, there is some suggestion that exposure to indoor SVOCs and health outcomes may be associated-or neither. • Irrelevant-not addressing a topic covered by the review; lacking information on exposure to indoor SVOCs and its health outcomes.

Results and Discussion
As shown in Figure 1, out of the fifty-eight publications reviewed by the panel, thirtynine were determined to be irrelevant and seven were deemed to be suggestive (see Supplementary Materials, Table S1), while twelve were deemed to be (partially) conclusive and were used to create the consensus statement.
sure to indoor SVOCs and its health outcomes, and relationship between indoor SVOC exposure and its health outcomes.
• Relevant and suggestive (background)-although not conclusive, there is some suggestion that exposure to indoor SVOCs and health outcomes may be associated-or neither. • Irrelevant-not addressing a topic covered by the review; lacking information on exposure to indoor SVOCs and its health outcomes.

Results and Discussion
As shown in Figure 1, out of the fifty-eight publications reviewed by the panel, thirtynine were determined to be irrelevant and seven were deemed to be suggestive (see Supplementary Materials, Table S1), while twelve were deemed to be (partially) conclusive and were used to create the consensus statement. These 12 studies were carried out in eight provinces/municipalities in China, namely, Beijing, Tianjin, Shanghai, Chongqing, Yunnan, Liaoning, Heilongjiang, and Hunan Province. Figure 2 illustrates the location of these investigated areas. None of these studies covered the northwest region of China.
Step 1: Literature searching 5477 papers obtained from CNKI, WANFANG DATA, PubMed and Web of Science databases.

papers excluded
Step 3: Review Panel These 12 studies were carried out in eight provinces/municipalities in China, namely, Beijing, Tianjin, Shanghai, Chongqing, Yunnan, Liaoning, Heilongjiang, and Hunan Province. Figure 2 illustrates the location of these investigated areas. None of these studies covered the northwest region of China.
The health effects of PAHs were examined in six papers, while six papers investigated the associations between phthalate exposure and health outcomes. Only one paper investigated the health effects of PBDEs, OCPs, and PCBs [52]. Nie et al. found, compared to healthy children, children diagnosed with asthma had considerably higher concentrations of PBDEs in their indoor fine particulate matter (PM2.5) (41.1 pg/m 3 v.s. 23.8 pg/m 3 ). Indoor exposure to PBDEs may be linked to a risk of developing asthma in children [52]. Table 1 presents the findings on PAH exposure and its associations with human health. Out of six studies, four studies focused on PAH exposure and lung cancer [53][54][55][56], one on asthma [52], and one on the ability of population learning and memory [57].

Polycyclic Aromatic (PAHs) and Health Outcomes
Based on the reviewed studies in Table 1, it can be concluded that higher PAH exposure is extremely likely to be risk factor for lung cancer [53][54][55].
Generally, PAHs are lipophilic substances that simply pass through cell membranes after inhalation via passive diffusion. Following entrance into the lung, PAHs activate phase I metabolic enzymes through both aryl hydrocarbon (AhR)-dependent and -independent routes. The transformation of PAHs into their carcinogenic metabolites is a factor in the etiology of cancer [58]. B[a]P is typically utilized as a marker for overall exposure to carcinogenic PAHs [59]. The average B[a]P content in indoor air in our reviewed studies ranged from 0.01 µg/m 3 to 6.29 µg/m 3 , which exceeded both the WHO's and China's indoor air quality standards [60][61][62][63] (i.e., 0.001 µg/m 3 for B[a]P (24 h average)), especially in Xuanwei, where the rate of people with lung cancer was higher than in other cities in China. This could be explained by the continued use of solid fuels [55] for heating and cooking [28] by many of the residents. Exposure to indoor smoky coal combustion has been linked to an increased risk of lung cancer [64,65]. Coal is often used in rural places due to its abundance and low cost [66]. Although developing countries like China face more lung cancer caused by fossil fuels, a small number of studies have investigated this issue in developed countries. In Los Angeles, CA, a sample of Caucasian women, who were at risk of developing cancer reported previous exposure to coal/wood stoves and fireplaces at an early age [67]. A study conducted in eastern Europe and Britain demonstrated a 20-40% risk of developing lung cancer among those who used solid fuels in the kitchen, as opposed to those that used it only for heat [68].
Additionally, this review showed the influence of PAH exposure on other outcomes such as asthma and population learning. Nie et al. suggested that some common PAHs combined with indoor PM2.5 might be linked to the risk of developing asthma in children [52]. This is consistent with a comparable study conducted in Moravia, Czech Republic, which linked elevated PAH exposure to intrauterine growth retardation, as well as to asthma [69]. The health effects of PAHs were examined in six papers, while six papers investigated the associations between phthalate exposure and health outcomes.. Only one paper investigated the health effects of PBDEs, OCPs, and PCBs [52]. Nie et al. found, compared to healthy children, children diagnosed with asthma had considerably higher concentrations of PBDEs in their indoor fine particulate matter (PM2.5) (41.1 pg/m 3 v.s. 23.8 pg/m 3 ). Indoor exposure to PBDEs may be linked to a risk of developing asthma in children [52].

Polycyclic Aromatic (PAHs) and Health Outcomes
Table 1 presents the findings on PAH exposure and its associations with human health. Out of six studies, four studies focused on PAH exposure and lung cancer [53][54][55][56], one on asthma [52], and one on the ability of population learning and memory [57]. Evidence was also presented for the neuropsychological effects of PAHs following occupational exposure. He investigated coke oven workers in Chongqing, a municipality of China, with a series of neurobehavioral tests, along with urinary 1-hydroxypyrene (a metabolite of PAHs) tests and found that PAH exposure caused a decline in population learning and memory, with increased monoamine neurotransmitters among the workers [57]. A similar trend was observed in a Korean research study conducted by Cho et al., who found that PAH exposure was linked to a decline in memory function and verbal learning in healthy adults [70].

). Tension-Anxiety(T) and
Fatigue-Inertia(F) of the Profile of Mood States (POM S) in coke oven employees were substantially greater than in controls (p < 0.05). Compared to the coke oven workers, the scores of the oxygen installation workers were higher in the total digital span, average simple reaction time, the forward digital span, first right dotting, digit symbol, mean right dotting, and mean total dotting, and the differences were statistically significant (p < 0.05).
This review showed the primary source of PAHs was solid fuel combustion [53][54][55], such as with coal. Therefore, the health effects of indoor PAH exposure can be decreased by limiting the sources, replacing them with clean, alternative energy, and by providing adequate ventilation. The role of ventilation in decreasing PAH exposure was highlighted in a study that showed that women between the ages of 20 and 40 years old, who did not use the fume hood at all, had a 2.47 times higher likelihood of developing cervical cancer than those who used it all the time [71]. Table 2 presents the findings on PAE exposure and its associations with human health. All six existing studies focused on asthma and allergy health outcomes [4,6,[72][73][74][75].

Phthalates and Health Outcomes
The data in Table 2 show that most studies focused on the primary constituents of phthalates in homes such as DEHP, DBP, DEP, and DiBP, which were supposed to be associated with allergies, asthma, and other respiratory diseases. Two studies in Tianjin reported significant positive associations between DEP and DiBP and asthma, DEP and DEHP and dry cough among children, and DBP and rhinitis among younger adults. In the studies conducted in Shanghai, Beijing, and Hunan Province, there was no clear association between phthalate exposure and asthma and allergy. It is possible these studies were limited by their sample size and design (around ten samples in the Beijing study [4], twelve in Shanghai [6] and ten in Hunan [74]). Whether or not these sample sizes have an influence on these studies, the findings do highlight the necessity for improved documentation of phthalate measurements and research design in future investigations of indoor environments and health.
The prevalence of allergies and asthma has increased in developed countries, such as Western Europe, Australia, the USA, and New Zealand [76]. As developing regions, such as China, progress, the prevalence of asthma and allergies has also increased [77]. Over the past 30 years, there has been a significant change in the pollutants released indoors due to the increased use of plastics, synthetic wood products, wall coverings, polymeric floors, and cleaning agents [78]. The trend is apparent, as the standard of living is improving, as is the exposure to phthalates and the burden of diseases. This is consistent with comparable studies conducted in Sweden, which linked elevated eczema and rhinitis rates with BBzP and established the association between asthma and DEHP among children [79], which was subsequently confirmed by Bulgaria's ALLHOMES study [80]. Bamai et al. also found an association between phthalate and asthma and allergies among Japanese children and adults [81]. The link between phthalate exposure and nasal, airway, ocular, and dermal allergy outcomes was supported by a review study by Bølling et al. [82]. These epidemiological studies from our review and other countries offer evidence of the relationship between asthma and allergy and phthalate exposure.

Research Gaps and Future Considerations
Although China is vast, research on phthalates and their health effects has mostly been conducted on children in Central, South, North, and Eastern China, where the majority of China's big cities are situated [83]. Most studies related to PAHs and their health outcomes were conducted predominantly on adults who live in Southwest, East, and Northeast China. However, semi-volatile organic compounds affect people (children, adults, and the elderly) all across the country, depending on their living conditions, making nation-wide assessments necessary. Furthermore, despite the fact that this has been extensively studied outside of China, no study in our review sought to investigate the connection between SVOC exposure and the emergence of disorders in pregnant women and their offspring. Overall, our review shows that the number of studies is too limited to definitively link SVOC dosage to health outcomes. The mean concentrations of SVOCs in living rooms and bedrooms of thecontrol group (1590 µg/g and 2347.8 µg/g) were higher than the case group (1347.5 µg/g and 1754 µg/g) in winter. In summer, the mean concentrations of SVOCs in living rooms and bedrooms of the case group were higher than the control group (except one home, and two homes were detected with no SVOCs). To our knowledge, this paper is one of the first systematic reviews on the health effects of exposure to SVOCs in Chinese buildings. We find that the number of published studies in China is very limited, even though SVOC exposure is an extremely important topic. There is a need to know more about SVOCs to plan for a healthy future. To start, comprehensive studies are needed throughout China to account for rapid urbanization, changes in lifestyle, new indoor building materials, and the burden of new diseases due to modern chemical compounds such as SVOCs. This can serve as a stepping stone for more extensive studies in the future. The authors' suggestion to the relevant stakeholders would be to develop a Chinese standardized IAQ protocol that assesses SVOC levels, along with other toxins, and put forward policies in line with national and international requirements.

Conclusions
The objective of this review was to present a thorough summary of the available information on the impact of SVOC exposure on human health in Chinese built environments. In doing so, this review concluded that asthma and allergies may be linked to phthalate exposure, and lung cancer may be linked to PAH exposure. In order to improve indoor environments, along with safeguarding human health, SVOC levels have to be drastically reduced.