Endocrine-disrupting chemicals (EDCs) are exogenous substances that can interfere with hormone activity and endocrine system function of humans and animals, such as the synthesis, release, transport, binding to receptors and metabolism of endocrine hormones. They affect the cellular, molecular, and epigenetic functions of the endocrine system, interfering with the coordination and stability of the body (Darbre 2017; Harris and Waring 2012). EDCs are commonly present in various products as physical additives rather than chemically bounded compounds, as a result, they can be released into the environment through volatilization in the air and solubilization in aquatic media. Nowadays, EDCs have become world ubiquitous environmental contaminants and humans can be exposed to various EDCs via food, drinking water, and air, as well as many everyday products, such as plastics, detergents, personal care products, and toys, and children may endure more EDCs, as there are multiple parallel exposure pathways and incomplete metabolic systems (Predieri et al., 2021; Kabir et al., 2015; Tijani et al., 2016). For instance, toddlers in Canada exposed to bis(2-ethylhexyl) phthalate (DEHP) were found to have exposure levels of up to 19 μg/kg-bw/day (Tran et al., 2022). Several epidemiological studies have reported the presence of various types of EDCs in body fluids, with children being at a higher risk of adverse health effects compared to adults, such as mental decline, cancer, obesity, and reproductive impairment (Katsikantami et al., 2016). Compared with adults, the harmful effects of EDCs on children's health deserve extensive attention. Due to differences in personal lifestyle, the exposure pathways of typical EDCs in children can be very extensive and regionally specific, and therefore, it is crucial to investigate the EDCs that children are exposed to and identify potential sources of exposure.

Indirect monitoring of human exposure to EDCs can be achieved by assessing their concentration in different environmental media, such as air, water, food, and personal care products. Previous studies have investigated the presence of EDCs in foods, products, and personal care items (Tijani et al., 2016; Pereira et al., 2019). However, the accurate reflection of the true level of human exposure to EDCs through environmental media is challenging due to the complex, diverse, and discontinuous sources of exposure. Instead, the direct determination of EDCs in human body fluids or tissues provides a more accurate assessment of exposure levels (Kabir et al., 2015). To date, numerous studies have detected typical EDCs in human urine with targeted detection being the most commonly used method, in support of risk assessment. However, the majority of target analyses focus on a limited number of EDCs (e.g. phthalates, organochlorine compounds, or flame retardants), and cannot comprehensively monitor actual exposure to EDCs in children's urine. In recent years, high-resolution mass spectrometry (HRMS) coupled with separation techniques employs ionization sources paired with high-resolving power mass detectors that can identify unknown chemicals based on their isotopic fingerprints, observe accurate masses and MS/MS fragments resulting in more accurate mass measurements (Liu et al., 2019b). By establishing a mass spectrometry database, HRMS technology can quickly query and identify unknown compounds, making it an effective means for non-target analysis (NTA) of unknown EDCs (Hollender et al., 2018). In recent years, NTA has already been applied to detect environmental pollution sources (Brack et al., 2019), discover emerging environmental pollutants (Bletsou et al., 2015), and monitor the efficiency of environmental contaminant treatment technologies (McCord et al., 2020). NTA coupled with target analysis of typical EDCs can help us better understand the human body burden of EDCs (Musatadi et al., 2022; Tkalec et al., 2022).

The present study focuses on the target analysis of phthalate esters metabolites (mPAEs) and bisphenols (BPs), which are considered “non-persistent” chemicals and are typically eliminated from the body within 24 h (Collet et al., 2015; Thayer et al., 2015). BPA is reported to be rapidly metabolized to inactive phase II metabolites (glucuronidation and sulphation reactions that occur after phase I reactions), such as BPA-glucuronide and BPA-sulfate, as well as PAEs are rapidly metabolized to phase I metabolites (Frederiksen et al., 2007). Despite their short half-life, PAEs and BPs remain the most studied EDCs to date and require continued attention due to their ubiquitous release into the environment, food, and drinking water. Additionally, new typical BPA substitutes, such as bisphenol F (BPF), bisphenol AF (BPAF), and bisphenol S (BPS), have been reported to have similar or higher estrogenic activity compared to BPA and have been gradually detected in human urine (Chen et al., 2016; Karrer et al., 2019). Since Canada, Japan, and the European Union banned the use of BPA in some consumer goods (Adeyemi et al., 2020), BPF has been widely used in the production of epoxy resins and coatings (Rochester and Bolden 2015). Similarly, BPS has been widely used in phenolic resins and as an electroplating solvent (Rochester and Bolden 2015). BPS and BPF were also detected in a variety of daily items, including personal care products, thermal paper and food (Rochester and Bolden 2015). Dietary intake, dust intake and skin exposure are the most significant routes of exposure to BPs (Karrer et al., 2019), which may lead to children being exposed to BPs from various sources in different ways.

It is concerning that recent research has shown that mPAEs and BPs can activate or influence many receptors and signaling pathways, even at very low doses, which could explain the estrogenic effects, and also biological and health parameters influenced by these chemicals (Vandenberg et al., 2012). BPs, in addition to having strong estrogenic activities, can also bind to G protein-coupled receptors (GPCR) at very low doses, activating certain protein kinases and promoting the proliferation and differentiation of germ cells (Bouskine et al., 2009), such as G protein-coupled estrogen receptor (GPR30 or GPER) related mitogen-activated protein kinase (MAPK) signaling (Wang et al., 2017). GPER was found to play a role in mood disorders, anxiety, and Autism Spectrum Disorder (ASD), which usually starts in early childhood, and increasing studies have shown that patients with generalized anxiety disorder and depression have higher serum GPER levels compared to healthy controls (Prossnitz and Barton, 2011; Findikli et al., 2016; Campisi et al., 2019).

Guangzhou and Hong Kong, as two economically developed and southern areas of the People's Republic of China, are located in the Guangdong-Hong Kong-Macau Greater Bay Area (GBA), a world-class urban agglomeration. Despite similarities in their diets, with Hong Kong incorporating more Western-style elements, there are differences in the living environment between the two regions. This study aimed to investigate the exposure of EDCs in the urine of children and their parents from Guangzhou and Hong Kong. A combination of targeted analysis with high-performance liquid chromatography-tandem triple quadrupole mass spectrometry (HPLC-MS/MS) to quantitatively analyze BPs and mPAEs, NTA with high-performance liquid chromatography-tandem time-of-flight mass spectrometry (HPLC-QTOF-MS), as well as a questionnaire survey was used in the present study. The correlation between EDCs levels in parents and children, as well as children (3–6 years old) and children (aged 7–12 years), were analyzed. Consequently, this study seeks to explore potential differences in EDC exposure between the two regions and to identify potential sources of EDCs by examining the internal exposure of typical EDCs in children in Guangzhou and Hong Kong. The study can help to provide basic information for the distribution of EDCs in children and their parents in the two places, and to distinguish if the Chinese and Western lifestyles provide significantly different sources of exposure, and what are the main sources.