Association of urinary phthalates metabolites concentration with emotional symptoms in Chinese university students

Highlights

• First study about phthalate exposure associated with emotional symptoms in Chinese university students.

• 990 urina sanguinis were collected for analysis of six phthalate metabolites concentrations.

• Chinese university students are widely exposed to phthalate and the detection rates range from 79.6% to 99.7%.

• Mono (2-ethyl-5-hydroxyhexyl) phthalate was positively associated with male emotional symptoms.

• Monobutyl phthalate was positively associated with female emotional symptoms.

Abstract

Previous studies have shown the associations between phthalates exposure and psychological behavior problems in children and adolescents, but such associations have not been fully elucidated in university students, especially among Chinese university students. This study aims to examine the association between urinary phthalates metabolites concentration and emotional symptoms in Chinese university students. A school-based cross-sectional survey was carried out among 990 university students aged 17–24 years from two universities in Anhui and Jiangxi provinces of China. Concentration of six phthalate metabolites in urine was determined by high-performance liquid chromatography-tandem mass spectrometry and the emotional symptoms were assessed by the 21-item Depression, Anxiety, and Stress Scale. The detection rate of six phthalate metabolites in urine ranged from 79.6% to 99.7%. The median concentration of six phthalate metabolites ranged from 2.90 to 119.64 ng/mL. The positive rates of depressive symptoms, anxiety symptoms, and stress were 17.4%, 24.8%, and 9.5%, respectively. After adjusting for the confounding variables, mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) was found to be associated with depressive symptoms (β = 8.84, P = 0.017), anxiety symptoms (β = 8.46, P = 0.015), and stress symptoms (β = 9.95, P = 0.012) in males; whereas, monobutyl phthalate (MBP) was found to be associated with depressive symptoms (β = 1.86, P = 0.002), anxiety symptoms (β = 1.81, P = 0.005), and stress symptoms (β = 1.48, P = 0.047) in females. Our study demonstrates that Chinese university students are widely exposed to phthalates; and high- and low-molecular weight phthalates are associated with emotional symptoms in males and females, respectively.

Introduction

Phthalates are widely used in the production of plastic products such as food packaging materials, food containers, cups, etc. (Schug et al., 2011; Vandenberg et al., 2012). Depending on the carbon chain length, phthalates are classified into low-molecular weight phthalates (LMWP) and high-molecular weight phthalates (HMWP). LMWP have 3–6 carbon atoms, and include dibutyl phthalate (DBP), diethyl phthalate (DEP), dimethyl phthalate (DMP), etc. DBP is used in large quantities for the production of polyvinyl chloride (PVC) products (e.g., building materials, industrial products, daily necessities) and medical supplies (e.g., medical devices, enteric-coated tablets) (Chou and Wright, 2006; Hernandez-Diaz et al., 2009; Katsikantami et al., 2016). DEP and DMP are widely used in the production of personal care products and cosmetics (e.g., shampoo, nail polish, soap, perfume) (Wittassek et al., 2011). Further, HMWP have 7–13 carbon atoms, and include di-2-ethylhexyl phthalate (DEHP), diisononyl phthalate (DiNP), benzyl butyl phthalate (BzBP), etc. (Clausen et al., 2004; Shu et al., 2019). HMWP are commonly used in the production of PVC products and daily necessities (Afshari et al., 2004; Carlstedt et al., 2013). Previous studies have reported that the treatment in Neonatal Intensive Care Unit (NICU) may be an important source of DEHP exposure. The concentrations of DEHP metabolites in premature neonates treated with an intravenous injection, endotracheal tube, orogastric tube, or nasogastric tube in NICU were found to be higher than in those without neonatal treatment (Su et al., 2012). MEHP concentrations in infants receiving intravenous hyperalimentation, umbilical vessel catheterization, indwelling gavage tube, and endotracheal intubation in NICU were found to be 5.1 times higher than those receiving bottle and/or gavage feedings primarily (Green et al., 2005).

Although the adverse effects of phthalates’ exposure on human health have attracted attention globally, they are still used in high quantities in the industries (Koo and Lee, 2004; Schug et al., 2011; Prusinski et al., 2016; Wang et al., 2019). Because of their physical and chemical properties, phthalates cannot bind tightly to the matrix polymer; therefore, they easily migrate from plastic products to the environment under certain physical and chemical conditions (Bosnir et al., 2007; Heudorf et al., 2007; Ustun et al., 2015; Katsikantami et al., 2016). Humans can be exposed to phthalates through dietary intake, respiratory inhalation, and cosmetic use; and dietary exposure is the most common route of exposure in humans (Zota et al., 2016; Munoz et al., 2018; Ding et al., 2019). The National Health and Nutrition Examination Survey showed that fast food consumption is the main source of exposure to DEHP and DiNP in the general population (Zota et al., 2014; Zota et al., 2016). Previous studies have shown that adolescents are generally exposed to phthalates, and the urinary phthalates metabolites detection rate was 75%–98% globally (Saravanabhavan et al., 2013; Chopra et al., 2014; Ding et al., 2019), and the estimated daily exposure was 810–4120 ng kg⁻¹·day⁻¹ (Hartmann et al., 2015; Gao et al., 2016; Ding et al., 2019).

A number of animal studies have found that the exposure to phthalates affects brain development, alters hippocampal formation, and induces emotional and behavioral alterations. Recent study has reported that prepubertal exposure to phthalates impaired the development of the dopaminergic system and caused neurobehavioral impairments in postpubertal rats, with more pronounced effects in males (Holahan et al., 2018). Exposure to DEHP during hippocampal development in rats reduced the cell density of both immature and mature neurons in the dentate gyrus and CA3 regions and reduced the expression of axonal markers in the CA3 distal stratum oriens in males; however, it had no effect on females (Della et al., 2006). Likewise, DEHP-induced oxidative stress led to neuronal cell death via mitochondrial fission of HT-22 cells in mouse hippocampus (Lee et al., 2019). Additionally, the exposure to DEHP in adolescent mice has been reported to reduce social ability and affect the anxiety-like behavior in adult female mice (Wang et al., 2016).

Further, the growing evidence suggests that exposure to phthalates may trigger adverse neurodevelopmental and intellectual developmental defects in children (Kim et al., 2011; Factor-Litvak et al., 2014). Birth cohort studies in Korea and Mexico showed that prenatal exposure to phthalates was associated with poor neurodevelopmental performance in children aged 6 months to 3 years; and maternal urinary DEHP concentration was negatively correlated with the mental and psychomotor developmental index in children aged 1–3 years (Kim et al., 2011; Kim et al., 2018). Furthermore, studies have shown that postnatal exposure to phthalates is associated with multiple psychological behaviors in children and adolescents. For instance, the Canadian Health Measures Survey found that urinary 1-methyl-4-benzylpiperazine (MBZP) concentration was significantly associated with emotional symptoms in female children (Arbuckle et al., 2016). Another nation-wide study in the United States showed that urinary phthalates metabolites levels in children aged 6–15 years were associated with attention deficit disorder; wherein, a positive dose-response relationship was observed, and the association was stronger in girls than the boys (Chopra et al., 2014).

It is important to note that mental health problems are common among adolescents globally (Patton et al., 2014; Patton et al., 2015). Mental disorders are the main reason for disability-adjusted life years in children aged 10–24 years (Mokdad et al., 2016; Kassebaum et al., 2017). In addition, emotional disorders such as depression, anxiety, and stress are the most common psychological problems during adolescence (Merikangas et al., 2010; An et al., 2014). Few studies have examined the association between phthalates exposure and psychological behavior problems in university students. The present study was aimed to investigate the association between phthalate exposure and emotional symptoms in Chinese university students.