Associations of urinary di-(2-ethylhexyl) phthalate metabolites with the residential characteristics of pregnant women

Highlights

• Living near the motor vehicle traffic may increase urinary concentrations of MEHP and MEHHP.

• Residential renovation may increase urinary concentrations of MEHP and MEHHP.

• Using air freshener may increase urinary concentrations of MEHP.

• Moldy walls may increase urinary concentrations of MEHP and MEHHP.

• Using household humidifier may decrease urinary concentrations of MEHP.

Abstract

Epidemiological evidence on the associations between urinary di-(2-ethylhexyl) phthalate (DEHP) metabolites and residential characteristics is limited. Therefore, we investigated the associations of urinary DEHP metabolites with the residential characteristics of pregnant women. We collected completed questionnaires and maternal spot urine samples from 616 random pregnant women in Shengjing Hospital of China Medical University in Shenyang. Urinary DEHP metabolites concentrations, including mono-(2-ethylhexyl) phthalate (MEHP) and mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), were measured and analyzed by Gas Chromatography-Mass Spectrometry (GC–MS). Multivariable linear regression models were performed to obtain regression estimates (β) and 95% confidence intervals (CIs) after adjustment for sociodemographic characteristics. In all participants, the geometric mean of MEHP and MEHHP concentrations were 4.25 ± 4.34 and 5.72 ± 2.65 μg/L, respectively. In multivariable analyses after adjusting for sociodemographic characteristics, distance from residence to motor vehicle traffic (≥150 m versus <20 m) was negatively associated with MEHP (β = −0.241, 95% CI: −0.448, −0.033) and MEHHP (β = −0.279, 95% CI: −0.418, −0.140) concentrations. Compared with the one that had not recently been renovated, a renovated home was associated with higher MEHP (β = 0.194, 95% CI: 0.064, 0.324) and MEHHP (β = 0.111, 95% CI: 0.024, 0.197) concentrations. Air freshener use was associated with higher MEHP (β = 0.322, 95% CI: 0.007, 0.636) concentrations. Moldy walls were positively associated with MEHP (β = 0.299, 95% CI: 0.115, 0.482) and MEHHP (β = 0.172, 95% CI: 0.050, 0.294) concentrations. In contrast, humidifier use was associated with a lower MEHP concentration (β = −0.167, 95% CI: −0.302, −0.032). Residential characteristics were probably associated with the DEHP exposure of pregnant women in Shenyang. Living near the motor vehicle traffic, residential renovation, air freshener use, and moldy walls are likely risk factors for increased DEHP exposure, whereas using household humidifier could be considered a protective measure to reduce DEHP exposure.

Introduction

Di-2-ethylhexyl phthalate (DEHP) is considered as a ubiquitous environmental endocrine disruptor (Erythropel et al., 2014; Rowdhwal and Chen, 2018). As part of a group of synthetic organic chemicals, DEHP is extensively used as a plasticizer to boost the plasticity, durability, and elasticity of polymeric products, such as rubber toys, medical plastic infusion bag and tubes, food packaging, household furniture, and polyvinylchloride (PVC) flooring (Calafat and McKee, 2006). Due to the massive production of DEHP about >2 million tons each year (Chou et al., 2018), human daily exposure to DEHP through the living environment has been an increasing concern as demonstrated by the findings of in vitro and in vivo environmental and toxicological studies. In general, people spend more time indoors than outdoors, thus the indoor environment accounts for a considerable proportion of our daily exposure to DEHP (Zhu et al., 2019). In previous literatures, the presence of DEHP and its metabolites in various environmental matrices, including indoor air (Song et al., 2015), dust samples (Bergh et al., 2011), and polluted air near traffic (Lu et al., 2019), have been investigated. The DEHP concentration in the indoor environment can vary by several orders of magnitude due to different residential characteristics, such as the inner moisture content (Hsu et al., 2017), building materials of the house (Takeuchi et al., 2014), and indoor temperature (Bi et al., 2015). In addition, residential environmental factors, including recent home renovation, pet ownership and indoor dampness, were associated with an increased risk of respiratory diseases and allergic dermatitis (Dong et al., 2013; Li and Kendrick, 1995; Mendell et al., 2018). To our knowledge, only a few epidemiological studies have examined the associations between DEHP exposure and residential characteristic. Liao et al. reported that there was no significant association between residential location, window frame material and urinary DEHP metabolites (Liao et al., 2018). Xu et al. found that DEHP sources characteristics as well as ventilation rate may influence the steady-state DEHP concentration and the resulting internal exposure (Xu et al., 2010). Therefore, it is convincible that the potential associations between DEHP exposure and residential characteristics need further investigation.

In the human body, DEHP is rapidly metabolized through a two-step kinetic phase: DEHP is first hydrolyzed to a monoester (mono-(2-ethyl-hexyl) phthalate [MEHP]) by relevant enzymes, namely, lipases and esterase; MEHP is further oxidized to its secondary metabolites, including mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) and 2-carboxymethylhexyl phthalate (MCMHP) (Koch et al., 2006). In general, the monoester or secondary oxidative metabolites of DEHP are the ultimate development toxicants (Koch et al., 2005). Zhao et al. indicated that the transformation rate of MEHP to MEHHP was more efficient in late pregnancy (Zhao et al., 2018). It was also a major metabolic pathway in humans for the transformation of MEHP to MEHHP (Ito et al., 2014). In particular, urinary MEHHP is a more sensitive and quantifiable biomarker of DEHP exposure compared with other DEHP metabolites (Barr et al., 2003; Silva et al., 2006; Tranfo et al., 2018). Increasing numbers of studies have reported urinary DEHP metabolites concentrations in general population (Huang et al., 2015), as well as specifically in pregnant women (Ferguson et al., 2017), and in children (Fromme et al., 2013; Langer et al., 2014). In addition, a single sample can provide a reasonably good estimate of individual exposure and reflect the long-term exposure to phthalates, even back to the exposure of 3 years ago (Frederiksen et al., 2013; Johns et al., 2015). Therefore, individuals' chronic exposure to DEHP from the environment can be estimated from urinary concentrations of DEHP metabolites.

Recently, the adverse effects of ubiquitous DEHP exposure on human health, particularly that of pregnant women, have attracted worldwide attention because epidemiologic studies revealed that positive associations of higher levels of DEHP metabolites with adverse reproductive health and birth outcomes, such as miscarriage, preterm birth, low birth weight, reduced anogenital distance, and behavioral syndromes in offspring development (Huang et al., 2019; Messerlian et al., 2016; Swan et al., 2015; Zhang et al., 2009; Zhao et al., 2017). Toxicological studies in laboratory animals also found that exposure to DEHP during the perinatal period may cause adverse impacts on the development of the neurological (Fu et al., 2019; You et al., 2018), immune (Kitaoka et al., 2013), reproductive system (Wang et al., 2016), even the transgenerational effects (Rattan et al., 2018). Sources of DEHP exposure are extensive, including diet, plastics, personal care products, and medical devices. Measuring related metabolites in urine is a reliable and valid method to assess the DEHP exposure of pregnant women (Grindler et al., 2018; Tsai et al., 2018). In addition, the Korean National Environmental Health Survey suggested that DEHP metabolites concentrations in urine of Korean female adults were generally higher than those reported from national biomonitoring programs in US and Canada populations (Park et al., 2019). Accordingly, urinary concentrations of the DEHP metabolites in pregnant women might provide a direct comparison of the DEHP exposure of various populations.

Thus, the aims of the present study were using urinary concentrations of the DEHP metabolites (MEHP and MEHHP) to evaluate DEHP exposure in pregnant women and investigating the associations of urinary DEHP metabolites with outdoor and indoor residential characteristics.