Identification and prioritization of the potent components for combined exposure of multiple persistent organic pollutants associated with gestational diabetes mellitus

https://doi.org/10.1016/j.jhazmat.2020.124905Get rights and content

Highlights

  • Combined effect of POPs mixture exposure on GDM risk was assessed in real scenario.

  • DLCs were identified as highest concerned POPs associated with GDM.

  • The GDM effect-based prioritized POPs were DLCs > PBDEs > PFAAs > PCBs.

Abstract

Persistent organic pollutants (POPs) remain a major point of concern worldwide, and surveillance monitoring of these contaminants presents a significant challenge. Here, we conducted an assessment of combined exposure to multiple POPs components [10 perfluoroalkyl acids (PFAAs), seven polybrominated diphenyl ethers (PBDEs), six polychlorinated biphenyls (PCBs) and 29 dioxin-like compounds (DLCs)] in relation to gestational diabetes mellitus (GDM) risk, and determined the identification and prioritization of potent components in these POPs mixtures. The results indicated a significant mixture effect and the combined exposure index estimated from multiple POPs components was associated with GDM and glucose homeostasis (P < 0.001). Based on the mixture effects on GDM, the procedure of prioritization identified DLCs as the components of the greatest concern, although at the lowest body burden in the population compared with PBDEs, PFAAs, and PCBs. For glucose homeostasis, BDE-153 was the chemical of top-ranked priority of concern. The final effect-based prioritized list of POPs was DLCs > PBDEs >PFAAs > PCBs. This prioritization is important for developing a more cost-effective regulation framework focusing on the POPs components of the greatest concern to human health.

Introduction

Persistent organic pollutants (POPs), such as polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs), polybrominated diphenyl ethers (PBDEs), and perfluoroalkyl acids (PFAAs), are halogenated chemicals with strong bonds between carbon and chlorine/bromine/fluorine which makes them resistant to environmental degradation and can remain in the environment for a long time once released. Due to their ubiquitous presence, all populations have background exposure mainly via the diet (Xu and Cai, 2015). To address this global issue, a groundbreaking United Nations treaty was signed in Stockholm in May 2001. Under the signed Stockholm Convention, countries agreed to reduce or eliminate the production, use, and release of POPs. Although following the convention and earlier phase-outs have largely resulted in a decline of these contaminants in the environment and in food, humans are currently still at potential risk caused by POPs exposure, with pregnant women, infants, and children having an even higher risk (Landrigan et al., 2018, Ouidir et al., 2019). On the other hand, POPs comprise groups of chemicals consisting of a large number of congeners and isomers, which leads to a significant challenge for surveillance monitoring and public health interventions concerning labor, material, and cost, especially for low- and middle-income countries (Ashraf, 2017, Cai and Jiang, 2006). The challenge implies practical demands for the prioritization of abatement strategies, and identification of priority pollutants to develop more cost-effective environmental regulations.

A previous attempt was made to rank the chronic risks of identified contaminants including POPs by only considering the type of critical effect they induce and whether the exposure is regular from daily food intake (Eskola et al., 2020). It failed to consider the real scenarios of mixture exposure and lacked support from real outcome data. Thus, this risk ranking lacks practicality and should be regarded as indicative only. Our recent study in pregnant women has indicated a significant association between gestational diabetes mellitus (GDM) and dioxin-like compounds (DLCs) (Liu et al., 2019a), and similar results have been observed for some PFAAs (Liu et al., 2019b), PBDEs (Liu et al., 2018) and non-dioxin like PCBs (Zhang et al., 2018). Consistent findings have been reported in numerous epidemiological studies with differences in study design, sample size, ethnic group, and measured covariates (Eslami et al., 2016, Matilla-Santander et al., 2017, Rahman et al., 2019, Shapiro et al., 2016, Vafeiadi et al., 2017, Wang et al., 2018, Zhang et al., 2015). These previous findings were mainly from a component-based approach that separately evaluated the association between each POPs or total exposure within a specific POPs group and GDM, and did not consider the mixture effect. Using separate regression models for each environmental exposure could hardly identify the certain etiological chemicals from the complex correlation pattern following POPs exposure (Braun et al., 2016). Moreover, widespread concern has been raised regarding the potential additive, synergistic, and antagonistic interactions in chemical mixtures (Rotter et al., 2018). Under this scenario, large groups of co-occurring pollutants may be reduced to a few mixture components or even one single component, which can be demonstrated to explain most of the overall risk, that is, the drivers of mixture risks (Drakvik et al., 2020).

To identify the priority substances from POPs mixture exposure that cause health risks in vulnerable populations, we combined an exposure dataset to conduct a multiple-pollutants analysis to assess the combined effects of POPs mixtures on GDM, to identify and prioritize of the critical components in these mixtures on the observed exposure-outcome association.

Section snippets

Study subjects

We combined exposure datasets from a prospective nested case-control study from August 2013 to June 2015. Details of the study design have been described previously (Liu et al., 2019b, Liu et al., 2018, Zhang et al., 2018). Briefly, healthy pregnant women who were free from prediabetes and did not have a family history of diabetes were invited to participate in this research during their first prenatal care visits at Xicheng Maternal and Child Health Hospital in Beijing, China. This

Characteristics of the study population

The final analysis in the cohort included 77 GDM cases [geometric mean age (range): 28.8 (23.0–37.0)] and 154 healthy controls [geometric mean age (range): 28.8 (21.0–37.0)] (Table 1). There was significant difference in terms of maternal body weight (P = 0.03) and height (P = 0.02) between the GDM cases and age-matched healthy controls. However, the BMI (kg/m2) calculated from weight (kg) and height squared (m2) was not significantly different between the two groups. The non-significant

Discussion

Determining the most etiologically relevant environment exposure factors is required to develop more targeted health interventions and more cost-effective regulation policies (Taylor et al., 2016). The key objective for the prioritization of substances and for monitoring programs should be the chemicals that might pose significant threats to human health. With the extensive measurement of multiple POPs in pregnant women, the risk of GDM following combined exposure to POPs was assessed by

Conclusion

In conclusion, based on a mixture exposure risk investigation in humans, exposure to POPs mixture exhibited significant combined effects on GDM and glucose homeostasis. Effect-based prioritization showed that DLCs in the POPs mixture were the most critical risk factors for GDM, and BDE-153 was most strongly associated with glucose homeostasis. The priority POPs were DLCs > PBDEs > PFAAs > PCBs based on combined exposure data and mixture risk assessment. The present findings provide the basis

Funding

This research was supported by the National Key Research and Development Program of China (grant number 2017YFC1600500) and the National Natural Science Foundation of China (grant numbers 21537001, 21477030, and 21507018).

CRediT authorship contribution statement

Xin Liu: Conceptualization, Formal analysis, Writing - original draft. Lei Zhang: Data curation, Software, Funding acquisition. Liangkai Chen: Methodology, Writing - review & editing. Jingguang Li: Funding acquisition, Project administration, Writing - review & editing. Jun Wang: Resources, Investigation. Yunfeng Zhao: Supervision, Data curation. Liegang Liu: Writing - review & editing. Yongning Wu: Writing - review & editing, Supervision.

Declaration of Competing Interest

The authors declare no competing interests.

Acknowledgments

The authors thank all the mothers who collaborated with the study and donated serum samples.

References (45)

  • T.W. Rogstad et al.

    Concentrations of vitamin A, E, thyroid and testosterone hormones in blood plasma and tissues from emaciated adult male Arctic foxes (Vulpes lagopus) dietary exposed to persistent organic pollutants (POPs)

    Environ. Res.

    (2017)
  • G.D. Shapiro et al.

    Exposure to organophosphorus and organochlorine pesticides, perfluoroalkyl substances, and polychlorinated biphenyls in pregnancy and the association with impaired glucose tolerance and gestational diabetes mellitus: the MIREC study

    Environ. Res.

    (2016)
  • M.M. Smarr et al.

    Persistent organic pollutants and pregnancy complications

    Sci. Total Environ.

    (2016)
  • M. Vafeiadi et al.

    Persistent organic pollutants in early pregnancy and risk of gestational diabetes mellitus

    Environ. Int.

    (2017)
  • Y. Wang et al.

    Association of serum levels of perfluoroalkyl substances with gestational diabetes mellitus and postpartum blood glucose

    J. Environ. Sci.

    (2018)
  • S. Wimmerová et al.

    Relative effect potency estimates of dioxin-like activity for dioxins, furans, and dioxin-like PCBs in adults based on cytochrome P450 1A1 and 1B1 gene expression in blood

    Environ. Int.

    (2016)
  • L. Zhang et al.

    Non-dioxin-like polychlorinated biphenyls in early pregnancy and risk of gestational diabetes mellitus

    Environ. Int.

    (2018)
  • C. Zhang et al.

    A prospective study of prepregnancy serum concentrations of perfluorochemicals and the risk of gestational diabetes

    Fertil. Steril.

    (2015)
  • W. Zhao et al.

    Development and validation of a radiomics nomogram for identifying invasiveness of pulmonary adenocarcinomas appearing as subcentimeter ground-glass opacity nodules

    Eur. J. Radiol.

    (2019)
  • M.A. Ashraf

    Persistent organic pollutants (POPs): a global issue, a global challenge

    Environ. Sci. Pollut. Res. Int.

    (2017)
  • V. Berg et al.

    Persistent organic pollutants and the association with maternal and infant thyroid homeostasis: a multipollutant assessment

    Environ. Health Perspect.

    (2017)
  • J.M. Braun et al.

    What can epidemiological studies tell us about the impact of chemical mixtures on human health?

    Environ. Health Perspect.

    (2016)
  • Cited by (10)

    • Live in same region, respond differently: Canine and human response to pollutants in placental accumulation

      2022, Chemosphere
      Citation Excerpt :

      Thus, it is seen that differences in anatomical features and molecules may affect the passage of placental transfer in species (Schmidt et al., 2021). Because growth retardation, behavioral problems, and thyroid insufficiency may be seen in fetuses exposed to POPs, many countries have conducted biomonitoring programs of POPs using mother-fetus-matched matrices, such as mother and cord blood, to demonstrate the relationship between maternal exposure to POPs and the health of infants (Jeong et al., 2018; Kim et al., 2015; Konishi et al., 2009; Liu et al., 2021). However, serum-based biomonitoring requires both invasive sample collection and only represents a temporary time point for assessing exposure to POPs.

    • Pentachlorophenol exposure in early pregnancy and gestational diabetes mellitus: A nested case-control study

      2022, Science of the Total Environment
      Citation Excerpt :

      Pregnant women undergo significant metabolic changes during pregnancy and are more susceptible to endocrine/metabolic-disrupting chemicals (Robinson et al., 2015). An increasing number of studies reported that exposure to synthetic chemicals might be closely associated with the progression of GDM (Rahman et al., 2019; Hou et al., 2021; Liu et al., 2021a), in addition to the traditional risk factors, such as advanced maternal age, family history of diabetes, and obesity (McIntyre et al., 2019). Associations between endocrine-disrupting chemicals (EDCs) and diabetes have also been reported (Li et al., 2018; Li et al., 2019a).

    • Inappropriately sweet: Environmental endocrine-disrupting chemicals and the diabetes pandemic

      2021, Advances in Pharmacology
      Citation Excerpt :

      For example, in one study a mixture of persistent organic pollutants (POPs) found in fish oil was shown to promote insulin resistance in rats (Ruzzin et al., 2010). Indeed, many studies examining PCB effects on metabolic outcomes have used PCB mixtures (Liu et al., 2021). Additionally, epidemiological advancements have allowed for the study of metal and metalloid mixtures in relation to diabetes risk, status, and control.

    View all citing articles on Scopus
    View full text