Biomonitoring of bisphenols A, F, S and parabens in urine of breastfeeding mothers: Exposure and risk assessment

Highlights

• MP, EP and BPA were detected at high frequencies in urine of breastfeeding mothers.

• Average concentrations were 18 μg/g cr (MP), 0.8 μg/g cr (EP) and 0.9 μg/g cr (BPA).

• Use of personal care products was associated with higher urinary levels of MP and PP.

• MP was also associated with the consumption of packaged and bakery products.

• Estimated exposure was lower than the reference values for risk assessment.

Abstract

In the present study we used human biomonitoring to assess the internal exposure and the risk to four parabens and three bisphenols in 103 Spanish breastfeeding mothers participating in the BETTERMIILK project. Urinary methylparaben (MP), ethylparaben (EP), propylparaben (PP) and butylparaben (BP) presented detection frequencies ranging from 12% (BP) to 92% (MP), while bisphenol A (BPA), bisphenol F (BPF) and bisphenol S (BPS) were detected in 76% (BPA) and 20% (BPF, BPS) of the mothers. Average paraben concentrations (geometric mean) ranged from 0.021 ng mL⁻¹ (BP) to 17.7 ng mL⁻¹ (MP), whereas bisphenols had geometric means concentrations from 0.042 ng mL⁻¹ (BPF) to 0.927 ng mL⁻¹ (BPA).

Except for BPA, the estimated daily intakes (EDI) were calculated in order to interpret urinary levels in a risk assessment context. The obtained EDIs ranged from 0.00042 mg/kg/day for PP to 0.0434 mg/kg/day for MP and EP. A hazard quotient (HQ) was calculated for BPA (0.0049) and parabens (0.001–0.004), showing no risk in the studied population.

Sociodemographic characteristics, food consumption, and usage patterns of personal care products (PCPs) were investigated as possible determinants of exposure. Use of makeup and skincare products were associated with higher concentrations of MP and PP, respectively. Regarding dietary habits, MP was also associated with the consumption of packaged and bakery products.

Introduction

Bisphenols and parabens are man-made chemicals used in various consumer products. Bisphenol A (BPA) is used in the manufacture of polycarbonate plastic and epoxy resins and is found in different products like cans (food and drink), dental sealants, thermal receipts, food packaging, and personal care products (PCPs). Due to its toxicity, BPA has been banned in the manufacture of infant feeding bottles in Europe since 2011. Consequently, bisphenol analogues like bisphenol S (BPS) and bisphenol F (BPF) are used as a substitution for BPA in some consumer products (Chen et al., 2016). Parabens (alkyl esters of p-hydroxybenzoic acid) are widely used as antimicrobial preservatives, especially in cosmetics, pharmaceutical products, and in food and beverages. Methylparaben (MP), ethylparaben (EP), propylparaben (PP) and butylparaben (BP) are the most commonly used parabens. The widespread use of parabens as preservatives arises from their low toxicity, broad inertness, worldwide regulatory acceptance, and low cost (Jardim et al., 2015). However, some authors have stressed the reproductive toxicity of these substances (Garcia et al., 2017; Schreiber et al., 2019). Diet is considered an important source of bisphenols. Certain food groups such as canned food, fish, meat, and poultry have been associated with bisphenol levels (Sanchis et al., 2017). Exposure to parabens may occur through ingestion, inhalation and dermal absorption (Darbre and Harvey, 2008).

After oral ingestion, BPA suffers a metabolic process and is excreted mainly as BPA-glucuronide in urine with a half-life of less than 6 h. The metabolism of bisphenol analogues (BPS and BPF) and excretion in urine is less known, but it seems to be similar to BPA (Rochester and Bolden, 2015). Parabens may conjugate to β-D-glucuronide and sulphate, which reduces their bioactivity and facilitates urinary excretion. Generally, parabens are rapidly absorbed, metabolized, and excreted in urine from the body. Following excretion, the parent compounds can be measured in urine and have been shown to be valid biomarkers of exposure (Guo et al., 2017). Sakhi et al. (2018) confirmed that parabens have a short elimination half-life in humans, normally between 1 and 7 h. Although these substances, both bisphenols and parabens, are non-persistent chemicals and have short elimination half-lives in humans, their widespread use and potential endocrine-disrupting properties have made them chemicals of concern (Sakhi et al., 2018).

European plastic material regulation has established the migration limit of 0.05 mg of BPA per kg of food (EU, 2011), has banned the use of BPA in baby bottles, and has prohibited the migration of BPA from varnishes or coatings applied to materials in contact with food for infants and children 0–3 years of age (EU, 2018). Taking into account the “general toxicity” of bisphenols, only a temporary tolerable daily intake (t-TDI) of 4 μg kg bw⁻¹day⁻¹ has been established for oral exposure to BPA (EFSA, 2015). In the case of parabens, the EU allows and regulates the use of parabens in cosmetic products, food, and skincare pharmaceutical products. In addition, EFSA has established an acceptable daily intake (ADI) of 0–10 mg kg bw⁻¹day⁻¹ for the sum of methyl and ethyl acid para-hydroxybenzoic esters based on studies which showed non-observed-adverse-effects-levels (NOAELs) for both parabens. To date, no ADI for PP, BP, BPF, and BPS has been established (EFSA, 2004).

Apart from BPA, BPF and BPS have already been included as prioritised substances to be determined in human biomonitoring (HBM) studies (HBM4EU, 2017). Several biomonitoring studies have been implemented in order to determine urinary levels of BPF and BPS (Liao et al., 2012; Yang et al., 2014; Zhou et al., 2014). Although some HBM studies for bisphenols and parabens in urine have been performed in female populations (Arbuckle et al., 2014; Buckley et al., 2016; Callan et al., 2013; Heffernan et al., 2016; Jiménez-Díaz et al., 2016; Pollack et al., 2016; Sakhi et al., 2018), only one has studied breastfeeding women (Hines et al., 2015). Lee et al. (2017) have studied the distribution of bisphenols in biological samples such as urine and human milk from pregnant women before delivery, at delivery, and 1 month after delivery. Levels of BPA in urine were 2.23 ng mL⁻¹ and 0.51 ng mL⁻¹ in human milk. Several studies have described levels of bisphenols (geometric mean of total BPA: 0.29 ngmL⁻¹) and parabens (mean MP: 2.18 ngmL⁻¹) in human milk (Dualde et al., 2019; Schlumpf et al., 2010). In previous studies, our research group determined the levels of bisphenols and parabens in human milk, and the exposure and the risk to breastfed infants was assessed (Dualde et al., 2019, 2020).

The ratios between milk and urine levels for parabens and bisphenols have been previously studied (Hines et al., 2015; Fisher et al., 2017).

Several biomonitoring studies use biomonitoring equivalents (BE) or HBMI and HBMII values as biological reference values in urine (Apel et al., 2017; Aylward and Hays, 2011). Except for BPA, there are no BE or HBM values described for the compounds studied in our work. Katsikantami et al. (2019) suggested using the estimated daily intake (EDI) based on the internal concentration of compounds in order to estimate the risk. Once an EDI was estimated for mothers, risk assessment was performed calculating the hazard quotient (HQ) which is the ratio between the EDI and the ADI of the substance (Katsikantami et al., 2019; Yusà et al., 2018).

The aim of the present study was: i) to determine the levels of three bisphenols (BPA, BPS, and BPF) and four parabens (MP, EP, PP and BP) in the urine of breastfeeding mothers living in Valencia, Spain participating in the BETTERMILK project; ii) to study the factors influencing the bisphenol and paraben levels; and iii) to estimate the exposure and the risk assessment to bisphenols and parabens for mothers.