This work was focused on evaluating the occurrence of endocrine-disrupting compounds (EDCs) in fish muscles, such as bisphenol analogues, personal care products, including some UV-filters and musk fragrances, and selected pesticides. A total of 238 muscle samples of three fish species (Platichthys flesus, Mugil cephalus, and Dicentrarchus labrax) of an important estuary ending in the North East Atlantic Ocean (Douro River estuary, Portugal), in different seasons of the year, was analysed. M. cephalus was the species with a greater occurrence of contaminants, mainly in fishes collected during the spring. Bisphenol A was the main bisphenol analogue detected with an average content of 23.1 μg/kg wet weight (w.w.). Among chemicals used in personal care products, galaxolide, tonalide, and 2-ethylhexyl salicylate, were the most often found, being present in 15.9% (2.2-538.4 μg/kg w. w.), 4.6% (1.1-57.8 μg/kg w. w.) and 3.4% (3.9-56.1 μg/kg w. w.) of the samples, respectively. About 14% of the samples contained residues of at least one pesticide, being alachlor, aldrin, p,p\'-DDT, permethrin, and prochloraz the main chemicals observed, varying from 0.1 μg/kg w. w. (p,p\'-DDT) to 37.8 μg/kg w. w. (prochloraz). The daily intake estimates of the most frequent EDCs found in the fish muscles suggested that there are no health concerns, based on the recommended weekly consumption of fish for adults.

The zebrafish eleutheroembryo model is increasingly used to assess the toxicity and developmental adverse effects of xenobiotics. However, the actual exposure is seldom measured (poorly accessible), while a predictive model could estimate these concentrations. The predictions with a new eleutheroembryo physiologically based pharmacokinetic (PBPK) model have been evaluated using datasets obtained from literature data for several bisphenols. The model simulated the toxicokinetics of bisphenols A (BPA), AF, F, and S through the eleutheroembryo tissues while considering the body and organ growth. We further improved the predictions by adding dynamic flows through the embryo and/or its chorion, impact of experimental temperature, metabolic clearance, and saturation of the absorption by Bayesian calibration. The model structure was determined using the BPA dataset and generalized to the other bisphenols. This model revealed the central role of the chorion in the compound uptake in the first 48 h post-fertilization. The predictions for the BPA substitutes estimated by our PBPK model were compared to available toxicokinetics data for zebrafish embryos, and 63% and 88% of them were within a twofold and fivefold error intervals of the corresponding experimental values, respectively. This model provides a tool to design new eleutheroembryo assays and evaluate the actual exposure.

Persistent organic pollutant exposures are well-documented in the Arctic, but fewer studies examined non-persistent chemicals, despite increased market food and consumer product consumption.
To measure phenol, paraben, phthalate, and alternative plasticizer concentrations in Inuit adults.
The study included 30 pooled urine samples from Qanuilirpitaa? 2017 Nunavik Inuit Health Survey (Q2017) participants. Creatinine-adjusted geometric mean concentrations (GM) and 95% confidence intervals (CI) were compared across sex, age, and regions, and compared to those in the Canadian Health Measures Survey (CHMS) and the First Nations Biomonitoring Initiative (FNBI).
Q2017 bisphenol-A concentrations were double the CHMS 2018-2019 concentrations [GM (95% CI): 1.98 (1.69-2.31) versus 0.71 (0.60-0.84) µg/g creatinine], but in line with FNBI [1.74 (1.41-2.13) µg/g creatinine]. Several phthalate concentrations were higher in Q2017 versus CHMS, particularly monobenzyl phthalate, which was was 19-fold higher in Q2017 versus CHMS 2018-2019 [45.26 (39.35-52.06) versus 2.4 (2.0-2.9) µg/g creatinine] and four-fold higher than FNBI. There were also four-fold higher concentrations of the two alternate plasticizer 2,2,4-trimethyl-1,3-pentanediol diisobutyrate (TIXB) metabolites in Q2017 compared to CHMS 2018-2019. Women and people living in Ungava Bay had generally higher concentrations of non-persistent chemicals.
The results suggest higher concentrations of certain non-persistent chemicals in Inuit versus the general Canadian population.
Few studies have explored non-persistent chemical distributions in Northern communities, despite the increasing consumer product and market food consumption. We analyzed 30 pooled samples from the Qanuilirpitaa? Nunavik Inuit Health Survey 2017 to assess exposures to common plasticizes and plastic constituents and compare their levels with the general Canadian population and First Nation groups. We observed particularly higher levels of bisphenol-A, of monobenzyl phthalate, and of two 2,2,4-trimethyl-1,3-pentanediol diisobutyrate (TXIB) metabolites among Nunavimmiut compared to the general Canadian population, notably among women and Ungava Bay residents. Larger studies are required to confirm our findings and identify potential adverse health effects from these exposures.

Bisphenol A (BPA), a synthetic compound widely used as a building block for polycarbonate plastics, has been declared in the European Union (EU) as a substance of very high concern (SVHC). A series of BPA alternatives and derivatives (bisphenols/BPs) with similar physical-chemical properties have been produced and used by companies for substituting it. To evaluate the estrogenic and androgenic binding activity of 26 BPs, a non-statistical in silico approach has been applied. The results of molecular docking analyses applied on six different nuclear receptors (NRs) have revealed that: i) some BPA metabolites could lower the harmful effects of BPA exposure; ii) BPS is a lower interactor for all NRs, but it does not appear safer at all for androgen receptor (AR), for which its binding activity is found similar to a pharmacological anti-androgen; iii) only a BP has been found as a safer compound for all NRs considered. Moreover, molecular dynamic simulation of three BPs on ERα have revealed that the presence of negative hydrophobic interactions could induce a decrease in receptor activity. Overall, the present results demonstrate that in silico methods could be a valid approach to screen estrogenic and androgenic activity of food contact materials (FCMs).

Bisphenols, as synthetic chemicals, have been widely detected in environmental and human samples. Epidemiological studies have reported relationships between bisphenol A (BPA) and type 2 diabetes mellitus (T2DM), but results are inconsistent. Additionally, the associations between other bisphenols (i.e., the substitutes of BPA) with T2DM have been scarcely reported. A case-control study was conducted to examine the associations of urinary bisphenols with T2DM by investigating 8 bisphenols in urine samples of 251 T2DM cases and 251 controls and using different statistic models. Urinary bisphenol AF (BPAF) and bisphenol S (BPS) concentrations were significantly positively associated with T2DM in the log-transformed statistical models and adjusted odd ratios (ORs) were separately 4.95 [95% confidence interval (CI): 3.15, 7.79] and 1.73 (95% CI: 1.37, 2.18), which was consistent with the results in categorical models (OR = 2.03; 95% CI: 1.31, 3.15; p = 0.001 for BPAF; OR = 3.83; 95% CI: 2.37, 6.20; p < 0.001 for BPS). In addition, in the categorical models, elevated odds of T2DM were observed in the second BPA quartile (OR = 2.58; 95% CI: 1.38, 4.80) and the third quartile (OR = 1.89; 95% CI: 1.03, 3.46), but not in the fourth quartile, which reflected a nonlinear association between urinary BPA and T2DM. Similarly, only significant positive association with T2DM was found in the second quartile of the sum of bisphenols (OR = 2.07; 95% CI: 1.12, 3.82). In the sensitivity analyses, the associations of bisphenols with T2DM remained consistent except for BPAF in the categorical model. Our study suggested that several urinary bisphenols were positively associated with T2DM.