Characterization of different contaminants and current knowledge for defining chemical mixtures in human milk: A review.

Hundreds of xenobiotics, with very diverse origins, have been detected in human milk, including contaminants of emerging concern, personal care products and other current-use substances reflecting lifestyle. The routes of exposure to these chemicals include dermal absorption, ingestion and inhalation. Specific families of chemicals are dominant among human milk monitoring studies (e.g., organochlorine pesticides, bisphenol A, dioxins), even though other understudied families may be equally toxicologically relevant (e.g., food-processing chemicals, current-use plasticizers and flame retardants, mycotoxins). Importantly, the lack of reliable human milk monitoring data for some individual chemicals and, especially, for complex mixtures, is a major factor hindering risk assessment. Non-targeted screening can be used as an effective tool to identify unknown contaminants of concern in human milk. This approach, in combination with novel methods to conduct risk assessments on the chemical mixtures detected in human milk, will assist in elucidating exposures that may have adverse effects on the development of breastfeeding infants.

Targeted screening of 11 bisphenols and 7 plasticizers in food composites from Canada and South Africa.

A sensitive method based on ultrasound-assisted liquid extraction coupled with liquid chromatography was applied to screen 18 plastic-related contaminants in 168 food composites (namely fish fillets, chicken breast, canned tuna, leafy vegetables, bread and butter) collected in Montreal (Canada), Pretoria and Vhembe (South Africa). Bisphenol A (BPA), bisphenol S (BPS) and seven plasticizers (di-n-butyl phthalate (DBP), diethyl phthalate (DEP), (2-ethylhexyl) phthalate (DEHP), di-(2-ethylhexyl) adipate (DEHA), di-isononyl phthalate (DINP), di-(isononyl)-cyclohexane-1,2-dicarboxylate (DINCH)) were detected in different foods from both countries. DBP and DEP were the most frequently detected contaminants in food collected in Montreal (75% for both) and DINP was the most frequently detected contaminant in food from South Africa (67%). DEHA concentration in packaged fish were significantly higher than the values for non-packaged fish (p < 0.01) suggesting that the packaging film can be one source of DEHA in fish.

Polybrominated Diphenyl Ethers in Human Follicular Fluid Dysregulate Mural and Cumulus Granulosa Cell Gene Expression.

Polybrominated diphenyl ethers (PBDEs), a major class of flame retardants incorporated into numerous consumer products, leach out into dust resulting in widespread exposure. There is evidence from in vitro and in vivo animal studies that PBDEs affect ovarian granulosa cell function and follicular development, yet human studies of their association with female infertility are inconclusive. Here, we tested the hypothesis that exposure to the PBDEs in follicular fluid is associated with dysregulation of gene expression in the mural and cumulus granulosa cells collected from women undergoing in vitro fertilization by intracytoplasmic sperm injection. The median concentration of the ∑ 10PBDEs detected in the follicular fluid samples (n = 37) was 15.04 pg/g wet weight. RNA microarray analyses revealed that many genes were differentially expressed in mural and cumulus granulosa cells. Highest vs lowest quartile exposure to the Σ 10PBDEs or to 2 predominant PBDE congeners, BDE-47 or BDE-153, was associated with significant effects on gene expression in both cell types. Mural granulosa cells were generally more sensitive to PBDE exposure compared to cumulus cells. Overall, gene expression changes associated with BDE-47 exposure were similar to those for ∑ 10PBDEs but distinct from those associated with BDE-153 exposure. Interestingly, exposure to BDE-47 and ∑ 10PBDEs activated the expression of genes in pathways that are important in innate immunity and inflammation. To the best of our knowledge, this is the first demonstration that exposure to these environmental chemicals is associated with the dysregulation of pathways that play an essential role in ovulation.

Thermal degradation of bisphenol A and bisphenol S in water and fish (cod and basa) fillets.

The thermal degradation of bisphenol A (BPA) and bisphenol S (BPS) was investigated in water and fish (cod, basa) fillets. Ultrasound assisted solvent extraction followed by high performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (HPLC-QTOF-MS) was used to analyze residues in fish. Good instrumental linearity (r2 > 0.99) and recoveries (83.3-128.4%) were achieved. BPA and BPS did not degrade (1 h; 100 °C) in water (<0.1% degradation) but degraded in fish matrices. The degradation percentage of BPA was 33.0 ± 1.5% and 35.4 ± 1.2% in incurred and spiked cod, respectively; and the degradation percentage of BPS was 34.7 ± 1.7% and 37.5 ± 1.4% in incurred and spiked basa, respectively. The degradation products in spiked samples were different from those in the incurred group under the same conditions. This first study on the thermal degradation of plastic-related chemicals in food using a non-targeted approach will contribute to the refining of food safety risk assessments.

Non-targeted screening of plastic-related chemicals in food collected in Montreal, Canada.

A non-targeted screening method based on ultrasound-assisted extraction followed by high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC-QTOF-MS) was developed to screen for the presence of plastic-related chemicals (PRCs) in different types of food (fish, chicken, canned tuna, leafy vegetables, bread and butter). Eleven bisphenols were used as targeted compounds. Instrument linearity (r2 ≥0.98), inter-day precision (RSD ≤9.0%) as well as method detection limits (MDLs below 3.6 ng g-1) were satisfactory. Recoveries of the eleven bisphenols ranged from 76% to 122% among the different food matrices. The method was applied to food collected from Montreal, Canada in 2017-2018. The non-targeted screening approach identified a range of contaminants in different food matrices, including BPA, BPS, bis(2-ethylhexyl) adipate, dibutyl adipate, hexadecyl methacrylate and Irganox®1076. Further research is suggested to investigate the concentration of these PRCs, the consumption habits of average and specific populations and the potential routes of contamination.

A Mixture Reflecting Polybrominated Diphenyl Ether (PBDE) Profiles Detected in Human Follicular Fluid Significantly Affects Steroidogenesis and Induces Oxidative Stress in a Female Human Granulosa Cell Line.

Brominated flame retardants are incorporated into consumer products to prevent flame propagation. These compounds leach into the domestic environment, resulting in chronic exposure. Pregnancy failure is associated with high levels of polybrominated diphenyl ethers (PBDEs), a major class of brominated flame retardants, in human follicular fluid, raising serious questions regarding their impact on female fertility. Our goal was to elucidate the effects of a mixture of PBDEs, similar to the profile found in human follicular fluid, on an immortalized human granulosa cell line, the KGN cell line. We showed that cell viability was altered and oxidative stress was induced as reflected by increased reactive oxygen species formation at 100 µM of the PBDE mixture. Transcriptomic analysis revealed that PBDE treatments of 1, 5, and 20 µM altered the expression of several genes involved in the reactive oxygen species signaling pathway. Significant dose-dependent reductions in progesterone and estradiol levels in the culture medium were measured after PBDE treatment; in parallel, the expression of genes involved in estradiol metabolism, namely CYP1A1, was up-regulated by 5 and 20 µM of the PBDE mixture. Treatment with 20 µM PBDE also increased the expression and secretion of the proinflammatory factor, IL-6, into the KGN cell culture medium. Our results demonstrate that PBDEs can alter human granulosa cell functions by inducing oxidative stress and disrupting steroidogenesis. These results indicate that PBDEs may be detrimental to ovarian functions and thus may adversely affect female reproductive health after chronic exposure.

Evaluating external contamination of polybrominated diphenyl ethers in human hair: clinical and research implications.

BACKGROUND: Human hair is a well-validated matrix for detecting a variety of xenobiotics, including drugs of abuse (cocaine, tetrahydrocannabinol, and morphine) and fatty acid ethyl ethers. Recent studies have shown that hair can also be useful in determining an individual's exposure to polybrominated diphenyl ethers (PBDEs), flame retardants that contaminate the dust in our daily environment. Hair processing before assay varies with each analyte; in particular, the wash protocol must be optimized to remove external contaminants while not affecting levels of the chemical of interest. The aim of this study was to determine whether hair needs to be washed before analysis for PBDEs, and if so, which protocol is most effective to ensure that the level of PBDEs is neither overestimated nor underestimated. METHOD: Individual hair samples from 10 adults (5 men and 5 women) were subjected to 4 different wash protocols: (1) no wash, (2) water, (3) 10% sodium dodecyl sulfate (SDS), and (4) hexane. Both the washes and hair were analyzed for 8 PBDEs by gas chromatography/mass spectrometry. RESULTS: The sum of PBDEs (ΣPBDEs) in the washes was (1) no wash: 0 pg/mg, (2) water: 0.39 ± 0.19 (mean ± SEM), (3) 10% SDS: 1.34 ± 0.68, and (4) hexane: 1.92 ± 0.87. The ΣPBDEs in the hair were: (1) no wash: 20.32 ± 3.05, (2) water: 20.30 ± 2.41, (3) 10% SDS: 19.27 ± 1.87, and (4) hexane: 16.91 ± 2.89. Washing with water, 10% SDS, and hexane decreased the PBDE levels by 1.9%, 7%, and 11.4%, respectively (P < 0.05). CONCLUSIONS: Thus, of the washes evaluated, water is the wash that had the least effect on total PBDE concentrations, providing the best evaluation of an individual's exposure to PBDEs.