Environmental Persistent Organic Pollutants (POPs) can alter the hormone homeostasis by mimicking, interfering or blocking the function of hormones; moreover POPs are hypothesized to modify the risk of breast cancer. The association between POPs and breast cancer has been widely studied but the conclusions are inconsistent. The present study examined the associations between serum levels of POPs and breast cancer with focus on the highly exposed Greenlandic Inuit population. The study design was a case-control study of Inuit women from Greenland. The participants were asked to complete a questionnaire with information on reproductive history and lifestyle and to provide a blood sample. The sampling was carried out in two time periods (2000–2003 and 2011–2014). The serum levels were determined of 14 polychlorinated biphenyls (PCBs), 11 organochlorine pesticides (OCPs), 16 perfluoroalkyl acids (PFAAs), 1 polybrominated biphenyl (PBB), and 9 polybrominated diphenyl ethers (PBDEs). Independent samples t-test was used to compare differences between cases and controls and odds ratios (OR) adjusted for identified confounders were obtained using logistic regression. The study population included 77 breast cancer cases and 84 controls. The majority of the measured compounds declined significantly from 2000 – 2003 to 2011–2014. However, for the perfluorinated carboxylic acids (PFCAs) an increase was observed. The serum levels were significantly higher in cases compared to controls for the majority of the compounds, and after adjusting for age the difference was maintained for ∑OCP, dichlorodiphenyldichloroethylene (p,p′-DDE), ∑PFAA, ∑perfluorinated sulfonic acids (PFSA), perfluorohexane sulfonate (PFHxS), and perfluorooctane sulfonate (PFOS). For the lipophilic POPs, high serum levels (middel/highest vs. lowest tertile) of ∑PCB, ∑estrgoenicPCB, PCB99, PCB138, PCB153, PCB170, PCB170, and PCB183 was associated with breast cancer risk; for the amphiphilic PFAAs, high serum levels of ∑PFAA, ∑PFCA, ∑PFSA, perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), PFHxS, and PFOS were associated with breast cancer risk. Significant, positive associations between breast cancer risk and PCBs and PFAAs were observed. The associations indicate that environmental exposure to POPs can be a factor increasing the risk for breast cancer in Inuit women.

Humans are exposed to a large number of chemicals from sources such as the environment, food, and consumer products. There is growing concern that human exposure to chemical mixtures, especially during critical periods of development, increases the risk of adverse health effects in newborns or later in life. Historically, the one-chemical-at-a-time approach has been applied both for exposure assessment and hazard characterisation, leading to insufficient knowledge about human health effects caused by exposure to mixtures of chemicals that have the same target. To circumvent this challenge researchers can apply in vitro assays to analyse both exposure to and human health effects of chemical mixtures in biological samples. The advantages of using in vitro assays are: (i) that an integrated effect is measured, taking combined mixture effects into account and (ii) that in vitro assays can reduce complexity in identification of Chemicals of Emerging Concern (CECs) in human tissues. We have reviewed the state-of-the-art on the use of receptor-based in vitro assays to assess human exposure to chemical mixtures and related health impacts. A total of 43 studies were identified, in which endpoints for the arylhydrocarbon receptor (AhR), the estrogen receptor (ER), and the androgen receptor (AR) were used. The majority of studies reported biological activities that could be associated with breast cancer incidence, male reproductive health effects, developmental toxicities, human demographic characteristics or lifestyle factors such as dietary patterns. A few studies used the bioactivities to check the coverage of the chemical analyses of the human samples, whereas in vitro assays have so far not regularly been used for identifying CECs in human samples, but rather in environmental matrices or food packaging materials. A huge field of novel applications using receptor-based in vitro assays for mixture toxicity assessment on human samples and effect-directed analysis (EDA) using high resolution mass spectrometry (HRMS) for identification of toxic compounds waits for exploration. In the future this could lead to a paradigm shift in the way we unravel adverse human health effects caused by chemical mixtures.

Prenatal exposure to per- and polyfluorinated substances (PFAS) may impair fetal growth. Our knowledge of the underlying mechanisms is incomplete. We used the Adverse Outcome Pathway (AOP)-helpFinder tool to search PubMed for studies published until March 2021 that examined PFAS exposure in relation to birth weight, oxidative stress, hormones/hormone receptors, or growth signaling pathways. Of these 1880 articles, 106 experimental studies remained after abstract screening. One clear finding is that PFAS are associated with oxidative stress in in vivo animal studies and in vitro studies. It appears that PFAS-induced reactive-oxygen species (ROS) generation triggers increased peroxisome proliferator-activated receptor (PPAR)γ expression and activation of growth signaling pathways, leading to hyperdifferentiation of pre-adipocytes. Fewer proliferating pre-adipocytes result in lower adipose tissue weight and in this way may reduce birth weight. PFAS may also impair fetal growth through endocrine effects. Estrogenic effects have been noted in in vivo and in vitro studies. Overall, data suggest thyroid-damaging effects of PFAS affecting thyroid hormones, thyroid hormone gene expression, and histology that are associated in animal studies with decreased body and organ weight. The effects of PFAS on the complex relationships between oxidative stress, endocrine system function, adipogenesis, and fetal growth should be further explored.

Persistent organic pollutants (POPs), including polychlorinated biphenyls (PCBs), organchlorine pesticides and perfluoroalkylated substances (PFASs) and heavy metals bioaccumulate in the marine food chain in the Arctic regions, and thus, the Greenlandic population has a higher body burden due to relatively high intake of marine mammals. We assessed the temporal trend for POPs, including PCB 153; 1,1-dichloro−2,2-bis (p-chlorophenyl)-ethylene (p,p’-DDE); oxychlordane; six PFASs; mercury; lead and selenium in Inuit from Ilulissat, Nuuk, and across Greenland (including thirteen towns/districts), from 1994 to 2015. Data showed a significant annual decrease of 6.85–8.61% for PCB153, 6.67–8.61% for p,p’-DDE, 6.11–9.52% for oxychlordane, 5.92–6.76% for mercury and 6.48–9.43% for lead in Inuit women from Nuuk, Ilulissat, and across thirteen Greenlandic districts. The blood selenium level of all Greenlandic women increased 1.01% annually, while the trend direction was negative for Nuuk women. A similar pattern was seen for men across Greenland, with a yearly decrease of 11.3% for PCB 153, 8.61% for p,p’-DDE, 15.6% for oxychlordane, 13.1% for mercury and 12.2% for lead. Perfluorooctane sulfonate, perfluorohexane sulfonate and perfluorooctanoic acid significantly decreased 5.82–11.7% annually for both women and men across Greenland. For perfluorononanoic acid, perfluorodecanoic acid and perfluoroundecanoic acid, we observed an increasing trend for women across Greenland. In conclusion, there was a decreasing trend of the regulated POPs and metals but a potential increasing trend of the nonregulated PFASs in the Greenlandic population between 1994 and 2015. The continuing biomonitoring of contaminants of concern is important to protect the Arctic population heath.

High concentrations of persistent organic pollutants (POPs) in blood of the Greenlandic population are well known. The exposure is mainly through traditional food intake, including marine mammals and seabirds. The present study aimed to follow up on POP concentrations (organochlorine pesticides, polychlorinated biphenyls, per- and polyfluoroalkyl substances, and halogenated flame retardants (HFRs)) and relations to lifestyle and diet of the mothers included in the Greenlandic ACCEPT cohort (3-5 years after inclusion in 2013-15) and to include the children's fathers. This new data collection in 2019-20 included blood samples for measurement of POP concentrations and lifestyle and food frequency questionnaires from 101 mothers and 76 fathers aged 24-55 years living in Nuuk, Sisimiut, and Ilulissat, Greenland. The mothers' intra-individual median percentage decrease in POP concentrations from inclusion to this follow-up (3-5 years later) was 16-58%, except for mirex (0% change). Median concentrations of POPs were 1.4-4.6 times higher in fathers than in mothers. The POPs differed by residential town with generally higher concentrations in Ilulissat compared to Sisimiut and Nuuk. We report, for the first time, novel HFRs in human samples from Greenland. However, concentrations were low and only dechlorane plus (with its anti-isomer) was detected in >50% of the samples. Most POPs correlated positively with age and n-3/n-6 fatty acid ratio. The lipophilic POPs correlated positively with the percentage of life lived in Greenland, whereas few POPs correlated positively with BMI, income (personal and household), education, and alcohol intake. The POPs generally associated positively with the intake of marine mammals, seabirds, and dried fish, while few POPs associated positively with Greenlandic fish intake. In contrast, POPs generally associated negatively with imported meat products intake. The study findings may be of interest for future dietary recommendations in Greenland. We discuss the potential explanations for the findings and suggestions for future research.

Exposure to lipophilic persistent organic pollutants (lipPOPs) elicits a number of species- and tissue-specific toxic responses, many of which involve the aryl hydrocarbon receptor (AhR). This study aims to measure the combined serum dioxin-like activity of lipPOPs in Greenlandic Inuit pregnant women and the associations with fetal growth indices. The combined dioxin-like activity of serum lipPOPs extracts was determined using the AhR reporter gene bioassay and expressed as pico-gram (pg) TCDD equivalent (TEQ) per gram serum lipid [AhR-TEQ (pg/g lipid)]. Significant AhR-TEQ was found in >87% of serum samples with the median level of 86.2 pg TEQ/g lipid. The AhR-TEQ level positively correlated with the marine food intake biomarker n-3/n-6 polyunsaturated fatty acids ratio, while negatively correlated with body mass index and parity. Women giving birth to infants with low birth weight (<2500 g) and length (<50 cm) had higher AhR-TEQ level compared to those with normal weight and length infants. For previous smokers, we found significant inverse associations between maternal AhR-TEQ level and fetal growth indices. In conclusion, exposure of Greenlandic Inuit pregnant women to dioxin-like compounds through traditional marine food can adversely influence the fetal growth via induced AhR activity. Smoking might have modifying effects.