Receptor research on xenohormone effects of human serum extracts containing the actual mixture of perfluorinated alkyl acids: a short review

Perfluorinated alkyl acids (PFAAs) are used in many household products including food contact materials. Hence, humans are continuously exposed, and the PFAAs are accumulated in human serum with half-lives up to 8.8 years. In humans, high PFAA serum levels have been associated with an increased risk of breast cancer and other adverse health effects such as lower birth weight and longer time to pregnancy which might be related to disruptions of various hormonal systems. For instance, direct cell exposure studies in vitro suggest that some PFAAs can transactivate the estrogen receptor (ER), antagonize the androgen receptor (AR) and has the potential to interfere with TH and AhR functions. Moreover, the PFAAs also showed cellular oxidative stress. Humans are exposed to an array of PFAAs, and the quantity and combination of these PFAAs in human serum differs between individuals. Hence, the toxicological studies of single PFAAs and simple mixtures might be insufficient to predict how the actual mixtures of PFAAs may affect humans. To get a better evaluation of the actual mixture effects, we developed a method to extract the actual mixture of PFAAs from human serum. Preliminary results showed that 17% of the PFAA serum fractions from pregnant women could significantly transactivate the ER, and 94% of the fractions could further increase the transactivity induced by the potent ER ligand 25 pM 17?-estradiol. As part of the international FETOTOX project (http://fetotox.au.dk/), we are currently extracting the actual PFAA serum mixture from 700 pregnant women to further elucidate whether the serum PFAA mixture can transactivate the ER at the levels found in human serum. We suggest that our method can in the future be used to study the actual serum PFAA mixture effects on both steroid hormone actions as well as other hormonal systems e.g. thyroid hormone function. In the current review we will discuss how our recently developed PFAA extraction method might be used in future research to assess the endocrine impact of PFAAs on human health

The influence of persistent organic pollutants in the traditional Inuit diet on markers of inflammation

Concentrations of persistent organic pollutants (POPs) are high in Inuit living predominately on the traditional marine diet. Adverse effects of POPs include disruption of the immune system and cardiovascular diseases that are frequent in Greenland Inuit. We aimed to assess the association between exposure to POPs from the marine diet and inflammation, taking into account other factors such as vitamin D. We invited Inuit and non-Inuit living in settlements or the town in rural East Greenland or in the capital city Nuuk. Participants completed a food frequency questionnaire and donated a blood sample for measurement of the two markers of inflammation YKL-40 and hsCRP, 25-hydroxy-vitamin D, eleven organochlorine pesticides (OCPs), fourteen polychlorinated biphenyls (PCBs), one polybrominated biphenyl, and nine polybrominated diphenyl ethers (PBDEs) adjusted to the serum lipid content. Participants were 50 through 69 years old, living in settlements, town or city (n = 151/173/211; 95% participation rate). ΣOCP, ΣPCB and ΣPBDE serum levels were higher in Inuit than in non-Inuit (p<0.001/ p<0.001/ p<0.001), in older individuals (p<0.001/p<0.001/p = 0.002) and in participants with the highest intake of Greenlandic food items (p<0.001/p<0.001/p<0.001). Both YKL-40 and hsCRP serum levels were higher in Inuit compared to non-Inuit (p<0.001/p = 0.001), and increased with age (p<0.001/p = 0.001) and with the intake of Greenlandic food items (p<0.001/p = 0.002). Multivariate analysis conformed to a marked influence on both YKL-40 and hsCRP by ΣOCP (p<0.001/p<0.001) and ΣPCBs (p<0.001/p = 0.001) after adjusting for age, BMI, vitamin D, alcohol and smoking. POP levels were associated with the intake of the traditional Inuit diet and with markers of inflammation. This supports a pro-inflammatory role of POPs to promote chronic diseases common to populations in Greenland. These data inform guidelines on 'the Arctic dilemma' and encourage follow-up on the ageing Arctic populations

Levels of Pesticides and Their Metabolites in Wistar Rat Amniotic Fluids and Maternal Urine upon Gestational Exposure.

Concentrations of pesticides and selected metabolites in rat urine and amniotic fluid were determined as biomarker upon oral administration of Wistar rats to two pesticide mixtures consisting of three to five pesticides (bitertanol, propiconazole, cypermethrin, malathion, and terbuthylazine). The pesticides and their metabolites were found in rat amniotic fluid and urine, generally in dose-response concentrations in relation to dosage. The measurement of the substances in the amniotic fluid indicated that the fetus was exposed to the pesticides as well as their metabolites. Moreover, the pesticides detected in urine demonstrated the exposure as well as the ability of the rat to excrete these compounds

Health effects associated with measured levels of contaminants in the Arctic

Published version. Source at http://dx.doi.org/10.3402/ijch.v75.33805 The Human Health Assessment Group has over the past decade recommended that effect studies be conducted in the circumpolar area. Such studies examine the association between contaminant exposure in the Arctic populations and health effects. Because foetuses and young children are the most vulnerable, effect studies are often prospective child cohort studies. The emphasis in this article is on a description of the effects associated with contaminant exposure in the Arctic. The main topics addressed are neurobehavioural, immunological, reproductive, cardiovascular, endocrine and carcinogenic effect. For each topic, the association between exposure and effects is described, and some results are reported for similar studies outside the Arctic

Overview of ongoing cohort and dietary studies in the Arctic

Published version. Source at http://dx.doi.org/10.3402/ijch.v75.33803 This article gives an overview of the ongoing cohort and dietary studies underlying the assessment of population health in the Arctic. The emphasis here is on a description of the material, methods and results or preliminary results for each study. Detailed exposure information is available in an article in this journal, whereas another paper describes the effects associated with contaminant exposure in the Arctic. The cohort descriptions have been arranged geographically, beginning in Norway and moving east to Finland, Sweden, Russia and the other Arctic countries and ultimately to the Faroe Islands. No cohort studies have been reported for Alaska or Iceland

Xenohormone transactivities are inversely associated to serum POPs in Inuit

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

The European Registered Toxicologist (ERT) : Current status and prospects for advancement

Acknowledgements We would like to thank the participants of the five workshops in which the issues presented in this paper were discussed and the revised guidelines prepared, as well as the EUROTOX Executive Committee and the societies of toxicology of Sweden, the Netherlands, Switzerland, Austria and France for their support which allowed the workshops to take place.Peer reviewedPostprin