New approach methods to assess developmental and adult neurotoxicity for regulatory use: a PARC work package 5 project.

In the European regulatory context, rodent in vivo studies are the predominant source of neurotoxicity information. Although they form a cornerstone of neurotoxicological assessments, they are costly and the topic of ethical debate. While the public expects chemicals and products to be safe for the developing and mature nervous systems, considerable numbers of chemicals in commerce have not, or only to a limited extent, been assessed for their potential to cause neurotoxicity. As such, there is a societal push toward the replacement of animal models with in vitro or alternative methods. New approach methods (NAMs) can contribute to the regulatory knowledge base, increase chemical safety, and modernize chemical hazard and risk assessment. Provided they reach an acceptable level of regulatory relevance and reliability, NAMs may be considered as replacements for specific in vivo studies. The European Partnership for the Assessment of Risks from Chemicals (PARC) addresses challenges to the development and implementation of NAMs in chemical risk assessment. In collaboration with regulatory agencies, Project 5.2.1e (Neurotoxicity) aims to develop and evaluate NAMs for developmental neurotoxicity (DNT) and adult neurotoxicity (ANT) and to understand the applicability domain of specific NAMs for the detection of endocrine disruption and epigenetic perturbation. To speed up assay time and reduce costs, we identify early indicators of later-onset effects. Ultimately, we will assemble second-generation developmental neurotoxicity and first-generation adult neurotoxicity test batteries, both of which aim to provide regulatory hazard and risk assessors and industry stakeholders with robust, speedy, lower-cost, and informative next-generation hazard and risk assessment tools.

Emerging and legacy contaminants in common minke whale from the Barents sea.

Persistent organic pollutants (POPs), including brominated flame retardants (BFRs), perfluoroalkyl substances (PFAS) and metals, can accumulate in marine mammals and be transferred to offspring. In this study, we analyzed 64 lipophilic POPs, including four emerging BFRs, in the blubber, liver and muscle of 17 adult common minke whales (Balaenoptera acutorostrata) from the Barents Sea to investigate occurrence and tissue partitioning. In addition, the placental transfer concentration ratios of 14 PFAS and 17 metals were quantified in the muscle of nine female-fetus pairs to investigate placental transfer. Legacy lipophilic POPs were the dominating compound group in every tissue, and we observed generally lower levels compared to previous studies from 1992 to 2001. We detected the emerging BFRs hexabromobenzene (HBB) and pentabromotoluene (PBT), but in low levels compared to the legacy POPs. We detected nine PFAS, and levels of perfluorooctane sulfonate (PFOS) were higher than detected from the same population in 2011, whilst levels of Hg were comparable to 2011. Levels of lipophilic contaminants were higher in blubber compared to muscle and liver on both a wet weight and lipid adjusted basis, but tissue partitioning of the emerging BFRs could not be determined due to the high number of samples below the limit of detection. The highest muscle ΣPFAS levels were quantified in fetuses (23 ± 8.7 ng/g ww), followed by adult males (7.2 ± 2.0 ng/gg ww) and adult females (4.5 ± 1.1 ng/g ww), showing substantial placental transfer from mother to fetus. In contrast, Hg levels in the fetus were lower than the mother. Levels were under thresholds for risk of health effects in the whales. This study is the first to report occurrence and placental transfer of emerging contaminants in common minke whales from the Barents Sea, contributing valuable new data on pollutant levels in Arctic wildlife.

Do changes in persistent organic pollutants after bariatric surgery cause endocrine disruption?

BACKGROUND: Bariatric surgery results in weight loss, marked endocrine changes and the release of persistent organic pollutants (POPs). The release of POPs might cause endocrine disruption. The study aimed to explore associations between POPs and adiponectin, leptin and ghrelin in subjects undergoing bariatric surgery. METHODS: The study included 63 subjects with severe obesity (men/women: 13/50), age (years): 45.0 (8.5), and BMI (kg/m2) 39.1 (3.4). Analyses of adiponectin, leptin and ghrelin and POPs (hexachlorobenzene (HCB), dichlorodiphenyldichloroethylene (p,p'-DDE), polychlorinated biphenyl (PCB) 118 (dioxin-like compound; dl), and sum 6 PCB (PCB 28, -52, -101, -138, -153, and -180) were performed before and 12 months after bariatric surgery. RESULTS: There were significant increases in adiponectin and all POPs and a fall in leptin after surgery. The main finding was the highly significant associations between adiponectin and all POPs. The increase in HCB explained 38% of the variation in adiponectin. CONCLUSIONS: If the POP-associated increase in adiponectin is a causal effect, the release of POPs might have important clinical consequences. Adiponectin has both positive and negative clinical effects exerted by essentially unknown mechanisms. The effects of released POPs on the metabolic functions in subjects undergoing bariatric surgery deserve further evaluation.

Spatial Variation in Contaminant Occurrence in Marine Fishes and Prawns from Coastal Tanzania.

There are limited data on organic contaminants in marine biota from coastal Tanzania, especially on the occurrence of industrial-use contaminants such as polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs). The present study, performed in 2018-2019 in coastal Tanzania and Zanzibar Island, aimed at assessing spatial variation in the occurrence of PCBs; brominated flame retardants (BFRs), including PBDEs; and organochlorine pesticides, including dichlorodiphenyltrichloroethane (DDT), among three locations that differ in degree of anthropogenic activity. Analyzed samples included edible tissues of marine fishes and prawns representing different trophic levels and habitats. The results indicate a mainland-island difference, with fishes and prawns collected on Zanzibar having significantly lower PCB and DDT concentrations but higher concentrations of hexachlorobenzene compared to the two mainland locations. The highest contaminant concentrations were found in fishes and prawns collected around central Dar es Salaam harbor, with median ΣPCBs ranging from 22.3 to 577 ng/g lipid weight and ΣDDTs from 22.7 to 501 ng/g lipid weight, suggesting local sources. Concentrations of PBDEs were similar among locations, suggesting more diffuse sources. None of the "newer-type" BFRs, including compounds introduced as replacements for PBDEs, were detected in the present study. Stable isotope values of carbon (δ13 C) and nitrogen (δ15 N) varied among locations, and the relationship between contaminants and δ15 N varied among locations and habitat (pelagic/demersal). Concentrations measured in the present study are below European guidelines for human consumption of fishes and prawns. However, industrial-use contaminants should be monitored in developing countries because they are contaminants of emerging concern as a result of increasing industrialization and global trade of used products and wastes. Environ Toxicol Chem 2022;41:321-333. © 2021 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Effects of an environmentally relevant PFAS mixture on dopamine and steroid hormone levels in exposed mice.

In the present study, we investigated the dopaminergic and steroid hormone systems of A/J mice fed environmentally relevant concentrations of a perfluoroalkyl substance (PFAS) mixture over a period of 10 weeks. The PFAS mixture was chosen based on measured PFAS concentrations in earthworms at a Norwegian skiing area (Trondheim) and consisted of eight different PFAS. Dietary exposure to PFAS led to lower total brain dopamine (DA) concentrations in male mice, as compared to control. On the transcript level, brain tyrosine hydroxylase (th) of PFAS exposed males was reduced, compared to the control group. No significant differences were observed on the transcript levels of enzymes responsible for DA metabolism, namely - monoamine oxidase (maoa and maob) and catechol-O methyltransferase (comt). We detected increased transcript level for DA receptor 2 (dr2) in PFAS exposed females, while expression of DA receptor 1 (dr1), DA transporter (dat) and vesicular monoamine transporter (vmat) were not affected by PFAS exposure. Regarding the steroid hormones, plasma and muscle testosterone (T), 11-ketotestosterone (11-KT) and 17ß-estradiol (E2) levels, as well as transcripts for estrogen receptors (esr1 and esr2), gonadotropin releasing hormone (gnrh) and aromatase (cyp19) were unaltered by the PFAS treatment. These results indicate that exposure to PFAS doses, comparable to previous observation in earthworms at a Norwegian skiing area, may alter the dopaminergic system of mice with overt consequences for health, general physiology, cognitive behavior, reproduction and metabolism.

High Levels of Legacy and Emerging Contaminants in Killer Whales (Orcinus orca) from Norway, 2015 to 2017.

Little is known of the movement or presence of unregulated, emerging contaminants in top predators. The aim of the present study was to conduct the first screening of legacy and emerging contaminants in multiple tissues of killer whales (Orcinus orca) from Norway and investigate tissue partitioning and maternal transfer. Blubber was collected from 8 killer whales in 2015 to 2017, in addition to muscle from 5 of the individuals, and kidney, liver, heart, and spleen from a neonate. We screened for 4 unregulated brominated flame retardants and found pentabromotoluene (PBT) and hexabromobenzene (HBB) at low levels in the blubber of all individuals (median PBT 0.091 ng/g lipid wt, median HBB 1.4 ng/g lipid wt). Levels of PBT and HBB (wet wt) were twice as high in the blubber than the muscle for each individual, confirming preferential accumulation in lipid-rich tissues. Perfluoroalkyl substances and total mercury levels were lower in the neonate than adults, suggesting less efficient maternal transfer of these substances. Polychlorinated biphenyl levels in blubber exceeded the threshold for onset of physiological effects (9 µg/g lipid wt) in 7 of the 8 whales, including the neonate. The presence of PBT and HBB in the neonate is the first evidence of maternal transfer of these unregulated contaminants in marine mammals. Our results are relevant for the continued environmental monitoring of contaminants in the Arctic. Environ Toxicol Chem 2021;40:1850-1860. © 2021 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Maternal exposure to a human based mixture of persistent organic pollutants (POPs) affect gene expression related to brain function in mice offspring hippocampus.

Male and female mice pups were exposed to a low and high dose of a human relevant mixture of persistent organic pollutants (POPs) during pregnancy and lactation. Most compounds detected in the dams were found in offspring brains. The mice offspring exhibited changed expression of hippocampal genes involved in cognitive function (Adora2a, Auts2, Crlf1, Chrnb2, Gdnf, Gnal, Kcnh3), neuroinflammation (Cd47, Il1a), circadian rhythm (Per1, Clock), redox signalling (Hmox2) and aryl hydrocarbon receptor activation (Cyp1b1). A few genes were differentially expressed in males versus females. Mostly, similar patterns of gene expression changes were observed between the low and high dose groups. Effects on learning and memory function measured in the Barnes maze (not moving, escape latency) were found in the high dose group when combined with moderate stress exposure (air flow from a fan). Mediation analysis indicated adaptation to the effects of exposure since gene expression compensated for learning disabilities (escape latency, walking distance and time spent not moving in the maze). Additionally, random forest analysis indicated that Kcnh3, Gnal, and Crlf1 were the most important genes for escape latency, while Hip1, Gnal and the low exposure level were the most important explanatory factors for passive behaviour (not moving). Altogether, this study showed transfer of POPs to the offspring brains after maternal exposure, modulating the expression level of genes involved in brain function.

Seasonal rainfall affects occurrence of organohalogen contaminants in tropical marine fishes and prawns from Zanzibar, Tanzania.

Seasonal differences in precipitation may affect contaminant dynamics in tropical coastal regions due to terrestrial runoff of contaminants to the marine environment after the rainy seasons. To assess the effect of seasonal rainfall on occurrence of organohalogen contaminants in a coastal ecosystem, marine fishes and prawns were collected off the coast of Zanzibar, Tanzania in January and August 2018, representing pre- and post-rainy season, respectively. Samples were analyzed for organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), brominated flame retardants (BFRs), including polybrominated diphenyl ethers (PBDEs) and emerging BFRs, as well as the dietary descriptors stable isotopes of carbon (δ13C) and nitrogen (δ15N). Across all species and seasons, mean contaminant concentrations ranged from below limit of detection (LOD) to 129 ng/g lipid weight (lw) ΣPCBs; 5.6-336 ng/g lw ΣOCPs; and < LOD -22.1 ng/g lw ΣPBDEs. Most of the emerging BFRs were below LOD. Contaminant concentrations generally increased with higher pelagic carbon signal (δ13C) and higher relative trophic position (δ15N). The ratio of DDE/ΣDDTs in fishes and prawns was lower in August than in January, suggesting runoff of non-degraded DDT into the marine system during or after the seasonal rainfall. Contaminant patterns of OCPs and PCBs, and concentrations of BFRs, differed between seasons in all species. A higher relative concentration-increase in lower halogenated, more mobile PCB and PBDE congeners, compared to higher halogenated congeners with lower mobility, between January and August aligns with a signal and effect of terrestrial runoff following the rainy season.

Alteration of neuro-dopamine and steroid hormone homeostasis in wild Bank voles in relation to tissue concentrations of PFAS at a Nordic skiing area.

Perfluoroalkyl substances (PFAS) are contaminants that are applied in a wide range of consumer products, including ski products. The present study investigated the neuro-dopamine (DA) and cellular steroid hormone homeostasis of wild Bank voles (Myodes glareolus) from a skiing area in Norway (Trondheim), in relation to tissue concentrations of PFAS. We found a positive association between brain DA concentrations and the concentration of several PFAS, while there was a negative association between PFAS and dopamine receptor 1 (dr1) mRNA. The ratio between DA and its metabolites (3,4-dihydroxyphenylacetic acid: DOPAC and homovanillic acid: HVA) showed a negative association between DOPAC/DA and several PFAS, suggesting that PFAS altered the metabolism of DA via monoamine oxidase (Mao). This assumption is supported by an observed negative association between mao mRNA and PFAS. Previous studies have shown that DA homeostasis can indirectly regulate cellular estrogen (E2) and testosterone (T) biosynthesis. We found no association between DA and steroid hormone levels, while there was a negative association between some PFAS and T concentrations, suggesting that PFAS might affect T through other mechanisms. The results from the current study indicate that PFAS may alter neuro-DA and steroid hormone homeostasis in Bank voles, with potential consequences on reproduction and general health.

Preying on seals pushes killer whales from Norway above pollution effects thresholds.

Killer whales (Orcinus orca) are at risk from high levels of biomagnifying pollutants, such as polychlorinated biphenyls (PCBs) and mercury (Hg). Previous toxicological risk assessments for the Norwegian killer whale population have assumed fish as the primary prey source, and assessed the population as below established effect thresholds. However, some individuals have recently been identified to also feed on seals. This study is the first to quantify levels of pollutants in seal-eating killer whales from northern Norway, and to measure Hg levels in the skin of killer whales worldwide. We found higher levels of all pollutants in seal-eating than fish-eating killer whales, including the emerging brominated flame retardants pentabromoethylbenzene (PBEB), pentabromotoluene (PBT) and hexabromobenzene (HBB). Sum polychlorinated biphenyls (ΣPCBs) in the blubber of seal-eaters (n = 7, geometric mean = 46 µg/g l.w.) were four times higher than fish-eaters (n = 24, geometric mean = 11 µg/g l.w.), which pushed all seal-eating individuals above multiple thresholds for health effects. Total Hg levels in skin of seal-eaters (n = 10, arithmetic mean = 3.7 µg/g d.w.) were twice as high as in fish-eaters (n = 28, arithmetic mean = 1.8 µg/g d.w.). Our results indicate that by feeding on higher trophic prey, the Norwegian killer whale population is at higher risk of health effects from pollution than previously assumed.

Isolation of the Tephrosia vogelii extract and rotenoids and their toxicity in the RTgill-W1 trout cell line and in zebrafish embryos.

This study focused on identifying the rotenoids from the Tephrosia vogelli plant (fish-poison-bean), investigating the toxic potency of a crude T. vogelii extract and individual rotenoids (tephrosin, deguelin and rotenone) in vitro and in vivo and assessing the mode of action. A trout (Onychorynhis mykiss) gill epithelial cell line (RTgill-W1) was used to determine the cytotoxicity of rotenoids and effects on cell metabolism. Zebrafish (Danio rerio) aged from 3 h post fertilization (hpf) to 72 hpf were used for testing the developmental toxicity. The crude T. vogelii plant extract significantly decreased the cellular metabolic activity and was cytotoxic at lower concentrations (5 and 10 nM, respectively), while tephrosin, deguelin and rotenone showed these effects at concentrations ≥ 50 nM. The crude T. Vogelli extract had the highest toxic potency and induced adverse health effects in zebrafish including deformities and mortality at the lowest concentration (5 nM) compared to rotenone (10 nM) and deguelin and tephrosin (50 nM). These results indicate that the crude T. Vogelii extracts are highly potent and the bioactivity of these extracts warrant further investigation for their potential use to treat parasites in human and veterinary medicine and as a natural alternative to pesticides.

Correction: Organic contaminants of emerging concern in Norwegian digestates from biogas production.

Correction for 'Organic contaminants of emerging concern in Norwegian digestates from biogas production' by Aasim M. Ali et al., Environ. Sci.: Processes Impacts, 2019, 21, 1498-1508.

Levels, Patterns, and Biomagnification Potential of Perfluoroalkyl Substances in a Terrestrial Food Chain in a Nordic Skiing Area.

Perfluoroalkyl substances (PFASs) are used in a wide range of consumer products, including ski products, such as ski waxes. However, there is limited knowledge on the release of PFASs from such products into the environment and the resultant uptake in biota and transport in food webs. We investigated levels, patterns, and biomagnification of PFASs in soil, earthworms (Eisenia fetida), and Bank voles (Myodes glareolus) from a skiing area in Trondheim, Norway. In general, there was higher PFAS levels in the skiing area compared to the reference area with no skiing activities. The skiing area was dominated by long-chained perfluorocarboxylic acids (PFCAs, ≥70%), while the reference area was dominated by short-chained PFCAs (>60%). The soil PFAS pattern in the skiing area was comparable to analyzed ski waxes, indicating that ski products are important sources of PFASs in the skiing area. A biomagnification factor (BMF) > 1 was detected for Bank volewhole/earthwormwhole for perfluorooctansulfonate in the skiing area. All other PFASs showed a BMF < 1. However, it should be noted that these organisms represent the base of the terrestrial food web, and PFASs originating from ski wax may result to higher exposure in organisms at the top of the food chain.

Organic contaminants of emerging concern in Norwegian digestates from biogas production.

The aim of this study was to analyze a variety of environmental organic contaminants of emerging concern (CEC) and their metabolites in representative digestate samples from Norwegian biogas production plants. Biogas digestates can be a valuable source for soil amendments and/or fertilizers in commercial agriculture. It is important to assess whether the digestates contain harmful contaminants in order to avoid unintended exposure of human consumers. In total 19 biogas digestates from 12 biogas production plants in Norway were collected and analyzed. Furthermore, process related parameters such as pretreatment of substrates, additives, flocculation and temperature conditions were considered for interpretation of the results. The CEC levels found in the digestates were shown to be dependent on the original composition of the substrate, dry-matter content, and conditioning of the substrate. The sunscreen octocrylene (147 µg L-1) and acetaminophen (paracetamol; 58.6 µg L-1) were found at the highest concentrations in liquid digestates, whereas octocrylene (>600 ng g-1, on a wet weight basis = ww) and the flame retardant TCPP (tris(1-chloro-2-propyl) phosphate, >500 ng g-1 ww) were found at the highest levels in solid digestates, exceeding even the upper limit of quantification (uLOQ) threshold. The highest levels of total CECs were measured in solid digestates (1411 ng g-1 ww) compared to liquid digestates (354 µg L-1 equals 354 ng g-1). The occurrence of CECs in digestate samples, even after extensive and optimized anaerobic digestion, indicates that the operational conditions of the treatment process should be adjusted in order to minimize CEC contamination.

Decreased plasma levels of perfluoroalkylated substances one year after bariatric surgery.

Per- and polyfluoroalkylated substances (PFASs) are classified as persistent organic pollutants (POPs), and known to be protein bound. The aim of the present study was to determine the levels of 17 different PFASs before and one year after bariatric surgery, and to assess whether weight loss and changed serum protein concentrations could be influencing factors. Plasma samples from 63 patients were analyzed for nine perfluoroalkyl carboxylic acids (PFCAs), three perfluoroalkane sulfonic acids (PFSAs), and five perfluoroalkyl sulfonamide based substances (PASF) before and after surgery. Protein determination was performed in the corresponding serum samples. Mean weight loss one year after surgery was 32.1 kg. The plasma levels of all PFASs decreased with 4-34% compared to preoperative values, and included perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), and perfluorobutane sulfonate (PFBS), which have been identified with increasing levels in the general population during recent years. Serum protein concentrations also decreased with 7-8%. Although protein levels were positively correlated with PFOA, PFBS, PFHxS and PFOS, regression analysis revealed that neither weight loss nor reductions in concentrations of serum protein could explain the decreased PFAS levels. The type of surgical procedure did not influence the changes of PFAS levels between the two sample points. A reduced food intake and alterations in absorptions of nutrients after bariatric surgery may have influenced the observed decreasing plasma levels of PFASs.

Increased levels of persistent organic pollutants in serum one year after a great weight loss in humans: Are the levels exceeding health based guideline values?

BACKGROUND: With the growing prevalence of obesity, an increased number of bariatric surgeries are being performed. Lipophilic persistent organic pollutants (POPs) are stored in adipose tissue, and an increased release of lipophilic POPs into the blood circulation may occur following rapid weight loss such as after bariatric surgery. OBJECTIVES: To evaluate and compare POP levels in serum before and after bariatric surgery, and to assess if the POP levels exceeded health based guideline values, with particular focus on women of childbearing age (WCBA). METHODS: Serum samples from 63 patients before and one year after bariatric surgery were analysed for organochlorine pesticides (OCPs); polychlorinated biphenyls (PCBs); and brominated flame retardants (BFRs). RESULTS: Mean weight loss one year after surgery was 32.1kg. The levels of all the analysed POPs in serum increased during the study period. Median levels of dichlorodiphenyldichloroethylene (p,p'-DDE), hexachlorobenzen (HCB) and PCB-153 increased from 90.2ng/g lipid weight (lw) to 158.5ng/glw, from 21.1ng/glw to 36.4ng/glw and from 48.7ng/glw to 71.5ng/glw, respectively. The highest percentage increase was observed for PCB -138, with 83.1%. BFRs were detected in low sample numbers and at low levels. Guideline values for ΣPCB6 in serum were exceeded for 5% of the participants. CONCLUSIONS: Weight loss after bariatric surgery resulted in increases of POPs levels in serum between 46.7%-83.1%. Guideline values for ΣPCB6 in serum were exceeded for 5% of the participants. For WCBA, the possible transfer of comparable levels to infants warrants further attention.

Gamma irradiation during gametogenesis in young adult zebrafish causes persistent genotoxicity and adverse reproductive effects.

The biological effects of gamma radiation may exert damage beyond that of the individual through its deleterious effects on reproductive function. Impaired reproductive performance can result in reduced population size over consecutive generations. In a continued effort to investigate reproductive and heritable effects of ionizing radiation, we recently demonstrated adverse effects and genomic instability in progeny of parents exposed to gamma radiation. In the present study, genotoxicity and effects on the reproduction following subchronic exposure during a gametogenesis cycle to 60Co gamma radiation (27 days, 8.7 and 53 mGy/h, total doses 5.2 and 31 Gy) were investigated in the adult wild-type zebrafish (Danio rerio). A significant reduction in embryo production was observed one month after exposure in the 53 mGy/h exposure group compared to control and 8.7 mGy/h. One year later, embryo production was significantly lower in the 53 mGy/h group compared only to control, with observed sterility, accompanied by a regression of reproductive organs in 100% of the fish 1.5 years after exposure. Histopathological examinations revealed no significant changes in the testis in the 8.7 mGy/h group, while in 62.5% of females exposed to this dose rate the oogenesis was found to be only at the early previtellogenic stage. The DNA damage determined in whole blood, 1.5 years after irradiation, using a high throughput Comet assay, was significantly higher in the exposed groups (1.2 and 3-fold increase in 8.7 and 53 mGy/h females respectively; 3-fold and 2-fold increase in 8.7 and 53 mGy/h males respectively) compared to controls. A significantly higher number of micronuclei (4-5%) was found in erythrocytes of both the 8.7 and 53 mGy/h fish compared to controls. This study shows that gamma radiation at a dose rate of ≥ 8.7 mGy/h during gametogenesis causes adverse reproductive effects and persistent genotoxicity (DNA damage and increased micronuclei) in adult zebrafish.

Parental gamma irradiation induces reprotoxic effects accompanied by genomic instability in zebrafish (Danio rerio) embryos.

Gamma radiation represents a potential health risk to aquatic and terrestrial biota, due to its ability to ionize atoms and molecules in living tissues. The effects of exposure to 60Co gamma radiation in zebrafish (Danio rerio) were studied during two sensitive life stages: gametogenesis (F0: 53 and 8.7mGy/h for 27 days, total doses 31 and 5.2Gy) and embryogenesis (9.6mGy/h for 65h; total dose 0.62Gy). Progeny of F0 exposed to 53mGy/h showed 100% mortality occurring at the gastrulation stage corresponding to 8h post fertilization (hpf). Control and F0 fish exposed to 8.7mGy/h were used to create four lines in the first filial generation (F1): control, G line (irradiated during parental gametogenesis), E line (irradiated during embryogenesis) and GE line (irradiated during parental gametogenesis and embryogenesis). A statistically significant cumulative mortality of GE larva (9.3%) compared to controls was found at 96 hpf. E line embryos hatched significantly earlier compared to controls, G and GE (48-72 hpf). The deformity frequency was higher in G and GE, but not E line compared to controls at 72 hpf. One month after parental irradiation, the formation of reactive oxygen species (ROS) was increased in the G line, but did not significantly differ from controls one year after parental irradiation, while at the same time point it was significantly increased in the directly exposed E and GE lines from 60 to 120 hpf. Lipid peroxidation (LPO) was significantly increased in the G line one year after parental irradiation, while significant increase in DNA damage was detected in both the G and GE compared to controls and E line at 72 hpf. Radiation-induced bystander effects, triggered by culture media from tissue explants and observed as influx of Ca2+ ions through the cellular membrane of the reporter cells, were significantly increased in 72 hpf G line progeny one month after irradiation of the parents. One year after parental irradiation, the bystander effects were increased in the E line compared to controls, but not in progeny of irradiated parents (G and GE lines). Overall, this study showed that irradiation of parents can result in multigenerational oxidative stress and genomic instability in irradiated (GE) and non-irradiated (G) progeny of irradiated parents, including increases in ROS formation, LPO, DNA damage and bystander effects. The results therefore highlight the necessity for multi- and transgenerational studies to assess the environmental impact of gamma radiation.

Increased blood levels of persistent organic pollutants (POP) in obese individuals after weight loss-A review.

Lipophilic persistent organic pollutants (POP) are stored in adipose tissue. Following rapid weight loss such as when induced by bariatric surgery, an increased release of potential harmful lipophilic compounds into the blood circulation may occur. Weight reduction is recommended for overweight and obese individuals in order to decrease risk of weight-related health problems. However, in cases of significant weight reduction POP become mobilized chemicals and consequently may adversely affect health, including endocrine disruption. The objective of the present investigation was to estimate quantitatively the level of mobilization of POP following weight loss over time. According to literature search criteria, 17 studies were identified with 2061 participants. Data from 5 of the studies with 270 participants were used to assess the change in blood levels of POP in percent per kilogram weight loss. Weight loss in the included studies varied from 4.4 to 64.8 kg. In all studies, the majority of POP concentrations in blood were found to rise following weight reduction. Blood concentrations following weight reduction were elevated by 2-4% per kilogram weight loss for most POP examined. The increased POP levels were still elevated 12 mo after intervention. Most research in this field, including animal studies, is carried out on a single compound or group of selected compounds, not taking the "cocktail effect" into consideration. This does not reflect the true range of POP to which humans are actually exposed. Few chronic investigations have been published and, in particular, few studies were available that compared the increase in POP concentrations with clinical consequences as individuals lost weight. These limitations call for caution in interpreting results. The benefits of losing weight still far outweigh the potential adverse health risks. However, further studies are recommended to determine the clinical significance of increased blood levels of POPs following rapid and excessive weight loss, particularly for women attending weight reduction treatment before pregnancy.

Endocrine effects of real-life mixtures of persistent organic pollutants (POP) in experimental models and wild fish.

A series of studies have assessed the occurrence, levels, and potential adverse effects of persistent organic pollutants (POP) in fish from Lake Mjøsa. In this lake, high levels of various POP were detected in biota. Fish from the nearby Lake Losna contain background levels of POP and served as reference (controls) in these studies. Significantly higher prevalence of mycobacteriosis and pathological changes were documented in burbot (Lota lota) from Mjøsa compared to burbot from Losna. Further, transcriptional profiling identified changes in gene expression in burbot from Mjøsa compared to burbot from Losna associated with drug metabolism enzymes and oxidative stress. POP extracted from burbot liver oil from the two lakes was used to expose zebrafish (Danio rerio) during two consecutive generations. During both generations, POP mixtures from both lakes increased the rate of mortality, induced earlier onset of puberty, and skewed sex ratio toward males. However, opposite effects on weight gain were found in exposure groups compared to controls during the two generations. Exposure to POP from both lakes was associated with suppression of ovarian follicle development. Analyses of genome-wide transcription profiling identified functional networks of genes associated with weight homeostasis, steroid hormone functions, and insulin signaling. In human cell studies using adrenocortical H295R and primary porcine theca and granulosa cells, exposure to lake extracts from both populations modulated steroid hormone production with significant difference from controls. The results suggest that POP from both lakes may possess the potential to induce endocrine disruption and may adversely affect health in wild fish.