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Farms utilizing sewage sludge and manure in their agronomic plant production are recognized as potential hotspots for environmental release of antibiotics and the resulting promotion of antibiotic resistance. As part of the circular economy, the use of biogas digestates for soil fertilizing is steadily increasing, but their potential contribution to the spreading of pharmaceutical residues is largely unknown. Digestates can be produced from a variety of biowaste resources, including sewage sludge, manure, food waste, and fish ensilage. We developed a method for the detection of 17 antibiotics and 2 steroid hormones and applied the method to detect pharmaceutical residues in digestates from most municipal biogas plants in Norway, covering a variety of feedstocks. The detection frequency and measured levels were overall low for most compounds, except a few incidents which cause concern. Specifically, relatively high levels of amoxicillin, penicillin G, ciprofloxacin, and prednisolone were detected in different digestates. Further, ipronidazole was detected in four digestates, although no commercial pharmaceutical products containing ipronidazole are currently registered in Norway. A simplified risk assessment showed a high risk for soil microorganisms and indicates the tendency for antibiotic-resistant bacteria for penicillin G and amoxicillin. For prednisolone and ipronidazole; however, no toxicity data is available for reliable risk assessments. Graphical abstract

Gulløyelarver (green lacewing larvae, Chrysoperla carnea) is a product for biological control. The application is for use against aphids in green-houses and tunnels. Gulløyelarver was used in Norway from 1985-1993. An assessment in 2001 concluded however that the use of products with Chrysoperla carnea could represent an environmental risk since it was not known if the species in the products were the same as the ones with natural occurrence in Scandinavia. In this regard, The Norwegian Food Safety Authority would like VKM to perform an assessment of possible risks related to health and environment in light of possible new data. VKM’s conclusions are as follows: Health: The larvae of Chrysoperla carnea have hollow jaws through which they can inject digestive enzymes into their prey. In contact with humans, the larvae are capable of delivering painful bites which may cause local swelling. Such bites are however not considered dangerous, and can be avoided with preventive measures. Allergic asthma and rhino conjunctivitis has been reported in persons working in the production of biological agents with Chrysoperla carnea, but it is the opinion of VKM that such effects are not likely to be relevant for users of the agents. Environment: A previous assessment in 2001 concluded that the use of products with Chrysoperla carnea represented an environmental risk because of the risk of genetic interference with natural populations of the species in Norway. Lacewings belonging to the Chrysoperla carnea complex are considered established and indigenous in Norway, and a recent study by the Norwegian Institute for Agricultural and Environmental Research (Bioforsk) strongly suggests that the lacewings in the commercial products belong to the same cryptic species complex as individuals sampled in Norway. In case the species in the products is different from those present in Norway, any genetic interference with local populations in Norway is prevented by differences in duetting songs. If an invertebrate biological control agent is indigenous and has limited direct or indirect effect on the environment, it is the opinion of VKM that it could be authorized for release in greenhouses or plastic tunnels. Chrysoperla carnea is polyphagous and cannibalistic. They prefer aphids, but may also consume other insects and mites. It is however the opinion of VKM that the environmental risk from this will be minimized in greenhouses and tunnels where the release will be in a contained environment and directed against aphid colonies. Establishment, host range and dispersal ability should be carefully reviewed, even if the species is indigenous. Chrysoperla carnea may establish in the greenhouse and plastic tunnels and may also possess the ability to disperse and survive in the field. However, it is the opinion of VKM that the direct and indirect effects of this are at most moderate, although it cannot be completely excluded that Chrysoperla carnea species in the products might also have properties that have not been reviewed.

Proman is a broad spectrum selective herbicide for potatoes grown outdoors, containing the active substance metobromuron. VKM’s Panel on Plant Protection Products has previously discussed questions concerning Proman raised by The Norwegian Food Safety Authority, and stated its opinion in a report of 21. January 2015 (http://www.vkm.no/dav/3c64afe035.pdf). Following this report, The Norwegian Food Safety Authority turned down the application to register Proman as a plant protection product in Norway. The applicant filed a complaint on this decision, and the VKM Panel has been asked to reassess its previous opinion in light of the information given by the applicant in the complaint. The VKM Panel has discussed the arguments put forward in the complaint. The arguments did not change the Panel’s main conclusions in the original assessment. Some changes in the wording of the conclusions were however done, in order to put more emphasis on areas of uncertainty. These are the standing conclusions of VKM’s Panel on Plant Protection Products: On the relevance of the carcinogenic effects observed in the rat carcinogenicity study; fibrosarcomas in females and pheochromocytomas and Leydig cell tumours in males: It is the opinion of VKM’s Panel for Plant Protection Products that the relevance of the observed incidences of mammary gland tumours and Leydig cell tumours in the rat carcinogenicity study is strengthened by the fact that the increases in tumours associated with exposure to metobromuron are observed in hormone responsive tissues. The panel concludes that the carcinogenic effects observed in the rat carcinogenicity study could be relevant for tumour induction in humans. Higher incidences of still dumbbell-shaped centres of thoracic vertebrae and nonossification of the 13th rib observed in the rat developmental toxicity study and whether these are considered to be malformations: VKM’s Panel on Plant Protection Products has discussed the classification of the different types of incomplete ossifications and concluded that incomplete ossification of sternebrae and non-ossification of the 13th rib in rats should by itself be considered to be variations, and not adverse developmental effects. On the other hand, the Panel agrees with ECHA that the “thoracic vertebral centres still dumbbell-shaped” should be considered as malformations, due to limited data and understanding of the mechanism underlying the observed slow reversal of these anomalies. Furthermore, it is the view of the Panel that the different types of retarded ossification induced by the exposure should be considered as a whole when assessing for developmental effects. Establishment of the NOAEL for the developmental toxicity study in rats and the reference value (ARfD): VKM’s Panel on Plant Protection Products supports the proposal of an ADI value of 0.008 mg/kg bw/day based on a NOAEL of 0.8 mg/kg bw/day from the 2-year study in mouse, and AOEL of 0.016 mg/kg bw/day based on the NOAEL of 1.6 mg/kg bw/day from the 1-year feeding study in dog. The panel suggests an alternative ARfD value of 0.03 mg/kg bw based on a LOAEL of 10 mg/kg bw /day for the observations of incomplete ossification in the rat developmental study. The anti-androgenic potential of metobromuron: The rat carcinogenicity study indicates that metobromuron may interact with the endocrine system. The data from the Hershberger in vivo rat study, the in vitro studies, as well as the comparison with demonstrated effects and mechanisms for flutamide and linuron is suggestive of an anti-androgenic effect. Thus, it is the opinion of the VKM Panel on Plant Protection Products that an anti-androgenic effect of metobromuron cannot be excluded.

The aim of this study was to assess the levels of heavy metals in both wild and farmed tilapia on Lake Kariba in Zambia and to evaluate the impact of intensive fish farming on wild tilapia. Three sites for wild fish (2 distant and 1 proximal to fish farms) and two fish farms were selected. One hundred fish (52 from distant sites; 20 near fish farms; 28 farmed fish) were sampled and muscle tissues excised for analysis of heavy metals (Mg, Fe, Zn, Al, Cu, Se, Co, Mo, As, Cr, V, Ni, Hg, Pb, Li, Cd, and Ag) by acid (HNO3) digestion and ICP-MS. All metals were found to be below the maximum limits (MLs) set by WHO/EU. Essential metals were higher in farmed tilapia, whereas non-essential metals were higher in wild tilapia. Significantly higher levels of essential metals were found in wild fish near the fish farms than those distant from the farms. Estimated weekly intake (EWI) for all metals were less than the provisional tolerable weekly intakes (PTWI). Target hazard quotients (THQ) and Hazard Indices (HI) were

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.

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.

Soil samples randomly taken from major e-waste sites in West Africa (Nigeria, Benin and Ghana) were examined for an extensive range of organic contaminants. Cytotoxicity measurements and assessment of activation of xeno-sensing receptors from fish (Atlantic cod) were employed as a battery of in vitro biological assays to explore the quality and toxicity profile of West African e-waste soil. The concentrations of the measured contaminants of emerging concerns (CECs) and persistent organic pollutants (POPs) in the e-waste soil differs significantly from the reference soil with chemical profiles typically dominated by legacy polybrominated diphenyl ethers (PBDEs) (405.8 μgkg

Nemasys G and Nemasys H with the nematode Heterorhabditis bacteriophora as the active organism is applied for as a plant protection product in Norway. Nemasys G is intended for use against the garden chafer (Phyllopertha horticola) in lawns and Nemasys H against black vine weevil (Otiorhynchus sulcatus) in strawberries and ornamentals. VKM was requested by the Norwegian Food Safety Authority to consider the possible health and environmental risk related to the properties of Nemasys G and Nemasys H; in particular to evaluate if the nematode is naturally occurring in Norway, the potential for establishing and spreading under Norwegian conditions, possible taxonomic challenges and assessment of the health risk related to its use. The assessment was finalized in October 2014 by VKM’s Panel on Plant Protection Products. VKM’s conclusions are as follows: Natural occurrence of the nematode: The nematode Heterorhabditis bacteriophora has not been observed in Norway, but is widespread world-wide in regions with continental and Mediterranean climates. In Europe it has been isolated in France, Germany, Hungary, Italy, Moldavia, Spain, Switzerland and the UK. Potential for establishing and spreading of the nematode under Norwegian conditions: The thermal preference of H. bacteriophora restricts its establishing. Short term establishment in the growing season is possible in parts of Norway. This nematode has however poor long term survival in soil, especially in the absence of suitable hosts, and the potential for long term establishment in Norway is considered to be low. Taxonomic challenges: There are no taxonomic challenges related to assessment of this nematode. Human health risk for operators: Exposure of user is considered to be low. The use of plant protection products containing Heterorhabditid nematodes against insects has not been associated with health effects on humans. The symbiotic bacteria Photorhabdus luminescens has not been linked to pathogenic effects in humans. It is therefore the view of VKM that the use of the nematode Heterorhabditis bacteriophora with the symbiotic bacteria Photorhabdus luminescens will have minimal health risk for operators.

In 2006 the, the Panel on Nutrition, Dietetic Products, Novel Food and Allergy in the Norwegian Scientific Committee for Food Safety (VKM) adapted a Danish model for assessing applications concerning food fortification into Norwegian conditions. The fortification model is presently used by the Norwegian Food Safety Authorities as a tool in the management of applications on food fortification. The model from 2006 was based on intake calculations from dietary surveys from 1997-2000. Since then, new national dietary surveys have been published. These are the comprehensive nationwide Norwegian dietary surveys among adults (Norkost 3, 2010-2011), among young children (Småbarnskost, 2007) and infants (Spedkost, 2006-2007). The Norwegian Food Safety Authority has requested VKM to implement the new data into the fortification model from 2006. In the model from 2006 it is assumed that 25% of the energy in the diet can be derived from fortified foods and drinks. Information from the Norwegian Food Safety Authority, including about a pilot study for Norkost 3 suggested that the overall intake of fortified foods and drinks was marginal. From management of applications for fortified foods, the Norwegian Food Safety Authority also experienced that there are few fortified foods on the market in Norway. The Norwegian Food Safety Authority has therefore requested VKM to evaluate whether the assumption that 25 energy percent (E%) deriving from fortified foods can be reduced to 15 E%, and if such a reduction will have health implications. In addition, the Norwegian Food Safety Authority has asked VKM to perform an evaluation of the safety factors in the model. VKM argues that the model for fortification should be based on the dietary intake of vitamins and minerals at the 95th percentile level in various age groups. This is in accordance with risk assessments performed in European Food Safety Authority (EFSA), and will assure that the dietary intake in a majority of the population will be covered, still within a reasonable secure use of dietary exposure calculations. Mean intake of vitamins and minerals from food supplements (among users only) was chosen, in an attempt to reduce the impact of those with a high intake of supplements. The intake at 95th percentile from the diet plus the mean nutrient intake from supplements is deducted from the tolerable upper intake level (UL) for each nutrient in each age group, giving the maximum amount of nutrients that can be “allocated” for food fortification. The maximum amount of a nutrient that can be “allocated” is then distributed over the energy intake at the 95th percentile level. In this manner an estimate is made showing which age group is most likely to have an excessive intake of a certain nutrient. VKM does not have access to any other information about available fortified foods on the Norwegian market than the information given by the Norwegian Food Safety Authority. However, based on this information, VKM considers that it seems reasonable that the energy intake from fortified foods is reduced to 15 E%. In this revised fortification model the assumption from 2006 that 25 E% of the total energy intake will be derived from fortified foods, have therefore been reduced to 15 E%. This adjustment implies that the addition of e.g. vitamin D, vitamin E, thiamine, riboflavin, niacin, folic acid, vitamin B12, vitamin C and calcium per 100 kcal can be increased without risk of exceeding UL. No changes are made for e.g. vitamin A, beta-carotene, magnesium, iron, zinc or copper. A more summary is presented in Table 1 and Appendix 1. The Panel on nutrition, dietetic products, novel food and allergy considers that this model for management of fortification will reduce health risk that could be caused by unauthorised food fortification.

The Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM) has at the request of the Norwegian Food Safety Authority (Mattilsynet) conducted an assessment of creatine in sports products (e.g. supplements). The evaluation has been performed by an ad hoc group, and assessed by the VKM Panel on nutrition, dietetic products, novel food and allergy. The evaluation of safety and possible risks of creatine supplementation in this opinion is based on previous reports, 23 original papers and 14 reviews from literature searches. Marketing and sales of sport products are increasing in the Nordic countries, with creatine supplements being one of four most common categories. In addition to be used by athletes, the use of creatine supplements seems to increase among general exercisers and young people. Creatine supplements are mainly used for their supposed effects on muscles mass and high intensity and short duration sport performances. Supplementation has been shown to result in higher concentration of creatine phosphate in the muscles, which is the limited substrate. For athletes, it is recommended a loading dose of 10-20 g/day for 4-7 days and a maintenance dose of 2-5 g/day for weeks or months. Some athletes continue the maintenance dose for several years. It is well documented that creatine supplementation has positive effects on muscle mass combined with strength training and performance during maximal exercise. There are however large individual variation in the response, and there are responders and non-responders. The new scientific literature, including long term studies, is in line with the EFSA (European Food Safety Authority) opinion from 2004. VKM Panel on nutrition, dietetic products, novel food and allergy supports the EFSA conclusion that supplementation of creatine in doses below 3 g/day is unlikely to pose any risks if the purity of the creatine compound is adequate. Scientific long-term studies with doses up to 5-10 g/day in adult athletes have shown no harmful effects, but there are no dose-response studies indicating a safe upper limit for creatine. The potential negative effects (impaired kidney function, weight gain and gastrointestinal disturbances) which have been published in non scientific journals and anecdotal reports have not found support in controlled systematic studies on healthy subjects. It has been indicated that individuals with impaired kidney functions should refrain from creatine supplements. Creatine-monohydrate is the most studied form of creatine supplements, and only creatine monohydrate has been included in the scientific investigations on adverse effects.

The Norwegian Scientific Committee for Food Safety (VKM) has appointed an ad hoc-group of experts to answer a request from the Norwegian Food Safety Authority regarding benefit and risk assessment of Lactobacillus paracasei ssp. paracasei F19 (F19) in processed cerealbased baby foods intended for small children 1-3 years. This assessment is based on the literature provided by the notifier as well as that found by a MEDLINE search. A notification regarding two products of processed cereal-based baby foods (hereafter called cereals), intended for small children and supplemented with the bacterium F19 initiated this work. A daily supply of a monoculture of a particular bacterial strain in large quantities to an age group without a fully established intestinal flora, may have unknown adverse effects. There are however, to our knowledge, no studies investigating possible short or long term adverse health effects of F19 in processed cereal-based baby food given to children 13 months onwards. The documentation and information provided by the notifier regarding the genetic stability of F19 in the two products during processing and storage, is considered insufficient and does not allow any conclusions to be drawn. Moreover, the documentation obtained is not conclusive regarding the antibiotic resistance pattern of the bacterial strain used in the products in question, as the information on different antibiotics is partly inconsistent. The information about specific localization (chromosomal, plasmid) of the resistance genes is not sufficient. Studies demonstrate that F19, as well as other bacterial strains considered probiotic, is able to “crosstalk” with enterocytes in mice and that the result of the “crosstalk” depends upon the microbiota present. Whether F19 has a similar “crosstalk-profile” in humans is unknown. However, as the strain is originally of human origin, it seems reasonable to assume that such “crosstalk” may occur. Thus, before giving F19 daily for months and years, it seems reasonable to ask for additional molecular and physiological studies to unravel the functional impact of possible changes in genetic expression in children. Lactobacillus infections do occasionally occur, mainly as bacteremia, endocarditis and localized infections (e.g. abscesses, peritonitis, and meningitis) in patients with severe underlying diseases. Most of them are elderly, but children are not excluded. The species most often isolated are L. casei and L. rhamnosus, followed by L. paracasei. The increasing use of immunosuppressive therapy and broad spectrum antibiotics which are ineffective against Lactobacillus, might increase the importance of these bacteria as possible pathogens. In order to be able to draw any conclusions regarding beneficial effects of F19, there is a need for randomized placebo-controlled studies in larger populations and in the relevant age group. According to EFSA, Lactobacillus paracasei ssp. paracasei F19 is sufficiently characterized. The documentation provided is, however, not sufficient to claim positive health effects and thus F19 is not proven to be probiotic. There are no published dose-response studies of F19 in children, neither regarding survival of F19 in the gastrointestinal tract, nor possible negative health effects. Thus the potential for negative health effects as e.g. spreading of antimicrobial resistance or unfavourable impact on the genetic expression in children related to the frequency and/or dose of a monoculture of F19 cannot be assessed.

Very low birth weight infants (VLBW, birth weight (BW) < 1500 g) are exposed to phthalates, parabens and bisphenol A (BPA) early in life. We estimated daily intake (EDI) of these excipients in 40 VLBW infants the first and fifth week of life while hospitalised. Based on urinary samples collected in 2010, EDI was calculated and compared to the tolerable daily intake (TDI) with hazard quotients (HQs) evaluated. A HQ > 1 indicates that EDI exceeded TDI with increased risk of adverse health effects. EDI was higher in VLBW infants compared to term-born infants and older children. VLBW infants born at earlier gestational age (GA), or with lower BW, had higher EDI than infants born at later GA or with higher BW. First week median EDI for BPA was higher than TDI in 100% of infants, in 75% for di(2-ethylhexyl) phthalate (DEHP), 90% for the sum of butyl benzyl phthalate (BBzP), di-n-butyl phthalate (DnBP), DEHP and di-iso-nonyl phthalate (DiNP) = ∑BBzP+DnBP+DEHP+DiNP, and in 50% of infants for propylparaben (PrPa), indicating increased risk of adverse effects. Fifth week EDI remained higher than TDI in all infants for BPA, in 75% for DEHP and ∑BBzP+DnBP+DEHP+DiNP, and 25% of infants for PrPa, indicating prolonged risk. Maximum EDI for di-iso-butyl phthalate was higher than TDI suggesting risk of adverse effects at maximum exposure. VLBW infants born earlier than 28 weeks GA had higher EDI, above TDI, for PrPa compared to infants born later than 28 weeks GA. Infants with late-onset septicaemia (LOS) had higher EDI for DEHP, ∑BBzP+DnBP+DEHP+DiNP and BPA, above TDI, compared to infants without LOS. More 75% of the infants' EDI for DEHP and ∑BBzP+DnBP+DEHP+DiNP, 25% for PrPa, and 100% of infants' EDI for BPA, were above TDI resulting in HQs 1, indicating increased risk of adverse health effects.

The aim of this study was to assess the levels of heavy metals in both wild and farmed tilapia on Lake Kariba in Zambia and to evaluate the impact of intensive fish farming on wild tilapia. Three sites for wild fish (2 distant and 1 proximal to fish farms) and two fish farms were selected. One hundred fish (52 from distant sites; 20 near fish farms; 28 farmed fish) were sampled and muscle tissues excised for analysis of heavy metals (Mg, Fe, Zn, Al, Cu, Se, Co, Mo, As, Cr, V, Ni, Hg, Pb, Li, Cd, and Ag) by acid (HNO

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 17β-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.

Persistent organic pollutants (POPs) including organochlorine pesticides, polychlorinated biphenyls (PCBs), and per- and polyfluoroalkylated substances (PFASs) are suspected endocrine disruptors. To evaluate the associations between POPs and thyroidal, reproductive, and adrenal hormones in a study population treated with bariatric surgery. Blood samples from a cohort of 63 participants before and 1 year after bariatric surgery were analyzed for 16 lipophilic POPs, 17 PFASs, and thyroidal, reproductive, and adrenal hormones. Participants reporting relevant medical conditions or interfering medication were excluded, and plausible confounders were corrected for in multiple regression analyses. Free thyroxine (fT4) showed a significant decrease from preoperative to postoperative follow-up, and regression analyses demonstrated that p,p'-dichlorodiphenyldichloroethylene (p,p-DDE) was inversely associated with the ratio free triiodothyronine/free thyroxine (fT3/fT4). Testosterone concentrations in male participants increased significantly in the study period, and sex hormone-binding globulin (SHBG) increased in both gender. Regression analyses showed positive associations between increased levels of lipophilic POPs and the raised postoperative testosterone and SHBG concentrations in males. For females, an inverse association between the sum perfluoroalkyl carboxylic acids (ΣPFCA) and SHBG was seen. Regression analyses of postoperative serum cortisol concentrations on changes in hexachlorobenzene (HCB) showed a non-significant inverse association. The results suggest that POPs may have an influence on the hypothalamic-pituitary-thyroid (HPT) and the hypothalamic-pituitary-gonadal (HPG) axes after bariatric surgery. Because of small sample sizes and discrepancy in the sampling time points pre- and postoperatively, the observed hormonal impacts of POPs must be interpreted as associative and not causative. Further studies are needed to confirm the findings.

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.

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 (δ 13C) and nitrogen (δ 15N). 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 (δ 13C) and higher relative trophic position (δ 15N). 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.

Very low birth weight infants (VLBW; birth weight < 1500 g) are treated with pharmaceuticals and medical equipment containing parabens and bisphenol A (BPA). Parabens are used in pharmaceuticals, whereas BPA in medical equipment where concentrations are rarely reported in hospitalised VLBW infants. We measured urinary concentrations of parabens and BPA and hypothesised high and increasing concentrations in infants born at lower gestational ages (GAs), and among infants with bronchopulmonary dysplasia (BPD) and late-onset septicaemia (LOS) due to higher exposure from pharmaceuticals and medical equipment. Urinary samples were collected during the first (n = 38) and fifth (n = 36) week of life. Methylparaben, ethylparaben, propylparaben, butylparaben, and BPA concentrations were measured using ultra high-performance liquid chromatography coupled to tandem mass spectrometry. VLBW infants had very high urinary concentrations of parabens and BPA compared to term infants and older children. The Σ paraben concentration was higher than detected in previous studies on premature infants. Lower GA at birth was associated with higher concentrations of parabens and BPA. Infants born before 28 weeks GA had higher first week concentrations of propylparaben (38.6 vs. 9.05 ng/mL, p = 0.007), butylparaben (0.28 vs. 0.09 ng/mL, p = 0.05) and fifth week concentrations of BPA (15.1 vs. 6.02 ng/mL, p = 0.02) than infants born after 28 weeks GA. Infants with LOS and BPD had higher fifth week concentrations of BPA than infants without LOS and BPD (LOS: 14.2 vs. 6.77 ng/mL, p = 0.07; BPD: 18.6 vs. 7.62 ng/mL, p = 0.05).

Persistent organic pollutants (POPs) can reach the fetal brain and contribute to developmental neurotoxicity. To explore the distribution of POPs to the fetal brain, we exposed chicken embryos to a POP mixture, containing 29 different compounds with concentrations based on blood levels measured in the Scandinavian human population. The mixture was injected into the allantois at embryonic day 13 (E13), aiming at a theoretical concentration of 10 times human blood levels. POPs concentrations in the brain were measured at 0.5, 1, 2, 4, 6, 24, 48, and 72 h after administration. Twenty-seven of the individual compounds were detected during at least one of the time-points analyzed. Generally, the concentrations of most of the measured compounds were within the order of magnitude of those reported in human brain samples. Differences in the speed of distribution to the brain were observed between the per- and polyfluoroalkyl substances (PFASs), which have protein binding potential, and the lipophilic polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs) and brominated flame retardants (BFRs). Based on pharmacokinetic modeling, PFASs were best described by a one compartment model. PFASs displayed relatively slow elimination (Kel) and persisted at high levels in the brain. Lipophilic OCPs and PCBs could be fitted to a 2-compartment model. These showed high levels in the brain relative to the dose administrated as calculated by area under the curve (AUC)/Dose. Altogether, our study showed that chicken is a relevant model to explore the distribution of POPs into the developing brain at concentrations which are relevant for humans.

The ability of persistent organic pollutants (POPs) with endocrine disrupting properties to interfere with the developing reproductive system is of increasing concern. POPs are transferred from dams to offspring and the high sensitivity of neonates to endocrine disturbances may be caused by underdeveloped systems of metabolism and excretion. The present study aimed to characterize the effect of in utero and lactational exposure to a human relevant mixture of POPs on the female mammary gland, ovarian folliculogenesis and liver function in CD-1 offspring mice. Dams were exposed to the mixture through the diet at Control, Low or High doses (representing 0x, 5000x and 100 000x human estimated daily intake levels, respectively) from weaning and throughout mating, gestation, and lactation. Perinatally exposed female offspring exhibited altered mammary gland development and a suppressed ovarian follicle maturation. Increased hepatic cytochrome P450 enzymatic activities indirectly indicated activation of nuclear receptors and potential generation of reactive products. Hepatocellular hypertrophy was observed from weaning until 30 weeks of age and could potentially lead to hepatotoxicity. Further studies should investigate the effects of human relevant mixtures of POPs on several hormones combined with female reproductive ability and liver function.

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.

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.

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

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 32.1 kg. 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 90.2 ng/g lipid weight (lw) to 158.5 ng/g lw, from 21.1 ng/g lw to 36.4 ng/g lw and from 48.7 ng/g lw to 71.5 ng/g lw, 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.

Proman is a new product containing the active substance metobromuron. The intended use is as a broad spectrum selective herbicide for potatoes grown outdoors. VKM’s Panel on Plant Protection Products has discussed the questions raised by The Norwegian Food Safety Authority in the Terms of reference and has stated the following opinion: On the relevance of the carcinogenic effects observed in the rat carcinogenicity study; fibrosarcomas in females and pheochromocytomas and Leydig cell tumours in males: It is the opinion of VKM’s Panel for Plant Protection Products that the relevance of the observed incidence in mammary gland tumours and Leydig cell tumours in the rat carcinogenicity study is strengthened by the fact that the tumours are observed in hormone responsive tissues. The panel concludes that the carcinogenic effects observed in the rat carcinogenicity study are likely to be relevant for tumours that are influenced by the endocrine system, also in humans. On the higher incidences of still dumbbell-shaped centres of thoracic vertebrae and nonossification of the 13th rib observed in the rat developmental toxicity study and whether these are considered to be malformations: VKM’s Panel on Plant Protection Products has discussed the classification of the different types of incomplete ossifications and concluded that incomplete ossification of sternebrae and non-ossification of the 13th rib in rats should by itself be considered to be variations, and not adverse developmental effects. On the other hand, the Panel agrees with ECHA that the “thoracic vertebral centres still dumbbell-shaped” should be considered as malformations, due to limited data and understanding of the mechanism underlying the observed slow reversal of these anomalies. Furthermore, it is the view of the Panel that the different types of retarded ossification induced by the exposure of metobromuron should be considered as a whole when assessing for developmental effects. On the establishment of the NOAEL for the developmental toxicity study in rats and the reference value (ARfD): VKM’s Panel on Plant Protection Products supports the proposal of an ADI value of 0.008 mg/kg bw/day based on a NOAEL of 0.8 mg/kg bw/day from the 2-year study in mouse, and VKM Report 2015: 03 5. AOEL of 0.016 mg/kg bw/day based on the NOAEL of 1.6 mg/kg bw/day from the 1-year feeding study in dog. An UF of 100 is applied. The panel suggests on the other hand an ARfD of 0.03 mg/kg bw based on a LOAEL of 10 mg/kg bw /day with the observations of incomplete ossification in the rat developmental study. An UF of 300 is applied. On the possible anti-androgenic potential of metobromuron: It is the view of the Panel that the rat carcinogenicity study suggests that metobromuron may possess endocrine disrupting potency. The data from the Hershberger in vivo rat study and the in vitro studies is also suggestive of a weak anti-androgenic effect. Thus, it is the opinion of the VKM Panel on Plant Protection Products that an anti-androgenic effect of metobromuron cannot be excluded.

In this report the following topic of pesticides and fate in Norway has been outlined covering: 1. Factors influencing degradation of pesticides. 2. Description and update of datasets on soil and climate in agricultural areas. 3. Normalization of field degradation data as input for modelling fate. 4. Use of degradation data from Norway in model scenarios. Norwegian laboratory degradation studies indicate that increased soil organic carbon content enhances degradation rates of pesticides that show low sorption (e.g. metalaxyl, bentazone) ,due to increased microbial activity. Whereas pesticides that sorb moderately to strongly to soil (e.g. boscalid, propiconazole), display reduced degradation as organic carbon increases as a consequence of sorption and reduced bioavailability. Recent DegT50 field studies display a large variation in fungicide degradation rates from Klepp in the south to Tromsø in the north. For the mobile herbicide bentazone, no effect of climate was observed, as degradation rates were coherent at all sites, probably due to rapid leaching. The climate (temperature) seems to be more determinate for fungicide degradation rates than the soil type. Fungicide degradation was slow at two northern sites having low soil temperatures, even though microbial biomass was hugely different at the sites. How soil temperature and moisture affects microbial activity and diversity in various soils, climates and crops is important for the understanding of degradation capacity in Norwegian soils and fields. Microbial activity could be related to both soil, climate and crops/cropping regime – as well as to the nature of the soil organic matter. The fact that DegT50 values are very much shorter than laboratory values at the same reference conditions, may point to some systematic error in the normalization procedure (e.g. the default simplifications in the Walker and Arrhenius equations), or that the parameters affecting degradation in the laboratory are different from the parameters that affect degradation in the field. Consequently, lab-derived and field-derived DegT50matrix values should be compared and interpreted with care. The large variations in normalized DegT50 values obtained in field studies in Norway as well as in other regions in Norway cannot be explained by differences in the associated parameters characterizing the soil and microbial community. It is therefore not possible to determine if a certain field study is more or less representative for “Norwegian conditions”. As a conservative approach, the highest, normalized DegT50 from the European field studies should be selected for the Norwegian risk assessment independent on geographic vicinity. As an alternative, when a sufficient number of data are available, a high percentile (e.g 80 or 90-percentile) should be used rather than the geomean. Each agricultural region in Norway is dominated by one specific soil type for each region. Albeluvisol, Cambisol, Umbrisol, Stagnosol and Histosol in respectively Eastern Norway south, Eastern Norway north, Rogaland, Trøndelag and North of Norway. New updates for Norway include especially Umbrisols and Histosols rich in organic matter. Albeluvisols, Cambisols and Stagnosols are representing the main soil types in the agricultural area in Norway. These are also included in the groundwater (Rustad and Heia) and surface water scenarios (Syverud) developed for Norway. Experience from pesticide fate in the organic rich soils on the south west coast and north of Norway is limited. Compared to the “normal” temperature and precipitation from 1961 to 1990 with a “new normal” from 1991 to 2014, the climate has changed. For the five described agricultural areas in Norway, annual temperature has increased in average 1 degrees for all five regions and seasons for the new normal. The rainfall has increased for all seasons and regions except for the Northern Norway (Holt in Tromsø) and summer season at Kvithamar (Trøndelag) with lower precipitation in June to September. Annually the precipitation has increased approximately 100 mm in average. The existing Norwegian scenarios in groundwater and surface water seem to be representative in the meaning of covering the main soil types in the central agricultural areas in South Eastern Norway. However there are no scenarios covering areas of South West and North of Norway containing soil with high organic content, slow degradation and heavy rainfall. Vulnerable areas are not included in these scenarios as the idea of the representativity of soil was to include the main soil types covering the most of the agricultural production areas. The vulnerable areas deals with smaller areas and has to be treated separately. Vulnerable areas are areas with high groundwater levels and sandy soil and mobile pesticides. Hilly areas with clay soil represent high risk of surface runoff with strongly sorbed pesticides. We are lacking experience from areas with high content of organic matter causing slow degradation, combined with heavy rainfall. A database with representative soils and climates for various crops should be established in Norway and utilized in a targeted risk assessment approach. Then, the degradation of pesticides to be used in for example fruit/berry cropping, could be evaluated in respect to representative and vulnerable soils and climates in fruit/berry regions in Norway. A correct risk assessment of pesticide degradation in Norwegian agricultural soils should take the varying climatic zones, the diversity in agricultural soils and crops in Norway into consideration before formulated pesticides are approved. Risk assessment should be based on soils and climates most prevalent for the crop to which the pesticide is to be applied, in addition, vulnerable areas with slow degradation and/or high leaching/runoff risk should be recognized.

The plant protection product Malakite (BAS 669 01 F), containing the active substances dithianon and pyrimethanil, is a fungicide against scab in pome fruits. Products containing these active plant protection substances are approved in Norway, but not with both substances in the same product. The Swedish Chemicals Agency (KemI) has as zonal Rapporteur Member State (zRMS) of the Northern Zone evaluated the product Malakite and decided on non-approval due to the observation of unacceptable effects in exposed birds, aquatic organisms, non-target arthropods and earthworms. On request from The Norwegian Food Safety Authority, the VKM Panel on Plant Protection Products has discussed the available data and the report prepared by KemI, and has concluded as follows on the questions raised: On the refinement of DT50 in long term risk assessment for birds: It is the view of the VKM panel that the refinement is not acceptable because the analysis using first order kinetics seems not in line with a realistic and sufficiently conservative approach for the data provided. Furthermore, field studies from more sites are required. On the long term cumulative effects of the active substances on birds: VKM shares the view of KemI, that the combined sub-lethal and reproduction effects should be assessed because the mode of action of the two ingredients has only been shown in fungi, and since the mechanisms in birds could be different. On the reduction of assessment factor for fish: VKM opposes to the reduction of assessment factor for dithianon in fish because the data from acute toxicity tests cannot be extrapolated to chronic toxicity, and because the factor should reflect not only the variation in interspecies sensitivity, but also the uncertainty involved in extrapolation from laboratory tests to the field situation. On the choice of end point in risk assessment for fish: The VKM panel considers the NOEC of dithianon for fish determined from the study at pH 7.9 not to be adequate for the more acidic Norwegian surface waters, and recommends using the data from the test performed at pH 6.5. On the formulation studies for aquatic organisms: It is the opinion of the VKM panel that the formulation studies may be used together with corresponding studies with the active ingredients as long as the studies compared are performed and evaluated according to the same principles. However, VKM notes that the formulation tests as well as the tests of the active ingredients have been performed at high pH values, which are not representative to most Norwegian surface waters. Thus, the toxic effect of dithianon shown in these tests are likely to be lower than expected under typical conditions in Norway. On the assessment factors for concentration addition in fish: It is the opinion of the VKM panel that a reduction in assessment factor for one component in a mixture cannot be used for a formulation containing components for which a similar reduction has not been accepted. On effect studies of active substances and formulations on non-target arthropods: The VKM panel shares the view of KemI that the risk assessment should be based on all available information, including the studies presented for the active substances. On the endpoint in earthworm risk assessment: VKM supports the view of KemI that the observed effects of pyrimethanil on reproduction of earthworms should be considered in the risk assessment of Malakite.

In 2016, farmed and wild milkfish (Chanos chanos) and mullet (Mugil cephalus) from Tanzania mainland (Mtwara) and Zanzibar islands (Pemba and Unguja) were collected for analyses of persistent organic pollutants (POPs). Fish livers were analysed for organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), brominated flame retardants (BFRs). Muscle tissue was used for analyses of perfluoroalkyl substances (PFASs). The major contaminant was p,p′-DDE. The highest p,p′-DDE concentration was found in wild milkfish from Mtwara (715.27 ng/g lipid weight (lw)). This was 572 times higher than the maximum level detected in farmed milkfish from the same area. The ratios of p,p′-DDE/p,p′-DDT in wild milkfish and mullet from Mtwara and Pemba indicate historical use of DDT. In contrast, ratios in farmed milkfish from Unguja and Mtwara, suggest recent use. The levels of HCB, HCHs and trans-nonachlor were low. ∑10PCBs levels were low, ranging from -180> -138. PBDEs were detected in low and varying levels in all locations. BDE-47 was the dominating congener, and the highest level was found in farmed milkfish from Jozani (1.55 ng/g lw). HBCDD was only detected in wild mullet from Pemba at a level of 16.93 ng/g lw. PFAS was not detected in any of the samples. POP levels differed between geographic areas and between farmed and wild fish. Human activities seem to influence levels on PCBs and PBDEs on Unguja.

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.

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.

The aim of the present study was to investigate effects of defined mixtures of polycyclic aromatic hydrocarbons (PAHs) and perfluoroalkyl substances (PFASs), at low, environmentally relevant (1× = L), or high (20× = H) doses, on biological responses in Atlantic cod (Gadus morhua). To this end, farmed juvenile cod were exposed at day 0 and day 7 via intraperitoneal (i.p.) injections, in a two-week in vivo experiment. In total, there were 10 groups of fish (n = 21-22): two control groups, four separate exposure groups of PAH and PFAS mixtures (L, H), and four groups combining PAH and PFAS mixtures (L/L, H/L, L/H, H/H). Body burden analyses confirmed a dose-dependent accumulation of PFASs in cod liver and PAH metabolites in bile. The hepatosomatic index (HSI) was significantly reduced for three of the combined PAH/PFAS exposure groups (L-PAH/H-PFAS, H-PAH/L-PFAS, H-PAH/H-PFAS). Analysis of the hepatic proteome identified that pathways related to lipid degradation were significantly affected by PFAS exposure, including upregulation of enzymes in fatty acid degradation pathways, such as fatty acid β-oxidation. The increased abundances of enzymes in lipid catabolic pathways paralleled with decreasing levels of triacylglycerols (TGs) in the H-PFAS exposure group, suggest that PFAS increase lipid catabolism in Atlantic cod. Markers of oxidative stress, including catalase and glutathione S-transferase activities were also induced by PFAS exposure. Only minor and non-significant differences between exposure groups and control were found for cyp1a and acox1 gene expressions, vitellogenin concentrations in plasma, Cyp1a protein synthesis and DNA fragmentation. In summary, our combined proteomics and lipidomics analyses indicate that PFAS may disrupt lipid homeostasis in Atlantic cod., This study was funded by Research Council of Norway through the dCod 1.0: decoding the systems toxicology of Atlantic cod project (Center for Digital Life Norway project no. 248840) and the iCod 2.0: Integrative environmental genomics of Atlantic cod project(project no. 244564). The authors wish to thank Frederike Keitel-Gröner for contributing to sampling, and Essa Ashan Khan for contributing to sampling and manuscript information. We also thank Hui-Shan Tung and Pål Olsvik for contributing to liver RT-qPCR preparation and analysis at the Institute of Marine Research (IMR). We further thank Inge Jonassen and Ketil Hylland for valuable input proteomics analysis, and on experiment and manuscript design, respectively.

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.

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. This is an open access article distributed under the terms of the Creative Commons CC-BY license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

This report describes a screening study of in all ninety-nine conventional and emerging per- and polyfluoroalkyl substances (PFASs) in the Nordic environment. In addition, extractable organic fluor ...

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.

Apoptosis is an integral element of development that may also be initiated by environmental contaminants. The aim of the present study was to assess potential changes in the regulation of apoptotic genes in zebrafish embryos following parental exposure to two natural mixtures of persistent organic pollutants (POP). The mixture from Lake Mjøsa contained exceptionally high concentrations of polybrominated diphenyl ethers (PBDE), as well as relatively high levels of polychlorinated biphenyls (PCB) and dichlorodiphenyltrichloroethane (DDT). The mixture from Lake Losna contained background concentrations of POP. Genes involved in the apoptotic machinery were screened for their expression profile at four time points during embryonic development. Thirteen and 15 genes involved in apoptosis were found to be significantly upregulated in the high-exposure and background exposure groups, respectively, compared with controls. Modulation of apoptotic genes was restricted only to the first time point, which corresponds with the blastula stage. Although there were substantial differences in POP concentrations between mixtures, genes underlying the apoptosis process showed almost similar responses to the two mixtures. In both exposure groups the main executors of apoptosis p53, casp 2, casp 6, cassp 8, and BAX displayed upregulation compared to controls, suggesting that these POP induce apoptosis via a p53-dependent mechanism. Upregulation of genes that play a critical role in apoptosis suggests that disturbance of normal apoptotic signaling during gametogenesis and embryogenesis may be one of the central mechanisms involved in adverse reproductive effects produced by POP in zebrafish.