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Given the increasing attention on the occurrence of microplastics in the environment, and the potential environmental threats they pose, there is a need for researchers to move quickly from basic understanding to applied science that supports decision makers in finding feasible mitigation measures and solutions. At the same time, they must provide sufficient, accurate and clear information to the media, public and other relevant groups (e.g., NGOs). Key requirements include systematic and coordinated research efforts to enable evidence-based decision making and to develop efficient policy measures on all scales (national, regional and global). To achieve this, collaboration between key actors is essential and should include researchers from multiple disciplines, policymakers, authorities, civil and industry organizations, and the public. This further requires clear and informative communication processes, and open and continuous dialogues between all actors. Cross-discipline dialogues between researchers should focus on scientific quality and harmonization, defining and accurately communicating the state of knowledge, and prioritization of topics that are critical for both research and policy, with the common goal to establish and update action plans for holistic benefit. In Norway, cross-sectoral collaboration has been fundamental in supporting the national strategy to address plastic pollution. Researchers, stakeholders and the environmental authorities have come together to exchange knowledge, identify knowledge gaps, and set targeted and feasible measures to tackle one of the most challenging aspects of plastic pollution: microplastic. In this article, we present a Norwegian perspective on the state of knowledge on microplastic research efforts. Norway's involvement in international efforts to combat plastic pollution aims at serving as an example of how key actors can collaborate synergistically to share knowledge, address shortcomings, and outline ways forward to address environmental challenges., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Exposure to persistent organic pollutants (POPs), encompassing chlorinated (Cl), brominated (Br) and perfluoroalkyl acid (PFAA) compounds is associated with adverse neurobehaviour in humans and animals, and is observed to cause adverse effects in nerve cell cultures. Most studies focus on single POPs, whereas studies on effects of complex mixtures are limited. We examined the effects of a mixture of 29 persistent compounds (Cl + Br + PFAA, named Total mixture), as well as 6 sub-mixtures on in vitro exposed rat cerebellar granule neurons (CGNs). Protein expression studies of cerebella from in vivo exposed mice offspring were also conducted. The selection of chemicals for the POP mixture was based on compounds being prominent in food, breast milk or blood from the Scandinavian human population. The Total mixture and sub-mixtures containing PFAAs caused greater toxicity in rat CGNs than the single or combined Cl/Br sub-mixtures, with significant impact on viability from 500x human blood levels. The potencies for these mixtures based on LC 50 values were Br + PFAA mixture > Total mixture > Cl + PFAA mixture > PFAA mixture. These mixtures also accelerated induced lipid peroxidation. Protection by the competitive N-methyl-D-aspartate (NMDA) receptor antagonist 3-((R)-2-Carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) indicated involvement of the NMDA receptor in PFAA and Total mixture-, but not Cl mixture-induced toxicity. Gene-expression studies in rat CGNs using a sub-toxic and marginally toxic concentration ((0.4 nM-5.5 µM) 333x and (1 nM-8.2 µM) 500x human blood levels) of the mixtures, revealed differential expression of genes involved in apoptosis, oxidative stress, neurotransmission and cerebellar development, with more genes affected at the marginally toxic concentration. The two important neurodevelopmental markers Pax6 and Grin2b were downregulated at 500x human blood levels, accompanied by decreases in PAX6 and GluN2B protein levels, in cerebellum of offspring mice from mothers exposed to the Total mixture throughout pregnancy and lactation. In rat CGNs, the glutathione peroxidase gene Prdx6 and the regulatory transmembrane glycoprotein gene Sirpa were highly upregulated at both concentrations. In conclusion, our results support that early-life exposure to mixtures of POPs can cause adverse neurodevelopmental effects., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

In mice, prenatal exposure to low doses of bisphenol A has been shown to affect neurogenesis and neuronal migration in cortex, resulting in disturbance of both neuronal positioning and the network formation between thalamus and cortex in the offspring brain. In the present study we investigated whether prenatal exposure to bisphenol A disturbs the neurodevelopment of the cerebellum. Two different model systems were used; offspring from two strains of mice from mothers receiving bisphenol A in the drinking water before mating, during gestation and lactation, and chicken embryos exposed to bisphenol A (in the egg) on embryonic day 16 for 24h before preparation of cerebellar granule cell cultures. In the cerebellum, tight regulation of the level of transcription factor Pax6 is critical for correct development of granule neurons. During the development, the Pax6 level in granule neurons is high when these cells are located in the external granule layer and during their migration to the internal granule layer, and it is then reduced. We report that bisphenol A induced an increase in the thickness of the external granule layer and also an increase in the total cerebellar Pax6 level in 11 days old mice offspring. In cultured chicken cerebellar granule neurons from bisphenol A injected eggs the Pax6 level was increased day 6 in vitro. Together, these findings indicate that bisphenol A may affect the granule neurons in the developing cerebellum and thereby may disturb the correct development of the cerebellum., (Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.)

Epidemiological studies have associated indoor phthalate exposure with increased incidences and severity of asthma in children and adults, and inflammatory effects have been suggested as a possible mechanism. Recent studies report that phthalates may activate mitogen-activated protein (MAP) kinase p38 and various peroxisome proliferator-activated receptor (PPAR) isoforms. Here we confirm and extend these findings by investigating possible signalling pathways activated in the murine monocyte-macrophage cell line RAW264.7, using mono-2-ethylhexylphthalate (MEHP) as a model compound. MEHP exposure (0.3-1.0 mM) for 3h increased tumour necrosis factor (TNF)-α release and changed the cellular morphology into elongated spindle-like appearance, resembling more differentiated anti-inflammatory macrophages (M2). This was accompanied by increased expression of the macrophage differentiation marker CD163. Western analysis showed phosphorylation of p38 and Akt after 30 min exposure. Experiments using specific inhibitors suggested that MEHP-induced activation of both p38 and the phosphoinositide-3 (PI3) kinase/Akt pathway were involved in the release of TNF-α; whereas only PI3kinase seemed to be involved in differentiation. In contrast, inhibitors of PPARα and γ reduced differentiation, but did not affect TNF-α release. In conclusion, MEHP induced cytokine release and triggered differentiation of RAW264.7 cells, possibly into M2-like macrophages, but different signalling pathways appear to be involved in these responses., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

We have characterized cell death in THP-1 cells after exposure to heat-treated spores from satratoxin G-producing Stachybotrys chartarum isolate IBT 9631, atranone-producing S. chartarum isolate IBT 9634, and sterigmatocystin-producing Aspergillus versicolor isolate IBT 3781, as well as the trichothecenes T-2 and satratoxin G. Spores induced cell death within 3-6 h, with Stachybotrys appearing most potent. IBT 9631 induced both apoptosis and necrosis, while IBT 9634 and IBT 3781 induced mostly necrosis. T-2 toxin and satratoxin G caused mainly apoptosis. Comet assay +/- formamidopyrimidine DNA glycosylase showed that only the spore exposures induced early (3h) oxidative DNA damage. Likewise, only the spores increased the formation of reactive oxygen species (ROS), suggesting that spores as particles may induce ROS formation and oxidative DNA damage. Increased Ataxia Telangiectasia Mutated (ATM) phosphorylation, indicating DNA damage, was observed after all exposures. The DNA damage response induced by IBT 9631 as well as satratoxin G was characterized by rapid (15 min) activation of p38 and H2AX. The p38 inhibitor SB 202190 reduced IBT 9631-induced H2AX activation. Both IBT 9631 and T-2 induced activation of Chk2 and H2AX after 3 h. The ATM inhibitor KU 55933, as well as transfection of cells with ATM siRNA, reduced this activation, suggesting a partial role for ATM as upstream activator for Chk2 and H2AX. In conclusion, activation of Chk2 and H2AX correlated with spore- and toxin-induced apoptosis. For IBT 9631 and satratoxin G, additional factors may be involved in triggering apoptosis, most notably p38 activation.

Airway inflammation is important in asthma pathogenesis. Recent epidemiological data have indicated an association between asthma symptoms in children and exposure to di(2-ethylhexyl) phthalate (DEHP). Thus, we have studied inflammatory responses in primary rat alveolar macrophages (AMs) after exposure to mono(2-ethylhexyl) phthalate (MEHP), the major primary metabolite of DEHP. First, we show that MEHP induces a dose-dependent release of the pro-inflammatory tumour necrosis factor-alpha (TNF-alpha) in AMs, giving a maximal (5-fold) increase at 0.7 mM. This concentration also induced some cell death. MEHP also induced phosphorylation of MAPK p38, while the p38 inhibitor SB 202190 reduced MEHP-induced TNF-alpha, suggesting a p38-dependent cytokine production. Next, we elucidated possible effects of MEHP on the 5-lipoxygenase (5-LO) pathway and found that MEHP caused increased leukotriene (LTB(4)) release. Further, we found that the 5-LO inhibitor nordihydrogualaretic acid (NDGA) significantly reduced both MEHP-induced TNF-alpha release and MEHP-induced formation of reactive oxygen species (ROS), supporting an involvement of the 5-LO pathway in MEHP induced inflammatory reactions. Last, we found that MK-886, a known inhibitor of peroxisome proliferator-activated receptor alpha (PPARalpha), increased the MEHP-induced TNF-alpha response. This indicates that MEPH-PPARalpha binding mediates an anti-inflammatory signal.

Phthalates are found in numerous consumer products, including interior materials like polyvinyl chloride (PVC). Several studies have identified phthalates in indoor air. A recent case-control study demonstrated associations between allergic symptoms in children and the concentration of phthalates in dust collected from their homes. Here we have analyzed the content of selected phthalates in particulate matter (PM): PM(10) and PM(2.5) filter samples collected in 14 different indoor environments. The results showed the presence of the phthalates di-n-butyl phthalate (DBP), butyl benzyl phthalate (BBP), dicyclohexyl phthalate (DCHP) and diethyl hexyl phthalate (DEHP) in the samples. The dominating phthalate in both PM(10) and PM(2.5) samples from all locations was DBP. More than a 10-fold variation in the mean concentration of total phthalates between sampling sites was observed. The highest levels of total phthalates were detected in one children's room, one kindergarten, in two primary schools, and in a computer room. The relative contribution of total phthalates in PM(10) and PM(2.5) was 1.1 +/- 0.3% for both size fractions. The contribution of total phthalates in PM(2.5) to total phthalates in PM(10) ranged from 23-81%, suggesting different sources. Of the phthalates that were analyzed in the PM material, DBP was found to be the major phthalate in rubber from car tyres. However, our analyses indicate that tyre wear was of minor importance for indoor levels of both DBP as well as total phthalates. Overall, these results support the notion that inhalation of indoor PM contributes to the total phthalate exposure.