Risk Governance of Emerging Technologies Demonstrated in Terms of its Applicability to Nanomaterials

Nanotechnologies have reached maturity and market penetration that require nano-specific changes in legislation and harmonization among legislation domains, such as the amendments to REACH for nanomaterials (NMs) which came into force in 2020. Thus, an assessment of the components and regulatory boundaries of NMs risk governance is timely, alongside related methods and tools, as part of the global efforts to optimise nanosafety and integrate it into product design processes, via Safe(r)-by-Design (SbD) concepts. This paper provides an overview of the state-of-the-art regarding risk governance of NMs and lays out the theoretical basis for the development and implementation of an effective, trustworthy and transparent risk governance framework for NMs. The proposed framework enables continuous integration of the evolving state of the science, leverages best practice from contiguous disciplines and facilitates responsive re-thinking of nanosafety governance to meet future needs. To achieve and operationalise such framework, a science-based Risk Governance Council (RGC) for NMs is being developed. The framework will provide a toolkit for independent NMs' risk governance and integrates needs and views of stakeholders. An extension of this framework to relevant advanced materials and emerging technologies is also envisaged, in view of future foundations of risk research in Europe and globally

Neuropsychological effects of chronic low-dose exposure to polychlorinated biphenyls (PCBs): A cross-sectional study

BACKGROUND: Exposure to indoor air of private or public buildings contaminated with polychlorinated biphenyls (PCBs) has raised health concerns in long-term users. This exploratory neuropsychological group study investigated the potential adverse effects of chronic low-dose exposure to specific air-borne low chlorinated PCBs on well-being and behavioral measures in adult humans. METHODS: Thirty employees exposed to indoor air contaminated with PCBs from elastic sealants in a school building were compared to 30 non-exposed controls matched for education and age, controlling for gender (age range 37–61 years). PCB exposure was verified by external exposure data and biological monitoring (PCB 28, 101, 138, 153, 180). Subjective complaints, learning and memory, executive function, and visual-spatial function was assessed by standardized neuropsychological testing. Since exposure status depended on the use of contaminated rooms, an objectively exposed subgroup (N = 16; PCB 28 = 0.20 μg/l; weighted exposure duration 17.9 ± 7 years) was identified and compared with 16 paired controls. RESULTS: Blood analyses indicated a moderate exposure effect size (d) relative to expected background exposure for total PCB (4.45 ± 2.44 μg/l; d = 0.4). A significant exposure effect was found for the low chlorinated PCBs 28 (0.28 ± 0.25 μg/l; d = 1.5) and 101 (0.07 ± 0.09 μg/l; d = 0.7). Although no neuropsychological effects exceeded the adjusted significance level, estimation statistics showed elevated effect sizes for several variables. The objectively exposed subgroup showed a trend towards increased subjective attentional and emotional complaints (tiredness and slowing of practical activities, emotional state) as well as attenuated attentional performance (response shifting and alertness in a cued reaction task). CONCLUSION: Chronic inhalation of low chlorinated PCBs that involved elevated blood levels was associated with a subtle attenuation of emotional well-being and attentional function. Extended research is needed to replicate the potential long-term low PCB effects in a larger sample

Spontaneous honeybee behaviour is altered by persistent organic pollutants

The effect of environmental pollutants on honeybee behaviour has focused mainly on currently used pesticides. However, honeybees are also exposed to persistent organic pollutants (POPs). The aim of this laboratory based study was to determine if exposure to sublethal field-relevant concentrations of POPs altered the spontaneous behaviour of foraging-age worker honeybees. Honeybees (Apis mellifera) were orally exposed to either a sublethal concentration of the polychlorinated biphenyl (PCB) mixture Aroclor 1254 (100 ng/ml), the organochlorine insecticide lindane (2.91 ng/ml) or vehicle (0.01% DMSO, 0.00015% ethanol in 1M sucrose) for 1–4 days. The frequency of single event behaviours and the time engaged in one of four behavioural states (walking, flying, upside down and stationary) were monitored for 15 min after 1, 2, 3 and 4 days exposure. Exposure to Aroclor 1254 but not lindane increased the frequency and time engaged in honeybee motor activity behaviours in comparison to vehicle. The Aroclor 1254—induced hyperactivity was evident after 1 day of exposure and persisted with repeated daily exposure. In contrast, 1 day of exposure to lindane elicited abdominal spasms and increased the frequency of grooming behaviours in comparison to vehicle exposure. After 4 days of exposure, abdominal spasms and increased grooming behaviours were also evident in honeybees exposed to Aroclor 1254. These data demonstrate that POPs can induce distinct behavioural patterns, indicating different toxicokinetic and toxicodynamic properties. The changes in spontaneous behaviour, particularly the PCB-induced chronic hyperactivity and the associated energy demands, may have implications for colony health

Microfluidic In Vitro Platform for (Nano)Safety and (Nano)Drug Efficiency Screening

Microfluidic technology is a valuable tool for realizing more in vitro models capturing cellular and organ level responses for rapid and animal‐free risk assessment of new chemicals and drugs. Microfluidic cell‐based devices allow high‐throughput screening and flexible automation while lowering costs and reagent consumption due to their miniaturization. There is a growing need for faster and animal‐free approaches for drug development and safety assessment of chemicals (Registration, Evaluation, Authorisation and Restriction of Chemical Substances, REACH). The work presented describes a microfluidic platform for in vivo‐like in vitro cell cultivation. It is equipped with a wafer‐based silicon chip including integrated electrodes and a microcavity. A proof‐of‐concept using different relevant cell models shows its suitability for label‐free assessment of cytotoxic effects. A miniaturized microscope within each module monitors cell morphology and proliferation. Electrodes integrated in the microfluidic channels allow the noninvasive monitoring of barrier integrity followed by a label‐free assessment of cytotoxic effects. Each microfluidic cell cultivation module can be operated individually or be interconnected in a flexible way. The interconnection of the different modules aims at simulation of the whole‐body exposure and response and can contribute to the replacement of animal testing in risk assessment studies in compliance with the 3Rs to replace, reduce, and refine animal experiments

Programming of metabolic effects in C57BL/6JxFVB mice by in utero and lactational exposure to perfluorooctanoic acid

Perfluorooctanoic acid (PFOA) is known to cause developmental toxicity and is a suggested endocrine disrupting compound (EDC). Early life exposure to EDCs has been implicated in programming of the developing organism for chronic diseases later in life. Here we study perinatal metabolic programming by PFOA using an experimental design relevant for human exposure. C57BL/6JxFVB hybrid mice were exposed during gestation and lactation via maternal feed to seven low doses of PFOA at and below the NOAEL used for current risk assessment (3–3000 μg/kg body weight/day). After weaning, offspring were followed for 23–25 weeks without further exposure. Offspring showed a dose-dependent decrease in body weight from postnatal day 4 to adulthood. Growth under high fat diet in the last 4–6 weeks of follow-up was increased in male and decreased in female offspring. Both sexes showed increased liver weights, hepatic foci of cellular alterations and nuclear dysmorphology. In females, reductions in perigonadal and perirenal fat pad weights, serum triglycerides and cholesterol were also observed. Endocrine parameters, such as glucose tolerance, serum insulin and leptin, were not affected. In conclusion, our study with perinatal exposure to PFOA in mice produced metabolic effects in adult offspring. This is most likely due to disrupted programming of metabolic homeostasis, but the assayed endpoints did not provide a mechanistic explanation. The BMDL of the programming effects in our study is below the current point of departure used for calculation of the tolerable daily intake.The authors wish to acknowledge the support of the biotechnicians from the team of Hans Strootman at the RIVM animal facilities. Further technical support was provided by Piet Beekhof, Hennie Hodemaekers, Sandra Imholz (RIVM), Mirjam Koster (UU), Stefan van Leeuwen (RIKILT), Jacco Koekkoek and Marja Lamoree (VU). This study was funded by the European Community’s Seventh Framework Programme [FP7/2007–2013] under grant agreement OBELIX 227391

Hexabromocyclododecanes (HBCDs) in the environment and humans: A review

Hexabromocyclododecanes (HBCDs) are brominated aliphatic cyclic hydrocarbons used as flame retardants in thermal insulation building materials, upholstery textiles, and electronics. As a result of their widespread use and their physical and chemical properties, HBCDs are now ubiquitous contaminants in the environment and humans. This review summarizes HBCD concentrations in several environmental compartments and analyzes these data in terms of point sources versus diffuse sources, biomagnification potential, stereoisomer profiles, time trends, and global distribution. Generally, higher concentrations were measured in samples (air, sediment, and fish) collected near point sources (plants producing or processing HBCDs), while lower concentrations were recorded in samples from locations with no obvious sources of HBCDs. High concentrations were measured in top predators, such as marine mammals and birds of prey (up to 9600 and 19 200 ng/g lipid weight, respectively), suggesting a biomagnification potential for HBCDs. Relatively low HBCD concentrations were reported in the few human studies conducted to date (median values varied between 0.35 and 1.1 ng/g lipid weight). HBCD levels in biota are increasing slowly and seem to reflect the local market demand. One important observation is the shift from the high percentage of the gamma-HBCD stereoisomer in the technical products to a dominance of the alpha-HBCD stereoisomer in biological samples. A combination of factors such as variations in solubility, partitioning behavior, uptake, and, possibly, selective metabolism of individual isomers may explain the observed changes in stereoisomer patterns. Recommendations for further work include research on how HBCDs are transferred from products into the environment upon production, use, and disposal. Time trends need to be analyzed more in detail, including HBCD stereoisomers, and more data on terrestrial organisms are needed, especially for humans. Whenever possible, HBCDs should be analyzed as individual stereoisomers in order to address their fate and effects

Contaminants in fish from Etnefjord, Norway.

1,2,5,6,9,10-hexabromocyclododecane (HBCDD) is one of the most frequently used brominated flame retardants (BFR) and is considered as an emerging environmental pollutant. Recently, high levels of HBCDD were reported in five different fish species from Etnefjord, which is a branch of the Hardangerfjord at the southwest coast of Norway. This report raised some serious concerns and the Norwegian Climate and Pollution Agency (Klif) therefore initiated a survey of HBCDD in cod and flounder from Etnefjorden in order to confirm the findings. In addition to HBCDD, the levels of other environmental pollutants were analyzed in the fish, namely polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), hexachlorocyclohexane (HCH), dichlorodiphenyltrichloroethane (DDT), mercury (Mg), lead (Pb), cadmium (Cd) and arsenic (As). The fish muscle filet and livers were prepared and analyzed using recognized and previously published methods. The levels of HBCDD in the fish were low, representing expected background concentrations. HBCDD was only detected in the cod livers with concentrations ranging 0.3-5.7 ng/g wet weight, corresponding to 1.3-8.2 ng/g on a lipid weight basis. Previously, it was reported a level of 30 000 ng/g lipid weight in cod filet, which is, as far as we know, the highest HBCDD concentration ever reported in cod. Our study could, therefore, not confirm the recent findings that showed high HBCDD concentrations in fish from the Etnefjord area. Also, the levels of the other pollutants were low. For example, the concentrations of DDT, PCB, HCH and Hg can, according to Klifs system for classification of environmental state, be regarded as background levels (class 1, slightly/negligible polluted). In conclusion, there are no recons to believe that cod and flounder in Etnefjorden is exposed to considerable amount of environmental pollutants, neither of HBCDD nor other contaminants. Only further analysis of sediments from the inner site of the fjord can, however, positively reveal a possible HBCDD source

Contaminants in fish from Etnefjord, Norway.

1,2,5,6,9,10-hexabromocyclododecane (HBCDD) is one of the most frequently used brominated flame retardants (BFR) and is considered as an emerging environmental pollutant. Recently, high levels of HBCDD were reported in five different fish species from Etnefjord, which is a branch of the Hardangerfjord at the southwest coast of Norway. This report raised some serious concerns and the Norwegian Climate and Pollution Agency (Klif) therefore initiated a survey of HBCDD in cod and flounder from Etnefjorden in order to confirm the findings. In addition to HBCDD, the levels of other environmental pollutants were analyzed in the fish, namely polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), hexachlorocyclohexane (HCH), dichlorodiphenyltrichloroethane (DDT), mercury (Mg), lead (Pb), cadmium (Cd) and arsenic (As). The fish muscle filet and livers were prepared and analyzed using recognized and previously published methods. The levels of HBCDD in the fish were low, representing expected background concentrations. HBCDD was only detected in the cod livers with concentrations ranging 0.3-5.7 ng/g wet weight, corresponding to 1.3-8.2 ng/g on a lipid weight basis. Previously, it was reported a level of 30 000 ng/g lipid weight in cod filet, which is, as far as we know, the highest HBCDD concentration ever reported in cod. Our study could, therefore, not confirm the recent findings that showed high HBCDD concentrations in fish from the Etnefjord area. Also, the levels of the other pollutants were low. For example, the concentrations of DDT, PCB, HCH and Hg can, according to Klifs system for classification of environmental state, be regarded as background levels (class 1, slightly/negligible polluted). In conclusion, there are no recons to believe that cod and flounder in Etnefjorden is exposed to considerable amount of environmental pollutants, neither of HBCDD nor other contaminants. Only further analysis of sediments from the inner site of the fjord can, however, positively reveal a possible HBCDD source