VKM’s methodology document for health and environmental risk assessments for use in the Panel on Plant Protection Products

Vitenskapskomiteen for mat og miljø (VKM) har oppdatert et metodedokument for helse og miljørisikovurderinger av plantevernmidler. Målet med oppdateringen er å gjenspeile gjeldende regelverk og praksis, og sikre kvaliteten på fremtidige risikovurderinger utført av faggruppen for plantevernmidler i VKM. Det forrige metodedokumentet er fra 2012, og oppdateringen var nødvendig for å tilpasse metodene til nytt EU-regelverk for plantevernmidler, og for å innarbeide nye datakrav og retningslinjer for plantevernmidler og biocider. Ved å oppdatere metodedokumentet, ønsket faggruppen å sikre at risikovurderingene de leverer er i tråd med gjeldende regelverket og vitenskapelig kunnskap. ​ ​Viktige endringer Dokumentet er oppdatert med henvisninger til nye forskrifter og veiledninger, om for eksempel biocider, nye typer plantevernmidler, og forenklet godkjenning/risikovurdering for mikrobielle stoffer. Det nye dokumentet inneholder også veiledning om fareidentifikasjon av stoffer med hormonforstyrrende egenskaper, alternative metoder for å redusere toksikologisk testing hos dyr, og vurdering av ikke-kostholdeksponering av plantevernmidler. Dokumentet inneholder oppdatert informasjon om metodikk knyttet til vurdering av plantevernmidlers egenskaper og skjebne i miljøet, inkludert norske jord- og klimaforhold, renseanlegg og drikkevannsrenseprosesser. Veiledning om risikovurdering for bier og andre insekter, akvatiske organismer, fugler, pattedyr og andre vertebrater, samt meitemark og andre jordlevende organismer, er også oppdatert. Innen flere av feltene er eller vil det bli etablert spesifikke beskyttelsesmål og trinnvise risikovurderinger. Samlet sett fungerer det oppdaterte metodedokumentet som en referanse for VKMs risikovurderingsarbeid for plantevernmidler, og sikrer at fremtidige vurderinger gjennomføres i samsvar med gjeldende regelverk og vitenskapelig kunnskap. ​ Metode VKM har benyttet en semi-systematisk tilnærming, ved å utarbeide et arbeidsdokument for innhenting og sammenstilling av nødvendig informasjon om nye datakrav fra gjeldende regelverk for plantevernmidler og biocider i EU. Dokumentet er godkjent av VKMs faggruppe for plantevernmidler.VKM’s methodology document for health and environmental risk assessments for use in the Panel on Plant Protection ProductspublishedVersio

Hepato(Geno)toxicity assessment of nanoparticles in a HepG2 liver spheroid model

(1) In compliance with the 3Rs policy to reduce, refine and replace animal experiments, the development of advanced in vitro models is needed for nanotoxicity assessment. Cells cultivated in 3D resemble organ structures better than 2D cultures. This study aims to compare cytotoxic and genotoxic responses induced by titanium dioxide (TiO), silver (Ag) and zinc oxide (ZnO) nanoparticles (NPs) in 2D monolayer and 3D spheroid cultures of HepG2 human liver cells. (2) NPs were characterized by electron microscopy, dynamic light scattering, laser Doppler anemometry, UV-vis spectroscopy and mass spectrometry. Cytotoxicity was investigated by the alamarBlue assay and confocal microscopy in HepG2 monolayer and spheroid cultures after 24 h of NP exposure. DNA damage (strand breaks and oxidized base lesions) was measured by the comet assay. (3) Ag-NPs were aggregated at 24 h, and a substantial part of the ZnO-NPs was dissolved in culture medium. Ag-NPs induced stronger cytotoxicity in 2D cultures (EC 3.8 µg/cm 2) than in 3D cultures (EC > 30 µg/cm 2), and ZnO-NPs induced cytotoxicity to a similar extent in both models (EC 10.1-16.2 µg/cm 2). Ag- and ZnO-NPs showed a concentration-dependent genotoxic effect, but the effect was not statistically significant. TiO-NPs showed no toxicity (EC > 75 µg/cm 2). (4) This study shows that the HepG2 spheroid model is a promising advanced in vitro model for toxicity assessment of NPs

VKM’s methodology document for health and environmental risk assessments for use in the Panel on Plant Protection Products

publishedVersio

Hazard assessment of nanomaterials using in vitro toxicity assays:Guidance on potential assay interferences and mitigating actions to avoid biased results

The movement towards an animal-free testing approach for risk assessment represents a key paradigm shift in toxicology. Risk assessment of engineered and anthropogenic nanoscale materials (NM) is dependent on reliable hazard characterization, which requires validated test methods and models, and increasingly on mechanistic insights into the mode of action. The properties that make NMs so advantageous for a wide range of commercial and industrial applications also pose a challenge when it comes to safety testing under in vitro and in chemico experimental settings. Their large reactive surface area makes NMs prone to interactions with assay reagents, readout signals, or intermediate steps of many test assays, leading to the potential for biased results and data inconsistencies, collectively referred to as interferences. Therefore, methods and protocols developed and validated for conventional chemicals often require adaptation and checking for reliability in NMs' toxicity assessment. This review presents the collected scientific knowledge on NMs-induced interferences for the most common in vitro toxicity assays and methods related to cytotoxicity, oxidative stress and inflammatory response evaluation. Our analysis of existing scientific literature showed that the challenge of NMs-induced interference was not explicitly addressed in more than 90% of the papers published up to 2014 reporting the safety and toxicity of NMs. In later years, increasing number of studies tackled the interference challenge in toxicity testing of NMs, which initiated exhaustive work on standardization and validation of existing regulatory-relevant in vitro test protocols and guidelines. Due to the specificity of the different NMs and the range of ways they can potentially interfere with in vitro assays, interference and fit-for purpose controls should be included for each NM type and method applied, unless label-free assays are selected. Here, we provide a decision tree to guide researchers on how to design experiments to avoid interferences during in vitro testing by taking appropriate mitigation actions and how to include proper interference controls in their experimental design where complete avoidance is not possible. The application of this decision tree will improve the reliability, comparability and reusability of in vitro toxicity data on engineered NMs or ENMs, increasing the relevance of in silico hazard data for use in risk assessment and in science-based risk governance of NMs. The approach is applicable more broadly also, to advanced materials and to hazard assessment of anthropogenic nanoscale materials such as microplastic and tyre-wear particles

Hazard assessment of nanomaterials using in vitro toxicity assays:Guidance on potential assay interferences and mitigating actions to avoid biased results

The movement towards an animal-free testing approach for risk assessment represents a key paradigm shift in toxicology. Risk assessment of engineered and anthropogenic nanoscale materials (NM) is dependent on reliable hazard characterization, which requires validated test methods and models, and increasingly on mechanistic insights into the mode of action. The properties that make NMs so advantageous for a wide range of commercial and industrial applications also pose a challenge when it comes to safety testing under in vitro and in chemico experimental settings. Their large reactive surface area makes NMs prone to interactions with assay reagents, readout signals, or intermediate steps of many test assays, leading to the potential for biased results and data inconsistencies, collectively referred to as interferences. Therefore, methods and protocols developed and validated for conventional chemicals often require adaptation and checking for reliability in NMs' toxicity assessment. This review presents the collected scientific knowledge on NMs-induced interferences for the most common in vitro toxicity assays and methods related to cytotoxicity, oxidative stress and inflammatory response evaluation. Our analysis of existing scientific literature showed that the challenge of NMs-induced interference was not explicitly addressed in more than 90% of the papers published up to 2014 reporting the safety and toxicity of NMs. In later years, increasing number of studies tackled the interference challenge in toxicity testing of NMs, which initiated exhaustive work on standardization and validation of existing regulatory-relevant in vitro test protocols and guidelines. Due to the specificity of the different NMs and the range of ways they can potentially interfere with in vitro assays, interference and fit-for purpose controls should be included for each NM type and method applied, unless label-free assays are selected. Here, we provide a decision tree to guide researchers on how to design experiments to avoid interferences during in vitro testing by taking appropriate mitigation actions and how to include proper interference controls in their experimental design where complete avoidance is not possible. The application of this decision tree will improve the reliability, comparability and reusability of in vitro toxicity data on engineered NMs or ENMs, increasing the relevance of in silico hazard data for use in risk assessment and in science-based risk governance of NMs. The approach is applicable more broadly also, to advanced materials and to hazard assessment of anthropogenic nanoscale materials such as microplastic and tyre-wear particles

Risk-benefit assessment of sunscreen: Opinion of the Panel on Food Additives, Flavourings, Processing Aids, Materials in Contact with Food, and Cosmetics of the Norwegian Scientific Committee for Food and Environment

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Risk-benefit assessment of sunscreen: Opinion of the Panel on Food Additives, Flavourings, Processing Aids, Materials in Contact with Food, and Cosmetics of the Norwegian Scientific Committee for Food and Environment

publishedVersio

Risk assessment of caffeine exposure from diet and personal care products. Opinion of the Panel on Food Additives, Flavourings, Processing Aids, Materials in Contact with Food, and Cosmetics of the Norwegian Scientific Committee for Food and Environment

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Risk-benefit assessment of sunscreen - Opinion of the Panel on Food Additives, Flavourings, Processing Aids, Materials in Contact with Food, and Cosmetics of the Norwegian Scientific Committee for Food and Environment

VKM has performed a risk-benefit assessment of sunscreen use and six UV filters. This task was undertaken on the initiative of a VKM Panel in response to the apparent paradox between the need for protective measures, such as use of sunscreens, to reduce Norway’s high incidence and mortality of skin cancer and a consumer concern for the safety of sunscreens. Concerns include safety of ingredients and sunscreens’ effect on vitamin D synthesis. Sunscreen products are legally regulated as cosmetic products in the EU, and only approved UV filters up to a maximum determined concentration are allowed in the ready-foruse preparation. VKM used a systematic approach to assess risks and benefits of sunscreen use and risks of six selected UV filters: bis-ethyl-hexyloxyphenol methoxyphenyl triazine (BEMT), butyl methoxydibenzoyl methane (BMDBM), 2-ethylhexyl salicylate (EHS), ethylhexyl triazone (EHT), octocrylene (OC), and titanium dioxide in nanoform (NP-TiO2). These UV filters are among the most frequently used in sunscreens on the Norwegian market. Sunscreen sprays and lip products were not included. Scientific publications and reports up to 2020 were retrieved to assess adverse and protective effects of sunscreen and adverse effects of UV filters. We assessed risk of bias in the studies and evidence for health outcomes with the aid of validity tools, and estimated exposure to each UV filter using probabilistic methods. The evidence showed that sunscreens were beneficial in protecting against certain skin cancers. Insufficient evidence precluded determination of the hazard associated with sunscreen use. The UV filters occurred in concentrations similar to or below the limits set in the EU cosmetics regulative. VKM considered that little to no hazard was associated with use of the six evaluated UV filters. VKM concludes that the risks related to use of the six evaluated UV filters are negligible since the real-life use of these UV filters is several-fold lower than the amounts that may cause any adverse health effect. The evidence for harmful health effects of sunscreens is insufficient to determine risk. Sunscreen use protects against certain skin cancers and is beneficial for the general Norwegian population.Risk-benefit assessment of sunscreen - Opinion of the Panel on Food Additives, Flavourings, Processing Aids, Materials in Contact with Food, and Cosmetics of the Norwegian Scientific Committee for Food and EnvironmentpublishedVersio

Risk-benefit assessment of sunscreen - Opinion of the Panel on Food Additives, Flavourings, Processing Aids, Materials in Contact with Food, and Cosmetics of the Norwegian Scientific Committee for Food and Environment

VKM has performed a risk-benefit assessment of sunscreen use and six UV filters. This task was undertaken on the initiative of a VKM Panel in response to the apparent paradox between the need for protective measures, such as use of sunscreens, to reduce Norway’s high incidence and mortality of skin cancer and a consumer concern for the safety of sunscreens. Concerns include safety of ingredients and sunscreens’ effect on vitamin D synthesis. Sunscreen products are legally regulated as cosmetic products in the EU, and only approved UV filters up to a maximum determined concentration are allowed in the ready-foruse preparation. VKM used a systematic approach to assess risks and benefits of sunscreen use and risks of six selected UV filters: bis-ethyl-hexyloxyphenol methoxyphenyl triazine (BEMT), butyl methoxydibenzoyl methane (BMDBM), 2-ethylhexyl salicylate (EHS), ethylhexyl triazone (EHT), octocrylene (OC), and titanium dioxide in nanoform (NP-TiO2). These UV filters are among the most frequently used in sunscreens on the Norwegian market. Sunscreen sprays and lip products were not included. Scientific publications and reports up to 2020 were retrieved to assess adverse and protective effects of sunscreen and adverse effects of UV filters. We assessed risk of bias in the studies and evidence for health outcomes with the aid of validity tools, and estimated exposure to each UV filter using probabilistic methods. The evidence showed that sunscreens were beneficial in protecting against certain skin cancers. Insufficient evidence precluded determination of the hazard associated with sunscreen use. The UV filters occurred in concentrations similar to or below the limits set in the EU cosmetics regulative. VKM considered that little to no hazard was associated with use of the six evaluated UV filters. VKM concludes that the risks related to use of the six evaluated UV filters are negligible since the real-life use of these UV filters is several-fold lower than the amounts that may cause any adverse health effect. The evidence for harmful health effects of sunscreens is insufficient to determine risk. Sunscreen use protects against certain skin cancers and is beneficial for the general Norwegian population.Risk-benefit assessment of sunscreen - Opinion of the Panel on Food Additives, Flavourings, Processing Aids, Materials in Contact with Food, and Cosmetics of the Norwegian Scientific Committee for Food and EnvironmentpublishedVersio