Re-evaluation of the existing health-based guidance values for copper and exposure assessment from all sources.

Copper is an essential micronutrient and also a regulated product used in organic and in conventional farming pest management. Both deficiency and excessive exposure to copper can have adverse health effects. In this Scientific Opinion, the EFSA 2021 harmonised approach for establishing health-based guidance values (HBGVs) for substances that are regulated products and also nutrients was used to resolve the divergent existing HBGVs for copper. The tightly regulated homeostasis prevents toxicity manifestation in the short term, but the development of chronic copper toxicity is dependent on copper homeostasis and its tissue retention. Evidence from Wilson disease suggests that hepatic retention is indicative of potential future and possibly sudden onset of copper toxicity under conditions of continuous intake. Hence, emphasis was placed on copper retention as an early marker of potential adverse effects. The relationships between (a) chronic copper exposure and its retention in the body, particularly the liver, and (b) hepatic copper concentrations and evidence of toxicity were examined. The Scientific Committee (SC) concludes that no retention of copper is expected to occur with intake of 5 mg/day and established an Acceptable Daily Intake (ADI) of 0.07 mg/kg bw. A refined dietary exposure assessment was performed, assessing contribution from dietary and non-dietary sources. Background copper levels are a significant source of copper. The contribution of copper from its use as plant protection product (PPP), food and feed additives or fertilisers is negligible. The use of copper in fertilisers or PPPs contributes to copper accumulation in soil. Infant formula and follow-on formula are important contributors to dietary exposure of copper in infants and toddlers. Contribution from non-oral sources is negligible. Dietary exposure to total copper does not exceed the HBGV in adolescents, adults, elderly and the very elderly. Neither hepatic copper retention nor adverse effects are expected to occur from the estimated copper exposure in children due to higher nutrient requirements related to growth.

In Silico Methods for Environmental Risk Assessment: Principles, Tiered Approaches, Applications, and Future Perspectives.

This chapter aims to introduce the reader to the basic principles of environmental risk assessment of chemicals and highlights the usefulness of tiered approaches within weight of evidence approaches in relation to problem formulation i.e., data availability, time and resource availability. In silico models are then introduced and include quantitative structure-activity relationship (QSAR) models, which support filling data gaps when no chemical property or ecotoxicological data are available. In addition, biologically-based models can be applied in more data rich situations and these include generic or species-specific models such as toxicokinetic-toxicodynamic models, dynamic energy budget models, physiologically based models, and models for ecosystem hazard assessment i.e. species sensitivity distributions and ultimately for landscape assessment i.e. landscape-based modeling approaches. Throughout this chapter, particular attention is given to provide practical examples supporting the application of such in silico models in real-world settings. Future perspectives are discussed to address environmental risk assessment in a more holistic manner particularly for relevant complex questions, such as the risk assessment of multiple stressors and the development of harmonized approaches to ultimately quantify the relative contribution and impact of single chemicals, multiple chemicals and multiple stressors on living organisms.

FEMA GRAS assessment of natural flavor complexes: Mint, buchu, dill and caraway derived flavoring ingredients.

In 2015, the Expert Panel of the Flavor and Extract Manufacturers Association (FEMA) initiated a re-evaluation of the safety of over 250 natural flavor complexes (NFCs) used as flavor ingredients. NFC flavor materials include a variety of essential oils and botanical extracts. The re-evaluation of NFCs is conducted based on a constituent-based procedure outlined in 2005 and updated in 2018 that evaluates the safety of NFCs for their intended use as flavor ingredients. This procedure is applied in the re-evaluation of the generally recognized as safe (GRAS) status of NFCs with constituent profiles that are dominated by alicyclic ketones such as menthone and carvone, secondary alcohols such as menthol and carveol, and related compounds. The FEMA Expert Panel affirmed the GRAS status of Peppermint Oil (FEMA 2848), Spearmint Oil (FEMA 3032), Spearmint Extract (FEMA 3031), Cornmint Oil (FEMA 4219), Erospicata Oil (FEMA 4777), Curly Mint Oil (FEMA 4778), Pennyroyal Oil (FEMA 2839), Buchu Leaves Oil (FEMA 2169), Caraway Oil (FEMA 2238) and Dill Oil (FEMA 2383) and determined FEMA GRAS status for Buchu Leaves Extract (FEMA 4923), Peppermint Oil, Terpeneless (FEMA 4924) and Spearmint Oil, Terpeneless (FEMA 4925).

Assessment of FD&C Yellow No. 6 (Sunset Yellow FCF) effects on sperm count, motility and viability in the rat in a 28-day toxicity study.

Sunset Yellow FCF was tested for 28-days in male Hsd:SD® rats for its potential effect on sperm quality parameters at dietary concentrations of 6,000, 12,000 and 18,000 ppm, corresponding to target doses of 500, 1000, and 1500 mg/kg bw/day. The measured average daily intake was 490, 944, and 1,475 mg/kg bw/day, based on feed consumption and stability of Sunset Yellow FCF in the diet. The animals fed diets with Sunset Yellow FCF presented no clinical signs of toxicity and no differences in feed consumption, body weights, organ weights, ophthalmology, hematology, clinical chemistry, urinalysis, or coagulation parameters that were considered adverse. No mortality or abnormalities were observed at necropsy, and no microscopic changes were observed in histopathology. Increased testes weights relative to body weight in animals of the middle and high intake groups were not associated with any abnormal findings in histopathology. Sperm quality evaluation presented no adverse effects on sperm motility, epididymal sperm count, homogenization-resistant spermatid count, or sperm morphological development. Therefore, in the absence of any adverse effects under the conditions of this study, the NOAEL for Sunset Yellow FCF was 1,475 mg/kg bw/day in male rats, corresponding to 18,000 ppm in the diet.

FEMA GRAS assessment of natural flavor complexes: Citrus-derived flavoring ingredients.

In 2015, the Expert Panel of the Flavor and Extract Manufacturers Association (FEMA) initiated a re-evaluation of the safety of over 250 natural flavor complexes (NFCs) used as flavoring ingredients. This publication is the first in a series and summarizes the evaluation of 54 Citrus-derived NFCs using the procedure outlined in Smith et al. (2005) and updated in Cohen et al. (2018) to evaluate the safety of naturally-occurring mixtures for their intended use as flavoring ingredients. The procedure relies on a complete chemical characterization of each NFC intended for commerce and organization of each NFC's chemical constituents into well-defined congeneric groups. The safety of the NFC is evaluated using the well-established and conservative threshold of toxicological concern (TTC) concept in addition to data on absorption, metabolism and toxicology of members of the congeneric groups and the NFC under evaluation. As a result of the application of the procedure, 54 natural flavor complexes derived from botanicals of the Citrus genus were affirmed as generally recognized as safe (GRAS) under their conditions of intended use as flavoring ingredients based on an evaluation of each NFC and the constituents and congeneric groups therein.