Naturally occurring bisphenol F in plants used in traditional medicine

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The TTC Approach in Practice and its Impact on Risk Assessment and Risk Management in Food Safety. A Regulatory Toxicologist's Perspective

There are many substances in food and drinking water from different contamination sources for which only insufficient or no toxicity data exist. In order to prioritize and preliminarily assess the human health risks, the threshold of toxicological concern (TTC) approach was developed between 1996 and 2004. This concept has since been applied increasingly by regulatory food safety authorities. In parallel, the safety of this approach has been discussed by stakeholders, primarily on a conceptual basis. However, real examples showing the practical benefits of this approach have not been discussed. In this paper, the technical feasibility, applicability, safety, and further benefits of the TTC approach are illustrated and discussed based on four real cases: 1) halogenated contaminants of unknown origin in the drinking water (polychlorinated butadienes), 2) an unwanted by-product from epoxy resin coatings in canned fish (Cyclo-di-BADGE), 3) two cyclic compounds occurring in polyamide food packaging materials and kitchen utensils, and 4) mycotoxins (from Alternaria). These examples from different fields of application clearly demonstrate that the results of the TTC approach are an extremely useful starting point for adequate decisions and actions (if necessary) by risk assessment and risk management in food safety

Azole fungicides affect mammalian steroidogenesis by inhibiting sterol 14 α-demethylase and aromatase

Azole compounds play a key role as antifungals in agriculture and in human mycoses and as non-steroidal antiestrogens in the treatment of estrogen-responsive breast tumors in postmenopausal women. This broad use of azoles is based on their inhibition of certain pathways of steroidogenesis by high-affinity binding to the enzymes sterol 14-alpha-demethylase and aromatase. Sterol 14-alpha-demethylase is crucial for the production of meiosis-activating sterols, which recently were shown to modulate germ cell development in both sexes of mammals. Aromatase is responsible for the physiologic balance of androgens and estrogens. At high doses, azole fungicides and other azole compounds affect reproductive organs, fertility, and development in several species. These effects may be explained by inhibition of sterol 14-alpha-demethylase and/or aromatase. In fact, several azole compounds were shown to inhibit these enzymes in vitro, and there is also strong evidence for inhibiting activity in vivo. Furthermore, the specificity of the enzyme inhibition of several of these compounds is poor, both with respect to fungal versus nonfungal sterol 14-alpha-demethylases and versus other P450 enzymes including aromatase. To our knowledge, this is the first review on sterol 14-alpha-demethylase and aromatase as common targets of azole compounds and the consequence for steroidogenesis. We conclude that many azole compounds developed as inhibitors of fungal sterol 14-alpha-demethylase are inhibitors also of mammalian sterol 14-alpha-demethylase and mammalian aromatase with unknown potencies. For human health risk assessment, data on comparative potencies of azole fungicides to fungal and human enzymes are needed.ISSN:1552-9924ISSN:0091-676

Migration of cyclo-diBA from coatings into canned food : method of analysis, concentration determined in a survey and in silico hazard profiling

Cyclo-diBA, the cyclic product formed from bisphenol A and bisphenol A diglycidyl ether during production of epoxy resins, was measured in canned food using reversed phase HPLC with fluorescence detection. Half (9 of 17) of the samples of canned fish in oil collected in April 2010 contained cyclo-diBA with an average concentration of 1025 μg/kg and a maximum of 1980 μg/kg. In September 2012, cyclo-diBA was detectable (25 μg/kg). Since no experimental toxicity data are available except for its cytotoxicity, an in silico hazard profiling was performed. Cyclo-diBA seems to be stable and of low reactivity. There is indication for considerable oral bioavailability and for the potential to accumulate in the human body. Cyclo-diBA can be metabolized into cyclic and acyclic compounds. Based on SAR assessment for cyclo-diBA and read-across from BADGE to linear cyclo-diBA metabolites, genotoxic effects are improbable. Specific binding of cyclo-diBA to nuclear receptors, such as ERβ, can be predicted, indicating a potential endocrine-disrupting potency. The limit by the EFSA guidelines of 50 μg/person/d for compounds shown not to be genotoxic as well as the TTC-based Cramer structural class III value of 90 μg/person/d could be exceeded several fold by high consumers of canned fish in oil with high brand loyalty. As a consequence, risk reduction measures were taken

Large-scale in silico screening of compounds contained in printing inks for food packaging materials

Providing sustainable and safe nutrition to the population is one of the main tasks of the modern food industry. While food packaging materials fulfill their invaluable protective role, certain substances can migrate from them into food. Switzerland is worldwide the only country, in which substances in printing inks for food packaging are regulated. Approx. 5000 substances are listed in Annex 10 of the Ordinance on Food Contact Materials FCM (SR 817.023. 21). Briefly, they were evaluated based on toxicity data and have a specific migration limit (part A). Alternatively, they should not be classified as CMR substances and not be detectable in food (< 10 ppb)(part B). In the order to identify potentially harmful compounds, we performed a virtual screening study along with a complex toxicokinetic characterization of chemical compounds contained in printing inks for FCM

Natural occurrence of bisphenol F in mustard

<p>Bisphenol F (BPF) was found in mustard up to a concentration of around 8 mg kg⁻¹. Contamination of the raw products or caused by the packaging could be ruled out. Also, the fact that only the 4,4ʹ-isomer of BPF was detected spoke against contamination from epoxy resin or other sources where technical BPF is used. Only mild mustard made of the seeds of <i>Sinapis alba</i> contained BPF. In all probability BPF is a reaction product from the breakdown of the glucosinolate glucosinalbin with 4-hydroxybenzyl alcohol as an important intermediate. Hot mustard made only from brown mustard seeds (<i>Brassica juncea</i>) or black mustard seeds (<i>Brassica nigra</i>) contained no BPF. BPF is structurally very similar to bisphenol A and has a similar weak estrogenic activity. The consumption of a portion of 20 g of mustard can lead to an intake of 100–200 µg of BPF. According to a preliminary risk assessment, the risk of BPF in mustard for the health of consumers is considered to be low, but available toxicological data are insufficient for a conclusive evaluation. It is a new and surprising finding that BPF is a natural food ingredient and that this is the main uptake route. This insight sheds new light on the risk linked to the family of bisphenols.</p

Evaluating the food safety and risk assessment evidence-base of polyethylene terephthalate oligomers: Protocol for a systematic evidence map

Polyethylene terephthalate (PET) oligomers are ubiquitous in PET used in food contact applications. Consumer exposure by migration of PET oligomers into food and beverages is documented. However, no specific risk assessment framework or guidance for the safety evaluating of PET oligomers exist to date.; The aim of this systematic evidence map (SEM) is to identify and organize existing knowledge clusters and associated gaps in hazard and exposure information of PET oligomers. Research needs will be identified as an input for chemical risk assessment, and to support future toxicity testing strategies of PET oligomers and regulatory decision-making.; Multiple bibliographic databases (incl. Embase, Medline, Scopus, and Web of Science Core Collection), chemistry databases (SciFinder-n, Reaxys), and gray literature sources will be searched, and the search results will be supplemented by backward and forward citation tracking on eligible records. The search will be based on a single-concept PET oligomer-focused strategy to ensure sensitive and unbiased coverage of all evidence related to hazard and exposure in a data-poor environment. A scoping exercise conducted during planning identified 34 relevant PET oligomers. Eligible work of any study type must include primary research data on at least one relevant PET oligomer with regard to exposure, health, or toxicological outcomes.; For indexed scientific literature, title and abstract screening will be performed by one reviewer. Selected studies will be screened in full-text by two independent reviewers. Gray literature will be screened by two independent reviewers for inclusion and exclusion.; Risk of bias analysis will not be conducted as part of this SEM.; Will be performed by one reviewer and peer-checked by a second reviewer for indexed scientific literature or by two independent reviewers for gray literature.; The extracted and coded information will be synthesized in different formats, including narrative synthesis, tables, and heat maps.; Zenodo: https://doi.org/10.5281/zenodo.6224302