Zubereitungen mit pflanzlichen Bestandteilen, wie sie in pflanzlichen Arzneimitteln, Medizinprodukten, Nahrungsergänzungsmitteln und Kosmetika enthalten sind, sind leicht zugänglich und können bei Anwendungsfehlern zu Nebenwirkungen oder Vergiftungen führen. Giftinformationszentren (GIZ) beantworten Expositionsanfragen. Ziel dieser Studie war es, Expositionsanfragen zu Zubereitungen mit pflanzlichen Bestandteilen am Gemeinsamen Giftinformationszentrum Erfurt (GGIZ) auszuwerten, um Präventionsansätze zu identifizieren. Es wurde eine statistische Auswertung der Expositionsanfragen am GGIZ für 2013–2022 durchgeführt. Daten aus 9 Bundesländern flossen ein. Berücksichtigt wurden Anfragen zu Einzelpräparaten, die mindestens 10-mal angefragt wurden. Die Symptomschwere wurde mit dem Poisoning Severity Score (PSS) und das Vergiftungsrisiko mit einem modifizierten Litovitz-Risikofaktor berechnet. 36 Zubereitungen mit 2512 Expositionen (Ø251,2/a; Trend τ = 0,8667, p = 0,0007) wurden identifiziert. 60,2

BACKGROUND:Preparations containing plant-derived components, such as those found in herbal medicinal products, medical devices, dietary supplements, and cosmetics, are readily accessible and may lead to adverse effects or poisoning if used incorrectly. Poison information centers (PICs) respond to exposure-related inquiries. The aim of this study was to analyze exposure inquiries concerning preparations with plant-derived components at the Joint Poison Information Center in Erfurt (GGIZ) in order to identify preventive approaches. METHODS:A statistical analysis of exposure inquiries received by the GGIZ from 2013 to 2022 was conducted. Data from nine federal states were included. Only inquiries related to single preparations that had been reported at least 10 times were considered. Symptom severity was assessed using the poisoning severity score (PSS), and poisoning risk was calculated using a modified Litovitz risk factor. RESULTS:A total of 36 preparations with 2512 exposures (mean 251.2/year; trend τ = 0.8667, p = 0.0007) were identified. Of those affected, 60.2% (1511) were toddlers. Most exposures (98.5%, 2474) occurred in the home environment. In 64.5% (1620) of cases, exposures were unintentional. Oral exposure accounted for 93.4% (2345) of cases. Of the exposures with known outcomes, 75.3% (1780/2365) remained asymptomatic, 23.5% (556/2365) resulted in minor/mild symptoms, 1% (24) in moderate symptoms, and 0.2% (5) in severe symptoms. Severe intoxications were associated with Colchysat® Bürger and Klosterfrau® Melissengeist concentrate. DISCUSSION:Toddlers represent a relevant risk group in the use of preparations containing plant-derived components. Preparations containing colchicine or ethanol may lead to fatal intoxications, particularly in cases of intentional exposure. It is recommended to store oral and topical preparations separately and out of reach of unauthorized persons, and to provide comprehensive education.

Coffee oil derived from spent coffee grounds of Coffea arabica is considered a novel food in the European Union (EU), requiring pre-market approval supported by comprehensive toxicological data. The effects of coffee oil on human health, particularly on blood parameters and liver enzymes, have been investigated in several studies. This review article summarizes the available toxicological literature on coffee oil, including its bioactive diterpenes cafestol and kahweol, which are known for their potential health effects. Considering the different modes of action of these two diterpenes, moderate consumption of coffee oil may be considered safe for healthy adults. Based on the changes in serum values in humans, this review provides initial estimations of LOAEL, NOAEL, and ADI for these diterpenes. The findings suggest that an intake of 225 mg of coffee oil per day might be considered safe assuming that coffee oil contains about 0.4% diterpenes. In summary, the assessment based on the published data indicates that (i) the consumption of coffee oil contained in any type of prepared coffee appears to be safe because the homeostasis of lipid levels in the blood is not significantly affected, and (ii) a low consumption of coffee oil as such might be acceptable but would require a refined risk assessment considering the exposure levels of the intended food product, which must be provided for novel food approval procedures.

Test systems enabling preclinical assessment of drug effects in relevant models are essential for optimizing the selection of candidate therapeutics before their further clinical translation. Xenograft tissue slice tandem co-culture (XTCC) models were developed as ex vivo systems for visualizing glioblastoma (GBM) tumor growth and invasion into the complex host tissue structures of the brain. Work here tested the XTCC model for delineating specific drug effects, in particular inhibition of invasion as major issue in GBM. The established chemotherapeutic Temozolomide (TMZ) and three promising candidates - two histone deacetylase inhibitors, Vorinostat and Entinostat, and the neuropeptide Apamin - were tested. XTCCs were generated by placing G55T2 or U87-MG cell-derived tumor xenograft tissue slices onto murine cortical brain slices. Upon drug treatment, effects on growth, invasion, proliferation, and apoptosis were analyzed by immunohistochemistry. Differences in invasion capacity were seen between the two cell lines. Profound invasion-inhibitory effects of 100 μM TMZ were accurately monitored and substantially higher than inhibition of the bulk tumor mass. Likewise, the extent of single-cell invasion into the normal brain tissue was massively inhibited by Vorinostat and especially by Entinostat, indicating that histone deacetylase inhibitor treatment is particularly efficient in inhibiting GBM cell invasion. Despite the absence of inhibitory effects of Apamin in 2D cell culture, G55T2 XTCCs revealed ∼70% reduced GBM invasion, associated with a substantial inhibition of proliferation as indicated by loss of Ki-67 positivity. Taken together, we show the suitability of the XTCC models for monitoring tumor growth and, in particular anti-invasive effects of drugs.

Cannabidiol (CBD), a non-psychotropic main component of the Cannabis plant, has been approved as a drug in the European Union (EU) under the name “Epidyolex”. However, its approval process as a food ingredient under the Novel Food Regulation was paused by the European Food Safety Authority (EFSA) due to a lack of safety data. Nevertheless, there is a growing, unregulated market in which CBD is advertised with various health claims and dosage instructions. Of particular concern is its toxic effect on the liver and possible reproductive toxicity in humans. Studies suitable for calculating the benchmark dose were identified from the available data. Animal studies yielded a benchmark dose lower confidence limit (BMDL) of 43 mg/kg bw/day, which translates into a safe human dose of approximately 15 mg/day. Only the Lowest-Observed-Adverse-Effect Level (LOAEL) of 4.3 mg/kg bw/day could be identified from the human data. This updated risk assessment confirmed a health-based guidance value (HBGV) of 10 mg/day based on human LOAEL. Despite the existing data gaps, preliminary regulation appears advisable because the current form of the gray CBD market is unacceptable from the standpoint of consumer safety and protection.

Approximately 8 million tons of dates (Phoenix dactylifera) are produced globally each year. The seeds of the fruit, which make up 10–15% of its weight, are typically discarded. Date seed coffee is a sustainable food system innovation rooted in the traditions of high date-producing regions. Dating back to the late 19th century, date seed coffee has evolved from a historical coffee substitute to a modern caffeine-free alternative. Date seed coffee has a long history of consumption in the European Union (EU). This indicates that it may not require novel food authorization. The composition of date seeds is evaluated in this review and a toxicological risk assessment for date seed coffee is conducted. Subchronic studies show that consuming date seed or date seed coffee has no adverse effects. Therefore, currently unavailable chronic toxicity, carcinogenicity, and reproductive toxicity studies may be unnecessary. However, for a comprehensive evaluation, it is recommended to conduct an in vitro mutagenicity test. This review provides information on the safety of date seed coffee and highlights the need for further research.

This study presents a new risk assessment of pulegone, a substance classified as possibly carcinogenic to humans (Group 2B) by the WHO International Agency for Research on Cancer (IARC). The analysis used data from a two-year carcinogenicity studies in rats and mice conducted by the National Toxicology Program (NTP) in 2011. Because of the absence of a no-observed adverse effect level (NOAEL) in these studies, the benchmark dose (BMD) approach was employed as an alternative risk assessment method. The lowest BMD lower confidence level (BMDL) of 4.8 mg/kg b.w./day among the eight endpoints served as the point of departure for calculating an acceptable daily intake (ADI) of 48 μg/kg b.w./day. This new ADI is significantly lower than the previously established tolerable daily intake of 0.1 mg/kg b.w./day set in 1997. The analysis also considered various genotoxicity studies, which indicate that pulegone's effects follow a nongenotoxic, thresholded mechanism. The estimated intake levels of pulegone in the European Union and USA were below the newly calculated ADI, suggesting a low health risk based on current consumption patterns.

Zusammenfassung Hintergrund Anfragen zu Fruchtpflanzen sind ein häufiger Konsultationsgrund von Giftinformationszentren, wobei hervorzuheben ist, dass es keine großen systematischen Studien zur Giftigkeit auf Grundlage von Expositionsdaten gibt. Ziel der Arbeit ist die Bestimmung des Vergiftungsrisikos durch Fruchtpflanzen in Deutschland. Methoden Retrospektive Untersuchung der Daten des Gemeinsamen Giftinformationszentrums Erfurt zu Vergiftungsanfragen bzgl. Fruchtpflanzen (2010–2019) mit ausführlicher Darstellung vorab publizierter Zwischenergebnisse, tabellarischer Handreichung und Pflanzenfotografien als Identifizierungshilfe sowie Trendanalysen. Ergebnisse Aus 16.088 Pflanzenexpositionen mit 16.700 Pflanzen wurden 214 verschiedene Fruchtpflanzenarten identifiziert. 45 Fruchtpflanzenarten (21 %) stellten sich als relevant (≥ 30 Anfragen) heraus, davon 6 (2,8 %) als hochrelevant (≥ 300 Anfragen). Allen relevanten Pflanzen wurde eine definierte Risikokategorie (RK) zugeordnet: RK 0 (2; 4,4 %), RK 1 (26; 57,8 %), RK 2 (12; 26,7 %) und RK 3 (5; 11,1 %). Von den Anfragen bezogen sich 6 % (459/7607) auf RK 0, 47,9 % (3645/7607) auf RK 1, 39,3 % auf RK 2 (2986/7607) und 6,8 % (517/7607) auf RK 3. 69,5 % (5284/7607) der Anfragen betrafen Kleinkinder (1 bis < 6 Jahre). Die Expositionsfolgen waren für alle Altersklassen zu 82 % symptomlos, 14,7 % leichtgradig, 3 % mittelschwer und 0,3 % schwer, wobei schwere Vergiftungen durch 7 Pflanzenarten verursacht wurden. Eine Intervention wurde in 66,8 % (5079) der Anfragen eingeleitet. Anfragen betrafen am häufigsten: Taxus baccata, Ligustrum vulgare, Physalis alkekengi, Prunus laurocerasus, Convallaria majalis, Mahonia spec., Sambucus spec., Lonicera spec., Sorbus aucuparia, Thuja spec., Hedera helix und Cotoneaster spec. Diskussion Vergiftungen durch Fruchtpflanzen in Deutschland sind selten. Es besteht allerdings ein hoher Informations- und Aufklärungsbedarf.

Chlorogenic and isochlorogenic acids are naturally occurring antioxidant dietary polyphenolic compounds found in high concentrations in plants, fruits, vegetables, coffee, and coffee by-products. The objective of this review was to assess the potential health risks associated with the oral consumption of coffee by-products containing chlorogenic and isochlorogenic acids, considering both acute and chronic exposure. An electronic literature search was conducted, revealing that 5-caffeoylquinic acid (5-CQA) and 3,5-dicaffeoylquinic acid (3,5-DCQA) are the major chlorogenic acids found in coffee by-products. Toxicological, pharmacokinetic, and clinical data from animal and human studies were available for the assessment, which indicated no significant evidence of toxic or adverse effects following acute oral exposure. The current state of knowledge suggests that long-term exposure to chlorogenic and isochlorogenic acids by daily consumption does not appear to pose a risk to human health when observed at doses within the normal range of dietary exposure. As a result, the intake of CQAs from coffee by-products can be considered reasonably safe.

Background. Inquiries about fruit plants are a frequent reason for consultation with poison information centers, although it should be emphasized that there are no large systematic studies on toxicity based on exposure data. The aim of this work is to determine the risk of poisoning by fruit plants in Germany.Methods. Retrospective study of data from the Erfurt Joint Poison Information Center on poisoning inquiries regarding fruit plants (2010-2019) with a detailed presentation of interim results, a tabular handout, plant photos as identification aids, and trend analyses.Results. From 16,088 plant exposures with 16,700 plants, 214 different fruit plant species were identified. Forty-five fruit plant species (21%) turned out to be relevant (>= 30 inquiries) and of these, 6 (2.8%) turned out to be highly relevant (>= 300 inquiries). All relevant plants were assigned a defined risk category (RC): RC 0 (2; 4.4%), RC 1 (26; 57.8%), RC 2 (12; 26.7%), and RC 3 (5; 11.1%). Regarding the inquiries, 6% (459/7607) were related to RC 0; 47.9% (3645/7607) to RC 1; 39.3% to RC 2 (2986/7607); and 6.8% (517/7607) to RC 3. Of the inquiries, 69.5% (5284/7607) were related to young children (1 to < 6 years). Exposure outcomes for all age groups were asymptomatic in 82%, mild in 14.7%, moderate in 3%, and severe in 0.3%, with severe poisoning caused by seven plant species. Interventions were initiated in 66.8% (5079) of the inquiries. Inquiries were most frequently related to Taxus baccata, Ligustrum vulgare, Physalis alkekengi, Prunus laurocerasus, Convallaria majalis, Mahonia spec., Sambucus spec., Lonicera spec., Sorbus aucuparia, Thuja spec., Hedera helix, and Cotoneaster spec.Discussion. Poisoning by fruit plants in Germany is rare. However, there is a great need for information and education.

BackgroundClassical two-dimensional (2D) cell culture as a drug or nanoparticle test system only poorly recapitulates in vivo conditions. Animal studies are costly, ethically controversial, and preclude large-scale testing. Methods and ResultsWe established a three-dimensional (3D) tissue slice air-liquid interface (ALI) culture model for nanoparticle testing. We developed an optimized procedure for the reproducible generation of large sets of tissue slices from tumor xenografts that retain their tissue architecture. When used for the analysis of nanoparticles based on chemically modified polyethylenimines (PEIs) to deliver siRNA or DNA, differences in transfection efficacy and cytotoxicity between nanoparticles were observed more clearly than in 2D cell culture. While nanoparticle efficacies between cell culture and the tissue slice model overall correlated, the tissue slice model also identified particularly suitable candidates whose efficacy was underestimated in 2D cell culture and had already been shown in previous in vivo studies. ConclusionThe ex vivo 3D tissue slice ALI culture model is a powerful system that allows the effective evaluation of biological nanoparticle efficacy and biocompatibility in an intact tissue environment. It is comparably inexpensive, time-saving, and follows the 3R principle, while allowing the identification of critical nanoparticle properties and optimal candidates for in vivo applications.

Coffee bean harvesting incurs various by-products known for their long traditional use. However, they often still end up being a waste instead of being used to their full potential. On the European market, coffee cherry (cascara) products are not yet common, and a novel food approval for beverages made from coffee cherry pulp was issued only recently. In this article, exposure and risk assessment of various products such as juice, jam, jelly, puree, and flour made from coffee cherry pulp and husk are reviewed. Since caffeine in particular, as a bioactive ingredient, is considered a limiting factor, safe intake will be derived for different age groups, showing that even adolescents could consume limited quantities without adverse health effects. Moreover, the composition can be influenced by harvesting methods and processing steps. Most interestingly, dried and powdered coffee cherry can substitute the flour in bakery products by up to 15% without losing baking properties and sensory qualities. In particular, this use as a partial flour substitute is a possible approach to counteract rising grain prices, transport costs, and disrupted supply chains, which are caused by the Russia–Ukraine war and changing climatic conditions. Thus, the supply of affordable staple foods could be partially ensured for the inhabitants of countries that depend on imported wheat and cultivate coffee locally by harvesting both beans and by-products.

BACKGROUND Questions on poisoning by plants are a common reason for inquiries to poison information centers (PIC). Over the years 2011-2020, plant poisoning was the subject of 15% of all inquiries to the joint poison information center in Erfurt, Germany (Gemeinsames Giftinformationszentrum Erfurt, GGIZ) that concerned poisoning in children (2.3% in adults). In this patient collective, plant poisoning occupied third place after medical drugs (32%) and chemical substances (24%), and was a more common subject of inquiry than mushroom poisoning (1.5%). METHODS This review is based on pertinent publications retrieved by a selective literature search in PubMed/TOXLINE on plant poisoning and on 12 epidemiologically and toxicologically relevant domestic species of poisonous plants in risk categories 2 and 3 (up to 2021). RESULTS Medical personnel should have basic toxicological knowledge of the following highly poisonous plants: wolfsbane (aconitum), belladonna, angel's trumpet, cowbane (cicuta virosa), autumn crocus, hemlock, jimson weed, henbane, castor bean (ricinus), false hellebore, foxglove (digitalis), and European yew. The intoxication is evaluated on the basis of a structured history (the "w" questions) and the clinical manifestations (e.g., toxidromes). Special analysis is generally not readily available and often expensive and time-consuming. In case of poisoning, a poison information center should be contacted for plant identification, risk assessment, and treatment recommendations. Specimens of plant components and vomit should be obtained, if possible, for further testing. Measures for the elimination of the poisonous substance may be indicated after a risk-benefit analysis. Specific antidotes are available for only a few types of plant poisoning, e.g., physostigmine for tropane alkaloid poisoning or digitalis antibodies for foxglove poisoning. The treatment is usually symptomatic and only rarely evidence-based. Individualized medical surveillance is recommended after the ingestion of large or unknown quantities of poisonous plant components. CONCLUSION The clinician should be able to recognize dangerous domestic species of poisonous plants, take appropriate initial measures, and avoid overdiagnosis and overtreatment. To improve patient care, systematic epidemiological and clinical studies are needed.

Traumatic brain injury (TBI) is a major cause of death and its accurate diagnosis is an important concern of daily forensic practice. However, it can be challenging to diagnose TBI in cases where macroscopic signs of the traumatic head impact are lacking and little is known about the circumstances of death. In recent years, several post-mortem studies investigated the possible use of biomarkers for providing objective evidence for TBIs as the cause of death or to estimate the survival time and time since death of the deceased. This work systematically reviewed the available scientific literature on TBI-related biomarkers to be used for forensic purposes. Post-mortem TBI-related biomarkers are an emerging and promising resource to provide objective evidence for cause of death determinations as well as survival time and potentially even time since death estimations. This literature review of forensically used TBI-biomarkers revealed that current markers have low specificity for TBIs and only provide limited information with regards to survival time estimations and time since death estimations. Overall, TBI fatality-related biomarkers are largely unexplored in compartments that are easily accessible during autopsies such as urine and vitreous humor. Future research on forensic biomarkers requires a strict distinction of TBI fatalities from control groups, sufficient sample sizes, combinations of currently established biomarkers, and novel approaches such as metabolomics and mi-RNAs.

Convection-enhanced delivery (CED) has been introduced as a concept in cancer treatment to generate high local concentrations of anticancer therapeutics and overcome the limited diffusional distribution, e.g., in the brain. RNA interference provides interesting therapeutic options to fight cancer cells but requires nanoparticulate (NP) carriers with a size below 100 nm as well as a low zeta potential for CED application. In this study, we investigated calcium phosphate NPs (CaP-NPs) as siRNA carriers for CED application. Since CaP-NPs tend to aggregate, we introduced a new terpolymer (o14PEGMA(1:1:2.5) NH3) for stabilization of CaP-NPs intended for delivery of siRNA to brain cancer cells. This small terpolymer provides PEG chains for steric stabilization, and a fat alcohol to improve interfacial activity, as well as maleic anhydrides that allow for both labeling and high affinity to Ca(II) in the hydrolyzed state. In a systematic approach, we varied the Ca/P ratio as well as the terpolymer concentration and successfully stabilized NPs with the desired properties. Labeling of the terpolymer with the fluorescent dye Cy5 revealed the terpolymer's high affinity to CaP. Importantly, we also determined a high efficiency of siRNA binding to the NPs that caused very effective survivin siRNA silencing in F98 rat brain cancer cells. Cytotoxicity investigations with a standard cell line resulted in minor and transient effects; no adverse effects were observed in organotypic brain slice cultures. However, more specific cytotoxicity investigations are required. This study provides a systematic and mechanistic analysis characterizing the effects of the first oligomer of a new class of stabilizers for siRNA-loaded CaP-NPs.