Occurrence of Alkenylbenzenes in Plants: Flavours and Possibly Toxic Plant Metabolites.

Alkenylbenzenes are naturally occurring secondary plant metabolites. While some of them are proven genotoxic carcinogens, other derivatives need further evaluation to clarify their toxicological properties. Furthermore, data on the occurrence of various alkenylbenzenes in plants, and especially in food products, are still limited. In this review, we tempt to give an overview of the occurrence of potentially toxic alkenylbenzenes in essential oils and extracts from plants used for flavoring purposes of foods. A focus is layed on widely known genotoxic alkenylbenzenes, such as safrole, methyleugenol, and estragole. However, essential oils and extracts that contain other alkenylbenzenes and are also often used for flavoring purposes are considered. This review may re-raise awareness of the need for quantitative occurrence data for alkenylbenzenes in certain plants but especially in final plant food supplements, processed foods, and flavored beverages as the basis for a more reliable exposure assessment of alkenylbenzenes in the future.

3-MCPD as contaminant in processed foods: State of knowledge and remaining challenges.

3-Chloro-1,2-propanediol (3-MCPD) and its fatty acid esters (FE) are present as contaminants in different processed foods. Based on the available toxicological data the potential risk of 3-MCPD and its FE to human health was assessed by risk assessment authorities, including the European Food Safety Authority (EFSA). Considering the available data, EFSA concluded that 3-MCPD is a non-genotoxic compound exhibiting secondary carcinogenic effects in rodents. A tolerable daily intake of 2 µg/kg body weight and day was derived by EFSA for free and ester-bound 3-MCPD in 2018. However, there are still different pending issues that have remained unclear until now. Here, we summarize the current knowledge regarding 3-MCPD and its FE with a focus on pending issues regarding exposure assessment via biomarkers as well as the identification of (toxic) metabolites formed after exposure to FE of 3-MCPD and their modes of action.

Myristicin and Elemicin: Potentially Toxic Alkenylbenzenes in Food.

Alkenylbenzenes represent a group of naturally occurring substances that are synthesized as secondary metabolites in various plants, including nutmeg and basil. Many of the alkenylbenzene-containing plants are common spice plants and preparations thereof are used for flavoring purposes. However, many alkenylbenzenes are known toxicants. For example, safrole and methyleugenol were classified as genotoxic carcinogens based on extensive toxicological evidence. In contrast, reliable toxicological data, in particular regarding genotoxicity, carcinogenicity, and reproductive toxicity is missing for several other structurally closely related alkenylbenzenes, such as myristicin and elemicin. Moreover, existing data on the occurrence of these substances in various foods suffer from several limitations. Together, the existing data gaps regarding exposure and toxicity cause difficulty in evaluating health risks for humans. This review gives an overview on available occurrence data of myristicin, elemicin, and other selected alkenylbenzenes in certain foods. Moreover, the current knowledge on the toxicity of myristicin and elemicin in comparison to their structurally related and well-characterized derivatives safrole and methyleugenol, especially with respect to their genotoxic and carcinogenic potential, is discussed. Finally, this article focuses on existing data gaps regarding exposure and toxicity currently impeding the evaluation of adverse health effects potentially caused by myristicin and elemicin.

The chemical structure impairs the intensity of genotoxic effects promoted by 1,2-unsaturated pyrrolizidine alkaloids in vitro.

1,2-unsaturated pyrrolizidine alkaloids (PAs) represent a large group of secondary plant metabolites exhibiting hepatotoxic, genotoxic, and carcinogenic properties upon bioactivation. To examine how the degree of esterification affects the genotoxic profile of PA we investigated cytotoxicity, histone H2AX phosphorylation, DNA strand break induction, cell cycle perturbation, micronuclei formation, and aneugenic effects in different cell models. Analysis of cytotoxicity and phosphorylation of histone H2AX was structure- and concentration-dependent: diester-type PAs (except monocrotaline) showed more pronounced effects than monoester-type PAs. Cell cycle analysis identified that diester-type PAs induced a S-phase arrest and a decrease in the occurrence of cells in the G1-phase. The same structure-dependency was observed by flow-cytometric analysis of PA-induced micronuclei in CYP3A4-overexpressing V79 cells. Analysis of centromeres induced by lasiocarpine in the micronuclei by fluorescence in situ hybridization indicated an aneugenic effect in V79h3A4 cells. Comet assays revealed no significant induction of DNA strand breaks for all investigated PAs. Overall, diester-type PAs induced more pronounced effects than monoester-type PAs. Furthermore, our results indicate aneugenic effects upon exposure towards lasiocarpine in vitro. These data improve our understanding how structural features of PA influence the genotoxic profile. Especially, the monoester-type PAs seem to induce less severe effects than other PAs.

Alkenylbenzenes in Foods: Aspects Impeding the Evaluation of Adverse Health Effects.

Alkenylbenzenes are naturally occurring secondary plant metabolites, primarily present in different herbs and spices, such as basil or fennel seeds. Thus, alkenylbenzenes, such as safrole, methyleugenol, and estragole, can be found in different foods, whenever these herbs and spices (or extracts thereof) are used for food production. In particular, essential oils or other food products derived from the aforementioned herbs and spices, such as basil-containing pesto or plant food supplements, are often characterized by a high content of alkenylbenzenes. While safrole or methyleugenol are known to be genotoxic and carcinogenic, the toxicological relevance of other alkenylbenzenes (e.g., apiol) regarding human health remains widely unclear. In this review, we will briefly summarize and discuss the current knowledge and the uncertainties impeding a conclusive evaluation of adverse effects to human health possibly resulting from consumption of foods containing alkenylbenzenes, especially focusing on the genotoxic compounds, safrole, methyleugenol, and estragole.

Aggregated aluminium exposure: risk assessment for the general population.

Aluminium is one of the most abundant elements in earth's crust and its manifold uses result in an exposure of the population from many sources. Developmental toxicity, effects on the urinary tract and neurotoxicity are known effects of aluminium and its compounds. Here, we assessed the health risks resulting from total consumer exposure towards aluminium and various aluminium compounds, including contributions from foodstuffs, food additives, food contact materials (FCM), and cosmetic products. For the estimation of aluminium contents in foodstuff, data from the German "Pilot-Total-Diet-Study" were used, which was conducted as part of the European TDS-Exposure project. These were combined with consumption data from the German National Consumption Survey II to yield aluminium exposure via food for adults. It was found that the average weekly aluminium exposure resulting from food intake amounts to approx. 50% of the tolerable weekly intake (TWI) of 1 mg/kg body weight (bw)/week, derived by the European Food Safety Authority (EFSA). For children, data from the French "Infant Total Diet Study" and the "Second French Total Diet Study" were used to estimate aluminium exposure via food. As a result, the TWI can be exhausted or slightly exceeded-particularly for infants who are not exclusively breastfed and young children relying on specially adapted diets (e.g. soy-based, lactose free, hypoallergenic). When taking into account the overall aluminium exposure from foods, cosmetic products (cosmetics), pharmaceuticals and FCM from uncoated aluminium, a significant exceedance of the EFSA-derived TWI and even the PTWI of 2 mg/kg bw/week, derived by the Joint FAO/WHO Expert Committee on Food Additives, may occur. Specifically, high exposure levels were found for adolescents aged 11-14 years. Although exposure data were collected with special regard to the German population, it is also representative for European and comparable to international consumers. From a toxicological point of view, regular exceedance of the lifetime tolerable aluminium intake (TWI/PTWI) is undesirable, since this results in an increased risk for health impairments. Consequently, recommendations on how to reduce overall aluminium exposure are given.

Risk assessment of pyrrolizidine alkaloids in food of plant and animal origin.

Acute liver toxicity, specifically in the form of hepatic veno-occlusive disease (HVOD), is known from reports on human poisonings following ingestions of 1,2-unsaturated pyrrolizidine alkaloids (PAs) containing herbs. Recently PA exposure via common foods contaminated via PA-producing plants raised concern, especially regarding the potential of genotoxicity and carcinogenicity. The health risks related to the estimated exposures to PAs from food were assessed. With respect to common foods, herbal teas and teas are the main sources through which consumers can be exposed to PAs. For high long-term consumption of these foods a possible health concern has been revealed in the assessment of chronic risks referring to a BMDL10 of 237 µg/kg bw per day recently established by EFSA based on model averaging for data on riddelliine. However, acute health damage from acute or short-term intake of PAs via common food is considered to be unlikely. Food supplements on the basis of PA-producing plants may significantly contribute to PA exposures and their intake is associated with risks of acute and chronic toxicity. However, no health risks have to be expected from the consumption of food supplements based on oil-based preparations of PA-producing plants, which were described to be free of PAs.

Safety Aspects of the Use of Quercetin as a Dietary Supplement.

The flavonoid quercetin is frequently found in low amounts as a secondary plant metabolite in fruits and vegetables. Isolated quercetin is also marketed as a dietary supplement, mostly as the free quercetin aglycone, and frequently in daily doses of up to 1000 mg d-1 exceeding usual dietary intake levels. The present review is dedicated to safety aspects of isolated quercetin used as single compound in dietary supplements. Among the numerous published human intervention studies, adverse effects following supplemental quercetin intake have been rarely reported and any such effects were mild in nature. Published adequate scientific data for safety assessment in regard to the long-term use (>12 weeks) of high supplemental quercetin doses (≥1000 mg) are currently not available. Based on animal studies involving oral quercetin application some possible critical safety aspects could be identified such as the potential of quercetin to enhance nephrotoxic effects in the predamaged kidney or to promote tumor development especially in estrogen-dependent cancer. Furthermore, animal and human studies with single time or short-term supplemental quercetin application revealed interactions between quercetin and certain drugs leading to altered drug bioavailability. Based on these results, some potential risk groups are discussed in the present review.

[Heat-induced contaminants in foodstuffs : Acrylamide, furan, and fatty acid esters of monochloropropanediols and glycidol]. / Erhitzungsbedingte Kontaminanten in Lebensmitteln : Acrylamid, Furan und Fettsäureester von Monochlorpropandiolen und Glycidol.

The production and preparation of foodstuffs may entail at high temperatures the generation of undesirable, potentially harmful compounds. Among the best investigated heat-induced contaminants are acrylamide, furan, and the fatty acid esters of glycidol and the monochloropropanediols. This article presents the main insights into the formation, toxicology, and exposure of these compounds. Acrylamide and glycidol were characterized as carcinogens with a genotoxic mechanism in animal experiments. Their content in foods should be minimized. For 3­monochloropropanediol (3-MCPD), a tolerable daily intake can be derived. In contrast, a complete risk assessment is currently not possible for furan and 2­MCPD owing to insufficient data.Many other heat-induced substances in foodstuffs were identified in addition to the compounds mentioned above, but for most no data on their toxicological properties and human exposure is available. Therefore, no risk assessment can currently be undertaken for these compounds. To prioritize this large number of compounds according to their possible hazard potential, it is reasonable to utilize computer modeling programs for the prediction of defined toxicological endpoints based on the molecular chemical structures. However, substances classed as a priority must be further investigated with regard to the toxicology and quantification of the food content of these compounds to allow a meaningful risk assessment.

Determination of beam parameters and coherence properties of laser radiation by use of an extended Hartmann-Shack wave-front sensor.

A combination of a Hartmann-Shack sensor and a standard far-field measurement on one single detector is proposed. The technique is fast and operates without movable parts, thus permitting a compact design. It is not only suited for characterization of the wave-front distribution but may also be considered for determination of the important parameters of beam width, beam divergence, and beam propagation ratio M2 of partially coherent laser beams. First results indicate that a fairly thorough beam characterization, including spatial coherence, propagation characteristics, and beam quality, can be achieved with this method.