Toxicological Assessment of Roasted Coffee Silver Skin (Testa of Coffea sp.) as Novel Food Ingredient.

Roasted coffee silver skin is a coffee by-product, the uses of which are currently limited, e.g., as fertilizer, for energy production, or animal feed. Due to a low content of fat and carbohydrates combined with a high content of fiber, polyphenols and proteins, roasted silver skin is a valuable possible food ingredient. Potential applications include partial flour replacement in bakery products, as antioxidant and providing protein or fiber sources in sports or functional foods. As no relevant consumption of isolated silver skin occurred before 1997 in the European Union (EU), it was classified as a novel food in need of premarketing approval. Novel food applications must meet legal requirements for compositional and toxicological information. This review presents information on silver skin composition and toxicological studies. Several in vitro studies and subchronic in vivo studies are available with negative results, not suggesting a need for further studies on carcinogenic effects, reproduction, or chronic toxicity. All available studies so far concluded that no toxic effects of silver skin were found or are to be expected. For a novel food application in the EU, further in vitro studies on mutagenic potential may be needed to close a formal data gap.

Assessment of black cumin (Nigella sativa L.) as a food ingredient and putative therapeutic agent.

The whole or ground seeds of the food ingredient Nigella sativa L., known in Western culture as "black cumin" or "black caraway", has a three-millennial history of use in Middle- and Far-Eastern cultures as a food ingredient. The seed and its extracts have also been increasingly reported as a successful therapeutic agent with efficacy often attributed to the presence of the powerful antioxidant, thymoquinone. However, quantitative analysis of the seed (especially the volatile fraction) yields widely variable results, which may be due to one or a combination of different crop origins or possible varietal differences, contamination/adulteration, method of extraction, stage of maturation of the extracted seed and other factors. Nonetheless, despite the reported wide variability in bioactive constituents, many publications cite quantifiable outcomes in in vitro and in vivo toxicity testing and in clinical trials. There are a few reports describing allergic reactions in humans when N. sativa extracts are applied to the skin. Notwithstanding the foregoing, N. sativa seeds, used as a food ingredient at historical levels of consumption and as traditionally practiced are safe and Generally Recognized As Safe.

Toxic element levels in ingredients and commercial pet foods.

Nowadays, there is a growing concern about contamination of toxic metals (TM) in pet food due to the great potential for health risks of these elements. TM concentrations in commercial pet foods (n = 100) as well as in ingredients used in their composition (n = 100) were analyzed and compared to the Food and Drug Administration (FDA) maximum tolerable level (MTL), and the TM concentrations found in the different sources of carbohydrate, protein, and fat were compared. The TM concentrations were determined by inductively coupled plasma with optical emission spectrometry (ICP-OES). Concentrations above the MTL for aluminum, mercury, lead, uranium, and vanadium were observed in both dog and cat foods, and the percentage of dog foods that exceeded the MTL of these TM were: 31.9%; 100%; 80.55%; 95.83%; and 75%, respectively, and in cat foods: 10.71%; 100%; 32.14%; 85.71%; 28.57%, respectively. The MTL values of these TMs and the mean values in dog foods (mg/kg dry matter basis) (MTL [mean ± standard deviation]) were: aluminum: 200 (269.17 ± 393.74); mercury: 0.27 (2.51 ± 1.31); lead: 10 (12.55 ± 4.30); uranium: 10 (76.82 ± 28.09); vanadium: 1 (1.35 ± 0.69), while in cat foods were: aluminum: 200 (135.51 ± 143.95); mercury: 0.27 (3.47 ± 4.31); lead: 10 (9.13 ± 5.42); uranium: 10 (49.83 ± 29.18); vanadium: 1 (0.81 ± 0.77). Dry foods presented higher concentrations of most TM (P < 0.05) than wet foods (P < 0.05). Among the carbohydrate sources, there were the highest levels of all TM except cobalt, mercury, and nickel in wheat bran (P < 0.05), while among the protein sources, in general, animal by-products had higher TM concentrations than plant-based ingredients. Pork fat had higher concentrations of arsenic, mercury, and antimony than fish oil and poultry fat. It was concluded that the pet foods evaluated in this study presented high concentrations of the following TM: aluminum, mercury, lead, uranium, and vanadium.

The First Report to Evaluate Safety of Cyanobacterium Leptolyngbya sp. KIOST-1 for Use as a Food Ingredient: Oral Acute Toxicity and Genotoxicity Study.

Leptolyngbya sp. KIOST-1 (LK1) is a newly isolated cyanobacterium that shows no obvious cytotoxicity and contains high protein content for both human and animal diets. However, only limited information is available on its toxic effects. The purpose of this study was to validate the safety of LK1 powder. Following Organisation for Economic Co-operation and Development (OECD) guidelines, a single-dose oral toxicity test in Sprague Dawley rats was performed. Genotoxicity was assessed using a bacterial reverse mutation test with Salmonella typhimurium (strains TA98, TA100, TA1535, and TA1537) and Escherichia coli WP2 uvrA, an in vitro mammalian chromosome aberration test using Chinese hamster lung cells, and an in vivo mammalian erythrocyte micronucleus test using Hsd:ICR (CD-1) SPF mouse bone marrow. After LK1 administration (2,500 mg/kg), there were no LK1-related body weight changes or necropsy findings. The reverse mutation test showed no increased reverse mutation upon exposure to 5,000 µg/plate of the LK1 powder, the maximum tested amount. The chromosome aberration test and micronucleus assay demonstrated no chromosomal abnormalities and genotoxicity, respectively, in the presence of the LK1 powder. The absence of physiological findings and genetic abnormalities suggests that LK1 powder is appropriate as a candidate biomass to be used as a safe food ingredient.

Food ingredient safety evaluation: Utility and relevance of toxicokinetic methods.

The use of toxicokinetic (TK) data is becoming more prevalent in the evaluation of food ingredient safety as more TK information is being incorporated in safety data packages. Data demonstrating "1) the extent of absorption, 2) tissue distribution, 3) pathways and rates of metabolism, and 4) rate(s) of elimination" of food ingredients and their metabolites of intermediate and high toxicological potential may be useful for planning and designing toxicity studies, selecting doses for toxicity studies, addressing species differences, and understanding the potential modes of action to evaluate their safety. TK data reported in the literature or generated from mechanistic TK studies can be analyzed using mathematical methods, including compartment and noncompartment TK methods, whose predictions can enhance interpretation of observed effects. Because of recent advancements, several approaches have been developed to improve sensitivity of analyses of available TK data and reduce uncertainty for evaluating safety of food ingredients. An example of advanced TK methods is physiologically-based TK (PBTK) modeling that incorporates physiological/biochemical parameters into a TK framework to predict internal exposure. In this review, we discuss the utility of some TK methods and explore their relevance and potential value for food ingredient safety evaluation. We also describe the strengths and limitations of these TK methods and discuss current challenges and opportunities for expanding their application for evaluating safety of food ingredients. This review represents a state of science report, and not a guidance document, on the utility and relevance of TK methods for the safety evaluation of food ingredients.

Applicability of in silico genotoxicity models on food and feed ingredients.

Evaluation of the genotoxic potential of food and feed ingredients is required in the development of new substances and for their registration. In addition to in vitro and in vivo assays, in silico tools such as expert alert-based and statistical models can be used for data generation. These in silico models are commonly used among the pharmaceutical industry, whereas the food industry has not widely adopted them. In this study, the applicability of in silico tools for predicting genotoxicity was evaluated, with a focus on bacterial mutagenicity, in vitro and in vivo chromosome damage assays. For this purpose, a test set of 27 food and feed ingredients including vitamins, carotenoids, and nutraceuticals with experimental genotoxicity data was constructed from proprietary data. This dataset was run through multiple models and the model applicability was analyzed. The compounds were generally within the applicability domain of the models and the models predicted the compounds correctly in most of the cases. Although the regulatory acceptance of in silico tools as single data source is still limited, the models are applicable and can be used in the safety evaluation of food and feed ingredients.

Genotoxicity and sub-chronic toxicity of MYOLUTION® (branched chain keto acids).

MYOLUTION®, which consists of a mixture of the branched chain keto acids, keto-leucine, keto-isoleucine and keto-valine, as their calcium salts, may potentially be used as a food ingredient based on the reported contributions of these compounds to muscle health and exercise performance. Tests on genotoxicity and sub-chronic toxicity were performed to evaluate the safety of branched chain keto acids. No genotoxic effects were observed in the bacterial mutation assay or the in vitro micronucleus assay in human lymphocytes. In the 28 day and 90 day repeated dose toxicity studies no test item related mortality or toxicological effects on clinical signs, body weight, food consumption, urine parameters, hematology, clinical biochemistry parameters, organ weight, gross pathological findings and histopathology were observed. Based on the studies described here, MYOLUTION® does not exert a genotoxic effect, and a no-observed-adverse-effect-level of 3318.38 mg/kg bw/day in males and 3733.28 mg/kg bw/day in females was determined in the 90 day repeated dose toxicity study.

Genotoxicity, acute and subchronic toxicity evaluation of savory food ingredients.

The potential toxicity of two savory food ingredients produced by fermentation of enzymatically hydrolyzed corn starch (Savory Base 100 and Savory Base 200) was evaluated individually in a bacterial reverse mutation assay, an in vitro mammalian cell gene mutation assay, an acute oral study and as a mixture in a 90-day dietary study. In the bacterial reverse mutation and in vitro mammalian cell gene mutation assays, neither ingredient was mutagenic at concentrations up to 5000 µg/plate and 5000 µg/mL, respectively in the presence and absence of metabolic activation. In the acute study, the no-observed-adverse-effect level (NOAEL) for each Savory Base 100 and Savory Base 200 in male and female rats was 2000 mg/kg body weight. In the 90-day study, the hematology and clinical chemistry findings and histopathological changes noted in the liver, heart and kidneys were deemed to be of no toxicological significance, as the mean values were within the historical control range, were not dose-dependent, occurred at a similar frequency in control groups, or only occurred in the control group. Considering these findings, the NOAEL for Savory Base 100 and Savory Base 200 was 2333 and 1167 mg/kg body weight, respectively, the highest dose tested in each case.