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Xanthobacter sp. SoF1 (SoF1) is an autotrophic hydrogen-oxidizing bacteria that produces protein-rich biomass and has potential to be an alternative protein source that is more environmentally sustainable than animal and plant derived proteins. A protein-rich powder derived from SoF1 was the test material in a 90-day repeated-dose oral toxicity study to explore major toxic effects, demonstrate target organs, and provide an estimate of a no-observed-adverse-effect level (NOAEL). Daily doses of 0 (vehicle only), 375, 750, and 1500 mg/kg bw/day of the test material were administered by gavage to 10 Han:WIST rats/sex/group. An additional group was administered 1290 mg/kg bw/day whey protein concentrate as positive control. No treatment-related adverse effects were observed, and no target organs were determined after 90/91 days of consecutive administration of the test item. A NOAEL of 1500 mg/kg bw/day was determined.
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Interest in microalgae products for use in food is increasing, as demands for sustainable and cost-effective food choices grow due to the escalating global population and increase in climate-related struggles with agriculture. Toxicological assessments of some species of microalgae have been conducted, but there were little data available for the oral consumption of the red microalgae Porphyridium purpureum and no data on genotoxicity. This article articulates a genotoxicity assessment and a 90-day repeated dose oral toxicity study in rats performed according to OECD guidelines. Under the experimental conditions applied, the test item did not induce gene mutations by base pair changes or frameshifts in the genome of the strains used in the bacterial reverse mutation test. Similarly, the test item did not induce structural chromosomal aberrations in V79 hamster lung cells. The test item also did not cause chromosomal damage in bone marrow of mice in the mammalian micronucleus test. The no observed adverse effect level (NOAEL) of the 90-day repeated dose oral toxicity study in rats was determined to be the highest dose tested, 3000 mg/kg bw/day. These data add to the body of evidence regarding the safety of P. purpureum for human consumption.
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Mulberry (genus Morus) leaves have long been used as a human food, especially in Asia, and animal feed. More recently, mulberry leaf extracts have been introduced as a convenient way to consume mulberry for non-nutritional functional effects. Reducose® 5% is an Morus alba leaf extract that has been highly purified and standardized to a content of 5 ± 0.5% 1-deoxynojirimycin, a naturally present polyhydroxylated piperidine alkaloid analog of D-glucose. This extract has previously been evaluated in acute and subacute (28-day) oral toxicity studies in which no adverse effects of the test item were observed in mice or rats, respectively. Due to continued and growing interest in the extract in multinational markets, we have now further investigated potential toxic effects in subchronic (90-day) oral toxicity study in male and female Han:WIST rats. The test item was administered at doses of 850, 1700, and 2550 mg/kg bw/day, and did not cause adverse effects in clinical signs, body weight development, clinical pathology, gross pathology, or histopathology in comparison to the vehicle-control group. The no-observed-adverse-effect-level was determined to be 2550 mg/kg bw/day. These results add to the existing body of both preclinical and clinical work relevant to the safety of the extract and of interest to regulators in various global markets.
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Currently, there is much interest in the sales and study of consumable Cannabis sativa L. products that contain relatively high levels of cannabidiol (CBD) and low levels of Δ-9-tetrahydrocannabinol. While there are published safety evaluations for extracts containing low concentrations of CBD, toxicological assessments for those with higher concentrations are still scant in the public domain. In this paper, genotoxicity tests and a 90-day repeated-dose toxicity study of an ethanolic extract of C. sativa containing ~85% CBD were performed following relevant OECD guidelines. No increased gene mutations were observed in a bacterial reverse mutation assay compared to controls up to the maximum recommended concentration of the guideline. An in vitro chromosomal aberration assay showed no positive findings in the short-term (3 h) treatment assays. Long-term treatment (20 h) showed an increased number of cells containing aberrations at the highest dose of 2 µg/mL, which was outside of historical control levels, but not statistically significantly different from the controls. An in vivo micronucleus study showed no genotoxic potential of the test item in mice. A 90-day repeated-dose gavage study using 0, 75, 125, and 175 mg/kg bw/day showed several slight findings that were considered likely to be related to an adaptive response to consumption of the extract by the animals but were not considered toxicologically relevant. These included increases in liver and adrenal weights compared to controls. The NOAEL was determined as 175 mg/kg bw/day, the highest dose tested (equivalent to approximately 150 mg/kg bw/day of CBD).
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There is a growing global interest in using peptides in the health industry for pharmaceuticals, cosmetics, and natural food products. Peptides contain two or more linked amino acids, whereas more than 50 amino acids are classified as polypeptides. Although there is a growing level of interest in the use of peptides in the health and wellness industry, there is a lack of literature pertaining to a specific tripeptide derived from arginine, alanine, and lysine (RAK) that is of interest for human dietary use. Therefore, a 90-day repeated-dose toxicity study was performed in rats to evaluate the subchronic oral toxicity of RAK. Eighty Han:WIST rats were administered RAK by gavage at doses of 0, 250, 500, or 1000 mg/kg bw/day. There were no mortalities or other treatment related effects, and no target organs were identified. A no-observed-adverse-effect-level (NOAEL) of 1000 mg/kg bw/day, the highest dose tested, was determined. This study will contribute to the body of research in regard to the safety of the use of RAK.
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Alanina , Lisina , Humanos , Ratos , Animais , Lisina/toxicidade , Alanina/toxicidade , Arginina/toxicidade , Nível de Efeito Adverso não Observado , Administração Oral , Testes de Toxicidade SubcrônicaRESUMO
Microorganisms have the potential to produce nutrient-rich products that can be consumed as food or feed. The protein-rich powder derived from heat treatment of the whole-cell biomass of polyhydroxybutyrate-deficient Cupriavidus necator, a metabolically versatile organism that uses elements found in the air, is an example of such a product. To assess the safety of the protein powder for use as a nutritional ingredient in human food, in accordance with internationally accepted standards, its genotoxic potential and repeated-dose oral toxicity were investigated. A bacterial reverse mutation test, an in vitro mammalian chromosomal aberration test, and an in vivo mammalian micronucleus test were performed. No evidence of mutagenicity or genotoxicity was found. Additionally, a 90-day repeated-dose oral toxicity study in rats was completed, in which a total of 100 male and female Wistar rats were exposed by gavage to daily doses of 1000, 2000, or 3000 mg/kg bw/day of the test material. Following 90 days of continuous exposure, no mortality or treatment-related adverse effects were observed and no target organs were identified. Therefore, a no observed adverse effect level was determined at 3000 mg/kg bw/day, the highest dose tested.
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Cupriavidus necator , Ratos , Masculino , Humanos , Feminino , Animais , Ratos Wistar , Pós/toxicidade , Nível de Efeito Adverso não Observado , Testes de Mutagenicidade , MamíferosRESUMO
There is an economic interest, both for food security and for the non-meat-eating population, in the development of novel, sustainable sources of high-quality protein. The green algae Chlamydomonas reinhardtii has already been developed for this purpose, and the closely related species, Chlamydomonas debaryana, is a complementary source that also presents some additional advantages, such as reduced production cost. To determine whether C. debaryana may have a similar safety profile to that of C. reinhardtii, a wild type strain was obtained, designated TS04 after confirmation of its identity, and subjected to a battery of preclinical studies. Genetic toxicity was evaluated using a bacterial reverse mutation test, an in vitro mammalian chromosomal aberration test, and an in vivo mammalian micronucleus test in a mouse model. No genotoxic potential (e.g., mutagenicity and clastogenicity) was observed in these tests under the employed conditions up to maximum recommended concentrations or doses. To assess general toxicity, a 90-day repeated-dose oral toxicity study was conducted in rats. No mortality or adverse effects were observed, and no target organs were identified up to the maximum feasible dose, due to solubility, of 4,000 mg/kg bw/day. The no-observed-adverse-effect level was determined as the highest dose tested. A digestibility study in simulated gastric fluid was conducted and determined that TS04 has low allergenic potential, exhibiting rapid digestion of proteins. Due to the negative results of our evaluation, it is reasonable to proceed with further development and additional investigations to contribute towards a safety assessment of the proposed use in food for human consumption.
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Chlamydomonas , Clorófitas , Camundongos , Ratos , Humanos , Animais , Biomassa , Nível de Efeito Adverso não Observado , Aberrações Cromossômicas , Chlamydomonas/metabolismo , MamíferosRESUMO
Veillonella atypica is a nonmotile, nonsporulating anaerobic bacteria commonly found in various human biofilms. V. atypica FB0054 was isolated from the gastrointestinal tract of marathon runners, who have increased amounts of this species after athletic events. Interestingly, the consumption of this strain by rodents has been shown to increase their treadmill endurance, leading to the hypothesis that consumption of this species may improve athletic performance in humans as well. Further evaluation, in humans, of the usefulness of this strain should be preceded by safety studies. Therefore, the genotoxic and subchronic toxicological potential was evaluated as a contribution to this effort. Genotoxicity investigation was performed using the in vivo comet assay and in vivo mammalian micronucleus assay due to the anaerobic characteristic of the strain. A 90-day, repeated-dose oral toxicity study was performed in rats up to 2200 mg/kg bw/d to investigate general toxicity and identify any target organs. Mitsuoka buffer, a solution shown to preserve the viability of anaerobic bacteria, was used as the vehicle. All three studies revealed no toxicological effects from exposure to FB0054 was isolated from the gastrointestinal tract of marathon runners, who have increased amounts of this species after athletic events. Interestingly, the consumption of this strain by rodents has been shown to increase their treadmill endurance, leading to the hypothesis that consumption of this species may improve athletic performance in humans as well. Further evaluation, in humans, of the usefulness of this strain should be preceded by safety studies. Therefore, the genotoxic and subchronic toxicological potential was evaluated as a contribution to this effort. Genotoxicity investigation was performed using the in vivo comet assay and in vivo mammalian micronucleus assay due to the anaerobic characteristic of the strain. A 90-day, repeated-dose oral toxicity study was performed in rats up to 2200 mg/kg bw/d to investigate general toxicity and identify any target organs. Mitsuoka buffer, a solution shown to preserve the viability of anaerobic bacteria, was used as the vehicle. All three studies revealed no toxicological effects from exposure to FB0054 at the highest doses tested.
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Dano ao DNA , Veillonella , Ratos , Humanos , Animais , Testes para Micronúcleos , Ensaio Cometa , Testes de Toxicidade Subcrônica , Testes de Mutagenicidade , MamíferosRESUMO
Gold nanocrystals (AuNC) are gold nanoparticles (AuNP) relatively homogenous in size at 8-28 nm with clean surfaces and crystalline structures. There are concerns and a lack of consensus in the scientific literature and major regulatory bodies regarding not only the safety of nanoparticles when consumed by humans, but exactly how to determine their safety and whether evidence from a nanoparticle with one set of physiochemical properties extends to one with a different set. Additionally, there are few general long-term toxicity data on AuNP. To our knowledge, the potential toxicity of AuNC specifically, with the above characteristics, or otherwise, has not been investigated in preclinical studies; thus, we conducted a battery of genetic toxicity tests and an oral repeated-dose toxicity test to further explore their safety. AuNC were not mutagenic or clastogenic in bacterial reverse mutation and in vitro mammalian chromosomal aberration tests, respectively, and did not exhibit in vivo genotoxicity in a micronucleus test in mice. In a 60-day, repeated-dose oral toxicity study, rats were administered 0, 2.5, 5, or 10 mg/kg bw/day of AuNC by gavage. No toxicity was identified. Therefore, a no observed adverse effect level was determined as 10 mg/kg body weight/day.
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Ouro/química , Ouro/toxicidade , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Animais , Linhagem Celular , Cricetinae , Feminino , Pulmão/citologia , Masculino , Camundongos , Testes para Micronúcleos , Nível de Efeito Adverso não Observado , Ratos , Ratos WistarRESUMO
Chlamydomonas reinhardtii is a nonpathogenic, nontoxigenic green algae used as a sustainable source of protein in foods. In order to mimic meat-like qualities, a strain rich in protoporphyrin IX (PPIX), an endogenous heme/chlorophyll precursor, was developed using an evolution and selection strategy, and investigations were carried out to evaluate the safety of the novel strain, C. reinhardtii (red), strain TAI114 (TAI114). Digestibility and proteomic evaluations were conducted to determine whether any potentially allergenic or toxic proteins occurred as the result of the mutation process. The genotoxic potential of pure PPIX was evaluated using a bacterial reverse mutation test, an in vitro mammalian chromosomal aberration test, and an in vivo mammalian micronucleus test. Finally, the novel TAI114 biomass was evaluated for general toxicity and identification of target organs in a 90-day repeated-dose oral toxicity study in rats. All proteins were rapidly degraded in pepsin at pH 2.0 suggesting low allergenic potential. The proteomic evaluation indicated that TAI114 biomass contains typical C. reinhardtii proteins. PPIX was unequivocally negative for genotoxic potential and no target organs or adverse effects were observed in rats up to the maximum feasible dose of 4000 mg/kg bw/day TAI114 biomass, which was determined to be the no-observed-adverse-effect-level (NOAEL). These results support the further development and risk characterization of TAI114 biomass as a novel ingredient for use in the meat analogue category of food.
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Proteômica , Protoporfirinas , Animais , Biomassa , Dano ao DNA , Mamíferos/metabolismo , Protoporfirinas/metabolismo , Protoporfirinas/toxicidade , RatosRESUMO
Lithium orotate, the salt of lithium and orotic acid, has been marketed for decades as a supplemental source of lithium with few recorded adverse events. Nonetheless, there have been some concerns in the scientific literature regarding orotic acid, and pharmaceutical lithium salts are known to have a narrow therapeutic window, albeit, at lithium equivalent therapeutic doses 5.5-67 times greater than typically recommended for supplemental lithium orotate. To our knowledge, the potential toxicity of lithium orotate has not been investigated in preclinical studies; thus, we conducted a battery of genetic toxicity tests and an oral repeated-dose toxicity test in order to further explore its safety. Lithium orotate was not mutagenic or clastogenic in bacterial reverse mutation and in vitro mammalian chromosomal aberration tests, respectively, and did not exhibit in vivo genotoxicity in a micronucleus test in mice. In a 28-day, repeated-dose oral toxicity study, rats were administered 0, 100, 200, or 400 mg/kg body weight/day of lithium orotate by gavage. No toxicity or target organs were identified; therefore, a no observed adverse effect level was determined as 400 mg/kg body weight/day. These results are supportive of the lack of a postmarket safety signal from several decades of human consumption.
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Suplementos Nutricionais/toxicidade , Compostos Organometálicos/toxicidade , Administração Oral , Animais , Linhagem Celular , Aberrações Cromossômicas/induzido quimicamente , Cricetulus , Dano ao DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Camundongos , Testes para Micronúcleos , Nível de Efeito Adverso não Observado , Compostos Organometálicos/administração & dosagem , Ratos , Testes de Toxicidade SubagudaRESUMO
Geranylgeraniol (GGOH) is an isoprenoid compound found in annatto seeds and an intermediate of the mevalonate pathway found within organisms serving various functions. Toxicological studies on its safety profile are not readily available. To assess the safety of GGOH, a molecularly distilled, food grade annatto oil, consisting of approximately 80% trans-GGOH, was subjected to a bacterial reverse mutation test, an in vitro mammalian chromosomal aberration test, and an in vivo mammalian micronucleus test in order to investigate its genotoxic potential and a 90-day repeated-dose oral toxicity study in rats in order to investigate its potential subchronic toxicity and identify any target organs. No evidence of mutagenicity or genotoxic activity was observed under the applied test systems. In the 90-day study, male and female Hsd. Han Wistar rats were administered daily doses of 0, 725, 1450, and 2900 mg/kg bw/day by gavage. Treatment-related adverse effects were observed in the forestomach at all dose levels and in the liver at the intermediate- and high-dose levels. Based on these results, the lowest observed adverse effect level (LOAEL) for local effects and the no observed adverse effect level (NOAEL) for systemic effects were determined as 725 mg/kg bw/day.
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Bixaceae/química , Carotenoides/química , Diterpenos/toxicidade , Mutagênicos/toxicidade , Extratos Vegetais/química , Administração Oral , Animais , Diterpenos/administração & dosagem , Feminino , Masculino , Testes de Mutagenicidade , Mutagênicos/administração & dosagem , Nível de Efeito Adverso não Observado , Ratos , Testes de Toxicidade SubcrônicaRESUMO
In this experimental work, sodium carboxymethyl beta-glucan (CMBG), a chemically altered beta-glucan, is evaluated for mutagenicity and sub-acute oral toxicity. Specifically, the tested material was CM-Glucan Nu, a food grade powder ≥90% CMBG derived from Saccharomyces cerevisiae. A bacterial reverse mutation test was performed and resulted in no mutagenicity. A 28-day, repeated-dose, oral (gavage) toxicity test on rats was performed at dose levels of 0, 500, 1000, and 2000 mg/kg bw/day. No mortality, target organs or other treatment related effects were observed. The no observed adverse effect level (NOAEL) was 2000 mg/kg bw/day, the highest dose tested, for both male and female Han:WIST rats.
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beta-Glucanas/toxicidade , Administração Oral , Animais , Escherichia coli/efeitos dos fármacos , Feminino , Masculino , Testes de Mutagenicidade , Nível de Efeito Adverso não Observado , Ratos Wistar , Saccharomyces cerevisiae/química , Salmonella typhimurium/efeitos dos fármacos , Testes de Toxicidade Subaguda , beta-Glucanas/administração & dosagemRESUMO
Humic substances are ubiquitous in soils and waters. These complex superstructures are derived from the decomposition of dead plant and animal matter and are vital to soil health. Their heterogenous composition is specific to their site of origin and is comprised of weakly bound aggregates of small organic compounds that can sequester minerals and make them available to plants. As such, they may possess potential nutritional value for humans, and extractions of fulvic and humic acids can be produced that could be suitable for such purposes. For this reason, we evaluated the toxicological profile of a specific preparation (blk. 333) of fulvic and humic acids derived from a lignite deposit in Alberta, Canada and found it to lack genotoxic potential in a bacterial reverse mutation test, in vitro mammalian chromosomal aberration test, and in vivo mammalian micronucleus test. No general or organ toxicity was observed in Wistar rats following 90 days of continuous exposure, and a no observed adverse effect level (NOEAL) was determined at 2000 mg/kg bw/day, the highest tested dose. Our results suggest the feasibility of further evaluation for development of the preparation as a nutritional supplement in food.
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Monomethylsilanetriol (MMST), a silicon-containing compound, has been sold in dietary supplements. However, toxicological studies on its safety profile are not readily available. To assess the safety of MMST stabilized in acacia gum, a novel delivery form of MMST, in accordance with internationally accepted standards, the genotoxic potential and repeated-dose oral toxicity of Living Silica® Acacia Gum Stabilized Monomethylsilanetriol (formerly known as Orgono Acacia Gum Powder®), a food grade product consisting of 80 ± 10% acacia gum and 2.8% (SD ± 10%) elemental silicon from MMST, was investigated. A bacterial reverse mutation test, an in vitro mammalian chromosomal aberration test, an in vivo mammalian micronucleus test, and a 90-day repeated-dose oral toxicity study in rats were performed. No evidence of mutagenicity or genotoxic activity was observed under the applied test systems. In the 90-day study, male and female Hsd.Han Wistar rats were administered daily doses of 0, 500, 1000, and 2000 mg/kg bw/day by gavage. No mortality or treatment-related adverse effects were observed, and no target organs were identified. Therefore, the no observed adverse effects level (NOAEL) was determined as 2000 mg/kg bw/day (201 mg MMST/kg bw/day), the highest dose tested.
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Goma Arábica/toxicidade , Testes de Mutagenicidade/métodos , Nível de Efeito Adverso não Observado , Silício/toxicidade , Administração Oral , Animais , Linhagem Celular , Cricetinae , Cricetulus , Relação Dose-Resposta a Droga , Feminino , Goma Arábica/administração & dosagem , Masculino , Camundongos , Ratos , Ratos Wistar , Silício/administração & dosagemRESUMO
A battery of OECD- and GLP-compliant toxicological studies was performed to assess the safety of a highly purified germanium sesquioxide, an organic form of the naturally occurring, nonessential trace element germanium. Germanium dioxide and germanium lactate citrate (inorganic germaniums) have been shown to induce renal toxicity, whereas germanium sesquioxide (an organic germanium) has been shown to have a more favorable safety profile. However, past toxicity studies on germanium sesquioxide compounds have not clearly stated the purity of the tested compounds. In the studies reported herein, there was no evidence of mutagenicity in a bacterial reverse mutation test or an in vitro mammalian chromosomal aberration test. There was no genotoxic activity observed in an in vivo mammalian micronucleus test at concentrations up to the limit dose of 2000 mg/kg bw/day. In a 90-day repeated-dose oral toxicity study in Han:WIST rats conducted at doses of 0, 500, 1000, and 2000 mg/kg bw/day by gavage, there were no mortalities, treatment-related adverse effects, or target organs identified. The no-observed-adverse-effect-level (NOAEL) was determined to be 2000 mg/kg bw/day.
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A battery of OECD- and GLP-compliant toxicological studies was performed on mango leaf extract (Mangifera indica) containing 60% mangiferin (MLE). No evidence of genotoxicity was found in a bacterial reverse mutation test (Ames). While evidence of clastogenic activity was noted in an in vitro chromosomal aberration test, an in vivo mammalian micronucleus test showed no findings up to the limit dose (2000 mg/kg bw). A 90-day repeated dose oral toxicity study was conducted in rats using doses of 0 (vehicle control), 500, 1000, and 2000 mg/kg bw/day. Based on the lack of mortality or toxic effects in the 90-day study, the NOAEL for MLE in Han:Wist male and female rats was determined to be 2000 mg/kg bw/day, the highest dose tested.
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Astragalus spp. and Panax spp. have a long history of traditional human use. A blend, InnoSlim®, of highly purified and fractionated root extracts from Astragalus membranaceus and Panax notoginseng has now been developed for human consumption; however, the unique constituent content of this blend has not been specifically evaluated with respect to safety. Therefore, the toxicological potential of the blend was formally investigated in a series of studies-genetic toxicity was evaluated in a bacterial reverse mutation test followed by an in vivo mammalian micronucleus test, and general toxicity was evaluated in a 28-day repeated-dose oral toxicity study in rats. No evidence of mutagenicity was observed in the bacterial tester strains used, and no evidence of in vivo chromosomal damage resulting in increased frequency of micronucleated cells was observed in male Crl:NMRI BR mice. No mortality or toxic effects were observed, and no target organs were identified, in male and female Han:WIST rats exposed to 0, 400, 800, or 1200 mg/kg bw/day of the blend by gavage for 28 consecutive days. The highest dose-1200 mg/kg bw/day-was determined to be the NOAEL. Based on these results, extrapolation towards a safe human consumption level can be explored.
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Colostrum has been consumed safely for many years as a food collected directly from cows. More recently, an ultrafiltrated bovine colostrum product has been developed; however, its safety in toxicology studies has not been extensively evaluated. To assess the safety of bovine colostrum ultrafiltrate, in accordance with internationally accepted standards, the genotoxic potential was investigated in a bacterial reverse mutation test, an in vitro chromosomal aberration test, and an in vivo mammalian micronucleus test. No mutagenicity or genotoxic activity was observed in these three tests. A 90-day repeated-dose oral toxicity study in Hsd.Han Wistar rats was conducted at doses of 0, 1050, 2100, and 4200â¯mg/kgâ¯bw/day by gavage. After 90 days of continuous exposure, no mortality or treatment-related adverse effects were observed, and no target organs were identified. The no-observed-adverse-effect level (NOAEL) was determined to be 4200â¯mg/kgâ¯bw/day, the highest dose tested.
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Colostro/química , Laticínios/análise , Laticínios/toxicidade , Administração Oral , Animais , Feminino , Masculino , Camundongos , Nível de Efeito Adverso não Observado , Gravidez , Ratos , Ratos Wistar , UltrafiltraçãoRESUMO
A battery of toxicological studies was conducted to aid in the safety assessment of an ethanolic extract of Ageratum conyzoides for use as an ingredient in food. In accordance with internationally accepted standards, a bacterial reverse mutation test, an in vitro mammalian chromosomal aberration test, an in vivo mammalian micronucleus test, and a 90-day repeated-dose oral toxicity study in rats were performed. In the first three applied test systems, no evidence of mutagenicity, clastogenicity or genotoxicity was revealed. Ageratum conyzoides did not cause mortality or toxic changes in Hsd.Han Wistar rats in the 90-day repeated dose oral (gavage) toxicity study at doses of 500, 1000 and 2000â¯mg/kgâ¯bw/d. The NOAEL was determined to be 2000â¯mg/kgâ¯bw/d for both male and female rats, the highest dose tested.