RESUMEN
Are all food ingredients, dietary supplement ingredients and even foods, required to meet the same safety standards? Are they all equally safe? If so, then why do the various categories have different expressions describing their safety, such as "reasonable certainty of no harm" for food ingredients and "reasonable expectation of no harm" for dietary supplement ingredients? The basis for these different expressions is that they are not standards of safety, but standards of proof of safety. Just as in criminal vs. civil courts, the threshold for proving guilt or fault is different, so too are there differences between various categories of consumer products regulated by the US Food and Drug Administration. This manuscript describes the threshold requirements for each standard, as well as to the identity of the decision makers on what is safe, their credentials as decision makers and the databases mandated for their use.
RESUMEN
The Modernization of Cosmetics Regulation Act of 2022 (MoCRA) amends the Food, Drug and Cosmetic Act (FDCA), elevating the standard of proof of safety (better known as a "safety standard") for cosmetics to the standard of a "reasonable certainty [of] safe."a standard equal to that of food ingredients. The standards of the proof of safety differ for various classes of FDA-regulated product categories e.g., cosmetics, dietary supplements, food ingredients and food itself. This manuscript describes the various standards of proof, the essential differences between the standards, key elements required to achieve a particular standard and, compares the standards to more familiar legal terms such as "a preponderance of the evidence" or "beyond reasonable doubt." The standards of proof for these product categories are also ranked according to increasing threshold for achievement of "safe" status. Lastly, this manuscript suggests how the requirements for the high standard of a "reasonable certainty of safe" (or "reasonable certainty of no harm") might be met.
Asunto(s)
Seguridad de Productos para el Consumidor , Cosméticos , United States Food and Drug Administration , Animales , Humanos , Seguridad de Productos para el Consumidor/normas , Seguridad de Productos para el Consumidor/legislación & jurisprudencia , Cosméticos/normas , Medición de Riesgo , Estados Unidos , United States Food and Drug Administration/normasRESUMEN
Altering caffeine's negative physiological effects and extending its duration of activity is an active area of research; however, deuteration as a means of achieving these goals is unexplored. Deuteration substitutes one or more of the hydrogen atoms of a substance with deuterium, a stable isotope of hydrogen that contains an extra neutron. Deuteration can potentially alter the metabolic profile of a substance, while maintaining its pharmacodynamic properties. d9-Caffeine is a deuterated isotopologue of caffeine with the nine hydrogens contained in the 1, 3, and 7 methyl groups of caffeine substituted with deuterium. d9-Caffeine may prove to be an alternative to caffeine that may be consumed with less frequency, at lower doses, and with less exposure to downstream active metabolites of caffeine. Characterization of d9-caffeine's genotoxic potential, pharmacodynamic, and pharmacokinetic behavior is critical in establishing how it may differ from caffeine. d9-Caffeine was non-genotoxic with and without metabolic activation in both a bacterial reverse mutation assay and a human mammalian cell micronucleus assay at concentrations up to the ICH concentration limits. d9-Caffeine exhibited a prolonged systemic and brain exposure time in rats as compared to caffeine following oral administration. The adenosine receptor antagonist potency of d9-caffeine was similar to caffeine.
Asunto(s)
Cafeína/farmacocinética , Administración Oral , Animales , Bacterias/efectos de los fármacos , Bacterias/genética , Encéfalo/metabolismo , Cafeína/administración & dosificación , Cafeína/sangre , Daño del ADN/efectos de los fármacos , Deuterio/química , Deuterio/metabolismo , Masculino , Estructura Molecular , Ratas , Ratas Sprague-DawleyRESUMEN
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.
Asunto(s)
Ingredientes Alimentarios/toxicidad , Nigella sativa/toxicidad , Animales , Dermatitis por Contacto/etiología , Relación Dosis-Respuesta a Droga , Humanos , Ratones , Nigella sativa/química , Nigella sativa/clasificación , Nigella sativa/crecimiento & desarrollo , Aceites Volátiles/administración & dosificación , Extractos Vegetales/farmacología , Plantas Medicinales/química , Plantas Medicinales/clasificación , Plantas Medicinales/toxicidad , Ratas , Semillas , Especias , Estados Unidos , United States Food and Drug Administration/normasRESUMEN
Phenylketonuria (PKU) is an autosomal recessive inherited disorder affecting one in every 10,000 to 15,000 newborn children in the US each year. PKU patients' metabolism of an essential amino acid, phenylalanine (PHE), is impaired, resulting in concentrations of PHE in the circulating blood and brain that are potentially toxic. Individuals with PKU restrict dietary intakes of PHE by consuming medical foods formulated with low PHE concentrations. In this study, an alkaline serine protease (ASP) expressed in Bacillus licheniformis strain 2709, which is composed of >90% protein with a concentration of <0.25% PHE, was heat deactivated (becoming deactivated ASP (DASP)) and evaluated for safe use as an ingredient in foods, including medical foods. DASP was non-mutagenic with and without metabolic activation up to 5000 µg DASP/plate. 14-Day dietary studies supported a Maximum Tolerated Dose (MTD) of 115000 ppm DASP. In a 90-day dietary toxicity study, CRL SD CD® rats were administered 0, 28750, 57500, 115500 ppm DASP in the diet. No DASP-related adverse effects were observed at the high dose. As such, a No Observable Adverse Effect Level (NOAEL) of 115,500 ppm DASP or 6224.1 mg DASP/kg bw/day (males) and 7500.9 mg DASP/kg bw/day (females) was established.
Asunto(s)
Serina Endopeptidasas/toxicidad , Animales , Dieta , Modelos Animales de Enfermedad , Esquema de Medicación , Escherichia coli , Femenino , Humanos , Masculino , Pruebas de Mutagenicidad , Fenilalanina , Fenilcetonurias/sangre , Ratas , Ratas Sprague-Dawley , Salmonella typhimurium , Serina Endopeptidasas/química , Serina Endopeptidasas/metabolismoRESUMEN
Naturally sourced food ingredients have been the beneficiary of legal, regulatory and consumer preference as the result of a widely shared assumption of safety. However, the natural substances consumed in modernity may have little to do with the historically consumed part of the plant or even the plant itself. Further, our initial impression of a safe plant derivative may well be false as the result of the use of different growth conditions or, changes in harvesting and processing conditions that may have brought about a higher level of toxic constituents. Despite the variability of plant constituents, manufacturers' standards are set according to the content of commercially desirable properties, rather than presence of potentially toxic constituents. Why then, after all the potential reservations regarding naturals, is there such an enmity toward synthetic chemicals (including single chemical fermentation products), which have been tested in a systematic manner for potential toxic effects and whose composition is well known as the result of consistent manufacturing techniques and analytical controls? The authors will describe the paradigms used for natural products safety review and compare them with the safety criteria required for an "artificial" food ingredient.
Asunto(s)
Productos Biológicos/análisis , Comportamiento del Consumidor , Plantas/química , Productos Biológicos/economía , Seguridad de Productos para el Consumidor , HumanosRESUMEN
UNLABELLED: Free N Clear is a sanitizing agent composed of United States Pharmacopeial Convention grade benzalkonium chloride (BAC), acetic acid, and methylparaben. Free N Clear is proposed for use as a sanitizing agent at a 1: 50 dilution (2% solution), which contains approximately 100 ppm BAC. As part of a program to assess its safety, a 2% solution of Free N Clear (diluted Free N Clear) was administered by gavage to Sprague-Dawley rats for 91d and tested for genetic toxicity in vitro and in vivo. In the 91d study, the no observable adverse-effect level of diluted Free N Clear in male and female Sprague-Dawley rats is 5000 mg/kg bw/day, the highest dose administered. Diluted Free N Clear was not mutagenic in a bacterial reverse mutation assay that tested concentrations extending into the toxic range, and did not increase the frequency of micronucleated polychromatic erythrocytes in bone marrow cells of male or female Sprague-Dawley rats when tested at the maximum permissible dose volume of 20 mL/kg bw. The results support safety of Free N Clear, when used at the concentration proposed for use. PRACTICAL APPLICATION: The significance of these findings will allow for the development of Free N Clear as a potential sanitizing agent for food.
Asunto(s)
Compuestos de Benzalconio/efectos adversos , Seguridad de Productos para el Consumidor , Conservantes de Alimentos/efectos adversos , Ácido Acético/efectos adversos , Ácido Acético/análisis , Animales , Compuestos de Benzalconio/análisis , Daño del ADN/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Femenino , Contaminación de Alimentos/prevención & control , Microbiología de Alimentos , Conservantes de Alimentos/análisis , Guías como Asunto , Masculino , Pruebas de Micronúcleos , Mutágenos/efectos adversos , Mutágenos/análisis , Parabenos/efectos adversos , Parabenos/análisis , Ratas , Ratas Sprague-Dawley , Pruebas de ToxicidadRESUMEN
Lactobacillus pentosus has a long history of use in cooked and uncooked fermented foods. Viable and heat-killed nonviable preparations of L. pentosus strain b240 were evaluated for short term and subchronic toxicity and genotoxic potential. Dose levels were determined through acute oral toxicity tests with viable (LD(50)>2500 mg/kg) and nonviable (LD(50)>2000 mg/kg) b240. In the short term study, rats received 2500 mg/kg/day (â¼1.7×10(11)cfu/kg/day) viable b240 for 28 days. In the subchronic study, rats received 500, 1000 or 2000 mg/kg/day (up to â¼3.0×10(12) cfu equivalents/kg/day) nonviable b240 for 91 days followed by a 28-day recovery. No mortalities occurred. No treatment-related effects were identified for general condition, body weight, food-water consumption, ophthalmology, urinalysis, hematology, blood chemistry, organ weights, histopathology and gross pathology. Although statistically significant effects were noted for several endpoints in the short term and subchronic studies, none were related to the test materials. The NOAEL for nonviable b240 was 2000 mg/kg/day, the highest dose tested. Additionally, nonviable b240 (≤ 5000 µg/plate) was not mutagenic in Salmonella typhimurium or Escherichia coli tester strains nor did nonviable b240 orally administered to rats at levels ≤ 2000 mg/kg/day for two days, induce a clastogenic response.
Asunto(s)
Microbiología de Alimentos , Lactobacillus/fisiología , Animales , Femenino , Dosificación Letal Mediana , Masculino , Pruebas de Mutagenicidad , Ratas , Ratas Sprague-DawleyRESUMEN
Although some investigators have hypothesized that ingestion of fructose from foods and beverages is responsible for the development of hyperlipidemia or obesity, a recent evidence-based review demonstrated that there was no relationship between the consumption of fructose in a normal dietary manner and the development of hyperlipidemia or increased weight in normal weight individuals. Because overweight and obese individuals may exhibit metabolic abnormalities such as insulin resistance, impaired glucose tolerance, hyperlipedemia, and/or alterations in gut hormones involved in appetite regulation, the findings of fructose studies performed in normal weight subjects may not be particularly relevant for overweight or obese subjects. A systematic assessment of the strength and quality of the studies and their relevance for overweight or obese humans ingesting fructose in a normal dietary manner has not been performed. The purpose of this review was to critically evaluate the existing database for a causal relationship between the ingestion of fructose in a normal, dietary manner and the development of hyperlipidemia or increased body weight in overweight or obese humans, using an evidence-based approach. The results of the analysis indicate that there is no evidence which shows that the consumption of fructose at normal levels of intake causes biologically relevant changes in triglycerides (TG) or body weight in overweight or obese individuals.
Asunto(s)
Peso Corporal , Dieta , Fructosa/efectos adversos , Fructosa/metabolismo , Triglicéridos/sangre , Adolescente , Adulto , Anciano , Índice de Masa Corporal , Medicina Basada en la Evidencia , Femenino , Fructosa/administración & dosificación , Intolerancia a la Glucosa/sangre , Intolerancia a la Glucosa/complicaciones , Humanos , Hiperlipidemias/sangre , Hiperlipidemias/complicaciones , Resistencia a la Insulina , Masculino , Persona de Mediana Edad , Obesidad/etiología , Obesidad/metabolismo , Adulto JovenRESUMEN
The aloe vera plant has a long history of safe use for oral and topical applications. This publication describes safety studies conducted on a proprietary high-purity aloe vera inner leaf fillet preparation, Qmatrix. In a 13-week study in rats, Qmatrix was administered via gavage at 0, 500, 1000 and 2000 mg/kg body weight (bw)/day. There were no significant changes in food or water consumption, body weight, serum biochemistry or hematology at any of the doses tested. Sporadic, significant increases were observed in some of the measured urinalysis parameters; however, these variations were not treatment-related, as most were observed only in one sex, not dose-dependent and within historical control values. Organ weights were unaffected, except for a statistically significant, though not dose-dependent, increase in absolute and relative weights of the right kidney in males at 500 and 2000 mg/kg bw/day, respectively. Histopathological analysis revealed no abnormal signs. Qmatrix was non-mutagenic in an Ames test and a chromosomal aberration test at concentrations up to 10,000 microg/plate, and in an in vivo bone marrow micronucleus test at doses up to 5000 mg/kg bw/day. Based on these results, Qmatrix is not genotoxic in vitro or in vivo and; has an oral NOAEL greater than 2000 mg/kg bw/day following 90 days of oral exposure.
Asunto(s)
Aloe/química , Seguridad de Productos para el Consumidor , Preparaciones de Plantas/toxicidad , Administración Oral , Animales , Células de la Médula Ósea/efectos de los fármacos , Línea Celular , Cricetinae , Relación Dosis-Respuesta a Droga , Femenino , Masculino , Ratones , Ratones Endogámicos ICR , Micronúcleos con Defecto Cromosómico/inducido químicamente , Pruebas de Micronúcleos , Nivel sin Efectos Adversos Observados , Hojas de la Planta/química , Preparaciones de Plantas/aislamiento & purificación , Preparaciones de Plantas/normas , Ratas , Ratas Sprague-Dawley , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/genética , Pruebas de Toxicidad CrónicaRESUMEN
In recent years, there has been episodic speculation that an increase in consumption of fructose from foods and beverages is an underlying factor responsible for the relatively recent increase in obesity and obesity-related diseases such as diabetes. Reports in support of this hypothesis have been published, showing that concentrations of triglycerides (TG) are higher and concentrations of insulin and hormones associated with satiety are lower in animals following the ingestion of fairly large quantities of fructose, compared to other carbohydrates. However, results from human studies are inconsistent. A possible reason for the inconsistent results is that they are dependent on the particular study population, the design of the studies, and/or the amount of fructose administered. A systematic assessment of the strength and quality of the studies and their relevance for healthy, normal weight humans ingesting fructose in a normal dietary manner has not been performed. The purpose of this review was to critically evaluate the existing database for a causal relationship between the ingestion of fructose in a normal, dietary manner and the development of hyperlipidemia or increased body weight in healthy, normal weight humans, using an evidence-based approach. The results of the analysis indicate that fructose does not cause biologically relevant changes in TG or body weight when consumed at levels approaching 95th percentile estimates of intake.
Asunto(s)
Dieta , Sacarosa en la Dieta/efectos adversos , Fructosa/efectos adversos , Estado de Salud , Hiperlipidemias/etiología , Obesidad/etiología , Índice de Masa Corporal , Sacarosa en la Dieta/administración & dosificación , Práctica Clínica Basada en la Evidencia , Análisis de los Alimentos , Fructosa/administración & dosificación , Humanos , Hiperlipidemias/prevención & control , Obesidad/complicaciones , Obesidad/prevención & controlRESUMEN
Although many foods contain toxins as a naturally-occurring constituent or, are formed as the result of handling or processing, the incidence of adverse reactions to food is relatively low. The low incidence of adverse effects is the result of some pragmatic solutions by the US Food and Drug Administration (FDA) and other regulatory agencies through the creative use of specifications, action levels, tolerances, warning labels and prohibitions. Manufacturers have also played a role by setting limits on certain substances and developing mitigation procedures for process-induced toxins. Regardless of measures taken by regulators and food producers to protect consumers from natural food toxins, consumption of small levels of these materials is unavoidable. Although the risk for toxicity due to consumption of food toxins is fairly low, there is always the possibility of toxicity due to contamination, overconsumption, allergy or an unpredictable idiosyncratic response. The purpose of this review is to provide a toxicological and regulatory overview of some of the toxins present in some commonly consumed foods, and where possible, discuss the steps that have been taken to reduce consumer exposure, many of which are possible because of the unique process of food regulation in the United States.
Asunto(s)
Seguridad de Productos para el Consumidor , Contaminación de Alimentos/legislación & jurisprudencia , Contaminación de Alimentos/prevención & control , Microbiología de Alimentos , Toxinas Biológicas/toxicidad , United States Food and Drug Administration/legislación & jurisprudencia , Culinaria , Exposición a Riesgos Ambientales , Humanos , Plantas Tóxicas , Salud Pública , Medición de Riesgo , Estados UnidosRESUMEN
Although a number of cases of hepatotoxicity are associated with the use of Hydroxycut weight management products, it has been alleged that their effects are primarily due to the presence of hydroxycitric acid (HCA, as Super CitriMax) in the formulations. However, while these products contain up to 20 different ingredients, some do not contain HCA. Case studies reported to date have not considered in depth the literature on the numerous animal and human studies that have been conducted on the safety and efficacy of HCA. No HCA-associated hepatotoxicity or treatment-related adverse effects have been reported in these studies, and thus it is premature to make the assumptions presented in the recent case studies regarding Hydroxycut. If it is established in well controlled studies that the use of these formulations with and/or without HCA can result in the occurrence or progression of hepatotoxicity, additional studies should be conducted to characterize the causative factor(s).
Asunto(s)
Fármacos Antiobesidad/efectos adversos , Citratos/toxicidad , Suplementos Dietéticos/efectos adversos , Hígado/efectos de los fármacos , Pérdida de Peso/efectos de los fármacos , Sistemas de Registro de Reacción Adversa a Medicamentos , Animales , Ensayos Clínicos como Asunto , HumanosRESUMEN
Bacillus cereus var. toyoi is a naturally occurring, non-toxigenic and non-pathogenic strain of B. cereus. Safety studies were conducted on a B. toyoi preparation (Toyocerin, including but not limited to enterotoxicity, eye irritation, genotoxicity, acute, subchronic and chronic toxicity studies and human clinical trials. In rabbits, Toyocerin did not exhibit enterotoxicity and was only slightly irritating to the eyes. It was non-mutagenic in an Ames assay at up to 10,000 microg/plate and did not exhibit clastogenic activity in a chromosomal aberration test at up to 450 mg/ml. It was non-toxic in acute and repeated-dose (30 and 60 days and 1 year) toxicity studies in rats and mice at up to 3 x 10(11)spores/kg bw/day. In an eight-day human clinical trial, Toyocerin did not cause any adverse effects in healthy male and female subjects at 1 x 10(9) and 1 x 10(10)spores/kg bw/day. In feeding trials, Toyocerin not cause any adverse effects in rabbits, pigs, chickens, turkeys and cattle at doses ranging from 8.5 x 10(7) to 4 x 10(9)spores/kg bw/day for durations of 2 weeks to 18 months. Taken together, these studies demonstrate that Toyocerin is safe at the doses tested.
Asunto(s)
Bacillus cereus/metabolismo , Proteínas Bacterianas/toxicidad , Aditivos Alimentarios/toxicidad , Infecciones por Bacterias Grampositivas/microbiología , Probióticos/toxicidad , Pruebas de Toxicidad/métodos , Alimentación Animal , Animales , Bovinos , Seguridad de Productos para el Consumidor , Cricetinae , Cricetulus , ADN Bacteriano/efectos de los fármacos , Femenino , Humanos , Íleon/microbiología , Íleon/patología , Masculino , Ratones , Conejos , Ratas , Ratas Wistar , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/genética , Esporas BacterianasRESUMEN
trans-Resveratrol is a naturally occurring polyphenolic compound found in a variety of foods, but predominantly in grapes. Safety studies were conducted on high-purity trans-resveratrol (Resvida), including skin and eye irritation, dermal sensitization, subchronic and reproductive toxicity, genotoxicity, and absorption, metabolism and excretion. Resvida was non-irritating to skin and eyes and non-sensitizing. It was non-mutagenic in a bacterial reverse mutation assay in Salmonella typhimurium and Escherichia coli, but exhibited clastogenic activity in a chromosomal aberration test in human lymphocytes. However, in an in vivo bone marrow micronucleus test in rats, Resvida was non-genotoxic. In a 28-day study, Resvida caused no adverse effects in rats at 50, 150 and 500 mg/kg bw/day. Similarly, in a 90-day study, Resvida did not cause any adverse effects in rats at up to 700 mg/kg bw/day; the highest dose tested. Resvida did not induce any adverse reproductive effects in an embryo-fetal toxicity study in rats at a dose of 750 mg/kg bw/day. Also, in vitro and in vivo absorption, metabolism, and excretion studies in Caco-2 cells, rat primary hepatocytes and male and female rats (in vivo) show that Resvida is readily absorbed, metabolized and excreted. These studies provide evidence that Resvida is well tolerated and non-toxic.
Asunto(s)
Antioxidantes/toxicidad , Estilbenos/toxicidad , Pruebas de Toxicidad , Animales , Antioxidantes/farmacocinética , Aberraciones Cromosómicas , Embrión de Mamíferos/efectos de los fármacos , Embrión de Mamíferos/embriología , Desarrollo Embrionario/efectos de los fármacos , Ojo/efectos de los fármacos , Ojo/patología , Femenino , Humanos , Ensayo del Nódulo Linfático Local , Masculino , Pruebas de Micronúcleos , Embarazo , Conejos , Ratas , Ratas Sprague-Dawley , Ratas Wistar , Reproducción/efectos de los fármacos , Resveratrol , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/genética , Pruebas de Irritación de la Piel , Estilbenos/farmacocinéticaRESUMEN
Rebaudioside A (Reb A) is a steviol glycoside isolated from the leaves of the Stevia rebaudiana plant. This non-nutritive, natural sweetener is reported to be 250-450 times sweeter than sucrose and has potential for wide use in the US diet, and is used in Japan and South America today. The safety of Reb A has been investigated in several recently published studies and information on genotoxicity is described herein. Reb A was investigated for its potential to induce genotoxicity in three in vitro and two in vivo assays (conducted according to OECD guidelines). Reb A was non-mutagenic in an Ames test using Salmonella typhimurium and Escherichia coli, in a chromosomal aberration test using Chinese Hamster V79 cells and in a mouse lymphoma assay using L5178Y+/- cells, all studies were conducted at concentrations up to 5000 microg/ml, with and without metabolic activation. Also, Reb A was non-genotoxic in a bone marrow micronucleus test in mice at doses up 750 mg/kg bw and in an unscheduled DNA synthesis test in rats at 2000 mg/kg bw. These studies provide additional evidence that Reb A is not genotoxic at the doses tested and further support the generally recognized as safe determination of Reb A.
Asunto(s)
Diterpenos de Tipo Kaurano/toxicidad , Mutágenos/toxicidad , Edulcorantes/toxicidad , Animales , Línea Celular Tumoral , Aberraciones Cromosómicas/efectos de los fármacos , Cricetinae , ADN/biosíntesis , ADN/genética , Reparación del ADN/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Femenino , Humanos , Linfoma/tratamiento farmacológico , Linfoma/patología , Masculino , Ratones , Pruebas de Micronúcleos , Pruebas de Mutagenicidad , RatasRESUMEN
Kola nut extract is used in the food industry as a flavoring ingredient. Kola nut extract is derived from the seeds of primarily two tropical Cola species (Cola nitida (Vent.) Schott et Endl. or Cola acuminata (Beauv.) Schott et Endl.) of the Family, Sterculiaceae. Present day consumption of kola nut extract is 0.69 mg/kg/day. Caffeine and theobromine are two important constituents of kola nuts. Although limited biological data are available for kola nut extract specifically, the published data of the major constituents of kola nuts suggest the pharmacological/toxicological properties of kola nut extract, parallel to those of a roughly equivalent dose of caffeine. Frank developmental/reproductive effects have not been reported and changes in offspring cannot be extrapolated to humans. A NOEL/NOAEL cannot be defined for repeated oral exposure to kola nut extract from available data. Notwithstanding the foregoing, U.S. consumers have a history of safe consumption of cola-type beverages containing kola nut extract that dates at least to the late 19th Century, with a significant global history of exposure to the intact kola nuts that date centuries longer.
Asunto(s)
Cola/toxicidad , Alimentos/toxicidad , Animales , Cola/química , Humanos , Masculino , Mutágenos/toxicidad , Neurotoxinas/toxicidad , Nueces/química , Extractos Vegetales/toxicidad , Ratas , Teratógenos/toxicidadRESUMEN
BACKGROUND: The relationship of dietary fiber to overall health is of great importance, as beneficial effects have been demonstrated with the use of fiber from diverse sources, some traditional, other novel. PolyGlycopleX (PGX) is a unique proprietary product composed of three water-soluble polysaccharides, that when processed using novel technology give rise to a final product - a soluble, highly viscous functional fiber. METHODS: Because of its potential use in food and dietary supplements, a randomized, double-blind, placebo controlled clinical study was conducted to evaluate the tolerance to PGX ingestion for 21 days, to a maximum dose level of 10 g per day, in healthy male and female volunteers. The main objective of the study was to evaluate the overall gastrointestinal (GI) tolerance, while secondary objectives were to evaluate possible changes in hematological, biochemical, urinary and fecal parameters. RESULTS: Results show that PGX is well tolerated as part of a regular diet with only mild to moderate adverse effects, similar to those seen with a moderate intake of dietary fiber in general, and fruits and vegetables. Because PGX is a highly viscous, functional fiber, it also demonstrates several physiological responses including, but not limited to maintaining healthy total and LDL cholesterol and uric acid levels.
Asunto(s)
Alginatos/administración & dosificación , Fibras de la Dieta/administración & dosificación , Polisacáridos Bacterianos/administración & dosificación , Adolescente , Adulto , Alginatos/efectos adversos , Fibras de la Dieta/efectos adversos , Suplementos Dietéticos/efectos adversos , Método Doble Ciego , Combinación de Medicamentos , Femenino , Tracto Gastrointestinal/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Polisacáridos Bacterianos/efectos adversosRESUMEN
Dietary fats in food are natural energy sources to animals and are included in the American Association of Feed Control Officials (AAFCO) manual as a requirement for dog food. Medium chain triglycerides are comprised of a glycerol backbone esterified to medium chain length (8-12 carbon) fatty acids (FA) and, in the context of this report, are all saturated FA. Unlike esterified long chain (>12 carbons) FA (long chain triglycerides or LCT), MCT are lower in caloric value, and are eliminated from the body more quickly than LCT. The objective of this study was to determine the safety of MCT when fed to beagles for 90 days at levels of 0%, 5%, 10%, and 15% MCT added to conventional feed. The beagles were monitored for signs of toxicity by clinical observations, body weight measurements, food consumption level, physical examinations, hematology and serum chemistry, ophthalmic examinations, and urinalysis. There were no signs of toxic effects observed in any of the animals that were related to feed, and the animal viability was 100% at the end of the study. Some animals exhibited significant increased blood urea nitrogen, potassium and cholesterol levels in the 10% and 15% MCT-fed groups. Also, in the same groups with elevated nitrogen, there were concomitant reductions in total blood protein and urine volumes. These changes in serum chemistry may be the result of protein sparing effects due to the high levels of MCT intake, and are not deemed to be pathological in nature. Animals receiving 15% MCT in feed had lower levels of food intake due to palatability issues. From the other examination parameters, there were no significant changes noted between groups receiving MCT and vehicle feed. No safety concerns were noted at any dose level, although an issue with palatability precluded identifying 15% as the highest dose level tested.