Safety evaluation of odd-chain fatty acid algal oil.

In the food industry, most fatty acid-rich oils are primarily composed of saturated even-chain fatty acids. However, saturated odd-chain fatty acids are potentially a beneficial alternative to other saturated fatty acid-containing oils. In this communication, we examine the safety of odd-chain fatty acid (OCFA) algal oil, a microalgal-sourced oil composed primarily of the saturated odd-chain fatty acids pentadecanoic acid and heptadecanoic acid. OCFA algal oil was assessed for toxicity in a 14-day palatability study and comprehensive 13-week dietary study at inclusion levels of 5%, 10%, and 15% in the diet, utilizing a DHA-rich algal oil as a comparator control. No adverse effects attributed to the consumption of OCFA algal oil were observed in either study. Therefore, we report a No Observable Adverse Effect Level (NOAEL) of 150,000 ppm (15% in the diet), equivalent to an OCFA algal oil intake of 7553.9 and 8387.7 mg/kg bw/day for male and female rats, respectively. The genotoxic potential of OCFA algal oil was also examined in an in vitro bacterial reverse mutation assay and in vivo mammalian bone marrow chromosome aberration test. OCFA algal oil was non-mutagenic in Salmonella typhimurium and Escherichia coli test strains and did not exhibit clastogenicity in vivo.

Comparative Genomics Provides Insights into the Taxonomy of Azoarcus and Reveals Separate Origins of Nif Genes in the Proposed Azoarcus and Aromatoleum Genera.

Among other attributes, the Betaproteobacterial genus Azoarcus has biotechnological importance for plant growth-promotion and remediation of petroleum waste-polluted water and soils. It comprises at least two phylogenetically distinct groups. The "plant-associated" group includes strains that are isolated from the rhizosphere or root interior of the C4 plant Kallar Grass, but also strains from soil and/or water; all are considered to be obligate aerobes and all are diazotrophic. The other group (now partly incorporated into the new genus Aromatoleum) comprises a diverse range of species and strains that live in water or soil that is contaminated with petroleum and/or aromatic compounds; all are facultative or obligate anaerobes. Some are diazotrophs. A comparative genome analysis of 32 genomes from 30 Azoarcus-Aromatoleum strains was performed in order to delineate generic boundaries more precisely than the single gene, 16S rRNA, that has been commonly used in bacterial taxonomy. The origin of diazotrophy in Azoarcus-Aromatoleum was also investigated by comparing full-length sequences of nif genes, and by physiological measurements of nitrogenase activity using the acetylene reduction assay. Based on average nucleotide identity (ANI) and whole genome analyses, three major groups could be discerned: (i) Azoarcus comprising Az. communis, Az. indigens and Az. olearius, and two unnamed species complexes, (ii) Aromatoleum Group 1 comprising Ar. anaerobium, Ar. aromaticum, Ar. bremense, and Ar. buckelii, and (iii) Aromatoleum Group 2 comprising Ar. diolicum, Ar. evansii, Ar. petrolei, Ar. toluclasticum, Ar. tolulyticum, Ar. toluolicum, and Ar. toluvorans. Single strain lineages such as Azoarcus sp. KH32C, Az. pumilus, and Az. taiwanensis were also revealed. Full length sequences of nif-cluster genes revealed two groups of diazotrophs in Azoarcus-Aromatoleum with nif being derived from Dechloromonas in Azoarcus sensu stricto (and two Thauera strains) and from Azospira in Aromatoleum Group 2. Diazotrophy was confirmed in several strains, and for the first time in Az. communis LMG5514, Azoarcus sp. TTM-91 and Ar. toluolicum TT. In terms of ecology, with the exception of a few plant-associated strains in Azoarcus (s.s.), across the group, most strains/species are found in soil and water (often contaminated with petroleum or related aromatic compounds), sewage sludge, and seawater. The possession of nar, nap, nir, nor, and nos genes by most Azoarcus-Aromatoleum strains suggests that they have the potential to derive energy through anaerobic nitrate respiration, so this ability cannot be usefully used as a phenotypic marker to distinguish genera. However, the possession of bzd genes indicating the ability to degrade benzoate anaerobically plus the type of diazotrophy (aerobic vs. anaerobic) could, after confirmation of their functionality, be considered as distinguishing phenotypes in any new generic delineations. The taxonomy of the Azoarcus-Aromatoleum group should be revisited; retaining the generic name Azoarcus for its entirety, or creating additional genera are both possible outcomes.

The influence of the host microbiome on 3,4-methylenedioxymethamphetamine (MDMA)-induced hyperthermia and vice versa.

Hyperthermia induced by 3,4-methylenedioxymethamphetamine (MDMA) can be life-threatening. Here, we investigate the role of the gut microbiome and TGR5 bile acid receptors in MDMA-mediated hyperthermia. Fourteen days prior to treatment with MDMA, male Sprague-Dawley rats were provided water or water treated with antibiotics. Animals that had received antibiotics displayed a reduction in gut bacteria and an attenuated hyperthermic response to MDMA. MDMA treated animals showed increased uncoupling protein 1 (UCP1) and TGR5 expression levels in brown adipose tissue and skeletal muscle while increased expression of UCP3 was observed only in skeletal muscle. Antibiotics prior to MDMA administration significantly blunted these increases in gene expression. Furthermore, inhibition of the TGR5 receptor with triamterene or of deiodinase II downstream of the TGR5 receptor with iopanoic acid also resulted in the attenuation of MDMA-induced hyperthermia. MDMA-treatment enriched the relative proportion of a Proteus mirabilis strain in the ceca of animals not pre-treated with antibiotics. These findings suggest a contributing role for the gut microbiota in MDMA-mediated hyperthermia and that MDMA treatment can trigger a rapid remodeling of the composition of the gut microbiome.

Stress, Anxiety, and Immunomodulation: A Pharmacological Analysis.

Stress and stressful events are common occurrences in our daily lives and such aversive situations bring about complex changes in the biological system. Such stress responses influence the brain and behavior, neuroendocrine and immune systems, and these responses orchestrate to increase or decrease the ability of the organism to cope with such stressors. The brain via expression of complex behavioral paradigms controls peripheral responses to stress and a bidirectional link exists in the modulation of stress effects. Anxiety is a common neurobehavioral correlate of a variety of stressors, and both acute and chronic stress exposure could precipitate anxiety disorders. Psychoneuroimmunology involves interactions between the brain and the immune system, and it is now being increasingly recognized that the immune system could contribute to the neurobehavioral responses to stress. Studies have shown that the brain and its complex neurotransmitter networks could influence immune function, and there could be a possible link between anxiogenesis and immunomodulation during stress. Physiological and pharmacological data have highlighted this concept, and the present review gives an overview of the relationship between stress, anxiety, and immune responsiveness.

Effects of a typical acute oral calcium load on arterial properties and endothelial function in healthy subjects.

BACKGROUND/OBJECTIVES: Often recommended, calcium supplements have been incriminated as increasing the risk of cardiovascular events, whereas dietary calcium has generally been exonerated. As a first step to address the vascular safety of such dietary measures at the clinical nutritionist toolbox, we sought to determine and compare the acute effects of a typical oral calcium load, provided either as a supplement or as food, on vascular parameters assessed noninvasively in healthy subjects. SUBJECTS/METHODS: In this acute, cross-over, random-order intervention, 11 young and healthy vitamin D-sufficient volunteers (8 women/3 men, 33±6.1 years, body mass index 22.6±2.3 kg/m(2)), ingested 600 mg of calcium twice, once as calcium citrate and the other time from dairy products. Biochemical, vascular and hemodynamic parameters, before and 2 h after each challenge, were compared. Arterial stiffness was studied by measuring pulse wave velocity, augmentation index and large (C1) and small (C2) arterial compliance. Endothelial function was assessed by flow-mediated dilation (FMD). RESULTS: Despite effective calcium loading accompanied by a significant 60% parathyroid hormone level reduction on both occasions, there were no clinically significant changes in the vascular parameters neither in comparison with baseline, nor between the studies. A decrease in heart rate with no change in cardiac output was noticed after the supplement. CONCLUSIONS: An effective calcium load has no clinically significant untoward effect on the vascular properties of young healthy subjects, regardless of its source. Additional studies should determine whether this holds true for chronic calcium supplementation, particularly in subjects with a priori vascular impairment.

Overexpression of Arabidopsis YUCCA6 in potato results in high-auxin developmental phenotypes and enhanced resistance to water deficit.

Indole-3-acetic acid (IAA), a major plant auxin, is produced in both tryptophan-dependent and tryptophan-independent pathways. A major pathway in Arabidopsis thaliana generates IAA in two reactions from tryptophan. Step one converts tryptophan to indole-3-pyruvic acid (IPA) by tryptophan aminotransferases followed by a rate-limiting step converting IPA to IAA catalyzed by YUCCA proteins. We identified eight putative StYUC (Solanum tuberosum YUCCA) genes whose deduced amino acid sequences share 50%-70% identity with those of Arabidopsis YUCCA proteins. All include canonical, conserved YUCCA sequences: FATGY motif, FMO signature sequence, and FAD-binding and NADP-binding sequences. In addition, five genes were found with ~50% amino acid sequence identity to Arabidopsis tryptophan aminotransferases. Transgenic potato (Solanum tuberosum cv. Jowon) constitutively overexpressing Arabidopsis AtYUC6 displayed high-auxin phenotypes such as narrow downward-curled leaves, increased height, erect stature, and longevity. Transgenic potato plants overexpressing AtYUC6 showed enhanced drought tolerance based on reduced water loss. The phenotype was correlated with reduced levels of reactive oxygen species in leaves. The results suggest a functional YUCCA pathway of auxin biosynthesis in potato that may be exploited to alter plant responses to the environment.

Energy cost of breathing at depth: effect of respiratory muscle training.

INTRODUCTION: Respiratory muscle training against resistance (RRMT) increases respiratory muscle strength and endurance as well as underwater swimming endurance. We hypothesized that the latter is a result of RRMT reducing the high energy cost of breathing at depth. METHODS: Eight subjects breathed air in a hyperbaric chamber at 55 fsw, both before and after RRMT. They rested for 10 minutes, cycled on an ergometer for 10 minutes (100 W), rested for 10 minutes, and then, while still at rest, they voluntarily mimicked the breathing pattern recorded during the exercise (isocapnic simulated exercise ventilation, ISEV). RESULTS: Post-RRMT values of V(E) at rest, exercise and ISEV were not different from those recorded pre-RRMT. Pre-RRMT minute-ventilation (V(E)) during ISEV was not different from the exercise ventilation (49.98 +/- 10.41 vs. 47.74 +/- 8.44 L/minute). The end-tidal PCO2 during ISEV and exercise were not different (44.26 +/- 2.54 vs. 44.49 +/- 4.49 mmHg) or affected by RRMT. Oxygen uptake (VO2) was 0.32 +/- 0.08 L/ minute at rest, 1.78 +/- 0.15 during exercise pre-RRMT, and not different post-RRMT. During ISEV, VO2 decreased significantly from pre-RRMT to post-RRMT (0.46 +/- 0.06 vs. 0.36 +/- 0.11 L/minute). Post-RRMT delta VO2/delta V(E) was significantly lower during ISEV than pre-RRMT (0.0094 +/- 0.0021 L/L vs. 0.0074 +/- 0.0023 L/L). CONCLUSION: RRMT significantly reduced the energy cost of ventilation, measured as delta VO2/delta V(E) during ISEV, at a depth of 55 fsw. Whether this change was due to reduced work of breathing and/or increased efficiency of the respiratory muscles remains to be determined.

Safety evaluation of a high lipid Whole Algalin Flour (WAF) from Chlorella protothecoides.

Microalgae such as Chlorella spp. have a long history of use in human food. A high lipid Whole Algalin Flour (WAF) composed of dried milled Chlorella protothecoides was evaluated for subchronic toxicity and genotoxic potential. Likelihood of food allergy potential was also evaluated by human repeat-insult patch test. In the subchronic study, rats were fed dietary levels of 25,000, 50,000 or 100,000 ppm WAF in feed for 93-94 days. No mortalities occurred. No treatment-related effects were identified for general condition, body weight, food consumption, ophthalmology, urinalysis, hematology, clinical chemistry, gross pathology, organ weights, and histopathology. Although statistically significant effects were noted for several endpoints, none was test-substance related. The no-observed-adverse-effect level (NOAEL) for WAF was based on consumption of the 100,000 ppm diet, the highest dietary concentration tested, and was 4807 mg/kg bw/d in male rats and 5366 mg/kg bw/d in female rats. Additionally, WAF (≤ 5000 µg/plate) was not mutagenic in Salmonella typhimurium or Escherichia coli tester strains nor did WAF induce a clastogenic response in bone marrow from mice given a single oral dose (2000 mg/kg bw). Further, WAF did not elicit skin sensitization in a repeat-insult dermal patch test which indicates little potential for food allergy.

Correction of the F508del-CFTR protein processing defect in vitro by the investigational drug VX-809.

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene that impair the function of CFTR, an epithelial chloride channel required for proper function of the lung, pancreas, and other organs. Most patients with CF carry the F508del CFTR mutation, which causes defective CFTR protein folding and processing in the endoplasmic reticulum, resulting in minimal amounts of CFTR at the cell surface. One strategy to treat these patients is to correct the processing of F508del-CFTR with small molecules. Here we describe the in vitro pharmacology of VX-809, a CFTR corrector that was advanced into clinical development for the treatment of CF. In cultured human bronchial epithelial cells isolated from patients with CF homozygous for F508del, VX-809 improved F508del-CFTR processing in the endoplasmic reticulum and enhanced chloride secretion to approximately 14% of non-CF human bronchial epithelial cells (EC(50), 81 ± 19 nM), a level associated with mild CF in patients with less disruptive CFTR mutations. F508del-CFTR corrected by VX-809 exhibited biochemical and functional characteristics similar to normal CFTR, including biochemical susceptibility to proteolysis, residence time in the plasma membrane, and single-channel open probability. VX-809 was more efficacious and selective for CFTR than previously reported CFTR correctors. VX-809 represents a class of CFTR corrector that specifically addresses the underlying processing defect in F508del-CFTR.

Seasonal variation of biomass and bioactive alkaloid content of goldenseal, Hydrastis canadensis.

Seasonal variations in biomass and alkaloid contents of goldenseal (Hydrastis canadensis) were investigated. Five-year-old plants gave 5x the yield of roots and rhizomes of two-year-old plants, and summer growth gave significant increases in root biomass but not rhizomes. Berberine contents of roots plus rhizomes did not vary significantly and were >3.4% in all samples. Hydrastine contents of 5 y roots plus rhizomes showed significant seasonal variation. These variations were due to significant changes in the hydrastine contents of the roots (1.3-1.9%), but not the rhizomes (2.2-2.8%). Goldenseal leaves plus stems had lower contents of hydrastine (0.4-0.8%) and berberine (1.0-1.5%).

Reliability of zygapophysial joint space measurements made from magnetic resonance imaging scans of acute low back pain subjects: comparison of 2 statistical methods.

OBJECTIVE: This purpose of this study was to assess the reliability of measurements made of the zygapophysial (Z) joint space from the magnetic resonance imaging scans of subjects with acute low back pain using new equipment and 2 different methods of statistical analysis. If found to be reliable, the methods of Z joint measurement can be applied to scans taken before and after spinal manipulation in a larger study of acute low back pain subjects. METHODS: Three observers measured the central anterior-to-posterior distance of the left and right L4/L5 and L5/S1 Z joint space from 5 subject scans (20 digitizer measurements, rounded to 0.1 mm) on 2 separate occasions separated by 4 weeks. Observers were blinded to each other and their previous work. Intra- and interobserver reliability was calculated by means of intraclass correlation coefficients and also by mean differences using the methods of Bland and Altman (1986). A mean difference of less than +/-0.4 mm was considered clinically acceptable. RESULTS: Intraclass correlation coefficients showed intraobserver reliabilities of 0.95 (95% confidence interval, 0.87-0.98), 0.83 (0.62-0.92), and 0.92 (0.83-0.96) for each of the 3 observers and interobserver reliabilities of 0.90 (0.82-0.95), 0.79 (0.61-0.90), and 0.84 (0.75-0.90) for the first and second measurements and overall reliability, respectively. The mean difference between the first and second measurements was -0.04 mm (+/-1.96 SD = -0.37 to 0.29), 0.23 (-0.48 to 0.94), 0.25 (-0.24 to 0.75), and 0.15 (-0.44 to 0.74) for each of the 3 observers and the overall agreement, respectively. CONCLUSIONS: Both statistical methods were found to be useful and complementary and showed the measurements to be highly reliable.

Dong Quai (angelica sinensis) in the treatment of hot flashes for men on androgen deprivation therapy: results of a randomized double-blind placebo controlled trial.

OBJECTIVE: To determine whether Dong Quai, a Chinese herbal compound purported to be efficacious in treating menopausal vasomotor symptoms, has a therapeutic benefit in treating hot flashes among prostate cancer patients receiving androgen deprivation therapy. METHODS: A randomized double-blind placebo controlled trial was conducted involving 22 men receiving luteinizing hormone-releasing hormone agonist therapy for prostate cancer with bothersome hot flashes. After recording a baseline log of the frequency, duration and severity of daily hot flashes, patients were randomly assigned in a 1:1 ratio to receive daily placebo or Dong Quai for 3 months. Vasomotor and adverse events were recorded daily. Blood work including serum prostate-specific antigen (PSA), international normalized ratio of prothrombin time and partial thromoboplastin time were recorded at baseline and at the termination of the study. RESULTS: Seventeen of the 22 patients enrolled completed the trial. Baseline vasomotor duration and severity were equivalent between the groups, however the number of hot flashes were significantly more in the Dong Quai group (p = 0.02). With respect to the change in number of hot flashes per day, there was a slight decrease in the mean number among the Dong Quai group which was insignificant. The absolute change and average percentage change in perceived hot flash severity was similar in both groups. There was no significant decrease in the duration of the hot flashes between the 2 groups. Disease progression based on either PSA increase or change in digital rectal exam was not observed in any patient. CONCLUSION: In this small pilot study, there were no significant differences in the severity, frequency or duration of hot flashes among men receiving placebo or Dong Quai.

Safety studies conducted on a proprietary high-purity aloe vera inner leaf fillet preparation, Qmatrix.

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.

Understanding basic behavioral support techniques as an alternative to sedation and anesthesia.

Patients with special needs often present a challenge for the dental care team. The exacting and surgical nature of dental procedures requires significant patient cooperation to ensure the safe delivery of care. Some individuals who have special care needs have difficulty cooperating during treatment, thus creating a potentially harmful situation. Modern dentistry, particularly pediatric dentistry, provides the dental team with a variety of strategies designed to enable the team to safely provide comprehensive care in the least restrictive manner. These techniques range from tell-show-do, to medical stabilization, to general anesthesia. The effective use of noninvasive, nonpharmacologic behavioral guidance/support techniques cannot only avoid the need for sedation or general anesthesia, they can teach the patient to develop coping skills that may enable them to receive comprehensive care in a traditional dental setting over a lifetime. Unfortunately, many providers are inadequately trained in behavioral support strategies. This paper presents a review of noninvasive, nonpharmacologic behavioral support techniques with discussion regarding their application to persons with special care needs.

The safety of PolyGlycopleX (PGX) as shown in a 90-day rodent feeding study.

BACKGROUND: This study was designed to evaluate the safety of PolyGlycopleX (PGX), a novel viscous dietary polysaccharide (fiber), when administered to Sprague Dawley(R) rats in the diet for 90 days. METHODS: Groups of ten male and ten female rats each consumed PGX mixed in the diet at levels of 0, 1.25, 2.5 or 5.0% for 90 days, then evaluated for toxicological effects on parameters that included neuromotor activity, body weight, clinical chemistry, urinalysis, hematology, and histopathology. RESULTS: Mean body weight, mean feed consumption and food efficiency in the treated groups were generally comparable to controls for both male and female rats. No changes were noted in neuromotor behavior, and histopathological analysis revealed no significant changes between treated and control animals. There were no differences in mean organ weight, organ-to-body weight or organ-to-brain weight values between controls and treated animals. Decreased red blood cell count occurred in the high dose males and increases in aspartate and alanine aminotransferase enzyme levels and triglycerides, while significant decreases in serum sodium, potassium and chloride concentrations were observed in the females fed 5.0% PGX. However, the decreased mineral concentrations may be the result of significantly increased urinary volume in both males and females at the high dose, with a concomitant decrease in urinary specific gravity (males and females) and protein concentration (females). These results were within historical control values, did not correlate with any histopathological changes, and were not considered adverse. CONCLUSION: The results indicate a no observed adverse effect level (NOAEL) for PGX at 5.0% of the diet, corresponding to an average daily intake of 3219 and 3799 mg/kg bw/day in male and female rats, respectively.

Respiratory muscle training improves swimming endurance at depth.

Respiratory muscle training (RMT) has been shown to improve divers swimming endurance at 4 feet of depth; however, its effectiveness at greater depths, where gas density and the work of breathing are substantially elevated has not been studied. The purpose of this study was to examine the effects of resistance respiratory muscle training (RRMT) on respiratory function and swimming endurance at 55 feet of depth (270.5 kPa). Nine male subjects (25.9 +/- 6.8 years) performed RRMT for 30 min/day, 5 d/ wk, for 4 wks. Pre- and Post RRMT, subjects swam against a pre-determined load (70% VO2 max) until exhausted. As indices of respiratory muscle strength, maximal inspiratory and expiratory pressures were measured before and immediately following the swims pre- and post-RRMT. These measurements showed that ventilation was significantly lower during the swims and, at comparable swim duration, that the respiratory muscles were considerably less fatigued following RRMT. The reduced ventilation was due to a lower breathing frequency following RRMT. The ventilatory changes following RRMT coincided with significantly increased swimming time to exhaustion (approximately 60%, 31.3 +/- 11.6 vs. 49.9 +/- 16.0 min, pre- vs. post-RRMT, p < 0.05). These results suggest respiratory muscle fatigue limits swimming endurance at depth as well as at the surface and RRMT improves performance.

In vivo study of response threshold in retinal degenerate model at different degenerate stages.

Retinal prostheses are being developed to apply electrical stimulation to the retina in order to restore vision of individuals who suffer from diseases such as retinitis pigmentosa (RP) and aged related macular degeneration (AMD). Various electrical stimulus parameters have been extensively studied in both experimental and clinical settings. Both electrophysiological and psychophysical results have shown that outer retina disease exhibit higher stimulus threshold in one degenerate group versus the control group. Fewer studies have been conducted to investigate the change in threshold currents as a function of different degenerate stages. We propose to study the electrophysiological change in degenerate rat retinas by using an in vivo recording method. We recorded retinal-driven superior colliculus cells response in two control groups and four degenerate groups. Current pulses of seven different stimulus pulse durations were applied to the retinas to obtain strength duration curve per group. Preliminary results showed that for the postnatal (P) day 90 and 180 degenerate groups, threshold currents were not significantly different from the normal control group (P90 and P230). For P300 degenerate group, the threshold currents progressively increased. For P760 degenerate group, threshold currents were significantly elevated across all the stimulus pulse durations tested. Charge densities calculated for P760 degenerate group exceeded the safe limit of the stimulating electrode. Cell morphology in all control and degenerate groups is still under investigation for a correlation study.

Acute and subchronic toxicity studies on Sel-Plex, a standardized, registered high-selenium yeast.

Selenium has been recognized as an essential nutrient for human health; however, its bioavailability is primarily dependent upon the type of selenium, elemental versus organic. In geographic areas low in selenium, there is the potential for animals (including humans) to become selenium deficient and this potential deficiency can be remedied by consumption of exogenous selenium, including selenium-enriched yeast (Saccharomyces cerevisiae) that contains high levels of organic selenium (e.g., selenized yeast). The present studies were conducted to investigate potential oral toxicity of a unique selenized yeast preparation (Sel-Plex) when administered to (1) adult female CHS Swiss mice ICo:OFI (IOPS Caw); (2) adult female CHS Sprague-Dawley rats; and (3) adult male and female Sprague-Dawley CD rats. For the 28- and 90-day toxicity studies, (1) adult male and female Sprague-Dawley CRL:CD(R)(SD) IGS BR strain rats and (2) adult male and female 6- to 7-month-old Beagle dogs were used. The LD50 for mice was >or=2000 mg Sel-Plex/kg (>or=4.06 mg Se/kg) and for rats, was greater than >or=2000 mg Sel-Plex/kg (>or=4.06 mg Se/kg). In the two 28-day studies, for rats, the no observed adverse effects level (NOAEL) was 50 mg Sel-Plex/kg/day (0.1 mg Se/kg/day), and for the dogs, the NOAEL was 22.5 mg Sel-Plex/kg/day (0.045 mg Se/kg/day). For the two 90-day studies, for rats the NOAEL for Sel-Plex was 114 mg/kg/day (0.23 mg Se/kg/day), and for dogs, the NOAEL was 30 mg Sel-Plex/kg/day (0.06 mg Se/kg/day): the latter being the NOAEL in the most sensitive species.

Genotoxicity studies on Sel-Plex, a standardized, registered high-selenium yeast.

Selenium, recognized as an essential nutrient for human health, is a component of proteins and enzymes required for various biological functions and is currently being used as a feed supplement for livestock in geographical areas that are naturally low in selenium. Selenium is structurally similar to sulfur, replacing the sulfur atom in stoichiometric amounts and thus functions through an association with proteins, termed selenoproteins. In geographic areas low in selenium, there is the potential for animals (including humans) to become selenium deficient and this potential deficiency can be remedied by consumption of exogenous selenium, including selenium-enriched yeast (Saccharomyces cerevisiae) that contains high levels of organic selenium (e.g., selenized yeast). A unique, standardized, registered high selenium food-grade baker's yeast (S. cerevisiae; Sel-Plex), was tested in the following battery of Genotoxicity assays; (1) a bacterial reverse mutation test (Ames test); (2) an in vitro mammalian chromosome aberration test; and (3) a mouse micronucleus test. Under the conditions of this assay, Sel-Plex showed no evidence of mutagenic activity in Salmonella typhimurium, in the bacterial reverse mutation test. Sel-Plex did not induce significant chromosomal aberrations in cultured human lymphocytes in the in vitro mammalian chromosome aberration test. Sel-Plex did not statistically increase the frequency or proportion of micronucleated immature erythrocytes in the mouse micronucleus test. Thus, from the studies presented here, the authors conclude that Sel-Plex is nongenotoxic.