Subchronic (90-day) toxicity assessment of Somacy-FP100, a lipopolysaccharide-containing fermented wheat flour extract from Pantoea agglomerans.

Pantoea agglomerans is a Gram-negative bacterium that is ubiquitous in the environment, colonizing animals, humans, and numerous plants, including cotton and wheat. A lipopolysaccharide-containing fermented wheat flour extract from P. agglomerans (Somacy-FP100) is proposed for use as a food ingredient for individuals seeking foods for healthy aging. Previously published genotoxicity studies with Somacy-FP100 reported its lack of genotoxicity in vitro, but a subchronic toxicity study has not yet been performed. Therefore, to demonstrate the safety of Somacy-FP100 for use as a food ingredient, a 90-day oral (gavage) toxicity study in rats was conducted. Male and female Han Wistar rats were administered vehicle (control) or Somacy-FP100 at 500, 1500, or 4500 mg/kg body weight/day at a dose volume of 10 mL/kg body weight, for at least 90 days. No test article-related adverse clinical signs or effects on body weight, food consumption, or clinical pathology were observed, and there were no macroscopic or microscopic findings related to the test article. Therefore, 4500 mg/kg body weight/day (the highest dose tested and highest feasible dose) was established as the no-observed-adverse-effect level. This absence of subchronic toxicity, in addition to the previously reported lack of genotoxicity, demonstrates the safety of Somacy-FP100 for use as a food ingredient.

Environmental neurotoxin-induced progressive model of parkinsonism in rats.

OBJECTIVE: Exposure to a number of drugs, chemicals, or environmental factors can cause parkinsonism. Epidemiologic evidence supports a causal link between the consumption of flour made from the washed seeds of the plant Cycas micronesica by the Chamorro population of Guam and the development of amyotrophic lateral sclerosis/parkinsonism dementia complex. METHODS: We now report that consumption of washed cycad flour pellets by Sprague-Dawley male rats induces progressive parkinsonism. RESULTS: Cycad-fed rats displayed motor abnormalities after 2 to 3 months of feeding such as spontaneous unilateral rotation, shuffling gait, and stereotypy. Histological and biochemical examination of brains from cycad-fed rats revealed an initial decrease in the levels of dopamine and its metabolites in the striatum (STR), followed by neurodegeneration of dopaminergic (DAergic) cell bodies in the substantia nigra (SN) pars compacta (SNc). alpha-Synuclein (alpha-syn; proteinase K-resistant) and ubiquitin aggregates were found in the DAergic neurons of the SNc and neurites in the STR. In addition, we identified alpha-syn aggregates in neurons of the locus coeruleus and cingulate cortex. No loss of motor neurons in the spinal cord was found after chronic consumption of cycad flour. In an organotypic slice culture of the rat SN and the striatum, an organic extract of cycad causes a selective loss of dopamine neurons and alpha-syn aggregates in the SN. INTERPRETATION: Cycad-fed rats exhibit progressive behavioral, biochemical, and histological hallmarks of parkinsonism, coupled with a lack of fatality.

Final report on the safety assessment of Peanut (Arachis hypogaea) Oil, Hydrogenated Peanut Oil, Peanut Acid, Peanut Glycerides, and Peanut (Arachis hypogaea) Flour.

Peanut (Arachis Hypogaea) Oil is the refined fixed oil obtained from the seed kernels of Arachis hypogaea. Hydrogenated Peanut Oil, Peanut Acid, and Peanut Glycerides are all derived from Peanut Oil. Peanut Flour is a powder obtained by the grinding of peanuts. The oils and glycerides function in cosmetic formulations as skin-conditioning agents. The acid functions as a surfactant-cleansing agent, and the flour functions as an abrasive, bulking agent and/or viscosity-increasing agent. In 1998, only Peanut Oil and Hydrogenated Peanut Oil were reported in use. When applied to the skin, Peanut Oil can enhance the absorption of other compounds. Hepatic changes were noted at microscopic examination of rats fed diets containing 15% edible Peanut Oil for 28 days, although no control group was maintained and the findings were also noted in rats fed fresh corn oil. United States Pharmacopeia (USP)-grade Peanut Oil was considered relatively nonirritating when injected into guinea pigs and monkeys. Technical-grade Peanut Oil was moderately irritating to rabbits and guinea pigs and mildly irritating to rats following dermal exposure. This same oil produced reactions in < or = 10% of 50 human males. Peanut Oil was not an ocular irritant in rabbits. Peanut Oil, either "laboratory expressed" or extracted using a food-grade solvent, was not carcinogenic to mice. Peanut Oil exerted anticarcinogenic activity when tested against known carcinogens. Peanuts are the food most likely to produce allergic and anaphylactic reactions. The major allergen is a protein that does not partition into Peanut Oil, Hydrogenated Peanut Oil, Peanut Acid, and Peanut Glycerides. Aflatoxins can be produced in stored agricultural crops such as peanuts, but do not partition into the oils, acids, or glycerides. Manufacturers were cautioned to make certain that the oils, acids, and glycerides are free of aflatoxins and protein. Formulators were cautioned that the oils, acids, or glycerides may enhance penetration and can affect the use of other ingredients whose safety assessment was based on their lack of absorption. The available studies on Peanut Oil supported the conclusion that Peanut Oil, Hydrogenated Peanut Oil, Peanut Acid, and Peanut Glycerides are safe for use in cosmetic formulations. Peanut (Arachis Hypogaea) Flour, however, is sufficiently different from the above ingredients such that its safety can not be supported by studies using the oil. The additional data needed for Peanut (Arachis Hypogaea) Flour are (1) concentration of use; (2) chemical specifications (i.e., aflatoxin and protein levels); (3) method of preparation; and (4) contact urticaria and dermal sensitization at concentration of use. Although data on aflatoxin levels are sought, it is expected that concentrations of aflatoxin should comply with U.S. government stipulations. Absent the additional data, it was concluded that the available data are insufficient to support the safety of Peanut (Arachis Hypogaea) Flour for use in cosmetic products.

A 90-day feeding study of lupin (Lupinus angustifolius) flour spiked with lupin alkaloids in the rat.

Three groups of 20 male and 20 female Sprague-Dawley rats were given diets based on lupin (Lupinus angustifolius) flour (55.4 g/100 g diet) that had been spiked to provide dietary concentrations of 250, 1050 or 5050 mg lupin alkaloids/kg diet. A control group of 20 males and 20 females received 50 mg/kg (derived from the background level of alkaloid in lupin flour). The rats were treated for a minimum of 90-98 days. A dose-related reduction in red blood cell count and haematocrit (HCT) occurred in both sexes after 45 days, and the mean cell volume (MCV) was decreased in all the male treatment groups. The reductions in HCT and MCV persisted in the males until termination of the study when decreased haemoglobin levels were also observed in the top-dose males. The relative liver weights of female rats showed a dose-related increase. Altered foci of liver parenchymal cells were seen in five females receiving dietary levels of 5050 mg/kg, in one female fed 250 mg/kg and in one male from each of the 250 mg/kg and 1050 mg/kg treatment groups. No foci were seen in the control group. Basophilic foci are uncommon in young rats suggesting that the low incidence in this study is compound related.

Toxicological evaluation of rapeseed products in a subacute feeding study in rats.

Groups of 15 male rats were fed ad libitum for 4 weeks standard diet containing 0, 2.5, 5 or 10% rapeseed protein isolate (RPI), 2.5, 5 or 10% rapeseed extraction residue (RER) or 10% casein. Body weight gain and food intake were recorded weekly. Clinical chemistry analyses, haematology, urinalysis, organ weights and histology were performed terminally. Serum alanine aminotransferase was decreased by RPI, RER and casein, while serum albumin only increased in rats fed RER. Microscopic examinations revealed abnormalities in liver and kidneys of animals at the 10% RPI, RER and casein levels. The absolute liver weights showed increases in the 5 and 10% RER groups and in the 10% RPI group. The relative kidney weights were reduced at all RER levels and in the 2.5% RPI group. Antithyroid activity of the rapeseed products were not noted.

[LD 50 and selenium concentration in the organs of rabbits following oral administration of sodium selenite and testing of the toxicity of Ursoselevit-Prämix]. / LD50 und Selenkonzentration in den Organen von Kaninchen nach oraler Applikation von Natriumselenit und Prüfung der Toxizität von Ursoselevit-Prämix

LD50/24hr was established in the first of a series of experiments on 72 rabbits for orally applied sodium selenite. The dosage was 8.62 mg/kg live weight, the confidence interval being (1 - alpha = 0.95) +/- 0.13 mg/kg. The value was four times as high following intravenous application. Complete lethality was recorded from 15 mg Na2SeO3/kg live weight within 21 hours. Thirty-six animals were involved in the second experiment of the series. They had 50 or 100 per cent Ursoselevit-Prämix (30 ppm Se) in their rations. Body mass development of the test animals was superior to that recorded from the controls in the first 50 days, after which limit the former declined strongly in a few days. Their general condition worsened. Postmortem findings, following slaughter, included catarrhal enteritis, toxic liver dystrophy, scattered pulpous tumours in the spleen, and interstitial nephritis. In the third experiment (50 per cent Ursoselevit-Prämix with 60 ppm Se in the rations), the test animals developed better than the controls during the first two months, after which point they exhibited the same clinical symptoms as those observed in the second experiment, stopped to put on weight, and eventually turned cachectic. The pathomorphological findings were identical with those obtained from the second experiment. The selenium concentrations in the organs of the test animals all were much higher than those of the controls. Their amounts in excess to base values were up to eleven times in the blood, nine times in the liver, twelve times in the kidneys, and 13 times in the muscles.