Co-exposure to commercial food product ingredient E341 and E551 triggers cytotoxicity in human mesenchymal stem cells.

Several nano-toxicological studies have assessed the prospective health risks of engineered nanostructures. Still, nanoscale ingredients from food products are not explored well, and only a few have attended to the possible effects of food additive-based nanoparticles in food. The physicochemical properties of food additives and their fate on human health are still unknown. To fill this knowledge gap, we examined the physicochemical characteristics of food product isolate E341/E551. Additionally, we assessed the consequence of these nanoscale E341 and E551 as co-exposure on human mesenchymal stem cells (hMSCs). The transmission electron microscope (TEM) images revealed that food product isolate (E341/E551) consists of nanoscale particles. The E551 and E341 have 20-50 nm and 70-200 nm diameters, respectively. Co-exposure of food additives SiO2 (E551) and Tricalcium phosphate (E341) effect on the cell viability, morphology, mitochondrial membrane potential, and reactive oxygen species (ROS) level of hMSCs were studied. The cell viability reduction, mitochondrial membrane potential loss, and ROS generation in E341/E551 co-exposed cells were observed. Our study suggests that E341/E551 co-exposure elevated the ROS level and mitochondrial membrane potential depletion at a high dose. The oxidative stress-related genes MDM3, TNFSF10, and POR have exhibited significant upregulation in the E341/E551 treatment group. These results conclude that long-term over-exposure to E341/E551 may be triggers health risks in a human. Further in vivo studies are required for food industry implications due to nanoscale ingredients in E341 and E551.

Food Additive Zinc Oxide Nanoparticles: Dissolution, Interaction, Fate, Cytotoxicity, and Oral Toxicity.

Food additive zinc oxide (ZnO) nanoparticles (NPs) are widely used as a Zn supplement in the food and agriculture industries. However, ZnO NPs are directly added to complex food-matrices and orally taken through the gastrointestinal (GI) tract where diverse matrices are present. Hence, the dissolution properties, interactions with bio- or food-matrices, and the ionic/particle fates of ZnO NPs in foods and under physiological conditions can be critical factors to understand and predict the biological responses and oral toxicity of ZnO NPs. In this review, the solubility of ZnO NPs associated with their fate in foods and the GI fluids, the qualitative and quantitative determination on the interactions between ZnO NPs and bio- or food-matrices, the approaches for the fate determination of ZnO NPs, and the interaction effects on the cytotoxicity and oral toxicity of ZnO NPs are discussed. This information will be useful for a wide range of ZnO applications in the food industry at safe levels.

Food additive sodium bisulfite induces intracellular imbalance of biothiols levels in NCM460 colonic cells to trigger intestinal inflammation in mice.

Sulfites and other preservatives are considered food additives to prevent pathogen growth in food, and they are generally regarded as safe since the late 1950s. However, the possible effects of sulfites on potential damage to host intestinal tissue remain largely unexplored. Given that endogenous sulfite mainly comes from the metabolism of biothiol, we attempted to clarify the relationship among biothiol levels, gut and food additives sulfite, including sodium bisulfite (NaHSO3), and the possible mechanism of sulfite affecting the intestine. In the present study, the NaHSO3 treatments markedly increased the homocysteine (Hcy) level but decreased the cysteine (Cys) level by promoting the expression of Hcy synthase and inhibiting the activities of cystathionine ß-synthase and cystathionine γ-lyase in NCM460 cells. The level of methionine (Met) was not significantly changed, but NaHSO3 promoted ROS-mediated NF-κB signaling pathway, and increased the expressions of proinflammatory cytokines by regulating the levels of Hcy and Cys in NCM460 cells. Vitamin B6 (VB6) supplementation successfully ameliorated NaHSO3-induced damage in NCM460 cells and the colon of Balb/c mice. Altogether, our study provided valuable insights into the safety evaluation of food preservatives. Besides, VB6 could be used as a promising candidate in novel therapies for sodium bisulfite-induced intestinal inflammation.

Antiproliferative, genotoxic and mutagenic potential of synthetic chocolate food flavoring / Potencial antiproliferativo, genotóxico e mutagênico do aroma de chocolate sintético para alimentos

Flavoring additives are of great technological importance for the food industry. However, there is little information regarding the toxicological properties of these micro-ingredients, especially at the cellular level. The present study used meristematic root cells of Allium cepa L. to evaluate the toxicity of a liquid, aroma and flavor synthetic chocolate additive, manufactured and widely marketed throughout Brazil and exported to other countries in South America. The flavoring concentrations evaluated were 100.00; 50.00; 25.00; 1.00; 0.50 and 0.25 µL/L, where the highest concentration established was one-hundred times lower than that commercially suggested for use. The concentration 100 µL/L substantially reduced cell division of meristems within 24- and 48-hours exposure. Concentrations from 100.00 to 0.50 µL/L resulted in a significant number of prophases to the detriment of the other phases of cell division, indicating an aneugenic activity, and induced a significant number of cellular changes, with emphasis on micronuclei, nuclear buds and chromosomal breaks. Under the established analysis conditions, with the exception of concentration 0.25 µL/L, the flavoring of chocolate caused cytotoxicity, genotoxicity and mutagenicity to root meristems.

Os aditivos aromatizantes têm grande importância tecnológica para a indústria de alimentos. Contudo, poucas são as informações quanto as propriedades toxicológicas desses microingredientes, especialmente, em nível celular. No presente estudo avaliou-se, sobre as células meristemáticas de raízes de Allium cepa L., a toxicidade de um aditivo sintético líquido de aroma e sabor de chocolate, fabricado e amplamente comercializado em todo Brasil, e exportado para outros países da América do Sul. As concentrações de aromatizante avaliadas foram 100,00; 50,00; 25,00; 1,00; 0,50 e 0,25 µL/L, onde a maior concentração estabelecida foi cem vezes menor que a sugerida comercialmente para uso. Com base na interpretação dos resultados, a concentração 100 µL/L reduziu substancialmente a divisão celular dos meristemas nas 24 e 48 horas de exposição. As concentrações 100,00 a 0,50 µL/L demonstraram número significativo de prófases em detrimento as outras fases da divisão celular, indicando ação aneugênica, e induziram número significativo de alterações celulares, com ênfase a micronúcleos, broto nucleares e quebras cromossômicas. Nas condições de análises estabelecidas, com exceção a concentração 0,25 µL/L, o aromatizante de chocolate causou citotoxicidade, genotoxicidade e mutagenicidade aos meristemas radiculares.

Genome-Wide DNA Methylation Alterations and Potential Risk Induced by Subacute and Subchronic Exposure to Food-Grade Nanosilica in Mice.

The intensive application of nanomaterials in the food industry has raised concerns about their potential risks to human health. However, limited data are available on the biological safety of nanomaterials in food, especially at the epigenetic level. This study examined the implications of two types of synthetic amorphous silica (SAS), food-grade precipitated silica (S200) and fumed silica Aerosil 200F (A200F), which are nanorange food additives. After 28-day continuous and intermittent subacute exposure to these SAS via diet, whole-genome methylation levels in mouse peripheral leukocytes and liver were significantly altered in a dose- and SAS type-dependent manner, with minimal toxicity detected by conventional toxicological assessments, especially at a human-relevant dose (HRD). The 84-day continuous subchronic exposure to all doses of S200 and A200F induced liver steatosis where S200 accumulated in the liver even at HRD. Genome-wide DNA methylation sequencing revealed that the differentially methylated regions induced by both SAS were mainly located in the intron, intergenic, and promoter regions after 84-day high-dose continuous exposure. Bioinformatics analysis of differentially methylated genes indicated that exposure to S200 or A200F may lead to lipid metabolism disorders and cancer development. Pathway validation experiments indicated both SAS types as potentially carcinogenic. While S200 inhibited the p53-mediated apoptotic pathway in mouse liver, A200F activated the HRAS-mediated MAPK signaling pathway, which is a key driver of hepatocarcinogenesis. Thus, caution must be paid to the risk of long-term exposure to food-grade SAS, and epigenetic parameters should be included as end points during the risk assessment of food-grade nanomaterials.

Eurycoma longifolia-Infused Coffee-An Oral Toxicity Study.

Coffee infused with the additive Eurycoma longifolia, also known as Tongkat ali (TA), has become widely available in the Malaysian market. Safety evaluations for consumption of the products have been called for due to the herbal addition. This study investigates the acute, subacute and chronic effects of a commercial TA coffee in Sprague Dawley rats when given in a single, repeated and prolonged dosage. The dosages of 0.005, 0.05, 0.30 and 2 g/kg body weight (BW) were used in the acute study and 0.14, 0.29 and 1 g/kg BW were used in the repeated dose studies. The in-life parameters measured were food and water intake, body weight and clinical observations. Blood were collected for hematology and clinical biochemistry analyses. All animals were subjected to full necropsies. Non-toxicity-related changes were observed in the food and water consumption parameters. Body weight showed normal increments and none of the animals had any clinical signs of toxicity. Microscopically assessed organ tissues did not reveal any abnormalities. There was significant decrease of platelet count in all the chronic study male treated groups. Significant elevation of renal profile parameters in both gender groups given 0.29 g/kg BW, along with liver and lipid profile elevation in some female groups of the chronic study were noted. No dose-dependent relationship was apparent in the dosage range tested, though these changes may suggest an initial safety indication to the TA coffee. The study concludes that the no observed adverse effect level (NOAEL) for this commercial TA coffee was 1 g/kg BW.

Genotoxicity of the food additive E171, titanium dioxide, in the plants Lens culinaris L. and Allium cepa L.

E171 (titanium dioxide, TiO2), an authorized foods and beverage additive, is also used in food packaging and in pharmaceutical and cosmetic preparations. E171 is considered to be an inert and non-digestible material, not storable in animal tissues, but the possible presence of TiO2 nanoparticles (NP) may present a risk to human health and the environment. We determined the presence of 15% TiO2 NP in a commercial E171 food additive product, by electron microscopy. The biological effects of E171 were assessed in Lens culinaris and Allium cepa for the following endpoints: percentage of germination, root elongation, mitotic index, presence of chromosomal abnormalities, and micronuclei. The results indicated low phytotoxicity but dose-dependent genotoxicity. We also observed internalization of TiO2 NP and ultrastructural alterations in the root systems.

Sodium nitrite negatively affects reproductive ability and offspring survival in female mice.

Sodium nitrite (NaNO2) is an industrial chemical that is frequently used as a food additive to prevent botulism and enhance glossiness, such as curing meat. In addition, in some regions, water source NaNO2 concentrations exceed standard regulatory levels. Whether the excessive intake of NaNO2 has toxic effects on female fertility and fetal development remain unknown. In this study, we administered ICR mice control saline, low-dose NaNO2 (60 mg/kg/day), or high-dose NaNO2 (120 mg/kg/day) by intragastric gavage for 21 days. We then assessed oocyte morphology, spindle-chromosome dynamics, mitochondrial distribution, ATP content, apoptotic cell numbers, DNA damage levels, histone modifications, reactive oxygen species (ROS) levels, and offspring survival. Results showed that NaNO2 treatment decreased oocyte number, impaired polar body extrusion, and increased zona pellucida thickness in oocytes. Furthermore, NaNO2 disrupted MII spindle integrity, caused abnormal mitochondrial distribution, decreased ATP content, and increased levels of ROS and H3K4me2. Moreover, the number of oocytes in early stages of apoptosis and with levels of DNA damage increased in NaNO2-treated mice along with decreased offspring numbers and survival rates. We demonstrated the negative effects of NaNO2 on female reproductive abilities in mice.

Investigation of the Antibacterial Activity and Subacute Toxicity of a Quercus crassifolia Polyphenolic Bark Extract for its Potential Use in Functional Foods.

Oak wood is used in barrels for wine aging. During aging, polyphenols are transferred from the barrels to the liquid. Although the bioactivity of oak polyphenols in wines has been extensively studied, no investigation exists on their toxicological properties, which limits their use as functional safe ingredients for other products. In this work, the chemical composition of a polyphenolic extract of Quercus crassifolia bark (QCBe) was studied by GC-MS. Its antibacterial properties on probiotic and pathogenic bacteria and its subacute-oral toxicity were determined as a way to understand the potential impact from its addition to fermented food as a functional ingredient. QCBe shows a selective inhibition of Escherichia coli compared with Lactobacillus bulgaricus and Streptococcus thermophylus. According to the toxicity evaluation, the subacute no-observed-adverse-effect-level was achieved at 11 mg/kg bw/day, whereas the subacute lowest-observed-adverse-effect-level for kidney damage was at 33 mg/kg bw/day. These results suggest that, given the fact an adverse effect was observed after subacute administration of this extract, further longer term toxicological studies are needed to provide sufficient safety evidence for its use in humans. PRACTICAL APPLICATION: Mexico's yogurt market is growing which creates opportunities for the development of some yogurt products as functional foods. As a first step to evaluate its potential use in yogurt formulation, the antibacterial effect of a Quercus crassifolia polyphenolic extract (QCBe) on probiotic bacteria and its subacute-oral toxicity in rats were studied. A low inhibition on probiotic bacteria growth was observed after QCBe addition to Lactobacillus bulgaricus and Streptococcus thermophylus cultures. Exposure to QCBe for a subacute duration resulted in renal injury in rats at dosages greater than or equal to 33 mg/kg/bw/day. This adverse effect indicates the importance of performing further long-term toxicological assessments prior to the addition of QCBe to a food like yogurt, which is regularly eaten by consumers.

Comprehensive evaluation of the flavonol anti-oxidants, alpha-glycosyl isoquercitrin and isoquercitrin, for genotoxic potential.

Quercetin and its glycosides possess potential benefits to human health. Several flavonols are available to consumers as dietary supplements, promoted as anti-oxidants; however, incorporation of natural quercetin glycosides into food and beverage products has been limited by poor miscibility in water. Enzymatic conjugation of multiple glucose moieties to isoquercitrin to produce alpha-glycosyl isoquercitrin (AGIQ) enhances solubility and bioavailability. AGIQ is used in Japan as a food additive and has been granted generally recognized as safe (GRAS) status. However, although substantial genotoxicity data exist for quercetin, there is very little available data for AGIQ and isoquercitrin. To support expanded global marketing of food products containing AGIQ, comprehensive testing of genotoxic potential of AGIQ and isoquercitrin was conducted according to current regulatory test guidelines. Both chemicals tested positive in bacterial reverse mutation assays, and exposure to isoquercitrin resulted in chromosomal aberrations in CHO-WBL cells. All other in vitro mammalian micronucleus and chromosomal aberration assays, micronucleus and comet assays in male and female B6C3F1 mice and Sprague Dawley rats, and Muta™ Mouse mutation assays evaluating multiple potential target tissues, were negative for both chemicals. These results supplement existing toxicity data to further support the safe use of AGIQ in food and beverage products.

Antiproliferative and genotoxic effects of nature identical and artificial synthetic food additives of aroma and flavor / Efeito antiproliferativo e genotóxico de aditivos alimentares de aroma e sabor sintéticos, dos tipos idêntico ao natural e artificial

Abstract This study aimed to analyze the antiproliferative and genotoxic potential of synthetic food flavorings, nature identical passion fruit and artificial vanilla. This assessment used root meristem cells of Allium cepa L., in exposure times of 24 and 48 hours and using doses of 0.2; 0.4 and 0.6 mL. Roots were fixed in Carnoy’s solution, hydrolyzed in hydrochloric acid, stained with acetic orcein and analyzed with optical microscope at 400× magnification, 5,000 cells for each treatment. For data analysis, it was used Chi-square test at 5%. Doses of 0.2 mL at ET 48 h; 0.4 and 0.6 mL at ET 24 and 48 h of passion fruit flavor, and the three doses of the vanilla flavor at ET 24 and 48 h significantly reduced the cell division rate in the meristems of roots, proving to be cytotoxic. Doses of 0.2; 0.4 and 0.6 mL of the passion fruit additive, and the three doses of vanilla tested, in the two exposure times, induced mitotic spindle changes and micronuclei formation in the cells of the test organism used, proving to be genotoxic. Therefore, under the studied conditions, flavoring solutions of vanilla and passion fruit, marketed nationally and internationally, significantly altered the functioning of the cell cycle in root meristem cells of A. cepa.

Resumo Neste trabalho teve-se por objetivo analisar o potencial antiproliferativo e genotóxico de aromatizantes alimentares sintéticos, idêntico ao natural de Maracujá, e artificial de Baunilha. Esta avaliação foi realizada por meio das células meristemáticas de raízes de Allium cepa L., nos tempos de exposição de 24 e 48 horas e nas doses de 0,2; 0,4 e 0,6 ml. As raízes foram fixadas em solução de Carnoy, hidrolisadas em ácido clorídrico e coradas com orceína acética. Analisou-se, em microscópio óptico em aumento de 400×, 5.000 células por grupo tratamento, e utilizou-se o teste estatístico Qui-quadrado a 5% para análise dos dados. Verificou-se que as doses de 0,2 ml, no TE 48 h; 0,4 e 0,6 ml, nos TE 24 e 48 h, do aromatizante de Maracujá, e as três doses analisadas, nos TE 24 e 48 h, do aditivo de Baunilha reduziram significativamente o índice de divisão celular dos meristemas de raízes, mostrando-se citotóxicas. As doses 0,2; 0,4 e 0,6 ml do aditivo de Maracujá, e a de 0,6 ml do aromatizante de Baunilha, nos dois tempos de exposição considerados, induziram alterações de fuso mitótico e micronúcleos as células do organismo de prova utilizado, mostrando-se genotóxicas. Portanto, nas condições analisadas, as soluções aromatizantes de Baunilha e Maracujá, comercializadas nacional e internacionalmente, alteraram significativamente o funcionamento do ciclo celular das células meristemáticas de raízes de A. cepa.

Antiproliferative and genotoxic effects of nature identical and artificial synthetic food additives of aroma and flavor.

This study aimed to analyze the antiproliferative and genotoxic potential of synthetic food flavorings, nature identical passion fruit and artificial vanilla. This assessment used root meristem cells of Allium cepa L., in exposure times of 24 and 48 hours and using doses of 0.2; 0.4 and 0.6 mL. Roots were fixed in Carnoy's solution, hydrolyzed in hydrochloric acid, stained with acetic orcein and analyzed with optical microscope at 400× magnification, 5,000 cells for each treatment. For data analysis, it was used Chi-square test at 5%. Doses of 0.2 mL at ET 48 h; 0.4 and 0.6 mL at ET 24 and 48 h of passion fruit flavor, and the three doses of the vanilla flavor at ET 24 and 48 h significantly reduced the cell division rate in the meristems of roots, proving to be cytotoxic. Doses of 0.2; 0.4 and 0.6 mL of the passion fruit additive, and the three doses of vanilla tested, in the two exposure times, induced mitotic spindle changes and micronuclei formation in the cells of the test organism used, proving to be genotoxic. Therefore, under the studied conditions, flavoring solutions of vanilla and passion fruit, marketed nationally and internationally, significantly altered the functioning of the cell cycle in root meristem cells of A. cepa.

Oral administration of potassium bromate induces neurobehavioral changes, alters cerebral neurotransmitters level and impairs brain tissue of swiss mice.

BACKGROUND: Potassium bromate (KBrO3) is widely used as a food additive and is a major water disinfection by-product. The present study reports the side effects of KBrO3 administration on the brain functions and behaviour of albino mice. METHODS: Animals were divided into three groups: control, low dose KBrO3 (100 mg/kg/day) and high dose KBrO3 (200 mg/kg/day) groups. RESULTS: Administration of KBrO3 led to a significant change in the body weight in the animals of the high dose group in the first, second and the last weeks while water consumption was not significantly changed. Neurobehavioral changes and a reduced Neurotransmitters levels were observed in both KBrO3 groups of mice. Also, the brain level of reduced glutathione (GSH) in KBrO3 receiving animals was decreased. Histological studies favoured these biochemical results showing extensive damage in the histological sections of brain of KBrO3-treated animals. CONCLUSIONS: These results show that KBrO3 has serious damaging effects on the central nervous system and therefore, its use should be avoided.

Toxicological and Genotoxicity Assessment of a Dihydroquercetin-Rich Dahurian Larch Tree (Larix gmelinii Rupr) Extract (Lavitol).

Safety assessment is reported of an orally ingested dihydroquercetin-rich extract (Lavitol) derived from the Dahurian larch tree, used as a food additive and as a dietary supplement ingredient. Dihydroquercetin, a potent antioxidant, is also known as taxifolin. The results of genotoxicity and toxicological tests (Comet assay, micronucleus test in human lymphocytes, chromosomal aberration test, subacute 7-day oral toxicity study, subchronic 90-day toxicology study with histopathologies, and, prenatal and postnatal developmental toxicity studies) on the extract provide further support for the safety of its consumption as a food supplement and food additive.

A 13-week subchronic toxicity study of ferric citrate in F344 rats.

Ferric citrate has been used as a food additive for supplementation of iron. We performed a 13-week subchronic toxicity study of ferric citrate in F344 rats with oral administration in the diet at concentrations of 0%, 0.25%, 1.0%, and 4.0%. Reduction of body weight gain was noted in 4.0% males and females. On hematology assessment, decreases of red blood cells and lymphocytes and increases of platelets and eosinophils were noted in 4.0% males and females. Serum biochemistry demonstrated increased iron and decreased total protein and transferrin in both sexes treated with 4.0% ferric citrate. In addition, an increase of serum inorganic phosphorus levels was noted in 4.0% females. Regarding organ weights, an increase of relative spleen weights was detected in 4.0% males and females and a decrease of absolute and relative heart weights in 4.0% females. On histopathological assessment, colitis with infiltration of eosinophils and hyperplasia of mucosal epithelium, eosinophilic infiltration in mesenteric lymph nodes, and increased hemosiderosis in spleen were observed as treatment-related toxicological changes in 4.0% males and females. Based on the results, the no-observed-adverse-effect level (NOAEL) of ferric citrate was estimated to be 1.0% (596 mg/kg bw/day for males and 601 mg/kg bw/day for females).

Subchronic and reproductive/developmental (screening level) toxicity of complexation products of iron trichloride and sodium tartrate (FemTA).

A complexation/reaction product, termed FemTA, of sodium tartrate [D(-)- and L(+)-tartaric acid and mesotartaric acid], sodium hydroxide, and iron trichloride may have use as an anticaking agent in salt preparations. FemTA is composed of about 4% sodium tartrate, approximately 10% mesotartaric acid, approximately 7% chloride, approximately 4% iron, approximately 7% sodium, approximately 0.3% sodium oxalate, and approximately 65% water. FemTA was tested in a 90-d oral toxicity study, which included a screening level reproductive/developmental toxicity phase, in Harlan Wistar rats. FemTA was administered by oral gavage at 500, 1000, and 2000 mg/kg body weight/d prior to and during mating, or about 20, 40, or 80 mg of iron/kg body weight/d, such that males received 90/91 d of treatment and females 104 to 109 d. Treatment was associated with inflammatory lesions of the lower GI tract at the mid- and high-dose levels, increased liver and kidney weights, increased serum bile acids and blood urea nitrogen, decreased chloride, and changes to hematological parameters consistent with inflammation. The effects were considered the result of iron overload. There were no effects on reproductive/developmental toxicity parameters. The no-observed-adverse-effect level (NOAEL), based on gastrointestinal tract effects was 500 mg/kg body weight/d. The NOAEL for reproductive/developmental toxicity was 2000 mg/kg body weight/d, the highest dose tested.

Characterisation and toxicological assessment of Neutral Methacrylate Copolymer for GRAS evaluation.

Neutral Methacrylate Copolymer is a fully polymerised copolymer used in the pharmaceutical industry to permit pH-independent delayed release of active ingredients from oral dosage forms. This function has potential use with food supplements and this article describes available information on the safety of the substance. Oral administration of radiolabelled copolymer to rats resulted in the detection of chemically unchanged copolymer in the faeces, with negligible absorption. Safety studies revealed no adverse toxicity following repeated administration at doses of up to 2000 mg/kg bw/d in a sub-chronic study in rats or 250 mg/kg bw/d in a sub-chronic study in dogs. No reproductive toxicity occurred at up to 2000 mg/kg bw/d in rats or rabbits. The substance shows no evidence of genotoxicity, has low acute toxicity and no irritation or sensitisation potential. An ADI value of 20 mg/kg bw was concluded from two alternative approaches. Daily exposure from use in dietary supplements is estimated as up to 10.0 mg/kg bw in adults and 13.3 mg/kg bw in children. There would therefore appear to be no safety concerns under the intended conditions of use. The information provided is intended to support an evaluation that the substance may be "generally recognized as safe" (GRAS).

Dammar resin, a non-mutagen, induces [corrected] oxidative stress and metabolic enzymes in the liver of gpt delta transgenic mouse which is different from a mutagen, 2-amino-3-methylimidazo[4,5-f]quinoline.

Dammar resin has long been used in foods as either a clouding or a glazing agent. In a recent study, 2% Dammar resin showed significant hepatocarcinogenicity in a rat 2-year bioassay. Therefore, for an accurate estimate of human risk, it is necessary to understand whether Dammar resin induces liver genotoxicity and the underlying mechanisms of its hepatocarcinogenicity. Modifying effects of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), a typical genotoxic carcinogen produced during cooking of protein-rich foods, was also studied in the present study. Exposure of gpt delta mice to Dammar resin at a dose of 2% for 12 weeks did not induce any obvious mutagenicity in the liver. However, the index of cell proliferation, the level of 8-OHdG, and bax, bcl-2, p53, cyp1a2, cyp2e1, gpx1 and gstm2 gene expression were all significantly increased when compared with the control group. In the IQ treatment group, at a dose of 300ppm, mutagenicity was readily detected, the index of cell proliferation increased, and p53, cyp2e1 and gpx1 gene expression was down-regulated in the liver. Down-regulation of p53, P450s, and gpx1 in the livers of IQ treated mice are consistent with its genotoxic mechanism of carcinogenicity observed in a 675-day study. In contrast, our results using gpt delta mice suggest that Dammar resin is not genotoxic. Instead, the Dammar resin-induced hepatocarcinogenicity seen in our previous 2-year study with rats may have been mediated by non-genotoxic mechanisms, including increased P450 enzyme activity, increased oxidative stress, altered gene expression, and promotion of cell proliferation.

Safety evaluation of a proprietary food-grade, dried fermentate preparation of Saccharomyces cerevisiae.

A safety evaluation was performed for EpiCor, a product produced by a proprietary fermentation process using Saccharomyces cerevisiae. Studies included the following assays: bacterial reverse mutation, mouse lymphoma cell mutagenicity, mitogenicity assay in human peripheral lymphocytes, and a cytochrome P450 ([CYP] CYP1A2 and CYP3A4) induction assessment as well as 14-day acute, 90-day subchronic, and 1-year chronic oral toxicity studies in rats. No evidence of genotoxicity or mitogenicity was seen in any of the in vitro or in vivo studies. The CYP assessment showed no interactions or inductions. No toxic clinical symptoms or histopathological lesions were observed in the acute, subchronic, or chronic oral toxicity studies in the rat. Results of the studies performed indicate that EpiCor does not possess genotoxic activity and has a low order of toxicity that is well tolerated when administered orally. The no observable adverse effect level (NOAEL) was 1500 mg/kg body weight (bw)/d for the 90-day study and 800 mg/kg bw/d for the 1 year study, for the highest doses tested.

The effect of monosodium glutamate on the cerebellar cortex of male albino rats and the protective role of vitamin C (histological and immunohistochemical study).

Monosodium glutamate (MSG) is a natural constituent of many foods and was reported to have neurotoxic effects. The aim of this study was to investigate the possible toxic effect of MSG on histological and glial fibrillary acidic protein (GFAP) immunohistochemical features of cerebellar cortex of albino rats and to evaluate the possible protective role of vitamin C against this effect. Thirty rats were divided into 3 equal groups. Group I, control; Group II, treated with 3 g/kg/day of MSG and Group III, received 100 mg/kg/day of vitamin C simultaneously with MSG. After 14 days, cerebellar tissues were obtained and processed to prepare sections stained with H&E, toluidine blue. The GFAP was detected immunohistochemically. Histological examination of group II showed degenerative changes as pyknotic Purkinje and granule cells with areas of degeneration surrounded by inflammatory cells in granular layer. However, group III showed more preserved histological structure of cerebellar cortex. Statistical analysis of area percent of the GFAP immunoreaction among studied groups showed significant increase in group III when compared with group I and group II. However, a non significant increase was detected in group II when compared with group I. In conclusion, MSG has neurotoxic effect leading to degenerative changes in neurons and astrocytes in cerebellar cortex of albino rats and vitamin C supplementation could protect from these changes. Getting more attention to the constituents of food products is recommended and vitamin C could be advised to protect people from food oxidants additives.