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Mutagenicity and DNA-damaging activity caused by decomposed products of potassium sorbate reacting with ascorbic acid in the presence of Fe salt

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Abstract

Although potassium sorbate (PS), ascorbic acid and ferric or ferrous salts (Fe-salts) are used widely in combination as food additives, the strong reactivity of PS and oxidative potency of ascorbic acid in the presence of Fe-salts might form toxic compounds in food during its deposit and distribution. In the present paper, the reaction mixture of PS, ascorbic acid and Fe-salts was evaluated for mutagenicity and DNA-damaging activity by means of the Ames test and rec-assay. Effective lethality was observed in the rec-assay. No mutagenicity was induced in either Salmonella typhimurium strains TA98 (with or without S-9 mix) or TA100 (with S-9 mix). In contrast, a dose-dependent mutagenic effect was obtained when applied to strain TA100 without S-9 mix. The mutagenic activity became stronger increasing with the reaction period. Furthermore, the reaction products obtained in a nitrogen atmosphere did not show any mutagenic and DNA-damaging activity. PS, ascorbic acid and Fe-salts were inactive when they were used separately. Omission of one component from the mixture of PS, ascorbic acid and Fe-salt turned the reaction system inactive. These results demonstrate that ascorbic acid and Fe-salt oxidized PS and the oxidative products caused mutagenicity and DNA-damaging activity.

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... It has been shown that sorbate in food products can react with the secondary amines, ascorbic acid and ferrous salts and form different adducts at high temperatures, which in turn leads to the food browning (Ferrand, Marc, Fritsch, Cassand, & de Saint Blanquat, 2000;Thakur, Singh, & Arya, 1994). But the potent reactivity of sorbate in the presence of iron salts such as gluconate, citrate, and ferric might leads to the formation of toxic compounds (Kitano, Fukukawa, Ohtsuji, Masuda, & Yamaguchi, 2002). Sorbic acid may also react with nitrite and produce mutagenic 1,4-dinitro-2 methylpyrrole compound that is stable at a wide range of pH (Pérez-Prior et al., 2008;Pérez-Prior et al., 2009). ...
... It has mutagenic and genotoxic effects on human blood cells and is toxic to human peripheral blood lymphocytes DNA (Mamur et al., 2010). It is frequently used with acid ascorbic and iron salts due to its more inhibition efficiency, however, these two materials tend to form mutagenic compounds that cause DNA damage (Kitano et al., 2002). Several studies have shown that sorbate can alter liver function and lead in allergy (Brahmachari & Pahan, 2007). ...
... 150 mg/kg Rec-assay and ames test (Kitano et al., 2002) P. Dehghan et al. Trends in Food Science & Technology 80 (2018) 123-130 ...
Article
The synthetic food additives such as potassium sorbate (PS) are commonly used as a more effective protectant in food and pharmaceutical industries. Recently, increased chronic diseases generated more concerns in consumers and government about preservatives. Regarding contradictory results that has been attained via various studies on application of food additives, the exact monitoring of additives remains controversial by governments. Various research results showed that the increased PS intake (>25 mg/kg) may lead to cytotoxic and genotoxic effects via producing mutagenic compounds and inducing chromosome aberrations, sister chromatid exchange, DNA breakage. The aforementioned factors can develop many chronic diseases especially diabetes mellitus, cancers and etc. Thus, it is necessary to investigate the effects of PS on public health and determine its mechanism of action on various organs and cells. Therefore, this article aimed to evaluate the PS safety through overview of its effects on various tissues, cells and biological macromolecules.
... As an example of this trend, it was found that KS, ascorbic acid and an iron salt such as Fe-EDTA, ferric citrate, ferrous gluconate, ferric pyrophosphate or ferrous sulphate might form toxic compounds. 8 According to the previously mentioned data, it is important to know how the system composition, the presence of other additives and conditions of storage can modify preservative stability and food safety. ...
... Kitano et al, 8 also reported that the degradation of sorbates in an aqueous solution of ascorbic acid was accelerated by the addition of Fe-EDTA. ...
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The effect of pH (3.5 or 5.0), packaging material (glass or polyethylene terephthalate, PET) and EDTA level (0.075 or 0.500 g kg−1) on sorbate stability in model aqueous systems was studied. At pH 3.5, the addition of 0.075 or 0.500 g kg−1 of EDTA showed a protective effect on sorbate stability in both types of packaging materials studied. In contrast, at pH 5.0 and using PET flasks, no effect of EDTA was observed. However, when the systems were packed in glass, EDTA presence increased sorbate degradation. The latter trend might be attributed to the greater iron scavenging ability exhibited by EDTA in those conditions. According to observed trends, in order to minimize sorbate destruction at pH 3.5, the use of glass flasks is recommended and an EDTA level of 0.075 g kg−1. At pH 5.0, however, it is better to use PET flasks, and in these conditions EDTA addition did not influence preservative destruction. The results stress the importance of considering the interactions between system pH, additives, level of use and packaging material in relation to food stability of new formulated products. Copyright © 2004 Society of Chemical Industry
... -Following treatment of the isolated lymphocytes for 1 h, significant PS (potassium sorbate)-induced DNA strand breaks were observed, at all concentrations….Potassium sorbateis clearly seen to be genotoxic to the human peripheral blood lymphocytes in vitro.‖ (Mamur, et al, 2009) Kitano, et al. (2002 state that -potassium sorbate, ascorbic acid and ferric or ferrous salts (Fe-salts) are used widely in combination as food additives‖, and determined to learn whether -the strong reactivity of PS and oxidative potency of ascorbic acid in the presence of Fesalts might form toxic compounds in food during its deposit and distribution. -They found that -ascorbic acid and Fe-salt oxidized Potassium sorbate and the oxidative products caused mutagenicity and DNA-damaging activity.‖ ...
... increases chromosomal aberrations; induces DNA strand breaks; Genotoxic to human lymphocytes (Mamur et al., 2010). Causes mutagenicity and DNA-damaging activity (Kitano, et al., 2002) An excitotoxin that causes neurons(brain cells) to become very excited/very active and incorporate large amounts of calcium into the cell. If neurons cannot pump the excess calcium out, they die. ...
... l-Ascorbic acid (H 2 AA in Scheme 1; Vitamin C) is used pharmaceutically to counteract scurvy and in the food industry as an antioxidant. [1][2][3][4][5] The coordination chemistry of ascorbic acid with metal ions such as iron and copper is of interest because of its many important biological functions. 6,7 Very few metal complexes of vitamin C (L-ascorbic acid) [7][8][9] have been structurally characterized, however. ...
Article
The purple triiron(II,III,III) complex, [Fe(3)Cl(2)(TMRASQ)(4)(HTMRA)(2)] x C(5)H(12) (1 x C(5)H(12)), where H(2)TMRA is a tetramethyl reductic acid, 4,4,5,5-tetramethyl-2,3-dihydroxy-2-cyclopenten-1-one, and HTMRASQ is the semiquinone form of this ligand, was prepared from (Et(4)N)(2)[Fe(2)OCl(6)] and H(2)TMRA and characterized by X-ray crystallography, Mössbauer spectroscopy, and redox titrations. The physical properties of the complex in solution are consistent with its mixed-valent character, as delineated by a solid-state structure analysis. Assignments of the iron and ligand oxidation states in the crystal were made on the basis of a valence bond sum analysis and the internal ligand geometry. As the first well-characterized iron complex of an ascorbic acid H(2)AA analogue, 1 provides insight into the possible coordination geometry of the family of complexes containing H(2)AA and its analogues. In the presence of air and H(2)TMRA, 1 is able to catalyze the oxidation of cyclohexane to cyclohexanol with remarkable selectivity, but the nature of the true catalyst remains unknown.
... Some foodstuffs having no genotoxicity in the natural state will become genotoxic on interaction with other substances, or from the influence of external factors such as heat; for example, potassium sorbate and ascorbic acid are edible food additives that possess genotoxicity in the presence of ferric (or ferrous) salt. 30,31 The results of all tested samples of the mycelium without the S9 mixture were similar to those of the fruiting body. While with the S9 mixture, WSP, aqueous extract heated for 10 min and unheated aqueous extract had an inhibitory effect against M45 − , the other three samples (CPS, CEM and aqueous extract heated for 30 min) did not have an inhibitory effect against M45 − or H17 + . ...
Article
While Pleurotus citrinopileatus is a widely used edible mushroom, little is known about its physiological effects. Extracts, including aqueous extract, water-soluble polysaccharide (WSP), crude protein solution (CPS) and residue from chloroform–ethyl acetate–methanol elution (CEM), were obtained first from fruiting bodies, through a solid-state culture, and then from the mycelium, through a submerged culture. This study explored the antigenotoxicity effects of these extracts from Pleurotus citrinopileatus via the Ames test and a spore rec-Assay. The results showed that, regardless of where the extract came from, the fruiting body or the mycelium, the antigenotoxicity effect was highest for CEM, followed by CPS, aqueous extract and WSP. The results of the Ames test indicated that, among several mutagens, CEM had the highest inhibition rate against AFBl in TA98 and TA100 and the lowest inhibition rate against NQNO. The concentrations of the various extracts were as follows: water extracts were 1 mg ml−1 and 5 mg ml−1 WSP, while CPS and CEM were 0.4 mg ml−1 and 2 mg ml−1, respectively; the higher the concentration of the extract, the higher the antimutagenicity effect. The results of the rec-Assay indicated that CEM had the highest anti-DNA-damaging activity with or without the S9 mixture; the higher the concentration, the more significant the effect (p < 0.05). The anti-DNA-damaging activities were lower in the water extract concentrations, at 30 µg disc−1 dry weight−1, while the WSP, CPS and CEM at 12, 150 and 60 µg disc−1, respectively, were high. Copyright © 2004 Society of Chemical Industry
... 111 For example, Kitano et al. demonstrated the possibility that decomposition products of potassium sorbate with ascorbic acid, which are widely used in combination as food additives in Japan, caused mutagenic and DNA-damaging activity. 112 They emphasized that it is necessary to evaluate the safety of chemicals used as food additives not only before their use, but also after their usage has been introduced. ...
Article
Accumulating evidence suggests that food customs are associated with quality of life in women of the reproductive age. In Japan, dietary limitation for cosmetic purposes, skipping food intake, intake of processed foods and the shift from Japanese to Westernized style food have increased among young women. These changes in food habits can cause inadequate intake of calories, micronutrients, unsaturated fat, phytestrogens and fiber as well as increasing environmental toxins. Furthermore, these food habits increase risk as a result of intake of food additives, anti-oxidants, processing agents and sweeteners, which have been demonstrated to be harmful to human health. These factors are speculated to not only influence the present lifestyle, but also to induce gynecologic disorders such as dysmenorrhea and irregular menstruation. The adverse effects of these dietary habits on pregnancy outcome and carcinogenesis of breast and ovarian cancers have also been demonstrated. In addition, latent development of organic diseases such as endometriosis, which are accompanied by dysmenorrhea, is a concern under the current nutritional environment in young women. Thus, it is an urgent issue to evaluate the present situation of eating habits in young Japanese women and estimate the influence of these habits on the quality of life including reproductive functions. (Reprod Med Biol 2004; 3: 107–114)
... Potassium sorbate is found to be toxic to human DNA in peripheral blood lymphocytes, and hence negatively affects immunity. It is often used with ascorbic acid and iron salts as they increase its effectiveness, but the two substances tend to form mutagenic compounds that damage the DNA (Kitano et al. 2002). Typically used concentrations of potassium sorbate are 0.025-0.1 %. ...
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Potassium sorbate is the potassium salt of sorbic acid, is a widespread and efficient antioxidant that has multiple functions in plants, traditionally associated with the reactions of photosynthesis; however, it has moderate toxicity to various species including rat, fish, bacteria and human health. The effects of potassium sorbate on the movement and photosynthetic parameters of Euglena gracilis were studied during short-term exposure. Potassium sorbate showed acute toxicity to the green flagellate E. gracilis affecting different physiological parameters used as endpoints in an automatic bioassay such as motility, precision of gravitational orientation (r-value), upward movement and alignment, with mean EC50 values of 2867.2 mg L(-1). The concentrations above 625 mg L(-1) of potassium sorbate induce an inhibition of the photosynthetic efficiency and electron transport rate and, in concentrations more than 2500.0 mg L(-1), the Euglena cells undergo a complete inhibition of photosynthesis even at low light irradiation.
... Potassium sorbate is found to be toxic to human DNA in peripheral blood lymphocytes, and hence negatively affects immunity. It is often used with ascorbic acid and iron salts as they increase its effectiveness, but the two substances tend to form mutagenic compounds that damage the DNA (Kitano et al. 2002). Typically used concentrations of potassium sorbate are 0.025-0.1 %. ...
... There are scientific evidences available to support this hypothesis. For instance, the additives of potassium sorbate, ascorbic acid and ferric or ferrous salts have been shown to cause mutagenicity and DNA-damaging activity, when all combined together, but not when used separately [11]. In another study, the synergistic effect of a mixture of six typical artificial food colors (erythrosine, allura red, new coccine, brilliant blue, tartrazine, and fast green) on the toxicity of carcinogen 3-amino-1,4-dimethyl-5H-pyrido [4,3-b] indole (Trp-P-1) has been investigated using primary cultured rat hepatocytes and found that the food-color mixture enhanced cytotoxicity of Trp-P-1 [12]. ...
Article
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No-Observed-Adverse Effect Level (NOAEL) of food additives has been long determined on the basis of toxicological studies. Acceptable Daily Intake (ADI) levels of food additives for human are derived from these NOAEL, and their legal limits are then established for the food products, intentionally added with food additives. However, recent studies demonstrated that consumption of some processed food containing certain food additives might have increased the risk of cancer in human although the legal limits of these additives in processed foods are well respected by the manufacturers. Possible reasons for increased carcinogenicity risk in processed foods containing these additives can be due to various factors: -interaction of additives with some food ingredients, -food processing may change the chemical formula of food additive to a formula to be acting similarly as carcinogenic compound, -a negative synergistic effects when combined with other additives, -improper storage conditions, and -unknown carcinogenic by-products occurring during the food processing. Due to the above mentioned factors we recommend that an additive, intentionally added to the food during processing must be traced officially for its carcinogenicity. In this review, we overviewed all of the food additives authorized in European Union. Therefore, the traceability issues of processed foods containing certain food additives, which have a negligible probability of carcinogenicity in legal limits, must be reinforced in the perspective of public health concerns.
... Son yıllarda Ames test sistemi ve pek çok mutajenite ve kanserojenite yöntemi ile devamlı yüz yüze kaldığımız elektromagnetik dalgaların mutajenik potansiyelleri araştırılmaktadır (Mc Cann et al., 1998;Charlet de Sauvagea et al., 2002). Gıda sanayinde çok fazla kullanılan gıda katkı maddeleri olan askorbik asit, Fe tuzları ve potasyum sorbat metabolitlerinin mutajenik etki gösterdiği de Ames test sistemi ile belirlenmiştir (Kitano et al., 2002). ...
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Çalışmamızda, bir adet çinko fosfat siman (Poscal), bir adet polikarboksilat siman (Aqualox) ve iki adet cam iyonomer simanın (Argion, Meron) mutajenik potansiyelleri üzerine inkübasyon süresinin, ekstraksiyon için kullanılan serum fizyolojik ile dimetil sülfoksitin (DMSO) ve metabolik aktivasyon sisteminin etkisi Salmonella / mikrozom test sistemi ile Salmonella typhimurium TA98, TA100, TA102 ve TA1535 suşları kullanılarak araştırılmıştır. Test edilen simanlardan Poscal’ın S.typhimurium TA98 suşunda (S9−, DMSO, 24 saat, 100 µl/petri) mutajenik etki, S.typhimurium TA1535 suşunda (S9−, serum fizyolojik, taze, 25 µl/petri) zayıf mutajenik etki gösterdiği; Aqualox’un S.typhimurium TA98 suşunda (S9+, DMSO, 24 saat, 12.5, 25, 50 ve 100 µl/petri; S9+, serum fizyolojik, 24 saat, 12.5 ve 25 µl/petri) mutajenik etki, S.typhimurium TA1535 suşunda (S9+, DMSO, serum fizyolojik, taze 100 µl/petri) zayıf mutajenik etki gösterdiği; Meron’un sadece S.typhimurium TA98 suşunda (S9−, DMSO, taze, 25, 50 ve 100 µl/petri) mutajenik etki gösterdiği; Argion’un ise S9 varlığı ve yokluğunda denenen tüm suşlarda mutajenik etki göstermediği bulunmuştur. Çalışma sonunda elde edilen sonuçlara SPSS 11.01 programı ile çok etkenli varyans çözümlemesi yapılarak değerlendirildiğinde, 0.05 ve 0.10 yanılma düzeyinde S9 fraksiyonunun, çözücü tipinin, inkübasyon süresinin ve farklı dozların mutajenik potansiyelin ortaya çıkarılmasında etkili olduğu belirlenmiştir.
... In human, some evidence of idiosyncratic intolerance to sorbate salts have been addressed [5]. In addition, potassium sorbate combined with ascorbic acid (vitamin C) is a chance for mutagenicity developed and DNA-damaging activity [10], while sodium benzoate causes carcinogenesis due to the cause of benzene, a carcinogenic agent. It may cause a danger to public health if the concentrations of the two preservatives exceed the regulated amounts. ...
Article
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Sodium benzoate and potassium sorbates are the two typical preservatives widely used in Vietnam and other countries. The maximum level (ML) of sodium benzoate and potassium sorbate in processed meat products imposed by Ministry of Public Health is 1000 ppm. Although there are warnings about overusing of these preservatives that related to human health, many manufacturers do not follow the regulations. The aim of this study was to survey and consider the amounts and presence of these preservatives in processed meat products by using High-performance liquid chromatography (HPLC) method. 90 samples of brands and no brands including Vietnamese pork rolls, pâtés, hams, sausages, and fermented pork rolls that available at markets in Ho Chi Minh City were analysed for these two preservatives. There was a preference for using sodium benzoate in all samples. Moreover, Vietnamese pork roll samples had the highest percentage of samples with preservatives concentrations exceeding the ML. Among 90 samples, sodium benzoate was detected in 52.2% of samples and 17.8% of them exceeded the ML, while potassium sorbate was found in 24.4% of samples and only 2.2% of them exceeded the regulated amount. 46.4% of Vietnamese pork rolls, 12.5% of pâtés, and 9.1% of fermented pork rolls had sodium benzoate exceeded the ML, whilst ham and sausage samples contained the concentrations inside the safety limits. Furthermore, only one sample of Vietnamese pork rolls and one sample of sausages had potassium sorbate concentrations surpassing the ML with the level of 1,717.57 mg/kg and 1,814.00 mg/kg, respectively. Furthermore, branded samples showed a significantly different result in compared with no branded samples. Of branded samples, exceeding sodium benzoate level ML was detected in 10% of samples and none of the samples found surpassing potassium sorbate limit amount. Nevertheless, 27.5% and 5% of unbranded samples had sodium benzoate and potassium sorbate higher than the authorized amounts, respectively. New strategies should be established to monitor the food safety issues.
... It follows that most producers involved in food industry are using food additives to achieve the desired organoleptic characteristics of each product (16). Unfortunately, however these additives may have adverse health effects as recent studies demonstrated such side effects (13,14). ...
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It has been reported that some of the food additives may cause sensitization, inflammation of tissues, and potentially risk factors in the development of several chronic diseases. Thus, we hypothesized that expressions of common inflammatory molecules - known to be involved in the development of various inflammatory conditions and cancers - are affected by these food additives. We investigated the effects of commonly used food preservatives and artificial food colorants based on the expressions of NFκB, GADD45α, and MAPK8 (JNK1) from the tissues of liver. RNA was isolated based on Trizol protocol and the activation levels were compared between the treated and the control groups. Tartrazine alone could elicit effects on the expressions of NFκB (p = 0.013) and MAPK8 (p = 0.022). Azorubine also resulted in apoptosis according to MAPK8 expression (p = 0.009). Preservatives were anti-apoptotic in high dose. Sodium benzoate (from low to high doses) dose-dependently silenced MAPK8 expression (p = 0.004 to p = 0.002). Addition of the two preservatives together elicited significantly greater expression of MAPK8 at half-fold dose (p = 0.002) and at fivefold dose (p = 0.008). This study suggests that some of the food preservatives and colorants can contribute to the activation of inflammatory pathways.
... However, the major reaction products from the interaction of sorbic acid with different amines (e.g., methylamine, ethylamine) are not mutagenic in the Ames assay or with HeLa cells and plasmid DNA. In contrast, the interaction of sorbic acid with nitrites (Namiki et al. 1980(Namiki et al. , 1981 and with ascorbic acid in the presence of iron salts (Kitano et al. 2002) can produce mutagenic reaction products in vitro. Because these latter food additives can be used simultaneously in certain food categories, it is possible that some individuals may consider the safety of those products to be at risk. ...
Article
Consumers' criteria for evaluating food safety have evolved recently from considering the food's potential to cause immediate physical harm to considering the potential long-term effects that consumption of artificial ingredients, including antimicrobial preservatives, would have on health. As bacteriostatic and bactericidal agents to prevent microbial spoilage, antimicrobials not only extend shelf life, but they also enhance the product's safety. Antimicrobials and their levels that may be used in foods are specified by regulatory agencies. This review addresses the safety of antimicrobials and the potential consequences of removing those that are chemically synthesized or replacing them with antimicrobials from so-called natural sources. Such changes can affect the microbiological safety and spoilage of food as well as reduce shelf life, increase wastage, and increase the occurrence of foodborne illnesses. Expected final online publication date for the Annual Review of Food Science and Technology Volume 8 is February 28, 2017. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
... It seems that this preservative can cause mutagenicity and DNA-damaging activity, genotoxicity affecting human peripheral blood lymphocytes in vitro as well as showing a weak genotoxic effect in Chinese hamster cells. [31][32][33][34][35] Although this compound may be considered as antimicrobial compound against ochratoxigenic molds, there is a need to keep potassium sorbate quantities at low levels in foods where it is added. An alternative strategy that can be used against ochratoxigenic Aspergillus spp. ...
Article
BACKGROUND Ochratoxin A (OTA) is a mycotoxin produced by several species of Aspergillus and Penicillium fungi. The presence of OTA in raisins is mainly related to the black Aspergillus spp. contamination. This toxin poses risks to human and animal health due to their high toxicity and carcinogenicity. Therefore, new strategies to avoid the risk associated to OTA are necessary. RESULTS In the present study, a comparison between the effects of the antifungal protein PgAFP and potassium sorbate (E‐202), on the growth of Aspergillus carbonarius, biosynthetic‐ and stress‐related gene expression and its OTA production at two water activity (aw) levels 0.95 and 0.93 aw, was carried out. The results showed that PgAFP successfully controlled OTA production, whereas E‐202, although was able to decrease Aspergillus carbonarius growth, caused a significant increase in OTA production by the fungus. CONCLUSION PgAFP protein, a biological compound with an antifungal activity, is safer to use compared to E‐202 and may be proposed as a food preservative and a useful biocontrol strategy to control ochratoxigenic A. carbonarius in raisins. This article is protected by copyright. All rights reserved
... Different studies on the stability of sorbates have been carried out in aqueous model systems (Hayatsu et al., 1975;Tanaka et al., 1976;Arya, 1980;Namiki et al., 1980;Osawa et al., 1980;Saxby et al., 1982;Hartman, 1983;Seow and Cheah, 1985a,b;Gerschenson et al., 1986;Obanu and Ledward, 1986;Arya and Thakur, 1988;Wedzicha and Brook, 1989;Khandelwal and Wedzicha, 1990;Ledward, 1990;Jung et al., 1992;Campos and Gerschenson, 1996;Campos et al., 1997;Ferrand et al., 1998aFerrand et al., ,b, 2000aCastro et al., 2002;Kitano et al., 2002;Perez-Prior et al., 2005, 2009Gliemmo et al., 2008;Lopes et al., 2012), foods, such as meat products (Campos et al., 1995), soybean cheese (Torres et al., 1989), orange squash product (Vidyasagar and Arya, 1983), juices and fish paste (Vidyasagar and Arya,1984) and intermediate moisture meat (Webster et al., 1986;Campos et al., 1995). ...
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In this opinion, the EFSA Panel on Food Additives and Flavourings (FAF Panel) was requested by the European Commission to carry out a scientific evaluation of an extended one-generation reproductive toxicity study (EOGRTS) to determine whether it would allow reconsideration of the temporary group acceptable daily intake (ADI) for sorbic acid (E 200) and potassium sorbate (E 202), established by the Panel on Food Additives and Nutrient Sources added to Food (ANS Panel) in 2015. From the EOGTRS, the FAF Panel identified a lower confidence limit of the benchmark dose (BMDL) of 1,110 mg sorbic acid/kg body weight (bw) per day. By applying a default uncertainty factor of 100, the Panel established a group ADI expressed as 11 mg sorbic acid/kg bw per day for sorbic acid (E 200) and its potassium salt (E 202). In addition, European Commission asked EFSA to review a report on the ‘Stability of sorbic acid (E 200) and its potassium salt (E 202) during food processing and storage’ provided by industry. No new information was provided in this report, and therefore, in this opinion, there was no re-assessment of the EFSA ANS opinion conclusions from 2015 regarding the stability of sorbates in food. © 2019 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.
... Furthermore, the consumption of high contents of SB in beverages was also linked with attention deficit hyperactivity disorder (ADHD) symptoms in children [33] and college students [34]. Potassium sorbate showed genotoxicity, mutagenicity, and DNA-damaging activity at high concentrations or combined with nitrites in vivo [35,36] and in vitro against human peripheral blood lymphocytes [37]. Thus, alternative options such as natural antimicrobial agents with significant antimicrobial efficacy to extend shelf life in cheese are needed and have received researchers' significant attention. ...
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The side effects and potential impacts on human health by traditional chemical additives as food preservatives (i.e., potassium and sodium salts) are the reasons why novel policies are encouraged by worldwide public health institutes. More natural alternatives with high antimicrobial efficacy to extend shelf life without impairing the cheese physicochemical and sensory quality are encouraged. This study is a comprehensive review of emerging preservative cheese methods, including natural antimicrobials (e.g., vegetable, animal, and protist kingdom origins) as a preservative to reduce microbial cheese contamination and to extend shelf life by several efforts such as manufacturing ingredients, the active ingredient for coating/packaging, and the combination of packaging materials or processing technologies. Essential oils (EO) or plant extracts rich in phenolic and terpenes, combined with packaging conditions and non-thermal methods, generally showed a robust microbial inhibition and prolonged shelf life. However, it impaired the cheese sensory quality. Alternatives including EO, polysaccharides, polypeptides, and enzymes as active ingredients/nano-antimicrobials for an edible film of coating/nano-bio packaging showed a potent and broad-spectrum antimicrobial action during shelf life, preserving cheese quality parameters such as pH, texture, color, and flavor. Future opportunities were identified in order to investigate the toxicological effects of the discussed natural antimicrobials' potential as cheese preservatives.
... Although considered safe for dogs and cats at a maximum content of 5000 mg/ kg semi-moist complete feed, it is recognised as a skin, eye and respiratory irritant (EFSA 2012a). It can also damage human white blood cells, in vitro (Mamur et al. 2010), and, when given with vitamin C and ferrous salts, cause mutagenicity and DNAdamaging activity (Kitano et al. 2002). ...
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A good, nutritious diet is essential for the health and well‐being of our domestic pets. Today, most pet dogs and cats are fed highly processed food bearing little resemblance to canine and feline ancestral diets. Additives are included in processed pet food to provide nutritional benefits, ensure food safety, and maintain the desirable features of colour, flavour, texture, stability and resistance to spoilage. This paper reviews the safety of various additives in processed pet food. Labelling, safety assessment, and ethical concerns regarding existing toxicity testing procedures are also considered. The adequacy of testing for many additives and the scientific basis for determining safety are questioned. Additives can be synthetic or ‘natural’ although the distinction can be blurred when naturally derived substances are synthesised in the laboratory, or extracted using a high level of physical and chemical processing. Although additives play important roles in processed food production, updated strategies and technologies may be required to establish their safety in the pet food industry.
... Moreover, most products contain a mixture of additives, the toxic effect of which may have not only additive, but also a synergistic nature. It is important to note that the products of these additives' oxidation formed during the production and storage of foods are also chemically active compounds and show mutagenic activity [4]. ...
Article
The presence of food additives in food products may be associated with the risk of their toxic effects on human body. Therefore, the study of approaches to testing their safety seems to be a particularly urgent task. The aim of this study was to determine the conditions for extracting food preservatives from the samples of preserved pureed vegetables for further bioassay of the extract obtained in the Allium test. Onion roots were used as a test object in this method. Two extraction methods of benzoic and sorbic acids added to pureed vegetables have been developed. Distilled water and acetone were used as extracting solutions. The extraction efficiency was evaluated on Shimadzu Prominence LC-20 liquid chromatograph (Japan) in the ultraviolet range, wavelength 235 nm (benzoic acid), 285 nm (sorbic acid). According to the results of studies using both water and acetone as extractants, the degree of preservatives extraction was approximately the same and quite high. In the quantitative calculation of the preservatives content in pureed vegetables, the value of the correction factor was 0.8. However, due to certain production characteristics of this product, i. e. the stage of cauliflower homogenization, obtaining an extract with acetone seems to be more acceptable for the Allium test conditions.
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In order to investigate the effect of sodium benzoate dosage on reproductive efficiency in mature male rats, the current study was conducted at the Faculty of Science, Qadisiyah University for the period from 15\10\2016 to 15\4\2017. Sixty adult male rats (aged 56 days and weighted 138±8.8 g) have been used in the present study. The rats have been divided randomly into three equal groups (20 rats to each group). The first group included the control (C) group and was injected with physiological saline solution daily. The second group was injected with sodium benzoate at a concentration of (50 mg\kg). The third group was injected with sodium benzoate at a concentration of (100 mg\kg). Each group was divided into two subgroups, each containing 10 rats, depending on the duration of the dosage, 2-3 weeks. After 24 hours on the last day of the experiment, animals were sacrificed, and testicular samples were taken for histopathological study. The result of the histological study on the testis showed a significant decrease in the composition of the sperm in the two groups (T1, T2) where the spermatozoa showed a small number of primary and secondary sperm cells as well as a decrease in the number of sperm and Leydig cells. This decrease increases with increasing concentration and duration compared to the control group. It is concluded from the results of the current experiment that the dosage of animals with sodium benzoate at a concentration of (50,100 mg\kg) body weight has a clear effect on the reproductive efficiency of male rats.
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Objective: According to Food Safety and Standards Authority of India (FSSAI) the preservatives, sodium benzoate and potassium sorbate belong to permitted class II preservatives. The aim of this study is to determine the concentration levels of these preservatives in food products that are consumed by school children and to assess the chronic dietary exposure by conducting the Total Diet Study (TDS). Methods: The quantitative determination was carried out by UV spectrophotometer. The absorbance for sodium benzoate and potassium sorbate were measured at 228 and 250 nm respectively. The 24-hour diet recall method was used to estimate the amount of food ate in last 24 hours. For estimation of preservative exposure dietary modelling techniques were utilized which combine the amount of preservative concentration present in that food with the amount of food consumed. Then the dietary exposure was assessed by considering the Acceptable Daily Intake (ADI). Results: The results include chemical concentration levels of the foods analyzed as well as estimated dietary exposures and contributions to the exposure from different foods. The obtained mean concentration of sodium benzoate was found to be425 ppm for sauces, 161 ppm for pickles and 80 ppm for soft drinks. Potassium sorbate was found to be 130 ppm for fruit juices,302 ppm for jellies and 380 ppm for jams. The highest mean dietary exposure for both the preservatives was observed in children of 2-7 years age group, the percentage exposure of sodium benzoate was 33% of the ADI and potassium sorbate was 17 % of the ADI. Conclusion: This study can enlighten the public on the consumption of preservative containing food products within the limit and encourages to eating fresh preservative free foods. © 2015, International Journal of Pharmacy and Pharmaceutical Science.
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To study the structure-function relationship of the oxidative-damage effect of ascorbic acid, we have focused on the interaction between plasmid DNA pUC19 and a series of ascorbic acid derivatives modified on different OH groups in the presence of transition metal ions. Some ascorbic acid derivatives can selectively cleave plasmid DNA from Form I to Form II in the presence of low concentration of Cu2+ just like ascorbic acid itself, while other derivatives oxidatively damage plasmid DNA slightly. We found that those derivatives with unattached 2-OH and 3-OH groups retain the ability to cleave the plasmid DNA. The derivatives that have been methylated on 2-OH or 3-OH can only cleave plasmid DNA softly, and those derivatives that have been protected on both 2-OH and 3-OH can hardly exert an oxidative damage on plasmid DNA under the same condition. Form these results, we can draw the conclusion that 2-OH and 3-OH groups of the ascorbic acid molecule contribute most to this biological activity.
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Introduction. In view of the ongoing research into the negative effects of fruit juice on human health, we aimed to study the subchronic toxicity of apple juice, a model mixture based on its components, and ethanol on biomass growth, cellular oxidative enzymes, and chromosomal abnormalities in Allium cepa roots. Study objects and methods. Our objects of study included clarified apple juice and its components such as fructose, glucose, sucrose, D-sorbitol, and malic acid. After treating Allium cepa roots with apple juice and a model mixture in different concentrations, we analyzed their toxic effects on biomass growth, malondialdehyde levels, as well as the nature and frequency of proliferative and cytogenetic disorders in the plant tissues. Results and discussion. The incubation in an aqueous solution of apple juice at a concentration of 1:5 inhibited the growth in root mass by 50% compared to the control (water). The mitotic index of cells decreased with higher concentrations of juice, reaching zero at a 1:5 dilution. The fructose and model solutions in the same concentrations appeared less toxic in relation to cell mitosis and root mass growth. Although malondialdehyde levels increased in the onion roots treated with juice and model solutions, they were twice as low as in the control due to the juice’s antioxidant activity. Adding 1% ethanol to the 1:2 diluted juice abolished the effect of acute toxicity on root growth and reduced malondialdehyde levels by 30%. Conclusion. The study revealed a complex of interdependent biomarkers of apple juice responsible for its subchronic toxicity in Allium cepa roots. These data can be used to create biological response models based on the approaches of systems biology and bioinformatics.
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Usually, foods are packaged with some preservative and such chemicals in the form of organic and inorganic preservative are being used for packaging different types of food. But in India, companies are using inorganic preservatives mostly and these inorganic preservatives are very harmful to human’s body. In this paper, a new model is developed to reduce the quantity of chemicals in packaged food. This problem is modelled by fuzzy inference and is also combined with graph theory methodology to provide a unique and defective solution. The side effect of each packaged food is to be measured using a fuzzy interference system. A real-life application on Haringhatachicken has been presented in this paper by using fuzzy inference logic and graph theory. At last, a comparison of the result has been demonstrated to justify the solution.
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The interaction between potassium sorbate (PSA) and bovine serum albumin (BSA) was investigated by fluorescence spectroscopy, resonance light-scattering (RLS) spectroscopy. The quenching mechanism was analyzed referring to PSA against the fluorescence and the resonance light scattering spectra of BSA. The apparent binding constants (KA) between PSA and BSA were 2.23×103 L·mol-1 (288 K), and 2.74×103 L·mol-1 (293 K), respectively. The corresponding binding sites values (n) were 1.02 and 0.99. The changes of negative entropy change and enthalpy indicate that the interaction of PSA and BSA was driven mainly by electrostatic interactions. The binding process was a spontaneous process in which Gibbs free energy change was negative. The effect of PSA on the conformation of BSA was analyzed by synchronous fluorescence spectroscopy. Furthermore, the binding distance r=2.83 nm between PSA and BSA was obtained based on the mechanism of Forster non-radiation energy transfer.
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Propolis phytochemical extracts prepared using a “green” method based on aqueous extraction with cyclodextrin were studied for antifungal activity as a natural alternative to sorbate in food spoilage. The synergistic antifungal effects between “propolis green extract” (PGE) and potassium sorbate (PS) were examined against three common food spoilage yeast species, Torulaspora delbrueckii, Millerozyma farinose, and Brettanomyces bruxellensis by culture, combined with flow cytometry for the evaluation of microbial injury. Growth kinetics showed that the antifungal effect was depended on the concentration of the PGE and the yeast species. Interestingly, flow cytometry revealed a synergy between PGE and PS on cell viability which was not evident by culture. The results suggest that PGE could be used for natural food preservation through direct cell death or microbial injury as part of hurdle technology. There is a growing demand for clean label foods, containing natural additives based on bioactives from plants, which can replace artificial ones, and can act as antioxidant and antimicrobial agents. Plant‐derived biomolecules (phenolic substances, terpenoids, and flavonoids) are widely studied for their functionality as food antioxidants and preservatives. They have already been incorporated in food matrixes in the form of extracts. Propolis green extract developed in the current study could be used as a natural antimicrobial in food matrices.
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In the etiology of breast malignancy, dietary habits and lifestyle-related risk factors in the coherence of cancer prevention guidelines, e.g., WCRF/AICR is well documented. Moreover, the consumption of staple food products rich in carbohydrate as major calorie resources such as potato, bread and ready to eat cereals are partly object to having roles in breast tumorigenesis. In the current review, the possible associations of preservatives and nutritive risk factors of staple foods in dietary patterns with breast cancer development based on the experimental and observational cohort-based studies was discussed. In this regard, the influence kinetics of insulin, insulin-like growth factor-1 and insulin-activated AMPK/Akt pathway on sorts of starch and protein is a concerning biologic concept in promoting the risk of tumorigenesis. Hence, Akt-dependent controlled proliferation, induced apoptosis and controlled oxidative stress in specific condition could be concentrated as the preventive strategies. Although preservatives such as sorbate, benzoate, and nitrate are considered GRAS, there are some issues concerning the safety of their applications, including the possibility of allergies and immunosuppressive effects from benzoate, the formation of carcinogenic nitrosamines from nitrites, and interaction sorbate with nitrite in the stomach which consequently can be resulted in production of a series of genotoxic compounds.
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Background: Potassium sorbate is the potassium salt of sorbic acid .It is considered the safest preservative as it is widely used in food preservative, however, it is not without side effects.in vivo and in vitro studies investigated that PS induced oxidative stress, which leads to tissues damage. Aim: This study was conducted using Female rats as a typical for the mammals' animals to determine the levels of oxidative stress biomarkers in serum and ovary , reproductive hormones and histological change that can cause after Exposure to potassium sorbate as a food additive in their diet. Methods: In present study ,60 adult virgin Females rat. It was divided into two secondary experimental groups represent a short and long-terms studies , each included 30 Females rat. Each secondary experimental group divided into three subgroups, each subgroup involved (10) rats. Females rats of control subgroups fed normal diets without adding potassium sorbate, the females rats of first and secondary subgroups (G1 and G2) feeding daily with PS in their diet at per cents 5% and 10% respectively .At the end of each term, females rats were sacrificed and blood samples were collected to estimated levels of oxidative stress biomarkers (MDA and CAT activity) and reproductive hormones (FSH,LH,PROG and E2) in serum .The ovaries, oviducts and uteri for detection of histological changes in reproductive organs, in addition to determine the levels of MDA and CAT activity in ovaries. Results: Consumption of PS at per cents 5% and 10% in the long-term causes a significant rise of MDA and significant decline of CAT enzyme activity in plasma. In ovaries tissues, MDA levels increase at per cents 5% and 10% in both periods short and long-terms. While the decline of CAT enzyme activity noted at 10% of PS in the long-term only. This study confirmed found a positive significant correlation between MDA of plasma and ovaries in the long-term .Also, there was a positive significant correlation between CAT activity of plasma and ovaries in short and long-terms. The levels of hormones FSH, LH, PROG and E2 decreased significantly at 10% of PS in the long-term study. While a high level of plasma E2 is observed at 10% of PS in the short-term study. The histopathological change observed in studied tissues especially females rats' that consumption of PS at per cent 10% for a short and long-terms, including, follicular atresia in oocytes of rat's ovaries, inflammation in oviducts and degeneration of endometrium in the uterus of females rats'. Conclusions: In this study, can conclude according to the obtained results that potassium sorbate can induce oxidative stress by elevation of MDA concentration and dimension of CAT enzyme activity that reverse negatively on sex hormonal and reproductive tract.
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Food additives are used in meat products for food safety, shelf life and food technology reasons. The types and levels of food additives used in processed meats must comply with the state regulations in order to process safe foods for human consumption. Food additive calculator which is a web-based version, provided by The Thai Food and Drug Administration to help the producers in calculating maximum use level of food additives for all kinds of foods including meats, is found too complicated for small entrepreneurs with inadequate knowledge. Web-based version is also not responsive design and display to users view and is not mobile user oriented. Therefore, this research was aimed to develop a user friendly and convenient mobile application on Android Mobile Operating System for calculating maximum permitted level of food additives used for meat products. This mobile application is designed for calculating four kinds of food additives widely used in ten different favorite meat products. The application gives a correct results of maximum level of each food additives based on the type and weight of meat products. Therefore, this application may be beneficial to reduce the health risk from food additive abuse in meat products.
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Sodium benzoate and potassium sorbate are extremely useful agents for food and beverage preservation, yet concerns remain over their complete safety. Benzoate can react with the ascorbic acid in drinks to produce the carcinogen benzene. A few children develop allergy to this additive while, as a competitive inhibitor of D-amino acid oxidase, benzoate can also influence neurotransmission and cognitive functioning. Model organism and cell culture studies have raised some issues. Benzoate has been found to exert teratogenic and neurotoxic effects on zebrafish embryos. In addition, benzoate and sorbate are reported to cause chromosome aberrations in cultured human lymphocytes; also to be potently mutagenic toward the mitochondrial DNA in aerobic yeast cells. Whether the substantial human consumption of these compounds could significantly increase levels of such damages in man is still unclear. There is no firm evidence that it is a risk factor in type 2 diabetes. The clinical administration of sodium benzoate is of proven benefit for many patients with urea cycle disorders, while recent studies indicate it may also be advantageous in the treatment of multiple sclerosis, schizophrenia, early-stage Alzheimer's disease and Parkinson's disease. Nevertheless, exposure to high amounts of this agent should be approached with caution, especially since it has the potential to generate a shortage of glycine which, in turn, can negatively influence brain neurochemistry. We discuss here how a small fraction of the population might be rendered—either through their genes or a chronic medical condition—particularly susceptible to any adverse effects of sodium benzoate.
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Twenty Schisandra samples were collected from different locations. Contents of 7 lignans in the samples were determined and analyzed by HPLC method coupled with hierarchical clustering analysis (HCA) and principal component analysis (PCA), and the antioxidant capacity of Schisandra from the different locations was evaluated by reducing power, ferric thiocyanate (FTC) and 2, 2′–diphenyl–1–picrylhydrazyl (DPPH) assay. The results showed that there was a significant difference in the content of lignans between Schisandra chinensis and Schisandra sphenanthera. The Schisandra sphenanthera samples in the southwest of China were significantly different from those from the other locations. The antioxidant capacity of Schisandra chinensis was significantly superior to that of Schisandra sphenanthera, and the main antioxidant components were schisandrol A, schisandrol B and schisandrin B based on the result of discrimination analyses. The differences in the chemical composition and antioxidant activity of lignans in Schisandra chinensis and Schisandra sphenanthera from the different locations were investigated in this study, which may provide an experimental basis for the quality control of Schisandra. This article is protected by copyright. All rights reserved.
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The study aimed to improve the quality characteristics of Turkish dry-fermented sausages (sucuk) using different concentrations of chitosan (CH) coating as superficial mold inhibitor. The sausages were treated (w/w) with chitosan (0.2%, CH1; 0.5%, CH2 and 1%, CH3), potassium sorbate (20%, PS), acetic acid (1%, AA) and distilled water. Treatment with PS and CH3 resulted in a remarkable reduction of mold and yeast counts in the sausages and on casings at the end of ripening. Total aerobic mesophilic bacteria and lactic acid bacteria (LAB) varied from 7.19-7.29 to 9.01-9.27 and from 6.37-6.44 to 8.53-8.93 log CFU/g at day 0 and 12, respectively. Treatment with chitosan did not affect the natural microbiota of the sausages. Enterobacteriaceae counts were lowered from 5.79-5.89 to 2.08-2.53 log CFU/g by chitosan. Moreover, the rate of lipid oxidation in the sausages decreased by chitosan treatment. Sensory attributes were also notably enhanced in the cooked sausages treated with chitosan.
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The oxidative modification of bovine serum albumin with an ascorbic acid-copper ion system was studied. Under physiological conditions (pH 7.2, ambient temperature), this system mainly caused the modification of amino acid residues in the protein, and its polymerization was scarcely observed. The results of spectrophotometric assays and amino and analysis of the protein clearly suggested the selective damage to tryptophan and histidine residues. The reaction could be retarded by catalase and Cu(II)-chelating agents, while superoxide dismutase and hydroxyl radical scavengers showed little effect. These specific reactions were explained by the site-specific formation of the oxygen-derived free radical followed by its reaction with a specific site of the protein. © 1988, Japan Society for Bioscience, Biotechnology, and Agrochemistry. All rights reserved.
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The oxidative modification of bovine serum albumin with an ascorbic acid-copper ion system was studied. Under physiological conditions (pH 7.2, ambient temperature), this system mainly caused the modification of amino acid residues in the protein, and its polymerization was scarcely observed. The results of spectrophotometry assays and amino and analysis of the protein clearly suggested the selective damage to tryptophan and histidine residues. The reaction could be retarded by catalase and Cu(II)-chelating agents, while superoxide dismutase and hydroxyl radical scavengers showed little effect. These specific reactions were explained by the site-specific formation of the oxygen-derived free radical followed by its reaction with a specific site of the protein.
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For efficient detection and evaluation of environmental chemical mutagens, the assay procedures must be simple and inexpensive. By the use of microorganisms as the repair test, chemicals that damage DNA may be selected very quickly. These DNA-damaging chemicals are likely to be mutagenic and carcinogenic as well as efforts of chromosome aberrations. Recent developments in techniques and mutagen screening by the rec-assay system using recombination-proficient and -deficient strains of Bacillus subtilis are reviewed in this article.
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We reexamined safety of some cosmetic materials on a hereditary toxicity. The cosmetic materials tested were preservatives, Sunscreens, antioxidants, hormones and surfactants. Mutagenicity assay were carried out for Rec-assay using Wild and Recombination-deficient strains of B. Subutilis and Reversion assay using Salmonella typhimurium TA98 and TA100 with or without the microsomal activation (±S-9mix). In addition to the above-described procedures, Rec-assay with irradiating fluorescent lump or cold incubation were carried out to some materials, such as sunscreens and antioxidants. Irg-DP300, a preservative, was weak rec-positive at very high concentration such as 5 mg/ disk, but negative on revession assay. Both 8-MOP and 0-201 newly found out as positive control of photo-rec assay were clearly rec-positive by irradiation of fluorescent lump, but all of sunscreens and antioxidants were negative. Estradiol, a hormone, induced slightly more revertants than control with S-9mix and three anion surfactants of sulfate derivatives (Surf-1, 2, 4) and two nonion surfactants of cetyl ether and lanolin alcohol derivatives (Surf-13, 14) also exhibited the same effects with or without S-9mix, but we couldn't sufficiently recognize these mutagenicity. These phenomena are yet obscure whether due to any reasons.
Article
Oxidative depolymerization of several polysaceharides induced by oxygen radical generating systems such as ascorbic acid-copper ion was investigated by the increases in their reducing powers and by gel-filtration. All polysaceharides used in these experiments were greatly depolymerized within 24 hr at room temperature. We thought that the main factors in the oxidation of these polysaceharides were the actions of hydroxyl radical (•OH) generated from the autoxidation of ascorbic acid. On the other hand, dextrans having molecular weights above 103-104 were more susceptible to the oxidation reaction with •OH than smaller oligosaccharides (MW<103), and we estimated that the formation of sugars-copper ion complexes was highly important to the oxidative depolymerization of polysaceharides.
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The degradation of several synthetic water-soluble polymers, such as poly (sodium acrylate) (PSA), poly (sodium methacrylate) (PSM), poly (sodium 2-ethylacrylate) (PSE), polyacrylamide, and polyethylene oxide), with L-ascorbic acid (ASA) was investigated in a phosphate buffer solution adjusted at pH 7 at 30 °C under introduction of air of constant flow rate. The progress of degradation was monitored by the reduction of relative viscosity of the reaction system. All these polymers were degraded easily. The degradability of the acrylate polymers increased in the order; PSE < PSA < PSM. The extent of consumption of ASA in these systems determined by the decrease in UV absorption based on ASA also increased in the order of PSE < PSA < PSM < control, so these polymers suppressed the oxidation of ASA. The initiation mechanism of the polymer degradation is discussed; ASA/O2 generates hydroxyl radical during the oxidation process, and the hydroxyl radical abstracts hydrogen atom from the polymer at α -position of the substituent of the monomer unit, or the hydroxyl radical accepts one electron from the carboxylate anion to generate the acyloxyl radical followed by decarboxylation, especially in the case of PSM. The activity of ASA/O2 in the polymer degradation was found to be significantly high as compared with commercial hydrogen peroxide. Thus, ASA/O2 would be effective for waste polymer treating agent.
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The mechanism of inactivation of a double-stranded DNA phage, phage J1 of Lactobacillus casei, by ascorbic acid was investigated. Bubbling air, oxidizing agents and transition metal ions enhanced the rate of inactivation of the phage by ascorbic acid. In contrast, bubbling nitrogen gas, other reducing agents and radical scavengers prevented the inactivation. The results indicated that the inactivating effect of ascorbic acid was oxygen dependent and caused by free radicals formed during the autoxidation of ascorbic acid. The target of ascorbic acid in the phage particle was not the tail protein but DNA. Ascorbic acid caused single-strand scissions in phage DNA, as exhibited by alkaline sucrose density gradient centrifugation analysis, and caused a slight decrease in the viscosity of DNA.
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In the presence of a catalytic amount of copper(II) ion, ascorbate stimulated the oxidative damage to the peptides via selective loss of histidine residues. The modified peptides yielded considerable amounts of ammonia and trace amounts of aspartate, glutamate, and serine with the acid treatment of the modified peptides. Such specific action of ascorbate toward the histidine residues gave rise to the depolymerization of polyhistidine accompanied by a significant loss of histidine residues. A 13C NMR study clearly revealed the preferential binding of Cu(II) ion to the histidine residue in a peptide. It is therefore estimated that the selective reaction of ascorbate to the histidine residue should be attributed to the specific reaction of the histidine residue with copper ion.
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This review evaluates the published work on sulphur dioxide and ascorbic and nitrous acid reactions with other food additives to form stable compounds. In some cases, such as between nitrite and sorbic acid, the compounds formed have a potentially higher toxicity than the original additives. No adverse effects have been demonstrated in real foods, however, probably due to the adoption of substantial safety margins between no-effect levels in animals and the maximum levels of additives to which humans could be exposed.The reactions discussed in this review are those most likely to occur in current additive usage. However, due to the large numbers of permitted food additives, many more interactions occur in foods that could lead to chemical reactions under favourable conditions.
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In the present work we intend to find an accurat methodology to establish in an easy way the mutagenic potential of drugs employed as food additives. For that purpose we first selected a microbiological system for performing this assay. The method assayed consisted of investigating the effect exerted on genetic recombination by the following chemical agents: Chloroacetic Acid, Iodoacetic Acid, Sorbic Acid, Potassium Metabisulfite, Sodium Nitrite, Auramine and Erythrossine. The activity of these agents was detected though their effect on the transformation of an auxotrophic strain of Bacillus subtilis. Comparative assays of reversion of characters have been made with strains of Salmonella typimurium already used by other authors. These assays have also been repeated with several auxotrophic strains of Bacillus subtilis and different genetic characters have been studied. Most results suggest that changes in the recombination process should have occured at different levels according with the drugs assayed. On the other hand, the results of reversion have not been significant enough. We think that more accuracy is afforded by both the recombination and the reversion assay developed to other for this kind of detection.
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The mutagenic activities of 11 N-nitrosamines were tested using Salmonella typhimurium TA100 and TA98. All the carcinogenic N-nitrosamines were mutagenic on TA100 with a drug-activating system from the rat liver, whereas N,N-diphenylnitrosamine, a non-carcinogen, was not mutagenic. None of the N-nitrosamines was mutagenic on TA98, except N,N-diethylnitrosamine which was weakly mutagenic. To detect the mutagenicity of N,N-dimethylnitrosamine, the pre-incubation of bacteria and N,N-dimethylnitrosamine with S-9 Mix before if was poured onto plates was obligatorily required. Dimethyl sulfoxide inhibited the mutagenic effect of N,N-dimethylnitrosamine.
Article
The genotoxic potential of sorbic acid and potassium sorbate was investigated in vivo and in vitro. Oral administration of sorbic acid (up to 5000 mg/kg body weight) did not induce sister chromatid exchanges or the formation of micronuclei in bone marrow cells of mice. Intraperitoneal treatment of rats with 400-1200 mg potassium sorbate/kg body weight did not alter the elution profile of DNA from isolated liver cells in the in vivo alkaline elution assay. Sorbic acid did not induce DNA repair in cultured human A549 cells in the unscheduled DNA synthesis (UDS) assay. In vitro incubation of the cells with 1-1000 micrograms potassium sorbate/ml, in the absence or presence of rat liver homogenate, did not result in the formation of DNA single-strand breaks in the alkaline elution assay. These results demonstrate that sorbic acid and its potassium salt are not genotoxic in vivo or in vitro. In contrast to sorbic acid and potassium sorbate, sodium sorbate is very sensitive to oxidative degradation; the main oxidation product was identified to be 4,5-oxohexenoate, which was mutagenic in the Ames test.
Article
Potassium sorbate and sodium sorbate were investigated for possible genotoxic actions using the Salmonella/mammalian-microsome test, HGPRT and sister chromatid exchange (SCE) test with Chinese hamster ovary cells, the micronucleus test on bone marrow cells of mice and Chinese hamsters, and the chromosome aberration and SCE test on Chinese hamsters. In all the in vitro tests no signs of genotoxicity were detected. Whereas no in vivo mutagenicity of potassium sorbate and sodium sorbate with freshly prepared aqueous solutions and with stored potassium sorbate was found, investigations with stored sodium sorbate revealed weak clastogenic activity by increased chromosome aberrations and elevated numbers of micronuclei at doses of 200 mg/kg body weight, but no induction of SCEs.
Article
There is ample evidence from studies in experimental animals that N-nitroso compounds are carcinogenic because in the body they form potent electrophilic alkylating agents. These reactive intermediates are formed by spontaneous decomposition in the case of nitrosoureas and related compounds, or by metabolic activation in the case of N-nitrosamines. The electrophiles subsequently react with DNA of target tissues to form altered bases which leads to the initiation of carcinogenesis. There is now convincing evidence that the biological activity of N-nitroso compounds in humans does not differ substantially from that in experimental animals. We can therefore predict with a high degree of confidence that N-nitroso compounds including nitrosamines are carcinogenic in man.
Article
Copper and iron ions at physiological concentrations catalyzed the decrease of viscosity of hyaluronic acid solutions brought about by ascorbic acid. This reaction required the presence of oxygen as did the reaction with ascorbic acid alone. The ascorbic acid was converted by iron and copper ions to products more active than itself. Dehydroascorbic acid and dihydroxymaleic acid were also active autoxidants. Ethylenediaminetetraacetic acid (EDTA) had no effect on the reaction with ascorbic acid alone. However, EDTA abolished the catalytic effect of copper ions but enhanced the effect of iron ions in the presence of ascorbic acid. Catalase was a strong inhibitor of the ascorbic acid system with and without iron or copper ions but was not as effective for ferrous ions in the absence of ascorbic acid.
Article
The kinetics of the uncatalyzed and the Cu(II) and Fe(III) ion catalyzed oxidation of ascorbic acid are measured at 25 and 0.4°. The rate of the uncatalyzed oxidation of ascorbic acid was found to be proportional to oxygen concentration at 20% and higher concentration of molecular oxygen. In the pH range investigated (2-5.5), only the monoionic species of ascorbic acid was found to be reactive toward molecular oxygen. For the spontaneous oxidation, a mechanism is proposed whereby molecular oxygen takes part directly in the oxidation of the ascorbate anion. The rates of the ferric and cupric ion catalyzed oxidations were found to be first order with respect to the concentration of molecular oxygen. For the catalyzed oxidation, a reaction path involving molecular oxygen bound to the metal-ascorbate complex is proposed. The catalytic activity of cupric ion was found to be more than that of ferric ion toward the oxidation of the ascorbate anion. In the oxidation of the neutral species, however, ferric ion is a better catalyst than cupric ion. The difference in the catalytic activity of the two metal ions toward the monoionic and neutral species of ascorbic acid is explained on the basis of the difference in their relative tendencies to form complexes with the two species of ascorbic acid. The mechanistic implications of the catalyzed and uncatalyzed reactions are discussed.
Article
The methods for detecting carcinogens and mutagens with the Salmonella mutagenicity test were described previously (Ames et al., 1975b). The present paper is a revision of the methods. Two new tester strains, a frameshift strain (TA97) and a strain carrying an ochre mutation on a multicopy plasmid (TA102), are added to the standard tester set. TA97 replaces TA1537. TA1535 and TA1538 are removed from the recommended set but can be retained at the option of the investigator. TA98 and TA100 are retained. We discuss other special purpose strains and present some minor changes in procedure, principally in the growth, storage, and preservation of the tester strains. Two substitutions are made in diagnostic mutagens to eliminate MNNG and 9-aminoacridine. Some test modifications are discussed.
Article
When mice were fed on a diet containing 15% sorbic acid for a period up to 6 months, ether extracts of the intestinal contents of the mice were not mutagenic with Salmonella typhimurium TA98, but the acidic components obtained by fractionating the ether extracts, showed slightly mutagenic activity with S. typhimurium TA98, and they required the addition of liver 9,000 xg supernatant fraction for mutagenic activation. These results suggested that mutagens were gradually produced in the intestine and moved into the liver where they were metabolically activated. It is possible to presume that liver carcinoma might be attributable to the production of these mutagens.
Article
Salmonella/microsome tests (Ames tests) and chromosomal aberration tests in vitro using a Chinese hamster fibroblast cell line were carried out on 190 synthetic food additives and 52 food additives derived from natural sources, all of which are currently used in Japan. Fourteen out of 200 tested in the Ames assay showed positive effects and 54 out of 242 were positive in the chromosome test. Three additives (erythorbic acid, chlorine dioxide and beet red) were positive only in the Ames test, although their mutagenic potentials were relatively weak, while 43 additives were positive only in the chromosome test. Eleven additives (calcium hypochlorite, cinnamic aldehyde, L-cysteine monohydrochloride, Food Green No. 3 (Fast Green FCF), hydrogen peroxide, potassium bromate, sodium chlorite, sodium hypochlorite, sodium nitrite, cacao pigment and caramel) were positive in both the Ames test and the chromosome test. The usefulness of such primary screening tests combining two different genetic end-points, gene mutation and chromosomal aberration, and some correlation between mutagenicity and carcinogenicity of food additives are discussed.
Article
The ability of sorbic acid and its potassium and sodium salts to induce chromosome aberrations, sister chromatid exchanges (SCE) and gene mutations in cultured Chinese hamster V79 cells was examined. Sodium sorbate caused significant induction of chromosome aberrations and SCE, and also induced 6-thioguanine-resistant mutations in a dose-dependent manner. The clastogenic potency of sodium sorbate was found to be less than one hundredth of that of the potent clastogen N-methyl-N'-nitro-N-nitrosoguanidine. The induction of SCE by sodium sorbate was twice the control level, whereas that by methyl methanesulphonate, a potent inducer of SCE, was 14 times the control level. The mutagenic potency of sodium sorbate was less than one-tenth that of ethyl methanesulphonate, a potent inducer of mutation, when compared at an equitoxic level. Sorbic acid and its potassium salt induced chromosome aberrations, but only at the highest doses tested. These compounds also induced 1.2 times the control level of SCE, but neither compound induced 6-thioguanine-resistant mutations. The cytogenetic activity of sodium sorbate was concluded not to be due to the effect of osmotic pressure or an impurity. These results indicate that sodium sorbate is a genotoxic agent, although its potency seems to be weak, and that sorbic acid and potassium sorbate are less genotoxic than the sodium salt.
Article
The role of Cu2+ on the DNA-breaking action of ascorbic acid (AsA) and triose reductone (TR) was studied with an agarose slab gel electrophoretic analysis. AsA and TR decomposed calf thymus DNA which had been pretreated with Cu2+, and their decomposing activity was proportional to the concentration of Cu2+ bound to the DNA. The DNA-Cu2+ complex had the ability to oxidize reductones. AsA and TR also decomposed the pretreated DNA with Cu2+ more markedly than that pretreated with Cu2+ and successively with EDTA. The DNA-breaking activity of AsA and TR showed no Cu2+-concentration dependency. The maximal fragmentation of DNA occurred at the concentration ratio of DNA and Cu2+ of 4:1. Excess concentration of Cu2+ decreased the activity of reductones. The present results indicate that the binding of Cu2+ to DNA molecules is also essential for the DNA-breaking action of AsA and TR in the presence of Cu2+ and that Cu2+ bound to DNA molecules has more effective promoting activity than free Cu2+.
Article
L-Ascorbic acid, when combined with either copper(II) ion or a copper(II)-tripeptide complex, extensively cleaved several viral DNAs and proteins under in vitro conditions. Neither ascorbate nor copper tripeptide (Cu2+-diglycyl-L-histidine) alone caused any apparent changes on these molecules. Various transition metal ions and reducing agents were examined under comparable conditions to determine the basic requirements for both DNA degradation and protein scission activities. Copper and iron are the two most effective transition metal ions examined that exhibit these activities in the presence of ascorbate. The addition of catalase, but not superoxide dismutase, can partially inhibit the scission of DNA in vitro, suggesting that H2O2 may be involved in these activities. Among the various reducing agents tested, ascorbate was most effective in causing DNA scission and protein cleavage, corroborating the possible role of H2O2 in the cleavage reactions. One of the products of the reactions of copper/ascorbate is probably the hydroxyl radical generated from H2O2, which can be formed from the oxidation of ascorbate.
Article
The urine of the mice fed on a 15% sorbic acid diet was treated with or without beta-glucuronidase and was fractionated by XAD-2 column chromatography. The non-polar urine fraction was slightly mutagenic towards TA 98 when metabolically activated, but not towards TA 100. From the comparison of thin-layer chromatograms between the intestinal and urinary samples, it was suggested that a part of the mutagens produced in the intestine was excreted in the urine. As for the lipid peroxidation, the levels of lipid peroxide in the liver of the mice fed on a 15% sorbic acid diet were lower than those in the control over the feeding period of 15 months. Moreover, there was a correlation between the concentration of sorbic acid (X) in the diet and the lipid peroxide level (Y) in mice fed on potassium sorbate diets, obeying the linear equation, Y=-8.39X+ 341 (p less than 0.01). However, the lipid peroxide levels of 15% sorbic acid group did not fit with the above equation, and was higher than those of 20.1% potassium sorbate group, which was equivalent to 15% sorbic acid group in respect of sorbic acid concentration. Accordingly, the difference of lipid peroxide levels between the two groups (15% sorbic acid and 20.1% potassium sorbate group) might reflect productive difference of the mutagens.
Article
The effect of reaction conditions on the yield of individual products in the reacted mixture of sorbic acid and sodium nitrite was investigated by using TLC and high-performance LC methods. It became clear that mutagenicity of the reaction mixture that reached maximum by the reaction at pH 3.5-4.2 is due to the formation of the product Y (l,4-dinitro-2-methylpyrrole) and ethylnitrolic acid (ENA). The yields of Y and ENA reached maxima at 30 min (at 60 °C), but ENA decreased thereafter. Y and ENA gave maximal yield at 8-fold excess of nitrite to sorbic acid, but their formation was detected even by reaction at 1:0.5 molar ratio. These chemical results well explained the observed pronounced effects of reaction conditions on biological activities. Ascorbic acid and cysteine above certain levels inhibit effectively the mutagen formation in this reaction system.
Article
Five synthetic food colours Food Red Nos 3, 40 and 102 and Food Blue Nos 1 and 2, and their UV irradiated products were tested for mutagenic activity by means of the Ames test using Salmonella typhimurium strains TA98 and TA100. Food colours were irradiated with UV light for 14 days. Food Red Nos 3, 40 and 102 and Food Blue No. 1 were non-mutagenic before and after irradiation. UV irradiated products of Food Blue No. 2 were mutagenic in TA98 with or without S-9 mix. The mutagenic activity increased with increasing irradiation period, reached maximum potency on day 6, and then decreased. Moreover, Food Blue No. 2 showed DNA-damaging activity after 14 days of irradiation in rec-assay using Bacillus subtilis strains H17 and M45. The capillary electrophoresis was applied for the analysis of UV irradiated products of Food Blue No. 2. The original peak of Food Blue No. 2 was decomposed into seven peaks after UV irradiation.
Article
Sorbic acid (E200) and its salts (potassium and calcium sorbate: E202 and E203) are allowed for use as preservatives in numerous processed foods. Sorbic acid had a conjugated system of double bonds which makes it susceptible to nucleophilic attack, sometimes giving mutagenic products. Under conditions typical of food processing (50-80 degrees C), we analysed the cyclic derivatives resulting from a double addition reaction between sorbic acid and various amines. Mutagenesis studies, involving Ames' test and genotoxicity studies with HeLa cells and plasmid DNA, showed that none of the products studied presented either mutagenic or genotoxic activities.
Jung et 0278-6915/02/$ -see front matter # All rights reserved. P I I : S
  • Ishidate
Ishidate et al., 1984; Mu¨ et al., 1990). Jung et 0278-6915/02/$ -see front matter # 2002 Elsevier Science Ltd. All rights reserved. P I I : S
The Health Effects of Nitrate, Nitrite and N-nitroso Compounds. Report of the Committee on Nitrate and Alterna-tive Curing Agents in Food
  • Nas Nrc
NAS/NRC (National Academy of Sciences/National Research Council), 1981. The Health Effects of Nitrate, Nitrite and N-nitroso Compounds. Report of the Committee on Nitrate and Alterna-tive Curing Agents in Food. National Academy Press, Washington, DC.
Food additives and their possible genetic toxicity. Archivos latino-americanos de nutrition 27
  • M Aquino
  • P Santini
Aquino, M., Santini, P., 1977. Food additives and their possible genetic toxicity. Archivos latino-americanos de nutrition 27, 411–424.
Food additive-additive interactions involving sulphur dioxide and ascorbic and nitrous acids
  • Adams