Abstract  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.

Abstract  Acute toxicity of four relatively new chelating agents and their equimolar manganese and cadmium complexes was studied. The chelating agents studied were gluconic acid (GA), beta-alaninediacetic acid (ADA), diethylenetriaminepentakismethylenephosphonic acid (DTPMP), and nitrilotriacetic acid (NTA). Three common bioassays, namely Daphnia magna, Raphidocelis subcapitata, and Photobacterium phosphoreum (Microtox bioassay) were applied. R. subcapitata proved the most sensitive to these compounds. With D. magna bioassay the LC(50) values were 600-900 mg/L with all other studied chelates and their Mn complexes, except Mn-GA, which yielded LC(50) value of 240 mg/L. The Cd-chelate complexes proved highly more toxic compared to Mn-chelate complexes or uncomplexed chelates exhibiting LC(50) values of 130-200 microg/L. However, Cd-DTPMP was an exception exhibiting LC(50) value of 2170 microg/L. That is to say, DTPMP proved the strongest chelating agent to reduce the Cd toxicity in the present study. The results from these bioassays were well in agreement to each other as well as with the results published elsewhere.

Abstract  Gluconate derivatives are presented as a category. Gluconic acid and its mineral salts freely dissociate to the gluconate anion and the respective cations. Glucono-delta-lactone (GDL), the 1,5-inner ester of gluconic acid, is formed from the free acid by the removal of water. On the basis of these spontaneous chemical rearrangements, glucono-delta-lactone, gluconic acid and its sodium, calcium and potassium salts can be considered as a category, with all members sharing the same representative moiety, the gluconate anion. Manufacturing and uses of the category members are also interlinked. The data summarized in this report are focused on the environmental and health effects from the gluconate anion and read-across to the lactone but do not deal with specific effects of the cations. Thus toxicological effects related to the cationic components are not part of the present report.

Abstract  Teratological test results are reported in four species of laboratory animals. Portions of these documents are not fully legible.

Abstract  Compound FDA 71-72, glucono-delta-lactone, was not genetically active, either directly or in the presence of organ homogenates, in any of the in vitro assays employed in this evaluation.

Abstract  The purpose of this study is to determine the bioavailability, biodistribution and toxicity of Biocal(TM), a new calcium source. Biocal(TM) is a calcium gluconate stabilized with glycine. A comparative study of this compound versus calcium gluconate was performed in Sprague-Dawley rats. Bioavailability studies were carried out by the labeling of both compounds with Ca-45. We administered a dose of 30 mg of Ca per kg of body weight p.o. to two groups of 7 male adult rats each. The urine elimination of the Ca-45, expressed as total accumulated percentage of Ca-45 activity in urine (Ae(infinity)), between the rats that received Biocal(TM) (Ae(infinity) = 2.436+/-1.337 %) and the rats that received calcium gluconate (Ae(infinity) = 1.241+/-0.473 %) were found to be statistically different (p<0.05). Biodistribution studies showed that the calcium from Biocal(TM) follows the same metabolic pathway as calcium from calcium gluconate. Values of radioactivity concentration of 97.1+/-1.3% and 98.7+/-1.6% were found in bone for Biocal(TM) and calcium gluconate, respectively. Toxicity studies of Biocal(TM) were carried out with 60 female and 60 male rats. The values of oral LD50 for female rats was 13.5 g/kg with a lower limit of 12.8 g/kg and upper limit of 14.3 g/kg. In the case of male rats the LD50 was 13.0 g/kg with a lower limit of 12.2 g/kg and upper limit of 13.9 g/kg. These values are higher with regard to the oral LD50 for calcium gluconate (10 g/kg). Our results demonstrate that calcium from Biocal(TM) has a higher bioavailability with the same metabolic behavior than calcium from calcium gluconate. The value of oral LD50 shows that the toxicity of Biocal(TM) is lower than that of the calcium gluconate. Therefore we conclude that Biocal(TM) has adequate properties to be considered as a promissory calcium compound to be used as dietary supplement or for food fortification. (C) 1999 Elsevier Science Inc.

Abstract  The efficacy of dietary calcium glucarate as a chemopreventative agent has been tested in the mouse skin tumorigenesis system. Skin tumorigenesis was initiated in mice of the CD-1 strain with 7,12-dimethylbenz(a)anthracene (DMBA), then promoted with twice weekly applications of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) for 13 weeks. The mice were fed a regular chow diet, or a chow diet fortified with calcium glucarate (128 mmol/kg diet), or with equimolar calcium as calcium gluconate (negative calcium control). When mice were fed calcium glucarate throughout both the initiation and promotion phases papilloma formation was inhibited by over 30%. Transfer of these DMBA-initiated, TPA promoted CD-1 mice to chow diet after 13 weeks on the calcium glucarate-supplemented diet, resulted in an increase in the number of skin papillomas within 3 weeks to the level of those seen in control animals maintained exclusively on the chow diet. When calcium glucarate feeding was restricted to either the initiation or promotion phases, papilloma formation was inhibited by 25%. Dietary calcium gluconate had no effect on papilloma formation in the CD-1 mouse system, but increased the calcium concentration in the skin to the same extent as that of calcium glucarate. The data indicate that the elevation of the normally low levels of glucarate in the body through supplementation, results in a marked alteration in the retention, activity and/or metabolism of xenobiotics.

Abstract  Recently was observed that pyrethroids decrease motor coordination and that calcium channels can be important targets for this effect. To contribute with this observation, this work studied the motor coordination and exploration (using hole-board apparatus), and locomotion (using open-field apparatus) of rats exposed to following treatments: permethrin (PM), PM plus calcium gluconate (CG) and PM plus amlodipine (AML). The results obtained show that CG or AML alone not changed the motor coordination while PM decreases it. CG kept the effect of permethrin; AML, however, decreased the values of permethrin to the control. Locomotor activity and exploration, which could confound results of motor coordination, were not modified by treatments. The concentration of PM in brain tissue was increased by the CG and AML. The neurosomatic index (weight brain/body weight) was increased by the PM and PM+CG. In conclusion, the combined results here obtained indicates that the calcium ion and the channels in which it is involved can be important targets for the toxic effect of pyrethroid insecticide permethrin on motor nerve activity of rats.

Abstract  Aim: The investigation of a genotoxic activity of the test item Gluconic acid technical 50/50 (batch SX4G6)provided by Members of the Gluconic Acid and its Derivatives REACH Consortium has been carried out in compliance with the OECD Guideline 473 (2014), using test for chromosome aberration by in vitro human lymphocyte metaphase analysis. Methods: In the experimental conditions with metabolic activation (5% of S9-mix) or without metabolic activation (4-hour treatment), no cytotoxicity was noted at the highest concentration tested of 10 mM, with 103.6 and 88.4% of mitotic index compared to the control, respectively. The concentration of 10 mM was retained as the maximum concentration to be tested in the assay with 5% of S9-mix and without metabolic activation following the 4-hour treatment. In return, when using a 20-hour treatment, a strong cytotoxicity was noted at the highest concentration tested of 10 mM, with 21% of mitotic index compared to the control. The immediately lower concentration of 5 mM induced a moderate cytotoxicity, with 63.8% of mitotic index compared to the control. Under these conditions, the concentration of 10 mM was retained as the maximum concentration to be tested in the assay without metabolic activation following the 20-hour treatment, but a narrowed range of concentrations was performed in order to reach a concentrations inducing 55±5% of cytotoxicity. Results: The test item Gluconic acid technical 50/50 did not induce any statistically significant increases in the frequency of aberrant cells excluding or including gaps or in the number of breaks per cell in the 4- hour treatment and in the 20-hour treatment without metabolic activation and in the 4-hour treatments with 5 % of S9-mix in human lymphocytes. Otherwise, no statistically significant increases in the number of cells with numerical aberrations were noted both with and without metabolic activation using a long or a short-term treatment.