The use of short-term tests to measure the preventive action of reducing agents on formation and activation of carcinogenic nitroso compounds

Lo, L.W.; Stich, H. F.

doi:10.1016/0027-5107(78)90247-6

Cited by 27 publications

(4 citation statements)

References 29 publications

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“…Other genotoxicity assays Lo and Stich (1978) demonstrated that sodium ascorbate at concentration below 1 × 10 -2 M had no detectable inhibitory effect on the ultraviolet-elicited DNA repair synthesis of primary human skin fibroblasts in culture. Galloway and Painter (1979) found that sodium ascorbate caused, at concentrations from 1 × 10 -4 to 1 × 10 -2 M for 27-29 hours, a dose-dependent increase in sister chromatid exchanges (SCEs) in CHO cells and from 5.4 × 10 -4 to 5.4 × 10 -3 M for 73 hours in human lymphocytes.…”

Section: Comet Assaymentioning

confidence: 99%

Scientific Opinion on the re‐evaluation of ascorbic acid (E 300), sodium ascorbate (E 301) and calcium ascorbate (E 302) as food additives

2015

EFS2

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The EFSA Panel on Food additives and Nutrient Sources added to Food (ANS Panel) provides a scientific opinion re‐evaluating the safety of ascorbic acid (E 300), sodium ascorbate (E 301) and calcium ascorbate (E 302) as food additives. The use of ascorbic acid and its salts as food additives was evaluated by the Joint FAO/WHO Expert Committee on Food Additives and by the Scientific Committee on Food. Ascorbic acid is absorbed from the intestine by a sodium‐dependent active transport process and, at low doses, the absorption is almost complete until a saturation point, after which increasing amounts of unabsorbed substance are excreted. Ascorbic acid and its salts have very low acute toxicities, and short‐term tests in animals showed little effect, and even so only at high doses. The Panel concluded that there is no genotoxicity concern for ascorbic acid, sodium ascorbate or calcium ascorbate. Long‐term carcinogenicity tests with ascorbic acid did not show any chronic toxicity, even at high doses, and also showed no signs of carcinogenicity. Prenatal developmental studies did not show adverse developmental effects. The Panel estimated the combined exposure to ascorbic acid (E 300), calcium ascorbate (E 301) and sodium ascorbate (E 302). The Panel concluded that, given the fact that adequate data on exposure and toxicity were available and no adverse effects were reported in animal studies, there is no safety concern for the use of ascorbic acid (E 300), sodium ascorbate (E 301) and calcium ascorbate (E 302) as food additives at the reported uses and use levels and there is no need for a numerical ADI for ascorbic acid and its salts.

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Section: Comet Assaymentioning

confidence: 99%

Scientific Opinion on the re‐evaluation of ascorbic acid (E 300), sodium ascorbate (E 301) and calcium ascorbate (E 302) as food additives

2015

EFS2

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“…Propyl Gallate inhibited the mutagenic activity of dimethylnitrosamine in a DNA-repair test. They suggested that antioxidants may act as antimutagens by preventing the formation of reactive carcinogens or by competing with proximate carcinogens or mutagens (Lo and Stitch 1978).…”

Section: Antimutagenesismentioning

confidence: 99%

Final Report on the Amended Safety Assessment of Propyl Gallate1

2007

Int J Toxicol

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Propyl Gallate is the n-propyl ester of gallic acid (3,4,5-trihydroxybenzoic acid). It is soluble in ethanol, ethyl ether, oil, lard, and aqueous solutions of polyethylene glycol (PEG) ethers of cetyl alcohol, but only slightly soluble in water. Propyl Gallate currently is used as an antioxidant in a reported 167 cosmetic products at maximum concentrations of 0.1%. Propyl Gallate is a generally recognized as safe (GRAS) antioxidant to protect fats, oils, and fat-containing food from rancidity that results from the formation of peroxides. Data on dermal absorption are not available, but Propyl Gallate is absorbed when ingested, then methylated, conjugated, and excreted in the urine. The biological activity of Propyl Gallate is consistent with its free-radical scavenging ability, with effects that include antimicrobial activity, enzyme inhibition, inhibition of biosynthetic processes, inhibition of the formation of nitrosamines, anesthesia, inhibition of neuromuscular response to chemicals, ionizing/ultraviolet (UV) radiation protection, chemoprotection, antimutagenesis, anticarcinogenesis and antitumorigenesis, antiteratogenesis, and anticariogenesis. Animal toxicity studies indicate that Propyl Gallate was slightly toxic when ingested, but no systemic effects were noted with dermal application. Propyl Gallate is a strong sensitizer when tested intradermally, less sensitizing when tested topically, and nonsensitizing topically at 0.1% in one study. In a second study, Propyl Gallate (15 mg dissolved in 8 ml vehicle) was sensitizing to guinea pigs. Acute eye irritation tests conducted on nine cosmetic formulations, each containing less than 1% Propyl Gallate, were negative. A phototoxicity study conducted on a cosmetic formulation containing 0.003% Propyl Gallate determined that the product was not phototoxic to guinea pigs. In one study, female rats fed 0.5 g Propyl Gallate had substantially increased fetal resorption rates when compared to controls, but in four other studies, Propyl Gallate at doses up to 2.04 g/kg was nonteratogenic in rats, rabbits, mice, and hamsters. In clinical cumulative irritancy tests, Propyl Gallate was nonirritating at concentrations up to 10%. Patch tests at concentrations less than 1% yielded positive elicitation responses. Repeat-insult patch tests using cosmetic formulations with 0.003% Propyl Gallate produced no irritation or sensitization. Propyl Gallate at a concentration of 10% in alcohol was nonphototoxic in 25 subjects. Cosmetic formulations, each containing 0.003% Propyl Gallate, produced no signs of photosensitization or phototoxicity in a total of 371 subjects. Although Propyl Gallate is not a skin irritant in clinical tests, the available data demonstrate that it is a skin sensitizer and that it may be a sensitizer at lower concentrations than originally thought, i.e., at concentrations less than 1%. In actual practice, cosmetic formulations contain Propyl Gallate at concentrations up to 0.1% and usage has increased over the past 20 years. In spite of the increased exposure...

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“…The effect of reducing agent on the nitrosation of methylguanidine (MG) and on the in vitro activation of dimethylnitrosamine (DMN) was examined by Lo and Stich (1978). In the MG nitrosation reaction, mixtures of 0.2 M MG, 0.6 M sodium nitrite, and, in some instances, 0.3 or 0.6 M Sodium Ascorbate were added to the DMN activation system.…”

Section: Effects On Nitrosamine Formationmentioning

confidence: 99%

“…The use of alkaline sucrose gradient procedure revealed a marked shift towards smaller DNA fragments when 1 × 10 −2 M was added to the S-9 preparations during DMN activation. Sodium Ascorbate (10 −2 M) inhibited DNA synthesis by 83.1% (Lo and Stich 1978). Douglass et al (1978) tested a number of effective nitrosation inhibitors in the methylene chloride-mediated nitrosating system.…”

Section: Effects On Nitrosamine Formationmentioning

confidence: 99%

Final Report of the Safety Assessment of L-Ascorbic Acid, Calcium Ascorbate, Magnesium Ascorbate, Magnesium Ascorbyl Phosphate, Sodium Ascorbate, and Sodium Ascorbyl Phosphate as Used in Cosmetics1

2005

Int J Toxicol

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L-Ascorbic Acid, Calcium Ascorbate, Magnesium Ascorbate, Magnesium Ascorbyl Phosphate, Sodium Ascorbate, and Sodium Ascorbyl Phosphate function in cosmetic formulations primarily as antioxidants. Ascorbic Acid is commonly called Vitamin C. Ascorbic Acid is used as an antioxidant and pH adjuster in a large variety of cosmetic formulations, over 3/4 of which were hair dyes and colors at concentrations between 0.3% and 0.6%. For other uses, the reported concentrations were either very low (<0.01%) or in the 5% to 10% range. Calcium Ascorbate and Magnesium Ascorbate are described as antioxidants and skin conditioning agents--miscellaneous for use in cosmetics, but are not currently used. Sodium Ascorbyl Phosphate functions as an antioxidant in cosmetic products and is used at concentrations ranging from 0.01% to 3%. Magnesium Ascorbyl Phosphate functions as an antioxidant in cosmetics and was reported being used at concentrations from 0.001% to 3%. Sodium Ascorbate also functions as an antioxidant in cosmetics at concentrations from 0.0003% to 0.3%. Related ingredients (Ascorbyl Palmitate, Ascorbyl Dipalmitate, Ascorbyl Stearate, Erythorbic Acid, and Sodium Erythorbate) have been previously reviewed by the Cosmetic Ingredient Review (CIR) Expert Panel and found "to be safe for use as cosmetic ingredients in the present practices of good use." Ascorbic Acid is a generally recognized as safe (GRAS) substance for use as a chemical preservative in foods and as a nutrient and/or dietary supplement. Calcium Ascorbate and Sodium Ascorbate are listed as GRAS substances for use as chemical preservatives. L-Ascorbic Acid is readily and reversibly oxidized to L-dehydroascorbic acid and both forms exist in equilibrium in the body. Permeation rates of Ascorbic Acid through whole and stripped mouse skin were 3.43 +/- 0.74 microg/cm(2)/h and 33.2 +/- 5.2 microg/cm(2)/h. Acute oral and parenteral studies in mice, rats, rabbits, guinea pigs, dogs, and cats demonstrated little toxicity. Ascorbic Acid and Sodium Ascorbate acted as a nitrosation inhibitor in several food and cosmetic product studies. No compound-related clinical signs or gross or microscopic pathological effects were observed in either mice, rats, or guinea pigs in short-term studies. Male guinea pigs fed a control basal diet and given up to 250 mg Ascorbic Acid orally for 20 weeks had similar hemoglobin, blood glucose, serum iron, liver iron, and liver glycogen levels compared to control values. Male and female F344/N rats and B6C3F(1) mice were fed diets containing up to 100,000 ppm Ascorbic Acid for 13 weeks with little toxicity. Chronic Ascorbic Acid feeding studies showed toxic effects at dosages above 25 mg/kg body weight (bw) in rats and guinea pigs. Groups of male and female rats given daily doses up to 2000 mg/kg bw Ascorbic Acid for 2 years had no macro- or microscopically detectable toxic lesions. Mice given Ascorbic Acid subcutaneous and intravenous daily doses (500 to 1000 mg/kg bw) for 7 days had no changes in appetite, weight gain, and general behavior; a...

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The use of short-term tests to measure the preventive action of reducing agents on formation and activation of carcinogenic nitroso compounds

Cited by 27 publications

References 29 publications

Scientific Opinion on the re‐evaluation of ascorbic acid (E 300), sodium ascorbate (E 301) and calcium ascorbate (E 302) as food additives

Scientific Opinion on the re‐evaluation of ascorbic acid (E 300), sodium ascorbate (E 301) and calcium ascorbate (E 302) as food additives

Final Report on the Amended Safety Assessment of Propyl Gallate1

Final Report of the Safety Assessment of L-Ascorbic Acid, Calcium Ascorbate, Magnesium Ascorbate, Magnesium Ascorbyl Phosphate, Sodium Ascorbate, and Sodium Ascorbyl Phosphate as Used in Cosmetics1

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