Cell culture as a test system for toxicity

Metcalfe, Su

doi:10.1111/j.2042-7158.1971.tb10197.x

Cited by 34 publications

(4 citation statements)

References 27 publications

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“…BHA and TBHQ inhibited the synthesis of DNA and RNA in I: pyriformis (Surak 1977;Surak et al 1976a). BHT inhibited RNA synthesis in Rhesua monkey kidney epithelial cells (Metcalfe 1971). In the latter case, a correlation was found between lipid solubility of a range of BHT analogues and the capacity to inhibit RNA synthesis.…”

Section: Mechanism Of Inhibition By Phenolic Antioxidantsmentioning

confidence: 88%

THE ANTIMICROBIAL ACTIVITY OF PHENOLIC ANTIOXIDANTS IN FOODS: A REVIEW¹

Raccach

1984

Journal of Food Safety

108

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Phenolic antioxidants such as butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) and monotertiary butylhydroquinone (TBHQ) are hindered phenols with antimicrobial activity. The antimicrobial activity of phenolic antioxidants appears to depend on the presence of a hydroxyl group on the molecule, the lipid solubility of the compound and the degree of steric hindrance. The use of phenolic antioxidants in food products is regulated by federal agencies. In general, these compounds are permitted in concentrations up to 200 ppm, based on the fat or oil content of the food product. Certain food products have special regulations. The antimicrobial activity of phenolic antioxidants has been studied in meat and its products, poultry and its products, milk and its products, seafood, rice, applesauce and food ingredients. The antimicrobial activity of phenolic antioxidants is modified by at least 10 factors such as microbial species/strain, stressed microorganisms, type and concentration of phenolic antioxidants, concentration of microbial challenge, combination of phenolic antioxidants, combination of phenolic antioxidants with other antimicrobials, combination of phenolic antioxidants with temperature and food additives, food components, carriers of phenolic antioxidants and the mode of addition of phenolic antioxidants. The antimicrobial activity of phenolic antioxidants in foods has been examined against growth and by‐products of bacteria (gram positive and negative, spore and nonspore formers, spoilage and pathogenic), molds and yeasts. The concentration of phenolic antioxidants that had antimicrobial activity in food products was in the range of 30–10,000 ppm. The mechanism of inhibition by phenolic antioxidants has been found to affect the function and composition of the cellular membrane, the synthesis of DNA, RNA, protein and lipid, and the function of the mitochondrion.

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Section: Mechanism Of Inhibition By Phenolic Antioxidantsmentioning

confidence: 88%

THE ANTIMICROBIAL ACTIVITY OF PHENOLIC ANTIOXIDANTS IN FOODS: A REVIEW¹

Raccach

1984

Journal of Food Safety

108

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“…A second study using monkey cells was performed by Metcalfe (1971). Concentrations up to 30 mg/g cells (in 1% DMSO) did not cause visible cytopathologic changes, although this dose inhibited the rate of cell multiplication in a dosedependent manner.…”

Section: Tablementioning

confidence: 99%

Final Report on the Safety Assessment of BHT

Lanigan¹,

Yamarik²

2002

Int J Toxicol

147

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BHT is the recognized name in the cosmetics industry for butylated hydroxytoluene. BHT is used in a wide range of cosmetic formulations as an antioxidant at concentrations from 0.0002% to 0.5%. BHT does penetrate the skin, but the relatively low amount absorbed remains primarily in the skin. Oral studies demonstrate that BHT is metabolized. The major metabolites appear as the carboxylic acid of BHT and its glucuronide in urine. At acute doses of 0.5 to 1.0 g/kg, some renal and hepatic damage was seen in male rats. Short-term repeated exposure to comparable doses produced hepatic toxic effects in male and female rats. Subchronic feeding and intraperitoneal studies in rats with BHT at lower doses produced increased liver weight, and decreased activity of several hepatic enzymes. In addition to liver and kidney effects, BHT applied to the skin was associated with toxic effects in lung tissue. BHT was not a reproductive or developmental toxin in animals. BHT has been found to enhance and to inhibit the humoral immune response in animals. BHT itself was not generally considered genotoxic, although it did modify the genotoxicity of other agents. BHT has been associated with hepatocellular and pulmonary adenomas in animals, but was not considered carcinogenic and actually was associated with a decreased incidence of neoplasms. BHT has been shown to have tumor promotion effects, to be anticarcinogenic, and to have no effect on other carcinogenic agents, depending on the target organ, exposure parameters, the carcinogen, and the animal tested. Various mechanism studies suggested that BHT toxicity is related to an electrophillic metabolite. In a predictive clinical test, 100% BHT was a mild irritant and a moderate sensitizer. In provocative skin tests, BHT (in the 1% to 2% concentration range) produced positive reactions in a small number of patients. Clinical testing did not find any depigmentation associated with dermal exposure to BHT, although a few case reports of depigmentation were found. The Cosmetic Ingredient Review Expert Panel recognized that oral exposure to BHT was associated with toxic effects in some studies and was negative in others. BHT applied to the skin, however, appears to remain in the skin or pass through only slowly and does not produce systemic exposures to BHT or its metabolites seen with oral exposures. Although there were only limited studies that evaluated the effect of BHT on the skin, the available studies, along with the case literature, demonstrate no significant irritation, sensitization, or photosensitization. Recognizing the low concentration at which this ingredient is currently used in cosmetic formulations, it was concluded that BHT is safe as used in cosmetic formulations.

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“…Cells were plated at 1O,OOO/cm2, and 50 ,ug/ml FF-I or HBB was added in a similar manner as described for treatment A. Following a 3-day incubation, the chemicals were removed, fresh medium added, and the cells incubated for another 4 days. At this time samples of cells were prepared for electron microscopic analysis and others for light microscopy.…”

Section: Chemicals and Spectral Analysismentioning

confidence: 99%

“…The use of cultured cells provides a sensitive assay to detect relative chemical toxicities, particularly at low and chronic levels (4), without the variables of absorption, excretion, and transport. Cultured cells have been used to study the toxicity of a variety of compounds, including the food additive butylated hydroxytoluene (4), and polychlorinated biphenyls (PCB) (5). For mouse embryo fibroblasts which demonstrate a strict growth pattern, remarkable postconfluence inhibition of cell division and have been well characterized (6,7).…”

Section: Introductionmentioning

confidence: 99%

Toxicity of firemaster FF-1 and 2,2',4,4',5,5'-hexabromobiphenyl in cultures of C3H/10T 1/2 mammalian fibroblasts.

Bairstow¹,

Hsia²,

Norback³

et al. 1978

Environ Health Perspect

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A procedure for purifying 2,2',4,4',5,5'-hexabromobiphenyl (HBB) from FireMaster FF-1 in gram amounts by crystallization is presented. Following purification, the structural assignment of HBB was made by using proton and carbon-13 nuclear magnetic resonance (NMR) spectroscopy, elemental analysis, and mass spectroscopy (MS). The growth of C3H/1OT 1/2 cells treated with 5, 37, 75, and 150 Ag of HBB and FF-1 per milliliter of medium was measured at 4, 8, and 13 days following treatment. FF-1 was more toxic at 37 and 75 ug/ml at both 4 and 8 days, but the same at 13 days. At 150 ,g/ml cell growth was completely inhibited by both compounds. Growth of cells was stimulated at 5 ,ug/ml, by HBB at 4 and 8 days, and FF-1 at 8 and 12 days. HCB was compared with HBB and FF-1 for cell growth toxicity at 37 and 75 ,ug/ml. At 75 ,g/ml, HCB was more toxic than HBB and FF-1 during the entire time period. At 37 ,mg/ml, HCB was more toxic than HBB and FF-1 at 4 and 8 days. Cells seeded at high densities and treated with HBB for three days lost the high degree of postconfluence inhibition of cell division observed in control cultures. Cells treated with FF-1 for three days did not adhere well to the plastic growth surface. Ultrastructural features of the HBB-and FF-1-treated cells included decreased surface villi and increased lysosomes relative to the control cells.

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Cell culture as a test system for toxicity

Cited by 34 publications

References 27 publications

THE ANTIMICROBIAL ACTIVITY OF PHENOLIC ANTIOXIDANTS IN FOODS: A REVIEW¹

THE ANTIMICROBIAL ACTIVITY OF PHENOLIC ANTIOXIDANTS IN FOODS: A REVIEW¹

Final Report on the Safety Assessment of BHT

Toxicity of firemaster FF-1 and 2,2',4,4',5,5'-hexabromobiphenyl in cultures of C3H/10T 1/2 mammalian fibroblasts.

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Cell culture as a test system for toxicity

Cited by 34 publications

References 27 publications

THE ANTIMICROBIAL ACTIVITY OF PHENOLIC ANTIOXIDANTS IN FOODS: A REVIEW1

THE ANTIMICROBIAL ACTIVITY OF PHENOLIC ANTIOXIDANTS IN FOODS: A REVIEW1

Final Report on the Safety Assessment of BHT

Toxicity of firemaster FF-1 and 2,2',4,4',5,5'-hexabromobiphenyl in cultures of C3H/10T 1/2 mammalian fibroblasts.

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Product

Resources

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THE ANTIMICROBIAL ACTIVITY OF PHENOLIC ANTIOXIDANTS IN FOODS: A REVIEW¹

THE ANTIMICROBIAL ACTIVITY OF PHENOLIC ANTIOXIDANTS IN FOODS: A REVIEW¹