Effect of coumarin, BHT and phenobarbitone onprotein synthesis in the rat liver

Nievel, John G.

doi:10.1016/s0015-6264(69)80464-5

Cited by 22 publications

(2 citation statements)

References 15 publications

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“…Within 30 minutes of exposure, BHT decreased DNA, RNA, and protein synthesis; the inhibition was reversible within 1 hour. Nievel (1969) reported that liver microsomes from female Wistar rats fed 450 mg/kg BHT for 7 days had increased incorporation of radioactive amino acids into protein in vitro, mostly into proteins of the ER.…”

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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Section: Tablementioning

confidence: 99%

Final Report on the Safety Assessment of BHT

Lanigan¹,

Yamarik²

2002

Int J Toxicol

147

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“…1966). Instead there was marked proliferation of agranular endoplasmic reticulum (Lane & Lieber 1967;Botham et al 1970), and an increase in the drug metabolizing enzymes (Gilbert & Golberg 1965) and an increase in protein synthesis in liver microsomes (Nievel 1969). Therefore, the haemorrhage due to BHT was not caused by necrosis of liver cells as in rats given hepatotoxin.…”

Section: Haemaiological Values Serum Components and Enzyme Activitiementioning

confidence: 99%

Haemorrhagic Toxicosis in Rats Given Butylated Hydroxytoluene

Takahashi

Hiraga

1981

Acta Pharmacologica et Toxicologica

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Vascular permeability, platelet function, blood coagulation and fibrinolytic activity were examined in Sprague-Dawley male rats given 1.20% butylated hydroxytoluene (BHT) in the diet for 1 week. BHT significantly increased the leakage of Evans blue from blood into epididymus. BHT inhibited the ADP-induced platelet aggregation and decreased the platelet factor 3 availability. Plasmaprothrombin, factors IX, X, VII and VIII were decreased in rats given BHT. Fibrinolytic activity was little influenced by BHT-feeding.

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Changes in Metabolic Stability of Structural and Enzyme Proteins in Experimental Hepatomegaly

Nievel

1977

Intracellular Protein Catabolism II

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Effect of coumarin, BHT and phenobarbitone onprotein synthesis in the rat liver

Cited by 22 publications

References 15 publications

Final Report on the Safety Assessment of BHT

Final Report on the Safety Assessment of BHT

Haemorrhagic Toxicosis in Rats Given Butylated Hydroxytoluene

Changes in Metabolic Stability of Structural and Enzyme Proteins in Experimental Hepatomegaly

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