Inhibition of Chemical Mutagenesis: An Application of Chromosome Aberration And DNA Synthesis Assays Using Cultured Mammalian Cells

Wei, Lan; Whiting, Robert F.; Stich, H. F.

doi:10.1007/978-1-4612-5847-6_38

Cited by 2 publications

(1 citation statement)

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“…BHT and its derivatives also modi ed the genotoxicity of other agents (Table 9), including X-rays and various chemicals (Stich 1991). Data from several studies suggested that the antimutagenic activity of BHT occurred via alterations of mutagen metabolism by liver microsomes, the combination with free radicals to form stable complexes, or by a reduction of peroxidative damage of DNA (Shamberger 1974;McKee and Tometsko 1979;Wei, Whiting, and Stich 1981;Hrelia et al 1987).…”

Section: Effect On Genotoxicity Of Other Agentsmentioning

confidence: 99%

Final Report on the Safety Assessment of BHT

Lanigan¹,

Yamarik²

2002

Int J Toxicol

142

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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: Effect On Genotoxicity Of Other Agentsmentioning

confidence: 99%