Evaluation of genotoxicity of tert.-butylhydroquinone in an hepatocyte-mediated assay with V79 Chinese hamster lung cells and in strain D7 of Saccharomyces cerevisiae

Rogers, Charles G.; Boyes, B.G.; Matula, T.I.; Stapley, R.

doi:10.1016/0165-1218(92)90014-q

Cited by 17 publications

(8 citation statements)

References 31 publications

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“…No induced-gene mutation by tBHQ has been observed in the Salmonella bacterial mutation assays in the absence or presence of rat liver S9 fraction [63][64][65][66]. Mitotic gene conversion and reverse mutation were not induced in strain D7 of Saccharomyces cerevisiae by exposure to 500 μg/ml tBHQ for 4 h. Incubation of the yeast cells with tBHQ for 24 h in growth medium activation also did not induce genotoxic activity [67]. tBBQ, a reactive metabolite of tBHQ, was reported to be cytotoxic but not genotoxic to V79 Chinese hamster lung cells [68].…”

Section: Genotoxicitymentioning

confidence: 71%

Chemoprotective and Carcinogenic Effects of tert-Butylhydroquinone and Its Metabolites

Gharavi¹,

Haggarty²,

El‐Kadi

2007

CDM

145

109

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Tert-butylhydroquinone (tBHQ) has been commonly used as a synthetic food antioxidant to prevent oils and fats from oxidative deterioration and rancidity due to its potent anti-lipid peroxidation activity. In North America, the maximum level of tBHQ allowed in fat products is 0.02% with an acceptable daily intake of 0-0.7 mg/kg body weight. Extensive studies have demonstrated that tBHQ exhibit anti-carcinogenic effect. The ability of tBHQ to induce phase II xenobiotic metabolizing enzymes through an Nrf2-dependent pathway is thought to be responsible for the observed protective effect of tBHQ. It has been proposed that tBHQ enhances Nrf2-mediated transcription by promoting reactive oxygen species-mediated dissociation of Nrf2-Keap1, Nrf2 stabilization, phosphatidylinositol 3-kinase (PI3K)/Akt activity, and MAPK pathway activation. In contrast to the beneficial effects of tBHQ, a number of studies have shown that chronic exposure to tBHQ may induce carcinogenicity. However, the precise mechanisms of tBHQ carcinogenicity are not well understood. The toxicity or carcinogenicity of tBHQ has been attributed to the formation of reactive GSH-conjugates, generation of reactive species, CYP1A1 induction, caspase activation and reduced GSH/ATP levels. This review provides an account of recent mechanisms proposed for both chemoprotective and carcinogenic effect of tBHQ.

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Section: Genotoxicitymentioning

confidence: 71%

Chemoprotective and Carcinogenic Effects of tert-Butylhydroquinone and Its Metabolites

Gharavi¹,

Haggarty²,

El‐Kadi

2007

CDM

145

109

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“…In another study using Salmonella typhimurium TA 97, TA 100, TA 102 and TA 104 strains with or without metabolic activation, TBHQ was shown not to be mutagenic (Hageman et al, 1988). This was also the result when TBHQ was tested in Saccharomyces cerevisiae strain D7 with and without metabolic activation (Rogers et al, 1992). In the same study using V79 CHL cells, TBHQ was shown to have inconsistent and weak activity in the frequency of SCE and in the mutation frequency of the HGPRT gene locus with or without metabolic activation, using hepatocytes.…”

Section: Genotoxicity Of Metabolitesmentioning

confidence: 77%

“…Negative: Salmonella typhimurium TA 98, TA 100, TA 1535, TA 1537 and TA 1538 with or without metabolic activation (Williams et al, 1990a) Salmonella typhimurium TA 97, TA 98, TA 100 and TA 102 with or without metabolic activation (Matsuoka et al, 1990) Salmonella typhimurium TA 97, TA 100, TA 102 and TA 104 with or without metabolic activation (Hageman et al, 1988) Saccharomyces cerevisiae strain D7 with and without metabolic activation (Rogers et al, 1992) Gene mutation…”

Section: Reverse Mutationmentioning

confidence: 99%

Scientific Opinion on the re-evaluation of butylated hydroxyanisole - BHA (E 320) as a food additive

2011

EFSA Journal

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The Panel on Food Additives and Nutrient Sources added to Food (ANS) delivers a scientific opinion re‐evaluating the safety of butylated hydroxyanisole (BHA) (E 320). BHA is a synthetic antioxidant authorised as a food additive in the EU that was previously evaluated by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) several times, the latest in 1989 and the EU Scientific Committee for Food (SCF) in 1989. Both committees established an ADI of 0.5 mg/kg bw/day, with that of the SCF being classified as temporary. Both ADIs were based on proliferative changes in the rat forestomach. The Panel was not provided with a newly submitted dossier and based its evaluation on previous evaluations, additional literature that became available since then and the data available following an EFSA public call for data. The Panel concluded that BHA does not raise concern with respect to genotoxicity. A large number of long‐term toxicity and carcinogenicity studies with BHA have been performed, demonstrating proliferative changes in the forestomach with BMDL10 values in the rat of 115 and 83 mg/kg bw/day. The Panel concluded that the present database does give reason to revise the ADI. The Panel considered that forestomach hyperplasia in rodents may no longer be relevant for human risk assessment. Based on a NOAEL of 100 mg/kg bw/day for growth retardation, increased mortality and behavioural effects in rat pups at higher dose levels, and using an uncertainty factor of 100 the Panel established an ADI of 1.0 mg/kg bw/day. This NOAEL also covers the BMDL10 values for forestomach hyperplasia observed in the rat. The Panel also concluded that at the current levels of use refined intake estimates are generally below the ADI of 1.0 mg/kg bw/day.

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“…The formation of 2-tertiary-butyl-p-benzoquinone (TBBQ) from the use of TBHQ in food is not considered to be a matter of concern. Litton Bionetics (1982a) HPRT assay CHO cells negative Beilman and Barber (1985) HPRT assay V79 cells negative Rogers et al (1992) Both in the absence and presence of rat or hamster hepatocytes.…”

Section: Conclusion and Recommendationsmentioning

confidence: 99%

Opinion of the Scientific Panel on food additives, flavourings, processing aids and materials in contact with food (AFC) on a request from the Commission related to tertiary-Butylhydroquinone (TBHQ)

2004

EFSA Journal

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Evaluation of genotoxicity of tert.-butylhydroquinone in an hepatocyte-mediated assay with V79 Chinese hamster lung cells and in strain D7 of Saccharomyces cerevisiae

Cited by 17 publications

References 31 publications

Chemoprotective and Carcinogenic Effects of tert-Butylhydroquinone and Its Metabolites

Chemoprotective and Carcinogenic Effects of tert-Butylhydroquinone and Its Metabolites

Scientific Opinion on the re-evaluation of butylated hydroxyanisole - BHA (E 320) as a food additive

Opinion of the Scientific Panel on food additives, flavourings, processing aids and materials in contact with food (AFC) on a request from the Commission related to tertiary-Butylhydroquinone (TBHQ)

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