Butylhydroxyanisole (Butylated hydroxyanisole)

Butylated hydroxyanisole

Rep Carcinog 2011;12:78-80.21850118

Butylated hydroxyanisole in perspective

Chem Biol Interact 1991;80(2):109-34.1934145 10.1016/0009-2797(91)90019-4

Butylated hydroxyanisole (BHA) is a synthetic food antioxidant used to prevent oils, fats and shortenings from oxidative deterioration and rancidity. This review depicts the current knowledge on BHA. The physical and chemical characteristics of BHA are summarized and its function as a food antioxidant is made clear. The toxicological characteristics of BHA and its metabolic fate in man and animal are briefly reviewed. Special emphasis is laid on the carcinogenicity of BHA in the forestomach of rodents and to related events in the forestomach and other tissues in experimental animals. At present there is sufficient evidence for carcinogenicity of BHA, but there is hardly any indication that BHA is genotoxic. Therefore risk assessment for this epigenetic carcinogen is based on non-stochastic principles. However, the mechanism underlying the tumorigenicity of BHA is not known. In the last part of this review an attempt is made to unravel the unknown mechanism of carcinogenicity. It is hypothesized that BHA gives rise to tumor formation in rodent forestomach by inducing heritable changes in DNA. Evidence is being provided that reactive oxygen species, in particular hydroxylradicals, may play a crucial role. The key question with respect to risk assessment for BHA is whether or not the underlying mechanism is thresholded, which is important for the choice of the appropriate model to assess the risk, if any, for man and to manage any potential risk.

Butylated hydroxyanisole (BHA)

Rep Carcinog 2002;10:40-2.15318380

Butylated hydroxyanisole alters rat 5α-reductase and 3α-hydroxysteroid dehydrogenase: Implications for influences of neurosteroidogenesis

Neurosci Lett 2017 Jul 13;653:132-138.28552457 10.1016/j.neulet.2017.05.034

Butylated hydroxyanisole is a synthetic antioxidant. It may affect the function of the nerve system. The objective of the present study is to investigate the direct effects of Butylated hydroxyanisole on rat brain neurosteroidogenic 5α-reductase 1 (SRD5A1), 3α-hydroxysteroid dehydrogenase (AKR1C14), and retinol dehydrogenase 2 (RDH2). Rat SRD5A1, AKR1C14, and RDH2 were cloned and expressed in COS1 cells, and the effects of Butylated hydroxyanisole on these enzyme activities were measured. Butylated hydroxyanisole inhibited SRD5A1, AKR1C14, and RDH2 with IC50 values of 4.731±0.079μM, 5.753±0.073μM, and over 100μM, respectively. Butylated hydroxyanisole is a competitive inhibitor for both SRD5A1 and AKR1C14. Docking analysis shows that Butylated hydroxyanisole binds to the dihydrotestosterone-binding site of AKR1C14. In conclusion, Butylated hydroxyanisole is a potent inhibitor of SRD5A1 and AKR1C14, thus reducing the formation of active neurosteroids.

Butylated hydroxyanisole: Carcinogenic food additive to be avoided or harmless antioxidant important to protect food supply?

Regul Toxicol Pharmacol 2021 Apr;121:104887.33556417 10.1016/j.yrtph.2021.104887

Tumor data from rodent bioassays are used for cancer hazard classification with wide-ranging consequences. This paper presents a case study of the synthetic antioxidant Butylated hydroxyanisole (BHA), which IARC classified as Group 2B ("possibly carcinogenic to humans") on the basis of forestomach tumors in rodents following chronic dietary exposure to high levels. IARC later determined that the mechanism by which BHA induces forestomach tumors is not relevant to humans; however, the classification has not been revoked. BHA was listed on California Proposition 65 as a direct consequence of the IARC classification, and there is widespread concern among consumers regarding the safety of BHA driven by the perception that it is a carcinogen. While many regulatory agencies have established safe exposure limits for BHA, the IARC classification and Proposition 65 listing resulted in the addition of BHA to lists of substances banned from children's products and products seeking credentials such as EPA's Safer Choice program, as well as mandatory product labeling. Classifications have consequences that many times pre-empt the ability to conduct an exposure-based risk-based assessment., It is imperative to consider human relevance of both the endpoint and exposure conditions as fundamental to hazard identification.