Alarming impact of the excessive use of tert-butylhydroquinone in food products: A narrative review

Abstract

Tert-butyl hydroquinone (TBHQ) is a food additive commonly used as a more effective protectant in the food, cosmetic and pharmaceutical industries. However, the long-term exposure to TBHQ at higher doses (0.7 mg/kg) results in substantial danger to public health and brings a series of side effects, including cytotoxic, genotoxic, carcinogenic, and mutagenic effects. As a result, the global burden of chronic diseases has fascinated consumers and governments regarding the safety assessment of food additives. Regarding contradictory reports of various research about the application of food additives, the accurate monitoring of food additives is urgent. Notwithstanding, there are reports of the therapeutic effects of TBHQ under pathologic conditions through activation of nuclear factor erythroid 2-related factor 2. Thus, further investigations are required to investigate the impact of TBHQ on public health and evaluate its mechanism of action on various organs and cells. Therefore, this review aimed to investigate TBHQ safety through an overview of its impacts on different tissues, cells, and biological macromolecules as well as its therapeutic effects under pathologic conditions.

Keywords: Adverse impact; Food additives; Food safety; Overdose; Tert-butylhydroquinone.

Graphical abstract

Fig. 1

: Structure of tert-butylhydroquinone.

Fig. 2

Mechanisms of antimicrobial activity of tert-butylhydroquinone. The TBHQ normally reacts with the cell membrane, resulting in disruption of the cell membrane and leakage of intracellular contents, followed by inhibition of macromolecular synthesis (e.g., DNA, RNA, lipid and protein) in microorganisms.

Fig. 3

Pathways of Tert-butyl hydroquinone absorption, metabolism and excretion in human body. More than 90% of TBHQ are absorbed after oral administration and distributed in the body by biomacromolecules (majorly serum albumin protein). It is metabolized and oxidized into TBBQ in the liver. In Phase Ⅰ, TBHQ is oxidized at the tert-butyl group of its structure by cytochrome P450 (monooxygenases, prostaglandin H synthase and lipoxygenase) or via autoxidation and/or Cu⁺² ion-catalyzed redox cycling to TBBQ as the reactive metabolite. In Phase Ⅱ, TBBQ conjugated with glutathione (GSH) by metabolizing enzymes such as glutathione S-transferase (GST), NADPH quinone oxidoreductase (NQO1), UDP-glucuronosyltransferase and epoxide hydrolase. humans, TBHQ was excreted in urine within 24 h as O-sulphate (73–88%) and O-glucuronide (15–22%) conjugates. However, unchanged TBHQ was not detected in urine. Rest of unabsorbed TBHQ (2.4–3.7%) are excreted in feces.

Fig. 4

Interaction of Tert-butyl hydroquinone with bovine serum albumin. TBHQ reacts with Subdomain IIA (Trp-212) of BSA and lead to changes in secondary-structure of this protein by reduction of α-helix contents.

Fig. 5

Interaction of tert-butylhydroquinone with deoxyribonucleic acid. TBHQ bind to CT-DNA changed DNA conformation from B-form to A-form.