01. What is TBHQ?

TBHQ is a synthetic antioxidant that is added to foods to prevent or delay oxidation.0xidation can cause food to lose flavor qualities,color, and can even lead to food become toxic;In addition, oxidation can cause vitamins to break down, therefore resulting in the loss of part of the food’s nutritional value.

TBHQ is an aromatic compound with the molecular formula C10H14O2，white

to light colored crystal or fine powder with a slightly aromatic odor, easily soluble in ethanol (60% at 25℃) and ether; It is soluble in oils, such as corn oil, soybean oil, cottonseed oil, with 10% at 25℃. While TBHQ  is insoluble in water (less than 1% at 20℃ and 5% at 95℃).The melting point is 126.5℃ to 128.5℃, the boiling point' is 295℃，the density is 1.05g/cm³，the molar mass is 166. 22 g/mol, and the pKa is 10.8. It has the characteristics of no discoloration when encountering iron and copper.

02. Is TBHQ toxic?

Paracelsus, the founder of toxicology, once pointed out that“everything contains toxins, and nothing is completely non- toxic: it is the dose that determines the toxicity of a substance." When discussing toxicity, we need to look at the dose first. Ethanol (found in alcoholic beverages) is toxic at high concentrations and can easily cause respiratory failure by suppressing breathing, but a drink or two helps to relax.

Studies have shown TBHQ have negative effects at high doses, but national regulatory agencies that allow the use of TBHQ all specify the amount of TBHQ that can be added to food, and the amount of TBHQ ingested from food is well within the safe limits determined by regulators. For example, the FDA allows the use of 200 ppm of TBHQ in the fat of many foods to delay oxidation and improve quality.

It has also been reported that TBHQ may be used as a treatment for chronic diseases. In vitro and in vivo studies,TBHQ acts as an antioxidant to activate Nrf2，a transcription factor important for oxidative stress reaction, it attenuates traumatic brain injury[1], liver damage[2], shows anti-inflammatory activity[3]，and prevents oxidative stress-induced death[4], and so on. According to Zhenwen Zhang’s study, a diet containing TBHQ (25 mg/kg) was reported to reduce brain injury, astrocyte hyperactivation, pro-inflammatory phenotype M1 and production of inflammatory cytokines(TNF-α, IL-1β, IL-6 and free radicals)，and decreases apoptosis and neuronal death in the cerebral cortex of rats after traumatic brain injury.

The metabolic pathways of TBHQ have been comprehensively studied in rats, dogs and humans. More than 90% of TBHQ is absorbed after oral administration in rats, dogs and humans, and distributed in the body through biological macromolecules (mainly serum albumin). In the first stage,TBHQ is metabolized and oxidized into TBBQ in the liver. In the second stage, TBBQ is bound to glutathione (GSH) by metabolic enzymes. In humans, TBHQ is excreted in the urine within 24 hours as a

combination of 0-sulfate (73-88%) and 0-glucosidate (15-22%)，and the remaining unabsorbed TBHQ (2.4-3. 7%) is excreted in the stool. The metabolic residues of TBHQ have been reported to be insignificant in the brain, liver, and kidney, and tissue retention of the compound has not been observed in rats.[5]

03 TBHQ is banned in some countries, so is it safe?

As an antioxidant, TBHQ has been used in common foods for decades and helps maintain the quality, safety and nutritional value of many foods we safely enjoy, Its safety has been approved by the US Food and Drug Administration (FDA) and the European Food Safety Authority (EFSA)，as well as by the Joint FAO/WHO Expert Committee on Food Additives (JECFA).

U.S. Food and Drug Administration (FDA) : The FDA classifies TBHQ as generally recognized as safe or “GRAS" and approved its use in food in 1972. TBHQ can be safely used as an antioxidant alone or in combination with BHA and/or BHT, with a maximum use of 0. 02% of the oil or fat content of the food.

European Food Safety Authority (EFSA):

TBHQ(E319) is listed as an authorized food additive in European Commission Regulation (EU) No 231/2012 and is classified as “additives other than pigments and sweeteners" . EFSA stated TBHQ is not carcinogenic in its 2004 safety assessment and in 2004 an ADI (acceptable daily intake) of 0. 7 mg/kg body weight (BW) was confirmed, which was established by JECFA in 1997. Regulation (EU)

2018/1481 sets the maximum amount of TBHQ to be applied in different food categories as "25 -400mg/kg".

Joint FAO/WHO Expert Committee on Food Additives (JECFA):

JECFA classified TBHQ as food additives and antioxidants, and set the ADI of TBHQ as "0-0. 7 mg/kg BW”in 1997.

In addition, TBHQ has been approved as a food antioxidant in more than 100 countries and regions around the world, including China, Australia, Brazil, France, Germany, the United Kingdom,India,Iran, and so on. It is widely used in edible oil, oily food and other products.

About FD TECH

FD TECH Food Ingredient Co., Ltd is based on nearly 40 years of ingenious research in

the food chemical industry, which is dedicated to the cultivation of food oil antioxidants, and striving to provide outstanding products and services to the world and create the best antioxidant solutions!

For more info. of TBHQ, welcome to your continuous attention: www.lpfoods-wy.com

reference：

[1]Z.-W.Zhang,et al.TBHQ improved neurological recovery after traumatic brain injury by inhibiting the overactivation of astrocytes.Brain Res.,1739(2020), Article 146818.

[2]R.Li,et al.Tert-butylhydroquinone mitigates carbon tetrachloride induced hepatic injury in mice.Int. J. Med. Sci.,17(14)(2020), p.2095

[3]X.P.Zeng,et al.Tert-butylhydroquinone protects liver against ischemia/reperfusion injury in rats through Nrf2-activating anti-oxidative activity.Transplant. Proc.,49(2)(2017), pp.366-372.

[4]J.Sun,X.Ren,J.W.Simpkins. Sequential up-regulation of SOD2 and HO-1 by tert-butylhydroquinone protects mitochondria during oxidative stress. Mol. Pharmacol.(2015) p.mol.115.098269.