Elsevier

Environmental Research

Volume 201, October 2021, 111531
Environmental Research

Analysis, occurrence, toxicity and environmental health risks of synthetic phenolic antioxidants: A review

https://doi.org/10.1016/j.envres.2021.111531Get rights and content

Highlights

  • Analytical methods of SPAs and TPs based on GC and HPLC were summarized.

  • BHA, and BHT and its TPs are frequently detected in various environmental matrices.

  • Human exposure to SPAs is minor compared with the ADIs.

  • The lack of PNECs may cause inaccurate risk assessment of SPAs.

Abstract:

The continuous improvement of living standards is related to higher requirements for the freshness and taste of food. For example, synthetic phenolic antioxidants (SPAs) are added to fats and fried foods as food additives to minimize the oxidative rancidity of oils and fats. Hence, the global use of SPAs is increasing year by year. Dibutyl hydroxytoluene is one of the widely used SPAs, often in combination with butyl hydroxyanisole or gallate SPAs. The extensive use of these compounds makes them and their transformation products to be widespread in various environmental matrices, including indoor dust, wastewater, river water, sewage sludge, and sediment, as well as human samples, such as nails and urine, at concentrations varying from nanogram per gram (ng/g) to microgram per gram (μg/g). Animal experiments have shown that high-dose SPA exposure is toxic, which may lead to DNA damage and mismatches and the development of cancerous tumors. Since the biosphere shares the same set of genetic codes, humans and animals have many identical or similar feedback mechanisms and information pathways. Therefore, the damage of SPAs to animals may also threaten human health. This review discusses the properties, occurrence, analysis, and environmental health risks of typical SPAs, including butyl hydroxyanisole, dibutyl hydroxytoluene, tert-butylhydroquinone, propyl gallate, octyl gallate, and lauryl gallate, used as food additives. In addition, AO2246, which is used in food packaging bags, is also considered. Future research directions on SPAs and their transformation products (TPs) are identified and discussed.

Introduction

In recent years, with the continuous development of the food industry, food safety has become a major issue, which influences the national economy and people's livelihood. This concern is mainly related to the food additives frequently used in the food industry, with particular attention being paid to their safety. Among food products, unsaturated fats and oils are particularly investigated, since the generated free radicals under the action of heat, light, metal ions, and oxygen favor the occurrence of oxidation processes, which affect their production and storage (Wang and Chen, 2010). In unsaturated fats, peroxide radicals combine with the hydrogen atoms to form hydrogenated peroxides, which continues the oxidation reaction (Yao, 2001). To avoid/delay these unfavorable processes and maintain the taste and look of foods, antioxidants are widely used as food additives in oils, fats, and fried foods.

Synthetic phenolic antioxidants (SPAs) are a family of high-efficiency, lipophilic, and excellent antioxidants, which are a component of many types of foods. Compared to naturally produced antioxidants such as tocopherols, which are produced by plants and animals, SPAs have the advantages of a stable structure, high thermal stability, and strong antioxidant capacity, and can be synthesized in large quantities to meet demand (Zhang et al., 2009). The main SPAs discussed in this review are butyl hydroxyanisole (BHA), dibutyl hydroxytoluene (BHT), tert-butyl hydroquinone (TBHQ), gallate antioxidants, i.e., propyl- (Pg), octyl- (Og), lauryl- (Dg). We also selected an antioxidant used in food packaging bags, namely AO2246, which migrates to food and enter the human body (Kang et al., 2018). Due to the high oxidation resistance and small effect on food color and taste, the production and consumption of SPAs in various countries are increasing year by year (Takahashi and Oishi, 2006; Liu, 2014; Huajing Industry Research Institute, 2019), which is also relies on the mature synthesis process of SPAs and the well-known food additive properties. In 2018, the usage of SPAs in China was 82418 tons, and the number is still increasing (Huajing Industry Research Institute, 2019). The most widely used SPA is BHT, which has been added to various foods and more than 1700 cosmetics, in a concentration of up to 0.5% (Liu and Mabury, 2018). BHT is often used in combination with BHA due to its low cost and low thermal stability (Ling, 2000). BHT can be converted into a variety of transformation products (TPs) in the natural environment and organisms (Liu and Mabury, 2020). The main TPs of BHT detected so far are 2,6-di-tert-butyl-1,4-benzoquinone (BHT-Q), 2,6–2 tertiary butyl-4-(hydroxymethyl) phenol (BHT-OH), 3,5-di-tert-butyl-4-hydroxybenzoic acid (BHT-COOH), 3,5–2 tertiary butyl-4-hydroxy benzaldehyde (BHT-CHO), and 2,6-di-tert-butyl4-hydroxy-4-methyl 2,5-cyclohexadienone (BHT-quinol) (Wang and Kannan, 2019).

However, the widespread use of SPAs has led to their presence in various environmental matrices (e.g., oil products, urban dust, water, soil, and sediment) and biological samples (e.g., marine molluscs, human serum, and urine) (Butte et al., 2001; Soliman et al., 2007; Gao et al., 2011; Liu et al., 2015a, 2017a; Wang et al., 2016, 2018a; Liu and Mabury, 2018). Moreover, the in vitro and in vivo toxicity of SPAs were also proved. For example, BHA has an obvious estrogen effect, which has a great impact on the reproductive development, also exhibiting teratogenic and carcinogenic effects at high concentrations (Grice, 1988; Kahl and Kappus, 1993; Jobling et al., 1995; Yang et al., 2018a). Pg has testicular toxicity, inducing male infertility through mitochondrial dysfunction and disruption of calcium homeostasis (Ham et al., 2019). TBHQ is the main metabolite of BHA, and it also has a certain estrogen effect, influencing the sex formation of zebrafish (Yang et al., 2018a). BHT and its transformation products have endocrine disrupting effects, being a typical tumor promoter and carcinogen (Umemura et al., 2006). Although AO2246 is not directly used as a food additive, it is generally used in food packaging bags (Kang et al., 2018). At present, studies have proved that food contact materials, such as food packaging bags, release chemical substances into food, and the migration of these chemical substances is beyond expectation (Qian et al., 2018). For instance, the migration of SPAs can occur under certain conditions, and its potential toxic effects are worthy of attention (Liu and Mabury, 2020).

So far, the review in researching these SPAs for food, especially in terms of environmental occurrence, biological toxicity, and environmental health risks, has been scarcely discussed. Therefore, it is of national and worldwide interest to systematically summarize and discuss all aspects related to the food SPAs. This review mainly focuses on the researches on SPAs and their transformation products (TPs) conducted in recent decades, with emphasis on the analytical methods for the detection of SPAs, as well as their environmental occurrence and toxicity. In the light of the reviewed results, preliminary evaluations of environmental risks as well as suggestions for future studies in this field of research are provided.

Section snippets

Structure

SPAs are a family of artificially synthesized free radical chain terminators that can inhibit or even prevent chain-initiated or chain-growth reactions by trapping proxy radicals and thus, achieving the antioxidant effects (Zhao, 2003). Generally, their chemical structure involves a phenol ring that is usually substituted in the ortho position with a hindering alkyl group. The chemical structures of the studied compounds are shown in Fig. 1. Therefore, they are also called hindered phenol

Analysis of SPAs and their transformation products

Currently, many analytical methods, such as spectrophotometry (Yin et al., 2000), Colorimetry (China Food Additives Production and Application Industry Association, 1999), and electrophoresis have been used to detect SPAs and their TPs in foods (Boyce and Spickett, 1999; Xiang, 2009). However, these methods were gradually discontinued due to low sensitivity, demanding and time-consuming sample preparation conditions. With the development of analytical science and technology, colorimetry, high

Occurrence in the environment and humans

As mentioned above, SPAs already populate almost all environmental media and regions as a result of the large-scale use of SPAs by humans in various fields of activity. On the other hand, this phenomenon is related to the ability of the compounds to circulate in the environment. For instance, they can be widely distributed throughout the world through rainfall and surface runoff (Fries and Püttmann, 2002). The concentrations of SPAs and TPs in various environment matrices are listed in Table 3.

Intake from food

As SPAs and TPs exist in a variety of environmental matrices, human exposure to these chemicals is inevitable. Food intake has been reported as the main sources of these contaminants for humans. There are studies reporting the estimated intakes of SPAs in adults and infants through food in Brazil, South Korea, China, and many other countries. In this review, the estimated daily intake (EDI, ng/kg bw/day) of residents exposed to SPAs and TPs through intake from food is discussed based on

Toxicological studies

SPAs are useful for food storage and preservation, but also cause potential ecological and human health risks. SPAs and TPs, released to the environment, can migrate over long distance (Fries and Püttmann, 2002). Therefore, the toxicities of SPAs and TPs should raise an alarm for both producers and consumers. However, the metabolism and degradation pathways of SPAs and TPs have not been fully grasped by researchers, and direct evidence for the cumulative effects of such compounds in vivo is not

Conclusions and outlook

SPAs, a class of excellent antioxidants, are widely used in food industry because they can effectively extend the preservation time of oily foods. With the increasing production and use, the inevitable release to the environment of SPAs causes potential risks to both environment and human health. In this review, the structure, properties, analytical methods, occurrence, and toxicity of SPAs and their TPs were comprehensively summarized, and their environmental risks assessed. As a result, of

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

This study was financially supported by the National Key Research and Development Program of China (2019YFC1604803 and 2018YFC1801602), National Natural Science Foundation of China (21806172 and 21677167), and the K.C. Wong Education Foundation of China (GJTD-2020-03).

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