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A review of the occurrence, metabolites and health risks of butylated hydroxyanisole (BHA)

Zhang, Xiao‐Jing, Diao, Mei‐ning, Zhang, Yin‐Feng·2023·Journal of the Science of Food and Agriculture
DOI 10.1002/jsfa.12676
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Abstract

Butylated hydroxyanisole (BHA) is mainly used as a food additive due to its antioxidant properties, which prevent or delay oxidation reactions and extend the storage life of products. The widespread use of BHA has led to its extensive presence in various environmental matrices and human tissues. Food intake is the main route of human exposure to BHA. Under different conditions, BHA can produce different metabolites, with tert‐butyl hydroquinone (TBHQ) being one of the major products. Several studies have shown that BHA could cause thyroid system damage, metabolic and growth disorders, neurotoxicity, and carcinogenesis. Mechanisms such as endocrine disruption, genotoxicity, disturbances of energy metabolism, reactive oxygen species (ROS) production, signaling pathways, and imbalances in calcium homeostasis appear to be associated with the toxic effects of BHA. Avoiding the toxic effects of BHA to the maximum extent possible is a top priority. Finding safe, non‐toxic and environmentally friendly alternatives to BHA should be the focus of subsequent research. In all, this review summarized the current situation related to BHA and might make recommendations for future research directions. © 2023 Society of Chemical Industry.

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Research works printed but not linked: 183

  1. Bampidis V, 2021, Safety and efficacy of a feed additive consisting of butylated hydroxyanisole (BHA) for use in cats (FEDIAF), EFSA J, 19
  2. Rychen G, 2018, Safety and efficacy of butylated hydroxyanisole (BHA) as a feed additive for all animal species, EFSA J, 16
  3. 10.1016/B978-1-78242-089-7.00003-8 · DOI
  4. Aguilar F, 2011, Scientific opinion on the re‐evaluation of butylated hydroxyanisole‐BHA (E 320) as a food additive, EFSA J, 9
  5. 10.1016/j.chroma.2010.08.020 · DOI
  6. 10.1016/j.tifs.2009.12.003 · DOI
  7. 10.1007/s002170050241 · DOI
  8. 10.1016/0009-2797(91)90019-4 · DOI
  9. 10.1016/j.jhazmat.2019.120794 · DOI
  10. 10.1016/j.foodchem.2006.12.025 · DOI
  11. EU, 2008, Regulation (EC) No 1333/2008 of the European parliament and of the council of 16 December 2008 on food additives, Off J Eur Union, 354, 16
  12. EU, 1995, European parliament and council directive No. 95/2/EC of 20 february 1995 on food additives other than colours and sweeteners off, J Eur Communities, 61, 23
  13. 10.1016/j.scitotenv.2019.03.495 · DOI
  14. 10.1016/j.envpol.2016.11.069 · DOI
  15. 10.1021/acs.est.5b04826 · DOI
  16. 10.1021/es011055j · DOI · Paper page
  17. 10.1016/S0043-1354(99)00027-5 · DOI
  18. 10.2175/106143006X111961 · DOI
  19. 10.1016/j.watres.2017.11.028 · DOI
  20. 10.1021/es505136k · DOI
  21. 10.1016/j.chroma.2014.11.042 · DOI
  22. 10.1016/j.jhazmat.2011.10.058 · DOI
  23. 10.1021/acs.est.9b04120 · DOI
  24. 10.1038/s41419-021-03994-0 · DOI
  25. 10.1016/S0278-6915(99)00085-X · DOI
  26. 10.1016/0278-6915(86)90302-9 · DOI
  27. 10.1021/acs.est.9b04709 · DOI
  28. 10.1021/acs.estlett.0c00104 · DOI
  29. 10.1016/j.envint.2019.04.028 · DOI
  30. 10.1016/j.envpol.2019.06.077 · DOI
  31. Benson AM, 1984, Kinetics of glutathione transferase, glutathione transferase messenger RNA, and reduced nicotinamide adenine dinucleotide (phosphate):quinone reductase induction by 2(3)‐tert‐butyl‐4‐hydroxyanisole in mice, Cancer Res, 44, 5256
  32. 10.1016/j.envres.2018.11.020 · DOI
  33. 10.1021/acs.estlett.8b00223 · DOI
  34. 10.1248/jhs1956.38.397 · DOI
  35. 10.4103/0973-7847.70902 · DOI · Paper page
  36. 10.1179/135100007X239252 · DOI
  37. 10.1007/s11746-000-0147-9 · DOI
  38. 10.1016/0300-483X(88)90234-X · DOI
  39. 10.1016/0300-483X(87)90004-7 · DOI
  40. 10.1016/0300-483X(87)90111-9 · DOI
  41. 10.1016/0278-6915(86)90282-6 · DOI
  42. 10.1016/0378-4274(85)90116-X · DOI
  43. Ansari GA, 1985, Tissue distribution and pharmacokinetics of 3‐t‐[methyl‐14C] butyl‐4‐hydroxyanisole in rats, Drug Metab Dispos, 13, 535, 10.1016/S0090-9556(25)08246-7 · DOI
  44. 10.1016/0278-6915(94)00125-8 · DOI
  45. 10.1093/carcin/14.3.347 · DOI
  46. 10.1016/S0278-6915(99)00091-5 · DOI
  47. 10.1016/j.scitotenv.2018.06.213 · DOI
  48. 10.1016/j.tox.2004.11.014 · DOI
  49. 10.1021/acs.est.1c07182 · DOI
  50. 10.1016/j.scitotenv.2019.135608 · DOI
  51. 10.1177/0960327120952140 · DOI
  52. 10.1093/carcin/13.9.1663 · DOI
  53. 10.1093/carcin/12.4.703 · DOI
  54. 10.1093/carcin/12.7.1341 · DOI
  55. 10.1016/0278-6915(85)90265-0 · DOI
  56. Ito N, 1983, Carcinogenicity of butylated hydroxyanisole in F344 rats, J Natl Cancer Inst, 70, 343
  57. 10.1021/acs.jafc.9b02899 · DOI
  58. 10.1016/j.scitotenv.2019.134775 · DOI
  59. 10.1021/acs.est.7b05057 · DOI
  60. 10.1089/dna.2012.1946 · DOI
  61. 10.1016/j.toxlet.2018.10.005 · DOI
  62. 10.1007/s00604-017-2643-z · DOI
  63. 10.1016/j.foodchem.2017.04.176 · DOI
  64. 10.1016/j.foodchem.2016.06.053 · DOI
  65. 10.1016/j.jfca.2005.12.005 · DOI
  66. 10.1016/S0963-9969(01)00164-8 · DOI
  67. 10.1016/S0308-8146(01)00373-9 · DOI
  68. 10.1016/S0021-9673(98)00601-3 · DOI
  69. 10.1016/S0308-8146(99)00205-8 · DOI
  70. 10.1007/978-1-4757-9351-2_19 · DOI
  71. 10.1080/10408399209527581 · DOI · Paper page
  72. 10.1016/j.jchromb.2021.122715 · DOI
  73. 10.1016/j.ecoenv.2022.113179 · DOI
  74. 10.1016/j.envres.2016.07.042 · DOI
  75. JECFA, WHO & FAO, 2000, Evaluation of certain food additives. Fifty‐first report of the joint FAO/WHO expert committee on food additives, W H O Tech Rep, 891, 1
  76. 10.1016/0278-6915(86)90285-1 · DOI
  77. Mancini FR, 2015, Dietary exposure to benzoates (E210‐E213), parabens (E214‐E219), nitrites (E249‐E250), nitrates (E251‐E252), BHA (E320), BHT (E321) and aspartame (E951) in children less than 3years old in France, Food Addit Contam Part A Chem Anal Control Expo Risk Assess, 32, 293
  78. 10.1021/acs.est.8b03322 · DOI
  79. 10.1016/0278-6915(84)90174-1 · DOI
  80. 10.1080/19440049.2010.508195 · DOI
  81. 10.1016/0278-6915(86)90300-5 · DOI
  82. Cummings SW, 1985, Metabolism of 3‐tert‐butyl‐4‐hydroxyanisole by microsomal fractions and isolated rat hepatocytes, Cancer Res, 45, 5617
  83. Armstrong KE, 1985, Metabolism of 3‐tert‐butyl‐4‐hydroxyanisole to 3‐tert‐butyl‐4,5‐dihydroxyanisole by rat liver microsomes, Cancer Res, 45, 1507
  84. 10.1002/bdd.2510040410 · DOI
  85. 10.1021/jf60122a015 · DOI
  86. 10.1021/jf00006a012 · DOI
  87. Shahid MA, 2022, StatPearls [Internet]
  88. Standring S, 2021, Gray's Anatomy e‐Book: The Anatomical Basis of Clinical Practice
  89. 10.1016/0278-6915(86)90309-1 · DOI
  90. 10.1016/0300-483X(82)90043-9 · DOI
  91. Darbre PD, 2015, Endocrine Disruption and Human Health
  92. 10.1016/j.jhep.2021.10.013 · DOI · Paper page
  93. 10.1152/physrev.00002.2020 · DOI
  94. 10.1038/nature05485 · DOI · Paper page
  95. 10.2337/diabetes.47.10.1643 · DOI
  96. Kalra A, 2021, Physiology, Liver
  97. 10.1007/s13238-017-0409-3 · DOI
  98. 10.1016/j.cub.2017.09.019 · DOI · Paper page
  99. 10.1038/emm.2015.122 · DOI · Paper page
  100. 10.1016/S0015-6264(72)80003-8 · DOI
  101. 10.1016/0304-3835(85)90171-5 · DOI
  102. 10.3382/ps.0560747 · DOI
  103. 10.1016/0272-0590(91)90120-S · DOI
  104. 10.1021/cb300573r · DOI
  105. 10.1021/jf503671m · DOI
  106. 10.1016/j.jbiotec.2016.08.019 · DOI
  107. 10.1016/0887-2333(88)90048-3 · DOI
  108. 10.1007/s10565-006-0153-6 · DOI
  109. 10.3322/caac.21660 · DOI · Paper page
  110. Wild CP, 2014, World Cancer Report 2014
  111. NTP (National Toxicology Program), 2021, Report on Carcinogens
  112. Ito N, 1984, Induction of forestomach hyperplasia by crude butylated hydroxyanisole, a mixture of 3‐tert and 2‐tert isomers, in Syrian golden hamsters is due to 3‐tert‐butylated hydroxyanisole, Gann, 75, 471
  113. Hirose M, 1986, Histologic and autoradiographic studies on the forestomach of hamsters treated with 2‐tert‐butylated hydroxyanisole, 3‐tert‐butylated hydroxyanisole, crude butylated hydroxyanisole, or butylated hydroxytoluene, J Natl Cancer Inst, 76, 143
  114. 10.1016/j.yrtph.2021.104887 · DOI
  115. 10.1016/0163-7258(96)00066-6 · DOI
  116. 10.1016/0197-0186(94)00105-4 · DOI
  117. 10.1002/dev.420070411 · DOI
  118. 10.1007/BF00421974 · DOI
  119. Scudder CL, 1969, Aggression and the orienting reflex in several genera and strains of mice, Agressologie, 10, 135
  120. Vorhees CV, 1981, Developmental neurobehavioral toxicity of butylated hydroxyanisole (BHA) in rats, Neurobehav Toxicol Teratol, 3, 321
  121. 10.1038/s41598-020-66379-x · DOI
  122. 10.2478/s13382-011-0022-2 · DOI
  123. 10.1289/ehp.98106s111 · DOI
  124. 10.1016/j.envint.2021.106433 · DOI
  125. 10.1021/jf052864f · DOI
  126. 10.1248/yakushi.123.443 · DOI
  127. 10.1289/ehp.95103s7113 · DOI
  128. 10.1289/ehp.95103582 · DOI
  129. 10.1002/jat.3601 · DOI
  130. 10.1021/tx800048m · DOI
  131. Zhu BT, 1997, Effect of dietary 2(3)‐tert‐butyl‐4‐hydroxyanisole on the metabolism and action of estradiol and estrone in female CD‐1 mice, Cancer Res, 57, 2419
  132. Cha YN, 1982, Comparative effects of dietary administration of 2(3)‐tert‐butyl‐4‐hydroxyanisole and 3,5‐di‐tert‐butyl‐4‐hydroxytoluene on several hepatic enzyme activities in mice and rats, Cancer Res, 42, 2609
  133. Pop A, 2013, Evaluation of the possible endocrine disruptive effect of butylated hydroxyanisole, butylated hydroxytoluene and propyl gallate in immature female rats, Farmacia, 61, 202
  134. 10.1016/j.tox.2005.05.027 · DOI
  135. 10.1093/toxsci/53.2.278 · DOI
  136. 10.1016/j.tiv.2016.01.012 · DOI
  137. Pop A, 2013, Endocrine disrupting effects of butylated hydroxyanisole (BHA‐E320), Clujul Med, 86, 16
  138. 10.1002/ijc.30450 · DOI
  139. Lednicer D, 2011, Steroid Chemistry at a Glance
  140. 10.1080/15376516.2016.1202367 · DOI
  141. 10.1159/000441034 · DOI
  142. Phillips DH, 2009, Genotoxicity: damage to DNA and its consequences, EXS, 99, 87
  143. 10.1124/mol.58.2.431 · DOI
  144. 10.1089/dna.2009.0906 · DOI
  145. 10.1016/0278-6915(86)90303-0 · DOI
  146. 10.1146/annurev-arplant-042817-040322 · DOI
  147. Devasagayam TP, 2004, Free radicals and antioxidants in human health: current status and future prospects, J Assoc Physicians India, 52, 794
  148. Patel RP, 1999, The biochemistry of nitric oxide and peroxynitrite: implications for mitochondrial function, Oxid Stress Dis, 2, 39
  149. 10.1093/carcin/16.3.477 · DOI
  150. Jhee EC, 1989, Effect of butylated hydroxyanisole pretreatment on aflatoxin B1‐DNA binding and aflatoxin B1‐glutathione conjugation in isolated hepatocytes from rats, Cancer Res, 49, 1357
  151. Durant S, 1988, Mouse embryo fibroblasts in culture: characteristics of arachidonic acid metabolism during early passages, Prostaglandins Leukotrienes Essent Fatty Acids, 32, 129
  152. 10.1016/0009-2797(83)90048-0 · DOI
  153. Saito M, 2003, Cytotoxicity and apoptosis induction by butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT), Anticancer Res, 23, 4693
  154. Nelson DL, 2008, Lehninger Principles of Biochemistry
  155. 10.1016/0014-5793(86)80180-6 · DOI
  156. 10.1248/bpb.27.295 · DOI
  157. 10.1002/(SICI)1097-0142(19960215)77:4<725::AID-CNCR19>3.0.CO;2-2 · DOI
  158. Nakagawa Y, 1994, On the mechanisms of 3‐tert‐butyl‐4‐hydroxyanisole‐ and its metabolites‐induced cytotoxicities in isolated rat hepatocytes, Eur J Pharmacol, 270, 341
  159. 10.1016/0006-2952(90)90301-Z · DOI
  160. 10.1016/0006-2952(88)90582-5 · DOI
  161. Krauss G, 2006, Biochemistry of Signal Transduction and Regulation
  162. 10.1074/jbc.272.46.28962 · DOI
  163. 10.1210/me.2004-0532 · DOI · Paper page
  164. 10.1016/j.steroids.2003.07.009 · DOI
  165. 10.1038/nrm1155 · DOI
  166. 10.1677/jme.0.0230299 · DOI
  167. 10.1016/0020-711X(88)90158-9 · DOI
  168. 10.4142/jvs.2015.16.1.17 · DOI
  169. 10.1080/10715760701868352 · DOI
  170. 10.1006/abbi.1996.0418 · DOI
  171. 10.1111/j.1365-3024.1985.tb00100.x · DOI
  172. 10.1093/carcin/13.4.585 · DOI
  173. 10.3181/00379727-192-42952 · DOI
  174. 10.2131/jts.39.739 · DOI
  175. 10.1093/mutage/2.4.293 · DOI
  176. Batzinger RP, 1978, Antimutagenic effects of 2(3)‐tert‐butyl‐4‐hydroxyanisole and of antimicrobial agents, Cancer Res, 38, 4478
  177. 10.1177/0960327115591378 · DOI
  178. 10.1093/gerona/63.11.1168 · DOI
  179. 10.1002/jbt.20281 · DOI
  180. 10.3390/cancers5041643 · DOI
  181. 10.1016/0272-0590(84)90101-5 · DOI
  182. 10.1016/0278-6915(86)90058-X · DOI
  183. 10.1016/S1011-1344(98)00172-9 · DOI

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Metadata

Authors
Zhang, X., Diao, M., & Zhang, Y.
Affiliations
Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine Qingdao University Qingdao China
ORCID
Venue
Journal of the Science of Food and Agriculture
Publisher
Wiley
Published
2023-05-16
Volume
103
Issue
13
Pages
6150-6166
ISSN
  • 0022-5142
  • 1097-0010
DOI
10.1002/jsfa.12676
Cited by
65
References
3
Language
en
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Funders
National Natural Science Foundation of China

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Zhang, X., Diao, M., & Zhang, Y. (2023). A review of the occurrence, metabolites and health risks of butylated hydroxyanisole (BHA). Journal of the Science of Food and Agriculture. https://doi.org/10.1002/jsfa.12676

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