-
International Journal of Toxicology Dec 2023The Expert Panel for Cosmetic Ingredient Safety reviewed updated information that has become available since their original assessment from 2002, along with updated...
The Expert Panel for Cosmetic Ingredient Safety reviewed updated information that has become available since their original assessment from 2002, along with updated information regarding product types, and frequency and concentrations of use, and reaffirmed their original conclusion that BHT is safe as a cosmetic ingredient in the practices of use and concentration as described in this report.
Topics: Butylated Hydroxytoluene; Butylated Hydroxyanisole; Antioxidants; Cosmetics
PubMed: 37751543
DOI: 10.1177/10915818231204256 -
Environmental Research Oct 1982
Review
Topics: Animals; Antioxidants; Butylated Hydroxytoluene; Chemical Phenomena; Chemistry; Drug Interactions; Guinea Pigs; Humans; Liver; Mice; Neoplasms; Rabbits; Rats
PubMed: 6754366
DOI: 10.1016/0013-9351(82)90002-0 -
Mutation Research Sep 1992Butylated hydroxytoluene (BHT) is an effective, widely used, low cost antioxidant. A host of studies examining the potential of BHT to cause point mutations have been... (Review)
Review
Butylated hydroxytoluene (BHT) is an effective, widely used, low cost antioxidant. A host of studies examining the potential of BHT to cause point mutations have been published. They include in vitro studies on various bacterial species and strains and on various types of mammalian cell lines as well as in vivo studies on Drosophila melanogaster, silk worms and also the mouse specific locus test (involving long-term exposure). Together these studies convincingly show the absence of a potential for BHT to cause point mutations. A great number of studies on many cell types and species have also been carried out to examine the potential of BHT to cause chromosome aberrations. In vitro studies have been published using plant cells and the WI-38, CHL, CHO, and V79 mammalian cell lines. In vivo studies have been carried out on somatic and/or germ cells of Drosophila melanogaster, rats and mice. Nearly all studies, especially those using validated test systems, indicate that BHT lacks clastogenic potential. In vitro studies on bacterial, yeast and various mammalian cell lines including DON, CHO, CHL cells and primary hepatocytes demonstrate the absence of interactions with or damage to DNA. Taking all the existing data into account, the weight of evidence suggests that BHT does not represent a relevant mutagenic/genotoxic risk to man.
Topics: Animals; Butylated Hydroxytoluene; Chromosome Aberrations; DNA Damage; Liver Neoplasms, Experimental; Mutagenicity Tests; Mutagens; Mutation
PubMed: 1381049
DOI: 10.1016/0165-1110(92)90043-9 -
Food and Chemical Toxicology : An... 1999Butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) are widely used antioxidant food additives. They have been extensively studied for potential... (Comparative Study)
Comparative Study Review
Butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) are widely used antioxidant food additives. They have been extensively studied for potential toxicities. This review details experimental studies of genotoxicity and carcinogenicity which bear on cancer hazard assessment of exposure to humans. We conclude that BHA and BHT pose no cancer hazard and, to the contrary, may be anticarcinogenic at current levels of food additive use.
Topics: Administration, Oral; Animals; Anticarcinogenic Agents; Antioxidants; Butylated Hydroxyanisole; Butylated Hydroxytoluene; Carcinogenicity Tests; Carcinogens; Consumer Product Safety; Diet; Dose-Response Relationship, Drug; Food Additives; Methylnitronitrosoguanidine; Mutagenicity Tests
PubMed: 10541460
DOI: 10.1016/s0278-6915(99)00085-x -
European Journal of Medicinal Chemistry Aug 2015Hindered phenols find a wide variety of applications across many different industry sectors. Butylated hydroxytoluene (BHT) is a most commonly used antioxidant... (Review)
Review
Hindered phenols find a wide variety of applications across many different industry sectors. Butylated hydroxytoluene (BHT) is a most commonly used antioxidant recognized as safe for use in foods containing fats, pharmaceuticals, petroleum products, rubber and oil industries. In the past two decades, there has been growing interest in finding novel antioxidants to meet the requirements of these industries. To accelerate the antioxidant discovery process, researchers have designed and synthesized a series of BHT derivatives targeting to improve its antioxidant properties to be having a wide range of antioxidant activities markedly enhanced radical scavenging ability and other physical properties. Accordingly, some structure-activity relationships and rational design strategies for antioxidants based on BHT structure have been suggested and applied in practice. We have identified 14 very sensitive parameters, which may play a major role on the antioxidant performance of BHT. In this review, we attempt to summarize the current knowledge on this topic, which is of significance in selecting and designing novel antioxidants using a well-known antioxidant BHT as a building-block molecule. Our strategy involved investigation on understanding the chemistry behind the antioxidant activities of BHT, whether through hydrogen or electron transfer mechanism to enable promising anti-oxidant candidates to be synthesized.
Topics: Animals; Antioxidants; Butylated Hydroxytoluene; Drug Design; Humans; Molecular Structure
PubMed: 26150290
DOI: 10.1016/j.ejmech.2015.06.026 -
Methods in Cell Biology 2021Lung cancer is one of the deadliest types of cancer and as such requires disease models that are useful for identification of novel pathways for biomarkers as well as to...
Lung cancer is one of the deadliest types of cancer and as such requires disease models that are useful for identification of novel pathways for biomarkers as well as to test therapeutic agents. Adenocarcinoma (ADC), the most prevalent type of lung cancer, is a subtype of non-small cell lung carcinoma (NSCLC) and a disease driven mainly by smoking. However, it is also the most common subtype of lung cancer found in non-smokers with environmental exposures. Chemically driven models of lung cancer, also called primary models of lung cancer, are important because they do not overexpress or delete oncogenes or tumor suppressor genes, respectively, to increase oncogenesis. Instead these models test tumor development without forcing a specific pathway (i.e., Kras). The primary focus of this chapter is to discuss a well-established 2-stage mouse model of lung adenocarcinomas. The initiator (3-methylcholanthrene, MCA) does not elicit many, if any, tumors if not followed by exposure to the tumor promoter (butylated hydroxytoluene, BHT). In sensitive strains, such as A/J, FVB, and BALB, significantly greater numbers of tumors develop following the MCA/BHT protocol compared to MCA alone. BHT does not elicit tumors on its own; it is a non-genotoxic carcinogen and promoter. In these sensitive strains, promotion is also associated with inflammation characterized by infiltrating macrophages, lymphocytes, and neutrophils, and other inflammatory cell types in addition to increases in total protein content reflective of lung hyperpermeability. This 2-stage model is a useful tool to identify unique promotion specific events to then test in future intervention studies.
Topics: Animals; Butylated Hydroxytoluene; Carcinogenesis; Lung; Methylcholanthrene; Mice; Mice, Inbred BALB C
PubMed: 33785163
DOI: 10.1016/bs.mcb.2020.07.003 -
Drug and Chemical Toxicology Jul 2022Butylated hydroxyanisole (BHA) and the chemically similar butylated hydroxytoluene (BHT) are widely used as antioxidants. Toxicity of BHA and BHT has been reported under...
Butylated hydroxyanisole (BHA) and the chemically similar butylated hydroxytoluene (BHT) are widely used as antioxidants. Toxicity of BHA and BHT has been reported under in vitro and in vivo experimental conditions. However, the mechanism of BHA-induced toxic effects in cells is unclear. In this study, the cytotoxic effects of BHA and differences in cell death mechanism for BHA and BHT were investigated in rat thymocytes by flow cytometric analysis using a fluorescent probe. We observed a significant increase in propidium iodide fluorescence in the population of cells treated with 100 μM and 300 μM BHA (dead cells). Thymocytes treated with 100 µM BHA showed increased intracellular Ca2+ and Zn2+ levels and depolarized cell membranes. BHA (30-100 µM) decreased non-protein thiol content of cells, indicating decreased glutathione content. Co-stimulation with 100 µM BHA and 300 µM H2O2 acted synergistically to increase cell lethality. Moreover, BHA significantly increased caspase-3 activity and the number of annexin-V-positive cells in a concentration-dependent manner, indicating apoptosis. However, BHT reduced caspase-3 activity and increased the number of annexin-V-negative dead cells, indicating non-apoptotic cell death. Our results reveal the toxicity of BHA could be attributed to increased levels of intracellular Ca2+ and Zn2+, resulting in an increased vulnerability of rat thymocytes to oxidative stress. In addition, we demonstrate that whereas BHA induced apoptosis, BHT induced non-apoptotic cell death in rat thymocytes. Therefore, these results may support the safety of BHA, but also demonstrate the importance of performing toxicity evaluation at the cellular level besides the tissue level.
Topics: Animals; Annexins; Antioxidants; Apoptosis; Butylated Hydroxyanisole; Butylated Hydroxytoluene; Calcium; Caspase 3; Hydrogen Peroxide; Rats; Zinc
PubMed: 34013795
DOI: 10.1080/01480545.2021.1894701 -
IARC Monographs on the Evaluation of... 1986
Topics: Animals; Butylated Hydroxytoluene; Chemical Phenomena; Chemistry; Dogs; Environmental Exposure; Female; Food Preservatives; Humans; Kinetics; Lethal Dose 50; Lung; Male; Mice; Mice, Inbred BALB C; Pregnancy; Rats; Rats, Inbred F344; Rats, Inbred Strains; Reproduction
PubMed: 3473001
DOI: No ID Found -
Free Radical Biology & Medicine 1996Butylated hydroxytoluene (BHT) is a synthetic antioxidant that is widely used as an additive in foodstuffs to prevent spoiling. The physical-chemical properties of BHT...
Butylated hydroxytoluene (BHT) is a synthetic antioxidant that is widely used as an additive in foodstuffs to prevent spoiling. The physical-chemical properties of BHT and many related phenols have been examined previously although the mechanisms by which it exerts its antioxidant properties are poorly understood. The reactivity of BHT with singlet oxygen [O2(1 delta g)] and a number of radical species has been examined using the techniques of time resolved luminescence and pulse radiolysis. In benzene solution BHT reacted with O2(1 delta g) at a bimolecular rate constant of 1.3 x 10(6)M-1s-1. The one-electron oxidized, phenoxyl type BHT radical was generated using pulse radiolysis and the absorption spectrum showed a maximum at 400 nm. BHT reacts slowly with many radical species and upper limits for the bimolecular rate constant for reaction with several electron transfer processes are presented. The antioxidant role of BHT is discussed in terms of its reactivity, localization, and stability.
Topics: Antioxidants; Butylated Hydroxytoluene; Food Additives; Free Radicals; Luminescent Measurements; Oxygen; Pulse Radiolysis; Singlet Oxygen; Spectrophotometry
PubMed: 8855452
DOI: 10.1016/0891-5849(96)00050-0 -
Human & Experimental Toxicology 2023Diethylnitrosamine (DEN), a hepatocarcinogen, is found in a variety of smoked and fried foods and was reported to be hepatotoxic in mice. Butylated hydroxytoluene (BHT)...
Diethylnitrosamine (DEN), a hepatocarcinogen, is found in a variety of smoked and fried foods and was reported to be hepatotoxic in mice. Butylated hydroxytoluene (BHT) is a potent antioxidant used in cosmetic formulations and as a food additive and preservative. As a result, BHT was studied as a potential inhibitor in the early stages of diethylnitrosamine (DEN)-induced HCC. Male Wistar albino rats ( = 24) were equally subdivided. Group 1 was the negative control; Group 2 and 3 administered BHT and DEN, respectively; Group 4 received BHT followed by DEN. Blood samples and rat livers were taken for biochemical and histological investigation. Hepatotoxicity was assessed by increased liver enzymes and HCC indicators, along with reduced antioxidant and pro-apoptotic factors. AFP, AFPL3, GPC3, GSH, SOD, MDA, CASP3 and BAX expression increased significantly after DEN treatment. DEN also reduced GPx, CAT, and CYP2E1 activity, and BCl-2 expression. Moreover, in the hepatic parenchyma, the DEN caused histological alterations. Pretreatment with BHT enhanced antioxidant status while preventing histopathological and most biochemical alterations. BHT pretreatment suppresses DEN-initiated HCC by decreasing oxidative stress, triggering intrinsic mitotic apoptosis, and preventing histopathological changes in liver tissue.
Topics: Rats; Male; Animals; Mice; Carcinoma, Hepatocellular; Antioxidants; Diethylnitrosamine; Butylated Hydroxytoluene; Liver Neoplasms; Rats, Wistar; Liver
PubMed: 36943693
DOI: 10.1177/09603271231165664