• Energy Research

The results of this study report the H 2 O 2 -driven microperoxidase-8 (MP8)-catalyzed dehalogenation of halophenols such as 4-fluorophenol, 4-chlorophenol, 4-bromophenol, and 2-fluorophenol in alcoholic solvents. In methanol, the conversion of the para-halophenols and 2-fluorophenol to, respectively, 4-methoxyphenol and 2-methoxyphenol, as the major dehalogenated products is observed. In ethanol, 4-ethoxyphenol is the principal dehalogenated product formed from 4-fluorophenol. Two mechanisms are suggested for this MP8-dependent alkoxylating dehalogenation reaction. In one of these mechanisms the oxene resonant form of compound I of MP8 is suggested to react with methanol forming a cofactor-peroxide-alkyl intermediate. This intermediate reacts with the reactive π-electrons of the substrate, leading to the formation of the alkoxyphenols and the release of the fluorine substituent as fluoride anion.

The results of this study report the H 2 O 2 -driven microperoxidase-8 (MP8)-catalyzed dehalogenation of halophenols such as 4-fluorophenol, 4-chlorophenol, 4-bromophenol, and 2-fluorophenol in alcoholic solvents. In methanol, the conversion of the para-halophenols and 2-fluorophenol to, respectively, 4-methoxyphenol and 2-methoxyphenol, as the major dehalogenated products is observed. In ethanol, 4-ethoxyphenol is the principal dehalogenated product formed from 4-fluorophenol. Two mechanisms are suggested for this MP8-dependent alkoxylating dehalogenation reaction. In one of these mechanisms the oxene resonant form of compound I of MP8 is suggested to react with methanol forming a cofactor-peroxide-alkyl intermediate. This intermediate reacts with the reactive π-electrons of the substrate, leading to the formation of the alkoxyphenols and the release of the fluorine substituent as fluoride anion.

In the present study, the cytochrome P450 mediated bioactivation of safrole to its proximate carcinogenic metabolite, 1'-hydroxysafrole, has been investigated for the purpose of identifying the human P450 enzymes involved. The 1'-hydroxylation of safrole was characterized in a variety of in vitro test systems, including Supersomes, expressing individual human P450 enzymes to a high level, and microsomes derived from cell lines expressing individual human P450 enzymes to a lower, average human liver level. Additionally, a correlation study was performed, in which safrole was incubated with a series of 15 human liver microsomes, and the 1'-hydroxylation rates obtained were correlated with the activities of these microsomes toward specific substrates for nine different isoenzymes. To complete the study, a final experiment was performed in which pooled human liver microsomes were incubated with safrole in the presence and absence of coumarin, a selective P450 2A6 substrate. On the basis of the results of these experiments, important roles for P450 2C9*1, P450 2A6, P450 2D6*1, and P450 2E1 were elucidated. The possible consequences of these results for the effects of genetic polymorphisms and life style factors on the bioactivation of safrole are discussed. Polymorphisms in P450 2C9, P450 2A6, and P450 2D6, leading to poor metabolizer phenotypes, may reduce the relative risk on the harmful effects of safrole, whereas life style factors, such as the use of alcohol, an inducer of P450 2E1, and barbiturates, inducers of P450 2C9, and polymorphisms in P450 2D6 and P450 2A6, leading to ultraextensive metabolizer phenotypes, may increase the relative risk.

In the present study, the cytochrome P450 mediated bioactivation of safrole to its proximate carcinogenic metabolite, 1'-hydroxysafrole, has been investigated for the purpose of identifying the human P450 enzymes involved. The 1'-hydroxylation of safrole was characterized in a variety of in vitro test systems, including Supersomes, expressing individual human P450 enzymes to a high level, and microsomes derived from cell lines expressing individual human P450 enzymes to a lower, average human liver level. Additionally, a correlation study was performed, in which safrole was incubated with a series of 15 human liver microsomes, and the 1'-hydroxylation rates obtained were correlated with the activities of these microsomes toward specific substrates for nine different isoenzymes. To complete the study, a final experiment was performed in which pooled human liver microsomes were incubated with safrole in the presence and absence of coumarin, a selective P450 2A6 substrate. On the basis of the results of these experiments, important roles for P450 2C9*1, P450 2A6, P450 2D6*1, and P450 2E1 were elucidated. The possible consequences of these results for the effects of genetic polymorphisms and life style factors on the bioactivation of safrole are discussed. Polymorphisms in P450 2C9, P450 2A6, and P450 2D6, leading to poor metabolizer phenotypes, may reduce the relative risk on the harmful effects of safrole, whereas life style factors, such as the use of alcohol, an inducer of P450 2E1, and barbiturates, inducers of P450 2C9, and polymorphisms in P450 2D6 and P450 2A6, leading to ultraextensive metabolizer phenotypes, may increase the relative risk.

AbstractThe world is changing at a pace, driven by global megatrends and their interactions. Megatrends, including climate change, the drive for sustainability, an aging population, urbanization, and geopolitical tensions, are producing an increasingly challenging environment for the provision of a safe and secure food supply. To ensure a robust, safe, and secure food supply for all, potential food safety impacts associated with these megatrends need to be understood, and mitigation and management plans must be implemented. This paper outlines the relevant megatrends, discusses their potential impact on food safety, and suggests steps to help ensure the production of safe food in the future. Megatrends are increasingly driving resource depletion, reducing the vitality of plants and animals, increasing the geographical spread of animal and plant pathogens, increasing the risk of mycotoxins, agrichemical residues, and antimicrobial‐resistant pathogens contaminating foods, and threatening to destabilize food systems and the food regulatory network. Science‐based actions, adopting continual and dynamic risk assessments, alongside the use of more sensitive and accurate methods for the detection of contaminants, may counter these challenges. The use of artificial intelligence, robotics and automation, the enhancement of food safety cultures, the continued education and training of workforces, and the implementation of risk‐based food regulations will help ensure preventative controls are in place. As low‐income countries and smallholder farmers are more likely to be exposed to the impact of these megatrends and less likely to have resources to counter them, geographical social inequality, unrest, and population migration are likely to be exacerbated unless urgent action is taken.

AbstractThe world is changing at a pace, driven by global megatrends and their interactions. Megatrends, including climate change, the drive for sustainability, an aging population, urbanization, and geopolitical tensions, are producing an increasingly challenging environment for the provision of a safe and secure food supply. To ensure a robust, safe, and secure food supply for all, potential food safety impacts associated with these megatrends need to be understood, and mitigation and management plans must be implemented. This paper outlines the relevant megatrends, discusses their potential impact on food safety, and suggests steps to help ensure the production of safe food in the future. Megatrends are increasingly driving resource depletion, reducing the vitality of plants and animals, increasing the geographical spread of animal and plant pathogens, increasing the risk of mycotoxins, agrichemical residues, and antimicrobial‐resistant pathogens contaminating foods, and threatening to destabilize food systems and the food regulatory network. Science‐based actions, adopting continual and dynamic risk assessments, alongside the use of more sensitive and accurate methods for the detection of contaminants, may counter these challenges. The use of artificial intelligence, robotics and automation, the enhancement of food safety cultures, the continued education and training of workforces, and the implementation of risk‐based food regulations will help ensure preventative controls are in place. As low‐income countries and smallholder farmers are more likely to be exposed to the impact of these megatrends and less likely to have resources to counter them, geographical social inequality, unrest, and population migration are likely to be exacerbated unless urgent action is taken.