DNT (2,4-dinitrotoluene), a volatile impurity in military-grade 2,4,6-trinitrotoluene (TNT)-based explosives, is a potential tracer for the detection of buried landmines and other explosive devices. We have previously described an Escherichia coli bioreporter strain engineered to detect traces of DNT and have demonstrated that the yqjF gene promoter, the sensing element of this bioreporter, is induced not by DNT but by at least one of its transformation products. In the present study, we have characterized the initial stages of DNT biotransformation in E. coli, have identified the key metabolic products in this reductive pathway, and demonstrate that the main DNT metabolite that induces yqjF is 2,4,5-trihydroxytoluene. We further show that E. coli cannot utilize DNT as a sole carbon or nitrogen source and propose that this compound is metabolized in order to neutralize its toxicity to the cells.
In: Carvalho , R N , Arukwe , A , Ait-Aissa , S , Bado-Nilles , A , Balzamo , S , Baun , A , Belkin , S , Blaha , L , Brion , F , Conti , D , Creusot , N , Essig , Y , Ferrero , V E V , Flander-Putrle , V , Fürhacker , M , Grillari-Voglauer , R , Hogstrand , C , Jonáš , A , Kharlyngdoh , J B , Loos , R , Lundebye , A-K , Modig , C , Olsson , P-E , Pillai , S , Polak , N , Potalivo , M , Sanchez , W , Schifferli , A , Schirmer , K , Sforzini , S , Stürzenbaum , S R , Søfteland , L , Turk , V , Viarengo , A , Werner , I , Yagur-Kroll , S , Zounková , R & Lettieri , T 2014 , ' Mixtures of chemical pollutants at European legislation safety concentrations: how safe are they? ' , Toxicological Sciences , vol. 141 , no. 1 , pp. 218-233 . https://doi.org/10.1093/toxsci/kfu118
The risk posed by complex chemical mixtures in the environment to wildlife and humans is increasingly debated, but has been rarely tested under environmentally relevant scenarios. To address this issue, two mixtures of 14 or 19 substances of concern (pesticides, pharmaceuticals, heavy metals, polyaromatic hydrocarbons, a surfactant, and a plasticizer), each present at its safety limit concentration imposed by the European legislation, were prepared and tested for their toxic effects. The effects of the mixtures were assessed in 35 bioassays, based on 11 organisms representing different trophic levels. A consortium of 16 laboratories was involved in performing the bioassays. The mixtures elicited quantifiable toxic effects on some of the test systems employed, including i) changes in marine microbial composition, ii) microalgae toxicity, iii) immobilization in the crustacean Daphnia magna, iv) fish embryo toxicity, v) impaired frog embryo development, and vi) increased expression on oxidative stress-linked reporter genes. Estrogenic activity close to regulatory safety limit concentrations was uncovered by receptor-binding assays. The results highlight the need of precautionary actions on the assessment of chemical mixtures even in cases where individual toxicants are present at seemingly harmless concentrations.
The risk posed by complex chemical mixtures in the environment to wildlife and humans is increasingly debated, but has been rarely tested under environmentally relevant scenarios. To address this issue, two mixtures of 14 or 19 substances of concern (pesticides, pharmaceuticals, heavy metals, polyaromatic hydrocarbons, a surfactant, and a plasticizer), each present at its safety limit concentration imposed by the European legislation, were prepared and tested for their toxic effects. The effects of the mixtures were assessed in 35 bioassays, based on 11 organisms representing different trophic levels. A consortium of 16 laboratories was involved in performing the bioassays. The mixtures elicited quantifiable toxic effects on some of the test systems employed, including i) changes in marine microbial composition, ii) microalgae toxicity, iii) immobilization in the crustacean Daphnia magna, iv) fish embryo toxicity, v) impaired frog embryo development, and vi) increased expression on oxidative stress-linked reporter genes. Estrogenic activity close to regulatory safety limit concentrations was uncovered by receptor-binding assays. The results highlight the need of precautionary actions on the assessment of chemical mixtures even in cases where individual toxicants are present at seemingly harmless concentrations.
In: Carvalho , R N , Arukwe , A , Ait-Aissa , S , Bado-Nilles , A , Balzamo , S , Baun , A , Belkin , S , Blaha , L , Brion , F , Conti , D , Creusot , N , Essig , Y , Ferrero , V E V , Flander-Putrle , V , Fürhacker , M , Grillari-Voglauer , R , Hogstrand , C , Jonáš , A , Loos , R , Lundebye , A-K , Modig , C , Olsson , P-E , Pillai , S , Polak , N , Potalivo , M , Sanchez , W , Schifferli , A , Schirmer , K , Sforzini , S , Stürzenbaum , S R , Søfteland , L , Turk , V , Viarengo , A , Werner , I , Yagur-Kroll , S , Zounková , R & Lettieri , T 2014 , ' Mixtures of Chemical Pollutants at European Legislation Safety Concentrations : How Safe are They? ' Toxicological sciences : an official journal of the Society of Toxicology , vol 14 , no. 1 , pp. 218-233 . DOI:10.1093/toxsci/kfu118
The risk posed by complex chemical mixtures in the environment to wildlife and humans is increasingly debated, but has been rarely tested under environmentally relevant scenarios. To address this issue, two mixtures of 14 or 19 substances of concern (pesticides, pharmaceuticals, heavy metals, polyaromatic hydrocarbons, a surfactant and a plasticizer), each present at its safety limit concentration imposed by the European legislation, were prepared and tested for their toxic effects. The effects of the mixtures were assessed in 35 bioassays, based on eleven organisms representing different trophic levels. A consortium of 16 laboratories was involved in performing the bioassays. The mixtures elicited quantifiable toxic effects on some of the test systems employed, including i) changes in marine microbial composition, ii) microalgae toxicity iii) immobilization in the crustacean Daphnia magna, iii) fish embryo toxicity, iv) impaired frog embryo development and v) increased expression on oxidative stress-linked reporter genes. Estrogenic activity close to regulatory safety limit concentrations was uncovered by receptor-binding assays. The results highlight the need of precautionary actions on the assessment of chemical mixtures even in cases where individual toxicants are present at seemingly harmless concentrations.