کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8883745 | 1625906 | 2018 | 14 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Transcriptomics provides mechanistic indicators of mixture toxicology for IMX-101 and IMX-104 formulations in fathead minnows (Pimephales promelas)
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کلمات کلیدی
MOAcRNANTOHMXRDXbelow detection limitsMCsBDLFathead minnow2,4-dinitroanisole - 2،4-دینیتروانیسول3-nitro-1,2,4-triazol-5-one - 3-نیترو-1،2،4-تریازول 5-یکDNAN - DNAHexahydro-1,3,5-trinitro-1,3,5-triazine - Hexahydro-1،3،5-trinitro-1،3،5-triazinePCA - PCAcomplementary RNA - RNA مکملROS - ROSPrinciple component analysis - تجزیه و تحلیل اجزای اصلKEGG یا Kyoto Encyclopedia of Genes and Genomes - دایرة المعارف ژن ها و ژنوم کیوتو Kyoto Encyclopedia of Genes and Genomes - دایره المعارف ژنتیک ژن ها و ژنوم کیوتوDAVID - دیویدToxicogenomics - سمژنگانشناسی95% confidence interval - فاصله اطمینان 95٪Insensitive munitions - مهمات غیر حساسInsensitive Munition - مونیتور غیر حساسMechanisms of action - مکانیسم عملMechanism of action - مکانیسم عملNitroguanidine - نیتروگنادینSynergism - همکاریToxic unit - واحد سمیdatabase for annotation, visualization and integrated discovery - پایگاه داده برای حاشیه نویسی، تجسم و کشف یکپارچهReactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم کشاورزی و بیولوژیک
علوم آبزیان
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Within the US military, new insensitive munitions (IMs) are rapidly replacing conventional munitions improving safety from unintended detonation. Toxicity data for IM chemicals are expanding rapidly, however IM constituents are typically deployed in mixture formulations, and very little is known about their mixture toxicology. In the present study we sought to characterize the mixture effects and toxicology of the two predominant IM formulations IMX-101 and IMX-104 in acute (48â¯h) larval fathead minnow (Pimephales promelas) exposures. IMX-101 consists of a mixture of 2,4-dinitroanisole (DNAN), 3-nitro-1,2,4-triazol-5-one (NTO), and nitroguanidine (NQ) while IMX-104 is composed of DNAN, NTO, and hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX). DNAN was the most potent constituent in IMX-101 eliciting an LC50 of 36.1â¯mg/L, whereas NTO and NQ did not elicit significant mortality in exposures up to 1040 and 2640â¯mg/L, respectively. Toxic unit calculations indicated that IMX-101 elicited toxicity representative of the component concentration of DNAN within the mixture. Toxicogenomic responses for the individual constituents of IMX-101 indicated unique transcriptional expression and functional responses characteristic of: oxidative stress, impaired energy metabolism, tissue damage and inflammatory responses in DNAN exposures; impaired steroid biosynthesis and developmental cell-signaling in NQ exposures; and altered mitogen-activated protein kinase signaling in NTO exposures. Transcriptional responses to the IMX-101 mixture were driven by the effects of DNAN where expression and functional responses were nearly identical comparing DNAN alone versus the fractional equivalent of DNAN within IMX-101. Given that each individual constituent of the IMX-101 mixture elicited unique functional responses, and NTO and NQ did not interact with DNAN within the IMX-101 mixture exposure, the overall toxicity and toxicogenomic responses within acute exposures to the IMX-101 formulation are indicative of “independent” mixture toxicology. Alternatively, in the IMX-104 exposure both DNAN and RDX were each present at concentrations sufficient to elicit lethality (RDX LC50â¯=â¯28.9â¯mg/L). Toxic-unit calculations for IMX-104 mixture formulation exposures indicated slight synergistic toxicity (ΣTU LC50â¯=â¯0.82, 95% confidence intervalâ¯=â¯0.73-0.90). Unique functional responses relative to DNAN were observed in the IMX-104 exposure including responses characteristic of RDX exposure. Based on previous transcriptomics responses to acute RDX exposures in fathead minnow larvae, we hypothesize that the potentially synergistic responses within the IMX-104 mixture are related to interactive effects of each DNAN and RDX on oxidative stress mitigation pathways.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Aquatic Toxicology - Volume 199, June 2018, Pages 138-151
Journal: Aquatic Toxicology - Volume 199, June 2018, Pages 138-151
نویسندگان
Kurt A. Gust, Guilherme R. Lotufo, Jacob K. Stanley, Mitchell S. Wilbanks, Pornsawan Chappell, Natalie D. Barker,