Identifying Toxic Biotransformation Products of the Insensitive Munitions Compound, 2,4-Dinitroanisole (DNAN), Using Liquid Chromatography Coupled to Quadrupole Time-of-Flight Mass Spectrometry (LC-QToF-MS)

Christopher I. Olivares, Leif M Abrell, Jon Chorover, Michael Simonich, Robert L. Tanguay, Maria Reye Sierra Alvarez, James A Field

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

As insensitive munitions (IMs) replace conventional explosives, releases of 2,4-dinitronanisole (DNAN) -an IM compound- are expected to increase in the environment. DNAN is readily biotransformed in soils, and while toxicity studies have evaluated DNAN, little attention has been given to its biotransformation products. In this work, we elucidated and semiquantitated product mixtures formed during anaerobic biotransformation of DNAN using high-resolution mass spectrometry techniques. DNAN underwent nitroreduction, and at later bioconversion stages, formed azo-dimers, accounting for the majority of end-products from DNAN anaerobic biotransformation. The chemical analyses were complemented by microbial (methanogenesis and Aliivibrio fischeri bioluminescence) and zebrafish embryo toxicity assays on mixtures of products formed, as well as individual compounds (biotransformation products and model azo-oligomers). Methanogens were severely inhibited during nitroreduction stages, but recovered at longer incubation times when azo-dimers were predominant. On the other hand, A. fischeri bioluminescence decreased at later biotransformation stages. When tested individually, the most toxic products to the microbial targets were the azo-oligomer models, while the least toxic species were 2,4-diaminoanisole and its N-acetylated analog. Zebrafish embryos showed few active developmental endpoints for the individual compounds tested, but 3-nitro-4-methoxyaniline and the model azo-dimer 2,2 Œ-dimethoxy-4,4 Œ-azodianiline had a lowest observable adverse effect level (LOAEL) of 6.4 ÊM. Overall, the interdisciplinary experimental design allowed to identify key transformation processes and products that alter toxicity beyond the parent compound.

Original languageEnglish (US)
Title of host publicationAssessing Transformation Products of Chemicals by Non-Target and Suspect Screening - Strategies and Workflows, Volume 1
PublisherAmerican Chemical Society
Pages133-145
Number of pages13
Volume1241
ISBN (Electronic)9780841231931
DOIs
StatePublished - 2016

Publication series

NameACS Symposium Series
Volume1241
ISSN (Print)00976156
ISSN (Electronic)19475918

Fingerprint

Poisons
Liquid chromatography
Mass spectrometry
Dimers
Bioluminescence
Toxicity
Oligomers
Methanogens
Bioconversion
Design of experiments
Assays
Biotransformation
2,4-dinitroanisole
Soils

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)

Cite this

Olivares, C. I., Abrell, L. M., Chorover, J., Simonich, M., Tanguay, R. L., Sierra Alvarez, M. R., & Field, J. A. (2016). Identifying Toxic Biotransformation Products of the Insensitive Munitions Compound, 2,4-Dinitroanisole (DNAN), Using Liquid Chromatography Coupled to Quadrupole Time-of-Flight Mass Spectrometry (LC-QToF-MS). In Assessing Transformation Products of Chemicals by Non-Target and Suspect Screening - Strategies and Workflows, Volume 1 (Vol. 1241, pp. 133-145). (ACS Symposium Series; Vol. 1241). American Chemical Society. https://doi.org/10.1021/bk-2016-1241.ch009

Identifying Toxic Biotransformation Products of the Insensitive Munitions Compound, 2,4-Dinitroanisole (DNAN), Using Liquid Chromatography Coupled to Quadrupole Time-of-Flight Mass Spectrometry (LC-QToF-MS). / Olivares, Christopher I.; Abrell, Leif M; Chorover, Jon; Simonich, Michael; Tanguay, Robert L.; Sierra Alvarez, Maria Reye; Field, James A.

Assessing Transformation Products of Chemicals by Non-Target and Suspect Screening - Strategies and Workflows, Volume 1. Vol. 1241 American Chemical Society, 2016. p. 133-145 (ACS Symposium Series; Vol. 1241).

Research output: Chapter in Book/Report/Conference proceedingChapter

Olivares, CI, Abrell, LM, Chorover, J, Simonich, M, Tanguay, RL, Sierra Alvarez, MR & Field, JA 2016, Identifying Toxic Biotransformation Products of the Insensitive Munitions Compound, 2,4-Dinitroanisole (DNAN), Using Liquid Chromatography Coupled to Quadrupole Time-of-Flight Mass Spectrometry (LC-QToF-MS). in Assessing Transformation Products of Chemicals by Non-Target and Suspect Screening - Strategies and Workflows, Volume 1. vol. 1241, ACS Symposium Series, vol. 1241, American Chemical Society, pp. 133-145. https://doi.org/10.1021/bk-2016-1241.ch009
Olivares CI, Abrell LM, Chorover J, Simonich M, Tanguay RL, Sierra Alvarez MR et al. Identifying Toxic Biotransformation Products of the Insensitive Munitions Compound, 2,4-Dinitroanisole (DNAN), Using Liquid Chromatography Coupled to Quadrupole Time-of-Flight Mass Spectrometry (LC-QToF-MS). In Assessing Transformation Products of Chemicals by Non-Target and Suspect Screening - Strategies and Workflows, Volume 1. Vol. 1241. American Chemical Society. 2016. p. 133-145. (ACS Symposium Series). https://doi.org/10.1021/bk-2016-1241.ch009
Olivares, Christopher I. ; Abrell, Leif M ; Chorover, Jon ; Simonich, Michael ; Tanguay, Robert L. ; Sierra Alvarez, Maria Reye ; Field, James A. / Identifying Toxic Biotransformation Products of the Insensitive Munitions Compound, 2,4-Dinitroanisole (DNAN), Using Liquid Chromatography Coupled to Quadrupole Time-of-Flight Mass Spectrometry (LC-QToF-MS). Assessing Transformation Products of Chemicals by Non-Target and Suspect Screening - Strategies and Workflows, Volume 1. Vol. 1241 American Chemical Society, 2016. pp. 133-145 (ACS Symposium Series).
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abstract = "As insensitive munitions (IMs) replace conventional explosives, releases of 2,4-dinitronanisole (DNAN) -an IM compound- are expected to increase in the environment. DNAN is readily biotransformed in soils, and while toxicity studies have evaluated DNAN, little attention has been given to its biotransformation products. In this work, we elucidated and semiquantitated product mixtures formed during anaerobic biotransformation of DNAN using high-resolution mass spectrometry techniques. DNAN underwent nitroreduction, and at later bioconversion stages, formed azo-dimers, accounting for the majority of end-products from DNAN anaerobic biotransformation. The chemical analyses were complemented by microbial (methanogenesis and Aliivibrio fischeri bioluminescence) and zebrafish embryo toxicity assays on mixtures of products formed, as well as individual compounds (biotransformation products and model azo-oligomers). Methanogens were severely inhibited during nitroreduction stages, but recovered at longer incubation times when azo-dimers were predominant. On the other hand, A. fischeri bioluminescence decreased at later biotransformation stages. When tested individually, the most toxic products to the microbial targets were the azo-oligomer models, while the least toxic species were 2,4-diaminoanisole and its N-acetylated analog. Zebrafish embryos showed few active developmental endpoints for the individual compounds tested, but 3-nitro-4-methoxyaniline and the model azo-dimer 2,2 Œ-dimethoxy-4,4 Œ-azodianiline had a lowest observable adverse effect level (LOAEL) of 6.4 {\^E}M. Overall, the interdisciplinary experimental design allowed to identify key transformation processes and products that alter toxicity beyond the parent compound.",
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