Zebrafish embryo toxicity of anaerobic biotransformation products from the insensitive munitions compound 2,4-dinitroanisole.

TitleZebrafish embryo toxicity of anaerobic biotransformation products from the insensitive munitions compound 2,4-dinitroanisole.
Publication TypeJournal Article
Year of Publication2016
AuthorsOlivares, CI, Sierra-Alvarez, R, Abrell, L, Chorover, J, Simonich, SLMassey, Tanguay, RL, Field, JA
JournalEnviron Toxicol Chem
Date Published2016 11
KeywordsAnaerobiosis, Aniline Compounds, Animals, Anisoles, Behavior, Animal, Biotransformation, Embryo, Nonmammalian, Embryonic Development, Explosive Agents, Mass Spectrometry, Phenylenediamines, Soil, Zebrafish

2,4-Dinitroanisole (DNAN) is an emerging insensitive munitions compound that readily undergoes anaerobic nitro-group reduction to 2-methoxy-5-nitroaniline (MENA) and 2,4-diaminoanisole (DAAN), followed by formation of unique azo dimers. Currently there is little knowledge on the ecotoxicity of DNAN (bio)transformation products. In the present study, mortality, development, and behavioral effects of DNAN (bio)transformation products were assessed using zebrafish (Danio rerio) embryos. The authors tested individual products, MENA and DAAN, as well as dimer and trimer surrogates. As pure compounds, 3-nitro-4-methoxyaniline and 2,2'-dimethoxy-4,4'-azodianiline caused statistically significant effects, with lowest-observable-adverse effect levels (LOAEL) at 6.4 μM on 1 or 2 developmental endpoints, respectively. The latter had 6 additional statistically significant developmental endpoints with LOAELs of 64 μM. Based on light-to-dark swimming behavioral tests, DAAN (640 μM) caused reduction in swimming, suggestive of neurotoxicity. No statistically significant mortality occurred (≤64 μM) for any of the individual compounds. However, metabolite mixtures formed during different stages of MENA (bio)transformation in soil were characterized using high-resolution mass spectrometry in parallel with zebrafish embryo toxicity assays, which demonstrated statistically significant mortality during the onset of azo-dimer formation. Overall the results indicate that several DNAN (bio)transformation products cause different types of toxicity to zebrafish embryos. Environ Toxicol Chem 2016;35:2774-2781. © 2016 SETAC.

Alternate JournalEnviron. Toxicol. Chem.
PubMed ID27058972
PubMed Central IDPMC5052101
Grant ListP30 ES000210 / ES / NIEHS NIH HHS / United States
P42 ES004940 / ES / NIEHS NIH HHS / United States
P42 ES016465 / ES / NIEHS NIH HHS / United States