title: The role of metabolism in the toxicity of 2,4,6-trinitrotoluene and its degradation products to the aquatic amphipod Hyalella azteca.
abstract: Toxicological data on the effects of the explosive, 2,4,6-trinitrotoluene (TNT), and its degradation products suggests an unpredictable toxicological response in aquatic organisms. Several studies suggest TNT becomes more toxic as it degrades while others suggest TNT becomes less toxic. This study focused on the toxicity of TNT and several degradation products as well as the role of oxidative metabolism in the toxicity of TNT. The aquatic invertebrate Hyalella azteca was used to evaluate the toxicity of TNT and four of its degradation products. The most reduced degradation product, 2,4-diamino, 6-nitrotoluene (2,4-DANT) was the most toxic to H. azteca. However, 2,4-DANT was only a minor metabolite in H. azteca. The influence of metabolism on the toxicokinetics of TNT was assessed indirectly through the use of a CYP450 inducer and inhibitor. Treatment of organisms with beta-napthoflavone (BNF), a CYP450 inducer, increased the toxicity of TNT and increased the rate of elimination and metabolism of TNT. Similar to BNF, organisms treated with clotrimazole (CTZ), a CYP450 inhibitor, resulted in increased toxicity and TNT metabolism. It is likely the ability to metabolize or bioactivate TNT to a more reactive intermediate plays a significant role in the sensitivity of organisms to TNT.
authors.affiliation: US Army Engineer Research and Development Center, 3909 Halls Ferry Road, Vicksburg, MS 39180, USA. jerre.g.sims@erdc.usace.army.mil
authors.forename: Jerre G
authors.initials: JG
authors.lastname: Sims
authors.forename: Jeffery A
authors.initials: JA
authors.lastname: Steevens
mesh_terms: D033304:Amphipoda / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001555:Benzene Derivatives / Q000493:pharmacokinetics / Q000633:toxicity*; D003022:Clotrimazole / Q000494:pharmacology; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D053834:Explosive Agents / Q000493:pharmacokinetics / Q000633:toxicity*; D014874:Water Pollutants, Chemical / Q000493:pharmacokinetics / Q000633:toxicity*; D019324:beta-Naphthoflavone / Q000494:pharmacology
chemical_list: D001555:Benzene Derivatives; D065607:Cytochrome P-450 Enzyme Inhibitors; D053834:Explosive Agents; D014874:Water Pollutants, Chemical; D019324:beta-Naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D003022:Clotrimazole