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Based on in vivo toxicity studies, there is good evidence that the test substance is absorbed via the gastrointestinal tract and to a lesser extent via the skin. There is also evidence of systemic distribution to the liver in male and female rats and the testes.  The liver may be a site of metabolism and the kidneys a possible route of excretion.  In rat liver microsomes, the substance undergoes nitroreduction leading to the formation of ATO (5-amino-1,2,4-triazol-3-one), a primary amine . NTO also undergoes an oxidative denitrification, providing urazole and nitrite

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Additional information

The metabolism of NTO was investigated (Le Campion et al, 1998). 14C5- and

14C3-labelled NTO 1 were synthesized to facilitate the elucidation of its bacterial and mammalian metabolism. The metabolites

formed were characterised, and the degradative pathways compared. The Bacillus licheniformis strain was isolated from

industrial waste containing high concentrations of the explosive (15 g/L). Microbial metabolism of NTO 1 proceeded

through an oxygen-insensitive nitroreduction leading to the primary amine ATO (5-amino-1,2,4,-triazol-3-one) 2, followed

by cleavage of the triazolone ring. The maximum microbial nitroreduction occurred at pH 6 in the presence of sucrose, while

the ring cleavage occurred at pH 8. A permanent control and adjustment of the pH was required to achieve the complete

degradation of NTO by B. licheniformis. The triazolone ring resulted from the hydrolysis of the ‘pseudo guanido’ group

(R–NH–C(NH2)=N–R'). Mammalian degradation of NTO was catalysed by dexamethasone-induced murine hepatic

microsomes, and influenced by the presence of oxygen. Thus, under a nitrogen atmosphere, NTO 1 is exclusively reduced to

the amine 2. In the presence of oxygen, besides a low amount of 2, 5-hydroxy-1,2,4-triazol-3-one urazole 3 is the major

metabolite formed. This compound is obtained through an oxidative denitrification of NTO accompanied by simultaneous

formation of nitrite. Both nitroreduction and oxidative-denitrification of NTO were NADPH-dependent and totally inhibited

by carbon monoxide. These observations suggest a possible implication of cytochrome P-450, which was confirmed by

inhibition and induction experiments. No ring cleavage was observed in the microsomal metabolism of NTO.