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Forensic Toxicology

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Open Access 01-01-2021 | Bupropion | Original Article

In vitro and in vivo studies of triacetone triperoxide (TATP) metabolism in humans

Authors: Michelle D. Gonsalves, Kevin Colizza, James L. Smith, Jimmie C. Oxley

Published in: Forensic Toxicology | Issue 1/2021

Abstract

Purpose

Triacetone triperoxide (TATP) is a volatile but powerful explosive that appeals to terrorists due to its ease of synthesis from household items. For this reason, bomb squad, canine (K9) units, and scientists must work with this material to mitigate this threat. However, no information on the metabolism of TATP is available.

Methods

In vitro experiments using human liver microsomes and recombinant enzymes were performed on TATP and TATP-OH for metabolite identification and enzyme phenotyping. Enzyme kinetics for TATP hydroxylation were also investigated. Urine from laboratory personnel collected before and after working with TATP was analyzed for TATP and its metabolites.

Results

While experiments with flavin monooxygenases were inconclusive, those with recombinant cytochrome P450s (CYPs) strongly suggested that CYP2B6 was the principle enzyme responsible for TATP hydroxylation. TATP-O-glucuronide was also identified and incubations with recombinant uridine diphosphoglucuronosyltransferases (UGTs) indicated that UGT2B7 catalyzes this reaction. Michaelis–Menten kinetics were determined for TATP hydroxylation, with K_m = 1.4 µM and V_max = 8.7 nmol/min/nmol CYP2B6_. TATP-O-glucuronide was present in the urine of all three volunteers after being exposed to TATP vapors showing good in vivo correlation to in vitro data. TATP and TATP-OH were not observed.

Conclusions

Since scientists working to characterize and detect TATP to prevent terrorist attacks are constantly exposed to this volatile compound, attention should be paid to its metabolism. This paper is the first to elucidate some exposure, metabolism and excretion of TATP in humans and to identify a marker of TATP exposure, TATP-O-glucuronide in urine.

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Title: In vitro and in vivo studies of triacetone triperoxide (TATP) metabolism in humans
Authors: Michelle D. Gonsalves
Kevin Colizza
James L. Smith
Jimmie C. Oxley
Publication date: 01-01-2021
Publisher: Springer Singapore
Keyword: Bupropion
Published in: Forensic Toxicology / Issue 1/2021
Print ISSN: 1860-8965
Electronic ISSN: 1860-8973
DOI: https://doi.org/10.1007/s11419-020-00540-z

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

In vitro and in vivo studies of triacetone triperoxide (TATP) metabolism in humans

Abstract

Purpose

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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