Urine tropenol ester levels in workers handling tiotropium bromide synthesis: implications for exposure prevention and biomonitoring
| Autor: | Bernd Roßbach, Axel Muttray, Michael Schneider |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Adult
Male medicine.drug_class Production cycle Anticholinergic agents Urine Pharmacology Toxicology Cholinergic Antagonists Young Adult 03 medical and health sciences 0302 clinical medicine Occupational Exposure Bronchodilator Biomonitoring Anticholinergic medicine Humans 030212 general & internal medicine Tiotropium Bromide business.industry analiza radnog mjesta antikolinergici međuproizvodi prevencija skopin ester Public Health Environmental and Occupational Health anticholinergic agents intermediates prevention scopine ester workplace analysis Tiotropium bromide 030210 environmental & occupational health Acute toxicity business Biological Monitoring Environmental Monitoring medicine.drug |
| Zdroj: | Arhiv za higijenu rada i toksikologiju Volume 70 Issue 2 |
| ISSN: | 0004-1254 1848-6312 |
| DOI: | 10.2478/aiht-2019-70-3206 |
| Popis: | Tropenol ester is a highly toxic anticholinergic substance and an intermediate used in industrial production of the bronchodilator tiotropium bromide. The aim of this study was to systematically test workers involved in its production for tropenol ester in urine to identify any exposure pathways and define additional preventive measures. Twelve workers performing tasks involving potential exposure to tropenol ester were repeatedly monitored at the end of each production cycle. Medical exams revealed no symptoms of acute poisoning with tropenol ester, but biological monitoring of urine showed 36 positive findings in 79 samples, with tropenol ester concentrations ranging between the detection limit of 54 pg/mL and 2160 pg/mL. We managed to establish the cause of only one positive finding, which was a hole in a protective glove, whereas the rest most likely occurred due to human error. Because of this, the plant decided to modify the production process by replacing tropenol ester with a safer intermediate. While it is the safest course of action, there where it cannot be taken, biological monitoring can be very helpful in raising awareness about exposure to toxic substances, including the new ones that have not been studied for their adverse potential. Tropenol ester je iznimno toksičan antikolinergik, koji se rabi za sintezu bronhodilatatora tiotropijeva bromida. Cilj je ovog ispitivanja bio sustavno testirati radnike koji njime barataju u proizvodnji na tropenol ester u mokraći ne bi li se ustanovili putevi izloženosti i poboljšale preventivne mjere. Ispitivanje je obuhvatilo 12 radnika kroz 12 proizvodnih ciklusa, a uzorkovanje se provodilo na kraju svakog ciklusa. Liječničkim se pregledom nisu otkrili nikakvi simptomi akutnog otrovanja tropenol esterom, ali se biomonitoringom otkrilo 36 pozitivnih uzoraka od njih 79. Razine tropenol estera u pozitivnim uzorcima kretale su se od granice detekcije (54 pg/mL) do 2160 pg/mL. Međutim, samo smo za jedan pozitivan nalaz uspjeli utvrditi uzrok. Radilo se o rupi u zaštitnoj rukavici. Za ostale pozitivne uzorke pretpostavljamo da upućuju na ljudsku pogrešku prilikom skidanja ili čišćenja opreme. Zbog nemogućnosti da utvrdimo uzroke izloženosti, tvornica je promijenila proizvodni proces i tropenol ester zamijenila sigurnijim međuproizvodom. Iako je to najsigurniji način za sprječavanje izloženosti opasnim tvarima u proizvodnji, tamo gdje to nije moguće, biomonitoring može biti itekako koristan za podizanje svijesti o izloženosti, osobito kod novih tvari čije štetno djelovanje za zdravlje još nije istraženo. |
| Databáze: | OpenAIRE |
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