Transplacental transfer and metabolism of diuron in human placenta. (1st October 2018)

• Record Type: Journal Article
• Authors: Mohammed, Ali Mustafa; Karttunen, Vesa; Huuskonen, Pasi; Huovinen, Marjo; Auriola, Seppo; Vähäkangas, Kirsi
• Is Part Of: Toxicology letters. Volume 295(2018)
• Page Start: 307
• Page End: 313
• Publication Date: 2018-10-01
• Subjects: Diuron -- Placental perfusion -- Placental kinetics -- Xenobiotic metabolism -- In vitro -- CYP1A1; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2018.07.012
• Languages: English
• ISSNs: 0378-4274

Abstract

Highlights: Diuron crosses human placenta with ease suggesting fetal exposure and hence fetotoxicity. Diuron is metabolized into a toxic metabolite in human placenta from smokers. Diuron is also metabolized in human placenta from non-smokers but only in high doses. CYP1A1 is responsible for the metabolism of diuron in human placenta. Abstract: Diuron is a broad-spectrum phenylurea derived herbicide which is commonly used across the globe. Diuron is toxic to the reproductive system of animals and carcinogenic to rat urothelium, and recently found to be genotoxic in human cells. In in vivo, it is metabolized predominately into 3-(3, 4-dichlorophenyl)-1-methyl urea (DCPMU) in humans and 3-(3, 4-dichlorophenyl)urea (DCPU) in animals. Information on diuron toxicokinetics and related toxicity in human placenta is absent. We have investigated the toxicokinetics of diuron in ex vivo human placental perfusion and in in vitro human placental microsomes and human trophoblastic cancer cells (BeWo). Diuron crossed human placenta readily in placental perfusion. Furthermore, diuron was metabolized into DCPMU in perfused placenta and in in vitro incubations using microsomes from placentas of smokers. In incubations with placental microsomes from non-smokers, and in BeWo cells, metabolism to DCPMU was detected but only with the highest used diuron concentration (100 μM). Diuron metabolism was inhibited upon addition of α-naphthoflavone, a CYP1A1 inhibitor, underscoring the role of CYP1A1 in the metabolism. In conclusion, it is evident that diuron crosses human placenta and diuron can be metabolized in the placenta to a toxic metabolite via CYP1A1. This implicates in vivo fetal exposure to diuron if pregnant women are exposed to diuron, which may result in fetotoxicity.