Urinary toxicokinetics of di-(isononyl)-cyclohexane-1,2-dicarboxylate (DINCH (R)) in humans following single oral administration

Völkel, Wolfgang; Kiranoglu, Mandy; Dettbarn, Gerhard; John, Andrea; Jessel, Sönke; Seidel, Albrecht und Fromme, Hermann (2016): Urinary toxicokinetics of di-(isononyl)-cyclohexane-1,2-dicarboxylate (DINCH (R)) in humans following single oral administration. In: Toxicology Letters, Bd. 248: S. 16-24

Abstract

Phthalates such as di-2-ethylhexyl phthalate (DEHP) were restricted due to their toxic mainly reprotoxic effects. Therefore compounds such as di-(isononyl)-cyclohexane-1,2-dicarboxylate (DINCH (R)) substitute these phthalates and the exposure of humanes to substitutes may occur. Here, kinetic data are presented to assess the exposure of humans. Male and female volunteers excreted nearly the complete orally administered dose (1 mg/kg b. w. corresponding to the tolerable daily intake of EFSA) of di-(isononyl)cyclohexane-1,2-dicarboxylate within 70 h. More than 75% were excreted within 24 h. Besides the main metabolite cyclohexane-1,2-dicarboxylic acid (CHDA) quantitated after hydrolysis four further metabolites of DINCH (R) are determined. Cyclohexane-1,2-dicarboxylic acid-mono-(7-hydroxy-4methyl) octyl ester (OH-MINCH) is the main secondary metabolite with about 14% of the administered dose. Differences in excretion of all metabolites between male and females are small. Based on the generated toxicokinetic data exposure of 20 humans is recalculated from their spot urine sample collected in 2014 and the exposure are clearly below the current tolerable daily intake of 1 mg/kg b. w. (C) 2016 Published by ELSEVIER.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin ; Medizin > Institut und Poliklinik für Arbeits-, Sozial- und Umweltmedizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0378-4274
• Sprache: Englisch