title: Urinary toxicokinetics of di-(isononyl)-cyclohexane-1,2-dicarboxylate (DINCH(®)) in humans following single oral administration.
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(®)) 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 (1mg/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 24h. Besides the main metabolite cyclohexane-1,2-dicarboxylic acid (CHDA) quantitated after hydrolysis four further metabolites of DINCH(®) are determined. Cyclohexane-1,2-dicarboxylic acid-mono-(7-hydroxy-4-methyl)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 1mg/kg b.w.
authors.affiliation: Department of Chemical Safety and Toxicology, Bavarian Health and Food Safety Authority, Pfarrstrasse 3, D-80538 Munich, Germany. Electronic address: wolfgang.voelkel@lgl.bayern.de.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Völkel
authors.affiliation: Department of Chemical Safety and Toxicology, Bavarian Health and Food Safety Authority, Pfarrstrasse 3, D-80538 Munich, Germany.
authors.forename: Mandy
authors.initials: M
authors.lastname: Kiranoglu
authors.affiliation: Biochemical Institute for Environmental Carcinogens (BIU), Prof. Dr. Gernot Grimmer-Foundation, Lurup 4, D-22927 Grosshansdorf, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Dettbarn
authors.affiliation: Biochemical Institute for Environmental Carcinogens (BIU), Prof. Dr. Gernot Grimmer-Foundation, Lurup 4, D-22927 Grosshansdorf, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: John
authors.affiliation: Biochemical Institute for Environmental Carcinogens (BIU), Prof. Dr. Gernot Grimmer-Foundation, Lurup 4, D-22927 Grosshansdorf, Germany.
authors.forename: Sönke
authors.initials: S
authors.lastname: Jessel
authors.affiliation: Biochemical Institute for Environmental Carcinogens (BIU), Prof. Dr. Gernot Grimmer-Foundation, Lurup 4, D-22927 Grosshansdorf, Germany.
authors.forename: Albrecht
authors.initials: A
authors.lastname: Seidel
authors.affiliation: Department of Chemical Safety and Toxicology, Bavarian Health and Food Safety Authority, Pfarrstrasse 3, D-80538 Munich, Germany; Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Ludwig-Maximilians-University, Ziemssenstrasse 1, D-80336 Munich, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Fromme
mesh_terms: D000284:Administration, Oral; D000328:Adult; D003509:Cyclohexanecarboxylic Acids / Q000008:administration & dosage / Q000633:toxicity / Q000652:urine*; D003998:Dicarboxylic Acids / Q000008:administration & dosage / Q000633:toxicity / Q000652:urine*; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000633:toxicity / Q000652:urine*; D005260:Female; D006207:Half-Life; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D012727:Sex Characteristics
chemical_list: D003509:Cyclohexanecarboxylic Acids; D003998:Dicarboxylic Acids; D004785:Environmental Pollutants; C558012:diisononyl 1,2-cyclohexanedicarboxylic acid
keywords: Biomonitoring; DINCH(®); Exposure; Hexamoll(®); Toxicokinetic