1.Quantification of biomarkers of environmental exposure to di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH) in urine via HPLC-MS/MS.
Schütze A1, Pälmke C, Angerer J, Weiss T, Brüning T, Koch HM. J Chromatogr B Analyt Technol Biomed Life Sci. 2012 May 1;895-896:123-30. doi: 10.1016/j.jchromb.2012.03.030. Epub 2012 Mar 28.
Di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH) is a major substitute for some high molecular weight phthalates that adversely affect reproductive function. Like for the phthalates a broad exposure of the population has to be expected. We postulated the DINCH monoester (MINCH) and secondary oxidized metabolites (OH-MINCH, cx-MINCH and oxo-MINCH) as human metabolites and possible biomarkers of DINCH exposure. We developed an on-line HPLC-MS/MS method for their determination in human urine. Identification was performed with authentic standard substances and quantification via isotope dilution. The analytical method is highly selective and sensitive with limits of quantification (LOQ) between 0.05 μg/l and 0.1 μg/l. In a pilot study with 22 volunteers from the general German population oxidized DINCH metabolites were found in above 80% of the samples. OH-MINCH was most abundant (mean 0.71 μg/l; maximum 3.69 μg/l) followed by cx-MINCH (0.61 μg/l; 2.
2.Biomonitoring of phthalate metabolites in the Canadian population through the Canadian Health Measures Survey (2007-2009).
Saravanabhavan G1, Guay M, Langlois É, Giroux S, Murray J, Haines D. Int J Hyg Environ Health. 2013 Nov;216(6):652-61. doi: 10.1016/j.ijheh.2012.12.009. Epub 2013 Feb 16.
Human exposure to phthalates occurs through multiple sources and pathways. In the Canadian Health Measures Survey 2007-2009, 11 phthalate metabolites, namely, MMP, MEP, MnBP, MBzP, MCHP, MCPP, MEHP, MEOHP, MEHHP, MnOP, and MiNP were measured in urine samples of 6-49 year old survey respondents (n=3236). The phthalate metabolites biomonitoring data from this nationally-representative Canadian survey are presented here. The metabolites MEP, MnBP, MBzP, MCPP, MEHP, MEOHP and MEHHP were detected in >90% of Canadians while MMP, MCHP, MnOP and MiNP were detected in <20% of the Canadian population. Step-wise regression analyses were carried out to identify important predictors of volumetric concentrations (μg/L) of the metabolites in the general population. Individual multiple regression models with covariates age, sex, creatinine, fasting status, and the interaction terms age×creatinine, age×sex and fasting status×creatinine were constructed for MEP, MnBP, MBzP, MCPP, MEHP, MEOHP and MEHHP.
3.Development of a multi-compartment pharmacokinetic model to characterize the exposure to Hexamoll® DINCH®.
Schütze A1, Lorber M2, Gawrych K1, Kolossa-Gehring M3, Apel P3, Brüning T1, Koch HM4. Chemosphere. 2015 Jun;128:216-24. doi: 10.1016/j.chemosphere.2015.01.056. Epub 2015 Feb 21.
We developed and calibrated a multi compartment pharmacokinetic (PK) model to predict urinary concentrations after oral exposure of four specific DINCH metabolites: MINCH, OH-MINCH, cx-MINCH, and oxo-MINCH. This descriptive model has 4 compartments: a "stomach" (SC) compartment, a "holding" (HC) compartment, a "blood" (BC) compartment and a "bladder" (BLC) compartment. DINCH is assumed to first deposit into the SC, with transfer split between the HC and the BC. Unmetabolized DINCH from the HC then transfers to the BC. The DINCH metabolism is assumed to occur in the BC before excretion via the BLC. At each urination event, all the metabolite mass in the BLC is excreted. The model was calibrated using published urine metabolite data from 3 different male volunteers, each orally dosed with 50mg DINCH. Full urine voids were taken for 48 h after dosage. The predicted values showed a good agreement with the observed urinary DINCH metabolite concentrations, with a Spearman correlation coefficient exceeding 0.
4.Entering markets and bodies: increasing levels of the novel plasticizer Hexamoll® DINCH® in 24 h urine samples from the German Environmental Specimen Bank.
Schütze A1, Kolossa-Gehring M2, Apel P2, Brüning T1, Koch HM3. Int J Hyg Environ Health. 2014 Mar;217(2-3):421-6. doi: 10.1016/j.ijheh.2013.08.004. Epub 2013 Aug 16.
DINCH (diisononylcyclohexane-1,2-dicarboxylate) was introduced into the world market in 2002 as a non-aromatic plasticizer and phthalate substitute. We analyzed 300 urine samples (24 h voids) of the German Environmental Specimen Bank (ESB for Human tissues, ESB Hum) for specific DINCH metabolites by on-line HPLC-MS/MS with isotope dilution quantification. Urine samples of the ESB Hum were from the years 1999, 2003, 2006, 2009 and 2012, chosen to investigate the appearance and a possible trend of DINCH exposure since its market introduction. No DINCH metabolites were detected in the 1999 and 2003 samples. From 2006 on, the percentage of samples with DINCH metabolites above the LOQ increased significantly over the years (7% in 2006, 43% in 2009 and 98% in 2012). The cyclohexane-1,2-dicarboxylic acid-mono(hydroxy-isononyl) ester (OH-MINCH) was the predominant metabolite. Median (and 95th percentile) concentrations (in μg/l) increased from <LOQ (0.