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

Völkel, Wolfgang; Kiranoglu, Mandy; Dettbarn, G.; John, Andrea; Jessel, Sönke; Seidel, Albrecht; Fromme, Hermann

doi:10.1016/j.toxlet.2016.02.010

Cited by 16 publications

(8 citation statements)

References 27 publications

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“…The alkyl side chain of this monoester is further oxidized to the cyclohexane-1,2-dicarboxylic acid-mono(hydroxyl-iso-nonyl) ester (OH-MINCH), the cyclohexane-1,2-dicarboxylic acid-mono(carboxy-iso-octyl) ester (cx-MINCH) and the cyclohexane-1,2-dicarboxylic acid-mono(oxo-iso-nonyl) ester (oxo-MINCH). These oxidized metabolites are the major DINCH metabolites excreted in urine and currently used for human-biomonitoring (HBM) purposes (Koch et al, 2013a;Schütze et al, 2015;Völkel et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Exposure of Portuguese children to the novel non-phthalate plasticizer di-(iso-nonyl)-cyclohexane-1,2-dicarboxylate (DINCH)

Correia-Sá

Schütze

Norberto

et al. 2017

Environment International

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Di-(iso-nonyl)-cyclohexane-1,2-dicarboxylate (DINCH) is used as substitute for high molecular weight phthalate plasticizers such as di-(2-ethylhexyl) phthalate (DEHP) and di-(iso-nonyl) phthalate (DINP). Due to a rapid substitution process we have to assume omnipresent and increasing DINCH exposures. The aim of this study was to evaluate DINCH exposure in 112 children (4-18years old) from Portugal, divided in two groups: 1) normal-/underweight following the usual diet; and 2) obese/overweight but under strict nutritional guidance. First morning urine samples were collected during the years 2014 and 2015. Oxidized DINCH metabolites (OH-MINCH, oxo-MINCH, cx-MINCH) were analyzed after enzymatic hydrolysis via on-line HPLC-MS/MS with isotope dilution quantification. We detected DINCH metabolites in all analyzed samples. Urinary median (95th percentile) concentrations were 2.14μg/L (15.91) for OH-MINCH, followed by 1.10μg/L (7.54) for oxo-MINCH and 1.08μg/L (7.33) for cx-MINCH. We observed no significant differences between the two child-groups; only after creatinine adjustment, we found higher metabolite concentrations in the younger compared to the older children. Median (95th percentile) daily DINCH intakes were in the range of 0.37 to 0.76 (2.52 to 5.61) μg/kg body weight/day depending on calculation model and subpopulation. Body weight related daily intakes were somewhat higher in Group 1 compared to Group 2, irrespective of the calculation model. However, in terms of absolute amounts (μg/day), DINCH intakes were higher in Group 2 compared to Group 1. In regard to age, we calculated higher intakes for the younger children compared to older children, but only with the creatinine-based model. This new data for southern European, Portuguese children adds information to the scarce knowledge on DINCH, confirming omnipresent exposure and suggesting higher exposures in children than adults. Significant sources and routes of exposure have yet to be unveiled. For now, all calculated daily intakes are far below established health benchmark levels (TDI, RfD). However, rapidly increasing exposures have to be expected over the next years.

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Section: Introductionmentioning

confidence: 99%

Exposure of Portuguese children to the novel non-phthalate plasticizer di-(iso-nonyl)-cyclohexane-1,2-dicarboxylate (DINCH)

Correia-Sá

Schütze

Norberto

et al. 2017

Environment International

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“…Cyclohexane-1,2-dicarboxylic acid is a major, but non-specific metabolite, while only 2 % or less is excreted as a simple monoester (monoisononyl-cyclohexane-1,2-dicarboxylate; MINCH). Other metabolites, formed by oxidation, are more promising as DINCH biomarkers, especially cyclohexane-1,2-dicarboxylate-mono-(7-hydroxy-4-methyl) octyl ester (OH-MINCH), with the average excretion rate of 10.7 % and 14.5 %, depending on the study, followed by cyclohexane-1,2-dicarboxylic mono oxoisononyl ester and cyclohexane-1,2-diarboxylic mono carboxyisononyl ester [ 81 , 82 ]. These metabolites were detected in the urine samples [ 82 , 83 ], however their distribution did not fully reflect the human excretion profiles.…”

Section: Identification Of Potential Wbe Biomarkers Of Human Exposurementioning

confidence: 99%

“…Other metabolites, formed by oxidation, are more promising as DINCH biomarkers, especially cyclohexane-1,2-dicarboxylate-mono-(7-hydroxy-4-methyl) octyl ester (OH-MINCH), with the average excretion rate of 10.7 % and 14.5 %, depending on the study, followed by cyclohexane-1,2-dicarboxylic mono oxoisononyl ester and cyclohexane-1,2-diarboxylic mono carboxyisononyl ester [ 81 , 82 ]. These metabolites were detected in the urine samples [ 82 , 83 ], however their distribution did not fully reflect the human excretion profiles. The authors of one of the studies pointed out that back-calculation from individual spot urine samples is likely unreliable to determine individual exposure, but could be used on a population scale [ 82 ].…”

Section: Identification Of Potential Wbe Biomarkers Of Human Exposurementioning

confidence: 99%

“…These metabolites were detected in the urine samples [ 82 , 83 ], however their distribution did not fully reflect the human excretion profiles. The authors of one of the studies pointed out that back-calculation from individual spot urine samples is likely unreliable to determine individual exposure, but could be used on a population scale [ 82 ]. In another study, the detection frequency of OH-MINCH was much lower (8 %), even below the detection frequency of MINCH (17 %) [ 78 ].…”

Section: Identification Of Potential Wbe Biomarkers Of Human Exposurementioning

confidence: 99%

“… Compound Biomarker Excretion rate (%) a Ref. Di-2-ethylhexyl adipate (DEHA) Mono-2-ethylhexyl adipate (MEHA) NA [ 76 ] b Mono-5-carboxy-2-ethylpentyl adipate (5cx-MEPA) 0.20 (0.17–0.24) [ 33 ] c Mono-2-ethylhydroxyhexyl adipate (5OH-MEHA) 0.07 (0.03–0.10) Mono-(2-ethyl-5-oxohexyl) adipate (5oxo-MEHA) 0.05 (0.01–0.06) Di(2-ethylhexyl) terephthalate (DEHTP) 1-Mono-(2-ethyl-5-carboxyl-pentyl) terephtahalate (5cx-MEPTP) 13.0 (7.0–20.4) [ 79 ] d 1-Mono-(2-ethyl-5-hydroxy-hexyl) terephtahalate (5OH-MEHTP) 1.8 (1.3–2.4) 1-Mono-(2-ethyl-5-oxo-hexyl) terephtahalate (5oxo-MEHTP) 1.0 (0.57–1.6) 1-Mono-(2-carboxyl-methyl-hexyl) terephtahalate (2cx-MEHTP) 0.28 (0.17–0.42) Di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH) Cyclohexane-1,2-dicarboxylate-mono-(7-hydroxy-4-methyl) octyl ester (OH-MINCH) 10.7 (7.7–12.9) [ 81 ] d 14.5 (9.2–17.6) [ 82 ] e Cyclohexane-1,2-dicarboxylic mono oxoisononyl ester (oxo-MINCH) 2.0 (1.5–2.6) [ 81 ] d 4.8 (2.9−7.5) [ 82 ] e Cyclohexane-1,2-diarboxylic mono carboxyisononyl ester (cx-MINCH) 2.0 (1.8–2.3) [ 81 ] ...…”

Section: Identification Of Potential Wbe Biomarkers Of Human Exposurementioning

confidence: 99%

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Wastewater-based epidemiology to assess human exposure to personal care and household products – A review of biomarkers, analytical methods, and applications

Senta

Rodríguez-Mozaz

Corominas

et al. 2020

Trends in Environmental Analytical Chemistry

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Humans are nowadays exposed to numerous chemicals in our day-to-day life, including parabens, UV filters, phosphorous flame retardants/plasticizers, bisphenols, phthalates and alternative plasticizers, which can have different adverse effects to human health. Estimating human’s exposure to these potentially harmful substances is, therefore, of paramount importance. Human biomonitoring (HBM) is the existing approach to assess exposure to environmental contaminants, which relies on the analysis of specific human biomarkers (parent compounds and/or their metabolic products) in biological matrices from individuals. The main drawback is its implementation, which involves complex cohort studies. A novel approach, wastewater-based epidemiology (WBE), involves estimating exposure from the analysis of biomarkers in sewage (a pooled urine and feces sample of an entire population). One of the key challenges of WBE is the selection of biomarkers which are specific to human metabolism, excreted in sufficient amounts, and stable in sewage. So far, literature data on potential biomarkers for estimating exposure to these chemicals are scattered over numerous pharmacokinetic and HBM studies. Hence, this review provides a list of potential biomarkers of exposure to more than 30 widely used chemicals and report on their urinary excretion rates. Furthermore, the potential and challenges of WBE in this particular field is discussed through the review of pioneer WBE studies, which for the first time explored applicability of this novel approach to assess human exposure to environmental contaminants. In the future, WBE could be potentially applied as an “early warning system”, which could promptly identify communities with the highest exposure to environmental contaminants.

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Hexamoll® DINCH , A Non‐phthalate Plasticizer by BASF (Case Study)

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Grimm

et al. 2023

Industrial Arene Chemistry

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

Cited by 16 publications

References 27 publications

Exposure of Portuguese children to the novel non-phthalate plasticizer di-(iso-nonyl)-cyclohexane-1,2-dicarboxylate (DINCH)

Exposure of Portuguese children to the novel non-phthalate plasticizer di-(iso-nonyl)-cyclohexane-1,2-dicarboxylate (DINCH)

Wastewater-based epidemiology to assess human exposure to personal care and household products – A review of biomarkers, analytical methods, and applications

Hexamoll® DINCH , A Non‐phthalate Plasticizer by BASF (Case Study)

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