Schütze André, Kolossa-Gehring Marike, Apel Petra, Brüning Thomas, Koch Holger M
Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-Universität Bochum (IPA), Bürkle-de-la-Camp-Platz 1, 44789 Bochum, Germany.
Federal Environment Agency (UBA), Corrensplatz 1, 14195 Berlin, Germany.
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 (0.09) in 2006, to <LOQ (1.02) in 2009 to 0.39 (2.09) in 2012. All oxidized DINCH metabolites (OH-MINCH, cx-MINCH, oxo-MINCH) correlated strongly among each other (ρ>0.75, p<0.001). The median (95th percentile) DINCH intake in 2012 was calculated to be 0.14 (1.07)μg/kg body weight/day which is considerably below daily intakes currently deemed tolerable. DINCH is regarded to have a preferred toxicological profile over certain anti-androgenic phthalates. The continuation of DINCH measurements in the ESB Hum and other human biomonitoring studies like the German Environmental Survey (GerES) allows tracking the development of DINCH body burdens, the distribution of exposure levels and daily intakes, providing basic data for future toxicological assessment and further epidemiological studies.
二异壬基环己烷 - 1,2 - 二羧酸酯（DINCH）于2002年作为一种非芳香族增塑剂和邻苯二甲酸酯替代品进入世界市场。我们采用在线高效液相色谱 - 串联质谱法（HPLC - MS/MS）结合同位素稀释定量分析了德国环境样本库（人体组织环境样本库，ESB Hum）的300份尿液样本（24小时尿量）中的特定DINCH代谢物。ESB Hum的尿液样本采集于1999年、2003年、2006年、2009年和2012年，旨在研究DINCH自进入市场以来的暴露情况及其可能的趋势。在1999年和2003年的样本中未检测到DINCH代谢物。从2006年起，DINCH代谢物含量高于定量限（LOQ）的样本百分比逐年显著增加（2006年为7%，2009年为43%，2012年为98%）。环己烷 - 1,2 - 二羧酸单（羟基异壬基）酯（OH - MINCH）是主要代谢物。中位数（及第95百分位数）浓度（μg/l）从2006年的<LOQ（0.09）增加到2009年的<LOQ（1.02），再到2012年的0.39（2.09）。所有氧化的DINCH代谢物（OH - MINCH、cx - MINCH、oxo - MINCH）之间都具有很强的相关性（ρ>0.75，p<0.001）。2012年DINCH的中位数（第95百分位数）摄入量经计算为0.14（1.07）μg/kg体重/天，远低于目前认为可耐受的每日摄入量。与某些具有抗雄激素作用的邻苯二甲酸酯相比，DINCH被认为具有更优的毒理学特性。在ESB Hum中持续进行DINCH测量以及开展其他人体生物监测研究，如德国环境调查（GerES），有助于追踪DINCH体内负荷的变化、暴露水平的分布以及每日摄入量，为未来的毒理学评估和进一步的流行病学研究提供基础数据。
