Isononanol(CAS: 2430-22-0), also known as Isononyl Alcohol or INA for short, has been a commercially manufactured chemical product since the 1940’s. Its value is to the plasticiser market as a precursor to Diisononyl Phthalate (DINP), Diisononyl Adipate (DINA), and Triisononyl Trimellitate (TINTM). Primarily used in the PVC market, products made from INA can be found in automotive parts, electrical wires, cables, conducting materials and numerous other products.
. Food Chem Toxicol. 2010 Jul;48 Suppl 4:S79-81. doi: 10.1016/j.fct.2010.05.034.
Fragrance material review on isononyl alcohol.
McGinty D(1), Scognamiglio J, Letizia CS, Api AM.
Author information: (1)Research Institute for Fragrance Materials Inc., 50 Tice Boulevard, Woodcliff Lake, NJ 07677, USA. [email protected]
A toxicologic and dermatologic review of isononyl alcohol when used as a fragrance ingredient is presented. Isononyl alcohol is a member of the fragrance structural group branched chain saturated alcohols. The common characteristic structural elements of the alcohols with saturated branched chain are one hydroxyl group per molecule, and a C(4)-C(12) carbon chain with one or several methyl side chains. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. A safety assessment of the entire branched chain saturated alcohol group will be published simultaneously with this document; please refer to Belsito et al. (2010) for an overall assessment of the safe use of this material and all other branched chain saturated alcohols in fragrances.
DOI: 10.1016/j.fct.2010.05.034 PMID: 20659642 [Indexed for MEDLINE]
. J Chromatogr B Analyt Technol Biomed Life Sci. 2007 Mar 1;847(2):114-25. doi: 10.1016/j.jchromb.2006.09.044. Epub 2006 Oct 20.
Determination of secondary, oxidised di-iso-nonylphthalate (DINP) metabolites in human urine representative for the exposure to commercial DINP plasticizers.
Koch HM(1), Müller J, Angerer J.
Author information: (1)Institut und Poliklinik für Arbeits-, Sozial-und Umweltmedizin, Schillerstrasse 25/29, 91054 Erlangen, Germany. [email protected]
Di-iso-nonylphthalate (DINP) is the major plasticizer for polyvinylchloride (PVC) polymers. Two DINP products are currently produced: DINP 1 and DINP 2. We analyzed the isononyl alcohol mixtures (INA) used for the synthesis of these two DINP plasticizer products and thus identified 4-methyloctanol-1 as one of the major constituents of the alkyl side chains of DINP 1 (8.7%) and DINP 2 (20.7%). Based on this isomer, we postulated the major DINP metabolites renally excreted by humans: mono-(4-methyl-7-hydroxy-octyl)phthalate (7OH-MMeOP), mono-(4-methyl-7-oxo-octyl)phthalate (7oxo-MMeOP) and mono-(4-methyl-7-carboxy-heptyl)phthalate (7carboxy-MMeHP). We present a fast and reliable on-line clean-up HPLC method for the simultaneous determination of these three DINP metabolites in human urine. We used ESI-tandem mass spectrometry for detection and isotope dilution for quantification (limit of quantification 0.5microg/l). Via these three oxidised DINP isomer standards, we quantified the excretion of all oxidised DINP isomers with hydroxy (OH-MINP), oxo (oxo-MINP) and carboxy (carboxy-MINP) functional groups. With this approach, we can for the first time reliably quantify the internal burden of the general population to DINP. Mean urinary metabolite concentrations in random samples from the general German population (n=25) were 14.9microg/l OH-MINP, 8.9microg/l oxo-MINP and 16.4microg/l carboxy-MINP. Metabolites strongly correlated with each other over all samples analyzed (R>0.99, p<0.0001).
DOI: 10.1016/j.jchromb.2006.09.044 PMID: 17055785 [Indexed for MEDLINE]
. Cell Death Discov. 2016 May 9;2:16010. doi: 10.1038/cddiscovery.2016.10. eCollection 2016.
Deorphanization and characterization of the ectopically expressed olfactory receptor OR51B5 in myelogenous leukemia cells.
Manteniotis S(1), Wojcik S(1), Göthert JR(2), Dürig J(2), Dührsen U(2), Gisselmann G(1), Hatt H(1).
Author information: (1)Department of Cell Physiology, Ruhr-University Bochum , Bochum, Germany. (2)Department of Hematology, University Hospital Essen , Essen, Germany.
The ectopic expression of olfactory receptors (ORs) in the human body has been of major interest in the past decade. Several studies have reported the expression of ORs not only in healthy tissues such as heart, sperm or skin cells, but also in cancerous tissues of the liver, prostate or intestine. In the present study, we detected the expression of OR51B5 in the chronic myelogenous leukemia (CML) cell line K562 and in white blood cell samples of clinically diagnosed acute myelogenous leukemia (AML) patients by reverse transcription-PCR and immunocytochemical staining. The known OR51B5 ligand isononyl alcohol increased the levels of intracellular Ca(2+) in both AML patient blood cells and K562 cells. With calcium imaging experiments, we characterized in greater detail the OR51B5-mediated signaling pathway. Here, we observed an involvement of adenylate cyclase and the downstream L-type and T-type calcium channels. In addition, the activation of OR51B5 leads to an inhibition of cell proliferation in K562 cells. In western blot experiments, we found that incubation with isononyl alcohol led to a reduction in p38-MAPK (mitogen-activated protein kinase) phosphorylation that might be responsible for the decreased cell proliferation. In the present study, we characterized the OR51B5-mediated signaling pathway downstream of the activation with isononyl alcohol, which leads to reduced proliferation and therefore provide a novel pharmacological target for CML and AML, the latter of which remains difficult to treat.
DOI: 10.1038/cddiscovery.2016.10 PMCID: PMC4979495 PMID: 27551504
. Exp Dermatol. 2017 Jan;26(1):58-65. doi: 10.1111/exd.13132.
Two olfactory receptors-OR2A4/7 and OR51B5-differentially affect epidermal proliferation and differentiation.
Tsai T(1), Veitinger S(1), Peek I(1), Busse D(1), Eckardt J(1), Vladimirova D(1), Jovancevic N(1), Wojcik S(1), Gisselmann G(1), Altmüller J(2), Ständer S(3), Luger T(4), Paus R(5), Cheret J(5), Hatt H(1).
Author information: (1)Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany. (2)Cologne Center for Genomics, University of Köln, Köln, Germany. (3)Department of Dermatology, Center for Chronic Pruritus, University Hospital Münster, Münster, Germany. (4)University Hospital Münster, Münster, Germany. (5)Department of Dermatology, Laboratory for Hair Research and Regenerative Medicine, University Hospital of Münster, Münster, Germany.
Olfactory receptors (ORs), which belong to the G-protein coupled receptor family, are expressed in various human tissues, including skin. Cells in non-olfactory tissues tend to express more than one individual OR gene, but function and interaction of two or more ORs in the same cell type has only been marginally analysed. Here, we revealed OR2A4/7 and OR51B5 as two new ORs in human skin cells and identified cyclohexyl salicylate and isononyl alcohol as agonists of these receptors. In cultured human keratinocytes, both odorants induce strong Ca2+ signals that are mediated by OR2A4/7 and OR51B5, as demonstrated by the receptor knockdown experiments. Activation of corresponding receptors induces a cAMP-dependent pathway. Localization studies and functional characterization of both receptors revealed several differences. OR2A4/7 is expressed in suprabasal keratinocytes and basal melanocytes of the epidermis and influences cytokinesis, cell proliferation, phosphorylation of AKT and Chk-2 and secretion of IL-1. In contrast, OR51B5 is exclusively expressed in suprabasal keratinocytes, supports cell migration and regeneration of keratinocyte monolayers, influences Hsp27, AMPK1 and p38MAPK phosphorylation and interestingly, IL-6 secretion. These findings underline that different ORs perform diverse functions in cutaneous cells, and thus offering an approach for the modulated treatment of skin diseases and wound repair.
DOI: 10.1111/exd.13132 PMID: 27315375 [Indexed for MEDLINE]
. Enzyme Microb Technol. 2019 Dec;131:109340. doi: 10.1016/j.enzmictec.2019.04.014. Epub 2019 Apr 29.
Preparation of diisononyl adipate in a solvent-free system via an immobilized lipase-catalyzed esterification.
Lee A(1), Kim H(1), Choi N(2), Yoon SW(1), Kim Y(3), Kim HR(4), Kim IH(5).
Author information: (1)Department of Public Health Sciences, Graduate School, Korea University, 145 Anam-Ro, Sungbuk-Gu, Seoul, 02841, Republic of Korea. (2)Department of Integrated Biomedical and Life Sciences, Graduate School, Korea University, 145 Anam-Ro, Sungbuk-Gu, Seoul, 02841, Republic of Korea. (3)Department of Nutritional Science and Food Management, Ewha Womans University, Seoul, 120-749, Republic of Korea. (4)School of Food Science and Biotechnology, Kyungpook National University, Daegu 702-701, Republic of Korea. (5)Department of Public Health Sciences, Graduate School, Korea University, 145 Anam-Ro, Sungbuk-Gu, Seoul, 02841, Republic of Korea; Department of Integrated Biomedical and Life Sciences, Graduate School, Korea University, 145 Anam-Ro, Sungbuk-Gu, Seoul, 02841, Republic of Korea. Electronic address: [email protected]
Diisononyl adipate is a plasticizer which has excellent property of low temperature resistance and is permitted in food contact materials. In this study, diisononyl adipate was synthesized from adipic acid and isononyl alcohol in a solvent-free system via immobilized lipase-catalyzed esterification. Liquid Eversa lipase from Thermomyces lanuginosus was immobilized on Lewatit VP OC 1600 carrier. The effects of temperature, substrate molar ratio, water activity of enzyme, vacuum, and enzyme loading on the reaction efficiency were investigated. Application of vacuum played a key role to achieve a 100% conversion. The optimal temperature, molar ratio (adipic acid to isononyl alcohol), water activity of enzyme, vacuum were 50 °C, 1:3, 0.75, 13.3 kPa, and 10% (based on weight of total substrate). Under these conditions, 100% conversion was achieved within 6 h.
DOI: 10.1016/j.enzmictec.2019.04.014 PMID: 31615683 [Indexed for MEDLINE]