| Revision as of 23:43, 13 August 2011 editCheMoBot (talk | contribs)Bots141,565 edits Updating {{chembox}} (no changed fields - added verified revid - updated 'DrugBank_Ref', 'UNII_Ref', 'ChEMBL_Ref', 'ChEBI_Ref', 'ChEBI_Ref') per Chem/Drugbox validation (report [[Wikipedia_talk:W← Previous edit |
Latest revision as of 19:47, 26 August 2024 edit undoSmokefoot (talk | contribs)Autopatrolled, Extended confirmed users, Pending changes reviewers, Rollbackers75,033 edits moving generic phthalate info to phthalates |
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| verifiedrevid = 440803965 |
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| ImageFile = Diisobutyl_Phthalate.png |
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| verifiedrevid = 444714897 |
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| ImageFile = Diisobutyl_Phthalate.png |
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| IUPACName = Diisobutyl phthalate |
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| ImageSize = 140 |
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| OtherNames = Diisobutyl ester of phthalic acic, Bis(2-methoxypropyl)ester,1,2-benzenedicarboxylic acid, Di(isobutyl)-1,2-benzenedicarboxylate, DIBP, DiBP, Palatinol IC |
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| ImageFile1 = Diisobutyl phthalate 3D spacefill.png |
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| Section1 = {{Chembox Identifiers |
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| ImageSize1 = 140 |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| PIN = Bis(2-methylpropyl) benzene-1,2-dicarboxylate |
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| OtherNames = Diisobutyl phthalate<br />Di-iso-butyl phthalate<br />Di(i-butyl)phthalate<br />Diisobutyl ester of phthalic acid<br />1,2-benzenedicarboxylic acid<br />Bis(2-methylpropyl)ester<br />Di(isobutyl) 1,2-benzenedicarboxylate<br />Isobutyl-O-phthalate<br />DIBP<br />DiBP<br />Palatinol IC |
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| Section1 = {{Chembox Identifiers |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID = 6524 |
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| ChemSpiderID = 6524 |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
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| KEGG = C15205 |
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| KEGG = C15205 |
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| ChEBI_Ref = {{ebicite|correct|EBI}} |
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| ChEBI = 79053 |
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| ChEMBL = 1370662 |
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| InChI = 1/C16H22O4/c1-11(2)9-19-15(17)13-7-5-6-8-14(13)16(18)20-10-12(3)4/h5-8,11-12H,9-10H2,1-4H3 |
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| InChI = 1/C16H22O4/c1-11(2)9-19-15(17)13-7-5-6-8-14(13)16(18)20-10-12(3)4/h5-8,11-12H,9-10H2,1-4H3 |
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| InChIKey = MGWAVDBGNNKXQV-UHFFFAOYAA |
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| InChIKey = MGWAVDBGNNKXQV-UHFFFAOYAA |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| CASNo = 84-69-5 |
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| CASNo = 84-69-5 |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| EINECS = 201-553-2 |
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| PubChem = 6782 |
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| UNII = IZ67FTN290 |
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| EINECS = 201-553-2 |
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| SMILES = O=C(OCC(C)C)c1ccccc1C(=O)OCC(C)C |
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| RTECS = TI1225000 |
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| PubChem = 6782 |
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| SMILES = O=C(OCC(C)C)c1ccccc1C(=O)OCC(C)C |
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| RTECS = TI1225000 |
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| Section2 = {{Chembox Properties |
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| Section2 = {{Chembox Properties |
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| C=16 | H=22 | O=4 |
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| Formula = C<sub>16</sub>H<sub>22</sub>O<sub>4</sub> |
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| Appearance = Colorless viscous liquid |
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| MolarMass = 278.35 g/mol |
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| Density = 1.038 g/cm<sup>3</sup> |
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| Appearance = Colorless viscous liquid |
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| MeltingPtC = -37 |
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| Density = 1.038 g/cm<sup>3</sup> |
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| MeltingPt_notes = |
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| MeltingPt = -37 °C (236 K) |
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| BoilingPt = 320 °C (593 K) |
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| BoilingPtC = 320 |
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| LogP = 4.11 |
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| Solubility = 1 mg/l at 20 °C |
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| LogP = 4.11 |
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| Solubility = 1 mg/L at 20 °C |
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| VaporPressure = 0.01 Pa at 20 °C |
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| VaporPressure = 0.01 Pa at 20 °C |
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| Section3 = {{Chembox Hazards |
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| Section3 = {{Chembox Hazards |
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| NFPA-H = 2 |
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| MainHazards = Harmful ('''Xn'''), Dangerous for the environment ('''N''') |
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| NFPA-H = 0 |
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| NFPA-F = 1 |
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| NFPA-F = 1 |
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| NFPA-R = 0 |
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| NFPA-R = 0 |
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| NFPA-S = |
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| GHSPictograms = {{GHS08}} |
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| NFPA-O = |
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| GHSSignalWord = Danger |
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| RPhrases = R50/53;R62;R63 |
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| HPhrases = {{H-phrases|360Df}} |
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| SPhrases = S36/37;S61 |
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| PPhrases = {{P-phrases|201|202|281|308+313|405|501}} |
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| FlashPt = 185 °C c.c. |
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| FlashPtC = 185 |
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| Autoignition = 400 °C |
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| FlashPt_notes = c.c. |
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| AutoignitionPtC = 400 |
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'''Diisobutyl phthalate''' ('''DIBP''') is a ] ester having the structural formula {{chem2|C6H4(COOCH2CH(CH3)2)2}}. It is formed by the ]ification of ] and ]. This and other phthalates are used as ]s due to their flexibility and durability. They are found in many industrial and personal products, such as lacquers, nail polish and cosmetics.<ref name=":4">{{Cite journal |last=Schettler |first=Ted |date=2006-02-07 |title=Human exposure to phthalates via consumer products |journal=International Journal of Andrology |language=en |volume=29 |issue=1 |pages=134–139 |doi=10.1111/j.1365-2605.2005.00567.x |pmid=16466533 |issn=0105-6263|doi-access=free }}</ref> DIBP can be absorbed via oral ingestion and dermal exposure.<ref name="PubChem">{{Cite web |title=Diisobutyl phthalate |url=https://pubchem.ncbi.nlm.nih.gov/compound/Diisobutyl-phthalate |access-date=2023-03-17 |work=PubChem |publisher=National Center for Biotechnology Information, U.S. National Library of Medicine |page=10 |language=en |id=6782}}</ref> When it comes to excretion, DIBP is first converted into the hydrolytic monoester monoisobutyl phthalate (MIBP). The primary excretory route is ], with ] excretion being noted in minor amounts. DIBP has lower density and freezing point than the related compound ] (DBP).<ref name="PubChem" /> |
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'''Diisobutyl Phthalate''' (DIBP) is prepared by ] process of ] and ]. Its structural formula is C<sub>6</sub>H<sub>4</sub>(COOCH<sub>2</sub>CH(CH<sub>3</sub>)<sub>2</sub>)<sub>2</sub>. Refractive index is 1.488 - 1.492 (20 °C, D). |
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DIBP is odorless plasticizer and has excellent heat and light stability. It is the lowest cost plasticizer for cellulose nitrate. DIBP has lower density and freezing point than DBP (], CAS No.: 84-74-2). It has similar properties as dibutyl phthalate and can be used as a substitute for it. |
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== Industry use == |
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DIBP is used in nitro cellulose plastic, nail polish, explosive material, lacquer manufacturing and used with ] applications. |
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It is used as a ] additive in a range of plastic and rubber materials.<ref name="PubChem" /> It has low volatility, which makes it ideal for use in products that require long-lasting flexibility, e.g. automotive parts, wire and cable insulation, and ].<ref name="OCSPP" /> It is dense and water-insoluble.<ref>{{cite web | title = Diisobutyl phthalate | id = CHEBI:79053 | work = ChEMBL | publisher = ELIXIR | url = https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:79053 }}</ref> |
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DIBP has been found to be relatively non-toxic, but high levels of exposure to the compound may cause irritation to the eyes, skin and respiratory tract.<ref name="PubChem" /> However, in recent years, concerns have been raised about the potential health risks of exposure to ]s, including DIBP. Therefore, several countries have restricted or even banned the use of certain phthalates in products.<ref name = "OCSPP">{{Cite web | work = Office of Chemical Safety and Pollution Prevention (OCSPP) | publisher = U.S. Environmental Protection Agency|date=2020-04-14 |title=Risk Evaluation for Di-isobutyl Phthalate - (1,2-Benzene- dicarboxylic acid, 1,2- bis-(2methylpropyl) ester) |url=https://www.epa.gov/assessing-and-managing-chemicals-under-tsca/risk-evaluation-di-isobutyl-phthalate-12-benzene |access-date=2023-03-17 |language=en}}</ref> DIBP has been detected in various environmental matrices, such as air, water, and ]. DIBP is known to ] in certain aquatic species<ref>{{cite journal | vauthors = Yan Y, Zhu F, Zhu C, Chen Z, Liu S, Wang C, Gu C | title = Dibutyl phthalate release from polyvinyl chloride microplastics: Influence of plastic properties and environmental factors | journal = Water Research | volume = 204 | pages = 117597 | date = October 2021 | pmid = 34482095 | doi = 10.1016/j.watres.2021.117597 | bibcode = 2021WatRe.20417597Y }}</ref> |
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The concentration of a metabolite of DIBP (Mono-isobutyl phthalate or MIBP) has been steadily increasing in the urine of Americans over the period 1999-2008.<ref name="CDCER">Center for Disease Control Fourth National Report on Human Exposure to Environmental Chemicals, Updated Tables, February 2011 . </ref> |
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==Contamination== |
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== Synthesis == |
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DIBP is synthesized by reaction of ] with isobutanol. Various ]s are used as a ], such as ], sulfonated graphene, or ]. Water is a byproduct. |
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Products in ] made from Hebo Natural Products Limited (禾博天然產物有限公司) of ] contained ] contaminated with DIBP, some 80,000 nutritional supplement capsules made with imported ginger powder were seized by the Public Health Department of Taiwan in June 2011.<ref>http://www.etaiwannews.com/etn/news_content.php?id=1627491&lang=eng_news&cate_rss=TAIWAN_eng</ref> |
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In addition, ] extract and olive leaf extract, both in powder form, were contaminated with DIBP and ]. Concentration of DIBP in the ginger extract powder was found to be 33,100 parts per million (ppm), that of DIBP in the soybean extract powder, 41 ppm, and that of DIBP and DBP in the olive leaf extract powder, 768 ppm and 441 ppm, respectively.<ref>http://www.chinapost.com.tw/taiwan/national/national-news/2011/06/15/306275/Plasticizer-found.htm China Post</ref> |
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Using sulfuric acid, the yield is 61% yield.<ref>{{Cite journal | vauthors = Hosangadi BD, Dave RH |date=1996-08-26 |title=An efficient general method for esterification of aromatic carboxylic acids |journal=Tetrahedron Letters |language=en |volume=37 |issue=35 |pages=6375–6378 |doi=10.1016/0040-4039(96)01351-2 |issn=0040-4039}}</ref> |
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==See also== |
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] |
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=== Optimization === |
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Sulfonated graphene is a ] that has several advantages over traditional liquid acids like sulfuric acid.<ref name=":0">{{Cite journal | vauthors = Garg B, Bisht T, Ling YC |date=2014-10-31 |title=Sulfonated graphene as highly efficient and reusable acid carbocatalyst for the synthesis of ester plasticizers |journal=RSC Advances |language=en |volume=4 |issue=100 |pages=57297–57307 |doi=10.1039/C4RA11205A |bibcode=2014RSCAd...457297G |issn=2046-2069}}</ref> Sulfonated graphene can be easily separated from the reaction mixture by ] and can be reused multiple times without reduction in activity.<ref>{{Cite journal | vauthors = Layek RK, Samanta S, Nandi AK |date=2012-03-01 |title=The physical properties of sulfonated graphene/poly(vinyl alcohol) composites |journal=Carbon |language=en |volume=50 |issue=3 |pages=815–827 |doi=10.1016/j.carbon.2011.09.039 |bibcode=2012Carbo..50..815L |issn=0008-6223}}</ref> Furthermore, sulfonated graphene is environmentally friendly, as it does not produce hazardous waste materials that are typically generated during the use of traditional liquid acid catalysts. This method has a 95% yield.<ref name=":0" /> |
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]s, such as {{chem2|FeCl3}}, can also be used as the catalyst.<ref name=":1">{{Cite journal | vauthors = Bajracharya GB, Koju R, Ojha S, Nayak S, Subedi S, Sasai H |date= January 2021 |title=Plasticizers: Synthesis of phthalate esters via FeCl3-catalyzed nucleophilic addition of alcohols to phthalic anhydride |journal=Results in Chemistry |language=en |volume=3 |pages=100190 |doi=10.1016/j.rechem.2021.100190 |s2cid= 240582041 |issn=2211-7156|doi-access=free }}</ref> The ] process can be run at lower temperatures (50-100 °C), and gives a yield of 86%.<ref name=":1" /> |
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== Available forms == |
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Diisobutyl phthalate is clear, colourless, oily liquid form with a mild odor.<ref name=":8">{{Cite web |title=Metabocard for Diisobutyl phthalate | id = HMDB0013835 |url=https://hmdb.ca/metabolites/HMDB0013835 |access-date=2023-03-17 | work = The Human Metabolome Database (HMDB) }}</ref> It is insoluble in water but soluble in many organic solvents.<ref>{{Cite web |title=DI-ISOBUTYL PHTHALATE {{!}} CAMEO Chemicals {{!}} NOAA |url=https://cameochemicals.noaa.gov/chemical/11095 |access-date=2023-03-17 |website=cameochemicals.noaa.gov}}</ref> |
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DIBP can be sold as a pure substance or as a component of mixtures with other phthalate plasticizers or chemicals. Examples are ] (DOP), ] (DINP), or ] (DEHP).<ref name=":7">{{Cite web |title=Phthalates - ECHA |url=https://echa.europa.eu/hot-topics/phthalates |access-date=2023-03-17 |website=echa.europa.eu |language=en-GB}}</ref> It may be used as a component in formulations of several products including ]s, paints, coatings and lubricants.<ref name = "OCSPP" /> DIBP also may be present in consumer products such as toys, vinyl flooring, food packaging, and as a plasticizer or as a component of plastic formulations.<ref name="OCSPP" /> In many of these products DIBP is now prohibited to be used in formulations according to ].<ref name=":7" /> |
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== Environmental reactions == |
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DIBP can undergo various reactions that may impact the environment. Examples include: |
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* ]: Hydrolyzation of DIBP can be done by enzymes, bacteria, and other microorganisms in the environment to form ] and ].<ref>{{cite journal | vauthors = Chatterjee S, Dutta TK | title = Metabolism of butyl benzyl phthalate by Gordonia sp. strain MTCC 4818 | journal = Biochemical and Biophysical Research Communications | volume = 309 | issue = 1 | pages = 36–43 | date = September 2003 | pmid = 12943660 | doi = 10.1016/S0006-291X(03)01513-4 }}</ref> This can lead to the breakdown and the eventual degradation of DIBP in the soil and water supply<ref>{{Cite web | publisher = PubChem, U.S. National Library of Medicine | title = Diisobutyl_phthalate | work = Hazardous Substances Data Bank (HSDB) | id = 5247 |url= https://pubchem.ncbi.nlm.nih.gov/source/hsdb/5247 |access-date=2023-03-18 }}</ref> |
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* ]: DIBP can undergo photodegradation by exposure to the sunlight. This can lead to the formation of several degradation products, including ], ], and other aldehydes.<ref>{{cite journal | vauthors = Wang C, Zeng T, Gu C, Zhu S, Zhang Q, Luo X | title = Photodegradation Pathways of Typical Phthalic Acid Esters Under UV, UV/TiO<sub>2</sub>, and UV-Vis/Bi<sub>2</sub>WO<sub>6</sub> Systems | journal = Frontiers in Chemistry | volume = 7 | pages = 852 | date = 2019 | pmid = 31921775 | doi = 10.3389/fchem.2019.00852 | pmc = 6923729 | doi-access = free }}</ref> |
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* ]: DIBP can be degraded by ]s in soil and in the water. This can transform it into other compounds such as ] and various ] derivatives.<ref>{{cite journal | vauthors = Lu Y, Tang F, Wang Y, Zhao J, Zeng X, Luo Q, Wang L | title = Biodegradation of dimethyl phthalate, diethyl phthalate and di-n-butyl phthalate by Rhodococcus sp. L4 isolated from activated sludge | journal = Journal of Hazardous Materials | volume = 168 | issue = 2–3 | pages = 938–943 | date = September 2009 | pmid = 19342169 | doi = 10.1016/j.jhazmat.2009.02.126 | bibcode = 2009JHzM..168..938L }}</ref> |
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* ]: DIBP can adsorb or sorb onto soil and sediment particles, which can limit its mobility and availability for biological or chemical degradations and reactions.<ref>{{Cite journal | vauthors = Lu T, Xue C, Shao J, Gu JD, Zeng Q, Luo S |date= October 2016 |title=Adsorption of dibutyl phthalate on Burkholderia cepacia, minerals, and their mixtures: Behaviors and mechanisms |journal=International Biodeterioration & Biodegradation |language=en |volume=114 |pages=1–7 |doi=10.1016/j.ibiod.2016.05.015 |bibcode= 2016IBiBi.114....1L |issn=0964-8305}}</ref> |
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* ]: DIBP can be oxidized in the presence of ozone or other reactive oxygen species. The formation of various oxidation products, including ]s, ]s, and ]s can be expected<ref>{{cite journal | vauthors = Huo Y, An Z, Li M, Sun J, Jiang J, Zhou Y, He M | title = The reaction laws and toxicity effects of phthalate acid esters (PAEs) ozonation degradation on the troposphere | journal = Environmental Pollution | volume = 295 | pages = 118692 | date = February 2022 | pmid = 34921942 | doi = 10.1016/j.envpol.2021.118692 | bibcode = 2022EPoll.29518692H | s2cid = 245248168 }}</ref> |
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These reactions can impact the persistence, ], and toxicity in the environment and may have implications for human and ] health. |
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== Mechanisms of actions == |
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=== PPARγ Pathway === |
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The effects of DiBP exposure are mainly realized through its activation of ] (PPARγ).<ref name=":2">{{cite journal | vauthors = Chen H, Chen K, Qiu X, Xu H, Mao G, Zhao T, Feng W, Okeke ES, Wu X, Yang L | display-authors = 6 | title = The reproductive toxicity and potential mechanisms of combined exposure to dibutyl phthalate and diisobutyl phthalate in male zebrafish (Danio rerio) | journal = Chemosphere | volume = 258 | pages = 127238 | date = November 2020 | pmid = 32563064 | doi = 10.1016/j.chemosphere.2020.127238 | bibcode = 2020Chmsp.25827238C | s2cid = 219959568 }}</ref> PPARs are ]-activated nuclear transcription factors, the family consists of ], ] and PPARγ.<ref>{{cite journal | vauthors = Michalik L, Auwerx J, Berger JP, Chatterjee VK, Glass CK, Gonzalez FJ, Grimaldi PA, Kadowaki T, Lazar MA, O'Rahilly S, Palmer CN, Plutzky J, Reddy JK, Spiegelman BM, Staels B, Wahli W | display-authors = 6 | title = International Union of Pharmacology. LXI. Peroxisome proliferator-activated receptors | journal = Pharmacological Reviews | volume = 58 | issue = 4 | pages = 726–741 | date = December 2006 | pmid = 17132851 | doi = 10.1124/pr.58.4.5 | s2cid = 2240461 }}</ref> There are two isoforms of PPARγ, PPARγ2 is mainly present on cells in ], whereas PPARγ1 is found on multiple cells like those in the gut, brain, blood vessels, and some ] and ]. ] through PPARs requires the formation of a ] with ] (RXR). Upon activation by DiBP this PPARγ/RXR heterodimer binds to a DNA sequence called the PPAR response element (PPRE).<ref>{{cite journal | vauthors = Feige JN, Gelman L, Tudor C, Engelborghs Y, Wahli W, Desvergne B | title = Fluorescence imaging reveals the nuclear behavior of peroxisome proliferator-activated receptor/retinoid X receptor heterodimers in the absence and presence of ligand | language = English | journal = The Journal of Biological Chemistry | volume = 280 | issue = 18 | pages = 17880–17890 | date = May 2005 | pmid = 15731109 | doi = 10.1074/jbc.M500786200 | doi-access = free }}</ref> Binding of the transcription factor to this response element can result in either up- or down-]. PPARγ is involved in ] and storage as well as ] through improving ] sensitivity,<ref>{{cite journal | vauthors = Koutnikova H, Cock TA, Watanabe M, Houten SM, Champy MF, Dierich A, Auwerx J | title = Compensation by the muscle limits the metabolic consequences of lipodystrophy in PPAR gamma hypomorphic mice | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 100 | issue = 24 | pages = 14457–14462 | date = November 2003 | pmid = 14603033 | pmc = 283613 | doi = 10.1073/pnas.2336090100 | doi-access = free | bibcode = 2003PNAS..10014457K }}</ref><ref name="pmid12663460">{{cite journal | vauthors = Savage DB, Tan GD, Acerini CL, Jebb SA, Agostini M, Gurnell M, Williams RL, Umpleby AM, Thomas EL, Bell JD, Dixon AK, Dunne F, Boiani R, Cinti S, Vidal-Puig A, Karpe F, Chatterjee VK, O'Rahilly S | display-authors = 6 | title = Human metabolic syndrome resulting from dominant-negative mutations in the nuclear receptor peroxisome proliferator-activated receptor-gamma | journal = Diabetes | volume = 52 | issue = 4 | pages = 910–917 | date = April 2003 | pmid = 12663460 | doi = 10.2337/diabetes.52.4.910 | doi-access = free }}</ref> so binding of DiBP leads to altered ] and insulin levels. DiBP also leads to a down-regulation of proteins involved in ] production, resulting in higher levels of ].<ref name=":2" /> |
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=== Cytokine-cytokine receptor pathway === |
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Another type of pathway affected by DiBP exposure is the ]-] pathway. There are two pathways affected: the ] (TNFRSF) and the ] pathway, both of which affect ].<ref name=":2" /> In ], there are two types of TNFRSF: tnfrsf1a and tnfrsf1b, the latter of which is down-regulated by DiBP. Tnfrsf1b is involved in regeneration and ] repair and its down-regulation has been shown to increase ] of sperm cells.<ref>{{cite journal | vauthors = Wang YQ, Li YW, Chen QL, Liu ZH | title = Long-term exposure of xenoestrogens with environmental relevant concentrations disrupted spermatogenesis of zebrafish through altering sex hormone balance, stimulating germ cell proliferation, meiosis and enhancing apoptosis | journal = Environmental Pollution | volume = 244 | pages = 486–494 | date = January 2019 | pmid = 30366296 | doi = 10.1016/j.envpol.2018.10.079 | bibcode = 2019EPoll.244..486W | s2cid = 53112695 }}</ref> ] (PLR) on the other hand is up-regulated as a result of DiBP exposure.<ref name=":2" /> Prolactin has many roles, including roles in cell regeneration and regulation of the ].<ref name="pmid12087074">{{cite journal | vauthors = Hair WM, Gubbay O, Jabbour HN, Lincoln GA | title = Prolactin receptor expression in human testis and accessory tissues: localization and function | journal = Molecular Human Reproduction | volume = 8 | issue = 7 | pages = 606–11 | date = July 2002 | pmid = 12087074 | doi = 10.1093/molehr/8.7.606 | doi-access = free }}</ref> High PLR concentrations as a result of phthalate exposure has been linked to reduced sperm concentrations in both adult men and zebra fish.<ref>{{cite journal | vauthors = Li S, Dai J, Zhang L, Zhang J, Zhang Z, Chen B | title = An association of elevated serum prolactin with phthalate exposure in adult men | journal = Biomedical and Environmental Sciences | volume = 24 | issue = 1 | pages = 31–39 | date = February 2011 | pmid = 21440837 | doi = 10.3967/0895-3988.2011.01.004 | bibcode = 2011BioES..24...31L }}</ref><ref name=":2" /> |
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== Metabolism == |
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]Upon entering circulation DiBP is quickly ] and excreted through ], with ]s reaching peak concentrations 2–4 hours after administration.<ref name=":3">{{cite journal | vauthors = Koch HM, Christensen KL, Harth V, Lorber M, Brüning T | title = Di-n-butyl phthalate (DnBP) and diisobutyl phthalate (DiBP) metabolism in a human volunteer after single oral doses | journal = Archives of Toxicology | volume = 86 | issue = 12 | pages = 1829–1839 | date = December 2012 | pmid = 22820759 | doi = 10.1007/s00204-012-0908-1 | s2cid = 253718517 }}</ref> The main metabolite of DiBP is mono-isobutyl phthalate (MiBP), which makes up 70% of the excretion products. MiBP can be oxidized to either 2OH-mono-isobutyl phthalate (2OH-MiBP) or 3OH-mono-isobutyl phthalate (3OH-MiBP), which make up 20% and 1% of the excretion products respectively. These reactions are likely catalyzed by ] in the liver.<ref>{{cite journal | vauthors = Carstens L, Cowan AR, Seiwert B, Schlosser D | title = Biotransformation of Phthalate Plasticizers and Bisphenol A by Marine-Derived, Freshwater, and Terrestrial Fungi | journal = Frontiers in Microbiology | volume = 11 | pages = 317 | date = 2020 | pmid = 32180766 | doi = 10.3389/fmicb.2020.00317 | pmc = 7059612 | doi-access = free }}</ref> The ratio between MiBP and the oxidized metabolites changes depending on the amount of time that has passed since exposure.<ref name=":3" /> The ratio between MiBP and 2OH-MiBP and that between MiBP and 3OH-MiBP show a similar trend. With the ratios being high, around 20-30:1, shortly after exposure and dropping gradually as more time passes to rest around 2-5:1. Therefore, a high ratio of oxidized metabolites to the monoester metabolite suggests that there was recent exposure to DiBP, within a few hours of measuring, while a lower ratio suggests that there has been more time since exposure. In addition to oxidation, MiBP can also undergo a ] reaction, resulting in the metabolite MiBP-glucuronide.<ref>{{cite journal | vauthors = Jeong SH, Jang JH, Cho HY, Lee YB | title = Toxicokinetics of diisobutyl phthalate and its major metabolite, monoisobutyl phthalate, in rats: UPLC-ESI-MS/MS method development for the simultaneous determination of diisobutyl phthalate and its major metabolite, monoisobutyl phthalate, in rat plasma, urine, feces, and 11 various tissues collected from a toxicokinetic study | journal = Food and Chemical Toxicology | volume = 145 | pages = 111747 | date = November 2020 | pmid = 32926938 | doi = 10.1016/j.fct.2020.111747 }}</ref> |
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== Toxicity == |
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There's insufficient data to determine if DIBP is associated with acute dermal or inhalation toxicity, eye or dermal irritation, or sensitization. There is evidence on DIBP being a ] toxicant. Exposure to the compound can induce changes in body weight, liver weight, reproductive effects, and developmental effects like testicular weight, ], fetal body weight, ] in male and female rats, and testicular testosterone production, among others.<ref>{{Cite web |date=2010 |title=Toxicity review of diisobutyl phthalate (DiBP) |url=https://www.cpsc.gov/PageFiles/125773/dibp.pdf | archive-url = https://web.archive.org/web/20130420132018/https://www.cpsc.gov/PageFiles/125773/dibp.pdf | archive-date = 20 April 2013 |access-date=2023-03-17 |website=www.cpsc.gov}}</ref> |
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] studies show that exposures to DIBP have grown recently, presumably as a result of DIBPs use as a substitute for other phthalates such as dibutyl phthalate (DBP) in plastics.<ref>{{cite journal | vauthors = Wittassek M, Wiesmüller GA, Koch HM, Eckard R, Dobler L, Müller J, Angerer J, Schlüter C | display-authors = 6 | title = Internal phthalate exposure over the last two decades--a retrospective human biomonitoring study | journal = International Journal of Hygiene and Environmental Health | volume = 210 | issue = 3–4 | pages = 319–333 | date = May 2007 | pmid = 17400024 | doi = 10.1016/j.ijheh.2007.01.037 | bibcode = 2007IJHEH.210..319W }}</ref><ref name=":10">{{cite journal | vauthors = Zota AR, Calafat AM, Woodruff TJ | title = Temporal trends in phthalate exposures: findings from the National Health and Nutrition Examination Survey, 2001-2010 | journal = Environmental Health Perspectives | volume = 122 | issue = 3 | pages = 235–241 | date = March 2014 | pmid = 24425099 | doi = 10.1289/ehp.1306681 | pmc = 3948032 }}</ref> In the United States, for instance, the prevalence of MIBP detection in urine has risen from 72% of the general population in 2001–2002 to 96% in 2009–2010, according to data from the ] (NHANES).<ref name=":10" /> |
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The main issue with phthalate exposure is typically male reproductive toxicity, which is a risk that many phthalates share.<ref>{{cite journal | vauthors = Yost EE, Euling SY, Weaver JA, Beverly BE, Keshava N, Mudipalli A, Arzuaga X, Blessinger T, Dishaw L, Hotchkiss A, Makris SL | display-authors = 6 | title = Hazards of diisobutyl phthalate (DIBP) exposure: A systematic review of animal toxicology studies | journal = Environment International | volume = 125 | pages = 579–594 | date = April 2019 | pmid = 30591249 | pmc = 8596331 | doi = 10.1016/j.envint.2018.09.038 | bibcode = 2019EnInt.125..579Y }}</ref> |
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== Effect on animals == |
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A study conducted on rats shows that high dosage of DIBP administered by ] to pregnant female rats between ] days (GD) 6 and 20, exhibited signs of ] and ]<ref name=":6">{{cite journal | vauthors = Saillenfait AM, Sabaté JP, Gallissot F | title = Developmental toxic effects of diisobutyl phthalate, the methyl-branched analogue of di-n-butyl phthalate, administered by gavage to rats | journal = Toxicology Letters | volume = 165 | issue = 1 | pages = 39–46 | date = August 2006 | pmid = 16516415 | doi = 10.1016/j.toxlet.2006.01.013 }}</ref> The growing male reproductive system was negatively impacted by DIBP, which is typical for phthalate esters. When phthalates are exposed ] during the process of male sexual differentiation, a phenotype known as "phthalate syndrome" is created. This syndrome is characterized by underdevelopment of the male reproductive system, decreased ] (AGD), retention of the nipple in a female-like manner, and germ cell toxicity, among other things.<ref>{{Cite journal | vauthors = Foster PM, Gray Jr LE |date=2008 |title=Casarett and Doull's toxicology: The basic science of poisons |url= |journal=Toxicology |volume= |issue= |pages=761–806 |doi= |issn=}}</ref><ref>{{cite journal | vauthors = Lioy PJ, Hauser R, Gennings C, Koch HM, Mirkes PE, Schwetz BA, Kortenkamp A | title = Assessment of phthalates/phthalate alternatives in children's toys and childcare articles: Review of the report including conclusions and recommendation of the Chronic Hazard Advisory Panel of the Consumer Product Safety Commission | journal = Journal of Exposure Science & Environmental Epidemiology | volume = 25 | issue = 4 | pages = 343–353 | date = 2015 | pmid = 25944701 | doi = 10.1038/jes.2015.33 | s2cid = 19276318 | doi-access = free }}</ref><ref name=":9">{{Cite book | author = National Research Council (U.S.). Committee on the Health Risks of Phthalates. National Academies Press |url=http://worldcat.org/oclc/586808833 |title=Phthalates and cumulative risk assessment : the task ahead |date=2008 |publisher=National Academies Press |isbn=978-0-309-12841-4 |oclc=586808833}}</ref> Therefore, these effects can be connected to decreased insulin-like-3 (]) hormone, which controls transabdominal testicular descent, decreased ] production in the testicles, which is essential for male sexual development, and disruption of seminiferous cord formation, ]s, and germ cell development via an unknown ] (MOA).<ref name=":9" /><ref>{{cite journal | vauthors = Johnson KJ, Heger NE, Boekelheide K | title = Of mice and men (and rats): phthalate-induced fetal testis endocrine disruption is species-dependent | journal = Toxicological Sciences | volume = 129 | issue = 2 | pages = 235–248 | date = October 2012 | pmid = 22700540 | doi = 10.1093/toxsci/kfs206 | pmc = 3491958 }}</ref><ref>{{cite journal | vauthors = Martino-Andrade AJ, Chahoud I | title = Reproductive toxicity of phthalate esters | journal = Molecular Nutrition & Food Research | volume = 54 | issue = 1 | pages = 148–157 | date = January 2010 | pmid = 19760678 | doi = 10.1002/mnfr.200800312 }}</ref> |
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Despite the limited studies in other species, research on ]<ref name=":5" /> shows that environmental exposure to DBP and DIBP can have serious consequences for fish offspring. As they go up the food chain and into polluted water, these phthalates can build up in aquatic organisms. Fish are susceptible to environmental toxins in their early lives, whether they are exposed to them directly or indirectly through their parents. |
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{| class="wikitable" |
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|Species |
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|Exposure Route |
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|Dose |
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|Effect |
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|Reference |
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|] |
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|Oral (by gavage) |
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|250, 500, 750, and 1000 mg/kg/day |
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|Pregnant females: Transient decrease in body weight gain, observed at 500 mg/kg and higher. Embryolethality and ] at 750 and 1000 mg/kg. |
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Male fetuses: Undescended testis at 500 mg/kg. The degree of transabdominal migration of testis in relation to the bladder were disturbed at 500 mg/kg and above. |
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|<ref name=":6" /> |
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|Zebrafish |
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|Chemical exposure |
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|10, 103 and 1038 μg L<sup>−1</sup>, (LC50) was 1037.7 μg L<sup>−1</sup> |
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|Parental individual DIBP exposure disturbed key genes in ] and phototransduction signal pathways, which could influence the eye development of F1 larvae. |
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|<ref name=":5">{{cite journal | vauthors = Chen H, Feng W, Chen K, Qiu X, Xu H, Mao G, Zhao T, Wu X, Yang L | display-authors = 6 | title = Transcriptomic responses predict the toxic effect of parental co-exposure to dibutyl phthalate and diisobutyl phthalate on the early development of zebrafish offspring | journal = Aquatic Toxicology | volume = 235 | pages = 105838 | date = June 2021 | pmid = 33910148 | doi = 10.1016/j.aquatox.2021.105838 | bibcode = 2021AqTox.23505838C | s2cid = 233447494 }}</ref> |
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|Wistar Rats |
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|Oral (by gavage) |
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|600 mg/kg |
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|Disrupt fetal testicular development. AGD was reduced at GD 19 and GD 20/21 in males and increased in females exposed to DIBP. It also reduced bodyweights of male and female fetuses. |
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|<ref>{{cite journal | vauthors = Borch J, Axelstad M, Vinggaard AM, Dalgaard M | title = Diisobutyl phthalate has comparable anti-androgenic effects to di-n-butyl phthalate in fetal rat testis | journal = Toxicology Letters | volume = 163 | issue = 3 | pages = 183–190 | date = June 2006 | pmid = 16458459 | doi = 10.1016/j.toxlet.2005.10.020 }}</ref> |
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|Sprague-Dawley Rats |
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|Oral (by gavage) |
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|100, 300, 600, and 900 mg/kg/day |
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|Reduced maternal body weight gain from 73 g in controls to 48 and 43 g in the 600 and 900 mg/kg/day dose groups, respectively. |
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|<ref>{{cite journal | vauthors = Howdeshell KL, Wilson VS, Furr J, Lambright CR, Rider CV, Blystone CR, Hotchkiss AK, Gray LE | display-authors = 6 | title = A mixture of five phthalate esters inhibits fetal testicular testosterone production in the sprague-dawley rat in a cumulative, dose-additive manner | journal = Toxicological Sciences | volume = 105 | issue = 1 | pages = 153–165 | date = September 2008 | pmid = 18411233 | doi = 10.1093/toxsci/kfn077 | doi-access = free }}</ref> |
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|Wistar Rats |
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|Oral (by gavage) |
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|600 mg/kg bw/day |
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|Reductions in fetal plasma ] levels and in fetal insulin levels. Prenatal exposure disrupts fetal testosterone production in male rats by reducing the expression of several genes and proteins involved in steroidogenesis. In females, increases ovarian ] gene expression. DIBP also affected PPAR expression in the liver and testes. |
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|<ref>{{cite journal | vauthors = Boberg J, Metzdorff S, Wortziger R, Axelstad M, Brokken L, Vinggaard AM, Dalgaard M, Nellemann C | display-authors = 6 | title = Impact of diisobutyl phthalate and other PPAR agonists on steroidogenesis and plasma insulin and leptin levels in fetal rats | journal = Toxicology | volume = 250 | issue = 2–3 | pages = 75–81 | date = September 2008 | pmid = 18602967 | doi = 10.1016/j.tox.2008.05.020 | bibcode = 2008Toxgy.250...75B }}</ref> |
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|- |
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|Sprague-Dawley Rats |
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|Oral |
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|100, 300, 600, or 900 mg/kg/day |
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|Significantly reduced T production. Reduced fetal AGD, T levels, and ]. |
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|<ref>{{cite journal | vauthors = Hannas BR, Lambright CS, Furr J, Evans N, Foster PM, Gray EL, Wilson VS | title = Genomic biomarkers of phthalate-induced male reproductive developmental toxicity: a targeted RT-PCR array approach for defining relative potency | journal = Toxicological Sciences | volume = 125 | issue = 2 | pages = 544–557 | date = February 2012 | pmid = 22112501 | pmc = 3262859 | doi = 10.1093/toxsci/kfr315 }}</ref> |
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|- |
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|Sprague-Dawley Rats |
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|Oral (by gavage) |
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|125, 250, 500, 625 mg/kg/day |
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|Doses ≥ 250 mg DIBP/(kg day) resulted in reduced AGD, and retained thoracic areolas/nipples at both early postnatal life, and adult necropsy. |
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|<ref>{{cite journal | vauthors = Saillenfait AM, Sabaté JP, Gallissot F | title = Diisobutyl phthalate impairs the androgen-dependent reproductive development of the male rat | journal = Reproductive Toxicology | volume = 26 | issue = 2 | pages = 107–115 | date = October 2008 | pmid = 18706996 | doi = 10.1016/j.reprotox.2008.07.006 | bibcode = 2008RepTx..26..107S }}</ref> |
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== See also == |
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* ] |
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* ] |
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* ] (DBP) |
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* ] |
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* ] |
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* ] |
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==References== |
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== References == |
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{{Reflist}} |
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{{Reflist}} |
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==External links== |
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== External links == |
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* {{ICSC|0829|08}} |
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* {{ICSC|0829|08}} |
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{{HealthIssuesOfPlastics}} |
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{{HealthIssuesOfPlastics}} |
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