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{{chembox |
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{{chembox |
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|Verifiedfields = changed |
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| verifiedrevid = 445158494 |
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|Watchedfields = changed |
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| Name = Bronopol |
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|verifiedrevid = 449585006 |
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| ImageFile = Bronopol skeletal.svg |
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| ImageFile2 = Bronopol 3D ball-and-stick.png |
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|Name = Bronopol |
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|ImageFile = Bronopol skeletal.svg |
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|ImageFile2 = Bronopol 3D ball-and-stick.png |
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| ImageSize = 200px |
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| ImageName = Bronopol |
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|ImageName = Bronopol |
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| IUPACName = 2-bromo-2-nitropropane-1,3-diol |
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|PIN = 2-Bromo-2-nitropropane-1,3-diol |
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| Section1 = {{Chembox Identifiers |
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|Section1={{Chembox Identifiers |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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|ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID = 2356 |
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|ChemSpiderID = 2356 |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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|ChEMBL_Ref = {{ebicite|changed|EBI}} |
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|ChEMBL = 1408862 |
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| UNII = 6PU1E16C9W |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
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|UNII_Ref = {{fdacite|correct|FDA}} |
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| KEGG = D01577 |
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|UNII = 6PU1E16C9W |
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|KEGG_Ref = {{keggcite|correct|kegg}} |
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| InChI = 1/C3H6BrNO4/c4-3(1-6,2-7)5(8)9/h6-7H,1-2H2 |
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|KEGG = D01577 |
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| InChIKey = LVDKZNITIUWNER-UHFFFAOYAZ |
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|PubChem = 2450 |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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|EC_number = 200-143-0 |
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| StdInChI = 1S/C3H6BrNO4/c4-3(1-6,2-7)5(8)9/h6-7H,1-2H2 |
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|RTECS = TY3385000 |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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|UNNumber = 3241 |
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| StdInChIKey = LVDKZNITIUWNER-UHFFFAOYSA-N |
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|InChI = 1/C3H6BrNO4/c4-3(1-6,2-7)5(8)9/h6-7H,1-2H2 |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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|InChIKey = LVDKZNITIUWNER-UHFFFAOYAZ |
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| CASNo = 52-51-7 |
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|StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| ATCvet = yes |
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|StdInChI = 1S/C3H6BrNO4/c4-3(1-6,2-7)5(8)9/h6-7H,1-2H2 |
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| ATCCode_prefix = D01 |
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|StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| ATCCode_suffix = AE91 |
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|StdInChIKey = LVDKZNITIUWNER-UHFFFAOYSA-N |
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| SMILES = (=O)C(Br)(CO)CO |
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|CASNo_Ref = {{cascite|correct|CAS}} |
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|CASNo = 52-51-7 |
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|SMILES = (=O)C(Br)(CO)CO |
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}} |
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|Section2={{Chembox Properties |
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|C=3 | H=6 | Br=1 | N=1 | O=4 |
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|Appearance = White solid |
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|Density =1.1 g/cm<sup>3</sup> |
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|MeltingPtC = 130 |
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|BoilingPtC = 140 |
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|BoilingPt_notes = (decomposes) |
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}} |
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|Section6={{Chembox Pharmacology |
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|ATCvet = yes |
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|ATCCode_prefix = D01 |
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|ATCCode_suffix = AE91 |
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}} |
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|Section8={{Chembox Hazards |
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|GHSSignalWord = Danger |
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|GHSPictograms = {{GHS05}}{{GHS07}}{{GHS09}} |
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|HPhrases = {{H-phrases|302|312|315|318|335|400}} |
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|PPhrases = {{P-phrases|261|264|270|271|273|280|301+312|302+352|304+340|305+351+338|310|312|321|322|330|332+313|362|363|391|403+233|405|501}} |
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}} |
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}} |
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| Section2 = {{Chembox Properties |
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| Formula = C<sub>3</sub>H<sub>6</sub>BrNO<sub>4</sub> |
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| MolarMass = 199.989 g/mol |
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| Appearance = Crystals / crystalline powder, varying from<br /> white to pale yellow depending on the grade |
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| Density = |
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| MeltingPt = 130 °C |
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| BoilingPt = 140 °C (decomposes) |
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}} |
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}} |
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}} |
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'''Bronopol''' (]; chemical name '''2-bromo-2-nitropropane-1,3-diol''') is an ] that is used as an ]. It is a white solid although commercial samples appear yellow. |
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The first reported synthesis of bronopol was in 1897.{{citation needed|date=April 2019}} |
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'''Bronopol''' (INN) is a highly active ] chemical compound whose ] is 2-bromo-2-nitropropane-1,3-diol. |
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Bronopol was invented by ], ] in the early 1960s and first applications were as a ] for ]s. Bronopol's low ]ian ] (at in-use levels) and exceptional activity against ] (especially the troublesome ] species) ensured that it became popular as a preservative in many consumer products such as ]s and ]. |
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Bromopol was invented by ] in the early 1960s and first applications were as a ] for ]s. Due to its low ]ian ] at in-use levels and high activity against ], especially ] species,<ref>{{cite journal|last1=Bryce|first1=D. M.|last2=Croshaw|first2=B.|last3=Hall|first3=J. E.|last4=Holland|first4=V. R.|last5=Lessel|first5=B.|title=The activity and safety of the antimicrobial agent bronopol (2-bromo-2-nitropropan-1, 3-diol)|journal=J. Soc. Cosmet. Chem.|date=1978|volume=29|pages=3–24|url=http://journal.scconline.org/pdf/cc1978/cc029n01/p00003-p00024.pdf|accessdate=5 April 2016|archive-url=https://web.archive.org/web/20161220185947/http://journal.scconline.org/pdf/cc1978/cc029n01/p00003-p00024.pdf|archive-date=20 December 2016|url-status=dead}}</ref> bronopol became popular as a preservative in many consumer products such as ]s and ]. It was subsequently adopted as an antimicrobial in other industrial environments such as ]s, ], and production facilities, as well as cooling water disinfection plants. |
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==Production== |
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Bronopol was subsequently taken up as an effective antimicrobial in many industrial environments such as ]s, ] and production facilities, as well as cooling water disinfection plants. |
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Bronopol is produced by the ] of di(hydroxymethyl)nitromethane, which is derived from ] by a ].<ref>Sheldon B. Markofsky "Nitro Compounds, Aliphatic" in ''Ullmann's Encyclopedia of Industrial Chemistry'', 2012, Wiley-VCH, Weinheim. {{doi|10.1002/14356007.a17_401.pub2}}</ref> World production increased from the tens of ]s in the late 1970s to current estimates in excess of 5,000 tonnes. Production today is the business of low cost producers, mainly in ]. |
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World production soared from the tens of ]nes in the late 1970s to current estimates in excess of 5,000 tonnes. This is quite something considering the effective use-concentration which can be as low as 0.0025% (25 parts per million). Manufacturing today is the business of low cost producers, mainly in ]. |
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Pharmaceutical products containing Bronopol are registered in a number of countries and Bronopol is the subject of a specific ] in the ] 1998. |
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==Applications== |
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==Applications== |
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{{more citations needed section|date=January 2017}} |
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Today, Bronopol is used in consumer products as an effective preservative agent, as well as a wide variety of industrial applications (almost any industrial water system is a potential environment for bacterial growth, leading to ] and ] problems - in many of these systems Bronopol can be a highly effective treatment). |
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Bronopol is used in consumer products as an effective preservative agent, as well as a wide variety of industrial applications (almost any industrial water system is a potential environment for bacterial growth, leading to ] and ] problems - in many of these systems bronopol can be a highly effective treatment). |
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The use of Bronopol in ] (], ]) has declined since the late 1980s due to the recognized potential for ] formation. |
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The use of bronopol in ] (], ]) has declined since the late 1980s due to the potential formation of ]s. While bronopol is not in itself a nitrosating agent, under conditions where it decomposes ''(] solution and/or elevated temperatures)'' it can liberate nitrite and low levels of formaldehyde and these decomposition products can react with any contaminant secondary amines or amides in a personal care formulation to produce significant levels of nitrosamines (due to the toxicity of these substances, the term 'significant' means levels as low as tens of parts per billion). |
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Manufacturers of personal care products are therefore instructed by regulatory authorities to avoid the formation of nitrosamines which might mean removing amines or amides from the formulation, removing bronopol from a formulation, or using nitrosamine inhibitors. |
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===The Nitrosamine Problem=== |
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Although fairly ubiquitous in our diet and the environment, and even produced within the ] from various foodstuffs, many nitrosamines are known or suspect ]s and therefore should be avoided in manufactured goods. |
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Bronopol has been restricted for use in cosmetics in Canada.<ref>{{cite web|title=Consumer product safety: Cosmetic ingredient hotlist|url=http://www.hc-sc.gc.ca/cps-spc/cosmet-person/hot-list-critique/hotlist-liste-eng.php#b1|publisher=Health Canada|accessdate=2017-01-24}}</ref> |
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Nitrosamines are relatively easily produced from secondary ]s and ]s in the presence of ] ]s (this is why they are formed in-vivo from foodstuffs). |
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While Bronopol is not in itself a nitrosating agent, under conditions where it decomposes ''(] solution and/or elevated temperatures)'' it can liberate nitrite and low levels of formaldehyde and these decomposition products can react with any contaminant secondary amines or amides in a personal care formulation to produce significant levels of nitrosamines (due to the toxicity of thes substances, the term 'significant' means levels as low as 10s of parts per billion). |
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Manufacturers of personal care products are therefore instructed by regulatory authorities to 'avoid the formation of nitrosamines' which might mean removing amines or amides from the formulation, removing Bronopol from a formulation, or using nitrosamine inhibitors. |
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==Physical and chemical properties== |
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==Physical and chemical properties== |
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===Appearance=== |
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===Appearance=== |
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Bronopol is supplied as ]s or crystalline powder, which may vary from white to pale yellow in colour depending on the grade of material being offered. The yellow colouration is due to chelation of iron during the manufacturing process. |
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Bronopol is supplied as ]s or crystalline powder, which may vary from white to pale yellow in colour depending on the grade. The yellow coloration is due to chelation of iron during the manufacturing process. |
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<!-- Deleted image removed: ] --> |
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===Melting point=== |
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===Melting point=== |
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As a pure material, Bronopol has a ] of about 130°C. However due to its ] characteristics, Bronopol undergoes a ] rearrangement at 100 to 105°C and this can often be wrongly interpreted as the melting point. |
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As a pure material, bronopol has a ] of about 130 °C. However, due to its ] characteristics, bronopol undergoes a ] rearrangement at 100 to 105 °C and this can often be wrongly interpreted as the melting point. |
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At temperatures above 140°C Bronopol will decompose ]ally releasing ] and oxides of ]. |
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At temperatures above 140 °C, bronopol decomposes ]ally releasing ] and ]. |
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===Solubility=== |
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===Solubility=== |
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Bronopol is readily soluble in water although the dissolution process is ]. Solutions containing up to 28% w/v are possible at ]. |
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Bronopol is readily soluble in water; the dissolution process is ]. Solutions containing up to 28% w/v are possible at ]. |
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Bronopol is poorly soluble in non-polar ]s but shows a high affinity for polar organic solvents. |
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Bronopol is poorly soluble in non-polar ]s but shows a high affinity for polar organic solvents. |
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{| border="1" cellpadding="5" |
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{| border="1" cellpadding="5" |
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|+ Solubilities at 22–25°C |
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|+ Solubilities at 22–25 °C |
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!Solvent!!%w/v |
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!Solvent!!%w/v |
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|align="center"|]||align="center"|28 |
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| align ="center"|]||align="center"|28 |
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|align="center"|]||align="center"|89 |
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| align ="center"|]||align="center"|89 |
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|align="center"|]||align="center"|56 |
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| align ="center"|]||align="center"|56 |
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|align="center"|]||align="center"|41 |
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| align ="center"|]||align="center"|41 |
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|align="center"|Liquid ]||align="center"|<0.5 |
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| align ="center"|]||align="center"|<0.5 |
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===Partition coefficient=== |
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===Partition coefficient=== |
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Study of the solubility data clearly shows that Bronopol has a high affinity for polar rather than non-polar environments. In two phase systems, Bronopol partitions preferentially into the polar (usually aqueous) phase. |
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Study of the solubility data shows that bronopol has a high affinity for polar rather than non-polar environments. In two-phase systems, bronopol partitions preferentially into the polar (usually aqueous) phase. |
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{| border="1" cellpadding="2" |
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{| border="1" cellpadding="2" |
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|+ Partition coefficients at 22–24°C |
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|+ Partition coefficients at 22–24 °C |
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!Solvent Combination!!Partition Co-efficient |
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!Solvent combination!!Partition coefficient |
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|align="center"|]/Water||align="center"|0.74 |
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| align ="center"|]/water||align="center"|0.74 |
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|align="center"|Liquid Paraffin/Water||align="center"|0.043 |
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| align ="center"|]/water||align="center"|0.043 |
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|align="center"|]/Water||align="center"|0.068 |
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| align ="center"|]/water||align="center"|0.068 |
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===Stability in aqueous solution=== |
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===Stability in aqueous solution=== |
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In aqueous solutions, Bronopol is most stable when the ] of the system is on the ] side of neutral. Temperature also has a significant effect on stability in alkaline systems. |
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In aqueous solutions, bronopol is most stable when the ] of the system is on the ] side of neutral. Temperature also has a significant effect on stability in alkaline systems. |
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===Degradation=== |
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===Degradation=== |
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When conditions are such that Bronopol decomposes in aqueous solution, very low levels of formaldehyde are produced. ''Liberated formaldehyde is not responsible for the biological activity associated with Bronopol''. |
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Under extreme alkaline conditions, bronopol decomposes in aqueous solution and very low levels of formaldehyde are produced.<ref>{{cite web | url = https://www.medscape.com/viewarticle/725087_8 | title = Allergic Contact Dermatitis: Topical Preservatives, Part I |website=Medscape.com}}</ref> Liberated formaldehyde is not responsible for the biological activity associated with bronopol. Other decomposition products detected after bronopol breakdown are ], ], bromonitroethanol and 2-hydroxymethyl-2-nitropropane-1,3-diol. |
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==Allergy== |
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Amongst other decomposition products detected after Bronopol breakdown are, bromide ion, nitrite ion, Bromonitroethanol and 2-Hydroxymethyl-2-nitropropane-1,3-diol. |
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]]] |
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In 2005–2006, it was the 15th-most-prevalent ] in ]s (3.4%) of people with suspected allergic contact dermatitis.<ref>{{cite journal|last1=Zug|first1=KA|last2=Warshaw|first2=EM|last3=Fowler|first3=JF Jr|last4=Maibach|first4=HI|last5=Belsito|first5=DL|last6=Pratt|first6=MD|last7=Sasseville|first7=D|last8=Storrs|first8=FJ|last9=Taylor|first9=JS|last10=Mathias|first10=CG|last11=Deleo|first11=VA|last12=Rietschel|first12=RL|last13=Marks|first13=J|title=Patch-test results of the North American Contact Dermatitis Group 2005-2006.|journal=Dermatitis: Contact, Atopic, Occupational, Drug|date=2009|volume=20|issue=3|pages=149–60|pmid=19470301|doi=10.2310/6620.2009.08097|s2cid=24088485}}</ref> It is used as a substitute for formaldehyde, a disinfectant and preservative, in solvents. It is prevalent in skin and personal care products and topical medications.<ref>{{cite web|url=https://www.smartpractice.com/dermatologyallergy/pdfs/allergens/Bronopol-Patient-Info.pdf|title=T.R.U.E. Test: 2-BROMO-2-NITROPROPANE-1,3-DIOL (BRONOPOL)|website=Smartpractice.com|access-date=17 March 2022|archive-date=15 February 2022|archive-url=https://web.archive.org/web/20220215175011/https://www.smartpractice.com/dermatologyallergy/pdfs/allergens/Bronopol-Patient-Info.pdf|url-status=dead}}</ref> |
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==See also== |
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==See also== |
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==References== |
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==References== |
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{{Reflist}} |
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==External links== |
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