Bronopol CAS 52-51-7
Introduction：Basic information about Bronopol CAS 52-51-7, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Bronopol Basic information
| Product Name: | Bronopol |
| Synonyms: | Bronopol 1g [52-51-7];Broken Ball;2-BroMo-2-nitropropane-1;3-diol (Bronopol);Bronopol(2-BroMo-2-nitro-1,3-propanedio1);2-BroMo-2-nitro-1,3-propanediol, 98% 25GR;Bronopol BNPD;Bronopol 0 |
| CAS: | 52-51-7 |
| MF: | C3H6BrNO4 |
| MW: | 199.99 |
| EINECS: | 200-143-0 |
| Product Categories: | Antibacterial agent;Antiseptic-water treatment-bactericide-Bronopol;Building Blocks;Chemical Synthesis;Organic Building Blocks;Oxygen Compounds;Polyols;CHEMICAL;Food additive;Biocide;water treatment agent;FUNGICIDE;Propanes/propenes;52-51-7 |
| Mol File: | 52-51-7.mol |
Bronopol Chemical Properties
| Melting point | 130-133 °C(lit.) |
| Boiling point | 358.0±42.0 °C(Predicted) |
| density | 2.0002 (rough estimate) |
| refractive index | 1.6200 (estimate) |
| Fp | 167°C |
| storage temp. | Inert atmosphere,Room Temperature |
| solubility | H2O: soluble100mg/mL, clear, colorless to faintly yellow |
| pka | 12.02±0.10(Predicted) |
| form | Crystals or Crystalline Powder |
| color | White to yellow |
| Odor | odorless |
| Water Solubility | 25 g/100 mL (22 ºC) |
| Merck | 14,1447 |
| BRN | 1705868 |
| Stability: | Stable. Hygroscopic. Incompatible with strong oxidizing agents, strong bases, strong reducing agents, acid chlorides and anhydrides, moisture. |
| Major Application | agriculture cleaning products cosmetics environmental food and beverages personal care |
| Cosmetics Ingredients Functions | PRESERVATIVE |
| Cosmetic Ingredient Review (CIR) | Bronopol (52-51-7) |
| InChI | 1S/C3H6BrNO4/c4-3(1-6,2-7)5(8)9/h6-7H,1-2H2 |
| InChIKey | LVDKZNITIUWNER-UHFFFAOYSA-N |
| SMILES | OCC(Br)(CO)[N+]([O-])=O |
| LogP | 1.150 (est) |
| CAS DataBase Reference | 52-51-7(CAS DataBase Reference) |
| NIST Chemistry Reference | Bronopol(52-51-7) |
| EPA Substance Registry System | Bronopol (52-51-7) |
Safety Information
| Hazard Codes | Xn,N |
| Risk Statements | 21/22-37/38-41-50 |
| Safety Statements | 26-37/39-61-36/37/39 |
| RIDADR | UN 3241 4.1/PG 3 |
| WGK Germany | 2 |
| RTECS | TY3385000 |
| F | 4.2-8-9-21 |
| TSCA | TSCA listed |
| HazardClass | 4.1 |
| PackingGroup | III |
| HS Code | 29055999 |
| Storage Class | 4.1B - Flammable solid hazardous materials |
| Hazard Classifications | Acute Tox. 4 Dermal Acute Tox. 4 Oral Aquatic Acute 1 Aquatic Chronic 1 Eye Dam. 1 Skin Irrit. 2 STOT SE 3 |
| Hazardous Substances Data | 52-51-7(Hazardous Substances Data) |
| Toxicity | LD50 in mice, rats (mg/kg): 350, 400 orally (Croshaw) |
| Description | Bronopol, a formaldehyde releaser, was reported as anallergen in dairy workers. In a recent case report,bronopol was contained in a lubricant jelly used forultrasound examination and caused contact dermatitisin a veterinary surgeon. |
| Chemical Properties | Bronopol is a white or almost white crystalline powder; odorless orwith a faint characteristic odor. |
| Originator | Bronosol,Green Cross,Japan,1977 |
| Uses | First synthesized in 1897, bronopol was primarily used as an effective preservative agent and possesses a wide spectrum of antibacterial activity and inhibits the growth of fungi and yeasts. It can be used in the formulation of a wide variety of cosmetic and personal care products, especially in leave-on and rinse-off shampoos, creams, lotions, rinses and eye makeup to protect the product integrity by preventing or slowing bacterial growth. Bronopol is used as a microbiocide/microbiostat in oil field systems, air washer systems, air conditioning/humidifying systems, cooling water systems, papermills, absorbent clays, metal working fluids, printing inks, paints, adhesives and consumer/institutional products. A formulating technical material is also registered. https://www.ulprospector.com https://www3.epa.gov |
| Uses | Bronopol has been used as reference standard in ultra performance liquid chromatography (UPLC) coupled to inductively coupled plasma mass spectrometry (UPLC-ICP-MS) method for determination of bromine containing preservatives from cosmetic products. |
| Definition | ChEBI: Bronopol is a nitro compound. |
| Production Methods | Bronopol is synthesized by the reaction of nitromethane withparaformaldehyde in an alkaline environment, followed bybromination. After crystallization, bronopol powder may be milledto produce a powder of the required fineness. |
| Manufacturing Process | A mixture of 441 g (3 mols) of calcium chloride dihydrate, 61 g (1 mol) ofnitromethane, 163 g (2 mols) of formalin (37% formaldehyde solution) and470 ml of water was cooled to 0°C and mixed with 5 g of calcium hydroxidewhile stirring. The temperature thereby rose to 30°C. As soon as thetemperature had fallen again, a further 32 g of calcium hydroxide (total of 0.5 mol) were added. The mixture was then cooled to 0°C and with intensivecooling and stirring, 159.8 g (1 mol, 51 ml) of bromine were dropped in at arate so that the temperature remained at around 0°C. After the addition wasended, the mixture was stirred for a further 2 hours, when the reactionproduct separated in crystalline form. The product was quickly filtered on asuction filter and the crystalline sludge obtained was taken up in 450 ml ofethylene chloride and dissolved at reflux. Then by addition of magnesiumsulfate, undissolved inorganic salts were separated and the solution wasslowly cooled whereby 140 g (70% yield) of 2-bromo-2-nitropropane-1,3-diolprecipitated in colorless crystals melting at 123°-124°C. |
| Therapeutic Function | Antiseptic |
| Biological Functions | Bronopol, 2-bromo-2-nitropropan-1,3-diol, is an aliphatic halogenonitro compound with potent antibacterial activity but limited activity against fungi(Guthrie, 1999).Its activity is reduced somewhat by 10% serum and to a greater extent by sulphydryl compounds, but is unaffected by 1% polysorbate or 0.1% lecithin. It has a half-life of about 96 daysat pH 8 and 25oC (Toler, 1985). Bronopol is most stable under acid conditons;the initial decomposition appears to involve the liberation of formaldehyde and the formulation of bromonitroethanol. A secondorder reaction involving bronopol and formaldehyde occurs simultaneously to produce 2-hydro-xymethyl-2-nitro-1,3-propanediol, which itself decomposes with the loss of formaldehyde. Bronopol has been employed extensively as a preservative for pharmaceuticalandcosmetic products.However, its use to preserve products containing secondary amines should be avoided as the by-product of this reaction is nitrosoamine which is carcinogenic. Details of the microbiological activity,chemical stability,toxicology and uses of bronopol are documented by Bryce et al. (1978),Croshaw & Holland (1984)，Toler (1985) and Rossmorc and Sondossi (1988). Dcnyer and Wallhausser (1990) have provided useful information about bronopol, the typical in-use concentration of which is 0.01-0.1% w/v. Sulphhydryl compounds act as appropriate neutralizers inpreservative efficacy tests. |
| General Description | White crystals. Ignite easily and burn readily. May detonate under strong shock. Decomposes when heated, evolving toxic gases. Toxic by skin absorption, inhalation or ingestion. |
| Air & Water Reactions | Highly flammable. Water soluble. |
| Reactivity Profile | Incompatible with strong oxidizing agents, strong bases, strong reducing agents, acid chlorides and acid anhydrides. 2-Bromo-2-nitro-1,3-propanediol is also incompatible with sulfhydryl compounds or with aluminum or iron containers (it is stable in contact with tin or stainless steel). |
| Hazard | Toxic by all routes of exposure; skin irritant. |
| Health Hazard | Fire may produce irritating and/or toxic gases. Contact may cause burns to skin and eyes. Contact with molten substance may cause severe burns to skin and eyes. Runoff from fire control may cause pollution. |
| Fire Hazard | Flammable/combustible material. May be ignited by friction, heat, sparks or flames. Some may burn rapidly with flare burning effect. Powders, dusts, shavings, borings, turnings or cuttings may explode or burn with explosive violence. Substance may be transported in a molten form at a temperature that may be above its flash point. May re-ignite after fire is extinguished. |
| Pharmaceutical Applications | Bronopol 0.01–0.1% w/v is used as an antimicrobial preservativeeither alone or in combination with other preservatives in topicalpharmaceutical formulations, cosmetics, and toiletries; the usualconcentration is 0.02% w/v. |
| Contact allergens | Bronopol is a preservative sometimes considered as a formaldehyde releaser. It was reported to be an allergen in cosmetics, cleaning agents, dairy workers, and a lubricant jelly used for ultrasound examination. https://www.smartpractice.com https://www.contactdermatitisinstitute.com |
| Safety Profile | Poison by ingestion, subcutaneous, intravenous, and intraperitoneal routes. Moderately toxic by skin contact. An eye and human skin irritant. An antiseptic. When heated to decomposition it emits very toxic fumes of NOx, and Br-. |
| Safety | Bronopol is used widely in topical pharmaceutical formulations andcosmetics as an antimicrobial preservative. Although bronopol has been reported to cause both irritant andhypersensitivity adverse reactions following topical use, it isgenerally regarded as a nonirritant and nonsensitizing material atconcentrations up to 0.1% w/v. At a concentration of 0.02% w/v,bronopol is frequently used as a preservative in ‘hypoallergenic’formulations. Animal toxicity studies have shown no evidence of phototoxicityor tumor occurrence when bronopol is applied to rodents topicallyor administered orally; and there is no in vitro or in vivo evidence ofmutagenicity; this is despite the demonstrated potential ofbronopol to liberate nitrite on decomposition, which in the presenceof certain amines may generate nitrosamines. Formation ofnitrosamines in formulations containing amines may be reducedby limiting the concentration of bronopol to 0.01% w/v andincluding an antioxidant such as 0.2% w/v alpha tocopherol or0.05% w/v butylated hydroxytoluene;(14) other inhibitor systemsmay also be appropriate. LD50 (dog, oral): 250 mg/kg LD50 (mouse, IP): 15.5 mg/kg LD50 (mouse, IV): 48 mg/kg LD50 (mouse, oral): 270 mg/kg LD50 (mouse, SC): 116 mg/kg LD50 (mouse, skin): 4.75 g/kg LD50 (rat, IP): 26 mg/kg LD50 (rat, IV): 37.4 mg/kg LD50 (rat, oral): 180 mg/kg LD50 (rat, SC): 170 mg/kg LD50 (rat, skin): 1.6 g/kg |
| storage | Bronopol is stable and its antimicrobial activity is practicallyunaffected when stored as a solid at room temperature and ambientrelative humidity for up to 2 years. The pH of a 1.0% w/v aqueous solution is 5.0–6.0 and fallsslowly during storage; solutions are more stable in acid conditions. Microbiological assay results indicate longer half-lives thanthose obtained by HPLC and thus suggest that degradationproducts may contribute to antimicrobial activity. Formaldehydeand nitrites are among the decomposition products, but formaldehydearises in such low concentrations that its antimicrobial effect isnot likely to be significant. On exposure to light, especially underalkaline conditions, solutions become yellow or brown-colored butthe degree of discoloration does not directly correlate with loss ofantimicrobial activity. The bulk material should be stored in a well-closed, nonaluminumcontainer protected from light, in a cool, dry place. |
| Incompatibilities | Sulfhydryl compounds cause significant reductions in the activity ofbronopol, and cysteine hydrochloride may be used as thedeactivating agent in preservative efficacy tests; lecithin/polysorbatecombinations are unsuitable for this purpose. Bronopol isincompatible with sodium thiosulfate, with sodium metabisulfite,and with amine oxide or protein hydrolysate surfactants. Owing toan incompatibility with aluminum, the use of aluminum in thepackaging of products that contain bronopol should be avoided. |
| Regulatory Status | Included in topical pharmaceutical formulations licensed in Europe.Included in the Canadian List of Acceptable Non-medicinalIngredients. |
| References | [1] Patent: WO2009/107133, 2009, A1. Location in patent: Page/Page column 22-24 |
Bronopol Preparation Products And Raw materials
| Raw materials | Methanol-->Diethyl ether-->Bromine-->Potassium hydroxide-->Formaldehyde-->Sodium Methoxide-->Nitromethane-->Dichloroethane-->1,3-Propanediol-->tribromonitromethane |
| Preparation Products | 2-Bromo-2-nitroethanol-->2,2-Dibromo-2-nitroethanol |
