Bronopol (2-Bromo-2-Nitropropane-1,3-Diol)  is a chemical compound, Bromine nitrate and consists of:

• Hydrogen (H): 6 atoms, 40.0% mol, 3.024% mass
• Oxygen (O): 4 atoms, 26.7% mol, 32.00% mass 
• Carbon (C): 3 atoms, 20.0% mol, 18.02% mass
• Nitrogen (N): 1 atom, 6.67% mol, 7.004% mass
• Bromine (Br): 1 atom, 6.67% mol, 39.95% mass

The name defines the structure of the molecule:

• 2-Bromo: indicates the presence of a bromine atom attached to the second carbon atom in the molecule.
• 2-Nitro: indicates the presence of a nitro (-NO2) group attached to the second carbon atom in the molecule.
• Propane-1,3-Diol:  is the base molecule, a propane molecule (a three-carbon alkane) with hydroxyl groups (-OH, which indicates the presence of alcohol) attached to the first and third carbon atoms.

The synthesis process takes place in several stages:

• Preparation of nitromethane and propylene oxide. These are the two main reagents used in the synthesis of Bronopol. Nitromethane is typically produced from propane, while propylene oxide can be produced from propylene.
• Reaction of nitromethane and propylene oxide. The two reagents are fed into a reaction vessel. The reaction is exothermic, that is, it releases heat and generally occurs at high temperatures and under pressure.
• Addition of bromo. After the initial reaction, bromine is added to the reaction mixture. This involves bromination of the product, forming 2-Bromo-2-Nitropropane-1,3-Diol.
• Purification. The reaction mixture is purified to isolate Bronopol and this phase includes treatments such as crystallization, filtration and drying.
• Quality control test. The final product is tested to ensure it meets the required specifications. This may involve testing for purity, moisture content and other physical and chemical properties

It occurs as a fine white powder, easily soluble in water, alcohol, propylene glycol, ethyl acetate, slightly soluble in oil and insoluble in acetone and chloroform. Stable under acidic conditions. When the aqueous solution is alkaline, it decomposes slowly and cannot be used with certain metals such as aluminium. It releases formaldehyde. This study found that the decompodsition process producing formaldehyde mainly depends on temperature and pH. Notably, the pH of the Bronopol-diluted buffer solution was the factor most influencing the release of formaldehyde. The release was markedly higher in alkaline buffer compared with acidic buffer. (Kajimura, K., Tagami, T., Yamamoto, T., & Iwagami, S. (2008). The release of formaldehyde upon decomposition of 2-bromo-2-nitropropan-1, 3-diol (bronopol). Journal of health science, 54(4), 488-492.)

What it is used for and where

Cosmetics

It is a restricted ingredient V/21 as a Relevant Item in the Annexes of the European Cosmetics Regulation 1223/2009. This study warns of: "Actual formaldehyde levels from formaldehyde releasers were analysed using a modified HPLC method: Doi et al. detected > 30 mg/kg (> 30 ppm) in 83 of 89 cosmetic product samples containing different FRs, and > 250 ppm in 44/89 samples (3). As summarised in a review by de Groot et al. “… all releasers (with the exception of 2-bromo-2-nitropropane-1,3-diol, for which adequate data are lacking) can, in the right circumstances of concentration and product composition, release >200 ppm formaldehyde, which may result in allergic contact dermatitis.”(Bernauer, U., Bodin, L., Chaudhry, Q., Coenraads, P.J., Dusinska, M., Ezendam, J., Gaffet, E., Galli, C.L., Granum, B.B., Panteri, E. and Rogiers, V., 2021. SCCS SCIENTIFIC ADVICE ON on the threshold for the warning ‘contains formaldehyde’in Annex V, preamble point 2 for formaldehyde-releasing substances-SCCS/1632/21–Scientific advice.)

Preservative. Any product containing organic, inorganic compounds, water, needs to be preserved from microbial contamination. Preservatives act against the development of harmful microorganisms and against oxidation of the product.

First synthesised in 1897, since 1980 it has been used as an antibacterial and antifungal agent to prevent the growth and reproduction of bacteria in personal care products and as a broad-spectrum antibiofilm agent particularly in leave-on and rinse-off shampoos, creams, lotions, rinses and eye make-up. It is added in the formulation of cosmetics such as shampoos, conditioners and creams in a sterilising concentration of 0.01% - 0.02%.

Medical

Since 1960, it has been a broad-spectrum antibacterial and antibiofilm agent and a promising candidate for the treatment of chronic wounds (1).

Other Uses

• Industrial water, plastic, wood: mould prevention, corrosion prevention, algae control as preservative and steriliser.
• Reference standard in ultra-performance liquid chromatography (UPLC) coupled to the coupled plasma mass spectrometry method.
• Inductively for the determination of bromine-containing preservatives from cosmetic products.
• In the agricultural sector against a wide range of plant pathogenic bacteria and is mainly used as a seed treatment agent as well as for the prevention and control of rice seedling diseases against bacterial blight caused by the cotton leaf spot pathogen.

Most significant studies

The aim of this study was to analyse the bacterial community in the production line of a calcium carbonate manufacturing company and to investigate possible causes of bacterial presence.  A formulation containing 7.5-15% (v v -1 ) bronopol 1.0-2.5% (v v v -1 ) (chloroisothiazolinone (CIT) + methylisothiazolinone (MIT)) proved to be most effective. Of the possible causes of bacterial presence, sporogenesis and absorption of the biocide to the carbonate particles are the least likely compared to bacterial absorption of the particles and the acquisition of biocide resistance (2).

In terms of allergy, however, according to data from the 2015 - 2016 Pediatric Contact Dermatitis Registry, the top 10 allergens for children (0-5 years) include nickel (42%), peru balsam (19%) (15%), neomycin (17%), formaldehyde (15%), cocamidopropyl betaine (15%), cobalt dichloride (14%), MCI / MI (12%), propylene glycol (9%), bacitracin, bronopol and wool alcohol (8%) (3).

In recent years, Bronopol (2-bromo-2-nitropropane-1,3-diol), a broad-spectrum biocide, has seen use as an effective and economically acceptable alternative in the treatment and control of Saprolegnia sp. a fungus of the family Saprolegniaceae (4), however, concerns are growing regarding its use within industry due to its acute toxicity to several fish species and its potentially harmful effects on human health (5).

Typical commercial product characteristics Bronopol

Appearance	White crystalline powder
Assay	99.0% – 101.0%
Boiling Point	358.0±42.0 °C at 760 mmHg
Melting Point	130-133°C
Flash Point	170.3±27.9°C
Density	2.0±0.1 g/cm3
pH	5.0-7.0
Impurity	<0.3%
Water	≤0.5%
Sulphated ash	≤0.1%
Water Solubility	25 g/100 mL (22ºC)
PSA	86.28000
LogP	1.72
Refraction Index	1.575
Vapor Pressure	0.0±1.8 mmHg at 25°C
Safety

• Molecular Formula    C₃H₆O₄BrN  C₃H₆BrNO₄
• Linear Formula  HOCH₂CBr(NO₂)CH₂OH
• Molecular Weight: 199.988 g/mol
• UNII: 6PU1E16C9W
• CAS   52-51-7  133248-96-1  179733-60-9  1135443-73-0
• EC Number: 200-143-0
• DSSTox Substance ID  
• IUPAC  2-bromo-2-nitropropane-1,3-diol
• InChI=1S/C3H6BrNO4/c4-3(1-6,2-7)5(8)9/h6-7H,1-2H2  
• InChl Key      LVDKZNITIUWNER-UHFFFAOYSA-N
• SMILES   C(C(CO)([N+](=O)[O-])Br)O
• MDL number  MFCD00007390
• PubChem Substance ID    329753983
• ChEBI  31306
• ICSC    0415
• Beilstein   1705868
• NSC   141021
• RTECS   TY3385000
• UN   3241
• RXCUI    1114345

Synonyms:

• Bronopol
• 2-Bromo-2-nitro-1,3-propanediol
• 2-Bromo-2-nitropropane-1,3-diol
• 2-Nitro-2-bromo-1,3-propanediol
• 2-bromo-2-nitro-propane-1,3-diol
• 2-bromanyl-2-nitro-propane-1,3-diol
• 1,3-Propanediol,2-bromo-2-nitro-
• .beta.-Bromo-.beta.-nitrotrimethyleneglycol
• Bronosol
• Bronocot
• Bronidiol
• Bronopolu
• beta-Bromo-beta-nitrotrimethyleneglycol
• Bronotak
• Onyxide 500
• Lexgard bronopol
• 1,3-Propanediol, 2-bromo-2-nitro-
• Bioban
• Myacide BT
• InChI=1/C3H6BrNO4/c4-3(1-6,2-7)5(8)9/h6-7H,1-2H2

References_________________________________________________________________

(1) Lee VE, O'Neill AJ. Potential for repurposing the personal care product preservatives bronopol and bronidox as broad-spectrum antibiofilm agents for topical application. J Antimicrob Chemother. 2019 Apr 1;74(4):907-911. doi: 10.1093/jac/dky520. 

(2) Odić D, Prah J, Avguštin G. Identification of bacterial contaminants from calcium carbonate filler production lines and an evaluation of biocide based decontamination procedures. Biofouling. 2017 Apr;33(4):327-335. doi: 10.1080/08927014.2017.1310848.

(3) Goldenberg A, Mousdicas N, Silverberg N, Powell D, Pelletier JL, Silverberg JI, Zippin J, Fonacier L, Tosti A, Lawley L, Wu Chang M, Scheman A, Kleiner G, Williams J, Watsky K, Dunnick CA, Frederickson R, Matiz C, Chaney K, Estes TS, Botto N, Draper M, Kircik L, Lugo-Somolinos A, Machler B, Jacob SE. Pediatric Contact Dermatitis Registry Inaugural Case Data. Dermatitis. 2016 Sep-Oct;27(5):293-302. doi: 10.1097/DER.0000000000000214. 

(4) Pottinger TG, Day JG. A Saprolegnia parasitica challenge system for rainbow trout: assessment of Pyceze as an anti-fungal agent for both fish and ova. Dis Aquat Organ. 1999 May 12;36(2):129-41. doi: 10.3354/dao036129.

(5) Piamsomboon P., Lukkana M., Wongtavatchai J. Safety and Toxicity Evaluation of Bronopol in Striped Catfish (Pangasianodon hypophthalmus) Thai. J. Vet. Med. 2013;43:477–481

Flores S, Montenegro I, Villena J, Cuellar M, Werner E, Godoy P, Madrid A. Synthesis and Evaluation of Novel Oxyalkylated Derivatives of 2',4'-Dihydroxychalcone as Anti-Oomycete Agents against Bronopol Resistant Strains of Saprolegnia sp. Int J Mol Sci. 2016 Aug 22;17(8):1366. doi: 10.3390/ijms17081366.