BRONOPOL

BRONOPOL

CAS Number: 52-51-7
Chemical formula: C3H6BrNO4
Molar mass: 199.988 g
EC Number: 200-143-0
UPAC name: 2-Bromo-2-nitropropane-1,3-diol

Bronopol (INN; chemical name 2-bromo-2-nitro-1,3-propanediol) is an organic compound that is used as an antimicrobial.
Bronopol is a white solid although commercial samples appear yellow.

The first reported synthesis of bronopol was in 1897.

Bronopol was invented by The Boots Company PLC in the early 1960s and first applications were as a preservative for pharmaceuticals.
Due to its low mammalian toxicity at in-use levels and high activity against bacteria, especially Gram-negative species, bronopol became popular as a preservative in many consumer products such as shampoos and cosmetics.
Bronopol was subsequently adopted as an antimicrobial in other industrial environments such as paper mills, oil exploration, and production facilities, as well as cooling water disinfection plants.

Production
Bronopol is produced by the bromination of di(hydroxymethyl)nitromethane, which is derived from nitromethane by a nitroaldol reaction.
World production increased from the tens of tonnes in the late 1970s to current estimates in excess of 5,000 tonnes. Manufacturing today is the business of low cost producers, mainly in China.

Applications
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 slime and corrosion problems - in many of these systems bronopol can be a highly effective treatment).

The use of bronopol in personal care products (cosmetics, toiletries) has declined since the late 1980s due to the potential formation of nitrosamines.
While bronopol is not in itself a nitrosating agent, under conditions where it decomposes (alkaline 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 10s of parts per billion).

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.

Bronopol has been restricted for use in cosmetics in Canada.

Physical and chemical properties
Appearance
Bronopol is supplied as crystals 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.

Melting point
As a pure material, bronopol has a melting point of about 130 °C. However, due to its polymorphic characteristics, bronopol undergoes a lattice rearrangement at 100 to 105 °C and this can often be wrongly interpreted as the melting point.

At temperatures above 140 °C, bronopol decomposes exothermically releasing hydrogen bromide and oxides of nitrogen.

Solubility
Bronopol is readily soluble in water; the dissolution process is endothermic. Solutions containing up to 28% w/v are possible at ambient temperature.

Bronopol is poorly soluble in non-polar solvents but shows a high affinity for polar organic solvents.

Partition coefficient
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.

Stability in aqueous solution
In aqueous solutions, bronopol is most stable when the pH of the system is on the acid side of neutral.
Temperature also has a significant effect on stability in alkaline systems.

Degradation
Under extreme alkaline conditions, bronopol decomposes in aqueous solution and very low levels of formaldehyde are produced.
Liberated formaldehyde is not responsible for the biological activity associated with bronopol.
Other decomposition products detected after bronopol breakdown are bromide ion, nitrite ion, bromonitroethanol and 2-hydroxymethyl-2-nitropropane-1,3-diol.

Biocidal Uses
Bronopol is being reviewed for use as a biocide in the EEA and/or Switzerland, for: disinfection, product preservation, preservation of fibres, leather, rubber, or polymers, preservation for liquid systems, controlling slimes, embalming or taxidermy.

Consumer Uses
Bronopol is used in the following products: cosmetics and personal care products, perfumes and fragrances, fertilisers and plant protection products.
Other release to the environment of this substance is likely to occur from: outdoor use as processing aid and indoor use as processing aid.

Widespread uses by professional workers
Bronopol is used in the following products: perfumes and fragrances, cosmetics and personal care products, fertilisers, plant protection products and washing & cleaning products.
This substance is used in the following areas: agriculture, forestry and fishing and formulation of mixtures and/or re-packaging.
Other release to the environment of this substance is likely to occur from: indoor use as processing aid and outdoor use as processing aid.
Formulation or re-packing
Bronopol is used in the following products: laboratory chemicals, perfumes and fragrances, cosmetics and personal care products, biocides (e.g. disinfectants, pest control products), fertilisers, plant protection products and washing & cleaning products.
Release to the environment of this substance can occur from industrial use: formulation of mixtures and formulation in materials.

XLogP3-AA: -0.6
Hydrogen Bond Donor Count    : 2
Hydrogen Bond Acceptor Count: 4
Rotatable Bond Count: 2
Exact Mass: 198.94802
Monoisotopic Mass: 198.94802
Topological Polar Surface Area: 86.3 Ų
Heavy Atom Count: 9
Formal Charge: 0
Complexity: 107
Isotope Atom Count: 0
Defined Atom Stereocenter Count: 0
Undefined Atom Stereocenter Count: 0
Defined Bond Stereocenter Count: 0
Undefined Bond Stereocenter Count: 0
Covalently-Bonded Unit Count: 1
Compound Is Canonicalized: Yes

Bronopol, or 2-Bromo-2-nitro-1,3-propanediol, is an organic compound with wide-spectrum antimicrobial properties.
First synthesized in 1897, bronopol was primarily used as a preservative for pharmaceuticals and was registered in the United States in 1984 for use in industrial bactericides, slimicides and preservatives.
Bronopol is used as a microbicide or microbiostat in various commercial and industrial applications, including oil field systems, air washer systems, air conditioning or humidifying systems, cooling water systems, papermills, absorbent clays, metal working fluids, printing inks, paints, adhesives and consumer products.
Compared to other aliphatic halogen-nitro compounds, bronopol is more stable to hydrolysis in aqueous media under normal conditions.
The inhibitory activity against various bacteria, including Pseudomonas aeruginosa, was demonstrated in vitro.
The agent is largely available commercially as an antibacterial for a variety of industrial purposes while it is predominantly available for purchase as a pet animal litter antibacterial at the domestic consumer level.
Nevertheless, ongoing contemporary re-evaluations of bronopol use in large markets such as Canada now place various compositional and product restrictions on the use of the agent in cosmetic products and in other products where it may not primarily be used in the role of a non-medicinal preservative antimicrobial.

Bronopol is an antimicrobial agent commonly used as a preservative in many types of cosmetics, personal care products, and topical medications.
Bronopol is used as an anti-infective, an antimicrobial, fungicide, germicide, bactericide, slimicide, and a wood preservative.
Bronopol is reportedly very effective against grampositive and gram-negative bacteria, particularly Pseudomonas aeruginosa as well as against fungi and yeasts. This substance may release formaldehyde and cross-reacts with other formaldehyde-releasing substances.

Uses
Washing Detergents
Adhesives and Glues
Agricultural Chemicals
Cleaning Agents
Construction Materials
Cooling Lubricants
Filling Agents
Flooring Agents
Indicators and Reagents
Kitty Litter
Metal Working Fluids
Kitty Litter
Paints
Finger paints
Papermills
Pesticides
Polishes
Printing Inks
Preservatives
Biocide
Toiletries and Cosmetics
Blushers
Cleansing lotions
Creams
Eyebrow pencils
Formaldehyde releaser
Foundations
Hair conditioners
Hair dressings
Humidifiers
Mascara
Moisturizers
Shampoos
Deodorants

Bronopol, or 2-Bromo-2-nitro-1,3-propanediol, is an organic compound with wide-spectrum antimicrobial properties.
First synthesized in 1897, bronopol was primarily used as a preservative for pharmaceuticals and was registered in the United States in 1984 for use in industrial bactericides, slimicides and preservatives.
Bronopol is used as a microbicide or microbiostat in various commercial and industrial applications, including oil field systems, air washer systems, air conditioning or humidifying systems, cooling water systems, papermills, absorbent clays, metal working fluids, printing inks, paints, adhesives and consumer products.
Compared to other aliphatic halogen-nitro compounds, bronopol is more stable to hydrolysis in aqueous media under normal conditions.
The inhibitory activity against various bacteria, including Pseudomonas aeruginosa, was demonstrated in vitro.
The agent is largely available commercially as an antibacterial for a variety of industrial purposes while it is predominantly available for purchase as a pet animal litter antibacterial at the domestic consumer level.
Nevertheless, ongoing contemporary re-evaluations of bronopol use in large markets such as Canada now place various compositional and product restrictions on the use of the agent in cosmetic products [L873] and in other products where it may not primarily be used in the role of a non-medicinal preservative antimicrobial

Bronopol as an active ingredient is registered as a commercial biocide and preservative in many industrial processes.
Registered biocidal uses include pulp and paper mills, water cooling towers, waste water treatment, evaporative condensers, heat exchangers, food pasteurizing plants, metalworking fluids, and oilfield applications.
In addition, preservative uses include household products (e.g., dishwashing liquids, laundry products), latex emulsions, polymer lattices, pigments, leather and milk samples for analysis.
Bronopol is also formulated into granular domestic end-use products in the form of cat litter

Pharmacodynamics
At concentrations of 12.5 to 50 μg/mL, bronopol mediated an inhibitory activity against various strains of Gram negative and positive bacteria in vitro.
The bactericidal activity is reported to be greater against Gram-negative bacteria than against Gram-positive cocci.
Bronopol was also demonstrated to be effective against various fungal species, but the inhibitory action is reported to be minimal compared to that of against bacterial species.
The inhibitory activity of bronopol decreases with increasing pH of the media.
Bronopol also elicits an anti-protozoal activity, as demonstrated with Ichthyophthirius multifiliis in vitro and in vivo.
It is proposed that bronopol affects the survival of all free-living stages of I. multifiliis 

Mechanism of action
It is proposed that bronopol generates biocide-induced bacteriostasis followed by a growth at an inhibited rate in bacteria, via two distinct reactions between bronopol and essential thiols within the bacterial cell.
Under aerobic conditions, bronopol catalyzes the oxidation of thiol groups, such as cysteine, to disulfides.
This reaction is accompanied by rapid consumption of oxygen, where oxygen acts as the final oxidant. During the conversion of cysteine to cystine, radical anion intermediates such as superoxide and peroxide are formed from bronopol to exert a direct bactericidal activity.
The oxidation of excess thiols alters the redox state to create anoxic conditions, leading to a second reaction involving the oxidation of intracellular thiols such as glutathione to its disulfide.
The resulting effects are inhibition of enzyme function, and reduced growth rate following the bacteriostatic period.
Under the anoxic conditions, the reaction between thiol and bronopol decelerates without the involvement of oxygen and the consumption of bronopol predominates.
Bronopol is ultimately removed from the reaction via consumption and resumption of bacterial growth occurs.

Metabolism
Bronopol undergoes degradation in aqueous medium to form bromonitroethanol from a retroaldol reaction with the liberation of an equimolar amount of formaldehyde.
Formaldehyde is a degradation product of bronopol, which may cause sensitization.
Bromonitroethanol further decomposes to formaldehyde and bromonitromethane.
Bromonitroethanol may also break down to release a nitrite ion and 2-bromoethanol.

Route of elimination
Metabolism studies indicate that bronopol is primarily excreted in the urine.
In rats, about 19% of dermally-applied bronopol was excreted in the urine, feces and expired air.
Following oral administration of 1 mg/kg radiolabelled bronopol in rats, approximately 81% and 6% of the administered radioactivity was recovered in the urine and expired air, respectively, within a period of 24 hours.
Following intravenous administration in rat, the recoveries in the urine and expired air were 74% and 9% of the dose, respectively 5.

Half-life
The half-life of bronopol in the biological systems is not reported in the literature.
The half-life value reported for bronopol reflects the environment fate of the compound.
When released into the air as vapours, bronopol is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals where the half life for this reaction is approximately 11 days.
The photolysis half-life is 24 hours in water but may be up to 2 days under natural sunlight

The presence of this ingredient on the List of Prohibited and Restricted Cosmetic Ingredients (the Cosmetic Ingredient Hotlist) indicates that there are potentially significant safety issues.
Bronopol cannot be used in topical natural health products except in accordance with the restrictions set out on the Hotlist unless additional evidence for safety is submitted.

Synonyms:
1,3-Propanediol, 2-bromo-2-nitro-
2-Bromo-2-nitro-1,3-propanediol
Bronopol
2-Bromo-2-nitropropan-1,3-diol
Onyxide 500
Bronocot
2-Nitro-2-bromo-1,3-propanediol
Bronidiol
Myacide AS
Nalco 92RU093
Canguard 409
BNPK
N 25
N 25 (antimicrobial)
Myacide BT
Bactrinol 100
Bioban
Myacide Pharma BP
Ultra-Fresh SAB
NSC 141021
BNPD
Pyceze
BE 6
BE 6 (bactericide)
Topcide 2520
2-Bromo-2-nitropropane-1,3-diol
Bronotak
Acticide L 30
Myacide AS Plus
Bioban BP Plus
Protectol BN 98
Protectol BN 99
Preventol P 100
Bactronol
Busan 1144
Bactrinashak
Bioban BP 40
Bioban BP 10
Protectol BN