Bronopol
Encyclopedia
Bronopol is a highly active antimicrobial
chemical compound whose chemical formula
is 2-bromo-2-nitropropane-1,3-diol.
Bronopol was invented by The Boots Company PLC, Nottingham, England in the early 1960s and first applications were as a preservative
for pharmaceuticals. Bronopol's low mammal
ian toxicity
(at in-use levels) and exceptional activity against bacteria
(especially the troublesome Gram-negative
species) ensured that it became popular as a preservative in many consumer products such as shampoo
s and cosmetics
.
Bronopol was subsequently taken up as an effective antimicrobial in many industrial environments such as paper mill
s, oil exploration
and production facilities, as well as cooling water disinfection plants.
World production soared from the tens of ton
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 China
.
Pharmaceutical products containing Bronopol are registered in a number of countries and Bronopol is the subject of a specific monograph
in the British Pharmacopoeia
1998.
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 recognized potential for nitrosamine
formation.
from various foodstuffs, many nitrosamines are known or suspect carcinogen
s and therefore should be avoided in manufactured goods.
Nitrosamines are relatively easily produced from secondary amine
s and amide
s in the presence of nitrite
ion
s (this is why they are formed in-vivo from foodstuffs).
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 thes 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.
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.
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 will decompose exothermic
ally releasing Hydrogen bromide
and oxides of Nitrogen
.
. Solutions containing up to 28% w/v are possible at ambient temperature.
Bronopol is poorly soluble in non-polar solvent
s but shows a high affinity for polar organic solvents.
of the system is on the acid
side of neutral. Temperature also has a significant effect on stability in alkaline systems.
Amongst other decomposition products detected after Bronopol breakdown are, bromide ion, nitrite ion, Bromonitroethanol and 2-Hydroxymethyl-2-nitropropane-1,3-diol.
Antimicrobial
An anti-microbial is a substance that kills or inhibits the growth of microorganisms such as bacteria, fungi, or protozoans. Antimicrobial drugs either kill microbes or prevent the growth of microbes...
chemical compound whose chemical formula
Chemical formula
A chemical formula or molecular formula is a way of expressing information about the atoms that constitute a particular chemical compound....
is 2-bromo-2-nitropropane-1,3-diol.
Bronopol was invented by The Boots Company PLC, Nottingham, England in the early 1960s and first applications were as a preservative
Preservative
A preservative is a naturally occurring or synthetically produced substance that is added to products such as foods, pharmaceuticals, paints, biological samples, wood, etc. to prevent decomposition by microbial growth or by undesirable chemical changes....
for pharmaceuticals. Bronopol's low mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
ian toxicity
Toxicity
Toxicity is the degree to which a substance can damage a living or non-living organisms. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a substructure of the organism, such as a cell or an organ , such as the liver...
(at in-use levels) and exceptional activity against bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
(especially the troublesome Gram-negative
Gram-negative
Gram-negative bacteria are bacteria that do not retain crystal violet dye in the Gram staining protocol. In a Gram stain test, a counterstain is added after the crystal violet, coloring all Gram-negative bacteria with a red or pink color...
species) ensured that it became popular as a preservative in many consumer products such as shampoo
Shampoo
Shampoo is a hair care product used for the removal of oils, dirt, skin particles, dandruff, environmental pollutants and other contaminant particles that gradually build up in hair...
s and cosmetics
Cosmetics
Cosmetics are substances used to enhance the appearance or odor of the human body. Cosmetics include skin-care creams, lotions, powders, perfumes, lipsticks, fingernail and toe nail polish, eye and facial makeup, towelettes, permanent waves, colored contact lenses, hair colors, hair sprays and...
.
Bronopol was subsequently taken up as an effective antimicrobial in many industrial environments such as paper mill
Paper mill
A paper mill is a factory devoted to making paper from vegetable fibres such as wood pulp, old rags and other ingredients using a Fourdrinier machine or other type of paper machine.- History :...
s, oil exploration
Oil exploration
Hydrocarbon exploration is the search by petroleum geologists and geophysicists for hydrocarbon deposits beneath the Earth's surface, such as oil and natural gas...
and production facilities, as well as cooling water disinfection plants.
World production soared from the tens of ton
Ton
The ton is a unit of measure. It has a long history and has acquired a number of meanings and uses over the years. It is used principally as a unit of weight, and as a unit of volume. It can also be used as a measure of energy, for truck classification, or as a colloquial term.It is derived from...
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 China
China
Chinese civilization may refer to:* China for more general discussion of the country.* Chinese culture* Greater China, the transnational community of ethnic Chinese.* History of China* Sinosphere, the area historically affected by Chinese culture...
.
Pharmaceutical products containing Bronopol are registered in a number of countries and Bronopol is the subject of a specific monograph
Monograph
A monograph is a work of writing upon a single subject, usually by a single author.It is often a scholarly essay or learned treatise, and may be released in the manner of a book or journal article. It is by definition a single document that forms a complete text in itself...
in the British Pharmacopoeia
British Pharmacopoeia
The British Pharmacopoeia is an annual published collection of quality standards for UK medicinal substances. It is used by individuals and organizations involved in pharmaceutical research, development, manufacture and testing....
1998.
Applications
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 slimeBiofilm
A biofilm is an aggregate of microorganisms in which cells adhere to each other on a surface. These adherent cells are frequently embedded within a self-produced matrix of extracellular polymeric substance...
and corrosion
Corrosion
Corrosion is the disintegration of an engineered material into its constituent atoms due to chemical reactions with its surroundings. In the most common use of the word, this means electrochemical oxidation of metals in reaction with an oxidant such as oxygen...
problems - in many of these systems Bronopol can be a highly effective treatment).
The use of Bronopol in personal care products (cosmetics
Cosmetics
Cosmetics are substances used to enhance the appearance or odor of the human body. Cosmetics include skin-care creams, lotions, powders, perfumes, lipsticks, fingernail and toe nail polish, eye and facial makeup, towelettes, permanent waves, colored contact lenses, hair colors, hair sprays and...
, toiletries) has declined since the late 1980s due to the recognized potential for nitrosamine
Nitrosamine
Nitrosamines are chemical compounds of the chemical structure R1N-N=O, some of which are carcinogenic.-Usages:Nitrosamines are used in manufacture of some cosmetics, pesticides, and in most rubber products. -Occurrences:...
formation.
The Nitrosamine Problem
Although fairly ubiquitous in our diet and the environment, and even produced within the stomachStomach
The stomach is a muscular, hollow, dilated part of the alimentary canal which functions as an important organ of the digestive tract in some animals, including vertebrates, echinoderms, insects , and molluscs. It is involved in the second phase of digestion, following mastication .The stomach is...
from various foodstuffs, many nitrosamines are known or suspect carcinogen
Carcinogen
A carcinogen is any substance, radionuclide, or radiation that is an agent directly involved in causing cancer. This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes...
s and therefore should be avoided in manufactured goods.
Nitrosamines are relatively easily produced from secondary amine
Amine
Amines are organic compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group. Important amines include amino acids, biogenic amines,...
s and amide
Amide
In chemistry, an amide is an organic compound that contains the functional group consisting of a carbonyl group linked to a nitrogen atom . The term refers both to a class of compounds and a functional group within those compounds. The term amide also refers to deprotonated form of ammonia or an...
s in the presence of nitrite
Nitrite
The nitrite ion has the chemical formula NO2−. The anion is symmetric with equal N-O bond lengths and a O-N-O bond angle of ca. 120°. On protonation the unstable weak acid nitrous acid is produced. Nitrite can be oxidised or reduced, with product somewhat dependent on the oxidizing/reducing agent...
ion
Ion
An ion is an atom or molecule in which the total number of electrons is not equal to the total number of protons, giving it a net positive or negative electrical charge. The name was given by physicist Michael Faraday for the substances that allow a current to pass between electrodes in a...
s (this is why they are formed in-vivo from foodstuffs).
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 thes 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.
Appearance
Bronopol is supplied as crystalCrystal
A crystal or crystalline solid is a solid material whose constituent atoms, molecules, or ions are arranged in an orderly repeating pattern extending in all three spatial dimensions. The scientific study of crystals and crystal formation is known as crystallography...
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.
Melting point
As a pure material, Bronopol has a melting pointMelting point
The melting point of a solid is the temperature at which it changes state from solid to liquid. At the melting point the solid and liquid phase exist in equilibrium. The melting point of a substance depends on pressure and is usually specified at standard atmospheric pressure...
of about 130°C. However due to its polymorphic
Polymorphism (materials science)
Polymorphism in materials science is the ability of a solid material to exist in more than one form or crystal structure. Polymorphism can potentially be found in any crystalline material including polymers, minerals, and metals, and is related to allotropy, which refers to chemical elements...
characteristics, Bronopol undergoes a lattice
Crystal structure
In mineralogy and crystallography, crystal structure is a unique arrangement of atoms or molecules in a crystalline liquid or solid. A crystal structure is composed of a pattern, a set of atoms arranged in a particular way, and a lattice exhibiting long-range order and symmetry...
rearrangement at 100 to 105°C and this can often be wrongly interpreted as the melting point.
At temperatures above 140°C Bronopol will decompose exothermic
Exothermic
In thermodynamics, the term exothermic describes a process or reaction that releases energy from the system, usually in the form of heat, but also in the form of light , electricity , or sound...
ally releasing Hydrogen bromide
Hydrogen bromide
Hydrogen bromide is the diatomic molecule HBr. HBr is a gas at standard conditions. Hydrobromic acid forms upon dissolving HBr in water. Conversely, HBr can be liberated from hydrobromic acid solutions with the addition of a dehydration agent, but not by distillation. Hydrogen bromide and...
and oxides of Nitrogen
Nitrogen
Nitrogen is a chemical element that has the symbol N, atomic number of 7 and atomic mass 14.00674 u. Elemental nitrogen is a colorless, odorless, tasteless, and mostly inert diatomic gas at standard conditions, constituting 78.08% by volume of Earth's atmosphere...
.
Solubility
Bronopol is readily soluble in water although the dissolution process is endothermicEndothermic
In thermodynamics, the word endothermic describes a process or reaction in which the system absorbs energy from the surroundings in the form of heat. Its etymology stems from the prefix endo- and the Greek word thermasi,...
. Solutions containing up to 28% w/v are possible at ambient temperature.
Bronopol is poorly soluble in non-polar solvent
Solvent
A solvent is a liquid, solid, or gas that dissolves another solid, liquid, or gaseous solute, resulting in a solution that is soluble in a certain volume of solvent at a specified temperature...
s but shows a high affinity for polar organic solvents.
| Solvent | %w/v |
|---|---|
| Water Water Water is a chemical substance with the chemical formula H2O. A water molecule contains one oxygen and two hydrogen atoms connected by covalent bonds. Water is a liquid at ambient conditions, but it often co-exists on Earth with its solid state, ice, and gaseous state . Water also exists in a... |
28 |
| Methanol Methanol Methanol, also known as methyl alcohol, wood alcohol, wood naphtha or wood spirits, is a chemical with the formula CH3OH . It is the simplest alcohol, and is a light, volatile, colorless, flammable liquid with a distinctive odor very similar to, but slightly sweeter than, ethanol... |
89 |
| Ethanol Ethanol Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a... |
56 |
| Isopropanol | 41 |
| Liquid Paraffin Paraffin In chemistry, paraffin is a term that can be used synonymously with "alkane", indicating hydrocarbons with the general formula CnH2n+2. Paraffin wax refers to a mixture of alkanes that falls within the 20 ≤ n ≤ 40 range; they are found in the solid state at room temperature and begin to enter the... |
<0.5 |
Partition coefficient
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.| Solvent Combination | Partition Co-efficient |
|---|---|
| Hexanol 1-Hexanol 1-Hexanol is an organic alcohol with a six-carbon chain and a condensed structural formula of CH35OH. This colorless liquid is slightly soluble in water, but miscible with ether and ethanol. Two additional straight chain isomers of 1-hexanol, 2-hexanol and 3-hexanol, exist, both of which... /Water |
0.74 |
| Liquid Paraffin/Water | 0.043 |
| Chloroform Chloroform Chloroform is an organic compound with formula CHCl3. It is one of the four chloromethanes. The colorless, sweet-smelling, dense liquid is a trihalomethane, and is considered somewhat hazardous... /Water |
0.068 |
Stability in aqueous solution
In aqueous solutions, Bronopol is most stable when the pHPH
In chemistry, pH is a measure of the acidity or basicity of an aqueous solution. Pure water is said to be neutral, with a pH close to 7.0 at . Solutions with a pH less than 7 are said to be acidic and solutions with a pH greater than 7 are basic or alkaline...
of the system is on the acid
Acid
An acid is a substance which reacts with a base. Commonly, acids can be identified as tasting sour, reacting with metals such as calcium, and bases like sodium carbonate. Aqueous acids have a pH of less than 7, where an acid of lower pH is typically stronger, and turn blue litmus paper red...
side of neutral. Temperature also has a significant effect on stability in alkaline systems.
Degradation
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.Amongst other decomposition products detected after Bronopol breakdown are, bromide ion, nitrite ion, Bromonitroethanol and 2-Hydroxymethyl-2-nitropropane-1,3-diol.