Part 1: The Evolution of Hydrogen Peroxide
Hydrogen peroxide was first discovered by Louis‐Jacques Thenard in the early 1800s. Thenard was a leading scientist in France at the time and described the chemical as “oxidizing water”. Developing methods to generate hydrogen peroxide, purifying it and experimenting with it showed that it had many interesting characteristics, in particular it was very reactive. He described various experiments using hydrogen peroxide in both its liquid and gas form, noting that it was very similar to water and upon heating it made a gas. He recommended the use of hydrogen peroxide for two particular applications: as a medicine (directly on the skin) and to restore old paintings (due to its cleaning ability).
During the late 1800s many industrialists discovered ways to generate large volumes of liquid hydrogen peroxide. This was to meet the growing demand for the chemical for various industrial applications such as bleaching textiles, making other chemicals, and even at high concentrations as a fuel or explosive. These various uses highlights how different the uses of hydrogen peroxide can be, varying from use at safe low concentrations to use of very dangerous high concentrations, greater than 60% in water.
Soon after its chemical discovery, it did not take long for its medical use to be appreciated. Probably the true pioneer in the medical use of hydrogen peroxide was Sir Benjamin Ward Richardson. He was a leading scientist of his time in Great Britain in his own right, but was also a student, friend and colleague of John Snow.
Snow is considered not only one of the leading founders of modern anesthesiology but is also one of the fathers of epidemiology. He was famous for linking an outbreak of cholera in London to water in a certain pump. It is interesting to note that this occurred prior to a true understanding of microbiology, and that such diseases were actually due to microorganisms. It is said he would only drink boiled water, which in London at the time was probably a smart idea.
Richardson continued his research in anesthesia and recommended the use of a new chemical, hydrogen peroxide, as an antiseptic. An antiseptic can be defined as a disinfectant used on the skin or mucous membranes. He noted advantages of healing wound infections (again unknown at the time to be due to microorganisms). This was first reported in 1856, but note that others such as DeSondalo also recommended the use of hydrogen peroxide as an aerosol or gas to refresh the air – again due to its potent activity against microorganisms and even neutralizing certain odorous chemical compounds.
It was around this same time that a revolution took place in our understanding of microorganisms and their impact on health. The prevailing theory of the time, often ascribed to the Greek philosopher Aristotle (384‐322 BC), was that ‘life’ arose spontaneously from inanimate matter or nonliving substances. However, as in most scientific areas, this was not accepted by all.
As far back as 1676 a Dutch man, Anton van Leeuwenhoek, described microscopic examinations which he referred to as “animalcules” or little animals. Interestingly they came in various shapes and sizes, and moved around. He even described that he could stop their movements by adding vinegar and pepper. Van Leeuwenhoek is often considered the true father of modern microbiology but may also be the first to have begun to understand the nature of disinfection.
Another example was in 1693, when Edmund King described similar experiments and in particular disinfection activity. But it was not until the various experiments and observations by the French man, Louis Pasteur, who claimed a remarkable conclusion at the time: omne vivum ex vivo, all life [is] from life. This was the first statement of the germ theory. Pasteur had a remarkable impact on human health, not only on our understanding of the causes of infectious diseases but also their prevention, for example the demonstration of immunization (first vaccines for rabies and anthrax) and the disinfection of liquids (the heat process bearing his name, pasteurization).
The combination of these events lead to the widespread use of liquid hydrogen peroxide for many therapeutic applications. Two important uses were for wounds and to treat diphtheria. Marchand at the time was a leading supplier of “peroxide of hydrogen” in the USA. In addition to antiseptic applications, its use expanded to general surface disinfection, cleaning, air fumigation, preservation and even as an internal drug (being given orally as a tonic). Hydrogen peroxide and other similar chemicals such as iodine, chlorine and even silver became widely used medically to prevent and treat infectious diseases.
The Antibiotic Era
During the early 1900s our understanding of microbiology developed and we learned how to grow and examine microorganisms in more detail. The emphasis was particularly on bacteria and their spores forms. In this time there were many detailed studies on hydrogen peroxide with mixed results. It appeared that the use of hydrogen peroxide could vary considerably and there was much debate on its true effects. Much of this can now be explained by the test methods used at the time and the many variables that could interfere with achieving reproducible results, such as the liquid hydrogen peroxide concentration, purity, exposure times, types (and amounts) of bacteria tested, etc. But during this time a new class of chemicals were identified that killed bacteria: antibiotics.
Although discovered years earlier, penicillin was first widely used during the Second World War (1939‐1945). Its impact was huge in the treatment of common bacterial infections. Fleming was recognized by sharing the 1945 Nobel Prize in the Physiology of Medicine with two others (Florey and Chain). Many considered that antibiotics made bacterial infections a worry of the past and the use of more traditional actives such as hydrogen peroxide declined. What was not realized at the time was the emergence of antibiotic resistance in bacteria, something we still continue to underestimate today.
Resurgence In Interest
In the meantime, the industrial applications of hydrogen peroxide grew. New methods of production, such as electrochemical, gave us pure and stable preparations (typically ranging from 3‐90%, depending on the application). Research continued on its chemical and biological activity; Schumb and colleagues at MIT, for example, consolidated a lot of the chemical work in the 1950s. Hydrogen peroxide was found naturally in cells, being referred to as nature’s own disinfectant/preservative. For medical and food applications, it continued to be used for antiseptic, disinfectant and even sterilization applications. In the USA in 1979 it was designated as being ‘generally regarded as safe’ for food applications. Hydrogen peroxide’s ability to inactivate microorganisms combined with the fact that it breaks down into safe by‐products (water and oxygen) made it an attractive disinfectant for many applications.
Let’s review liquid hydrogen peroxide from a chemical point of view. The chemical formula is very simple: H202. The natural decomposition products are water (H2O) and oxygen (O2). It is a clear water‐like liquid which has little to no odor. It is effective as a powerful oxidizing agent, destabilizing any molecule it can react with such as those that make up microorganisms.
For this reason hydrogen peroxide is an effective antimicrobial (often referred to in the class of ‘biocides’). In general, for medical applications hydrogen peroxide is provided in the 0.1‐60% range in water or as a mixture with other chemicals. Within this range, hydrogen peroxide actually has limited antimicrobial activity at concentrations <6% (requiring longer exposure times) but at high concentrations hydrogen peroxide can be more damaging to surfaces. As you go higher in concentrations hydrogen peroxide also becomes more dangerous to handle. Achieving the perfect balance, optimum activity with limited negative material effects, can be difficult. It is considered one of the safer biocides, environmentally, as it rapidly breaks down in the environment.
Hydrogen Peroxide (Liquid):
The advantages and disadvantages of hydrogen peroxide, and our understanding of them, have not changed much since the 1950s. It is certainly an effective antimicrobial but microbicidal activity is very dependent on its concentration. It is generally regarded as safe for food contact, but it is important to note that no chemical is completely safe and some are safer than others. Many of hydrogen peroxide’s safe advantages often become disadvantages at higher concentrations. As an ‘oxidizer’ it can aid in cleaning, for example when mixed with other chemicals it is used for whitening fabrics without the negative of bleaching. Hydrogen peroxide can also be safe on surfaces depending on its concentration.
Some key disadvantages are slow activity against tougher microorganisms (depending on its concentration) and that it can be inactivated by contact with certain surface materials, for example paper as it is made of cellulose, and soils such as blood.
In recent years our understanding of how to optimize the advantages while minimizing the disadvantages of hydrogen peroxide has improved. The optimizations can be considered under two types: liquid and gas applications. In liquid applications hydrogen peroxide can be combined with other chemicals that enhance or improve its activity while protecting the surface from damage. This is referred to as “formulation” and has been one area of improvement. For example, different types of surface disinfectant formulations have been developed with rapid activity against microorganisms and for use for different disinfection applications, including flexible endoscopes, as alternatives to traditional aldehyde‐based disinfectants. An example is a formulation that only contains 2% hydrogen peroxide but is overall enhanced in activity with other chemicals.
Another application is by turning liquid hydrogen peroxide into a gas. It was shown that hydrogen peroxide in gas form was much more effective than liquid and could be used at much lower concentrations.
If we consider the physical chemistry of hydrogen peroxide, it is very similar to water and can take three different forms: a solid (ice), a liquid and a gas. Note that steam (or water gas) is invisible and is only visible when it starts to get cooler and return to a liquid….what we actually see is a mixture of gas and liquid together. This is also the same for hydrogen peroxide in gas form.
Water and hydrogen peroxide both prefer to be in liquid form; when in the gas form they are also referred to as “vapors”. Remember, the gas (or vapor) can be in a pure gas form or can be a mixture of a gas/liquid. Other terms for this form can be aerosol, condensed, saturated or wet gas. Water and hydrogen peroxide are similar but different at the point at which they form a solid, liquid, or gas depending on temperature, pressure and the concentration (or volume) of the chemical.
This is another way of thinking about the different forms hydrogen peroxide can take and introduces some new terms, such as freezing, evaporation and condensation. You will see from the image on the right that the gas returns to a liquid by condensation. You will also see that in addition to the three phases, we learn another term: Plasma. It is the fourth form of matter and is achieved by adding even more energy to gas to cause it to break apart or ionize. Plasma is very reactive and very short lived; it can only be maintained, in this case, by continually adding energy under specific conditions.
Hydrogen Peroxide Gas
So let’s look at how hydrogen peroxide gas is made. Liquid hydrogen peroxide in water is heated to give a gas of hydrogen peroxide and water. The temperature becomes important, as the temperature will determine how much hydrogen peroxide/water can stay in a gas form without condensation. When in a gas form, hydrogen peroxide is typically used in the 0.1 mg to 10 mg/L range, which is actually very low but also very effective against microorganisms including bacterial spores.
To compare efficacy of gaseous hydrogen peroxide, understand that at 1mg/L hydrogen peroxide gas can kill 1 log of bacterial spores in about 1 minute (this time is called the D‐value). As the concentration increases the microbicidal activity increases as well (e.g., the D‐valve at 10mg/L is a few seconds). Hydrogen peroxide gas breaks down over time and on reaction with various surfaces turning into water and oxygen.
Forming Condensed Gas
So overall, hydrogen peroxide can be used in liquid form, gas (or vapor) form but also as a condensed gas. While the gas form is essentially ‘dry’ the condensed gas form is considered ‘wet’. That’s enough chemistry for now…