1.    Overview of Ethylene Oxide

Ethylene oxide is an organic chemical compound with the chemical formula C₂H₄O. Strong ability to sterilization, and can kill bacteria (and spores), mold and fungi. No metal corrosion. No residual odor. Especially suitable to be used as a gaseous sterilizing agent for some items and materials that cannot tolerate high temperature disinfection.

Ethylene oxide was officially discovered in 1859, and had already been used as a disinfectant and sterilizing agent in industrial production by 1936. It is the second generation of chemical disinfectant after formaldehyde, and is the most important one among the current four low temperature sterilization technologies (i.e. low temperature plasma, low temperature formaldehyde steam, ethylene oxide and glutaraldehyde). Owing to its excellent penetrability, all kinds of packagings and product structures do not block it, and hence there will be no sterilization Dead Angle under effective verification.  

Ethylene oxide can not only be used as an independent sterilizing agent, but also as an intermediate to prepare a variety of chemicals. It is widely used in washing, pharmaceutical, printing and dyeing industries, and can be used as a starting agent of the detergents in chemical and relative industries.

However, owing to its reactivity, ethylene oxide can react with diverse compounds and participate in the addition reactions that result in ring-opening. It is flammable and explosive, inapplicable for long-distance transportation, and hence with a distinct regionality.

With a very strong penetration, ethylene oxide can lead to the non-specific alkylation of microbial protein, DNA and RNA active groups (such as carboxyl group, hydrogen group, thiamine and hydroxyl group), so that the normal biochemical reaction and metabolism would be blocked and the death of microorganisms would be caused.

2. Hazards of Ethylene Oxide

The International Agency for Research on Cancer (IARC) of World Health Organization published a preliminary compilation of the List of Carcinogens for reference on Oct 27, 2017. Ethylene oxide is in the list of Carcinogens I.

Ethylene oxide has a strong ability to sterilization, but the main side effect is that ethylene oxide itself is a carcinogen and can leave a residue. Long-term exposure to it can cause acute poisoning. Mild symptoms include headache, dizziness, nausea and vomiting. Severe symptoms range from hand and foot weakness, body muscle tremor to even coma. Ethylene oxide is a flammable, explosive and toxic gas, which volatilizes easily at room temperature. An explosion can be caused when its concentration is too high.

3. Regulatory Status

As a broad-spectrum sterilizing agent, ethylene oxide can kill a variety of microorganisms at room temperature. However, owing to the residues left in the sterilized products, many countries have eliminated the use of ethylene oxide in food fumigation. Germany even has zero tolerance that ethylene oxide used in food fumigation is prohibited as early as 1981. In 2017 Health Canada removed ethylene oxide from the List of Permitted Food Additives with Other Accepted Uses, and defined it as a fumigant pesticide to be regulated only under the Pesticides Act. When high levels of ethylene oxide residues in sesame seeds from India was detected in 2020, DGCCRF also took a zero tolerance policy to get 100% control over the samples involved. Disinfection Technical Specification 2002 of China clearly stipulates that ethylene oxide is not applicable in food sterilization.

Ethylene oxide is a toxic carcinogen. No need to be too panic if with little exposure or ingestion by accident. However, in order to control the risks of food safety, it is necessary for both the regulatory authorities and food manufacturers to detect and monitor ethylene oxide in foods. Here are the limits for ethylene oxide residuals by regions.

1）China

√ Per GB/T 22497-2008 standard, ethylene oxide is banned to be used in food processing. It can only be used as a fumigant to treat TCK wheat.

√ Per GB/T 16886.7-2015 standard, ethylene oxide can be used for sterilization in medical devices with the residue limits as follows.

2) The United States

√ Per California Proposition 65, ethylene oxide is classified as a carcinogen with developmental and reproductive toxicity.

√ Per 21CFR §180.151, ethylene oxide can be used as an antimicrobial or insecticide with the residue limits in foods as follows.

√ Per 21CFR §180.151, the limits of 2-chloro-ethanol (commonly called ethylene chlorohydrin, the reaction product of ethylene oxide) in foods is stipulated as below, when it is used as a fumigant.

3）The European Union

√ Per Commission Regulation (EU) 231/2012 of Mar 22, 2012, the use of ethylene oxide is banned in sterilization of food additives.

√ Per Commission Regulation (EU) 396/2005 and (EU) 2015/868, the maximum residue limit (MRL) is generally regarded as 0.01mg/kg, except for those pesticides and limits that are not specifically specified in the directive. The maximum residue limit of ethylene oxide in the interior or surface of some products is basically 0.02-0.1mg/kg as shown in the following table.

Based on above information, in order to avoid the issue of ethylene oxide residuals that are out of range happens to any final products, the manufacturers need to make a good control in two aspects. On the one hand, to strengthen the residue control of ethylene oxide of the raw materials and excipients. Only those raw materials and excipients in compliance with the regulatory requirements of the product sales region can be used. On the other hand, to strengthen microbial control in the production process, to avoid the residue issue that are out of range happens to any final products due to the use of ethylene oxide sterilization in the production process. Manufacturers need to be responsible for the quality and safety of the final products, and the health and safety of the public.