Health Risks

All chemical sterilants are designed to kill microorganisms and chemicals that kill microbes are hazardous to humans because of the shared biochemical design shared by all life on this planet. The key to toxicology is concentration; for example, the difference between the hypochlorite used in bleach and that used to chlorinate water is one of concentration. The former if ingested would be highly dangerous and would at a minimum necessitate a trip to the emergency room, whereas the lower dosage used in the production of safe drinking water has arguably contributed the most significant advance to human health in the last millennium. 

The chemical sterilants fall into two main chemical categories that describe their modes of sterilization and conversely their modes of toxicity. The two groups are the alkylating agents such as ethylene oxide and the oxidizing agents such as Hydrogen Peroxide and Ozone. The alkylating agents cause numerous symptoms upon exposure, including irritation and adverse reproductive effects. However, EtO is classified by IARC as a known human carcinogen, and is listed in the RTECS database as a mutagen and tumorigen resulting from its ability to alkylate DNA. The concentration at which the risk of these latter effects becomes significant is much lower than the concentration needed for primary irritation and other direct action symptoms, and the exposure levels are set much lower than even the odor threshold (see table below).

The oxidizing agents tend to act as primary irritants if exposed to humans resulting in irritation to the eyes upon exposure to the gas or vapor, nose and mouth through inhalation and skin upon contact with the liquid (hydrogen peroxide solution). Because the oxidants are mainly irritants, symptoms of their exposure usually develop quickly and the exposure levels are set based upon their irritant properties.

All of today’s chemical sterilants have been heavily studied and safe exposure limits have been developed for these chemicals that depend upon the timescale of the exposure. The National Institute for Occupational Safety and Health (NIOSH) has established Immediately Dangerous to Life and Health (IDLH) exposure limits. These provide the concentration that will either cause injury within a short term exposure or cause symptoms such as watering eyes that will impede escape within 30 minutes of exposure. From the table below it can be seen that the IDLH values for ethylene oxide is 700 ppm, Hydrogen Peroxide is 75 ppm, and ozone is 5 ppm. In terms of acute symptoms of exposure, Ozone is by far the most severe, followed by Hydrogen Peroxide and lastly Ethylene Oxide.

Comparative Toxicities of the Sterilant Gases

Another important exposure limit is the eight hour time weighted average. The Occupational Safety and Health Administration (OSHA) values were based on the 8 hour threshold limit values developed by the American Conference of Government and Industrial Hygienists (ACGIH). These chemical exposure limits are intended to provide an exposure rate whereby most employees can safely be safely exposed to the chemical for 8 hours a day, five days a week, continuously without significant adverse effect. The original OSHA PEL for EtO was 50 ppm, but this was reduced to 1 ppm in the mid 1980s once EtO became a suspected human carcinogen. Similarly, the OSHA short term 15 minute time weighted average exposure limit for EtO (excursion limit) was set to 5 ppm because EtO was a suspected human carcinogen.

The eight hour PEL thus represents an exposure limit that should provide a safe work environment based on chemical toxicity and injury as well as longer term risks from cancer etc. The PEL for Eton and Hydrogen Peroxide is similar, 1.0 ppm for both gases. The eight hour PEL for Ozone is only 0.1 ppm, one tenth that of EtO and Hydrogen Peroxide.

Since the OSHA 1910.1047 standard for EtO was issued, EtO has been reclassified as a known human carcinogen by the International Agency for Research on Cancer (IARC). To date there is no convincing evidence of carcinogenicity of Hydrogen Peroxide in humans, though the IARC lists it as a suspected animal carcinogen. Ozone is not believed to have carcinogenic activity.

Many government agencies have issued reports about the health hazards of the sterilant gases. Some useful summaries included the Agency for Toxic Substances and Disease Registry on the Medical Management Guidelines for Hydrogen Peroxide and Ethylene Ooxide and the Canadian Centre for Occupational Health and Safety has discussed the hazards of exposure to Ozone. Exposure to extremely low concentrations of ozone initially increases the reactivity of the airways to other inhaled substances and causes an inflammatory response in the respiratory tissue. E.g after only ~0.1 ppm. This response occurs almost immediately following exposure to ozone and persists for at least 18 hours. Other symptoms observed following acute exposures to 0.25-0.75 ppm include cough, shortness of breath, tightness of the chest, a feeling of an inability to breathe (dyspnea), dry throat, wheezing, headache and nausea.

Both NIOSH and OSHA have web pages devoted to the hazards and safe use of Ethylene Oxide.