Ethylene oxide (EO) gas mainly causes irritation of the nose, throat and respiratory tract; it also causes central nervous system effects such as headache, nausea, and vomiting. With high exposures, drowsiness, headache, weakness, irregular gait and loss of consciousness may occur. A review of 41 case reports found the main symptom was vomiting, recurring periodically for hours, accompanied by nausea and headache. Another report described nausea and vomiting in 3 employees who became drenched with a 1% EO solution for 2 hours. Exposure of a nurse to 500 ppm (estimated) for 2 or 3 minutes caused nausea, stomach spasms, lightheadedness, temporary unconsciousness and seizures. Random twitching of the muscles, nausea and tiredness occurred over the next 24 hours. Full recovery occurred within 3 weeks. Exposure of 2 employees to greater than 700 ppm (estimated; the odour threshold) for up to 30 minutes caused headache and diarrhea, which disappeared in 70 hours. Irritation of the throat, mouth dryness, itching, dizziness and weakness was observed 3 other employees. These symptoms disappeared within 21 days.
Persistent non-allergic asthma (reactive airways syndrome) developed in an employee exposed to EO above 700 ppm 4 hours/day for 4 days. Symptoms included coughing, wheezing and shortness of breath. This individual developed impaired lung function due to scarring of the lungs (pulmonary fibrosis). Similar effects were not observed in 5 other employees similarly exposed.
Four men were exposed to over 700 ppm EO intermittently for 2 to 8 weeks due to accidentally leakage of a sterilizer. Three men developed peripheral neuropathy (damage to peripheral nerves; i.e., those outside the brain and spine) with headache, weakness in the extremities, incoordination and irregular gait.
EO gas can probably produce irritation, mainly on wet or oily parts of the skin.
The degree of irritation caused by EO solutions is determined by the solution concentration and the length of exposure. The most harmful concentrations are in the 50% range. More concentrated solutions evaporate quickly while more dilute solutions are less irritating. Typical effects included a tingling and chilling sensation as EO evaporates, followed by swelling, redness and sometimes hives 1-5 hours after exposure. Blisters, when they occurred, appeared after 6 to 12 hours. Complete healing usually occurred within 3 weeks. A case report described 3 employees who were drenched with a 1% EO solution for 2 hours. Large, intense blisters developed several hours after the exposure. EO residues on sterilized face masks, gloves and surgical gowns have also been reported to cause severe irritation. The evaporation of liquid EO from skin may cause frosting of the tissue if large quantities are involved. Blisters may develop later. Small amounts produce no effects.
A review of cases of exposure to EO gas showed that slight irritation was occasionally reported. Exposure to 500 ppm (estimated) for 2-3 minutes was not reported to cause eye effects. Following a blast of EO into the eye, there was no immediate discomfort. However, within 2-3 hours the eye became uncomfortable. Within 24 hours, the eye was completely normal. Limited animal and human information suggests that liquid EO is a moderate to severe eye irritant. EO solution squirted directly into the eye and flushed immediately with water caused irritation that lasted 1 day. One case report describes a corneal burn in a person exposed to EO. The burn healed within 48 hours.
EO is a gas at normal room temperature and pressure. There are no reports of human ingestion of EO solutions. Animal information suggests that EO solutions are toxic following ingestion. Symptoms of central nervous system depression, as described for inhalation exposure, would be expected. Ingestion is not a typical route of occupational exposure.
In many long-term exposures situations, particularly in hospital employees involved in sterilizing instruments, some tasks which involve fairly high exposure may only be performed occasionally. Thus, relatively low time-weighted average exposure concentrations may mask incidental, higher exposures. Three studies of employees with exposure ranging from less than 0.25 ppm to 10 ppm (time-weighted average) for 6 months to 14 years have not shown significant blood, liver, kidney or immune system changes. Changes in kidney function, as evidenced by protein in the urine (proteinuria), were increased in one study. Other studies have shown similar results.
EFFECTS ON THE NERVOUS SYSTEM: Several studies have reported nervous system effects in employees exposed to less than 1 to 4.7 ppm (8-hour time-weighted average), with daily short-term peaks of 250 to 700 ppm for 0.5 to 20 years. Damage to the nerves which provide feeling and movement in the extremities (peripheral neuropathy) is most commonly observed. Symptoms include numbness in the feet and fingers, muscular weakness in the lower limbs, reduced hand-eye coordination, reduced nerve velocity in the calf muscle, and nerve fibre affects. Many of the studies are limited by factors such as the small number of employees studied and incomplete exposure information. No conclusions can be drawn from a case report of long-term low-level exposure (4.2 ppm, 8-hour time-weighted average; 10 years) involving sterilization of equipment with EO. This report suggested EO exposure was related to impaired thinking ability (cognitive impairment) and sensory loss.
EFFECTS ON THE SKIN: Dry, red, itchy skin (dermatitis) and burns may result from residues in gloves, clothing or footwear that has been sterilized with EO.
SKIN SENSITIZATION: EO may cause allergic skin reactions, but no firm conclusions can be drawn based on the available information. A case report describes a nurse who developed an allergic reaction to an EO sterilized rubber glove. The authors indicated that the reaction may have been to EO or to an EO- glove reaction product. No other details are available. One historical report described a "sensitivity" reaction in 3/8 volunteers repeatedly exposed to EO. A few other case reports describe sensitivity developing following non-occupational EO contact. Some of the reports do not describe a typical allergic reaction. Reports of severe allergic reactions developing in dialysis patients after being exposed to medical equipment sterilized with EO are not relevant to occupational exposures.
RESPIRATORY SENSITIZATION: EO may be a respiratory sensitizer but no firm conclusions can be drawn based on the available information. Occupational asthma has been reported among seven medical staff exposed to EO. In most of the cases, there was also exposure to other chemicals which have also been associated occupational asthma, e.g. latex and formaldehyde. In general, it is not possible to conclude that EO alone caused the asthmatic symptoms and/or that pre-existing conditions did not contribute to the effect.
EFFECTS ON THE EYES: Limited evidence suggests that there may be an increased risk of developing cataracts in employees exposed to relatively high EO levels.
The International Agency for Research on Cancer (IARC) has concluded that there is limited evidence for the carcinogenicity of EO in humans and sufficient evidence for carcinogenicity in experimental animals. The overall IARC evaluation is that EO is carcinogenic to humans (Group 1). The US National Toxicology Program lists EO as a chemical which may reasonably be anticipated to be a carcinogen. The American Conference of Governmental Industrial Hygienists (ACGIH) has designated EO as an A2 (suspected human carcinogen).
In humans exposed to EO, the most frequently reported association has been with lymphatic and hematopoietic cancer (i.e., cancer of blood-forming tissues like those in bone marrow). These studies have examined two groups - hospital employees using EO as a sterilant and chemical employees manufacturing or using EO. Hospital employees generally have clearly identified EO exposure. A large mortality study of this group observed significantly more deaths from hematopoietic cancer and leukemia among men. In a follow-up study, there was a positive trend in all lymphatic and hematopoietic cancer mortality for cumulative EO exposure. In another study, the only significant increase in mortality was caused by non-Hodgkin's lymphoma in men. Studies of chemical industry employees are more difficult to interpret because often there is exposure to other chemicals. Nevertheless, the observations are compatible with the small but consistent excesses of lymphatic and hematopoietic cancer observed in hospital employees. In one study, chemical workers licensed to handle EO experienced increased mortality due to lymphosarcoma, reticulosarcoma (a kind of malignant tumour in the lymphatic system) and hematopoietic tissue cancers.
In a small study, 37 male employees exposed to 5-10 ppm EO for an average of 10.7 years did not have more reproductive disorders compared to non-exposed employees. However, reproductive capacity was not evaluated. No conclusions can be drawn from a few studies which showed disturbances in menstrual cycle because of design limitations. EO has produced harmful effects on the reproductive capability of male and female animals by directly affecting the germ cells (sperm and the fertilized egg).
No firm conclusions can be drawn from a limited study which suggests that EO exposure may be related to increased miscarriages in hospital employees. Exposures were estimated to be 0.1-0.5 ppm (time-weighted average) with peaks up to 250 ppm. Employees were exposed to EO, glutaraldehyde and formaldehyde, information was gathered by questionnaire which may have led to reporting biases, exposure information was limited and only a small number of employees were studied. No conclusions can be drawn from another poorly conducted study in which pregnant women exposed to EO had more pregnancy complications and a higher rate of miscarriages. Animal information suggests that EO can cause reduced birth weight, but maternal toxicity was not fully evaluated. It is also toxic to animal germ cells (sperm and fertilized eggs).
There is no information available.
EO is readily absorbed by inhalation (retention 75-80%). Once absorbed, EO is rapidly distributed throughout the body. EO is metabolized by 2 different routes. Excretion of metabolites takes place in the urine generally within 24 hours following exposure. A small amount is excreted as carbon dioxide and unchanged ethylene glycol in the exhaled air or as metabolites in the feces.
Document last updated on October 6, 1998
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