Introduction

Ethylene oxide (EtO) is a colorless gas produced commercially since the 1920s. It is used as an agricultural fungicide, a fumigant for foodstuffs and textiles, and as an intermediate in the production of ethylene glycol, polyester fibers, and film(1).

EtO is an alkylating agent that has been linked with tissue irritation, peripheral and central neurological effect, increased chromosomal aberrations and sister-chromatid exchange (2-4) Inhaled EtO is quickly absorbed in the lungs and distributed rapidly throughout all tissues; it forms dose-related hemoglobin adducts in people and rodents, and dose-related DNA adducts in rodents (2).

Since the 1950s, ethylene oxide (EtO) is used extensively in health care institutions for sterilization of heat-sensitive materials and is considered irreplaceable for this purpose(1). Although the volume of EtO used for sterilization is relatively small, exposure of hospital workers to EtO can occur even in the usual operation of properly maintained sterilizers. Malfunction of equipment or improper procedures might have resulted in high levels of exposure(1)

Exposure levels in sterile supply departments of hospitals depend mostly on the scale and technique of the process used and the temporary peak levels that occur mainly during loading and unloading of the sterilizers. Exposure may also occur in the desorption room and other nearby rooms(1).

In this case report, we present a 35 year old ethylene oxide sterilization worker who worked in sterilization for 6 years and had trombositopenia due to etylene oxide toksication.

Case Presentation

We present a 35 year old non smoker who was employed as a EtO sterilization worker for 6 years presenting with ethylene oxide toksication. As he felt exhaustion, fatigue and causeless petechial bleeding he underwent some labaratory tests. Ä°n his CBS he had a decrease in platelet counts. His platelet count was 125000/mm3 then decreased to 100.000, 98.000 and gradually to 85.000/mm3. In his first routine medical surveillance, before working in EtO sterilization room, there was no hematological disorders and his CBS was: Hb:13.8 g/dl, htc 41.3, WBC:5.1 and plt:158.000/mm3. Venous blood (3 mL) was withdrawn into ethylenediamine-tetraacetic acid vacutainer tubes to measure hematological markers such as CBC tests. All of the blood tests were analyzed in one central laboratory according to standard hematological methods. All blood samples were taken between 8:00 and 10:00 am and were transported by 10:30 am to the same clinical laboratory. CBC tests were analyzed in Becman Coulter HMX. Standard quality control was performed once daily in the morning. In the sterilization room he is working there was no specific aeration inside the sterilizer and there was no safety closing measures for the sterilizer door: and it was possible to open the door during a sterilization cycle and before the end of the process (in order to provide for any immediate needs of the surgical unit). The room next to the sterilizer was used for unloading and storage of the sterilized medical items in the aeration chamber. Individual protective devices were very seldom used. He had no medical history related to this problem and in his hematology consultation, it came evident that he had never exposed to any other known factor predisposing for haematological disorder. He was allowed to have a holiday from the unit he is working then he was shifted to another unit and mandatory changes are done in the sterilization room and his platelet counts began to rise gradually.

Discussion

Epidemiological studies have associated EtO exposure with hematological diseases (anemia, leukopenia, leukemia), stomach cancer, and reproductive problems(3-5). The International Agency for Research on Cancer (IARC) has determined that EtO is a definite human carcinogen, based on limited evidence from epidemiologic studies showing increased hematopoetic cancer, supported by positive human cytogenetic evidence, and on sufficient evidence from animal studies for hematopoietic and other cancers (2).

Since the reduction of the permissible exposure limit to 1 ppm 8-hour time-weighted average (TWA), little is known about the expression of the appearance and fluctuation of the incidence of biological markers(6). One of the concerns is the implication and practice of including complete blood counts (CBC) with white blood cell (WBC) differential as biological markers in the medical surveillance program for workers exposed to EtO, as was recommended by the Occupational Safety and Health Administration (OSHA)(7). On the basis of these hematological changes in EtO-exposed workers and the expected radiomimetic effects of EtO as an alkylating agent, the authors recommend regular medical surveillance similar to that provided for radiological workers (eg, blood count and chromosome analysis)(7). Homeostasis (a balanced physiological system) of the blood elements is maintained in part by the steady-state maintenance of the populations of pluripotent stem cells, differentiating progenitor stem cells, and maturing functional cells. This physiological system is a good indicator of hazardous impact, because fluctuation in one population will be reflected by changes in other populations, both in bone marrow and peripheral blood, as the system compensates and later returns to normal state(7).

In Shaham et al’s study(7) they examined 134 blood samples, including 88 of the control group and 46 of the workers of the exposed group, they found that the mean absolute numbers of the eosinophils, red blood cells, the percentage of the hematocrit, the mean absolute number of the monocytes were significantly higher in the group of exposure and the mean absolute numbers of the lymphocytes and platelets were significantly lower in exposure group compared with the controls. In our case we also found a significant decrease in platelet counts without exposing to any other predisposing factors. As far as we are concerned this shift in differential is because of immunological sensitization to EtO in the bone marrow over a long period of exposure, causing gradual depression of lymphocytes and platelets. Because a bone marrow test is not routine in healthy people, we based our assumption on a study done by Popp et al(8), they evaluated the perturbations in bone marrow and peripheral blood elements of mice exposed to non-lethal doses of EtO and found that bone marrow populations and leukocytes in the peripheral blood fluctuated largely from their normal homeostatic level during the exposure period, mainly in the early phase. The granulocytes were elevated and the lymphocytes disappeared from circulation. The opposite pattern was seen in the bone marrow, in which the granulocytes were depleted and the lymphocytes increased by almost two fold. These data indicate that the granulocyte pool in the marrow was released into the peripheral circulation in response to the exposure to EtO(7). Although initially justified on the basis of expected hematological effects of high EtO exposure, studies published after 1984 question the efficacy of CBC and WBC differentials as components of medical surveillance for low levels of EtO exposure. The usefulness of CBC and WBC differentials to diagnose EtO-associated leukemia or preleukemic stage is questionable. The presence of eosinophilia can indicate chronic myelogenous leukemia and stomach cancer, both known outcomes of EtO exposure(9). We also recommend the use of the CBCs with WBC differentials in routine medical surveillance for EtO exposure should be reexamined.

Shaulte et al (10)discussed the moleculer ,cytogenetic and hematologic effects of ethylene oxide and they found a statistically significant decrease in hematocrit and hemoglobin levels, an increase in lymphocyte percentages and a relative decrease in neutrophil percentages. La Montagne(11) et al observed an apparent relative lymphocytosis which persisted over 3-4 years in sterilization workers.In our case we observed trombositopenia.

In Bisanti et al’s study they made a cohort of 1971 chemical workers who were licenced to handle ethylene oxide followed by 44 years (1940-1984) favored the hypothesis of a higher risk of cancer in occupational exposure to ethylene oxide and also lympatic and haematopeietic cancers(12). Another cohort study with Teta MJ et al (13)with ethylene oxide workers followed by 48 years did not support association of ethlyene oxide with all cancer types combined, leukaemia, non Hodgkin lymphoma or brain, pancreatic or stomach cancers but they found a decrease in leukocyte counts. In our case we found a decrease in platelet counts of our patient regardless of any other hematologic reasons. In Currier et al’s(14) study they found no difference in haematologic or blood chemistry levels but the exposed group had urine protein concentrations above the reference rate. In Darell et al’s study(15) , they showed that there was no significant association of eleveted sister kromatid exchange with ethylene oxide exposure nor they found an association between EtO exposure and genetic indicators. In Steenland et al ‘s(16) study they also did not found a risk of human cancer from ethlyene oxide exposure. In our case no hematologic malignancies have been arisen in our patient.

In Korpela et al’s study(17) they observed that ethylene oxide teds to flow upward from a sterilizer following completion of a normal operating cycle. Although ethylene oxide is heavier than air, it appears that the 30 minute air flush following completion of sterilization cycle, provides sufficient dilution so that the mixture tends to follow the natural warm air currents. Variability observed in the measurement of peak concentrations and durations is believed to be largerly a factor of the products being sterilized, the type of packaging used and the length of exposure time. Because the longest duration for which ethylene oxide levels were observed to persist was 12 minutes, worker exposure can be effectively reduced if after opening the door, the operator leaves the area at least for 15 minutes. Exposures can be further minimized if the sterilizer is located in an isolated room and provided with an automated device to open the chamber door upon completion of the sterilization cycle.

The environmental concentrations and the personal exposure levels of EtO in the sterilization rooms were dependent on the quality and quantity of the aeration process after the sterilization and the performance of the ventilation system. In the EtO gas sterilization process, a material to be sterilized is packed in a bag in advance of the sterilization. Gases and vapors can pass through the bag but particulate matters cannot. Therefore, when EtO gas is supplied into the sterilizer with the materials packed in the bags, the gas is diffused into the bag until the EtO gas concentration in the bag is in equilibrium with that in the sterilizer. Just after the sterilization, therefore, a high concentration of EtO gas is contained in the bag, and the EtO gas gradually diffuses to the outside of the bag. To remove the residual gas in the bag, various aeration methods have been considered. In an hospital, aeration was carried out by introducing fresh air into the sterilizer continuously for an 8-hour period, in an other one the sterilized materials were stored for one day in the sterilizer, air in the sterilizer was replaced by fresh air continuously for more than 30 minutes(18,19).

EtO is widely used in operating theatre sterilization units. Because of a current lack of an adequate substitute, EtO will remain a significant occupational hazard for the foreseeable future. It should be kept in mind that EtO exposure could cause thrombocytopenia in personal working in sterilization units of operating theatres.