Ethylene oxide-type hypersensitivity reactions in G-CSF mobilized, peripheral blood hematopoietic progenitor cell donors and review.

BACKGROUND: Ethylene oxide (EtO) is a volatile, ringed toxic ether used to sterilize heat-labile plastics including apheresis sets. In the 1980s, EtO-associated severe hypersensitivity reactions during hemodialysis led to widespread adoption of alternative sterilization for dialysis kits but not apheresis tubing sets. We now report several cases of EtO-type hypersensitivity reactions in autologous donors undergoing hematopoietic progenitor cell collection (HPCC). MATERIALS AND METHODS: A 10-year retrospective review of allergic EtO-type reactions in adults undergoing HPCC on the COBE Spectra and SPECTRA Optia was performed. Donor medical history and absolute eosinophil counts were compared between cases and 34 HPCC controls. Published EtO reactions during extracorporeal procedures were reviewed with statistical analysis. Graphics and statistics were performed using commercial software. RESULTS: Three autologous HPCC donors experienced EtO-type reactions within 15 min of initiating HPCC, for a 10-year incident rate of 0.08% per procedure and 0.18% per donor. All three reactions occurred using the Spectra Optia and IDL tubing set, for an Optia/IDL specific rate of 0.2% per procedure and 0.5% per donor. There was no correlation between EtO reactions, eosinophil counts, or saline prime dwell times. No patient had classic predisposing risk factors for EtO hypersensitivity. Two patients required medical intervention whereas the third responded by pausing the procedure and slowing the inlet rate. CONCLUSION: EtO-type hypersensitivity reactions can be observed during HPCC, especially with the Optia IDL tubing set. EtO reactions may be missed due to their rarity and staff unfamiliarity with this clinical entity.

Ethylene oxide emissions and incident breast cancer and non-Hodgkin lymphoma in a US cohort.

BACKGROUND: Ethylene oxide (EtO) is a carcinogenic gas used in chemical production and to sterilize medical equipment that has been linked to risk of breast and lymphohematopoietic cancers in a small number of occupational studies. We investigated the relationship between environmental EtO exposure and risk of these cancers. METHODS: Using the US Environmental Protection Agency's Toxics Release Inventory, we estimated historical exposures for National Institutes of Health-AARP Diet and Health Study participants enrolled in 1995-1996. We constructed 2 metrics at 3, 5, and 10 km: 1) distance between residences and EtO-emitting facilities, weighted by the proportion of time the home was downwind of each facility, and 2) distance-weighted, wind direction-adjusted average airborne emissions index (AEI=∑[lbs EtO/km2]). We estimated risk (hazard ratio [HR], 95% confidence interval [CI]) of incident breast cancer (in situ and invasive) among postmenopausal women (n = 173 670) overall and by tumor estrogen receptor status and non-Hodgkin lymphoma in the full cohort (n = 451 945). RESULTS: We observed an increased risk of breast cancer associated with EtO-emitting facilities within 10 km (HR[≤10vs>10] = 1.05, 95% CI = 1.00 to 1.10) that appeared stronger for in situ (HR[≤10vs>10] = 1.13, 95% CI = 1.00 to 1.27) than invasive (HR[≤10vs>10] = 1.03, 95% CI = 0.97 to 1.09) disease. Risk of breast cancer in situ was also increased in the top AEI quartiles, and associations weakened with larger distances (HR[Q4vs0] = 1.60, 95% CI = 0.98 to 2.61; HR[Q4vs0] = 1.28, 95% CI = 0.92 to 1.79; HR[Q4vs0] = 1.25, 95% CI = 1.02 to 1.53 at 3, 5, and 10 km, respectively). No differences in breast cancer risk were observed by estrogen receptor status. We found no clear pattern of increased non-Hodgkin lymphoma risk. CONCLUSIONS: A novel potential association between EtO emissions and risk of in situ, but not invasive, breast cancer warrants additional evaluation.

Anaphylaxis From Ethylene Oxide-Sterilized Dialysis Tubing and Needles: A Case Report.

Hypersensitivity reactions to ethylene oxide-sterilized dialyzers have been well described. Although ethylene oxide is no longer used to sterilize most dialyzers, it is used on other pieces of dialysis equipment. We present a case of a 78-year-old man who experienced dialysis-related anaphylaxis attributed to an IgE-mediated allergy to dialysis tubing and needles sterilized with ethylene oxide. Shortly after transitioning from a tunneled catheter to an arteriovenous fistula, he developed multiple episodes of intradialytic hypotension and syncope within minutes of starting dialysis. Laboratory evaluation revealed marked leukocytosis, eosinophilia, and elevated anti-ethylene oxide IgE antibody. After pretreatment with corticosteroids and antihistamines, the rinsing of dialysis tubing, and transition of access back to a tunneled catheter, he tolerated subsequent dialysis treatments. Review of his history revealed chronic eosinophilia since the time of hemodialysis initiation. We hypothesize his eosinophilia and mast cell degranulation began upon initial exposure to ethylene oxide and hemodialysis equipment. When use of the arteriovenous fistula was resumed, he was exposed to a higher "dose" of ethylene oxide due to the use of needles. The higher antigenic stimuli triggered a memory immune response, leading to mast cell degranulation and repeated anaphylactic episodes that were overcome by minimization of ethylene oxide-sterilized equipment, corticosteroid pretreatment, and the anti-IgE Fc monoclonal omalizumab.

Ethylene oxide review: characterization of total exposure via endogenous and exogenous pathways and their implications to risk assessment and risk management.

This review is intended to provide risk assessors and risk managers with a better understanding of issues associated with total exposures of human populations to ethylene oxide from endogenous and exogenous pathways. Biomonitoring of human populations and lab animals exposed to ethylene oxide has relied upon the detection of hemoglobin adducts such as 2-hydroxyethylvaline (HEV), which provides a useful measure of total exposure to ethylene oxide from all pathways. Recent biomonitoring data from CDC provide an excellent characterization of total exposure to ethylene oxide to the general U.S. population by demographic factors such as age, gender, and race as well as smoking habit, which might be comparable to previous measurements reported for humans and lab animals. The biochemical pathways including gastrointestinal (production by bacteria) and systemic (enzymatic production) pathways by which endogenous ethylene is generated and converted to ethylene oxide are described. The relative importance of endogenous pathways and exogenous pathways via ambient air or tobacco smoke was quantified based upon available data to characterize their relative importance to total exposure. Considerable variation was noted for HEV measurements in human populations, and important sources of variation for all pathways are discussed. Issues related to risk assessment and risk management of human populations exposed to ethylene oxide are provided within the context of characterizing total exposure, and data needs for supporting future risk assessment identified.

Anaphylaxis following administration of extracorporeal photopheresis for cutaneous T cell lymphoma.

Extracorporeal photopheresis is a non-invasive therapy used for the treatment of a range of T cell disorders, including cutaneous T cell lymphoma. During extracorporeal photopheresis, peripheral blood is removed from the patient and the white blood cells are separated from whole blood via centrifugation. The white blood cells are exposed to psoralen (a photosensitizing agent) and ultraviolet A radiation, causing cell apoptosis. The apoptotic leukocytes are subsequently re-infused into the patient, resulting in the production of tumor suppressor cells and clinical improvement. Extracorporeal photopheresis is generally regarded as safe with few side effects. We report a dermatology patient who developed anaphylaxis after receiving extracorporeal photopheresis for the treatment of leukemic mycosis fungoides. We suspect that our patient's anaphylaxis resulted from exposure to an agent used in extracorporeal photopheresis.

Ethylene Oxide Exposure Attribution and Emissions Quantification Based on Ambient Air Measurements near a Sterilization Facility.

Ethylene oxide (EtO) is a known carcinogen and mutagen associated with increased incidence of breast and blood cancers. The largest medical sterilization facility in Michigan had been assessed by the U.S. Environmental Protection Agency as imposing an additional cancer risk greater than one in one thousand in nearby neighborhoods. This prompted the Michigan Department of Environmental Quality (now referred to as the Department of Environment, Great Lakes, and Energy) to conduct an air quality modeling study of the ambient EtO impacts of the sterilization facility, followed by 24 h Summa canister sampling and TO-15 analysis in two phases. Inverse modeling of the measured 24 h EtO concentrations during the second phase yielded estimates of 594 lbs/year for the facility's total emissions of EtO and 0.247 µg/m3 for the urban background concentration. The inverse-modeled emissions are similar to reported emissions by the facility operator based on indoor air measurements and simple mass balance assumptions, while the inferred background concentration agrees with estimates from other field investigations. The estimated peak 24 h exposure to EtO caused by the sterilization facility in nearby neighborhoods was 1.83 µg/m3 above the background level, corresponding to an additional cancer risk of approximately one in one hundred, if assumed to represent annual mean exposure.

Ethylene oxide and risk of lympho-hematopoietic cancer and breast cancer: a systematic literature review and meta-analysis.

PURPOSE: To conduct a systematic literature review and meta-analysis of studies of lympho-hematopoietic cancers (LHC) and breast cancer risk among persons occupationally exposed to ethylene oxide (EO). METHODS: We performed a literature search for articles available in PubMed and Web of Science databases to identify literature and subsequently systematically searched the reference lists of identified studies, published review papers and meta-analyses, as well as relevant government or regulatory documents. We qualitatively reviewed 30 studies and conducted meta-analyses on 13 studies. Pooled risk estimates were calculated using random effects models, stratifying by occupational group, cancer type and decade of publication. RESULTS: The overall meta-relative risks (meta-RRs) for LHC and breast cancer, respectively, were 1.48 (95% CI 1.07-2.05) and 0.97 (95% CI 0.80-1.18). The meta-RR's for LHC among EO production and EO sterilization workers were 1.46 (95% CI 0.85-2.50) and 1.07 (95% CI 0.87-1.30), respectively. We observed higher risks of LHC in the earlier published studies, compared to the later studies, and the meta-RR's for the 1980s, 1990s, 2000s, and the 2010s, respectively, were 3.87 (95% CI 1.87-8.01), 1.38 (95% CI 0.85-2.25), 1.05 (95% CI 0.84-1.31), and 1.19 (95% CI 0.80-1.77). CONCLUSIONS: The most informative epidemiology studies, which were published in the 2000s and 2010s, do not support the conclusion that exposure to EO is associated with an increased risk of LHC or breast cancer.

Determination of N-(2-hydroxyethyl)valine in globin of ethylene oxide-exposed workers using total acidic hydrolysis and HPLC-ESI-MS2.

Ethylene oxide (EO), an industrial intermediate and gaseous sterilant for medical devices, is carcinogenic to humans, which warrants minimization of exposure in the workplaces. The principal analytical strategy currently used in biomonitoring of exposure to EO consists in the conversion of N-(2-hydroxyethyl) adduct at the N-terminal valine (HEV) in globin to a specific thiohydantoin derivative accessible to GC-MS analysis (modified Edman degradation, MED). Though highly sensitive, the method is laborious and, at least in our hands, not sufficiently robust. Here we developed an alternative strategy of HEV determination based on acidic hydrolysis (AH) of globin followed directly by HPLC-ESI-MS2 analysis. Limit of quantitation is ca. 25 pmol HEV/g globin. Comparative analyses of globin samples from EO-exposed workers by both the AH-based and MED-based methods provided results that correlated well with each other (R2 > 0.95) but those obtained with AH were significantly more accurate (according to external quality control programme G-EQUAS) and repeatible (5% and 6% for intra-day and between-day analyses, respectively). In conclusion, the new AH-based method surpassed MED being similarly sensitive, much less laborious and more reliable, thus applicable as an effective tool for biomonitoring of EO in exposure control and risk assessment.

Prevalence of delayed-type and immediate-type hypersensitivity in healthcare workers with hand eczema.

BACKGROUND: Occupational contact dermatitis is common in healthcare workers. Although irritant contact dermatitis resulting from wet work is the most frequently reported cause, healthcare workers also constitute high-risk group for the development of allergic contact dermatitis and contact urticaria. OBJECTIVES: To evaluate the prevalence of delayed-type and immediate-type hypersensitivity in 120 healthcare workers with hand eczema. METHODS: One hundred and twenty healthcare workers from three major hospitals in Denmark with self-reported hand eczema within the last year participated in the study. Patch tests included baseline series plus selected allergens, and prick tests included standard inhalational allergens plus natural rubber latex and chlorhexidine. Levels of IgE specific for latex, chlorhexidine and ethylene oxide were measured. RESULTS: Of the participants, 53% had positive patch test reactions. The most frequent positive patch test reactions were to nickel, thiomersal, fragrances, rubber chemicals, and colophonium. The prevalence of natural rubber latex allergy as diagnosed by prick testing was 2.5%, and chlorhexidine allergy (both contact allergy and IgE-mediated allergy) was found in <1%. Ethylene oxide allergy was not identified in any of the participants. CONCLUSIONS: Our results confirm previous reports on contact allergy patterns in healthcare workers. Testing for natural rubber latex allergy is still important, but increased risks of chlorhexidine and ethylene oxide allergy could not be confirmed.

Type I allergic hypersensitivity reactions due to ethylene oxide sterilised leucocyte filters in patients with thalassaemia: report of four cases.

Ethylene oxide (EO) is a highly reactive gas used in sterilisation of heat sensitive medical devices, such as infusion sets, cannulae, intubation materials, ventriculoperitoneal shunts, dialysis catheters and stents. Allergic reactions due to EO have been reported in haemodialysis patients, patients undergoing extracorporeal photopheresis and donors of plasmapheresis. Clinical manifestations vary considerably and generally do not allow differentiation between IgE-mediated anaphylaxis and anaphylactoid reactions. We report four patients with thalassaemia who experienced anaphylaxis during transfusion due to ethylene oxide sterilised leucocyte filters. The aim of this report is to highlight the fact that frequently transfused patients can have allergic reactions due to EO particles left in leucocyte filters.

Relationship between everyday use cosmetics and female breast cancer.

Data of the European Cancer Registries indicate that the incidence of breast cancer, which is the most common cancer among women, tends to increase not only in postmenopausal but also in very young women. The potential causes of breast cancer are genetic predisposition, long -term hormonal replacement therapy, alcohol, environmental pollution, and possibly modern lifestyle. The controversial results of several studies suggest that certain everyday-use products (including cosmetic ingredients) may be linked to breast cancer. Some of these ingredients, such as ethylene oxide, have recently been classified by the International Agency for Research for Cancer as carcinogenic and mutagenic to humans, with sufficient evidence of carcinogenicity for breast cancer. Other ingredients, such as xenoestrogens, are chemicals which have an estrogen -like effect or disrupt the normal metabolism of the natural estrogen and thus act as carcinogens. Some of them have been shown to result in DNA damage in animal and human mammary epithelial cells and, therefore, have the potential to generate genomic instability in the breast tissue. Examples of xenoestrogens with such properties include parabens, aluminium salts, phthalates, or bisophenol A. No sufficient epidemiological data on humans have been published so far, and the effects of a mixture of chemicals to which women are exposed during lifetime on the incidence of breast cancer have not been investigated. However, the results of the available studies emphasize the need for analysis of adverse environmental factors, which, in addition to a genetic predisposition and natural aging, may contribute to the increased incidence of breast cancer.

[Cytotoxicity of PVC tubes sterilized in ethylene oxide after gamma radiation exposure]. / Citotoxicidade de tubos de PVC esterilizados em óxido de etileno após exposição à radiação gama.

Do materials sterilized using gamma rays become toxic when re-sterilized in ethylene oxide? This question guided the objective of this study, which was to investigate the potential cytotoxic effect of PVC sterilized by gamma radiation and re-sterilized with EO by the agar diffusion method in cell cultures. Nine PVC tubes were subjected to gamma radiation sterilization and were re-sterilized in EO. The tubes were divided into a total of 81 units of analysis that were tested so as to represent the internal and external surfaces and mass of each tube. It was concluded that the PVC materials sterilized in gamma radiation and re-sterilized in EO are not cytotoxic.

Citotoxicidade de tubos de PVC esterilizados em óxido de etileno após exposição à radiação gama / Cytotoxicity of PVC tubes sterilized in ethylene oxide after gamma radiation exposure / Citotoxicidad de tubos de PVC esterilizados en óxido de etileno luego de exposición a la radiación gamma

Materiais esterilizados em raios gama, ao serem re-esterilizados em óxido de etileno (EO), formam substâncias tóxicas? Esta questão norteou o objetivo deste estudo, que foi investigar o potencial efeito citotóxico do PVC esterilizado em radiação gama e re-esterilizado em EO pelo método da difusão em ágar em culturas celulares. Nove tubos de PVC foram submetidos à esterilização em radiação gama e re-esterilizados em EO. Os tubos foram divididos em um total de 81 unidades de análise, que foram testadas de forma a representar as superfícies internas, externas e massa de cada tubo. Concluiu-se que os materiais de PVC esterilizados em Radiação Gama e consecutivamente re-esterilizados em EO não são citotóxicos.

Do materials sterilized using gamma rays become toxic when re-sterilized in ethylene oxide? This question guided the objective of this study, which was to investigate the potential cytotoxic effect of PVC sterilized by gamma radiation and re-sterilized with EO by the agar diffusion method in cell cultures. Nine PVC tubes were subjected to gamma radiation sterilization and were re-sterilized in EO. The tubes were divided into a total of 81 units of analysis that were tested so as to represent the internal and external surfaces and mass of each tube. It was concluded that the PVC materials sterilized in gamma radiation and re-sterilized in EO are not cytotoxic.

Los materiales esterilizados con rayos gama, al ser re-esterilizados en óxido de etileno (EO), ¿forman substancias tóxicas? Esta pregunta orientó el objetivo del presente estudio, que fue investigar el potencial efecto citotóxico del PVC esterilizado en radiación gamma y re-esterilizado en EO por el método de difusión en agar en cultivos celulares. Nueve tubos de PVC fueron sometidos a esterilización por radiación gamma y re-esterilizados en EO. Se les aplicaron en total 81 unidades de análisis, las cuales fueron testeadas de manera tal de representar las superficies internas, externas y la masa de cada tubo. Se concluyó en que los materiales de PVC esterilizados con Radiación Gamma y, posteriormente, con EO, no son citotóxicos.

Analysis of protein adducts as biomarkers of short-term exposure to ethylene oxide and results of follow-up biomonitoring.

An accidental exposure of six workers to ethylene oxide (EO) provided the rationale for a biomonitoring and follow-up study, whose aim was to analyse protein adduct kinetics and examine the differentiation between accidental and environmental exposure, e.g., from tobacco smoke. For this purpose, the decrease in the concentration of the haemoglobin adduct N-2-hydroxyethylvaline (HEV) was followed during a five-month period after the accident, together with N-2-cyanoethylvaline (CEV) and urinary cotinine, two well-established biomarkers for smoking. The follow-up study showed that EO adduct concentrations significantly increased after a short but presumably high exposure. Initial biomonitoring revealed HEV levels above 500 pmol g(-1) globin in all cases, with a maximum of about 2,400 pmol g(-1) globin. This compares to a German EKA value (exposure equivalent for carcinogenic substances) for a daily 8-h-exposure to 1 ppm EO of 90 µg L(-1) blood (~3,900 pmol g(-1) globin). The adduct levels dropped in accordance with the expected zero-order kinetics for a single exposure. After the five-month observation interval, the HEV concentrations in blood reflected the individual background from tobacco smoking. The results of this study show that even a short exposure to ethylene oxide may result in a significant rise in haemoglobin adduct levels. Although protein adducts and their occupational-medical assessment values are considered for long-term exposure surveillance, they can also be used for monitoring accidental exposures. In these cases, the calculation of daily 'ppm-equivalents' may provide a means for a comparison with the existing assessment values.

In vivo oxidation and surface damage in retrieved ethylene oxide-sterilized total knee arthroplasties.

BACKGROUND: Gas sterilization (eg, ethylene oxide [EtO] and gas plasma) was introduced for polyethylene to reduce oxidation due to free radicals occurring during radiation sterilization. Recently, oxidation has been observed in polyethylenes with undetectable levels of free radicals, which were expected to be oxidatively stable. It is unclear whether in vivo oxidation will occur in unirradiated inserts sterilized with EtO. QUESTIONS/PURPOSES: We analyzed the oxidation, mechanical behavior, and surface damage mechanisms of tibial inserts of a single design sterilized using EtO. METHODS: We collected 20 EtO-sterilized tibial inserts at revision surgeries. We assessed oxidative using Fourier transform infrared spectroscopy and mechanical properties using the small punch test. Surface damage was assessed using damage scoring techniques and micro-CT. RESULTS: Oxidation indexes were low and uniform between the regions. The subtle changes did not affect the mechanical properties of the polymer. The dominant surface damage modes included burnishing, abrasion, and third-body wear. There was no evidence of delamination in the retrievals. CONCLUSIONS: The retrieved EtO-sterilized UHMWPE retrievals remained stable with respect to both oxidative and mechanical properties for up to 10 years in vivo. We did observe slight measurable amounts of oxidation in the inserts; however, it was far below levels that would be expected to compromise the strength of the polymer. CLINICAL RELEVANCE: Due to the stable oxidative and mechanical properties, EtO-sterilized tibial components appear to be an effective alternative to gamma-sterilized inserts, at least in short-term implantations.

Multicomponent synthetic polymers with viral-mimetic chemistry for nucleic acid delivery.

The ability to deliver genetic material for therapy remains an unsolved challenge in medicine. Natural gene carriers, such as viruses, have evolved sophisticated mechanisms and modular biopolymer architectures to overcome these hurdles. Here we describe synthetic multicomponent materials for gene delivery, designed with features that mimic virus modular components and which transfect specific cell lines with high efficacy. The hierarchical nature of the synthetic carriers allows the incorporation of membrane-disrupting peptides, nucleic acid binding components, a protective coat layer, and an outer targeting ligand all in a single nanoparticle, but with functionality such that each is utilized in a specific sequence during the gene delivery process. The experimentally facile assembly suggests these materials could form a generic class of carrier systems that could be customized for many different therapeutic settings.

Anaphylaxis to ethylene oxide - a rare and overlooked phenomenon?

Spina bifida patients have been reported to be at increased risk of anaphylactic reactions during general anaesthesia. Following a reaction, latex is often incriminated as spina bifida patients are known to have an increased incidence of latex allergy. Ethylene oxide (EO) has recently been suggested to be an alternative cause, but in many cases reported in the literature, it seems that EO has not been considered as a cause. EO is a highly reactive gas widely used to sterilise heat-sensitive medical devices, and traces of EO can be found in many of the same products as latex. We present the case of a spina bifida patient with a known latex allergy, where EO was found to be the cause of an anaphylactic reaction during general anaesthesia. In addition, we describe measures taken during preparation of a subsequent general anaesthesia to minimise exposure to EO. Spina bifida patients seem to be at increased risk of sensitisation against EO due to repeated exposure, but only limited literature is available. To ensure that EO is considered as a cause in these cases, we recommend that testing for latex and EO go hand in hand following an anaphylactic reaction in this high-risk population.

Ethylene oxide allergy in patients on hemodialysis waiting for kidney transplantation: logistical nightmare or challenge? A case report.

Ethylene oxide (EO) is widely used as a sterilization gas for heat-sensitive devices. In EO-sensitized patients, this type of sterilization can cause rare but major allergic reactions such as hives, rash, asthma, or anaphylactic shock. Hemodialysis patients in particular are at risk of developing hypersensitivity to EO. In these patients, surgical interventions should be planned far in advance allowing a thorough EO-free preparation of all equipment needed for the surgery as well as for the pre-, peri-, and postoperative care. In contrast to elective surgery, kidney transplantation with allografts from deceased donors cannot be planned; exact timing is unpredictable. Furthermore, transplantation may take place years after patients have been put on the waiting list. Listing of patients sensitive for EO is therefore a logistical and medical challenge for all health care professionals involved in the patient's care (eg, surgeons, nephrologists, anesthetists, nurses, pharmacists, and sterilization specialists). This case report describes a patient with chronic kidney disease stage V who developed EO allergy during hemodialysis while waiting for a kidney transplantation. Diagnosis was made based on clinical signs and confirmed biochemically (including a positive radioallergosorbent test). Because the only treatment is avoidance of contact with EO-sterilized materials, a strict EO-free protocol was developed to allow an uneventful transplantation thereafter. Subsequently, 4 newly diagnosed EO-sensitive patients on the active kidney transplantation waiting list were diagnosed, and 1 of these patients has been transplanted successfully. EO allergy in patients on the waiting list for kidney transplantation is a unique challenging situation which, to the best of our knowledge, has not been reported yet for kidney transplantation. This report further highlights the logistical preparation of a renal transplantation, including anesthesiologic, surgical, and postoperative care.

An integrated occupational health consultation model for the medical supply manufacturing industry.

In this research, we designed a three-stage consultation procedure and eight major consultation items in order to construct an integrated occupational health consultation model that emphasizes both inspection and consultation. The main characteristics of the proposed model include cooperation among governmental departments, combining non-governmental professional consulting organizations, and establishing partnerships with industrial associations. This model has clear active and passive performance indicators and includes technical guidance during consultation as well as the exit mechanism after consultation. This consultation model enables small- and medium-sized enterprises to achieve environmental improvements with minimum investment. Companies that improved after consultation have a mean ethylene oxide exposure concentration, for the time weighted average, that dropped from 7.36 ± 16.88 ppm to 0.76 ± 1.35 ppm (p<0.01). In addition, the overall company compliant item ratio for regulations increased from 34.1% to 89.7%. The above results demonstrate the integrated occupational health consultation model assists small- and medium-sized enterprises in reducing exposure concentrations at operational sites. Our results further demonstrate the feasibility of successfully implementing the proposed consultation model within Taiwan's medical supply manufacturing industry.