Table 2.1. Cohort studies of ethylene oxide and lymphohaematopoeitic cancer

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Table.. Cohort studies of ethylene oxide and lymphohaematopoeitic cancer Hogstedt et al. (979a, 98), Sweden 89 operators with regular exposure to ethylene oxide and 78 maintenance staff with intermittent exposure, employed for > year at a chemical plant, followed 9 85 Operators Maintenance staff [0] [5] Estimated average exposure before 9, 5 5 ppm [9 5 mg/m ]; one CML, one acute leukaemia, one CLL Morgan et al. (98), (reported in Shore et al., 99) 77 men employed in 955 77 at a chemical plant for > 5 years with potential exposure to ethylene oxide, followed 955 85 Industrial hygiene survey in 977 0.0 (0..9) 0.0 (0.0.) s in 977 < 0 ppm [8 mg/m ]; included cases of Hodgkin disease Thiess et al. (98), Germany 0 male employees in a company in western Germany who worked for at least months in ethylene oxide production, followed to June 980 Myeloid leukaemia Lymphatic sarcoma.7 NR Hogstedt et al. (98), Sweden 0 workers employed > year in production of sterilized supplies, followed 978 8 (00 09) [5] Estimated average past exposure in storeroom, 0 ppm [ mg/m ]; one AML was part of a cluster which had originally prompted the study; one acute blastic leukaemia Hogstedt et al. (98), Sweden 55 chemical workers and maintenance and technical personnel employed at a chemical plant, followed 9 8 Air sampling and interview with experienced staff CML. expected from all causes TWA exposures, 8 ppm [.8. mg/m ] in 9 7; 0..0 ppm [0.7. mg/m ] in 977 8

Table.. Cohort studies of ethylene oxide and lymphohaematopoeitic cancer Hogstedt (988), Sweden Follow-up of Hogstedt et al. (979a,b, 98) All cohort Men 7 9. (NR).5 (. 7.7) Blood and lymphatic malignancies All cohort Men 9.59 (NR). (.7 5.7) Kiesselbach et al. (990), Germany 58 employees from chemical companies exposed to ethylene oxide for > months during 98 8, followed to December 98 5.00 (0..) 0.85 (0.0.) No data on exposure levels; risk estimates may have been seriously biased since most in cohort were not ascertained from death certificates. Benson & Teta (99), 78 men intermittently exposed to ethylene oxide in a chlorohydrin unit since 99, followed to 988 8.9 (.7 5.80) Primarily exposed to ethylene chlorohydrin, ethylene dichloride and bischloroethyl ether Teta et al. (99), 89 men potentially exposed to ethylene oxide since 90 at chemical plants but who never worked in chlorohydrin unit, followed to 988 Lymphosarcoma and reticulosarcoma 7 5 0. (0..).0 (0..5). (0..5) Norman et al. (995), workers employed in 97 80 at a sterilizing plant that used ethylene oxide, followed for cancer incidence to 957.85 (p = 0.)

Table.. Cohort studies of ethylene oxide and lymphohaematopoeitic cancer Hagmar et al. (99, 995), Sweden 70 workers employed for > months during 9 85 at plants where medical equipment was sterilized with ethylene oxide, followed for cancer incidence to 990 > 0. ppm years with induction period of 0 years.8 (0.5.88). (0.0 8.8) 7. (0.87 5.8) Swaen et al. (99), Belgium 0 employees of a chemical manufacturer between 9 and 99 Hodgkin lymphoma OR 8.5 (. 9.9) Nested case-control analysis Olsen et al. (997), men employed for > year and potentially engaged for > month in ethylene or propylene chlorohydrin production since 9 at chemical plants, followed to 99 Ever in ethylene chlorohydrin production Ever in ethylene chlorohydrin production with allowance for 5- year induction period from first exposure 0.9 (0..8). (0.5.) Bisanti et al. (99), Italy 97 male chemical workers licensed to handle ethylene oxide for > year during 98 8, followed 90 8 Lymphosarcoma and reticulosarcoma.5 (0.9 5.5).8 (.9 7).9 (0. 7.0) The leukaemia occurred in men with < 5 years of exposure and < 0 years after first exposure. Kardos et al. (00), Hungary 99 women employed on a hospital ward using ethylene oxide sterilizer in 97 9, followed 987 99.8 expected from all causes Deaths in the cohort ascertained from a different source from the reference rates

Table.. Cohort studies of ethylene oxide and lymphohaematopoeitic cancer Coggon et al. (00) United Kingdom 7 workers employed in production or use of ethylene oxide at chemical companies in 95 85, followed to December 000 05 workers potentially exposed to ethylene oxide in sterilization units at 8 hospitals during 9 8, followed to December 000 Environmental and personal monitoring since 977 (0 08) Hodgkin lymphoma (0) NHL (00) Multiple myeloma (0) Hodgkin lymphoma NHL. (0.9.).0 (0.0 7.8).8 (0.8.5).0 (0. 5.9) 0.55 (0.0.0).98 (0.08.).59 (0..) Update of Gardner et al. (989). Measured TWA concentrations < 5 ppm [9 mg/m ] in almost all jobs but with occasional peaks up to several hundred ppm; exposures probably higher in past Steenland et al. (00) 8 5 workers employed at industrial plants that used ethylene oxide for sterilization since 9 with months exposure to ethylene oxide, followed to 998. Update of Steenland et al. (99) and Stayner et al. (99) data over time based on a large number of measurements coupled with data of historical process changes, to quantitatively estimate cumulative exposure to ethylene oxide. (00-08) 0 99 00 79 80 99 > 500 Lymphoid-cell line tumours (00,0,0,0) Men with 5- year lag (results from Cox regression) Cum. exp. in 0 >0 99 00 79 80 99 > 500 79 8 0 8 8.00 (0.79.) 0.77 (NR). (NR).0 (NR) 0.9 (NR).00 0.90 (0. 5.).89 (0.5.8).7 (0.5.55).7 (.0.) p-trend = 0. Adjusted for age, race (white/non-white), date of birth (within 5 years); in an internal case control analysis (excluding small plant), log cumulative exposure to ethylene oxide lagged by 5 years significantly related to mortality from cancers in men (p = 0.0), but not in women; duration of exposure, peak exposure and average exposure less predictive of mortality from LH cancer; similar pattern observed for lymphoid-cell tumours

Table.. Cohort studies of ethylene oxide and lymphohaematopoeitic cancer Steenland et al. (00) Contd. Hodgkin lymphoma (0) 0 99 00 79 80-99 > 500 0. (0.5.) 0 (NR) 0.99 (NR).97 (NR).0 (NR) NHL (00,0) 0 99 00 79 80 99 > 500 7 8 9.00 (0.7.5) 0.7 (NR). (NR) 0.85 (NR). (NR) Multiple myeloma (0) 0 99 00 79 80 99 > 500 5 0.9 (0.5 0.87) 0. (NR).89 (NR) 0.9 (NR).0 (NR) (0-08) 0 99 00 79 80 99 > 500 9 0 0.99 (0.7.).5 (NR).0 (NR) 0.9 (NR) 0. (NR) 5

Table.. Cohort studies of ethylene oxide and lymphohaematopoeitic cancer (Swaen, et al. 009) 0 men employed in ethylene oxide production 95-988 and > January 90, vital status through 00 matrix ( eras and levels) + work histories to calculate cumulative doses All lymphohematopoetic (00-08) 0-5 ppm-year 5-5 ppm-year 5 + ppm-year 9.0 (0.-.) 0.89 (0.-.7) 0.59 (0.-.) US national comparison rates Age, year of death Hazard Ratio per ppm-yr (lymphoid only) 0.99 (0.985-.0) 0. (0.0-.95) 0.5 (0.-.) Leukemia (0-08) 0-5 ppm-year 5-5 ppm-year 5 + ppm-year 0.78 (0.-.).5 (0.5-.) 0.50 (0.0-.8) 0.998 (0.99-.0).9 (0.7-7.77) 0. (0.05-.50) (Valdez-Flores, et al. 00) 0 men employed in ethylene oxide production 95-988 and > January 90, vital status through 00 and 7,9 (9859 female, 7 male) of the 8, 5 workers employed at industrial plants that used ethylene oxide for sterilization since 9 matrix ( eras and levels) + work histories to calculate cumulative doses Haematopoetic (00-08) Leukemia (0-08) Non-Hodgkin lymphoma Hodgkin disease 0 0 0.97 (0.79-.7) 0.97 (0.70-.).0 (0.7-.) 0.9 (0.-.00) US national comparison rates Age, year of death Analysis of one facility in Kanawha Valley, West Virginia, (production workers) and facilities in (sterilizers) AML, acute myelogenous leukaemia; CI, confidence interval; CLL, chronic lymphocytic leukaemia; CML, chronic myelogenous leukaemia; ICD, International Classification of Diseases; LH, lymphohaematopoeitic; NHL, non-hodgkin lymphoma; NR, not reported; SIR, standardized incidence ratio;, standardized mortality ratio; TWA, time-weighted average