Ethylene oxide exposure

Two epidemiological studies of workers exposed to ethylene oxide revealed increased rates of leukemia. In one smdy, two cases of leukemia (0.14 expected) and three stomach cancers (0.4 expected) were observed. The other study found three cases of leukemia (0.2 expected). Because these workers had exposures to other potential carcinogens, the findings cannot be linked with certainty to ethylene oxide. The small cohort size, the small number of deaths, and uncertainties about exposure level have also been noted." A number of other studies have not found an increased rate of cancer mortality from ethylene oxide exposure. A mortality study of over 18,000 ethylene oxide workers from 14 plants producing medical supplies and foodstuffs did not find an excess of leukemia or brain, stomach, or pancreatic cancers. There was, however, an increase in non-Hodgkin lymphoma in male workers. A follow-up of 1896 ethylene oxide production workers did not find an increase in mortality from leukemia, non-Hodgkin lymphoma, or brain, pancreatic, or stomach cancers. ... 

Rowland AS, Baird DD, Shore DL, et al Ethylene oxide exposure may increase the... 

Weller E, Long N, Smith A, Williams P, Ravi S, Gill J, Henessey R, Skornik W, Brain J, Kimmel C, Kimmel G, Holmes L, Ryan L (1999) Dose-rate effects of ethylene oxide exposure on developmental toxicity. Toxicol Sci, 50(2) 259-270. 

Process Conditions for Ethylene Oxide. Exposure to ethylene oxide lasted 4, 6.5, and 15 hr. To keep the relative humidity at the necessary percent (1, 2, 3), water vapor was added to the chamber of the VDF. Exposure of the books to ethylene oxide occurred at either room temperature or at an elevated temperature. When the maximum temperature in the chamber in the latter case was set for approximately 40 °C, it took about 60 min to get to 33 °C and 3 hr to reach the maxium value. The temperature changes of the gas throughout the chamber after closing the chamber door were determined by placing a series of thermocouples both inside and outside of the books at different positions on the cart. A maximum difference of 11 °C was recorded upon entry of the gas into the chamber between a pair of these thermocouples positioned on the bottom shelf. The difference was reduced to 1°C after 8 min of exposure. Temperatures at the various positions were monitored throughout the entire experiment. 

Christensen, D.E. Changing EtO sterilizer cycles to reduce ethylene oxide exposure levels. Med. Dev. Diagn. Ind. 1984, 6, 27-35. 

Jay WM, Swift TR, Hull DS. Possible relatiorrship of ethylene oxide exposure to cataract formation. Am J Ophthalmol 1982 93(6) 727-32. 

Estrin WJ, Cavaheri SA, Wald P, Becker CE, Jones JR, Cone JE. Evidence of neurologic dysfunction related to long-term ethylene oxide exposure. Arch Neurol 1987 44(12) 1283-6. 

Crystal HA, Schaumburg HH, Grober E, Fuld PA, Lipton RB. Cognitive impairment and sensory loss associated with chronic low-level ethylene oxide exposure. Neurology 1988 38(4) 567-9. 

Sobaszek A, Hache JC, Frimat P, Akakpo V, Victoire G, Furon D. Working conditions and health effects of ethylene oxide exposure at hospital sterilization sites. J Occup Environ Med 1999 41(6) 492-9. 

Florack El, Zielhuis GA. Occupational ethylene oxide exposure and reproduction. Int Arch Occup Environ Health 1990 62(4) 273-7. 

Chalupa B, Synkova J, Sevcik M The assessment of electroencephalographic changes and memory disturbances in acute intoxications with industrial poisons. British Journal of Industrial Medicine 17 238-241,1960 Cherry N, Venables H, Waldron HA, et al Some observations on workers exposed to methylene chloride. British Journal of Industrial Medicine 38 351-355, 1981 Crystal HA, Schaumburg HH, Grober E, et al Cognitive impairment and sensory loss associated with chronic low-level ethylene oxide exposure. Neurology 38 567-569, 1988... 

Estrin WJ, Cavalieri SA, Wald P, et al Evidence of neurologic dysfunction related to long-term ethylene oxide exposure. Arch Neurol 44 1283-1286, 1987 Estrin WJ, Bowler RM, Lash A, et al Neurotoxicological evaluation of hospital sterilizer workers exposed to ethylene oxide. Clin Toxicol 28 1-20,1990 Fukushima T, Abe K, Nakagawa A, et al Chronic ethylene oxide poisoning in a factory manufacturing medical appliances. Journal of Social and Occupational Medicine 36 118-123,1986... 

Hurlbut KM, Bernstein JN, Burgess JL, et al Bell s palsy and frontal lobe functional deficit from ethylene oxide exposure (abstract). Vet Hum Toxicol 34 357, 1992 Kelafant GA, Berg RA, Schleenhaker R Toxic encephalopathy due to 1,1,1-trichloro-ethane exposure. Am J Ind Med 25 439-446,1994 Klees JE, Lash A, Bowler RM, et al Neuropsychologic impairment in a cohort of hospital workers chronically exposed to ethylene oxide. Clin Toxicol 28 21-28,1990 Lauwerys R, Herbrand J, Buchet JP, et al Health surveillance of workers exposed to tetrachloroethylene in dry-cleaning shops. Int Arch Occup Environ Health 52 69-77, 1983... 

Ristow GE, Cornelius D The neurological manifestations of chronic ethylene oxide exposure (abstract). Ann Neurol 20 136,1986 Seeber A Neurobehavioral toxicity of long-term exposure to tetrachloroethylene. Neu-rotoxicol Teratol 11 579-583, 1989... 

A variety of techniques have been applied for sterilizing microfluidic cell culture chips and covered by reviews [12, 25] and references therein, such as autoclaving, UV light, oxygen plasma, gamma irradiation, ethylene oxide exposure and perfusion with ethanol, hypochlorite or sodium hydroxide. The applicability of the different techniques primarily depends, aside from what is available in a laboratory, on the type of system and the fabrication material. Autoclaving is an effective method but not suitable for chips fabricated of thermoplastic polymers. The applied temperature and pressure... 

The excipient manufacturer must document the sanitizing of critical processing equipment such as centrifuges and dryers. Any manipulation of sterile excipients post-sterilization must be performed as a validated aseptic process. This is particularly important for those excipients which are not further sterilized prior to packaging into final containers. In some instances, the compendial monographs may specify that an excipient which does not meet parenteral grade standards be labelled as not suitable for use in the preparation of injectable products. Ethylene oxide is sometimes used for the sterilization of powders. The manufacture should validate that the ethylene oxide exposure does, in fact, produce a sterile product. 

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