Cytogenetic effects of ethylene oxide, with an emphasis on population monitoring

Cytogenetic assays are an integral component of the battery of short-term a ssays that are used for the hazard identification component of a cancer ris k assessment. The protocol for the conduct of such assays for maximal sensi tivity for detecting clastogenicity has to be attendant to the mechanism of induction of the endpoint being assessed and the fact that several aberrat ion types are cell lethal necessitates that analysis be for cells at their first posttreatment metaphase. Cytogenetic assays for human populating moni toring have been used for predicting potential for carcinogenicity in human s. However, the assays as typically conducted are not appropriate for chron ic exposures because nontransmissible alterations are assessed. The use of fluorescent in situ hybridization (FISH) techniques for the assessment of t ransmissible changes such as reciprocal translocations are required to make population monitoring studies interpretable, and for removing same of the concern over the influence of confounders on outcome. The database for the cytogenetic effects of ethylene oxide in vitro and in vivo, with an emphasi s on human population monitoring, has been critically reviewed. Based on th e endpoints studied, the size of the study groups, the information on expos ure, the nature of any exposure response data, and the possible influence o f confounders (i.e., control matching), it is concluded that acute, high ex posures to ethylene oxide with sampling shortly (a few days) after exposure can be detected by increases in chromosome aberrations or SCE in periphera l lymphocytes. Such increases are indicators of exposure to a genotoxic che mical and not predictors of subsequent adverse health effects to individual s. The effect of chronic and/or low level (less than about 25 ppm) exposure s cannot be reliably evaluated using current methods. The use of FISH, for example, for assessing reciprocal translocation freque ncies (as a measure of transmissible events) will greatly improve the abili ty to detect chronic exposures to clastogenic chemicals.