Cytogenetic Effects of Ethylene Oxide, with an Emphasis on Population Monitoring

Abstract

Cytogenetic assays are an integral component of the battery of short-term assays that are used for the hazard identification component of a cancer risk assessment. The protocol for the conduct of such assays for maximal sensitivity for detecting clastogenicity has to be attendant to the mechanism of induction of the endpoint being assessed and the fact that several aberration types are cell lethal necessitates that analysis be for cells at their first posttreatment metaphase. Cytogenetic assays for human populating monitoring have been used for predicting potential for carcinogenicity in humans. However, the assays as typically conducted are not appropriate for chronic exposures because nontransmissible alterations are assessed. The use of fluorescent in situ hybridization (FISH) techniques for the assessment of transmissible changes such as reciprocal translocations are required to make population monitoring studies interpretable, and for removing some of the concern over the influence of confound-ers on outcome. The database for the cytogenetic effects of ethylene oxide in vitro and in vivo, with an emphasis on human population monitoring, has been critically reviewed. Based on the endpoints studied, the size of the study groups, the information on exposure, the nature of any exposure response data, and the possible influence of confounders (i.e., control matching), it is concluded that acute, high exposures to ethylene oxide with sampling shortly (a few days) after exposure can be detected by increases in chromosome aberrations or SCE in peripheral lymphocytes. Such increases are indicators of exposure to a genotoxic chemical and not predictors of subsequent adverse health effects to individuals. The effect of chronic and/or low level (less than about 25 ppm) exposures cannot be reliably evaluated using current methods.

The use of FISH, for example, for assessing reciprocal translocation frequencies (as a measure of transmissible events) will greatly improve the ability to detect chronic exposures to clastogenic chemicals.

KEYWORDS: :

• chromosome aberrations
• sister chromotid exchanges
• ethylene oxide
• population monitoring
• in vitro assays
• in vivo assays.