Quantitative estimation of the genetic risk associated with the induction of heritable translocations at low-dose exposure: ethylene oxide as an example.

ABSTRACT

This paper explores how quantitative risk assessment methods might be extended to analysis of risks to the human germ line. High inhalation exposures to ethylene oxide are reported to cause heritable translocations in male mice with a steep and nonlinear dose-response-curve. We explore quantitative estimation of risk to humans from low exposures based on these animal data, addressing questions of tissue dosimetry for this alkylating agent, expected equivalency of doses across species, germ-cell sensitivity, and extrapolation of dose-response relationship to low exposure levels. Various dose-response models are discussed in terms of their applicability to genetic end points and their ability to reflect the underlying basis of induced heritable translocations.