In vivo dosimetry of ethylene oxide and propylene oxide in the cynomolgus monkey

In mammals, including the cynomolgus monkey, a striking difference between the potencies of ethylene oxide (EO)* and propylene oxide (PO) with respect to induction of certain clastogenic effects has previously been observed. In order to clarify to what extent such differences can be ascribed to a difference in detoxification rate, cynomolgus monkeys were administered an equimolar mixture of the two epoxides at two dose levels, and the blood doses were determined by measurement of the degree of alkylation of N-terminal valines in hemoglobin (Hb). For the highest exposure a saturation in the detoxification of PO was evident from a marked increase in adduct level. At the lower exposure, the dose in blood resulting from exposure to PO was about one fourth of that from EO. Although playing a great role, differences in detoxification rate, therefore, cannot fully account for the much lower clastogenic potency of PO, which has been found in earlier studies. Furthermore, the determination of doses in blood gives data on relationship between in vivo dose and exposure dose (accounting for detoxification), with relevance for risk estimation.