Methods for biological monitoring of propylene oxide exposure in Fischer 344 rats

Propylene oxide (PO) is used as an intermediate in the chemical industry. H uman exposure to PO may occur in the work place. Propylene, an important in dustrial chemical and a component of for example, car exhausts and cigarett e smoke, is another source of PO exposure. Once taken up in the organism, t his epoxide alkylates macromolecules, Such as haemoglobin and DNA. The aim of the present investigation was to compare two methods for determination o f in vivo dose, the steady state concentration of PO in blood of exposed ra ts and the level of haemoglobin adducts. Male Fischer 344 rats were exposed for 4 weeks (6 h/day, 5 days/week) to PO at a mean atmospheric concentrati on of 500 ppm (19.9 mu mol/l). Immediately after the last exposure blood wa s collected in order to determine the steady state concentration of PO. Fre e PO was measured in blood samples of three animals by means of a head spac e method to be 37 +/- 2 mu mol/l blood (mean +/- S.D.). Blood samples were also harvested for the measurement of haemoglobin adducts. N-2-Hydroxypropy l adducts with N-terminal valine in haemoglobin were quantified using the N -alkyl Edman method with globin containing adducts of deuterium-substituted PO as an internal standard and N-D,L-2-hydroxypropyl-Val-Leu-anilide as a reference compound. Tandem mass spectrometry was used for adduct quantifica tion. The adduct levels were < 0.02 and 77.7 +/- 4.7 nmol/g globin (mean +/ - S.D.) in control animals (n = 7) and in exposed animals (n = 34), respect ively. The adduct levels expected at the end of exposure were calculated to be 71.7 +/- 4.1 nmol/g globin (mean +/- S.D.) using the measured steady st ate concentration of PO in blood and taking into account the growth of anim als, the life span of erythrocytes, the exposure conditions and the second order rate constant for adduct formation. The good agreement between the es timated and measured adduct levels indicates that both end-points investiga ted are suitable for biological monitoring. (C) 1999 Elsevier Science Irela nd Ltd. All rights reserved.