Estimation of rat blood:air partition coefficients of volatile organic chemicals using reconstituted mixtures of blood components.
The objective of the present study was to estimate the rat blood:air partition coefficients (PC) of some volatile organic chemicals (VOCs) using reconstituted mixtures of blood components. Based on previous observations, three blood components (water, lipid, hemoglobin) should be necessary in the case of lipophilic VOCs (e.g. bromoform (BF), chlorobenzene (CB) chloroform (CF), and ethylbenzene (EB)) whereas a mixture of oil (lipid surrogate) and water should be adequate to estimate the blood:air PC (P(b:a)) of other VOCs (e.g. butyl methyl ether (BME), t-butyl methyl ether (tBME), diethyl ether (ETH), isooctane (ISO), methyl ethyl ketone (MEK), and alpha-pinene (PIN)). Vial equilibration studies showed that the matrix:air PCs for the oil+water samples were similar or greater than those of rat blood (mean+/-S.E., n=7-8) for BME (11.1+/-2.0 vs. 6.64+/-1.4), tBME (15.0+/-4 vs. 15.0+/-2), ETH (9.50 +/-1.16 vs. 9.24+/-0.75), ISO (2. 88+/-0.5 vs. 1.92+/-0.4), MEK (159.3+/-8 vs. 139+/-6), and PIN (20. 5+/-2.7 vs. 16.9+/-1.8), whereas they were significantly lower for BF (19.0+/-3.4 vs. 161+/-5), CF (3.4+/-0.75 vs. 16.9+/-1.1), CB (8. 3+/-2.35 vs. 61.8+/-2.8), and EB (7.13+/-1.6 vs. 50.8+/-1.3). These results suggest that additional consideration of solubility/binding in blood proteins is essential in order to adequately determine rat P(b:a) of BF, CB, CF, and EB. The PCs determined using whole blood were comparable to those obtained using a reconstituted mixture of n-octanol (lipid surrogate), water and hemoglobin (mean+/-S.E., n=3-4) for BF (154+/-1.5), CB (55+/-6), CF (15+/-0.87), and EB (30+/-1.5). The results of the present study suggest that VOC partitioning into three blood components, namely, water, lipids and hemoglobin determines to a large extent the magnitude of their blood:air PCs.
Béliveau
M
M
Groupe de Recherche en Toxicologie Humaine (TOXHUM), Université de Montréal, C.P. 6128, Succursale Centre-ville, Québec, H3C 3J7, Montreal, Canada.
Krishnan
K
K
D000388:Air; D000818:Animals; D006454:Hemoglobins / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D010599:Pharmacokinetics; D051381:Rats; D011916:Rats, Inbred F344; D012995:Solubility; D014835:Volatilization
D006454:Hemoglobins