Estimation of rat blood:air partition coefficients of volatile organic chemicals using reconstituted mixtures of blood components

被引：16

作者：

Béliveau, M ^{[1
]}

Krishnan, K ^{[1
]}

机构：

[1] Univ Montreal, Grp Rech Toxicol Humaine, TOXHUM, Montreal, PQ H3C 3J7, Canada

来源：

TOXICOLOGY LETTERS | 2000年 / 116卷 / 03期

基金：

加拿大自然科学与工程研究理事会;

关键词：

blood : air partition coefficients; VOCs; pharmacokinetics; PBPK modeling;

D O I：

10.1016/S0378-4274(00)00219-8

中图分类号：

R99 [毒物学（毒理学）];

学科分类号：

100405 ;

摘要：

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 cc-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. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.

引用

页码：183 / 188

页数：6

共 16 条

[1]

Fiserova-Bergerova V., 1983, MODELING INHALATION, P3

[2] DETERMINATION AND PREDICTION OF TISSUE-GAS PARTITION-COEFFICIENTS [J].

FISEROVABERGEROVA, V ;

DIAZ, ML .

INTERNATIONAL ARCHIVES OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH, 1986, 58 (01) :75-87

[3] PARTITION-COEFFICIENTS OF LOW-MOLECULAR-WEIGHT VOLATILE CHEMICALS IN VARIOUS LIQUIDS AND TISSUES [J].

GARGAS, ML ;

BURGESS, RJ ;

VOISARD, DE ;

CASON, GH ;

ANDERSEN, ME .

TOXICOLOGY AND APPLIED PHARMACOLOGY, 1989, 98 (01) :87-99

[4]

JOHANSON G, 1988, BRIT J IND MED, V45, P561

[5] PARTITION-COEFFICIENTS OF SOME ACETATE ESTERS AND ALCOHOLS IN WATER, BLOOD, OLIVE OIL, AND RAT-TISSUES [J].

KANEKO, T ;

WANG, PY ;

SATO, A .

OCCUPATIONAL AND ENVIRONMENTAL MEDICINE, 1994, 51 (01) :68-72

[6]

Krishnan Kannan, 1994, P149

[7] MECHANISM OF TRANSPORT AND DISTRIBUTION OF ORGANIC-SOLVENTS IN BLOOD [J].

LAM, CW ;

GALEN, TJ ;

BOYD, JF ;

PIERSON, DL .

TOXICOLOGY AND APPLIED PHARMACOLOGY, 1990, 104 (01) :117-129

[8]

PERBELLINI L, 1985, BRIT J IND MED, V42, P162

[9] Molecular structure-based prediction of the partition coefficients of organic chemicals for physiological pharmacokinetic models [J].

Poulin, P ;

Krishnan, K .

TOXICOLOGY METHODS, 1996, 6 (03) :117-137

[10]

Poulin P, 1999, TOXICITY ASSESSMENT ALTERNATIVES, P115

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