PHYSIOLOGICALLY BASED TOXICOKINETIC MODELING OF 3 WATERBORNE CHLOROETHANES IN RAINBOW-TROUT (ONCORHYNCHUS-MYKISS)

被引:63
作者
NICHOLS, JW [1 ]
MCKIM, JM [1 ]
LIEN, GJ [1 ]
HOFFMAN, AD [1 ]
BERTELSEN, SL [1 ]
机构
[1] ASCI CORP,DULUTH,MN 55804
关键词
D O I
10.1016/0041-008X(91)90040-L
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
A physiologically based toxicokinetic model for fish was used to simulate the uptake and disposition of three waterborne chloroethanes in rainbow trout (Oncorhynchus mykiss). Trout were exposed to 1,1,2,2-tetrachloroethane, pentachloroethane, and hexachloroethane in fish respirometer-metabolism chambers to assess the kinetics of chemical accumulation in arterial blood and chemical extraction efficiency from inspired water. Chemical residues in tissues were measured at the end of each experiment. Trout exposed to tetrachloroethane were close to steady-state in 48 hr. Fish exposed to pentachloroethane were near steady-state in 264 hr. Extraction efficiency data showed that systemic (extrabranchial) elimination of both chemicals was small. Hexachloroethane continued to accumulate in fish exposed for 600 hr. Parameterized with chemical partitioning data obtained in vitro, the model accurately simulated the uptake of all three chloroethanes in blood and tissues and their extraction from inspired water. These results provide support for the basic model structure and the accuracy of physiological input parameters. © 1991.
引用
收藏
页码:374 / 389
页数:16
相关论文
共 34 条
[1]   QUANTITATIVE RELATIONS IN THE PHYSIOLOGICAL CONSTITUTIONS OF MAMMALS [J].
ADOLPH, EF .
SCIENCE, 1949, 109 (2841) :579-585
[2]  
AHMAD N, 1984, EPA600S384009 PROJ S
[3]   PHYSIOLOGICALLY BASED PHARMACOKINETICS AND THE RISK ASSESSMENT PROCESS FOR METHYLENE-CHLORIDE [J].
ANDERSEN, ME ;
CLEWELL, HJ ;
GARGAS, ML ;
SMITH, FA ;
REITZ, RH .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 1987, 87 (02) :185-205
[4]   TEMPERATURE-DEPENDENCE OF CARDIAC-OUTPUT AND REGIONAL BLOOD-FLOW IN RAINBOW-TROUT, SALMO-GAIRDNERI RICHARDSON [J].
BARRON, MG ;
TARR, BD ;
HAYTON, WL .
JOURNAL OF FISH BIOLOGY, 1987, 31 (06) :735-744
[5]   PHARMACOKINETIC MODELING OF DOGFISH SHARK (SQUALUS-ACANTHIAS) - DISTRIBUTION AND URINARY AND BILIARY-EXCRETION OF PHENOL RED AND ITS GLUCURONIDE [J].
BUNGAY, PM ;
DEDRICK, RL ;
GUARINO, AM .
JOURNAL OF PHARMACOKINETICS AND BIOPHARMACEUTICS, 1976, 4 (05) :377-388
[6]  
Clewell H J 3rd, 1985, Toxicol Ind Health, V1, P111
[7]   A SIMPLE FLOW-LIMITED MODEL FOR EXCHANGE OF ORGANIC-CHEMICALS AT FISH GILLS [J].
ERICKSON, RJ ;
MCKIM, JM .
ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY, 1990, 9 (02) :159-165
[8]   DETERMINING KINETIC CONSTANTS OF CHLORINATED ETHANE METABOLISM IN THE RAT FROM RATES OF EXHALATION [J].
GARGAS, ML ;
ANDERSEN, ME .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 1989, 99 (02) :344-353
[9]   MODELING THE TISSUE SOLUBILITIES AND METABOLIC-RATE CONSTANT (VMAX) OF HALOGENATED METHANES, ETHANES, AND ETHYLENES [J].
GARGAS, ML ;
SEYBOLD, PG ;
ANDERSEN, ME .
TOXICOLOGY LETTERS, 1988, 43 (1-3) :235-256
[10]   PHYSIOLOGICALLY BASED PHARMACOKINETIC MODELING - PRINCIPLES AND APPLICATIONS [J].
GERLOWSKI, LE ;
JAIN, RK .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1983, 72 (10) :1103-1127