A pharmacokinetic analysis of interspecies extrapolation in dioxin risk assessment

被引：18

作者：

Lawrence, GS ^{[1
]}

Gobas, FAPC ^{[1
]}

机构：

[1] SIMON FRASER UNIV, SCH RESOURCE & ENVIRONM MANAGEMENT, BURNABY, BC V5A 1S6, CANADA

来源：

CHEMOSPHERE | 1997年 / 35卷 / 03期

关键词：

D O I：

10.1016/S0045-6535(97)00108-2

中图分类号：

X [环境科学、安全科学];

学科分类号：

08 ; 0830 ;

摘要：

This study entails a pharmacokinetic analysis of the relationship between the external dose of 2,3,7,8-tetrachlorodibenzo-rho-dioxin (dioxin, TCDD) and resulting concentrations of TCDD in internal tissues and organs of humans and rodent species. The methodology is based on the development and testing of physiologically based pharmacokinetic models for several rodent species and humans. The results indicate that the relationship between the external dose of TCDD and resulting TCDD concentrations in liver and adipose tissue of humans and various species of rats and mice can vary by as much as 725 fold, illustrating that humans and experimental animals differ considerably in their ability to convert external dosages of dioxin to tissue concentrations. Interspecies scaling factors are reported to express the differences in tissue concentrations of dioxin between mice, rats and humans in response to an equivalent external dose. The significance of these findings for conducting human cancer and ecological risk assessments is discussed. It is recommended that pharmacokinetic differences be considered explicitly in risk estimation, while separately recognizing interspecies differences in pharmacodynamics (sensitivity). (C) 1997 Elsevier Science Ltd.

引用

页码：427 / 452

页数：26

共 71 条

[1] MECHANISMS OF TCDD-INDUCTION OF CLEFT-PALATE - INSIGHTS FROM INVIVO AND INVITRO APPROACHES [J].

ABBOTT, BD ;

DILIBERTO, JJ ;

BIRNBAUM, LS .

CHEMOSPHERE, 1992, 25 (1-2) :75-78

[2] CARCINOGEN RISK ASSESSMENT [J].

ALBERT, RE .

ENVIRONMENTAL HEALTH PERSPECTIVES, 1989, 81 :103-105

[3] CORRELATION BETWEEN CARCINOGENIC POTENCY OF CHEMICALS IN ANIMALS AND HUMANS [J].

ALLEN, BC ;

CRUMP, KS ;

SHIPP, AM .

RISK ANALYSIS, 1988, 8 (04) :531-544

[4] MODELING RECEPTOR-MEDIATED PROCESSES WITH DIOXIN - IMPLICATIONS FOR PHARMACOKINETICS AND RISK ASSESSMENT [J].

ANDERSEN, ME ;

MILLS, JJ ;

GARGAS, ML ;

KEDDERIS, L ;

BIRNBAUM, LS ;

NEUBERT, D ;

GREENLEE, WF .

RISK ANALYSIS, 1993, 13 (01) :25-36

[5] PCDD AND PCDF EXPOSURE AND LEVELS IN HUMANS IN GERMANY [J].

BECK, H ;

BROSS, A ;

MATHAR, W .

ENVIRONMENTAL HEALTH PERSPECTIVES, 1994, 102 :173-185

[6] THE MECHANISM OF DIOXIN TOXICITY - RELATIONSHIP TO RISK ASSESSMENT [J].

BIRNBAUM, LS .

ENVIRONMENTAL HEALTH PERSPECTIVES, 1994, 102 :157-167

[7] FACTORS AFFECTING THE TOXICITY OF DIOXIN-LIKE TOXICANTS - A MOLECULAR APPROACH TO RISK ASSESSMENT OF DIOXINS [J].

BROWN, MM ;

MCCREADY, TL ;

BUNCE, NJ .

TOXICOLOGY LETTERS, 1992, 61 (2-3) :141-147

[8]

BULL RJ, 1993, MANAGEMENT OPERA MAR, P49

[9] MODELING OF THE TOXICOKINETICS OF POLYCHLORINATED DIBENZO-P-DIOXINS AND DIBENZOFURANS IN MAMMALIANS, INCLUDING HUMANS .1. NONLINEAR DISTRIBUTION OF PCDD/PCDF BODY BURDEN BETWEEN LIVER AND ADIPOSE TISSUES [J].

CARRIER, G ;

BRUNET, RC ;

BRODEUR, J .

TOXICOLOGY AND APPLIED PHARMACOLOGY, 1995, 131 (02) :253-266

[10] THE IMPORTANCE OF PHARMACOKINETICS IN DETERMINING THE RELATIVE POTENCY OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN AND 2,3,7,8-TETRACHLORODIBENZOFURAN [J].

DEVITO, MJ ;

BIRNBAUM, LS .

FUNDAMENTAL AND APPLIED TOXICOLOGY, 1995, 24 (01) :145-148

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