The acquisition and application of absorption, distribution, metabolism and excretion (ADME) data in agricultural chemical safety assessments

被引：100

作者：

Barton, HA

Pastoor, TP

Baetcke, K

Chambers, JE

Diliberto, J

Doerrer, NG

Driver, JH

Hastings, CE

Iyengar, S

Krieger, R

Stahl, B

Timchalk, C

机构：

[1] ILSI, Hlth & Environm Sci Inst, Washington, DC 20005 USA

[2] US EPA, Natl Ctr Computat Toxicol, Res Triangle Pk, NC 27711 USA

[3] Syngenta Crop Protect, Greensboro, NC USA

[4] US EPA, Off Pesticide Programs, Washington, DC 20460 USA

[5] Mississippi State Univ, Mississippi State, MS 39762 USA

[6] US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA

[7] Infoscicom, Manassas, VA USA

[8] BASF Corp, Res Triangle Pk, NC USA

[9] Bayer CropSci, Monheim, Germany

[10] Univ Calif Riverside, Riverside, CA 92521 USA

[11] Bayer CropSci, Sophia Antipolis, France

[12] Pacific NW Natl Lab, Richland, WA 99352 USA

来源：

CRITICAL REVIEWS IN TOXICOLOGY | 2006年 / 36卷 / 01期

关键词：

absorption; ADME; agricultural chemicals; distribution; excretion; metabolism; pharmacokinetics; tiered testing;

D O I：

10.1080/10408440500534362

中图分类号：

R99 [毒物学（毒理学）];

学科分类号：

100405 ;

摘要：

A proposal has been developed by the Agricultural Chemical Safety Assessment (ACSA) Technical Committee of the ILSI Health and Environmental Sciences Institute (HESI) for an improved approach to assessing the safety of crop protection chemicals. The goal is to ensure that studies are scientifically appropriate and necessary without being redundant, and that tests emphasize toxicological endpoints and exposure durations that are relevant for risk assessment. Incorporation of pharmacokinetic studies describing absorption, distribution, metabolism, and excretion is an essential tool for improving the design and interpretation of toxicity studies and their application for safety assessment. A tiered approach is described in which basic pharmacokinetic studies, similar to those for pharmaceuticals, are conducted for regulatory submission. Subsequent tiers provide additional information in an iterative manner, depending on pharmacokinetic properties, toxicity study results, and the intended uses of the compound.

引用

页码：9 / 35

页数：27

共 109 条

[21] Human variability in polymorphic CYP2D6 metabolism: is the kinetic default uncertainty factor adequate? [J].