Biologically-based dose-response model for neurotoxicity risk assessment

被引:13
|
作者
Slikker, W [1 ]
Scallet, AC [1 ]
Gaylor, DW [1 ]
机构
[1] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA
关键词
neurotoxicity risk assessment; biologically-based dose-response model; excitotoxic amino acids; domoic acid; quantitative histological techniques;
D O I
10.1016/S0378-4274(98)00335-X
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
Domoic acid is a tricarboxylic amino acid that is structurally-related to kainic acid and glutamic acid. It is produced by phytoplankton that may contaminate seafood. To determine domoate's toxicological effects and their pathogenesis, cynomolgus monkeys were dosed intravenously at one of a range of bolus doses from 0.25 to 4.0 mg/kg. Histochemical staining, using silver methods, revealed degenerating axons and cell bodies. Doses in the range of 0.5-1.0 mg/kg produced a small area of silver grains restricted to axons of the hippocampal CA2 stratum lucidum, the most sensitive brain area identified. Quantitation of the abundance of these silver grains yielded continuous dose-response data. A four step quantitative risk estimation approach was used: (1) determination of a dose-response model; (2) determination of the distribution of measurements (variability) about the model; (3) determination of an adverse or abnormal level with the use of the control data; and (4) estimation of the probability that a measure is beyond the abnormal level as a function of dose. The currently used safety-factor (S-F) approach, the benchmark (BM) approach and this quantitative (Q) approach was used to assess the same data set. Assuming a 5% oral absorption of domoic acid, acceptable doses would be achieved if subjects ate 200 g of seafood containing 12, 6 and 10 ppm domoic acid for the S-F, BM and Q approaches, respectively. This quantitative approach uses all the available data, takes into account the variability of the data and provides an actual risk at a given dose of domoic acid. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:429 / 433
页数:5
相关论文
共 50 条
  • [1] A biologically-based dose-response model for developmental toxicology
    Leroux, BG
    Leisenring, WM
    Moolgavkar, SH
    Faustman, EM
    RISK ANALYSIS, 1996, 16 (04) : 449 - 458
  • [2] Integration of biologically-based dose-response functions into cancer risk assessment for populations and individuals
    Conolly, RB
    Gaylor, DW
    Lutz, WK
    TOXICOLOGY AND APPLIED PHARMACOLOGY, 2004, 197 (03) : 170 - 171
  • [3] Towards the development of a biologically based dose-response model of lead neurotoxicity
    Gilbert, ME
    AMERICAN ZOOLOGIST, 1997, 37 (04): : 389 - 398
  • [4] Developmental neurotoxicity of inhaled methanol: a quantitative, dose-response risk assessment model
    Slikker, W
    Gaylor, DW
    VOLATILE ORGANIC COMPOUNDS IN THE ENVIRONMENT - RISK ASSESSMET AND NEUROTOXICITY, 1997, 3 (03): : 191 - 197
  • [5] Neuroprotection or neurotoxicity - Impact of discontinuous dose-response curves on risk assessment
    Slikker, W
    Duhart, H
    Gaylor, D
    Imam, S
    NEUROPROTECTIVE AGENTS, 2003, 993 : 158 - 158
  • [6] Perspective on biologically-based approaches to dioxin risk assessment
    Greenlee, William F.
    Andersen, Melvin E.
    Lucier, George W.
    Risk Analysis, 1991, 11 (04)
  • [7] A PERSPECTIVE ON BIOLOGICALLY-BASED APPROACHES TO DIOXIN RISK ASSESSMENT
    GREENLEE, WF
    ANDERSEN, ME
    LUCIER, GW
    RISK ANALYSIS, 1991, 11 (04) : 565 - 568
  • [8] An evaluation of the USEPA Proposed Approaches for applying a biologically based dose-response model in a risk assessment for perchlorate in drinking water
    Clewell, Harvey J., III
    Gentry, P. Robinan
    Hack, C. Eric
    Greene, Tracy
    Clewell, Rebecca A.
    REGULATORY TOXICOLOGY AND PHARMACOLOGY, 2019, 103 : 237 - 252
  • [9] Biologically based dose-response model for liver tumors induced by trichloroethylene
    Chen, CW
    ENVIRONMENTAL HEALTH PERSPECTIVES, 2000, 108 : 335 - 342
  • [10] What Role for Biologically Based Dose-Response Models in Estimating Low-Dose Risk?
    Crump, Kenny S.
    Chen, Chao
    Chiu, Weihsueh A.
    Louis, Thomas A.
    Portier, Christopher J.
    Subramaniam, Ravi P.
    White, Paul D.
    ENVIRONMENTAL HEALTH PERSPECTIVES, 2010, 118 (05) : 585 - 588