SURVEY OF THE QSAR AND INVITRO APPROACHES FOR DEVELOPING NONANIMAL METHODS TO SUPERSEDE THE INVIVO LD50 TEST

被引:35
作者
PHILLIPS, JC
GIBSON, WB
YAM, J
ALDEN, CL
HARD, GC
机构
[1] MRC, TOXICOL UNIT, WOODMANSTERNE RD, CARSHALTON SM5 4EF, SURREY, ENGLAND
[2] BRITISH IND BIOL RES ASSOC, CARSHALTON SM5 4DS, SURREY, ENGLAND
[3] PROCTER & GAMBLE CO, MIAMI VALLEY LABS, CINCINNATI, OH 45239 USA
关键词
D O I
10.1016/0278-6915(90)90112-Z
中图分类号
TS2 [食品工业];
学科分类号
0832 ;
摘要
Quantitative structure-activity relationship (QSAR) studies and in vitro studies in which correlations with LD50 have been sought are reviewed. QSAR methods have shown some success in relating LD50 to certain physicochemical properties of the compound, particularly lipophilicity, but have been less successful in correlating LD50 with electronic properties of molecules (related to reactivity) or structural variables. It is concluded that insufficient evidence is available to determine whether QSAR methods can be of general use in predicting the acute toxicity (LD50) of chemicals, and that until further work is undertaken to develop QSARs for a much wider range of homologous series of compounds, this situation is unlikely to be resolved. New chemical descriptors that are more directly relevant to the mechanism of toxic action of the chemical should be identified. Cytotoxicity in vitro is poorly correlated with LD50, but good correlations have been obtained between toxicity in vivo and in vitro, using systems in which the toxic endpoint reflects the probable mechanism(s) of acute toxicity of the test chemical (e.g. the assessment of neurotoxins using neural cell systems). Therefore, it seems that the successful application of in vitro methods requires a better understanding of the mechanisms of acute toxicity in vivo and the development of mammalian cell culture systems that can model more closely the metabolic fate of the chemicals in vivo. © 1990.
引用
收藏
页码:375 / 394
页数:20
相关论文
共 121 条
[1]  
ACOSTA D, 1985, IN VITRO CELL DEV B, V21, P495
[2]   QUANTITATIVE STRUCTURE ACTIVITY RELATIONSHIP STUDIES OF ACUTE TOXICITY (LD50) IN A LARGE SERIES OF HERBICIDAL BENZIMIDAZOLES [J].
ADAMSON, GW ;
BAWDEN, D ;
SAGGERS, DT .
PESTICIDE SCIENCE, 1984, 15 (01) :31-39
[3]  
ANDRYSOVA O, 1972, PHYSIOL BOHEMOSLOV, V21, P63
[4]  
[Anonymous], 1981, OECD GUIDELINES TEST, DOI 10. 1787/9789264070363-en
[5]   IMPORTANCE OF THE HYDROPHOBIC SULFOXIDE SUBSTITUENT ON NONTOXIC ANALOGS OF SPARSOMYCIN [J].
ASH, RJ ;
FITE, LD ;
BEIGHT, DW ;
FLYNN, GA .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1984, 25 (04) :443-445
[6]  
Autian J., 1973, Environmental Health Perspectives, P3
[7]  
AUTIAN J, 1975, Environmental Health Perspectives, V11, P141, DOI 10.2307/3428337
[8]  
BADILESCU II, 1980, NEOPLASMA, V27, P261
[9]  
BALLS M, 1983, ACTA PHARMACOL TOX, V52, P115
[10]  
BARACU I, 1981, REV ROUM BIOCHIM, V18, P175