PHYSICOCHEMICAL PROPERTIES OF NONREACTIVE VOLATILE ORGANIC-CHEMICALS TO ESTIMATE RD50 - ALTERNATIVES TO ANIMAL STUDIES

被引:43
作者
ALARIE, Y
NIELSEN, GD
ANDONIANHAFTVAN, J
ABRAHAM, MH
机构
[1] DANISH NATL INST OCCUPAT HLTH, DK-2100 COPENHAGEN O, DENMARK
[2] UCL, DEPT CHEM, LONDON WC1H 0AJ, ENGLAND
关键词
D O I
10.1006/taap.1995.1172
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
This article presents the correlations obtained between the results on the potency of nonreactive airborne chemicals as sensory irritants and several of their physicochemical properties. The potency of airborne sensory irritants obtained from a reflexively induced decrease in respiratory frequency has been measured in the past using mice. Typically, their potency has been expressed as the exposure concentration necessary to decrease respiratory frequency by 50% (RD50). A large database of RD50 values is now available and such values are highly correlated with occupational exposure guidelines such as threshold limit values (TLVs). We used the nonreactive volatile organic chemicals from this database, for which relevant physicochemical variables are available or can be calculated. These variables were vapor pressure (P) or Ostwald gas-liquid partition coefficients (L). The liquids used for L values were n-hexadecane, octanol, N-formylmorpholine, tri-(2-ethyl-hexyl)phosphate, and olive oil. Excellent correlations were found between log RD50 and log P, as well as between log RD50 and log L(16), log L(Oct), log L(NFM), log L(EHP), or log L(Oil). It follows that as an alternative to the bioassay, these physicochemical variables can be used to estimate RD50 of nonreactive volatile organic chemicals. Appropriate exceptions to general estimation of RD50 values from physicochemical variables are also presented, as well as the most appropriate estimates which can be obtained within homologous series. (C) 1995 Academic Press, Inc.
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页码:92 / 99
页数:8
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