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

This article presents the correlations obtained between the results on the potency of nonreactive airborne chemicals as sensory irritants an d several of their physicochemical properties. The potency of airborne sensory irritants obtained from a reflexively induced decrease in res piratory frequency has been measured in the past using mice. Typically , their potency has been expressed as the exposure concentration neces sary 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 d atabase, 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)pho sphate, and olive oil. Excellent correlations were found between log R D50 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 alternati ve to the bioassay, these physicochemical variables can be used to est imate RD50 of nonreactive volatile organic chemicals. Appropriate exce ptions to general estimation of RD50 values from physicochemical varia bles are also presented, as well as the most appropriate estimates whi ch can be obtained within homologous series. (C) 1995 Academic Press, Inc.