The Contribution of Acute Toxicity in Animals to Occupational Exposure Limits of Chemical Substances

Abstract

The correlations of lethal doses of various industrial chemicals for rats and mice with occupational exposure limit values were investigated. 50% lethal dose (LD₅₀) values obtained by oral (p.o.) and intraperitoneal (i.p.) injection and 50% lethal concentration (LC₅₀) values obtained by inhalation exposure were collected from Registry of Toxic Effects of Chemical Substances (RTECS). Threshold Limit Value (Time-Weighted Average) (TLVs-TWA) and Threshold Limit Value (Short Term Exposure Limit) (TLVs-STEL) recommended by American Conference of Governmental Industrial Hygienists (ACGIH) were used as exposure limits. TLVs-TWA or TLVs-STEL and LD₅₀ or LC₅₀ values obtained for the rats were plotted on logarithmic scales on the ordinate and abscissa, respectively. High correlations were obtained between these parameters. The order of correlations was: TLVs-STEL vs. LC₅₀s>TLVs-TWA vs. LC₅₀s>TLVs-TWA vs. LD₅₀s i.p.>TLVs vs. LD₅₀s p.o. The same calculations for the relationship between TLVs and lethal doses in mice were also performed. The order of the three types of correlations was same as that of the rats; however, correlation coefficients for TLVs-STEL vs. LC₅₀s and for TLVs-TWA vs. LC₅₀s obtained in mice were smaller than those in rats. TLVs-TWA are, therefore, well correlated with LC₅₀ values rather than LD₅₀ values, particularly with those in rats. High correlations between TLVs-STEL vs. LC₅₀s were also obtained, as had been expected before calculation. The equation: TLV-TWA=10^b×(LC₅₀)^a can be obtained from these plottings, where the values a and b are taken from each linear regression line. TLV-TWA for each chemical can be calculated by using LC₅₀ and the equation. The upper and lower 95% confidence limits for calculated TLV-TWA were TLV-TWA (calculated from LC₅₀)×22.9 and TLV-TWA (calculated)/22.9, respectively, where LC₅₀ for rats expressed in ppm×hr was used.