Estimated human inhalation toxicity values for Sarin (GB) were calculated using a new two independent (concentration, exposure time), one dependent (toxic response), non-linear dose response (toxicity) model combined with re-evaluated allometric equations relating to animal and human respiration. Historical animal studies of GB toxicity containing both exposure and fractional animal response data were used to test the new process. The final data set contained 6621 animals, 762 groups, 37 studies and 7 species. The toxicity of GB for each species was empirically related to exposure concentration (C; mg m(-3)) and exposure time (T; min) through the surface function Y = b0 + b1 Log10C + b2 Log10T or Y = b0 + b2 Log10C(n)T where Y is the Normit, b0, b1 and b2 are constants and n is the 'toxic load exponent' (Normit is PROBIT - 5). Between exposure times of 0.17 and 30 min, the average value for n in seven species was 1.35 +/- 0.15. The near parallel toxic load equations for each species and the linear relationship between minute volume/body weight ratio and the inhalation toxicity (LCt50) for GB were used to create a pseudo-human data set and then an exposure time/toxicity surface for the human. The calculated n for the human was 1.40. The pseudo-human data had much more variability at low exposure times. Raising the lower exposure limit to 1 min, did not change the LCt50 but did result in lower variability. Raising the lower value to 2 min was counterproductive. Based on the toxic load model for 1-30 min exposures, the human GB toxicities (LCt01, LCt05, LCt50 and LCt95) for 70 kg humans breathing 15 l min(-1) were estimated to be 11, 16, 36 and 83; 18, 25, 57 and 132 and 24, 34, 79 and 182 mg x min m(-3) for 2, 10 and 30 min exposures, respectively. These values are recommended for general use for the total human population. The empirical relationships employed in the calculations may not be valid for exposure times >30 min.
Most of the historical data for the toxicity of sarin (GB) was collected for exposure times of <10 min in attempts to establish the utility of and defence against this agent in offensive military use. However, information concerning the toxicity of GB (and other nerve agents) from longer exposures of 1-12 h is critical for all personnel who must work in or close to low-level concentrations of chemical for extended periods and for all personnel, dressed in Individual Protective Equipment, who need to know when, and if, it is safe to take off these cumbersome garments.The data presented for the toxicity of GB to mice for whole-body exposures of 20 min to 12 h are intended to form part of an ongoing, multi-species effort aimed at establishing toxicity estimates for humans for these longer exposure times: LCT50 values of 430, 540, 900, 1210 and 2210 mg.min m(-3) or LC50 values of 21.5, 9.0, 5.0, 3.4 and 3.1 mg m(-3) were obtained for mice for 20-, 60-, 180-, 360- and 720-min exposures to GB, respectively. The data for longer exposures do not follow Haber's rule (LCT50=CT). The 20- and 60-min data fit the 'toxic load model' involving CnT that was established previously from historical data for 0.17-30 min GB exposures to mice. The LCT(50) and LC50 values for 3, 6 and 12 h are progressively higher (toxicity lower) than predicted by either Haber's rule or the toxic load model.
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