title: GB toxicity reassessed using newer techniques for estimation of human toxicity from animal inhalation toxicity data: new method for estimating acute human toxicity (GB).
abstract: 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.
authors.affiliation: Defence R&D Canada Suffield, Box 4000, Medicine Hat, Alberta, Canada T1A 8K6. Richard.Bide@drdc-rddc.gc.ca
authors.forename: R W
authors.initials: RW
authors.lastname: Bide
authors.forename: S J
authors.initials: SJ
authors.lastname: Armour
authors.forename: E
authors.initials: E
authors.lastname: Yee
mesh_terms: D000465:Algorithms; D000818:Animals; D001717:Birds; D002415:Cats; D002619:Chemical Warfare Agents / Q000633:toxicity*; D003627:Data Interpretation, Statistical; D004285:Dogs; D004330:Drosophila; D006168:Guinea Pigs; D000882:Haplorhini / Q000502:physiology; D006801:Humans; D019570:Inhalation Exposure; D007928:Lethal Dose 50; D051379:Mice; D017711:Nonlinear Dynamics; D011237:Predictive Value of Tests; D011817:Rabbits; D051381:Rats; D012524:Sarin / Q000008:administration & dosage / Q000633:toxicity*; D012756:Sheep; D013045:Species Specificity; D013552:Swine
chemical_list: D002619:Chemical Warfare Agents; D012524:Sarin