Estimation of Human Toxicity From Animal Inhalation Toxicity Data: 2 (Abridged). GB Toxicity Reassessed Using Newer Techniques for Estimation of Human Toxicity
Abstract
Estimated human inhalation toxicity values for sarin (GB) were calculated using a new 3D, nonlinear dose response model combined with new allometric equations relating 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 6,621 animals, 762 groups, 37 studies, and 7 species. The toxicity of GB for each species was empirically related to exposure concentration (C; mg/m(exp 3)) and exposure time (T; min) through the surface function Y = b(sub 0) + b(sub 1) Log(sub 10) C + b(sub 2) Log(sub 10)T or Y = b(sub 0) + b(sub 2) Log(sub 10) C(exp n)T where Y is the PROBIT, b(sub 0), b(sub 1), and b(sub 2) are constants and n is the toxic load exponent. Between exposure times 0.17 and 30 minutes, the average value for n in 7 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 (LCt(sub 50)) 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 1.38 +/- 0.01. The pseudo-human data had much more variability at low exposure times. Raising the lower exposure limit to 1 minute did not change the LCt(sub 50) but did result in lower variability. Raising the lower value to 2 minutes was unproductive. Based on the toxic load model for 1-30 minute exposures, the n value was 1.40 and the human GB toxicities (LCt(sub 01), LCt(sub 05), LCt(sub 50), and LCt(sub 95)) for 70 kg humans breathing 15 L/minute were estimated to be 11, 16, 36, and 83; 18, 25, 57, and 132; 24, 34, 79, and 182 mg.min/m(exp 3) for 2, 10, and 30 minute 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 minutes. (96 re7
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2004
- Accession Number
- ADA426350
Entities
People
- E. Yee
- R. W. Bide
- S. J. Armour