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GB toxicity reassessed using newer techniques for estimation of human toxicity from animal inhalation toxicity data: New method for estimating acute human toxicity (GB)
Author(s) -
Bide R. W.,
Armour S. J.,
Yee E.
Publication year - 2005
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.1074
Subject(s) - toxicity , inhalation , inhalation exposure , toxicology , acute toxicity , chemistry , toxicokinetics , biology , medicine , anesthesia , organic chemistry
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 = b 0 + b 1 Log 10 C + b 2 Log 10 T or Y = b 0 + b 2 Log 10 C n T where Y is the Normit, b 0 , b 1 and b 2 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 (LCt 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 1.40. The pseudo‐human data had much more variability at low exposure times. Raising the lower exposure limit to 1 min, did not change the LCt 50 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 (LCt 01 , LCt 05 , LCt 50 and LCt 95 ) 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.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. Copyright © 2005 Crown in the right of Canada. Published by John Wiley & Sons, Ltd.