Deviations from Haber's Law for multiple measures of acute lung injury in chlorine-exposed mice.
Chlorine gas is considered a chemical threat agent that can cause acute lung injury. Studies in the early 20th century on war gases led Haber to postulate that the dose of an inhaled chemical expressed as the product of gas concentration and exposure time leads to a constant toxicological effect (Haber's Law). In the present work, mice were exposed to a constant dose of chlorine (100 ppm-h) delivered using different combinations of concentration and time (800 ppm/7.5 min, 400 ppm/15 min, 200 ppm/30 min, and 100 ppm/60 min). Significant effects of exposure protocol on survival evaluated 6 h after exposure were observed, ranging from 0% for the 7.5-min exposure to 100% for the 30- and 60-min exposures. Multiple parameters indicative of lung injury were examined to determine if any aspects of lung injury were differentially affected by the exposure protocols. Most parameters (pulmonary edema, neutrophil influx, and levels of protein, immunoglobulin M, and the chemokine KC [Cxcl1] in lavage fluid) indicated that lung injury was most pronounced for the 15-min exposure and least for the 60-min exposure. In contrast, changes in pulmonary function at baseline and in response to inhaled methacholine were similar following the three exposure regimens. The results indicate that the extent of lung injury following chlorine inhalation depends not only on total dose but also on the specifics of exposure concentration and time, and they suggest that evaluation of countermeasures against chlorine-induced lung injury should be performed using multiple types of exposure scenarios.
Hoyle
Gary W
GW
Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, Louisville, Kentucky 40202, USA. Gary.Hoyle@louisville.edu
Chang
Weiyuan
W
Chen
Jing
J
Schlueter
Connie F
CF
Rando
Roy J
RJ
D055371:Acute Lung Injury / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D000280:Administration, Inhalation; D000818:Animals; D002619:Chemical Warfare Agents / Q000633:toxicity*; D002713:Chlorine / Q000008:administration & dosage / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D023381:Endpoint Determination; D019570:Inhalation Exposure; D008136:Longevity / Q000187:drug effects; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D009929:Organ Size / Q000187:drug effects; D013047:Specific Pathogen-Free Organisms
D002619:Chemical Warfare Agents; D002713:Chlorine
Arch Toxicol. 1993;67(7):478-90
8239997
Am J Respir Crit Care Med. 2003 Sep 1;168(5):568-74
12724121
J Appl Toxicol. 1998 Jul-Aug;18(4):249-55
9719424
Toxicology. 2005 Nov 5;215(1-2):48-56
16076519
Am J Physiol Lung Cell Mol Physiol. 2008 Nov;295(5):L733-43
18708632
J Appl Physiol (1985). 1999 Jun;86(6):1984-93
10368365
Public Health Rep. 2007 Nov-Dec;122(6):784-92
18051671
J Appl Physiol (1985). 1996 May;80(5):1841-9
8727575
J Appl Physiol (1985). 2007 Jan;102(1):221-30
17008432
Am J Clin Pathol. 1971 Oct;56(4):430-42
5113398
Eur Respir J. 1997 May;10(5):1100-7
9163653
Am J Physiol Lung Cell Mol Physiol. 2010 Sep;299(3):L289-300
20525917
Toxicol Appl Pharmacol. 1979 Jun 15;49(1):77-88
473205
Inhal Toxicol. 2008 Jul;20(9):783-93
18645717
Am Ind Hyg Assoc J. 1978 Feb;39(2):129-38
565136
J Appl Physiol (1985). 2002 Jul;93(1):263-70
12070213
J Appl Toxicol. 1994 Nov-Dec;14(6):405-9
7884144
J Appl Physiol (1985). 2004 Jun;96(6):2019-27
14660507
Am Rev Respir Dis. 1969 Mar;99(3):374-9
5765629
Am J Physiol Lung Cell Mol Physiol. 2010 Jun;298(6):L830-6
20348278
Toxicology. 2000 Aug 14;149(1):21-34
10963858
Respir Res. 2008 Jun 12;9:51
18549493
Lung. 2005 May-Jun;183(3):151-67
16078037
J Occup Med. 1962 Mar;4:152-4
14452652
J Appl Physiol (1985). 1992 Jan;72(1):168-78
1537711