{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T05:34:25Z","timestamp":1770356065043,"version":"3.49.0"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,8]]},"DOI":"10.1093\/toxsci\/kfn098","type":"journal-article","created":{"date-parts":[[2008,5,22]],"date-time":"2008-05-22T00:25:25Z","timestamp":1211415925000},"page":"320-331","source":"Crossref","is-referenced-by-count":21,"title":["Brown Norway Rat Asthma Model of Diphenylmethane-4,4\u2032-Diisocyanate (MDI): Analysis of the Elicitation Dose-Response Relationship"],"prefix":"10.1093","volume":"104","author":[{"given":"J\u00fcrgen","family":"Pauluhn","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2008,5,20]]},"reference":[{"key":"key\n\t\t\t\t20170315214628_bib1","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1152\/japplphysiol.00821.2003","article-title":"Unrestrained plethysmography is an unreliable measure of airway responsiveness in BALB\/c and C57BL\/6 mice","volume":"97","year":"2004","journal-title":"J. Appl. Physiol."},{"key":"key\n\t\t\t\t20170315214628_bib2","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/S0091-6749(99)70415-X","article-title":"Specific IgG response to monomeric and polymeric diphenylmethane diisocyanate conjugates in subjects with respiratory reactions to isocyanates","volume":"103","year":"1999","journal-title":"J. Allergy Clin. Immunol."},{"key":"key\n\t\t\t\t20170315214628_bib3","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1165\/ajrcmb.31.3.1","article-title":"The use and misuse of Penh in animal models of lung disease","volume":"31","year":"2004","journal-title":"Am. J. Respir. Cell. Mol. Biol."},{"key":"key\n\t\t\t\t20170315214628_bib4","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1289\/ehp.9557","article-title":"Skin exposure to isocyanates: Reasons for concern","volume":"115","year":"2007","journal-title":"Environ. Health Perspect."},{"key":"key\n\t\t\t\t20170315214628_bib5","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/0300-483X(94)03007-O","article-title":"A two-centre study for the evaluation and validation of an animal model for the assessment of the potential of small molecular weight chemicals to cause respiratory allergy","volume":"96","year":"1995","journal-title":"Toxicology"},{"key":"key\n\t\t\t\t20170315214628_bib6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.taap.2007.10.008","article-title":"Respiratory sensitization and allergy: Current research approaches and needs","volume":"226","year":"2008","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"key\n\t\t\t\t20170315214628_bib7","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1146\/annurev.immunol.22.012703.104716","article-title":"Asthma: Mechanisms of disease persistence and progression","volume":"22","year":"2004","journal-title":"Annu. Rev. Immunol."},{"key":"key\n\t\t\t\t20170315214628_bib8","first-page":"1","article-title":"Guideline of the Council dated November 24, 1986 on the reconciliation of legal and administrative regulations of the member countries for the protection of animals used for studies and other scientific purposes","volume":"29","author":"Directive 86\/609\/EEC","year":"1986","journal-title":"J. Eur. Community Legal Specifications L358"},{"key":"key\n\t\t\t\t20170315214628_bib9","volume-title":"Deutsche Forschungsgemeinschaft (DFG)\u2014MAK- und BAT-Wert-Liste. Senatskommission zur Pr\u00fcfung gesundheitssch\u00e4dliche Arbeitsstoffe Mitteilung 43. Diphenylmethan-4,4\u2032-diisocyanat","author":"DFG-MAK","year":"2007"},{"key":"key\n\t\t\t\t20170315214628_bib10","first-page":"175","article-title":"The immunology of allergic contact dermatitis: The DNCB story","volume":"5","year":"1990","journal-title":"Adv. Dermatol."},{"key":"key\n\t\t\t\t20170315214628_bib11","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1111\/j.1365-2133.2007.08162.x","article-title":"The relationships between exposure dose and response in induction and elicitation of contact hypersensitivity in humans","volume":"157","year":"2007","journal-title":"Br. J. Dermatol."},{"key":"key\n\t\t\t\t20170315214628_bib12","first-page":"507","article-title":"Low-dose exposure to antigen induces sub-clinical sensitization","volume":"81","year":"1990","journal-title":"Clin. Exp. Immunol."},{"key":"key\n\t\t\t\t20170315214628_bib13","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.yrtph.2003.07.001","article-title":"Proposal for a risk assessment methodology for skin sensitization based on sensitization potency data","volume":"38","year":"2003","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"key\n\t\t\t\t20170315214628_bib14","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1152\/japplphysiol.00526.2002","article-title":"Assessment of respiratory mechanics in small animals: The simpler the better?","volume":"93","year":"2002","journal-title":"J. Appl. Physiol."},{"key":"key\n\t\t\t\t20170315214628_bib15","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1111\/j.1365-2222.1992.tb00193.x","article-title":"Specific immunological and bronchopulmonary responses following intradermal sensitization to free trimellitic anhydride in guinea pigs","volume":"22","year":"1992","journal-title":"Clin. Exp. Allergy"},{"key":"key\n\t\t\t\t20170315214628_bib16","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1067\/mai.2002.123533","article-title":"A novel mouse model of diisocyanate-induced asthma showing allergic-type inflammation in the lung after inhaled antigen challenge","volume":"109","year":"2002","journal-title":"J. Allergy Clin. Immunol."},{"key":"key\n\t\t\t\t20170315214628_bib17","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1016\/j.fct.2004.06.017","article-title":"Thresholds of elicitation depend on induction conditions. Could low level exposure induce sub-clinical allergic states that are only elicited under the severe conditions of clinical diagnosis?","volume":"42","year":"2004","journal-title":"Food Chem. Toxicol."},{"key":"key\n\t\t\t\t20170315214628_bib18","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1164\/ajrccm.160.5.9806170","article-title":"Neutrophilic inflammation in severe persistent asthma","volume":"160","year":"1999","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"key\n\t\t\t\t20170315214628_bib19","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1097\/00130832-200404000-00006","article-title":"Animal models for diisocyanate asthma: Answers for lingering questions","volume":"4","year":"2004","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"key\n\t\t\t\t20170315214628_bib20","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1046\/j.1440-1843.1999.00196.x","article-title":"Evidence for neutrophil activation in occupational asthma","volume":"4","year":"1999","journal-title":"Respirology"},{"key":"key\n\t\t\t\t20170315214628_bib21","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1111\/j.1365-2222.1988.tb02911.x","article-title":"Experiences of specific IgE in asthma due to diisocyanates","volume":"18","year":"1988","journal-title":"Clin. Allergy"},{"key":"key\n\t\t\t\t20170315214628_bib22","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1164\/ajrccm.149.3.8118626","article-title":"Predictive value of airways hyperresponsiveness and circulating IgE for identifying types of responses to toluene diisocyanate inhalation challenge","volume":"149","year":"1994","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"key\n\t\t\t\t20170315214628_bib23","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1002\/jat.872","article-title":"Pulmonary responses and recovery following single and repeated inhalation exposure of rats to polymeric methylene diphenyl diisocyanate aerosols","volume":"22","year":"2002","journal-title":"J. Appl. Toxicol."},{"key":"key\n\t\t\t\t20170315214628_bib24","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1089\/08942680252908566","article-title":"Carbon dioxide accumulation during small animal, whole body plethysmography: Effects on ventilation, indices of airway function, and aerosol deposition","volume":"15","year":"2002","journal-title":"J. Aerosol Med."},{"key":"key\n\t\t\t\t20170315214628_bib25","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1183\/09031936.03.00026403","article-title":"Murine models of asthma","volume":"22","year":"2003","journal-title":"Eur. Respir. J."},{"key":"key\n\t\t\t\t20170315214628_bib26","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1165\/rcmb.F248","article-title":"Translational review\u2014Modeling allergic asthma in mice\u2014Pitfalls and opportunities","volume":"27","year":"2002","journal-title":"Am. J. Respir. Cell. Mol. Biol."},{"key":"key\n\t\t\t\t20170315214628_bib27","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1046\/j.1365-2222.2000.00911.x","article-title":"Airway inflammation in a murine model of chronic asthma: Evidence for a local humoral immune response","volume":"30","year":"2000","journal-title":"Clin. Exp. Allergy"},{"key":"key\n\t\t\t\t20170315214628_bib28","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1165\/rcmb.2002-0048OC","volume":"27","year":"2002","journal-title":"Am. J. Respir. Cell. Mol. Biol."},{"key":"key\n\t\t\t\t20170315214628_bib29","first-page":"641","article-title":"Airway inflammation and functional changes after exposure to different concentrations of isocyanates","volume":"10","year":"2002","journal-title":"J. Allergy Clin. Immunol."},{"key":"key\n\t\t\t\t20170315214628_bib30","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1046\/j.1365-2222.2000.00743.x","article-title":"Late asthmatic reaction with airway inflammation but without airway hyperresponsiveness","volume":"30","year":"2000","journal-title":"Clin. Exp. Allergy"},{"key":"key\n\t\t\t\t20170315214628_bib31","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1136\/thx.53.2.152","article-title":"Can reactive airways function syndrome (RADS) transform into occupational asthma due to \u201csensitization\u201d to isocyanates?","volume":"53","year":"1998","journal-title":"Thorax"},{"key":"key\n\t\t\t\t20170315214628_bib32","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1034\/j.1398-9995.2002.02164.x","article-title":"Neutrophilic airway inflammation and IL-17","volume":"57","year":"2002","journal-title":"Allergy"},{"key":"key\n\t\t\t\t20170315214628_bib33","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1183\/09031936.00091307","article-title":"Penh is not a measure of airway resistance!","volume":"30","year":"2007","journal-title":"Eur. Respir. J."},{"key":"key\n\t\t\t\t20170315214628_bib34","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1164\/ajrccm.159.6.9806159","article-title":"Occupational asthma caused by isocyanates: Patterns of asthmatic reactions to increasing day-to-day doses","volume":"159","year":"1999","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"key\n\t\t\t\t20170315214628_bib35","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1164\/ajrccm.158.1.let1","article-title":"Noninvasive measurement of airway responsiveness in allergic mice using barometric plethysmography","volume":"158","year":"1998","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"key\n\t\t\t\t20170315214628_bib36","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1152\/japplphysiol.00815.2002","article-title":"Interpreting Penh in mice","volume":"94","year":"2003","journal-title":"J. Appl. Physiol."},{"key":"key\n\t\t\t\t20170315214628_bib37","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1164\/ajrccm.161.2.9902094","article-title":"Prolonged allergen exposure induces structural airway changes in sensitized rats","volume":"161","year":"2000","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"key\n\t\t\t\t20170315214628_bib38","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1183\/09031936.02.00255402","article-title":"Repeated allergen exposure changes collagen composition in airways of sensitized Brown Norway rats","volume":"20","year":"2002","journal-title":"Eur. Respir. J."},{"key":"key\n\t\t\t\t20170315214628_bib39","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1164\/rccm.2109011","article-title":"Effect of age on allergen-induced structural airway changes in Brown Norway rats","volume":"165","year":"2002","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"key\n\t\t\t\t20170315214628_bib40","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1007\/s002040000114","article-title":"Acute inhalation toxicity of polymeric diphenylmethane-4,4\u2032-diisocyanate (MDI) in rats: Time course of changes in bronchoalveolar lavage","volume":"74","year":"2000","journal-title":"Arch. Toxicol."},{"key":"key\n\t\t\t\t20170315214628_bib41","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1080\/08958370252809068","article-title":"Short-term inhalation toxicity of polyisocyanate aerosols in rats: Comparative assessment of irritant-threshold concentrations by bronchoalveolar lavage","volume":"14","year":"2002","journal-title":"Inhal. Toxicol."},{"key":"key\n\t\t\t\t20170315214628_bib42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0300-483X(03)00285-3","article-title":"Respiratory hypersensitivity to trimellitic anhydride in Brown Norway rats: Analysis of dose-response following topical induction and time course following repeated inhalation challenge","volume":"194","year":"2003","journal-title":"Toxicology"},{"key":"key\n\t\t\t\t20170315214628_bib43","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1080\/08958370490434060","article-title":"Comparative analysis of pulmonary irritation by measurements of Penh and protein in bronchoalveolar lavage fluid in Brown Norway rats and Wistar rats exposed to irritant aerosols","volume":"16","year":"2004","journal-title":"Inhal. Toxicol."},{"key":"key\n\t\t\t\t20170315214628_bib44","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1080\/08958370500224631","article-title":"Brown Norway Rat asthma model of diphenylmethane-4,4\u2032-diisocyanate","volume":"17","year":"2005","journal-title":"Inhal. Toxicol."},{"key":"key\n\t\t\t\t20170315214628_bib45","article-title":"MDI lung sensitization following topical induction: Investigation of induction dose-response","year":"2006"},{"key":"key\n\t\t\t\t20170315214628_bib46","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.yrtph.2007.09.003","article-title":"Brown Norway rat asthma model of diphenylmethane-4,4\u2032-diisocyanate (MDI): Impact of vehicle for topical induction","volume":"50","year":"2008","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"key\n\t\t\t\t20170315214628_bib47","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1080\/089583799197140","article-title":"Respiratory hypersensitivity to diphenylmethane-4,4\u2032-diisocyanate in guinea-pigs: Comparison with trimellitic anhydride","volume":"11","year":"1999","journal-title":"Inhal. Toxicol."},{"key":"key\n\t\t\t\t20170315214628_bib48","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1002\/jat.831","article-title":"Respiratory hypersensitivity to trimellitic anhydride in Brown Norway rats: A comparison of endpoints","volume":"22","year":"2002","journal-title":"J. Appl. Toxicol."},{"key":"key\n\t\t\t\t20170315214628_bib49","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1080\/089583799196637","article-title":"Two-week inhalation toxicity of polymeric diphenylmethane-4,4\u2032-diisocyanate (PMDI) in rats: Analysis of biochemical and morphological markers of early pulmonary response","volume":"11","year":"1999","journal-title":"Inhal. Toxicol."},{"key":"key\n\t\t\t\t20170315214628_bib50","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.etp.2004.10.002","article-title":"Experimental approaches to evaluate respiratory allergy in animal models","volume":"56","year":"2005","journal-title":"Exp. Toxicol. Pathol."},{"key":"key\n\t\t\t\t20170315214628_bib51","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1080\/08958370590898434","article-title":"Repeated inhalation challenge with diphenylmethane-4,4\u2032-diisocyanate in Brown Norway rats leads to a time-related increase of neutrophils in bronchoalveolar lavage after topical induction","volume":"17","year":"2005","journal-title":"Inhal. Toxicol."},{"key":"key\n\t\t\t\t20170315214628_bib52","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/0300-483X(94)90108-2","article-title":"Induction of respiratory hypersensitivity to diphenylmethane-4,4\u2032-diisocyanate (MDI) in guinea pigs. Influence of route of exposure","volume":"88","year":"1994","journal-title":"Toxicology"},{"key":"key\n\t\t\t\t20170315214628_bib53","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1111\/j.1365-2133.1990.tb08236.x","article-title":"The influence of area of application on sensitization by dinitrochlorobenzene","volume":"122","year":"1990","journal-title":"Br. J. Dermatol."},{"key":"key\n\t\t\t\t20170315214628_bib54","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1165\/ajrcmb.17.6.2849","article-title":"Kinetics and quantification of eosinophil and neutrophil recruitment to allergic lung inflammation in a Brown Norway rat model","volume":"17","year":"1997","journal-title":"Am. J. Respir. Cell. Mol. Biol."},{"key":"key\n\t\t\t\t20170315214628_bib55","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1164\/ajrccm.163.3.2005010","article-title":"Temporal association between airway hyperresponsiveness and airway eosinophilia in ovalbumin-sensitized mice","volume":"163","year":"2001","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"key\n\t\t\t\t20170315214628_bib56","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.yrtph.2007.11.008","article-title":"Skin sensitization in chemical risk assessment: report of a WHO\/IPCS international workshop focusing on dose-response assessment","volume":"50","year":"2008","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"key\n\t\t\t\t20170315214628_bib57","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/BF00406191","article-title":"Isocyanate-induced asthma: Results of inhalation tests with TDI, MDI and methacholine","volume":"63","year":"1991","journal-title":"Int. Arch. Occup. Environ. Health"},{"key":"key\n\t\t\t\t20170315214628_bib58","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1111\/j.1365-2133.1986.tb06646.x","article-title":"The effect of altering area of application and dose per unit area on sensitization by DNCB","volume":"115","year":"1986","journal-title":"Br. J. Dermatol."}],"container-title":["Toxicological Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/toxsci\/article-pdf\/104\/2\/320\/10999254\/kfn098.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,5,11]],"date-time":"2019-05-11T15:30:46Z","timestamp":1557588646000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/toxsci\/article\/1654745\/Brown"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,5,20]]},"references-count":58,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2008,5,20]]},"published-print":{"date-parts":[[2008,8]]}},"URL":"https:\/\/doi.org\/10.1093\/toxsci\/kfn098","relation":{},"ISSN":["1096-6080","1096-0929"],"issn-type":[{"value":"1096-6080","type":"print"},{"value":"1096-0929","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,5,20]]}}}