title: Rats repeatedly exposed to toluene diisocyanate exhibit immune reactivity against methyl isocyanate-protein conjugates.
abstract: BACKGROUND
  Volatile monoisocyanates are formed through thermal degradation when products containing polyurethane are heated. Repeated exposure to diisocyanates, such as toluene diisocyanate (TDI) are a well-known cause of occupational asthma. However, although monoisocyanates are abundant in occupational settings, there are few data concerning their ability to provoke immune reactions and asthma. We compared immune reactivity and respiratory disease following single or repeated inhalation exposures to the monoisocyanates methyl isocyanate (MIC) and isocyanic acid (ICA) with the effects of TDI.
  
  
  METHODS
  Isocyanates were administrated either as single vapor exposures or as repeated intranasal instillations in rats. Adverse health effects were monitored by analyzing airway inflammation, respiratory function and weight gain. Immune reactivity caused by repeated exposures was studied by analysis of isocyanate-specific antibodies and airway infiltration of immune competent cells.
  
  
  RESULTS
  Repeated exposures to TDI induced airway infiltration of neutrophils and lymphocytes, while neither MIC nor ICA provoked a detectable inflammatory response. Antibodies against isocyanate-albumin conjugates were detected in serum after both exposures to TDI and MIC, but not to ICA. TDI-exposed rats also displayed IgG antibodies against MIC-albumin conjugates. Even though MIC did not induce airway inflammation, single exposure provoked an increase in airway resistance and repeated exposures caused weight loss similar to that of TDI.
  
  
  CONCLUSIONS
  Airway exposure to TDI produces an antibody response not only against TDI but also against MIC-protein conjugates. This indicates that immune reactivity against abundant monoisocyanates in occupational environments can occur in individuals pre-sensitized with low abundance but highly sensitizing diisocyanates.
authors.affiliation: Division of CBRN Defence and Security, Swedish Defence Research Agency, FOI, Umeå, Sweden. linda.elfsmark@foi.se
authors.forename: Linda
authors.initials: L
authors.lastname: Svensson-Elfsmark
authors.forename: Bo L
authors.initials: BL
authors.lastname: Koch
authors.forename: Asa
authors.initials: A
authors.lastname: Gustafsson
authors.forename: Anders
authors.initials: A
authors.lastname: Bucht
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001249:Asthma / Q000097:blood / Q000139:chemically induced / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D017953:Isocyanates / Q000276:immunology*; D008297:Male; D046912:Multiprotein Complexes / Q000276:immunology*; D020556:Neutrophil Infiltration / Q000187:drug effects; D016273:Occupational Exposure / Q000009:adverse effects; D051381:Rats; D011916:Rats, Inbred F344; D017208:Rats, Wistar; D012129:Respiratory Function Tests; D014051:Toluene 2,4-Diisocyanate / Q000008:administration & dosage* / Q000009:adverse effects; D015430:Weight Gain / Q000187:drug effects
chemical_list: D000939:Epitopes; D007074:Immunoglobulin G; D017953:Isocyanates; D046912:Multiprotein Complexes; D014051:Toluene 2,4-Diisocyanate; C008461:methyl isocyanate