title: Chemical determinants of occupational hypersensitivity pneumonitis.
abstract: BACKGROUND
  Workplace inhalational exposures to low molecular weight (LMW) chemicals cause hypersensitivity pneumonitis (HP) as well as the more common manifestation of respiratory hypersensitivity, occupational asthma (OA).
  
  
  OBJECTIVE
  To explore whether chemical causation of HP is associated with different structural and physico-chemical determinants from OA.
  
  
  METHODS
  Chemical causes of human cases of HP and OA were identified from searches of peer-reviewed literature up to the end of 2011. Each chemical was categorized according to whether or not it had been the attributed cause of at least one case of HP. The predicted asthma hazard was determined for each chemical using a previously developed quantitative structure-activity relationship (QSAR) model. The chemicals in both sets were independently and 'blindly' analysed by an expert in mech anistic chemistry for a qualitative prediction of protein cross-linking potential and determination of lipophilicity (log K ow).
  
  
  RESULTS
  Ten HP-causing chemicals were identified and had a higher median QSAR predicted asthma hazard than the control group of 101 OA-causing chemicals (P < 0.01). Nine of 10 HP-causing chemicals were predicted to be protein cross-linkers compared with 24/92 controls (P < 0.001). The distributions of log K ow indicated higher values for the HP list (median 3.47) compared with controls (median 0.81) (P < 0.05).
  
  
  CONCLUSIONS
  These findings suggest that chemicals capable of causing HP tend to have higher predicted asthma hazard, are more lipophilic and are more likely to be protein cross-linkers than those causing OA.
authors.affiliation: Centre for Occupational and Environmental Health, Centre for Epidemiology, Institute of Population Health, Faculty of Medical and Human Sciences, The University of Manchester, Manchester M13 9PL, UK, martin.seed@manchester.ac.uk.
authors.forename: M J
authors.initials: MJ
authors.lastname: Seed
authors.affiliation: School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool L3 3AF, UK.
authors.forename: S J
authors.initials: SJ
authors.lastname: Enoch
authors.affiliation: Centre for Occupational and Environmental Health, Centre for Epidemiology, Institute of Population Health, Faculty of Medical and Human Sciences, The University of Manchester, Manchester M13 9PL, UK.
authors.forename: R M
authors.initials: RM
authors.lastname: Agius
mesh_terms: D000395:Air Pollutants, Occupational / Q000009:adverse effects*; D000542:Alveolitis, Extrinsic Allergic / Q000139:chemically induced* / Q000517:prevention & control; D001249:Asthma / Q000139:chemically induced* / Q000517:prevention & control; D006801:Humans; D008970:Molecular Weight; D009784:Occupational Diseases / Q000139:chemically induced* / Q000517:prevention & control; D016273:Occupational Exposure / Q000009:adverse effects*; D009930:Organic Chemicals / Q000009:adverse effects* / Q000633:toxicity; D010865:Pilot Projects; D018570:Risk Assessment; D013329:Structure-Activity Relationship
chemical_list: D000395:Air Pollutants, Occupational; D009930:Organic Chemicals
keywords: Hypersensitivity pneumonitis; occupational chemicals; occupational respiratory disease; toxic inhalation.