Toxicology of Industrial Compounds

J.PAULUHN 133
Figure 9.1 Time-response curves for respiratory rate from mice, rats and guineapigs
during single 45-min exposures to appoximately 5 mg m −3 phenyl isocyanate.
Data were normalized on pre-exposure values during 15-min air exposure. Data
points for each concentration are the mean of four animals and were averaged for
45 s.
of conscious guinea-pigs that were sensitized to and challenged with 4,4′diphenylmethane-diisocyanate
(MDI) aerosol or trimellitic anhydride
(TMA) dust as well as their corresponding proteinconjugates was
monitored plethysmographically. The airway hyper-responsiveness to
subsequently increased inhaled acetylcholine (ACh) concentrations was
assessed 1 day after the hapten challenge (Pauluhn, 1994). In most
instances, selected morphological features of the airways (increased
number of eosinophils in the bronchial mucosa and lung associated lymph
nodes) were also taken into account.
Collectively, it was noticed that elicitation of respiratory hypersensitivity
is concentration-dependent and that challenge concentrations should
slightly exceed the threshold concentration for irritation. The evaluation of
eosinophils in subepithelial tissues and lung associated lymph nodes
appears to provide an important independent adjunct to measurements of
respiratory function. The combined assessment of specific pathologic
features such as eosinophilic infiltration and the evaluations of several