Toxicology of Industrial Compounds

10
Mechanisms of Pulmonary Sensitization
IAN KIMBER
Zeneca Central Toxicology Laboratory, Macclesfield
Introduction
A wide range of chemicals is known to cause allergic contact dermatitis. It
is apparent, however, that chemicals also have the potential to provoke other
forms of allergy and of growing concern is pulmonary sensitization.
Examples of chemicals identified as human respiratory allergens are listed
in Table 10.1. Respiratory allergic hypersensitivity is characterized by
pulmonary reactions which occur normally in only a proportion, and
frequently in only a small proportion, of exposed individuals. In those who
are sensitized, respiratory reactions can be provoked by atmospheric
concentrations of the causative chemical allergen which were tolerated
previously and which are without effect in the non-sensitized population
(Newman Taylor, 1988). Almost invariably there is a latent period between
the onset of exposure and the development of respiratory symptoms such
as asthma and rhinitis.
By definition, allergy, including sensitization of the respiratory tract,
results from the stimulation of specific immune responses by the causative
agent. Although it is assumed frequently that effective allergic sensitization
of the respiratory tract results largely or wholly from inhalation exposure,
this is not necessarily the case. Allergic reactions manifest in a particular
organ commonly result from the local provocation by the inducing agent of
a systemically sensitized individual. There is no reason to suppose that the
quality of immune response necessary for sensitization of the respiratory
tract may not result from exposure to the chemical allergen at a different
site. Consistent with this is evidence that occupational respiratory allergy
may be caused by dermal contact with the chemical (Karol, 1986; Nemery
and Lenaerts, 1993). Furthermore, it has been reported that respiratory
rate changes can be provoked by inhalation exposure of guinea pigs
sensitized previously by either topical or subcutaneous treatment with the
same chemical (Karol et al., 1981; Rattray et al., 1994). Despite the fact
that, in practice, pulmonary sensitization may not be caused exclusively by