Toxicology of Industrial Compounds

The most common chemical causes of occupational asthma include the
iso- cyanates and the acid anhydrides. This chapter will examine these two
groups in more detail.
Isocyanates
C.A.C.PICKERING 151
The polyisocyanates and their oligomers are the most important cause of
chemically induced asthma. These organic compounds are synthesised by
the reaction of amines with phosgene. There are a number of related
compounds the most important of which are 2,4- and 2,6-toluene
diisocyanate (TDI), methylene diphenyldiisocyanate (MDI), hexamethylene
diisocyante (HDI), napthalene diisocyanate (NDI), isophorone diisocyanate
(IPDI), and polyisocyanates derived from HDI and MDI.
The incidence of occupational asthma due to diisocyanates varies widely.
It is influenced by the type of compound and its vapour pressure. TDI and
HDI are highly volatile at room temperature, whereas MDI has to be
heated to above 60°C to volatilise. It is thought that approximately 5% of
an exposed working population will develop occupational asthma after
exposure to TDI (Diem et al., 1982). Because of the known respiratory
problems associated with exposure to isocyanates with high vapour
pressure properties, new isocyanate compounds with low vapour pressure
properties have been developed particularly for use in the paint spraying
industry. Recent studies however continue to demonstrate significant levels
of occupational asthma despite the use of recommended respiratory
protection (Seguin et al., 1987, Welinder et al., 1988). Bronchial
provocation studies with HDI- and MDI-derived polyisocyanates have
confirmed their ability to cause occupational asthma. Airborne iso-cyanate
prepolymers appear to be able to induce asthma to the same or greater
frequency as isocyanate monomers.
High exposures to isocyanate vapours, such as occur in a major
industrial spillage, cause acute rhinitis, lacrymation, cough and wheezing
leading to subsequent sensitisation. In some individuals this type of
exposure induces persistent asthma—reactive airways dysfunction
syndrome (RADS). Respiratory sensitisation may occur at very low levels
of exposure. Pepys et al. (1972) described a boat builder who became
sensitised to TDI at exposure levels of between 0.00173 and 0.0018 ppm.
Similarly White et al. (1980) reported respiratory symptoms and the
development of IgE antibodies to TDI, in machinists manufacturing carseat
covers exposed to levels of TDI of between 0.0003 and 0.003 ppm. It is
more usual, in the author’s experience, for the sensitised individual to
provide a history of short lived peak exposures to isocyanates which have
clearly been above the current threshold limit value. These intermittent
relatively high level exposures may be important in the sensitisation