Toxicology of Industrial Compounds

152 OCCUPATIONAL ASTHMA INDUCED BY CHEMICAL AGENTS
process. Once sensitised, a worker may have his symptoms initiated by very
low exposure levels of isocyanates.
Diisocyanate asthma is usually but not always associated with the
presence of nonspecific bronchial hyperreactivity. The majority of workers
who develop occupational asthma remain symptomatic requiring regular
treatment permanently after cessation of exposure (Allard et al., 1989).
The duration of exposure with symptoms before diagnosis has a major
influence on recovery patterns. In a group of 43 isocyanate workers with
occupational asthma, those who had fully recovered were exposed with
symptoms for 1.6 years, those who had improved, 2.8 years and those who
had not improved, 5.4 years (Pisati et al., 1993). The resolution or
improvement in occupational asthma takes place over a 2 year period after
cessation of exposure, symptoms still present at 2 years should be regarded
as permanent. Most epidemiological studies have not identified any specific
risk factors including atopic status, smoking or nonspecific bronchial
hyperreactivity.
The laboratory identification of specific antibodies to diisocyanates has
proved of very limited value. Diisocyanate specific IgE is demonstrable in
only 10–20% of sensitised individuals and have also been identified in
individuals with no history of asthma (Butcher et al., 1983). Similarly
specific IgG antibodies to diisocyanates have been described in workers
both with and without evidence of disease.
At the present time the recommended long-term exposure limit (8 h
TWA reference period) for diisocyanates is 0.02 mg m −3 and the short-term
exposure limit (10 min reference period) is 0.07 mg m −3 in the UK. There is
discussion at the present time as to whether levels should be lower in order
to prevent the development of diisocyanate asthma. However since most
workers with diisocyanate airways disease describe exposures in excess of
the current recommended exposure levels the prevalence of occupational
asthma in a workforce without such exposures is not known. There need to
be improvements in hygiene control to prevent these peak exposures to
isocyanates.
Acid anhydrides
The acid anhydrides are a group of low molecular weight chemicals used as
curing agents in the production of epoxy and alkyd resins and in the
production of plasticisers such as dioctyl phthalate. Acid anhydrides exert
diverse effects on man both as sensitisers, irritants or both. The most
frequently used anhydrides, all of which have been described causing
occupational asthma, are phthalic anhydride (PA), trimellitic anhydride
(TMA), tetrachlorophthalic anhydride (TCPA) and maleic anhydride
(MA). In addition himic anhydride and pyromellitic dianhydride (PMDA)
have been described as causing asthma.