Toxicology of Industrial Compounds

The direct toxicity of anhydrides involves irritation of the mucus
membranes and skin which may result in eye lesions, epistaxis, pulmonary
congestion, haemoptysis and skin burns (Venables, 1989).
Occupational asthma is most frequently reported due to PA, less
commonly to TMA, TCPA and MA and finally there are single case reports
of asthma due to HA, HHPA and PMDA (Venables, 1989). A second type
of response to acid anhydrides has also been described and is termed the
‘late respiratory systemic syndrome’ (LRRS). This is characterised by the
development of influenzal type symptoms, fever, generalised acheing and
malaise, late in the working shift or in the evening after work. These
symptoms may occur in isolation or in association with asthma. It is not
clear whether this response is immunologically mediated or a nonspecific
response to high levels of anhydride exposure. Lastly, exposure to TMA,
probably at high exposure levels, has been described as causing severe
pulmonary haemorrhage requiring both blood transfusion and mechanical
ventilation (Rivera et al., 1989).
Serum IgE and IgG antibodies to acid anhydrides have been identified.
IgE antibodies appear to be more specifically associated with occupational
asthma. Howe et al. (1983) reported seven cases of TCPA asthma all of
whom had IgE antibody to TCPA, compared with 8% of 300 exposed
workers without TCPA asthma; 29% of this exposed nonasthmatic
population had IgG antibodies to TCPA.
The exposure levels of acid anhydrides that initiate sensitisation are
poorly understood. TMA at levels of 1.7–4.7 mg m −3 (Zeiss et al., 1977)
and 0.007–2.1 mg m −3 (Bernstein et al., 1983; McGrath et al., 1984) have
been described causing occupational asthma. PA at 0.03–15 mg m −3 has
also been reported as causing asthma (Wernfors et al., 1986). As in other
forms of occupational asthma, the early identification of cases of acid
anhydride induced asthma and their removal from exposure is of prime
importance.
Reactive airways dysfunction syndrome
C.A.C.PICKERING 153
Reactive airways dysfunction syndrome (RADS) or irritant-induced asthma
was first described in 1985 (Brooks et al., 1985). The criteria used in
diagnosis include a high level exposure to an irritant fume, vapour or smoke,
the development of respiratory symptoms within minutes or hours of
exposure, in an individual with no previous history of respiratory symptoms,
with persistence of symptoms and physiological abnormalities for more
than 1 year. A variety of different chemical exposures have been described
inducing this syndrome including: chlorine (Moore and Sherman, 1991),
glacial acetic acid (Kern, 1991), hydrochloric acid (Promisloff et al., 1990)
and miscellaneous chemical exposures (Brooks et al., 1985). A comparison
between cases of occupational asthma and RADS (Gautrin et al., 1994)