Sensitivities to chemicals are characterized by symptoms in multiple organ systems in response to low-level chemical exposures. This paper reviews studies of controlled exposures to odorants and to mixtures of
volatile organic compounds. Sensitive subgroups include subjects who met Cullen's 1987 criteria for
multiple chemical sensitivity (MCS), Gulf War veterans with
chronic fatigue syndrome and chemical sensitivity (CFS/CS), and subjects with specific self-reported sensitivities to methyl terbutyl
ether (
MTBE) in
gasoline (
MTBE-sensitive). All studies include comparison of age- and sex-matched healthy controls. Studies of olfaction did not support unusual sensitivity, defined as lower odor thresholds, among MCS subjects; however, a dose-response pattern of symptoms was observed in response to suprathreshold concentrations of phenyl
ethyl alcohol. In blinded, controlled exposures to clean air,
gasoline,
gasoline/11%
MTBE, and
gasoline/15%
MTBE, a threshold effect was observed with
MTBE-sensitive subjects reporting significantly increased symptoms to
gasoline/15%
MTBE exposure. Autonomic arousal (heart and respiration rate; end-tidal CO2) in response to odor of chemical mixtures may mediate symptoms for subjects with generalized chemical sensitivities, but not for those whose sensitivities are confined to specific chemicals. For example, Gulf War veterans with CFS/CS experienced reduced end-tidal CO2 when exposed to diesel fumes, while exposure to
MTBE did not produce any psychophysiologic changes in
MTBE-sensitive subjects. Controlled olfactory and exposure studies reveal that significant responses can be observed in chemically sensitive subjects even when de-adaptation has not occurred. However, these studies suggest that symptoms are not necessarily accompanied by changes in physiologic arousal. Subject characteristics play a critical role in outcomes.