exposure; bronchial provocation studies are usually negative but on occasion they may be positive (Hendrick and Lane, 1977; Nordman et al., 1985). Two studies that investigated immunologic sensitization reported negative challenges even in those individuals with specific IgE to formaldehyde (Dykewicz et al., 1991; Grammer et al., 1992). Thus, immunologically mediated asthma resulting from formaldehyde exposure has yet to be proved. Other volatile organic chemicals such as toluene and turpentine can act as irritants but are not specific sensitizers.

Exposure and Risk

Various air sampling and personal monitoring techniques are used to measure chemical exposures (Eller, 1984), but they are not without limitations. For example, intermittent samples may not reflect an individual's actual exposure because of variations in the exposure levels of the chemical. In addition, only a few allergenic chemicals such as TDI and TMA have threshold limit values (TLVs) set by the American Conference of Governmental Industrial Hygienists (ACGIH, 1986) or permissible exposure limits (PELs) set by the Occupational Safety and Health Administration (OSHA; CFR, 1991).

TLVs and PELs are generally established to help prevent chemical toxicity among workers. Thus, they may have no relevance to levels of chemicals that may sensitize an individual or provoke allergic responses and that may be many orders of magnitude below toxic levels. Very few studies report threshold levels for human exposure to chemicals that elicit allergic responses, and those that do describe exposure concentrations present them only as estimates. A Japanese study of 41 workers exposed to two enzymes and three antibiotics showed that the incidence of occupational allergy was correlated with the frequency and concentration of exposure to allergens (Chida, 1986). In other studies, approximately 50 TMA workers were evaluated in a facility that reduced worker exposure over time by improved ventilation, work practices, and respiratory protection. The levels of antibody in workers decreased with decreasing exposure to TMA (Boxer et al., 1987; Grammer et al., 1991b). In a study of isocyanate workers, the group with the highest exposure had the highest prevalence of positive antibody (Grammer et al., 1991a). In a study of 500 workers at a TMA manufacturing facility, five categories of exposure were identified (Zeiss et al., 1992). Only workers in the highest exposure categories developed specific antibody and allergic reactions to TMA.

In contrast to human studies, estimates of exposure in animal models are considerably more accurate. Studies have reported a concentration-dependent immunologic response in a guinea pig model of TDI asthma (Karol, 1983) and a threshold concentration and concentration-immunologic



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