Setting acceptable exposure limits for toluene diisocyanate on the basis of different airway effects observed in animals

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Little epidemiological data are available to enable the development of a dose-response relationship for the effects of isocyanates, powerful sensitizing agents in humans. Remarkably, most classes of effects have been reproduced in some animal models and parallels between animals and man are impressive. In this paper animal data concerning different effects of TDI on the respiratory system were used to calculate acceptable exposure levels for humans. Animal data on respiratory irritation, sensitization, airway hyperresponsiveness, and gradual loss of pulmonary function are discussed. Two different approaches for extrapolation to man were applied to these data. The two models used to extrapolate animal data to man gave similar results. The extrapolations lead to acceptable exposure varying from 6 to 46 ppb. Most international acceptable levels for occupational airborne TDI exposure are within this range. Interestingly, the lowest standard is obtained using the data on respiratory irritation. It is, however, concluded that there is no critical (adverse) effect to define acceptable toluene diisocyanate exposure since the data were obtained from different studies and the accuracy of the applied extrapolation approach might depend on the biological effect considered. We recommend prior testing of "alternative" diisocyanates in one of the animal models described and calibrated for TDI.