ASSESSMENT OF RESPIRATORY HYPERSENSITIVITY IN GUINEA-PIGS SENSITIZED TO TOLUENE DIISOCYANATE - IMPROVEMENTS ON ANALYSIS OF RESPIRATORY RESPONSE

Groups of guinea pigs of the Hartley strain were sensitized to toluene diisocyanate (TDI) by combined single intradermal injection and repea ted inhalation exposure (3 h/day for 5 consecutive days) to 0, 3.8, 11 , 26, 46, and 51 mg TDI/m(3) air. One group of animals was sensitized by intradermal injection only. Sham-exposed and TDI-polyisocyanate res in-sensitized guinea pigs served as controls. Three weeks after the fi rst encounter with the inducing agent, animals were challenged with th e free TDI (approximately 0.5 mg/m(3)) and 1 week later with TDI-guine a pig serum albumin conjugate. Breathing patterns were analyzed by obj ective mathematical procedures taking into account the intensity and d uration of the respiratory rate exceeding +/-3 standard deviations of the individual prechallenge exposure period. In none of the animals ch allenged with TDI were conclusive immediate-onset respiratory response s identified. During the TDI conjugate challenge a characteristic incr ease in respiratory rate was observed in all groups sensitized with TD I. In each of the sham and TDI-resin control groups, 1 of 16 animals r esponded mildly to the conjugate challenge. With regard to analysis of the development of asthma-like dyspnea, the results obtained suggest that respiratory response can suitably be defined by objective mathema tical analysis of breathing patterns. Moreover, the ''duration'' of re sponse exceeding +3 x standard deviation of prechallenge baseline data appears to show less variability when compared to the ''intensity'' o f response (area). It can be concluded that this method of evaluation of respiratory response may be useful to compare more quantitatively t his type of data and serves the objective of decreasing potential inte rlaboratory variability. (C) 1997 Society of Toxicology.