Assessment of Respiratory Hypersensitivity in Guinea Pigs Sensitized to Toluene Diisocyanate: Improvements on Analysis of Respiratory Response

Abstract

Groups of guinea pigs of the Hartley strain were sensitized to toluene diisocyanate (TDI) by combined single intradermal injection and repeated inhalation exposure (3 h/day for 5 consecutive days) to 0, 3.8, 11, 26, 46, and 51 mg TDI/m³air. One group of animals was sensitized by intradermal injection only. Sham-exposed and TDI–polyisocyanate resin-sensitized guinea pigs served as controls. Three weeks after the first encounter with the inducing agent, animals were challenged with the free TDI (approximately 0.5 mg/m³) and 1 week later with TDI–guinea pig serum albumin conjugate. Breathing patterns were analyzed by objective mathematical procedures taking into account the intensity and duration of the respiratory rate exceeding ±3 standard deviations of the individual prechallenge exposure period. In none of the animals challenged with TDI were conclusive immediate-onset respiratory responses identified. During the TDI conjugate challenge a characteristic increase in respiratory rate was observed in all groups sensitized with TDI. In each of the sham and TDI–resin control groups, 1 of 16 animals responded 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 mathematical analysis of breathing patterns. Moreover, the “duration” of response exceeding +3 × standard deviation of prechallenge baseline data appears to show less variability when compared to the “intensity” of response (area). It can be concluded that this method of evaluation of respiratory response may be useful to compare more quantitatively this type of data and serves the objective of decreasing potential interlaboratory variability.