Sensory irritation response to inhaled aldehydes after formaldehyde pretreatment

Pretreatment of Fischer-344 (F-344) rats with formaldehyde (HCHO) induces significant cross tolerance to the sensory irritation properties of Cl2. The purpose of this study was to determine if HCHO pretreatment would cause sensory irritation cross tolerance to other inhaled aldehydes. Male F-344 rats, weighing 190 to 210 g, were pretreated with 15 ppm HCHO, 6 hr/day for 9 days, and challenged on the 10th day with a saturated (acetaldehyde, propionaldehyde, and butyraldehyde), unsaturated (acrolein and crotonaldehyde), or cyclic (cyclohexanecarboxaldehyde, 3-cyclohexene-1-carboxaldehyde, and benzaldehyde) aldehyde. The sensory irritation response in these animals was quantified by measuring respiratory rate depression in a head-only inhalation chamber using plethysmographic techniques. Control animals were challenged identically without prior pretreatment. In naive (nonpretreated) animals, the concentration eliciting a 50% decrease in respiratory rate (RD50) was 23 ppm or less for unsaturated aliphatic aldehydes. For cyclic and saturated aliphatic aldehydes, the RD50 ranged from 600 to 1000 ppm and 3000 to 6800 ppm, respectively. Formaldehyde pretreatment resulted in cross tolerance only with acetaldehyde (RD50 increased 3.5-fold) and acrolein (RD50 increased 5-fold). These results indicate that the development of cross tolerance following HCHO pretreatment is not a general phenomenon. Prediction of acceptable concentrations of occupational exposure for the prevention of sensory irritation in humans has been based primarily on RD50 data for mice. Comparison of the RD50 values obtained for rats in this investigation with previously published results for mice varied by over one-half an order of magnitude, thereby disputing the usefulness of data from F-344 rats in setting threshold limit values for the prevention of sensory irritation.