Currently acute inhalation toxicity is a required test for pesticide active ingredients (AIs) and formulated plant protection products (PPPs). As there are no accepted alternative methods for testing of this endpoint, animal experiments are required. The outcome of the test used for regulating the chemicals is “lethal concentration 50”, the concentration that will kill 50% of the exposed animals (LC50). In this study, we investigated an alternative method for determining the effect of inhaled substances on the lungs. We studied 11 PPPs for their ability to inhibit lung surfactant (LS) function in vitro, and subsequently evaluated if this predicted changes in breathing patterns of exposed mice. Six of the eleven PPPs inhibited LS function, and eight changed the breathing pattern of exposed mice. Most of these caused changes indicative of sensory irritation (6), three caused changes indicative of pulmonary irritation and two caused a reduction in tidal volume (one product cause all three changes). The results from the in vitro inhibition of LS function predicted changes in respiration of exposed mice with a sensitivity of 65% and a specificity of 66%. Testing the effect of inhaled substances on LS function is not a method accepted as an alternative to animal testing in regulatory guidelines, however the test can be used to test the molecular initiating event in an adverse outcome pathway currently under evaluation by the OECD.
Inhibition of lung surfactant function as an alternative method to predict lung toxicity following exposure to plant protection products
Pesticide Research no. 218