Interpreting Dose-Response Relation for Exposure to Multiple Sound Impulses in the Framework of Immunity

Abstract

Hearing loss is a common military health problem and it is closely related to exposures to impulse noises from blast explosions and weapon firings. In a study based on test data of chinchillas and scaled to humans (Military Medicine, 181: 59-69), an empirical injury model was constructed for exposure to multiple sound impulses of equal intensity. Building upon the empirical injury model, we conduct a mathematical study of the hearing loss injury caused by multiple impulses of non-uniform intensities. We adopt the theoretical framework of viewing individual sound exposures as separate injury causing events, and in that framework, we examine synergy for causing injury (fatigue) or negative synergy (immunity) or independence among a sequence of doses. Starting with the empirical logistic dose-response relation and the empirical dose combination rule, we show that for causing injury, a sequence of sound exposure events are not independent of each other. The phenomenological effect of a preceding event on the subsequent event is always immunity. We extend the empirical dose combination rule, which is applicable only in the case of homogeneous impulses of equal intensity, to accommodate the general case of multiple heterogeneous sound exposures with non-uniform intensities. In addition to studying and extending the empirical dose combination rule, we also explore the dose combination rule for the hypothetical case of independent events, and compare it with the empirical one. We measure the effect of immunity quantitatively using the immunity factor defined as the percentage of decrease in injury probability attributed to the sound exposure in the preceding event. Our main findings on the immunity factor are: 1) the immunity factor is primarily a function of the difference in SELA (A- weighted sound exposure level) between the two sound exposure events; it is virtually independent of the magnitude of the two SELA values as long as the difference is fixed; 2) the immunity factor increases monotonically from 0 to 100% as the first dose is varied from being significantly below the second dose, to being moderately above the second dose. The extended dose-response formulation developed in this study provides a theoretical framework for assessing the injury risk in realistic situations.