A systematic review of experimental animal studies on microbial bioaerosols: Dose-response data for the derivation of exposure limits.

Although exposure to high levels of microbial bioaerosols can be linked to the deterioration of the human respiratory system, precise exposure levels responsible for such effects are still unknown. A previous systematic review concluded that there was not enough information in the studies in humans to derive an exposure-response relationship. Thus, the aim of this systematic review was to derive exposure limits for microbial bioaerosols based on health effects in experimental animal studies. A systematic search was done in MEDLINE (PubMed) for long-term in vivo exposure of the respiratory system via inhalation of a quantified microbial bioaerosol. A total of n = 301 studies were retrieved. Abstract screening using predefined inclusion and exclusion criteria was followed by full-text screening and standardized data extraction of study characteristics and measured outcomes. As a result, four suitable studies were identified where mice or guinea pigs were exposed for 4-12 weeks to a previously described mixture of fungal spores or conidia via inhalation. The number of macrophages, neutrophils, eosinophils and lymphocytes following subchronic exposure has been reported by all included papers and suggested a dose- and time-dependent relationship. Significant inflammation was observed following subacute exposure to Aspergillus fumigatus. However, the outcomes of the studies could not be directly compared due to the large degree of variation and poor description of the exposure conditions. It is our conclusion that more experimental research needs to be done with the specific aim of establishing a No-Observed-Adverse-Effect Level (NOAEL) and a Lowest-Observed-Adverse-Effect Level (LOAEL) for exposure to microbial bioaerosols in ambient air. Expertise of both exposure and outcome assessment should be brought together to enable standardization of experimental animal studies with properly generated aerosols aiming to derive health-based exposure limits.