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.

Evaluation of exposure-response relationships for health effects of microbial bioaerosols - A systematic review.

Studies suggest adverse health effects following exposure to bioaerosols in the environment and in particular at workplaces. However, there is still a lack of health-related exposure limits based on toxicological or epidemiological studies from environmental health or from the working environment. The aim of this study was to derive health-based exposure limits for bioaerosols that can protect the general population as group "at risk" via environmental exposure using analysis of peer-reviewed studies related to occupational medicine, indoor air and environmental health. The derivation of exposure limits should be conducted by the members of a bioaerosol expert panel according to established toxicological criteria. A systematic review was performed in Medline (PubMed) including studies containing both data on exposure measurements and observed health outcomes. In addition, literature recommended by the experts was considered. A comprehensive search strategy was generated and resulted in a total of n=1569 studies in combination with the literature recommendations. Subsequently, abstracts were screened using defined exclusion criteria yielding a final number of n=44 studies. A standardized extraction sheet was used to combine data on health effects and exposure to different bioaerosols. After full-text screening and extraction according to the defined exclusion criteria n=20 studies were selected all related to occupational exposures comprising the working areas wood processing, farming, waste processing and others. These studies were analyzed in collaboration with the bioaerosol expert network in terms of suitability for derivation of health-related exposure limits. The bioaerosol expert network concluded that none of the analyzed studies provided suitable dose-response relationships for derivation of exposure limits. The main reasons were: (1) lack of studies with valid dose-response data; (2) diversity of employed measuring methods for microorganisms and bioaerosol-emitting facilities; (3) heterogeneity of health effects; (4) insufficient exposure assessment. However, several indicator parameters and exposure concentrations could be identified for different bioaerosol-emitting facilities. Nevertheless, health-related exposure limits are urgently needed especially in approval procedures of facilities like composting plants or livestock farms emitting bioaerosols in the neighbourhood of residents. In the regulatory toxicology framework, it is common to use animal experimental studies for derivation of general exposure limits if appropriate environmental epidemiological studies on harmful substances are lacking. This might be another possibility to obtain health-related exposure limits for specific bioaerosol parameters. Furthermore, we recommend to use suitable measurable outcome parameters related to bioaerosols; to measure bioaerosols according to a protocol representative for exposure pattern and duration at the particular work place; to develop standardized detection methods for indicator parameters; to combine different detection methods to compensate for the limitations of each method; to apply new analysis methods to identify the real risk potential.