Endotoxin exposure assessment - measurement and characterization

Abstract

Endotoxin, one of the specific agents in organic dust that cause health effects, is part of the cell wall of Gram-negative bacteria. Gram-negative bacteria are present on for instance the surfaces of plants and in animal feces, and their occurrence, growth and amplification is influenced by many factors. As a consequence, endotoxin levels may be highly variable and occurs exposure to endotoxin in various industries. Inhalation exposure is thought to be the major route of exposure. Endotoxin exposure was investigated among workers of various agricultural industries and sewage treatment plants. Exposure was found to be generally high in agricultural industries, and moderate to low in sewage treatment workers. These studies were combined with eight other exposure studies in a database, which showed that endotoxin exposure was highly variable. In general more variability between workers than with workers (from day to day) was found. Several determinants of exposure could be determined. For example, dustiness of the product, contact with animals or plant material and bulk production were associated with higher endotoxin exposure, which ‘wet’ processes were associated with lower exposure levels. Information about exposure levels and variance components were input for the formulation of a measurement strategy for the assessment of endotoxin exposure. This strategy has a tiered approach, and every phase can result in a conclusion that the exposure situation is acceptable, advice on control measures or a more precise estimation of the exposure situation. The emphasis is on control measures when the circumstances indicate (elevated) endotoxin exposure. For exposure assessment and possible comparison with an occupational exposure limit (OEL) the procedure for measurement and analysis of airborne endotoxin is very important, and preferably standardized. Existing gaps in European guidelines were explored and investigated by means of full experimental designs and the use of parallel collected inhalable dust samples, in which the effects on and interactions with airborne endotoxin concentration of filter type, transport conditions, sample storage, extraction solution, extract storage and assay solution were investigated in several working environments. This led to the recommendation to use glass-fiber filters, transport with desiccation, frozen sample storage, extraction in PFW with 0.05% Tween-20 with rocking/shaking, frozen storage of extracts, and dilution and LAL analysis in PFW. With this information a protocol for standardization of endotoxin exposure assessment can be fully specified. Although it is yet unknown whether endotoxin will be part of the public or private part of the current (new) Dutch occupational exposure limit system, both the government and industry can use the intended health-based recommended OEL of the Health Council, which is a tool for controlling exposure and reduce the risk of health effects for workers. Standardization of methods is important to be able to compare results and for compliance testing, and this thesis provides information on some of the issues around introducing an OEL for endotoxin. Generally, one should be aware that endotoxin exposure poses a potential threat to the working population, which should be rendered into monitoring and controlling this exposure