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Updated: Jul 4, 2026

Intravenous Endotoxin Challenge in Healthy Humans: An Experimental Platform to Investigate and Modulate Systemic Inflammation
Published on: May 16, 2016
Variability in endotoxin exposure levels and consequences for exposure assessment
Suzanne Spaan1, Jody Schinkel, Inge M Wouters
1Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht University, PO Box 80178, 3508 TD Utrecht, The Netherlands. S.Spaan@uu.nl
Objectives:
Workers in many industries are exposed to endotoxins, which may cause adverse health effects. In exposure assessment, information about exposure variability is essential. However, variability in exposure has rarely been investigated for biological agents and more specifically for endotoxin. Therefore, variance components and determinants of exposure were studied in a large database with >2000 endotoxin measurements.
Methods:
Data from 10 individual studies were combined to create a database with 2010 personal inhalable dust and endotoxin measurements, of which 1650 were repeated measurements. Exposure groups were defined based on job codes. Between- and within-worker variance components were estimated for different grouping strategies, and determinants of exposure were studied using mixed effects models.
Results:
Inhalable dust and endotoxin exposure levels are summarized for 46 industries and 4 broadly defined sectors. The between-worker variability exceeded the within-worker variability overall and within sectors and subsectors, and variance components were larger for endotoxin than for dust. Between-worker variability also exceeded within-worker variability in nearly half of the exposure groups based upon industries or job code within industries for endotoxin exposure and in 10% of the groups for dust exposure. Among other things, dustiness of the process, contact with animals, bulk production, presence of plant material or a cyclic process appeared as determinants of exposure, which largely explained the between-worker variability.
Conclusions:
Exposure groups were much less homogeneous for endotoxin exposure than for dust exposure. This is distinctly different than for chemical exposure. Large variability in measured exposure levels is inherent to endotoxin exposure, which is caused in part by determinants that influence growth of microorganisms. These findings have major consequences for the design of future occupational intervention and epidemiological studies. The measurement effort needs to be greater than exposure assessment for chemical agents which demonstrate lower exposure variability, especially when evaluating endotoxin exposure for compliance testing. The established determinants of exposure give direction for potential exposure control, although more information about determinants of day-to-day variability in exposure is still needed to be able to effectively control endotoxin exposure.
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