Stereology determining sampling precision

#STEREOLOGY DETERMINING SAMPLING PRECISION HOW TO#

The severity of histopathological lesions indicates the extent of particle toxicity and the type of lesions provide insight into the potential mode of action. In vivo respiratory toxicology studies also include the histopathological analysis of the lungs to investigate adverse effects of particles. Whereas in vitro tests are helpful for quick toxicity screening, long term effects in the respiratory tract are usually only assessed by in vivo toxicology studies. This is of particular need with the quickly emerging field of nanotechnology and the constant development of new nanoparticles (NP <100 nm in all three dimensions, ISO/TS 27687:2008) with unknown effects. Research on respiratory particle toxicology and risk assessment therefore attempts not only to investigate effects of individual particles and sources, but also effects of particle characteristics in general such as shape, size and composition in order to promote predictability of newly generated particles. By dealing with the investigation of multiple physical, chemical and biological parameters at the same time, particle and fiber toxicology becomes a challenging field. However, the source and composition of airborne particles is vast - including for example combustion derived particles from traffic and industry, cigarette smoke, silica dust, welding fumes, asbestos, biological particles such as pollen and fungi as well as engineered nanomaterials of various compositions. The characteristics and severity of particle and fiber-induced pathology depend on exposure time and concentration as well as on particle characteristics such as chemical composition, size, structure and surface composition. Most often noxious inhaled particles trigger a pulmonary inflammatory response which can initiate the development of sub-chronic or chronic pulmonary diseases including pneumonitis, silicosis, asbestosis, chronic obstructive pulmonary disease (COPD), emphysema, asthma, fibrosis or cancer. The inhalation of harmful particles can lead to adverse health effects and pathological changes in the respiratory tract. Thus, we hope that this article will stimulate scientists in particle and fiber toxicology research to implement stereological techniques in their studies, thereby promoting an unbiased 3D assessment of pathological lesions associated with particle exposure. The article further aims at pointing out common pitfalls in quantitative histopathology and at providing some suggestions on how respiratory toxicology can be improved by stereology.

#STEREOLOGY DETERMINING SAMPLING PRECISION HOW TO#

In this review we therefore provide an overview on different histopathological lesions in the respiratory tract associated with particle and fiber toxicology and on how to apply stereological methods in order to correctly quantify and interpret histological lesions in the respiratory tract.

Nevertheless, it can be challenging to express histopathological changes by morphometric parameters such as volume, surface, length or number only. The most accurate way of obtaining unbiased quantitative information about three-dimensional (3D) features of tissues, cells, or organelles from two-dimensional physical or optical sections is by means of stereology, the gold standard of image-based morphometry.

This approach not only comprises a potential subjective bias, depending on the examinerвЂ™s judgment, but also conveys the risk that mild alterations escape the investigatorвЂ™s eye. Conventional pathological evaluations are usually performed by scoring histological lesions in order to obtain вЂњquantitativeвЂќ information and an estimation of the severity of the lesion. For this reason, toxicology studies on effects of inhalable particles and fibers often include an assessment of histopathological alterations in the upper respiratory tract, the trachea and/or the lungs. The inhalation of airborne particles can lead to pathological changes in the respiratory tract.

Stereology determining sampling precision