Title
Extended histopathology in immunotoxicity testing: Interlaboratory validation studies
Author
Germolec, D.R.
Nyska, A.
Kashon, M.
Kuper, C.F.
Portier, C.
Kommineni, C.
Johnson, K.A.
Luster, M.I.
TNO Voeding
Publication year
2004
Abstract
There has been considerable interest in the use of expanded histopathology as a primary screen for immunotoxicity assessment. To determine the utility of a semiquantitative histopathology approach for examining specific structural and architectural changes in lymphoid tissues, a validation effort was initiated. This study addresses the interlaboratory reproducibility of extended histopathology, using tissues from studies of ten test chemicals and both negative and positive controls from the National Toxicology Program's immunotoxicology testing program. We examined the consistency between experienced toxicologic pathologists, who had varied expertise in immunohistopathology in identifying lesions in immune tissues, and in the sensitivity of the individual and combined histopathological endpoints to detect chemical effects and dose response. Factor analysis was used to estimate the association of each pathologist with a so-called "common factor" and analysis-of-variance methods were used to evaluate biases. Agreement between pathologists was highest in the thymus, in particular, when evaluating cortical cellularity of the thymus; good in spleen follicular cellularity and in spleen and lymph node-germinal center development; and poorest in spleen red-pulp changes. In addition, the ability to identify histopathological change in lymphoid tissues was dependent upon the experience/training that the individual pathologist possessed in examining lymphoid tissue and the apparent severity of the specific lesion. © Society of Toxicology 2004; all rights reserved.
Subject
Biology
Physiological Sciences
Histopathology
Immunology
Immunopathology
Lymph node
Pathology
Risk assessment
Spleen
Thymus
chemical agent
analysis of variance
animal cell
animal tissue
article
cellular distribution
concentration response
controlled study
disease severity
error
experience
factorial analysis
female
germinal center
health program
histopathology
immunopathology
immunotoxicity
intermethod comparison
laboratory test
lymph node
lymphatic system disease
lymphoid tissue
medical education
medical expert
mouse
nonhuman
observer variation
organogenesis
pathologist
quantitative analysis
reproducibility
screening test
sensitivity analysis
spleen cell
thymus
tissue injury
tissue structure
toxicity testing
validation process
Allergy and Immunology
Animals
Computational Biology
Data Interpretation, Statistical
Dose-Response Relationship, Drug
Histology
Immune System
Laboratories
Models, Statistical
Reproducibility of Results
Terminology
Toxicology
To reference this document use:
http://resolver.tudelft.nl/uuid:25e76f0a-67c1-4ea4-a221-862c1ed5d2dc
DOI
https://doi.org/10.1093/toxsci/kfh049
TNO identifier
237658
ISSN
1096-6080
Source
Toxicological Sciences, 78 (1), 107-115
Document type
article