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Extended histopathology in immunotoxicity testing: interlaboratory validation studies.

Authors
Germolec-DR; Nyska-A; Kashon-M; Kuper-CF; Portier-C; Kommineni-C; Johnson-KA; Luster-MI
Source
Toxicol Sci 2004 Mar; 78(1):107-115
NIOSHTIC No.
20024707
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.
Keywords
Histopathology; Immunotoxins; Laboratory-testing; Pathology; Quantitative-analysis; Lymph-nodes; Immune-system-disorders; Risk-analysis
Contact
Laboratory of Molecular Toxicology, National Institute of Environmental Health Sciences, 111 Alexander Drive, P.O. Box 12233, Research Triangle Park, North Carolina 27709, USA
CODEN
TOSCF2
Publication Date
20040301
Document Type
Journal Article
Email Address
germolec@niehs.nih.gov
Fiscal Year
2004
NTIS Accession No.
NTIS Price
Issue of Publication
1
ISSN
1096-6080
NIOSH Division
HELD
Priority Area
Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
Source Name
Toxicological Sciences
State
NC; WV
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