title: Best practices for evaluation of bone marrow in nonclinical toxicity studies.
abstract: This manuscript is intended to provide a best practice approach to accurately and consistently assess toxicant-induced bone marrow effects of test articles. In nonclinical toxicity studies, complete blood count data in conjunction with the histological examination of the bone marrow are recommended as the foundation for assessing the effect of test articles on the hematopoietic system. This approach alone can be used successfully in many studies. However, in some situations it may be necessary to further characterize effects on the different hematopoietic lineages, either by cytological or flow cytometric evaluation of the bone marrow. Both modalities can be used successfully, and which one is selected will depend on the expertise, preference of the facility, and the nature of the change in the bone marrow. Other specialized techniques such as clonogenic assays or electron microscopy are used rarely to further characterize hematotoxicity. The indications and techniques to successfully employ histological, cytological, or flow cytometric evaluation as well as clonogenic assays and electron microscopy are reviewed.
authors.affiliation: Pfizer, Inc., Groton, Connecticut, USA. william.j.reagan@pfizer.com
authors.forename: William J
authors.initials: WJ
authors.lastname: Reagan
authors.forename: Armando
authors.initials: A
authors.lastname: Irizarry-Rovira
authors.forename: Florence
authors.initials: F
authors.lastname: Poitout-Belissent
authors.forename: Anne Provencher
authors.initials: AP
authors.lastname: Bolliger
authors.forename: Shashi K
authors.initials: SK
authors.lastname: Ramaiah
authors.forename: Greg
authors.initials: G
authors.lastname: Travlos
authors.forename: Dana
authors.initials: D
authors.lastname: Walker
authors.forename: Denise
authors.initials: D
authors.lastname: Bounous
authors.forename: Gail
authors.initials: G
authors.lastname: Walter
mesh_terms: D000818:Animals; D019985:Benchmarking; D001853:Bone Marrow / Q000473:pathology*; D003585:Cell Biology / Q000592:standards; D005069:Evaluation Studies as Topic; D005434:Flow Cytometry / Q000592:standards; D017408:Guidelines as Topic; D006410:Hematopoiesis; D006413:Hematopoietic System; D006653:Histology / Q000592:standards; D006801:Humans; D013194:Staining and Labeling; D014116:Toxicology / Q000592:standards