Abstract |
The occurrence of mesenteric lymph node angiomas (benign vascular neoplasms including lymphangioma and hemangioma) in untreated control rats in 2-year carcinogenicity studies can range from rare to common depending on the strain used. This lesion is most common in male rats. Factors and conditions that may contribute to the etiopathogenesis of lymph node angiomas in rats include: (1) genetic drift, (2) congenital/developmental malformation, (3) sinus vascular transformation/venous obstruction of outflow, (4) "inflammatory" pseudo- tumors, and/or (5) defects of endothelial lymphatic vascular secretion/permeability. Lymph node angiomas in humans are extremely rare, not reported in mesenteric lymph nodes, and more common in females than males. The evaluation of increased mesenteric lymph node angiomas in rats for overall human safety risk assessment of novel pharmaceutical therapeutics should consider: genotoxicity of the test article, occurrence of vascular neoplasms in other locations in rats and in mice, occurrence of proliferative vascular lesions in nonclinical toxicology studies in non-rodent species, dose/exposure response, and pathophysiologic/morphologic differences and similarities of lymph node angiomas between rats and humans. Angiomas are independent lesions from angiosarcomas and are not precursors for angiosarcomas in either humans or animals. Mesenteric lymph node angiomas in rats are unlikely to be relevant for human risk assessment of pharmaceutical agents.
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Authors | Zaher A Radi, Daniel Morton |
Journal | Regulatory toxicology and pharmacology : RTP
(Regul Toxicol Pharmacol)
Vol. 64
Issue 3
Pg. 435-41
(Dec 2012)
ISSN: 1096-0295 [Electronic] Netherlands |
PMID | 23088954
(Publication Type: Journal Article)
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Copyright | Copyright © 2012 Elsevier Inc. All rights reserved. |
Topics |
- Animals
- Drug Design
- Drug-Related Side Effects and Adverse Reactions
- Female
- Hemangioma
(epidemiology, etiology)
- Humans
- Lymph Nodes
(pathology)
- Lymphangioma
(epidemiology, etiology)
- Male
- Mesentery
(pathology)
- Mice
- Rats
- Risk Assessment
(methods)
- Sex Factors
- Species Specificity
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