Toxicopathology of the developing immune system: investigative and development strategies.
Developmental immunotoxicity (DIT) has gained attention with the recognition that environmental chemicals can potentially affect the developing immune system and the incidence of childhood allergic diseases. Preclinical safety assessment of pharmaceuticals for men and women of childbearing potential as well as for pediatric and juvenile indications may require DIT assessments. Draft documents from environmental and chemical regulatory agencies propose strategies that use the rat as a test species and incorporate histopathology and functional testing as endpoints. While there are no guidelines for DIT assessment of pharmaceuticals, current discussions suggest that combining immunotoxicity and developmental and reproductive toxicology studies may serve this purpose. Knowledge of the principles and applications of DIT will facilitate participation in strategy development and effective conduct of relevant studies.
Sanofi aventis, US Inc, Bridgewater, New Jersey 08807-0800, USA.
Daniel
D
Weinstock
David B
DB
Lewis
George A
GA
Parker
Joseph
J
Beyer
Mark
M
Collinge
Thomas P
TP
Brown
Noel
N
Dybdal
D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects; D064420:Drug-Related Side Effects and Adverse Reactions / Q000139:chemically induced* / Q000276:immunology; D005260:Female; D047109:Fetal Development / Q000187:drug effects* / Q000276:immunology; D007107:Immune System / Q000187:drug effects* / Q000196:embryology / Q000254:growth & development; D007154:Immune System Diseases / Q000139:chemically induced* / Q000503:physiopathology; D007109:Immunity / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D051381:Rats; D018570:Risk Assessment; D018675:Toxicity Tests / Q000379:methods; D015262:Xenobiotics / Q000009:adverse effects*
D000911:Antibodies, Monoclonal; D015262:Xenobiotics