title: Early life stage toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in zebrafish (Danio rerio).
abstract: Toxicity and histopathology of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in zebrafish (Danio rerio) early life stages was characterized from 12 to 240 hr postfertilization (hpf) following water-borne exposure of newly fertilized eggs. TCDD did not increase egg mortality (0-48 hpf), nor did it affect time to hatching (48-96 hpf). Egg doses of 1.5 ng [3H]TCDD/g or greater elicited toxic responses in zebrafish larvae. Pericardial edema and craniofacial malformations were first observed at 72 hpf, followed by the onset of yolk sac edema (96 hpf) and mortality (132 hpf). At 240 hpf the ED50s for pericardial edema, yolk sac edema, and craniofacial malformations were 2.2, 2.1, and 1.9 ng [3H]TCDD/g egg, respectively. The LD50, determined at 240 hpf, was 2.5 ng [3H]TCDD/g egg. Severe hemodynamic changes, observed as slowed blood flow in vascular beds of the trunk, head, and gills and slowed heart rate, occurred in TCDD-treated zebrafish prior to or coincident with the onset of gross signs of toxicity. Histological examination of TCDD-treated zebrafish revealed a variety of epithelial tissue lesions including arrested gill development and ballooning degeneration and/or necrosis of the renal tubules, hepatocytes, pancreas, and all major brain regions. Mesenchymal tissue lesions included subcutaneous edema in the head, trunk, and yolk sac, edema of the pericardium and skeletal muscle, and underdevelopment of the swim bladder. This demonstration of zebrafish responsiveness to TCDD early life stage toxicity coupled with the considerable information on developmental biology and genetics of zebrafish provides a foundation for future investigations into the mechanism of TCDD developmental toxicity.
authors.affiliation: School of Pharmacy, University of Wisconsin, Madison 53706, USA.
authors.forename: T R
authors.initials: TR
authors.lastname: Henry
authors.forename: J M
authors.initials: JM
authors.lastname: Spitsbergen
authors.forename: M W
authors.initials: MW
authors.lastname: Hornung
authors.forename: C C
authors.initials: CC
authors.lastname: Abnet
authors.forename: R E
authors.initials: RE
authors.lastname: Peterson
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000209:etiology* / Q000473:pathology; D000818:Animals; D002319:Cardiovascular System / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced; D004625:Embryo, Nonmammalian / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D006339:Heart Rate / Q000187:drug effects; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D012039:Regional Blood Flow / Q000187:drug effects; D012886:Skull / Q000002:abnormalities / Q000187:drug effects / Q000196:embryology; D013045:Species Specificity; D015017:Yolk Sac / Q000187:drug effects / Q000473:pathology; D015027:Zebrafish / Q000196:embryology* / Q000254:growth & development; D015053:Zygote / Q000187:drug effects
chemical_list: D000072317:Polychlorinated Dibenzodioxins