Cardiovascular teratogenicity of 2,3,7,8-tetrachlorodibenzo- p-dioxin in the chick embryo

Abstract

Cardiovascular morphogenesis in the chick embryo occurs between Days 2 and 8 of development. Fertile, White-Leghorn, chicken eggs were treated on Day 0 of development with TCDD or vehicle and the embryos were evaluated for cardiovascular malformations on Day 14. Nine doses of TCDD ranging from 0.009 to 77.5 pmol/egg were used with at least 20 eggs per dose. TCDD caused a dose-related increase in the incidence of cardiovascular malformations. In control embryos the incidence was 28% and it increased to about 60% in embryos treated with the highest doses of TCDD. The higher incidence was not due to an increase in a particular type of cardiovascular malformation, but rather an increase in all types: ventricular septal defects, aortic arch anomalies, aortic arch anomalies in combination with a ventricular septal defect, and conotruncal malformations. TCDD treatment did not alter the mean wet or dry weight of the embryos suggesting that the malformations were not secondary to alterations in whole embryo water content or growth. Some TCDD-treated embryos exhibited subcutaneous edema but the incidence was low, 7% of all treated embryos, and not dose related. Lethality was about 10% higher in the TCDD treatment groups than control. However, the higher lethality was apparently not responsible for the greater incidence of malformations. This was suggested by the cardiovascular malformation incidence in the TCDD groups being similar when determined separately for surviving embryos and for surviving plus dead embryos. Other malformations found in TCDD-treated embryos were stunted, malformed legs and crossed beaks associated with microopthalmia. The incidence of these latter malformations was low, 1–3%, making it difficult to ascribe their occurrence to TCDD.