Use of Emerging Models for Developmental Toxicity Testing - Zebrafish: Methods for Assessing Drug Safety and Toxicity - page 25

Chapter 3

Use of Emerging Models for
Developmental Toxicity
Testing

Patricia McGrath
Phylonix, Cambridge, MA, USA

3.1 IMPORTANCE OF ASSESSING DEVELOPMENTAL
TOXICITY

Approximately 50% of all pregnancies in the United States result in a sick baby or
prenatal or post natal death. Furthermore, major developmental defects, including
neural tube and heart deformities, occur in approximately 120,000 of the 4 million
infants born in the United States each year. Developmental toxicity profiles of most
chemicals and approved drugs have not been extensively evaluated and conventional
mammalian assays using fetuses are laborious and expensive.

3.2 CURRENT METHODS FOR ASSESSING
DEVELOPMENTAL TOXICITY

In vivo mammal segment studies using female rats or rabbits are standardized screens
for assessing developmental and reproductive toxicity (DART). The entire repro-
ductive cycle is divided into three segments: Segment I is designated for reproductive
toxicity and does not include fetal examination, Segment II encompasses the period
from implantation through major organogenesis, and Segment III focuses on late
pregnancy through post natal development. Segment II involves exposing pregnant
animals during the period of major organogenesis and structural development. Dosing
for Segment II studies consists of a control group and three or four compound
concentrations; each group is comprised of 20 pregnant dams. The dams are sacrificed