Developmental Toxicity Assessment in Zebrafish - Zebrafish: Methods for Assessing Drug Safety and Toxicity - page 22

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Penicillin G
Isoniacide
Ascorbic acid
Diphenylhudantoin
Cytosine arabinoside
Retinol
9- cis -Rerinoic acid
Valproic acid
Dimethyl phthalate
RAR alpha agonist compd 1
RAR alpha agonist compd 2
RAR beta agonist

100

80

60

40

20

0
0.001

10 4 0.01 0.1 1 10 100 1000

Concentration ( μ m)

Figure 2.3 Lethality curves in zebrafish. (See the color version of this figure in Color Plates section.)

presented a 75% success rate in identifying nonteratogenic compounds and a 100%
success rate in identifying teratogens. The accuracy for predicting relative teratogenic
potency was excellent with a 92% success rate in predicting accuracy.

2.4 DISCUSSION

Here we describe 6hpf to 5dpf as the time frame for compound treatment; however,
different time points including 24hpf for compound treatment initiation to 2dpf for
compound termination have been used by other researchers (Henry et al., 1997;
Prasch et al., 2003). Shorter treatment time increases throughput and is generally
adequate for assessing effects in both the cardiovascular and nervous systems;
however, it is not considered adequate for assessing compound effects on the
developing digestive system, which develops at a later time point. Another consid-
eration for these studies is the effect of the chorion membrane on compound
availability.
Although the typical zebrafish developmental toxicity screen includes 14-21
parameters, animal transparency offers the unique opportunity to design screens to
address specific interests. The parameters and TI definition used by the pharmaceu-
tical industry and government agencies charged with responsibility for protecting
citizens and the environment from effects of hazardous chemicals may differ. For
example, since the retinoid class of drugs is known to induce neurological defects in
humans, to determine compound toxicity on the developing nervous system, specific
compartments in the brain, such as brain ventricle, can be assessed. For agrichemicals
and pesticides, environmental concerns may warrant evaluation of all discernable