Zebrafish: A Predictive Model for Assessing Cancer Drug-Induced Organ Toxicity - Zebrafish: Methods for Assessing Drug Safety and Toxicity - page 141

11.3.5 No Observable Effect Concentration

To determine the concentration that did not cause observable effects, we generated
percent incidence curves by determining percent incidence for each drug concen-
tration as described in Section 11.2. Based on these curves, we estimated NOEC as
10

m M (17-DMAG), 10 m M (HDAC inhibitor X), 2 m M (paclitaxel), and 300 m M

(SMA-838).

Table 11.5 Comparison of Toxicity of 17-DMAG in Zebrafish, Mammals, and Humans

Toxicity Zebrafish Rat Dog Human

Heart Nonreversible

pericardial
edema and
bradycardia at
100 mM

No toxic effects
observed

No toxic effects
observed

Heart block,
atrial fib/
flutter, atrial
dysrhythmia,
QTc
prolongation,
bradycardia

Confirmed with
cell death
assay

CNS Nonreversible

tissue
degeneration
at 500 mM

No toxic effects
observed

No toxic effects
observed

Neuropathy

Confirmed with
cell death
assay

Liver Nonreversible

liver
degeneration
at 50 mM;
hemorrhage at
1500 mM

" ALT, AST,
ALP, TBA at
lethal dose
(5mg/kg;
C max ¼2 mM)

" ALT, AST,
ALP, GGT at
nonlethal dose
(0.75mg/kg;
C max ¼
0.3-0.4 mM)

" ALT, AST

Confirmed with
cell death
assay

Liver necrosis at
5mg/kg

Gall bladder and
liver necrosis
at lethal dose
(1.5mg/kg)

Kidney Moderate trunk

edema at
100 mM

No toxic effects
observed

No toxic effects
observed

" K, # Na

No cell death
observed