Assessment of Effects on Visual Function in Larval Zebrafish - Zebrafish: Methods for Assessing Drug Safety and Toxicity - page 190

(a)

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40

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0

0 3 10 30

[Quinine] (μM)

(b)

100

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0 30 100 300

[Allopurinol] (μM)

Figure 15.3 Assessment of OMR in zebrafish larvae at 8dpf after 5 days treatment with (a) quinine, rated
as positive, and (b) allopurinol, rated as negative. The mean and standard error are shown for six runs. Each
run used a group of 10 larvae. Statistical significance was calculated using a Student's t-test, comparing
control to treated groups. P < 0.05. (Reprinted fromRichards et al. (2008) with permission fromElsevier.)

compounds in larval zebrafish with the data available from other in vivo and in vitro
models or the clinic. Thirteen out of 19 positive compounds produced the expected
effect while 6 of the 8 negative compounds were correctly predicted. Representative
data obtained for quinine (positive) and allopurinol (negative) are shown in Fig. 15.3.
This study gave an overall predictivity of 70% for the OMR assay with a sensitivity of
68% and a specificity of 75%. Two false positives were observed, bisoprolol and
spironolactone. Visual inspection of the larvae treated with these two compounds had
suggested that a motility defect might be present at the highest concentrations tested.
This was confirmed by testing larvae treated with bisoprolol and spironolactone in a
locomotor activity assay and OKR assay as described in Section 15.3.2.2. There were
two false negatives, sodium iodate and indomethacin, detected in the study. False
negatives could arise where compounds are poorly absorbed by the larvae and
tissue exposure levels are too low to have an effect. This is particularly likely to
be the case where an MTC could not be determined. Determination of concentrations