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Environmental Sciences Europe

Table 3 Summary of Comparative analysis for individual substances that are expected to provoke hyperactivity, hypoactivity and unclear activity

From: Hypo- or hyperactivity of zebrafish embryos provoked by neuroactive substances: a review on how experimental parameters impact the predictability of behavior changes

Chemical

Number of entries per chemical

Mode of action (MoA)c

Expected activity based on MoA

Q1: Do similar methods give consistent hypo- or hyperactivity?

Q2: Do different methods give consistent hypo- or hyperactivity?

Q3: Regardless of the method used, is the observed activity consistent with the expected activity?b

Q4: Are effect concentrations varying within a factor of 10 when hypo- or hyperactivity is consistent?

Risk of Bias factorsa

Behavioral test method

References

Aconitine

3

Activation of voltage-gated sodium ion channel

Hyperactivity

No

Yes

Yes: LMR(L/D) = 1/2; PMR = 1/1

Yes

Exposure duration

PMR; LMR (L/D)

[2, 31, 60]

Chlorpyrifos

22

Acetylcholinesterase Inhibitor

Hyperactivity

Yes for STC

No

Yes: STC = 2/2; PMR = 0/1; LMR = 1/10; LMR(L/D) = 2/9

No

Exposure duration; Exposure concentration; Endpoint parameter

STC; PMR; LMR(L/D); LMR

[14, 16, 24, 41, 53, 54, 56, 69, 71, 80, 89, 93, 106, 112, 120, 125]

Diazinon

12

Acetylcholinesterase inhibitor

Hyperactivity

No: Some studies show no effect

No

Yes: STC = 0/2; PMR = 0/1; LMR = 0/3; LMR(L/D) = 1/6

No

Exposure concentration; developmental stage; Endpoint parameter; Exposure duration

STC; PMR; LMR; LMR(L/D)

[16, 61, 68, 89, 99, 101, 109, 117, 120, 125]

Endosulfan

4

GABA-gated chloride channel antagonist

Hyperactivity

Yes

No

Yes: STC = 0/1; PMR = 0/1; LMR(L/D) = 2/2

No

Exposure duration; Endpoint parameter; developmental stage

PMR; STC; LMR(L/D)

[25, 68, 87, 89]

Isoproterenol

4

Beta-adrenergic receptor agonists

Hyperactivity

Yes

No

Yes: PMR = 3/3; LMR(L/D) = 0/1

Yes

Developmental stage; exposure concentration

PMR; LMR(L/D)

[21, 39, 60]

Nicotine

7

Nicotinic acetylcholine receptor agonist

Hyperactivity

Yes for LMR

Yes

Yes: STC = 1/2; PMR = 0/1; LMR = 2/2; LMR(L/D) = 1/2

No

Exposure duration; Endpoint parameter; Analysis duration

STC; PMR; LMR; LMR(L/D)

[2, 14, 68, 79, 86, 89, 113]

Pentylenetetrazole (PTZ)

16

Inhibiting GABAa receptor

Hyperactivity

Yes

Yes

Yes: LMR = 6/7; LMR(L/D) = 9/9

Yes

Light conditions; exposure concentration

LMR; LMR(L/D)

[1, 5, 7, 10, 14, 31, 32, 70, 74, 85, 109, 115, 124]

Abamectin

5

Activation of GABA-gated chloride channel; glutamate-gated chloride channel

Hypoactivity

Yes

Yes

Yes: STC = 4/4; PMR = 1/1

No

Material used for exposure vessel

STC; PMR

[86, 87, 89, 118, 121]

Carbamazepine

6

Sodium channel blocker

Hypoactivity

Yes

Yes

Yes: STC = 1/1; PMR = 0/1; LMR = 2/3; LMR(L/D) = 1/1

Yes

Exposure duration; exposure concentration

STC; PMR; LMR; LMR(L/D)

[9, 10, 14, 77, 89, 121]

Diazepam

5

Stimulates GABA receptor

Hypoactivity

Yes

Yes

Yes: PMR = 2/2; LMR = 1/1; LMR(L/D) = 1/2

No

Exposure concentration; exposure duration; Endpoint parameter

PMR; LMR; LMR(L/D)

[10, 21, 24, 60, 110]

Emamectin benzoate

3

Activation of GABA-gated chloride channel; glutamate-gated chloride channel

Hypoactivity

Yes

Yes

Yes: STC = 2/2; PMR = 1/1

No

Exposure well size; endpoint parameter

STC; PMR

[86, 89, 121]

Levetiracetam

3

Inhibiting voltage-dependent calcium channel

Hypoactivity

No

Yes

Yes: LMR = 1/2; LMR(L/D) = 1/1

Yes

Exposure duration; developmental stage; exposure concentration; light conditions

LMR; LMR(L/D)

[9, 10, 77]

Valproate

12

Inhibition of GABA transaminase or voltage-gated sodium channel

Hypoactivity

No

Yes

Yes: PMR = 1/1; LMR = 1/4; LMR(L/D) = 5/7

No

Exposure concentration; exposure duration

PMR; LMR(L/D); LMR

[4, 9, 10, 14, 22, 24, 70, 77, 89, 115, 127, 128]

Acetaminophen

9

Cyclooxygenase Inhibitors

Not clear

No

No

NA

NA

Exposure duration; exposure concentration; developmental stage

STC; PMR; LMR; LMR(L/D)

[24, 89, 90, 105, 122]

Apomorphine

4

Stimulation of post-synaptic dopamine D2-type receptors

Not clear

Yes

Yes

NA

No

Light conditions; developmental stage

PMR, LMR, LMR(L/D)

[21, 30, 51, 60]

Haloperidol

4

Dopamine receptor antagonist

Not clear

Yes

No

NA

Yes

Endpoint parameter; exposure concentration; Developmental stage; zebrafish strain

LMR; LMR(L/D); PMR

[40, 51, 81, 89]

Methimazole

4

Binds to thyroid peroxidase to inhibit conversion of iodide to iodine

Not clear

NA

Yes

NA

No

Exposure duration

STC; PMR; LMR; LMR(L/D)

[34, 89, 105]

Retinoic acid

4

Retinoic acid receptor agonist

Not clear

Yes

Yes

NA

Yes

Endpoint parameter

STC; PMR; LMR(L/D)

[4, 89, 119]

  1. aExperimental parameters related to exposure design and effect measurement were considered to identify risk of bias factors that may lead to deviating outcomes. The rational for selecting an experimental parameter as risk of bias for each comparison are appropriately described in the Additional file 1. The number of times each experimental parameter occurred as a risk of bias was used to estimate the most influential parameters
  2. bThe numerator is the number of consistent results while the denominator is total number of results. Results obtained in Question 3 were used to estimate the percentage concordance for organophosphates, avermectins and anticonvulsants
  3. cMode of action was obtained from different sources including http://www.drugbank.ca and published literature
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