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. 2022 Nov 21;10(4):49. doi: 10.3390/jdb10040049

Table 2.

Studies utilising zebrafish (Danio rerio) to determine developmental and neurotoxic effects of organophosphate insecticides. dpf; days post-fertilisation. hpf; hours post-fertilisation.

Organophosphate(s) Dosage(s) * Gene(s) Involved ** Exposure Period Observations Reference
Chlorpyrifos (CPF) CPF: 10 & 100 ng/mL - 0–5 dpf
  • -

    increased impaired spatial discrimination

  • -

    both decreased (10 ng/mL) and increased (100 ng/mL) response latency in adult zebrafish

 [58]
Chlorpyrifos (CPF) CPF: 100 ng/mL - 0–5 dpf
  • -

    decreased swimming activity

 [59]
Malathion (MAL) MAL: 2.5 & 3 mg/L - 3 hpf–5 dpf
  • -

    increased mortality

  • -

    decreased hatching rates

  • -

    decreased body length

  • -

    and decreased surface area of eye.

 [60]
Malathion (MAL) MAL: 0.25, 0.5, 1, 3 & 5 mM - Adult (sexually mature)
  • -

    decreased Adenosine Di-Phosphate (ADP) and Adenosine Tri-Phosphate (ATP) levels

 [61]
Diazinon (DZN) DZN: 2000 & 3000 μg/L - 8 hpf–96 hpf
  • -

    increased heart rate

  • -

    increased mortality

  • -

    increased morphological irregularities (axial and tail deformities, yolk sac/heart oedema, eye irregularities

  • -

    reduced pigmentation

  • -

    decreased hatching rate

 [62]
Chlorpyrifos (CPF) CPF: 0.25, 0.5, 0.75 & 1 mg/L - Acute: 5 dpf for 2 h
Sub-chronic: ≤1 hpf–11dpf
  • -

    Acute—increased (≥0.25 mg/L) and decreased (≥0.75 mg/L) locomotor activity.

  • -

    Sub-chronic—increased behavioural irregularities

 [63]
Chlorpyrifos (CPF) CPF: 300, 1500 & 3000 nM Rohon-Beard Development/Axonogenesis: agrin↓, cntn2↓, ntf3↓, sema3d↓ 3 hpf–27 hpf/51 hpf/72 hpf/4 dpf
  • -

    increased mortality

  • -

    increased phenotypes (axial curvature, reduced body size and reduced pigmentation)

  • -

    decreased functioning AChE

  • -

    increased average chevron angle (somites)

  • -

    decreased HNK-1-positive cells

  • -

    decreased axonogenesis-related genes

 [64]
Chlorpyrifos (CPF) CPF: 0.29 μM - 0–5 dpf
  • -

    significantly increased startle response

  • -

    increased transmitter turnover in larvae

  • -

    decreased dopamine/serotonin levels in adults

 [65]
Chlorpyrifos-oxon (CPF metabolite) CPF: 300 nM 0.1 μg/L, 3 μg/L 3 hpf–75 hpf
  • -

    Defective peripheral neuron development

 [66]
Dichlorvos (DCV) DCV: 20.81, 25 & 66.78 mg/L - 0 hpf–96 hpf
  • -

    decreased hatching rates

  • -

    increased pericardial oedema

  • -

    increased spinal irregularities

  • -

    decreased swimming activity

 [67]
Dichlorvos (DCV)

Phoxim (PHO)		 DCV: N/A
PHO: 0.469, 0.513, 0.700 & 1.28 mg/L		 - Adult (sexually mature)
  • -

    DCV:

  • -

    low toxicity (determined by LC50)

  • -

    PHO:

  • -

    intermediate and high levels of toxicity (determined by LC50)

 [4]
Chlorpyrifos (CPF) CPF: 0.6 μM - 1 ypf for 24 h
  • -

    decreased swim rates

  • -

    increased freeze response

  • -

    decreased AChE in muscle

 [68]
Chlorpyrifos (CPF) CPF: 0.01, 0.1 & 1 μM - 6 hpf–24/48/72 hpf
  • -

    decreased functioning AChE

  • -

    increased TCPy (trichloro-2-pyridinol)

  • -

    decreased functioning primary/secondary motor neurons, axonal growth and sensory neurons.

 [69]
Chlorpyrifos (CPF)

Diazinon (DZN)

Parathion (PA)		 CPF: 0.3, 3 & 30 μM
DZN: 10 & 30 μM
PA: 10 & 30 μM		 - 6 hpf–5 dpf
  • -

    Both CPF and DZN:

  • -

    increased mortality

  • -

    decreased functioning AChE

  • -

    decreased locomotor activity

  • -

    PA:

  • -

    increased mortality

  • -

    decreased functioning AChE

 [70]
Chlorpyrifos (CPF) CPF: 0.01 & 0.1 μM - 0–7 dpf
  • -

    decreased swim speed

  • -

    decreased anxiety-like behaviour

  • -

    increased behavioural irregularities

  • -

    shortened body lengths and tail defects

 [71]
Monocrotophos (MCP) MCP: 0.001 & 0.100 mg/L Sexual Differentiation: cyp19a1a↑, cyp19a1b↑, foxl2↑, dmrt1↓, B-actin, ef1-a 72 hpfV–16 dpf
  • -

    increased proportion of females

  • -

    alteration in expression of sexual differentiation genes

 [72]
Chlorpyrifos (CPF)
Dichlorvos (DCV)
Diazinon (DZN)		 CPF: 1, 10, 100 & 1000 μM
DCV: 100 & 1000 μM
DZN: 100 & 1000 μM		 - 1 hpf–5 dpf
  • -

    CPF:

  • -

    increased mortality

  • -

    increased kyphosis

  • -

    decreased spine length

  • -

    increased spontaneous movement

  • -

    and decreased heart rate

  • -

    DCV:

  • -

    increased mortality

  • -

    increased spontaneous movement.

  • -

    DZN:

  • -

    increased mortality

  • -

    increased pericardial oedema

 [73]
Chlorpyrifos (CPF) CPF: 30, 100 & 300 μg/L Gfap, Mbp↓, Elavl3↑, Ngn1↑, Nestin↑, Shha↑ 0–5 dpf
  • -

    significantly decreased hatching rates

  • -

    increased spine and yolk sac abnormalities

  • -

    significantly decreased heart rates

  • -

    significantly decreased swim speed/distance

 [50]
Chlorpyrifos (CPF) CPF: 200 & 400 μg/L - 2 hpfV–72 hpf
  • -

    decreased AChE activity

  • -

    increased AChE gene expression

  • -

    increased glutathione (GSH) levels

 [74]
Dichlorvos (DCV) DCV: 6, 19, & 32 mg/L Oxidative Stress: Nrf2 (many other associated genes within the Nrf2 pathway also examined) 6–12 mpf
  • -

    decreased cholinesterase (ChE) levels in the heart/brain

  • -

    increased myo-degeneration

  • -

    increased testis degeneration

  • -

    increased pancreas zymogen granule depletion

  • -

    decreased glycogen in liver

  • -

    altered expression of genes involved in Nrf2 signalling

 [75]
Monocrotophos (MCP) MCP: 10, 20, 30, 40, 50 & 60 mg/L - 4 hpf–96 hpf
  • -

    moderate toxicity (determined by LC50)

  • -

    decreased body length

  • -

    decreased heart rate

  • -

    decreased functioning AChE levels

 [1]
Monocrotophos (MCP) MCP: 100 μg/L HPI Axis: Crf, Gr↓, POMC↓, P45011β, 11B-HSD2, StAR, 20B-HSD2↑, MC2R↓, TAT, PEPCK Adult (sexually mature)—21 d exposure
  • -

    decreased whole-body cortisol

  • -

    increased/decreased hypothalamic-pituitary-inter-renal (HPI) axis associated genes

 [76]
Chlorpyrifos (CPF) CPF: 2 & 5 μM - Adult (sexually mature)
  • -

    increased oxidative stress

  • -

    decreased neurotransmitter metabolism

  • -

    increased energy exhaustion

 [77]
Chlorpyrifos (CPF)
Phoxim (PHO)		 CPF: 0.28- 13.03 mg/L
PHO: 0.89–26.48 mg/L		 - Embryo (1 hpf), larvae (72 hpf) and juvenile (1 mpf)—96 h exposure
  • -

    CPF was determined to be more toxic than PHO (determined by LC50)

 [78]
Diazinon (DZN) DZN: 6.5 mg/L - 6 hpf–5 dpf
  • -

    Moderate toxicity (determined by LC50)

 [2]
Dichlorvos (DCV) DCV: 15 mg/L - Adult (sexually mature) 4–5 m—24 h exposure
  • -

    increased levels of malondialdehyde (MDA) in liver/kidney

  • -

    increased glutathione (GSH) in liver/kidney/brain

  • -

    increased superoxide dismutase in liver

  • -

    decreased levels of superoxide dismutase in brain

  • -

    decreased catalase in kidney/brain.

 [79]
Malathion (MAL) MAL: 250, 500 & 1000 μg/L HPG Axis: vtg1, vtg2, era↑, erB1, erB2, cyp19a1a, cyp19a1b↑ 6 dpf–10 dpf
  • -

    low toxicity (determined by LC50)

  • -

    upregulation of gene expression within the hypothalamic-pituitary-gonadal (HPG) axis

 [80]
Chlorpyrifos (CPF)
Diazinon (DZN)		 CPF: 1, 10, & 25 μM
DZN: 10 & 100 μM		 - 6 hpf–102 hpf
  • -

    CPF:

  • -

    increased mortality

  • -

    decreased hatching rates

  • -

    increased spinal lordosis

  • -

    reduced activity

  • -

    DZN:

  • -

    increased mortality

  • -

    increased pericardial oedema

  • -

    decreased mitochondrial bioenergetics

 [18]
Monocrotophos (MCP) MCP: 0.125, 0.625 & 1.25 uL/L 24–72 hpf
  • -

    DNA damage observed in peripheral blood

 [81]
Phosalone (PSL) PSL: 86–505 μg/L - 8 wpf–96 h exposure
  • -

    decreased functioning AChE

  • -

    decreased carboxylesterase (CaE)

  • -

    increased glutathione (GSH)

 [82]
Chlorpyrifos (CPF) CPF: 30, 100 & 300 μg/L Oxidative stress: Mn-Sod↑/↓, Cu/Zn-Sod↓, Gpx↓, Cat↓, Ucp2↓, bc12, Cox1↓ Glycolysis/Lipid: Gk↓, HK1, Pk↓, Pepckc↓, Aco↓, CPt1↓, Ppar-A↓, Acc1↓, Srebp 1a↓, Ppar-y↓, Fas↓, Fabp6, Apo↓, Dgat↓, LDLR↓, HMGCR, Fabp5 Adult (sexually mature)
  • -

    increased levels of gut mucus

  • -

    decreased y-Protobacteria in gut

  • -

    decreased oxidative stress genes in gut and liver

  • -

    and decreased glycolysis and lipid metabolism-related genes

 [56]
Chlorpyrifos (CPF) CPF: 30, 100 & 300 μg/L Cardiovascular: Mef2c↓, Bmp4↓, VEGFR-2, JunB↑, Tbx2
Lipid: Ppar-a, Ppar-y↓, Srebp 1a, Acc1, Fas↓, Cpt1↓, Aco, Apo↓, Fabp5, Fabp6↓, Dgat↓, LDLR 		2 hpf–7 dpf
  • -

    decreased lipid accumulation in heart

  • -

    decreased triglyceride and total cholesterol

  • -

    increased cellular apoptosis of heart tissue

  • -

    decreased lipid metabolism genes

 [83]
Diazinon (DZN)
Dichlorvos (DCV)
Malathion (MAL)
Parathion (PA)		 DZN: 0.1 & 100 μg/L
DCV: N/A
MAL: 100 μg/L
PA: 0.1 μg/L		 Cholinergic: AChE↑/↓
Neurodegeneration: c-Fos, lingo-1b↑, grin-1b↓ 		5 hpf–5 dpf
  • -

    DZN:

  • -

    decreased swimming distance

  • -

    decreased velocity

  • -

    increase in AChE associated gene expression inhibited functioning AChe

  • -

    increased carboxylesterase activity

  • -

    DCV:

  • -

    increased AChE associated genes.

  • -

    MAL:

  • -

    decreased swimming distance

  • -

    decreased velocity

  • -

    increase in AChE associated gene expression

  • -

    increase in neurodegenerative associated gene expression

  • -

    increased carboxylesterase activity

  • -

    PA:

  • -

    decrease in AChE associated gene expression

  • -

    and decrease in neurodegenerative associated gene expression

 [84]
Dichlorvos (DCV) DCV: 1, 5 & 10 mg/L - 1 hpf–7 dpf
  • -

    decreased body length

  • -

    decreased heart rates

  • -

    decreased surface area of eye

  • -

    decreased escape responses

  • -

    decreased speed

  • -

    decreased mobile time

 [85]
Sumithion (SMT) SMT: 1 mg/L - Adult (sexually mature)—96h exposure
  • -

    increased blood glucose levels

  • -

    increased frequency of micronucleus in erythrocytes

  • -

    increased erythrocyte cellular and nuclear abnormalities

 [86]
Chlorpyrifos (CPF) CPF: 1 & 3 μM - Adult (sexually mature) 6–8 m—2/5 w exposure
  • -

    increased anxiety related activity (Novel Tank Diving Test)

  • -

    increased approach response in shoaling assay

  • -

    increased predator avoidance activity (predator avoidance assay)

 [87,88]
Chlorpyrifos (CPF)
Malathion (MAL)
 CPF: 0.019, 0.077, 0.31, 0.41, 1.01, 1.53 & 6.15 mg/L
MAL: 0.039, 0.16, 0.62, 2.90, 8.04, 8.54 & 12.45 mg/L		 Oxidative Stress: Cat, CuSod, MnSod
Immunity: Cxcl↓, IL↑, Tnf↑/↓
Apoptosis: Cas8↑/↓, Cas9, P53, Bax
Endocrine: TRa, TRb↓, ERa, Tsh↓, Crh, cyp19a↑ 		1 hpf–96 hpf
  • -

    Both CPF and MAL:

  • -

    severe toxicity at larvae, juvenile and adult stages (compared to embryo stage)

  • -

    significant changes in expression of immunity, apoptosis, and endocrine related genes

 [57]
Sumithion (SMT) SMT: 0.1, 0.2, 0.4, 0.8 & 1.6 mg/L - Embryo/larvae
  • -

    increased mortality in embryos and larvae

  • -

    decreased hatching rates

  • -

    increased morphological irregularities in embryos (damaged/underdeveloped and darkened yolk sac, broken chorion, and aberrant notochord formation)

  • -

    increased morphological irregularities in larvae (yolk sac ulcerations/swelling and oedema, heart damage, lesion at caudal region, uninflated swim bladder, head malformation, jaw irregularities, and notochord abnormalities).

 [89]
Chlorpyrifos (CPF) CPF: 1μM - Adult (sexually mature)—5 w exposure
  • -

    decreased brain cholinesterase (ChE) activity

  • -

    increased fleeing score.

 (Hawkey, 2021)
Diazinon (DZN) DZN: 0.4, 1.25 & 4.0 μM 5–120 hpf
  • -

    Changes in Mitochondrial oxygen utilization in the brain and testes

 [90]
Malathion (MAL)
Chlorpyrifos (CPF)		 MAL: 5, 50 ug/L
CPF: 0.1 & 3 ug/L		 0–14 dpf
  • -

    increases in reactive oxygen species

  • -

    induction of oxidative stress

 [91]
Chlorpyrifos (CPF) Caspase 3↓, Bcl-2↓, Adult—8–12 months old
14 day exposure
  • -

    Significantly elevated ROS levels

  • -

    Elevated Reactive nitrogen species levels in high CPF dosage groups

 [92]

* All dosages listed are associated with the observations summarised here, other dosages in the individual studies may have been used, but did not impact on development, behaviour or gene expression. ** ↑ and ↓ arrows indicate where there has been a significant increase or decrease in a particular gene as a response of organophosphate (OP) exposure—where no arrow shows, no significant change was noted.