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Table 2 Evidence of developmental neurotoxicity caused by pesticides belonging to groups with likely common mechanisms of neurotoxicity

From: Potential developmental neurotoxicity of pesticides used in Europe

Group of pesticides (n)* Mechanism of neurotoxicity Developmental neurotoxicity reported in humans References Developmental neurotoxicity reported in animals References
Organophosphates (8) Inhibition of AChE (+ interference with signaling cascades at low doses) Reflex abnormalities in neonates + affected mental development [7, 8] Altered programming of synaptic development in rats (Chlorpyrifos) [50, 51]
   Reduced head circumference in infants + anomalies in primitive reflexes (Chlorpyrifos) [61, 9] Behavioural abnormalities including changes in locomotor skills and cognitive performance in rats and mice (Chlorpyrifos) [4346]
   Reduced birth weight and length + developmental delay at 3 years of age (Chlorpyrifos) [62, 10]   
   Visuospatial deficits (prenatal exposure) + increased reaction time (current exposure in children) [11]   
   Reduced short term memory and attention (Methyl parathion) [12]   
Carbamates (5) Inhibition of AChE (+ oxidative stress) No reports were found   No reports were found  
Pyrethroids (7) Prolongation of kinetics of voltage-gated sodium channels    Increased motor activity, lack of habituation, changes in mAChR density in mice [8588]
     Learning changes in rats [89]
     Changes in motor activity in rats [90]
     Changes in sexual behaviour and higher activity of the dopaminergic system in rats [91]
     Changes in mAChR expression in rats [92, 93]
     Changes in blood-brain permeability in rats [94]
     Affected development of reflexes, swimming ability, open field activity in mice (parental exposure prior to mating) [96]
Dithiocarbamates (EBDCs) (6) Generation of ROS (metal chelating capacity, uncoupling of mitochondrial electron transport chain)
The EBDC metabolite, ETU, inhibits thyroid peroxidase (synthesis of thyroid hormones)
   Maneb (in combination with paraquat) induces loss of dopaminergic neurons in substantia nigra pars compacta in mice [132]
     The metabolite of EBDCs, ETU, induces malformations of the nervous system (corresponding to thyroid insufficiency) in rats Reviewed in [126]
Chlorophenoxy herbicides (11) Not completely known: includes membrane damage, generation of free radicals, perhaps uncoupling of oxidative phosphorylation A case of cephalic malformations and severe mental retardation in infant whose parents were heavily exposed to 2,4-D [150] Hypomyelination in chicks
(2,4-D)
[151]
     Deficit in myelin lipid deposition in rats
(2,4-D)
[152]
     Delayed CNS development in rats
(2,4-D)
[153]
     Increased size and densitiy of serotonin-reactive neuronal somata and increased fiber length in dorsal and medial raphe nuclei in rats
(2,4-D)
[154]
     Oxidative stress in specific brain areas (midbrain, striatum, prefrontal cortex) in rats
(2,4-D)
[155]
     Behavioural effects in rats including delay of righting reflex, negative geotaxis + motor abnormalities, excessive grooming and vertical head movements, hyperactivity
(2,4-D)
[156]
Bipyridyl herbicides (1) Induction of oxidative stress    Involvement of developmental exposure to paraquat in later development of PD like features in mice [174]
     Paraquat (in combination with maneb) induces loss of dopaminergic neurons in substantia nigra pars compacta in mice [132]
  1. *The number in parenthesis is the total number of pesticides from each group currently authorised for use in the EU as of August 2008. Only major evidence on developmental neurotoxicity in humans or in laboratory animals has been included.