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) | [43–46] | ||
| 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 | [85–88] | ||
| 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] |