Table 1.
Representative neurotoxic chemicals and how they can impact brain development through multiple mechanisms
| Chemical class | Chemical name | Exposure level | Windows of exposure | Species | Oxidative stress effects | Neurotransmitter effects | Neuroendocrine effects | Immune effects | Behavioral phenotype |
|---|---|---|---|---|---|---|---|---|---|
| Metal | Lead | 1000 ppm | Gestation and lactation | Rat | Disruption of pro- and antioxidant balance [37] | ||||
| 2000 or 10,000 ppm | Lactation | Rat | Increased synaptosomal catecholamines [38] | ||||||
| 1000 ppm | Gestation | Rat | Alterations in HPG axis [39] | ||||||
| 30 or 130 ppm | Lactation | Mouse | Reduction of microglia [40] | ||||||
| OP pesticide | CPF | 1, 2, 5, 10, 20, or 40 mg/kg | Gestation and lactation | Rat | Increased biomarkers of oxidative stress [41] | ||||
| 1 or 5 mg/kg | Gestation | Rat | Disruption of serotonergic gene expression and signal transduction [42] | ||||||
| 1 or 5 mg/kg | Gestation and lactation | Rat | Reduced brain thyroxine [43] | ||||||
| 0.1, 0.3, 1 mg/kg | Gestation and lactation | Rat | Induced neuroinflammation [44] | Altered learning behavior | |||||
| Component of Plastic | BPA | 5 or 10 μg/ml | Gestation and lactation | Mouse | Increased biomarkers of oxidative stress [45] | ||||
| 25 ng/kg, 25 μg/kg, 5 mg/kg | Postnatal | Rat | Increased inhibitory GABA signaling [46] | ||||||
| 2.5–2700 μg/kg | Gestation and lactation | Rat | Downregulation of estrogen and melanocortin receptors [47] | Anxiogenic behavior | |||||
| 1 mg/L, 5 μg/kg, 50 μg/kg, or 50 mg/kg | Gestation and lactation | Rat and vole | Altered microglia colonization [48•] | ||||||
| Flame Retardant | PBDEs | 0, 2.06, 20.6, or 41.2 μM | NA | Rat (primary hippocampal neurons, isolated from fetus) | ROS production, DNA damage, and apoptosis [49] | Loss or reversal of behavioral sex differences | |||
| 0.45, 0.9, or 9.0 mg/kg | Neonatal | Mouse | Reduced cholinergic nicotinic receptors [50] | Disrupted spontaneous, learning, and memory behaviors | |||||
| 1.7, 10.2, or 30.6 mg/kg | Gestation and lactation | Rat | Hypothyroxinemia in exposed dams and their offspring [51] | Cognitive impairments | |||||
| 0.0075, 0.075, 0.75, or 7.5 mg/kg | Gestation | Mouse | Activation of microglia [52] |
This table is not meant to be exhaustive but instead contains representative examples from the rodent literature of each mechanism of neurotoxicity highlighted in this review. In some studies, multiple outcomes were observed. For each chemical listed, there is an abundance of confirmatory evidence demonstrating developmental neurotoxicity in other species, including humans
NA not available