Environmental neurotoxicants are pollutants that can negatively affect many cellular metabolic-processes through different pathways: neuroendocrine/thyroid hormone disruption (Pb, methyl-Hg, organochlorines, and polychlorinated biphenyls-PCB), oxidative stress (Pb, methyl-Hg, organochlorines, and chlorpyrifos), dopamine dysfunction (Pb, methyl-Hg, As, chlorpyrifos, pyrethroids, and organochlorines) (Heyer and Meredith, 2017; Rock and Patisaul, 2018). Pistollato et al. (2020) studied neurotoxic substances (associated with cognitive deficits – learning and memory impairment in children) of different chemical classes: metals (Pb and methylmercury), pesticides (chlorpyrifos), industrial pollutants (bisphenol A and PCB138), and drugs (valproic acid). Chemicals with a ‘similar’ mode of action (on synaptogenesis, neurite outgrowth, and brain-derived neurotrophic factor) were evaluated by immunocytochemistry and high content imaging analysis. They showed (through in vitro and in silico models) that non-cytotoxic, very low toxic, or moderately toxic concentrations induce developmental neurotoxic effects in mixtures (Pistollato et al., 2020). However, extrapolation of experimental studies to interpret epidemiological data needs caution. Tsatsakis et al. (2019) reported that a cocktail of 13 chemicals at very low doses showed dose-dependent stimulation, rather than inhibition of the nervous system.

Depending on their metabolism and dose, there can be short-term or persistent neurotoxicants, both with long-term health consequences beyond their acute effects. Children are especially vulnerable to neurotoxic exposures that occur during pregnancy and after birth because they respond differently from adults. Most of the exposures in the more sensitive stages of neurodevelopment (ND) occur through maternal environmental exposure during pregnancy and lactation. Therefore, monitoring maternal exposure to environmental neurotoxic substances represents the best surrogate for the unborn and the breastfeeding child.

Environmental neurotoxic chemicals can pose a risk to the neurodevelopment (ND) of children during critical periods of early life, which depend on acquisition, metabolism, and storage during pregnancy and lactation. Half-life of neurotoxic substances in the maternal organism can last from days to years (LaKind et al., 2019). Due to short half-life, pesticides like organophosphate (OP) are rapidly metabolized and eliminated in urine (Barr and Angerer, 2006). Most neurotoxic substances can be characterized as persistent, bioaccumulative chemicals. Therefore, such neurotoxicants (NTs) can pose a neurodevelopmental risk long before conception. Nevertheless, it is important to realize that persistent pollutants (organic or inorganic com,pounds) can occur simultaneously with other NTs that may have a shorter half-life.

Due to contamination of fruits and vegetables with pesticides/residues, most exposure in urban populations occurs continuously through food consumption, but in rural settings, contamination can occur due to occupational and para-occupational exposures. Hertz-Picciotto et al. (2018) estimated the use of OP as 13,404 tonnes for 6 South American countries and 4342 tons for 11 Caribbean and Central American countries. Indeed, measuring passive air sampling in the proximity of schools in Costa Rica, Córdoba Gamboa et al., 2020 detected 10 different pesticides (insecticides, nematicides, fungicides) in more than half of samples. Forde et al. (2015) reported comparatively high urine concentrations of pesticides in Caribbean countries. However, there are other settings that may favor exposure to specific neurotoxicants.

In South American countries (Brazil, Venezuela, Ecuador, Perú, French Guyana) Hg is largely used in artisanal small-scale gold mining (Kristensen et al., 2014); this activity fluctuates with the world price of gold (Branco et al., 2017). To a lesser extent, Hg is used in ritualistic “Santerias” (sprinkling Hg or burning it in a candle to obtain the favor of divinities), or, as a skin-lightning product in soaps and detergents (Masur, 2011). Contamination by Pb can occur from urban environmental pollution (Calderón-Garcidueñas et al., 2013) and cottage ceramic-industry (Counter et al., 2000), and from mining settings along with other neurotoxic metals.

Yáñez et al. (2002) raised crucial questions regarding health assessments and the types of chemical mixtures afflicting developing countries, vicinity of smelters, mines, waste disposal sites, agricultural areas, and at home. Abreu-Villaça and Levin (2017) reviewed exposure to insecticides (organochlorines, organophosphates, pyrethroids, carbamates and neonicotinoids) and off-target ND effects on humans. Comprehensive reviews assessing ND outcomes can be found elsewhere dealing with exposures to environmental substances, like insecticides (Burns et al., 2013) and metal mixtures (Dórea, 2019a, 2019b).

In addition to direct exposure to neurotoxicants, it is recognized that socioeconomic and nutrition-dependent factors can modulate neurodevelopment. Wehby and McCarthy (2013) studied wealth gradients in child neurodevelopment in four Latin American countries (Argentina; Brazil; Chile; Ecuador) and found this relationship to be country-specific; it varied with population demographics, health, and socioeconomic characteristics. They noticed a great disparity in the years of school attendance by mothers; the percentage of Brazilian mothers not having attended secondary school was higher (46%) than mothers from Chile (31%), Argentina (25%), and Ecuador (16%) (Wehby and McCarthy, 2013). Indeed, childhood socioeconomic disadvantage measured as rural living, poor childhood health, illiteracy, farmer occupation, and insufficient income were associated with elderly cognitive impairment in seven LAC cities (Nguyen et al., 2008).

Recently, Malin et al. (2018) showed that both good prenatal and childhood nutrition models contribute to more favorable neurodevelopment (Malin et al., 2018). They also showed that poor nutrition indices could lead to poorer ND (Malin et al., 2018). Indeed, in the Brazilian Amazon, poverty, lack of health infrastructure, and isolation are of concern in children’s cognitive development (Fonseca et al., 2007). Nevertheless, in urban areas, delayed cognitive assessment was significantly associated with stunting (Paine et al., 1992). In other Latin America and the Caribbean (LAC) countries, stunting has been significantly associated with psychomotor development (Lasky et al., 1981) and fine motor skills (Cravioto et al., 1966) in Guatemalan children, and altered behavior in Mexican children (Fernald and Grantham-McGregor, 1998). Additionally, living at high altitudes in South American countries is an increased risk factor for neurodevelopment of younger (Wehby, 2013) and older children (Hogan et al., 2010). In the complex scenarios of LAC countries, there are a myriad of environmental interactions with neurotoxicants that could counteract, add or attenuate ND effects. Indeed, Flores-Ramírez et al. (2016) reported that in rural impoverished Mexico there are high percentages (28–49%) of children with chronic malnutrition carrying an additional burden of detectable levels of four or more neurotoxicants. Children (70–82%) in these communities are exposed to NT metals (Mn, Pb, As, and F) and persistent pollutants (dichlorophenyldichloroethylene-DDE, hexachlorobenzene-HCB) (Flores-Ramírez et al., 2016).

The estimate of the Pan American Health Organization (PAHO) for the first decade of this century was that 100,000 children (<5 years of age) in the LAC, would die each year from hazards related to the physical, chemical, and biological environment (Laborde et al., 2015). The authors called attention to environmental threats to the health of over 300 million children living in the LAC region. In addition to “traditional hazards of indoor air pollution and contaminated drinking water”, there are exposures to “urban air pollution, toxic synthetic chemicals, pesticides, heavy metals, unsustainable urban growth, hazardous wastes including electrical and electronic waste (e-waste)” (Laborde et al., 2015).

The objective of this review is to integrate studies on overarching neurodevelopmental issues associated with environmental neurotoxicants in the LAC countries, putting into perspective environmental contaminants (neurotoxic metals, pesticides and metabolites), time (pre- and postnatal) and mode of exposure.