Developmental neurotoxicity of succeeding generations of insecticides

Abstract

Insecticides are by design toxic. They must be toxic to effectively kill target species of insects. Unfortunately, they also have off-target toxic effects that can harm other species, including humans. Developmental neurotoxicity is one of the most prominent off-target toxic risks of insecticides. Over the past seven decades several classes of insecticides have been developed, each with their own mechanisms of effect and toxic side effects. This review covers the developmental neurotoxicity of the succeeding generations of insecticides including organochlorines, organophosphates, pyrethroids, carbamates and neonicotinoids. The goal of new insecticide development is to more effectively kill target species with fewer toxic side effects on non-target species. From the experience with the developmental neurotoxicity caused by the generations of insecticides developed in the past advice is offered how to proceed with future insecticide development to decrease neurotoxic risk.

Keywords: Development; Neonicotinoids; Neurotoxicity; Organochlorines; Organophosphates; Pyrethroids: carbamates.

Figure 1

Periods of exposure and NOAEL (no-observed-adverse-effect level) proportions in log scale based on animal model studies listed in table 1. Only doses and periods of exposure that elicited significant effects are reported. The NOAELs for neurotoxic effects of DDT (25 mg/kg; (ATSDR 2002), and of Lindane (6 mg/kg; (WHO 2004) were chosen based on acute, oral administration in adult rats. The symbol “■” represents single dose, “—” represents longer periods of exposure and “.....” represents dose change. Lactation/infancy extends from PN1 to PN27 (PN=postnatal day). Adolescence assumed to begin at PN28.

Figure 2

Periods of exposure and percentages of the NOAEL (no-observed-adverse-effect level) proportions in log scale based on animal model studies listed in table 3. Only doses and periods of exposure that elicited significant effects are reported. For Chlorpyrifos, the NOAEL for cholinesterase inhibition in brain (0.1 mg/kg/day; (WHO 2009) was chosen based on subchronic, oral administration in adult rats. The symbol “■” represents single dose, “—” represents longer periods of exposure, “.....” represents dose change and “- - -” indicates a time interval between multiple exposures. Lactation/infancy extends from PN1 to PN27 (PN=postnatal day). Adolescence assumed to begin at PN28.

Figure 3

Periods of exposure and percentages of the NOAEL (no-observed-adverse-effect level) proportions in log scale based on animal model studies listed in table 6. Only doses and periods of exposure that elicited significant effects are reported. For Carbofuran (0.1 mg/kg/day; (FAO 2002), and of Carbosulfan (0.5 mg/kg; (Wolterink and van Hoeven Arentzen 2003), the NOAEL for for cholinesterase inhibition in brain was chosen based on acute, oral administration in adult rats. The symbol “■” represents single dose and “—” represents longer periods of exposure. Lactation/infancy extends from PN1 to PN27 (PN=postnatal day). Adolescence assumed to begin at PN28.

Figure 4

Periods of exposure and percentages the NOAEL (no-observed-adverse-effect level) proportions in log scale based on animal model studies listed in table 8. Only doses and periods of exposure that elicited significant effects are reported. The NOAEL for neurotoxic effects of Permethrin (25 mg/kg/day; (ATSDR 2003) was chosen based on acute, oral administration in adult rats. The symbol “■” represents single dose and “—” represents longer periods of exposure. Lactation/infancy extends from PN1 to PN27 (PN=postnatal day). Adolescence assumed to begin at PN28.

Figure 5

Periods of exposure and percentages of the NOAEL (no-observed-adverse-effect level) proportions in log scale based on animal model studies listed in table 9. Only doses and periods of exposure that elicited significant effects are reported. The NOAEL for neurotoxic effects of Deltamethrin (5 mg/kg/day; (INCHEM 2000) was chosen based on acute, oral administration in adult rats. The symbol “■” represents single dose and “—” represents longer periods of exposure. Lactation/infancy extends from PN1 to PN27 (PN=postnatal day). Adolescence assumed to begin at PN28.

Figure 6

Periods of exposure and percentages of the NOAEL (no-observed-adverse-effect level) proportions in log scale based on animal model studies listed in table 10. Only doses and periods of exposure that elicited significant effects are reported. The NOAEL for neurotoxic effects of Imidacloprid (9 mg/kg; (EPA 2006) was chosen based on acute, oral administration in adult rats. As for Clothianidin, the NOAEL (60 mg/kg; (EPA 2003) was chosen based on subchronic, oral administration in adult rats. The symbol “■” represents single dose and “—” represents longer periods of exposure. Lactation/infancy extends from PN1 to PN27 (PN=postnatal day). Adolescence assumed to begin at PN28.