Developmental Neurotoxicity of Pyrethroid Insecticides: Critical Review and Future Research Needs

Pyrethroid insecticides have been used for more than 40 years and account for 25% of the worldwide insecticide market. Although their acute neurotoxicity to adults has been well characterized, information regarding the potential developmental neurotoxicity of this class of compounds is limited. There is a large age dependence to the acute toxicity of pyrethroids in which neonatal rats are at least an order of magnitude more sensitive than adults to two pyrethroids. There is no information on age-dependent toxicity for most pyrethroids. In the present review we examine the scientific data related to potential for age-dependent and developmental neurotoxicity of pyrethroids. As a basis for understanding this neurotoxicity, we discuss the heterogeneity and ontogeny of voltage-sensitive sodium channels, a primary neuronal target of pyrethroids. We also summarize 22 studies of the developmental neurotoxicity of pyrethroids and review the strengths and limitations of these studies. These studies examined numerous end points, with changes in motor activity and muscarinic acetylcholine receptor density the most common. Many of the developmental neurotoxicity studies suffer from inadequate study design, problematic statistical analyses, use of formulated products, and/or inadequate controls. These factors confound interpretation of results. To better understand the potential for developmental exposure to pyrethroids to cause neurotoxicity, additional, well-designed and well-executed developmental neurotoxicity studies are needed. These studies should employ state-of-the-science methods to promote a greater understanding of the mode of action of pyrethroids in the developing nervous system

Acute Human Self-Poisoning with Imidacloprid Compound: A Neonicotinoid Insecticide

Background: Deliberate self-poisoning with older pesticides such as organophosphorus compounds are commonly fatal and a serious public health problem in the developing world. The clinical consequences of self-poisoning with newer pesticides are not well described. Such information may help to improve clinical management and inform pesticide regulators of their relative toxicity. This study reports the clinical outcomes and toxicokinetics of the neonicotinoid insecticide imidacloprid following acute self-poisoning in humans. Methodology/Principal Findings: Demographic and clinical data were prospectively recorded in patients with imidacloprid exposure in three hospitals in Sri Lanka. Blood samples were collected when possible for quantification of imidacloprid concentration. There were 68 patients (61 self-ingestions and 7 dermal exposures) with exposure to imidacloprid. Of the self-poisoning patients, the median time to presentation was 4 hours (IQR 2.3–6.0) and median amount ingested was 15 mL (IQR 10–50 mL). Most patients only developed mild symptoms such as nausea, vomiting, headache and diarrhoea. One patient developed respiratory failure needing mechanical ventilation while another was admitted to intensive care due to prolonged sedation. There were no deaths. Median admission imidacloprid concentration was 10.58 ng/L; IQR: 3.84–15.58 ng/L, Range: 0.02–51.25 ng/L. Changes in the concentration of imidacloprid in serial blood samples were consistent with prolonged absorption and/or saturable elimination. Conclusions: Imidacloprid generally demonstrates low human lethality even in large ingestions. Respiratory failure and reduced level of consciousness were the most serious complications, but these were uncommon. Substitution of imidacloprid for organophosphorus compounds in areas where the incidence of self-poisoning is high may help reduce deaths from self-poisoning

The ontogeny of antipredator behavior: age differences in California ground squirrels (Otospermophilus beecheyi) at multiple stages of rattlesnake encounters

Newborn offspring of animals often exhibit fully functional innate antipredator behaviors, but they may also require learning or further development to acquire appropriate responses. Experience allows offspring to modify responses to specific threats and also leaves them vulnerable during the learning period. However, antipredator behaviors used at one stage of a predator encounter may compensate for deficiencies at another stage, a phenomenon that may reduce the overall risk of young that are vulnerable at one or more stages. Few studies have examined age differences in the effectiveness of antipredator behaviors across multiple stages of a predator encounter. In this study, we examined age differences in the antipredator behaviors of California ground squirrels (Otospermophilus beecheyi) during the detection, interaction, and attack stages of Pacific rattlesnake (Crotalus oreganus) encounters. Using free-ranging squirrels, we examined the ability to detect free-ranging rattlesnakes, snake-directed behaviors after discovery of a snake, and responses to simulated rattlesnake strikes. We found that age was the most important factor in snake detection, with adults being more likely to detect snakes than pups. We also found that adults performed more tail flagging (a predator-deterrent signal) toward snakes and were more likely to investigate a snake’s refuge when interacting with a hidden snake. In field experiments simulating snake strikes, adults exhibited faster reaction times than pups. Our results show that snake detection improves with age and that pups probably avoid rattlesnakes and minimize time spent in close proximity to them to compensate for their reduced reaction times to strikes