Neurodevelopmental consequences of gestational and lactational exposure to pyrethroids in rats

Abstract

Indiscriminate use of pyrethroids has raised serious health related concerns, especially about their effects on children. The present study was designed to assess the developmental neurotoxicity of two pyrethroids; bifenthrin (BIF) and β-cyfluthrin (CYF) administered at 1/15 of LD in rats. Pregnant females were exposed to the test compounds orally throughout gestation and lactation periods. Neonates were weighed and sexed at birth and were observed for any gross abnormality. Growth, viability and weaning indices were calculated during the lactation period. Exposure to both the compounds did not alter the physical developmental parameters viz. eye opening, pinna detachment, and fur appearance. CYF significantly impaired growth and survivability of pups. Behavioral endpoints assessed in neonates (surface righting, pivoting, and negative geotaxis reflex) as well as adults (motor activity and motor coordination) exhibited marked effect of CYF treatment. Administration of BIF to pregnant dams impaired pivoting in neonates. Decreased locomotion in the open-field and impaired rota-rod performance were also witnessed in BIF-exposed animals. Enhanced oxidative stress was seen in corpus striatum, cerebellum, and hippocampus regions of the brain; reduced catalase, superoxide dismutase, and glutathione peroxidase activities were measured in BIF and CYF treated weanlings. Acetylcholinesterase activity was also found to be lowered following administration of both compounds at PND 21. The present results suggest that exposure to pyrethroids during critical periods of growth can induce long term effects on the behavior of animals. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1761-1770, 2016.

Developmental neurotoxicity of succeeding generations of insecticides

“…Gestational exposure to type I PIs alters brain vascular formation (Imanishi and others 2013), increases blood-brain barrier permeability (Sinha and others 2004), increases oxidative stress both shortly and long after the end of exposure (Sinha and others 2006), causes functional deficits in the cholinergic muscarinic system (Eriksson and Nordberg 1990), decreases monoamine levels and neocortical and hippocampal thicknesses during postnatal development (Imanishi and others 2013). These effects are accompanied by delayed physical and motor development, decreased locomotor activity, impaired motor coordination (Imanishi and others 2013; Syed and others 2015) and deficient learning and memory (Sinha and others 2006) even at adulthood.…”

“…Experimental studies in animal models demonstrate that gestational exposure to high doses of type II pyrethroids elicits severe effects such as increased resorptions and neonatal death, decreased brain regions weight and delayed physical and motor development in rodents (Husain and others 1992; Syed and others 2015). However, significant effects are also identified at low doses.…”

Non-target toxicity of novel insecticides

“…Pregnant dams treated with 10 mg kg -1 bw of deltamethrin showed transient neurotoxicity and weight loss, but no effect on testosterone synthesis was observed in their male offspring (171). Beta-cyfluthrin and bifenthrin affected behaviour in adult and neonate rats, which may be related to a drop in AChE activity and the elevated oxidative stress in their brains (172). Another study also showed that the blood-brain barrier of infant rats was more permeable to deltamethrin than that of older rats (173).…”

Utilizing urinary biomarkers in Egyptian adolescent applicators and non-applicators to characterize pesticide exposure to λ-cyhalothrin, α-cypermethrin, chlorpyrifos and profenofos applied on cotton crops over time

“…The general PYR metabolite associated with exposures is 3phenoxybenzoic acid (3-PBA). There are also specific metabolites for α-Cypermethrin, cis/trans-3-(2,2-dichlorovinyl)-2,2-dimethylycyclopropanecarboxylic acid (cis/trans-DCCA), cis-3-(2,2-dibromovinyl)-2,2dimethylcyclopropane carboxylic acid (-DBCA) (cis-DBCA or DBCA), a deltamethrin specific metabolite; and 4-fluoro-3phenoxybenzoic acid (FPBA), a cyfluthrin specific metabolite (Bradberry et al, 2005a;Bradberry, et al, 2005b;Chen et al, 2015;Chuang et al, 2011;Clifton et al, 2013;Elflein et al, 2003a;Ellison et al, 2011;Haudenschild, et al, 2014;Heudorf, et al, 2006;Leng, et al, 2006;McKelvey, et al, 2013;Scollon, et al, 2009;Syed et al, 2015;Wolansky et al, 2008).…”

“…PYRs are detoxified by rapid metabolized in the liver through two distinct pathways dependent on their structure, a cytochrome P450 catalyzed oxidation and hydrolysis catalyzed by esterases (Leng, et al, 2006;Miyamoto, 1976;Scollon, et al, 2009;Syed, et al, 2015;Wang, et al, 2016). Hydrolysis is the primary mode of PYR metabolism that occurs rapidly in the liver producing inactive metabolites in the urine.…”