Developmental effects of chlorpyrifos extend beyond neurotoxicity: critical periods for immediate and delayed-onset effects on cardiac and hepatic cell signaling.

Abstract

The fetal and neonatal neurotoxicity of chlorpyrifos (CPF) and related insecticides is a major concern. Developmental effects of CPF involve mechanisms over and above cholinesterase inhibition, notably events in cell signaling that are shared by nonneural targets. In the present study, we evaluated the immediate and long-term effects of CPF exposure of rats during different developmental windows [gestational days (GD) 9-12 or 17-20, postnatal days (PN) 1-4 or 11-14] on the adenylyl cyclase (AC) signaling cascade in the heart and liver. In addition to basal AC activity, we assessed the responses to direct AC stimulants (forskolin, Mn 2+ ); to isoproterenol and glucagon, which activate signaling through specific membrane receptors; and to sodium fluoride, which activates the G-proteins that couple the receptors to AC. Few immediate effects on AC were apparent when CPF doses remained below the threshold for systemic toxicity. Nevertheless, CPF exposures on GD9-12, GD17-20, or PN1-4 elicited sex-selective effects that emerged by adulthood (PN60), whereas later exposure (PN11-14) elicited smaller, nonsignificant effects, indicative of closure of the window of vulnerability. Most of the effects were heterologous, involving signaling elements downstream from the receptors, and thus were shared by multiple inputs; superimposed on this basic pattern, there were also selective alterations in receptor-mediated responses. These results suggest that the developmental toxicity of CPF extends beyond the nervous system, to include cell signaling cascades that are vital to cardiac and hepatic homeostasis. Future work needs to address the potential implications of these effects for cardiovascular and metabolic disorders that may emerge long after the end of CPF exposure.

Adverse Effects of Organophosphorus Insecticides on Macrophage Activity in Persons at High Risk for Parasitic Infection

“…In the Kingdom of Saudi Arabia (KSA), chlorpyrifos (CPF) (O, O'-diethyl3, 5, 6-trichloro-2-pyridinyl-phosphoro-thioate), a broadspectrum organo-phosphorous (OP) insecticide, has been widely used for the control of agricultural pests [2]. It has been reported that OP compounds are highly toxic to vertebrates [3] and CPF is particularly considered to be neurotoxic [4], cardiotoxic, hepatotoxic [5] and immunotoxic [6].…”

Expressing urine from a gel disposable diaper for biomonitoring using phthalates as an example

“…This period of susceptibility also extends into the neonatal period in experimental animals . For instance, Meyer et al (2004) studied the immediate and long-term effects of exposure of neonatal rats to the organophosphate pesticide chlorpyrifos on gestation days 9-12 and 17-20 or postnatal days 1-4 and 11-14. Cardiac responses were measured by pharmacological challenge of adenylyl cyclase activity with forskolin, isoproteronol, and glucagons.…”

Aspectos bioéticos en el control y aplicación de plaguicidas en Chile

“…Producto de esto y de las investigaciones que informaban sobre los problemas de salud, se creó en Estados Unidos, en 1965, la Agencia para la Protección del Medio Ambiente (EPA), encargada desde entonces de evaluar los beneficios y peligros de los plaguicidas, siendo sus investigaciones un referente en los demás países del mundo sobre su eficacia y efectos(3). ción muscular, cambios en la frecuencia cardíaca y broncoespasmo, progresando a convulsiones y coma (1,4,(12)(13)(14)(15)(16).…”