Inhibitor Report for: Thiobencarb

European eels (Anguilla anguilla) were exposed to sublethal thiobencarb concentrations in a continuous flow-through system for 4 days. Brain, muscle, and gill acetylcholinesterase (AChE) activities were evaluated after 2, 12, 24, 48, 72, and 96 h herbicide exposure. Thiobencarb induced significant inhibitory effects on the total and specific AChE activity of A. anguilla, ranging from >30-40% inhibition in eel brain and gills to >50% inhibition in muscle tissue 2 h after the initial exposure. In a second experiment, eels were exposed to thiobencarb for 96 h and then allowed a period of recovery in pesticide-free water. Following 1 week of recovery, the AChE activity of affected eels approached control level. Fish transferred to clean water recovered specific AChE activities in the studied tissues slowly in the next 8 days (without toxicant), reaching about 60-80% of the normal levels in brain and muscle tissue around the 4th day after the beginning of the recovery period (in clean water). Specific AChE activity in the gills from eels transferred to clean water recovered its normal value while total AChE activity remained depressed (29%) in this tissue 8 days later. Many behavioral changes such as lowering of motility with loss of equilibrium, uncoordinated movements, and increase in the levels of respiratory frequency were observed during exposure to the herbicide.

Thiobencarb (S-(4-chlorobenzyl)-N,N-diethyl thiol carbamate) has been one of the herbicides previously associated with fish kills in agricultural drains near the Sacramento/San Joaquin rivers and their Delta. This area is an important spawning ground for fish, and thus there are concerns over possible toxic effects on early life stages of fishes. To define targets of thiobencarb embryotoxicity and to determine the degree of protection afforded by the chorion, medaka (Oryzias latipes) embryos were exposed under static nonrenewal conditions. Responses to exposures initiated at blastula or at initiation of heart beat (stages 10 and 23, respectively) were assessed. In addition, enzymatically dechorionated embryos (stage 13, gastrula) were exposed and compared to responses in embryos with intact chorions. Embryos were observed daily for development and for gross abnormalities including: bradycardia, pericardial edema, hemostasis, poor yolk resorption, cephalic and spinal deformities, and abnormal hatching. A subset was also evaluated for histologic alterations. Based on gross abnormalities, the concentration of thiobencarb affecting 50% (EC(50)) of embryos exposed at blastula was 3.6 mg/l, while the putative no observable effect concentration (NOEC) was 1.0 mg/l. For embryos exposed at onset of heart beat (stage 23), these values were 4.1 and 2.5 mg/l, respectively. Dechorionated embryos tended to be more sensitive than their chorionated cohorts (LC(50)=2.5 vs. 1.0 mg/l). Liver histologic alterations were seen in chorionated embryos at EC(50) levels and higher. Stage-specific toxicity was evident; nevertheless, the EC(50) and NOEC values for embryos treated at stage 10 and stage 23 were similar.

Thiobencarb (S-(4-chlorobenzyl)-N,N-diethyl thiol carbamate), a dithiocarbamate herbicide, was found to cause neuronal dysfunction in adult and neonate albino rats. In general, organocarbamates exert their action by inhibiting acetylcholinesterase (AChE) activity. Thiobencarb inhibited both acetylcholinesterase and adenosine triphosphatase (ATPase) activities in rat brain. Withdrawal of thiobencarb treatment resulted in the recovery of AChE activity to a normal level, whereas there was no recovery of Na(+)-K(+)-ATPase activity in either neonate or adult rat brains. The results suggest that neuronal dysfunction caused by thiobencarb is mainly due to the inhibition of ATPase activity rather than to the inhibition of AChE activity.

Thiobencarb is a representative herbicide used on rice paddies. Because thiobencarb is used extensively on agricultural lands, especially on paddy fields, there is a high risk of unintended leaks into aquatic ecosystems. For this reason, several studies have investigated and reported on the toxicity of thiobencarb to aquatic species. In European eels, thiobencarb affected acetylcholinesterase levels in plasma and impaired adenosine triphosphatase activity in their gills. In medaka, thiobencarb-exposed embryos showed lower viability. However, molecular mechanisms underlying thiobencarb-mediated embryotoxicity have yet to be clarified. Therefore, the objective of our study was to investigate its mechanism of toxicity using zebrafish embryos. The viability of zebrafish embryos decreased upon exposure to thiobencarb and various phenotypic abnormalities were observed at concentrations lower than the lethal dose. The developmental toxicity of thiobencarb was mediated by pro-inflammatory cytokines (il1b, cxcl8, cxcl18b, and cox2a) and excessive generation of reactive oxygen species due to the downregulation of genes such as catalase, sod1, and sod2, which encode antioxidant enzymes. In addition, severe defects of the cardiovascular system were identified in response to thiobencarb exposure. Specifically, deformed cardiac looping, delayed common cardinal vein (CCV) regression, and interrupted dorsal aorta (DA)-posterior cardinal vein (PCV) segregation were observed. Our results provide an essential resource that demonstrates molecular mechanisms underlying the toxicity of thiobencarb on non-target organisms, which may contribute to the establishment of a mitigation strategy.

European eels (Anguilla anguilla) were exposed to sublethal thiobencarb concentrations in a continuous flow-through system for 4 days. Brain, muscle, and gill acetylcholinesterase (AChE) activities were evaluated after 2, 12, 24, 48, 72, and 96 h herbicide exposure. Thiobencarb induced significant inhibitory effects on the total and specific AChE activity of A. anguilla, ranging from >30-40% inhibition in eel brain and gills to >50% inhibition in muscle tissue 2 h after the initial exposure. In a second experiment, eels were exposed to thiobencarb for 96 h and then allowed a period of recovery in pesticide-free water. Following 1 week of recovery, the AChE activity of affected eels approached control level. Fish transferred to clean water recovered specific AChE activities in the studied tissues slowly in the next 8 days (without toxicant), reaching about 60-80% of the normal levels in brain and muscle tissue around the 4th day after the beginning of the recovery period (in clean water). Specific AChE activity in the gills from eels transferred to clean water recovered its normal value while total AChE activity remained depressed (29%) in this tissue 8 days later. Many behavioral changes such as lowering of motility with loss of equilibrium, uncoordinated movements, and increase in the levels of respiratory frequency were observed during exposure to the herbicide.

Thiobencarb (S-(4-chlorobenzyl)-N,N-diethyl thiol carbamate) has been one of the herbicides previously associated with fish kills in agricultural drains near the Sacramento/San Joaquin rivers and their Delta. This area is an important spawning ground for fish, and thus there are concerns over possible toxic effects on early life stages of fishes. To define targets of thiobencarb embryotoxicity and to determine the degree of protection afforded by the chorion, medaka (Oryzias latipes) embryos were exposed under static nonrenewal conditions. Responses to exposures initiated at blastula or at initiation of heart beat (stages 10 and 23, respectively) were assessed. In addition, enzymatically dechorionated embryos (stage 13, gastrula) were exposed and compared to responses in embryos with intact chorions. Embryos were observed daily for development and for gross abnormalities including: bradycardia, pericardial edema, hemostasis, poor yolk resorption, cephalic and spinal deformities, and abnormal hatching. A subset was also evaluated for histologic alterations. Based on gross abnormalities, the concentration of thiobencarb affecting 50% (EC(50)) of embryos exposed at blastula was 3.6 mg/l, while the putative no observable effect concentration (NOEC) was 1.0 mg/l. For embryos exposed at onset of heart beat (stage 23), these values were 4.1 and 2.5 mg/l, respectively. Dechorionated embryos tended to be more sensitive than their chorionated cohorts (LC(50)=2.5 vs. 1.0 mg/l). Liver histologic alterations were seen in chorionated embryos at EC(50) levels and higher. Stage-specific toxicity was evident; nevertheless, the EC(50) and NOEC values for embryos treated at stage 10 and stage 23 were similar.

Thiobencarb (S-(4-chlorobenzyl)-N,N-diethyl thiol carbamate), a dithiocarbamate herbicide, was found to cause neuronal dysfunction in adult and neonate albino rats. In general, organocarbamates exert their action by inhibiting acetylcholinesterase (AChE) activity. Thiobencarb inhibited both acetylcholinesterase and adenosine triphosphatase (ATPase) activities in rat brain. Withdrawal of thiobencarb treatment resulted in the recovery of AChE activity to a normal level, whereas there was no recovery of Na(+)-K(+)-ATPase activity in either neonate or adult rat brains. The results suggest that neuronal dysfunction caused by thiobencarb is mainly due to the inhibition of ATPase activity rather than to the inhibition of AChE activity.