Assessment of acetylcholinesterase activity in Clarias gariepinus as a biomarker of organophosphate and carbamate exposure.

The objective of this study was to investigate the response of acetylcholinesterase (AChE) activities in Clarias gariepinus in response to Organophosphates (Ops) and carbamate exposure. The AChE activities were determined in plasma, and eye and brain homogenates of unexposed and exposed fish using Ellman's method and 5,5'-dithiobis-2-nitrobenzoic acid (DTNB) chromophore. The baseline AChE activities in plasma, eyes and brain tissues in unexposed fish were comparable between males and females (P > 0.05). Concentrations of pesticides that inhibited 50% (IC(50)) of AChE activities in brain homogenates following in vitro exposures were 0.003, 0.03, 0.15, 190, 0.2, 0.003 and 0.002 microM for carbaryl, chlorfenvinphos, diazinon, dimethoate, fenitrothion, pirimiphosmethyl and profenofos, respectively. The in vivo dose-effect relationships were assessed using chlorfenvinphos and carbaryl at different concentrations that ranged from 0.0003 to 0.06 microM and 0.0005 to 0.05 microM, respectively. Acetylcholinesterase activities were comparable in plasma, and eye and brain homogenates from control and carbaryl-exposed fish. Following exposure of fish to chlorfenvinphos at concentrations above 0.03 microM, a significant inhibition of AChE activities in plasma (84%) and eye homogenate (50%) was observed. The AChE activities in brain homogenate were comparable between chlorfenvinphos-exposed fish and controls. Because carbaryl cause reversible inhibition of AChE activities was found to be more potent than chlorfenvinphos that cause irreversible inhibition following in vitro exposure. Contrary, carbaryl was less potent than chlorfenvinphos after in vivo exposure possibly due to more rapid biotransformation of carbaryl than chlorfenvinphos. Findings from this study have demonstrated that inhibition of AChE activity in C. gariepinus is a useful biomarker in assessing aquatic environment contaminated by anticholinesterases.

Assessment of the toxicological interaction of sertraline with cholinesterase inhibiting insecticides in aquatic insects using the black fly, Simulium vittatum IS-7.

Sertraline is a selective serotonin reuptake inhibitor (SSRI) prescribed as an antidepressant. Although SSRIs are known to block serotonin reuptake sites on cell membranes, they also have been shown to inhibit acetylcholinesterase (AChE) activity. Thus, the interaction of these chemicals with other AChE inhibitors, namely, organophosphate and carbamate insecticides, is of interest. In addition, these insecticides have been shown to interact with serotonergic neuronal pathways creating questions as to how these chemicals might interact. In this study, the interactive effect of sertraline (SSRI) in binary combinations with carbaryl (carbamate insecticide) and diazinon (organophosphate insecticide) was assessed using a 48-h acute toxicity test with black fly larvae, Simulium vittatum IS-7. Results showed that observed mortality was bracketed by the independent action model and concentration addition model with the independent action model slightly underestimating mortality and the concentration addition model slightly overestimating mortality. Varying the concentration of the chemicals in the mixture did not indicate that sertraline was interacting with the insecticides to make them more toxic or vice versa. These results indicate that sertraline and the insecticides are likely eliciting toxicity at separate neuronal pathways since no interaction was observed.

Assessment of absorbed doses of carbaryl and associated health risks in a group of horticultural greenhouse workers.

OBJECTIVE: This study was undertaken to estimate the absorbed doses of carbaryl and the associated health risks in a group of horticultural greenhouse workers in the Province of Quebec, Canada, using a toxicokinetic modeling approach. METHODS: A mathematical model was developed to relate the absorbed dose of carbaryl, the evolution of its body burden and that of its metabolites and the urinary excretion rate of biomarkers. The free parameters of this model were determined using published time course data in volunteers exposed to carbaryl under controlled conditions. The model was used to determine cumulative urinary amounts of 1-naphthol that would be excreted by a typical worker exposed to a pre-established no-observed-adverse-effect level (NOAEL) dose; this biomarker amount was then taken as a biological reference value below which the risks of health effects were considered negligible. As a measure of the applicability of this approach to practical situations, the model was used to estimate the dose of carbaryl absorbed by each greenhouse worker, starting from his/her cumulative urinary excretion time courses of 1-naphthol over a 24-h period following the onset of a work exposure. Their cumulative 1-naphthol levels were then compared to the biological reference value obtained from the model and the NOAEL dose. RESULTS: Following the onset of a work exposure to carbaryl, a clear increase in the urinary excretion rate of 1-naphthol was observed in most workers. The reconstructed absorbed doses were found to vary between 3.3 and 143 nmol/kg of body weight (bw) depending on the working conditions. Simulations of the observed cumulative urinary excretion time course of each worker also showed that exposure appeared to occur mainly (a) through inhalation for the applicators and individuals without direct contact with treated plants and (b) through the dermal route for individuals manipulating treated plants. Although the workers under study clearly appeared to have been exposed to carbaryl in the greenhouses, 24-h cumulative 1-naphthol levels ranged from 4.8 to 65.1% of the proposed biological reference value of 32 nmol/kg bw in 24-h urine collections following the onset of a work exposure. CONCLUSION: This suggests that the workers under study probably did not incur a serious health risk under the normal exposure conditions prevailing during the study period.

A randomization test-based method for risk assessment in neurotoxicology.

A current trend in risk assessment for systemic toxicity (noncancer) endpoints is to utilize the observable range of the dose-effect curve in order to estimate the likelihood of obtaining effects at lower concentrations. Methods to accomplish this endeavor are typically based on variability in either the effects of fixed doses (benchmark approaches), or on variability in the doses producing a fixed effect (probabilistic or tolerance-distribution approaches). The latter method may be particularly desirable because it can be used to determine variability in the effect of an agent in a population, which is an important goal of risk assessment. This method of analysis, however, has typically been accomplished using dose-effect data from individual subjects, which can be impractical in toxicology. A new method is therefore presented that can use traditional groups-design data to generate a set of dose-effect functions. Population tolerances for a specific effect can then be estimated from these model dose-effect functions. It is based on the randomization test, which assesses the generality of a data set by comparing it to a data set constructed from randomized combinations of single point estimates. The present article describes an iterative line-fitting program that generates such a data set and then uses it to provide risk assessments for two pesticides, triadimefon and carbaryl. The effects of these pesticides were studied on the locomotor activity of laboratory rats, a common neurobehavioral end point. Triadimefon produced dose-dependent increases in activity, while carbaryl produced dose-dependent decreases in activity. Risk figures derived from the empirical distribution of individual dose-effect functions were compared to those from the iterative line-fitting program. The results indicate that the method generates comparable risk figures, although potential limitations are also described.