| Organophosphorus pesticides (OP) are widely used in the control of insects around the home and in agriculture practice in China. It has broad-spectrum in controlling insecticide, short residual period and low price, which are easy to be accepted by farmer. OP residue is the most outstanding issue in pesticide residue in food. Risk assessment of single OP in food was fully evaluated, but human exposure to OP, whether occupationally or environmentally, is rarely limited to a single OP. People are always sequential or concurrent exposure in OP pesticides, which health hazard to people was be appraised. According to the research progress at home and abroad, this project was studied deeply and systematically in the interactive action, acute neurotoxicity, effects on metabolic enzyme, male rats reproductive toxicity and relative gene expression so as to reveal damage to organism and provide scientific data for the risk assessment of mixtures of OP pesticides.The acute oral toxicity (LD50) of two OP pesticides was evaluated by Horns method on equal toxicity doses. The mixtures of two OP pesticides omethoate plus phoxim, omethoate plus dichlorovos, dichlorvos plus phoxim, and dichlorovos plus methyl parathion showed additive effects; dichlorovos plus chlorpyrifos and omethoate plus methyl patathion showed synergistic effects; dichlorovos plus chlorpyrifos showed antagonistic effects. On the basis of the results, the mixture of omethoate and chlorpyrifos were used to launch the following research.The interactive toxicity of chemical mixture is closely related to metabolic enzyme. The interactive effect on critical metabolism enzyme was studied so as to elucidate the mechanism of synergistic acute neurotoxicity. Omehoate and chlorpyrifos were mixed with 1/2 LD50 dose, and lavage mixture to SD rats .The interactive effects on carboxylesterase (CE) and cholinesterase activity (ChE) in liver and blood serum was evaluated by the means of both concomitant treatments using 2×3 factorial design .Results indicated that the AchE activity of brain tissue was significantly decreased by 60% comparing with control group after exposure to the mixture. The neurotoxicity occurred. The mixture can be decrease significantly CE activity of liver and blood serum After exposure for 4 and 8 hours, the synergistic effect showed up. The decrease of CE activity was one of the possible mechanisms that resulted in synergistic neurotoxicity.The effects of chlorpyrifs and omehoate on the reproductive function in male SD rats were studied and got the no obserber adverse effect level (NOAEL) of the two OP pesticides that providing scientific supports for those risk assessment. The Results showed: chlorpyrifs and omehoate can induce male reproductive toxicity, and had a significant fall in the total sperm count, the percentage of sperm mobility and increase 0f the sperm abnormality; and lead to injury of testicular follicle. The amount of spermatogenic cell decreased,and it was occure with degeneration, defluxion, dropsy. The mechanism of produceing male toxicity goes as follows. Firstly, Omethoate can significantly increase FSH and T in testicular tissue, decrease the amount of sertolic cells which revealed SC as the target site of omethoate; chlorpyrifs can increase LH, decrease T and amount of cell of leydig which signed the leydig's cell as the target cell of chlorpyrifs. Secondly, the activites of lactate dehydrogenase (LDH), alkaline phosphatase (AKP), acid phosphatas (ACP) andγ-glutamyltransferase (γ-GT) were changed after exposure to omethoate or chlorpyrifs, which had correlations with the decrease of sperm quality. At last, the antioxygen balance was broken down, which destroyed the normal dynamic equilibrium of apoptosis of spermatogenic cell to sustain spermatogenesis process. There was another possible mechanism to cause male reproductive toxicity. The NOAEL of omehoate is 0.44mg/kg, and one of chlorpyrifs is 0.82mg/kg.The mixture of omethoate and chlorpyrifs can produce male reproductive toxicity, which interactive toxicity showed synergistic effect. Mixture can significantly increase the epididymal viscera coefficients and decrease total sperm count, the percentage of sperm mobility, which has synergistic effect. By the electron microscope and light microscope, the following can be observed: atrophia of the contorted seminiferous tubules, decrease of sperm and SC amount, sperm shedding from SC, decrease of sperms'abnormity, necrosisi of sperm and SC. The mechanism of producing interactive male toxicity is following. Firstly, the activites of lactate dehydrogenase (LDH), alkaline phosphatase (AKP), acid phosphatas (ACP) andγ-glutamyltransferase (γ-GT) were changed after exposure to mixtures, which show synergistic effects. There was joint action in FSH and T after exposure to omthoate and chlorpyrifs, which the effect of sertolic cell has synergistic effect. As the effect on LH of mixture is additive, the synergistic effect mainly showed damage to SC.In this project, the SC culture mold was used to study mechanism of male reproductive toxicity after exposure to omehoate and chlorpyrifs. The fluorescence semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) technique was utilized to explore effects of insecticide mixtures on the expression of androgen binding protein (ABP), inhibin B mRNA in testis SC of SD rats. The expression of ABP mRNA in SC dropped significantly, which showed synergistic effects. It is rectified that mixture can strongly destroy the balance of spermatogenesis process, and the extent are more extensive than the total toxicity of individual insecticide separately; One of the mechanisms resulting in synergistic male reproductive is that mixture synergistically decreased the expression of ABP mRNA .OP pesticides can produce synergistic acute neurotoxicity and subchronic male reproductive, which has more powerful toxicity than the add one of single OP pesticides. The risk to people's health increased after being exposed to phosphate mixtures, so it's necessary to consider the increase of toxicity after mixing pesticides when formulate the maximum residue limit that is proper and reasonable to protect people's health. |
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