Progress 04/01/00 to 03/31/06
Outputs
Project was renewed and continued under project #MIS 522060 Accession #0206658.
Impacts
2006. No outcomes to report.
Publications
- 2006. No publications to report.
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Progress 01/01/05 to 12/31/05
Outputs
Detoxication of 12 organophates (OP's) by liver and serum carboxylesterase (CbxE) and paraoxonase (PON) was compared for adult, juvenile and neonatal rats. All OP's tested except methyl coumaphos oxon were detoxified by adult liver CbxE but extent of detoxication varied widely (from 12% for diazoxon to 99% for chlorpyrifos oxon). For all OP's, detoxication was lower for juvenile liver CbxE and lowest for the enzyme from neonates. Detoxication by serum CbxE was lower than by liver CbxE at all ages. Only 4 OP's were detoxified by PON and, as with CbxE, activites were highest in adults and lowest in neonates. Results suggest that the observed greater sensitivity of young animals to some OP's in comparison to adults is the result of lower detoxication capacity.
Impacts
The potential greater sensitivity of infants to pesticide exposure than adults is a matter of serious concern to regulatory agencies. Understanding the magnitude and toxicological basis of any increased sensitivity is needed for proper regulation of pesticide registration and usage.
Publications
- No publications reported this period
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Progress 01/01/04 to 12/30/04
Outputs
Studies of comparative detoxication of organophosphates (OP's) by neonate, juvenile and adult rat esterases were continued. Of 12 OP's studied, only 3 were significantly detoxified by A-esterase of adults, and only 1 was detoxified by neonate A-esterase. Adult B-esterase detoxified 10 of the 12 OP's tested while neonate B-esterase detoxified only 4. Exposure of adult rats to dieldrin, a previously-used, highly persistent organochlorine insecticide, resulted in increased levels of both A- and B-esterases in the liver.
Impacts
Studies of OP mixtures provide essential information required of establishment of acceptable exposure levels during the ongoing reregistration of many OP's by the EPA. Studies of detoxication by animals of various ages provides information useful in predicting differences in toxicities of OP's to adults vs children. There are reports that young animals are more sensitive, but this may not be true for all OP's.
Publications
- No publications reported this period
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Progress 01/01/03 to 12/31/03
Outputs
Studies of detoxication of mixtures of organophosphates (OP') by esterases were completed. Of 10 binary mixtures of 4 OP's, none showed interference of detoxication of any compound by the other. Results suggest, therefore, that mixtures of OP's should be no more toxic than toxicity predicted by the sum of their individual toxicities. Studies of comparative detoxication of OP's by esterases of neonate, juvenile and adult rats were initiated. Of 12 chemicals tested, 3 are rapidly detoxified by liver and serum A-esterases of adults, and 2 are detoxified less rapidly, while 7 are unaffected by these enzymes. Neonates and juveniles have appreciably less A-esterase than adults. B-esterases also detoxify OP's but by a different mechanism. Of the 4 dimethyl phosphates tested, none are detoxified by either type of esterase.
Impacts
Studies of OP mixtures provide essential information required of establishment of acceptable exposure levels during the ongoing reregistration of many OP's by the EPA. Studies of detoxication by animals of various ages provides information useful in predicting differences in toxicities of OP's to adults vs children. There are reports that young animals are more sensitive, but this may not be true for all OP's.
Publications
- Carr, R.L., H.W. Chambers, J.E. Chambers, S.F. Oppenheimer and J.R. Richardson. 2003. Modelling the interactions of mixtures of organophosphorus insecticides with cholinesterase. Electronic Journal of Differential Equations Conf. 10, pp. 89-99.
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Progress 01/01/02 to 12/31/02
Outputs
Detoxication of 5 organophosphates (OP's) by carboxylesterases was determined by incubation of the OP in rat liver homogenate or rat serum followed by measurement of residual OP via acetylcholinesterase inhibition. In addition, detoxication of the 10 binary mixtures added simultaneously to the test preparation, and of the 20 binary mixtures added sequentially, was determined. Expected residual OP concentrations for mixtures were calculated from data for individual compounds using a potency-additive model and expressed as dosage equivalents of a single component. For all mixtures tested, the observed residual OP agreed with expected values. Thus, at least for the 5 OP's studied, no greater-than-additive effects would be expected for exposure to OP mixtures.
Impacts
The study of OP mixtures is a critical component of the risk assessment process required by the Food Quality Protection Act (FQPA). Since most known instances of synergistic effects of mixtures of toxicants is the result of interference with the detoxication of one compound by the other, studies of detoxication of mixtures will be of value in predicting likelihood of greater-than-additive toxicity.
Publications
- Chambers, J.E., J.S. Boone, R.L. Carr, H.W. Chambers and D.L. Straus. 2002. Biomarkers as predictors in health and ecological risk assessment. Human and Ecol. Risk Assess. 8(1): 165-176.
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Progress 01/01/01 to 12/31/01
Outputs
Detoxication of organophosphorus insecticides (OP's) by rat liver and serum esterases was investigated for single compounds and for binary mixtures. Carboxylesterase (CbxE) detoxified methyl paraoxon (MPO), paraoxon (PO), diazoxon (DO), chlorpyrifos-oxon (CO) and azinphos-methyl-oxon (AMO) stoichiometrically by acting as an alternate phosphorylation site. All binary mixtures showed detoxication as predicted from data of individual OP's. Malaoxon was hydrolyzed catalytically by CbxE, and rate of detoxication was decreased in mixtures, especially with PO, CO and DO. A-Esterases catalytically degraded CO and DO, but not any of the other OP's tested. A-Esterase activity was not decreased in any binary mixture containing CO or DO.
Impacts
Detoxication of organophosphorus insecticides (OP's) by rat liver and serum esterases was investigated for single compounds and for binary mixtures. Carboxylesterase (CbxE) detoxified methyl paraoxon (MPO), paraoxon (PO), diazoxon (DO), chlorpyrifos-oxon (CO) and azinphos-methyl-oxon (AMO) stoichiometrically by acting as an alternate phosphorylation site. All binary mixtures showed detoxication as predicted from data of individual OP's. Malaoxon was hydrolyzed catalytically by CbxE, and rate of detoxication was decreased in mixtures, especially with PO, CO and DO. A-Esterases catalytically degraded CO and DO, but not any of the other OP's tested. A-Esterase activity was not decreased in any binary mixture containing CO or DO.
Publications
- Hamadian, E.I. and H.W. Chambers. 2001. Susceptibility and mechanisms underlying the relative tolerance to five organophosphorus insecticides in tobacco budworms and corn earworms. Pestic. Biochem. Physiol. 69: 35-47.
- Chambers, H.W., J.S. Boone, R.L. Carr and J.E. Chambers. 2001. Chemistry of organophosphates. In Handbook of Pesticide Toxicology, Vol. 2, Agents, 2nd ed. Ed., R. Kreiger, J. Doull, D. Ecobichon, E. Hodgson, L. Reiter, J. Ross, J. Seiber and D. Gammon. Academic Press. pp. 913-917.
- Chambers, J.W., R.L. Carr, J.S. Boone and H.W. Chambers. 2001. Metabolism of organophosphates. In Handbook of Pesticide Toxicology, Vol. 2, Agents, 2nd ed. Ed., R. Kreiger, J. Doull, D. Ecobichon, E. Hodgson, L. Reiter, J. Ross, J. Seiber and D. Gammon. Academic Press. pp. 919-927.
- Carr, R.L., H.W. Chambers, J.A. Guarisco, J.R. Richardson, J. Tang and J.E. Chambers. 2001. Effects of repeated oral postnatal exposure to chlorpyrifos on open-field behavior in juvenile rats. Toxicol. Sci. 59: 260-267.
- Richardson, J.E., H.W. Chambers and J.E. Chambers. 2001. Analysis of the additivity of in vitro inhibition of cholinesterase by mixtures of chlorpyrifos-oxon and azinphos-methyl-oxon. Toxicol. Appl. Pharmacol. 172: 128-139.
- Chambers, J.E., J.S. Boone, R.L. Carr, H.W. Chambers and D.L. Straus. 2002. Biomarkers as predictors in health and ecological risk assessment. Human and Ecol. Risk Assess. (In Press).
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Progress 01/01/00 to 12/31/00
Outputs
Emphasis of project is to investigate the greater sensitivity of juveniles to organophosphate (OP) poisoning, and the toxicology of mixtures of OP's. In particular, the significance of aliesterases and A-esterases are being considered. Preliminary studies in rats have shown that very young animals have much lower levels of both types of esterases, juveniles are much more sensitive to poisoning than adults. For methyl parathion, which is poorly detoxified by esterases, difference in acute toxicity between the two ages is small. Parathion is intermediate in both detoxication by esterases and differential juvenile/adult toxicity. Studies with OP mixtures to date have been limited to the target enzyme acetylcholinesterase (AChE). Of the mixtures tested, inhibition of AChE by combinations of two OP's is not significantly different from that predicted from the potency of the individual compounds.
Impacts
It would be premature to predict a possible impact of these studies since they are of a highly basic nature and in the early stages. It is hoped, however, that data will be generated which will be of value to regulatory agencies in the areas of child safety and complex mixtures (a concern of the Food Quality Protection Act).
Publications
- No publications reported this period
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