Appendix 2-5: Rejected ecotox bibliography for Chlorpyrifos



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We tested whether mechanistically based screening assays can rapidly provide information on the potential for compounds to affect key enzymes and receptor targets, thus identifying those compounds requiring further in-depth analysis. METHODS: A library of 176 synthetic chemicals was prepared and examined in a high-throughput screening (HTS) manner using nine enzyme-based and five receptor-based bioassays. RESULTS: All the assays have high Z' values, indicating good discrimination among compounds in a reliable fashion, and thus are suitable for HTS assays. On average, three positive hits were obtained per assay. Although we identified compounds that were previously shown to inhibit a particular enzyme class or receptor, we surprisingly discovered that triclosan, a microbiocide present in personal care products, inhibits carboxylesterases and that dichlone, a fungicide, strongly inhibits the ryanodine receptors. CONCLUSIONS: Considering the need to rapidly screen tens of thousands of anthropogenic compounds, our study shows the feasibility of using combined HTS assays as a novel approach toward obtaining toxicologic data on numerous biological end points. The HTS assay approach is very useful to quickly identify potentially hazardous compounds and to prioritize them for further in-depth studies.
Keywords: Receptors, Aryl Hydrocarbon -- drug effects
Keywords: Animals
Keywords: Receptors, Estrogen -- drug effects
Keywords: Receptors, Androgen -- drug effects
Keywords: Naphthoquinones
Keywords: Humans
Keywords: Naphthoquinones -- pharmacology
Keywords: High-Throughput Screening Assays -- methods
Keywords: Carboxylesterase
Keywords: Triclosan -- toxicity
Keywords: Environmental Studies
Keywords: Receptors, Androgen
Keywords: dichlone
Keywords: Receptors, Aryl Hydrocarbon
Keywords: Ryanodine Receptor Calcium Release Channel
Keywords: Toxicology -- methods
Keywords: Carboxylesterase -- antagonists & inhibitors
Keywords: Ryanodine Receptor Calcium Release Channel -- drug effects
Keywords: Triclosan
Keywords: Receptors, Estrogen
Copyright - Copyright National Institute of Environmental Health Sciences Dec 2009
Language of summary - English
Pages - 1867-72
ProQuest ID - 222639093
Last updated - 2012-10-17
Place of publication - Research Triangle Park
Corporate institution author - Morisseau, Christophe; Merzlikin, Oleg; Lin, Amy; He, Guochun; Feng, Wei; Padilla, Isela; Denison, Michael S; Pessah, Isaac N; Hammock, Bruce D
DOI - 1943895271; 50348501; 67001; ENHP; 20049205; INODENHP0006174681
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Owens CV Jr, Lambright C, Bobseine K, Ryan B, Gray LE Jr, Gullett BK, et al. 2007. Identification of estrogenic compounds emitted from the combustion of computer printed circuit boards in electronic waste. Environ Sci Technol 41:8506-8511.
Pessah IN, Durie EL, Schiedt MJ,Zimani I. 1990. Anthraquinonesensitized Ca^sup 2+^ release channel from rat cardiac sarcoplasmic reticulum: possible receptor-mediated mechanism of doxorubicin cardiomyopathy. MoI Pharmacol 37:503-514.
Pessah IN, Stambuk RA, Casida JE. 1987. Ca^sup 2+^-activated ryanodine binding: mechanisms of sensitivity and intensity modulation by Mg^sup 2+^, caffeine, and adenine nucleotides. MoI Pharmacol 31:232-238.
Roegge CS, Morris JR, Villareal S, Wang VC, Powers BE, Klintsova AY, et al. 2006. Purkinje cell and cerebellar effects following developmental exposure to PCBs and/or MeHg. Neurotoxicol Teratol 28:74-85.
Rogers JM, Denison MS. 2000. Recombinent cell bioassay for endocrine disrupters: development of stably transfected human ovarian cell line for the detection of estrogenic and anti-estrogenic chemicals. In Vitr Mol Toxicol 3:67-82.
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Satoh T, Hosokawe M. 2006. Structure, function and regulation of carboxylesterases. Chem Biol Interact 162:195-211.
Scialli AR. 2008. The challenge of reproductive and developmental toxicology under REACH. Regul Toxicol Pharmacol 51:244-250.
Shan G, Hammock BD. 2QQ1. Development of sensitive esterase assays based on alpha-cyano-containlng esters. Anal Biochem 299:54-62.
Silliman CC, Wang M. 2006. The merits of in vitro versus in vivo modeling in investigation of the immune system. Environ Toxicol Pharmacol 21:123-134.
Steinmetz R, Young PC, Caperell-Grant A, Gize EA, Madhukar BV, Ben-Jonathan N, et al. 1998. Novel estrogenic action of the pesticide residue beta-hexachlorocyclohexane in human breast cancer cells. Cancer Res 56:5403-5409.
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Zhang J, Chung TDY, Oldenburg KR. 1999. A simple statistical parameter for use in evaluation and validation of high throughput screening assays. J Biomol Screen 4:67-73.
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Bellinger, Andrew M., Mongillo, Marco 2008 "Stressed out: the skeletal muscle ryanodine receptor as a target of stress" Journal of Clinical Investigation 118 2 445-453
58. Berridge, MJ. 2006. Calcium microdomains: organization and function. Cell Calcium. 40:405-412.
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CHEN, C. W., HURD, C. 1997 "Transcriptional activation of the human estrogen receptor by DDT isomers and metabolites in yeast and MCF-7 cells" Biochemical Pharmacology 53 8 1161-1172
DENISON, M. S., HEATH-PAGLIUSO, S. 1998 "The ah receptor : A regulator of the biochemical and toxicological actions of structurally diverse chemicals" Bulletin of Environmental Contamination and Toxicology 61 5 557-568
DENISON, Michael S., NAGY, Scott R. 2003 "Activation of the aryl hydrocarbon receptor by structurally diverse exogenous and endogenous chemicals" Annual Review of Pharmacology and Toxicology 43 309-334
Dixon M (1972) The graphical determination of Km and Ki. Biochem J 129: 197-202
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Feng, Wei, Liu, Guohua 1999 "Site-selective modification of hyperreactive cysteines of ryanodine receptor complex by quinones" Molecular Pharmacology 55 5 821-831
Gad SC. 2006. Introduction, In: Animal Models in Toxicology, 2nd ed (Gad SC. ed). New York:Informa Healthcare, 1-18.
Garrison PM, Tullis K, Aarts JM, Brouwer A, Giesy JP, Denison MS. 1996. Species-specific recombinant cell lines as bioassay systems for the detection of 2,3,7,8tetrachlorodibenzo-p-dioxin-like chemicals. Fundam Appl Toxicol 30:194-203.
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Han, Dalho, Nagy, Scott R. 2004 "Comparison of recombinant cell bioassays for the detection of Ah receptor agonists" Biofactors 20 1 11-22
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Maranghi, Francesca, Rescia, Michele 2007 "Lindane may modulate the female reproductive development through the interaction with ER-beta: an in vivo-in vitro approach" Chemico-Biological Interactions 169 1 1-14
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Scialli, Anthony R. 2008 "The challenge of reproductive and developmental toxicology under REACH" Regulatory Toxicology and Pharmacology 51 2 244-250
Shan, G M, Hammock, B D 2001 "Development of sensitive esterase assays based on alpha-cyano-containing esters" Analytical Biochemistry 299 1 54-62
Silliman, C C, Wang, M 2006 "The merits of in vitro versus in vivo modeling in investigation of the immune system" Environmental Toxicology and Pharmacology 21 2 123-134
Steinmetz, Rosemary, Young, Peter C M 1996 "Novel estrogenic action of the pesticide residue beta-hexachlorocyclohexane in human breast cancer cells" Cancer Research 56 23 5403-5409
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928. Moser, V C; Padilla, S, and Moser, V C. Esterase Metabolism of Cholinesterase Inhibitors Using Rat Liver in Vitro. 2011 Mar 15; 281, (1-3): 56-62.


Rec #: 43489
Keywords: IN VITRO
Notes: Chemical of Concern: CPY
Abstract: Abstract: A variety of chemicals, such as organophosphate (OP) and carbamate pesticides, nerve agents, and industrial chemicals, inhibit acetylcholinesterase (AChE) leading to overstimulation of the cholinergic nervous system. The resultant neurotoxicity is similar across mammalian species; however, the relative potencies of the chemicals across and within species depend in part on chemical-specific metabolic and detoxification processes. Carboxylesterases and A-esterases (paraoxonases, PON) are two enzymatic detoxification pathways that have been widely studied. We used an in vitro system to measure esterase-dependent detoxification of 15 AChE inhibitors. The target enzyme AChE served as a bioassay of inhibitor concentration following incubation with detoxifying tissue. Concentration-inhibition curves were determined for the inhibitor in the presence of buffer (no liver), rat liver plus calcium (to stimulate PONs and thereby measure both PON and carboxylesterase), and rat liver plus EGTA (to inhibit calcium-dependent PONs, measuring carboxylesterase activity). Point estimates (concentrations calculated to produce 20, 50, and 80% inhibition) were compared across conditions and served as a measure of esterase-mediated detoxification. Results with well-known inhibitors (chlorpyrifos oxon, paraoxon, methyl paraoxon, malaoxon) were in agreement with the literature, serving to support the use of this assay. Only a few other inhibitors showed slight or a trend towards detoxification via carboxylesterases or PONs (mevinphos, aldicarb, oxamyl). There was no apparent PON- or carboxylesterase-mediated detoxification of the remaining inhibitors (carbofuran, chlorfenvinphos, dicrotophos, fenamiphos, methamidophos, methomyl, monocrotophos, phosphamidon), suggesting that the influence of esterases on these chemicals is minimal. Thus, generalizations regarding these metabolic pathways may not be appropriate. As with other aspects of AChE inhibitors, their metabolic patterns appear to be chemical-specific.
Keywords: Detoxification
Keywords: nerve agents
Keywords: Calcium
Keywords: Acetylcholinesterase
Keywords: esterase
Keywords: monocrotophos
Keywords: Cholinergic nerves
Keywords: Aryldialkylphosphatase
Keywords: Chlorfenvinphos
Keywords: Paraoxon
Keywords: Cholinesterase
Keywords: Metabolic pathways
Keywords: X 24330:Agrochemicals
Keywords: Pharmacy And Pharmacology
Keywords: Carbofuran
Keywords: methamidophos
Keywords: Aldicarb
Keywords: Carboxylesterase
Keywords: Enzymes
Keywords: organophosphates
Keywords: Pesticides (carbamates)
Keywords: fenamiphos
Keywords: Chlorpyrifos
Keywords: Neurotoxicity
Keywords: Pesticides
Keywords: Liver
Keywords: Phosphamidon
Keywords: Toxicology Abstracts
Keywords: Pons
Keywords: Metabolism
Date revised - 2011-10-01
Language of summary - English
Pages - 56-62
ProQuest ID - 886635749
SubjectsTermNotLitGenreText - Detoxification; nerve agents; Calcium; Acetylcholinesterase; esterase; monocrotophos; Cholinergic nerves; Aryldialkylphosphatase; Chlorfenvinphos; Paraoxon; Cholinesterase; Metabolic pathways; methamidophos; Carbofuran; Enzymes; Carboxylesterase; Aldicarb; organophosphates; Pesticides (carbamates); Chlorpyrifos; fenamiphos; Pesticides; Neurotoxicity; Liver; Phosphamidon; Pons; Metabolism
Last updated - 2011-12-13
Corporate institution author - Moser, V C; Padilla, S
DOI - OB-da29cd6d-c467-4928-bf77csamfg201; 14515423; 0300-483X English

929. Mosquin, Paul L; Licata, Amy Collins; Liu, Bing; Sumner, Susan C J, and Okino, Miles S. Reconstructing Exposures From Small Samples Using Physiologically Based Pharmacokinetic Models and Multiple Biomarkers. 2009 Mar; 19, (3): 284-97.


Rec #: 44989
Keywords: HUMAN HEALTH
Notes: Chemical of Concern: CPY
Abstract: Abstract: This study examines the use of physiologically based pharmacokinetic (PBPK) models for inferring exposure when the number of biomarker observations per individual is limited, as commonly occurs in population exposure surveys. The trade-off between sampling multiple biomarkers at a specific time versus fewer biomarkers at multiple time points was investigated, using a simulation-based approach based on a revised and updated chlorpyrifos PBPK model originally published. Two routes of exposure, oral and dermal, were studied as were varying levels of analytic measurement error. It is found that adding an additional biomarker at a given time point adds substantial additional information to the analysis, although not as much as the addition of another sampling time. Furthermore, the precision of the estimates of exposed dose scaled approximately with the analytic precision of the biomarker measurement. For acute exposure scenarios such as those considered here, the results of this study suggest that the number of biomarkers can be balanced against the number of sampling times to obtain the most efficient estimator after consideration of cost, intrusiveness, and other relevant factors.
Keywords: Reproducibility of Results
Keywords: Humans
Keywords: Chlorpyrifos -- blood
Keywords: Insecticides -- urine
Keywords: Likelihood Functions
Keywords: Environmental Studies
Keywords: Chlorpyrifos
Keywords: Biological Markers -- blood
Keywords: Insecticides
Keywords: Insecticides -- pharmacokinetics
Keywords: Biological Markers
Keywords: Biological Markers -- urine
Keywords: Biological Markers -- metabolism
Keywords: Chlorpyrifos -- pharmacokinetics
Keywords: Models, Theoretical
Keywords: Insecticides -- blood
Keywords: Chlorpyrifos -- urine
Copyright - Copyright Nature Publishing Group Mar 2009
Language of summary - English
Pages - 284-97
ProQuest ID - 219569528
Last updated - 2012-11-20
Place of publication - Tuxedo
Corporate institution author - Mosquin, Paul L; Licata, Amy Collins; Liu, Bing; Sumner, Susan C J; Okino, Miles S
DOI - 1646259551; 41927201; 68909; ENNP; 18461092; NTPGENNPjes200817 English

930. Mouslim, C. ; Aittaleb, M.; Hume, R. I., and Akaaboune, M. A Role for the Calmodulin Kinase Ii-Related Anchoring Protein (ΑKap) in Maintaining the Stability of Nicotinic Acetylcholine Receptors.


Rec #: 49989
Keywords: NO TOXICANT
Notes: Chemical of Concern: CPY
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ABSTRACT: αkap, a muscle specific anchoring protein encoded within the Camk2a gene, is thought to play a role in targeting multiple calcium/calmodulin kinase II isoforms to specific subcellular locations. Here we demonstrate a novel function of αkap in stabilizing nicotinic acetylcholine receptors (AChRs). Knockdown of αkap expression with shRNA significantly enhanced the degradation of AChR α-subunits (AChRα), leading to fewer and smaller AChR clusters on the surface of differentiated C2C12 myotubes. Mutagenesis and biochemical studies in HEK293T cells revealed that αkap promoted AChRα stability by a ubiquitin-dependent mechanism. In the absence of αkap, AChRα was heavily ubiquitinated, and the number of AChRα was increased by proteasome inhibitors. However, in the presence of αkap, AChRα was less ubiquitinated and proteasome inhibitors had almost no effect on AChRα accumulation. The major sites of AChRα ubiquitination reside within the large intracellular loop and mutations of critical lysine residues in this loop to arginine increased AChRα stability in the absence of αkap. These results provide an unexpected mechanism by which αkap controls receptor trafficking onto the surface of muscle cells and thus the maintenance of postsynaptic receptor density and synaptic function.
MESH HEADINGS: Animals
MESH HEADINGS: Blotting, Western
MESH HEADINGS: Calcium-Calmodulin-Dependent Protein Kinase Type 2/*metabolism
MESH HEADINGS: Cell Line
MESH HEADINGS: Cysteine Proteinase Inhibitors/pharmacology
MESH HEADINGS: DNA, Complementary/biosynthesis/genetics
MESH HEADINGS: Fluorescent Antibody Technique
MESH HEADINGS: Humans
MESH HEADINGS: Immunoprecipitation
MESH HEADINGS: Leupeptins/pharmacology
MESH HEADINGS: Mice
MESH HEADINGS: Microscopy, Confocal
MESH HEADINGS: Muscle Cells/physiology
MESH HEADINGS: Muscle Fibers, Skeletal/metabolism
MESH HEADINGS: Mutagenesis, Site-Directed
MESH HEADINGS: Patch-Clamp Techniques
MESH HEADINGS: Plasmids/genetics
MESH HEADINGS: RNA, Small Interfering/pharmacology
MESH HEADINGS: Real-Time Polymerase Chain Reaction
MESH HEADINGS: Receptors, Nicotinic/genetics/metabolism/*physiology
MESH HEADINGS: Transfection eng

931. Moussaoui, Yacine; Tuduri, Ludovic; Kerchich, Yacine; Meklati, B Y; Eppe, Gauthier, and Moussaoui, Yacine. Atmospheric Concentrations of Pcdd/Fs, Dl-Pcbs and Some Pesticides in Northern Algeria Using Passive Air Sampling. 2012 Jul; 88, (3): 270-277.


Rec #: 42679
Keywords: FATE
Notes: Chemical of Concern: CPY
Abstract: Abstract: Two monitoring campaigns were conducted in northern Algeria to assess the contamination level of pesticides and persistent organic pollutants (POPs) in ambient air. Six pesticides ( alpha - and gamma -hexachlorocyclohexane, fenitrothion, malathion, chlorpyrifos and lambda -cyhalothrin) were monitored at two different sampling locations during the first campaign. The passive sampling was performed at a semi urban/industrial site but also in a rural area between July to September 2008. The pesticides levels, analyzed by GC/MS/MS, ranged from 16pgm-3 to 11ngm-3. The second campaign was carried out from May to November 2009. The polychlorodibenzo-p-dioxins, dibenzofurans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (dl-PCBs) concentrations were evaluated at an urban/industrial and at an industrial site. The PCDD/Fs and dl-PCBs, analyzed by HRGC/HRMS, ranged from 249 to 923fg TEQ m-3. In addition to passive sampling, active sampling using an isokinetic sampler was also performed at an industrial waste incinerator. The PCDD/Fs and dl-PCBs found was 268pg TEQ m-3. This paper presents the first measurements of PCDD/Fs, dl-PCBs and pesticides in rural, urban and industrial areas of northern Algeria.
Keywords: Contamination
Keywords: Dioxins
Keywords: Malathion
Keywords: Industrial wastes
Keywords: Agricultural Chemicals
Keywords: M2 551.510.42:Air Pollution (551.510.42)
Keywords: Pollutants
Keywords: Environment Abstracts; Meteorological & Geoastrophysical Abstracts; Aqualine Abstracts; Water Resources Abstracts; Pollution Abstracts
Keywords: Industrial Wastes
Keywords: Air sampling
Keywords: Sampling
Keywords: PCDD
Keywords: Atmospheric pollution
Keywords: SW 3050:Ultimate disposal of wastes
Keywords: persistent organic pollutants
Keywords: P 0000:AIR POLLUTION
Keywords: Samplers
Keywords: Chlorpyrifos
Keywords: AQ 00007:Industrial Effluents
Keywords: Pesticides
Keywords: Incinerators
Keywords: Persistent organic pollutants
Keywords: Monitoring
Keywords: Algeria
Keywords: ENA 01:Air Pollution
Keywords: Rural areas
Date revised - 2012-05-01
Language of summary - English
Location - Algeria
Pages - 270-277
ProQuest ID - 1017977408
SubjectsTermNotLitGenreText - Atmospheric pollution; Rural areas; Chlorpyrifos; Industrial wastes; persistent organic pollutants; Pesticides; Air sampling; Persistent organic pollutants; Incinerators; Dioxins; Malathion; PCDD; Agricultural Chemicals; Contamination; Pollutants; Industrial Wastes; Sampling; Monitoring; Samplers; Algeria
Last updated - 2012-09-10
British nursing index edition - Chemosphere [Chemosphere]. Vol. 88, no. 3, pp. 270-277. Jul 2012.
Corporate institution author - Moussaoui, Yacine; Tuduri, Ludovic; Kerchich, Yacine; Meklati, B Y; Eppe, Gauthier
DOI - 7bdd568a-4484-4597-b497csamfg201; 16730500; 0045-6535 English

932. Mu, Yusong and Carroll, Mark J. Thatch and Soil Pesticide Degradation and Microbial Activity as Influenced by Turf Cultivation Practices. 2009: (UMI# 1465512 ).


Rec #: 51809
Keywords: FATE
Notes: Chemical of Concern: CPY
Abstract: Abstract: Pesticide degradation in turf is complicated by presence of an organic matter enriched layer called thatch. It is not well understood how the extensive pesticide sorption capacity of thatch may affect the aerobic degradation of pesticides in thatch. Hollow tine cultivation and vertical mowing are two commonly used cultivation practices used to control thatch.
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