Appendix 2-5: Rejected ecotox bibliography for Chlorpyrifos



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We utilized a bitransgenic mouse lung tumor model that expressed the human Ki-ras(G12C) allele in a tetracycline-inducible, lung-specific manner. Treatment for 12 months with 500 microg/ml of doxycycline (DOX) allowed for maximal expression of the human Ki-ras(G12C) allele in the lung, and resulted in the development of focal hyperplasia and adenomas. We determined if different levels of mutant RAS expression would influence the phenotype of the lung lesions. Treatment with 25, 100 and 500 microg/ml of DOX resulted in dose-dependent increases in transgene expression and tumor multiplicity. Microscopic analysis of the lungs of mice treated with the 25 microg/ml dose of DOX revealed infrequent foci of hyperplasia, whereas mice treated with the 100 and 500 microg/ml doses exhibited numerous hyperplastic foci and also adenomas. Immunohistochemical and RNA analysis of the downstream effector pathways demonstrated that different levels of mutant RAS transgene expression resulted in differences in the expression and/or phosphorylation of specific signaling molecules. Our results suggest that the molecular alterations driving tumorigenesis may differ at different levels of mutant Ki-ras(G12C) expression, and this should be taken into consideration when inducible transgene systems are utilized to promote tumorigenesis in mouse models.
MESH HEADINGS: Animals
MESH HEADINGS: Anti-Bacterial Agents/pharmacology
MESH HEADINGS: Dose-Response Relationship, Drug
MESH HEADINGS: Doxycycline/pharmacology
MESH HEADINGS: Gene Dosage/*physiology
MESH HEADINGS: Genes, ras/*genetics
MESH HEADINGS: Immunohistochemistry
MESH HEADINGS: Lung Neoplasms/*chemically induced/*genetics
MESH HEADINGS: Mice
MESH HEADINGS: Phenotype
MESH HEADINGS: RNA, Messenger/biosynthesis/genetics
MESH HEADINGS: Reverse Transcriptase Polymerase Chain Reaction
MESH HEADINGS: Signal Transduction/*drug effects
MESH HEADINGS: Transgenes/drug effects eng

282. Dang, Z.; Cheng, Y.; Chen, H. M.; Cui, Y.; Yin, H. H.; Traas, T.; Montforts, M., and Vermeire, T. Evaluation of the Daphnia magna Reproduction Test for Detecting Endocrine Disruptors. 2012; 88, 514-523.


Rec #: 2290
Keywords: REFS CHECKED,REVIEW
Call Number: NO REFS CHECKED (ATZ,BFT,CPY,DCA,DCF,DZ,ESS,FRM,FYC,OXT,PCP,PCZ,PPCP,PPCP2011,STRP,SZ,TBF,TDF,TFR,TTC,VCZ), NO REVIEW (ATZ,BFT,CPY,DCA,DCF,DZ,ESS,FRM,FYC,OXT,PCP,PCZ,PPCP,PPCP2011,STRP,SZ,TBF,TDF,TFR,TTC,VCZ)
Notes: Chemical of Concern: 24DC,ACY,ATZ,BFT,BPA,CHD,CPY,DBNPA,DCA,DCF,DES,DHD,DZ,EED,EPRN,ESS,FRM,FXT,FYC,HDP,IBP,KTZ,MRX,OXT,PCP,PCZ,PHTH,PPCP,PPCP2011,PRN,PYX,SRL,STRP,SZ,TBF,TDF,TFR,TTC,VCZ

283. Danis, T. G.; Karagiozoglou, D. T.; Tsakiris, I. N.; Alegakis, A. K., and Tsatsakis, A. M. Evaluation of pesticides residues in Greek peaches during 2002-2007 after the implementation of integrated crop management. 2011; 126, (1): 97-103.


Rec #: 58699
Keywords: FOOD
Notes: Chemical of Concern: CPY
Abstract: Abstract: The incidence and levels of pesticide residues in peaches grown using Integrated Crop Management (ICM) methods in Pella and Imathia, districts of Macedonia, Northern Greece, are hereby presented. A total of 1150 peach samples were collected pre-harvest (June-September) and were analysed during the period of 2002-2007. Residual levels of selected insecticides, fungicides and acaricides were determined by Gas Chromatography-Mass Spectrometry following solid phase extraction. The monitoring program is extended up to 31 pesticides. Twenty-two of them were measured above detection limit, and 8 of them were found present every year. Insecticides represent the highest incidence amongst pesticide categories (654 positive samples, 56.9%) while chlorpyrifos is the most frequent within the category (491 positive samples). The incidence of pyrethrins was the highest in 2007 (26.8%) while bifenthrin was detected most frequently within this category (67 positive samples in 2007). Traceable levels of pesticides were lower than the Maximum Residues Limits (MRLs) in all peach samples. Variances in incidence and levels of pesticides are attributed to some extent to the weather conditions as well as due to abidance by the guidelines of agronomists during blowing and harvest period. Monitoring in agricultural products could be employed as the first step in a chain of biomonitoring studies in humans, and may also be proven to be a good and ample indicator of exposure. (C) 2010 Elsevier Ltd. All rights reserved.
Keywords: Monitoring, Pesticide residues, Peach, Integrated crop management
ISI Document Delivery No.: 715BJ

284. Danner, R.; Chaudhari, S. N.; Rosenberger, J.; Surls, J.; Richie, T. L.; Brumeanu, T. D., and Casares, S. Expression of Hla Class Ii Molecules in Humanized Nod.rag1ko.il2rgcko Mice Is Critical for Development and Function of Human T and B Cells.


Rec #: 50189
Keywords: HUMAN HEALTH
Notes: Chemical of Concern: CPY
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ABSTRACT: BACKGROUND: Humanized mice able to reconstitute a surrogate human immune system (HIS) can be used for studies on human immunology and may provide a predictive preclinical model for human vaccines prior to clinical trials. However, current humanized mouse models show sub-optimal human T cell reconstitution and limited ability to support immunoglobulin class switching by human B cells. This limitation has been attributed to the lack of expression of Human Leukocyte Antigens (HLA) molecules in mouse lymphoid organs. Recently, humanized mice expressing HLA class I molecules have been generated but showed little improvement in human T cell reconstitution and function of T and B cells.
ABSTRACT: METHODS: We have generated NOD.Rag1KO.IL2RγcKO mice expressing HLA class II (HLA-DR4) molecules under the I-E(d) promoter that were infused as adults with HLA-DR-matched human hematopoietic stem cells (HSC). Littermates lacking expression of HLA-DR4 molecules were used as control.
ABSTRACT: RESULTS: HSC-infused HLA-DR4.NOD.Rag1KO.IL-2RγcKO mice developed a very high reconstitution rate (>90%) with long-lived and functional human T and B cells. Unlike previous humanized mouse models reported in the literature and our control mice, the HLA-DR4 expressing mice reconstituted serum levels (natural antibodies) of human IgM, IgG (all four subclasses), IgA, and IgE comparable to humans, and elicited high titers of specific human IgG antibodies upon tetanus toxoid vaccination.
ABSTRACT: CONCLUSIONS: Our study demonstrates the critical role of HLA class II molecules for development of functional human T cells able to support immunoglobulin class switching and efficiently respond to vaccination.
MESH HEADINGS: Animals
MESH HEADINGS: B-Lymphocytes/cytology/*immunology
MESH HEADINGS: CD8-Positive T-Lymphocytes/cytology/immunology
MESH HEADINGS: Hematopoietic Stem Cells/cytology/metabolism
MESH HEADINGS: Histocompatibility Antigens Class II/*immunology
MESH HEADINGS: Homeodomain Proteins/*metabolism
MESH HEADINGS: Humans
MESH HEADINGS: Immunization
MESH HEADINGS: Immunoglobulin Class Switching
MESH HEADINGS: Immunoglobulins/blood
MESH HEADINGS: Interleukin Receptor Common gamma Subunit/*deficiency/metabolism
MESH HEADINGS: Killer Cells, Natural/cytology/immunology
MESH HEADINGS: Kinetics
MESH HEADINGS: Lymphoid Tissue/immunology
MESH HEADINGS: Mice
MESH HEADINGS: Mice, Inbred C57BL
MESH HEADINGS: Mice, Inbred NOD
MESH HEADINGS: Mice, Knockout
MESH HEADINGS: T-Lymphocytes/cytology/*immunology
MESH HEADINGS: T-Lymphocytes, Regulatory/cytology/immunology
MESH HEADINGS: Tetanus Toxin/immunology eng

285. Darko, G; Akoto, O, and Darko, G. Dietary Intake of Organophosphorus Pesticide Residues Through Vegetables From Kumasi, Ghana. 2008 Dec; 46, (12): 3703-3706.


Rec #: 45379
Keywords: FOOD
Notes: Chemical of Concern: CPY
Abstract: Abstract: Contamination and health risk hazards of organophosphorus pesticides residues in vegetables were studied. Ethyl-chlorpyrifos, observed at an average level of 0.211+/-0.010mgkg super(-) super(1) in 42% of tomato, 0.096+/-0.035mgkg super(-) super(1) in 10% of eggplant and 0.021+ /-0.013mgkg super(-) super(1) in 16% of pepper was below the 0.5mgkg super(-) super(1) MRL. Dichlorvos was the most frequently detected residue in all the samples analyzed. Levels of malathion in tomatoes (0.120+ /-0.101mgkg super(-) super(1)) and pepper (0.143+/-0.042mgkg super(-) super(1)) exceeded the MRL of 0.1mgkg super(-) super(1). Health risks were found to be associated with methyl-chlorpyrifos, ethyl-chlorpyrifos, and omethioate in tomatoes and methyl-chlorpyrifos, ethyl-chlorpyrifos, dichlorvos, monocrotophos and omethioate in eggplant. Routine monitoring of these pollutants in food items is required to prevent, control and reduce the pollution and to minimize health risks.
Keywords: Food And Food Industries
Keywords: Diets
Keywords: Ghana
Keywords: Pesticides (organophosphorus)
Keywords: Vegetables
Keywords: Pesticide residues
Keywords: Food
Keywords: dichlorvos
Keywords: monocrotophos
Keywords: X 24320:Food Additives & Contaminants
Keywords: Ingestion
Keywords: Food contamination
Keywords: P 6000:TOXICOLOGY AND HEALTH
Keywords: Dietary intake
Keywords: Malathion
Keywords: Lycopersicon esculentum
Keywords: Pollutants
Keywords: Pollution Abstracts; Toxicology Abstracts
Keywords: Pollution
Keywords: Dichlorvos
Date revised - 2012-09-01
Language of summary - English
Location - Ghana
Pages - 3703-3706
ProQuest ID - 289765653
SubjectsTermNotLitGenreText - Pesticides (organophosphorus); Vegetables; Pollutants; Food; monocrotophos; Food contamination; Dietary intake; Malathion; Pollution; Dichlorvos; Diets; Pesticide residues; dichlorvos; Ingestion; Lycopersicon esculentum; Ghana
Last updated - 2012-11-09
Corporate institution author - Darko, G; Akoto, O
DOI - OB-MD-0009022556; 8836332; 0278-6915 English

286. Das, P. C.; Cao, Y.; Rose, R. L.; Cherrington, N., and Hodgson, E. Enzyme Induction and Cytotoxicity in Human Hepatocytes by Chlorpyrifos and N,N-Diethyl-M-Toluamide (Deet).


Rec #: 79169
Keywords: HUMAN HEALTH
Notes: Chemical of Concern: CPY
Abstract: ABSTRACT: Xenobiotics, including drugs and environmental chemicals, can influence cytochrome P450 (CYP) levels by altering the transcription of CYP genes. To minimize potential drug-pesticide and pesticide-pesticide interactions it is important to evaluate the potential of pesticides to induce CYP isoforms and to cause cytotoxicity in humans. The present study was designed to examine chlorpyrifos and DEET mediated induction of CYP isoforms and also to characterize their potential cytotoxic effects on primary human hepatocytes. DEET significantly induced CYP3A4, CYP2B6, CYP2A6 and CYP1A2 mRNA expression while chlorpyrifos induced CYP1A1, CYP1A2 and CYP3A4 mRNA, and to a lesser extent, CYP1B1 and CYP2B6 mRNA in primary human hepatocytes. Chlorpyrifos and DEET also mediated the expression of CYP isoforms, particularly CYP3A4, CYP2B6 and CYP1A1, as shown by CYP3A4-specific protein expression, testosterone metabolism and CYP1Al-specific activity assays. DEET is a mild, while chlorpyrifos is a relatively potent, inducer of adenylate kinase and caspase-3/7, an indicator of apoptosis, while inducing 15-20% and 25-30% cell death, respectively. Therefore, DEET and chlorpyrifos mediated induction of CYP mRNA and functional CYP isoforms together with their cytotoxic potential in human hepatocytes suggests that exposure to chlorpyrifos and/or DEET should be considered in human health impact analysis.
MESH HEADINGS: Adenylate Kinase/metabolism
MESH HEADINGS: Caspase 3/metabolism
MESH HEADINGS: Caspase 7/metabolism
MESH HEADINGS: Cell Death/drug effects
MESH HEADINGS: Cells, Cultured
MESH HEADINGS: Chlorpyrifos/*toxicity
MESH HEADINGS: Cytochrome P-450 CYP1A1/metabolism
MESH HEADINGS: Cytochrome P-450 CYP3A/metabolism
MESH HEADINGS: Cytochrome P-450 Enzyme System/biosynthesis/genetics
MESH HEADINGS: DEET/*toxicity
MESH HEADINGS: Dose-Response Relationship, Drug
MESH HEADINGS: Enzyme Induction/drug effects
MESH HEADINGS: Gene Expression Regulation, Enzymologic/drug effects
MESH HEADINGS: Hepatocytes/*drug effects/enzymology
MESH HEADINGS: Humans
MESH HEADINGS: Insect Repellents/*toxicity
MESH HEADINGS: Insecticides/*toxicity
MESH HEADINGS: Isoenzymes/biosynthesis/genetics
MESH HEADINGS: RNA, Messenger/genetics
MESH HEADINGS: Tumor Cells, Cultured eng

287. Das, Yavuz Kursad; Kaya, Sezai, and Das, Yavuz Kursad. Organophosphorus Insecticide Residues in Honey Produced in Turkey. 2009 Sep; 83, (3): 378-383.


Rec #: 48339
Keywords: FOOD
Notes: Chemical of Concern: CPY
Abstract: Abstract: In this study, a number of 15 organophoshorus (OP) insecticides were investigated in 275 honey samples in 33 different cities of Turkey, using gas chromatography electron capture detector. The limit of determination values was detected between 0.25 and 9.55ngg super(-1). The correlation coefficients obtained from calibration curves of the OP standards were found to be between 0.992 and 0.999. No insecticide residue was detected in the samples analyzed. This result is highly significant because of its impacts on public health and food safety.
Keywords: Health & Safety Science Abstracts; Pollution Abstracts; Environment Abstracts; Environmental Engineering Abstracts; Toxicology Abstracts
Keywords: Organophosphorus compounds
Keywords: Residues
Keywords: Food
Keywords: Turkey
Keywords: Insecticide residues
Keywords: EE 10:General Environmental Engineering
Keywords: Food contamination
Keywords: P 6000:TOXICOLOGY AND HEALTH
Keywords: ENA 02:Toxicology & Environmental Safety
Keywords: Environmental Studies
Keywords: Public health
Keywords: Insecticides
Keywords: Gas chromatography
Keywords: X 24330:Agrochemicals
Keywords: H 4000:Food and Drugs
Keywords: Honey
Keywords: Urban areas
Date revised - 2010-02-01
Language of summary - English
Location - Turkey
Pages - 378-383
ProQuest ID - 809525063
SubjectsTermNotLitGenreText - Insecticides; Gas chromatography; Food; Honey; Public health; Organophosphorus compounds; Residues; Insecticide residues; Food contamination; Urban areas; Turkey
Last updated - 2011-10-25
Corporate institution author - Das, Yavuz Kursad; Kaya, Sezai
DOI - OB-MD-0010969011; 11767831; 0007-4861; 1432-0800 English

288. Dasgupta, S.; Banerjee, K.; Dhumal, K. N., and Adsule, P. G. Optimization of Detection Conditions and Single-Laboratory Validation of a Multiresidue Method for the Determination of 135 Pesticides and 25 Organic Pollutants in Grapes and Wine by Gas Chromatography Time-of-Flight Mass Spectrometry. 2011; 94, (1): 273-285.


Rec #: 58739
Keywords: FOOD
Notes: Chemical of Concern: CPY
Abstract: Abstract: This paper describes single-laboratory validation of a multiresidue method for the determination of 135 pesticides, 12 dioxin-like polychlorinated biphenyls, 12 polyaromatic hydrocarbons, and bisphenol A in grapes and wine by GC/time-of-flight MS in a total run time of 48 min. The method is based on extraction with ethyl acetate in a sample-to-solvent ratio of 1:1, followed by selective dispersive SPE cleanup for grapes and wine. The GC/MS conditions were optimized for the chromatographic separation and to achieve highest S/N for all 160 target analytes, including the temperature-sensitive compounds, like captan and captafol, that are prone to degradation during analysis. An average recovery of 80-120% with RSD <10% could be attained for all analytes except 17, for which the average recoveries were 70-80%. LOQ ranged within 10-50 ng/g, with <25% expanded uncertainties, for 155 compounds in grapes and 151 in wine. In the incurred grape and wine samples, the residues of buprofezin, chlorpyriphos, metalaxyl, and myclobutanil were detected, with an RSD of <5% (n = 6); the results were statistically similar to previously reported validated methods.
ISI Document Delivery No.: 719QA

289. Dasgupta, Soma; Banerjee, Kaushik; Patil, Sangram H; Ghaste, Manoj; Dhumal, K N; Adsule, Pandurang G, and Dasgupta, Soma. Optimization of Two-Dimensional Gas Chromatography Time-of-Flight Mass Spectrometry for Separation and Estimation of the Residues of 160 Pesticides and 25 Persistent Organic Pollutants in Grape and Wine. 2010 Jun 11; 1217, (24): 3881-3889.


Rec #: 47879
Keywords: CHEM METHODS
Notes: Chemical of Concern: CPY
Abstract: Abstract: Two-dimensional gas chromatography (GC x GC) coupled with time-of-flight mass spectrometric (TOFMS) method was optimized for simultaneous analysis of 160 pesticides, 12 dioxin-like polychlorinated biphenyls (PCBs), 12 polyaromatic hydrocarbons (PAHs) and bisphenol A in grape and wine. GC x GC-TOFMS could separate all the 185 analytes within 38 min with >85% NIST library-based mass spectral confirmations. The matrix effect quantified as the ratio of the slope of matrix-matched to solvent calibrations was within 0.5-1.5 for most analytes. LOQ of most of the analytes was <=10 mu g/L with nine exceptions having LOQs of 12.5-25 mu g/L. Recoveries ranged between 70 and 120% with <20% expanded uncertainties for 151 and 148 compounds in grape and wine, respectively, with intra-laboratory Horwitz ratio <0.2 for all analytes. The method was evaluated in the incurred grape samples where residues of cypermethrin, permethrin, chlorpyriphos, metalaxyl and etophenprox were detected at below MRL.
Keywords: polyaromatic hydrocarbons
Keywords: Cypermethrin
Keywords: Solvents
Keywords: X 24320:Food Additives & Contaminants
Keywords: Permethrin
Keywords: Toxicology Abstracts; Pollution Abstracts
Keywords: Mass spectroscopy
Keywords: Bisphenol A
Keywords: Metalaxyl
Keywords: polychlorinated biphenyls
Keywords: Pollutants
Keywords: Gas chromatography
Keywords: Pesticides
Keywords: Vitaceae
Keywords: PCB
Keywords: Wine
Date revised - 2010-07-01
Language of summary - English
Pages - 3881-3889
ProQuest ID - 744626807
SubjectsTermNotLitGenreText - polyaromatic hydrocarbons; Cypermethrin; Solvents; Permethrin; Mass spectroscopy; Bisphenol A; polychlorinated biphenyls; Metalaxyl; Pollutants; Gas chromatography; Pesticides; PCB; Wine; Vitaceae
Last updated - 2011-12-14
British nursing index edition - Journal of Chromatography A [J. Chromatogr.]. Vol. 1217, no. 24, pp. 3881-3889. 11 Jun 2010.
Corporate institution author - Dasgupta, Soma; Banerjee, Kaushik; Patil, Sangram H; Ghaste, Manoj; Dhumal, K N; Adsule, Pandurang G
DOI - 209947ea-4f79-4cb6-9dffcsamfg201; 13139516; 0021-9673 English

290. Davidson, A. L.; Dassa, E.; Orelle, C., and Chen, J. Structure, Function, and Evolution of Bacterial Atp-Binding Cassette Systems.


Rec #: 51229
Keywords: HUMAN HEALTH
Notes: Chemical of Concern: CPY
Abstract:
ABSTRACT: SUMMARY: ATP-binding cassette (ABC) systems are universally distributed among living organisms and function in many different aspects of bacterial physiology. ABC transporters are best known for their role in the import of essential nutrients and the export of toxic molecules, but they can also mediate the transport of many other physiological substrates. In a classical transport reaction, two highly conserved ATP-binding domains or subunits couple the binding/hydrolysis of ATP to the translocation of particular substrates across the membrane, through interactions with membrane-spanning domains of the transporter. Variations on this basic theme involve soluble ABC ATP-binding proteins that couple ATP hydrolysis to nontransport processes, such as DNA repair and gene expression regulation. Insights into the structure, function, and mechanism of action of bacterial ABC proteins are reported, based on phylogenetic comparisons as well as classic biochemical and genetic approaches. The availability of an increasing number of high-resolution structures has provided a valuable framework for interpretation of recent studies, and realistic models have been proposed to explain how these fascinating molecular machines use complex dynamic processes to fulfill their numerous biological functions. These advances are also important for elucidating the mechanism of action of eukaryotic ABC proteins, because functional defects in many of them are responsible for severe human inherited diseases.
MESH HEADINGS: ATP-Binding Cassette Transporters/genetics/metabolism/*physiology
MESH HEADINGS: Adenosine Triphosphate/metabolism
MESH HEADINGS: Amino Acid Motifs
MESH HEADINGS: Amino Acid Sequence
MESH HEADINGS: Biological Transport
MESH HEADINGS: Evolution, Molecular
MESH HEADINGS: Gram-Negative Bacteria/genetics/metabolism/*physiology
MESH HEADINGS: Models, Molecular
MESH HEADINGS: Phylogeny
MESH HEADINGS: Protein Structure, Secondary
MESH HEADINGS: Sequence Alignment eng

291. Davidson, C.; Stanley, K., and Simonich, S. M. Contaminant residues and declines of the Cascades frog (Rana cascadae) in the California Cascades, USA. 2012; 31, (8): 1895-1902.


Rec #: 58769
Keywords: SURVEY
Notes: Chemical of Concern: CPY
Abstract: Abstract: Populations of Cascades frogs (Rana cascadae) have declined precipitously in the Mount Lassen area, but remain abundant in the other half of their California range in the Klamath Mountains. To evaluate the role of contaminants in Cascade frog declines, we sampled sediment and
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