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1.
Cancer Epidemiol ; 85: 102410, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37413804

RESUMO

BACKGROUND: In the United States (US), the average annual increase in the incidence of prostate cancer (PCa) has been 0.5% between 2013 and 2017. Although some modifiable factors have been identified as the risk factors for PCa, the effect of lower ratio of omega-6 to omega-3 fatty acids intake (N-6/N-3) remains unknown. Previous studies of the Agricultural Health Study (AHS) reported a significant positive association between PCa and selected organophosphate pesticides (OPs) including terbufos and fonofos. OBJECTIVE: The aim of this study was to evaluate the association between N-6/N-3 and PCa and any interaction between N-6/N-3 and 2 selected OPs (i.e., terbufos and fonofos) exposure. DESIGN AND PARTICIPANTS: This case-control study, nested within a prospective cohort study, was conducted on a subgroup of the AHS population (1193 PCa cases and 14,872 controls) who returned their dietary questionnaire between 1999 and 2003 MAIN OUTCOME MEASURES: PCa was coded based on the International Classification of Diseases of Oncology (ICD-O-3) definitions and obtained from the statewide cancer registries of Iowa (2003-2017) and North Carolina (2003-2014). STATISTICAL ANALYSIS: Multivariate logistic regression analysis was applied to obtain the odds ratios adjusted (aORs) for age at dietary assessment (years), race/ethnicity (white, African American, other), physical activity (hours/week), smoking (yes/no), terbufos (yes/no), fonofos (yes/no), diabetes, lycopene intake (milligrams/day), family history of PCa, and the interaction of N-6/N-3 with age, terbufos and fonofos. Pesticide exposure was assessed by self-administrated questionnaires collecting data on ever/never use of mentioned pesticides during lifetime as a yes/no variable. Assessing the P value for the interaction between pesticides and N-6/N-3, we used the continuous variable of "intensity adjusted cumulative exposure" to terbufos and fonofos. This exposure score was based on duration, intensity and frequency of exposure. We also conducted a stratified regression analysis by quartiles of age. RESULTS: Relative to the highest N-6/N-3 quartile, the lowest quartile was significantly associated with a decreased risk of PCa (aOR=0.61, 95% CI: 0.41-0.90), and quartile-specific aORs decreased toward the lowest quartile (Ptrend=<0.01). Based on the age-stratified analysis, the protective effect was only significant for the lowest quartile of N-6/N-3 among those aged between 48 and 55 years old (aORs=0.97, 95% CI, 0.45-0.55). Among those who were exposed to terbufos (ever exposure reported as yes in the self-report questionnaires), lower quartiles of N-6/N-3 were protective albeit nonsignificant (aORs: 0.86, 0.92, 0.91 in quartiles 1,2, and 3, respectively). No meaningful findings were observed for fonofos and N-6/N-3 interaction. CONCLUSION: Findings showed that lower N-6/N-3 may decrease risk of PCa among farmers. However, no significant interaction was found between selected organophosphate pesticides and N-6/N-3.


Assuntos
Inseticidas , Exposição Ocupacional , Praguicidas , Neoplasias da Próstata , Masculino , Humanos , Pessoa de Meia-Idade , Fonofos , Estudos Prospectivos , Estudos de Casos e Controles , Praguicidas/efeitos adversos , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/prevenção & controle , Compostos Organofosforados , Inquéritos e Questionários , Organofosfatos , North Carolina/epidemiologia , Iowa/epidemiologia , Exposição Ocupacional/efeitos adversos
2.
Chemosphere ; 325: 138403, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36921778

RESUMO

The enzyme-catalyzed metabolic biotransformation of xenobiotics plays a significant role in toxicology evolution and subsequently environmental health risk assessment. Recent studies noted that the phase I human flavin-dependent monooxygenase (e.g., FMO3) can catalyze xenobiotics into more toxic metabolites. However, details of the metabolic mechanisms are insufficient. To fill the mechanism in the gaps, the systemic density functional theory calculations were performed to elucidate diverse FMO-catalyzed oxidation reactions toward environmental pollutants, including denitrification (e.g., nitrophenol), N-oxidation (e.g., nicotine), desulfurization (e.g., fonofos), and dehalogenation (e.g., pentachlorophenol). Similar to the active center compound 0 of cytochrome P450, FMO mainly catalyzed reactions with the structure of the tricyclic isoalloxazine C-4a-hydroperoxide (FADHOOH). As will be shown, FMO-catalyzed pathways are more favorable with a concerted than stepwise mechanism; Deprotonation is necessary to initiate the oxidation reactions for phenolic substrates; The regioselectivity of nicotine by FMO prefers the N-oxidation other than N-demethylation pathway; Formation of the P-S-O triangle ring is the key step for desulfurization of fonofos by FMO. We envision that these fundamental mechanisms catalyzed by FMO with a computational method can be extended to other xenobiotics of similar structures, which may aid the high-throughput screening and provide theoretical predictions in the future.


Assuntos
Nicotina , Oxigenases , Humanos , Oxigenases/metabolismo , Fonofos/metabolismo , Xenobióticos/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Biotransformação , Flavinas/metabolismo , Microssomos Hepáticos/metabolismo
3.
J Food Prot ; 81(7): 1087-1092, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29897273

RESUMO

We developed an innovative approach that couples headspace solid-phase microextraction (SPME) with surface-enhanced Raman spectroscopy (SERS) to detect a volatile pesticide (i.e., fonofos) in a liquid complex matrix (i.e., apple juice). A gold nanoparticles-coated fiber was fabricated by reducing gold(III) on a chemically etched stainless steel wire to extract pesticide, using SPME. The fabricated fibers were then tested by a headspace-SPME method and a dip-SPME method, followed by SERS detection of fonofos in water and apple juice samples. Using the headspace-SPME method, we can detect as low as 5 ppb of fonofos in water and apple juice, compared with the dip-SPME method, which cannot detect lower than 10 ppb in water and 50 ppb in apple juice. This study demonstrated the potential capability of the headspace-SPME-SERS method for rapid (within 30 min) and sensitive detection of volatile and vaporizable compounds in complex matrices. The developed method could be a potential alternative approach to the gas chromatography method. Future work is needed to optimize the fiber by minimizing signal variation, and it should be tested in a variety of targeted compounds and matrices.


Assuntos
Fonofos/análise , Sucos de Frutas e Vegetais/análise , Malus , Praguicidas , Fonofos/isolamento & purificação , Ouro , Malus/química , Nanopartículas Metálicas , Praguicidas/análise , Praguicidas/isolamento & purificação , Microextração em Fase Sólida/métodos , Análise Espectral Raman/métodos
4.
Arch Environ Contam Toxicol ; 63(4): 471-83, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22903630

RESUMO

Applications of pesticides in areas of agricultural production have been an environmental concern for the past several decades. Varying-sized watersheds draining regions of intense agriculture in the Maritime Provinces of Canada were monitored between 2003 and 2007 to determine the major in-use pesticides and to gain an understanding of the risks posed to aquatic ecosystems. A questionnaire collected from farmers in one watershed intensively cropped with potato indicated that 43 pesticides were applied with 18 of them being detected in that watershed. Our results across the Maritime region suggested that detection frequencies ranged from 0.0 to 22 % during the study period. Chlorothalonil, linuron, metalaxyl, and metribuzin were detected in 17-22 % of samples collected during rainfall events every year. Other pesticides, such as azinphos-methyl, atrazine, cypermethrin, permethrin, fonofos, and ß-endosulfan were detected in ≤17 % of the samples during some years of the study. Concentrations of several pesticides were found to exceed their Canadian Council of Ministers of the Environment (CCME) aquatic life water-quality guidelines in pulses after rain events. The highest proportion of detections exceeding a CCME guideline was for chlorothalonil at 12.9 %, ß-endosulfan at 6.0 %, and linuron at 3.4 %. Despite indications that remedial measures offer protection to aquatic environments, spatial and temporal gaps in the data prevented a full evaluation. A dedicated long-term multiple-watershed monitoring program for this region of Canada is therefore recommended.


Assuntos
Agricultura , Monitoramento Ambiental/métodos , Praguicidas/análise , Poluentes Químicos da Água/análise , Atrazina/análise , Azinfos-Metil/análise , Canadá , Endossulfano/análise , Fonofos/análise , Permetrina/análise , Piretrinas/análise , Chuva/química , Rios/química
5.
Environ Health Perspect ; 119(12): 1726-32, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21810555

RESUMO

BACKGROUND: Previous research indicates increased prostate cancer risk for pesticide applicators and pesticide manufacturing workers. Although underlying mechanisms are unknown, evidence suggests a role of oxidative DNA damage. OBJECTIVES: Because base excision repair (BER) is the predominant pathway involved in repairing oxidative damage, we evaluated interactions between 39 pesticides and 394 tag single-nucleotide polymorphisms (SNPs) for 31 BER genes among 776 prostate cancer cases and 1,444 male controls in a nested case-control study of white Agricultural Health Study (AHS) pesticide applicators. METHODS: We used likelihood ratio tests from logistic regression models to determine p-values for interactions between three-level pesticide exposure variables (none/low/high) and SNPs (assuming a dominant model), and the false discovery rate (FDR) multiple comparison adjustment approach. RESULTS: The interaction between fonofos and rs1983132 in NEIL3 [nei endonuclease VIII-like 3 (Escherichia coli)], which encodes a glycosylase that can initiate BER, was the most significant overall [interaction p-value (pinteract) = 9.3 × 10-6; FDR-adjusted p-value = 0.01]. Fonofos exposure was associated with a monotonic increase in prostate cancer risk among men with CT/TT genotypes for rs1983132 [odds ratios (95% confidence intervals) for low and high use compared with no use were 1.65 (0.91, 3.01) and 3.25 (1.78, 5.92), respectively], whereas fonofos was not associated with prostate cancer risk among men with the CC genotype. Carbofuran and S-ethyl dipropylthiocarbamate (EPTC) interacted similarly with rs1983132; however, these interactions did not meet an FDR < 0.2. CONCLUSIONS: Our significant finding regarding fonofos is consistent with previous AHS findings of increased prostate cancer risk with fonofos exposure among those with a family history of prostate cancer. Although requiring replication, our findings suggest a role of BER genetic variation in pesticide-associated prostate cancer risk.


Assuntos
Reparo do DNA/genética , Fonofos/efeitos adversos , Variação Genética , Exposição Ocupacional/efeitos adversos , Praguicidas/efeitos adversos , Neoplasias da Próstata/induzido quimicamente , Neoplasias da Próstata/epidemiologia , Estudos de Casos e Controles , Genótipo , Humanos , Funções Verossimilhança , Modelos Logísticos , Masculino , N-Glicosil Hidrolases/genética , North Carolina/epidemiologia , Razão de Chances , Polimorfismo de Nucleotídeo Único/genética , Neoplasias da Próstata/genética , Medição de Risco
6.
Cancer Res ; 70(22): 9224-33, 2010 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-20978189

RESUMO

Genome-wide association studies have identified 8q24 region variants as risk factors for prostate cancer. In the Agricultural Health Study, a prospective study of licensed pesticide applicators, we observed increased prostate cancer risk with specific pesticide use among those with a family history of prostate cancer. Thus, we evaluated the interaction among pesticide use, 8q24 variants, and prostate cancer risk. The authors estimated odds ratios (OR) and 95% confidence intervals (95% CI) for interactions among 211 8q24 variants, 49 pesticides, and prostate cancer risk in 776 cases and 1,444 controls. The ORs for a previously identified variant, rs4242382, and prostate cancer increased significantly (P<0.05) with exposure to the organophosphate insecticide fonofos, after correction for multiple testing, with per allele ORnonexposed of 1.17 (95% CI, 0.93-1.48), per allele OR(low) of 1.30 (95% CI, 0.75-2.27), and per allele ORhigh of 4.46 (95% CI, 2.17-9.17; P-interaction=0.002, adjusted P-interaction=0.02). A similar effect modification was observed for three other organophosphate insecticides (coumaphos, terbufos, and phorate) and one pyrethroid insecticide (permethrin). Among ever users of fonofos, subjects with three or four risk alleles at rs7837328 and rs4242382 had approximately three times the risk of prostate cancer (OR, 3.14; 95% CI, 1.41-7.00) compared with subjects who had zero risk alleles and never used fonofos. We observed a significant interaction among variants on chromosome 8q24, pesticide use, and risk of prostate cancer. Insecticides, particularly organophosphates, were the strongest modifiers of risk, although the biological mechanism is unclear. This is the first report of effect modification between 8q24 and an environmental exposure on prostate cancer risk.


Assuntos
Cromossomos Humanos Par 8/genética , Doenças Profissionais/genética , Praguicidas/envenenamento , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/genética , Adulto , Idoso , Cumafos/envenenamento , Fonofos/envenenamento , Estudo de Associação Genômica Ampla , Humanos , Incidência , Iowa/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , North Carolina/epidemiologia , Doenças Profissionais/induzido quimicamente , Doenças Profissionais/epidemiologia , Razão de Chances , Compostos Organotiofosforados/envenenamento , Permetrina/envenenamento , Forato/envenenamento , Estudos Prospectivos , Neoplasias da Próstata/induzido quimicamente , Neoplasias da Próstata/epidemiologia , Medição de Risco , Fatores de Risco
7.
Environ Toxicol Chem ; 27(2): 452-60, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18348626

RESUMO

From 1994 to 1999 in the Lower Fraser Valley region of southwest Canada, fonofos (Dyfonate G) was recommended for control of introduced wireworm (Agriotes spp.) pests on potato and other root crops. As part of a wildlife-monitoring program, we collected 15 raptors, including 12 bald eagles (Haliaeetus leucocephalus), found dead or debilitated on or near agricultural lands with severely inhibited brain and/or plasma cholinesterase activity and fonofos residues in ingesta. Bird remains, in nine cases waterfowl, were identified in the ingesta samples. Another seven bald eagles had severe cholinesterase inhibition, but without evidence of fonofos residues. During two winters from 1996 to 1998, 420 ha of potato fields, half of which had been treated the previous spring with fonofos and the remainder untreated, were searched weekly for evidence of wildlife mortality. Search efficiency was assessed with placed duck carcasses. Waterfowl outnumbered other species in field-use counts and comprised the greatest proportion of birds found dead. We found 211 wildlife remains, most scavenged; 35 intact carcasses were suitable for postmortem examination and/or toxicology analyses. Cholinesterase activity was assayed in brains of 18 waterfowl, five of which had severely depressed activity (average inhibition 74%; range, 69-78%). The gastrointestinal tract of a mallard found in a field treated with granular product contained 49 microg/g fonofos residues, linking waterfowl mortality with labelled use of the product. These findings demonstrate the risk of both primary and secondary poisoning by anticholinesterase insecticides where wildlife make intensive use of farmed fields.


Assuntos
Anseriformes , Doenças das Aves/induzido quimicamente , Fonofos/envenenamento , Resíduos de Praguicidas/envenenamento , Aves Predatórias , Animais , Canadá , Colinesterases/sangue , Besouros/efeitos dos fármacos , Poluentes Ambientais/análise , Poluentes Ambientais/envenenamento , Feminino , Fonofos/análise , Conteúdo Gastrointestinal/química , Masculino
8.
Environ Toxicol Chem ; 26(9): 1949-54, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17705656

RESUMO

A large number of organophosphorous insecticides (OPs) are chiral compounds, and yet enantioselectivity in their environmental fate and effects is rarely addressed. In the present study, we isolated individual enantiomers of three OPs, profenofos, fonofos, and crotoxyphos, and evaluated enantioselectivity in their inhibition of acetylcholinesterase (AChE). Acetylcholinesterase inhibition by the enantiomers and racemates was determined in vivo in the aquatic invertebrate Daphnia magna and in Japanese medaka (Oryzias latipes) as well as in vitro with electric eel (Electrophorus electricus) and human recombinant AChEs. The overall results showed variable sensitivity between AChE enzymes from different species as well as variable magnitude of enantioselectivity in enzyme inhibition. The (-)-enantiomer of profenofos was 4.3- to 8.5-fold more inhibitory to AChE in vivo, whereas (-)-fonofos was 2.3- to 29-fold more potent than the corresponding (+)-enantiomer. The (+)-enantiomer of crotoxyphos was 1.1- to 11-fold more inhibitory to AChE than the (-)-enantiomer. In contrast, the in vitro results showed (+)-profenofos to be 2.6- to 71.8-fold more inhibitory than the (-)-enantiomer and (-)-crotoxyphos to be 1.6- to 1.9-fold more active than the (+)-enantiomer. The reversed direction of enantioselectivity observed between the in vivo and in vitro assays suggests enantioselectivity within toxicodynamic processes such as uptake, biotransformation, or elimination. Findings from the present study provide evidence of enantioselectivity in the AChE inhibition of chiral OPs in nontarget organisms and indicate the need to consider enantiomers individually when assessing environmental risk of these chiral pesticides.


Assuntos
Acetilcolinesterase/metabolismo , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Inseticidas/química , Inseticidas/farmacologia , Compostos Organotiofosforados/química , Compostos Organotiofosforados/farmacologia , Animais , Clorpirifos/química , Clorpirifos/farmacologia , Cromatografia Líquida de Alta Pressão , Fonofos , Estrutura Molecular , Compostos Organofosforados/química , Compostos Organofosforados/farmacologia , Organotiofosfatos/química , Organotiofosfatos/farmacologia , Oryzias/metabolismo , Estereoisomerismo
9.
Ecotoxicol Environ Saf ; 66(1): 65-73, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16324745

RESUMO

The acute toxicity of fonofos and phosphamidon on three age classes of Artemia salina was evaluated. An increase in toxicity of these organophosphorous (OP) insecticides was found following longer development of A. salina. The effects of pretreatment with the nonselective muscarinic antagonist atropine, the two reversible acetylcholinesterease inhibitors physostigmine and pyridostigmine, and the cholinesterase-reactivating oxime 2-pyridine aldoxime methoiodide (2-PAM), as individual and combined pretreatments, on OP-induced lethality in 24 h Artemia were also investigated. The lethal action of both OP insecticides was prevented by pretreatment of 24 h Artemia with atropine and 2-PAM, while physostigmine proved ineffective against intoxication with both OP insecticides and pyridostigmine exhibited a low synergic effect. In both cases, the inhibitory effects of combinations of atropine (10(-5)M) plus 2-PAM were greater than those elicited by either drug alone, with the maximum protection afforded being 100%. Combined pretreatment of atropine (10(-5)M) plus physostigmine practically abolished the lethal effects induced by both insecticides. Pretreatment with 2-PAM (10(-6)M) plus physostigmine afforded maximal protection of 100% and 76% on the lethality induced by fonofos and phosphamidon, respectively. The data obtained suggest that the combination of atropine plus 2-PAM or physostigmine and the combined pretreatment of 2-PAM plus physostigmine are effective in the prevention of the lethal effects induced by fonofos and phosphamidon in A. salina larvae.


Assuntos
Artemia/efeitos dos fármacos , Inibidores da Colinesterase/toxicidade , Fonofos/toxicidade , Inseticidas/toxicidade , Fosfamidona/toxicidade , Fatores Etários , Animais , Atropina/farmacologia , Carbamatos/farmacologia , Inibidores da Colinesterase/farmacologia , Reativadores da Colinesterase/farmacologia , Fonofos/antagonistas & inibidores , Inseticidas/antagonistas & inibidores , Larva/efeitos dos fármacos , Antagonistas Muscarínicos/farmacologia , Fosfamidona/antagonistas & inibidores , Compostos de Pralidoxima/farmacologia , Testes de Toxicidade
10.
Environ Health Perspect ; 114(12): 1838-42, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17185272

RESUMO

BACKGROUND: The Agricultural Health Study (AHS) is a prospective cohort study of licensed pesticide applicators from Iowa and North Carolina enrolled 1993-1997 and followed for incident cancer through 2002. A previous investigation in this cohort linked exposure to the organophosphate fonofos with incident prostate cancer in subjects with family history of prostate cancer. OBJECTIVES: This finding along with findings of associations between organophosphate pesticides and cancer more broadly led to this study of fonofos and risk of any cancers among 45,372 pesticide applicators enrolled in the AHS. METHODS: Pesticide exposure and other data were collected using self-administered questionnaires. Poisson regression was used to calculate rate ratios (RRs) and 95% confidence intervals (CIs) while controlling for potential confounders. RESULTS: Relative to the unexposed, leukemia risk was elevated in the highest category of lifetime (RR = 2.24; 95% CI, 0.94-5.34, Ptrend = 0.07) and intensity-weighted exposure-days (RR = 2.67; 95% CI, 1.06-6.70, Ptrend = 0.04), a measure that takes into account factors that modify pesticide exposure. Although prostate cancer risk was unrelated to fonofos use overall, among applicators with a family history of prostate cancer, we observed a significant dose-response trend for lifetime exposure-days (Ptrend = 0.02, RR highest tertile vs. unexposed = 1.77, 95% CI, 1.03-3.05; RRinteraction = 1.28, 95% CI, 1.07-1.54). Intensity-weighted results were similar. No associations were observed with other examined cancer sites. CONCLUSIONS: Further study is warranted to confirm findings with respect to leukemia and determine whether genetic susceptibility modifies prostate cancer risk from pesticide exposure.


Assuntos
Agricultura , Fonofos/envenenamento , Neoplasias/induzido quimicamente , Exposição Ocupacional/efeitos adversos , Adulto , Doenças dos Trabalhadores Agrícolas/induzido quimicamente , Doenças dos Trabalhadores Agrícolas/epidemiologia , Estudos de Coortes , Saúde da Família , Feminino , Fonofos/análise , Humanos , Incidência , Iowa/epidemiologia , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Neoplasias/genética , North Carolina/epidemiologia , Exposição Ocupacional/análise , Exposição Ocupacional/estatística & dados numéricos , Intoxicação por Organofosfatos , Compostos Organofosforados/análise , Compostos Organotiofosforados/análise , Compostos Organotiofosforados/envenenamento , Praguicidas/análise , Praguicidas/envenenamento , Distribuição de Poisson , Estudos Prospectivos , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/etiologia , Neoplasias da Próstata/genética , Análise de Regressão , Fatores de Risco , Inquéritos e Questionários
11.
Drug Metab Dispos ; 34(9): 1606-14, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16790556

RESUMO

Cytochromes P450 (P450s) are major catalysts in the metabolism of xenobiotics and endogenous substrates such as estradiol (E2). It has previously been shown that E2 is predominantly metabolized in humans by CYP1A2 and CYP3A4 with 2-hydroxyestradiol (2-OHE2) the major metabolite. This study examines effects of deployment-related and other chemicals on E2 metabolism by human liver microsomes (HLM) and individual P450 isoforms. Kinetic studies using HLM, CYP3A4, and CYP1A2 showed similar affinities (Km) for E2 with respect to 2-OHE2 production. Vmax and CLint values for HLM are 0.32 nmol/min/mg protein and 7.5 microl/min/mg protein; those for CYP3A4 are 6.9 nmol/min/nmol P450 and 291 microl/min/nmol P450; and those for CYP1A2 are 17.4 nmol/min/nmol P450 and 633 microl/min/nmol P450. Phenotyped HLM use showed that individuals with high levels of CYP1A2 and CYP3A4 have the greatest potential to metabolize E2. Preincubation of HLM with a variety of chemicals, including those used in military deployments, resulted in varying levels of inhibition of E2 metabolism. The greatest inhibition was observed with organophosphorus compounds, including chlorpyrifos and fonofos, with up to 80% inhibition for 2-OHE2 production. Carbaryl, a carbamate pesticide, and naphthalene, a jet fuel component, inhibited ca. 40% of E2 metabolism. Preincubation of CYP1A2 with chlorpyrifos, fonofos, carbaryl, or naphthalene resulted in 96, 59, 84, and 87% inhibition of E2 metabolism, respectively. Preincubation of CYP3A4 with chlorpyrifos, fonofos, deltamethrin, or permethrin resulted in 94, 87, 58, and 37% inhibition of E2 metabolism. Chlorpyrifos inhibition of E2 metabolism is shown to be irreversible.


Assuntos
Inibidores da Colinesterase/toxicidade , Inibidores do Citocromo P-450 CYP1A2 , Inibidores das Enzimas do Citocromo P-450 , Estradiol/análogos & derivados , Fígado/efeitos dos fármacos , Carbaril/toxicidade , Clorpirifos/toxicidade , Citocromo P-450 CYP1A2/genética , Citocromo P-450 CYP1A2/metabolismo , Citocromo P-450 CYP3A , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Relação Dose-Resposta a Droga , Estradiol/metabolismo , Feminino , Fonofos/toxicidade , Humanos , Técnicas In Vitro , Cinética , Fígado/enzimologia , Masculino , Microssomos Hepáticos , Medicina Militar , Proteínas Recombinantes/antagonistas & inibidores , Proteínas Recombinantes/metabolismo
12.
J Agric Food Chem ; 50(7): 1922-8, 2002 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-11902934

RESUMO

The metabolism of fonofos, a thiophosphonate insecticide, was investigated in mature lettuce (Latuca sativa), beet (Beta vulgaris), and wheat (Triticum aestivum). Six new metabolites were identified by LC-MS and LC-MS-MS analysis using fast atom bombardment (FAB) and packed capillary LC columns with application of the on-column focusing technique. These methods provided the sensitivity required to identify unknown metabolites that were present in the mature plants at only 20-230 ppb. Structural elucidation was facilitated by use of fonofos labeled with both carbon-14 and carbon-13 in the phenyl ring. In all three plants fonofos was converted to a glucose conjugate of thiophenoxylactic acid. Oxidation of the glucose conjugate gave isomeric sulfoxides in all species examined. Thiophenoxylactic acid was found esterified to malonic acid in lettuce. In beets, S-phenylcysteine was found as its malonic acid amide. A second metabolite unique to beets was N-(malonyl)-[2[(ethoxyethylphosphinothionyl)oxy]phenyl]cysteine. This novel structure was confirmed by synthesis.


Assuntos
Beta vulgaris/química , Fonofos/análise , Fonofos/metabolismo , Triticum/química , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Esterificação , Cromatografia Gasosa-Espectrometria de Massas , Glucose/metabolismo , Espectroscopia de Ressonância Magnética , Malonatos/metabolismo , Oxirredução , Sensibilidade e Especificidade , Espectrometria de Massas de Bombardeamento Rápido de Átomos
13.
Bioorg Med Chem ; 8(3): 653-6, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10732982

RESUMO

Molecular interaction between enantiomeric fonofos oxon (O-ethyl S-phenyl ethylphosphonothiolate) and acetylcholinesterase (AChE) of Torpedo californica was evaluated by using the Cerius2 program. It was suggested that the difference in the inhibitory activity of the two enantiomers of fonofos oxon on AChE is due to the steric hindrance in binding to the AChE active site.


Assuntos
Acetilcolinesterase/química , Acetilcolinesterase/metabolismo , Fonofos/análogos & derivados , Animais , Sítios de Ligação , Inibidores da Colinesterase/química , Inibidores da Colinesterase/metabolismo , Simulação por Computador , Fonofos/química , Fonofos/metabolismo , Ligantes , Modelos Moleculares , Ligação Proteica , Estrutura Terciária de Proteína , Estereoisomerismo , Relação Estrutura-Atividade , Torpedo
14.
Rosario; s.n; 2000. 74 p. tab, graf.
Tese em Espanhol | LILACS | ID: lil-278331

RESUMO

El objetivo de este estudio de tipo descriptivo y transversal fue observar los motivos de consulta a fonoaudiología, los diagnósticos fonoaudiológicos, los tipos de consulta fonoaudiológica y los agentes de derivación, en una población de pacientes de diversas edades que asistieron al consultorio de fonoaudiología del Instituto Médico Regional de la ciudad de Gálvez en el período comprendido entre enero de 1998 ydiciembre de 1999. Se trabajó con fuente secundaria de datos, historias clínicas de 99 pacientes confeccionadas por la fonoaudióloga a cargo del consultorio: 77 menores de 18 años y 22 de 18 años o más. El 77,8 por ciento de consultas fueron realizadas por pacientes menores de 18 años de edad. En este grupo etáreo las alteraciones en el habla son el motivo de consulta más frecuente (42,9 por ciento), mientras que en los pacientes de 18 años o más, las alteraciones de la voz son las que ocupan el primer lugar (72,7 por ciento). El diagnóstico fonoaudiológico, que presenta el mayor porcentaje en pacientes menores de 18 años es el de insuficiencia respiratoria nasal (35 por ciento) y en los de 18 añois o más, disfonía (72,8 por ciento). Se observó que en el grupo de pacientes menores de 18 años el 50,6 por ciento consulta en forma derivada y en el de 18 años o más, el 68,2 por cientolo hace de igual manera. El pediatra es el agente de derivación que ocupa el primer lugar entre aquellos pacientes menores de 18 años (41,0 por ciento), mientras que en pacientes de 18 años o más es el otorrinolaringólogo el que ocupa dicho lugar (73,3 por ciento)


Assuntos
Humanos , Adulto , Fonofos , Transtornos da Articulação/diagnóstico , Transtornos da Articulação/epidemiologia , Epidemiologia Descritiva
15.
Rosario; s.n; 2000. 74 p. tab, graf. (53977).
Tese em Espanhol | BINACIS | ID: bin-53977

RESUMO

El objetivo de este estudio de tipo descriptivo y transversal fue observar los motivos de consulta a fonoaudiología, los diagnósticos fonoaudiológicos, los tipos de consulta fonoaudiológica y los agentes de derivación, en una población de pacientes de diversas edades que asistieron al consultorio de fonoaudiología del Instituto Médico Regional de la ciudad de Gálvez en el período comprendido entre enero de 1998 ydiciembre de 1999. Se trabajó con fuente secundaria de datos, historias clínicas de 99 pacientes confeccionadas por la fonoaudióloga a cargo del consultorio: 77 menores de 18 años y 22 de 18 años o más. El 77,8 por ciento de consultas fueron realizadas por pacientes menores de 18 años de edad. En este grupo etáreo las alteraciones en el habla son el motivo de consulta más frecuente (42,9 por ciento), mientras que en los pacientes de 18 años o más, las alteraciones de la voz son las que ocupan el primer lugar (72,7 por ciento). El diagnóstico fonoaudiológico, que presenta el mayor porcentaje en pacientes menores de 18 años es el de insuficiencia respiratoria nasal (35 por ciento) y en los de 18 añois o más, disfonía (72,8 por ciento). Se observó que en el grupo de pacientes menores de 18 años el 50,6 por ciento consulta en forma derivada y en el de 18 años o más, el 68,2 por cientolo hace de igual manera. El pediatra es el agente de derivación que ocupa el primer lugar entre aquellos pacientes menores de 18 años (41,0 por ciento), mientras que en pacientes de 18 años o más es el otorrinolaringólogo el que ocupa dicho lugar (73,3 por ciento)(AU)


Assuntos
Humanos , Adulto , Fonofos , Transtornos da Articulação/diagnóstico , Transtornos da Articulação/epidemiologia , Epidemiologia Descritiva
16.
Rosario; s.n; 2000. 74 p. tab, graf. (102955).
Tese em Espanhol | BINACIS | ID: bin-102955

RESUMO

El objetivo de este estudio de tipo descriptivo y transversal fue observar los motivos de consulta a fonoaudiología, los diagnósticos fonoaudiológicos, los tipos de consulta fonoaudiológica y los agentes de derivación, en una población de pacientes de diversas edades que asistieron al consultorio de fonoaudiología del Instituto Médico Regional de la ciudad de Gálvez en el período comprendido entre enero de 1998 ydiciembre de 1999. Se trabajó con fuente secundaria de datos, historias clínicas de 99 pacientes confeccionadas por la fonoaudióloga a cargo del consultorio: 77 menores de 18 años y 22 de 18 años o más. El 77,8 por ciento de consultas fueron realizadas por pacientes menores de 18 años de edad. En este grupo etáreo las alteraciones en el habla son el motivo de consulta más frecuente (42,9 por ciento), mientras que en los pacientes de 18 años o más, las alteraciones de la voz son las que ocupan el primer lugar (72,7 por ciento). El diagnóstico fonoaudiológico, que presenta el mayor porcentaje en pacientes menores de 18 años es el de insuficiencia respiratoria nasal (35 por ciento) y en los de 18 añois o más, disfonía (72,8 por ciento). Se observó que en el grupo de pacientes menores de 18 años el 50,6 por ciento consulta en forma derivada y en el de 18 años o más, el 68,2 por cientolo hace de igual manera. El pediatra es el agente de derivación que ocupa el primer lugar entre aquellos pacientes menores de 18 años (41,0 por ciento), mientras que en pacientes de 18 años o más es el otorrinolaringólogo el que ocupa dicho lugar (73,3 por ciento)(AU)


Assuntos
Humanos , Adulto , Fonofos , Transtornos da Articulação/diagnóstico , Transtornos da Articulação/epidemiologia , Epidemiologia Descritiva
17.
Rosario; s.n; 2000. 74 p. tab, graf. (11221).
Tese em Espanhol | BINACIS | ID: bin-11221

RESUMO

El objetivo de este estudio de tipo descriptivo y transversal fue observar los motivos de consulta a fonoaudiología, los diagnósticos fonoaudiológicos, los tipos de consulta fonoaudiológica y los agentes de derivación, en una población de pacientes de diversas edades que asistieron al consultorio de fonoaudiología del Instituto Médico Regional de la ciudad de Gálvez en el período comprendido entre enero de 1998 ydiciembre de 1999. Se trabajó con fuente secundaria de datos, historias clínicas de 99 pacientes confeccionadas por la fonoaudióloga a cargo del consultorio: 77 menores de 18 años y 22 de 18 años o más. El 77,8 por ciento de consultas fueron realizadas por pacientes menores de 18 años de edad. En este grupo etáreo las alteraciones en el habla son el motivo de consulta más frecuente (42,9 por ciento), mientras que en los pacientes de 18 años o más, las alteraciones de la voz son las que ocupan el primer lugar (72,7 por ciento). El diagnóstico fonoaudiológico, que presenta el mayor porcentaje en pacientes menores de 18 años es el de insuficiencia respiratoria nasal (35 por ciento) y en los de 18 añois o más, disfonía (72,8 por ciento). Se observó que en el grupo de pacientes menores de 18 años el 50,6 por ciento consulta en forma derivada y en el de 18 años o más, el 68,2 por cientolo hace de igual manera. El pediatra es el agente de derivación que ocupa el primer lugar entre aquellos pacientes menores de 18 años (41,0 por ciento), mientras que en pacientes de 18 años o más es el otorrinolaringólogo el que ocupa dicho lugar (73,3 por ciento)(AU)


Assuntos
Humanos , Adulto , Fonofos , Transtornos da Articulação/diagnóstico , Transtornos da Articulação/epidemiologia , Epidemiologia Descritiva
19.
J Econ Entomol ; 91(2): 410-8, 1998 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-9589627

RESUMO

Chemical insecticides and entomopathogenic nematodes have been independently used to suppress corn rootworm damage in maize. We report on the mortality response of larvae of the western corn rootworm, Diabrotica virgifera virgifera LeConte, to the combined treatment with 1 of 3 insecticides (terbufos, fonofos, and tefluthrin) and the entomopathogenic nematode Steinernema carpocapsae Weiser (Mexican strain). Corn rootworm mortality with combinations of the insecticides terbufos or fonofos and S. carpocapsae was typically additive for the 2 agents. Evidence of antagonism between these agents was sometimes observed. The combination of tefluthrin with S. carpocapsae frequently resulted in a synergistic response and a 24% average increase in expected mortality. The influence of the tefluthrin appears to be isolated to an effect on the rootworm larvae. Synergism also was observed when tefluthrin was combined with the nematode Heterorhabditis bacteriophora Poinar (Lewiston strain). The combined use of tefluthrin with an entomopathogenic nematode may offer an integrated approach to increase the efficacy of entomopathogenic nematodes for insect control.


Assuntos
Besouros , Inseticidas , Controle Biológico de Vetores , Rhabditoidea , Zea mays , Animais , Fonofos , Larva , Compostos Organotiofosforados
20.
J Chromatogr A ; 778(1-2): 161-70, 1997 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-9299733

RESUMO

The stability of four pesticides (desethylatrazine, fenamiphos, fenitrothion and fonofos) was examined under different storage conditions after preconcentration in disposable solid-phase extraction (SPE) cartridges containing new polymer sorbent materials (Hysphere-1, IST EnviroLut and LiChrolut). Complete recovery for all the compounds was observed in precolumns kept at -20 degrees C for 1 month when preconcentrating 26 ml of ground water sample spiked at 10 micrograms/l. Degradation of fenamiphos and fenitrothion occurred in precolumns stored at 4 degrees C and at room temperature after 1 month. Fonofos was stable when compared to their storage in C18 precolumns. Problems in the quantification of the analytes after storage at 4 degrees C and at room temperature were encountered due to the presence of many interfering peaks in the chromatograms. Analysis of blanks with C18 precolumns was carried out, to determine the interferences. The stability of the pesticides was also examined in acidifed and non-acidified ground water in order to compare it to the stability of pesticides stored on SPE cartridges. Significant losses of fenamiphos and fenitrothion were achieved and were related to the pH of the water sample and their chemical structure. Finally, the new polymeric sorbent Hysphere-I was evaluated in terms of breakthroughs and compared with those of C18, obtaining higher recoveries for desethylatrazine.


Assuntos
Cromatografia Líquida/métodos , Praguicidas/química , Polímeros/química , Atrazina/química , Estabilidade de Medicamentos , Armazenamento de Medicamentos/métodos , Fenitrotion/química , Fonofos/química , Água Doce/química , Herbicidas/química , Inseticidas/química , Compostos Organofosforados/química , Reprodutibilidade dos Testes , Espectrofotometria Ultravioleta , Temperatura , Fatores de Tempo
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