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1.
Int J Mol Sci ; 19(3)2018 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-29510578

RESUMO

In insects, cytochrome P450 monooxygenases (P450s or CYPs) are known to be involved in the detoxification and metabolism of insecticides, leading to increased resistance in insect populations. Spodoptera exigua is a serious polyphagous insect pest worldwide and has developed resistance to various insecticides. In this study, a novel CYP3 clan P450 gene CYP9A105 was identified and characterized from S. exigua. The cDNAs of CYP9A105 encoded 530 amino acid proteins, respectively. Quantitative real-time PCR analyses showed that CYP9A105 was expressed at all developmental stages, with maximal expression observed in fifth instar stage larvae, and in dissected fifth instar larvae the highest transcript levels were found in midguts and fat bodies. The expression of CYP9A105 in midguts was upregulated by treatments with the insecticides α-cypermethrin, deltamethrin and fenvalerate at both LC15 concentrations (0.10, 0.20 and 5.0 mg/L, respectively) and LC50 concentrations (0.25, 0.40 and 10.00 mg/L, respectively). RNA interference (RNAi) mediated silencing of CYP9A105 led to increased mortalities of insecticide-treated 4th instar S. exigua larvae. Our results suggest that CYP9A105 might play an important role in α-cypermethrin, deltamethrin and fenvalerate detoxification in S. exigua.


Assuntos
Sistema Enzimático do Citocromo P-450/genética , Proteínas de Insetos/genética , Inseticidas/farmacocinética , Piretrinas/farmacocinética , Spodoptera/genética , Animais , Sistema Enzimático do Citocromo P-450/metabolismo , Inativação Metabólica , Proteínas de Insetos/metabolismo , Spodoptera/metabolismo
2.
Food Chem Toxicol ; 115: 329-335, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29574011

RESUMO

The goal of this work is to study the presence of 17 different pyrethroids and chlorpyrifos in animal origin food samples, including chicken, beef, fish, eggs and milk. The samples were analyzed by GC/NCI-MS/MS in order to determine their insecticide concentration levels, the relation between the amount of insecticides and the lipid content, as well as their isomeric composition. Bifenthrin, cypermethrin, cyhalothrin, permethrin, deltamethrin and chlorpyrifos have been detected in real samples. The highest levels find were verified for chlorpyrifos (45.7 µg L-1, 17.5 µg kg-1 ww) and cypermethrin (2.75 µg L-1, 14.7 µg kg-1 ww) in milk and beef, respectively. The estimate of daily intake showed that none of these insecticides exceeded the safety limits of the acceptable daily intake values. A strong correlation between the amount of pesticides and lipid content was found for beef, fish and chicken samples. Regarding the isomers, a predominance of cis isomers in samples contaminated with cypermethrin was verified.


Assuntos
Clorpirifos/análise , Exposição Dietética , Contaminação de Alimentos/análise , Inseticidas/análise , Resíduos de Praguicidas/análise , Piretrinas/análise , Adulto , Animais , Biotransformação , Brasil , Clorpirifos/farmacocinética , Laticínios/análise , Ovos/análise , Feminino , Cromatografia Gasosa-Espectrometria de Massas/métodos , Humanos , Inseticidas/farmacocinética , Masculino , Carne/análise , Nível de Efeito Adverso não Observado , Resíduos de Praguicidas/farmacocinética , Piretrinas/farmacocinética , Medição de Risco , Alimentos Marinhos/análise
3.
J Expo Sci Environ Epidemiol ; 28(6): 599-614, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29284785

RESUMO

A toxicokinetic model has been optimized to describe the time profiles of common biomarkers of exposure to permethrin and cypermethrin: trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acids (trans-DCCA) and 3-phenoxybenzoic acid (3-PBA). The model then served to reproduce urinary time courses in exposed agricultural workers and predict corresponding absorbed doses. It allowed for the prediction of the main routes of exposure in workers during the study period. Modeling showed that simulating exposure mostly by the oral route, during the 3-day biomonitoring period, provided best-fits to the urinary time courses of most workers. This is compatible with an inadvertent oral exposure during work. According to best-fit scenarios, absorbed doses in workers reconstructed with the model reached a maximum of 2.4 µg/kg bw/day and were below the absorbed dose limits associated with an exposure to the reference dose values established by the U.S. Environmental Protection Agency (0.06 and 0.25 mg/kg bw/day for cypermethrin and permethrin, respectively) and the Acceptable Operator Exposure Level set by the European Commission (0.06 mg/kg bw/day for cypermethrin). Modeling was further used to derive biological reference values for cypermethrin and permethrin exposure. Respective values of 7 and 29 nmol/kg bw/day of trans-DCCA, and 3 and 13 nmol/kg bw/day of 3-PBA were obtained. None of the workers presented values above these biological reference values.


Assuntos
Inseticidas/farmacocinética , Exposição Ocupacional/análise , Permetrina/farmacocinética , Piretrinas/farmacocinética , Administração Oral , Benzoatos/farmacocinética , Fazendeiros , Humanos , Inseticidas/sangue , Inseticidas/urina , Permetrina/sangue , Permetrina/urina , Praguicidas , Piretrinas/sangue , Piretrinas/urina , Quebeque , Valores de Referência , Absorção Cutânea , Toxicocinética
4.
Drug Chem Toxicol ; 41(1): 33-41, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28633599

RESUMO

Deltamethrin (DLM) is a well-known pyrethroid insecticide which is widely used in the agriculture and home pest control due to restriction on the sale of organophosphate. DLM induced apoptosis is well known but its mechanism is still unclear. This study has been designed to find out its mechanism of apoptosis with the help of computational methods along with in vivo methods. The QikProp and ProTox results have shown that DLM has good oral absorption. The docking results reveal that DLM has a strong binding affinity toward the CD4, CD8, CD28 and CD45 receptors. Further, to understand the toxicity of DLM on lymphoid cells, a single dose of DLM (5 mg/kg, oral for seven days) has been administered to male Balb/c mice and cytotoxicity (MTT assay), oxidative stress indicators (glutathione, reactive oxygen species) and apoptotic markers (caspase-3 activity, DNA fragmentation) have been assessed in thymic and splenic single cell suspensions. Lowering of body weight, cellularity and loss in cell viability have been observed in DLM treated mice. The significant increase in ROS and GSH depletion in spleen and thymus, indicate the possible involvement of oxidative stress. The spleen cells appear more susceptible to the adverse effects of DLM than thymus cells. Further, for the amelioration of its effect, two structurally different bioactive herbal extracts, piperine and curcumin have been evaluated and have shown the cytoprotective effect by inhibiting the apoptogenic signaling pathways induced by DLM.


Assuntos
Alcaloides/farmacologia , Antioxidantes/farmacologia , Benzodioxóis/farmacologia , Curcumina/farmacologia , Inseticidas/toxicidade , Nitrilas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Piperidinas/farmacologia , Alcamidas Poli-Insaturadas/farmacologia , Piretrinas/toxicidade , Baço/efeitos dos fármacos , Timo/efeitos dos fármacos , Alcaloides/química , Animais , Antioxidantes/química , Apoptose/efeitos dos fármacos , Benzodioxóis/química , Caspase 3/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Curcumina/química , Citoproteção , Glutationa/metabolismo , Inseticidas/química , Inseticidas/farmacocinética , Masculino , Camundongos Endogâmicos BALB C , Simulação de Acoplamento Molecular , Nitrilas/química , Nitrilas/farmacocinética , Piperidinas/química , Alcamidas Poli-Insaturadas/química , Ligação Proteica , Conformação Proteica , Piretrinas/química , Piretrinas/farmacocinética , Espécies Reativas de Oxigênio/metabolismo , Receptores Imunológicos/química , Receptores Imunológicos/metabolismo , Baço/metabolismo , Baço/patologia , Relação Estrutura-Atividade , Timo/metabolismo , Timo/patologia , Fatores de Tempo
5.
Chemosphere ; 181: 682-689, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28476008

RESUMO

Vector-borne diseases have increased pesticide use in urban areas (UA) and agricultural areas (AA) in Mexico. Breast milk can be contaminated by pesticide exposure. The objective of the study was to measure breast milk intake by deuterium oxide dilution as well as organochlorine and pyrethroid transfer from mother to infant in AA and UA of Sonora, Mexico. Human milk intake was determined by the 'dose-to-mother' technique using deuterium oxide (D2O) dilution. Mothers' body composition was also assessed by this technique and the intercept method. Pyrethroids (deltamethrin, cypermethrin and cyhalothrin) and organochlorine pesticide residues (p,p'- DDT, p,p'- DDE, p,p'- DDD) in breast milk samples were measured by gas chromatography. Sixty-two lactating women and their infants participated in the study, 32 lived in the UA and 30 lived in the AA. Breast milk intake was approximately 100 mL higher in the AA than in the UA 799 ± 193 and 707 ± 201 mL/day, respectively (p < 0.05). The concentrations of p,p'- DDT and cypermethrin levels in breast milk were higher in the UA than in the AA (p < 0.05 and p = 0.001, respectively). None of the pyrethroids and organochlorine pesticides studied surpassed the Acceptable Daily Intake (ADI) in milk for humans according to EPA and FAO/WHO. In conclusion, breast milk intake was higher in the AA compared to the UA. The p,p'- DDT and cypermethrin levels in breast milk were higher in the UA compared to the AA. Since pesticide levels in human milk did not exceed the ADI, breastfeeding is still a safe practice and should be encouraged.


Assuntos
Aleitamento Materno/efeitos adversos , Óxido de Deutério/farmacocinética , Leite Humano/química , Praguicidas/análise , Adulto , Agricultura , Cromatografia Gasosa , Feminino , Humanos , Hidrocarbonetos Clorados/análise , Hidrocarbonetos Clorados/farmacocinética , Lactente , México , Mães , Praguicidas/farmacocinética , Piretrinas/análise , Piretrinas/farmacocinética , Adulto Jovem
6.
J Toxicol Environ Health A ; 79(2): 83-91, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26817658

RESUMO

Exposure to pyrethroid pesticides is a potential cause for concern. The objective of this study was to examine the in vivo dermal absorption of bifenthrin, deltamethrin, and permethrin in the rat. Dorsal hair on adult male Long-Evans rats was removed. The next day, the skin was dosed with 1750 nmol (312.5 nmol/cm(2)) of radiolabeled (5 µCi) bifenthrin, deltamethrin, or permethrin in acetone. A nonoccluding plastic cover was glued over the dosing site. The animals were placed in metabolism cages to collect excreta. At 24 h postdosing, the skin was washed with soap and water, and rats in one group were euthanized and their tissues were collected. The skin was removed and tape stripped. The remaining animals were returned to the metabolism cages after the wash for 4 d. These rats were then euthanized and handled as already described. Excreta, wash, tape strips, tissues, and carcass were analyzed for pyrethroid-derived radioactivity. The wash and tape strips removed >50% of the dose and skin retained 9-24%. Cumulative radioactivity in excreta was 0.5-7% at 24 h and 3-26% at 120 h. Radioactivity in tissues was <0.3% of the dose, while carcass retained 2 to 5%. Assuming absorption equals cumulative recovery in skin (washed and tape stripped), excreta, tissues, and carcass, absorption was permethrin ~ bifenthrin > deltamethrin at 24 h and permethrin > deltamethrin > bifenthrin at 120 h. Using the parallelogram approach with published in vitro data, human dermal absorption of these pyrethroids was estimated to be <10% of the dose.


Assuntos
Inseticidas/farmacocinética , Piretrinas/farmacocinética , Absorção Cutânea , Animais , Carga Corporal (Radioterapia) , Fezes/química , Inseticidas/urina , Marcação por Isótopo , Masculino , Nitrilas/farmacocinética , Nitrilas/urina , Permetrina/farmacocinética , Permetrina/urina , Piretrinas/urina , Ratos , Ratos Long-Evans , Distribuição Tecidual
7.
Environ Toxicol Chem ; 35(2): 435-45, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26267556

RESUMO

Co-occurrence of pesticides such as synthetic pyrethroids and metals in aquatic ecosystems raises concerns over their combined ecological effects. Cypermethrin, 1 of the top 5 synthetic pyrethroids in use, has been extensively detected in surface water. Cadmium (Cd) has been recognized as 1 of the most toxic metals and is a common contaminant in the aquatic system. However, little information is available regarding their joint toxicity. In the present study, combined toxicity of cypermethrin and Cd and the underlying mechanisms were investigated. Zebrafish embryos and adults were exposed to the individual contaminant or binary mixtures. Co-exposure to cypermethrin and Cd produced synergistic effects on the occurrence of crooked body, pericardial edema, and noninflation of swim bladder. The addition of Cd significantly potentiated cypermethrin-induced spasms and caused more oxidative stress in zebrafish larvae. Cypermethrin-mediated induction of transcription levels and catalytic activities of cytochrome P450 (CYP) enzyme were significantly down-regulated by Cd in both zebrafish larvae and adults. Chemical analytical data showed that in vitro elimination of cypermethrin by CYP1A1 was inhibited by Cd. The addition of Cd caused an elevation of in vivo cypermethrin residue levels in the mixture-exposed adult zebrafish. These results suggest that the enhanced toxicity of cypermethrin in the presence of Cd results from the inhibitory effects of Cd on CYP-mediated biotransformation of this pesticide. The authors' findings provide a deeper understanding of the mechanistic basis accounting for the joint toxicity of cypermethrin and Cd.


Assuntos
Cádmio/toxicidade , Inseticidas/toxicidade , Piretrinas/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra , Anormalidades Induzidas por Medicamentos/patologia , Sacos Aéreos/anormalidades , Sacos Aéreos/patologia , Animais , Antioxidantes/metabolismo , Citocromo P-450 CYP1A1/antagonistas & inibidores , Citocromo P-450 CYP1A1/metabolismo , Sinergismo Farmacológico , Edema/induzido quimicamente , Edema/patologia , Expressão Gênica/efeitos dos fármacos , Inseticidas/farmacocinética , Larva , Dose Letal Mediana , Pericárdio/patologia , Resíduos de Praguicidas/toxicidade , Piretrinas/farmacocinética , Cauda/anormalidades
8.
Biomed Environ Sci ; 27(6): 426-35, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24961852

RESUMO

OBJECTIVE: To characterize the pharmacokinetics and distribution profiles of deltamethrin in miniature pig tissues by gas chromatography-mass spectrometry (GC-MS). METHODS: Pharmacokinetics and distribution of deltamethrin in blood and tissues of 30 miniature pigs were studied by GC-MS after oral administration of deltamethrin (5 mg/kg bw). Data were processed by 3P97 software. RESULTS: The serum deltamethrin level was significantly lower in tissues than in blood of miniature pigs. The AUC0-72 h, Cmax, of deltamethrin were 555.330 ± 316.987 ng h/mL and 17.861 ± 11.129 ng/mL, respectively. The Tmax, of deltamethrin was 6.004 ± 3.131 h. CONCLUSION: The metabolism of deltamethrin in miniature pigs is fit for a one-compartment model with a weighting function of 1/C2. Deltamethrin is rapidly hydrolyzed and accumulated in miniature pig tissues.


Assuntos
Nitrilas/farmacocinética , Piretrinas/farmacocinética , Absorção , Animais , Cromatografia Gasosa-Espectrometria de Massas , Modelos Animais , Suínos , Porco Miniatura , Distribuição Tecidual
9.
Chem Biol Interact ; 203(3): 588-96, 2013 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-23566885

RESUMO

Metabonomic analysis, clinical chemical analysis and histopathology were used to investigate the toxic effects of subchronic exposure to dichlorvos, deltamethrin, and a combination of these two pesticides, in rats. Weight loss, hind limb weakness and histopathological changes in kidney tissue were only observed in rats exposed to high doses of deltamethrin, or a combination of deltamethrin and dichlorvos. Urinary metabonomic analysis indicated that exposure to a mixture of dichlorvos and deltamethrin was followed by increases in urinary lactate, dimethylamine, N-glycoprotein (NAC) and glycine similar to those observed in rats treated with either dichlorvos or deltamethrin alone. Serum metabonomic analysis suggests that dichlorvos induced an increase in lactate and alanine and a decrease in dimethylglycine (DMG), NAC and very low- and low-density lipoprotein (VLDL/LDL). High levels of lactate and low levels of NAC and VLDL/LDL were observed in the deltamethrin treatment group. Treating rats with a mixture of dichlorvos and deltamethrin caused an increase in serum lactate, trimethylamine-N-oxide (TMAO), choline and alanine, with the highest levels of these metabolites observed in those that received the highest dose. Exposure to a mixture of dichlorvos and deltamethrin also resulted in a decrease in serum acetone, DMG, NAC, and VLDL/LDL. Changes in serum TMAO, alanine, choline and acetone in this treatment group were higher than in rats treated with either dichlorvos or deltamethrin. These results suggest that exposing rats to subchronic doses of dichlorvos, deltamethrin, or a combination of these pesticides, disrupted the energy metabolism of the liver and reduced kidney function.


Assuntos
Diclorvós/toxicidade , Inseticidas/toxicidade , Nefropatias/induzido quimicamente , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Nitrilas/toxicidade , Piretrinas/toxicidade , Animais , Peso Corporal/efeitos dos fármacos , Diclorvós/farmacocinética , Dimetilaminas/urina , Quimioterapia Combinada , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/fisiologia , Glicina/urina , Glicoproteínas/urina , Membro Posterior , Inseticidas/farmacocinética , Rim/patologia , Rim/fisiopatologia , Nefropatias/patologia , Lactatos/urina , Lipoproteínas/sangue , Fígado/metabolismo , Fígado/patologia , Masculino , Metabolômica , Debilidade Muscular/induzido quimicamente , Nitrilas/farmacocinética , Piretrinas/farmacocinética , Ratos , Ratos Wistar , Redução de Peso
10.
Toxicol Lett ; 200(1-2): 41-5, 2011 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-21035527

RESUMO

Human volunteer studies have been conducted by orally administering the pesticides deltamethrin (0.01 mg/kg/day) or pirimicarb (0.02 mg/kg/day) at the acceptable daily intake (ADI) together with chlorpyrifos-methyl (0.01 mg/kg/day), in order to investigate any potential interactions that may occur during dietary exposure. Deltamethrin and pirimicarb are metabolised in vivo by hydrolytic enzymes, which may be susceptible to inhibition by esterase-inhibiting compounds, such as chlorpyrifos-methyl. Urine samples were collected at time points up to at least 48 h post-exposure and metabolites were quantified. Urinary metabolite excretion data obtained from the mixed exposures were compared with data obtained from the same individuals given a dose of each individual pesticide on a separate occasion. Metabolite excretion profiles for both pesticides administered as a mixed dose with chlorpyrifos-methyl were qualitatively similar to those obtained for the individual doses. Peak excretion of deltamethrin and pirimicarb metabolites occurred at around 4h post-exposure for both the individual and the mixed exposure scenarios, and metabolite excretion was almost complete within 24h. No statistically significant differences were found between the individual and mixed doses for either metabolite excretion half-life or metabolite levels quantified in 24-h total urine collections. The data presented here indicate that no significant toxicokinetic interactions occur between either deltamethrin or pirimicarb and chlorpyrifos-methyl when orally administered together at the ADI.


Assuntos
Carbamatos/farmacocinética , Clorpirifos/farmacocinética , Inseticidas/farmacocinética , Nitrilas/farmacocinética , Piretrinas/farmacocinética , Pirimidinas/farmacocinética , Administração Oral , Adulto , Carbamatos/administração & dosagem , Carbamatos/efeitos adversos , Clorpirifos/administração & dosagem , Clorpirifos/efeitos adversos , Interações Medicamentosas , Feminino , Meia-Vida , Humanos , Inseticidas/administração & dosagem , Inseticidas/efeitos adversos , Masculino , Concentração Máxima Permitida , Pessoa de Meia-Idade , Nitrilas/administração & dosagem , Nitrilas/efeitos adversos , Piretrinas/administração & dosagem , Piretrinas/efeitos adversos , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Adulto Jovem
11.
Toxicol Appl Pharmacol ; 246(1-2): 29-37, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20398685

RESUMO

Dermal exposure to pyrethroid pesticides can occur during manufacture and application. This study examined the in vitro dermal absorption of pyrethroids using rat and human skin. Dermatomed skin from adult male Long Evans rats or human cadavers was mounted in flow-through diffusion cells, and radiolabeled bifenthrin, deltamethrin or cis-permethrin was applied in acetone to the skin. Fractions of receptor fluid were collected every 4h. At 24h, the skins were washed with soap and water to remove unabsorbed chemical. The skin was then solubilized. Two additional experiments were performed after washing the skin; the first was tape-stripping the skin and the second was the collection of receptor fluid for an additional 24 h. Receptor fluid, skin washes, tape strips and skin were analyzed for radioactivity. For rat skin, the wash removed 53-71% of the dose and 26-43% remained in the skin. The cumulative percentage of the dose at 24 h in the receptor fluid ranged from 1 to 5%. For human skin, the wash removed 71-83% of the dose and 14-25% remained in the skin. The cumulative percentage of the dose at 24 h in the receptor fluid was 1-2%. Tape-stripping removed 50-56% and 79-95% of the dose in rat and human skin, respectively, after the wash. From 24-48 h, 1-3% and about 1% of the dose diffused into the receptor fluid of rat and human skin, respectively. The pyrethroids bifenthrin, deltamethrin and cis-permethrin penetrated rat and human skin following dermal application in vitro. However, a skin wash removed 50% or more of the dose from rat and human skin. Rat skin was more permeable to the pyrethroids than human skin. Of the dose in skin, 50% or more was removed by tape-stripping, suggesting that permeation of pyrethroids into viable tissue could be impeded. The percentage of the dose absorbed into the receptor fluid was considerably less than the dose in rat and human skin. Therefore, consideration of the skin type used and fractions analyzed are important when using in vitro dermal absorption data for risk assessment.


Assuntos
Inseticidas/farmacocinética , Piretrinas/farmacocinética , Absorção Cutânea , Adulto , Animais , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Humanos , Técnicas In Vitro , Masculino , Nitrilas/farmacocinética , Permetrina/farmacocinética , Ratos , Ratos Long-Evans
12.
Environ Sci Technol ; 42(22): 8419-25, 2008 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-19068827

RESUMO

Chemical methods to assess bioavailability in soil and sediment often use synthetic polymers that mimic uptake of organic compounds in organisms or microbial degradation. In this paper we have assessed a biomimetic extraction method using hydroxyl-beta-cyclodextrin (HP-beta-CD) to estimate uptake of the two insecticides alpha-cypermethrin (alpha-CYP) and chlorfenvinphos (CFVP) in the earthworm Eisenia fetida. Additionally, a novel approach was developed to estimate the efficiency of biomimetic extractions. The study revealed that HP-beta-CD is a suitable surrogate for estimating the bioaccessibility of hydrophobic chemicals in soil. If one uses a 3.5 times higher amount of HP-beta-CD than soil, effective and reproducible extractions can be achieved within 48 h. Atthese conditions, inclusion of dissolved chemicals by HP-beta-CD mimics uptake of a given compound into earthworms and takes into account sorption-related aspects that control biological uptake. The data indicate that, with increasing hydrophobicity, the affinity of organic chemicals to HP-beta-CD does not increase to the same degree as to soil organic matter. Therefore, a high surplus of HP-beta-CD is necessaryto provide a sufficient extraction capacity in biomimetic extractions.


Assuntos
Clorfenvinfos/farmacocinética , Inseticidas/farmacocinética , Oligoquetos/metabolismo , Piretrinas/farmacocinética , beta-Ciclodextrinas/farmacocinética , Adsorção , Animais , Disponibilidade Biológica , Clorfenvinfos/química , Interações Hidrofóbicas e Hidrofílicas , Inseticidas/química , Piretrinas/química , Solo , Poluentes do Solo/química , Poluentes do Solo/farmacocinética , beta-Ciclodextrinas/química
13.
Environ Sci Technol ; 41(17): 6124-8, 2007 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-17937291

RESUMO

Despite the fact that the biological processes of chiral compounds are enantioselective, the endocrine disruption activity and uptake of chiral contaminants with respect to enantioselectivity has so far received limited research. In this study, the estrogenic potential and uptake of the enantiomers of a newer pyrethroid insecticide, bifenthrin (BF), were investigated. Significant differences in estrogenic potential were observed between the two enantiomers in the in vitro human breast carcinoma MCF-7 cell proliferation assay (i.e., the E-SCREEN assay) and the in vivo aquatic vertebrate vitellogenin enzyme-linked immunosorbent assay (ELISA). In the E-SCREEN assay, the relative proliferative effect ratios of 1S-cis-BF and 1R-cis-BF were 74.2% and 20.9%, respectively, and the relative proliferative potency ratios were 10% and 1%, respectively. The cell proliferation induced by the two BF enantiomers may be through the classical estrogen response pathway via the estrogen receptor (ER), as the proliferation induced by the enantiomers could be completely blocked when combined with 10-6 mol/L of the ER antagonist ICI 182,780. Measurement of vitellogenin induction in Japanese medaka (Oryzias latipes) showed that, at an exposure level of 10 ng/mL, the response to 1S-cis-BF was about 123 times greater than thattothe Renantiomer. Significant selectivity also occurred in the uptake of BF enantiomers in the liver and other tissues of J. medaka. These results together suggest that assessment of the environmental safety of chiral insecticides should consider enantioselectivity in acute and chronic ecotoxicities such as endocrine disruption.


Assuntos
Proliferação de Células/efeitos dos fármacos , Estrogênios/farmacocinética , Oryzias/metabolismo , Piretrinas/farmacocinética , Poluentes Químicos da Água/farmacocinética , Animais , Neoplasias da Mama/patologia , Ensaio de Imunoadsorção Enzimática , Estrogênios/química , Feminino , Humanos , Inseticidas/farmacocinética , Inseticidas/toxicidade , Fígado/patologia , Piretrinas/química , Receptores de Estrogênio/metabolismo , Estereoisomerismo , Distribuição Tecidual , Células Tumorais Cultivadas , Vitelogeninas/análise , Poluentes Químicos da Água/química
14.
Ther Drug Monit ; 29(2): 150-63, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17417068

RESUMO

Extensive use of synthetic pesticides for agricultural and nonagricultural purposes began in the past 50 years. As a result of their wide and extensive application, exposure to hazardous pesticides is a concern to the general population and occupationally exposed persons. Robust methods are therefore needed for measuring markers of pesticide exposure. This article presents a review of the most recently published analytical methodologies and instrumentations developed for and applied to biological monitoring of exposure to pesticides of various classes. Most of the methods reviewed here are based on chromatography combined with mass spectrometry detection. This work clearly demonstrates that although gas chromatography still appears to be the most widely employed technique for pesticide analysis in various biological samples, recently a trend has been observed toward the use of liquid chromatography coupled with tandem mass spectrometry.


Assuntos
Exposição Ambiental/análise , Praguicidas/análise , Praguicidas/farmacocinética , Acetatos/análise , Acetatos/farmacocinética , Líquido Amniótico/química , Cromatografia Líquida , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Hidrocarbonetos Clorados/análise , Hidrocarbonetos Clorados/farmacocinética , Mecônio/química , Organofosfatos/análise , Organofosfatos/farmacocinética , Praguicidas/urina , Gravidez , Piretrinas/análise , Piretrinas/farmacocinética , Espectrometria de Massas em Tandem
15.
Regul Toxicol Pharmacol ; 47(3): 274-87, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17239512

RESUMO

The evaluation of the degree of percutaneous penetration of agrochemicals is a key part of risk assessment for operators. The availability of suitable and predictive experimental models is crucial, in particular in the case of lipophilic compounds which persist in the stratum corneum (SC). Regulatory models (rat in vivo, human and rat in vitro) and the innovative human skin grafted onto nude mice (HuSki) model were compared for their ability to predict the human skin absorption. Radiolabelled malathion, lindane and cypermethrin (4microg/cm(2)) were topically applied to each model. The % of applied dose absorbed and that present in skin and SC were evaluated at 24h. Additionally, the absorption profile of cypermethrin was evaluated in the in vivo rat and HuSki models for up to 11 days. We found that the human in vitro and HuSki models closely predicted the human skin absorption at 24h, while rat models overestimated the human skin absorption. Furthermore, our experiments with cypermethrin indicated that evaluation of % percutaneous absorption over extended periods of time was feasible with the HuSki model. In our studies the HuSki model overcame the limitations of the regulatory models and is promising to realistically refine the dermal absorption assessment of topically applied chemicals.


Assuntos
Inseticidas/farmacocinética , Modelos Animais , Absorção Cutânea , Transplante de Pele , Animais , Feminino , Hexaclorocicloexano/farmacocinética , Humanos , Malation/farmacocinética , Masculino , Camundongos , Camundongos Nus , Piretrinas/farmacocinética , Ratos , Ratos Wistar , Medição de Risco
16.
J UOEH ; 26(4): 423-30, 2004 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-15624354

RESUMO

The tumor-promoting activities of 5 commercial compounds used in termiticides were measured by a cell-transformation assay employing Bhas 42 cells. Their initiating activities were also measured by the microsuspension assay employing S. typhimurium TA98 and TA100 strains. The results of the transformation assay confirmed the tumor-promoting activities of fenitrothion, silafluofen and bifenthrin. Furthermore, the mutagenicity of S-421 and fenitrothion were also confirmed. Consideration of 2-stage carcinogenesis suggests that concurrent use of and long-term exposure to these compounds that have tumor-promoting and initiator activity, and compounds exhibiting either type of activity individually should be avoided as much as possible.


Assuntos
Transformação Celular Neoplásica/induzido quimicamente , Inseticidas/farmacocinética , Inseticidas/toxicidade , Biotransformação , Éteres/farmacocinética , Éteres/toxicidade , Fenitrotion/farmacologia , Fenitrotion/toxicidade , Testes de Mutagenicidade , Compostos de Organossilício/farmacocinética , Compostos de Organossilício/toxicidade , Permetrina/farmacocinética , Permetrina/toxicidade , Piretrinas/farmacocinética , Piretrinas/toxicidade , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética
17.
J Anal Toxicol ; 28(4): 238-41, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15189673

RESUMO

The aim of this work was to detect and quantitate residues of the pyrethroid insecticide cypermethrin in the milk of a lactating dairy cow. The efficiency of the method was settled through recovery experiments in which certain amounts of the pyrethroid cypermethrin were spiked up to milk. For this purpose, the matrix solid-phase dispersion method was applied followed by clean-up with silica-gel column. The extracts obtained were analyzed by gas chromatography-ion trap mass spectrometry. With the aid of the selected ion storage technique, it was feasible to select specific ions from the analyte of interest, which could be separated from the organic matrix. After the establishment of optimum conditions for the detection of pyrethroid residues of cypermethrin, samples of milk were collected from a cow submitted to a veterinary treatment for elimination of parasites using an insecticide with 50 g/L of active ingredient in its formula. The data obtained showed milk contamination with a maximum concentration of 0.168 mg/kg 24 h after insecticide treatment. Considering the maximum residual limit for cypermethrin in milk of 0.010 mg/kg, samples collected 15 and 24 h after treatment showed concentrations about 16 times above this value, and samples collected 11 days after treatment showed concentrations about 7 times above this value. Seventeen days after treatment, cypermethrin was not detected in the milk.


Assuntos
Contaminação de Alimentos/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Inseticidas/análise , Leite/química , Resíduos de Praguicidas/análise , Piretrinas/análise , Administração Tópica , Animais , Bovinos , Feminino , Inseticidas/administração & dosagem , Inseticidas/farmacocinética , Lactação , Piretrinas/administração & dosagem , Piretrinas/farmacocinética , Padrões de Referência
18.
Toxicol In Vitro ; 18(1): 13-9, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-14630057

RESUMO

The objective of this study was to investigate the effect of ascorbic acid (AA) on the in vitro cytotoxicity of cypermethrin (CM), and on glutathione (GSH) metabolism in rat hepatocytes. In vitro cell viability, lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) leakage were measured, as indicators of hepatic damage, at 1, 15 and 30 min of exposure to CM. Glutathione and the activities of glutathione-S-transferase (GST) and gamma glutamyl transpeptidase (gamma-GT) were also measured. CM hepatotoxicity increased in a time and dose-dependent manner. In the presence of 30 microM CM, ALT and AST also increased 49 and 130% (P < 0.05), respectively, indicating metabolic hepatocyte damage. AA (1 mM) was capable to preserve 100% of cell integrity and modulated ALT and AST. Furthermore, CM induced a 27% reduction in the endogenous antioxidant GSH, and increased 203% GST and 283% gamma-GT (P < 0.05), indicating an oxidative insult. The presence of AA showed chemopreventive capacity against CM, recovering 60% of GSH and a 54% decrease in gamma-GT activity. These results suggest that AA in a 1:33 (CM:AA) ratio can modulate up to 90% of the damage caused to the cells by CM. It also demonstrates that AA can act as a primary antioxidant and hepatoprotector in rat hepatocytes.


Assuntos
Ácido Ascórbico/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Piretrinas/efeitos adversos , Alanina Transaminase/antagonistas & inibidores , Alanina Transaminase/metabolismo , Animais , Ácido Ascórbico/fisiologia , Aspartato Aminotransferases/antagonistas & inibidores , Aspartato Aminotransferases/metabolismo , Sobrevivência Celular/fisiologia , Dimetil Sulfóxido/farmacologia , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Glutationa/antagonistas & inibidores , Glutationa/efeitos dos fármacos , Glutationa/fisiologia , Glutationa Transferase/antagonistas & inibidores , Glutationa Transferase/fisiologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/enzimologia , Hepatócitos/metabolismo , L-Lactato Desidrogenase , Fígado/citologia , Fígado/efeitos dos fármacos , Masculino , Perfusão , Piretrinas/antagonistas & inibidores , Piretrinas/farmacocinética , Ratos , Ratos Wistar , Fatores de Tempo , gama-Glutamiltransferase/metabolismo
19.
Biochem Biophys Res Commun ; 280(1): 85-91, 2001 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-11162482

RESUMO

A metabolic activation system with an S9 fraction or liver microsomes was applied to a reporter gene assay in vitro for the screening of estrogenicity of chemicals. The endpoint (luciferase) was luciferase induction in cells transfected with a reporter plasmid containing an estrogen-responsive element linked to the luciferase gene. Compounds were applied to the reporter gene assay system after pretreatment or simultaneous treatment with an S9 fraction or liver microsomes. Both trans-stilbene and methoxychlor themselves showed no or little estrogenicity, but when they were treated with an S9 fraction or liver microsomes, they demonstrated strong effects, indicating their metabolites to be estrogenic. When four pyrethroid insecticides were subjected to this assay system, however, they showed no estrogenicity even with liver microsome or S9 mix treatment.


Assuntos
Estradiol/farmacologia , Genes Reporter , Luciferases/genética , Metoxicloro/farmacologia , Microssomos Hepáticos/metabolismo , Estilbenos/farmacologia , Animais , Biotransformação , Neoplasias da Mama , Carcinógenos/farmacocinética , Carcinógenos/farmacologia , Combinação de Medicamentos , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Glycyrrhiza , Células HeLa , Humanos , Inseticidas/farmacocinética , Inseticidas/toxicidade , Metoxicloro/farmacocinética , Paeonia , Plasmídeos , Piretrinas/farmacocinética , Piretrinas/toxicidade , Ratos , Estilbenos/farmacocinética , Transfecção/métodos , Células Tumorais Cultivadas
20.
Artigo em Inglês | MEDLINE | ID: mdl-10661713

RESUMO

Topical bioassays using propoxur, chlorpyrifos, and lambda-cyhalothrin were conducted on eight cockroach species. Based on lethal dose values, the relative toxicities of the insecticide classes were generally pyrethroid > carbamate > organophosphorous. Lambda-Cyhalothrin and propoxur were more toxic toward the Blattidae as compared with the Blattellidae. The order of lambda-cyhalothrin toxicity was Periplaneta americana > Periplaneta brunnea = Periplaneta australasiae = Periplaneta fuliginosa = Blatta orientalis > Blattella asahinai = Blattella germanica > Blattella vaga. The order of propoxur toxicity was B. orientalis > P. americana > P. brunnea = P. australasiae > B. asahinai > P. fuliginosa = B. germanica > B. vaga. The order of chlorpyrifos toxicity was P. americana > B. asahinai = B. vaga > B. orientalis = P. australasiae = P. brunnea > B. germanica = P. fuliginosa. Detoxification enzyme activities for each species also were measured and compared with insecticide toxicity. Propoxur LD50 was significantly (P = 0.01; r = 0.81) correlated with glutathione S-transferase activity. Lambda-Cyhalothrin LD50 correlated with methoxyresorufin O-demethylase activity (P = 0.01; r = 0.81), carboxylesterase activity (P = 0.03; r = - 0.75), general esterase activity (P = 0.02; r = - 0.79), and cockroach weight (P = 0.01; r = -0.95).


Assuntos
Baratas/efeitos dos fármacos , Inseticidas/farmacologia , Animais , Clorpirifos/farmacocinética , Clorpirifos/farmacologia , Baratas/enzimologia , Baratas/metabolismo , Esterases/metabolismo , Glutationa Transferase/metabolismo , Inativação Metabólica , Inseticidas/farmacocinética , Nitrilas , Oxirredutases/metabolismo , Propoxur/farmacocinética , Propoxur/farmacologia , Piretrinas/farmacocinética , Piretrinas/farmacologia
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