RESUMO
The main organochlorinated compounds used on agricultural crops are often recalcitrant, affecting nontarget organisms and contaminating rivers or groundwater. Diuron (N-(3,4-dichlorophenyl)-N',N'-dimethylurea) is a chlorinated herbicide widely used in sugarcane plantations. Here, we evaluated the ability of 13 basidiomycete strains of growing in a contaminated culture medium and degrading the xenobiotic. Dissipation rates in culture medium with initial 25 mg/L of diuron ranged from 7.3 to 96.8%, being Pluteus cubensis SXS 320 the most efficient strain, leaving no detectable residues after diuron metabolism. Pycnoporus sanguineus MCA 16 removed 56% of diuron after 40 days of cultivation, producing three metabolites more polar than parental herbicide, two of them identified as being DCPU and DCPMU. Despite of the strong inductive effect of diuron upon laccase synthesis and secretion, the application of crude enzymatic extracts of P. sanguineus did not catalyzed the breakdown of the herbicide in vitro, indicating that diuron biodegradation was not related to this oxidative enzyme.
Assuntos
Basidiomycota/metabolismo , Biodegradação Ambiental , Diurona/farmacocinética , Herbicidas/farmacocinética , Poluentes Químicos da Água/farmacocinética , Agaricales/metabolismo , Basidiomycota/efeitos dos fármacos , Basidiomycota/crescimento & desenvolvimento , Sistema Enzimático do Citocromo P-450/metabolismo , Diurona/toxicidade , Herbicidas/toxicidade , Hidrocarbonetos Clorados/farmacocinética , Hidrocarbonetos Clorados/toxicidade , Lacase/metabolismo , Modelos Biológicos , Nitrogênio/metabolismo , Polyporaceae/metabolismo , Floresta Úmida , Poluentes Químicos da Água/toxicidadeRESUMO
The objective of this study is to evaluate the influence of placental concentrations of some organochlorine pesticides on newborn's anthropometric measurements (height, weight, head circumference & ponderal index). For this study, we have collected 90 placental tissue samples for the measurement of Dichlorodiphenyltrichloroethane (DDT) & Hexachlocyclohexane (HCH) by Gas Chromatography equipped with Electron Capture Detector (GC-ECD). Regression analysis were performed between outcome variables such as birth weight, birth height, head circumference, ponderal index and independent variable i.e., organochlorine pesticide concentrations. In case of birth weight, there was a substantial decrease of 5.81, 1.94, 4.71, and 2.64 g for 1 ppb (µg/L) increase in placental α-HCH, ß-HCH, γ-HCH, and total HCH concentrations respectively. Significant decrease of 2.02 and 0.43 kg/m3 in ponderal index was found with 1 µg/L increase of total-HCH and total DDT concentrations in placenta. The results of this study support an association between environmental exposure to organochlorine pesticides and anthropometric development of the fetus leading to a significant reduction in its birth weight and ponderal index, slight and non-significant reduction in birth height and head circumference. Efforts should be made to reduce exposure of women of reproductive age in relation to long-term impact on health.
Assuntos
Antropometria , Hidrocarbonetos Clorados , Praguicidas , Placenta , Peso ao Nascer , Cefalometria , DDT , Monitoramento Ambiental , Feminino , Humanos , Hidrocarbonetos Clorados/farmacocinética , Hidrocarbonetos Clorados/toxicidade , Recém-Nascido , Placenta/química , GravidezRESUMO
1,3-Dichloropropene (1,3-D) showed a statistically increased incidence of bronchioloalveolar adenomas in male B6C3F1 mice at 60 ppm air concentration during previous chronic inhalation testing. No tumors were observed in female mice, nor in either sex of F344 rats up to 60 ppm, the highest dose tested. Therefore, to understand if lung tumors observed in high dose male mice are due to saturation of metabolic clearance, the linearity of 1,3-D concentrations in mouse blood was investigated on day 15 of repeated nose-only inhalation exposure to 0, 10, 20, 40, 60, 90, and 120 ppm (6 h/d, 7 d/week). Additional groups were included at 20, 60, and 120 ppm for blood collection at 1.5 and 3 h of exposure and up to 25 or 40 min post-exposure to determine area-under-the-curve. The data provide multiple lines of evidence that systemic exposures to 1,3-D in the mouse become nonlinear at inhalation exposure levels of 30 ppm or above. A reduction in minute volume occurred at the highest exposure concentration. The glutathione (GSH)-dependent metabolism of 1,3-D results in significant depletion of GSH at repeated exposure levels of 30 ppm and above. This loss of GSH results in decreased metabolic clearance of this test material, with a concomitant increase of the 1,3-D isomers in circulating blood at exposure concentrations ≥30 ppm. Shifts in the ratio of cis- and trans-1,3-D also support nonlinear toxicokinetics well below 60 ppm. Based on this data, a kinetically derived maximum dose for 1,3-D in mice for repeated exposures should be at or below 30 ppm. These results support non-relevance of 1,3-D-induced benign pulmonary tumorigenicity in mice for human health risk assessment.
Assuntos
Adenoma/induzido quimicamente , Compostos Alílicos/toxicidade , Carcinógenos/toxicidade , Hidrocarbonetos Clorados/toxicidade , Neoplasias Pulmonares/induzido quimicamente , Pulmão/efeitos dos fármacos , Modelos Teóricos , Adenoma/metabolismo , Compostos Alílicos/sangue , Compostos Alílicos/farmacocinética , Animais , Carcinógenos/metabolismo , Carcinógenos/farmacocinética , Transformação Celular Neoplásica/induzido quimicamente , Transformação Celular Neoplásica/metabolismo , Relação Dose-Resposta a Droga , Feminino , Hidrocarbonetos Clorados/sangue , Hidrocarbonetos Clorados/farmacocinética , Exposição por Inalação , Pulmão/metabolismo , Neoplasias Pulmonares/metabolismo , Masculino , Camundongos , Dinâmica não Linear , Ratos Endogâmicos F344 , Taxa Respiratória/efeitos dos fármacos , Medição de Risco , Fatores Sexuais , Distribuição Tecidual , ToxicocinéticaRESUMO
OBJECTIVE: Persistent organic pollutants (POPs) are lipophilic environmental toxicants that accumulate in adipose tissue. Weight loss leads to mobilization and increased redistribution of these toxicants. Many are obesogens and endocrine disruptors. Increased exposure could pose long-term health risks. The study objective was to measure the changes in serum concentrations of lipophilic POPs during significant weight loss. METHODS: This study enrolled 27 patients at a university hospital in a longitudinal, 6-month, observational study examining changes in POP blood levels after bariatric surgery. The primary outcome was the changes in the concentrations of 24 polychlorinated biphenyls (PCBs), 9 organochlorine pesticides (OCPs), 11 polybrominated diphenyl ethers, 2,2',4,4',5,5'-hexabromobiphenyl, and 4 perfluorochemicals (PFCs). RESULTS: Older adults (those born before 1976) had baseline levels of PCBs, OCPs, and PFCs that were two- to fivefold higher than younger adults (those born after 1976). Older adults had greater increases in PCBs, OCPs, and polybrominated diphenyl ethers associated with weight loss. Conversely, younger adults had greater increases in PFCs associated with weight loss. On average, blood POP levels increased as weight loss occurred. CONCLUSIONS: Although weight loss is considered beneficial, the release and redistribution of POPs to other lipid-rich organs such as the brain, kidneys, and liver warrant further investigation. Interventions should be considered to limit organ exposure to POPs when weight loss interventions are planned.
Assuntos
Tecido Adiposo/metabolismo , Cirurgia Bariátrica , Poluentes Ambientais/sangue , Poluentes Ambientais/farmacocinética , Obesidade Mórbida/cirurgia , Tecido Adiposo/química , Adulto , Fatores Etários , Análise Química do Sangue , Exposição Ambiental/análise , Poluentes Ambientais/análise , Feminino , Seguimentos , Éteres Difenil Halogenados/análise , Éteres Difenil Halogenados/sangue , Éteres Difenil Halogenados/farmacocinética , Humanos , Hidrocarbonetos Clorados/análise , Hidrocarbonetos Clorados/sangue , Hidrocarbonetos Clorados/farmacocinética , Fígado/química , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/sangue , Obesidade Mórbida/metabolismo , Praguicidas/análise , Praguicidas/sangue , Praguicidas/farmacocinética , Bifenilos Policlorados/análise , Bifenilos Policlorados/sangue , Bifenilos Policlorados/farmacocinética , Período Pós-Operatório , Distribuição Tecidual , Redução de Peso/fisiologiaRESUMO
Concentration of organochlorine pesticides (OCPs) (α-, ß-, γ- hexachlorocyclohexane (HCH), dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyldichloroethane (DDD), dichlorodiphenyldichloroethylene (DDE)) in four species of Pacific salmon (pink, chum, chinook, and sockeye) are presented. OCPs in salmon organs increased in the following order: muscle < liver < eggs < male gonads. Concentrations of the OCP in salmon organs increased in following order: DDEâ¯<â¯Î³-HCHâ¯<â¯α-HCH. The level of pollutants in salmon is compared with the sanitary and epidemiological norms of Russia and other countries. Cancer and noncancer hazard ratios through consumption of salmon in Russian Far East for both men and women also were summarized. Noncancer and cancer hazard ratio values were far below threshold values (<1.0).
Assuntos
Inocuidade dos Alimentos , Hidrocarbonetos Clorados/análise , Resíduos de Praguicidas/análise , Salmão/metabolismo , Poluentes Químicos da Água/análise , Animais , Feminino , Humanos , Hidrocarbonetos Clorados/farmacocinética , Masculino , Resíduos de Praguicidas/farmacocinética , Medição de Risco , Federação Russa , Distribuição Tecidual , Poluentes Químicos da Água/farmacocinéticaRESUMO
Total 22 organochlorine pesticides (OCPs) compounds and 31 polychlorinated biphenyls (PCBs) congeners in mangrove sediments and tissues (leaf, branch, root and fruit) of nine species from three Mangrove Reserves of China were studied. The mean concentrations of total DDTs, HCHs, OCPs and PCBs in sediments were 2.84, 0.06, 3.84 and 0.17â¯ngâ¯g-1 dw, while those in tissues were 1.85, 0.22, 9.43 and 1.61â¯ngâ¯g-1 dw, respectively. The elevated OCPs and PCBs levels in mangrove leaves may be caused by atmospheric sedimentation. The biota sediment accumulation factor (BSAF) values of both OCPs (mean: 3.4) and PCBs (mean: 9.9) are generally larger than one, implying mangroves' bioaccumulation and their ability to intercept pollutants. The BSAFs of PCBs in mangrove tissues were negatively correlated with the PCB congener's octanol-water partition coefficients (KOW, Râ¯=â¯0.58, nâ¯=â¯31, pâ¯<â¯0.001), suggesting that lower chlorinated CB congeners are more bioaccumulative in mangroves. In order to better understanding the fate of these organochlorine compounds, the cycling (including the standing accumulation, the annual absorption, the annual net retention, the annual return, and the turnover period) of OCPs and PCBs in the Mangrove Reserves were estimated, and the results indicated that mangroves are playing important roles in retaining OCPs and PCBs.
Assuntos
Avicennia/metabolismo , Hidrocarbonetos Clorados/farmacocinética , Praguicidas/farmacocinética , Bifenilos Policlorados/farmacocinética , China , Monitoramento Ambiental/métodos , Sedimentos Geológicos/química , Hidrocarbonetos Clorados/análise , Praguicidas/análise , Bifenilos Policlorados/análise , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/farmacocinéticaRESUMO
Trophodynamics and chiral signatures of organochlorine pesticides (OCPs), including dichlorodiphenyltrichloroethanes (DDTs), hexachlorocyclohexanes (HCHs), and chlordanes in a food web from Zhoushan Fishing Ground, China, were studied. Residues of OCPs in all teleost fishes were within food safety levels. Strong positive correlations were found between trophic levels (TLs) and wet weight concentrations of target chemicals, with trophic magnification factors (TMFs) from 4.17 to 9.77. Lipid contents and TLs significantly correlated, which indirectly affect the bioaccumulation processes of OCPs. The consistently racemic EF values of α-HCH, as well as invariability of the relative proportions of HCH isomers in different marine species implied that HCHs in animals originate directly from the surrounding environment. However, in vivo biotransformation and/or elimination of o,p'-DDT cannot be precluded. TMFs of the individual enantiomers further suggest that the influence of achiral biotransformation is too minor to induce enantioselective biomagnification of chiral OCPs through the studied food web.
Assuntos
Cadeia Alimentar , Hidrocarbonetos Clorados/análise , Hidrocarbonetos Clorados/farmacocinética , Praguicidas/análise , Praguicidas/farmacocinética , Animais , Organismos Aquáticos , Biotransformação , Isótopos de Carbono/análise , Cetáceos/metabolismo , China , Monitoramento Ambiental , Hidrocarbonetos Clorados/química , Lipídeos/análise , Isótopos de Nitrogênio/análise , Praguicidas/química , Estereoisomerismo , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/química , Poluentes Químicos da Água/farmacocinética , Zooplâncton/química , Zooplâncton/efeitos dos fármacosRESUMO
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 JovemRESUMO
Background. Many individuals have been exposed to organochlorinated pesticides (OCPs) through food, water, air, dermal exposure, and/or vertical transmission. Due to enterohepatic reabsorption and affinity to adipose tissue, OCPs are not efficiently eliminated from the human body and may accrue in tissues. Many epidemiological studies demonstrate significant exposure-disease relationships suggesting OCPs can alter metabolic function and potentially lead to illness. There is limited study of interventions to facilitate OCP elimination from the human body. This study explored the efficacy of induced perspiration as a means to eliminate OCPs. Methods. Blood, urine, and sweat (BUS) were collected from 20 individuals. Analysis of 23 OCPs was performed using dual-column gas chromatography with electron-capture detectors. Results. Various OCPs and metabolites, including DDT, DDE, methoxychlor, endrin, and endosulfan sulfate, were excreted into perspiration. Generally, sweat samples showed more frequent OCP detection than serum or urine analysis. Many OCPs were not readily detected in blood testing while still being excreted and identified in sweat. No direct correlation was found among OCP concentrations in the blood, urine, or sweat compartments. Conclusions. Sweat analysis may be useful in detecting some accrued OCPs not found in regular serum testing. Induced perspiration may be a viable clinical tool for eliminating some OCPs.
Assuntos
Hidrocarbonetos Clorados/farmacocinética , Praguicidas/farmacocinética , Suor/química , Adulto , Idoso , Cromatografia Gasosa , DDT/farmacocinética , Diclorodifenil Dicloroetileno/farmacocinética , Endossulfano/análogos & derivados , Endossulfano/farmacocinética , Endrin/farmacocinética , Poluentes Ambientais/farmacocinética , Feminino , Humanos , Masculino , Metoxicloro/farmacocinética , Pessoa de Meia-Idade , Adulto JovemRESUMO
Organochlorine pesticides (OCPs) have caused increasing global concern due to their high toxicity, persistence, bioaccumulation, and significant adverse effects on human health. This study was to explore the interaction effects between OCPs and isoflavones. Six kinds of OCPs and 2 kinds of isoflavones-genistein and daidzein were included to study their effect on MCF-7 cells in vitro. Eighty-one female Sprague-Dawley rats were randomized to 9 groups according to factorial design to study the interaction effect between isoflavones and γ-HCH. Compared to organochlorine pesticides alone group, proliferation rate of MCF-7 cells was lower in 100 µmol/L genistein + organochlorine pesticides and 100 µmol/L daidzein + organochlorine pesticides group (p < 0.05). In vivo study showed that there are interaction effects on kidney weight and liver weight when treated with isoflavones and γ-HCH. The changes in uterine morphology and positive expression of ERα showed inhibition effects between isoflavones and γ-HCH. In conclusion, the data suggests that there are interactions between isoflavones and OCPs in vitro and in vivo.
Assuntos
Bioensaio/métodos , Poluentes Ambientais/farmacocinética , Isoflavonas/farmacocinética , Praguicidas/farmacocinética , Praguicidas/urina , Suor/metabolismo , Cromatografia Gasosa/métodos , Feminino , Humanos , Hidrocarbonetos Clorados/sangue , Hidrocarbonetos Clorados/farmacocinética , Hidrocarbonetos Clorados/urina , Isoflavonas/sangue , Isoflavonas/urina , Masculino , Pessoa de Meia-Idade , Praguicidas/sangue , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Tissue concentrations of persistent organochlorine pesticides in laboratory-exposed largemouth bass (Micropterus salmoides) and in bass collected from Lake Apopka, FL were determined by both total mass and lipid normalized mass to better understand the bioaccumulation pathways of contaminants. In the laboratory study, male bass were orally administered a single dose of a mixture of two pesticides (p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) and dieldrin) and then fed uncontaminated food for 28 days. Gastrointestinal tract, liver, brain, gonad, kidney, spleen, and muscle were collected for chemical analysis. Different profiles were observed by total contaminant mass in tissues compared to lipid normalized mass. On a lipid normalized basis, p,p'-DDE was highest in the gastrointestinal tract followed by the liver, gonad, spleen, muscle, kidney and then brain. Dieldrin, on the other hand, was highest in the gastrointestinal tract and spleen and then followed by the gonad, muscle, liver, kidney, and brain. Distribution of the chemicals among the organs differed by their log KOW values and generally followed the blood flow path after the gastrointestinal tract. The low contaminant levels found in kidney and brain suggest insufficient time for equilibration into these tissues, especially into the brain where the blood-brain barrier may be slow to traverse. In Lake Apopka fish, dichlorodiphenyltrichloroethanes (DDXs, sum of p,p'-DDE, p,p'-DDD, and p,p'-DDT), Drins (sum of aldrin, dieldrin, and endrin), and hexachlorocyclohexanes (HCHs) were found. For DDXs, the lipid normalized concentrations in each tissue were about the same, as predicted from theory. For Drins and HCHs, the lipid normalized concentrations were similar for kidney, spleen, brain, gonad and muscle, but much lower in the gastrointestinal tract and liver, probably because of metabolism occurring in those tissues.
Assuntos
Bass/metabolismo , Hidrocarbonetos Clorados/análise , Lagos/química , Praguicidas/análise , Poluentes Químicos da Água/análise , Animais , Bass/crescimento & desenvolvimento , DDT/análise , DDT/farmacocinética , Diclorodifenil Dicloroetileno/análise , Diclorodifenil Dicloroetileno/farmacocinética , Dieldrin/metabolismo , Dieldrin/farmacocinética , Hexaclorocicloexano/análise , Hexaclorocicloexano/farmacocinética , Hidrocarbonetos Clorados/farmacocinética , Masculino , Modelos Teóricos , Especificidade de Órgãos , Praguicidas/farmacocinética , Distribuição Tecidual , Poluentes Químicos da Água/farmacocinéticaRESUMO
Dechlorane Plus (DP) is a proposed alternative to the legacy flame retardant decabromodiphenyl ether (BDE-209), a major component of Deca-BDE formulations. In contrast to BDE-209, toxicity data for DP are scarce and often focused on mice. Validated dietary in vivo exposure of the marine bivalve (Mytilus galloprovincialis) to both flame retardants did not induce effects at the physiological level (algal clearance rate), but induced DNA damage, as determined by the comet assay, at all concentrations tested. Micronuclei formation was induced by both DP and BDE-209 at the highest exposure concentrations (100 and 200 µg/L, respectively, at 18% above controls). DP caused effects similar to those by BDE-209 but at lower exposure concentrations (5.6, 56, and 100 µg/L for DP and 56, 100, and 200 µg/L for BDE-209). Moreover, bioaccumulation of DP was shown to be concentration dependent, in contrast to BDE-209. The results described suggest that DP poses a greater genotoxic potential than BDE-209.
Assuntos
Éteres Difenil Halogenados/toxicidade , Hidrocarbonetos Clorados/toxicidade , Mytilus/efeitos dos fármacos , Compostos Policíclicos/toxicidade , Animais , Ensaio Cometa , Dano ao DNA/efeitos dos fármacos , Ecotoxicologia/métodos , Exposição Ambiental/efeitos adversos , Retardadores de Chama/farmacocinética , Retardadores de Chama/toxicidade , Éteres Difenil Halogenados/farmacocinética , Hidrocarbonetos Clorados/farmacocinética , Testes de Mutagenicidade/métodos , Mytilus/fisiologia , Compostos Policíclicos/farmacocinéticaRESUMO
Nonabsorbable dietary lipid reduces the absorption of dietary PCBs and increases the excretion of previously absorbed stored PCBs. Absorption of all PCB congeners will presumably be interrupted by nonabsorbable lipid; however excretion will be enhanced only for PCBs that have not been metabolized and also for their lipophilic metabolites. Our study with the nonabsorbable lipid, olestra, in a controlled trial in Anniston residents with elevated PCB levels demonstrated that it is possible to enhance removal of PCBs from the body in the clinically meaningful time frame of 1 year. The rate of disappearance of PCBs in participants who ate 15 g/day of olestra was significantly faster than the rate determined during the 5 years prior to intervention. The rate of disappearance was not changed from the pretrial rate in participants who ingested vegetable oil. Consideration of the role of body weight and fat is an important factor in the design of intervention trials of this kind, and the results of this trial suggest that the level of body fat in individuals will influence the rate of removal from the body. Previously reported data from animals and from a case report indicate that weight loss combined with nonabsorbable dietary lipid will maximize removal of PCBs and presumably other stored organochlorine compounds. The design of future intervention trials should include a focus on body fat levels and changes. Future trials should also include the testing of dietary compounds other than olestra that have affinity for PCBs, such as plant-derived polyphenols.
Assuntos
Gorduras na Dieta/administração & dosagem , Hidrocarbonetos Clorados/farmacocinética , Óleos de Plantas/administração & dosagem , Bifenilos Policlorados/farmacocinética , Tecido Adiposo , Alabama , Animais , Ácidos Graxos , Feminino , Humanos , Hidrocarbonetos Clorados/química , Aprendizagem , Lipídeos , Masculino , Bifenilos Policlorados/química , Projetos de Pesquisa , Sacarose/análogos & derivadosRESUMO
trans-Bisthioglycosylated tetrakis(fluorophenyl)chlorin (7) was designed as a powerful photodynamic therapy (PDT) photosensitizer based on the findings of our systematic studies. We show here that the trans-bisthioglycosylated structure of 7 enhanced its uptake by HeLa cells and that the chlorin ring of 7 increased the efficiency of reactive oxygen species generation under the standard condition of our photocytotoxicity test. The versatility of 7 in PDT treatment was established using weakly metastatic B16F1 melanoma cells, metastatic 4T1 breast cancer cells, the RGK-1 gastric carcinoma mucosal cell line, and three human glioblastoma cell lines (U87, U251, and T98G). The pharmacokinetics of 7 in mice bearing 4T1 breast cancer cells showed a high tumor-to-skin concentration ratio (approximately 60) at 24 h after intraperitoneal injection. The PDT efficacy of 7 in vivo was approximately 250-times higher than that of mono-l-aspartyl chlorin e6 (9) in mice bearing 4T1 breast cancer cells.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Hidrocarbonetos Clorados/química , Hidrocarbonetos Clorados/uso terapêutico , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico , Animais , Mama/efeitos dos fármacos , Mama/patologia , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Feminino , Halogenação , Humanos , Hidrocarbonetos Clorados/síntese química , Hidrocarbonetos Clorados/farmacocinética , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/farmacocinéticaRESUMO
Silicone polymers are used for a wide array of applications from passive samplers in environmental studies, to implants used in human augmentation and reconstruction. If silicone sequesters toxicants throughout implantation, it may represent a history of exposure and potentially reduce the body burden of toxicants influencing the risk of adverse health outcomes such as breast cancer. Objectives of this research included identifying a wide variety of toxicants in human silicone implants, and measuring the in vivo absorption of contaminants into silicone and surrounding tissue in an animal model. In the first study, eight human breast implants were analyzed for over 1400 organic contaminants including consumer products, chemicals in commerce, and pesticides. A total of 14 compounds including pesticides such as trans-nonachlor (1.2-5.9ng/g) and p,p'-DDE (1.2-34ng/g) were identified in human implants, 13 of which have not been previously reported in silicone prostheses. In the second project, female ICR mice were implanted with silicone and dosed with p,p'-DDE and PCB118 by intraperitoneal injection. After nine days, silicone and adipose samples were collected, and all implants in dosed mice had p,p'-DDE and PCB118 present. Distribution ratios from silicone and surrounding tissue in mice compare well with similar studies, and were used to predict adipose concentrations in human tissue. Similarities between predicted and measured chemical concentrations in mice and humans suggest that silicone may be a reliable surrogate measure of persistent toxicants. More research is needed to identify the potential of silicone implants to refine the predictive quality of chemicals found in silicone implants.
Assuntos
Tecido Adiposo/química , Implantes de Mama , Monitoramento Ambiental/métodos , Praguicidas/análise , Silicones/análise , Animais , Carga Corporal (Radioterapia) , Diclorodifenil Dicloroetileno/análise , Diclorodifenil Dicloroetileno/farmacocinética , Feminino , Humanos , Hidrocarbonetos Clorados/análise , Hidrocarbonetos Clorados/farmacocinética , Camundongos , Camundongos Endogâmicos ICR , Praguicidas/farmacocinéticaRESUMO
Chloropicrin (trichloronitromethane) is a widely used soil fumigant and an old chemical warfare agent. The metabolism of chloropicrin is not well known in mammals but nitromethane has been shown to be one of its main metabolites. Here, a fast and simple headspace gas chromatography with mass spectrometry method was applied for the measurement of nitromethane from aqueous samples. The analytical method was validated using stable isotope labeled internal standard and a small sample volume of 260 µL. No conventional sample preparation steps were needed. The method was accurate (relative standard deviations ≤1.5%) and linear (R(2) = 0.9996) within the concentration range of 0.1-6.0 µg/mL. This method was used to measure nitromethane in in vitro incubations with human and pig liver cell fractions containing enzymes for xenobiotic metabolism, exposed to chloropicrin. The results indicate that the presence of glutathione is necessary for the formation of nitromethane from chloropicrin. Also, nitromethane was formed mostly in liver cytosol fractions, but not in microsomal fractions after the incubation with chloropicrin. Our results suggest that although nitromethane is not the unequivocal biomarker of chloropicrin exposure, this method could be applied for screening the elevated levels in humans after chloropicrin exposure.
Assuntos
Hidrocarbonetos Clorados/análise , Técnicas de Diluição do Indicador , Metano/análogos & derivados , Nitroparafinas/análise , Animais , Biomarcadores/análise , Substâncias para a Guerra Química/análise , Substâncias para a Guerra Química/farmacocinética , Substâncias para a Guerra Química/toxicidade , Feminino , Fumigação , Cromatografia Gasosa-Espectrometria de Massas/métodos , Humanos , Hidrocarbonetos Clorados/farmacocinética , Hidrocarbonetos Clorados/toxicidade , Técnicas In Vitro , Fígado/efeitos dos fármacos , Fígado/metabolismo , Metano/análise , Metano/farmacocinética , Metano/toxicidade , Nitroparafinas/farmacocinética , Nitroparafinas/toxicidade , Praguicidas/análise , Praguicidas/farmacocinética , Praguicidas/toxicidade , Sus scrofaRESUMO
The feeding habits of a gray whale (Eschrichtius robustus) and a Pacific walrus (Odobenus rosmarus divergens), caught from the western Bering Sea in the summers of 2010 and 2011, have been studied, and concentration of persistent organochlorine pesticides (OCPs) in their organs determined. The total OCP concentration (∑HCH+∑DDT) in muscles and liver of the gray whales varies from 297 to 3581 and from 769 to 13,808 ng/g lipids, respectively. The total OCP concentration (∑HCH+∑DDT) in muscles and liver of the Pacific walruses varies from 197 to 5659 and from 4856 to 90,263 ng/g lipids, respectively. The specifics of diet as a source of pesticide accumulation in these two marine mammal species are discussed.
Assuntos
Hidrocarbonetos Clorados/farmacocinética , Praguicidas/farmacocinética , Morsas/metabolismo , Baleias/metabolismo , Animais , Regiões Árticas , DDT/análise , DDT/farmacocinética , Monitoramento Ambiental/métodos , Feminino , Hidrocarbonetos Clorados/análise , Fígado/metabolismo , Masculino , Músculo Esquelético/metabolismo , Oceanos e Mares , Praguicidas/análise , Distribuição Tecidual , Morsas/fisiologia , Baleias/fisiologiaRESUMO
A highly selective and sensitive method based on gas chromatography-tandem mass spectrometry (GC-MS/MS) to identify and quantify persistent organochlorine pesticides, (18 compounds including primary compounds and metabolites), in animal internal organs (kidneys, liver, and brain) has been developed. Tandem mass spectrometric conditions were individually optimized for each target compound in Multiple Reaction Monitoring (MRM) mode to obtain maximum sensitivity. Prior to instrumental analysis, a sample preparation method based on matrix solid phase dispersion (MSPD) followed by acidic digestion with sulfuric acid to reduce matrix co-extractives was employed. Analyses of real samples were carried out on coypus (Myocastor coypus) from the autumn slaughter of 19 animals. In the analyzed samples, three of the target compounds, namely DDE-pp' (DDT metabolite), HCB and lindane, were detected. Their concentration levels fell in the ranges of 0.003-0.007, 0.003-0.025, and 0.003-0.021 mg kg(-1) (0.005, 0.010, and 0.010 mg kg(-1) on average) in the case of DDE-pp', HCB and lindane, respectively. Although low quantities of organochlorine pesticides do not pose an immediate danger to consumers' health, they should be of public health concern considering long-term, low-dose exposure.
Assuntos
Hidrocarbonetos Clorados/farmacocinética , Praguicidas/análise , Praguicidas/farmacocinética , Roedores , Animais , Poluentes Ambientais/análise , Poluentes Ambientais/farmacocinética , Cromatografia Gasosa-Espectrometria de Massas/métodos , Hexaclorocicloexano/análise , Hexaclorocicloexano/farmacocinética , Hidrocarbonetos Clorados/análise , Polônia , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodos , Distribuição TecidualRESUMO
Organochlorine pesticides (OCPs) accumulated by semipermeable membrane device (SPMD) -based virtual organisms (VOs) and local feral fish were studied in Three Gorges Reservoir (TGR), China. VOs were deployed at seven sites in TGR for two periods in 2009 and 5 species of fish with different living habitats and feeding habits collected in the same periods from two counties in TGR. 28 OCPs were analyzed and the concentration and profile of OCPs in fish were quite different from those in VOs. The lipid-based concentrations of OCPs in fish ranged from 225.7 ng/g lw to 1996.4 ng/g lw which were much higher than those in VOs which ranged from 17.3 to 112.4 ng/g lw. Dichlorodiphenyltrichloroethanes (DDTs) were the prevalent OCPs in the investigated fish, while hexachlorobenzene (HCB) was the dominant compound in VOs. DDT in the few fish sample analyzed was not of concern based on chemical contaminant limits of non-carcinogenic effect.
Assuntos
Monitoramento Ambiental/métodos , Peixes/metabolismo , Hidrocarbonetos Clorados/análise , Praguicidas/análise , Poluentes Químicos da Água/análise , Recursos Hídricos , Animais , China , Hidrocarbonetos Clorados/farmacocinética , Membranas Artificiais , Modelos Teóricos , Músculo Esquelético/química , Praguicidas/farmacocinética , Poluentes Químicos da Água/farmacocinéticaRESUMO
Quantifying the competing rates of intake and elimination of persistent organic pollutants (POPs) in the human body is necessary to understand the levels and trends of POPs at a population level. In this paper we reconstruct the historical intake and elimination of ten polychlorinated biphenyls (PCBs) and five organochlorine pesticides (OCPs) from Australian biomonitoring data by fitting a population-level pharmacokinetic (PK) model. Our analysis exploits two sets of cross-sectional biomonitoring data for PCBs and OCPs in pooled blood serum samples from the Australian population that were collected in 2003 and 2009. The modeled adult reference intakes in 1975 for PCB congeners ranged from 0.89 to 24.5ng/kgbw/day, lower than the daily intakes of OCPs ranging from 73 to 970ng/kgbw/day. Modeled intake rates are declining with half-times from 1.1 to 1.3years for PCB congeners and 0.83 to 0.97years for OCPs. The shortest modeled intrinsic human elimination half-life among the compounds studied here is 6.4years for hexachlorobenzene, and the longest is 30years for PCB-74. Our results indicate that it is feasible to reconstruct intakes and to estimate intrinsic human elimination half-lives using the population-level PK model and biomonitoring data only. Our modeled intrinsic human elimination half-lives are in good agreement with values from a similar study carried out for the population of the United Kingdom, and are generally longer than reported values from other industrialized countries in the Northern Hemisphere.