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1.
Arch Toxicol ; 93(10): 2849-2862, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31428841

RESUMO

Human biomonitoring provides information about chemicals measured in biological matrices, but their interpretation remains uncertain because of pharmacokinetic (PK) interactions. This study examined the PKs in blood from Long-Evans rats after a single oral dose of 0.4 mg/kg bw of each pesticide via a mixture of the 17 pesticides most frequently measured in humans. These pesticides are ß-endosulfan; ß-hexachlorocyclohexane [ß-HCH]; γ-hexachlorocyclohexane [γ-HCH]; carbofuran; chlorpyrifos; cyhalothrin; cypermethrin; diazinon; dieldrin; diflufenican; fipronil; oxadiazon; pentachlorophenol [PCP]; permethrin; 1,1-dichloro-2,2bis(4-chlorophenyl)ethylene [p,p'-DDE]; 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane [p,p'-DDT]; and trifluralin. We collected blood at 10 min to 48-h timepoints in addition to one sample before gavage (for a control). We used GS-MS/MS to measure the pesticide (parents and major metabolites) concentrations in plasma, determined the PK parameters from 20 sampling timepoints, and analyzed the food, litter, and cardboard in the rats' environment for pesticides. We detected many parents and metabolites pesticides in plasma control (e.g., diethyl phosphate [DEP]; PCP; 3-phenoxybenzoic acid [3-PBA]; 3,5,6-trichloro-2-pyridinol [TCPy], suggesting pre-exposure contamination. The PK values post-exposure showed that the AUC0-∞ and Cmax were highest for TCPy and PCP; ß-endosulfan, permethrin, and trifluralin presented the lowest values. Terminal T1/2 and MRT for γ-HCH and ß-HCH ranged from 74.5 h to 117.1 h; carbofuran phenol presented the shortest values with 4.3 h and 4.8 h. These results present the first PK values obtained through a realistic pattern applied to a mixture of 17 pesticides to assess exposure. This study also highlights the issues of background exposure and the need to work with a relevant mixture found in human matrices.


Assuntos
Exposição Ambiental/análise , Monitoramento Ambiental/métodos , Poluentes Ambientais/análise , Praguicidas/farmacocinética , Administração Oral , Animais , Monitoramento Biológico , Cromatografia Gasosa , Feminino , Humanos , Ratos , Ratos Long-Evans , Espectrometria de Massas em Tandem
2.
Environ Geochem Health ; 40(1): 175-187, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27783194

RESUMO

Twenty-one organochlorine pesticides (OCPs) were measured in the muscle of six predominant waterbird species from Jianghan Plain, Hubei Province, Central China. Among OCPs, DDTs were the most prevalent compounds, with average concentration ranging from 31.1 to 1445 ng/g lipid weight. Little egrets (Egretta garzetta) and Chinese pond herons (Ardeola bacchus) showed significantly higher concentrations of OCPs (p < 0.05) due to their dietary habits and migratory patterns. There were no statistically significant differences (p > 0.05) for most OCPs between sex and age groups. The accumulation profiles of HCHs and DDTs suggested that these OCPs in Jianghan Plain were largely derived from historical usage. Risk assessment indicated that heptachlor could be likely to pose adverse health effects on people consuming ducks in Jianghan Plain.


Assuntos
Agricultura , Aves , Hidrocarbonetos Clorados/análise , Praguicidas/análise , Fatores Etários , Migração Animal , Animais , Aves/classificação , Aves/fisiologia , China , Cromatografia Gasosa , Exposição Dietética , Monitoramento Ambiental , Comportamento Alimentar , Feminino , Humanos , Hidrocarbonetos Clorados/farmacocinética , Masculino , Músculos/metabolismo , Praguicidas/farmacocinética , Medição de Risco , Fatores Sexuais , Especificidade da Espécie , Distribuição Tecidual
3.
Regul Toxicol Pharmacol ; 90: 197-205, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28916468

RESUMO

Although an internationally-adopted in vitro dermal absorption test guideline is available (OECD Test Guideline 428), the replacement of the in vivo approach in North America for pesticide formulations has not occurred due to concern over the reliability and consistency of the in vitro results. A 2012 workshop convened a panel of experts in the conduct of in vitro studies used for pesticide risk assessment, together with North American regulators, to examine techniques for in vitro dermal absorption testing. Discussions led to the recommended "best practices" for the conduct of in vitro dermal absorption studies provided herein. The workshop participants also developed recommendations for reporting study results in order to improve the quality and consistency of the data submitted to regulatory agencies in North America. Finally, a case study is presented that illustrates the use of the "triple-pack" approach; the studies, conducted for the registration of sulfoxaflor, follow the standardized recommendations provided at the workshop. In addressing the concerns of these regulators and of the regulated community, and providing harmonized recommendations to facilitate comparative data analyses, it is anticipated that wider acceptance of in vitro dermal absorption studies alone can be achieved for pesticide risk assessment.


Assuntos
Exposição Ambiental/efeitos adversos , Órgãos Governamentais/normas , Praguicidas/toxicidade , Projetos de Pesquisa/normas , Absorção Cutânea , Testes de Toxicidade/normas , Administração Cutânea , Animais , Humanos , Técnicas In Vitro/métodos , Técnicas In Vitro/normas , Modelos Animais , América do Norte , Praguicidas/farmacocinética , Guias de Prática Clínica como Assunto , Ratos , Reprodutibilidade dos Testes , Medição de Risco/métodos , Pele/efeitos dos fármacos , Pele/metabolismo
4.
J Environ Sci Health B ; 52(2): 138-146, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27820679

RESUMO

Estimates of dermal permeability (Kp), obtained by fitting an updated human PBPK model for malathion to previously reported data on excreted urinary metabolites after 29 volunteers were dermally exposed to measured values of [14C]malathion dermal load (L), were used to examine the empirical relationship between Kp and L. The PBPK model was adapted from previously reported human biokinetic and PBPK models for malathion, fit to previously reported urinary excretion data after oral [14C]malathion intake by volunteers, and then augmented to incorporate a standard Kp approach to modeling dermal-uptake kinetics. Good to excellent PBPK-model fits were obtained to all of 29 sets of cumulative urinary metabolite-excretion data (ave. [±1 SD] R2 = 0.953 [±0.064]). Contrary to the assumption that Kp and L are independent typically applied for dermally administered liquids or solutions, the 29 PBPK-based estimates of Kp obtained for malathion exhibit a strong positive association with the 2/3rds power of L (log-log Pearson correlation = 0.925, p = ∼0). Possible explanations of this observation involving physico-chemical characteristics and/or in vivo cutaneous effects of malathion are discussed. The PBPK model presented, and our observation that Kp estimates obtained by fitting this model to human experimental urinary-excretion data correlate well with L2/3, allow more realistic assessments of absorbed and metabolized dose during or after a variety of scenarios involving actual or potential dermal or multi-route malathion exposures, including for pesticide workers or farmers who apply malathion to crops.


Assuntos
Malation/farmacocinética , Modelos Biológicos , Radioisótopos de Carbono/farmacocinética , Radioisótopos de Carbono/urina , Feminino , Humanos , Cinética , Malation/administração & dosagem , Masculino , Permeabilidade , Praguicidas/farmacocinética , Absorção Cutânea
5.
Mar Pollut Bull ; 111(1-2): 483-487, 2016 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-27344286

RESUMO

PCBs and OCPs were analyzed in fish (bass) taken along Chinese coastal fisheries. In the bass muscle, PCB, DDT and HCH concentrations were in the range of 1.02-2.2ng/g, 0.44-1.74 and 2.84-106.11ng/gww, respectively. Spatial distribution showed that the concentrations of target contaminants in bass from south fisheries were in general much lower than those from north fisheries in China. The ratios of OCP congeners suggested that technical DDT was not the main input and a recent usage of lindane or old technical HCH residuals could be the source of HCHs. The OCC concentrations in liver (127-442.43ng/gww) from selected samples were 8-12 and 10-14 times higher than those in gills and muscles, respectively. Based on the maximum allowable fish assumption rate (CRlim and CRmm), it could cause human health risk, by consuming bass samples taken from highly contaminated fisheries including QD and ST.


Assuntos
Bass , Hidrocarbonetos Clorados/análise , Bifenilos Policlorados/análise , Poluentes Químicos da Água/análise , Animais , China , DDT/análise , Exposição Ambiental , Monitoramento Ambiental , Pesqueiros , Contaminação de Alimentos/análise , Hexaclorocicloexano/análise , Humanos , Hidrocarbonetos Clorados/farmacocinética , Praguicidas/análise , Praguicidas/farmacocinética , Bifenilos Policlorados/farmacocinética , Medição de Risco/métodos , Distribuição Tecidual , Poluentes Químicos da Água/farmacocinética
6.
PLoS One ; 11(4): e0153287, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27070781

RESUMO

In intensive agricultural systems runoff is one of the major potential diffuse pollution pathways for pesticides and poses a risk to surface water. Ditches are common in the Po Valley and can potentially provide runoff mitigation for the protection of watercourses. The effectiveness depends on ditch characteristics, so there is an urgent need for site-specific field trials. The use of a fugacity model (multimedia model) can allows recognition of the mitigation main processes. A field experiment was conducted in order to evaluate the mitigation capacity of a typical vegetated ditch, and results were compared with predictions by a fugacity model. To evaluate herbicide mitigation after an extreme runoff, the ditch was flooded with water containing mesotrione, S-metolachlor and terbuthylazine. Two other subsequent floods with uncontaminated water were applied 27 and 82 days later to evaluate herbicides release. Results show that the ditch can immediately reduce runoff concentration of herbicides by at least 50% even in extreme flooding conditions. The half-distances were about 250 m. As a general rule, a runoff of 1 mm from 5 ha is mitigated by 99% in 100 m of vegetated ditch. Herbicides retention in the vegetated ditch was reversible, and the second flood mobilized 0.03-0.2% of the previous one, with a concentration below the drinking water limit of 0.1 µg L(-1). No herbicide was detected in the third flood, because the residual amount in the ditch was too low. Fugacity model results show that specific physical-chemical parameters may be used and a specific soil-sediment-plant compartment included for modelling herbicides behaviour in a vegetated ditch, and confirm that accumulation is low or negligible for herbicides with a half-life of 40 days or less. Shallow vegetated ditches can thus be included in a general agri-environment scheme for the mitigation of pesticides runoff together with wetlands and linear buffer strips. These structures are present in the landscape, and their environmental role can be exploited by proper management.


Assuntos
Praguicidas/toxicidade , Poluição Química da Água/prevenção & controle , Agricultura/métodos , Conservação dos Recursos Naturais , Drenagem Sanitária/métodos , Inundações , Meia-Vida , Herbicidas/farmacocinética , Herbicidas/toxicidade , Itália , Modelos Teóricos , Praguicidas/farmacocinética , Plantas/metabolismo , Gestão de Riscos , Solo/química , Poluentes Químicos da Água/farmacocinética , Poluentes Químicos da Água/toxicidade
7.
Chemosphere ; 145: 148-56, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26688251

RESUMO

Due to their widespread usage, people are exposed to pesticides on a daily basis. Although these compounds may have adverse effects on their health, there is a gap in the data and the methodology needed to reliably quantify the risks of non-occupational human dermal exposure to pesticides. We used Franz cells and human skin in order to measure the dermal absorption kinetics (steady-state flux, lag time and permeability coefficient) of Carbendazim and Simazine. These parameters were then used to refine the dermal exposure model and a probabilistic simulation was used to quantify risks resulting from exposure to pesticide-polluted waters. The experimentally derived permeability coefficient was 0.0034 cm h(-1) for Carbendazim and 0.0047 cm h(-1) for Simazine. Two scenarios (varying exposure duration and concentration, i.e. environmentally relevant and maximum solubility) were used to quantify the human health risks (hazard quotients) for Carbendazim and Simazine. While no risks were determined in the case of either scenario, the permeability coefficient, which is concentration independent and donor, formulation, compound and membrane specific, may be used in other scenarios and exposure models to quantify more precisely the dermally absorbed dose during exposure to polluted water. To the best of our knowledge, the dermal absorption kinetics parameters defined here are being published for the first time. The usage of experimental permeability parameters in combination with probabilistic risk assessment thus provides a new tool for quantifying the risks of human dermal exposure to pesticides.


Assuntos
Benzimidazóis/farmacocinética , Carbamatos/farmacocinética , Modelos Biológicos , Praguicidas/farmacocinética , Simazina/farmacocinética , Absorção Cutânea , Pele/efeitos dos fármacos , Adulto , Feminino , Humanos , Técnicas In Vitro , Cinética , Masculino , Pessoa de Meia-Idade , Permeabilidade , Medição de Risco , Pele/metabolismo
8.
Regul Toxicol Pharmacol ; 68(3): 412-23, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24491967

RESUMO

Dermal absorption is an integral part of non-dietary human safety risk assessments for agrochemicals. Typically, dermal absorption data for agrochemical active substances are generated from the undiluted formulation concentrate and its spray dilutions. European Food Safety Authority (EFSA) guidance, which combines highly conservative default values, very limited opportunities for read-across from existing data and other overly conservative conclusions, was the driver for this assessment. To investigate the reliability of the EFSA guidance, a homogeneous data-set of 190 GLP and OECD guideline compliant in vitro human skin studies, chosen to match the test method preferred by EU data requirements, was evaluated. These studies represented a wide range of active substances, formulation types, and concentrations. In alignment with EFSA guidance on human exposure assessment, a conservative estimate of absorption (95th percentile) was chosen to define defaults, which were also based on the EFSA worst-case assumption that all material in skin, excluding the first two tape strips, is absorbed. The analysis supports dermal absorption defaults of 6% for liquid concentrates, 2% for solid concentrates, and 30% for all spray dilutions, irrespective of the active substance concentration. Relatively high dermal absorption values for organic solvent-based formulations, compared to water-based or solid concentrates, support their use as worst-case surrogate data for read-across to other formulation types. The current review also shows that dermal absorption of sprays does not increase linearly with increasing dilution, and provides a novel, science-based option for extrapolation from existing data.


Assuntos
Praguicidas/farmacocinética , Absorção Cutânea , Animais , Humanos , Técnicas In Vitro , Medição de Risco , Pele/metabolismo
9.
Environ Sci Technol ; 47(9): 4365-74, 2013 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-23560461

RESUMO

Physiologically based pharmacokinetic (PBPK) modeling in marine mammals is a challenge because of the lack of parameter information and the ban on exposure experiments. To minimize uncertainty and variability, parameter estimation methods are required for the development of reliable PBPK models. The present study is the first to develop PBPK models for the lifetime bioaccumulation of p,p'-DDT, p,p'-DDE, and p,p'-DDD in harbor porpoises. In addition, this study is also the first to apply the Bayesian approach executed with Markov chain Monte Carlo simulations using two data sets of harbor porpoises from the Black and North Seas. Parameters from the literature were used as priors for the first "model update" using the Black Sea data set, the resulting posterior parameters were then used as priors for the second "model update" using the North Sea data set. As such, PBPK models with parameters specific for harbor porpoises could be strengthened with more robust probability distributions. As the science and biomonitoring effort progress in this area, more data sets will become available to further strengthen and update the parameters in the PBPK models for harbor porpoises as a species anywhere in the world. Further, such an approach could very well be extended to other protected marine mammals.


Assuntos
Teorema de Bayes , Cadeias de Markov , Método de Monte Carlo , Praguicidas/farmacocinética , Phocoena/metabolismo , Poluentes Químicos da Água/farmacocinética , Animais , DDT/farmacocinética , Diclorodifenil Dicloroetileno/farmacocinética , Diclorodifenildicloroetano/farmacocinética
10.
Environ Mol Mutagen ; 54(2): 99-111, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23355095

RESUMO

Exposure to organochlorine pesticides was studied in a group of mother-infant pairs living in a rural area where agriculture is the main economic activity. Fumigation in this zone is performed with airplanes, thus affecting the inhabited areas around them, including schools. Heparinized venous blood of mothers and umbilical cords was used to evaluate the olive tail moment in the comet assay, and micronuclei, chromatin buds, and nucleoplasmic bridges in peripheral blood lymphocytes. Cord blood samples were taken at the moment of birth only from natural and normal parturitions. Determinations of hexachlorobenzene, aldrin, heptachlor epoxide, oxichlordane, t and c-chlordane, cis-nonachlor, mirex, alpha and beta-endosulfan, alpha, beta and gamma hexachlorocyclohexane, and p'p'-DDT, p'p'-DDE were conducted to establish the differential distribution of the toxicants between compartments, i.e., mother and umbilical cord. Significantly higher pesticide levels were found in umbilical cord plasma than in mothers' plasma for almost all compounds tested, except DDE and oxychlordane. Significantly higher olive tail moments were found in umbilical cords than in mothers, whereas micronuclei frequencies were higher in mothers than in umbilical cords. However, neither the levels of micronuclei nor the olive tail moment were correlated with pesticide levels. Given that no other exposure to toxic compounds has been identified in this region, the lack of correlation between genotoxicity biomarkers and pesticide levels may be due to the variability of the exposure and to endogenous processes related to lipid mobility during pregnancy, the metabolism of the compounds, and individual susceptibilities.


Assuntos
Agricultura , Dano ao DNA , Exposição Ambiental/análise , Hidrocarbonetos Clorados/sangue , Troca Materno-Fetal , Praguicidas/sangue , Ensaio Cometa , Exposição Ambiental/efeitos adversos , Monitoramento Ambiental/métodos , Monitoramento Ambiental/estatística & dados numéricos , Feminino , Sangue Fetal/citologia , Humanos , Hidrocarbonetos Clorados/farmacocinética , Hidrocarbonetos Clorados/toxicidade , Recém-Nascido , Limite de Detecção , Linfócitos/patologia , Exposição Materna/efeitos adversos , Troca Materno-Fetal/genética , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Testes para Micronúcleos , Praguicidas/farmacocinética , Praguicidas/toxicidade , Gravidez , População Rural
11.
J Chem Inf Model ; 52(11): 3099-105, 2012 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-23092397

RESUMO

Absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties play key roles in the discovery/development of drugs, pesticides, food additives, consumer products, and industrial chemicals. This information is especially useful when to conduct environmental and human hazard assessment. The most critical rate limiting step in the chemical safety assessment workflow is the availability of high quality data. This paper describes an ADMET structure-activity relationship database, abbreviated as admetSAR. It is an open source, text and structure searchable, and continually updated database that collects, curates, and manages available ADMET-associated properties data from the published literature. In admetSAR, over 210,000 ADMET annotated data points for more than 96,000 unique compounds with 45 kinds of ADMET-associated properties, proteins, species, or organisms have been carefully curated from a large number of diverse literatures. The database provides a user-friendly interface to query a specific chemical profile, using either CAS registry number, common name, or structure similarity. In addition, the database includes 22 qualitative classification and 5 quantitative regression models with highly predictive accuracy, allowing to estimate ecological/mammalian ADMET properties for novel chemicals. AdmetSAR is accessible free of charge at http://www.admetexp.org.


Assuntos
Algoritmos , Aditivos Alimentares/química , Praguicidas/química , Medicamentos sob Prescrição/química , Software , Animais , Qualidade de Produtos para o Consumidor , Bases de Dados de Compostos Químicos , Aditivos Alimentares/farmacocinética , Aditivos Alimentares/toxicidade , Humanos , Internet , Modelos Logísticos , Praguicidas/farmacocinética , Praguicidas/toxicidade , Medicamentos sob Prescrição/farmacocinética , Medicamentos sob Prescrição/toxicidade , Relação Estrutura-Atividade
12.
J Expo Sci Environ Epidemiol ; 22(6): 574-83, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22692365

RESUMO

Semi-volatile chemicals like pesticides and polychlorinated biphenyls (PCB) tend to accumulate in house dust. This may result in residues of some parts per million (p.p.m.), closely associated with health impairments and diseases like cancer. To explain these associations, we must establish whether a relevant absorption from house dust into human organisms occurs, and most crucially the release of chemicals, that is, their bioaccessibility. Digestive as well as dermal bioaccessibilities were examined using in-vitro methods. On average, the digestive bioaccessibility was ~40% for the pesticides and ~60% for the PCB. The dermal penetration availability reached ~60% for the pesticides and ~70% for the PCB (percentages of the concentrations in the dust). Based on the bioaccessibility, an estimate of internal exposure was calculated and expressed as percentages of acceptable or tolerable daily intake (ADI/TDI) values. Exposure via the respiratory tract proved to be very low. Exposure via the digestive tract had maximum values of 4% for pesticides and 12% for PCB. Dermal exposure was much higher. Even for average concentrations in house dust (≈0.5 p.p.m.), children exposed to DDT and PCB showed up to 300% of the ADI/TDI values, and adults about 60%. With high concentrations of contaminants in house dust, the maximum doses absorbed through the skin reached 5000%.


Assuntos
Poeira , Exposição Ambiental , Praguicidas/farmacocinética , Bifenilos Policlorados/farmacocinética , Disponibilidade Biológica , Feminino , Humanos , Técnicas In Vitro , Masculino
13.
Neurotoxicology ; 33(4): 823-32, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22327016

RESUMO

Most human health risk assessments are based on animal studies that can be conducted under conditions where exposure to multiple doses of a single chemical can be controlled. Data from epidemiology studies also provide valuable information about human exposure and response to pesticides. Human studies have the potential of evaluating neurobehavioral and other outcomes that may be more difficult to evaluate in animals. The human data together with animal data can contribute to a weight-of-evidence analysis in the characterization of human health risks. Epidemiology data do, however, pose challenges with respect to characterizing human health risks. Similarly, animal data at high doses or routes of exposure not typical for humans also pose challenges to dose-response evaluations needed for risk assessments. This paper summarizes some of the presentations given at a symposium held at the Xi'an, China, International Neurotoxicology Conference held in June 2011. This symposium brought together scientists from government, industry and academia to discuss approaches to evaluating and conducting animal and human neurotoxicity studies for risk assessment purposes, using the pesticides paraquat and chlorpyrifos as case studies.


Assuntos
Projetos de Pesquisa Epidemiológica , Síndromes Neurotóxicas/epidemiologia , Testes de Toxicidade , Animais , Clorpirifos/efeitos adversos , Clorpirifos/farmacocinética , Relação Dose-Resposta a Droga , Humanos , Modelos Animais , Paraquat/efeitos adversos , Paraquat/farmacocinética , Praguicidas/efeitos adversos , Praguicidas/farmacocinética , Medição de Risco , Fatores de Risco , Testes de Toxicidade/métodos
14.
Artigo em Inglês | MEDLINE | ID: mdl-21660819

RESUMO

Chloro-s-triazines have been a mainstay of preemergent pesticides for a number of decades and have generally been regarded as having low human toxicity. Atrazine, the major pesticide in this class, has been extensively studied. In a number of experimental studies, exposure to high doses of atrazine resulted in increased weight loss not attributable to decreased food intake. Chronic studies of atrazine and simazine and their common metabolites show an elevated incidence of mammary tumors only in female Sprague Dawley (SD) rats. On the basis of the clear tumor increase in female SD rats, atrazine was proposed to be classified as a likely human carcinogen by US Environmental Protection Agency (EPA) in 1999. With Fischer rats, all strains of mice, and dogs, there was no evidence of increased incidence of atrazine-associated tumors of any type. Evidence related to the pivotal role of hormonal control of the estrus cycle in SD rats appears to indicate that the mechanism for mammary tumor induction is specific to this strain of rats and thus is not relevant to humans. In humans the menstrual cycle is controlled by estrogen released by the ovary rather than depending on the LH surge, as estrus is in SD rats. However, the relevance of the tumors to humans continues to be debated based on endocrine effects of triazines. No strong evidence exists for atrazine mutagenicity, while there is evidence of clastogenicity at elevated concentrations. Atrazine does not appear to interact strongly with estrogen receptors α or ß but may interact with putative estrogen receptor GPR30 (G-protein-coupled receptor). A large number of epidemiologic studies conducted on manufacturing workers, pesticide applicators, and farming families do not indicate that triazines are carcinogenic in these populations. A rat-specific hormonal mechanism for mammary tumors has now been accepted by US EPA, International Agency for Research on Cancer, and the European Union. Chlorotriazines do influence endocrine responses, but their potential impact on humans appears to be primarily on reproduction and development and is not related to carcinogenesis.


Assuntos
Atrazina/toxicidade , Carcinógenos Ambientais/toxicidade , Praguicidas/toxicidade , Reprodução/efeitos dos fármacos , Triazinas/toxicidade , Animais , Atrazina/química , Atrazina/farmacocinética , Testes de Carcinogenicidade , Carcinógenos Ambientais/química , Carcinógenos Ambientais/farmacocinética , Cães , Sistema Endócrino/efeitos dos fármacos , Exposição Ambiental/análise , Estro/efeitos dos fármacos , Feminino , Humanos , Masculino , Neoplasias Mamárias Animais/induzido quimicamente , Camundongos , Testes de Mutagenicidade , Praguicidas/química , Praguicidas/farmacocinética , Ratos , Ratos Endogâmicos F344 , Ratos Long-Evans , Medição de Risco , Triazinas/química , Triazinas/farmacocinética
15.
Environ Health Perspect ; 118(1): 125-30, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20056589

RESUMO

BACKGROUND: A physiologically based pharmacokinetic (PBPK) model would make it possible to simulate the dynamics of chemical absorption, distribution, metabolism, and elimination (ADME) from different routes of exposures and, in theory, could be used to evaluate associations between exposures and biomarker measurements in blood or urine. OBJECTIVE: We used a PBPK model to predict urinary excretion of 3,5,6-trichloro-2-pyridinol (TCPY), the specific metabolite of chlorpyrifos (CPF), in young children. METHODS: We developed a child-specific PBPK model for CPF using PBPK models previously developed for rats and adult humans. Data used in the model simulation were collected from 13 children 36 years of age who participated in a cross-sectional pesticide exposure assessment study with repeated environmental and biological sampling. RESULTS: The model-predicted urinary TCPY excretion estimates were consistent with measured levels for 2 children with two 24-hr duplicate food samples that contained 350 and 12 ng/g of CPF, respectively. However, we found that the majority of model outputs underpredicted the measured urinary TCPY excretion. CONCLUSIONS: We concluded that the potential measurement errors associated with the aggregate exposure measurements will probably limit the applicability of PBPK model estimates for interpreting urinary TCPY excretion and absorbed CPF dose from multiple sources of exposure. However, recent changes in organophosphorus (OP) use have shifted exposures from multipathways to dietary ingestion only. Thus, we concluded that the PBPK model is still a valuable tool for converting dietary pesticide exposures to absorbed dose estimates when the model input data are accurate estimates of dietary pesticide exposures.


Assuntos
Modelos Biológicos , Praguicidas/farmacocinética , Praguicidas/toxicidade , Adulto , Animais , Biomarcadores/urina , Criança , Pré-Escolar , Clorpirifos/farmacocinética , Clorpirifos/toxicidade , Estudos Transversais , Exposição Ambiental , Monitoramento Ambiental , Contaminação de Alimentos/análise , Humanos , Resíduos de Praguicidas/urina , Piridonas/urina , Ratos , Medição de Risco
16.
Integr Zool ; 5(1): 37-43, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21392320

RESUMO

In New Zealand, the vertebrate pesticide sodium fluoroacetate (Compound 1080) is aerially applied in baits for control of the brush-tailed possum Trichosurus vulpecula (Kerr, 1792). Maori, the indigenous people of New Zealand, have raised concerns about 1080 impacts on culturally-important species. Here, we outline two steps taken to help Maori assess 1080 risk. First, field research was undertaken to determine if naturally-occurring plants utilized by a Maori community for food and medicine would take up 1080 from baits. Single baits were placed at the base of individual plants of two species, pikopiko (Asplenium bulbiferum) and karamuramu (Coprosma robusta). Plants were sampled at various times up to 56 days, and samples were analyzed for 1080 content. No 1080 was detected in any of the pikopiko samples, whereas 1080 was detected in karamuramu, at a maximum concentration of 5 ppb after seven days, and 2.5 ppb after 14 days. This concentration decreased to 0 at 28 days, indicating that 1080 was not persistent. The results of the present study suggest there is negligible risk of humans being poisoned by consuming plants that have taken up 1080 from baits. To allay community concerns that minute concentrations of 1080 might influence the medicinal properties of plants, it is suggested that a withholding period of 30 days after 1080 control operations could be adopted. Second, after further consultation we undertook a review of the scientific literature relating to 1080 impacts on additional non-target species of cultural importance to Maori. The information was presented on an interactive foodweb database that allowed the collection and presentation of a large volume of complex information about 1080 in a holistic and pictorial fashion. This database was presented to many Maori communities throughout New Zealand, and feedback was overwhelmingly positive. The database is likely to play a key role in informing these communities about 1080, and is seen as an important new tool to help these communities make their own risk assessments.


Assuntos
Gleiquênias/efeitos dos fármacos , Fluoracetatos/toxicidade , Controle de Pragas/métodos , Praguicidas/toxicidade , Rubiaceae/efeitos dos fármacos , Trichosurus/metabolismo , Animais , Bases de Dados Factuais , Gleiquênias/metabolismo , Fluoracetatos/farmacocinética , Humanos , Nova Zelândia , Praguicidas/farmacocinética , Grupos Populacionais , Medição de Risco , Rubiaceae/metabolismo , Fatores de Tempo
18.
Ecotoxicol Environ Saf ; 67(3): 333-40, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17239949

RESUMO

The hard clam is an economically important bivalve and is abundant along the East Coast of the US. The goal of this research was to evaluate the sensitivity of this test species as compared to that of other benthic and epibenthic organisms. Toxic effects of cadmium (inorganic metal), DDT (organochlorine pesticide), and fluoranthene (polycyclic aromatic hydrocarbon) exposure in sediments (10-day) and seawater (24-h) on juvenile (212-350-microm) hard clams Mercenaria mercenaria were determined. The aqueous 24-h LC(50) values were 0.42 mg/L cadmium (95% CL=0.35-0.45 mg/L), 0.61 mg/L DDT (95% CL=0.40-0.95 mg/L), and 0.65 mg/L fluoranthene (95% CL=0.44-1.23 mg/L). Results of sediment toxicity tests indicated that the 10-day LC(50) values were 1.66 mg/kg cadmium (95% CL=1.21-2.28 mg/kg), 5.8 mg/kg DDT (95% CL=4.8-8.3mg/kg), and 1.75 mg/kg fluoranthene (95% CL=1.38-2.09 mg/kg). Based on comparisons to toxicity data for other marine species, these findings suggest that the juvenile clam is one of the more sensitive species to a variety of contaminants and may be a valuable indicator for potential sediment toxicity.


Assuntos
Bioensaio/métodos , Exposição Ambiental , Sedimentos Geológicos/química , Mercenaria/efeitos dos fármacos , Poluentes Químicos da Água/análise , Animais , Cádmio/farmacocinética , Cádmio/toxicidade , DDT/farmacocinética , DDT/toxicidade , Fluorenos/farmacocinética , Fluorenos/toxicidade , Dose Letal Mediana , Mercenaria/fisiologia , Praguicidas/farmacocinética , Praguicidas/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/farmacocinética , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Água do Mar , Fatores de Tempo , Poluentes Químicos da Água/toxicidade
19.
Med Lav ; 97(2): 430-7, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17017381

RESUMO

Nearly 50% of the world labour force is employed in agriculture. Over the last 50 years, agriculture has deeply changed with a massive utilisation of pesticides and fertilisers to enhance crop protection and production, food quality and food preservation. Pesticides are also increasingly employed for public health purposes and for domestic use. Pesticide are unique chemicals as they are intrinsically toxic for several biological targets, are deliberately spread into the environment, and their toxicity has a limited species selectivity. Pesticide toxicity depends on the compound family and is generally greater for the older compounds; in humans, they are responsible for acute poisonings as well as for long term health effects, including cancer and adverse effects on reproduction. Due to their intrinsic toxicity, in most countries a specific and complex legislation prescribes a thorough risk assessment process for pesticides prior to their entrance to the market (pre-marketing risk assessment). The post-marketing risk assessment takes place during the use of pesticides and aims at assessing the risk for exposed operators. The results of the risk assessment are the base for the health surveillance of exposed workers. Occupational exposure to pesticides in agriculture concerns product distributors, mixers and loaders, applicators, bystanders, and rural workers re-entering the fields shortly after treatment. Assessing and managing the occupational health risks posed by the use of pesticides in agriculture is a complex but essential task for occupational health specialists and toxicologists. In spite of the economic and social importance of agriculture, the health protection of agricultural workforce has been overlooked for too many years, causing an heavy tribute paid in terms of avoidable diseases, human sufferance, and economic losses. Particularly in the developing countries, where agricultural work is one of the predominant job, a sustainable model of development calls for more attention to occupational risks in agriculture. The experience of many countries has shown that prevention of health risk caused by pesticides is technically feasible and economically rewarding for the individuals and the whole community. A proper risk assessment and management of pesticide use is an essential component of this preventative


Assuntos
Doenças dos Trabalhadores Agrícolas/induzido quimicamente , Agricultura , Praguicidas/efeitos adversos , Medição de Risco , Gestão de Riscos , Doenças dos Trabalhadores Agrícolas/diagnóstico , Doenças dos Trabalhadores Agrícolas/epidemiologia , Doenças dos Trabalhadores Agrícolas/prevenção & controle , Agricultura/legislação & jurisprudência , Diagnóstico Precoce , União Europeia , Contaminação de Alimentos , Humanos , Exposição por Inalação , Marketing/legislação & jurisprudência , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/legislação & jurisprudência , Exposição Ocupacional/normas , Resíduos de Praguicidas/efeitos adversos , Resíduos de Praguicidas/análise , Praguicidas/análise , Praguicidas/farmacocinética , Praguicidas/normas , Vigilância da População , Vigilância de Produtos Comercializados/normas , Risco , Medição de Risco/legislação & jurisprudência , Medição de Risco/métodos , Gestão de Riscos/legislação & jurisprudência , Gestão de Riscos/métodos , Absorção Cutânea , Estados Unidos
20.
Sci Total Environ ; 366(1): 148-53, 2006 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-16797674

RESUMO

In order to reveal the efficacy of the Artemia cysts chorion as barrier to the organophosphorus pesticide chlorpyrifos, whole and decapsulated cysts have been exposed to 10 mg L(-1) chlorpyrifos in sea water during hydration and hatching phase, separately. The concentration of chlorpyrifos in capsulated and decapsulated cysts after exposure has been determined in order to elucidate the efficacy of chorion as protection to the embryo. The results obtained demonstrate the ability of the cysts chorion to obstruct the pass of chlorpyrifos molecules through this protection structure. Thus, the concentration of chlorpyrifos in exposed decapsulated cysts is higher than in exposed whole cysts. Moreover, after removing the chorion of exposed cysts, the concentration of chlorpyrifos in the embryo was lower than that of cysts exposed, what would demonstrate the retention of chlorpyrifos molecules by the shell. Hatching was not severely affected by exposure to the insecticide whereas survival at 44 h of the nauplii exposed to chlorpyrifos was significantly different from the controls. Survival of nauplii hatched from exposed decapsulated cysts was higher than that from those hatched from exposed whole cysts, probably because of the lower vitality of the latter, due to depletion of energy reserves during hatching.


Assuntos
Clorpirifos/toxicidade , Crustáceos/efeitos dos fármacos , Praguicidas/toxicidade , Taxa de Sobrevida , Poluentes Químicos da Água/toxicidade , Animais , Clorpirifos/farmacocinética , Crustáceos/embriologia , Crustáceos/fisiologia , Monitoramento Ambiental , Peixes , Cadeia Alimentar , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Compostos Organofosforados/farmacocinética , Compostos Organofosforados/toxicidade , Praguicidas/farmacocinética , Água do Mar , Fatores de Tempo , Poluentes Químicos da Água/farmacocinética
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