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1.
Pediatrics ; 144(6)2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31685698

RESUMO

BACKGROUND: Forty-five states permit religious exemptions to school immunization laws; 15 allow personal belief exemptions. Updated religious exemption estimates are lacking, and it is unclear if personal belief exemption availability impacts religious exemption rates. We aimed to (1) update religious exemption trends in kindergartners, (2) compare states' proportions of kindergartners with religious exemptions by personal belief exemption availability, and (3) describe whether the proportion of kindergartners with religious exemptions changed in Vermont after it eliminated personal belief exemptions in 2016. METHODS: We analyzed Centers for Disease Control and Prevention data on exemptions for children entering kindergarten from 2011 to 2018, including 295 state-years in our final analysis. Using a quasi-binomial regression analysis, we compared mean proportions of kindergartners with religious exemptions in states allowing both nonmedical exemptions against states with religious exemptions only, adjusting for policy strength and school year. RESULTS: States with religious and personal belief exemptions were one-fourth as likely to have kindergartners with religious exemptions as states with religious exemptions only (risk ratio 0.25; 95% confidence interval 0.16-0.38). After Vermont's policy change, the mean proportion of kindergartners with a religious exemption increased from 0.5% to 3.7%. States were significantly more likely to have kindergartners with religious exemptions during the 2017-2018 school year compared with the 2011-2012 school year (P = .04). CONCLUSIONS: Religious exemption rates appear to be associated with personal belief exemption availability, may be subject to a replacement effect on personal belief exemption elimination, and are increasing. Researchers and policy makers should confirm findings with individual-level studies and reconsider the purpose and nature of religious exemption laws.

2.
Environ Health Perspect ; 127(9): 97009, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31566444

RESUMO

BACKGROUND: Thyroid hormone receptors (TRs) are critical endocrine receptors that regulate a multitude of processes in adult and developing organisms, and thyroid hormone disruption is of high concern for neurodevelopmental and reproductive toxicities in particular. To date, only a small number of chemical classes have been identified as possible TR modulators, and the receptors appear highly selective with respect to the ligand structural diversity. Thus, the question of whether TRs are an important screening target for protection of human and wildlife health remains. OBJECTIVE: Our goal was to evaluate the hypothesis that there is limited structural diversity among environmentally relevant chemicals capable of modulating TR activity via the collaborative interagency Tox21 project. METHODS: We screened the Tox21 chemical library (8,305 unique structures) in a quantitative high-throughput, cell-based reporter gene assay for TR agonist or antagonist activity. Active compounds were further characterized using additional orthogonal assays, including mammalian one-hybrid assays, coactivator recruitment assays, and a high-throughput, fluorescent imaging, nuclear receptor translocation assay. RESULTS: Known agonist reference chemicals were readily identified in the TR transactivation assay, but only a single novel, direct agonist was found, the pharmaceutical betamipron. Indirect activation of TR through activation of its heterodimer partner, the retinoid-X-receptor (RXR), was also readily detected by confirmation in an RXR agonist assay. Identifying antagonists with high confidence was a challenge with the presence of significant confounding cytotoxicity and other, non-TR-specific mechanisms common to the transactivation assays. Only three pharmaceuticals-mefenamic acid, diclazuril, and risarestat-were confirmed as antagonists. DISCUSSION: The results support limited structural diversity for direct ligand effects on TR and imply that other potential target sites in the thyroid hormone axis should be a greater priority for bioactivity screening for thyroid axis disruptors. https://doi.org/10.1289/EHP5314.

4.
Fam Med ; 51(3): 227-233, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30676638

RESUMO

BACKGROUND AND OBJECTIVES: There are several trends compelling physicians to acquire team-based skills for interprofessional care. One underdeveloped area of team-based skills for physicians is integrated behavioral health (IBH) in primary care. We used a Delphi method to explore what skills were needed for residents to practice integrated behavioral health. METHODS: We conducted a literature review of IBH competencies and found 41 competencies across seven domains unique to physicians. Using a modified Delphi technique, we recruited family medicine educators to rate each competency as "essential," "compatible," or "irrelevant." We also shared findings from the Delphi study with a focus group for additional feedback. RESULTS: Twenty-one participants (12 physicians, nine behavioral health providers) completed all three rounds of the Delphi survey resulting in a list of 21 competencies. The focus group gave additional feedback. CONCLUSIONS: Participants chose skills that required physicians to share responsibilities across the entire care team, were not redundant with standard primary care, and necessitated strong communication ability. Many items were revised to reflect team-based care and a prescribed physician role as a team facilitator. Next steps include determining how these competencies fit with a variety of medical providers and creating effective training programs that develop competency in IBH.


Assuntos
Medicina do Comportamento , Prestação Integrada de Cuidados de Saúde/métodos , Técnica Delfos , Medicina de Família e Comunidade/educação , Internato e Residência , Grupos Focais , Humanos , Equipe de Assistência ao Paciente , Médicos
5.
Int J Pharm Compd ; 23(1): 47-49, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30668535

RESUMO

What do you do when something goes wrong in your cleanroom? What do you do when a sterility test fails and what are the implications of such a failure? What should you do when your environmental monitoring or personnel monitoring provides results that exceed your action levels? A root cause analysis is needed in any situation where action levels are exceeded or tests are out of specification. However, should the questions be what can be done to prevent these occurrences, and how can the development be noticed before they occur? In this article, we will discuss going beyond the recommendations of United States Pharmacopeia Chapter <797> to attempt to build a program that limits the possibility of contamination through monitoring of the facility, personnel, and procedures in aseptic processing. We will also discuss other resources published by the U.S. Food and Drug Administration that address monitoring of sterile compounding and aseptic processing.


Assuntos
Composição de Medicamentos/métodos , Dano ao Paciente , Esterilização/normas , Contaminação de Medicamentos , Humanos , Controle de Qualidade , Estados Unidos
6.
Int J Pharm Compd ; 22(5): 401-404, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30384338

RESUMO

Compounders engaged in making sterile preparations need to employ a quality assurance system of documented policies and procedures to attempt to reduce the possibility of contamination. The quality-assurance program will be monitored through the facility's quality control system. Compounders should be aware of the requirements of each state they are licensed in as well as the inspection observations commonly noted in 483s issued by the U.S. Food and Drug Administration. In part 1 of this 2-part article, we discuss the currently evolving regulatory environment and why sterile compounding requires planning and monitoring to deliver quality compounds to patients. Part 2 will examine the United States Pharmacopeia's discussion on the principles of quality assurance and quality control in sterile compounding.


Assuntos
Composição de Medicamentos/normas , Contaminação de Medicamentos/prevenção & controle , Garantia da Qualidade dos Cuidados de Saúde , Controle de Qualidade , Farmacopeias como Assunto , Esterilização , Estados Unidos , United States Food and Drug Administration
7.
Int J Pharm Compd ; 22(6): 475-478, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30384348

RESUMO

Compounders engaged in making sterile preparations need to employ a quality-assurance system of documented policies and procedures to attempt to reduce the possibility of contamination. The quality-assurance program will be monitored through the facility's quality-control system. Compounders should be aware of the requirements of each state they are licensed in as well as the inspection observations commonly noted in 483s issued by the U.S. Food and Drug Administration. Part 1 of this 2-part article discussed the currently evolving regulatory environment and why sterile compounding requires planning and monitoring to deliver quality compounds to patients. Part 2 examines the United States Pharmacopeia's discussion on the principles of quality assurance and quality control in sterile compounding.


Assuntos
Serviços Comunitários de Farmácia/normas , Composição de Medicamentos/normas , Contaminação de Medicamentos/prevenção & controle , Fidelidade a Diretrizes/normas , Controle de Infecções/normas , Preparações Farmacêuticas/normas , Garantia da Qualidade dos Cuidados de Saúde/normas , United States Food and Drug Administration/normas , Antissepsia/normas , Humanos , Farmacêuticos/normas , Farmacopeias como Assunto/normas , Guias de Prática Clínica como Assunto/normas , Controle de Qualidade , Esterilização/normas , Estados Unidos
8.
FP Essent ; 471: 11-15, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30107104

RESUMO

Physician burnout affects patients and physicians. Recent studies estimate that more than half of all physicians in the United States currently are experiencing burnout. Burnout can include symptoms of emotional exhaustion, depersonalization, cognitive weariness, physical fatigue, and disengagement. It can lead to physical and psychological conditions in physicians and decrease patient safety, quality of care, and satisfaction. The health care work environment appears to be the main contributing factor in the current high rates of physician burnout. Although individual- and organizational-level interventions appear to be effective in reducing burnout, there is no conclusive evidence regarding which intervention or combination of interventions alleviates symptoms. Physicians can reduce burnout with use of mindfulness and stress management techniques. Beyond the level of the individual physician, employers and payers should recognize the benefits of supporting physician well-being and making medical practice a rewarding and healthy experience.


Assuntos
Esgotamento Profissional/etiologia , Esgotamento Profissional/prevenção & controle , Esgotamento Profissional/psicologia , Médicos de Família/psicologia , Humanos , Fatores de Risco
9.
Int J Pharm Compd ; 22(4): 303-312, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30021186

RESUMO

Compounding pharmacists must separately and collectively evaluate multiple aspects of a compounded sterile preparation when determining their beyond-use date. Considerations include the microbiological risk level, storage temperature, chemical stability, batch size, and whether or not a sterility test will be performed. The United States Pharmacopeia Chapter <797> provides guidance on the maximum beyond-use date allowed solely based on the microbiological risk level associated with the compounding of a sterile preparation. Compounders should select the shortest beyond-use date between the risk-level based beyond-use date and the chemical stability of the compound. When compounding pharmacists intend to provide a compounded sterile preparation with a beyond-use date that exceeds the risk-level based recommendations in United States Pharmacopeia Chapter <797>, they must ensure that their formulations are sterility tested in compliance with United States Pharmacopeia Chapter <71>. United States Pharmacopeia Chapter <71> compliance includes conducting method suitability that is applicable to the strength and batch size that they plan to prepare. Chemical stability must be a separate consideration for each formulation.


Assuntos
Composição de Medicamentos , Estabilidade de Medicamentos , Esterilização
11.
Crit Rev Toxicol ; 46(10): 900-910, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27848393

RESUMO

Regulatory non-clinical safety testing of human pharmaceuticals typically requires embryo-fetal developmental toxicity (EFDT) testing in two species (one rodent and one non-rodent). The question has been raised whether under some conditions EFDT testing could be limited to one species, or whether the testing in a second species could be decided on a case-by-case basis. As part of a consortium initiative, we built and queried a database of 379 compounds with EFDT studies (in both rat and rabbit animal models) conducted for marketed and non-marketed pharmaceuticals for their potential for adverse developmental and maternal outcomes, including EFDT incidence and the nature and severity of adverse findings. Manifestation of EFDT in either one or both species was demonstrated for 282 compounds (74%). EFDT was detected in only one species (rat or rabbit) in almost a third (31%, 118 compounds), with 58% (68 compounds) of rat studies and 42% (50 compounds) of rabbit studies identifying an EFDT signal. For 24 compounds (6%), fetal malformations were observed in one species (rat or rabbit) in the absence of any EFDT in the second species. In general, growth retardation, fetal variations, and malformations were more prominent in the rat, whereas embryo-fetal death was observed more often in the rabbit. Discordance across species may be attributed to factors such as maternal toxicity, study design differences, pharmacokinetic differences, and pharmacologic relevance of species. The current analysis suggests that in general both species are equally sensitive on the basis of an overall EFDT LOAEL comparison, but selective EFDT toxicity in one species is not uncommon. Also, there appear to be species differences in the prevalence of various EFDT manifestations (i.e. embryo-fetal death, growth retardation, and dysmorphogenesis) between rat and rabbit, suggesting that the use of both species has a higher probability of detecting developmental toxicants than either one alone.


Assuntos
Desenvolvimento Fetal/efeitos dos fármacos , Substâncias Perigosas/toxicidade , Modelos Animais , Testes de Mutagenicidade/métodos , Teratogênios/toxicidade , Anormalidades Induzidas por Medicamentos , Animais , Coelhos , Ratos
13.
Toxicol Sci ; 152(2): 323-39, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27208079

RESUMO

Chemical toxicity can arise from disruption of specific biomolecular functions or through more generalized cell stress and cytotoxicity-mediated processes. Here, responses of 1060 chemicals including pharmaceuticals, natural products, pesticidals, consumer, and industrial chemicals across a battery of 815 in vitro assay endpoints from 7 high-throughput assay technology platforms were analyzed in order to distinguish between these types of activities. Both cell-based and cell-free assays showed a rapid increase in the frequency of responses at concentrations where cell stress/cytotoxicity responses were observed in cell-based assays. Chemicals that were positive on at least 2 viability/cytotoxicity assays within the concentration range tested (typically up to 100 µM) activated a median of 12% of assay endpoints whereas those that were not cytotoxic in this concentration range activated 1.3% of the assays endpoints. The results suggest that activity can be broadly divided into: (1) specific biomolecular interactions against one or more targets (eg, receptors or enzymes) at concentrations below which overt cytotoxicity-associated activity is observed; and (2) activity associated with cell stress or cytotoxicity, which may result from triggering specific cell stress pathways, chemical reactivity, physico-chemical disruption of proteins or membranes, or broad low-affinity non-covalent interactions. Chemicals showing a greater number of specific biomolecular interactions are generally designed to be bioactive (pharmaceuticals or pesticidal active ingredients), whereas intentional food-use chemicals tended to show the fewest specific interactions. The analyses presented here provide context for use of these data in ongoing studies to predict in vivo toxicity from chemicals lacking extensive hazard assessment.


Assuntos
Bioensaio/métodos , Estresse Fisiológico , Testes de Toxicidade/métodos , Humanos , Técnicas In Vitro
14.
Surg Endosc ; 29(11): 3086-9, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25631109

RESUMO

INTRODUCTION: Panelists at SAGES 2013 suggested that inadvertent vagotomy was the cause of the bloating, diarrhea, and delayed gastric emptying that is sometimes seen after complex foregut reconstructions that require extensive esophageal dissection. Is it correct to ascribe these symptoms to vagotomy and imply that a drainage procedure should always accompany truncal vagotomy? To examine the long-term sequelae of truncal vagotomy alone, the present report examines clinical outcomes of 49 patients who had truncal vagotomy without drainage at the time of placement of an adjustable gastric band. METHODS: Forty-nine patients underwent truncal vagotomy with laparoscopic adjustable gastric banding in an Investigational Review Board approved clinical trial to determine whether the addition of a vagotomy would increase weight loss when compared to gastric banding alone. The details of this trial were presented at SAGES in 2010 [1]. The patients in this study have been followed for over 5 years. RESULTS: Forty-nine patients have been followed for a mean of 5.6 years. All except one have experienced a loss of hunger and cessation of gastric borborygmus. One patient showed mild delayed gastric emptying when evaluated for GERD. None of the patients experienced intractable diarrhea. CONCLUSIONS: These outcomes do not support the prevailing surgical recommendation and dogma that vagotomy should always be accompanied by a drainage procedure. Furthermore, these outcomes would suggest that it is misleading to ascribe inadvertent vagotomy as the cause of the bloating, diarrhea, and delayed gastric emptying that may occasionally be reported by patients after difficult esophageal dissections.


Assuntos
Drenagem , Gastroplastia/métodos , Laparoscopia , Complicações Pós-Operatórias/prevenção & controle , Vagotomia Troncular , Feminino , Seguimentos , Gastroparesia/etiologia , Gastroparesia/prevenção & controle , Humanos , Masculino , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos
15.
Plant Dis ; 99(7): 982-993, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30690976

RESUMO

The near-full-length 18S ribosomal DNA (rDNA) gene and internal transcribed spacer 1 region were amplified and sequenced from 52 nematode populations belonging to 28 representative species in 13 families recovered from turfgrasses in North Carolina (38 populations) and South Carolina (14 populations). This study also included 13 nematode populations from eight other plant hosts from North Carolina for comparison. Nematodes were molecularly characterized and the phylogenetic relationships were explored based on 18S rDNA sequences. Phylogenetic analysis using Bayesian inference was performed using five groups of the plant-parasitic nematode populations Tylenchids, Criconematids, Longidorids, Xiphinematids, and Trichodorids. The 65 nematode populations were clustered correspondingly within appropriate positions of 13 families, including Belonolaimidae, Caloosiidae, Criconematidae, Dolichodoridae, Hemicycliophoridae, Hoplolaimidae, Heteroderidae, Longidoridae, Meloidogynidae, Paratylenchidae, Pratylenchidae, Telotylenchidae, and Trichodoridae. This study confirms previous morphological-based identification of the plant-parasitic nematode species found in turfgrasses and provides a framework for future studies of plant-parasitic nematodes associated with turfgrasses based upon DNA sequences and phylogenetic relationships.

16.
Neurotoxicology ; 44: 204-17, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24997244

RESUMO

Spontaneous activity in neuronal cultures on microelectrode arrays (MEAs) is sensitive to effects of drugs, chemicals, and particles. Multi-well MEA (mwMEA) systems have increased throughput of MEAs, enabling their use for chemical screening. The present experiments examined a subset of EPA's ToxCast compounds for effects on spontaneous neuronal activity in primary cortical cultures using 48-well MEA plates. A first cohort of 68 compounds was selected from the ToxCast Phase I and II libraries; 37 were positive in one or more of 20 individual ToxCast Novascreen assays related to ion channels (NVS_IC), with the remainder selected based on known neuroactivity. A second cohort of 25 compounds was then tested with 20 originating from the ToxCast Phase I and II libraries (not hits in NVS_IC assays) and 5 known negatives from commercial vendors. Baseline activity (1h) was recorded prior to exposing the networks to compounds for 1h, and the weighted mean firing rate (wMFR) was determined in the absence and presence of each compound. Compounds that altered activity by greater than the weighted change of DMSO-treated wells plus 2SD were considered "hits". Of the first set of 68 compounds, 54 altered wMFR by more than the threshold, while in the second set, 13/25 compounds were hits. MEAs detected 30 of 37 (81.1%) compounds that were hits in NVS_IC assays, as well as detected known neurotoxicants that were negative in NVS_IC assays, primarily pyrethroids and GABAA receptor antagonists. Conversely, wMFR of cortical neuronal networks on MEAs was insensitive to nicotinic compounds, as only one neonicotinoid was detected by MEAs; this accounts for the bulk of non-concordant compounds between MEA and NVS_IC assays. These data demonstrate that mwMEAs can be used to screen chemicals efficiently for potential neurotoxicity, and that the results are concordant with predictions from ToxCast NVS_IC assays for interactions with ion channels.


Assuntos
Citotoxinas/toxicidade , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Testes de Toxicidade/instrumentação , Animais , Células Cultivadas , Córtex Cerebral/citologia , Microeletrodos , Ratos Long-Evans
17.
Sci Rep ; 4: 5664, 2014 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-25012808

RESUMO

The U.S. Tox21 program has screened a library of approximately 10,000 (10K) environmental chemicals and drugs in three independent runs for estrogen receptor alpha (ERα) agonist and antagonist activity using two types of ER reporter gene cell lines, one with an endogenous full length ERα (ER-luc; BG1 cell line) and the other with a transfected partial receptor consisting of the ligand binding domain (ER-bla; ERα ß-lactamase cell line), in a quantitative high-throughput screening (qHTS) format. The ability of the two assays to correctly identify ERα agonists and antagonists was evaluated using a set of 39 reference compounds with known ERα activity. Although both assays demonstrated adequate (i.e. >80%) predictivity, the ER-luc assay was more sensitive and the ER-bla assay more specific. The qHTS assay results were compared with results from previously published ERα binding assay data and showed >80% consistency. Actives identified from both the ER-bla and ER-luc assays were analyzed for structure-activity relationships (SARs) revealing known and potentially novel ERα active structure classes. The results demonstrate the feasibility of qHTS to identify environmental chemicals with the potential to interact with the ERα signaling pathway and the two different assay formats improve the confidence in correctly identifying these chemicals.


Assuntos
Receptor alfa de Estrogênio/agonistas , Receptor alfa de Estrogênio/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/farmacologia , Linhagem Celular , Genes Reporter/efeitos dos fármacos , Células HEK293 , Ensaios de Triagem em Larga Escala/métodos , Humanos , Ligantes , Ligação Proteica/efeitos dos fármacos , Relação Estrutura-Atividade
18.
Environ Sci Technol ; 48(15): 8706-16, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24960280

RESUMO

Thousands of environmental chemicals are subject to regulatory review for their potential to be endocrine disruptors (ED). In vitro high-throughput screening (HTS) assays have emerged as a potential tool for prioritizing chemicals for ED-related whole-animal tests. In this study, 1814 chemicals including pesticide active and inert ingredients, industrial chemicals, food additives, and pharmaceuticals were evaluated in a panel of 13 in vitro HTS assays. The panel of in vitro assays interrogated multiple end points related to estrogen receptor (ER) signaling, namely binding, agonist, antagonist, and cell growth responses. The results from the in vitro assays were used to create an ER Interaction Score. For 36 reference chemicals, an ER Interaction Score >0 showed 100% sensitivity and 87.5% specificity for classifying potential ER activity. The magnitude of the ER Interaction Score was significantly related to the potency classification of the reference chemicals (p < 0.0001). ERα/ERß selectivity was also evaluated, but relatively few chemicals showed significant selectivity for a specific isoform. When applied to a broader set of chemicals with in vivo uterotrophic data, the ER Interaction Scores showed 91% sensitivity and 65% specificity. Overall, this study provides a novel method for combining in vitro concentration response data from multiple assays and, when applied to a large set of ER data, accurately predicted estrogenic responses and demonstrated its utility for chemical prioritization.


Assuntos
Disruptores Endócrinos/análise , Receptor alfa de Estrogênio/agonistas , Receptor beta de Estrogênio/agonistas , Ensaios de Triagem em Larga Escala , Modelos Químicos , Algoritmos , Animais , Bioensaio , Antagonistas de Estrogênios/análise , Receptor alfa de Estrogênio/antagonistas & inibidores , Receptor beta de Estrogênio/antagonistas & inibidores , Estrogênios/análise , Humanos , Células MCF-7 , Praguicidas , Transdução de Sinais
19.
Basic Clin Pharmacol Toxicol ; 115(1): 69-76, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24684691

RESUMO

A significant challenge in toxicology is the 'too many chemicals' problem. Human beings and environmental species are exposed to tens of thousands of chemicals, only a small percentage of which have been tested thoroughly using standard in vivo test methods. This study reviews several approaches that are being developed to deal with this problem by the U.S. Environmental Protection Agency, under the umbrella of the ToxCast programme (http://epa.gov/ncct/toxcast/). The overall approach is broken into seven tasks: (i) identifying biological pathways that, when perturbed, can lead to toxicity; (ii) developing high-throughput in vitro assays to test chemical perturbations of these pathways; (iii) identifying the universe of chemicals with likely human or ecological exposure; (iv) testing as many of these chemicals as possible in the relevant in vitro assays; (v) developing hazard models that take the results of these tests and identify chemicals as being potential toxicants; (vi) generating toxicokinetics data on these chemicals to predict the doses at which these hazard pathways would be activated; and (vii) developing exposure models to identify chemicals for which these hazardous dose levels could be achieved. This overall strategy is described and briefly illustrated with recent examples from the ToxCast programme.


Assuntos
United States Environmental Protection Agency/legislação & jurisprudência , United States Environmental Protection Agency/normas , Bases de Dados Factuais , Humanos , Modelos Biológicos , Nível de Efeito Adverso não Observado , Farmacocinética , Medição de Risco , Testes de Toxicidade/métodos , Estados Unidos , Xenobióticos/toxicidade
20.
Chem Res Toxicol ; 25(7): 1287-302, 2012 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-22519603

RESUMO

The field of toxicology is on the cusp of a major transformation in how the safety and hazard of chemicals are evaluated for potential effects on human health and the environment. Brought on by the recognition of the limitations of the current paradigm in terms of cost, time, and throughput, combined with the ever increasing power of modern biological tools to probe mechanisms of chemical-biological interactions at finer and finer resolutions, 21st century toxicology is rapidly taking shape. A key element of the new approach is a focus on the molecular and cellular pathways that are the targets of chemical interactions. By understanding toxicity in this manner, we begin to learn how chemicals cause toxicity, as opposed to merely what diseases or health effects they might cause. This deeper understanding leads to increasing confidence in identifying which populations might be at risk, significant susceptibility factors, and key influences on the shape of the dose-response curve. The U. S. Environmental Protection Agency (EPA) initiated the ToxCast, or "toxicity forecaster", program 5 years ago to gain understanding of the strengths and limitations of the new approach by starting to test relatively large numbers (hundreds) of chemicals against an equally large number of biological assays. Using computational approaches, the EPA is building decision support tools based on ToxCast in vitro screening results to help prioritize chemicals for further investigation, as well as developing predictive models for a number of health outcomes. This perspective provides a summary of the initial, proof of concept, Phase I of ToxCast that has laid the groundwork for the next phases and future directions of the program.


Assuntos
Poluentes Ambientais/toxicidade , Gestão de Riscos , Bioensaio , Técnicas de Apoio para a Decisão , Poluentes Ambientais/química , Humanos , Desenvolvimento de Programas , Estados Unidos , United States Environmental Protection Agency
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