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1.
Popul Stud (Camb) ; 74(1): 23-38, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31699001

RESUMO

This study estimates the future utilization of medically assisted fertility treatments in Australia, focusing on assisted reproductive technologies (ARTs), intrauterine insemination (IUI), and ovulation induction. A multistate cohort component population projection model is used to determine future fertility rates from 2016 to 2026 by age and education level. These are combined with information on recent trends in use and success rates to indirectly estimate future age-specific probabilities of fertility treatment utilization. The number of ART cycles is expected to increase by 61 per cent between 2016 and 2026 if treatment success rates remain at 2015 levels, or by 34 per cent if recent improvements in ART success rates continue. The model also predicts that numbers of IUI cycles and ovulation induction cycles will decrease by 17 and 3 per cent, respectively. This research confirms the importance of including both technological improvements and socio-demographic changes when predicting future fertility treatment utilization.


Assuntos
Técnicas de Reprodução Assistida/tendências , Adolescente , Adulto , Fatores Etários , Austrália , Escolaridade , Feminino , Humanos , Inseminação Artificial/tendências , Estudos Longitudinais , Pessoa de Meia-Idade , Indução da Ovulação/tendências , Gravidez , Fatores Socioeconômicos , Adulto Jovem
2.
Hum Reprod ; 34(11): 2173-2183, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31725877

RESUMO

STUDY QUESTION: How did general practitioners (GPs) (family physicians) manage infertility in females and males in primary care between 2000 and 2016? SUMMARY ANSWER: The number of GP infertility consultations for females increased 1.6 folds during the study period, with 42.9% of consultations resulting in a referral to a fertility clinic or specialist, compared to a 3-fold increase in the number of consultations for men, with 21.5% of consultations resulting in a referral. WHAT IS KNOWN ALREADY: Infertility affects one in six couples and is expected to increase with the trend to later childbearing and reports of declining sperm counts. Despite GPs often being the first contact for infertile people, very limited information is available on the management of infertility in primary care. STUDY DESIGN, SIZE, DURATION: Data from the Bettering the Evaluation and Care of Health programme were used, which is a national study of Australian primary care (general practice) clinical activity based on 1000 ever-changing, randomly selected GPs involved in 100 000 GP-patient consultations per year between 2000 and 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS: Females and males aged 18-49 years attending GPs for the management of infertility were included in the study. Details recorded by GPs included patient characteristics, problems managed and management actions (including counselling/education, imaging, pathology, medications and referrals to specialists and fertility clinics). Analyses included trends in the rates of infertility consultations by sex of patient, descriptive and univariate analyses of patient characteristics and management actions and multivariate logistic regression to determine which patient and GP characteristics were independently associated with increased rates of infertility management and referrals. MAIN RESULTS AND THE ROLE OF CHANCE: The rate of infertility consultations per capita increased 1.6 folds for women (17.7-28.3 per 1000 women aged 18-49 years) and 3 folds for men over the time period (3.4-10.2 per 1000 men aged 18-49 years). Referral to a fertility clinic or relevant specialist occurred in 42.9% of female infertility consultations and 21.5% of male infertility consultations. After controlling for age and other patient characteristics, being aged in their 30s, not having income assistance, attending primary care in later years of the study and coming from a non-English-speaking background, were associated with an increased likelihood of infertility being managed in primary care. In female patients, holding a Commonwealth concession card (indicating low income), living in a remote area and having a female GP all indicated a lower adjusted odds of referral to a fertility clinic or specialist. LIMITATIONS, REASONS FOR CAUTION: Data are lacking for the period of infertility and infertility diagnosis, which would provide a more complete picture of the epidemiology of treatment-seeking behaviour for infertility. Australia's universal insurance scheme provides residents with access to a GP, and therefore these findings may not be generalizable to other settings. WIDER IMPLICATIONS OF THE FINDINGS: This study informs public policy on how infertility is managed in primary care in different patient groups. Whether the management actions taken and rates of secondary referral to a fertility clinic or specialist are appropriate warrants further investigation. The development of clinical practice guidelines for the management of infertility would provide a standardized approach to advice, investigations, treatment and referral pathways in primary care. STUDY FUNDING/COMPETING INTEREST(S): This paper is part of a study being funded by an Australian National Health and Medical Research Council project grant APP1104543. G.C. reports that she is an employee of The University of New South Wales (UNSW) and Director of the National Perinatal Epidemiology and Statistics Unit (NPESU), UNSW. The NPESU manages the Australian and New Zealand Assisted Reproductive Technology Database on behalf of the Fertility Society of Australia. W.L. reports being a part-time paid employee and minor shareholder of Virtus Health, a fertility company. R.N. reports being a small unitholder in a fertility company, receiving grants for research from Merck and Ferring and speaker travel grants from Merck. TRIAL REGISTRATION NUMBER: NA.


Assuntos
Infertilidade Feminina/terapia , Infertilidade Masculina/terapia , Atenção Primária à Saúde , Encaminhamento e Consulta , Adolescente , Adulto , Austrália/epidemiologia , Feminino , Fertilização in vitro , Clínicos Gerais , Acessibilidade aos Serviços de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Gravidez , Contagem de Espermatozoides , Adulto Jovem
3.
Demography ; 55(5): 1777-1802, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30264185

RESUMO

Australia has one of the largest percentages of immigrant populations in the developed world with a highly regulated system of immigration control and regular censuses to track their changes over time. However, the ability to explain the population change through the demographic components of immigration, emigration, and death by age and sex is complicated because of differences in measurement and sources of information. In this article, we explore three methods for reconciling the demographic accounts from 1981 to 2011 for the Australia-born and 18 foreign-born population groups. We then describe how the immigrant populations have changed and what has contributed most to that change. We find that the sources of immigrant population change have varied considerably by age, sex, country of birth, and period of immigration. Immigrants from Europe are currently the oldest and slowest-growing populations, whereas those from elsewhere are growing rapidly and exhibit relatively young population age structures. Studying these patterns over time helps us to understand the nature of international migration and its long-term contributions to population change and composition.


Assuntos
Diversidade Cultural , Dinâmica Populacional/tendências , Grupos Raciais/estatística & dados numéricos , Distribuição por Idade , Austrália/epidemiologia , Censos , Coleta de Dados/métodos , Demografia , Emigrantes e Imigrantes , Humanos , Distribuição por Sexo , Fatores Socioeconômicos
4.
Popul Stud (Camb) ; 72(3): 339-355, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29873285

RESUMO

International migration flows are considered the most difficult demographic component to forecast and, for that reason, models for forecasting migration are few and relatively undeveloped. This is worrying because, in developed societies, international migration is often the largest component of population growth and most influential in debates about societal and economic change. In this paper, we address the need for better forecasting models of international migration by testing a hierarchical (bilinear) model within the Bayesian inferential framework, recently developed to forecast age and sex patterns of immigration and emigration in the United Kingdom, on other types of migration flow data: age- and sex-specific time series from Sweden, South Korea, and Australia. The performances of the forecasts are compared and assessed with the observed time-series data. The results demonstrate the generality and flexibility of the model and of Bayesian inference for forecasting migration, as well as for further research.


Assuntos
Emigração e Imigração/estatística & dados numéricos , Modelos Teóricos , Fatores Etários , Austrália , Teorema de Bayes , Países Desenvolvidos , Humanos , Dinâmica Populacional , Reprodutibilidade dos Testes , República da Coreia , Fatores Sexuais , Suécia
5.
BMC Nephrol ; 15: 125, 2014 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-25069485

RESUMO

The recent emergence of an apparently new form of chronic kidney disease of unknown aetiology (CKDu) has become a serious public health crisis in Sri Lanka. CKDu is slowly progressive, irreversible, and asymptomatic until late stages, and is not attributable to hypertension, diabetes, or other known aetiologies. In response to the scope and severity of the emerging CKDu health crisis, the Sri Lanka Ministry of Health and the World Health Organization initiated a collaborative research project from 2009 through 2012 to investigate CKDu prevalence and aetiology. The objective of this paper is to discuss the recently published findings of this investigation and present additional considerations and recommendations that may enhance subsequent investigations designed to identify and understand CKDu risk factors in Sri Lanka or other countries.


Assuntos
Países em Desenvolvimento/estatística & dados numéricos , Exposição Ambiental/estatística & dados numéricos , Intoxicação por Metais Pesados , Intoxicação/epidemiologia , Feminino , Humanos , Masculino
6.
J Environ Monit ; 14(1): 85-93, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22048778

RESUMO

An observational field study was conducted to assess the feasibility of a community duplicate diet collection method; a dietary monitoring tool that is population-based. The purpose was to establish an alternative procedure to duplicate diet sampling that would be more efficient for a large, defined population, e.g., in the National Children's Study (NCS). Questionnaire data and food samples were collected in a residence so as not to lose the important component of storage, preparation, and handling in a contaminated microenvironment. The participants included nine Hispanic women of child bearing age living in Apopka, FL, USA. Foods highly consumed by Hispanic women were identified based on national food frequency questionnaires and prioritized by permethrin residue concentrations as measured for the Pesticide Data Program. Participants filled out questionnaires to determine if highly consumed foods were commonly eaten by them and to assess the collection protocol for the food samples. Measureable levels of permethrin were found in 54% of the samples. Questionnaire responses indicated that the collection of the community duplicate diet was feasible for a defined population.


Assuntos
Inquéritos sobre Dietas/métodos , Dieta/estatística & dados numéricos , Exposição Ambiental/análise , Poluentes Ambientais/análise , Contaminação de Alimentos/estatística & dados numéricos , Praguicidas/análise , Características de Residência/estatística & dados numéricos , Adolescente , Adulto , Exposição Ambiental/estatística & dados numéricos , Poluição Ambiental/estatística & dados numéricos , Feminino , Análise de Alimentos , Humanos , Pessoa de Meia-Idade , Compostos Organofosforados/análise , Ácidos Ftálicos/análise , Piretrinas/análise , Inquéritos e Questionários , Adulto Jovem
7.
Environ Plan A ; 44(11): 2664-2686, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23236221

RESUMO

Population projection models that introduce uncertainty are a growing subset of projection models in general. In this paper, we focus on the importance of decisions made with regard to the model specifications adopted. We compare the forecasts and prediction intervals associated with four simple regional population projection models: an overall growth rate model, a component model with net migration, a component model with in-migration and out-migration rates, and a multiregional model with destination-specific out-migration rates. Vector autoregressive models are used to forecast future rates of growth, birth, death, net migration, in-migration and out-migration, and destination-specific out-migration for the North, Midlands and South regions in England. They are also used to forecast different international migration measures. The base data represent a time series of annual data provided by the Office for National Statistics from 1976 to 2008. The results illustrate how both the forecasted subpopulation totals and the corresponding prediction intervals differ for the multiregional model in comparison to other simpler models, as well as for different assumptions about international migration. The paper ends end with a discussion of our results and possible directions for future research.

8.
Popul Res Policy Rev ; 41(5): 1917-1930, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35992563

RESUMO

International migration is an important source of population change and economic development for Pacific Island countries. Migration from the Pacific Island region contributes to labour recruitment in countries like Australia, New Zealand and the United States. However, there are substantial gaps in the understanding of overall migration patterns in this region, impeding the development of relevant policies. In the absence of good migration statistics, we propose and present an alternative approach to examining the levels of migration in the Pacific Island region using model-based estimates. Three sets of recently produced migration flow estimates are consulted to explore the immigration and emigration levels and key migration corridors in the Pacific Island region between 2000 and 2019. Where reported migration statistics are available, we evaluate the performance of model-based estimates and highlight if there are problems with the reported data. This research brief demonstrates the value of model-based estimates to inform migration in the Pacific Island region.

9.
Toxicol Appl Pharmacol ; 242(3): 290-8, 2010 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-19883674

RESUMO

Polybrominated diphenyl ethers (PBDEs) are used commercially as additive flame retardants and have been shown to transfer into environmental compartments, where they have the potential to bioaccumulate in wildlife and humans. Of the 209 possible PBDEs, 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) is usually the dominant congener found in human blood and milk samples. BDE-47 has been shown to have endocrine activity and produce developmental, reproductive, and neurotoxic effects. The objective of this study was to develop a physiologically based pharmacokinetic (PBPK) model for BDE-47 in male and female (pregnant and non-pregnant) adult rats to facilitate investigations of developmental exposure. This model consists of eight compartments: liver, brain, adipose tissue, kidney, placenta, fetus, blood, and the rest of the body. Concentrations of BDE-47 from the literature and from maternal-fetal pharmacokinetic studies conducted at RTI International were used to parameterize and evaluate the model. The results showed that the model simulated BDE-47 tissue concentrations in adult male, maternal, and fetal compartments within the standard deviations of the experimental data. The model's ability to estimate BDE-47 concentrations in the fetus after maternal exposure will be useful to design in utero exposure/effect studies. This PBPK model is the first one designed for any PBDE pharmaco/toxicokinetic description. The next steps will be to expand this model to simulate BDE-47 pharmacokinetics and distributions across species (mice), and then extrapolate it to humans. After mouse and human model development, additional PBDE congeners will be incorporated into the model and simulated as a mixture.


Assuntos
Poluentes Ambientais/farmacocinética , Exposição Materna , Troca Materno-Fetal , Modelos Biológicos , Bifenil Polibromatos/farmacocinética , Animais , Feminino , Feto/metabolismo , Éteres Difenil Halogenados , Humanos , Masculino , Gravidez , Ratos , Ratos Sprague-Dawley , Especificidade da Espécie , Distribuição Tecidual
10.
Popul Trends ; (141): 92-111, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20927031

RESUMO

We compare official population projections with Bayesian time series forecasts for England and Wales. The Bayesian approach allows the integration of uncertainty in the data, models and model parameters in a coherent and consistent manner. Bayesian methodology for time-series forecasting is introduced, including autoregressive (AR) and stochastic volatility (SV) models. These models are then fitted to a historical time series of data from 1841 to 2007 and used to predict future population totals to 2033. These results are compared to the most recent projections produced by the Office for National Statistics. Sensitivity analyses are then performed to test the effect of changes in the prior uncertainty for a single parameter. Finally, in-sample forecasts are compared with actual population and previous official projections. The article ends with some conclusions and recommendations for future work.


Assuntos
Previsões/métodos , Crescimento Demográfico , Teorema de Bayes , Coleta de Dados/métodos , Inglaterra , Humanos , País de Gales
11.
Front Psychol ; 10: 1263, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31231280

RESUMO

Numerous studies have established the influence of detrimental home conditions on child cognition and behavior; however, fewer have assessed these outcomes in the context of relatively "normal" range of home environmental conditions. Given the exquisite sensitivity to the environment of the neural substrates that undergird executive functioning (EF) and behavioral self-regulation in children, it is possible that a range of conditions within the home, even in the absence of maltreatment or economic deprivation, may impact these outcomes. The purpose of the present exploratory investigation was to further define the relationship between features of the home environment using the HOME inventory (a structured interview and observation of parent and child) and several dimensions of child EF and behavioral problems. In addition, this study sought to elucidate potentially differential associations between home and parent-reported neighborhood conditions-a hypothetically less direct influence on cognition in this age group-and level of child functioning. A battery of EF performance tasks and a widely-used checklist of behavioral problems were administered to 66 children, 8-11 years old from a lower middle income, working class sample. Results showed significant relationships between the home environment and several dimensions of EF and behavioral problems. In contrast, neighborhood conferred additional effects only on rule-breaking and aggression, not cognition, which is consistent with evidence that externalizing behavior in this age group becomes increasingly oriented toward outside influences. These findings warrant follow-up studies to establish causality. A broader program of research designed to delve further into the relationship between nuanced influences from the home and child cognition and behavior has implications for parenting strategies that foster healthy development. Neighborhood contexts should also be considered during early and mid-adolescent years based on existing studies and findings reported herein suggesting that this period of newfound autonomy and the heightened significance of peer relationships may influence externalizing behaviors, with implications for protective courses of action.

12.
Popul Res Policy Rev ; 37(6): 1053-1077, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30546179

RESUMO

Australia is a major immigration country and immigrants currently represent around 28% of the total population. The aim of this research is to understand the long-term consequences of this immigration and, particularly, how migrants respond to opportunities within the country after arriving through the process of subsequent (internal) migration. The focus is on major immigrant groups in Australia, including persons born in the United Kingdom, New Zealand, China and India, and how their patterns differ from persons born in Australia. To conduct this analysis, we have gathered data for a 35-year period based on quinquennial census data. We also obtained birthplace-specific mortality data for constructing multiregional life tables for the immigrant populations. Subsequent migration is important for understanding population redistribution, and the relative attractiveness of destinations within host countries. Our results highlight the importance of subsequent migration and the diversity of migration behaviours amongst different immigrant groups in the context of overall declines in internal migration since 1981.

13.
Eur J Popul ; 33(1): 33-53, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28286353

RESUMO

European Union (EU) enlargements in 2004 and 2007 were accompanied by increased migration from new-accession to established-member (EU-15) countries. The impacts of these flows depend, in part, on the amount of time that persons from the former countries live in the latter over the life course. In this paper, we develop period estimates of duration expectancy in EU-15 countries among persons from new-accession countries. Using a newly developed set of harmonised Bayesian estimates of migration flows each year from 2002 to 2008 from the Integrated Modelling of European Migration (IMEM) Project, we exploit period age patterns of country-to-country migration and mortality to summarize the average number of years that persons from new-accession countries could be expected to live in EU-15 countries over the life course. In general, the results show that the amount of time that persons from new-accession countries could be expected to live in the EU-15 nearly doubled after 2004.

14.
Environ Health Perspect ; 114(6): 936-42, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16759998

RESUMO

Although biomonitoring has been used in many occupational and environmental health and exposure studies, we are only beginning to understand the complexities and uncertainties involved with the biomonitoring process--from study design, to sample collection, to chemical analysis--and with interpreting the resulting data. We present an overview of concepts that should be considered when using biomonitoring or biomonitoring data, assess the current status of biomonitoring, and detail potential advancements in the field that may improve our ability to both collect and interpret biomonitoring data. We discuss issues such as the appropriateness of biomonitoring for a given study, the sampling time frame, temporal variability in biological measurements to nonpersistent chemicals, and the complex issues surrounding data interpretation. In addition, we provide recommendations to improve the utility of biomonitoring in farmworker studies.


Assuntos
Agricultura , Monitoramento Ambiental , Praguicidas/farmacocinética , Praguicidas/toxicidade , Humanos , Pele/metabolismo
15.
Environ Health Perspect ; 114(6): 961-8, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16760001

RESUMO

Developing internally valid, and perhaps generalizable, farmworker exposure studies is a complex process that involves many statistical and laboratory considerations. Statistics are an integral component of each study beginning with the design stage and continuing to the final data analysis and interpretation. Similarly, data quality plays a significant role in the overall value of the study. Data quality can be derived from several experimental parameters including statistical design of the study and quality of environmental and biological analytical measurements. We discuss statistical and analytic issues that should be addressed in every farmworker study. These issues include study design and sample size determination, analytical methods and quality control and assurance, treatment of missing data or data below the method's limits of detection, and post-hoc analyses of data from multiple studies. Key words: analytical methodology, biomarkers, laboratory, limit of detection, omics, quality control, sample size, statistics.


Assuntos
Agricultura , Exposição Ocupacional , Humanos , Sensibilidade e Especificidade
16.
J R Stat Soc Ser A Stat Soc ; 179(4): 1007-1024, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27773971

RESUMO

Age and sex patterns of migration are essential for understanding drivers of population change and heterogeneity of migrant groups. We develop a hierarchical Bayesian model to estimate such patterns for international migration in the European Union and European Free Trade Association from 2002 to 2008, which was a period of time when the number of members expanded from 19 to 31 countries. Our model corrects for the inadequacies and inconsistencies in the available data and estimates the missing patterns. The posterior distributions of the age and sex profiles are then combined with a matrix of origin-destination flows, resulting in a synthetic database with measures of uncertainty for migration flows and other model parameters.

18.
Demography ; 52(3): 1035-59, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25962866

RESUMO

In this article, we develop a fully integrated and dynamic Bayesian approach to forecast populations by age and sex. The approach embeds the Lee-Carter type models for forecasting the age patterns, with associated measures of uncertainty, of fertility, mortality, immigration, and emigration within a cohort projection model. The methodology may be adapted to handle different data types and sources of information. To illustrate, we analyze time series data for the United Kingdom and forecast the components of population change to the year 2024. We also compare the results obtained from different forecast models for age-specific fertility, mortality, and migration. In doing so, we demonstrate the flexibility and advantages of adopting the Bayesian approach for population forecasting and highlight areas where this work could be extended.


Assuntos
Teorema de Bayes , Coeficiente de Natalidade/tendências , Emigração e Imigração/tendências , Previsões/métodos , Modelos Estatísticos , Mortalidade/tendências , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Dinâmica Populacional , Fatores Sexuais , Reino Unido , Adulto Jovem
19.
Environ Health Perspect ; 111(3): 293-6, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12611657

RESUMO

Six arsenic species [arsenate, arsenite, arsenocholine, arsenobetaine, monomethyl arsonic acid, and dimethyl arsinic acid] present in human urine were determined using ion-exchange chromatography combined with inductively coupled plasma mass spectrometry (IC-ICP-MS). Baseline separation was achieved for all six species as well as for the internal standard (potassium hexahydroxy antimonate V) in a single chromatographic run of less than 30 min, using an ammonium carbonate buffer gradient (between 10 and 50 mM) at ambient temperature, in conjunction with cation- and anion-exchange columns in series. The performance of the method was evaluated with respect to linearity, precision, accuracy, and detection limits. This method was applied to determine the concentration of these six arsenic species in human urine samples (n = 251) collected from a population-based exposure assessment survey. Method precision was demonstrated by the analysis of duplicate samples that were prepared over a 2-year analysis period. Total arsenic was also determined for the urine samples using flow injection analysis coupled to ICP-MS. The summed concentration of the arsenic species was compared with the measured arsenic total to demonstrate mass balance.


Assuntos
Arsênio/química , Arsênio/urina , Calibragem , Cromatografia por Troca Iônica/métodos , Humanos , Espectrometria de Massas/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Manejo de Espécimes , Temperatura
20.
Toxicol Sci ; 76(1): 121-30, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12915717

RESUMO

Risk assessments often must consider exposures that vary over time or for which the exposure duration of concern differs from the available data, and a variety of extrapolation procedures have been devised accordingly. The present experiments explore the relationship(s) between exposure concentration (C) and time (t) to investigate procedures for assessing the risks of short-term solvent exposures. The first hypothesis tested was that the product of C x t would produce a constant health effect (Haber's rule). The second hypothesis tested was that exposure conditions produce effects in proportion to the tissue concentrations created. Awake, adult, male Long-Evans (LE) rats were exposed to trichloroethylene (TCE) vapor in a head-only exposure chamber while pattern onset/offset visual evoked potentials (VEPs) were recorded. Exposure conditions were designed to provide C x t products of 0 ppm/h (0 ppm for 4 h) or 4000 ppm/h created through four exposure scenarios: 1000 ppm for 4 h; 2000 ppm for 2 h; 3000 ppm for 1.3 h; or 4000 ppm for 1h (n = 9-10/concentration). The amplitude of the VEP frequency double component (F2) was decreased significantly by exposure; this decrease was related to C but not to t or to the C x t product, indicating that Haber's rule did not hold. The mean amplitude (+/- SEM in muV) of the F2 component in the control and treatment groups measured 4.4 +/- 0.5 (0 ppm/4 h), 3.1 +/- 0.5 (1000 ppm/4 h), 3.1 +/- 0.4 (2000 ppm/2 h), 2.3 +/- 0.3 (3000 ppm/1.3 h), and 1.9 +/- 0.4 (4000 ppm/1 h). A physiologically based pharmacokinetic (PBPK) model was used to estimate the concentrations of TCE in the brain achieved during each exposure condition. The F2 amplitude of the VEP decreased monotonically as a function of the estimated peak brain concentration but was not related to the area under the curve (AUC) of the brain TCE concentration. In comparison to estimates from the PBPK model, extrapolations based on Haber's rule yielded approximately a 6-fold error in estimated exposure duration when extrapolating across only a 4-fold change in exposure concentration. These results indicate that the use of a linear form of Haber's rule will not predict accurately the risks of acute exposure to TCE, nor will an estimate of AUC of brain TCE. However, an estimate of the brain TCE concentration at the time of VEP testing predicted the effects of TCE across exposure concentrations and durations.


Assuntos
Poluentes Atmosféricos/toxicidade , Encéfalo/efeitos dos fármacos , Potenciais Evocados Visuais/efeitos dos fármacos , Tricloroetileno/toxicidade , Administração por Inalação , Poluentes Atmosféricos/sangue , Poluentes Atmosféricos/farmacocinética , Animais , Encéfalo/metabolismo , Encéfalo/fisiologia , Masculino , Estimulação Luminosa , Ratos , Ratos Long-Evans , Distribuição Tecidual , Tricloroetileno/sangue , Tricloroetileno/farmacocinética
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