RESUMEN

BACKGROUND: Occupational and environmental exposures during the prenatal period may be associated with adverse pregnancy outcomes and lifelong health effects. Yet, identification and evaluation of these potential hazards is lacking in routine obstetric care. AIMS: To assess the feasibility of incorporating a self-administered occupational and environmental exposure questionnaire into obstetric clinics. METHODS: A cross-sectional survey assessed prenatal clinic patients at a public hospital who were currently employed and <20 weeks gestation. Questionnaires evaluated job characteristics, workplace and hobby exposures, protective equipment use and symptoms during pregnancy. RESULTS: Of 69 participants (96% response rate), 46% were predominantly Spanish-speaking. Primary occupations were caregiver (16%), cleaner (14%) and administrative assistant (14%). Overall, 93% were exposed to a workplace hazard, with most participants reporting physical stressors (82%) or organic solvent exposure (78%). Most women (74%) used some personal protective equipment. Nearly half (54%) reported at least one non-pregnancy symptom, and 52% were referred for follow-up with an occupational medicine practitioner. Household and hobby-related chemical exposures were common in our sample (91%). We observed moderate consistency between job task and chemical use responses: 67-99% of intentionally redundant questions were fully or partially matched. Closed- compared to open-ended activity questions identified a higher proportion of physical stressors (82% versus 12%) and cleaning product (76% versus 30%) exposures. CONCLUSIONS: A self-administered questionnaire is an effective screening tool for identifying women with occupational and hobby-related exposures during pregnancy. Consistent incorporation of exposure assessment into prenatal care can improve clinical communications and early interventions for at-risk pregnant women.

Asunto(s)

Contaminantes Ambientales/efectos adversos , Pasatiempos , Tamizaje Masivo/métodos , Exposición Materna/prevención & control , Exposición Profesional/prevención & control , Encuestas y Cuestionarios/normas , Adulto , Estudios Transversales , Femenino , Humanos , Embarazo

RESUMEN

The environment is an underutilized pathway to breast cancer prevention. Current research approaches and funding streams related to breast cancer and the environment are unequal to the task at hand. We undertook the California Breast Cancer Prevention Initiatives, a four-year comprehensive effort to set a research agenda related to breast cancer, the environment, disparities and prevention. We identified 20 topics for Concept Proposals reflecting a life-course approach and the complex etiology of breast cancer; considering the environment as chemical, physical and socially constructed exposures that are experienced concurrently: at home, in the community and at work; and addressing how we should be modifying the world around us to promote a less carcinogenic environment. Redirecting breast cancer research toward prevention-oriented discovery could significantly reduce the incidence and associated disparities of the disease among future generations.

Asunto(s)

Neoplasias de la Mama/prevención & control , Carcinógenos Ambientales/efectos adversos , Transformación Celular Neoplásica/patología , Exposición a Riesgos Ambientales/efectos adversos , Glándulas Mamarias Humanas/efectos de los fármacos , Proyectos de Investigación , Conducta de Reducción del Riesgo , Neoplasias de la Mama/inducido químicamente , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , California , Transformación Celular Neoplásica/inducido químicamente , Transformación Celular Neoplásica/metabolismo , Conducta Cooperativa , Femenino , Disparidades en el Estado de Salud , Disparidades en Atención de Salud , Humanos , Comunicación Interdisciplinaria , Estilo de Vida , Glándulas Mamarias Humanas/metabolismo , Glándulas Mamarias Humanas/patología , Embarazo , Desarrollo de Programa , Medición de Riesgo , Factores de Riesgo , Transducción de Señal/efectos de los fármacos

RESUMEN

An endocrine-disrupting chemical (EDC) is an exogenous chemical, or mixture of chemicals, that can interfere with any aspect of hormone action. The potential for deleterious effects of EDC must be considered relative to the regulation of hormone synthesis, secretion, and actions and the variability in regulation of these events across the life cycle. The developmental age at which EDC exposures occur is a critical consideration in understanding their effects. Because endocrine systems exhibit tissue-, cell-, and receptor-specific actions during the life cycle, EDC can produce complex, mosaic effects. This complexity causes difficulty when a static approach to toxicity through endocrine mechanisms driven by rigid guidelines is used to identify EDC and manage risk to human and wildlife populations. We propose that principles taken from fundamental endocrinology be employed to identify EDC and manage their risk to exposed populations. We emphasize the importance of developmental stage and, in particular, the realization that exposure to a presumptive "safe" dose of chemical may impact a life stage when there is normally no endogenous hormone exposure, thereby underscoring the potential for very low-dose EDC exposures to have potent and irreversible effects. Finally, with regard to the current program designed to detect putative EDC, namely, the Endocrine Disruptor Screening Program, we offer recommendations for strengthening this program through the incorporation of basic endocrine principles to promote further understanding of complex EDC effects, especially due to developmental exposures.

Asunto(s)

Disruptores Endocrinos/normas , Disruptores Endocrinos/toxicidad , Salud Pública/normas , Sociedades Médicas , Humanos

RESUMEN

OBJECTIVE: Though many contaminants are released into the atmosphere, in the US only six air pollutants-ozone, particulate matter, sulfur dioxide, carbon monoxide, nitrogen dioxide, and lead-are closely monitored and carefully assessed for health significance. Other pollutants, even if highly toxic, are neither widely monitored nor routinely assessed at the national level. The goal of this study was to analyze the availability of information needed to characterize the health significance of hazardous air pollutants, focusing on urban areas in California. METHODS: The authors compared different approaches to identifying which contaminants should be considered hazardous air pollutants of potential health concern; reviewed the availability of toxicity values for these pollutants; and analyzed the usefulness of air monitoring data from California agencies for determining populations risks, by comparing method detection limits with health benchmarks. RESULTS: Approaches to identifying air contaminants of possible health concern differ. Toxicity values are not available for many hazardous air pollutants, including those identified in the Clean Air Act. In California, monitoring data are available for many, though not all, pollutants of concern. Monitoring methods for several pollutants do not have adequate sensitivity to detect all relevant concentrations. CONCLUSION: The information necessary to fully assess the health significance of hazardous air pollutants is not currently available.

Asunto(s)

Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Interpretación Estadística de Datos , Salud Ambiental , Monitoreo del Ambiente/métodos , Monitoreo del Ambiente/normas , Salud Urbana/estadística & datos numéricos , Contaminación del Aire/legislación & jurisprudencia , Contaminación del Aire/estadística & datos numéricos , Benchmarking , California , Monitoreo del Ambiente/legislación & jurisprudencia , Monitoreo del Ambiente/estadística & datos numéricos , Medicina Basada en la Evidencia , Humanos , Modelos Estadísticos , Evaluación de Necesidades , Salud Pública , Medición de Riesgo , Sensibilidad y Especificidad , Estados Unidos , United States Environmental Protection Agency

RESUMEN

Food consumption is an important route of human exposure to pesticides and industrial pollutants. Average dietary exposures to 37 pollutants were calculated for the whole United States population and for children under age 12 years by combining contaminant data with food consumption data and summing across food types. Pollutant exposures were compared to benchmark concentrations, which are based on standard toxicological references, for cancer and noncancer health effects. Average food ingestion exposures for the whole population exceeded benchmark concentrations for arsenic, chlordane, DDT, dieldrin, dioxins, and polychlorinated biphenyls, when nondetects were assumed to be equal to zero. For each of these pollutants, exposure through fish consumption accounts for a large percentage of food exposures. Exposure data for childhood age groups indicated that benchmark concentrations for the six identified pollutants are exceeded by the time age 12 years is reached. The methods used in this analysis could underestimate risks from childhood exposure, as children have a longer time to develop tumors and they may be more susceptible to carcinogens; therefore, there may be several additional contaminants of concern. In addition, several additional pollutants exceeded benchmark levels when nondetects were assumed to be equal to one half the detection limit. Uncertainties in exposure levels may be large, primarily because of numerous samples with contaminant levels below detection limits.

Asunto(s)

Monitoreo del Ambiente/normas , Contaminación de Alimentos , Residuos Industriales , Plaguicidas , Adolescente , Adulto , Anciano , Benchmarking/normas , Niño , Fenómenos Fisiológicos Nutricionales Infantiles , Preescolar , Bases de Datos Factuales/normas , Monitoreo Epidemiológico , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Estados Unidos/epidemiología

RESUMEN

Of the 188 hazardous air pollutants (HAPs) listed in the Clean Air Act, only a handful have information on human health effects, derived primarily from animal and occupational studies. Lack of consistent monitoring data on ambient air toxics makes it difficult to assess the extent of low-level, chronic, ambient exposures to HAPs that could affect human health, and limits attempts to prioritize and evaluate policy initiatives for emissions reduction. Modeled outdoor HAP concentration estimates from the U.S. Environmental Protection Agency's Cumulative Exposure Project were used to characterize the extent of the air toxics problem in California for the base year of 1990. These air toxics concentration estimates were used with chronic toxicity data to estimate cancer and noncancer hazards for individual HAPs and the risks posed by multiple pollutants. Although hazardous air pollutants are ubiquitous in the environment, potential cancer and noncancer health hazards posed by ambient exposures are geographically concentrated in three urbanized areas and in a few rural counties. This analysis estimated a median excess individual cancer risk of 2.7E-4 for all air toxics concentrations and 8600 excess lifetime cancer cases, 70% of which were attributable to four pollutants: polycyclic organic matter, 1,3 butadiene, formaldehyde, and benzene. For noncancer effects, the analysis estimated a total hazard index representing the combined effect of all HAPs considered. Each pollutant contributes to the index a ratio of estimated concentration to reference concentration. The median value of the index across census tracts was 17, due primarily to acrolein and chromium concentration estimates. On average, HAP concentrations and cancer and noncancer health risks originate mostly from area and mobile source emissions, although there are several locations in the state where point sources account for a large portion of estimated concentrations and health risks. Risk estimates from this study can provide guidance for prioritizing research, monitoring, and regulatory intervention activities to reduce potential hazards to the general population. Improved ambient monitoring efforts can help clarify uncertainties inherent in this analysis.

Asunto(s)

Contaminantes Atmosféricos/efectos adversos , Salud Pública , Medición de Riesgo , Acroleína/efectos adversos , Acroleína/análisis , Contaminantes Atmosféricos/análisis , Contaminación del Aire/efectos adversos , Contaminación del Aire/prevención & control , Benceno/efectos adversos , Benceno/análisis , Butadienos/efectos adversos , Butadienos/análisis , California , Carcinógenos/efectos adversos , Carcinógenos/análisis , Cromo/efectos adversos , Cromo/análisis , Exposición a Riesgos Ambientales , Monitoreo del Ambiente , Formaldehído/efectos adversos , Formaldehído/análisis , Política de Salud , Prioridades en Salud , Humanos , Neoplasias/etiología , Exposición Profesional , Compuestos Policíclicos/efectos adversos , Compuestos Policíclicos/análisis , Salud Rural , Estados Unidos , United States Environmental Protection Agency , Salud Urbana , Emisiones de Vehículos/efectos adversos , Emisiones de Vehículos/prevención & control

RESUMEN

A public health concern regarding hazardous air pollutants (HAPs) is their potential to cause cancer. It has been difficult to assess potential cancer risks from HAPs, due primarily to lack of ambient concentration data for the general population. The Environmental Protection Agency's Cumulative Exposure Project modeled 1990 outdoor concentrations of HAPs across the United States, which were combined with inhalation unit risk estimates to estimate the potential increase in excess cancer risk for individual carcinogenic HAPs. These were summed to provide an estimate of cancer risk from multiple HAPs. The analysis estimates a median excess cancer risk of 18 lifetime cancer cases per 100,000 people for all HAP concentrations. About 75% of estimated cancer risk was attributable to exposure to polycyclic organic matter, 1,3-butadiene, formaldehyde, benzene, and chromium. Consideration of some specific uncertainties, including underestimation of ambient concentrations, combining upper 95% confidence bound potency estimates, and changes to potency estimates, found that cancer risk may be underestimated by 15% or overestimated by 40-50%. Other unanalyzed uncertainties could make these under- or overestimates larger. This analysis used 1990 estimates of concentrations and can be used to track progress toward reducing cancer risk to the general population.

Asunto(s)

Contaminantes Atmosféricos/efectos adversos , Carcinógenos/efectos adversos , Neoplasias/etiología , Adolescente , Adulto , Anciano , Niño , Preescolar , Estudios Epidemiológicos , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Modelos Teóricos , Salud Pública , Reproducibilidad de los Resultados , Medición de Riesgo

RESUMEN

The Clean Air Act identifies 189 hazardous air pollutants (HAPs), or "air toxics," associated with a wide range of adverse human health effects. The U.S. Environmental Protection Agency has conducted a modeling study with the Assessment System for Population Exposure Nationwide (ASPEN) to gain a greater understanding of the spatial distribution of concentrations of these HAPs resulting from contributions of multiple emission sources. The study estimates year 1990 long-term outdoor concentrations of 148 air toxics for each census tract in the continental United States, utilizing a Gaussian air dispersion modeling approach. Ratios of median national modeled concentrations to estimated emissions indicate that emission totals without consideration of emission source type can be a misleading indicator of air quality. The results also indicate priorities for improvements in modeling methodology and emissions identification. Model performance evaluation suggests a tendency for underprediction of observed concentrations, which is likely due, at least in part, to a number of limitations of the Gaussian modeling formulation. Emissions estimates for HAPs have a high degree of uncertainty and contribute to discrepancies between modeled and monitored concentration estimates. The model's ranking of concentrations among monitoring sites is reasonably good for most of the gaseous HAPs evaluated, with ranking accuracy ranging from 66 to 100%.

Asunto(s)

Contaminantes Atmosféricos/análisis , Sustancias Peligrosas/análisis , Modelos Teóricos , Estados Unidos

RESUMEN

Relatively little is known about the spectrum of health effects, and the scope and level of ambient air concentrations of those pollutants regulated under the Clean Air Act as "hazardous air pollutants". The U.S. Environmental Protection Agency's (USEPA) Cumulative Exposure Project uses currently available emissions inventories, from a variety of source types, and an atmospheric dispersion model to provide estimates of ambient concentrations for 148 hazardous air pollutants (HAPs) in over 60,000 census tracts for the year 1990. This paper uses currently available hazard information for those pollutants and provides a database of potential regulatory threshold concentrations of concern, or "benchmark concentrations," and a methodology for prioritizing and characterizing the quality of the data. In order to demonstrate application of the database and prioritization scheme to outputs from the Cumulative Exposure Project, comparisons were made with the maximum modeled concentration of each individual hazardous air pollutant across the census tracts. Of the 197 benchmark concentrations for cancer and non-cancer (long- and short-term exposures) effects compiled for the study, approximately one half were exceeded with a predominance of exceedance of cancer benchmarks. While the number of benchmark concentrations available to fully characterize potential health effects of these pollutants was limited (approximately 80 percent of HAPs identified as cancer concerns had benchmark concentrations for cancer and 50 percent of all HAPs had non-cancer benchmark concentrations) and there was greater uncertainty in derivation of maximum modeled air concentrations than other levels, the comparison between the two was a useful approach for providing an indication of public health concern from hazardous air pollutants.

Asunto(s)

Contaminantes Atmosféricos/efectos adversos , Exposición a Riesgos Ambientales , Sustancias Peligrosas/efectos adversos , Sistemas de Información , United States Environmental Protection Agency , Humanos , Medición de Riesgo , Estados Unidos

RESUMEN

Occupational and toxicological studies have demonstrated adverse health effects from exposure to toxic air contaminants. Data on outdoor levels of toxic air contaminants have not been available for most communities in the United States, making it difficult to assess the potential for adverse human health effects from general population exposures. Emissions data from stationary and mobile sources are used in an atmospheric dispersion model to estimate outdoor concentrations of 148 toxic air contaminants for each of the 60,803 census tracts in the contiguous United States for 1990. Outdoor concentrations of air toxics were compared to previously defined benchmark concentrations for cancer and noncancer health effects. Benchmark concentrations are based on standard toxicological references and represent air toxic levels above which health risks may occur. The number of benchmark concentrations exceeded by modeled concentrations ranged from 8 to 32 per census tract, with a mean of 14. Estimated concentrations of benzene, formaldehyde, and 1,3-butadiene were greater than cancer benchmark concentrations in over 90% of the census tracts. Approximately 10% of all census tracts had estimated concentrations of one or more carcinogenic HAPs greater than a 1-in-10,000 risk level. Twenty-two pollutants with chronic toxicity benchmark concentrations had modeled concentrations in excess of these benchmarks, and approximately 200 census tracts had a modeled concentration 100 times the benchmark for at least one of these pollutants. This comprehensive assessment of air toxics concentrations across the United States indicates hazardous air pollutants may pose a potential public health problem.

Asunto(s)

Contaminación del Aire , Salud Pública , Exposición a Riesgos Ambientales , Sustancias Peligrosas , Medición de Riesgo , Estados Unidos

RESUMEN

Recent studies have found associations between particulate air pollution and total and adult mortality. The relationship between particulate air pollution and mortality among infants has not been examined in the United States. This study evaluates the relationship between postneonatal infant mortality and particulate matter in the United States. Our study involved analysis of cohorts consisting of approximately 4 million infants born between 1989 and 1991 in states that report relevant covariates; this included 86 metropolitan statistical areas (MSAs) in the United States. Data from the National Center for Health Statistics-linked birth/infant death records were combined at the MSA level with measurements of particulate matter 10 microns or less (PM10) from the EPA's Aerometric Database. Infants were categorized as having high, medium, or low exposures based on tertiles of PM10. Total and cause-specific postneonatal mortality rates were examined using logistic regression to control for demographic and environmental factors. Overall postneonatal mortality rates were 3.1 among infants with low PM10 exposures, 3.5 among infants with medium PM10 exposures, and 3.7 among highly exposed infants. After adjustment for other covariates, the odds ratio (OR) and 95% confidence intervals (CI) for total postneonatal mortality for the high exposure versus the low exposure group was 1.10 (1.04, 1.16). In normal birth weight infants, high PM10 exposure was associated with respiratory causes [OR = 1.40, (1.05, 1.85)] and sudden infant death syndrome [OR = 1.26, (1.14, 1.39)]. For low birth weight babies, high PM10 exposure was associated, but not significantly, with mortality from respiratory causes [OR = 1.18, (0.86, 1.61)]. This study suggests that particulate matter is associated with risk of postneonatal mortality. Continued attention should be paid to air quality to ensure optimal health of infants in the United States.

Asunto(s)

Contaminación del Aire/efectos adversos , Mortalidad Infantil , Peso al Nacer , Causas de Muerte , Humanos , Recién Nacido , Muerte Súbita del Lactante/etiología , Estados Unidos

RESUMEN

In this study, we used measurements of occupational exposures to pesticides in agriculture to evaluate health risks and analyzed how the federal regulatory program is addressing these risks. Dose estimates developed by the State of California from measured occupational exposures to 41 pesticides were compared to standard indices of acute toxicity (LD50) and chronic effects (reference dose). Lifetime cancer risks were estimated using cancer potencies. Estimated absorbed daily doses for mixers, loaders, and applicators of pesticides ranged from less than 0.0001% to 48% of the estimated human LD50 values, and doses for 10 of 40 pesticides exceeded 1% of the estimated human LD50 values. Estimated lifetime absorbed daily doses ranged from 0.1% to 114,000% of the reference doses developed by the U.S. Environmental Protection Agency, and doses for 13 of 25 pesticides were above them. Lifetime cancer risks ranged from 1 per million to 1700 per million, and estimates for 12 of 13 pesticides were above 1 per million. Similar results were obtained for field workers and flaggers. For the pesticides examined, exposures pose greater risks of chronic effects than acute effects. Exposure reduction measures, including use of closed mixing systems and personal protective equipment, significantly reduced exposures. Proposed regulations rely primarily on requirements for personal protective equipment and use restrictions to protect workers. Chronic health risks are not considered in setting these requirements. Reviews of pesticides by the federal pesticide regulatory program have had little effect on occupational risks. Policy strategies that offer immediate protection for workers and that are not dependent on extensive review of individual pesticides should be pursued.

Asunto(s)

Enfermedades de los Trabajadores Agrícolas , Exposición Profesional , Salud Laboral/legislación & jurisprudencia , Plaguicidas , Plaguicidas/toxicidad , United States Environmental Protection Agency/legislación & jurisprudencia , Adulto , Anciano , Enfermedades de los Trabajadores Agrícolas/inducido químicamente , Enfermedades de los Trabajadores Agrícolas/prevención & control , California , Humanos , Dosificación Letal Mediana , Persona de Mediana Edad , Neoplasias/inducido químicamente , Exposición Profesional/efectos adversos , Exposición Profesional/legislación & jurisprudencia , Plaguicidas/normas , Ropa de Protección , Medición de Riesgo , Estados Unidos

RESUMEN

This paper compares two methods for global optimization of physiologically based toxicokinetic models: Monte Carlo optimization, which searches randomly for the optimum; and the simplex method, which updates systematically an array of parameter values. Two measures of goodness-of-fit are also contrasted: criterion function and likelihood. A 14-parameter model of benzene distribution in rats is used to illustrate these techniques. Simplex optimization yields better fits overall. However, the measurement of uncertainty offered by Monte Carlo simulations is a major argument in favor of their use.

Asunto(s)

Benceno/farmacocinética , Modelos Biológicos , Toxicología , Animales , Benceno/toxicidad , Humanos , Funciones de Verosimilitud , Modelos Estadísticos , Método de Montecarlo

RESUMEN

OBJECTIVE: We examined the relationship between workplace smoking policies and smoking prevalence and cigarette consumption. METHODS: California residents were questioned by telephone with the 1990 California Tobacco Survey. All respondents (11,704) above age 18 years who were employed indoors were used. Respondents were asked about smoking status, workplace smoking policy, desire to quit, and smoking history. Logistic regression was used to determine the relationship of workplace smoking policy to smoking status, accounting for demographic variables. RESULTS: Prevalence of regular smokers was significantly lower in smoke-free workplaces than in those with no restrictions (13.7% vs 20.6%, P < .001). Continuing regular smokers in smoke-free workplaces smoked fewer cigarettes than those in workplaces with no restrictions (296 vs 341 packs per year, P < .001). More comprehensive smoking policies were associated with smokers more likely to contemplate quitting (P = .014). CONCLUSIONS: Employees in smoke-free workplaces have a lower smoking prevalence and, among continuing smokers, lower cigarette consumption than individuals working where smoking is permitted. We estimate cigarette consumption among employees indoors is 21% below that if there were no smoking restrictions in California workplaces. Furthermore, if all California workplaces were smoke-free, cigarette consumption among employees would be 41% below that if there were no workplace smoking restrictions, approximately a $406 million annual loss in sales to the tobacco industry. This study supports the hypothesis that smoke-free workplace policies are an effective public health measure for decreasing smoking prevalence and cigarette consumption among continuing smokers.

Asunto(s)

Exposición Profesional/prevención & control , Fumar/epidemiología , Contaminación por Humo de Tabaco/prevención & control , Adolescente , Adulto , California/epidemiología , Femenino , Humanos , Modelos Logísticos , Masculino , Oportunidad Relativa , Prevención del Hábito de Fumar , Control Social Formal

RESUMEN

There has been an increasing interest in physiologically based pharmacokinetic (PBPK) models in the area of risk assessment. The use of these models raises two important issues: (1) How good are PBPK models for predicting experimental kinetic data? (2) How is the variability in the model output affected by the number of parameters and the structure of the model? To examine these issues, we compared a five-compartment PBPK model, a three-compartment PBPK model, and nonphysiological compartmental models of benzene pharmacokinetics. Monte Carlo simulations were used to take into account the variability of the parameters. The models were fitted to three sets of experimental data and a hypothetical experiment was simulated with each model to provide a uniform basis for comparison. Two main results are presented: (1) the difference is larger between the predictions of the same model fitted to different data sets than between the predictions of different models fitted to the dame data; and (2) the type of data used to fit the model has a larger effect on the variability of the predictions than the type of model and the number of parameters.

Asunto(s)

Modelos Biológicos , Xenobióticos/farmacocinética , Animales , Benceno/farmacocinética , Benceno/toxicidad , Cinética , Masculino , Método de Montecarlo , Ratas , Ratas Endogámicas F344 , Factores de Riesgo , Xenobióticos/toxicidad

RESUMEN

We assess the goodness of fit of three physiologically based models of benzene pharmacokinetics to experimental data in Fischer-344 rats. These models were independently developed and published. Large differences in the quality of the fit are observed. In addition, the parameter values leading to acceptable fits are spread over the entire range of physiologically plausible values and can be quite different from average or standard values. On the other hand, choosing standard values for the parameters does not ensure good predictions of all tissue levels. These results emphasize the difficulty of a rigorous calibration of physiological models, and the need for further research in this area, including precise experimental determination of parameter values. Physiological models are powerful tools, but for risk assessment purposes simpler models, making equivalent use of the crucial data, are probably preferable.

Asunto(s)

Benceno/farmacocinética , Modelos Biológicos , Animales , Benceno/administración & dosificación , Simulación por Computador , Masculino , Método de Montecarlo , Ratas , Ratas Endogámicas F344 , Distribución Tisular