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Biomedical subjects

R C Spear

Publications and source records attributed to R C Spear.

At least 19 recordsLinked to original sources
PubMed1995

Dynamic model comparing the bionomics of two isolated Culex tarsalis (Diptera: Culicidae) populations: model development.

The population dynamics of Culex tarsalis in the Coachella and southern San Joaquin valleys of California were studied using Monte Carlo simulations. Multiple years of abundance data were averaged to extract a generalized seasonal pattern for each site. These patterns were used to establish qualitative goodness-of-fit criteria to assess model output and to evaluate the importance of model parameters in simulating mosquito population trends. The parameters associated with the degree of temperature and density dependency on larval mortality were found to be important components in determining whether or not the output was classified as having passed or failed on the basis of our criteria, whereas autogeny and the heterogeneity of developmental time were found not to be important.

Animals↗
PubMed1995

Dynamic model comparing the bionomics of two isolated Culex tarsalis (Diptera: Culicidae) populations: sensitivity analysis.

A simulation model described (Eisenberg et al. 1994a) was used to compare the population dynamics of Culex tarsalis Coquillett in the Coachella and southern portion of the San Joaquin Valleys of California. Model outputs were classified as a pass if they met criteria that defined typical seasonal abundance patterns established by CO2 and New Jersey light trap data. The sensitivity of this classification to the model parameters was assessed by running multiple simulations for each valley site. Parameter sets associated with a pass were first analyzed separately for each valley and then compared. The two study sites were distinguished by the distributional characteristics of two parameters associated with temperature dependency. One of these parameters described the temperature dependence of larval mortality and the other the temperature dependence of adult egg development. We hypothesize that these isolated Cx. tarsalis populations evolved separately to maximize survival in their respective temperature regimes by adapting to different optimal larval survival temperatures and egg-development rates.

Analysis of Variance↗
PubMed1994

Workplace and environmental air contaminant concentrations measured by open path Fourier transform infrared spectroscopy: a statistical process control technique to detect changes from normal operating conditions.

Open path Fourier transform infrared (OP-FTIR) spectroscopy is a new air monitoring technique that can be used to measure concentrations of air contaminants in real or near-real time. OP-FTIR spectroscopy has been used to monitor workplace gas and vapor exposures, emissions from hazardous waste sites, and to track emissions along fence lines. This paper discusses a statistical process control technique that can be used with air monitoring data collected with an OP-FTIR spectrometer to detect departures from normal operating conditions in the workplace or along a fence line. Time series data, produced by plotting consecutive air sample concentrations in time, were analyzed. Autocorrelation in the time series data was removed by fitting dynamic models. Control charts were used with the residuals of the model fit data to determine if departures from defined normal operating conditions could be rapidly detected. Shewhart and exponentially weighted moving average (EWMA) control charts were evaluated for use with data collected under different room air flow and mixing conditions. Under rapidly changing conditions the Shewhart control chart was able to detect a leak in a simulated process area. The EWMA control chart was found to be more sensitive to drifts and slowly changing concentrations in air monitoring data. The time series and statistical process control techniques were also applied to data obtained during a field study at a chemical plant. A production area of an acrylonitrile, 1,3-butadiene, and styrene (ABS) polymer process was monitored in near-real time. Decision logics based on the time series and statistical process control technique introduced suggest several applications in workplace and environmental monitoring. These applications might include signaling of an alarm or warning, increasing levels of worker respiratory protection, or evacuation of a community, when gas and vapor concentrations are determined to be out-of-control.

Air Pollutants↗
PubMed1994

Benzene toxicokinetics in humans: exposure of bone marrow to metabolites.

A three compartment physiologically based toxicokinetic model was fitted to human data on benzene disposition. Two separate groups of model parameter derivations were obtained, depending on which data sets were being fitted. The model was then used to simulate five environmental or occupational exposures. Predicted values of the total bone marrow exposure to benzene and cumulative quantity of metabolites produced by the bone marrow were generated for each scenario. The relation between cumulative quantity of metabolites produced by the bone marrow and continuous benzene exposure was also investigated in detail for simulated inhalation exposure concentrations ranging from 0.0039 ppm to 150 ppm. At the level of environmental exposures, no dose rate effect was found for either model. The occupational exposures led to only slight dose rate effects. A 32 ppm exposure for 15 minutes predicted consistently higher values than a 1 ppm exposure for eight hours for the total exposure of bone marrow to benzene and the cumulative quantity of metabolites produced by the bone marrow. The general relation between the cumulative quantity of metabolites produced by the bone marrow and the inhalation concentration of benzene is not linear. An inflection point exists in some cases leading to a slightly S shaped curve. At environmental levels (0.0039-10 ppm) the curve bends upward, and it saturates at high experimental exposures (greater than 100 ppm).

Air↗
PubMed1994

Parameter variability and the interpretation of physiologically based pharmacokinetic modeling results.

For the past several years we have been working with models of benzene distribution and metabolism, principally in the rat, but more recently in humans. Our biologically related objectives have been primarily to assist our laboratory-based colleagues in their quest for understanding of the mechanisms by which benzene exerts its toxic action. A secondary goal has been to develop or adapt models useful in risk assessment applications. We have also had methodological goals that relate to applications of sensitivity analysis on the one hand, but more fundamentally to the connection between experimental data and model structure and parameterization. This paper presents an overview of our work in these areas.

Animals↗
PubMed1992

A probability model for assessing exposure among respirator wearers: Part I--Description of the model.

The basic respirator equation states that the contaminant level inside a respirator (CI) is the product of the contaminant level outside the respirator (CO) and the decimal fraction penetration (P). On the basis of this relation, the authors present a probability model for the lognormal total distribution of CI levels among a respirator-wearing population; the model accounts for between-wearer and within-wearer variability in both CO levels and P values. The assumptions underlying the model are shown to be consistent with current knowledge about the variability in CO levels and P values. The model provides the basis for assessing the probability of overexposure to acute toxicants and to chronic toxicants among a respirator-wearing population.

Air Pollutants, Occupational↗
PubMed1992

A probability model for assessing exposure among respirator wearers: Part II-Overexposure to chronic versus acute toxicants.

A model describing the lognormal total distribution of contaminant levels inside a respirator (CI) is applied to assessing the probability of toxicant overexposure among a population of respirator wearers; the model accounts for between-wearer and within-wearer variability in ambient exposure levels (CO) and decimal fraction respirator penetration (P) values. The three exceedance probabilities are defined as PrI, the proportion of all CI levels over the permissible exposure limit (PEL); PrII, the proportion of wearers with an arithmetic mean CI level over the PEL; and PrIII, the proportion of wearers with a 95th percentile CI value over the PEL. PrII is considered that fraction of the population overexposed to a chronic toxicant; PrIII is considered that fraction overexposed to an acute toxicant. The behavior of PrII and PrIII over a range of exposure parameters is explored. An important observation is that a respirator-wearing population can have a substantial fraction of toxicant overexposure even though two conditions are met: (1) the P values for the population satisfy the criterion for the assigned protection factor (APF); and (2) the population arithmetic mean CO level is at or below the maximum use concentration (MUC), defined as APF x PEL. The authors recommend that the current MUCs for air-purifying respirators be reduced by one-half to reduce the potential respirator-wearing population fraction of overexposure and that appropriate exposure surveillance programs for all wearers be mandated.

Acute Disease↗
PubMed1992

Comparative testing of an FTIR remote optical sensor with area samplers in a controlled ventilation chamber.

A portable Fourier transform infrared remote optical sensing spectrometer was deployed and tested in a constant ventilation test chamber by using a tracer gas source. Continuous beam path measurements were collected and compared to air samples obtained from a computer-controlled, multiple-point sampling array connected to a flame ionization detector. Measurements were gathered at two different room ventilation rates and at two different dispersion conditions. A homogeneous dispersion condition had a uniform tracer concentration over the beam path and an inhomogeneous dispersion condition had a nonuniform tracer concentration distribution over the length of the beam path. Overall, the beam measurements and the point sample readings showed good agreement regardless of the room ventilation rate. Comparative data obtained from the inhomogeneous dispersion conditions did have higher variability, probably as a result of the different spatial and temporal resolution of the two sampling techniques. The tests demonstrate that a remote sensing system can be applied to an indoor room scale setting, but the dispersion of contaminant in the beam path is an important factor to consider when interpreting the beam data.

Air Pollutants, Occupational↗
PubMed1992

Structure and parameterization of pharmacokinetic models: their impact on model predictions.

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.

Animals↗
PubMed1991

Comparison of three physiologically based pharmacokinetic models of benzene disposition.

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.

Animals↗
PubMed1991

Mechanisms of benzene carcinogenesis: application of a physiological model of benzene pharmacokinetics and metabolism.

A physiological pharmacokinetic model for benzene, incorporating metabolic transformations, is used to explore why benzene, but not phenol--its primary metabolite--is carcinogenic at many sites in rats. The model has been parametrized using in vitro or in vivo experimental data. Ranges, rather than fixed values, were assigned to the parameters. The model-predicted levels of phenol and hydroquinone in the tissues are consistently higher when phenol, rather than benzene, is administered. This result demonstrates that the differential carcinogenicity of the two compounds is not explainable in the context of this pharmacokinetic analysis. It also indicates that the phenol-hydroquinone pathway alone is unlikely to account for the carcinogenic effects of benzene. Other metabolites must therefore also be involved.

Administration, Inhalation↗
PubMed1991

Environmental versus analytical variability in exposure measurements.

Measurements of 8-hr time-weighted average (TWA) exposures are subject to environmental variability and collection and analytical error. Environmental variability can be represented by the geometric standard deviation (GSD) of the lognormally distributed 8-hr TWAs; analytical variability can be represented by the coefficient of variation (CV) of the normally distributed collection and analytical errors. A mathematical expression is derived for the variance of the measured 8-hr TWAs as a function of the GSD of the true daily average exposures and the total CV of the industrial hygiene method used in monitoring. For typical values of the GSD and CV, environmental variability is far more important than analytical variability in determining the variance of the measured 8-hr TWAs. A resulting policy implication is that the Occupational Safety and Health Administration inappropriately focuses on analytical variability when determining compliance with its permissible exposure limits.

Bias↗
PubMed1991

Modeling benzene pharmacokinetics across three sets of animal data: parametric sensitivity and risk implications.

Typically, the uncertainty affecting the parameters of physiologically based pharmacokinetic (PBPK) models is ignored because it is not currently practical to adjust their values using classical parameter estimation techniques. This issue of parametric variability in a physiological model of benzene pharmacokinetics is addressed in this paper. Monte Carlo simulations were used to study the effects on the model output arising from variability in its parameters. The output was classified into two categories, depending on whether the output of the model on a particular run was judged to be generally consistent with published experimental data. Statistical techniques were used to examine sensitivity and interaction in the parameter space. The model was evaluated against the data from three different experiments in order to test for the structural adequacy of the model and the consistency of the experimental results. The regions of the parameter space associated with various inhalation and gavage experiments are distinct, and the model as presently structured cannot adequately represent the outcomes of all experiments. Our results suggest that further effort is required to discern between the structural adequacy of the model and the consistency of the experimental results. The impact of our results on the risk assessment process for benzene is also examined.

Animals↗
PubMed1991

A dose response relation for noise induced hypertension.

The effect of industrial noise on the prevalence of hypertension was studied in a group of 1101 female workers in a textile mill in Beijing in 1985. Essentially the entire group had worked in specific workshops in this mill for all their working lives and all had worked for at least five years. The noise levels within the plant were assessed and appear to have been constant since 1954 resulting in well defined noise exposures for these workers. A cross sectional design was used in which blood pressures were determined and questionnaires administered to the workers over a two month period. As well as demographic information, data were gathered on personal and family history of hypertension, current use of prescription drugs, alcohol, tobacco, and salt in the diet. Logistic regression indicated that exposure to noise is a significant determinant of prevalence of hypertension, but third in order of importance behind family history of hypertension and use of salt. Each of the predictor variables exerted an independent influence on risk of hypertension. Cumulative exposure to noise was not an important dose related variable suggesting that, for those susceptible to the effect, hypertension was manifested within the first five years of exposure.

Adult↗
PubMed1990

Variability in protection afforded by half-mask respirators against styrene exposure in the field.

Concentrations of styrene were measured in the breathing zone and inside the facepiece of air-purifying half-mask respirators of 13 workers for three to six 1-hr periods while they were engaged in the production of fiberglass-reinforced products. These data were used to estimate the protection afforded by the respirators. In arriving at these estimates, it was necessary to correct the concentration measured inside the mask for pulmonary retention of styrene by the workers. Workers were classified as sprayers or as other production line workers not directly carrying out spraying operations. An analysis of variance showed no evidence of differences in the level of protection afforded by the respirators between the two job classes. A second analysis of variance showed that protection varied between workers as well as for a single worker during different wearing periods. The geometric standard deviation (GSD) between workers was 1.92, the common within-worker GSD was 2.93, and the total GSD was 3.51. One-half of a population of wearers with similar protection would be expected to experience long-term average workplace protection factors in excess of 44 and one-half below that value. The observation of between-worker and within-worker variability in protection indicates that both sources of variability have to be taken into account in the specification of maximum use concentrations.

Air Pollutants, Occupational↗
PubMed1989

OSHA's permissible exposure limits: regulatory compliance versus health risk.

Workplace exposures to airborne chemicals are regulated in the U.S. by the Occupational Safety and Health Administration (OSHA) via the promulgation of permissible exposure limits (PELs). These limits, usually defined as eight-hour time-weighted average values, are enforced as concentrations never to be exceeded. In the case of chronic or delayed toxicants, the PEL is determined from epidemiological evidence and/or quantitative risk assessments based on long-term mean exposures or, equivalently, cumulative lifetime exposures. A statistical model was used to investigate the relation between the compliance strategy, the PEL as a limit never to be exceeded, and the health risk as measured by the probability that an individual's long-term mean exposure concentration is above the PEL. The model incorporates within-worker and between-worker variability in exposure, and assumes the relevant distributions to be log-normal. When data are inadequate to estimate the parameters of the full model, as it is in compliance inspections, it is argued that the probability of a random measurement being above the PEL must be regarded as a lower bound on the probability that a randomly selected worker's long-term mean exposure concentration will exceed the PEL. It is concluded that OSHA's compliance strategy is a reasonable, as well as a practical, means of limiting health risk for chronic or delayed toxicants.

Air Pollutants, Occupational↗
PubMed1987

Integrating uncertainty and interindividual variability in environmental risk assessment.

An integrated, quantitative approach to incorporating both uncertainty and interindividual variability into risk prediction models is described. Individual risk R is treated as a variable distributed in both an uncertainty dimension and a variability dimension, whereas population risk I (the number of additional cases caused by R) is purely uncertain. I is shown to follow a compound Poisson-binomial distribution, which in low-level risk contexts can often be approximated well by a corresponding compound Poisson distribution. The proposed analytic framework is illustrated with an application to cancer risk assessment for a California population exposed to 1,2-dibromo-3-chloropropane from ground water.

California↗