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A J Bailer

Publications and source records attributed to A J Bailer.

At least 19 recordsLinked to original sources
PubMed1998

Trends in rates of occupational fatal injuries in the United States (1983-92).

OBJECTIVES: An updated version of a national surveillance system of traumatic occupational fatalities was used to explore adjusted and unadjusted trends in rates of fatal injury. METHODS: Data from the national traumatic occupational fatalities surveillance system were combined with data on employment from the United States Bureau of Labor Statistics. Poisson regression was then used to examine trends in rates of occupational fatality injuries while controlling for demographic and workplace characteristics. RESULTS: Adjusted annual changes in rates of fatal injuries ranged from a decline of 6.2% for workers in technical and administrative support occupations--for example, health, science, and engineering technicians, pilots, computer programmers--to an increase of 1.6% in machine operators, assemblers, and inspectors. For industries, annual changes ranged from a decline of 5.3% for workers in public administration--for example, justice, public order, and safety workers--to an increase of 2.6% for workers in the wholesale trade. By comparison, the annual decline over all industries and occupations was 3.1%. In many industries and occupations, an effect modification of annual trends by the age of the worker was also found with the oldest workers experiencing either no decline or a significant increase in rates of fatal injuries. CONCLUSIONS: This general pattern of decline, adjusted for the effects of demographic characteristics of the worker population, is encouraging; however, increases in rates of fatal injuries found in particular industries and occupations, suggest appropriate targets for increased injury prevention efforts.

Accidents, Occupational↗
PubMed1998

Incorporating hormesis in the routine testing of hazards.

The phenomenon of subtoxic stimulation of organism response is not uncommon in aquatic toxicology experiments. We describe the presence of hormesis in both growth and reproduction experiments in aquatic toxicology where these responses are observed in both animals and plants and at different trophic levels of an ecosystem. The implications of ignoring hormetic responses in the analysis of toxicity data are discussed. In particular, we note that specification of models that explicitly cannot accommodate or remove potential effects of hormesis may lead to biased potency estimates. Further, the presence of hormesis has implications for the design of toxicology experiments, with the spacing of concentration test conditions being critical.

Animals↗
PubMed1998

Added risk and inverse estimation for count responses in reproductive aquatic toxicology studies.

One of the experimental designs used to evaluate the toxicity of certain chemicals in aquatic organisms focuses on reproductive output. Toxic effects are manifested through a reduced level of reproduction in exposed organisms. Historically, evaluating risks in this context has focused on changes in the mean reproduction in a population of organisms. In this paper, we focus on the toxic effects at the level of the individual organism. This new method for count responses involves added risk, the probability of the production of young being suppressed below certain specified levels in individuals exposed to a particular concentration level relative to the probability of that level of suppression in control organisms. This probability serves as the basis of the individual-based risk estimation procedures. In particular, inverse estimation of the concentration associated with a specified added risk and estimates of the added risk associated with a particular concentration are discussed in the context of a negative binomial regression model. Confidence intervals are constructed for both of these quantities using the delta method. These methods are illustrated with a study of an aquatic organism, Ceriodaphnia dubia, exposed to the herbicide nitrofen.

Animals↗
PubMed1997

Estimating benchmark concentrations and other noncancer endpoints in epidemiology studies.

Methods for evaluating the hazards associated with noncancer responses with epidemiologic data are considered. The methods for noncancer risk assessment have largely been developed for experimental data, and are not always suitable for the more complex structure of epidemiologic data. In epidemiology, the measurement of the response and the exposure is often either continuous or dichotomous. For a continuous noncancer response modeled with multiple regression, a variety of endpoints may be examined: (1) the concentration associated with absolute or relative decrements in response; (2) a threshold concentration associated with no change in response; and (3) the concentration associated with a particular added risk of impairment. For a dichotomous noncancer response modeled with logistic regression, concentrations associated with specified added/extra risk or with a threshold responses may be estimated. No-observed-effect concentrations may also be estimated for categorizations of exposures for both continuous and dichotomous responses but these may depend on the arbitrary categories chosen. Respiratory function in miners exposed to coal dust is used to illustrate these methods.

Age Factors↗
PubMed1997

An introduction to the use of physiologically based pharmacokinetic models in risk assessment.

Many extrapolation issues surface in quantitative risk assessments. The extrapolation from high-dose animal studies to low-dose human exposures is of particular concern. Physiologically based pharmacokinetic (PBPK) models are often proposed as tools to mitigate the problems of extrapolation. These models provide a representation of the disposition, metabolism, and excretion of xenobiotics that are believed to possess the potential of inducing adverse human health responses. Given a model of xenobiotic disposition that is applicable for multiple species and appropriate for nonlinearity of the xenobiotic biotransformation process, better extrapolation may be possible. Unfortunately, the true structure of these models (e.g. number of compartments, type of metabolism, etc.) is seldom known, and attributes of these models (tissue volumes, partition coefficients, etc.) are often experimentally determined and often only central measures of these quantities are reported. We describe the use of PBPK models in risk assessment, the structural and parameter uncertainty in these models, and provide a simple illustration of how these characteristics can be incorporated in a statistical analysis of PBPK models. Additional complexity in the analysis of variability in the models is also outlined. This discussion is illustrated using data from methylene chloride.

Animals↗
PubMed1995

Modeling epidemiologic studies of occupational cohorts for the quantitative assessment of carcinogenic hazards.

Epidemiologic studies of occupational cohorts have played a major role in the quantitative assessment of risks associated with several carcinogenic hazards and are likely to play an increasingly important role in this area. Relatively little attention has been given in either the epidemiologic or the risk assessment literature to the development of appropriate methods for modeling epidemiologic data for quantitative risk assessment (QRA). The purpose of this paper is to review currently available methods for modeling epidemiologic data for risk assessment. The focus of this paper is on methods for use with retrospective cohort mortality studies of occupational groups for estimating cancer risk, since these are the data most commonly used when epidemiologic information is used for QRA. Both empirical (e.g., Poisson regression and Cox proportionate hazards model) and biologic (e.g., two-stage models) models are considered. Analyses of a study of lung cancer among workers exposed to cadmium are used to illustrate these modeling methods. Based on this example it is demonstrated that the selection of a particular model may have a large influence on the resulting estimates of risk.

Cadmium↗
PubMed1995

Exploratory analysis of population genetic assessment as a water quality indicator. I. Pimephales notatus.

Biological sampling has been implemented to assess water quality in many states. The purpose of this study was to examine whether genetic diversity and structure of Pimephales notatus could serve as effective biomarkers of exposure to anthropogenic stressors by comparing genetic measures with other biological indicators of water quality. Fish were collected from 15 sites on eight streams by the Ohio Environmental Protection Agency as part of their stream water quality evaluation program. Values for the Index of Biotic Integrity (IBI) and the Invertebrate Community Index (ICI) were determined for these 15 sites. Starch gel electrophoresis was used to collect genetic data for seven variable enzyme loci. Genetic diversity measures were not associated with site IBI or ICI values. However, the range of site IBI and ICI values was limited. The proportion of individuals not expressing esterase locus 3 could be used to predict IBI; IBI decreased as the proportion of nonexpression increased. Allele and genotype frequency differences were observed between sites on the Little Scioto River, the one stream with a large difference in IBI and ICI values between sites. This study suggested that allele and genotype frequencies may have been impacted without affecting overall species diversity.

Alleles↗
PubMed1995

Exploratory analysis of population genetic assessment as a water quality indicator. II. Campostoma anomalum.

Biological monitoring programs to assess contaminant-induced impacts in aquatic systems are being developed and implemented by several federal agencies and many states. Genetic diversity and allozyme frequency may be valuable indicators of such impact because they are both sensitive to exposure and ecologically relevant in populations. The purpose of this study was to examine whether genetic diversity and structure of Campostoma anomalum populations could serve as effective biomarkers of exposure to anthropogenic stress by comparing genetic measures with other biological indicators of water quality. Fish were collected from 14 sites on seven streams by the Ohio Environmental Protection Agency as part of their stream water quality evaluation program. Values for the Index of Biological Integrity (IBI) and the Invertebrate Community Index (ICI) were determined for these 14 sites. Starch gel electrophoresis was used to collect genetic data for eight variable enzyme loci. Genetic diversity measures were not associated with site IBI or ICI values. However, the range of site IBI and ICI values was limited. Allele and genotype frequencies were significantly different at the point source compared to sites upstream and downstream indicating that genetic structure may be an indicator of water quality that is sensitive enough to detect change prior to species loss.

Acid Phosphatase↗
PubMed1994

The impact of exercise and intersubject variability on dose estimates for dichloromethane derived from a physiologically based pharmacokinetic model.

Andersen et al. and Reitz et al. have developed physiologically based pharmacokinetic models for the human metabolism of methylene chloride (dichloromethane; DCM) and have advanced the hypothesis that the carcinogenicity of DCM is related to target organ metabolism of DCM by glutathione S-transferase (GST). The models included physiological parameters appropriate for humans at rest and metabolic parameters based on average rates of DCM metabolism. Increasing the model parameters describing cardiac output, alveolar ventilation, and blood flows to tissues from resting values to values consistent with light work conditions, and assuming a 25 ppm exposure for an 8-hr work day, increases the estimated GST-metabolized dose for human liver by a factor of 2.9 compared to the GST-metabolized does estimated of Reitz et al. These modifications also increase the GST-metabolized dose to the lung by 2.4-fold. If the model is also modified to reflect individual variation in DCM metabolism (in addition to the modifications for light work conditions), the estimated GST-metabolized dose for human liver ranges from 0 to as much as 5.4-fold greater than the dose estimated by Reitz et al. The GST-metabolized dose to the lung ranges from 0 to as much as 3.6-fold greater than the dose estimated by Reitz et al. These results indicate that some occupationally-exposed individuals may receive GST-metabolized doses several-fold greater than the Reitz et al. human dose estimates.

Adipose Tissue↗
PubMed1994

Statistical approaches for analyzing mutational spectra: some recommendations for categorical data.

In studies examining the patterns or spectra of mutational damage, the primary variables of interest are expressed typically as discrete counts within defined categories of damage. Various statistical methods can be applied to test for heterogeneity among the observed spectra of different classes, treatment groups and/or doses of a mutagen. These are described and compared via computer simulations to determine which are most appropriate for practical use in the evaluation of spectral data. Our results suggest that selected, simple modifications of the usual Pearson X2 statistic for contingency tables provide stable false positive error rates near the usual alpha = 0.05 level and also acceptable sensitivity to detect differences among spectra. Extensions to the problem of identifying individual differences within and among mutant spectra are noted.

Base Sequence↗
PubMed1994

Estimating upper confidence limits for extra risk in quantal multistage models.

Multistage models are frequently applied in carcinogenic risk assessment. In their simplest form, these models relate the probability of tumor presence to some measure of dose. These models are then used to project the excess risk of tumor occurrence at doses frequently well below the lowest experimental dose. Upper confidence limits on the excess risk associated with exposures at these doses are then determined. A likelihood-based method is commonly used to determine these limits. We compare this method to two computationally intensive "bootstrap" methods for determining the 95% upper confidence limit on extra risk. The coverage probabilities and bias of likelihood-based and bootstrap estimates are examined in a simulation study of carcinogenicity experiments. The coverage probabilities of the nonparametric bootstrap method fell below 95% more frequently and by wider margins than the better-performing parametric bootstrap and likelihood-based methods. The relative bias of all estimators are seen to be affected by the amount of curvature in the true underlying dose-response function. In general, the likelihood-based method has the best coverage probability properties while the parametric bootstrap is less biased and less variable than the likelihood-based method. Ultimately, neither method is entirely satisfactory for highly curved dose-response patterns.

Animals↗
PubMed1994

Model-based time extrapolation for quantal response studies.

It is often desired to compare chemicals with respect to toxicity for purposes of priority setting in regulation. Long-term carcinogenicity studies are frequently used as the basic data for such exercises. When the results of these studies for different chemicals are compared, many confounders potentially arise. One confounder is that these studies may have been conducted for different study lengths. In this case, converting the results of these studies to a common "standard" time length would be of interest. We propose an adjustment to modify the results of a study with a particular study length to a standard time length. This adjustment is based on a simple stochastic model for carcinogenicity studies. We illustrate the application of this adjustment with an example of a chemical that has been studied by the National Toxicology Program.

Animals↗
PubMed1993

Comparing toxicologic and epidemiologic studies: methylene chloride--a case study.

Exposure to methylene chloride induces lung and liver cancers in mice. The mouse bioassay data have been used as the basis for several cancer risk assessments. The results from epidemiologic studies of workers exposed to methylene chloride have been mixed with respect to demonstrating an increased cancer risk. The results from a negative epidemiologic study of Kodak workers have been used by two groups of investigators to test the predictions from the EPA risk assessment models. These two groups used very different approaches to this problem, which resulted in opposite conclusions regarding the consistency between the animal model predictions and the Kodak study results. The results from the Kodak study are used to test the predictions from OSHA's multistage models of liver and lung cancer risk. Confidence intervals for the standardized mortality ratios (SMRs) from the Kodak study are compared with the predicted confidence intervals derived from OSHA's risk assessment models. Adjustments for the "healthy worker effect," differences in length of follow-up, and dosimetry between animals and humans were incorporated into these comparisons. Based on these comparisons, we conclude that the negative results from the Kodak study are not inconsistent with the predictions from OSHA's risk assessment model.

Animals↗
PubMed1993

Time-to-tumour risk assessment for 1,3-butadiene based on exposure of mice to low doses by inhalation.

The excess risk for cancer due to lifetime occupational exposure to 1,3-butadiene at the proposed US Occupational Safety and Health Administration standard of 2 ppm was estimated on the basis of a quantitative risk assessment. The risk assessment was based on a recent study by the US National Toxicology Program of the carcinogenicity of butadiene in B6C3F1 mice, using exposure concentrations ranging from 6.25 to 625 ppm butadiene and controls. Cancer risks were estimated using a multistage Weibull time-to-tumour model; the dose was based on the external butadiene concentration, owing to the low-dose linearity of butadiene metabolism. The parameters of the time-to-tumour model were estimated for seven tumour sites in male mice and nine in female mice. The risk estimates were extrapolated from mice to humans on the basis of body weight raised to the three-fourths power, and the median lifespan of mice was equated to a human lifespan of 74 years. Estimates of excess risk for lifetime occupational exposure (8 h/day, 5 days/week, 50 weeks/year, for 45 years) to 2 ppm butadiene ranged from 0.2 per 10,000 workers, based on female mouse heart haemangiosarcomas, to 600 per 10,000 workers, based on female mouse lung tumours. An analysis was performed to assess the effects of varying the modelling assumptions (incidental versus fatal tumours, inclusion or exclusion of the 625-ppm dose group, and basis for interspecies scaling) on the risk estimates from the female mouse lung tumour model. Depending on the assumptions, estimates of lifetime excess risk derived from the female mouse lung model ranged from 60 per 10,000 to 1600 per 10,000. These results suggest that exposures to butadiene in the work place should be reduced to the lowest feasible level.

Administration, Inhalation↗
PubMed1993

A measure of tumorigenic potency incorporating dose-response shape.

Many researchers have considered the problem of ranking chemical agents based on their carcinogenic potency. Sawyer et al. (1984, Biometrics 40, 27-40) proposed a carcinogenic potency estimate that incorporates both intercurrent mortality and background tumor rates. Since then, many authors have either generalized the method outlined by Sawyer et al. or developed their own method based on a slightly different adjustment for treatment-related changes in survival. None of these methods, however, has estimated the shape of the dose-response curve and incorporated such an estimate in potency estimation. In this manuscript, a measure of tumorigenic potency is proposed that utilizes the estimated shape of the dose-response relationship, in addition to estimated dose effects, in order to rank chemicals on the basis of carcinogenic risk. Comparison of this new measure to that of Sawyer et al. is done using a large database of animal carcinogenicity experiments from the National Cancer Institute and the National Toxicology Program.

Animals↗
PubMed1993

An index of tumorigenic potency.

A new index of tumorigenic potency is derived using a survival-adjusted quantal response estimator given by Bailer and Portier (1988, Biometrics 44, 417-431). The small-sample bias and mean squared error properties of this estimator are explored using computer simulations of animal carcinogenicity experiments and are compared to the characteristics of the TD50, an estimator proposed by Sawyer et al. (1984, Biometrics 40, 27-40). It is observed that this new index tends to have smaller bias and mean squared error relative to the TD50 over varying shapes of the tumor onset distribution, levels of tumor lethality, and levels of treatment lethality.

Animals↗
PubMed1990

A note on fitting one-compartment models: non-linear least squares versus linear least squares using transformed data.

Drug concentrations in one-compartment systems are frequently modeled using a single exponential function. Two methods of estimation are commonly used for determining the parameters of such a model. In the first method, non-linear least-squares regression is used to calculate the parameters. In the second method, the data are first transformed by a logarithmic function, and then the log-concentration data are fit using linear least-squares regression. The assumptions for fitting these models are discussed with special emphasis on which data points are most influential in determining parameter values. The similarities between fitting a linear regression model to the log-concentration data and fitting a weighted regression model to the original data are noted. An example is presented that illustrates the differences in fitting a model to the log-transformed data versus fitting unweighted and weighted models to the original-scale data.

Animals↗