Significance of the Dermal Route of Exposure to Risk Assessment

The skin is a route of exposure that needs to be considered when conducting a risk assessment. It is necessary to identify the potential for dermal penetration by a chemical as well as to determine the overall importance of the dermal route of exposure as compared with inhalation or oral routes of exposure. The physical state of the chemical, vapor or liquid, the concentration, neat or dilute, and the vehicle, lipid or aqueous, is also important. Dermal risk is related to the product of the amounts of penetration and toxicity. Toxicity involves local effects on the skin itself and the potential for systemic effects. Dermal penetration is described in large part by the permeability constant. When permeability constants are not known, partition coefficients can be used to estimate a chemical's potential to permeate the skin. With these concepts in mind, a tiered approach is proposed for dermal risk assessment. A key first step is the determination of a skin-to-air or skin-to-medium partition coefficient to estimate a potential for dermal absorption. Building a physiologically-based pharmacokinetic (PBPK) model is another step in the tiered approach and is useful prior to classical in vivo toxicity tests. A PBPK model can be used to determine a permeability constant for a chemical as well as to show the distribution of the chemical systemically. A detailed understanding of species differences in the structure and function of the skin and how they relate to differences in penetration rates is necessary in order to extrapolate animal data from PBPK models to the human. A study is in progress to examine anatomical differences for four species.     

A measure of slope-rotatability for second order response surface experimental designs

In the design of experiments for estimating the slope of a response surface, slope-rotatability is a desirable property. In this paper, a measure is introduced that enables us to assess the degree of slope-rotatability for a given response surface design. The measure takes the value zero if and only if the design is slope-rotatable, and becomes larger as the design deviates from a slope-rotatable design. Examples of applying this measure to some response surface designs are also given.     

Analytical approximations for iterated bootstrap confidence intervals

Standard algorithms for the construction of iterated bootstrap confidence intervals are computationally very demanding, requiring nested levels of bootstrap resampling. We propose an alternative approach to constructing double bootstrap confidence intervals that involves replacing the inner level of resampling by an analytical approximation. This approximation is based on saddlepoint methods and a tail probability approximation of DiCiccio and Martin (1991). Our technique significantly reduces the computational expense of iterated bootstrap calculations. A formal algorithm for the construction of our approximate iterated bootstrap confidence intervals is presented, and some crucial practical issues arising in its implementation are discussed. Our procedure is illustrated in the case of constructing confidence intervals for ratios of means using both real and simulated data. We repeat an experiment of Schenker (1985) involving the construction of bootstrap confidence intervals for a variance and demonstrate that our technique makes feasible the construction of accurate bootstrap confidence intervals in that context. Finally, we investigate the use of our technique in a more complex setting, that of constructing confidence intervals for a correlation coefficient.     

Improved Monte Carlo inference for models with additive error

Some statistical models defined in terms of a generating stochastic mechanism have intractable distribution theory, which renders parameter estimation difficult. However, a Monte Carlo estimate of the log-likelihood surface for such a model can be obtained via computation of nonparametric density estimates from simulated realizations of the model. Unfortunately, the bias inherent in density estimation can cause bias in the resulting log-likelihood estimate that alters the location of its maximizer. In this paper a methodology for radically reducing this bias is developed for models with an additive error component. An illustrative example involving a stochastic model of molecular fragmentation and measurement is given.     

Pseudo–Modelling of Outliers for Estimation of Regression And Time Series Models

This paper documents situations where the variance inflation model for outliers has undesirable properties. The model is commonly used to accommodate outliers in a Bayesian analysis of regression and time series models. The alternative approach provided here does not suffer from these undesirable properties but gives inferences similar to those of the variance inflation model when this is appropriate. It can be used with regression, time series, and regression with correlated errors in a unified way, and adheres to the scientific principle that inference should be based on the data after obvious outliers have been discarded. Only one parameter is required for outliers; it is interpretable as the a priori willingness to remove observations from the analysis.     

Joint impact of multiple observations on a subset of variables in multiple linear regression

In multiple linear regression analysis, each observation affects the fitted regression equation differently and has varying influences on the regression coefficients of the different variables. Chatterjee & Hadi (1988) have proposed some measures such as DSSE_ij (Impact on Residual Sum of Squares of simultaneously omitting the ith observation and the jth variable), F_j (Partial F-test for the jth variable) and F_j(i) (Partial F-test for the jth variable omitting the ith observation) to show the joint impact and the interrelationship that exists among a variable and an observation. In this paper we have proposed more extended form of those measures DSSE_IJ, F_J and F_J(I) to deal with the interrelationships that exist among the multiple observations and a subset of variables by monitoring the effects of the simultaneous omission of multiple variables and multiple observations.     

Using a computer simulation game to teach family time use concepts

A computer simulation game designed to give students insights into family time use concepts has been used in an introductory family resource management class at Ohio State University and other universities. The game allows for planning for time use changes over the family life cycle. The game can give students insights into economic and sociological models of time use. It is possible that future versions of the game could be used in family counseling.His research interests include derivation of optimal decision-making rules for families and family financial management.Her research interests include financial management over the life course including financial ratios, baby boomers, and retirement. She received her Ph.D. in 1993 from The Ohio State University in Family Resource Management.His research interests include the time trade-offs made between couples, financial planning over the life cycle, and the interaction of time and money between families and their home-based businesses. He received his Ph.D. in 1993 from The Ohio State University in Family Resource Management.     

On the derivation of a full life table from mortality data recorded in five-year age groups

Mortality data are often gathered using 5-year age groups rather than individual years of life. Furthermore, it is common practice to use a large open-ended interval (such as 85 and over) for mortality data at the older ages. These limitations of the data pose problems for the actuary or demographer who wishes to compile a full and accurate life table using individual years of life. The author devises formulae which handle these problems. He also devises methods for handling mortality during the 1st year of life and for dealing with other technical problems which arise in the compilation of the full life table from grouped data.     

Effects of migration on family structure

This paper examines the situation and problems of migration on family structure, with emphasis on family reunification. The study is based on conditions and practices in Western Europe and Mediterranean countries relating to temporary labor migration. Most migrant workers have no intention of settling permanently and return to their country within a few years. The International Labour Office estimated in 1974 that at least 1/2 the migrant workers in Western Europe live without their families. Generally, migrants send for their families only when they are employed, earning adequate wages, and have adequate housing. Some reasons why migrants live apart from their families include 1) the receiving country discourages family immigration because it does not coincide with the economic necessities of migration policy and 2) some sending countries discourage it to ensure that the migrant worker returns to his own country. The main danger arising from family separation is that it frequently leads to the break up of the family. The leading European authorities recognize as a fundamental right the freedom of a migrant worker and his family to lead a normal family life in the receiving country. The author outlines the conditions for admission for residence and employment of migrant spouses and children for the Federal Republic of Germany, France, Belgium, Switzerland, the Netherlands, Sweden, Norway, Austria, Luxembourg, and the United Kingdom. All countries require that the head be in regular employment for some time and be able to provide his family with suitable housing. Other problems concerning the arrival of migrant spouses and children include 1) acquiring employment and social information and counseling, 2) education of children, 3) obtaining vocational training and adaptation and 4) achieving entitlement to social security benefits. The effects of migration in the family context in sending countries include 1) providing activities for migrants to maintain cultural links with their countries of origin and 2) acquiring the nationality of the receiving countries. Countries should facilitate the admission to employment of migrant spouses and children, by maintaining provisions for the reuniting of families and imposing no limits on admission to residence; and 2) by overcome obstacles to admission to employment, by observing existing recommendations. In conclusion, governments should give family cohesion 1st priority, regardless of regulations.