Methods for investigating age differences in the effects of prolonged exposures

Abstract

People experience physiological changes with age which may lead to changes in sensitivity to many kinds of exposure. In situations of prolonged, low level exposure, differences in the effects of exposures received at different ages may be difficult to evaluate, since study members receive low level exposures over a range of ages. Such investigations require examination of the effects of different age‐patterns of exposure. Three approaches to investigating age‐related variability in the effects of prolonged exposures are described: subcohort analyses; the use of smooth weighting functions; and, the evaluation of separate effects of cumulative exposures received at different age ranges. Each method can contribute to the overall evaluation of age‐specific exposure effects. These methods are illustrated with occupational cohort data for employees of Oak Ridge National Laboratory. The methods presented in this paper should facilitate examination of the effects of aging on sensitivity to prolonged exposures. Am. J. Ind. Med. 33:123–130, 1998. © 1998 Wiley‐Liss, Inc.

Environmental Toxicants Induced Male Reproductive Disorders: Identification and Mechanism of Action

“…This is a significant step forward in assessing the potential human toxicity of a class of chemicals known to be reproductive and developmental toxicants in rodents. Improved methods for analysis of exposure, especially of age and time effects, are likely to impact the characterization of occupational exposure in these studies (Richardson and Wing 1998). Current research approaches usually consider the action of single, unique toxicants on outcomes of interest, creating yet another challenge to drafting a reproductive hazards agenda.…”

Radiation and mortality of workers at Oak Ridge National Laboratory: positive associations for doses received at older ages.

“…An exception to the low overall mortality rates among ORNL workers as compared to the general population, however, is the observed excess mortality due to leukemia and illdefined causes (7,8 (8). Subsequent analyses of that subcohort reported that associations between radiation dose and cancer mortality were primarily due to radiation doses accrued at older ages (10,11,24).…”

“…Statistical analyses of radiation-mortality associations were conducted using the Poisson regression method (16,11 After evaluation of the data, we determined that a single term could be used to adjust for age at risk centered at 52.5 years in a log-log relationship for cancer causes of death and in a log-linear relationship for noncancer causes (22). This is similar to previous analyses of mortality of workers at the ORNL and has been demonstrated to be an efficient method for adjusting for age at risk (23,24 …”

“…Previous studies of this workforce have reported excess leukemia mortality as compared to the general population (7,8) and positive associations between cumulative external ionizing radiation dose and cancer mortality among white males at the ORNL who had not been employed at other DOE facilities (8,9). Subsequent analyses found that these dose-response associations were primarily due to the association between cancer mortality and radiation doses received at older ages (10,11). In contrast to previous studies, which focused on radiation-mortality associations among white males at the ORNL who had not been employed at other DOE facilities (7)(8)(9), we describe analyses that include all ORNL workers for whom data were adequately complete.…”

An occupational reproductive research agenda for the third millennium.

“…This is a significant step forward in assessing the potential human toxicity of a class of chemicals known to be reproductive and developmental toxicants in rodents. Improved methods for analysis of exposure, especially of age and time effects, are likely to impact the characterization of occupational exposure in these studies (Richardson and Wing 1998).…”