Biomedical subjects
Renate D Kimbrough
Publications and source records attributed to Renate D Kimbrough.
Overview of exposure, toxicity, and risks to children from current levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin and related compounds in the USA.
Studies of children indicate that exposure of the general population to low levels of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) does not result in any clinical evidence of disease, although accidental exposure to high levels either before or after birth have led to a number of developmental deficits. Breast-fed infants have higher exposures than formula-fed infants, but studies consistently find that breast-fed infants perform better on developmental neurologic tests than their formula-fed counterparts, supporting the well-recognized benefits of breast feeding. Children receive higher exposures to PCDD/Fs from food than adults on a body-weight basis but those exposures are below the World Health Organization's tolerable daily intake. Laboratory rodents appear to be at least an order of magnitude more sensitive than humans to the aryl hydrocarbon receptor-mediated effects of these substances, which makes them poor surrogates for predicting quantitative risks but makes them good models for establishing safe levels of human exposure by organizations mandated to protect public health. Any exposure limit for PCDD/Fs based on developmental toxicity in sensitive laboratory animals can be expected to be especially protective of human health, including the health of infants and children. Because body burdens and environmental levels continue to decline, it is unlikely that children alive today in the USA will experience exposures to PCDD/Fs that are injurious to their health.
A mortality update of male and female capacitor workers exposed to polychlorinated biphenyls.
This analysis represents a 5-year update of our mortality study of 7075 PCB exposed capacitor workers that now includes 1654 deaths and 235,984 person-years of observation with follow-up through 1998. In hourly males and females the observed number of deaths from all-cancers and all-causes were similar to the expected numbers. In salaried males all-cause and all-cancer mortality were significantly below the expected. In salaried females, all-cause mortality was significantly below the expected and all-cancer mortality was below the expected, but not significantly. We again failed to find any significant excess mortality in the a priori cancers of concern or in any other cancers in the total cohort or in the highly exposed portion of the cohort. These results expand on our previous observations and as before the data fail to demonstrate any causal association between occupational PCB exposure and excess cancer mortality or any other causes of death.
Human exposure to polychlorinated biphenyls and health effects: a critical synopsis.
Polychlorinated biphenyls (PCBs) are a mixture of chemicals. Some congeners of the mixture are highly persistent both in the environment and in humans. Although PCBs have not been used commercially since about 1977 in the US, they can still be detected in human blood and tissues in this country. PCB levels are declining and are often no longer detectable in younger people. A cursory review of recent animal studies is provided. Studies to determine whether PCBs cause cancer in humans, neurobehavioural effects, abnormal thyroid and immune function in children and low birth weight are discussed in more detail. These studies are inconclusive and do not provide clinical evidence that PCBs at levels encountered with human exposure produce adverse health effects. The differences in PCB blood or tissue concentrations between controls and cases, or between the upper and lower end of various environmentally exposed groups of children or adults, are small. Although some effects are statistically significantly different, they do not appear to be biologically significant. Many studies on the effects of PCBs are difficult to interpret because the range of normal values for clinical and neurobehavioural tests are not provided or appropriately considered, there was no, or inadequate, control for potential confounders. In occupational mortality studies, exposures were much higher. In some studies, various specific cancers were elevated. However, these appear to be chance observations resulting from multiple comparisons since the increase of specific cancers was not consistent between studies and was no longer present in some cohorts when studies were repeated at a later date with longer follow-up. Overall, the data fail to demonstrate conclusive adverse health effects of PCBs at concentrations encountered with human exposures.
Polychlorinated biphenyls, TEQs, children, and data analysis.
The data analyses in the publications reviewed in Kimbrough et al (1) and Kimbrough and Krouskas (2) are discussed. All of the studies involve infants exposed in utero to small amounts of polychlorinated biphenyls (PCBs) and/or other chlorinated hydrocarbons. Because of missing sampling data, attrition of the cohorts over time, the use of TEQvalues (toxic equivalence) for some congeners of PCBs (polychlorinated biphenyls), PCDDs (polychlorinated dibenzo-p-dioxins) and PCDFs (polychlorinated dibenzofurans), the correlations reported by the authors between chemical exposure and adverse outcomes are not convincing. For the most part the exposures in these cohorts in the US and in Europe were within the ranges observed in the general population, and in many biological samples the level of organochlorines were below the limit of detection of the analytical method. Appropriate evaluation of such data is difficult given the many existing confounders. Many comparisons were made in the different studies. The observed differences were not consistent across studies and most likely occurred by chance. None of the observed differences reported in the children represent clinical disease.