Biomedical subjects
Publications and source records attributed to S S Olin.
Research needed to better understand the similarities and differences between children and adults in their inherent susceptibilities to toxicants is briefly outlined. The focus is on cancer, immune system effects, and neurotoxicity. A full report of the ILSI Working Group that developed these recommendations is available from the ILSI Risk Science Institute.
For each essential trace element, there are two ranges of intake associated with adverse health effects: intakes that are too low and can lead to nutritional deficits and intakes that are too high and can lead to toxicity. Between these two ranges, there is a range of safe and adequate intakes that is compatible with good health; the challenge is to define that range quantitatively. The exposure limit for toxicity traditionally has been determined by dividing a "no-observed-adverse-effect level," often from studies in experimental animals, by a series of uncertainty factors. Dietary allowances to meet nutritional requirements, on the other hand, have been based primarily on data in humans. Uncertainty, variability and limitations in the data base tend to increase estimates of nutritional requirements and decrease estimated toxic exposure limits, driving the values closer together. Chromium (III) and zinc are contrasting cases. Other factors, such as bioavailability, selection of the critical effect and interactions also can play important roles. Close coordination between the nutrition and toxicology communities, as envisioned in the NRC Food and Nutrition Board initiative on Dietary Reference Intakes, is essential in establishing acceptable ranges of intake for trace elements.
No study has yet reported specifically on the early behavior of individuals later diagnosed with schizotypal personality disorder (SPD). This study examines prospectively collected teacher reports on school behavior as a means of assessing childhood precursors of SPD. Thirty-six DSM-III-R diagnosed schizotypal subjects were compared with four other groups: 31 schizophrenia patients, 37 diagnosed as nonpsychotic mentally ill, 68 who were not mentally ill but had mothers with schizophrenia, and 60 who were not mentally ill and had normal parents. These individuals were compared on a teachers' school report questionnaire obtained when the subjects averaged 15.1 years old. Those who later developed SPD were found to be more passive and unengaged and more hypersensitive to criticisms compared with the nonschizophrenia groups. Similar results were found when males and females were examined separately, except that males who developed SPD were found to be less disruptive and hyperexcitable compared with males with schizophrenia; females with SPD did not differ from females with schizophrenia. A receiver operating characteristic analysis found these factors to predict 73.5 percent of future SPDs; the ability of these factors to predict future SPDs is comparable for males and females. These findings suggest that preschizotypal traits may be identified in late childhood or adolescence.
The estimation of carcinogenic risks from exposure to chemicals has become an integral part of the regulatory process in the United States within the past decade. With it have come considerable controversy and debate over the scientific merits and shortcomings of the methods and their impact on risk management decisions. In this paper we highlight selected topics of current interest in the debate. As an indication of the level of public concern, we note the major recent reports on risk assessment from the National Academy of Sciences and the U.S Environmental Protection Agency's proposed substantial revisions to its Guidelines for Carcinogen Risk Assessment. We identify and briefly frame several key scientific issues in cancer risk assessment, including the growing recognition of the importance of understanding the mode of action of carcinogenesis in experimental animals and in humans, the methodologies and challenges in quantitative extrapolation of cancer risks, and the question of how to assess and account for human variability in susceptibility to carcinogens. In addition, we discuss initiatives in progress that may fundamentally alter the carcinogenesis testing paradigm.
Determining how findings of chemically induced carcinogenic effects in rodents can properly be interpreted for human health poses a continuing challenge to the risk assessment community. One approach begins by comparing and contrasting carcinogenic process in rodents and humans, identifying biologically significant similarities and differences and gaps in scientific knowledge and understanding. Russo and Russo (in this issue) use just such an approach to evaluate the current state of scientific understanding of the comparative mechanisms of mammary tumorigenesis in humans and rodents, particularly the role of reproductive hormones. This commentary describes the basis for this review and suggests some of the implications the report may have for human health risk assessment and for future research.
Some of the most challenging problems that toxicologists confront are determining how biological effects of components in a complex mixture may interact, determining how these interactions affect the overall toxicity of the mixture, and determining how to incorporate this information into risk assessments of chemical mixtures. There has been considerable effort in this area since the publication of the U.S. Environmental Protection Agency's guidelines for risk assessment of chemical mixtures in 1986. This paper reviews the terminology used to describe chemical interactions and the methodologies that have been developed for conducting risk assessments of chemical mixtures. Particular attention is directed towards an examination of the applicability and validity of the methods for the assessment of risk posed by exposure to environmentally relevant concentrations of chemical mixtures. Limited, yet compelling, data are reviewed that suggest that for noncancer endpoints, adverse effects are unlikely to occur when the individual components in the mixture are present at levels well below their respective thresholds. Synergistic or antagonistic effects, not readily predicted from the mechanisms of action of the individual components, are possible when the mixture components are present at levels equal to or above their individual thresholds. Finally, synergistic carcinogenic effects have been observed in animal studies of mixtures, even at relatively low doses.
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We examined teachers' reports to determine early patterns of school behavior that identify children who were diagnosed schizophrenic in adulthood. High risk subjects (n = 207) in the Copenhagen High Risk for schizophrenia project were examined on a 25-item questionnaire completed by teachers. A likelihood ratio approach was used to create a classification index relating school report to DSM-IIIR diagnoses made 31 years later. A standard receiver operating characteristic (ROC) analysis was used to evaluate the efficacy of the classification indices for distinguishing preschizophrenics from children who later developed schizotypal disorder, other nonpsychotic disorders, and no mental illness. Different items predicted schizophrenia in males and females. To a significantly greater degree than their controls, preschizophrenic males were lonely and rejected, behaved inappropriately, were disciplinary problems, emotionally high strung, and were more likely to have repeated a grade; preschizophrenic females were nervous and passive. Both preschizophrenic males and females were judged by teachers to be vulnerable to future psychotic problems. These findings are consistent with our preliminary findings, as well as with other research. They highlight the ability of teachers to identify school behaviors that may be used to select future schizophrenics for early intervention.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.