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M S Legator

Publications and source records attributed to M S Legator.

At least 145 records · Page 8Linked to original sources
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Use of in vivo genetic toxicity data for risk assessment.

Mutagenicity studies have been used to identify specific agents as potential carcinogens or other human health hazards; however, they have been used minimally for risk assessment or in determining permissible levels of human exposure. The poor predictive value of in vitro mutagenesis tests for carcinogenic activity and a lack of mechanistic understanding of the roles of mutagens in the induction of specific cancers have made these tests unattractive for the purpose of risk assessment. However, the limited resources available for carcinogen testing and large number of chemicals which need to be evaluated necessitate the incorporation of more efficient methods into the evaluation process. In vivo genetic toxicity testing can be recommended for this purpose because in vivo assays incorporate the metabolic activation pathways that are relevant to humans. We propose the use of a multiple end-point in vivo comprehensive testing protocol (CTP) using rodents. Studies using sub-acute exposure to low levels of test agents by routes consistent with human exposure can be a useful adjunct to methods currently used to provide data for risk assessment. Evaluations can include metabolic and pharmacokinetic endpoints, in addition to genetic toxicity studies, in order to provide a comprehensive examination of the mechanism of toxicity of the agent. A parallelogram approach can be used to estimate effects in non-accessible human tissues by using data from accessible human tissues and analogous tissues in animals. A categorical risk assessment procedure can be used which would consider, in order of priority, genetic damage in man, genetic damage in animals that is highly relevant to disease outcome (mutation, chromosome damage), and data from animals that is of less certain relevance to disease. Action levels of environmental exposure would be determined based on the lowest observed effect levels or the highest observed no effect levels, using sub-acute low level exposure studies in rodents. As an example, the known genotoxic effects of benzene exposure at low levels in man and animals are discussed. The lowest observed genotoxic effects were observed at about 1-10 parts per million for man and 0.04-0.1 parts per million in subacute animal studies. If genetic toxicity is to achieve a prominent role in evaluating carcinogens and in characterizing germ-cell mutagens, minimal testing requirements must be established to ascertain the risks associated with environmental mutagen exposure. The use of the in vivo approach described here should provide the information needed to meet this goal.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
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Advantages of a combined testing protocol (CTP) with multiple endpoints: the reverse tier approach.

A multi-endpoint CTP approach provides an efficient procedure to investigate the hazards of chemicals in our environment. Genotoxicity to multiple tissues is assessed after an exposure of limited duration by using a variety of sensitive short-term tests. Resources are thus conserved and results obtained without long delays. Additional information helpful in understanding the observed genotoxic effects is readily obtained in the same experiment by inclusion of additional nongenotoxic endpoints. Numbers of animals required to test chemicals are substantially decreased by increasing the amount of information obtained from each animal. Flexibility is a basic asset of a CTP approach. Therefore, pharmacokinetics of the test chemical or mixture and concerns about subpopulations of exposed humans can guide all aspects of the design of CTP protocol including the animal species, the exposure protocol and the endpoints. The procedures selected for evaluating potential mutagens should be based primarily on the usefulness of the information generated and secondarily on the cost and resources required to perform the procedure. The most expensive procedure is that procedure which does not generate useful information, regardless of the initial cost. The CTP as presently discussed is an attempt to maximize useful information in the most efficient manner possible. Although considerably more expensive than in vitro procedures, the protocol is far less expensive than conducting individual short-term animal procedures, and a fraction of the cost and time required to perform a typical cancer bioassay. Chemicals that are of major concern, for example as in the case of extensive human exposure, would be a prime candidate for initial testing by this methodology.

Animals↗
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Health effects from chronic low-level exposure to hydrogen sulfide.

The acute toxic effects of hydrogen sulfide have been known for decades. However, studies investigating the adverse health effects from chronic, low-level exposure to this chemical are limited. In this study, the authors compared symptoms of adverse health effects, reported by residents of two communities exposed mainly to chronic, low-levels of industrial sources of hydrogen sulfide, to health effects reported by residents in three reference communities in which there were no known industrial sources of hydrogen sulfide. Trained interviewers used a specially created, menu-driven computer questionnaire to conduct a multi-symptom health survey. The data-collection process and questions were essentially the same in the reference and exposed communities. The two exposed communities responded very similarly to questions about the major categories. When the authors compared responses of the exposed communities with those of the reference communities, 9 of the 12 symptom categories had iterated odds ratios greater than 3.0. The symptoms related to the central nervous system had the highest iterated odds ratio (i.e., 12.7; 95% confidence interval = 7.59, 22.09), followed by the respiratory category (odds ratio = 11.92; 95% confidence interval = 6.03, 25.72), and the blood category (odds ratio = 8.07; 95% confidence interval = 3.64, 21.18). Within the broader health categories, individual symptoms were also elevated significantly. This study, like all community-based studies, had several inherent limitations. Limitations, and the procedures the authors used to minimize their effects on the study outcomes, are discussed. The results of this study emphasize the need for further studies on the adverse health effects related to long-term, chronic exposure to hydrogen sulfide.

Adolescent↗
PubMedDate not supplied

The health effects of living near cement kilns; a symptom survey in Midlothian, Texas.

Cement kilns are major sources of toxic air emissions. Regulations based on demonstrated concentrations of specific chemicals, and risk assessments with inherent limitations and uncertainties, are the current methods of preventing exposure to 'unsafe' emission levels. Monitoring data are frequently incomplete. These limitations mandate that residents residing near cement kilns be evaluated for adverse health effects. This study reports findings from a symptom survey conducted in Midlothian, Texas, which adds to the limited but growing body of knowledge showing that persons living near cement kilns are experiencing increased respiratory effects. This cross-sectional study uses randomized sampling and an extensive health questionnaire, covering 12 physiological systems, to determine differences in reported health symptoms between the study community (Midlothian, Texas, n = 58) and the reference community (Waxahachie, Texas, n = 54). Findings indicate significant elevations in reported respiratory symptoms in the study community (p-value 0.002). Although the comparatively small sample size is a limitation, the fact that only 'respiratory effects' were highly significant supports the efficacy of this investigation. Respiratory effects would be the major anticipated outcome from the known exposures under investigation. This specificity of response (i.e., elevation in respiratory symptoms only), indicates that 'response bias' was not a significant factor in this study.

Adolescent↗