Systematic review of epidemiological and toxicological evidence on health effects of fluoride in drinking water.

INTRODUCTION: Fluoride is a naturally occurring substance that is also added to drinking water, dental hygiene products, and food supplements for preventing dental caries. Concerns have been raised about several other potential health risks of fluoride. OBJECTIVE: To conduct a robust synthesis of evidence regarding human health risks due to exposure to fluoride in drinking water, and to develop a point of departure (POD) for setting a health-based value (HBV) for fluoride in drinking water. METHODS: A systematic review of evidence published since recent reviews of human, animal, and in vitro data was carried out. Bradford Hill considerations were used to weigh the evidence for causality. Several key studies were considered for deriving PODs. RESULTS: The current review identified 89 human studies, 199 animal studies, and 10 major in vitro reviews. The weight of evidence on 39 health endpoints was presented. In addition to dental fluorosis, evidence was considered strong for reduction in IQ scores in children, moderate for thyroid dysfunction, weak for kidney dysfunction, and limited for sex hormone disruptions. CONCLUSION: The current review identified moderate dental fluorosis and reduction in IQ scores in children as the most relevant endpoints for establishing an HBV for fluoride in drinking water. PODs were derived for these two endpoints, although there is still some uncertainty in the causal weight of evidence for causality for reducing IQ scores in children and considerable uncertainty in the derivation of its POD. Given our evaluation of the overall weight of evidence, moderate dental fluorosis is suggested as the key endpoint until more evidence is accumulated on possible reduction of IQ scores effects. A POD of 1.56 mg fluoride/L for moderate dental fluorosis may be preferred as a starting point for setting an HBV for fluoride in drinking water to protect against moderate and severe dental fluorosis. Although outside the scope of the current review, precautionary concerns for potential neurodevelopmental cognitive effects may warrant special consideration in the derivation of the HBV for fluoride in drinking water.

A value of information framework for assessing the trade-offs associated with uncertainty, duration, and cost of chemical toxicity testing.

A number of investigators have explored the use of value of information (VOI) analysis to evaluate alternative information collection procedures in diverse decision-making contexts. This paper presents an analytic framework for determining the value of toxicity information used in risk-based decision making. The framework is specifically designed to explore the trade-offs between cost, timeliness, and uncertainty reduction associated with different toxicity-testing methodologies. The use of the proposed framework is demonstrated by two illustrative applications which, although based on simplified assumptions, show the insights that can be obtained through the use of VOI analysis. Specifically, these results suggest that timeliness of information collection has a significant impact on estimates of the VOI of chemical toxicity tests, even in the presence of smaller reductions in uncertainty. The framework introduces the concept of the expected value of delayed sample information, as an extension to the usual expected value of sample information, to accommodate the reductions in value resulting from delayed decision making. Our analysis also suggests that lower cost and higher throughput testing also may be beneficial in terms of public health benefits by increasing the number of substances that can be evaluated within a given budget. When the relative value is expressed in terms of return-on-investment per testing strategy, the differences can be substantial.

Quantifying the 60-Year Contribution of Japanese Zoos and Aquariums to Peer-Reviewed Scientific Research.

With the shift in their social roles, modern zoos and aquariums are required to develop scientific research. Although zoos and aquariums worldwide have reported an increase in the number of papers they publish and the diversification of their fields in recent decades, the specific circumstances in Japan are slightly unclear. We listed peer-reviewed papers authored by Japanese zoos and aquariums using search engines and quantitatively evaluated the changes in the number of papers published over 62 years. Our results showed that papers published in Japan have increased remarkably since the 1990s, and research fields have diversified as in the rest of the world. In particular, joint research with research institutes has seen an upward trend, and the instances of English-language papers have increased. Meanwhile, the content of the research was biased. In zoos, research on animal welfare has been increasing, but the focus was heavily biased toward captive mammals. Aquariums contributed to the understanding of local ecosystems through the fundamental study of wildlife, but there were fewer papers on improving husbandry. Our results indicated that while research by Japanese zoos and aquariums is developing, research on welfare, conservation, and education regarding native endangered species must still be improved.

A Framework that Considers the Impacts of Time, Cost, and Uncertainty in the Determination of the Cost Effectiveness of Toxicity-Testing Methodologies.

Regulatory agencies are required to evaluate the impacts of thousands of chemicals. Toxicological tests currently used in such evaluations are time-consuming and resource intensive; however, advances in toxicology and related fields are providing new testing methodologies that reduce the cost and time required for testing. The selection of a preferred methodology is challenging because the new methodologies vary in duration and cost, and the data they generate vary in the level of uncertainty. This article presents a framework for performing cost-effectiveness analyses (CEAs) of toxicity tests that account for cost, duration, and uncertainty. This is achieved by using an output metric-the cost per correct regulatory decision-that reflects the three elements. The framework is demonstrated in two example CEAs, one for a simple decision of risk acceptability and a second, more complex decision, involving the selection of regulatory actions. Each example CEA evaluates five hypothetical toxicity-testing methodologies which differ with respect to cost, time, and uncertainty. The results of the examples indicate that either a fivefold reduction in cost or duration can be a larger driver of the selection of an optimal toxicity-testing methodology than a fivefold reduction in uncertainty. Uncertainty becomes of similar importance to cost and duration when decisionmakers are required to make more complex decisions that require the determination of small differences in risk predictions. The framework presented in this article may provide a useful basis for the identification of cost-effective methods for toxicity testing of large numbers of chemicals.