A workshop on the Scientific Issues Relevant to Assessment of Health Effects from Exposure to Methylmercury was held in Raleigh, North Carolina, November 18-20, 1998. At that time, most discussions focused on two of the major epidemiologic studies, e. g., Seychelles child development study and Faroese birth cohort study, associating methylmercury exposure with an array of developmental measures in children. These two studies seemed to provide different conclusions on the potential health effects of methylmercury and significant uncertainties remained because of issues related to exposure, neurobehavioral endpoints, confounders and statistics, and design. Since then, each group researching the Seychellois or Faroes cohort has reported some new findings on the risk assessment of methylmercury. This article is intended to present an overview of the above research, as well as benchmark dose calculations. One implication is that neuropsychological measures may depend on social and cultural factors including race and language, and another is that a key to resolve whether the exposure has harmed the fetus appears to lie in neurophysiological measures such as brainstem auditory evoked potentials and electrocardiographic R-R interval variability. In addition, it is likely that the findings published tend to underestimate the neurotoxic effects of developmental methylmercury exposure. In light of the precautionary principle, a conclusion on health effects of low-level dietary exposures to methylmercury needs to be drawn from all available data including the New Zealand study.

View full abstract

Hypospadias and cryptorchidism are common congenital anomalies. Recently, increases in the prevalence of hypospadias and cryptorchidism have been reported in various countries, including Japan. As male sexual differentiation is critically dependent on normal androgen concentrations, increased exposure to environmental factors affecting androgen homeostasis during fetal life (i. e. EDCs with estrogenic or anti-androgenic effects) may cause hypospadias or cryptorchidism. However, the results from the International Clearinghouse for Birth Defects Monitoring System (ICBDMS), hospital-based studies in each country and population-based studies in Japan are different, because in the present system there are some problems such as the standardization of diagnostic criteria and the difference of the time of diagnosis, we hope to improve the monitoring system method.
Previous papers have reported that hypospadias and cryptorchidism were associated with maternal exposure to progesterone, estrogen, diethylstilbestrol (DES) and pesticide. However, there are few studies evaluating the quantity of endocrine disrupting chemicals, using biological samples.
In the future, a well-designed epidemiological study is needed to elucidate the relation between endocrine disrupting chemicals and genital development.

View full abstract

The reporter gene expression method CALUX^(R) cell bioassay has proven to be a very valuable screening technique for assessing toxic equivalents of dioxin and dioxin-like compounds, because it detects all AhR ligands in a variety of sample matrices. Used with the two specially elaborated clean-up procedures, CALUX^(R) cell bioassay was established for various environmental and biological samples. Consequently, the CALUX-TEQ values are correlated with high correlation coefficiencies to WHO-TEQ values derived from HRGC/HRMS. CALUX^(R) assay has been applied to the screening and quarantine of food items with possible dioxin contaminations in the EU. In addition, the method has been applied to biological samples such as serum, breast milk and fat tissues. Several reported studies demonstrated that CALUX^(R) cell assay is a useful tool and applicable in human epidemiological studies. We need to establish multi-national comparative studies in the field of dioxin contamination.

View full abstract

Silicosis patients not only suffer from respiratory disorders but also from autoimmune diseases. To clarify the mechanisms involved in the occurrence of the dysregulation of autoimmunity found in silicosis patients, we have been focusing on investigation of the Fas and Fas-related molecules in the Fas-mediated apoptotic pathway, since Fas is one of the most important molecules regulating autoimmunity in mainly T cells. Our findings showed that silicosis patients exhibited elevated serum soluble Fas levels, increased relative expression of soluble Fas and DcR 3 genes in peripheral blood mononuclear cells, other highly detectable variant messages of Fas transcripts, relatively decreased expression of several physiological inhibitors (Sentrin, I-Fline, ICAD/DFF45, and survivin), and dominancy of lower membrane Fas expressers in lymphocytes when compared with healthy volunteers. These parameters also constitute immunological factors with serum immunogulobulin G and the titer of anti-nuclear autoantibodies. In addition, anti-caspase 8 autoantibody and anti-Fas autoantibody were also detected in the serum from silicosis patients, and a functional assay showed that anti-Fas antibody stimulated Fas-mediated apoptosis. Taken together, we hypothesize that there are two subpopulations of silicosis lymphocytes. One is a long-term survival fraction including a self-recognizing fraction showing lower membrane Fas and inhibition of Fas/Fas ligand bindings in the extracellular region. The other is a fraction exhibiting apoptosis caused by silica/silicates, recruiting from bone marrow, showing higher membrane Fas and sensitive to anti-Fas autoantibody. Further investigations should be performed to confirm the effects of silica/silicates on the human immune system.

View full abstract

Objectives: The objective of this study was to estimate the indoor thermal environment and the air-conditioning pattern in bedrooms during sleeping time, and to evaluate the relationship between the indoor thermal environment and the dwelling characteristics in Nagoya, Japan.
Methods: Temperature, relative humidity and information on dwelling characteristics were obtained from 84 dwellings in summer and 100 dwellings in winter from 1995 to 2001.
Results: The mean percentage of bedrooms air-conditioned during sleeping time was 23% when cooled in summer and 7% when heated in winter. The mean temperature and relative humidity in bedrooms during sleeping time was 27.7°C and 62% in summer, and 13.1°C and 61% in winter, respectively. The temperatures in bedrooms during sleeping time were found to comply with the recommended values for an indoor thermal environment (24-28°C in summer and 15-21°C in winter) in 39% of the dwellings in summer and 24% of them in winter. The mean temperature in bedrooms during sleeping time was significantly higher in apartments than in separate houses (p<0.01) in winter, although there was no significant difference of mean temperature between apartments and houses in summer. There was no significant difference in mean relative humidity between apartments and houses in both summer and winter.
Conclusion: Although the mean temperature in bedrooms during sleeping time varied widely depending on the type of dwelling, there also appeared to be differences between apartments and houses with respect to the temperature in bedrooms during sleeping time in winter.

View full abstract

Recently concern over the hazards posed by chemicals to children has become more active. Many chemicals have been introduced into the market within the past several decades. These chemicals are used widely in consumer products and dispersed in the environment. Children are at risk of exposure to such chemicals. Scientific understanding has also improved about the vulnerability of children to chemical hazards. As children represent the future of our societies, protecting their health is an important issue. Thus, many actions are being undertaken by international organizations, e. g., the World Health Organization and the United Nations, and regulatory bodies in Japan, the US and the EU, based on the probable vulnerability of infants and children to chemicals. In this paper, these efforts and state measures are summarized, the characteristics of children at risk assessed, and the list of chemicals concerning child health as well as future actions in Japan are presented.

View full abstract

In 1999 the Japanese Government implemented the Dioxin Counter-Measure Law, which based on a tolerable daily intake (TDI) of dioxin and related compounds of 4pg-TEQ/kg/day. We here review and explain how the TDI was established by the joint advisory board organized under the Ministry of Health and Welfare and the Environment Agency, based upon the available scientific findings at that time. We also report on the current dioxin risk assessment situation, focusing upon re-evaluation of the toxic equivalency factor scheme, which has been discussed in the most recent international scientific conferences.

View full abstract

In the recent year, a summit of the environment ministers of the G8 nations including the U. S. A., U. K, and Japan, presented the “Declaration of the G8 Environment Leaders on Children's Environmental Health” in which G8 countries agreed to actively address this issue. Fetuses and infants are more liable than adults to be affected by hazardous chemicals, being more sensitive to them due to their small body weight, and are more likely to come into contact with them due to the fact that they tend to play extensively on the floor and ground, and frequently bring whatever they have in their hands to their mouths. However, those who have high sensitivity, including children, are often not well-considered by our present legal system and risk assessment practices for protecting people from chemical substances. This material summarizes the proceedings of the symposium, in order to exchange opinions internationally and develop domestic professional human resources. Also, it introduces what researchers, governments, and NGOs from the U. S, EU, WHO, and Canada are working on, as well as the program of the Ministry of the Environment in Japan.

View full abstract