The Sasaki Foundation was established as a nonprofit research foundation in 1939 by Dr. Takaoki Sasaki. The Sasaki Foundation has been formed by two organizations: institute (the Sasaki Institute) and hospital (the Kyoundo Hospital). Until now, many excellent basic studies in the medical field, especially regarding cancer research, have been conducted in the Sasaki Institute. At a period of 1920s, Dr. Sasaki already proposed a new scientific field, namely "chemical pathology", this concept corresponding to today's "toxicologic pathology", and among studies conducted under the concept, the most remarkable and epoch-making study is "the induction of hepatic cancer in rats by o-aminoazotoluole, one of azo dyes" by Drs. Sasaki (First Director of the Sasaki Institute) and Tomizo Yoshida (2nd Director). Since then, in the institute (especially Department of Pathology), numerous studies concerning risk assessment of chemicals have been conducted from the standpoint of toxicity/carcinogenicity.

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A pathological assessment plays an essential role in the risk assessment of chemicals. Because such an assessment depends on the observation-based evaluation by individual researchers, high skill and sufficient experience of the researchers are requested to maintain the accuracy and reliability of the assessment. Education and training for toxicologic pathologists are thus very important but has not been sufficiently being performed in Japan. In order to overcome this, Dr. Akihiko Maekawa, Director of the Sasaki Institute, Sasaki Foundation, established the Sasaki Institute Education Meeting Series for Toxicologic Pathology of Laboratory Animal in 1993. The series continued for 15 years to educate and train early- and mid-carrier toxicologic pathologists of academia, industry and regulatory agencies up to year 2005. This article was written by Dr. Isao Narama, Professor of Pathology, Setsunan University who contributed to the series and is by himself educating and training young people, to introduce the importance of the education and training of toxicologic pathologists for the risk assessment/management of chemicals.
<Abstract written by Dr. Dai Nakae (Department of Pathology, Sasaki Institute, Sasaki Foundation), the organizer of this special program of the journal>

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Articles in this special program of the journal describe the significance of the risk assessment/management for the assurance and maintenance of human health and welfare, and the importance of toxicologic pathology in such an attempt. The Sasaki Institute (Department of Pathology) has been contributing to the risk assessment/management of chemicals, by doing researches on the detection of toxicity/carcinogenicity of chemicals, the elucidation of its underlying mechanisms, and the influence of chemicals toward particular pathological situations (e.g., carcinogenesis), using animal models extrapolative to the human situations. Among them, this article introduces findings from researches on a hepatocarcinogenic model of rats fed a choline-deficient, L-amino acid-defined diet.

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A mutant strain, Nagase analbuminemic rat (NAR), was established from Sprague-Dawley (SD) rats, and is inherited as an autosomal recessive analbuminemic trait. NAR is characterized by an extraordinarily low serum albumin level and hyperlipidemia. Despite the absence of serum albumin, total serum protein level in the NAR is similar to that of SD rats, because the absence of serum albumin is compensated by increase of globulin fractions. The carcinogenic effects of many chemical carcinogens were examined in NAR and control SD rats, because albumin is known to be a carrier protein of many endogenous and exogenous compounds including bile acids, steroid hormones, drugs and toxins as well as carcinogens. As a result, NAR has been found useful for studies on the pharmacological and/or physiological function of albumin and on the mechanism of carcinogenesis.

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Recently, environmental pollution with man-made chemicals having weak estrogenic effects, which may disturb the endocrine systems of wildlife and human beings, has become an important social problem. In particular, effects of perinatal exposure to such endocrine disrupting chemicals (EDCs) are a focus of attention, because of their potential to act as estrogens and influence on the growth and differentiation of organs. In rodents, the reproductive tract undergoes rapid growth and differentiation within the first 2 weeks of postnatal life named 'critical point' or 'a unique window of vulnerability', because this period is very sensitive with regard to exogenous estrogens or androgens. In female mammals, inappropriate neonatal exposure to these hormones is known to induce the serious effects on the reproductive system, called 'androgenization' due to irreversible disruption of the hypothalamo-pituitary-gonadal control system immediately after birth. This paper will be presented effects of neonatal exposure to estrogenic EDCs for different periods on the female reproductive system including uterine carcinogenesis using 2-stage uterine cancer model in Donryu rat. As a result, the neonatal exposure for different periods induced different types of uterine adenocarcinomas, suggesting that two different pathways driven by androgenization or delayed anovulatory syndrome, the latter being incomplete androgenization, dependent upon exposure periods develop the tumors.

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Toxicologists who can evaluate toxicology data and plan regulatory management systems are insufficient in number in Japan. This is mainly due to lack of programs dedicated to toxicology in the education system. For example, except for my department (the Department of Molecular Toxicology at the Nagoya City University Graduate School of Medical Sciences), there are no graduate courses for the toxicologist. Education for toxicologists is mainly carried out in graduate courses in medical, veterinary, and pharmaceutical schools along with research work not directly relevant to toxicology. These courses do not include lectures or research devoted to toxicology as the primary subject matter. The Sasaki Institute, where the Department of Pathology is located, has an experienced, enthusiastic staff who have expertise in toxicology in general and in one or more specific fields of study encompassed by this discipline. This institute has contributed greatly to the training of graduate and postgraduate students aiming for a seat on the board of toxicologists.

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It was the 11^th SIDS, the Screening Information Data Set, Initial Assessment Meeting (SIAM-11, held at Orland, USA) where the initial assessment documents prepared by the International Council of Chemical Associations (ICCA) for the first time were reviewed by the authorities. In this report, the brief summary of the document for 6,6'-di-tert-Butyl-2,2'-methylene di-p-cresol submitted by Sumitomo Chemical Co., Ltd. is introduced. During the review process, the theoretical investigations on the uptake limitations of this substance to aquatic organisms in relation to the steric effect of the molecule were additionally made since the validity of the test results with aquatic organisms was suspected by the authorities. The outline of this discussion on the bioavailability of the substance in water is also introduced.

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These days, Integrated Management of Chemicals gets position as Social Responsibility, and voluntary action is becoming much more important for every sectors of society. In this context, we have developed and validated the index which can evaluate advancement of integrated management of chemicals, for the purpose of society's improvement in this field. The Index consists of Science-axis, Capacity-axis and Performance-axis. In this paper, we report the first survey for various types of companies by this index. The survey was done from June to August in 2004. The content of the survey is company activity concerning hazard of chemicals. From analysis of the survey, the differences in activity between company as supplier of chemicals and company as user of chemicals are found. Also, some issues for improvement of integrated management of chemicals are found.

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We carried out the questionnaire survey to Japanese companies in 2004 and 2005 in order to grasp the present conditions for integrated chemicals management system. This survey was carried out to ask about hazard assessment mainly on the actions relating to MSDS (Material Safety Data Sheet). The questionnaire items were evolved around three axes, i.e. enrichment of science basis (a Science axis), ability of persons and organization (a Capacity axis), and achievement, situation of cooperation with clients, and/or information disclosure to society (a Performance axis). We divided companies into suppliers (the supply side of chemicals) and users (the use and processing side of chemicals). Suppliers carried out higher activities than users. Especially chemical companies carried out actions of higher level than the other types of industry. As a general trend, there was not much difference between the result of 2004 and that of 2005, a sign of improvement was recognized in some actions. In order to grasp the tendency of chemical management, continuous survey is needed. Because the new survey based on the risk basis is needed, the survey should be expanded to exposure assessment, risk assessment and risk management.

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We have now almost grasped the overall picture and the implementation issues for Intgrated Risk Management of Chemical Substances, advocated through Chapter 19 – Agenda 21 of UNCED in 1992. The 21^st century, in which it has evolved from concept to practice, is the age in which Social Responsibility is strongly urged. Perceived as a principal managerial pillar influential to both profit and risk management, it is beginning to be closely linked to various fields of management, eg. planning/designing, research/development, and production/sales. And, procedures are being carried out in rapid speed worldwide to secure enhanced structure in legal/institutional aspect, scientific aspect, and human resource aspect. Now that it is developing into Comprehensive Integrated Management of Chemical Substances fostering global competitiveness, Capacity Building in compliance with the international flow through restructuring of legal systems, enrichment of scientific knowledge that serves as a basis for the management, and strengthening of human resources, is a pressing issue in Japan.

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The 20th SIDS (Screening Information Data Set) Initial Assessment Meeting was held in Paris at OECD headquarters on 19th-21st April 2005. The initial assessment documents of 45 substances were submitted, and 43 were agreed at the meeting. The Japanese Government submitted the initial assessment documents of three substances, 2-furanmethanol, tetrahydro- (CAS: 97-99-4), phthalimide (CAS: 85-41-6) and sodium nitrite (CAS: 7632-00-0), and all three documents were agreed at the meeting. This paper reports the summary record of the 20th SIDS Initial Assessment Meeting.

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