Works of the risk assessment for the Japanese Chemical Substances Control Law (CSCL)
What is the CSCL?
It is a law to prevent environmental pollution caused by chemical substances that pose a risk of impairing human health and interfere with the inhabitation and growth of flora and fauna.
(Please see the details in the website for Ministry of Economy, Trade and Industry (METI))
Our role:
For the human health risk assessment of existing and new chemicals in the CSCL, we prepare drafts of toxicity evaluation reports for the screening assessments of new and general chemicals and for risk assessment of priority assessment chemical substances. We also give scientific advices to the Ministry of Health, Labour and Welfare.
(Please see “Evaluation/Assessment Flow of CSCL” and “Flow of Risk Assessment of Existing Chemicals” in the document prepared by the METI.
Toxicity data sharing:
We perform Ames tests, in vitro mammalian chromosome aberration tests and Combined repeated-dose and reproductive/developmental oral toxicity studies on existing chemicals for their screening assessment (MHLW's existing chemical safety survey program). The results and summaries of the existing chemical safety survey program have been published in the Japan Existing Chemical Database (JECDB) to share valuable toxicity data with domestic and foreign risk assessment organizations.
Work on Positive list system on Food Utensils, Containers and Packaging
Food containers and wrapping films are used for various purposes such as keeping the quality of food and drinks and carrying them. They are made mainly from synthetic resins and had been managed by the negative list system and the independent self-regulation by industry groups.
Under the recent diversification of products and the increase of importing, a positive list regulation was introduced in June 2020. (Due to partial revision of the Food Sanitation Law, etc. promulgated on June 13, 2018).
The negative list system allows the use of chemical substances in principle and then sets the restricted substances, whereas the positive list system allows only the use of substances whose safety has been evaluated. In Division of Risk Assessment, we collect the toxicological information of thousands of the listed substances and support to validate the positive list, aiming for rational risk assessment based on the scientific evidences
Research on risk assessment and management for the drinking water quality
The drinking water quality is controlled as shown in the diagram in Japan. The Drinking Water Quality Standards (DWQSs) and the target values of these items are established basis of life-time exposure to contaminants in drinking water. We are searching and updating toxicity data for these items and reviewing new methodology for hazard evaluation of chemicals. We are providing the information to the MHLW for consecutive revision of the DWQSs and the target values. Our resent effort is that we proposed subacute guidance values as the chemical concentration in the drinking water, which is useful when the concentration of contaminants exceed temporary the level of the DWQSs under accidental situation.
Making assessment to designate Poisonous and Deleterious Substances
The purpose of this low is to provide necessary control on Poisonous Substances and Deleterious Substances from the viewpoint of health and hygiene. In order to achieve this purpose, chemical substances that are likely to cause health hazards mainly due to acute toxicity are designated as poisonous or deleterious substances.
Our works !!
Chemical substances are designated as Poisonous and Deleterious Substances by the expert meetings of the Ministry of Health, Labor and Welfare. We make the assessment reports for the expert meetings and contribute to prevention of health hazards due to acute toxicity.
Research on chemical safety assessment using in silico approaches
It is a major issue how to perform safety assessments of huge numbers of chemicals without sufficient test data. Furthermore, from the perspective of animal welfare, there is a growing trend to reduce animal testing. In response to these movements, there is a strong international demand to improve the technical level of in silico toxicity prediction methods, i.e., computational toxicity prediction, to expand its scope of application, and to implement it in safety assessment.
Constructing of toxicity databases and their international sharing
In order to develop accurate in silico toxicity prediction methods, it is necessary to utilize the reliable toxicity test data. Our Division of Risk Assessment is constructing reliable toxicity databases. We are also promoting the international sharing of the databases in collaboration with research institutions and public agencies both in Japan and abroad.
Evaluating and improving current methods, developing novel methods
We are analyzing the data in those toxicity databases, to evaluate and improve the current models of various in silico toxicity prediction methods (TTC, QSAR, Read-across). Through these analyses and evaluations, we are also advancing the development of novel models.
Case studies on Integrated Approaches to Testing and Assessment (IATA)
In addition to the in silico toxicity prediction methods, we are working on the case study on toxicity prediction by Integrated Approaches to Testing and Assessment (IATA). IATA is an integrated approach which combines diverse data obtained by so-called New Approach Methodologies (NAM) such as toxicokinetics, metabolism and in vitro bioactivity. Based on the results of these case studies, we are listing and organizing the problems and learnings in the way of implementing the toxicity prediction in safety assessment.
Development of chemical safety big database and AI-platform to support human safety assessment of pharmaceuticals, foods and household chemicals
As a collaborative project with Division of Genome Safety Science, Division of Cellular and Molecular Toxicology and Division of Medicinal Safety Science, we are developing chemical safety big database and AI-platform to support human safety assessment of pharmaceuticals, foods and household chemicals.
Efforts for promoting regulatory acceptance of in silico toxicity prediction data
Moreover, we join work groups led by the domestic and international agencies to develop opinion or guidance of in silico approaches.
BMD methods can determine the threshold dose by fitting various statistical models for dose-response analyses and support chemical risk assessments.
We have been performed several researches on the BMD methods for risk assessments in Japan.
Outcome of our previous research provided a database of dichotomous and continuous data derived from various repeated-dose toxicity studies and the data were used in simulation analyses in the research.
We also provide a guidance document to support Japanese risk assessors to use the BMD methods. These outcomes are published in our website (https://dra4.nihs.go.jp/bmd/) (in Japanese).
Recently, several new researches on the BMD methods are underway.
Contribution to the OECD EHS activities
The OECD’s work on chemical safety and biosafety is carried out under the Environment, Health and Safety (EHS) Programme.
Division of Risk Assessment (DRA) continues to participate in the following work areas of the EHS Programme and the Working Groups/Parties.
Development of Integrated Approaches for Testing and Assessment (IATA*) documents for grouping chemicals under the IATA Case Studies Project
Providing toxicity tests data to the OECD QSAR Toolbox
*What is an AOP?: An AOP is an analytical construct that describes a sequential chain of causally linked events at different levels of biological organisation that lead to an adverse health or ecotoxicological effect (see figure below). AOPs are the central element of a toxicological knowledge framework being built to support chemical risk assessment based on mechanistic reasoning
Schematic representation of the AOP illustrated with reference to a number of pathways
*What are IATA?: IATA are pragmatic, science-based approaches for chemical hazard characterisation that rely on an integrated analysis of existing information coupled with the generation of new information using testing strategies
*Why we use AOPs for IATA?: IATA can include a combination of methods and can be informed by integrating results from one or many methodological approaches [(Q)SAR, read-across, in chemico, in vitro, ex vivo, in vivo] or omic technologies (e.g. toxicogenomics).
