Safety Examination of Existing Chemicals and Safety Programmes in Japan

1. Introduction

Japan has suffered some serious environmental pollution problems with polychlorinated biphenyls (PCB), such as pollution exposure of sea animals in 1966 and chlorobiphenyl poisoning of edible oil in 1968. This environmental pollution by PCB led to serious social problems. At the same time, it contributed to the awareness of hazard and necessity to establish the safety of chemicals on a global basis. In 1973, the Law concerning Examination and Regulation of Manufacture, etc. of Chemical Substances was passed for promotion of safety programmes for chemicals in our environment.

In the 1970's, pollution of ground water caused by organic chloride solvents including trichloroethylene was recognized and this led to the Law concerning Examination and Regulation of Manufacture, etc. of Chemical Substances to be revised to its present form regarding safety programmes for chemicals.

The following covers progress in recent safety programmes for existing and new chemicals.

2. Control of chemicals under the Law concerning Examination and Regulation of Manufacture, etc. of Chemical Substances and Outline of examination for new chemicals

1) Under the Law concerning Examination and Regulation of Manufacture, etc. of Chemical Substances, the manufacture or import of new chemicals must be submitted to the designated country agencies, which then examine the chemicals on the basis of the submissions. In Japan, the Ministry of Health and Welfare examines toxicity and the Ministry of International Trade and Industry examines decomposition and accumulation.

With respect to toxicity examination, the data from two kinds of genetic toxicity tests (both bacterial and non-bacterial in vitro tests) and a 28-day repeat dose toxicity test are submitted for initial screening by the expert committee on chemicals of the living environment council.

After this examination, any chemical which is difficult to decompose, tends to accumurate and may be harmful to human health with chronic exposure is classified into "Class I specified chemical substances", while those which have low accumulation but do not readily decompose corresponding to those which may be harmful to human health when continually taken, are classified into "Designated chemical substances". The hazard potential of some designated chemical substances are examined as deemed necessary from the environmental point of view. Some of them are placed in the "Class II specified chemical substances" category. New chemicals are all assessed for safety assurance through the above described prior examination system.

2) Test facilities which execute tests for safety should meet the requirements of GLP. In order to fulfill them, the facilities require inspection. Moreover, test substances, irrespective of whether general chemical substances or drugs, should conform to GLP related to safety tests. The facility which meets the requirements of the drugs GLP is considered to conform to the chemicals GLP. In that case, the limitations for types of tests which conform to GLP are placed as appropriate.

3) The "Class I specified chemical substances" category contains 9 substances including PCB, chlordane and tributyltin oxide (TBTO). The "Class II specified chemical substances" category designates 23 substances including trichloroethylene, tetrachloroethylene, carbon tetrachloride, 7 triphenyltin compounds and 13 tributyltin compounds. Moreover, the "Designated chemical substances" category contains 257 substances including chloroform.

3. Safety programmes for existing chemicals in Japan

1) In Japan, about 23,000 chemicals (excluding those with production of less than 1 ton) are now on the market. About 19,000 of them were already on the market before establishment of the Law concerning Examination and Regulation of Manufacture, etc. of Chemical Substances, requiring safety examination through a series of toxicity tests. These chemicals which had been manufactured or imported at the establishment of the Law concerning Examination and Regulation of Manufacture, etc. of Chemical Substances have successively been examined by the responsible agencies and classified into the "Class I specified chemical substances" category as appropriate.

2) In addition to the OECD HPV chemicals testing programmes described in the following clause, Japan has its own programmes. Chemicals which are widely used in this country have been examined in such conventional programmes.

In Japan, the Biological Safety Research Center, National Institute of Health Sciences, plays a leading role in conducting the safety tests and classifying chemicals which may affect human health into Designated chemical substances or Class II specified chemical substances. The results of the safety tests are announced in the annual reports of the Biological Safety Research Center, National Institute of Health Sciences and in scientific journals where appropriate.

4. International cooperation on safety programmes for existing chemicals

1) Japan and other developed countries have prior evaluation systems for new chemicals. Today, about 70,000 to 80,000 chemicals are used on the earth, most of them, however, without any detailed safety data. In Japan, only some new chemicals are examined through safety tests every year.

Since execution of safety tests for chemicals requires a large expenditure of money and time, it has been pointed out that different countries should examine these chemicals in cooperation.

2) The developed countries continue to check the safety of particular high production volume chemicals. Because there are too many existing chemicals and resources needed for testing, it was advocated in the OECD that the safety tests for the chemicals should be shared among member countries.

3) At the minister-level conference in 1987, the OECD decided that member countries should conduct safety tests for allotted chemicals. After co-work by the member countries on the basis of this decision, it was decided that about 1600 chemicals with high production levels should be examined. 467 chemicals were selected as chemicals with high production volume (HPV) with insufficient data for evaluation of their safety. These chemicals were then further divided. First of all, 147 of them were designated as 1st examination chemicals, planned for testing in the three years from 1991. Japan was assigned 33 chemicals, in proportion to its resources and the tests of these chemicals were completed by 1993. Japan conducted the screening tests for the chemicals, in four phases, from 1991 to 1994.

Many chemicals have been added to the originally selected 467 chemicals, resulting in a present of 648. The number of the chemicals to be tested from 1994 in the 2nd examination, therefore, now stands at 501. Testing is expected to be completed by 2000.

With respect to the tests in Japan, the Ministry of Health and Welfare conducts toxicity tests, the Ministry of International Trade and Industry conducts decomposition and accumulation tests and the Environment Agency conducts tests on ecological effects.

Thus, assessment of world-wide HPV chemicals should be completed by 2000 through international cooperation in the OECD.

4) In order to establish which and how many toxicity tests should be performed for each chemical substance, it is necessary to firstly generate awareness of the tests which have already been conducted in the different countries in the world. For the OECD HPV Programmes, review meetings are held to determine progress through each phase and to examine the data which have accumulated in the member counties.

5) The OECD have promoted safety programmes for existing HPV chemicals as well as the other OECD chemicals programmes, including introduction of GLP to the facilities that execute tests, development and improvement of the test guidelines for the toxicity tests, and cooperation of risk reduction programmes for harmful chemicals among member countries. The chemical data from each country are stored in the EXICHEM database, which was developed by the OECD chemicals programme section.

6) Japan has developed new toxicity test methods and improved the Conventional test methods in cooperation with the OECD member countries.

Safety examination for existing HPV chemicals involves a single dose toxicity test, a 28-day repeat dose toxicity test and genetic toxicity tests as well as a developmental toxicity test. Further, a preliminary reproduction toxicity test has been developed as a screening test for the developmental toxicity test. Simultaneously, a ReproTox test which combines the preliminary reproduction toxicity test and the repeat dose toxicity test has been introduced. The applicability of this new test was studied by the Biological Safety Research Center, National Institute of Health Sciences, where an OECD specialist meeting was held in October in 1992 because of its comprehensive data collection.

5. Safety programmes for chemicals contained in household goods

1) Article 3 of the Law for the Control of Household Products Containing Harmful Substances provides for responsibilities of manufacturers and importers to secure safety of household products. They must study chemicals which are contained in household products and how they might affect human health, and take measures to prevent injury caused by such chemicals. Thus, the law prescribes that manufacturers and importers must have a full understanding of the manufacturing methods of household goods, chemicals contained therein and their toxicity.

Moreover, the law designates harmful chemicals from the view of human health and prescribes standards for allowable contents of chemicals and containers of the products. Sales of products which do not meet the standards are prohibited. Contents and containers have been prescribed for 17 chemicals.

Surveillance officers in each city or prefecture strictly check and survey the household products which are sold in the departments, supermarkets and retail stores, for the above standards, and give instructions where appropriate.

2) Voluntary standards related to safety and hygiene of household goods Groups of manufacturers and importers in relevant industries have been promoting self-support efforts in safety programmes in order to prevent injury caused by chemicals in household goods. Since it is very desirable to create voluntary standards for safety assurance, the Ministry of Health and Welfare gives guidance and advice for establishment of such standards, which have already been established for household goods such as wet wipers, bacteria and mildew removal agents for home use, insecticides for home use, rinsing agents for home use, spot removers for home use, perfumes/deodorants/deodorizers, bacteria and mildew proof agents for home use, and rinsing agents and/or preservatives for contact lenses.

The standards generally include ingredients, contents, quality control such as test items for quality assurance, labeling, containers and manufacturing processes. Moreover, some voluntary standards indicate the use of certification marks.

6. Provision of Material Safety Date Sheet (MSDS)

The MSDS system was established, effective as from April, 1993, by the Ministry of Health and Welfare, the Ministry of International Trade and Industry, and the Ministry of Labor in order to enhance safety for treatment of chemicals. The system requires manufacturers and importers to prepare MSDS and deliver them to the next makers or traders concerned. The MSDS should contain information on safety procedures for chemicals which present a danger or hazard in items of explosion, ignition and acute/chronic toxicity properties. The information includes the name of the product, types of danger or hazard, treatment in case of emergency, treatment in case of a fire, notes for treatment and storage, preventive measures for exposure and notes for disposal.

With respect to this system, the "Guideline related to information supply on chemical safety" was notified by the Minister of Public Welfare and the Minister of Labor, as of March 26, 1993.

7. Action to UNCED Agenda 21

With the recent high interest in environmental problems, the United Nations decided to hold top-level conferences for examination of the environment and development. After many preparative meetings, the United Nations Conference on Environment and Development (UNCED) was held, in Brazil, in June, 1992. At the conference, Agenda 21 was adopted as the action plan for 21th century. It includes sound management of chemicals.

Agenda 21 states the following seven programme areas for action.

1) Expanding and accelerating international assessment of chemical risks

2) Harmonization of classification and labeling of chemicals

3) Information exchange on toxic chemicals and chemical risks

4) Establishment of risk reduction programmes

5) Strengthening of national capabilities and capacities for management of chemicals

6) Prevention of illegal international traffic in toxic and dangerous products

7) Strengthening of international cooperation related to some programme areas

Chapter 19 in Agenda 21 states detailed programmes concerning the above areas.

Each country has created plans for execution of the programmes to 2000, and international organizations including IPCS, OECD and ILO have also prepared the execution plans. An Inter-Governmental Forum held in April, 1994, in Sweden, was attended by United Nations' member countries and many international organizations,

From now, the forum will periodically be held and international programmes for toxic chemicals can be expected to be effectively promoted by this cooperation.

[Japan conducted the screening tests]
Phase 1 OECD Testing Chemicals
CAS No. Name of Chemicals
0-55-3 4-Methylbenzenesulfonamide
77-99-6 2-Ethyl-2-hydroxymethyl-l,3-propanediol
99-09-2 3-Nitrobenzenamine
126-30-7 2,2-Dimethyl-l,3-propandediol
147-14-6 Phthalocyanine Blue
156-43-4 4-Ethoxybenzenamine
536-90-3 3-Methoxybenzenamine
584-03-2 1,2-Butanediol
3209-22-1 1,2-Dichloro-3-nitrobenzene

Phase 2 OECD Testing Chemicals
78-97-7 2-Hydroxypropanenitrile
95-73-8 2,4-Dichloro-l-methylbenzene
105-05-5 1,4-Diethylbenzene
107-66-4 Dibutyl phosphate
109-69-3 1-Chlorobutane
482-89-3 3H-Indol-3-one, 2-(1,3-dihydro-3-oxo-2H-indol-2-ylidene)-1,2-dihydro-
2581-34-2 3-Methyl-4-nitrophenol
4461-52-3 Methoxymethanol
5281-04-9 D&C Red No.7
6846-50-0 2,2,4-Trimethyl-l,3-pentanediol diisobutyrate
24800-44-0 Tripropylene glycol
26444-49-5 Diphenyl cresyl phosphate

Phase 3 OECD Testing Chemicals
81-11-8 4,4',-Diaminostilbene-2,2'-disulfonic acid
82-45-1 1-Aminoanthraquinone
89-61-2 1,4-Dichloro-2-nitrobenzene
105-99-7 Dubutyladipate
108-44-1 m-Toluidine
118-69-4 1,3-Dichloro-2-methylbenzene
512-56-1 Trimethyl phosphate
611-06-3 2,4-Dichloro-l-nitrobenzene
623-91-6 Diethyl fumarate
1879-09-0 2-(1,1-Dimethylethyl)-4,6-dimethylphenol
4979-32-2 N,N-Dicyclohexylbenzothiazole-2-sulfenamide
5392-40-5 Citral

Phase 4 OECD Testing Chemicals
77-73-6 Dicyclopentadiene
89-83-8 Thymol
90-02-8 2-Hydroxybenzaldehyde
98-08-8 Trifiuoromethylbenzene
98-54-4 p-tert-Butylphenol
98-83-9 1-Methylethenylbenzene
105-99-7 Dibutyl adipate
110-02-1 Thiophene
110-63-4 1,4-Butanediol
111-41-1 N-(Aminoethyl)ethanolamine
111-82-0 Methyl dodecanoate
115-77-5 Pentaerythritol
760-23-6 3,4-Dichloro-l-butene
923-26-2 2-Hydroxypropyl methacrylate
1120-21-4 Undecane
1338-41-6 Sorbitan monooctadecanoate
3319-31-1 Tris(2-ethylhexyl) 1,2,4-benzenetricarboxylate