The Fujifilm Group strictly conducts the appropriate management of chemical substances in the entire process of planning, development, commercialization, production, and marketing. In this section, we will introduce the Safety Evaluation Center, which evaluates the safety of chemical substances necessary for such a mission.
About the Safety Evaluation Center
The Safety Evaluation Center plays an important role in evaluating the overall safeness of various chemical substances, materials, and products developed and used by the Fujifilm Group. We are committed to ensuring the safety of chemical substances used in the following various products before delivering products that consider human health and the environment to our society. The part of such safety evaluation is carried out by the Safety Evaluation Center, an internationally recognized and highly trusted testing facility.
Role of the Safety Evaluation Center
The Safety Evaluation Center was established in 1975 as a testing unit of the Environmental Management Division to conduct safety testing for chemical substances. The role of the Safety Evaluation Center is to evaluate the safety of various chemical substances, materials, and products developed and used by the Fujifilm Group from the early stage of development to the commercialization stage in order to minimize any risks to the environment and the health of humans. More specifically, the center serves as a GLP compliant test facility that is internationally recognized and highly trusted, and conducts various tests such as testing of chemical substances for legal compliance, testing of product safety, and testing for occupational health and safety.
Recently, the Fujifilm Group has expanded its business to include highly functional materials and healthcare products. To develop new products with high environmental quality, we also enhance and expand safety evaluation technologies. More precisely, in order to develop safe products, we have introduced a safety database environment accessible by material developers and developed advanced technologies such as toxicity screening method for cytotoxicity, gene expression, etc. and toxicity prediction methodologies using computers.
Test Items Conducted by the Safety Evaluation Center
The Safety Evaluation Center conducts various safety tests for the following purposes:
Development of safe chemical substances, materials, and products
Occupational health and safety
Compliance with law and regulations (the Chemical Substances Control Act, etc.)
Initiatives of the Safety Evaluation Center
Status of the Safety Evaluation Center as a GLP Compliant Test Facility
As a GLP compliant test facility, the Safety Evaluation Center conducts internationally viable and highly reliable tests.
The term “GLP” stands for “Good Laboratory Practice,” meaning a certification system for test laboratories that are reliably and functionally organized with structures and facilities satisfying certain standards. Test reports issued by a GLP compliant test facility can be used for the domestic application for new chemical substances as well as the overseas application for mutual acceptance of data by member countries.
The Safety Evaluation Center serves as a GLP compliant test facility for the following test items in compliance with the Chemical Substances Control Act (Act on the Evaluation of Chemical Substances and Regulation of Their Manufacture, etc.):
- Under the supervision of the Ministry of Economy, Trade and Industry of Japan (certified in 1986): Biodegradation test, Bioaccumulation test / Partition coefficient test
- Under the supervision of the Ministry of Health, Labour and Welfare of Japan (certified in 1990): Ames test / Chromosome aberration test
Support for the Long-range Research Initiative (LRI)
The International Council of Chemical Associations*2 promotes the Long-range Research Initiative (LRI) with respect to chemical substances that may affect the environment and the health of humans. Fujifilm supports the LRI activities by participating as a sponsor and a committee member.
In November 2020, the staff of the Safety Evaluation Center received the "5th Japan Chemical Industry Association LRI Award", which is awarded to young researchers who have made outstanding research achievements.
Animal Welfare Initiatives by the Fujifilm Group
In the process of developing chemical/medical products, there may be cases where experiments on animals are required to verify that such products are safe and effective in human beings. From the standpoint of animal ethics, however, animal experiments should be used only when they are really necessary. The Fujifilm Group has established the Animal Ethics Regulations and appropriately manages animal experiments in compliance with the Act on Welfare and Management of Animals and relevant ordinances.
The director of each animal testing facility at every group company should formulate the Regulations for Animal Experiments and establish an Animal Experiment Committee. They are also required to appropriately manage animal experiments and implement educational training and self-checks*4. In addition, since 2009, employees involved in animal experiments from each group company regularly gather together to share information relating to animal ethics and facilitate improvements.
Furthermore, the Safety Evaluation Center has been actively working on the development of alternative methods for animal testing from the standpoint of animal welfare*5.
Initiatives by the Safety Evaluation Center for Alternative Methods for Animal Testing
The Safety Evaluation Center is actively developing alternative methods for sensitization testing, irritation testing, etc. from the standpoint of animal welfare*6 as well as participating in joint studies on alternative methods. We also develop prediction methodologies using computers and utilize them in actual safety evaluations.
Development of an Alternative Test for Skin Sensitization
Fujifilm has developed “Amino acid Derivative Reactivity Assay (ADRA),” an alternative test for skin sensitization to evaluate whether a chemical substance induces an allergic reaction in the skin without using animal testing. In June 2019, ADRA was adopted in the OECD (Organisation for Economic Co-operation and Development) Test Guidelines*7.
ADRA can evaluate a wider variety of chemical substances by making use of a reagent with high detection sensitivity developed with FUJIFILM’s high technology for chemical synthesis and molecular design than conventional method (Direct Peptide Reactivity Assay (DPRA)*8).
In June 2022, ADRA was adopted in OECD Test Guidelines as a test method for skin sensitization of mixtures, allowing for skin sensitization assessment of mixtures multi-constituent in addition to a mono-constituent substance to date. This is because that ADRA has been applicable to natural extracts, which often contain unknown ingredients, to enable them to be evaluated by gravimetric approach and fluorescence detection in recent years, and that test methods have been recognized in OECD. At present, we are providing reagent kit, ADRA Kit, which can easily perform ADRA, and a contract service for skin sensitization assessment using the kit at FUJIFILM Wako Pure Chemical Corporation. On the occasion that ADRA has been internationally recognized as a standardized assessment method, we will contribute to the further dissemination of test methods that evaluate the safety of chemicals without using laboratory animals.
Theory of ADRA
The Japanese Society for Alternatives to Animal Experiments
The 35th Annual Meeting (2022)
“Ring study of ADRA, in chemico alternative test method for skin sensitization, aimed at revised guideline”, “The applicability of ADRA in predicting skin sensitization by combining multiple alternative methods for the OECD DASS chemical set”, “Assessment of commercial polymers with and without reactive groups using Amino acid Derivative Reactivity Assay (ADRA) based on both molar concentration approach and gravimetric approach”
The 33rd Annual Meeting (2020)
“Clarification of problems and causes for three substances out of Proficiency substances listed in ADRA test guideline (OECD TG 442C),” “Verification of applicability for IATA in case of used ADRA with optimized test chemical concentration,” “Detection minute amounts of the ADRA and comparison with other skin sensitization test method,” and “Establishing and improving predictive capacity of the ADRA test method for skin sensitization potential with an optimal molar concentration of test chemical solution”
The 32nd Annual Meeting (2019)
“Development of photo-amino acid derivative reactivity assay (p-ADRA): a novel in chemico alternative method for predicting photoallergy,” “The underlying factors that explain why nucleophilic reagents rarely coelute with test chemicals in the ADRA,” “Prediction for skin sensitization and photo-allergy of quasi cosmetics using ADRA and photo-ADRA,” “Precipitation of hydrophobic test chemicals in the reaction solution by ADRA and DPRA, alternative test methods for skin sensitization,” and “Oxidation of NAC in DMSO solvent in ADRA and its effect on sensitization prediction accuracy”
The 31st Annual Meeting (2018)
“A Newly Developed Means of HPLC-Fluorescence Analysis for Predicting the Skin Sensitization Potential of Multi-Constituent Substances Using ADRA” and “Verification of usefulness in case of used ADRA in skin sensitization prediction by combining multiple alternative methods”
The 30th Annual Meeting (2017)
“Multi-laboratory validation study of the ADRA as novel in chemico alternative test method for skin sensitization: 2nd report,” “Development of a novel in chemico alternative test method for skin sensitization (ADRA) without using molecular weight for test chemical solution ” and “Study of factorial analysis and countermeasure of oxidation of Cys-derivative reagent (NAC) using in the ADRA (Amino acid Derivative Reactivity Assay) as the alternative test method for skin sensitization”
The 29th Annual Meeting (2016)
“Reporting of training and transfer outcome for validation study of alternative method （ADRA） for skin sensitization using Cys and Lys derivatives”
The Japanese Society of Toxicology
The 47th Annual Meeting (2020)
“Application to prediction for respiratory sensitization using in chemico Amino acid Derivative Reactivity Assay (ADRA) having developed for skin sensitization”
The 46th Annual Meeting (2019)
“Development of the photo amino acid derivative reactivity assay (Photo-ADRA); newly in chemico alternative method for predicting photoallergy” and “Development of ADRA test method using fluorescence detection and application to multicomponent mixture”
The 45th Annual Meeting (2018)
“In chemico DPRA and ADRA test methods for skin sensitization -principle and issues-”
The 44th Annual Meeting (2017)
“A Multi-laboratory validation study of the in chemico ADRA test method for skin sensitization: 1st report”
Journal of Applied Toxicology, 42 (2022) 1078-1090
“Within- and between-laboratory reproducibility and predictive capacity of amino acid derivative reactivity assay (ADRA) using a 0.5 mg/mL test chemical solution: Results of the study for reproducibility confirmation implemented in five participating laboratories”
Chemical Research Toxicology, 34 (2021) 1749-1758
“Cause Clarification of Cysteine Oxidation by Active Species Generated during the Oxidation Process of Cinnamaldehyde and Impact on an In Chemico Alternative Method for Skin Sensitization Using a Nucleophilic Reagent Containing Cysteine.”
Journal of Applied Toxicology, 41 (2021) 303-329
“Improving predictive capacity of the Amino acid Derivative Reactivity Assay test method for skin sensitization potential with an optimal molar concentration of test chemical solution.”
Journal of Applied Toxicology, 40 (2020) 655-678
“Development of photo-amino acid derivative reactivity assay: a novel in chemico alternative method for predicting photoallergy.”
Journal of Applied Toxicology, 40 (2020) 843-854
“Oxidation of a cysteine-derived nucleophilic reagent by dimethyl sulfoxide in the amino acid derivative reactivity assay. ”
Journal of Toxicological Science, 44 (2019) 821-832
“The amino acid derivative reactivity assay with fluorescence detection and its application to multi-constituent substances.”
Journal of Applied Toxicology, 39 (2019) 1492-1505
“The within- and between-laboratory reproducibility and predictive capacity of the in chemico amino acid derivative reactivity assay: Results of validation study implemented in four participating laboratories.”
Journal of Toxicological Science, 44 (2019) 585-600
“Applicability of amino acid derivative reactivity assay for prediction of skin sensitization by combining multiple alternative methods to evaluate key events.”
Journal of Pharmacological and Toxicological Methods, 100 (2019) 106624
“Precipitation of test chemicals in reaction solutions used in the amino acid derivative reactivity assay and the direct peptide reactivity assay.”
Toxicology in vitro, 59 (2019) 161-178
“A newly developed means of HPLC-fluorescence analysis for predicting the skin sensitization potential of multi-constituent substances using ADRA.”
Journal of Pharmacological and Toxicological Methods, 97 (2019) 67-79
“Expanding the applicability of the amino acid derivative reactivity assay: Determining a weight for preparation of test chemical solutions that yield a predictive capacity identical to the conventional method using molar concentration and demonstrating the capacity to detect sensitizers in liquid mixtures.”
Journal of Pharmacological and Toxicological Methods, 96 (2019) 95-105
“The underlying factors that explain why nucleophilic reagents rarely co-elute with test chemicals in the ADRA.”
Journal of Applied Toxicology, 39 (2019) 191-208
”Cause of and countermeasures for oxidation of the cysteine-derived reagent used in the amino acid derivative reactivity assay.”
Journal of Applied Toxicology, 35 (2015) 1348-1360
“A novel in chemico method to detect skin sensitizers in highly diluted reaction conditions.”
Journal of Pharmacological and Toxicological Methods, 70 (2014) 94-105
“Development of a prediction method for skin sensitization using novel cysteine and lysine derivatives.”
Initiative on Alternative Methods for Skin Irritation, Eye Irritation, and Skin Corrosion Tests
We have participated in several joint studies on alternative methods. These include alternatives to the skin irritation test using an artificial skin model, to the eye irritation test using an artificial cornea model, and to the skin corrosion test using an artificial skin model. In this way, we strive to contribute to the establishment of new alternative methods.
In April 2020, for the purpose of ensuring the occupational safety of our employees, we started using this artificial skin model to evaluate the skin irritation of chemical substances for products.
Conference Presentations (at the Japanese Society for Alternatives to Animal Experiments)
Alternative Methods for Skin Irritation Tests
The 24th Annual Meeting (2011) “Additional multisite study of reconstructed human epidermis, LabCyte EPI-MODEL24 skin irritation test”
Alternative Methods for Eye Irritation Tests
The 25th Annual Meeting (2012) “Collaboration study on eye irritation alternative method with human corneal model; LabCyte CORNEA-MODEL24”
The 27th Annual Meeting (2014) “Comparing measurement methods of cell-viability in LabCyte CORNEA-MODEL24”
The 29th Annual Meeting (2016) “Me-too validation study of reconstructed human corneal epithelial model, LabCyte CORNEA-MODEL24 eye irritation test method”
Alternative Methods for Skin Corrosion Tests
The 30th Annual Meeting (2017) “Me-too Validation Study of Reconstructed Human Epidermal Model, LabCyte EPI-MODEL24 Skin Corrosivity Test Method”
Initiatives to Develop Safety Prediction Methods Using Computers
We are also actively working on the development of computer-based methodologies to predict harmful effects based on the structural characteristics of chemical substances. We have presented a new prediction method for skin sensitization at the Japanese Society for Alternatives to Animal Experiments, etc.*9 Utilizing the knowledge and experience of experts that have been accumulated for a long time since the establishment of the Safety Evaluation Center, we are developing a prediction method for molecular design and chemical substance search in the early stage of development.