This is a summary report of FSCJ (Food Safety Commission of Japan) workshop entitled “Future Challenges and Opportunities in Developing Methodologies for Improved Human Risk Assessments, which held in November 2018. Scientific advancements have facilitated the development of new methods for chemical risk assessments with the expansion of toxicological databases. They are promising tools to overcome challenges, such as situations of data insufficiency, estimation of internal exposure and prediction of hazard, and enable us to improve our human health risk assessment in food safety. In this review, current understandings on developments in chemical risk assessments, especially focusing on Threshold of Toxicological Concern (TTC) approach, non-testing and in-silico approaches (e.g. read-across), and physiologically based pharmacokinetics (PBPK) modeling are discussed as possible promising tools. It also discusses future challenges and opportunities regarding social environment buildings in which all stakeholders including scientific experts, risk managers and consumers are able to accept these new risk assessment technologies. International collaboration would increase and enhance the efficiency in forming innovative ideas and in translating them into regulatory practices. It would strengthen technical capacity of experts who contribute to regulatory decisions and also promote acceptance of new methodologies among stakeholders. Cross-sectional collaboration such as making good use of human data of pharmaceutical drugs will facilitate a development of fresh tools for food safety domains. Once a new methodology is recognized in risk assessment agencies as implementable, it needs to be acknowledged and accepted by wider range of different stakeholders. Such stakeholders include scientific experts who conduct risk assessment for the risk assessment agencies, food industries and consumers. Transparency in the risk assessment work performed by regulatory agencies should strengthen their credibility and promote the acceptance of risk assessment including the new methodologies used in it. At the same time, efforts should be continued by regulatory agencies to further communicate with consumers about the concept of risk-based assessment as well as the concept of uncertainty.

To elucidate the effect of citric acid on the stability of dissolved ozone, half-lives of ozone in a citric acid solution was investigated. Prolongation of the half-life of ozone was clearly shown in the presence of citric acid in ozonized water. In the presence of ethylenediaminetetraacetic acid (EDTA), the half-life of ozone was decreased. The addition of various concentrations of citric acid to the EDTA solution, however, reversed the half-life in a concentration-dependent manner. These indicate that citric acid suppresses ozone self-decomposition in water. A citric acid-mediated suppression mechanism of ozone self-decomposition involving hydroxy radical (HO•) was proposed as follows: HO• formed by the radical chain reaction process of ozone is scavenged by a way of abstracting the hydrogen atom bound to a carbon atom located α-position of a carbonyl group. The radical chain reaction of ozone is, thus, suppressed. These findings demonstrate that the addition of citric acid to ozonized water is useful for the stabilization of ozone. This ability may contribute to the application of ozone sterilization in food production processes.

Aseptically filled Tofu was necessary to be refrigerated under the previous standards for tofu. Food Safety Commission of Japan (FSCJ) was requested by the Ministry of Health, Labour and Welfare (MHLW) to assess a food safety risk to human health on changing the standards to ambient temperature storage. Clostridium botulinum and Bacillus cereus can be significant hazards. Assuming that manufacturing procedures including sterilizing processes follow the MHLW-indicated condition, under a full hygienic control, C. botulinum and B. cereus would not exist in the final products. Therefore, FSCJ concludes that there are no substantial risks of human health irrespective of the change in the storage standard for aseptically filled Tofu.

The Food Safety Commission of Japan (FSCJ) conducted a risk assessment of fosfomycin (CAS No. 23155-02-4), using documents submitted for the ‟re-examination” of veterinary medicinal products. The data used for the assessment include ADME of fosfomycin Ca, residue of fosfomycin Ca and of fosfomycin Na, acute toxicity of fosfomycin Ca and fosfomycin Na. Data on subacute toxicity, reproductive and developmental toxicity, genotoxicity and microbiological effect are also included. The lowest-observed-adverse-effect level (LOAEL) in these toxicity studies was 175 mg (titer)/kg body weight (bw) per day based on adverse effects including diarrhea, autopsy findings such as erosion, hyperplasia, and exfoliation of glandular stomach mucosa, and histopathological findings such as erosion of the stomach and ileum mucosa observed as adverse effects in the 35-day subacute toxicity study in rats. Fosfomycin was not teratogenic in rats and rabbits. FSCJ considered that fosfomycin is not a genotoxic carcinogen. The toxicological ADI of fosfomycin was established to be 0.175 mg/kg bw per day by applying a safety factor of 1000 based on the LOAEL of 175 mg (titer)/kg bw per day. On the other hand, the microbiological ADI was calculated to be 0.019 mg/kg bw per day, which is lower than the toxicological ADI. Thus, FSCJ established the ADI for fosfomycin as 0.019 mg/kg bw per day.