GN01 is a new antiviral medicine acting against Korean Sacbrood virus (KSBV) of honeybees. It contains 5 mg/mL of active ingredient, double stranded RNAs(dsRNA), that homologous to KSBV ribonucleic acid coding coat protein (VP1) of virus and inducing RNA interference (RNAi). RNA medicine is generally recognized as safe for rapid breakage by intrinsic ribonuclease and limited absorption from gastrointestinal tract. However, there were no data of repeat-dose toxicity in laboratory animals for dsRNA targeting SBV. This study was performed to investigate toxicity of GN01 in SD rats after weekly oral dosing for 28 days and to determine its no-observed-adverse-effect-level (NOAEL). Male and female SD rats were orally administered with GN01 at 0, 25, 50 and 100 mg/kg bw/day of dsRNA once per week for 28 days (total 5 administrations). The highest dose 100 mg/kg bw/day was determined based on the maximum volume injectable (20 mL/kg bw) via gavage. During treatment period, clinical signs, functional and sensory responses, body weights, food and water consumption, ophthalmological findings and urinalysis were investigated. After treatment period, hematological and clinical biochemistry tests and examination of necropsy findings, organ weights and histopathological lesions were performed. There were no significant differences between all test groups and vehicle control group in all measured parameters. Therefore, the NOAEL of GN01 was determined 100 mg/kg bw/day, the highest dose administered. In conclusion, repeated oral administration of GN01, a dsRNA medicinal product, is safe even at the maximum available dose in rats.

Antimicrobials in human medicine are classified by The World Health Organization (WHO) into three groups: critically important antimicrobials (CIA), highly important antimicrobials (HIA), and important antimicrobials (IA). CIA are antibiotic classes that satisfy two main criteria: that they are the sole or the only available limited therapeutic option to effectively treat severe bacterial infections in humans (Criterion 1), and infections where bacteria are transmitted to humans from non-human sources or have the potential to acquire resistance genes from non-human sources (Criterion 2). WHO emphasizes the need for cautious and responsible use of the CIA to mitigate risk and safeguard human health. Specific antimicrobials within the CIA with a high priority for management are reclassified as “highest priority critically important antimicrobials (HP-CIA)” and include the 3rd generation of cephalosporins and the next generation of macrolides, quinolones, glycopeptides, and polymyxins. The CIA list is the scientific basis for risk assessment and risk management policies that warrant using antimicrobials to reduce antimicrobial resistance in several countries. In addition, the CIA list ensures food safety in the food industry, including for the popular food chain companies McDonald's and KFC. The continuous update of the CIA list reflects the advancement in research and emerging future challenges. Thus, active and deliberate evaluation of antimicrobial resistance and the construction of a list that reflects the specific circumstances of a country are essential to safeguarding food security.

In this study, we described a suitable prioritisation scheme on these exempted drugs and established fundamental rules for residue monitoring enforcement in Korea. The principles of exempted materials were established. Based on these established criteria, 75 materials with high priority were selected and grouped. Among these materials, we have decided that 25 substances required further review for monitoring. Important factors for determining the priority for monitoring, product factor during the recent 4 years, veterinary medicine factors, including applied symptoms and component conditions, animal factors, including applied animals, and toxicological factors including acceptable daily intake (ADI), establishment of residual quantity permitted (MRL) or withdrawal periods, various provisory clauses and so on were set. High priority substances were acethylsalicylic acid, bromhexine, chlorpheniramine, and acetaminophen. In addition, we surveyed and provided analysis on the above mentioned materials in this study. The derived results will be suggested to the Animal and Plant Quarantine Agency (QIA) for development of guidelines of policy direction and the effective targeting for their monitoring program.

본 연구는 환자용 균형영양식으로 제조하여 감마선 조사처리를 통해 살균한 모델식품의 유전독성 여부를 평가하기 위해 수행되었다. 4 kGy 이상의 흡수선량으로 감마선 조사처리한 시료에서 생균수가 1 log CFU/g의 검출한계 이하로 나타났기 때문에 살균을 위한 조사처리 선량으로 4 kGy를 설정하였다. 복귀돌연변이 유발성 평가 결과, 모델식품의 열수 추출물과 메탄올 추출물은 처리한 용량과 대사활성계존재 여부와는 상관없이 음성대조구(멸균증류수 또는 DMSO)와 유사한 수준의 복귀돌연변이 발생빈도를 나타내었다. 염색체 이상 시험에서 실험군들의 정상 염색체의 수는 음성대조군과 유사하였으며, 용량 및 대사활성계에 대한 비의존성을 나타내어 염색체 이상 유발능은 없는 것으로 판단하였다. 또한 최고 2,000 mg/kg 체중의 농도로 모델식품을 경구 투여한 마우스의 골수세포에서도 소핵 다염성적 혈구의 발생빈도는 음성대조군에 비해 유의적인 차이를 나타내지 않았다. 따라서 4 kGy의 흡수선량으로 감마선 조사처리한 환자용 균형영양식은 본 실험 조건하에서 유전독성을 나타내지 않는 것으로 사료된다.