의약물질의 환경위해성 평가 체계 구축 방안

Title
의약물질의 환경위해성 평가 체계 구축 방안
Authors
박정임
Co-Author
최경호; 김영희; 정진용; 김창수; 김남희; 김명현
Issue Date
2006-12-30
Publisher
한국환경정책·평가연구원
Series/Report No.
연구보고서 : 2006-05
Page
174 p.
URI
http://repository.kei.re.kr/handle/2017.oak/19244
Language
영어
Keywords
Environmental risk assessment- Korea (Republic of)
Abstract
Pharmaceuticals are very beneficial to people’s quality of life and cure to disease. Animal drugs are also indispensable for successful livestock farming. The environmental consequences of using pharmaceuticals have been generally ignored because of advantages of using drugs. As chemical products, however, pharmaceuticals face unique environmental challenges. We are currently recognizing pharmaceutical substances as yet another group of potentially harmful water pollutants. Prior to this report, "Pharmaceuticals in the Environment and Management Approaches in Korea (KEI, 2005)" provided an overview of issues related to the input, occurrence and fate of pharmaceuticals in the environment, the risks, as well as reviewing the environmental risk assessments developed for regulatory purposes in the EU, Canada, and the US. The study also proposed a list of proactive agendas for managing human pharmaceuticals in the environment. This study aims to prioritize pharmaceutical substances for aquatic environment risk assessment (ERA) and to provide a basis for developing the most proper and sensible strategy for pharmaceutical ERA. This report consists of two sections. The first section (Chapters 2 and 3) is about prioritizing pharmaceuticals for aquatic environment risk assessment in Korea, and the second section (Chapters 4 through 6) is devoted to conducting an ERA for selected antibiotics in order to assess the preliminary ERA strategy. The foremost chemical risk management ranking and scoring systems in the US, Canada, and European countries were reviewed. Upon examining and comparing CHEMS-1 and EURAM, both systems were found to be very similar in their general approach. Only certain parameters used for scoring exposure and toxicity were different. However, when utilizing these systems for prioritizing potentially hazardous pharmaceutical products, several intrinsic limitations were encountered. Metabolic rates and STP removal efficiencies are not considered in these exposure models. In addition, the physicochemical characteristics of pharmaceuticals differ from those of conventional persistent chemicals. Therefore, to assess the fate and transport of pharmaceuticals realistically in the environment a unique exposure modeling scheme which is different from the one used for persistent organic compounds is required. Toxicity information that focuses almost exclusively on acute toxicity data may also result in significant underestimations in the risk assessment of pharmaceuticals, since very high acute-to-chronic ratios (ACRs) are often noted for pharmaceuticals. Therefore, a novel CRS system, which addresses these issues, is required to appropriately rank the priority of pharmaceuticals for environmental evaluation. Since it may be nearly impossible to monitor and evaluate the occurrences and potential environmental risks of all active pharmaceutical ingredients, it is prudent to attempt to identify and develop a list of pharmaceuticals that deserve more immediate attention. A preliminary list of the primary pharmaceuticals of concern was developed from an inventory of human and veterinary pharmaceuticals manufactured in Korea. For human pharmaceuticals, the net amount of active ingredient produced was determined and used to rank its potential to exist in the environment. According to both EMEA and US FDA guidelines, the amount of drug produced is important in the initial screening process. For veterinary pharmaceuticals, drug production amount along with its potential to enter the environment were considered in determining priority. Three antibiotics including roxithromycin, trimethoprim, and chloramphenicol were chosen from among the top ranked pharmaceuticals of interest for further environmental risk assessment. Sampling studies were conducted to measure the concentration levels of these pharmaceuticals at various sites in Korea. The study results indicated that the flow-rate conditions in the body of water sampled appear to have an immediate impact on the pharmaceutical levels. Water samples collected from STP influent or effluent water showed higher levels of the test compounds than the levels observed in ambient water samples. The 95% upper confidence limit (UCL) of the mean concentration was chosen as the representative ’measured environmental concentration (MEC)’ for each compound. Toxicology studies on various biological organisms using the three test antibiotics, along with literature reviews, were undertaken to establish the drug’s PNEC. The MEC was divided by the appropriate PNEC to derive the hazard quotient (HQ) of a given compound. No test antibiotic was identified to have an HQ greater than one, suggesting their tendency for potential environmental impact may be low. It should be noted that however, only standard ecotoxicity data mostly from acute exposures were available. There is a need for studies with more subtle but ecologically meaningful endpoints, e.g., reproduction, endocrine disruption, and effects on multiple levels of biological organizatons to better understand environmental consequences of pharmaceuticals in the environment. On the basis of findings presented in this report, further research was suggested in several areas. These include: 1) characterizing parameters that influence environmental concentrations of pharmaceuticals, 2) developing an exposure model framework that could be applied for a more accurate estimation of PECs for pharmaceuticals that are used both in human and veterinary medicine, and 3) developing sensitive and ecologically meaningful measures of hazard assessment.

Table Of Contents

I. Introduction
1. Research Background and Rationale
2. Review of Recent Research in Korea
3. Scope and Objectives
PART I. Prioritization of Pharmaceuticals of Concern in Korean Environment
II. Are the Existing Ranking Systems for Chemicals Applicable to Pharmaceuticals, too?
1. Introduction
2. Overview of Prioritization Methodologies for Chemicals
A. CHEMS-1
B. EURAM
3. Conclusion

III. Prioritizing Pharmaceuticals for Aquatic Risk Assessment in Korea
1. Prioritizing Human Pharmaceutical Substances for Environmental Risk Management in Korea
A. Literature Review on Prioritization Tools
B. Data Collection and Coalition
2. Prioritization of Veterinary Medicines for Environmental Health Management in Korea
A. Introduction
B. Materials and Method
C. Results
D. Discussion
E. Conclusion
3. Preliminary List of Pharmaceuticals of Concern
PART II. Environmental Risk Assessment for Selected Antibiotics in Korean Aquatic Environment
IV. Environmental Occurrence of Selected Antibiotics in Han River basin
1. Identification of Candidate Antibiotic Substances
A. Measures Employed for Prioritization of Pharmaceuticals
B. Potential to Enter the Environment
C. Fate in the Environment
D. Ecotoxicity
E. Prioritization of Human and Veterinary Antibiotics
2. Analytical Method Development and Validation
A. Materials
B. Sampling and Sample Preparation
C. LC-ESI-Tandem MS Analysis System
D. Optimization of SPE Method
E. HPLC-ESI-Tandem-MS Method Development and Validation
3. Determination of Selected Antibiotics
A. Site Selection and Sampling
B. Sample Analysis
V. Acute Aquatic Toxicities of Selected Antibiotics
1. Introduction
2. Materials and Method
A. Chemicals
B. Bioassays
C. Statistical Analysis
3. Acute Aquatic Toxicities of the Selected Antibiotics
4. Implications and Future Challenges
VI. Environmental Risk Assessment for the Selected Antibiotics
1. Introduction
2. Environmental Risk Assessment for the Selected Antibiotics
A. Environmental Concentrations of Pharmaceuticals
B. Measured Environmental Concentrations of the Test Pharmaceuticals
C. Derivation of Predicted No Effect Concentrations (PNECs) of Pharmaceuticals
D. Characterization of Environmental Risk
3. Challenges in Environmental Risk Assessment of Pharmaceuticals and Suggestions
A. Parameters that Influence Environmental Concentrations of Pharmaceuticals
B. Sensitive Measures of Biological Impact
C. Parameters to be Incorporated in Addressing Pharmaceuticals in the Environment
VII. Discussion and Conclusions
1. Summary of Findings
A. Review of the Existing Chemical Ranking and Scoring System
B. Prioritization of Pharmaceuticals of Concern in the Korean Environment
C. Risk Assessment of the Selected Antibiotics
2. Recommendations for Future Research
A. Parameters that Influence Environmental Concentrations of Pharmaceuticals
B. Use of an Integrated Exposure Model for Human and Veterinary Pharmaceuticals
C. Development of Sensitive Endpoints of Ecological Relevance
[Appendix] Human Pharmaceutical Substances Produced
7,000 kg in 2003
Abstract in Korean

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