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부록 1: 기술서류(TD) 및 화학물질안전성 보고서(CSR) 작성절차(안) 8

1. IUCLID 5 시스템 작성 방법 9

가. IUCLID 5 시스템의 주요 기능 및 항목 9

나. IUCLID 5 시스템 실제 작성 예 11

2. 유해성 평가 18

가. 유해성 평가의 주요 단계 18

나. 정보수집과 평가 18

다. 물리화학적 성질 18

라. DNEL(Derived No-Effect Level)값 산출 19

(1) DNEL 산출 시 고려 인자 19

(2) DNEL 값 산출 단계 20

마. 환경에 대한 유해성 평가항목 20

(1) 수생독성(Aquatic toxicity) 20

(2) 침전독성(Sediment toxicity) 20

(3) 하수처리(Sewage treatment(tretment))에서 미생물 독성 20

(4) 분해(degradation)/ 생분해(biodegradation) 20

(5) 수질생물농축(Bioconcentration) 21

(6) 육지(terrestrial)생물농축 21

(7) 조류에 대한 장기독성 (Long-term toxicity to birds) 21

(8) 육상생물독성(Terrestrial toxicity) 21

(9) PNEC(Predicted No-Effect Concentration) 21

(10) 담수에서의 PNEC 산출 22

(11) 해수에서의 PNEC 산출 22

(12) 퇴적토와 토양(sediment and soil)에서의 PNEC 산출 23

(13) 폐수처리계에서의 PNEC 산출 24

(14) 포식자/상위포식자간 2차 독성의 PNEC 산출 25

3. 노출평가 27

가. 노출시나리오 (Exposure Scenario) 27

(1) 노출시나리오 구성 28

(2) 노출시나리오 개발 프로세스 29

(3) 노출시나리오의 핵심정보 30

(4) Use Descriptor System을 활용한 용도정보 수집/입력 30

나. 노출평가 31

(1) 노출평가 Tool 소개 32

(가) EUSES (the European Union System for the Evaluation of Substances) 32

(나) ECETOC TRA (Targeted Risk Assessment) 34

(다) COSHH Essentials (Control of Substances Hazardous to Health Regulations) 35

(라) ConsExpo (Consumer Exposure) 35

4. 위해도결정 39

가. 평가절차 39

(1) 물리화학적 특성에서의 위해도 결정 39

(2) 인체 건강 위해도결정 40

(가) 유해성 및 노출 정보 수집(Step 1 and 2) 40

(나) 정량 및 반 정량적 위해도결정(Step 3) 40

(다) 정량적 및 반-정량적 위해도결정 설명 43

(3) 환경 위해도결정 44

(가) Step 1 and 2: 유해 및 노출정보 수집 46

(나) Step 3: RCR 계산 46

(4) 전반적인 노출평가(Overall exposure) 52

(5) Step 6: CSA의 반복 가능성 결정 52

(6) Step 7: CSA 마침 52

부록 2. Dibutyl phthalate에 대한 TD/CSR 작성본 54

부록 3. Chemical safety report 264

Contents 266

PART A 270

1. Summary of risk management measures 270

2. Declaration that risk management measures are implemented 270

3. Declaration that risk management measures are communicated 270

PART B 271

1. Identity of the substance and physical and chemical properties 271

1.1. Name and other identifiers of the substance 271

1.2. Composition of the substance 272

1.3. Physicochemical properties 273

2. Manufacture and uses 274

2.1. Manufacture 274

2.2. Identified uses 274

2.3. Uses advised against 277

3. Classification and labelling 278

3.1. Classification and labelling Annex I of Directive 67/548/EEC 278

3.2. Self classification(s) and labelling 279

4. Environmental fate properties 280

4.1. Degradation 280

4.1.1. Abiotic degradation 280

4.1.2. Biodegradation 280

4.2. Environmental distribution 284

4.2.1. Adsorption/desorption 284

4.2.2. Volatilisation 284

4.3. Bioaccumulation 285

4.3.1. Aquatic bioaccumulation 285

4.3.2. Summary and discussion of bioaccumulation 286

5. Human health hazard assessment 287

5.1. Toxicokinetics(absorption, metabolism, distribution and elimination) 287

5.1.1. Non-human information 287

5.1.2. Human information 289

5.1.3. Summary and discussion on toxicokinetics 290

5.2. Acute toxicity 292

5.2.1. Non-human information 292

5.2.2. Human information 295

5.2.3. Summary and discussion of acute toxicity 295

5.3. Irritation 296

5.3.1. Skin 296

5.3.2. Eye 296

5.3.3. Respiratory tract 297

5.3.4. Summary and discussion of irritation 298

5.4. Corrosivity 298

5.5. Sensitisation 298

5.5.1. Skin 298

5.5.2. Summary and discussion of sensitisation 299

5.6. Repeated dose toxicity 299

5.6.1. Non-human information 299

5.6.2. Human information 305

5.6.3. Summary and discussion of repeated dose toxicity 306

5.7. Mutagenicity 308

5.7.1. Non-human information 308

5.7.2. Human information 313

5.7.3. Summary and discussion of mutagenicity 314

5.8. Carcinogenicity 315

5.8.1. Non-human information 315

5.8.2. Human information 316

5.8.3. Summary and discussion of carcinogenicity 316

5.9. Toxicity for reproduction 316

5.9.1. Effects on fertility 316

5.9.2. Developmental toxicity 319

5.9.3. Summary and discussion of reproductive toxicity 322

5.10. Derivation of DNEL(s)/DMELs 323

5.10.1. Overview of typical dose descriptors for all endpoints 323

5.10.2. Correction of dose descriptors if needed(for example route-to-route extrapolation), application of assessment factors and derivation of the endpoint specific DN(M)EL 325

5.10.3. Selection of the critical DNEL(s)/DEMLs and/or qualitative/semi-quantitative descriptor for critical health effects 328

6. Human health hazard assessment of physicochemical properties 330

7. Environmental hazard assessment 331

7.1. Aquatic compartment(including sediment) 331

7.1.1. Toxicity data 331

7.1.2. Calculation of Predicted No Effect Concentration(PNEC) 338

7.2. Terrestrial compartment 339

7.2.1. Toxicity data 339

7.2.2. Calculation of Predicted No Effect Concentration(PNEC_soil) 343

7.3. Atmospheric compartment 343

7.4. Microbiological activity in sewage treatment systems 345

7.4.1. Toxicity to aquatic micro-organisms 345

7.4.2. PNEC for sewage treatment plant 345

7.5. Non compartment specific effects relevant for the food chain(secondary poisoning) 346

7.5.1. Toxicity to birds and mammals 346

7.5.2. Calculation of PNECoral(secondary poisoning)(이미지참조) 347

8. PBT and VPVB assessment 348

8.1. Asessment of PBT/vPvB properties - Comparison with the Criteria of Annex XIII 348

8.1.1. Persistence Assessment 348

8.1.2. Bioaccumulation Assessment 348

8.1.3. Toxicity Assessment 349

8.1.4. Summary and overall Conclusions on PBT or vPvB Properties 349

8.2. Emission Characterisation 349

9. Exposure assessment 351

9.1. Scenario 1; Production of dibutyl phthalate 353

9.1.1. Exposure scenario 353

9.1.2. Exposure estimation 360

10. Risk characterisation 371

11. References 373

〈표 1〉 IUCLID 5의 주요 기능 10

〈표 2〉 DNEL 산출 시 필요한 단위명칭 19

〈표 3〉 담수에서의 PNEC 산출을 위한 안전계수(Assessment factor) 22

〈표 4〉 해수에서의 PNEC 산출을 위한 안전계수(Assessment factor) 23

〈표 5〉 토양에서의 PNEC 산출을 위한 안전계수(Assessment factor) 24

〈표 6〉 폐수처리계에서의 PNEC 산출을 위한 안전계수(Assessment factor) 24

〈표 7〉 포유류종에서 NOAEL에서 NOEC의 변환계수 26

〈표 8〉 포유류와 조류독성 외삽에서의 안전계수 26

〈표 9〉 최종노출시나리오의 표준형식 28

〈표 10〉 노출결정인자 (Determinants of exposure) 30

〈표 11〉 근로자(Workers)에 대한 (반)정량적 위해도결정 41

〈표 12〉 소비자를 위한 (반) 정량적 위해도결정 43

〈표 13〉 육지에서의 위해성 평가를 고려한 전체적인 PEC/PNEC 비 46

〈표 14〉 해수에서의 위해성 평가를 고려한 전체적인 PEC/PNEC 46

〈표 15〉 수생매체에 대한 위해도 결정 표 49

〈표 16〉 육상매체에 대한 위해도 결정 표 50

〈표 17〉 폐수처리계에서의 위해도 결정 표 50

Table 1: Substance identity 271

Table 2: Constituents 272

Table 3: Impurities 272

Table 4: Overview of physicochemical properties 273

Table 5: Information on uses and releases from uses 275

Table 6: Use descriptors and NACE codes for all involved industrial processes 276

Table 7: Classification according to Directive 67/548/EEC criteria 279

Table 8: Modified Sturm test. Biodegradation rate of DBP and the corresponding positive control, sodium benzoate over 28 days. The standard deviation in based on 4 separate parallels. 281

Table 9: Percentages of DBP Metabolites Excreted in Rat Urine 287

Table 10: Distribution of orally administered DBP 288

Table 11: Biliary, fecal and urinary evcretion of DBP in rats 288

Table 12: DBP total absorption results across donors 289

Table 13: DBP flux(㎍/㎠/h) results across donors 289

Table 14: LD50 8g/kg bw for the acute oral toxicity of DBP 293

Table 15: Acute oral toxicity of two nail preparations 293

Table 16: Other acute oral toxicity 293

Table 17: Other results for rabbit eye irritation 297

Table 18: Repeated dose toxicity for oral-subchronic toxicity 300

Table 19: Observations of repeated dose toxicity for oral 300

Table 20: Results of repeated dose toxicity for inhalation 303

Table 21: Induction of Trifluorothymidine Resistance in L5178Y Mouse Lymphoma Cells by Dibutyl Phthalate 309

Table 22: Mutagenicity of Dibutyl Phthalate in Salmonella typhimurium 311

Table 23: Frequency of Micronuclei in Peripheral Blood Erythrocytes of Mice Following Treatment with Dibutyl Phthalate in Feed for 13 weeks 312

Table 24: Summary of mutagenicity tests(In vivo) 313

Table 25: Summary of Two-Generation Reproduction Studies on DBP 318

Table 26: Maternal findings in rats given dietary DBP on days 11-21 of pregnancy 321

Table 27: Available dose descriptors per endpoint for a DBP as a result of its hazard assessment 324

Table 28: Corrected dose descriptors per endpoint and endpoint-specific DNEL/DMEL for the relevant exposure pattern 326

Table 29: DN(M)ELs for workers 328

Table 30: DN(M)ELs for the general population 328

Table 31: Summary of short-term effects on fish 331

Table 32: Summary of short-term effects on Lepomis macrochirus 332

Table 33: Summary of long-term effects on fish 332

Table 34: Other results for long-term toxicity on fish 332

Table 35: Summary of short-term toxicity of aquatic invertebrates 333

Table 36: Summary of long-term toxicity of aquatic invertebrates 334

Table 37: The influence of DBP on the growth and reproduction of Daphnia magna 335

Table 38: Summary of algae and aquatic plants 335

Table 39: Sediment organisms 336

Table 40: Chemical characteristics of the Toxicants 336

Table 41: Distribution of the contaminants between solid and aqueous phase 337

Table 42: Other results for sediment toxicity 337

Table 43: PNEC aquatic 338

Table 44: PNEC sediment 339

Table 45: Result for toxicity to soil macro-organisms 340

Table 46: Summary of the effects of DBP on survival, reproduction, and growth of the springtail Folsomia fimetaria 340

Table 47: The EC10 and EC50 values for DBP on adult survival output after different storage times of DBP-spiked soil. Effect concentrations are based on initial concentrations after spiking, not measured concentrations at test start. 341

Table 48: Toxicity to terrestrial plants(1) 341

Table 49: Effect of 1,2-Benzenedicarboxylic acid, Dibutyl ester on Zea mays Accumulation 342

Table 50: Effect of 1,2-Benzenedicarboxylic acid, Dibutyl ester on Zea mays Growth(1) 342

Table 51: Effect of 1,2-Benzenedicarboxylic acid, Dibutyl ester on Zea mays Growth(2) 342

Table 52: Toxicity to terrestrial plants(2) 343

Table 53: PNEC for terrestrial compartment 343

Table 54: Summary of toxicity for atmospheric compartment 343

Table 55: Summary of toxicity on aquatic micro-organisms 345

Table 56: PNEC sewage treatment plant 345

Table 57: Toxicity to birds 346

Table 58: Summary of calculation PNEC for laboratory mammals 347

Table 59: Overview on exposure scenarios and coverage of substance life cycle 352

Table 60: Duration, frequency and amount 353

Table 61: Duration, frequency and amount 353

Table 62: Duration, frequency and amount 354

Table 63: Duration, frequency and amounts related article service life 354

Table 64: Characteristics of the substance or preparation 355

Table 65: Characteristics of article 355

Table 66: Operational conditions related to respiration, skin contact and ingestion 356

Table 67: Technical fate of substance and losses from process/use to waste, waste water and air 357

Table 68: Risk management measures for industrial site 357

Table 69: Risk management measures for wide dispersive use 358

Table 70: Risk management measures related to consumers' use 359

Table 71: Fractions of substance in waste and waste management measures 360

Table 72: Acute exposure concentrations to workers 360

Table 73: Summary of acute exposure concentrations to workers 361

Table 74: Long-term exposure concentrations to workers 361

Table 75: Summary of long-term exposure concentration to workers 361

Table 76: Acute exposure concentrations to consumers 362

Table 77: Summary of acute exposure concentrations to consumers 362

Table 78: Long term exposure concentrations to consumers 362

Table 79: Summary of long term exposure concentrations to consumers 363

Table 80: Concentration for oral exposure of humans via the environment 363

Table 81: Total daily dose for oral exposure of humans via the environment 364

Table 82: Releases to the environment 364

Table 83: Summary of the releases to the environment 364

Table 84: Concentrations in sewage 365

Table 85: Predicted Exposure Concentrations (PEC) in sewage 365

Table 86: Local concentrations in water 366

Table 87: Predicted Exposure Concentrations (PEC) in aquatic compartment 366

Table 88: Local concentrations in sediment 367

Table 89: Predicted Exposure Concentrations (PEC) in sediments 367

Table 90: Local concentrations in soil 368

Table 91: Predicted Exposure Concentrations (PEC) in soil and groundwater 368

Table 92: Local concentrations in air 369

Table 93: Predicted Exposure Concentration (PEC) in air 369

Table 94: Local concentration relevant for secondary poisoning 370

Table 95: Predicted Exposure Concentration in food (PECoral) for secondary poisoning 370

〈그림 1〉 IUCLID 5 메인화면 9

〈그림 2〉 IUCLID 5 로딩 및 로그인 화면 11

〈그림 3〉 IUCLID 5 내 13개 주요 항목 목록 13

〈그림 4〉 IUCLID 5의 메인화면: "Section Tree" 14

〈그림 5〉 분류 및 표지(Classification and Labelling) 입력사항 15

〈그림 6〉 생태독성(●)에 대한 기술서류 작성의 예(이미지참조) 16

〈그림 7〉 급성독성에 대한 기술서류 작성 예 17

〈그림 8〉 노출시나리오 용도 27

〈그림 9〉 노출시나리오 개발 단계 별 진행내역 29

〈그림 10〉 Use Descriptor System 31

〈그림 11〉 EUSES-Tool의 기본적인 구조 32

〈그림 12〉 ECETOC TRA의 웹 화면 35

〈그림 13〉 ConsExpo-Tool 36

〈그림 14〉 CSA에서의 위해도결정 평가 절차 39

〈그림 15〉 환경 위해성 평가를 위한 일반적인 절차 45

Figure 1: Structural formula for DBP 271

Figure 2: Scenario of overall flow of DBP through manufacturing processes in 2007(Tonnes DBP/year) 277

Figure 3: Metabolic pathways for phthalates 291

Figure 4: Metabolic scheme for di-n-butyl phthalate[ECB,2003] 292