Persistent Organic Pollutants in Human Milk

Foreword
Preface
Contents
About the Editors and Contributors
List of Abbreviations and Acronyms
Part I: Introduction
	Human Milk Surveys on Persistent Organic Pollutants from a Historical Perspective
		1 Introduction
		2 POPs Analysed in Human Milk in the Course of Time
			2.1 Organochlorine Pesticides
			2.2 Polychlorinated Biphenyls
			2.3 Brominated Flame Retardants
				2.3.1 Polybrominated Biphenyls
				2.3.2 Polybrominated Diphenylethers
				2.3.3 Hexabromocyclododecanes
			2.4 Polychlorinated Dibenzo-p-Dioxins, Dibenzofurans and dl-PCB
			2.5 Chlorinated Paraffins
			2.6 Per- and Polyfluoroalkyl Substances
			2.7 Further POPs of Interest
		3 First and Second Round of WHO Field Studies on Human Milk in the 1980s and 1990s
		4 Lessons Learned from the Early Human Milk Surveys
		References
	Overview of WHO- and UNEP-Coordinated Human Milk Studies and Their Link to the Stockholm Convention on Persistent Organic Poll...
		1 Introduction
		2 Development of WHO/UNEP-Coordinated Exposure Studies Over Time
			2.1 WHO Exposure Studies 1987-1988 (First Round) and 1992-1993 (Second Round)
			2.2 WHO Exposure Study 2000-2003 (Third Round)
			2.3 Stockholm Convention on Persistent Organic Pollutants: Expansion of Objectives and Analytes
			2.4 Pilot Study
			2.5 Joint WHO/UNEP Study 2005-2007 (Fourth Round)
			2.6 Joint WHO/UNEP Study 2008-2012 (Fifth Round)
			2.7 UNEP-Studies 2014-2015 (Sixth Round) and 2016-2019 (Seventh Round)
			2.8 Self-Funded Countries
		3 Concepts and Protocols
			3.1 Protocols
			3.2 Collection of Individual Samples
			3.3 Number of Individual Samples and Representative Pooled Samples
			3.4 Preparation of Individual and Pooled Samples
			3.5 Cost-Effectiveness of Analysis of Pooled Samples
			3.6 Variation of Individual Samples
			3.7 Reference Laboratories
			3.8 Biosafety
		4 Analytes of Interest: Expansion Over Time
		5 Assessment of Time Trends
		6 Participating Countries and Number of Samples
			6.1 Regional Distribution
			6.2 Regional Participation Over Time
				6.2.1 African Group
				6.2.2 Asia-Pacific Group
				6.2.3 Group of Latin American and Caribbean Countries (GRULAC)
				6.2.4 Eastern European Group
				6.2.5 Western European and Others Group (WEOG)
		7 Summary and Conclusions
		References
	The Stockholm Convention, Global Monitoring Plan and its Implementation in Regional and Global Monitoring Reports
		1 Background Information on the Stockholm Convention
		2 Development of Arrangements for POPs Monitoring
		3 Organizational Framework for POPs Monitoring and its Further Development
			3.1 Expert Groups
			3.2 Guidance Document
			3.3 GMP Implementation Plan
		4 Outputs of the Global Monitoring Plan
			4.1 Regional and Global POPs Monitoring Reports
			4.2 Improved Interoperability and Access to Global POPs Data in Electronic Format
		5 Effectiveness Evaluation
		References
Part II: Analytical Methods and Quality Control
	Analysis and Quality Control of WHO- and UNEP-Coordinated Human Milk Studies 2000-2019: Polychlorinated Biphenyls, Polychlorin...
		1 Introduction
		2 Materials and Methods
			2.1 Analytical Procedure and Analytes
			2.2 Toxic Equivalents (TEQ)
			2.3 Sum Parameter for Non-dioxin-like PCB (``Indicator PCB´´)
		3 Development of Regulations and Standards for Analytical Criteria over Time
			3.1 Historical Background (2000-2001)
			3.2 Limits of Quantification
			3.3 Upper-bound and Lower-bound Results for WHO-TEQ and PCB6 and Acceptable Differences
			3.4 Amendments of EU Regulations; EU Guidance Documents
			3.5 Global Monitoring Plan
		4 Quality Control
			4.1 Procedural Blank Samples
			4.2 Freeze Drying and Particular PCB-related Aspects
			4.3 Vegetable Oil Samples Fortified at Different Levels as in-house Reference Material
			4.4 Quality Control Samples as in-house Reference Material and Precision
			4.5 Duplicate Analysis and Precision
			4.6 Pooled Human Milk Samples Remaining from WHO Interlaboratory Assessment Study 1995-1996 as Quality Control Samples 2000-20...
			4.7 Participation in Proficiency Tests and Trueness
			4.8 Accreditation
		5 Summary and Conclusions
		Appendix
		References
	Analysis and Quality Control of WHO- and UNEP-Coordinated Human Milk Studies 2000-2019: Organochlorine Pesticides and Industri...
		1 Introduction
		2 Materials and Methods
			2.1 Determination of Nonpolar Substances According to EN1528 (DIN EN 1528-1:1997-1-4)
			2.2 Analysis of Chlordecone and Pentachlorophenol According to the QuEChERS Method
		3 Analytical Criteria
		4 Quality Control
			4.1 Quality Control Samples
				4.1.1 Nonpolar Substances (Method EN1528; Spiked Samples)
					Aldrin
					Chlordane
					DDT
					Dicofol (4,4)
					Dieldrin
					Endosulfan
					Endrin
					Heptachlorepoxide
					Hexachlorobenzene
					Hexachlorobutadiene
					Hexachlorocyclohexanes (α-HCH, beta-HCH, gamma-HCH)
					Mirex
					Pentachloroanisole
					Toxaphene
				4.1.2 Chlordecone and Pentachlorophenol (QuEChERS Method; Spiked Samples)
					Chlordecone
					Pentachlorophenol (PCP)
				4.1.3 Summary: Trueness and Precision Derived from Spiked Quality Control Samples
			4.2 Remainders of Samples from Proficiency Tests as in-house Reference Material
			4.3 Participation in Proficiency Tests for Pesticide Residues
				4.3.1 Chlordane
				4.3.2 DDT
				4.3.3 Dieldrin
				4.3.4 Endosulfan
				4.3.5 Endrin
				4.3.6 Hexachlorobenzene (HCB)
				4.3.7 Hexachlorocyclohexanes (HCH)
				4.3.8 Heptachlorepoxide
				4.3.9 Mirex
				4.3.10 Toxaphene
				4.3.11 Average Deviation
			4.4 Accreditation
		5 Conclusion
		References
	Analysis and Quality Control of WHO- and UNEP-Coordinated Human Milk Studies 2000-2019: Polybrominated Diphenyl Ethers, Hexabr...
		1 Introduction
		2 Analytical Criteria
		3 Polybrominated Diphenyl Ethers (PBDE)
			3.1 Analytes
			3.2 Extraction
				3.2.1 Separation of the Cream (Lipid) Layer by Centrifugation
				3.2.2 Twisselmann Hot Extraction
				3.2.3 Addition of Internal Standards
			3.3 Clean-up
				3.3.1 Partly Automated Clean-up Procedure
				3.3.2 Fully Automated Clean-up Procedure
			3.4 GC-HRMS Measurement
			3.5 Quality Control
				3.5.1 Procedural Blank Samples
				3.5.2 Quality Control Samples as In-House Reference Material
				3.5.3 Participation in Proficiency Tests
		4 Hexabromocyclododecanes (HBCDD)
			4.1 Analytical Procedure and Analytes
			4.2 Quality Control
				4.2.1 Procedural Blank Samples
				4.2.2 Quality Control Samples as In-House Reference Material
				4.2.3 Participation in Proficiency Tests
		5 Chlorinated Paraffins (CP)
			5.1 Analytical Procedure and Analytes
				5.1.1 Sample Preparation
				5.1.2 Analysis
					Semi-quantitative Analysis (GC-EI-MS/MS)
					Homologue Group Specific Analysis (GC-ECNI-Orbitrap-HRMS)
			5.2 Quality Control
				5.2.1 Initial Method Validation
					Method Validation: GC-EI-MS/MS
					Method Validation: GC-ECNI-Orbitrap-HRMS
				5.2.2 Quality Control Samples
				5.2.3 Participation in Interlaboratory Studies
		6 Polychlorinated Naphthalenes (PCN)
			6.1 Analytical Procedure and Analytes
				6.1.1 Sum Parameter for Selected PCN
				6.1.2 Toxic Equivalents (TEQ)
				6.1.3 Limits of Quantification and Acceptable Differences Between Upper-Bound and Lower-Bound Results for PCN-TEQ
			6.2 Quality Control
				6.2.1 Procedural Blank Samples
				6.2.2 Fortified Raw Milk and Butter Samples as In-House Reference Material
				6.2.3 Quality Control Samples as In-House Reference Material and Precision
				6.2.4 External Validation
				6.2.5 Participation in Interlaboratory Studies
		7 Accreditation
		Appendix
		References
Part III: WHO/UNEP-Coordinated Exposure Studies 2000-2019: Results of Chlorinated and Brominated POPs and Discussion
	WHO- and UNEP-Coordinated Exposure Studies 2000-2019: Findings of Polychlorinated Biphenyls, Polychlorinated Dibenzo-p-Dioxins...
		1 Introduction
		2 General Aspects
			2.1 Link to the General Introduction (Countries, UN Regions, Protocol)
			2.2 Number of Samples, Aggregation of Data and Analysis
			2.3 Cost-Effectiveness and Possible Range of Individual Samples Using Pooled Samples
			2.4 Toxic Equivalency Factors (TEF) and Toxic Equivalents (TEQ)
			2.5 Lower and Upper Bounds TEQ Concentrations
			2.6 Non-dioxin-like PCB
			2.7 Use of Terms for TEQ
			2.8 Human Exposure and Congener Patterns
		3 Overall Comparison of Concentrations of TEQ and Non-dioxin-like PCB Among UN Regions
			3.1 TEQ
			3.2 Non-dioxin-like PCB
		4 The Five WHO- and UNEP-Coordinated Studies from 2000 to 2019
		5 Detailed Comparison of Concentrations on a Regional Group Scale
			5.1 African Group
			5.2 Asia-Pacific Group
				5.2.1 Asia Subgroup
				5.2.2 Pacific Islands Subgroup
			5.3 Group of Latin American and Caribbean Countries (GRULAC)
			5.4 Eastern European Group
			5.5 Western European and Others Group (WEOG)
		6 Correlation Between Indicator PCB and Dioxin-like PCB and Between Dioxin-like PCB and PCDF
		7 Summary
		Appendix
		References
	WHO- and UNEP-Coordinated Exposure Studies 2000-2019: Findings of Organochlorine Pesticides and Industrial Chemicals
		1 Introduction
		2 General Aspects
			2.1 Countries, UN Regions, Protocol, and Analytes Selected
			2.2 Number of Samples and Aggregation of Data
			2.3 Analysis and Complexes of DDT, Chlordane, Heptachlor, Endrin, and Endosulfan
			2.4 Background Concentrations
		3 Results and Discussion
			3.1 DDT
				3.1.1 General Comparison of Ranges
				3.1.2 African Group
				3.1.3 Asia-Pacific Group
					Asia Subgroup
					Pacific Islands Subgroup
				3.1.4 Group of Latin American and Caribbean Countries (GRULAC)
				3.1.5 Eastern European Group
				3.1.6 Western European and Others Group (WEOG)
		4 Hexachlorocyclohexanes (Alpha-HCH, Beta-HCH, and Gamma-HCH)
			4.1 General Comparison of Beta-HCH Ranges
			4.2 African Group
			4.3 Asia-Pacific Group
				4.3.1 Asia Subgroup
				4.3.2 Pacific Islands Subgroup
			4.4 Group of Latin American and Caribbean Countries (GRULAC)
			4.5 Eastern European Group
			4.6 Western European and Others Group (WEOG)
		5 Hexachlorobenzene (HCB)
			5.1 General Comparison of HCB Ranges
			5.2 African Group
			5.3 Asia-Pacific Group
				5.3.1 Asia Subgroup
				5.3.2 Pacific Islands Subgroup
			5.4 Group of Latin American and Caribbean Countries (GRULAC)
			5.5 Eastern European Group
			5.6 Western European and Others Group (WEOG)
		6 Other Organochlorine Pesticides
			6.1 Aldrin, Dieldrin
			6.2 Chlordane
			6.3 Endrin
			6.4 Heptachlor
			6.5 Mirex
			6.6 Toxaphene
			6.7 Chlordecone
			6.8 Endosulfan
			6.9 Pentachlorophenol (PCP), Pentachloroanisole (PCA)
			6.10 Dicofol
		7 Organochlorine Industrial Chemicals
			7.1 Pentachlorobenzene (PeCB)
			7.2 Hexachlorobutadiene (HCBD)
		8 Summary
		References
	WHO- and UNEP-Coordinated Exposure Studies 2000-2019: Findings of Polybrominated Substances (PBDE, HBCDD, PBB 153, PBDD/PBDF)
		1 Introduction
		2 General Aspects
			2.1 Link to the General Introduction (Countries, UN Regions, Protocol)
			2.2 Analysis of Polybrominated Substances
			2.3 Number of Samples and Aggregation of Data
			2.4 Methods of Statistical Data Treatment for Time Trends of PBDE in Countries with Repeated Participation
			2.5 Background Concentrations Versus High Concentrations After Exposure
		3 Polybrominated Diphenyl Ethers (PBDE)
			3.1 Sum of Six PBDE Congeners (BDE-47, BDE-99, BDE-100, BDE-153, BDE-154, BDE-183)
			3.2 Temporal Tendencies for the Sum of Six PBDE Congeners Derived from Countries with Repeated Participation
				3.2.1 African Group
				3.2.2 Asia-Pacific Group
				3.2.3 Group of Latin American and Caribbean Countries (GRULAC)
				3.2.4 Eastern European Group
				3.2.5 Western European and Others Group (WEOG)
				3.2.6 Global Level
			3.3 Decabromodiphenyl Ether (BDE-209)
			3.4 Congener Patterns
		4 Hexabromocyclododecanes (HBCDD)
		5 Hexabromobiphenyl (PBB 153)
		6 Polybrominated Dibenzodioxins and Furans (PBDD/PBDF)
		References
	WHO- and UNEP-Coordinated Human Milk Studies 2000-2019: Findings of Chlorinated Paraffins
		1 Introduction
			1.1 Production and Environmental Fate
			1.2 Toxicological Aspects
			1.3 Classification as POP and Regulatory Situation
			1.4 CP as Target Analytes in the WHO/UNEP-Coordinated Human Milk Studies on Persistent Organic Pollutants
		2 Materials and Methods
			2.1 Sample Collection
			2.2 Sample Preparation
			2.3 Measurement of SCCP and MCCP
			2.4 Quality Control
			2.5 Assessment of Temporal Trends
			2.6 Grouping of Countries into UN Regional Groups
		3 Results for Samples Collected 2009-2019
			3.1 Global Overview of Sum of CP Levels
			3.2 A Closer Look by Geographical Area
			3.3 Relation to Other POPs 2015-2019
		4 Considerations on CP Homologue Patterns
			4.1 UN Regional Group Characteristics
			4.2 Sub-groups within UN Regional Groups
			4.3 Differences Depending on Sampling Region
		5 Conclusions
		References
	WHO- and UNEP-Coordinated Exposure Studies 2000-2019: Findings of Polychlorinated Naphthalenes
		1 Introduction
		2 General Aspects
			2.1 Link to the General Introduction (Countries, UN Regions, Protocol, Samples)
			2.2 Analysis
		3 Results and Discussion
			3.1 Sum of Measured PCN Congeners ( 26 PCN)
			3.2 PCN Patterns
			3.3 Dioxin-Like Properties
				3.3.1 Relative Potency of PCN
				3.3.2 Calculation of PCN-TEQ, Part 1: Lower-Upper Bound Results; Co-Eluting Congeners PCN 52/60 and 64/68
				3.3.3 Calculation of PCN-TEQ, Part 2: Co-Eluting Congeners PCN 66/67
			3.4 PCN-TEQ Results
			3.5 Contribution of PCN-TEQ to the Cumulative TEQ (Including the Overall Sum of PCDD, PCDF, and Dioxin-like PCB Toxic Equivale...
		References
Part IV: Assessments
	Time Trends in Human Milk Derived from WHO- and UNEP-Coordinated Exposure Studies, Chapter 1: Polychlorinated Biphenyls, Polyc...
		1 Introduction
		2 General Aspects
			2.1 Minimization of Sources of Variation
			2.2 Samples and UN Regional Groups
			2.3 Sum Parameters and Long-term Quality Control
			2.4 Methods of Statistical Data Treatment
			2.5 Background Concentrations Versus High Concentrations after Exposure
		3 Non-Dioxin-Like Polychlorinated Biphenyls (Indicator PCB, ΣPCB6)
			3.1 European and Non-European Countries
			3.2 Global Level and Comparison Between UN Regional Groups
			3.3 African Group
			3.4 Asia-Pacific Group
			3.5 Group of Latin American and Caribbean Countries (GRULAC)
			3.6 Eastern European Group
			3.7 Western European and Others Group (WEOG)
		4 Toxic Equivalents of PCDD and PCDF (WHO-PCDD/PCDF-TEQ)
			4.1 Global Level and Comparison Between UN Regional Groups
			4.2 African Group
			4.3 Asia-Pacific Group
			4.4 Group of Latin American and Caribbean Countries (GRULAC)
			4.5 Eastern European Group
			4.6 Western European and Others Group (WEOG)
		5 Total Toxic Equivalents of PCDD, PCDF and Dioxin-Like PCB (WHO2005-TEQ)
			5.1 Global Level and Comparison Between UN Regional Groups
			5.2 African Group
			5.3 Asia-Pacific Group
			5.4 Group of Latin American and Caribbean Countries (GRULAC)
			5.5 Eastern European Group
			5.6 Western European and Others Group (WEOG)
		6 Summary and Conclusions
		References
	Time Trends in Human Milk Derived from WHO- and UNEP-Coordinated Exposure Studies, Chapter 2: DDT, Beta-HCH and HCB
		1 Introduction
		2 General Aspects
			2.1 Minimization of Sources of Variation; Samples and UN Regional Groups; Long-Term Quality Control
			2.2 ``DDT Complex´´ as Sum Parameter for DDT
			2.3 Methods of Statistical Data Treatment: Trends vs. Tendencies
			2.4 Background Concentration
		3 DDT
			3.1 Global level and comparison between UN Regional Groups
			3.2 African Group
			3.3 Asia-Pacific Group
			3.4 Group of Latin American and Caribbean Countries (GRULAC)
			3.5 Eastern European Group
			3.6 Western European and Others Group (WEOG)
			3.7 Dependence of Decrease (Decrease Rate Constants) on Concentration
		4 Beta-Hexachlorocyclohexane (beta-HCH)
			4.1 Global Level and Comparison between UN Regional Groups
			4.2 African Group
			4.3 Asia-Pacific Group
			4.4 Group of Latin American and Caribbean Countries (GRULAC)
			4.5 Eastern European Group
			4.6 Western European and Others Group (WEOG)
			4.7 Dependence of Decrease (Decrease Rate Constants) on Concentration
		5 Hexachlorobenzene (HCB)
			5.1 Global Level and Comparison Between UN Regional Groups
			5.2 African Group
			5.3 Asia-Pacific Group
			5.4 Group of Latin American and Caribbean Countries (GRULAC)
			5.5 Eastern European Group
			5.6 Western European and Others Group (WEOG)
			5.7 Dependence of Decrease (Decrease Rate Constants) on Concentration
		6 Summary and Conclusions
		References
	Time Trends in Human Milk Derived from WHO- and UNEP-Coordinated Exposure Studies, Chapter 3: Perfluoroalkyl Substances (PFAS)
		1 Introduction
		2 Material and Methods
			2.1 Source of Data
			2.2 Methods of Statistical Data Treatment: Trends vs. Tendencies
		3 Results and Discussion
			3.1 PFOS
				3.1.1 Estimation of Temporal Trends by Differentiation into Three Periods between 2008 and 2019
				3.1.2 African Group
				3.1.3 Asia-Pacific Group
				3.1.4 Group of Latin American and Caribbean Countries (GRULAC)
				3.1.5 Eastern European Group
				3.1.6 Western European and Others Group (WEOG)
				3.1.7 Worldwide
			3.2 PFOA
				3.2.1 Estimation of Temporal Trends by Differentiation into Three Periods between 2008 and 2019
				3.2.2 African Group
				3.2.3 Asia-Pacific Group
				3.2.4 Group of Latin American and Caribbean Countries (GRULAC)
				3.2.5 Eastern European Group
				3.2.6 Western European and Others Group (WEOG)
				3.2.7 Worldwide
			3.3 PFHxS
				3.3.1 African Group
				3.3.2 Asia-Pacific Group
				3.3.3 Group of Latin American and Caribbean Countries (GRULAC)
				3.3.4 Eastern European Group
				3.3.5 Western European and Others Group (WEOG)
				3.3.6 Worldwide
		Appendix
		References
	Risk-Benefit Analysis for the Breastfed Infant Based on the WHO- and UNEP Human Milk Surveys for Dioxin-like Compounds
		1 Introduction
		2 Global Measurements and Time Trends
		3 Most Sensitive Endpoint for the Breastfed Infant
		References
Part V: Summary, Conclusions and Outlook
	Overall Conclusions and Key Messages of the WHO/UNEP-Coordinated Human Milk Studies on Persistent Organic Pollutants
		1 Introduction
		2 Efficient and Effective Tool with Global Coverage as Key Contributor to the Global Monitoring Plan (GMP)
			2.1 Possibility to Determine the Complete Set of Analytes of Interest
			2.2 Assurance of the Reliability and Comparability of Results over a Long Period (2000-2019) for the Wide Range of Analytes of...
			2.3 Cost-Effectiveness
			2.4 Capacity Building and Global Human Milk Bank
			2.5 Conclusion
		3 Regional Group Differentiation
			3.1 PCB
			3.2 DDT
		4 Assessment of Time Trends
			4.1 DDT
			4.2 PCB
			4.3 Toxic Equivalents of PCDD and PCDF (WHO-PCDD/PCDF-TEQ [2005])
			4.4 Chlorinated Paraffins
		5 Relative Importance of POPs
			5.1 Dioxin-Like Compounds
			5.2 Non-dioxin-Like Chlorinated and Brominated POPs
			5.3 Perfluoroalkyl Substances (PFAS)
		6 Overall Conclusions
		Appendix
			Regional Differentiation
				Toxic equivalents of PCDD/PCDF and Dioxin-like PCB (WHO2005-TEQ)
				Beta-HCH
				HCB
				Dieldrin
				PBDE
				PFOS
				Chlorinated Paraffins
			Assessments of Time Trends
				Beta-HCH
				HCB
				PBDE
				PFOS
		References
	Outlook (Towards Future Studies on Human Milk)
		1 Introduction
		2 New Candidate Chemicals, New Requirements
		3 New Approaches
		4 Needs for the Future
		References