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CHEMICAL RISK ASSESSMENT &
CHALLENGES FACING THE FOOD
INDUSTRY (化学品风险评估以及食品
行业所面临的挑战)Paul Hepburn, PhD
Director Food SafetySafety & Environmental Assurance Centre, UnileverUK
1
>190 COUNTRIES我们的产品在190个国家有售
2015 TURNOVER:
€53.3 BILLION
2015营业额533亿欧元
EMPLOYEES WORLDWIDE 全球雇员
172,000
EMERGING MARKETS REPRESENT新兴市场占营业额
58% OF TURNOVER
UNILEVER IS A GLOBAL COMPANY (全球性公司)
Personal Care
Home Care
Refreshment
Foods
Unilever Foodsolutions
Water
UNILEVER CHINA BRAND PORTFOLIO18+ BRANDS IN MARKET
水
ShanghaiChina
TrumbullUSA
Port Sunlight UK
BangaloreIndia
VlaardingenThe Netherlands
ColworthUK
• More than 6,000 R&D professionals (至少6000余名专业人员)
SIX MAJOR R&D CENTRES (6大主要研发中心)
SAFETY & ENVIRONMENTAL ASSURANCE CENTRE (SEAC)
Unilever’s centre of excellence in Safety & Sustainability Science (联合利华卓越的安全与可持续科学中心)
We provide authoritative scientific evidence & expertise to identify, assess & manage:
Risks for our Consumers, Workers and Environment (消费者，员工以及环境的安全)Safety of products & supply chain technology
Environmental Impacts (对环境的影响)Sustainability of Unilever’s brands, products & supply chain
KEY SEAC SCIENCE AREAS
(安全与环境保障中心6个主要的科学领域)6毒理学 微生物学 分析和机理化学
职业安全环境科学
环境和可持续发展
RISK ASSESSMENT PRINCIPLES (风险评估原则)
Acute toxicity Allergy (type I) Systemic toxicity
- sub-chronic- chronic
Reproductive toxicology Teratogenicity Genotoxicity Carcinogenicity
Ingestion:-Food & drink
Risk = f (Hazard x Exposure)
Toxicological Hazard
Exposure
1. Hazard Identification
2. Hazard Characterisation
3. Exposure Assessment
4. Risk Characterisation
TRADITIONAL RISK ASSESSMENT STRATEGY (传统的风险评估策略)
NOAEL
Targeted Testing
ADI* = NOAEL ÷ 100
Exposure < ADI
Exposure > ADI
* Acceptable Daily Intake
Ingredient level
Amount of product
Absorption factor
Consumer habits
Toxicology data
Human data
Predictive chemistry
Frequency consumption
Biological equivalence
Safe history of use
Overall safety evaluation –define acceptability
1. Hazardidentification
2. Hazard characterisation
3. Exposure assessment
4. Risk characterisation
RISK-BASED APPROACH - FOOD SAFETY (基于风险的方法 -食品安全)
Threshold Toxicological
Concern
20TH CENTURY TOXICOLOGY (20世纪的毒理学)Animal testing (动物测试)
Risk Assessment (风险评估)
Regulations (法律法规)
• Benchmark dose (Crump, 1984)
• PBPK (Clewell & Anderson, 1985)
• Chemical specific adjustment factors (Renwick, 1993)
• Threshold of toxicological concern (Munro et al, 1996)
• Margins of exposure for genotoxic carcinogens (JECFA, 2005)
• History of safe use (Constable et al, 2007)
• Post market monitoring (Hepburn et al, 2008)
• Increase in animal numbers -1950s onwards
• Testing guidelines e.g. OECD, US FDA Redbook
• Inbred animal strains
• Animal diets
• Good laboratory Practice (GLP)
• etc….
• US Pure Food & Drug Act (1906)
• US Food, Drug & Cosmetic Act (1938)
• Food Additive Amendment (1958)- GRAS
- Delaney Clause (carcinogens)
• Colour Additive Amendment (1960)
• Since 1970 -FDA review of GRAS substances
• Novel foods regulations (e.g. EU
1997)
THE WORLD IS CHANGING (变化的世界)
Rapid advances in scientific knowledge (科学知识) e.g. genomics, exposure science
Huge Technological advances (技术进步) e.g. HTS, informatics, computational toxicology
Speed of innovation (创新速度) creating novel materials e.g. nano, biotechnology
Scientific value of animal studies being challenged (动物测试的科学价值遭遇挑战)
Consumer demands to stop animal testing (消费者对于停止动物测试的要求)
Too many chemicals (太多的化学品) – not enough animals/money/time !
US NRC/NAS REPORT (2007): A FRAMEWORK FOR CHANGE (变化的框架)
“Advances in toxicogenomics, bioinformatics, systems biology and computational toxicology could transform toxicity testing from a system based on whole-animal testing to one founded primarily on in vitro methods that evaluate changes in biological processes using cells..of human origin.”
NAS REPORT EMPHASIZED ….
“IN VITRO METHODS SHOULD BE THE PREFERRED WAY
TO DO TESTING” (体外实验应该作为测试的首选方法)
… a not-so-distant future where all routine toxicity testing will be conducted in human cells or cell lines in vitro by evaluating perturbations of cellular responses in a suite of toxicity pathway (毒理学通路) assays.
PATHWAYS BASED TOXICOLOGY
(基于通路的毒理学)
Exposure MolecularInitiating
Event
OrganelleEffects Cellular
Effects
TissueEffects
OrganEffects
OrganSystemsEffects
IndividualEffects
PopulationEffects
Toxicity Pathway
Mode of Action
Adverse Outcome Pathway
Adapted from Crofton 2010; OECD.
• MIE - the initial interaction between a chemical and a biomolecule or biosystem that can be linked to an outcome via a pathway (Allen et al, 2014)
• MIE can be the point of entry to predicting AOP(s)
THE MOLECULAR INITIATING EVENT (MIE)(分子起始事件)
Top-Down (从上往下) Bottom-Up (从下往上)20th Century Toxicology 21st Century Toxicology(20世纪毒理学) (21世纪毒理学)
Exposure
Tissue Dose
Biologic Interaction
Perturbation
Low Dose
BiologicInputs
NormalBiologicFunction
Morbidityand
Mortality
Cell Injury
Adaptive StressResponses
Early CellularChanges*
Higher DoseHigher yet
PERTURBATION OF ‘TOXICITY PATHWAYS’ (毒理学通路的扰动)
Krewski. J Toxicol Environ Health B Crit Rev. 2010 Feb;13(2-4):51-138
INDICATORS OF REGULATORY CHANGE(法律法规的变化)
OECD (2013) – Guidance on developing and assessing AOPs
US FDA’s Toxicological Principles for the Safety Assessment of Food Ingredients (“Redbook”)
- “… update will reflect current science”
European Food Safety Authority (EFSA)
• Reviewed modern methodologies and test strategies (EFSA, 2014)
• Declared “alternatives to animal testing as one of the most pressing priorities” (FDE Congress, 2015)
• Risk assessment in 21st Century (RISK21)• Application of genomics to mechanism based risk assessment• Framework for intelligent non-animal methods for safety
assessment
• New approaches to chemical risk assessment for food/ingredients
• Alternatives to animal testing
• Next generation risk assessment
Ne
xt G
en
era
tio
n R
isk
Ass
ess
me
nt
Ap
pro
ach
es
ILSI – A STRATEGIC PARTNER (国际生命科学协会 –我们的战略伙伴)
Advance understanding of scientific issues related to Nutrition& Food Safety
THE CHALLENGES (挑战)
Scientists need to embrace the new paradigm shift in
toxicology (欢迎毒理学中的新转变)
Move towards a future which does not involve animal
testing (进入一个没有动物测试未来)Exposure – better quality data on food consumption (暴露
量 –质量更高的食品消费量数据)
Risk assessment needs to evolve to accommodate the new science (融入新的科学)
Need for trained scientists (受过良好培训的科学家)
Facilitate regulatory acceptance (法律法规的接受和认同)
INDUSTRY
STAKEHOLDER PARTNERSHIPS (相关参与方的合作)….development and acceptance of new approaches
ACADEMIA (学术界)
GOVERNMENT /REGULATORS (政府和法律法规部门)
INDUSTRY (工业界)
CONSUMER TRUST
(消费者的信任)
o To have safe food (安全的食品)
o Embrace new science (接受新的科学) (no going back)
o Capacity building (training, 培训)- Current safety assessors (当前的安全评估人员)
- Future talent (未来的人才)
o Acceptance – regulators and consumers （法规和消费者的接受和认可）
o An appropriate forum (一个合适的平台) e.g. ILSI
Common needs/interests (共同的需求和兴趣):
EXAMPLE: UNILEVER (例子：联合利华)
RESEARCH & TRAINING COLLABORATIONS IN CHINA (和中国的研究和培训合作)
Supporting education of future safety
scientists with Peking University & Chinese Society of Toxicology
Research partnerships with AMMS & RCEES
on 21st Century Safety Science
Working with Government Scientists
(和政府部门的科学家一起工作)
Risk assessment methodology –cosmetic safety
without animal testing
Research (科学研究)
Training – Academia (学术界的培训)
SAFETY SCIENCE IN 21ST CENTURY (21世纪的安全科学)- AN EVOLVING & IMPROVING DISCIPLINE
http://www.tt21c.org/
