Risk Assessment: From Hazard Identification to Global Impact

“Shielding food safety and security by enabling the foresight of fungal spoilage and mycotoxins threats in the Mediterranean region under climate change conditions” FunShield4Med Summer School 1 July 2023 Parma , Italy Dr. Eleni Kollia Chemist MSc/Pharmacist HORIZON-WIDERA-2021-ACCESS-03-01 Risk Assessment: From Hazard Identification to Global Impact •Every year, millions of people around the world suffer from foodborne illnesses & poisoning •These can be caused by harmful agents such as bacteria, viruses, parasites, and chemicals •It's crucial to have effective measures in place to ensure that the food we eat is safe We can determine the likelihood and severity of harm and make informed decisions to protect public health Risk Assessment Quantifying Risks and Ensuring Food Safety Quantifying magnitude and exposure of harmful effects Scientific evaluation of the occurrence’s probability of known or potential adverse health effects resulting from human exposure to food-borne hazards. Risk assessment ? Risk assessment is a systematic process that helps us identify, evaluate, and manage potential risks associated with harmful agents or activities. Hazard Identification Hazard Characterization Exposure Assessment Risk Characterization Risk Assessment Framework 12 34 The Four Steps of Risk Assessment About “Hazard” and “Risk” Hazard Biological, chemical, physical agent (in foods/ feeds) with the potential to cause an adverse health effect. Risk A function of the probability of an adverse health effect and the severity of that effect consequential to a hazard About “Hazard” and “Risk” Example: •Driving a car is a hazard because it involves the potential for harm (e.g. accidents, collisions) •The risk associated with driving varies depending on factors such as the driver's experience, the condition of the vehicle, and the road conditions. WHAT CAN STUDIES TELL US? That the chemical can be a hazard It has a particular adverse effect at a particular dose Lowest dose (threshold) No effect or lowest effect level Is there a dose-response effect? Hazard Characterization Hazard Characterization Outputs 1. Shape of the dose-response curve 2. Identification of thresholds of toxicity 3. Determine appropriate safety factors 4. Establish reference health standards, if possible 1. Hazard Identification 2. Hazard Characterization 3. Exposure Assessment 4. Risk Characterization Evaluation of adverse health effect •Biological extrapolation •Dose-response and dose-effect relationships •Understanding of the doses involved and related responses Understanding the dose-response relationship: - is it problem at low doses? - is it problem at high doses only? Hazard Characterization 1. Hazard Identification 2. Hazard Characterization 3. Exposure Assessment 4. Risk Characterization •Key component in policy-making for controlling human health risks •Measurement of health effects prevalence at each dose level •Dose-response curve: Plots the results, showcasing the relationship between dose and health effects •Toxic (non-carcinogenic) and carcinogenic effects assessed separately, even if an agent can cause both •Importance: Helps understand the toxicity of substances and set appropriate exposure limits •Enables policymakers to make informed decisions to safeguard public health •Dose-response assessment aids in the establishment of regulations and guidelines for toxin control. Hazard Characterization Toxicity Assessment Severity of response Dose-response relationship Graphical representation of the relationship between the dose of a toxic agent and the proportion of a population experiencing adverse health effects. Animal and human studies provide dose-response data Hazard Characterization Dose-response relationship What is a Response ? •Change from normal state •Response (symptoms) could be on the molecular, cellular, organ or organism •Local Vs Systemic •Immediate Vs Delayed •Graded Vs Quantal THRESHOLD - lowest dose which causes an effect, below this dose, no toxicity is observed NAOEL –highest dose employed at which no adverse effect was observed (derived experimentally) LAOEL - lowest dose at which there was an observed adverse effect (derived experimentally) Hazard Characterization Toxicity Assessment Toxic but non-carcinogenic agent Is determined by toxicity animal studies & divided by UFs (product of Uncertainty Factors) to convert it to human NOAEL NOAEL As this value gets higher Risk Assessment becomes less reliable Disandvantages of NOAEL Is subject to dose selection Uncertainties is not made visible, or they are ignored NOEL can not be compared between different studies The true effect size remains unknown change in response Lower confident limit Shifting from NOAEL to BMD: A Comprehensive Approach in Establishing Health-Based Guidance Values What Is Benchmark Dose (BMD) and Benchmark Response (BMR) A benchmark dose (BMD) is a dose or concentration that produces a predetermined change in the response rate of an adverse effect. This predetermined change in response is called the benchmark response (BMR). Normally, the default BMR is 5% or 10%change in the response rate of an adverse effect relative to the response of control group depending on whether response data is continuous or quantal Consequently, the BMDL can be defined as a dose level at which the observed effect is smaller than the benchmark response (BMR). % Response 5% response Use mathematic models to establish a dose-response curve which will predict (with 95% confidence) the dose which will give a particular % response in the population. EFSA (European Food Safety Authority), 2009. Guidance of the Scientific Committee on a request from 1235 EFSA on the use of the benchmark dose approach in risk assessment. EFSA Journal 2009, 1150, 11236 72. Shifting from NOAEL to BMD: BMD is a range, rather than a fixed number RP Uncertainty reflected from BMDU/BMDL ratio (BMDL10 or BMDL05) 95% confidence level90% confidence level Epidemiological data - less precise - highly relevant Animal toxicity data - more precise - less relevant OUTCOMES • Some understanding of kinetic and metabolism • Identify target organs • Possible mechanism of action • Dose-response relationship • Evidence of a threshold/NOEL etc. Hazard Characterization Toxicity Assessment aims to estimate the levels of the hazard present in food and feed. through sampling and analysis of representative samples collected from various stages of the food and feed supply chain. By considering consumption patterns and practices, researchers can determine the potential exposure levels of individuals or populations to hazards Toxicity benchmarks, such as the Tolerable Daily Intake (TDI) or Provisional Maximum Tolerable Daily Intake (PMTDI), are established to define safe exposure levels for humans. Exposure Assessment Estimation of intake 1. Hazard Identification 2. Hazard Characterization 3. Exposure Assessment 4. Risk Characterization Evaluates the extent of exposure to the hazard Exposure Assessment Estimation of intake 1. Hazard Identification 2. Hazard Characterization 3. Exposure Assessment 4. Risk Characterization An exposure assessment for a particular agent is based on: 1. The amount of the chemical in food 2. The level of food consumption Probability of occurrence and severity of potential adverse health effect Risk Characterization 1. Hazard Identification 2. Hazard Characterization 3. Exposure Assessment 4. Risk Characterization Integration of information gathered from exposure assessment and hazard characterization to formulate recommendations applicable to risk management involves integrating the hazard, exposure, and toxicity data to assess the overall risk associated with mycotoxin contamination. quantitatively or qualitatively evaluate the likelihood and severity of adverse health effects resulting from mycotoxin exposure. This information is essential in informing risk management strategies and decision-making processes aimed at reducing or mitigating mycotoxin risks in the food and feed supply chain. Risk Characterization Outcomes ❖Estimation of risk ❖Identification of at-risk (sensitive) populations ❖Uncertainties in the assessment The Nature of Advice to Risk Managers Risk Characterization 1. Quantitative advice •level of risk at given exposure (difficult to obtain) •ADI/ TWI (most common) •margin of exposure (useful in some cases) 2. Qualitative advice •conditional approval (eg, only particular production method allowed; only certain uses allowed) •minimize exposure (as low as reasonable achievable) •avoid intake by certain groups 1. Levels in food should be as low as reasonably achievable (unavoidable contaminant) 2. Avoidance of foods from certain sources (highly contaminated soils) 3. Avoidance of certain ingredients from use in food altogether (toxic plants) 4. Avoidance of certain process (eg, ethylene oxide sterilization of spices) 5. Modification of production process (soy sauce production) 6. Reduction of intake of certain foods (eg, lupin seeds) Risk Characterization OutcomeQualitative advice regarding risk Responsibility of scientific committees e.g. JEFCA, EFSA Risk assessors and managers with the public Responsibility of regulators e.g. Codex committees, EU commission Risk Analysis Framework For conducting a risk assessment study about a chemical hazard, we need: Human-animal studies data Occurrence data Exposure-Consumption data FOOD CONSUMPTION DATA The EFSA Comprehensive European Food Consumption Database provides a compilation of existing national information on food consumption at individual level Details on how the Comprehensive Database is used are published in the Guidance of EFSA. The latest version of the Comprehensive Database, updated in 2018, contains results from a total of 60 different dietary surveys carried out in 25 different Member States covering 119,458 individuals. Within the dietary studies, subjects are classified in different age classes as follows: Infants:< 12 months old Toddlers:≥12 months to <36 months old Other children:≥36 months to <10 years old Adolescents:≥10 years to <18 years old Adults:≥18 years to <65 years old Elderly:≥65 years to <75 years old Very elderly:≥75 years old European Food Safety Authority; Use of the EFSA Comprehensive European Food Consumption Database in Exposure Assessment. EFSA Journal 2011; 9( 3):2097. [34 pp.]. doi:10.2903/j.efsa.2011.2097 ECONOMIC IMPACTS BY NUMBERS 25%of the world’s crops are affected by mycotoxins each year, of which aflatoxins are the most notorious (FAO, 2000) 1 billion metric tons annual losses of foods and food products Losses of livestock and poultry due to aflatoxin-contaminated feeds Worldwide annual losses of due to aflatoxin contamination $1.2 billion in commerce African economies lose $450 million each year Mycotoxin Global Distribution 2022 Common mycotoxins Aspergillus & Penicillium spp Fusarium spp Aspergillus flavus & parasiticus Fusarium spp Fusarium spp Occurrence Consequently, it is crucial to implement rigorous mycotoxin risk assessment and mitigation strategies throughout the supply chain to ensure the safety and quality of these agricultural products. Aflatoxins Aflatoxins are bisfuranocoumarin compounds produced primarily by toxigenic strains of the fungi Aspergillus flavus and Aspergillus parasiticus. Aspergillus parasiticus Aspergillus flavus AFB1and AFB2AFB1, AFB2, AFG1and AFG2 ❖AFM1and AFM2are the hydroxylated metabolites of AFB1and AFB2 The aflatoxin-producing fungi are found especially in areas with a hot, humid climate and aflatoxins are found in food as a result of both preand post-harvest fungal contamination. The rate and degree of contamination depends on temperature, humidity, soil and storage conditions. Climate change is expected to have an impact on the presence of AFB1in Europe. Chemical structures, CAS number, molecular formula and molecular weight of aflatoxins B1, B2, G1, G2, M1and M2 Major Mycotoxins and Risk Assessment •Toxic substances that contaminate food crops •The major mycotoxins include aflatoxins, fumonisins, ochratoxin A, deoxynivalenol, and zearalenone •Risk assessments have been conducted on these mycotoxins to determine their impact on food safety guidelines •Uncertainties surrounding the risk assessments for some mycotoxins •Continuous research efforts in this area to ensure the safety of our food supply. Mycotoxins in Human Food: Risk Assessment and Risk Management Addressing Global Challenges ✓Mycotoxin risks in food: Global significance ✓Human right to mycotoxin-free food (UNEP, WHO-IPCS) ✓Major impacts on human health, animal health, and market access (FAO/WHO/UNEP, 1999) Need for Global Attention •Lack of sufficient attention and action •Incomplete knowledge of mycotoxins and associated health risks •Poor communication of risks to policymakers in affected regions •Low perceived value of interventions compared to other medical priorities •Multiple intervention points before and after harvest •Minimal impact of regulations on subsistence farmers' food quality •Interdisciplinary nature of the problem, requiring collaboration Importance of Mycotoxin Risk Assessment ❑Protecting human and animal health ❑Ensuring food and feed safety ❑Regulatory compliance ❑Trade considerations EFSA's role Collects and evaluates occurrence data on mycotoxins in food and feed. Offers scientific advice to risk managers for establishing maximum levels of mycotoxins in food and feed. Considers risks to human and animal health and sets Tolerable Daily Intakes for various mycotoxins. Assesses human and animal exposure using occurrence data, including specific population groups and different animal species. Examines carry-over levels of mycotoxins from feed to foods of animal origin. Identifies feed materials as potential sources of mycotoxin exposure. Ensures continuity of data collection by integrating new occurrence data into existing databases and supporting the creation of new ones. EU framework EU legislation protects consumers by: Setting maximum levels for mycotoxins in food and feed to ensure they are not harmful to human or animal health Keeping mycotoxin levels as low as reasonably achievable following recommended good agricultural, storage and processing practices. Exposure to mycotoxins occurs mostly by ingestion and poses a serious health threat to both humans and livestock It is a major health concern due to its widespread occurrence and potential adverse effects. Diet is the main source of exposure Dietary risk is crucial to understand the extent of population exposure through eating habits OCHRATOXIN RISK ASSESSMENT OVER YEARS: EVALUATING POTENTIAL HAZARD •2006, EFSA CONTAM Panel published an opinion related to OTA in food –OTA exhibits nephrotoxic, neurotoxic, and teratogenic effects in animals, especially at higher doses, lead to kidney and liver tumors in rodents when exposed chronically –Evidence suggests that OTA induces DNA damage primarily through oxidative stress rather than direct interaction –Tolerable weekly intake (TWI) of 120 ng OTA/kg bw established based on a LOAEL of 8μg/kg bw per day for early markers of renal toxicity in pigs. •1991, JECFA (Joint FAO/WHO Expert Committee on Food Additives) has issued OTA evaluations –Provisional tolerable weekly intake (PTWI) of 112 ng/kg bw was established, based on a LOEL of 8μg/kg bw per day •2020, EFSA CONTAM Panel concluded that: –There is clear evidence for carcinogenic effects of OTA. –As a consequence, the TWI of 120 ng OTA/kg bw as established in 2006 is no longer valid Milestones of Evaluating Ochratoxin A *EFSA (European Food Safety Authority), 2005. Opinion of the Scientific Committee on a request from EFSA relatedto a harmonised approach for risk assessment of substances which are both genotoxic and carcinogenic. EFSA Journal 2005;3(10):282, 33 pp. EFSA updated their 2006 opinion on ochratoxin A (OTA) in response to a request from the European Commission •Animal studies →OTA is associated with kidney toxicity and tumor formation •Genotoxic properties of OTA and its modes of action →not fully understood •Uncertainties in the mode of action for kidney carcinogenicity →a healthbased guidance value (HBGV) was not established •Margin of exposure (MOE) approach was used to assess the risk. •Benchmark dose lower limits (BMDL10) were calculated for non-neoplastic and neoplastic effects based on animal studies •Chronic dietary exposure to OTA varied across different consumer groups •Comparisons between exposure levels and BMDL10 values indicated a low health concern for most consumer groups, except for high consumers in younger age groups, which raised a possible health concern •The assessment acknowledged a high level of uncertainty, suggesting that the risk may be overestimated. •EFSA's updated assessment emphasizes the need for further research and understanding of the genotoxicity and health risks associated with OTA in food. Exposure MOE →level of exposure in which harm to human heath is not expected to occur, divided by an estimated level of human exposure For substances that are both genotoxic and carcinogenic, the EFSA Scientific Committee stated that an MOE of 10,000 or higher, if based on the BMDL10 from an animal carcinogenicity study, would be of low concern from a public health point of view (EFSA, 2005). Greater MOE indicates a larger safety margin between the potential impact on human health and the level of exposure to a substance. Regulatory Measures and Food Supply Regulatory measures play a crucial role in ensuring food safety Protection of consumers from harmful contaminants Implementing of these measures can be challenging for both producers and regulators Regulatory measures help to prevent outbreaks of foodborne illness, protect public health, and promote consumer confidence in the food supply Creation of level playing field for producers, ensuring that all products meet the same standards regardless of their origin. Risk Assessment for Major Mycotoxins •Aflatoxins, fumonisins, ochratoxin A, deoxynivalenol, zearalenone •Conducting risk assessments for each mycotoxin •Assessing associated risks and implications for human health Risk Management: Practical Approaches •Focus on managing mycotoxin risks in food •Strategies for effective risk management: ✓Post-harvest handling and storage techniques ✓Monitoring and surveillance programs ✓Regulatory measures and enforcement ✓Early Warning Systems Ensuring Food Safety: A Comprehensive Risk Analysis Framework for Mycotoxins Involve a combination of preventive measures, regulations, and control strategies aimed at minimizing mycotoxin contamination Good Agricultural Practices (GAPs) Good Manufacturing Practices (GMPs) Hazard Analysis and Critical Control Points (HACCP) to minimize mycotoxin contamination during cultivation, harvesting, storage, processing, and transportation Risk Assessment for Major Mycotoxins •Aflatoxins, fumonisins, ochratoxin A, deoxynivalenol, zearalenone •Conducting risk assessments for each mycotoxin •Assessing associated risks and implications for human health Risk Management: Practical Approaches •Focus on managing mycotoxin risks in food •Strategies for effective risk management: ✓Good Agricultural Practices (GAP) ✓Post-harvest handling and storage techniques ✓Monitoring and surveillance programs ✓Regulatory measures and enforcement ✓Early Warning Systems Importance of Risk Communication •Enhancing risk communication and public education •Promoting awareness and understanding of mycotoxins •Targeting countries at high risk: ✓Informing policymakers and stakeholders ✓Empowering consumers to make informed choices Ensuring Food Safety: A Comprehensive Risk Analysis Framework for Mycotoxins Communication and Monitoring (1) ✓Public Awareness This involves disseminating information through various channels, such as public health campaigns,educational programs, websites, and social media platforms. ✓Stakeholder Engagement Regular communication helps in sharing information, discussing best practices, and addressing concerns. ✓Risk Communication This involves providing details about potential health effects, exposure routes, preventive measures, and regulatory actions. Communication and Monitoring ✓Sampling and Analysis This includes collecting representative samples from different stages of the supply chain, using appropriate sampling techniques, and employing validated analytical methods for mycotoxin detection. ✓Regulatory Monitoring They may conduct routine inspections, surveillance programs, and random sampling to assess the compliance of food and feed products with maximum allowable mycotoxin limits. ✓Early Warning Systems These systems involve continuous monitoring of environmental conditions, crop growth, and fungal activity to identify conditions favorable for mycotoxin production. ✓Data Sharing Effective monitoring also requires sharing monitoring data among relevant stakeholders, including regulatory agencies, industry associations, and research institutions. This facilitates the identification of emerging mycotoxin risks, collaborative research efforts, and the development of mitigation strategies. Conclusion •Mycotoxin risk assessment is essential for protecting public health •Mycotoxin risks demand global attention and action •Continuous monitoring and research are crucial •Collaboration between stakeholders is key •Risk assessment and management are crucial for ensuring food safety •Addressing interdisciplinary challenges and improving risk communication are essential steps As consumers, we must demand that our food is safe and hold those responsible accountable As scientists, we must ensure that our food supply is safe for all [email protected]a.gr