DR.D.KANUNGO ADDITIONAL DIRECTOR GENERAL(Rtd.) Ministry of Health - - PowerPoint PPT Presentation

DR.D.KANUNGO

ADDITIONAL DIRECTOR GENERAL(Rtd.)

Ministry of Health and FW

& Chairperson Scientific Panel on Pesticide and Antibiotic Residues FSSAI

UNDERSTANDING GLOBAL PRACTICES IN RISK ANALYSIS OF CHEMICAL CONTAMINANTS

Geeta ,Chapter-17 Verse8-10

The Food which is stale, tasteless, putrid, decomposed, foul and impure as well as the remnants of others is dear to one in nescience.

Srimad Bhagwat Geeta Chapter 17 Verse-10

• Over 200 diseases are caused by unsafe

food containing harmful bacteria, parasites, viruses, chemical substances.

• 2 million deaths occur every year from

contaminated food or drinking water.(Estimated)

The Food and Agriculture Organization of the United Nations (FAO) and World Health Organization (WHO) have a long history of collaboration in the Safety Evaluation of Chemicals in food. This activity began in 1956, when the first meeting

• f the Joint FAO/WHO Expert Committee on Food

Additives (JECFA) was convened by the two

• rganizations, and was strengthened in the early

1960s

Codex Alimentarius Commission (CAC)

• Organization of FAO/WHO- Since 1962
• Responsible for developing standards,

guidelines

• Recommendations on the quality and

safety of food to protect the health of consumers

• Ensure fair practices in food trade

Codex Alimentarius Commission (CAC)- Executive Committee

General Subject Committees

• CCCF

Codex Committee on Contaminants in Foods

• CCFA

Codex Committee on Food Additives

• CCFH

Codex Committee on Food Hygiene

• CCFICS

Codex Committee on Food Import and Export Inspection and Certification Systems

• CCFL

Codex Committee on Food Labelling

• CCGP

Codex Committee on General Principles

• CCMAS Codex Committee on Methods of Analysis

and Sampling

• CCNFSDU Codex Committee on Nutrition and Foods

for Special Dietary Uses

• CCPR

Codex Committee on Pesticide Residues

• CCRVDF Codex Committee on Residues of

Veterinary Drugs in Foods

Commodity Committees

• CCCPL Codex Committee on

Cereals, Pulses and Legumes

• CCFFV Codex Committee on

Fresh Fruits and Vegetables

• CCFO Codex Committee on Fats

and Oils

• CCPFV Codex Committee on

Processed Fruits and Vegetables

• CCS Codex Committee on Sugars
• CCSCH Codex Committee on

Spices and Culinary Herbs

Scientific basis for Codex work

• Codex committees - apply Risk Analysis
• Independent scientific advice by expert bodies
• JECFA - Joint FAO/WHO Expert Committee on

Food Additives

• JMPR - Joint FAO/WHO Meeting on Pesticide

Residues

• JEMRA - Joint FAO/WHO Expert Meetings on

Microbiological Risk Assessment

Contaminants in the diet

❖ Environmental pollutants, such as

• heavy metals ,industrial chemicals,

❖ Mycotoxins, ❖ Migrants from packaging materials ❖ Other substances not authorized for use in food. ❖ EMRL Food contaminants are generally unavoidable

CODEX EVALUATES THE CONTAMINANTS THROUGH THE PROCESS OF RISK ANALYSIS

Selection of compounds on the agenda

AGENDA

FAO /WHO

JECFA SECRETARIATE May add on its own PRIORITY LIST CCCF

MEMBER STATES

   

Earlier meetings of JECFA.



How do we characterize contaminants in food

• The data on total diet
• Concentrations of contaminants in foods
• Details on sampling plans
• Analytical methods used to generate the

data.-LOQ

• Substances consumed in large amounts-May

have impurity of contaminants

Risk analysis

Risk analysis has been defined by CAC as “a process consisting of three components: risk assessment, risk management and risk communication”, which are themselves defined .

(FAO/WHO, 2008):

RISK ANALYSIS

Risk Assessment

• Hazard identification
• Hazard characterization
• Exposure assessment
• Risk characterization

Risk Management

• Risk evaluation
• Option assessment
• Option implementation
• Monitoring and review

Risk Communication

• Interactive exchange of

information and opinions concerning risks

What is risk assessment?

• Uses data, etc. to estimate the probability that

harm will occur as a result of exposure to specific hazards.

– IDENTIFY REAL OR POTENTIAL HAZARD – DETERMINE PROBABILITY OF IT HAPPENING – ASSESS SEVERITY ON HEALTH, ENVIRONMENT, ECONOMY, OR SOCIAL IMPACT

Role of Risk Assessment in Risk Analysis for Food Chemicals

• Risk assessment -the central scientific

component of risk analysis

• Make decisions to protect health in the face of

scientific uncertainty.

• Characterizing the potential hazards and the

associated risks to life and health resulting from exposure of humans to chemicals present in food over a specified period.

What is risk? What is Hazard?

Hazard Vs Risk

• Hazard: Inherent property of an agent or

situation having the potential to cause adverse effects when an organism, system or (sub)population is exposed to that agent.

• Risk: The probability of an adverse effect in

an organism, system or (sub)population caused under specified circumstances by exposure to an agent. (WHO/IPCS,2004)

DK 21

Hazard identification Hazard characterization Exposure assessment Risk characterization

RISK ASSESSMENT

Four-step process for human health risk assessments:

Step 1 - Hazard Identification Examines whether a substance has the potential to cause harm to humans and/or ecological systems, and if so, under what circumstances. Step 2 - Dose Response Assessment Examines the numerical relationship between exposure and effects. .

Four-step process for human health risk assessments

Step 3 - Exposure Assessment Examines what is known about the frequency, timing, and levels of contact with a substance. Step 4 - Risk Characterization Examines how well the data support conclusions about the nature and extent of the risk from exposure to chemicals.

Hazard Identification

Hazard Identification Hazard characterization Exposure assessment Risk characterization

Is there a problem? How do you know?

Hazard identification

Purpose

• To evaluate the weight of evidence for adverse

health effects, based on assessment of all available data on toxicity and mode of action. Designed to primarily address two questions:

• 1) Nature of any health hazard to humans that an

agent may pose and

• 2) Circumstances under which an identified

hazard may be expressed.

Hazard identification is based on analyses of a variety of data

• Toxicological studies
• 1) in vitro studies, using cultured organisms or

cells or tissue preparations from laboratory animals or humans; - reduced, refined or replaced But No Guidance value

• 2) in vivo studies in laboratory animals or

humans.

• OECD Guideline
• Data generated -GLP

HAZARD IDENTIFICATION

Animal Studies

• Mouse
• Rat
• Rabbit
• Guineapigs

DATA ON TOXICITY

• Acute Toxicity Studies
• Short term toxicity Studies
• Metabolism in Animals (Pharmacodynamics

and toxicokinetics)

• Genotoxicity
• Immunotoxicity

DATA ON TOXICITY(cont)

• Carcinogenicity
• Effect on reproduction
• Developmental Toxicity
• Neurotoxicity
• Information on Effect on Human being

• The extent of toxicological testing required

depends on the nature and use of the substance under consideration.

• Not all of the tests necessarily in order to reach a

conclusion on the risk assessment for a particular substance.

• Tiered testing approaches are used in which

screening tests or a limited number of standard toxicity studies are conducted, which may be sufficient for risk assessment or may trigger necessary further investigations.

Interpretation of findings

• Critical evaluation of study designs and their

findings and interpretation of the results are the most important steps in risk assessment

• Assessment of many toxicological end-points,
• Weight of evidence approach
• Evidence of dose–response relationships
• An overall assessment of the available data

Dose–response assessment

• Dose–response assessment is a major part of

the hazard characterization within the risk assessment paradigm.

• Dose–response assessment is used to develop

risk assessment advice and to derive health- based guidance values.

Dose–response modelling have six basic steps.

• Data selection,
• Model selection,
• Statistical linkage
• Parameter estimation
• Implementation
• Evaluation of the results of the analysis.

DERIVATION OF POD

• NOAEL
• LOAEL
• BMDL

Dose-response Assessment and Endpoint Selection : Definitions

Endpoint : Toxic Effect upon which the risk assessment is based Lowest Observed Adverse Effect Level (LOAEL): Lowest dose from a study at which adverse toxic effects were observed No Observed Adverse Effects Level (NOAEL): The dose below the LOAEL at which no adverse toxic effects are observed Point of Departure (POD): Any dose level used to quantify risk (generic)

NOAEL / LOAEL Dose Spacing

NOAEL / LOAEL dose spacing usually ranges between 2X and 10X. True NOAEL will be somewhere between the NOAEL and LOAEL Will always lead to a conservative (protective) hazard estimate

Dose-response Assessment and Endpoint Selection Endpoints selected for risk assessment must be the most sensitive endpoint for each population, and relevant to humans. Most sensitive (protective)  Most protective POD Relevant Toxicity seen in animal studies could also occur in humans

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Table A.2.2 . Subchronic, Chronic and Other Toxicity Profile Guideline No. Study Type MRID No. (year)/ Classification /Doses Results 870.3050 28-Day Oral (rat)

ppm: 0 – 20 – 50 – 200 – 2000 – 20000 mg/kg/day: M: 0 – 1.53 – 3.88 – 15.1 – 152 – 1575 F: 0 – 1.63 – 4.17 – 16.1 – 156 – 1605 NOAEL (M/F) = 15.1 / 16.1 mg/kg/day LOAEL (M/F) = 152 /156 mg/kg/day based on: liver: ↑(m/f)– periportal fatty change, ↑wt [abs/rel (m/f)] ↓(f)– ALP ↑(f)– GPT

870.3050 28-Day Oral (mice)

ppm: 0 – 20 – 200 – 2000 – 20000 mg/kg/day: M: 0 – 2.73 – 26.9 – 265 – 2678 F: 0 – 2.88 – 30.0 – 299 – 3024 NOAEL (M/F) = 26.9 / 30.0 mg/kg/day LOAEL (M/F) = 265 / 299 mg/kg/day based on: liver: ↑(m/f)– hypertrophy (centrilobular hepatocytes);↑(m)– [dark-colored + fatty change (centrilobular hepatocytes)]

870.3050 28-Day Oral (dog)

ppm: 0 – 40 – 400 – 4,000 – 40,000 mg/kg/day: M: 0 – 1.12 – 10.7 – 101 – 1111 F: 0 – 1.10 – 12.0 – 120 – 1180 NOAEL (M/F) = 10.7 / 12.0 mg/kg/day LOAEL (M/F) = 101 / 120 mg/kg/day based on: ↑(m/f)– ALP

Guidance Value for Contaminants

• Tolerable Daily Intake (TDI)
• Provisional maximum tolerable daily intake (PMTDI)
• Provisional tolerable weekly intake (PTWI)
• Provisional tolerable monthly intake (PTMI).
• “Provisional” expresses the tentative nature of the evaluation,

when there is a paucity of reliable data on the consequences of human exposure at levels approaching those with which JECFA is concerned.

• PMTDIs are established for food contaminants that are known not

to accumulate in the body.

• For contaminants that may accumulate within the body over a

period of time, JECFA has used the PTWI and PTMI.

TDI = Point of Departure (e.g.,NOAEL) Uncertainty Factors

Tolerable Daily Intake (TDI)

Deriving health-based guidance value(TDI)

• Selection of the appropriate data and

determination of the NOAEL

• Divide by “Safety factor” or “Uncertainty

Factor”

• Safety factor-Usually 100
• But recently it is variable with the concept of

Chemical Specific Adjustment Factor(CASF)

KINETICS DYNAMICS KINETICS DYNAMICS

SPECIES DIFFERENCES HUMAN VARIABILITY

The use of uncertainty or safety factors

Uncertainty or safety factors are used to extrapolate from a group of test animals to an average human and from average humans to potentially sensitive sub-populations. Up to an additional 10x to protect children

10 10

Hazard identification Hazard characterization Exposure assessment Risk characterization

Hazard characterization

What will happen if you eat the food with the contaminant

Dietary exposure assessment of chemicals in food

• Food consumption data are combined with

data on the

• concentration of chemicals in food
• Food consumption X Concentration of the

chemical in the food

• Result is compared with the Guidance value

Risk Assessment of Contaminants present in low concentration in Food

• Flavouring substances,
• Processing aids,
• Extraction solvents and enzymes used in food

production

• Substances leaching from packaging material

One such approach is the threshold of toxicological concern (TTC) concept.

Exposure assessment of food Contaminants

May be described more narrowly as “The qualitative and/or quantitative evaluation of the likely intake of chemical agents via food as well as exposure from

• ther sources if relevant” (FAO/WHO,

2008).

Dietary exposure assessment of Contaminants

• Occurrence of the contaminant in the diet
• Concentrations of the contaminant in the diet,
• Consumption patterns of the foods containing the

contaminant

• Likelihood of consumers eating large amounts of the

foods in question (high consumers)

• Contaminant being present in these foods at high

levels.

• Usually a range of intake or exposure estimates

provides (e.g. for average consumers and for high consumers),

Risk characterization

• Fourth step of the risk assessment process,

integrating information from the hazard characterization and exposure assessment to produce scientific advice for Risk Managers.

• Legal standard(Maximum Level-ML) prescribed
• A small or occasional dietary exposure in excess
• f ML based on a subchronic or chronic study

does not necessarily imply that adverse health effects will occur in humans.

• Built in Uncertainty factor/variable

Setting of health-based guidance values

• The setting of health-based guidance values

provides quantitative information from risk assessment for risk managers, enabling them to make decisions concerning the protection

• f human health.

What Risk Characterization provides

• Estimation of the potential risk to

human health under different exposure scenarios.

• Describe the nature, relevance and

magnitude of any risks to human health

Information and Advice to Risk Managers

• Quantitative information
• Qualitative information

Qualitative information

❖Statements or evidence that the chemical is

• f no toxicological concern owing to the

absence of toxicity even at high exposure levels; ❖Statements or evidence that the chemical is safe in the context of specified uses ❖Recommendations to avoid, minimize or reduce exposure.

Quantitative information

❖A comparison of dietary exposures with health-based guidance values; ❖ Estimates of risks at different levels of dietary exposure; ❖Risks at minimum and maximum dietary intakes ❖Margins of exposure

Risk Management

 Distinct from risk assessment,  Weighs policy alternatives, in consultation with all interested parties,  Consideris risk assessment and other factors relevant for the health protection of consumers and for the promotion of fair trade practices  If needed, selecting appropriate prevention and control options

Risk Communication

Interactive exchange of information and

• pinions throughout the risk analysis process

concerning risk, risk-related factors and risk perceptions, among risk assessors, risk managers, consumers, industry, the academic community and other interested parties, including the explanation of risk assessment findings and the basis of risk management decisions.

CONCLUSION

• Challenges for Risk Assessment (Availability of

trained experienced personnel)

• Challenges for Risk Management
• Challenges for Risk Communication
• Challenges for Enforcement (Representative

sampling /availability reliable analytical method)

• Challenge for applied food research

1.3 billion tonnes of food is lost or wasted each year

Cut down food waste today & every day

Thank you for your kind attention

• Dr. Debrabata Kanungo

kanungo294@gmail.com