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Toxicology Demystified Toxicology Demystified Toxicology Demystified Toxicology Demystified –––– Understanding Safety & Understanding Safety & Understanding Safety & Understanding Safety &

Health Risks in the WorkplaceHealth Risks in the WorkplaceHealth Risks in the WorkplaceHealth Risks in the Workplace

KengKengKengKeng----Meng Khoo, PhD, LLM (Commercial Law),Meng Khoo, PhD, LLM (Commercial Law),Meng Khoo, PhD, LLM (Commercial Law),Meng Khoo, PhD, LLM (Commercial Law),

Regulatory Affairs Regional Director (Asia Pacific, Regulatory Affairs Regional Director (Asia Pacific, Regulatory Affairs Regional Director (Asia Pacific, Regulatory Affairs Regional Director (Asia Pacific, Africa, Middle East & Turkey)Africa, Middle East & Turkey)Africa, Middle East & Turkey)Africa, Middle East & Turkey)

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BoogeymanBoogeymanBoogeymanBoogeyman

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BoogeymanBoogeymanBoogeymanBoogeyman

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Boogeyman – an amorphous imaginary being used by adults to frighten children into behaving.

The monster has no specific appearance, and conceptions about it can vary drastically from household to household within the same community; in many cases, he has no set appearance in the mind of an adult or child, but is simply a non-specific embodiment of terror.

- Wikipedia

Goya's "Here Comes the Boogey-Man" (Aquí viene el Coco) c.1797

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Perception of safety risks (real or imaginary) can be very emotive!!!

Risk PerceptionRisk PerceptionRisk PerceptionRisk Perception

Risk perception by consumer/customer must not be underestimated!

� It does matter!

� Basis of media attention and political pressure, which both affect regulation!

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We have a B-2-B model -

BUT whether the customer is from retail or institutional, their perception matters!

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Child working in a lead battery recycling factory, Bangladesh(Still Pictures/Peter Arnold Inc)

This child will suffer from the effects of lead poi soning for a lifetime and will not be able to reach his intellectual pote ntial!

Boogeyman Revealed!

Why what is real and what is perceived matters!

Why even a basic understanding of safety and toxicology matters!

Why education and awareness matters!

Why I am here today!

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Power To Discover The Truth

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“It is not the truth that makes you free. It is your possession of the power to discover the truth. Our dilemma is that we do not know how to provide that power.”

Richard Lewontin(New York Review of Books, Jan 7, 1997)

Daily Encounters with ChemicalsDaily Encounters with ChemicalsDaily Encounters with ChemicalsDaily Encounters with Chemicals

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• We encounter chemicals almost every day

- Filling your car with petrol- Cleaning the bathroom or kitchen- Applying pesticides - Using cleaning products at work- Formulating in the lab

Chemicals can cause injury or illness if not handled properly!

Even water can kill under certain circumstances!!!

Hazard vs Risk?Hazard vs Risk?Hazard vs Risk?Hazard vs Risk?

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Hazard

Risk

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Key Words To Understand!

Risk =Hazard X Exposure

Dose / Response / Route

Individual Sensitivity

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Key Words To Understand!

We know the hazards of

crossing the highways!

Hazard = Intrinsic properties of a particular agent or situation

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Key Words To Understand!

- Young person judges the speed ofapproaching car and decides to run acrossthe street!

We routinely combine our knowledge of hazard, exposure and individual

susceptibility to judge the risk of harm!

- Old person waits for traffic light to change!

- Decision based on judgment about the riskof being hit by car!

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Key Words To Understand!

- Process is complex and often controversialbecause data may not be available or there isconflicting information!

- Process combines all known information about thehazards and determine the potential for harm !

- Risk/Safety assessment is not an ABSOLUTE anddepends on data available at the time and thesubject matter expert

Formal process of determining the potential of an agent/chemical/ingredient to cause

harm = risk/safety assessment

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Key Words To Understand!

• A standard and harmonized system to describe and cl assify against agreed limits, hazard properties with poten tial danger to man or the environment

• Constitutes the basis of safety labeling to warn th e user about potential hazards

• GHS is a hazard-based classification system

Reminder: HAZARD is different from RISK!

What is hazard classification?

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Key Words To Understand!

- Market for sunscreens in EU April 2001 –––– media attention andconsumer anxiety

- Article by Schlumpf et al (2001) suggesting several sunscre ens haveestrogenic activity (HAZARD!) from an in vitro test with cancer cellline and an in vivo rat uterotrophic assay

- Controversial interpretations of the results (RISK FOR HUM ANHEALTH!) caused consumer concerns

- In actual fact, the activity found in Schlumpf et al was very l owcompared to exposure with estrogenic substances in food(flavonoids) and current hormonal therapy (e.g. birth cont rol pill,morning after pill, post menopausal therapy)

Risk, Hazard & Risk Perception in Cosmetics

Paracelsus

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“All substances are poisons; there is none which is not a poison.

The right dose differentiates a poison from a remedy.”

Paracelsus (1493-1541)

Examples of Why Safety and Toxicology Examples of Why Safety and Toxicology Examples of Why Safety and Toxicology Examples of Why Safety and Toxicology MattersMattersMattersMatters

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Childhood Lead ExposureOrganic Mercury in Fish

From S. Gilbert’s Principles of Toxicology

Childhood Lead ExposureChildhood Lead ExposureChildhood Lead ExposureChildhood Lead Exposure

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Dioscorides, 2 nd BC

“Lead Makes the Mind Give Way”

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Blood Lead LevelsBlood Lead LevelsBlood Lead LevelsBlood Lead Levels

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40

30

25

20

1510

0

510

1520

25

30

3540

Blo

od L

ead

(ug/

dl)

CDC1973

CDC1975

CDC1985

WHO1986

EPA1986

CDC1990

Agency and Year

Acceptable Childhood Blood Lead Levels

The CDC set the blood lead level of concern for children at 10 micrograms per deciliter, but also states that adverse effects exist at all levels!

Organic Mercury in FishOrganic Mercury in FishOrganic Mercury in FishOrganic Mercury in Fish

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Discharge in Minamata Bay,Japan

Fetal Effects of MeHg

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Life-long effects!

Toxicity ranked by amount that causes Toxicity ranked by amount that causes Toxicity ranked by amount that causes Toxicity ranked by amount that causes death death death death

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Ethyl alcohol 10,000Salt (sodium chloride) 4,000Iron (Ferrous sulfate) 1,500Morphine 900Mothballs 500(paradichlorobenzene)

Aspirin 250DDT 250Cyanide 10Nicotine 1Tetrodotoxin (from fish) 0.01Dioxin (TCDD) 0.001Botulinum Toxin 0.00001

AgentAgentAgentAgent LDLDLDLD----50 (mg/kg)50 (mg/kg)50 (mg/kg)50 (mg/kg)

What is LD-50?

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Exposure & Absorption

1) Skin (dermal)2) Lung (inhalation)

3) Oral (gut)

Route of exposure

Frequency Of Exposure

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7 Beers in 1 Hour or7 Beers in 1 Week (1 Beer/Day)

Harmful effects of a chemical are often dependent on the frequency of exposure and the time between exposures!

1 or 7 Cups of Coffee in 1 Day

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Distribution

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Where A Chemical Goes

(body water, fat, bone)

Where A Chemical Accumulates

Metabolism

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How The Body Breaks The Chemical Down?

What The Chemical Turns Into?

How Fast?

Communicating Information

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• Product labels- Hazard, risk, directions for use, safety precautions

• Safety data sheets- Usually for use at work (occupational setting)- Available to public on request

• Other means- Package inserts- Internet

Communicating Information – Why Training on Chemical Safety/Risk?

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• Regulators and customers may want to have information about potential harms (right to know):- foreseeable use

- foreseeable misuse- accident situations

• Need to differentiate between hazard vs risk to avoi d:- confusion that the same chemical is more toxic tha n previously due to a change in hazard classification (GHS)- clarify that although chemical has intrinsic properties/toxicity, proper safety training on hand ling will minimize risk (exposure to chemical hazards)

Hazard Communication

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Examples of Chemical Hazards

Physical Hazards:- Flammable - Explosive- Reactive

Health Hazards:- Corrosive- Toxic

Hazards do not inform user of the risk – If handled in an unsafe manner, risk of exposure to hazards (intrinsic toxicity of chemicals) is high; if handled in a safe manner, risk is low although the intrinsic properties may be high!

Training on understanding risk/hazard and safe use is a value-add to customers!

Safe Handling and Use

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PPE (Personal Protection Equipment)

- Dust masks and respirators- Glasses, goggles, and face shields- Gloves- Foot protection- Aprons or full-body suits

Use PPE correctly and under the appropriate circumstances!

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Safe Handling and Use

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First Aid Instructions

- Eyes: Flush with water for 15 minutes- Skin: Wash with soap and water- Inhalation: Move to fresh air- Swallowing: Get emergency medical assistance

Sometimes accidents happen and users need to be awareof what to do under those circumstances!

Safe Handling and Use

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Spills and Leaks

- Evacuate the area- Notify a supervisor or the emergency response team

Sometimes accidents happen and users need to be awareof what to do under those circumstances!

Importance of Labels

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- Identity of the chemical- Name, address and emergency phone number of the manufacturer- Physical and health hazards- Special handling instructions- Basic PPE recommendations- First aid, fire response, spill cleanup

The label will not communicate the degree of risk!How safe is the use of the product? Depends on the nature of the hazards and potential

exposure (exposure minimal if safety precautions are taken)!

Value-add of such communication to customer!

Importance of MSDS

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- Chemical and manufacturer’s identity- Hazardous raw materials- Physical and chemical characteristics- Fire, explosion, and reactivity

- Health hazards- Routes of entry- Exposure levels (PEL or TLV)- Symptoms of exposure- First-Aid and emergency information

- Personal Protective Equipment (PPE)- Safe handling and storage- Spills and leaks- Compliance issues

Like label, does not communicate the degree of risk!

Hazard Communication Summary

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Train customers on:- Identify chemical hazards by reading labels and MSDSs- Follow warnings and instructions, or ask supervisor if in doubt- Use the correct personal protective equipment- Practice sensible, safe work habits- Learn emergency procedures

Label or MSDS does not communicate the degree of risk!

If asked how safe is the product?Answer would be if follow the proper precautions as above, the

safety risk can be minimized – every chemical will have its own intrinsic hazards and no chemical is 100% safe

Safe use depends on awareness of hazards and practicing sensible, safe work habits to minimize safety risk!

When to submit for safety assessment When to submit for safety assessment When to submit for safety assessment When to submit for safety assessment Formulation

� If formulation is leveraged from an EU/US product (e.g. MNC), can typically leverage on the safety assessment from those regions – no need to reinvent the wheel

� If a formulation is tweaked (e.g. introduction of a new ingredient)

� If the formulation is the same (leveraged from EU/US) but RM sources change due to cost-improvement projects (e.g. change to China ingredient supplier) – safety review of the RM

Is there any contaminants/traces/impurities of concern?

A single RM switch may not be a concern for a finished product but if there are multiple switches, there may be a concern for contaminants/traces/impurities

E.g. Heavy metal content in mined materials (talc)

Pesticide content in plant-based ingredients

BSE statement (certificate of origin) for animal-based ingredients (statements to confirm that a product is “free of TSE/BSE” are not scientifically possible)

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PostPostPostPost----marketing surveillancemarketing surveillancemarketing surveillancemarketing surveillance

�Once a product is cleared for use, it is Once a product is cleared for use, it is Once a product is cleared for use, it is Once a product is cleared for use, it is important to monitor adverse reactions important to monitor adverse reactions important to monitor adverse reactions important to monitor adverse reactions when it enters the market placewhen it enters the market placewhen it enters the market placewhen it enters the market place

� Continuous confirmation to give consumer Continuous confirmation to give consumer Continuous confirmation to give consumer Continuous confirmation to give consumer the level of safety reasonably expected the level of safety reasonably expected the level of safety reasonably expected the level of safety reasonably expected

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Power To Discover The Truth

“It is not the truth that makes you free. It is your possession of the power to discover the truth. Our dilemma is that we do not know how to provide that power.”

Richard Lewontin(New York Review of Books, Jan 7, 1997)

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