Terms and Definitions for ENSC 201 Test #1 (Lectures 1-6 inclusive)

NOTE: For the steps to performing an ERA (environmental risk assessment) there were "extra" steps in the slides not mentioned in the original outline given in an earlier slide. I have designated these "extra" steps by adding a " .5" to the preceding original step if I put them on a separate flashcard

Toxicology

Toxicology

The study of the ways poisons interact with biological systems

Toxicant

A substance that will cause a harmful effect when administered to a living organism

Toxin

A toxicant produced by a living organism (or by a biological process)

Receptor

The organism or system affected

Hazard

The ability of a chemical to produce toxicity in the receptor (harm, adverse response)

Exposure

Pathway for substance to be transferred to a receptor (frequency, duration, route)

Risk

The probability that the hazard will occur under defined conditions (incl. exposure)

Mathematical model (of risk, hazard, and exposure)

Risk = Hazard x Exposure

Ecotoxicology/Environmental toxicology

The branch of toxicology concerned with the study of toxic effects, caused by natural or synthetic pollutants, to the constituents of ecosystems, animal (including human), vegetable and microbial, in an integral context

Roots of environmental toxicology

Roots founded in environmental and resource management, “classical” toxicology (human)

5 major differences between classical and environmental/ecological toxicology

1. Objective

2. Experimental options

3. Nature of concern

4. Dose

5. Test methods

Objective of classical vs environmental/ecological toxicology

Classical: Protection of humans (1 species plus a few surrogates)

Environmental/ecological: Protection of many diverse species (about 35,000,000) and ecosystem structure and function

Experimental options of classical vs environmental/ecological toxicology

Classical: Investigations limited to human surrogates (mice, rats, guinea pigs, monkeys etc),

Environmental/ecological: Organisms, model ecosystems, and real ecosystems can be subjected to direct experimentation

Nature of concern for classical vs environmental/ecological toxicology

Classical: Focus on the individual and human

Environmental/ecological: Not all species of concern are known (may protect the most sensitive or “valued” species) – effects are managed at the level of populations, communities or ecosystems

Dose for classical vs environmental/ecological toxicology

Classical: Chemical exposure is measured directly by known routes of administration; control the dose taken by the individual

Environmental/ecological: Dose is unknown, estimated indirectly through concentrations in air, water, sediment, food, etc - focus is on controlling the environment

Test methods for classical vs environmental/ecological toxicology

Classical: Methods to assess exposure, toxicity, and risk are well-developed and standardized

Evironmental/ecological: Methods are relatively new, not consistently standardized, and often must be adapted to each new species or ecosystem tested

View on environmental toxicology in history

In general, industrial activity was considered integral to prosperity and pollution was tolerated

2 types of paradigm shift (end of WWII)

1. Dilution paradigm – “solution to pollution is dilution”

2. Boomerang paradigm- “what you throw away can

   come back to hurt you”

“Radium Girls”

Female factory workers who painted radium onto watch dials during early 1920s (US Radium Corporation); suffered “suspicious” deaths or illness due to radium poisoning

“Great Smog” of London, England (Dec. 1952)

Period of cold weather (lots of coal burning) and anticyclone weather event (inversion trapping air) resulting in smog

• 4000 deaths (100,000 illnesses)

• Leads to Clean Air Act – phase out of coal burning

Cause of “Modern Environmental Movement”

The publication of Rachel Carson’s “Silent Spring” in 1962

Result of “Modern Environmental Movement”

• Public, the scientific community and legislative

  bodies gained awareness of the potential for harm from chemical substances in the environment

• Formal scientific study of adverse environmental effects of chemicals begins

• Environmental activists had a role in these phenomena

Result of industry and government boom (1960s-80s)

• Exponential increase in the number of synthetic industrial chemicals

  • Agricultural chemicals

  • Industrial chemicals

  • Therapeutic drugs

• Increase in litigation

• Mandatory testing and regulation

Result of growth of environmental technology (1960s-80s)

• Analytical chemistry and monitoring technologies advanced

  • i.e gas chromatography with new detectors

• Monitoring shows sources, enables regulation

• Local or “point source” releases of pollutants mostly understood and regulated

• Diffuse pollution remains issue (long range transport

8 principles from Canadian Environmental Protection Act (CEPA) (1999)

1. Sustainable development

2. Pollution prevention

3. Virtual elimination

4. Ecosystem approach

5. Precautionary principle

6. Intergovernmental cooperation

7. Polluter-pays principle

8. Science-based decision making

Sustainable development (CEPA)

Development that meets the needs of the present without compromising the ability of future generations to meet their own needs

Virtual elimination (CEPA)

Reduction of releases to the environment of a substance to a level below which its release cannot be accurately measured

Precautionary principle (CEPA)

Where there are threats of serious or irreversible damage, lack of full scientific certainty shall not be used as a reason for postponing cost- effective measures to prevent environmental degradation

Science-/evidence-based decision making (CEPA)

Integral role of science and traditional aboriginal knowledge (where available) in decision-making and that social, economic and technical issues are to be considered in the risk management process

How toxic effects begin

Reaction between a chemical and some component of living tissue

Xenobiotic

Foreign to the body

Anthropogenic

Human-made

How toxicity is assessed

By toxicity tests (conducted in a laboratory) which expose groups of organisms to a range of doses/concentrations for a set period of time and record their responses

3 characteristics of toxicity tests

1. Controlled experiments

2. Rapid, relatively inexpensive

3. Often conducted with individual substances

Dose-/exposure-response relationship

The quantitative relationship between exposure and measure of damage to organism or groups of organisms

2 variables in dose-/exposure-response relationship

1. Dose

2. Response

2 assumptions of dose-response relationship

1. Response is due to the toxicant

2. Response is related to the amount of exposure (dose/concentration)

2 types of standardized test methods for dose-response relationships

1. Extrapolate from one species to another

   1. Similar to human toxicology; mice/rats are surrogate species to humans

2. Standard tests with select species

   1. E.g. Environment and Climate Change Canada

      biological test methods

4 toxicant routes of exposure

1. Inhalation

2. Ingestion

3. Dermal

4. Injection (into tissues or body fluid)

Inhalation

Toxicant inhaled into pulmonary system, lungs

Ingestion

Toxicant ingested into gastro-intestinal system, gut

Dermal

Toxicant interacts with surface of organism, skin
2 TYPES

2 types of toxins absorbed by dermal absorption

1. Lipophilic molecules (diffuse through the lipid-rich bilayer of the cell membrane)

   1. Large lipophilic molecules —> steric hindrance

2. Small uncharged polar molecules (diffuse through the cell membrane)

   1. CO2, glycerol and H2O —> Depends on chemical gradient; slow

Dose

Amount of toxicant taken up by organism (internal)

Concentration

Amount of toxicant in external media (e.g. water, soil, air)

Acute exposure

Short duration (< 96 h), often single dose

Chronic exposure

Longer duration, continuous exposure to toxicant

2 axes of toxicity tests graphs

1. Exposure (x axis)

2. Response (y axis)

2 ways data is collected for dose-response graph

1. Quantal response (All-or-none (e.g. death, cancer))

2. Graded response (Variable degree (e.g. heart rate, respiration))

Endpoint

Quantifiable response related to exposure

Nutrient

A substance that is needed for growth

Nutrient graph

Non-nutrient graph

NOEC (No Observed Effect Concentration)

• Highest concentration where no effects are observed

• Identical to control

LOEC (Lowest Observed Effect Concentration)

Lowest concentration that is significantly different from the control

Hormesis

A harmful substance gives stimulating/beneficial effects to living organisms in small quantities

LD50 (median lethal dose)

Toxicant dose that kills 50% of test population at time t

LC50 (median lethal concentration)

Toxicant concentration that kills 50% of test population at time t

ED50 (median effective dose)

Toxicant dose that caused a response in 50% of the population at time t

EC50 (median effective concentration)

Toxicant concentration that caused a response in 50% of the population at time t

How to express toxicological values (e.g LC50, EC50)

Need to include the duration of exposure time (t) with endpoint values (e.g. 96 h LC50 = 32 mg/L)

2 ways to plot toxicity data

1. Time-based plot

2. Dose/concentration-based plot

Time-based plot

One test concentration over time

• x-axis = time

• y-axis = response

Dose/concentration-based plot

Multiple concentrations at fixed time period

• x-axis = dose/concentration

• y-axis = response

How LC50 relates to toxicity

HIGHER LC50 = LESS toxic

4 reasons why toxicity testing is important

1. Standardized assessment of chemicals/effluents

2. Basis for monitoring effluent/environmental quality

3. Provides data for setting standards to limit environmental levels of contaminants

4. Responses can predict ecological response

Disadvantage of labratory-based testing

Toxicity testing under realistic conditions is much more complex than determining the effects of single substances on single species under controlled laboratory conditions

2 kinds of model ecosystems

1. Microcosms

2. Mesocosms (i.e experimental ponds)

Unique approach for environmental toxicology

Biological indicators and biological monitoring can be used

Indicator species

Species sensitive to some factor(s) of concern (e.g. acidity, air pollution)

• Change in distribution or density of indicator species

• Cannot always be quantitative but may show trends

Biochemical markers

The subcellular response of the living organisms is used to indicate the effect of a substance, departure from normal status

• Bioindicator examples: Heat shock protein (HSP), Cytochrome P450, Metallothionein

Mixture toxicity

Many contaminants are found in mixtures (i.e petroleum hydrocarbons, PCBS) so we must account for joint effects of contaminants in mixtures

4 types of joint effects in mixture toxicity

1. Potentiation

2. Additivity

3. Synergism

4. Antagonism

Potentiation

The activation of a contaminant that is normally non-toxic by itself

Additivity (2 kinds)

1. Concentration additivity- toxicants have same mode of action so effect is calculated as the sum

2. Response additivity– toxicants have different mode of action, but similar effects so not always predicted by summing the effects

Mode of action

Low-level cellular changes to function or anatomy due to the action of a toxicant on an organism

Synergism

The effect of the mixture is greater than the sum of each toxicant

Antagonism

The effect of the mixture is less than the sum of effects of each contaminant

Some challenges with animal testing

• Expensive

• # of substances

• Results not always transferable

• Ethics

3 R’s of Animal Use Alternatives

1. Replacement (e.g., cell lines, tissues, computer modeling)

2. Reduction

3. Refinement (modifications to procedures to reduce animal suffering)

Risk assessment

Process to estimate the probability of adverse effects following the use/release of a pollutant (retroactive and proactive)

Retroactive risk assessment

Assessment of risk of an existing contamination

Proactive risk assessment

Proactive process that deals with planned or proposed release of waste/effluent

2 components of risk assessments

1. Human health risk assessment

2. Ecological risk assessment (ERA)

4 steps of an ecological risk assessment (ERA)

1. Problem formulation

2. Exposure assessment

3. Hazard assessment

4. Risk characterization

Problem formulation (Step 1)

• Frame the project, including final goals and nature of potential adverse effects

• Formulate approaches and tools used to assess risk

• 5 key things to consider

5 key things to consider in problem formulation (Step 1)

1. Site-management goals (e.g., restoration for parkland use)

2. Regulatory context for the site

3. Review historical site information— look at site description, use, ecological or traditional significance

4. Determine fate of contaminants of concern (COC)

5. Clarify protection goals and associated acceptable effect levels

Site description (Step 1.5)

• Site size, contamination sources and fate

• Point-source vs non-point source

• Geography of site to determine the transport of COCs

• Concentrations of COCs and relevant guidelines/ background levels

• Wildlife survey and review (e.g., interviews, monitoring)

• Identify important species, such as keystone species, species at risk

• Build conceptual site model (CSM)

Exposure assessment (Step 2)

• Determine how organisms in the ecosystem will be exposed to contaminants (e.g in air, soil, sediment, food)

• Assess degree of exposure (total dose of contaminants for each receptor in the ecosystem)

• Use methods to estimate exposure doses (abiotic and biotic)

2 methods to estimate exposure doses (abiotic and biotic)

1. Direct – less uncertainty, many parameters cannot be estimated (soil pH), site-relevant information

2. Estimation using models – more variability, relies on information from other sites that may not be relevant

Hazard assessment (Step 3)

• Characterize expected effects due the exposure concentrations (previously determined)

• Determine toxicity reference value (direct vs indirect)

• Develop site-specific remediation objective (below the TRVs)

Toxicity reference value (TRV)

The dose/concentration expected to cause a unacceptable level of effect in the receptor (can be direct or indirect)

Types of studies used for toxicity reference values (TRVs)

1. Site-specific controlled study

2. Site-specific field study

3. Indirect field and control studies

4 pros of site-specific controlled studies

1. Directly test toxicity of media from a site by controlling variables (i.e temp and lighting)

2. Precise and specifically relevant to the site

3. Contaminant mixtures are directly addressed

4. Remedial goals may be determined with higher confidence

3 cons of site-specific controlled studies

1. Sample preparation may alter the media (affecting form and bioavailability)

2. If using a surrogate species, hard to determine accuracy of sensitivity prediction

3. Acute vs chronic study limitations

4 pros of site-specific field studies

1. Highest relevance to site

2. Takes into account spatial distribution and bioavailability of the COCs

3. Compliment lab studies

4. Reduce uncertainty and reliance of some assumptions (i.e predator-prey relationships, migration)

2 cons of site-specific field studies

1. Time and scale are limiting factors

2. Other factors such as competition can make it difficult to detect sublethal effects

2 pros of indirect field and control studies

1. Compiles data from pre-existing studies

2. Used to estimate TRVs for receptors at the site

4 cons of indirect field and control studies

1. Hard to find data for mixtures relevant to the site

2. Test species irrelevant to site

3. Abiotic factors not relevant to site

4. Degree of biotransformation / weather of contaminant differs from site

Use of Species-Sensitivity Distributions

TRVs can be used to create SSDs in order to determine acceptable effect levels (AEL)