Further description:-  Toxicological information 

Glossary Entry
The degree to which a chemical, biological or physical agent elicits a deleterious or adverse effect 
upon the biological system of an organism exposed to the substance over a designated time period
Toxicological Information

Toxicological Information

 

Definitions

It is important to understand the toxic effects of chemical, biological or physical agents (“agents”) in order to determine the level of exposure that can be tolerated prior to deleterious or adverse effects occurring. When the toxic effects of such an agent are applied in the assessment of contaminated land, a number of key concepts must be considered:

 

Exposure

The term ‘exposure’ can be defined qualitatively or quantitatively.  Exposure is commonly (qualitatively) defined as:

 

“Contact made between the agent and the outer boundary of an organism” (adapted from http://www.epa.gov/iris/gloss8.htm#e.)

 

Exposure is generally quantified as the amount, or concentration, of the agent in soil, water or air available for uptake and/or intake by an organism.

 

Intake versus Uptake

Intake describes the entry of an agent into an organism (e.g. via ingestion).  Uptake is used to describe the absorption of the agent into the circulatory system of an organism (e.g. absorption of an agent through human skin into the blood).  Both intake and uptake are quantified in terms of a dose, as a mass (of an agent) per body weight per period of time.

 

Local Effects versus Systemic Effects

Some agents have an adverse effect in or at a localised part of the organism, for example an acid coming into contact with human skin.

 

Other agents have an adverse effect on a part of the organism distant from the point of entry, following absorption and distribution of the agent within the organism.  For example, the liver within a human body may be most susceptible to the effects of an agent that has been absorbed into the blood stream, in comparison to the other organs.

 

The majority of agents cause systemic effects, but some agents can cause both a local and a systemic effect.

 

Acute versus Chronic

The toxicological effects of an agent are dependent on the time of exposure.  Some agents elicit a deleterious or adverse effect on an organism over a short period of time – an acute effect – whilst other agents elicit an adverse effect over a longer period of time – a chronic effect.  An acute effect occurs over a period of seconds, days or weeks.  Chronic exposure usually relates to a period of time in the order of magnitude of a year or more, with adverse effects often delayed and/or long-lasting.

 

Threshold versus Non-threshold

Agents can also be split into two groups in terms of the type of toxicological response they generate in an organism:

 

(a)            Threshold Agents

Agents are defined as “threshold agents” when there is a dose below which there is no measurable effect in the organism.  For example, the hydrocarbon ethylbenzene is a threshold agent.

 

(b)            Non-Threshold Agents

Agents are defined as “non-threshold agents” when there is not a dose below which there is no measurable effect in the organism.  Any exposure to such an agent, such as genotoxic or mutagenic carinogens, may generate an adverse response in the organism. 

 

Mutagenicity and Genotoxicity

·                   Mutagenicity refers to the induction of permanent transmissible changes in the amount or structure of genetic material of cells or organisms. These changes, "mutations", may involve a single gene or gene segment, a block of genes, or whole chromosomes.

 

·                   Genotoxicity is a broader term and refers to potentially harmful effects on genetic material, which may be mediated directly or indirectly, and which are not necessarily associated with mutagenicity.

 

Specifically, a mutagenic or genotoxic event is accepted as a critical stage in the initiation phase of carcinogenesis.  (Definitions from ETAD, the Ecological and Toxicological Association of Dyes and Organic Pigments Manufacturers, www.etad.com).

 

Quantification of the Toxicity of an Agent

 

The toxicological effect of an agent on an organism is quantified in terms of a tolerable or acceptable daily intake (or uptake).  Such quantification conventionally relies on studies into the effect of an agent on animals (e.g. rats), but preferably uses data directly applicable to the target population (e.g. epidemiological studies of human populations).  The results of the animal studies commonly involve the extrapolation of the data for use in estimating the toxicological effect of an agent on a different organism population.  The end result aims to define a No Observed Adverse Effect Level (NOAEL), in terms of daily intake of an agent per body weight of the organism.  The World Health Organisation defines NOAEL as:

 

“The greatest concentration or amount of a substance [agent], found in experiment or observation, which causes no detectable adverse effects on the target organism under defined conditions of exposure.”

 

In order for this data to be used in the risk assessment process, an acceptable (or tolerable) daily dose must be derived, usually by the application of safety or uncertainty factors to the NOAEL.  In some cases, the data are used to define an acceptable (or tolerable) concentration of an agent in a particular media (soil, water air), with inbuilt assumptions as to the level of exposure by the target organism population.

 

Use of Toxicological Information in Risk Assessment

 

There are a number of approaches employed by risk assessment models to calculate risk levels.  These approaches are discussed below, using the most common nomenclature for each approach (adapted from Arcadis GMI, 2003).

 

Carcinogenic Slope Factor (CSF) – non-threshold agents

The predicted lifetime averaged daily dose is multiplied by a CSF (1/(mgcontaminant/kgbody weight.day) ) to calculate the individual excess lifetime cancer risk (IELCR).

 

Reference Dose (RfD) – threshold and non-threshold agents

The predicted daily dose is divided by an RfD (mgcontaminant/kgbody weight.day) to calculate a risk index (RI).  This calculation of risk levels is predominantly used for threshold agents.  However for non-threshold agents, an RfD is presented instead of a CSF, whereby the acceptable lifetime excess cancer risk is included in the derivation of the RfD.  The predicted (most commonly lifetime averaged) daily dose is divided by the RfD to calculate an RI, as for threshold agents. 

 

Unit Risk Factor (URF) – non-threshold agents

For inhalation exposure pathways within some risk assessment models, a dose is not calculated.  Instead, the receptor point concentration – the predicted air concentration– is multiplied by a URF (1/(mgcontaminant/m3air) ), providing an IELCR as for the slope factor approach.

 

Tolerable Concentration in Air (TCA) – threshold agents

As for inhalation exposure to a non-threshold agent, a dose is not calculated.  Instead, the receptor point concentration – the predicted air concentration– is divided by a TCA (mgcontaminant/m3air), providing an RI as for the reference dose approach. 

 

The table below summarises the toxicological approach for a number of risk assessment models, which are designed to produce risk levels as an output:

 

 

System

Toxicological Approach

Non-Threshold Agents

Threshold Agents

RfD

CLEA

Risc-Human

Vlier-Humaan

UMS

CLEA

RBCA

RISC

Risc-Human

ROME

UMS

Vlier-Humaan

CSF

RBCA

RISC

ROME

 

TCA

Risc-Human

Vlier-Humaan

RBCA

Risc-Human

Vlier-Humaan

URF

RBCA

 

 

It should be noted that a number of different terms are used for the above approaches within the different systems e.g. CLEA defines an “Index Dose” for Non-Threshold agents and a “Tolerable Daily Intake” for Threshold agents.

 

 

 

Authors
Katy Baker
Arcadis Geraghty and Miller International, Ltd, United Kingdom

Who does what?
Helen Hayward
Arcadis Geraghty and Miller International Ltd, United Kingdom

Who does what?