Assignment Paper

Short Answer Questions

Quesfion 1: Distinguish between acute, sub-acute and chronic toxicity tests. What may other types

of Toxicity tests be used to identify toxicological hazards°.

Acute toxicity is a syndrome of adverse effects caused by a substance that results from multiple or

single exposures. The adverse effects in acute toxicity occur 14 days after the exposure to a specific class of danger. Acute toxicity entails the registration of body weight, autopsy, and mortality with the weight of the organ.
Sub-acute toxicity is defined as the adverse effects that arise as a result of continuous or multiple

exposures between 24 hours. Sub-acute toxicity is the administration of toxic elements from 1 -28 days with

mortality registration. The body weight in this toxicity is higher than in acute toxicity.

Chronic toxicity involves the administration of toxic elements from a period of one day to up to six months. This is the toxicity with the highest the mortality and body weight registration (Shaw, 1998). Additional types of toxicity tests that may be utilized to identify toxicological hazards include
developmental toxicity, mutagenicity studies, reproduction smdies, and general metabolism studies.

Quesfion 2: Define the exposure route and exposure pathway. Provide examples of why the effects of a hazard may vary with eaposure route and between acutu and chronic exposure?

An exposure route is a channel followed by a substance that is hazardous to enter an organism after there has been an exposure through: ingestion, inhalation. and dermal ingestion. Meanwhile, an exposure pathway refers to a way in which a person comes into contact with a substance that is hazardous. There are examples of exposure pathways, which includes: ingestion, direct contact, and inhalation.
The various exposure routes have varying effects with inhalation having an adverse impact as

compared to the other two. The effects also vary with the extent of exposure that is acute and chronic (Davis, 1996). The effects of a hazard may be more adverse on chronic than acute exposure. An example is smoking substances compared to oral ingestion of a hazard. Smoking has high effects as compared to ingestion.
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Question 3: Descriiie the common ways of characterizing the dose-response relationships. Describe the differerice betweeri the threshold and non-threshold approve

Classification of substances as either toxic or beneficial is multifactorial and involves a complex relationship between organism and substance that is often dependent of several variables. Therefore, utilisation of a dose-response relationship is instead recommended to calculate exposure risk. The dose-
response relationship is often observed at the individual level, observing the specific organisms’ response

to a hazardous substance at an increasing doses, or at a population level, examining the dispersal of reactions

to different doses in a population of individual beings.

The dose-response relationship can be further characterized into either threshold approaches or non-threshold approaches. The former are used to desGribe agents that are non-carcinogenic utilising information from toxicity examinations and epidemiological studies to determine an innocuous threshold. Whilst threshold approaches are utilised for any potential cancer forming agents. and it is assumed that any
dose or concentration may cause toxicity. The threshold approach includes identification of the lethal dose

(LD;t = the maximum dose required to cause 50% mortality within the population), the maximum tolerated dose (the maximum dose that could be exposed to long term without causing harm), the no observed adverse effect level fNOAEL = the highest dosa in which no at effects are observed), and the lowest observed adver O L = the lowest dose administered to elicit an adverse outcome in a population of“ exposed indix iduals).
The rna in threshold index utilised is the reference dosa (Rfd), which is an estimate of the daily exposure to an agent assumed to be unharmful to a human throughout their lifetime, and is dependent on NOAEL and modifying factors (e.g. pharmocokinetics) among other variables. Whilst the non-threshold approach includes the cancer slope factor (CSF), which is the determined by the slope of the low dose region of the dose-response curva graph, which is considered linear. The CSF is the highest estimate of the

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most likely response to unit chemical exposure throughout a lifetime, therefore a higher CSF, the higher

the toxicity.

Quesfion 4: How do we determine if exposure to a hazard may cause an adverse health effect?

Control of risks from exposure to hazardous substances and chemicals requires scientific examination and ideally, quantitative and qualitative evidence of potential effects at given exposure levels (International Program on Chemical Safety [IPCS], 1999). As identified by the International Program on Chemical Safety (1999) and The World Health Organisation (WHO, 2008) identification of predictions of harm requires conducting an exposure assessment which is the process of predicting or calculating the degree, incidence and extent of exposure to a specific agent whilst also considering characteristics of the
population or individual exposed.

The IPCS (2004) has determines three main elements involved in exposure assessment; ‘scenario’. ‘model’ and ‘parameter’ (WHO, 2008). The ‘scenario’ involves utilisation of current knowledge and postulations to determine distinct situations in which probable experience of exposure risk may occur (WHO 2008). This includes sources of exposure such as eating certain types of fi›od or water, or likely situations in which one would come into contact with harmful pathogens. ‘Model’ refers to a risk assessment that utilizes an algorithm or mathematical processes to determine exposure risk, often in the
form of software (WHO, 2008). Whilst lastly parameter. refers to the input required for a model. which may be physical constants, calibmtion constants or additional inputs placed into a model that are variable overtime, space or among individuals or populations (WHO, 2008). Therefore, it is evident that identification of exposure risk is complex and variable depending on the situation, population and hazardous substance and requires a complicated assessment to determine potential risk.

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Quesfion 5: DeBne exposure and describe six (6) important elements to consider during

environmental exposure assessment.

According to the WHO (2008), exposure is defined as the interaction between an agent and a target,

in which interaction occurs on an exposure surface throughout a specific exposure period. Environmental exposure assessment includes six main components: l) hazard identification, 2) hazard characterisation, 3) exposure assessment, 4) risk ohamcterisation 5) risk management and 6) risk communication. These are
discussed further below (WHO, 2008).

The identification of hazard involves identifying the type and nature of the adverse effects that a substance has the potential to produce. Hazard characterisation involves qualitative and when possible, quantitative exploration of the hazardous agent. Exposure assessment involves assessment of the enormity and extent of the effeGt of exposure to humans or populations from the agent. Meanwhile, risk
characterisation involves the qualitative and quantitative identification of risks.

Risk management comprises the coordinated and economical application of resources to minimise, monitor and mitigate the probability of impactful or hazardous effects (WHO, 2008). Risk communication involves efforts made by stakeholders to communicate risks in an informative, cost-effective and secure manner. Subsequently risks can be removed. contained or managed. Containment may include landfills and drums and other contaminant mechanisms. Hazards undergo environmental transport and fate—the media through which the contaminants move after being released. The third element of hazard risk management is to consider exposure areas or points where people can come into contact with the medium that is contaminated. Subsequently there must be an exposure route, through which individuals physically contact
the hazard. The fifth element involved in hazard risk managerrient is controlling potentially exposed subsets

of’the population and providing guidance on how to best chamcterise this population (Yassi et al., 2001).

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References

Davis, B.K. & Klein, A.K. 1996, ‘Medium-specific ad multimediiim risk assessment’, in A.M. Fan & L.W. Chang (eds), Toxicolog and nsk assessment: principles, methods, and apphcations, MareelDekker, New York, pp. 282-287

Michael P. Holsapple, Kendall B. Wallace (2008). Dose response considemtions in risk assessment—An overview of reoent ILSI activities. Toxicology letters.

Shaw, I., & Chadwick, 1. (1998). Principles ofenvironmental toxicology. CRC Prass.

World Health Organisation (WHO). (2008). Uncertainty and data quality in exposure assessment, Harmonization Project Document No. 6. World Health Organisation, the International Labour Organization and the Unitad Nations Environment Programme. Retrieved from www.who.int/ipcs/pub1ications/rnethodsfharmonization/exposure assessment.pdf

Yassi, A. et al. 2001. Cost effectiveness and cost benefit analysis of interventions. In basic envimnmental health. Oxford university press, Oxford. Ppl72-179.