RISK ASSESSMENT OF CHIRAL POLLUTANTS

Chemical risk assessment provides critical quantitative and qualitative data for determining environmental and human safety regarding chemical exposure (Hussain and Kegili, 2020). Risk assessment has to take into account whether exposing an organism to a specific chemical will result in adverse health effects. Moreover, the exposure to the hazardous chemical should be also considered. Therefore, in order to characterize risk, one must first establish the degree of exposure as well as the magnitude of the hazard. The processes of determining the degree of exposure and magnitude of hazard are called exposure and hazard assessment (i.e., hazard identification and hazard characterization), respectively. Hence, risk assessment comprises the highly interconnected stages of hazard evaluation, exposure assessment, and risk characterization (Benford. 2017). Chemical exposure occurs via multiple pathways such as inhalation, ingestion, and dermal contact. For example, humans can be exposed to chiral brominated flame retardants through dermal contact while using cosmetics, ingestion of contaminated milk, or inhalation of contaminated indoor dust. The type and degree of effects associated with exposure to a specific chemical are often dependent on the dose and length of exposure (Hussain and Kegili. 2020). However, the adverse effects are also influenced by the sex, age, weight, and life history of the target organism. Therefore, hazard assessment is not only related with the toxicological profile of the chemical, but also with the biological aspects of the target organism. Chiral pollutants complicate risk assessment due to possible enantioselectivity in toxicological and fate profiles. Table 1.3 shows the aims and tools used at various stages of risk assessment and the challenges posed by chirality at each stage.

TABLE 1.3

An Overview of the Steps Involved in Risk Assessment of Chiral Contaminants in Food and the Environment (Benford, 2017; Hussain and Kegili, 2020)

Risk Assessment Step

Aim

Tools

Implications of Chirality

Hazard identification

To determine the type and nature of biological response inherently caused by a contaminant to a biomolecule, cell, tissue, organ, organism, population, or community.

Short-term toxicity tests (e.g.. genotoxicity. mutagenicity, reproductive toxicity, immunotoxicity, and developmental toxicity) and quantitative structure-activity relationship models.

Three scenarios are possible for compounds with a single chiral element:

a. The enantiomers have equal potency.

b. One enantiomer is more potent.

c. Enantiomers target different toxicity pathways.

Hazard characterization

To qualitatively or quantitatively establish the inherent properties of a contaminant that have the potential to elicit adverse effects.

To establish interspecies variations in toxicodynamics and toxicokinetics.

Dose-response relationship in various species.

Three scenarios are possible for compounds with a single chiral element:

a. The enantiomers have similar dose-response curves.

b. The enantiomers have different dose-response curves in one species.

c. Interspecies differences in enantiomer toxicity.

Exposure assessment

To determine the occurrence of a chemical in food or in the environment through monitoring programs, total diet analyses, or targeted surveys.

Chemical analysis using various analytical tools such as gas chromatography, liquid chromatography, and capillary electrophoresis.

Enantiomeric composition is determined using enantioselective analysis, which can be a challenge. Four scenarios are possible:

a. Chiral contaminant occurs in the food or in the environment as racemic mixture.

b. Chiral contaminant occurs in the food or in the environment as a non-racemic mixture.

c. An enantiopure contaminant converts to its antipode (e.g., naproxen in the environment).

d. An enantiopure chemical is commercially available on the market.

TABLE 1.3 (Continued)

An Overview of the Steps Involved in Risk Assessment of Chiral Contaminants in Food and the Environment (Benford, 2017; Hussain and Kegili, 2020)

Risk Assessment Step

Aim

Tools

Implications of Chirality

Risk characterization

To quantitatively define the magnitude and nature of risk.

Health-based guidance value (e.g., acceptable daily intake and maximum acceptable concentration).

Uncertainties arising from the scenarios in hazard identification, hazard characterization, and exposure assessment are compounded into the risk characterization when stereochemistry is overlooked. Several scenarios are possible, but the main ones are:

a. The risk is accurate if the enantiomers have the same fate and toxicity (very unlikely).

b. The risk is overestimated when the most abundant enantiomer is the less toxic.

c. The risk is underestimated when the most abundant enantiomer is the most toxic.

The implications of chirality on each step of the risk assessment are included. The simplest scenario whereby a contaminant has one chiral element is considered.

Despite the increase in research interest on stereochemistry in the food and in the environment, enantioselectivity in distribution, fate, and toxicity is often overlooked when estimating the risk of chiral pollutants (Stanley and Brooks, 2009). Analytical determinations in the food or in the environment are usually performed considering enantiomers as a unique entity, and racemic mixtures are often used to determine the health effects of chiral compounds. However, ignoring the enantiospecific biological effects and fate of chiral pollutants introduces uncertainties in the risk assessment. Stanley and Brooks (2009) proposed treating enantiomers as additive mixtures when they have different potencies but as racemate when they have similar potencies.

 
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