Risk assessment is a powerful tool for developing, implementing, evaluating, and amending chemical regulations. Regulations rely on accurate estimation of the risk posed by a chemical to humans or the environment. Risk assessment provides a formal framework for quantitatively assessing the effects of chemical exposure to a target species. Hence, risk assessment can be formally defined as a formal process for determining the probability that an adverse biological effect will occur following chemical exposure. This definition shows that risk assessment involves quantitatively assessing the effects of the chemical on humans or the environment (effect assessment) as well as assessing the degree of exposure (exposure assessment). Quantitative assessment of the exposure and effects of chemical contaminants is critical for providing evidence that can link chemical exposure to community and population level biological responses. By expressing contaminant risk quantitatively, it becomes easier for policy- and decision-makers to establish the extent of the pollution problem. Understanding the chemical pollution problem is essential for developing effective pollutant control and mitigation strategies as well as ecological restoration programs.

Challenges in Risk Assessment

Synthetic chemicals that are highly persistent (P), bioaccumulative (B), and toxic (T) have been recognized as high priority pollutants (Alonso et al., 2008; Pizzo et al., 2016). Highly persistent chemicals are difficult to regulate because their effects continue even after their environmental loading has stopped. As a result, the Stockholm Convention was established to provide recommendations and guidelines on priority persistent organic pollutants (Liu et al., 2016; Marvin et al., 2011; Raubenheimer and Mcllgorm, 2018). Synthetic chemicals with high hydrophobicity can enter the food chain by bioaccumulating in organisms (Gramatica and Papa, 2003; Nfon and Cousins, 2007; Walters et al., 2016). The amount of the contaminant that bioaccumulates in the organisms may increase with increase in trophic level. This process w'hereby the concentration of the contaminant increases from primary producers up to the apex predator is called biomagnification. When trophic biomagnification occurs, contaminants pose greater risk in organisms that are at higher trophic levels. In addition, acute oral, dermal, and inhalation toxicity tests on species such as Daphnia magna, fish, and rats is traditionally used to identify priority pollutants (Crane et al., 2006; Creton et al., 2010; Lammer et al., 2009).

The PBT model is recognized by most national and international chemical regulators as a powerful tool for hazard assessment of chemical contaminants (Lillicrap et al., 2016; Pizzo et al., 2016). For example, the European Chemical Agency (ECHA) maintains an inventory of chemicals undergoing a PBT or a “very persistent and very bioaccumulative” (vPvB) assessment under the Registration, Evaluation. Authorization, and Restriction of Chemicals program (European Medicines Agency, 2015). As of March 2020, the ECHA PBT assessment list contains 176 substances including pyrene, chlorpyrifos, chlorinated paraffins, and tamoxifen. Table 12.2 summarizes the criteria set by ECHA for evaluating PBT and vPvB compounds.

TABLE 12.2

A Summary of PBT and vPvB Criteria Recommended by the European Union (Adapted from ECHA, 2017)


PBT Criteria

vPvB Criteria



Persistent contaminants have a half-life of at least:

  • • 60 days in marine water.
  • • 40 days in freshwater or estuarine waters.
  • • 180 days in sediment.
  • • 120 days in freshwater or estuarine sediment.
  • • 120 days in soil.

Very persistent contaminants (vP) have a half-life of at least:

  • • 60 days in marine water, freshwater or estuarine waters.
  • • 180 days in marine water, freshwater or estuarine sediment.
  • • 180 days in soil.

Results and other information are obtained from:

  • • Ready biodegradability tests.
  • • Enhanced ready and inherent biodegradability tests.
  • In silico methods (e.g., QSAR biodegradation models).
  • • Field studies or monitoring studies.
  • • Simulation testing in soil, surface water, and sediment.


Bioaccumulative compounds have at least:

  • • A bioconcentration factor higher than 2000 in aquatic.
  • • Octanol-water partition coefficient. L°c ^ow ^

Very bioaccumulative compounds (vB) have at least:

• A bioconcentration factor higher than 2000 in aquatic.

Results and other information are obtained from:

  • • Octanol-water partitioning coefficient tests.
  • • Estimated by QSAR models.
  • • Bioaccumulation study.
  • • Human biomonitoring studies.
  • • Assessment of toxicokinetic behavior.


Toxic compounds have:

  • • A long-term EC 10 or no-observed effect concentration (NOEC) < 0.01 mg L 1 in aquatic species.
  • • A classification of 1A or IB carcinogen.”
  • • A classification of 1A or IB germ cell mutagen.”
  • • A classification of 1A. IB. and 2 reproductive toxicity.”
  • • A specific target organ toxicity after repeated exposure category of 1 or 2.b

Results and other information are obtained from:

  • • Short-term aquatic toxicity testing in aquatic species.
  • • Long-term toxicity testing in invertebrates and fish.
  • • Reproductive toxicity with birds.
  • • Growth inhibition study on aquatic plants.
  • • Chronic toxicity study on animals

3 Classification is according to REACH regulation EC No. 1272/2008. b Classification is according to REACH Regulation EC No. 1272/2008.

Recent Advances in Risk Assessment

A recent publication prepared by the European Food Safety Agency (EFSA) for members of the European Union provided critical guidelines for assessing the risk of chiral pesticides (Bura et al„ 2019). For example, the guidance document: (i) succinctly stated that enantiomers should be treated

TABLE 12.3

A Summary of the European Food Safety Agency Recommendations on Dietary and Environmental Risk Assessment of Chiral Active Substances and Metabolites (Bura et al., 2019)







  • • Non-enantioselective analysis is sufficient when the pesticide is marketed as racemic mixture while enantioselective analysis is required for active substances non- racemic pesticides.
  • • Quantification may be achieved using matrix-matched standards, although stable isotope labelled analogues are recommended.


• Enantioselective analysis in the environment and human body fluids using stable isotope labelled standards is recommended.




  • • Stereoisomers should be treated separately even those considered inactive, impurities, or transformation products.
  • • Racemization during storage, use, or in the environment should be considered.


  • • Enantiomers with varying environmental fate and toxicities should probably have separate risk quotients.
  • • Enantiomers are considered to have significantly different (eco)toxicological properties when they have (eco)toxicological endpoints that vary by a factor of three.



• Enantiomer specificity in mammalian absorption, distribution, metabolism, and excretion should be addressed.




  • • Changes in enantiomeric composition are not expected to influence genotoxicity hazard identification given that all the enantiomers in the residue are sufficiently represented in the test mixture.
  • • In general toxicity testing, changes in enantiomeric composition that do not exceed an enantiomeric excess of 10%. are not expected to influence the pesticide residue hazard and risk assessment.
  • • Read-across approach can be used to establish whether there are enantiomer specific differences in the toxicological profile and/or toxicological potency.

Food residues


  • • Establish the effect of storage conditions on the chiral stability of the pesticide residues in food.
  • • Determination of the enantiomeric composition of pesticide residues in food and agricultural produce is recommended.

Environmental fate and behavior


  • • Evaluate the enantiomeric composition of chiral pesticides in soils to which non-target species may be exposed.
  • • Assumed that leaching and adsorption in soil or sediments and environmental behavior in air were non-enantioselective.
  • • Preferential transformation and chiral inversion of racemic mixtures and single enantiomers should be investigated using aerobic mineralization or water/sediment studies.

as different compounds in risk assessments, as a general rule; (ii) recommended that manufacturers should consider the chirality of the compounds during pesticide development and approval; and (iii) provided guidelines for both dietary risk assessment and environmental risk assessment. Table 12.3 provides a summary of the recommendations of the guidance document.

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