CHIRAL ENVIRONMENTAL CONTAMINANTS
This section discusses the main groups of chiral pollutants that have been detected in the environment, namely pesticides, pharmaceuticals and illicit drugs, personal care products, and other chiral persistent organic pollutants (POPs). Discussions in this section are focused on the use, source, and physicochemical properties of the group of compounds. An overall emphasis will be given on the nature of chirality and its implications on the use.
Sources of Contaminants
The immeasurable sources of production, usage, and disposal of thousands of substances frequently used in medicine (human and veterinary), industry, agriculture, household, among others, led to the extensive occurrence of organic pollutants in the environment (Sousa et al„ 2018), including the chiral ones. Their release into the environment even at residual levels leads to their possible accumulation in the environmental compartments, which can originate potential harmful effects to ecosystems and to human health (Sousa et ah, 2018). Contaminants can be originated from (i) domestic/hospital wastew'ater effluents (the main pathway in the case of pharmaceuticals/estrogens); (ii) livestock and aquaculture; (iii) agriculture runoff; (iv) landfill leachates; and (v) industrial waste- water (Barbosa et ah, 2016). Figure 1.3 illustrates these sources of contamination that are common to chiral pollutants.
In this sense, their widespread occurrence in wastewater, surface and ground water, drinking water, sludge, soils, and air, as well as through the food web has led to a growing interest on the topic of chiral pollutants, and research on this subject has been increasing in the last two decades (Figure 1.4). Interestingly, approximately 65% of the papers retrieved from a Scopus search (up to May 29, 2020), using as keywords “chiral” and “pollutant” or “contaminant,” were published in the last decade.
The enantiomeric fraction (EF) is the most used monitoring tool to assess the fate of chiral substances and their metabolites in the environment. EF is defined as the proportion between the concentration of one enantiomer and the sum of the concentrations of both enantiomers (Ribeiro et al„ 2012c). An EF of 0.5 indicates that the composition is racemic, whereas an EF of 0 or 1 means that the compound is enantiomerically pure (Ribeiro et al., 2012c). In turn, a proportion of two enantiomers different than 1:1 gives an EF between 0 and 1 and different to 0.5, with an enrichment of one enantiomer. Tiritan et al. (2018) recently reviewed and discussed the many different notations that have been used to express the measured enantiomeric ratios and highlighted that
FIGURE 1.3 Sources of environmental chiral (and achiral) contaminants.
this issue is challenging for a proper data comparison. That critical review recommends the use of enantiomeric ratio (e.r. %) as obtained from the chromatograms (e.g., 80:20 (R.S), indicating 80% of (R)-enantiomer or conversely 20% of (S)-enantiomer, with enantiomeric enrichment of the (/?)- form). The authors concluded that EF is also suitable since it is obtained by an equivalent approach but using a normalized scale (Tiritan et al., 2018). Anyway, the elution order can always be used when the absolute configuration of the enantiomers is not known (Tiritan et ah, 2018).
The evaluation of EF variations in the environmental compartments allows a comprehensive understanding of the chemical transformations, the biotransformation, and the processes involved in the transfer between compartments, as well as the different ecotoxicological properties resulting from their enantioselective interaction with other natural chiral molecules (Ribeiro et ah, 2020). The knowledge obtained by enantioselective analysis is nowadays considered a valuable tool for
FIGURE 1.4 Evolution of the number of publications retrieved from Scopus search (May 29,2020), using as keywords “chiral" and “pollutant" or “contaminant.” epidemiological and forensic purposes; namely, to track sources of contamination, to detect illicit discharges, and to study the usage patterns (Ribeiro et al., 2018).
A number of groups of chiral compounds used as racemic mixtures or enantiomerically pure compounds can contaminate the environment, namely pesticides, pharmaceuticals and illicit or abuse drugs, polycyclic aromatic hydrocarbons (PAHs), among others.
Agricultural activities are one of the most relevant sources of pesticides due to their intensive usage to protect plants and improve crop yields (Sousa et al., 2018). In fact, pesticides represent a large group of substances belonging to several classes, namely herbicides, insecticides, and fungicides (Maia et al., 2017). Other groups of pesticides include insect repellents, nematicides, mollus- cicides, rodenticides, and also plant growth regulators (Maia et al., 2017). Besides the vast number of pesticides that are widely applied worldwide, these compounds can easily achieve other environmental compartments rather than soils, namely air, surface water, and groundwater (Maia et al., 2017). In fact, this broad group of compounds is the most studied of environmental pollutants concerning enantiomeric composition, with a number of reports showing their occurrence, distribution (Faller et al., 1991), biodegradation, and toxicity in many matrices including biota (Carlsson et al., 2014; Hiihnerfuss et al., 1993; Jantunen and Bidleman, 1996).
Most studies on chiral pesticides are focused on: (i) insecticides (including the banned organochlorine pesticides (OCPs) such as a-HCH, o,//-DDT (dichlorodiphenyltrichloroethane), chlordane and toxaphene congers, but also the synthetic pyrethroids), (ii) fungicides (triazole), and (iii) herbicides (diclofop-methyl, lactonfen fluazifop-butyl, fluroxypyr methylheptyl ester, fenaxaprop-ethyl, etc.) (Xu et al., 2018).
As an example, the enantiomers of some phenylpyrazole chiral insecticides (e.g., fipronil, ethiprole, and flufiprole) were very recently reported as stereoselective endocrine disruptors (Hu et al., 2020). One of these phenylpyrazole insecticides, fipronil, was studied regarding its genomic mechanisms responsible for the enantiotoxicity and the authors found that the anxiety-like behavior enantioselectively induced in embryonic and larval zebrafish was ascribed to DNA methylation changes (Qian et al., 2019). Another study focused on the potential endocrine-disrupting effects of the chiral triazole fungicide prothioconazole and its metabolite suggested that the stereoselective effects of both the parent fungicide and its metabolite were partially attributed to enantiospecific receptor binding affinities (Zhang et al., 2019). The possible enantioselective agonistic/antagonis- tic effects on corticosteroids receptors and the influence on the production of corticosteroids were also assessed for eight chiral herbicides (Shen et al., 2020). Although neither the racemates or the enantiomers of all the studied chiral herbicides exhibited agonistic activity to glucocorticoid or mineralocorticoid receptors at non-cytotoxic concentrations, antagonism was found for rac- propisochlor and (S)-imazamox and (R)-napropamide (Shen et al., 2020). Rac-propisochlor and rac-/(/?)-napropamide reduced the secretion of cortisol, while this glucocorticoid was induced by rac-diclofop-methyl and its two enantiomers. Exposure to rac-propisochlor, (S)-diclofop-methyl or rac-/(5)-/(/?)-acetochlor, and rac-/(5)-/(R)-lactofen inhibited the aldosterone production (Shen et al., 2020). This enantioselective disruption of corticosteroid homeostasis was suggested for chiral herbicides (Shen et al.. 2020).
Besides stereoselectivity in biodegradation pathways and ecotoxicity, chiral pesticides may enantioselectively bioaccumulate through the food web. This process can be followed by studying the chiral signatures, as reported by Zhou et al. (2018a). In that study evaluating the accumulation of the enantiomers in biota, it was shown that the majority of the target marine organisms had residues of non-racemic OCPs. The accumulation of pesticides through the food web was also demonstrated by the presence of banned pesticides in aquatic organisms, even many years after ban, which is ascribed to the persistence and lipophilic nature of many of them (Carlsson et al., 2014).
A very recent review collected information on another important phenomenon, which is the influence of local environmental conditions in the enantioselective behavior (Sanganyado et al., 2020). The authors highlighted that the possible interactions between the chiral pollutants and the external agents inducing homochirality is very complex and influenced by local environment conditions, including pH, redox conditions, humic acids, organic carbon, and organic nitrogen (Sanganyado et al., 2017). The pH and redox conditions of soils may affect the enantioselectivity degradation in this environmental compartment, as demonstrated for metalaxyl (Buerge et al., 2003). More recently, some reports have been published addressing other factors that may impact the enantioselectivity of pesticides. The EFs determined for the chiral o,p'- DDT. trans-chlordane, and cis-chlordane showed that these OCPs were mostly non-racemic in the soils (Zheng et al., 2020). The authors calculated the deviation of EFs from racemic and found that the deviations of cis-chlordane was highly correlated w'ith organic carbon and the carbon-nitrogen ratio, suggesting that the enantioselective biodegradation of chiral compounds in soils may be affected by those factors by interfering with the microbial activity (Zheng et al., 2020). Another recent study demonstrated the impact of coexistent metals in aquatic environments in the environmental risk of pyrethroids, which are chiral insecticides (Yang et al., 2017). The authors studied the influence of metals on the known enantioselective toxicity and biotransformation of this class of pesticides in zebrafish (Yang et al., 2017). In that study, the effects of cadmium, copper, and lead on the enantioselective toxicity and metabolism of cis-bifenthrin were explored and the authors suggested that the simultaneous exposure to metals might affect the stereoselective biodegradation of pyrethroids and originate a stereoselective accumulation of the active enantiomer, which results in higher toxicity of pyrethroids to exposed fish.
Based on the massive use of chiral pesticides and nanomaterials, a study on the effect of carbon nanotubes on the toxicity of indoxacarb as co-existing pollutant showed that multi-walled carbon nanotubes could affect its enantioselective toxicity in zebrafish (Wang et al., 2020). The authors found a superior expression of some genes in the livers of males and brains of females, meaning a higher toxicity, after exposure to (S)-indoxacarb in comparison to those zebrafish treated with (R)- indoxacarb. These studies open a new' research interest required to study the mechanisms underlying the effects of the interactions between achiral substances as metals or nanomaterials and the enantiomers in living organisms. Thus, these factors should be considered in future risk assessment exercises.