Sorption, plant uptake and metabolism of benzodiazepines

Abstract

Reuse of treated wastewater for irrigation of crops is growing in arid and semi-arid regions, whilst increasing amounts of biosolids are being applied to fields to improve agricultural outputs. Due to incomplete removal in the wastewater treatment processes, pharmaceuticals present in treated wastewater and biosolids can contaminate soil systems. Benzodiazepines are a widely used class of pharmaceuticals that are released following wastewater treatment. Benzodiazepines are represented by a class of compounds with a range of physicochemical properties and this study was therefore designed to evaluate the influence of soil properties on the sorption behaviour and subsequent uptake of seven benzodiazepines (chlordiazepoxide, clonazepam, diazepam, flurazepam, oxazepam, temazepam and triazolam) in two plant species. The sorption and desorption behaviour of benzodiazepines was strongly influenced by soil type and hydrophobicity of the chemical. The partitioning behaviour of these chemicals in soil was a key controller of the uptake and accumulation of benzodiazepines by radish (Raphanus sativus) and silverbeet (Beta vulgaris). Benzodiazepines such as oxazepam that were neutral, had low sorption coefficients (K) or had pH-adjusted log octanol-water partition coefficients (log D, pH6.3) values close to 2 had the greatest extent of uptake. Conversely, benzodiazepines such as flurazepam that had an ionised functional groups and greater K values had comparatively limited accumulation in the selected plant species. Results also revealed active in-plant metabolism of benzodiazepines, potentially analogous to the known metabolic transformation pathway of benzodiazepines in humans. Along with this observed biological transformation of benzodiazepines in exposed plants, previously work has established the widespread presence of the plant signalling molecule γ-amino butyric acid (GABA), which is specifically modulated by benzodiazepines in humans. This highlights the need for further assessment of the potential for biological activity of benzodiazepines following their plant uptake.

Formation of biologically active benzodiazepine metabolites in Arabidopsis thaliana cell cultures and vegetable plants under hydroponic conditions

“…Our results were in agreement with recent findings in Carter et al (2018), in which they observed the formation of nordiazepam, temazepam and oxazepam in radish and silverbeet plants exposed to diazepam and chlordiazepoxide. They similarly showed nordiazepam to be the major metabolite with oxazepam and temazepam constituting a much smaller fraction at the end of 28 d cultivation in soil.…”

Insight into the distribution of pharmaceuticals in soil-water-plant systems

“…Therefore, BCFs calculated on the basis of pharmaceutical concentration in bulk soil are not comparable among the studies using different soils because of the varying affinities of pharmaceuticals to soils. For instance, soil-based BCFs of seven benzodiazepines in radish could vary by up to 86.0 times between two soils (Carter et al, 2018). The difference of soil-based BCFs between three soils for caffeine, carbamazepine, and lamotrigine in tomato or cucumber can up to 20.0, 7.8, and 245 times, respectively (Goldstein et al, 2014).…”

Untitled

“…Wu et al (2015) studied the fate of pharmaceuticals and personal care products added to soil irrigated with treated wastewater or biosolid-amended soil. Carter et al (2018) studied the sorption, plant uptake, and metabolism of benzodiazepines, a widely used class of pharmaceuticals that are recalcitrant to wastewater treatment. According to the authors, the mechanisms involved in pharmaceutical uptake and transport in plants are very complex.…”