Can pharmaceutical drugs used to treat Covid-19 infection leads to human health risk? A hypothetical study to identify potential risk

Abstract

This is the first study to assess human health risks due to the exposure of 'repurposed' pharmaceutical drugs used to treat Covid-19 infection. The study used a six-step approach to determine health risk estimates. For this, consumption of pharmaceuticals under normal circumstances and in Covid-19 infection was compiled to calculate the predicted environmental concentrations (PECs) in river water and in fishes. Risk estimates of pharmaceutical drugs were evaluated for adults as they are most affected by Covid-19 pandemic. Acceptable daily intakes (ADIs) are estimated using the no-observed-adverse-effect-level (NOAEL) or no observable effect level (NOEL) values in rats. The estimated ADI values are then used to calculate predicted no-effect concentrations (PNECs) for three different exposure routes (i) through the accidental ingestion of contaminated surface water during recreational activities only, (ii) through fish consumption only, and (iii) through combined accidental ingestion of contaminated surface water during recreational activities and fish consumption. Higher risk values (hazard quotient, HQ: 337.68, maximum; 11.83, minimum) were obtained for the combined ingestion of contaminated water during recreational activities and fish consumption exposure under the assumptions used in this study indicating possible effects to human health. Amongst the pharmaceutical drugs, ritonavir emerged as main drug, and is expected to pose adverse effects on r human health through fish consumption. Mixture toxicity analysis showed major risk effects of exposure of pharmaceutical drugs (interaction-based hazard index, HI_int: from 295.42 (for lopinavir + ritonavir) to 1.20 for chloroquine + rapamycin) demonstrating possible risks due to the co-existence of pharmaceutical in water. The presence of background contaminants in contaminated water does not show any influence on the observed risk estimates as indicated by low HQ_add values (<1). Regular monitoring of pharmaceutical drugs in aquatic environment needs to be carried out to reduce the adverse effects of pharmaceutical drugs on human health.

Keywords: Covid-19; Novel coronavirus; PECs; Pharmaceuticals; Risk estimation; Rivers.

Graphical abstract

Fig. 1

Schematic representation of methodology adopted to determine human health risk exposure though accidental ingestion of surface water, fish consumption, and both the routes. PEC is the predicted environmental concentration of drugs; PNEC is the predicted no-effect concentration of drugs; HQ is the hazard quotient.

Fig. 2

Flow chart of the methodology used to determine risk estimates. PEC_{river_NDD} is PEC in river (surface water) under normal drug dose; PEC_{river_Covid-19} is the PEC in river for drug dose used to treated Covid-19 infection; PNEC_RA is the predicted no effect concentration due to the accidental ingestion of contaminated surface water during recreational activities; PNEC_fish is the predicted no effect concentration due to fish consumption exposure; PNEC_RA+fish is the combined predicted no effect concentration due to the accidental ingestion of contaminated surface water during recreational activities and fish consumption exposure. HQ_RA is the hazard quotient exposure to the accidental ingestion of contaminated water during recreational activities; HQ_fish is hazard quotient during fish consumption exposure; HQ_RA+fish is the hazard quotient during combined exposure to the accidental ingestion of contaminated water during recreational activities and fish consumption.

Fig. 3

Sensitivity index analysis of HQ variables of pharmaceutical drugs for three different exposure routes.