Human health risk assessment from the presence of human pharmaceuticals in the aquatic environment

Abstract

Assessments for potential impact to human health from environmental exposures were carried out for 44 active pharmaceutical ingredients (APIs) marketed by GlaxoSmithKline (GSK), representing approximately 22 general pharmacological classes exhibiting a broad spectrum of therapeutic activities. These assessments use the considerable amount of information available on the human pharmacology and toxicology of the APIs to develop acceptable daily intakes (ADIs) which are believed to be without pharmacological or toxicological effect. With the exception of the anti-cancer drugs and some antibiotics, the minimum dose producing the intended therapeutic effect was typically used as the point of departure for calculation of ADIs. The ADI values were used to generate predicted no effect concentrations from environmental exposure for human health (PNEC_HHs) from drinking water or fish consumption. These PNECs were compared to predicted environmental concentrations (PECs) calculated using the regional assessment models PhATE™ for North America and GREAT-ER for Europe. Risk was characterized by calculating the ratio of the 90th percentile PECs to the PNEC_HHs. For the APIs reported here, these ratios are less than one for all of the compounds, varying from 7 × 10⁻² to 6 × 10⁻¹¹, indicating that based upon currently available data, these compounds do not appear to pose an appreciable risk to human health from potential environmental exposure from drinking water and fish consumption.

Introduction

Pharmaceutical products are designed to cure and treat disease, improve health, and increase life span. However, associated with use of pharmaceuticals is a potential for either the active pharmaceutical ingredients (APIs) or their metabolites to enter the aquatic environment through patient use or disposal. Some of these APIs or their metabolites are not completely removed in wastewater treatment systems, and therefore could persist long enough to enter drinking water systems. Human exposure could then occur from consumption of water or by consumption of aquatic organisms such as fish which have accumulated pharmaceutical residues.

As a result of improvements in analytical techniques, trace quantities of APIs and/or metabolites of APIs have been reported in wastewater treatment plant effluents, surface waters, drinking water, and groundwater (Halling-Sorensen et al., 1998, Ternes, 2001, Heberer, 2002, Heberer et al., 2002, Kolpin et al., 2002, Versteeg et al., 2005). Only a few reports address the potential effects to human health from the presence of trace levels of APIs in the environment (Christensen, 1998, Schulman et al., 2002, Webb et al., 2003, Jones et al., 2004; Schwab et al., 2005). These report no significant anticipated impact to human health from indirect environmental exposures from the low levels found in environmental samples. No studies showing any adverse effects for human pharmaceuticals from drinking water or fish consumption have been reported to date.

Many pharmaceutical companies are actively investigating the potential effects of trace levels of APIs in surface waters on human health and the environment. This paper evaluates the potential for trace levels of APIs in selected GlaxoSmithKline (GSK) marketed products in surface waters in North America and Europe to affect human health, as represented by effects from exposure through drinking water and fish consumption. This work relies upon predicted concentrations derived using the PhATE™ model (Pharmaceutical Assessment and Transport Evaluation) (Anderson et al., 2004) for North America and the GREAT-ER (Geo-referenced Regional Exposure Assessment Tool for European Rivers) model for the EU (Feijtel et al., 1997). Using these models provides the advantage of evaluating the potential effect on human health associated with API concentrations below detection limits in surface waters. Where available, measured environmental concentrations (MECs) reported in the scientific literature may also be used in risk assessments. However, for the compounds considered here, there were insufficient MECs available for a meaningful analysis. In addition, it should be noted that some of the APIs under discussion (e.g., albuterol, amoxycillin, cimetidine, ranitidine, trimethoprim, etc.) although found in GSK products, are not proprietary, and therefore the source of these APIs in any environmental samples is likely to be of mixed corporate origins. However, the total quantities assumed to be discharged into the environment from patient use were obtained from IMS Health (IMS Health, 2006) and include products obtained by sale from all sources, including both prescription and OTC products, and proprietary and generic APIs.