Ecotoxic pharmaceuticals, personal care products, and other emerging contaminants: A review of environmental, receptor-mediated, developmental, and epigenetic toxicity with discussion of proposed toxicity to humans

ABSTRACT Pharmaceuticals and personal care products (PPCPs), other emerging contaminants (ECs), and metabolites thereof are ubiquitous in the environment, both built and natural. While such compounds have been environmentally present for some time, new pharmaceuticals and replacements for other ECs phased out due to regulatory limitations are continually being introduced to market. Non-target lower organisms are exposed through affected water, atmospheric emissions, precipitation, sediments, among other routes. Biological disruption/dysfunction (such as endocrine, developmental, and epigenetic disruption) has been reported in lower organisms exposed to trace levels of PPCPs and other ECs. Such disruption/dysfunction may not be exclusively present as traditional toxic response (e.g., cancer or death) but may only slightly alter natural biological processes as a result of exposure to an exogenous chemical (e.g., an increased heart rate or altered size of dorsal fat pads in fish). The epigenome and endocrine system appear to be relatively sensitive to many PPCPs/ECs, particularly during early development. Humans are exposed to ECs such as plasticizers and perfluorinated compounds (PFCs) mainly through ingestion (food and contaminated liquid) as well as interaction with day-to-day products (detergents, musk compounds in fragrances, etc.). Few, if any, studies have investigated trace-level toxicity of such ECs to humans as direct-exposure trials are highly unethical. However, numerous epidemiological links exist between the presence of contaminants in humans (blood, urine, and tissues) and the occurrence of diseases or other phenotypic alterations. Despite mounting interest and research, such trace-level effects on humans are greatly debated and often criticized. This paper reviews the current understanding of PPCP/EC toxicity. Discussion of general biological disruption/dysfunction of the following seven classes of PPCP/ECs is included: analgesics, antibiotics, antineoplastic compounds, beta-blockers, endocrine disrupting compounds, PFCs, and plasticizers. A review of receptor-mediated toxicity, non-monotonic dose response relationships, developmental toxicity, and environmental epigenetics is also included. Lastly, an overview of the proposed toxicity to humans is provided including discussion of significant criticism and direction of future research.