Ecotoxicology of human pharmaceuticals.

For decades, studies of endocrine-disrupting chemicals (EDCs) have challenged traditional concepts in toxicology, in particular the dogma of “the dose makes the poison,” because EDCs can have effects at low doses that are not predicted by effects at higher doses. Here, we review two major concepts in EDC studies: low dose and nonmonotonicity. Low-dose effects were defined by the National Toxicology Program as those that occur in the range of human exposures or effects observed at doses below those used for traditional toxicological studies. We review the mechanistic data for low-dose effects and use a weight-of-evidence approach to analyze five examples from the EDC literature. Additionally, we explore nonmonotonic dose-response curves, defined as a nonlinear relationship between dose and effect where the slope of the curve changes sign somewhere within the range of doses examined. We provide a detailed discussion of the mechanisms responsible for generating these phenomena, plus hundreds of examples from...

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Hormones and endocrine-disrupting chemicals: Low-dose effects and nonmonotonic dose responses

https://research.birmingham.ac.uk/portal/files/41988116/Anekwe_et_al_2017.pdf

Pharmaceuticals and personal care products (PPCPs) in the freshwater aquatic environment

https://apps.who.int/iris/bitstream/10665/78102/1/WHO_HSE_PHE_IHE_2013.1_eng.pdf

State of the Science of Endocrine Disrupting Chemicals - 2012

Biological degradation of pharmaceuticals in municipal wastewater treatment: proposing a classification scheme.

Prescription and nonprescription drugs have been detected in rivers and streams in Europe and the United States. Sewage treatment plants (STPs) are an important source of these contaminants, but few data exist on the spatial distribution of drugs in surface waters near STPs. Samples of surface water were collected in the summer and fall of 2000 at open-water sites in the lower Great Lakes (Lake Ontario and Lake Erie), at sites near the two STPs for the city of Windsor (ON, Canada), and at sites in Hamilton Harbour (ON, Canada), an embayment of western Lake Ontario that receives discharges from several STPs. In a follow-up study in the summer of 2002, samples of surface water and final effluent from adjacent STPs were collected from sites in Hamilton Harbour and Windsor. In addition, surface water and STP effluent samples were collected in Peterborough (ON, Canada). All samples of surface water and STP effluents were analyzed for selected acidic and neutral drugs. In the survey of Hamilton Harbour and Windsor conducted in 2000, acidic drugs and the antiepileptic drug carbamazepine were detected at ng/L concentrations at sites that were up to 500 m away from the STP, but the hydrological conditions of the receiving waters strongly influenced the spatial distribution of these compounds. Drugs were not detected at open-water locations in western Lake Erie or in the Niagara River near the municipality of Niagara-on-the-Lake (ON, Canada). However, clofibric acid, ketoprofen, fenoprofen, and carbamazepine were detected in samples collected in the summer of 2000 at sites in Lake Ontario and at a site in the Niagara River (Fort Erie, ON, Canada) that were relatively remote from STP discharges. Follow-up studies in the summer of 2002 indicated that concentrations of acidic and neutral drugs in surface waters near the point of sewage discharge into the Little River (ON, Canada) STP were approximately equal to the concentrations in the final effluent from the STP. Caffeine and cotinine, a metabolite of nicotine, were generally present in STP effluents and surface waters contaminated by drugs. The antidepressant fluoxetine and the antibiotic trimethoprom were also detected in most STP effluents and some surface water samples. For the first time, the lipid regulating drug atorvastatin was detected in samples of STP effluent and surface water.

Distribution of acidic and neutral drugs in surface waters near sewage treatment plants in the lower Great Lakes, Canada

The potential for nitrate to affect amphibian survival was evaluated by examining the areas in North America where concentrations of nitrate in water occur above amphibian toxicity thresholds. Nitrogen pollution from anthropogenic sources enters bodies of water through agricultural runoff or percolation associated with nitrogen fertilization, livestock, precipitation, and effluents from industrial and human wastes. Environmental concentrations of nitrate in watersheds throughout North America range from 100 mg/L. Of the 8,545 water quality samples collected from states and provinces bordering the Great Lakes, 19.8% contained nitrate concentrations exceeding those which can cause sublethal effects in amphibians. In the laboratory lethal and sublethal effects in amphibians are detected at nitrate concentrations between 2.5 and 100 mg/L. Furthermore, amphibian prey such as insects and predators of amphibians such as fish are also sensitive to these elevated levels of nitrate. From this we conclude that nitrate concentrations in some watersheds in North America are high enough to cause death and developmental anomalies in amphibians and impact other animals in aquatic ecosystems. In some situations, the use of vegetated buffer strips adjacent to water courses can reduce nitrogen contamination of surface waters. Ultimately, there is a need to reduce runoff, sewage effluent discharge, and the use of fertilizers, and to establish and enforce water quality guidelines for nitrate for the protection of aquatic organisms.

Nitrogen pollution: an assessment of its threat to amphibian survival.

Glyphosate in surface waters of southern Ontario (Canada) was studied over a 2-year period. A small percentage of samples exhibited glyphosate concentrations greater than the analytical limit of quantitation (17 μg a.e./L), and the maximum concentration of glyphosate measured was 40.8 μg/L. No samples of roughly 500 analyzed exceeded the Canadian Water Quality Guideline of 65 μg a.e./L considered protective of aquatic life. Typical concentrations of glyphosate in amphibian habitats were well below a range of toxicity thresholds for aquatic organisms, and were thus judged to be unlikely to pose a substantial risk to either sensitive amphibian larvae or other aquatic biota.

John Struger

Papers

Distribution of acidic and neutral drugs in surface waters near sewage treatment plants in the lower Great Lakes, Canada

Nitrogen pollution: an assessment of its threat to amphibian survival.

Occurrence of Glyphosate in Surface Waters of Southern Ontario

Double-Crested Cormorants of the Great Lakes: Changes in Population Size, Breeding Distribution and Reproductive Output between 1913 and 1991

Factors influencing the occurrence and distribution of neonicotinoid insecticides in surface waters of southern Ontario, Canada.