Mixture Of Pharmaceuticals And Personal Care Products Research Articles

Transcriptomic profiles of brains in juvenile Atlantic cod (Gadus morhua) exposed to pharmaceuticals and personal care products from a wastewater treatment plant discharge

Pharmaceuticals and personal care products (PPCPs) are frequently detected in marine environments, posing a threat to aquatic organisms. Our previous research demonstrated the occurrence of neuroactive compounds in effluent and sediments from a wastewater treatment plant (WWTP) in a fjord North of Stavanger, the fourth-largest city in Norway. To better understand the influence of PPCP mixtures on fish, Atlantic cod (Gadus morhua) were caged for one month in 3 locations: site 1 (reference), site 2 (WWTP discharge), and site 3 (6.7 km west of discharge). Transcriptomic profiling was conducted in the brains of exposed fish and detection of PPCPs in WWTP effluent and muscle fillets were determined. Caffeine (47.8 ng/L), benzotriazole (10.9 ng/L), N,N-diethyl-meta-toluamide (DEET) (5.6 ng/L), methyl-1H-benzotriazole (5.5 ng/L), trimethoprim (3.4 ng/L), carbamazepine (2.1 ng/L), and nortriptyline (0.4 ng/L) were detected in the WWTP effluent. Octocrylene concentrations were observed in muscle tissue at all sites and ranged from 53 to 193 ng/g. Nervous system function and endocrine system disorders were the top enriched disease and function pathways predicted in male and female fish at site 2, with the top shared canonical pathways involved with estrogen receptor and Sirtuin signaling. At the discharge site, predicted disease and functional responses in female brains were involved in cellular assembly, organization, and function, tissue development, and nervous system development, whereas male brains were involved in connective tissue development, function, and disorders, nervous system development and function, and neurological disease. The top shared canonical pathways in females and males were involved in fatty acid activation and tight junction signaling. This study suggests that pseudopersistent, chronic exposure of native juvenile Atlantic cod from this ecosystem to PPCPs may alter neuroendocrine and neuron development.

Environmental Risks of Pharmaceutical Mixtures in Aquatic Ecosystems: Reflections on a Decade of Research.

Pharmaceuticals and personal care products (PPCPs) occur as variable mixtures in surface waters receiving discharges of human and animal wastes. A key question identified a decade ago is how to assess the effects of long-term exposures of these PPCP mixtures on nontarget organisms. We review the recent progress made on assessing the aquatic ecotoxicity of PPCP mixtures-with a focus on active pharmaceutical ingredients-and the challenges and research needs that remain. New knowledge has arisen from the use of whole-mixture testing combined with component-based approaches, and these studies show that mixtures often result in responses that meet the concentration addition model. However, such studies have mainly been done on individual species over shorter time periods, and longer-term, multispecies assessments remain limited. The recent use of targeted and nontargeted gene analyses has improved our understanding of the diverse pathways that are impacted, and there are promising new "read-across" methods that use mammalian data to predict toxicity in wildlife. Risk assessments remain challenging given the paucity of ecotoxicological and exposure data on PPCP mixtures. As such, the assessment of PPCP mixtures in aquatic environments should remain a priority given the potential for additive-as well as nontarget-effects in nontarget organisms. In addition, we need to improve our understanding of which species, life stages, and relevant endpoints are most sensitive to which types of PPCP mixtures and to expand our knowledge of environmental PPCP levels in regions of the globe that have been poorly studied to date. We recommend an increased use of new approach methodologies, in particular "omics," to advance our understanding of the molecular mechanics of mixture effects. Finally, we call for systematic research on the role of PPCP mixtures in the development of antimicrobial resistance. Environ Toxicol Chem 2024;43:549-558. © 2023 SETAC.

Profiling of the spatiotemporal distribution, risks, and prioritization of pharmaceuticals and personal care products in coastal waters of the northern Yellow Sea, China

Pharmaceuticals and personal care products (PPCPs) have aroused global concerns due to their ubiquitous occurrence and detrimental effects. The spatiotemporal distributions of 64 PPCPs and their synergetic ecological risks were comprehensively investigated in the seawater of Yantai Bay, and 1 H-benzotriazole (BT), ethenzamide, phenazone, propyphenazone, 4-hydroxybenzophenone and N, N′-diphenylurea were first determined in the seawater of China. Fifty-six PPCPs were detected and their concentrations were 27.5–182 ng/L, with BT contributing around 58.0%. Higher PPCP concentrations were observed in winter and spring, with the concentrations of antioxidants, analgesic/anti-inflammatory drugs and human-used antibiotics significantly higher in winter, while those of aquaculture-used antibiotics and UV filters significantly higher in summer, which was closely related with their usage patterns. Positive correlations were observed for PPCP concentrations between surface and bottom water, except summer, during which time the weak vertical exchange and varied environmental behaviors among different PPCPs resulted in the distinct compositions and concentrations. Terrestrial inputs and mariculture resulted in higher PPCP concentrations in the area located adjacent to the coast and aquaculture bases. The PPCP mixtures posed medium to high risk to crustaceans, and bisphenol A was identified as a high-risk pollutant that needs special attention.

PPCPs in coastal wastewater treatment plant effluent and uptake by Pacific oysters (Crassostrea gigas): Findings from a laboratory experiment

Municipal wastewater treatment plant (WWTP) effluent is a primary source of pharmaceuticals and personal care products (PPCPs) to the marine environment, as most of these compounds are not fully removed during the treatment process. Continual discharge from WWTPs into coastal areas may act as a stressor by continually exposing organisms to a suite of PPCPs. To quantify organismal exposure to PPCP mixtures, we conducted a 12-week lab experiment that exposed Pacific oysters to effluent from two Oregon coastal WWTPs of different discharge capacities (permitted as <1 million gallons/day and >1 million gallons/day; or < or >3.785 million liters/day) at a dilution of 25 %. Composite samples of weekly collected effluent and a subset of freeze-dried oysters from experiment week 12 were analyzed for PPCPs. Though challenges with food availability inhibited our ability to confidently identify effects of the contaminants on growth and fitness, the experiment allowed us to examine uptake of contaminants from effluent into an estuarine bivalve of commercial importance. We detected 30 PPCPs and three alkylphenols in effluent and 13 PPCPs and four alkylphenols in oyster tissue, indicating high rates of release from secondary treatment and significant potential for marine organism exposure to and uptake of PPCPs in rural coastal areas.

Comprehensive profiling of the distribution, risks and priority of pharmaceuticals and personal care products: A large-scale study from rivers to coastal seas

Pharmaceuticals and personal care products (PPCPs) have captured global concern due to their detrimental effects on aquatic organisms. Thirty PPCPs were analyzed in the water of the Jiaozhou Bay watershed, the Yellow Sea (YS) and the East China Sea (ECS) in China to investigate the distribution and risk of PPCPs from rivers to coastal seas, which are not yet well documented. The results showed the prevalence of the target PPCPs with a downward trend in detection frequencies and total concentrations from rivers (675 ng/L on average) to bay (166 ng/L) and to coastal seas (103 ng/L). Antibiotics and personal care products (PCPs) were dominated by amoxicillin (AMOX) and p-hydroxybenzoic acid, respectively, while the dominant estrogens were inconsistent in different regions. Spatially, the total PPCP concentrations were higher in the ECS than that in the YS due to the larger quantity of sewage flowing into the ECS. Additionally, higher total PPCP concentrations were appeared in the southeastern waters outside the Yangtze estuary and Hangzhou Bay of the ECS. The PPCP mixtures might pose medium to high risk to aquatic organisms in general. The total risk quotient (RQT) of antibiotics and PCPs to algae was higher than that to crustacean and fish, while estrogens may cause the greatest damage to fish. Despite the higher PPCP concentrations in river water than in seawater, the RQT of PPCPs in bay water was generally higher than that in river water, which may be associated with the susceptibility of marine organisms. Furthermore, the high-risk pollutants that need special concern in different regions were clarified, showing that AMOX, 17ß-estradiol, and estriol deserve the highest-priority in rivers, bay, and coastal waters, respectively.

Does Environmental Exposure to Pharmaceutical and Personal Care Product Residues Result in the Selection of Antimicrobial-Resistant Microorganisms, and is this Important in Terms of Human Health Outcomes?

The environment plays a critical role in the development, dissemination, and transmission of antimicrobial resistance (AMR). Pharmaceuticals and personal care products (PPCPs) enter the environment through direct application to the environment and through anthropogenic pollution. Although there is a growing body of evidence defining minimal selective concentrations (MSCs) of antibiotics and the role antibiotics play in horizontal gene transfer (HGT), there is limited evidence on the role of non-antibiotic PPCPs. Existing data show associations with the development of resistance or effects on bacterial growth rather than calculating selective endpoints. Research has focused on laboratory-based systems rather than in situ experiments, although PPCP concentrations found throughout wastewater, natural water, and soil environments are often within the range of laboratory-derived MSCs and at concentrations shown to promote HGT. Increased selection and HGT of AMR by PPCPs will result in an increase in total AMR abundance in the environment, increasing the risk of exposure and potential transmission of environmental AMR to humans. There is some evidence to suggest that humans can acquire resistance from environmental settings, with water environments being the most frequently studied. However, because this is currently limited, we recommend that more evidence be gathered to understand the risk the environment plays in regard to human health. In addition, we recommend that future research efforts focus on MSC-based experiments for non-antibiotic PPCPS, particularly in situ, and investigate the effect of PPCP mixtures on AMR. Environ Toxicol Chem 2024;43:623-636. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Occurrence of pharmaceuticals and personal care products in bottled water and assessment of the associated risks

The occurrence of 187 pharmaceuticals and personal care products (PPCPs) was investigated in bottled water samples (35 and 33 from Chinese and foreign brands, respectively). Forty-four compounds belonging to 14 PPCP categories were detected in 56 of the 68 bottled water samples. Further, more than 35% of water samples contained at least three PPCPs, and in one particular sample, 11 different PPCPs were detected. Macrolides constituted the most prevalent PPCP category, and salbutamol, erythromycin, and azithromycin showed the highest detection frequency (17.6%). The thermal stabilities of the 187 PPCPs were determined, and the results obtained showed that only 35 out of the 187 compounds were degraded by more than 50% after boiling for 5 min. Even though the risk quotients (RQs) of detected PPCPs showed low risk levels, the RQs of 13 compounds with RQs ≥ 0.0001 were 2–4 fold higher in infants than in other life stages. Moreover, further studies are necessary to evaluate the toxicity of PPCP mixtures, the effects of PPCPs on human intestinal microbiota, and their risk of induction of drug-resistant bacteria and drug-resistant genes.

Chronic exposure to PPCPs mixture at environmentally relevant concentrations (ERCs) altered carbohydrate and lipid metabolism through gut and liver toxicity in zebrafish.

Pharmaceuticals and personal care products (PPCPs) have been widely distributed and posed ecotoxicological risks in the aquatic environment. This study aims to evaluate the toxic effects after chronic exposure to PPCPs mixture at the environment relevant concentrations (ERCs). Our results indicated that PPCPs induced serious metabolic effects by disturbing the carbohydrate and lipid metabolism pathways. Chronic exposure caused a significant reduction in the hepatosomatic index (HSI), the gut weight ratios, and histological alterations in liver and gut tissues. Further, exposure to the combined PPCPs disrupted the carbohydrate metabolism via significant upregulation of hk1, gk, pck1, and insr genes. The lipid metabolism was affected with higher ppars expression levels that increased the fatty acid β-oxidation and ultimately decreased the lipidogenesis. Moreover, the altered responses of the insulin growth factor (IGF) pathway more in male gut tissue than that of female revealed sex-dependent disturbance in the gut homeostasis induced by PPCPs mixture. In conclusion, chronic exposure to PPCPs mixtures at ERCs can induce developmental effects and metabolic dysfunction in both male and female fish. The consumption and environmental disposal of these PPCPs should be regulated to ensure ecological health and environmental safety.

Seasonal occurrence, removal, mass loading and environmental risk assessment of 55 pharmaceuticals and personal care products in a municipal wastewater treatment plant in Central Greece

A comprehensive study, which contains the seasonal occurrence, removal, mass loading and environmental risk assessment of 55 multi-class pharmaceuticals and personal care products (PPCPs), took place in the wastewater treatment plant (WWTP) of Volos, Greece. A one year monitoring study was performed and the samples were collected from the influent and the effluent of the WWTP. Solid phase extraction was used for the pre-concentration of the samples followed by an LC–DAD–ESI/MS analysis. Positive samples were further confirmed by liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS). The maximum concentrations of the PPCPs varied between 21ng/L and 15,320ng/L in the influents and between 18ng/L and 9965ng/L in the effluents. The most commonly detected PPCPs were the diuretic furosemide, the beta-blockers atenolol and metoprolol, the analgesics paracetamol, nimesulide, salicylic acid and diclofenac and the psychomotor stimulant caffeine. The removal efficiencies ranged between negative and high removal rates, demonstrating that the WWTP is not able to efficiently remove the complex mixture of PPCPs. The estimated mass loads ranged between 5.1 and 3513mg/day/1000 inhabitants for WWTP influent and between 4.1 to 2141mg/day/1000 inhabitants for WWTP effluent. Finally, environmental risk assessment has been regarded a necessary part of the general research. According to the results produced from the calculation of the risk quotient on three trophic levels, the anti-inflammatory drug diclofenac and the antibiotics, trimethoprim and ciprofloxacin, identified to be of high potential environmental risk for acute toxicity, while diclofenac also for chronic toxicity.

Pharmaceuticals and personal care products in waters: occurrence, toxicity, and risk.

Pharmaceuticals and personal care products (PPCP) are compounds with special physical and chemical properties that address the care of animal and human health. PPCP have been detected in surface water and wastewater in the ng/L to µg/L concentration range worldwide. PPCP ecotoxicity has been studied in a variety of organisms, and multiple methods have been used to assess the risk of PPCP in the environment to ecological health. Here we review the occurrence, effects, and risk assessment of PPCP in aquatic systems, as well as the sustainability of current methods for managing PPCP contamination in aquatic systems. The major points are the following: (1) a number of PPCP present potential concerns at environmentally relevant concentrations. PPCP mixtures may produce synergistic toxicity. (2) Various methods have been used for the ecological risk assessment of PPCP in aquatic systems. There are similarities in these methods, but no consensus has emerged regarding best practices for the ecological risk assessment of these compounds. (3) Human health risk assessments of PPCP contamination in aquatic systems have generally indicated little cause for concern. However, there is a lack of information regarding whether antibiotic contamination in wastewater and aquatic systems could lead to an increase in clinically relevant antibiotic-resistant bacteria and antibiotic-resistant genes. (4) Over the next century, the combination of increasing global population size and potential droughts may result in reduced water availability, increased need for water reuse, and increasing concentrations of PPCP in wastewaters. The current wastewater treatment methods do not remove all PPCP effectively. This, coupled with the possibility that antibiotics may promote the development of antibiotic-resistant bacteria and antibiotic-resistant genes, leads to concerns about the sustainability of global water supplies.

Pharmaceuticals and personal care products alter the holobiome and development of a medically important mosquito

The increasing demand for fresh water has forced many countries to use reclaimed wastewater for agricultural purposes. This water contains pharmaceuticals and personal care products (PPCPs) that remain biologically active following passage through wastewater treatment plants. Run-off from farms and contaminated water from treatment facilities exposes aquatic ecosystems to PPCPs. This study examined the effects of PPCPs on a lower trophic organism. Culex quinquefasciatus larvae were reared in water contaminated with environmentally relevant concentrations of common PPCPs. Acetaminophen alone and a mixture of contaminants were found to increase developmental time of larvae. Susceptibility to Bti increased in larvae exposed to antibiotics, acetaminophen, or a mixture of PPCPs. Antibiotics, hormones, and the mixture altered the mosquito bacterial microbiome. Overall, the results indicate that at environmentally relevant concentrations, PPCPs in reclaimed water can have biologically important effects on an ecologically and medically important lower trophic level insect.

International scientists' priorities for research on pharmaceutical and personal care products in the environment

Pharmaceuticals and personal care products (PPCPs) are widely discharged into the environment via diverse pathways. The effects of PPCPs in the environment have potentially important human and ecosystem health implications, so credible, salient, and legitimate scientific evidence is needed to inform regulatory and policy responses that address potential risks. A recent "big questions" exercise with participants largely from North America identified 22 important research questions around the risks of PPCP in the environment that would help address the most pressing knowledge gaps over the next decade. To expand that analysis, we developed a survey that was completed by 535 environmental scientists from 57 countries, of whom 49% identified environmental or analytical chemistry as their primary disciplinary background. They ranked the 22 original research questions and submitted 171 additional candidate research questions they felt were also of high priority. Of the original questions, the 3 perceived to be of highest importance related to: 1) the effects of long-term exposure to low concentrations of PPCP mixtures on nontarget organisms, 2) effluent treatment methods that can reduce the effects of PPCPs in the environment while not increasing the toxicity of whole effluents, and 3) the assessment of the environmental risks of metabolites and environmental transformation products of PPCPs. A question regarding the role of cultural perspectives in PPCP risk assessment was ranked as the lowest priority. There were significant differences in research orientation between scientists who completed English and Chinese language versions of the survey. We found that the Chinese respondents were strongly orientated to issues of managing risk profiles, effluent treatment, residue bioavailability, and regional assessment. Among English language respondents, further differences in research orientation were associated with respondents' level of consistency when ranking the survey's 15 comparisons. There was increasing emphasis on the role of various other stressors relative to PPCPs and on risk prioritization as internal decision making consistency increased. Respondents' consistency in their ranking choices was significantly and positively correlated with SETAC membership, authors' number of publications, and longer survey completion times. Our research highlighted international scientists' research priorities and should help inform decisions about the type of hazard and risk-based research needed to best inform decisions regarding PPCPs in the environment. Disciplinary training of a scientist or engineer appears to strongly influence preferences for research priorities to understand PPCPs in the environment. Selection of participants and the depth and breadth of research prioritization efforts thus have potential effects on the outcomes of research prioritization exercises. Further elucidation of how patterns of research priority vary between academic and government scientists and between scientists and other government and stakeholders would be useful in the future and provide information that helps focus scientific effort on socially relevant challenges relating to PPCPs in the environment. It also suggests the potential for future collaborative research between industry, government, and academia on environmental contaminants beyond PPCPs.

Effects of triclocarban, N,N‐diethyl‐meta‐toluamide, and a mixture of pharmaceuticals and personal care products on fathead minnows (Pimephales promelas)

Pharmaceuticals and personal care products (PPCPs) have been detected widely in aquatic ecosystems, but little is known about their mechanisms of toxicity. We exposed adult fathead minnows (Pimephales promelas) for 48 h to triclocarban (1.4 µg/L), N,N-diethyl-meta-toluamide (DEET; 0.6 µg/L), or a mixture of PPCPs consisting of atenolol (1.5 µg/L), caffeine (0.25 µg/L), diphenhydramine (0.1 µg/L), gemfibrozil (1.5 µg/L), ibuprofen (0.4 µg/L), naproxen (1.6 µg/L), triclosan (2.3 µg/L), progesterone (0.2 µg/L), triclocarban (1.4 µg/L), and DEET (0.6 µg/L). Quantitative real-time polymerase chain reaction revealed an upregulation in vitellogenin (vtg) in livers of females and males exposed to triclocarban. Also, an upregulation of hepatic lipoprotein lipase (lpl) and a downregulation of androgen receptor (ar) and steroidogenic acute regulatory protein (star) were observed in testes. The group treated with DEET only showed a significant decrease in ar in females. In contrast, the PPCP mixture downregulated vtg in females and males and expression of estrogen receptor alpha (erα), star, and thyroid hormone receptor alpha 1 (thra1) in testes. The authors' results show that the molecular estrogenic effects of triclocarban are eliminated (males) or reversed (females) when dosed in conjunction with several other PPCP, once again demonstrating that results from single exposures could be vastly different from those observed with mixtures. Environ Toxicol Chem 2014;33:910-919. © 2013 SETAC.

Biological removal of pharmaceuticals and personal care products during laboratory soil aquifer treatment simulation with different primary substrate concentrations

Pharmaceuticals and personal care products (PPCPs) have been detected in bodies of water worldwide, yet their effects on the environment are not fully understood. Recent toxicity studies suggest that mixtures of PPCPs at low concentrations may be detrimental to exposed organisms, highlighting the need to remove PPCPs from wastewater treatment plant effluent before it is discharged to the environment. In this study, the utility of biofilm-based PPCP removal as a means to prevent environmental PPCP contamination was investigated. The removal of 14 PPCPs, each at an initial concentration of 10 μg/L, was studied in laboratory sand columns inoculated with wastewater treatment plant effluent. The examined PPCPs included biosol, biphenylol, p-chloro-m-cresol, p-chloro-m-xylenol, chlorophene, sodium diclofenac, gabapentin, gemfibrozil, 5-fluorouracil, ibuprofen, ketoprofen, naproxen, triclosan, and valproic acid. Ten of the PPCPs were removed by greater than 95% during column passage, while the four other compounds proved more recalcitrant. The effect of the concentration (either 50 or 1000 μg/L) of an easily degradable primary substrate (acetate) supplied along with the mixture of PPCPs was examined. Most of the tested PPCPs were removed consistently by the biofilms regardless of the concentration of acetate, although the extent of removal for three compounds showed dependence on acetate concentration, and two behaved with no reproducible pattern over time. Biofilm protein measurements indicated that the mixture of PPCPs supplied to columns suppressed biofilm growth, suggesting toxicity of the PPCPs to the biofilm communities. This laboratory-scale experiment suggests that biofilm-based water treatment strategies, such as soil aquifer treatment and slow sand filtration, may be well-suited for the removal of many PPCPs from impacted water.

Individual and Mixture Effects of Selected Pharmaceuticals and Personal Care Products on the Marine Phytoplankton Species Dunaliella tertiolecta

Pharmaceuticals and personal care products (PPCPs) entering the environment may have detrimental effects on aquatic organisms. Simvastatin, clofibric acid, diclofenac, carbamazepine, fluoxetine, and triclosan represent some of the most commonly used and/or detected PPCPs in aquatic environments. This study analyzed the individual and mixture toxicity of these six PPCPs to the marine phytoplankton species Dunaliella tertiolecta using a standard 96-hour static algal bioassay protocol. All PPCPs tested had a significant effect on D. tertiolecta population cell density. However, of the six PPCPs tested, only triclosan yielded toxicity at typical environmental concentrations. The 96-hour EC(50) values for triclosan, fluoxetine, simvastatin, diclofenac, and clofibric acid were 3.55 microg/L, 169.81 microg/L, 22,800 microg/L, 185,690 microg/L, and 224,180 microg/L, respectively. An EC(50) value could not be determined for carbamazepine; however, the highest concentration tested (80,000 microg/L) reduced cell density by 42%. Both mixtures tested-simvastatin-clofibric acid and fluoxetine-triclosan-demonstrated additive toxicity. The presence of PPCP mixtures may decrease the toxicity threshold for phytoplankton populations. Detrimental effects on phytoplankton populations could ultimately impact nutrient cycling and food availability to higher trophic levels. The results of this study are a first step toward identifying the risk of PPCPs to estuarine organisms and may benefit environmental resource managers.