A Systematic Review of the Environmental Persistence, Toxicity Pathways and Policy Implications of (EE2) Across Urban and Agricultural Systems

A Systematic Review of the Environmental Persistence, Toxicity Pathways and Policy Implications of (EE2) Across Urban and Agricultural Systems

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International Journal of Engineering Research & Technology (IJERT)

ISSN: 2278-0181

Vol. 14 Issue 10, October – 2025

Fae Marie L. Cablao, Louis Genesis B. Patdu, Greg Andie M. Barbuena, Mike John Pedido, Jose Adrian R. Daguison, Gecelene C. Estorico Environmental Science and Chemical Technology

Technological University of the Philippines – Taguig Km 14 East Service Road, Western Bicutan, Taguig City

Abstract Synthetic hormones such as 17-ethinylestradiol (EE), a key component of oral contraceptives, have emerged as persistent environmental micropollutants due to their incomplete removal in conventional wastewater treatment systems. This systematic review (20202025) synthesized 22 peer-reviewed studies examining EEs occurrence, persistence, toxicity, and removal efficiency across aquatic, soil, and agricultural environments. Results reveal that influent concentrations consistently exceed effluent levels, confirming the limited efficiency of current treatment technologies. EEs toxicity and bioassay data highlight its ability to disrupt endocrine systems, induce reproductive abnormalities, and alter ecosystem stability even at nanogram-level concentrations. Elevated levels observed in soil (~85), sediments (~80), crops (~65), and water (~60) demonstrate its mobility and bioaccumulation through the soil plantwater continuum, posing risks of chronic exposure and food-chain transfer. Collectively, these findings identify EE as a high-risk and bioactive contaminant, underscoring the urgent need for policy reform, advanced treatment innovations, and sustained environmental monitoring to mitigate its ecological and human health impacts.

Keywords Hormonal Contraceptives, Endocrine-Disrupting Compounds, Wastewater Treatment, Soil Persistence, Environmental Toxicology, Urban and Agricultural Ecosystems, Ecological Risk

1. INTRODUCTION

   Pharmaceutical residues have emerged as a growing environmental concern in recent decades, largely due to the continuous global use of synthetic hormones and antibiotics. Among these compounds, hormonal contraceptives especially those containing 17-ethinylestradiol (EE)have attracted increasing attention because of their persistence and strong endocrine-disrupting properties. These synthetic estrogens are only partially metabolized in the human body and are excreted into wastewater, where conventional treatment processes often fail to completely remove them.

   Studies conducted in various countries, including the Philippines, have confirmed the presence of estrogenic contaminants in aquatic environments such as Laguna Lake and several river systems in Metro Manila. Domestic wastewater,

   sewage discharge, and urban runoff are major sources of these endocrine-disrupting compounds (EDCs). Furthermore, the reuse of untreated or partially treated wastewater for irrigation increases the risk of soil contamination and potential food-chain transfer.

   Even at trace concentrations, EE can disrupt hormonal systems in aquatic organisms, leading to feminization of male fish, reproductive failure, and population decline. The detection of EE in agricultural soils and edible crops also raises serious concerns about human exposure, particularly in tropical regions where wastewater treatment facilities are often outdated or insufficient.

   Given these risks, understanding the persistence and toxicological behavior of EE in tropical environments is essential for designing context-appropriate management strategies. This is especially relevant to the Philippines, where rapid urbanization and limited wastewater infrastructure make the environment more vulnerable to pharmaceutical pollution. Therefore, this systematic review aims to synthesize recent studies (20202025) on the occurrence, persistence, and toxicological impacts of hormonal contraceptive residues, particularly EE, in urban and agricultural systems. By integrating international and regional findings, this study identifies major environmental pathways, biological effects, and research gaps that need to be addressed to protect both ecosystems and public health.

2. METHODOLOGY

   This systematic review employed a structured and transparent approach to collect, evaluate, and synthesize published scientific literature from 2020 to 2025 concerning the environmental persistence and toxicological impacts of hormonal contraceptive residuesparticularly 17- ethinylestradiol (EE)in urban and agricultural environments. The overall process followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) framework to ensure rigor, transparency, and replicability throughout the selection and synthesis process.

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   1. Study Area

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      biota), detection method, concentration range, and removal

      Although this research did not involve direct fieldwork, it considered studies conducted in both urban wastewater systems and agricultural environments where hormonal contraceptive residues have been documented. Emphasis was given to tropical and developing regions, including the Philippines, to highlight variations in wastewater infrastructure, agricultural practices, and exposure pathways that may influence EE persistence and mobility.

   2. Data Sources

      Relevant peer-reviewed articles were retrieved from ScienceDirect, Google Scholar, and PubMed, which provide extensive coverage of environmental toxicology and wastewater management studies. Supplementary materials were also obtained from the reference lists of recent review papers and publicly available environmental monitoring reports to ensure inclusion of both global and regionally relevant research.

   3. Search and Screening Process

      A systematic search was performed using Boolean operators and key terms such as ethinylestradiol AND wastewater AND toxicity, hormonal contraceptives AND soil contamination, and endocrine disruptors AND agricultural environments. Searches were limited to studies published between January 2020 and April 2025. Duplicates and unrelated records were manually removed.

      The PRISMA 2020 guidelines were applied to organize the identification, screening, eligibility, and inclusion phases (as summarized in Figure 1). This ensured a consistent and unbiased selection of literature relevant to the study objectives.

   4. Laboratory Analysis

      Studies were included if they met the following conditions:

      1. Published between 2020 and 2025,

      2. Focused on EE or similar estrogenic compounds in water, soil, or biota, and

      3. Provided quantitative or qualitative data on environmental persistence or toxicity.

      Exclusion criteria included:

      1. Medical or pharmacological studies not related to environmental effects,

      2. Non-peer-reviewed papers, theses, or inaccessible sources, and

      3. Publications dated before 2020.

      These criteria ensured that only credible, recent, and environmentally relevant studies were analyed.

   5. Data Extraction and Synthesis

      From each eligible study, key information was extracted, including publication year, country, sample type (water, soil, or

      efficiency. Reported degradation mechanisms and biological effects were also categorized into thematic areas such as environmental occurrence, persistence, and toxicity.

      Due to methodological variability among studies, no meta- analysis was conducted. Instead, descriptive and comparative synthesis was used to identify global patterns and knowledge gaps. Reported EE concentrations were also compared against the Predicted No-Effect Concentration (PNEC) to assess potential ecological risks.

   6. Search Results

      A total of 132 studies were initially identified across all databases. After removing duplicates and irrelevant papers, 85 studies remained for eligibility screening. Following a detailed full-text review, 22 studies met all inclusion criteria and were selected for final synthesis. These studies represented research conducted in Asia, Europe, and the Americas, including several that provided valuable regional data from the Philippines and neighboring Southeast Asian countries.

      The results of the screening process, summarized in Figure 1 (PRISMA Flow Diagram), show that research interest in estrogenic contaminationparticularly EEhas grown steadily in recent years. This upward trend reflects increasing scientific attention to the environmental persistence and ecological risks of hormonal contraceptives.

   7. Data Extraction

      For each selected study, essential informationincluding the publication year, country of origin, sample matrix (water, soil, or biota), detection method, and reported EE concentrations was systematically extracted and summarized. Additional data related to removal efficiency, degradation mechanisms, and biological effects were organized into thematic categories. This structured approach allowed for a clear comparative evaluation of EEs behavior, persistence, and ecological impacts across different environmental compartments.

   8. Statistical Analysis

      A formal meta-analysis was not performed due to variations in experimental designs, reporting formats, and analytical methods among the selected studies. Instead, a descriptive and comparative analysis was conducted to identify common patterns of occurrence, persistence, and toxicity. Frequency analysis was applied to determine the most frequently reported environmental pathways, while reported concentration ranges were compared with the Predicted No-Effect Concentration (PNEC) to assess potential ecological risks. This qualitative synthesis provided a more comprehensive understanding of the global and regional implications of hormonal contraceptive residues in the environment.

3. RESULTS AND DISCUSSION

   A total of 1,254 studies were initially identified through database searches and reference screening. After removing duplicates and irrelevant materials, 85 were reviewed for

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   eligibility. From these, 22 studies met the inclusion criteria and were synthesized for this review.

   The PRISMA flow diagram (Figure 1) summarizes the

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   1. Environmental Occurrence

      Inclusion

      (22 Studies included in final review)

      Eligibility

      (38 Full-text articles assessed)

      Screening

      (85 Screened after duplicates removed)

      Identification

      (132 Records identified from ScienceDirect,

      selection process and shows how only studies with verified data on 17-ethinylestradiol (EE) persistence, removal, and toxicity were retained.

      Figure 1. PRISMA Flow Diagram of Study Selection (2020 2025)

      The diagram illustrates the rigorous selection process. The large number of excluded studies emphasizes the scarcity of reliable, peer-reviewed research that quantitatively assesses EE in wastewater, soil, and agricultural systems.

      Together, these studies reveal the widespread presence of EE and its incomplete removal in wastewater treatment systems. The discussion below integrates their findings into four main themes:

      1. environmental occurrence,

      2. treatment and removal efficiency,

      3. soil persistence and plant uptake, and

      4. ecotoxicological effects followed by toxicity threshold analysis and research gap identification.

      Figure 2. Comparative Concentrations of 17-Ethinylestradiol (EE2) in Agricultural and Urban Wastewater Influent and Effluent (20202025)

      Figure 2 illustrates the comparative concentrations of 17- ethinylestradiol (EE) in urban and agricultural wastewater influent and effluent from 2020 to 2025, revealing that influent samples consistently exhibited higher concentrations than effluent samples. Urban influent recorded the highest EE levels, ranging from 110 ng/L in 2020 to 80 ng/L in 2025, reflecting continuous inputs from domestic wastewater, hospital discharges, and pharmaceutical residues. Agricultural influent concentrations, ranging from 90 ng/L to 68 ng/L, were slightly lower but still significant due to livestock and fertilizer runoff.

      In contrast, effluent concentrations from both sources showed marked reductions, with urban effluents decreasing from 25 ng/L to 12 ng/L and agricultural effluents from 20 ng/L to 10 ng/L, demonstrating that biological treatment systems effectively lower but do not completely eliminate EE. These findings emphasize that despite improvements in wastewater treatment processes, both urban and agricultural systems continue to contribute measurable levels of synthetic estrogenic compounds to the environment.

   2. Wastewater Treatment and Removal Efficiency

      Figure 3. Removal Efficiency of 17-Ethinylestradiol (EE2) across Agricultural and Urban Wastewater Treatment Methods

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      Figure 3 illustrates the comparative removal performance of various wastewater treatment methods applied to urban and agricultural systems between 2020 and 2025. The results demonstrate substantial differences in efficiency, reflecting each methods operational complexity and technological level. Conventional biological treatments, such as activated sludge and oxidation ditch processes, achieved removal efficiencies between 7090%, yet still discharged effluent EE concentrations above the Predicted No-Effect Concentration (PNEC) for aquatic organisms. These findings indicate that standard municipal systems remain inadequate for complete estrogenic compound degradation, primarily due to the limited biodegradability and strong sorption of EE to sludge matrices. In contrast, advanced and hybrid technologiesincluding ozonation, activated carbon adsorption, membrane bioreactors (MBR), and electrochemical oxidationdemonstrated significantly higher removal rates, often exceeding 95% efficiency. The hybrid MBRozonation configuration exhibited near-complete elimination (~99%), with effluent levels well below ecological risk thresholds. This synergy highlights the value of coupling biological and oxidative processes for effective micropollutant removal.

      Constructed wetlands and biochar-enhanced filtration, although moderately effective (6080%), remain promising alternatives for small-scale or agricultural applications in tropical regions due to their sustainability and cost-efficiency. However, their performance is influenced by hydraulic retention time, temperature, and organic load varability.

      Overall, Figure 3 underscores that technological advancement correlates strongly with EE removal performance. While conventional methods reduce bulk organic matter, they are insufficient for trace micropollutants. Advanced oxidation and adsorption-based systems offer the most reliable degradation potential but may require optimization to balance cost, energy demand, and scalability.

      The data emphasize that improving EE removal in both urban and agricultural wastewater systems is essential to prevent downstream contamination and endocrine disruption in aquatic environments. The integration of low-cost hybrid solutions, adapted for tropical conditions, represents a viable path forward for achieving sustainable and high-efficiency treatment.

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      Table 1. Summary of Reported Concentrations and Removal Efficiencies of 17-Ethinylestradiol (EE2) in Wastewater (20202025)

      Treatment	Influent	Effluent	Removal	Effects on Humans and
      Method	Concentration	Concentratio	Efficiency	Environment	Remarks	Study / Year
      	(ng/L)	n (ng/L)	(%)

      Conventional Activated Sludge

      7,890 549 93.0

      Endocrine disruption in fish; potential risk to drinking water.

      Effective, but residual EE exceeded PNEC for aquatic life.

      Tang et al. (2021)

      Oxidation Ditch Process

      680 180 73.5

      Persistent estrogenic activity; sludge contamination risk.

      Incomplete biodegradation; high sludge adsorption.

      Kibambe et al. (2020)

      Ozonation (Advanced Treatment)

      310 10 96.8

      Minimal ecological risk post- treatment.

      Near-complete

      degradation; costly. Klaic et al. (2022)

      Membrane Bioreactor (MBR)

      410 25 94.0

      Reduced estrogenic load; low environmental toxicity.

      Efficient; requires

      membrane maintenance. Chen et al. (2021)

      Constructed

      Wetlands (Pilot) 250 65 74.0

      Residual hormone may affect aquatic reproduction.

      Feasible for small-scale,

      tropical climates. Sumpter (2024)

      Activated Carbon

      Adsorption 550 20 96.4 Negligible estrogenic risk in

      effluent.

      Strong adsorption capacity; periodic regeneration needed.

      Oliveira et al. (2023)

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      UV Photolysis

      480 60 87.5

      Reduced endocrine effects; minor byproduct formation.

      Effective under optimized exposure; energy- intensive.

      Pham et al. (2022)

      Electrochemical	600	15	97.5	Intermediate compounds require further monitoring	Rapid degradation; may produce toxic	Gao et al. (2025)
      Oxidation					intermediates.
      Biochar-	720	85	88.2	Moderate reduction in estrogenic	Sustainable approach using agricultural waste.	Lopez et al. (2023)
      Enhanced Filtration				activity
      Hybrid MBR + Ozonation	500	5	99.0	Negligible ecological or human risk	Excellent synergy; high operational cost	Nguyen et al. (2024)

      Legend

      EE2 17-Ethinylestradiol; PNEC safe level for aquatic life. Passed safe; Failed unsafe; Marginal borderline.

      Table 1 shows the reported concentrations and removal efficiencies of 17-ethinylestradiol (EE) in wastewater under various treatment methods from 2020 to 2025. The data indicate that advanced and hybrid technologies, particularly Hybrid MBR + Ozonation and Electrochemical Oxidation, achieved the highest removal efficiencies (99.0% and 97.5%), with effluent levels below the ecological safety threshold. These results demonstrate that advanced oxidation processes are the most reliable for EE degradation.

      In contrast, conventional treatments such as the Activated Sludge Process and Oxidation Ditch System showed lower removal rates (7393%), leaving residual EE concentrations above the Predicted No-Effect Concentration (PNEC). Although cost-effective, these methods remain inadequate for complete hormone removal.

      Constructed wetlands and biochar-based systems exhibited moderate efficiency, suitable for small-scale applications but requiring further optimization. Overall, the data highlight that technological complexity correlates with removal performance, reinforcing the need for sustainable, high-efficiency systems tailored to tropical wastewater conditions.

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      Table 2. Identified Research Gaps, Underlying Problems, and Recommended Actions Related to EE Environmental Persistence (20202025)

      Area of Concern	Identified Problem / Limitation	Why This is a Problem	Missing or Inaccurate Aspects	Recommended Action / Future Direction	Reference
      	Limited EE	Without consistent	Most data come from	Establish nationwide EE
      Environmental	monitoring in tropical	data, trends and	developed nations;	monitoring programs focusing on	Ana et al. (2020) [2]; University
      Monitoring	and developing	seasonal variations	tropical regions	high-risk areas and seasonal	of the Philippines (2023) [15]
      	countries.	cannot be assessed.	underrepresented.	variations.
      	Few studies on EE	Gap prevents	Most studies are lab-	Conduct field-based monitoring of	Chen et al. (2021) [3]; Adeel et
      Soil and Crop	accumulation in soil	accurate risk	scale; field data are	crop uptake and soil persistence in	al. (2023) [2]
      Contamination	and transfer to crops.	assessment of food-	scarce	tropical climates.
      		chain exposure
      			Lack of studies	Implement pilot projects using
      Wastewater	Conventional systems	Residues	comparing cost,	low-cost hybrid methods (e.g.,	Tang et al. (2021) [14]; Sumpter
      Treatment	cannot fully remove	contaminate surface	scalability, long-term	wetlands + ozonation) for tropical	(2024) [13];
      Efficiency	EE.	waters and	performance of	regions.
      		sediments.	advanced systems.
      	Limited data on	Limits understanding	Toxicity thresholds	Expand risk models to include soil
      Ecotoxicological	terrestrial and	of EE effects across	rarely adapted to	organisms, plants, and cumulative	Rehberger et al. (2020) [12]; da
      Risk Assessment	microbial impacts.	ecosystems	environmental	multi-species effects.	Silva (2025) [4]
      			context.
      	No EE standards in	Without guidelines,	No integration into	Align national regulations with EU
      Policy and	wastewater policies in	treatment plants lack	RA 9275 or related	standards (<0.035 ng/L effluent)	Klaic et al. (2022) [7]
      Regulation	developing countries.	discharge	policies.	and integrate EE monitoring.
      		benchmarks.

      Table 2 summarizes the major research gaps and challenges related to EE environmental persistence between 2020 and 2025. The most critical issues include limited monitoring in tropical regions, incomplete field-based studies on soil and crop contamination, and inefficient conventional treatment systems. These gaps hinder accurate risk assessment and long-term management of EE contamination.

      To address these limitations, the table recommends nationwide EE monitoring, field validation studies, and pilot testing of low-cost hybrid treatment methods such as wetlands integrated with ozonation. It also emphasizes the lack of ecotoxicological data beyond aquatic species and the absence of regulatory standards for EE under national wastewater policies like RA 9275. Aligning Philippine regulations with international benchmarks and expanding ecological risk assessments are therefore essential to reduce EE pollution and support evidence-based environmental policy.

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   3. Soil Persistence and Plant Uptake

      Figure 4. Environmental Persistence of 17-Ethinylestradiol (EE2) in Water, Soil, and Plant Systems

      As shown in Figure 4, 17-ethinylestradiol (EE) exhibits varying persistence across environmental matrices, with concentrations following the order soil (85 ng/L) > sediments (80 ng/L) > crops (65 ng/L) > water (60 ng/L). This distribution pattern reflects the compounds strong absorption to organic matter and particulate surfaces, causing it to accumulate more in solid media than in water. EEs hydrophobic structure and low biodegradability allow it to bind tightly to soil particles, making soil the primary environmental sink for the compound (Adeel et al., 2023).

      The high level in soils (85 ng/L) suggests that EE is not only deposited from contaminated irrigation or biosolid application but also retained for extended periods due to limited microbial degradation and minimal photolysis. Warm tropical conditions and high organic carbon content can further slow its breakdown, extending its environmental half-life. This persistence may interfere with soil microbial enzyme activity, altering nutrient cycling and soil fertility (Adeel et al., 2023). Sediments (80 ng/L) act as a secondary reservoir, absorbing EE from overlying waters and releasing it back when disturbed by floods or dredging. In aquatic environments, this sediment water exchange sustains chronic low-level contamination, even after treatment or dilution. Although water samples (60 ng/L) show comparatively lower EE levels due to dilution and partial removal during wastewater treatment, these concentrations still exceed the predicted no-effect concentration (PNEC) for aquatic life (< 1 ng/L), indicating potential endocrine disruption and reproductive toxicity in fish and other aquatic species (Rehberger et al., 2020; da Silva, 2025).

      The detection of EE in crop tissues (65 ng/L) highlights an alarming pathway of bioaccumulation and food-chain transfer. Chen et al. (2021) found that plants can absorb EE through both roots and leaf surfaces, especially when irrigated with treated wastewater or grown in contaminated soils. Although plants may metabolize part of the compound, unmetabolized residues can remain in edible tissues, posing long-term exposure risks to humans who consume these crops. Studies also suggest that prolonged use of reclaimed water can lead to progressive accumulation of EE in agricultural soils, further

      intensifying its uptake by vegetation over time (Nguyen et al., 2024).

      The pattern illustrated in Figure 4 demonstrates that EEs persistence is not confined to aquatic systems; rather, it circulates among soil, sediment, water, and crop compartments. This cycle enables continuous re-entry into the environment, even after initial removal from wastewater. Consequently, EEs environmental presence extends its ecological footprintaffecting soil health, water quality, and food safety simultaneously.

      In summary, the elevated concentrations in soil and sediment emphasize that EE behaves as a long-term contaminant, capable of resisting degradation and crossing ecosystem boundaries. Its measurable accumulation in crop tissues underscores a pressing concern for agro-environmental contamination and potential human exposure. These findings reinforce the need for integrated monitoring programs and sustainable wastewater management, particularly in tropical regions where irrigation reuse and high temperatures can amplify EE persistence.

   4. Ecotoxicological Effects

      Figure 5. Ecotoxicological Effects of 17-Ethinylestradiol (EE2) on Aquatic and Terrestrial Organisms

      Figure 5 summarizes the comparative ecotoxicological impact scores of 17-ethinylestradiol (EE) across key biological targets in aquatic and terrestrial environments. The results demonstrate that EEs effects extend beyond aquatic ecosystems, with varying degrees of intensity across organism groups.

      According to Figure 5, fish reproductive effects received the highest impact score (~90), followed by aquatic ecosystem disruption (~85), soil microbial effects (~75), and plant biochemical changes (~65). This ranking highlights the compounds strong affinity for aquatic biota and its role as a potent endocrine-disrupting chemical (EDC) even at sub-ng/L concentrations.

      In aquatic organismsparticularly zebrafish (Danio rerio) and tilapia (Oreochromis niloticus)EE induces vitellogenin production in males, gonadal abnormalities, and reduced fertility, leading to population decline and intersex

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      development (Rehberger et al., 2020; da Silva, 2025). These reproductive impairments directly translate to broader aquatic ecosystem disruption, as altered population ratios disturb trophic dynamics and reduce biodiversity stability.

      The next most affected category, soil microbial effects, reflects EEs persistence after wastewater reuse or sludge application. Adeel et al. (2023) and Chen et al. (2021) reported that EE interferes with enzymatic processes critical for nutrient cyclingnotably dehydrogenase urease, and phosphatase activityresulting in decreased nitrogen fixation and slower organic-matter decomposition. These biochemical disruptions compromise soil fertility and microbial diversity, emphasizing EEs indirect but significant role in terrestrial ecosystem imbalance.

      Finally, plant biochemical changes, while comparatively lower in relative impact, still reveal concerning physiological disturbances. EE exposure in crops irrigated with reclaimed water causes reduced chlorophyll content, root inhibition, and hormonal imbalance, particularly affecting germination and growth (Chen et al., 2021). This suggests potential bioaccumulation in edible parts, linking environmental contamination with food safety concerns.

      Collectively, the data in Figure 5 illustrate that EE exerts multi- level and cross-ecosystem effects, with aquatic reproductive systems serving as the most sensitive endpoints. Its persistence and bioactivity across species underscore the need for integrated ecotoxicological risk assessment frameworksones that address not only water contamination but also downstream soil and crop health.

   5. Environmental Toxicity Threshold Analysis

   Figure 6. Therapeutic Index Curve Showing ED, TD, and LD Relationships

   Figure 6 presents the Therapeutic Index Curve illustrating the effective dose (ED), toxic dose (TD), and lethal dose (LD) of 17-ethinylestradiol (EE) based on relative response levels across different organisms. While these metrics are traditionally applied in pharmacology, they provide a valuable comparative framework to understand EEs dose-dependent environmental toxicity.

   Based on Figure 6, the ED occurs at approximately 30 mg/kg, indicating the concentration at which half of the exposed

   population begins to exhibit measurable endocrine responses, such as vitellogenin induction or hormone imbalance. This aligns with reports from Chen et al. (2021) and Adeel et al. (2023), which describe biological alterations in aquatic organisms even at nanogram-per-liter levels, suggesting that EEs effective concentration in the environment is extremely low relative to its toxic threshold.

   The TD, observed near 60 mg/kg, marks the onset of toxic physiological effects, including reproductive failure, hepatic stress, and oxidative enzyme suppression in fish and amphibians. This point represents a critical ecological risk threshold where sublethal but irreversible damages occur in exposed species. The relatively narrow gap between ED and TD in the curve implies a low safety margin, emphasizing EEs high potency as an endocrine disruptor.

   Meanwhile, the LD, positioned at around 80 mg/kg, corresponds to concentrations that lead to organism mortality, predominantly through endocrine system collapse or bioaccumulation-induced toxicity. While such high concentrations are uncommon in the environment, localized accumulation in sediments and biota (as shown in Figure 4 and 5) may cause chronic exposure equivalent to near-toxic doses in sensitive species.

   The steep slope between these dose-response points reflects EEs nonlinear toxicity pattern, where small increases in dose rapidly amplify biological response. This property makes EE particularly concerning in ecosystems where continuous inputsuch as wastewater effluentsleads to cumulative bioactivity even at low concentrations.

   In ecological terms, this graph reinforces findings from Figure 5, where fish and aquatic organisms exhibited the highest impact scores. The proximity of ED to TD indicates that the margin between safe and harmful exposure is extremely thin, meaning that even minimal environmental residues can trigger harmful endocrine effects.

   Collectively, the trends in Figure 6 underscore EEs potent, cumulative, and low-threshold toxicity, confirming its classification as a high-risk micropollutant. These findings call for stricter regulation of its discharge concentrations, advanced removal technologies in wastewater systems, and consistent monitoring to prevent ecological and potential human health consequences.The patterns observed across environmental compartments highlight the need to translate these findings into effective management frameworks. The following section discusses the corresponding policy and risk management implications.

   G. Policy and Risk Management Implications

   The cumulative results illustrated in Figures 2 to 6 highlight the urgent need for comprehensive policy intervention and risk management strategies concerning the persistence and toxicity of 17-ethinylestradiol (EE) in aquatic and terrestrial systems. The consistently higher influent concentrations shown in Figure

   2 emphasize that conventional wastewater treatment plants (WWTPs) remain inadequate in completely removing estrogenic compounds. Even after secondary treatment,

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   residual EE persists in the effluent, contributing to long-term environmental contamination.

   The toxicological and ecological findings in Figures 3 and 5 further strengthen the case for stricter regulatory standards. The elevated impact scores for fish reproductive effects (90) and aquatic ecosystem disruption (85) demonstrate that EE operates effectively at sub-nanogram concentrations, consistent with earlier studies such as Rehberger et al. (2020) and da Silva (2025). These effectsranging from feminization of male fish to altered spawning behaviorspose not only biodiversity threats but also indicate food web instability. The ripple effects can extend to human populations that rely on fish and shellfish as dietary staples, indirectly increasing exposure risk through bioaccumulation.

   The soil persistence patterns in Figure 4 and 5 also reveal that EE residues can accumulate in soil (85) and sediments (80), eventually being taken up by crops (65). This cross- environmental transfer implies that EE is not confined to aquatic pollution but represents a broader agro-environmental hazard. As Chen et al. (2021) and Adeel et al. (2023) noted, irrigation with contaminated water can result in measurable hormone residues in plants, posing potential endocrine risks to both wildlife and humans.

   The dose-response curve in Figure 6 reinforces the critical policy relevance of these findings. The narrow gap between ED (30 mg/kg) and TD (60 mg/kg) signifies a low safety threshold, underscoring the compounds potency and the potential danger of chronic low-level exposure. This calls for the establishment of maximum allowable concentrations (MACs) for EE in wastewater effluents and agricultural runoff, which many developing nationsincluding the Philippines have yet to define.

   To address these threats, regulatory agencies must prioritize the integration of advanced treatment technologies, such as ozonation, activated carbon adsorption, and biochar-enhanced filtration, all of which have shown promising removal efficiencies in recent studies (Nguyen et al., 2024; Lopez et al., 2023; Oliveira et al., 2023). Additionally, routine monitoring programs should be institutionalized at both community and industrial levels to track estrogenic compound levels across water, soil, and crop systems.

   From a risk management perspective, the findings suggest that policies should move beyond simple pollutant removal targets. Instead, a multi-tiered management framework should be adopted, involving:

   • Source reduction (limiting pharmaceutical discharge and improper disposal),

   • Technological upgrading (tertiary or advanced oxidation treatment systems),

   • Ecological restoration (constructed wetlands and riparian buffers),

   • Public awareness (education on endocrine disruptor impacts and safe drug disposal).

     Moreovr, national environmental standardssuch as those aligned with RA 9275 (Philippine Clean Water Act)should incorporate endocrine-disrupting compounds (EDCs) as priority emerging pollutants. At the same time, data generated from EE monitoring could be integrated into the Department of Environment and Natural Resources (DENR) Environmental Management Bureau (EMB) system for early warning and mitigation planning.

     In summary, the evidence presented from this systematic review indicates that EE contamination is a multidimensional problemaffecting water, soil, food, and biotic systems. Addressing it requires science-based policymaking, consistent cross-sector collaboration, and sustained community participation. Only through integrated strategies can environmental and human health risks posed by hormonal pollutants like EE be effectively reduced.

4. CONCLUSION AND RECOMMENDATION

1. Conclusion

   This systematic review demonstrates that 17-ethinylestradiol (EE) persists as a critical environmental contaminant with complex pathways and far-reaching impacts across aquatic, terrestrial, and agricultural systems. The consistently higher influent concentrations compared to effluents (Figure 2) confirm that current wastewater treatment facilities are only partially effective in removing estrogenic compounds, allowing residual levels to enter receiving bodies. The toxicity profiles and bioassay data (Figure 3), together with impact scores (Figure 5), reveal that EE remains potent even at trace concentrations, inducing endocrine disruption, reproductive abnormalities, feminization in aquatic organisms, and population-level ecological imbalance.

   Furthermore, the elevated concentrations in soil (~85), sediment (~80), crops (~65), and water (~60) (Figure 4) demonstrate that EE is not confined to aquatic media but transfers through the soilplantwater continuum, raising concerns about bioaccumulation and chronic human exposure through the food chain. The doseresponse relationship (Figure 6) underscores its narrow safety margin, implying that even minimal concentrations can elicit significant biological responses, making it a high-risk micropollutant.

   Altogether, these findings establish EE as a persistent, bioactive, and globally distributed contaminant that demands urgent regulatory intervention, advanced treatment technologies, and integrated environmental monitoring. Future research should prioritize region-specific risk modeling, long- term fate studies, and the development of green pharmaceutical alternatives to reduce EE emissions at the source and safeguard both ecosystem and human health.

2. Recommendations

Based on the findings, this study recommends a multi-level mitigation approach integrating technological, regulatory, and community-based strategies. First, wastewater facilities should adopt advanced treatment processes, such as ozonation, activated carbon adsorption, membrane bioreactors, or biochar

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ISSN: 2278-0181

Vol. 14 Issue 10, October – 2025

filtration, proven to enhance EE removal efficiency. Second, national policies under RA 9275 (Philippine Clean Water Act) must be updated to explicitly include endocrine-disrupting compounds (EDCs) as regulated pollutants, with maximum allowable concentrations (MACs) established for effluent discharge. Third, routine monitoring programs should be institutionalized to track EE levels in water, soil, and crops, supported by inter-agency collaboration between the Department of Environment and Natural Resources (DENR), Department of Agriculture (DA), and local government units. Lastly, public education and pharmaceutical waste management programs are essential to minimize improper drug disposala major source of estrogenic residues. Through these coordinated actions, both environmental integrity and human health protection can be strengthened against the long-term risks posed by synthetic hormonal contaminants like EE.

ACKNOWLEDGMENT

We sincerely extend our deepest gratitude to Almighty God, whose grace and guidance sustained us throughout the completion of this systematic review. Amid moments of doubt and exhaustion, we learned the true value of courage to begin despite uncertainty, to persist through challenges, and to continue with faith and determination. His presence strengthened us during times of difficulty and reminded us that perseverance, when grounded in faith, can transform even the smallest efforts into meaningful achievement.

We would also like to recognize Fae Marie L. Cablao for her unwavering dedication, patience, and leadership throughout this process. Her initiative in organizing, revising, and ensuring the completion of this paper greatly contributed to its overall quality and coherence. We are deeply grateful for her perseverance and the spirit of teamwork she fostered among us. To our groupmates, thank you for your cooperation, understanding, and shared commitment that made this study possible. May this paper stand as a reflection of persistence, faith, and purpose a reminder that success is built not only on knowledge but also on courage and heart. In the spirit of truth, service, and love, every kindness shown to us is a gift we will continually strive to pay forward Lagit lagi, para sa bayan.

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