Abstract

Carbamazepine is a pharmaceutical used in patients with seizures and bipolar disorder, which has been found in wastewater and many water resources. This is due to the inadequate disposal of pharmaceutical waste and the lack of treatment of municipal wastewater, as is the case in Colombia. The two main hydrographic basins of Colombia are the Cauca and Magdalena rivers, which are inhabited by the endemic species Striped Catfish (Pseudoplatystoma magdaleniatum). This has become an endangered species for various reasons, including the high contamination level of these rivers. In 2019, mature adult P. magdaleniatum of both sexes were caught in the Cauca river in Colombia. This was in order to assess the concentration of vitellogenin, as a biomarker of endocrine disruption, resulting from exposure to different levels of concentration of the emerging contaminant carbamazepine for 4 months. These tests were carried out in a fish farm. A significant decrease in the vitellogenin concentration was verified in females at concentrations of 25 µg l-1 and 50 µg l-1, and in males at 50 µg l-1 of carbamazepine, with a significance level of p˂0.05. Carbamazepine could cause a negative feedback in gonadotropin secretion, acting as an estrogen mimicker that causes a decrease in the level of vitellogenin.

Introduction

The Cauca river receives wastewater discharges from many municipalities, including those from the third largest city in Colombia, Cali (about 3,000,000 inhabitants). The Cauca and Magdalena rivers are one of the main hydrographic basins in Colombia, as well as being important for the country as a source of fishing production. The economic development of these hydrographic basins, and the concentration of 80% of the country’s human population in these areas, threaten the conservation of ichthyofauna (Galvis and Mojica, 2007). These rivers cover approximately 22% of the territory and receive approximately 60% of the total contamination of the country’s surface waters (Escobar, 2002).

P. magdaleniatum is an endemic and migratory species distributed in the Magdalena-Cauca river basin (Buitrago-Suárez and Burr, 2007). It was classified as a critically endangered threatened species in the red book of freshwater species in Colombia, due to its strong fishing pressure and the deterioration of its habitat (Zárate, et al., 1988). The decrease, of more than 90%, in catches in the last 30 years, together with an increase in the proportion young specimens of small size in the catches, are basic indicators of the fragile state of the Striped Catfish population in the Magdalena basin (Mojica, et al., 2012). In 1973 the catch size was 87 cm (Arias, 1985), which by 1988 had decreased to 54 cm (Zárate, et al., 1989) which illustrates the significant reduction in the supply of this resource.

While pharmaceutical products improve quality of life for humans, the excessive use of these and the fact that wastewater is not properly treated, or not treated at all, have led to the presence of these products in surface waters (Puckowski et al., 2016). Evidence of endocrine disruption caused by pharmaceutical and cleaning products has been reported in animals such as fish (Harries, et al., 2000; Sanchez et al., 2011; Oladejo et al., 2013), affecting their reproduction and development. (Falconer et al. 2006). The presence of endocrine disruptors in aquatic organisms (Konwick et al., 2006; Kolle et al., 2012; Valdés et al., 2014) is considered a problem for the public health of the human population, since many aquatic organisms, such as fish, are highly consumed, as is the case in Colombia. This could also affect the livelihoods of people dedicated to selling fish such as catfish, since endocrine disruption could affect the reproductive capacity of fish (Shioda and Wakabayashi, 2000), and therefore decrease fish production. The risk to the health of the human population posed by compounds of this nature, such as carbamazepine (CMZ), is aggravated by its bioaccumulation in aquatic and terrestrial organisms (Vernouillet et al., 2010), which has been reported mainly in fish (Daughton and Brooks, 2011; Du, et al., 2014; Zhao, et al., 2017).

Alteration in the behavior of aquatic species populations has been evidenced. This can lead to ecological extinction, which is defined as “the reduction of a species to such a low level that, although it is still present in a community, no longer interacts significantly with other species (Estes et al., 1989). This in turn could lead to important ecological changes in aquatic ecosystems (Santos et al. 2010; Brodin et al. 2014; Klaminder et al., 2014; Saaristo et al., 2017).

CMZ has been detected at concentrations from 100 ng l-1 to several mg l-1 in wastewater and surface water (Clara et al. 2005; Bahlmann et al., 2014). This is consistent with its increased use as an antiseptic and anticonvulsant, mainly in the treatment of schizophrenia and bipolar disorders (Miao and Metcalfe, 2003), and the difficulty in removing it in treatment plants (Zhang et al., 2008; Bahlmann et al., 2014; Mehinto, et al., 2016). Exposure to pharmaceuticals can lead to significant responses and adverse outcomes in aquatic organisms (Mehinto et al., 2010; Sánchez, et al., 2011). For example, it could alter the normal production of hormones and proteins essential for the correct functioning of the reproductive system in fish (Corcoran et al., 2010). This is because vitellogenin (VTG), a precursor of the yolk protein, is produced in the liver of the female in response to stimulation by estrogenic chemicals, while in male and juvenile fish VTG is absent or present at very low concentrations (Desforges et al., 2010). Male VTG is a biomarker in the detection of endocrine disruption by chemicals, the presence of VTG in the liver and plasma of juvenile male fish having been used as biomarkers to assess levels of environmental contaminants (Sumpter and Jobling 1995; Kime 1999; Scholz et al. 2004; Reinen et al., 2010). This is because this protein is altered by the presence of emerging pollutants in surface waters, such as CMZ, which is found in aquatic ecosystems worldwide at concentrations of 0.03 to 11.6 μg l-` (Bahlmann et al., 2012; Puckowski, et al., 2016).

Qiang et al, (2016) found that CMZ inhibits the growth and development of zebrafish embryos and larvae. Sex steroid hormones play an important role in sexual differentiation, sexual development, and normal reproduction in fish (Lubzens et al., 2010; Rougeot et al., 2007). Therefore, alteration in the amount of these could affect the normal reproduction process in individuals. Despite the ecotoxicological importance of this, information on the metabolism of pharmaceuticals in various aquatic organisms is still lacking (Mazur and Kenneke, 2008; Mehinto et al., 2010; Connors et al. 2013; Jones et al., 2012).

Due to the effects of this emerging pollutant on aquatic organisms, the objective of this research was to evaluate the effect of exposure to CMZ on vitellogenin concentration in P. magdaleniatum fish.

Methodology

Obtaining the biological material

Eighteen sexually mature, apparently healthy, adult P. magdaleniatum were captured in the Cauca river in the “Bajo Cauca” region of Antioquia (N: 07°50.804 W: 75° 12.314) between January and March 2019. The catfish were transferred to the fish research center of the University of Córdoba’s (CINPIC, Montería, Córdoba, Colombia). In accordance with the large fish transfer protocols a rectangular plastic tank (1.5 x 0.5 x 0.5 m), with a constant aeration system for the fish, was used. Each fish was placed in a 100 cm long polyvinyl chloride tube with the ends covered with mesh.

Although the fish were mature when caught, they were not used immediately. The fish were adapted together to the size of the tanks in the laboratory with water from the river where the fish were captured until the beginning of the experiments. For the beginning of the experimental phase in September 2019, when the fish began a new cycle of gonadal maturation, the fish were transferred to tanks conditioned with a biofloc system using clean water from the CINPIC water distribution system, where the execution of the experimental phase was carried out.

Before starting the experiments, it was verified that the reproducers of Striped Catfish had the characteristics of sexual maturity. In females the papilla was dilated and the abdomen bulging, and the males had a flow of sperm when abdominal pressure was applied. In addition, the average maturity size of the species was measured, and was found to be between 52 and 60 cm (Valderrama, et al., 1988), which served as another indicator of sexual maturity.

Striped Catfish have two marked reproduction peaks, coinciding with the maximum water level, from April to June and September to October (Mojica, et al. 2012). A four-month duration of the trial was considered, because the formation of sexual products and gonadal maturation in Neotropical rheophilic fish, such as Striped Catfish, takes between three and four months (Atencio et al., 2013; Atencio et al., 2014). Furthermore, in tropical rivers, fish reproduction is generally temporary and there is a synchronization between the reproductive processes and the increase in the water level caused by the hydrological regime (Montreuil et al. 2001), which is a critical environmental factor for gonadal maturation and reproduction. As established by Sánchez (2012) and Saborido-Rey (2008), the gonadal development process is related more to exogenous factors (photoperiod, temperature, presence of adults of the opposite sex) than to the endogenous factors (processes and physiological conditions) that lead to vitellogenesis. Therefore, large capacity tanks that could simulate a maximum water level were chosen, and these were shared between females and males, taking into account that these exogenous factors influence the endogenous factors that favor gonadal development.

A standard solution of 1000 mg l-1 of CMZ was prepared. From this solution, 154 ml was used to dope a tank (6173 l) with 25 µg l-1, and 309 ml to dope the other tank (6323 l) with 50 µg l-`. This doping was carried out one week before the exposure of the catfish to CMZ, checking the concentration every three days. The CMZ concentration was maintained in a biofloc system that had prepared one month before. Adult males and females (n = 18) of P. magdaleniatum were randomly separated into three groups (3 males and three females/treatment), and placed in water with different concentrations of CMZ as follows: 0 µg l-1 (baseline fish), 25 µg l-1 and 50 µg l-1. They were kept under these conditions for four months (Figure 1). The baseline fish were placed together in a 500 m3 capacity tank. The 25 µg l-1 group were placed together in a 6173 l tank, with a dissolved oxygen concentration of 5.8 ± 0.9 mg l-1, oxygen saturation percentage of 90.4 ± 3.4%, temperature of 28.4 ± 0.4 ° C, pH of 7.8 ± 0.2, and ammonia concentration of 0.36 ± 0.2 mg l-1. The 50 µg l-1 group were placed together in a 6323 l tank with 50 µg l-1 of CMZ with a dissolved oxygen concentration of 4.9 ± 0.1 mg l-1, oxygen saturation percentage of 89.7 ± 4.3%, temperature of 28.5 ± 0.3 ° C, pH of 7.8 ± 0.08, and ammonia concentration of 0.37 ± 0.2 mg l-1.

Fig. 1.

Experimental design of adult P. magdaleniatum fish exposed to three levels of CMZ concentration.

Fig. 1.

Experimental design of adult P. magdaleniatum fish exposed to three levels of CMZ concentration.

The weight and length presented by the fish before being exposed to the levels of the contaminant do not show significant variation with respect to the final conditions of the specimens after exposure to CMZ (Table 1).

Table 1.

Length and weight of P. magdaleniatum fish from the experimental design.

FemalesMales
Exposure time0 µg l-125 µg l-150 µg l-10 µg l-125 µg l-150 µg l-1
0 months Length (cm) 64.66 ± 1.24 61.3 ± 4.0 59.3 ± 2.1 58.6 ± 2.0 59 ± 4.5 57.6 ± 3.2 
Weight (g) 2000 ± 81.6 1916 ± 236.2 1736 ± 212.1 1850 ± 147.1 1700 ± 264.5 1600 ± 264.5 
4 months Length (cm) 61.6 ± 3.2 61.5 ± 3.2 68.8 ± 12.3 56.8 ± 1.0 61.3 ± 5.0 61.3 ± 1.6 
Weight (g) 1566 ± 169.9 1721 ± 175.2 1716 ± 426.3 1179 ± 76.8 1661 ± 332.5 1766 ± 84.8 
FemalesMales
Exposure time0 µg l-125 µg l-150 µg l-10 µg l-125 µg l-150 µg l-1
0 months Length (cm) 64.66 ± 1.24 61.3 ± 4.0 59.3 ± 2.1 58.6 ± 2.0 59 ± 4.5 57.6 ± 3.2 
Weight (g) 2000 ± 81.6 1916 ± 236.2 1736 ± 212.1 1850 ± 147.1 1700 ± 264.5 1600 ± 264.5 
4 months Length (cm) 61.6 ± 3.2 61.5 ± 3.2 68.8 ± 12.3 56.8 ± 1.0 61.3 ± 5.0 61.3 ± 1.6 
Weight (g) 1566 ± 169.9 1721 ± 175.2 1716 ± 426.3 1179 ± 76.8 1661 ± 332.5 1766 ± 84.8 

The concentration of CMZ in water was measured and corrected weekly during the fish adaptation process. Analysis of water samples from tanks followed the EPA method 1694 (Pharmaceutical and personal care products in water, 2007) with slight modifications. An Acquity UPLC H-class system coupled to Xevo TQD (Waters, Manchester, UK) was used in the analyzes. The chromatographic method was used for the quantification of CMZ in water.

During the execution of the treatments the catfish were fed with 100 fish (Yellow Mojarra and Sardines Cocobolo) per tank each week.

Methodology for collecting blood samples from female and male P. magdaleniatum

To take blood samples from each of the catfish, a deep circular container containing water from the tank where the fish was in captivity was used, facilitating the maintenance of the water quality conditions described above. Before taking blood samples the specimens were sedated with 50 mg l-1 of eugenol for an exposure time of three minutes. Samples were then obtained through a puncture in the caudal vascular bundle, extracting 3 to 4 ml of blood per individual in a vacutainer tube (Vacuette ®, Greiner Bio one, USA) with ethylene diamine acetic acid (EDTA) anticoagulant.

After 4 months of exposure of the fish to the three levels of CMZ concentration, blood samples were collected again from sexually mature adult males and females. Next, the samples were centrifuged between 2000 to 3000 r.p.m. for 20 minutes. The supernatant for VTG analysis was then collected with the enzyme linked immunosorbent assay (ELISA) kit (MyBiosource, USA), before VTG levels were determined with a detection range of 10 ng ml-1 - 480 ng ml-1 and 1.0 ng ml-1 sensitivity.

ELISA kit methodology

The enzyme linked immunosorbent assay (ELISA) kit (MyBiosource, USA) was used to determine the concentration of VTG in blood samples. A 6-point curve was made from standards A (0 ng ml-1), B (30 ng ml-1), C (60 ng ml-1), D (120 ng ml-1), E (240 ng ml-1) and F (480 ng ml-1) in duplicate.

The analysis method for VTG with the ELISA kit followed the manufacturer’s instructions in the assay procedure as shown in the manual Cat No: MBS779081, without any modification.

Statistical analysis

The effects of the following factors that could influence the VTG concentration were analyzed: CMZ concentration (0 µg l-1, 25 µg l-1 and 50 µg l-1) with three levels; times of exposure (start and end of each treatment) with two levels; and the interaction of the levels chosen for each of these in the VTG. An analysis of variance (ANOVA) with a significance level of 5% was performed on the results, through R Project Statistical computing. The Tukey test of multiple comparisons was then performed as a post hoc test, complying with normality, homogeneity of variance, randomness, data independence and homoscedasticity, with multiple comparisons tests between treatments with a significance value of p˂0.05 considered statistically significant.

Results

Plasma VTG concentrations of P. magdaleniatum

Results showed significant statistical differences (p ˂ 0.05) between treatments. Exposure time and concentration of CMZ influenced the decrease in VTG. In this study, the selected P. magdaleniatum females showed a significant reduction (p ˂ 0.05) in plasma concentration of VTG after four months exposure to CMZ concentrations at 25 µg l-1 and 50 µg l-1 (Figure 2).

Fig. 2.

Plasma VTG concentration (ng ml-1) in males and females of P. magdaleniatum exposed to CMZ.

Note: Treatments with different letters differ significantly (p ˂ 0.05) between time and two levels of CMZ concentration.

Fig. 2.

Plasma VTG concentration (ng ml-1) in males and females of P. magdaleniatum exposed to CMZ.

Note: Treatments with different letters differ significantly (p ˂ 0.05) between time and two levels of CMZ concentration.

Similarly, male fish showed a significant difference between treatment at 0 µg l-1 and 50 µg l-1, with vitellogenin concentration decreasing by 30% after 4 months of treatment. Significant differences were not shown between the treatments of 0 µg l-1 and 25 µg l-1, as seen in Figure 2.

Based on the results obtained, it was evidenced that, for females and males, treatments decreased VTG concentration after exposure to CMZ after 4 months exposure at 25 µg l-1 and 50 µg l-1 for 4 months. However the concentration of VTG in males in treatment at 25 µg l-1 when compared to treatment at 0 µg l-1 it was not significant.

Discussion

The environmental conditions of the Cauca river in the “Bajo Cauca” region, where the catfish used in the experimentation were obtained, are not good. As a result, fish caught from the natural environment in the Cauca river, that were used as baseline fish (0 µg l-1) to indicate average VTG values at the beginning of treatments, did not show a significant difference in the concentration of VTG between females and males. However, according to Sumpter and Jobling (1995) the appearance of VTG in the blood plasma of male fish is an important biomarker, used to detect the exposure of fish to estrogenic endocrine disruptors possibly found in their natural habitats, such as pharmaceuticals including ibuprofen, paracetamol, phenazone, CMZ, and nonylphenols, which are known to be xenoestrogens (Moeder, et al. 2000). This could cause an endocrine alteration in males, taking into account that synthesis of VTG is higher in females when they are at the peak of their reproductive cycle. For example, feminization of male fish, observed in British rivers, is attributed to the presence of estrogenic compounds, according to Desbrow et al., 1998. The male VTG production gene is inactive when the fish is in favorable and normal conditions in its habitat (Gupta and Verma, 2020), so it can be inferred that the conditions of the natural environment where the fish came from were not favorable, leading to disruptive processes in the synthesis of VTG.

This means that the water contains a large amount of pollutants. For example, of 14 points sampled to determine CMZ in different points of the Cauca river (Colombia), 2 points showed concentrations between 8 and 10.66 μg l-1 of CMZ, 6 showed concentrations between the limit of quantification (0.001 μg l-1) and 2 μg l-1, and 6 showed concentrations lower than the limit of quantification (Delgado, 2019). The concentration of CMZ used in the experimentation with catfish was equal to or greater than 25 μg l-1, a concentration that is above that found in natural water in Colombia. In this study it was decided to use concentrations of CMZ above the concentrations found in the Cauca river, to make the effect of CMZ more noticeable in the individuals studied. Treatments with exposure to 25 μg l-1 and 50 μg l-1 of CMZ for females and exposure to 50 μg l-1 for males decreased the concentration of VTG with respect to treatment at 0 μg l-1 of CMZ after 4 months of exposure. CMZ concentration in water was verified, in order to establish how much CMZ needed to be added to maintain the initial CMZ concentration level. Therefore, one of the most important factors in the decrease in VTG concentration was CMZ. The decrease in the concentration of VTG with respect to the concentration evaluated in the baseline fish and the initial measurement at time zero for both sexes can be explained, according to Solé et al., 2003, by the negative feedback stimulus of the secretion of gonadotropin by estrogen mimickers, which is responsible for the decrease in the level of VTG without a decrease in the level of 17 β-estradiol. Other studies in the UK, Europe, Japan, and North America have shown that the reproductive abnormalities exhibited by fish are consistent with exposure to concentrations of estrogens, estrogen chemicals, and estrogen mimickers present in treated wastewater (Solé, et al., 2000; Christiansen et al., 2002). Thus, in this case, CMZ could act as an estrogenic mimicker, causing VTG decrease in the Striped Catfish evaluated.

Despite the results, it is not ruled out that other factors could have influenced VTG levels, although exposure of Striped Catfish to CMZ for 4 months was a significant factor that could have influenced the decrease in VTG. However, measurement was made at only one point of time after the start of the treatments. Therefore, it cannot be inferred that time was a factor that influenced the decrease in VTG. Arnold et al., 1996, attribute a possible decrease in the VTG level to the histological alterations of estrogen receptors in the liver. Meanwhile, Barucca et al., 2006, suggest that an increase in the levels of VTG in females promotes ovarian development and an increase in VTG in males may be the result of estrogenic chemicals which also suppress testicular development and maturation of sperm.

Furthermore, throughout the reproductive cycle, seasonal changes occur in the biochemical composition (water, lipids, glycogen and proteins) of fish tissues. This is especially so for females, where hepatic metabolism is stimulated during vitellogenesis (Lubzens et al., 2010). However, when fish are exposed to an additional factor in their habitat such as CMZ, VTG production can be altered.

Conclusions

The results obtained in this study showed a significant reduction in the synthesis of VTG in females for concentrations of 25 and 50 μg l-1 and in males at 50 μg l-1 of CMZ, with respect to the baseline fish treatments (0 μg l-1), with no effect of the exposure time. Thus, CMZ could cause a negative feedback in gonadotropin secretion, acting as a mimicker of estrogens responsible for a decrease in the level of VTG.

Therefore, it is suggested that other studies are carried out with different CMZ concentrations and on other aquatic organisms. Exposure to CMZ also presents a risk to other species, and so it is important to determine the concentration levels of this compound that could alter their reproductive system.

Declaration of conflicting interest

I certify that this manuscript is an unpublished research work and is not submitted for publication in another journal. I also state that all authors are aware of the inclusion of their names by the co-authors in this article, have participated in all steps for drafting the manuscript and have no conflicts of interest.

Acknowledgements

We thank the Fish Research Center group of the University of Córdoba, led by Professor Víctor Atencio, who supported the experimental phase of this research work. We also thank the University of Antioquia for the approval of the experimental phase in Act 99 on September 29, 2015 by the Ethics Committee for animal testing.

Funding

Finally, we thank the Pollution Diagnosis and Control Group (GDCON) and Colciencias for financing the project.

References

Arias, P. A.
1985
.
Las ciénagas de Colombia (The wetlands of Columbia. In Spanish.)
.
INDERENA-Rev. Divulgación Pesquera
.
22
(
3
),
38
-
70
.
Arnold, H., Pluta, H., Braunbeck, T.,
1996
.
Sublethal effects of prolonged exposure to disulfoton in rainbow trout (oncorhynchus mykiss): Cytological alterations in the liver by a potent acetylcholine esterase inhibitor
.
Ecotox. Environ. Safe.
34
(
1
),
43
-
55
.
Atencio, V., Kerguelén, E., Naar, E., Petro, R.,
2013
.
Desempeño reproductivo del bocachico Prochilodus magdalenae inducido dos veces en un mismo año. (Reproductive performance of the bocachico Prochilodus magdalenae induced twice in the same year. In Spanish.)
.
Rev. MVZ Córdoba
18
(
1
),
3304
-
3310
.
Atencio, V., Monsalve, J., Hernández, M., Espinosa, J., Pardo-Carrasco, S.,
2014
.
Reproductive performance of the catfish Sorubim cuspicaudus hormonally induced twice in the same year
.
Proceedings of World Aquaculture Adelaide 2014
;
2014 jun 7-14
;
World Aquaculture Society, Adelaide (South Australia)
.
Bahlmann, A., Carvalho, J.J., Weller, M.G., Panne, U., Schneider, R.J.,
2012
.
Immunoassays as high-throughput tools: Monitoring spatial and temporal variations of carbamazepine, caffeine and cetirizine in surface and wastewaters
.
Chemosphere
89
(
11
),
1278
-
1286
.
Bahlmann, A., Brack, W., Schneider, R. J., Krauss, M,
2014
.
Carbamazepine and its metabolites in wastewater: Analytical pitfalls and occurrence in germany and portugal
.
Water Res.
57
,
104
-
114
.
Barucca, M., Canapa, A., Olmo, E., Regoli, F.,
2006
.
Analysis of vitellogenin gene induction as a valuable biomarker of estrogenic exposure in various Mediterranean fish species
.
Environ. Res.
101
(
1
),
68
-
73
.
Brodin, T., Piovano, S., Fick, J., Klaminder, J., Heynen, M., Jonsson, M.,
2014
.
Ecological effects of pharmaceuticals in aquatic systems— impacts through behavioural alterations
.
Philos. Trans. R. Soc. Lond.
,
B, Biol. Sci.
369
(
1656
),
1
-
10
.
Buitrago-Suárez, U. A., Burr, B. M.,
2007
.
Taxonomy of the catfish genus pseudoplatystoma bleeker (siluriformes: Pimelodidae) with recognition of eight species
.
Zootaxa
. (
1512
),
1
-
38
.
Christiansen, L., Winther-Nielsen, M., Helweg, C.,
2002
.
Feminization of fish: the effect of estrogenic compounds and their fate in sewage treatment plants and nature
.
Danish Environmental Protection Agency
729
,
1
184
.
Clara, M., Strenn, B., Gans, O., Martinez, E., Kreuzinger, N., Kroiss, H.,
2005
.
Removal of selected pharmaceuticals, fragrances and endocrine disrupting compounds in a membrane bioreactor and conventional wastewater treatment plants
.
Water Res.
39
(
19
),
4797
-
4807
.
Connors, K. A., Du, B., Fitzsimmons, P. N., Hoffman, A. D., Chambliss, C. K., Nichols, J. W., Brooks, B. W.,
2013
.
Comparative pharmaceutical metabolism by rainbow trout (oncorhynchus mykiss) liver S9 fractions
.
Environ. Toxicol. Chem.
32
(
8
),
1810
-
1818
.
Corcoran, J., Winter, M.J., Tyler, Ch.,
2010
.
Pharmaceuticals in the aquatic environment: A critical review of the evidence for health effects in fish
.
Crit. Rev. Toxicol.
40
(
4
),
287
-
304
.
Daughton, C. G. Brooks, B. W.,
2011
.
Environmental contaminants in wildlife: Interpreting tissue concentrations
.
Taylor and Francis
.
8
,
281
-
341
.
Delgado, N.,
2019
.
Diagnóstico y remoción de contaminantes emergentes en aguas superficiales y cloacales. Tesis de doctorado. (Diagnosis and removal of emerging pollutants in surface and sewage waters (Thesis). In Spanish.)
.
Universidad Nacional de la Plata
,
Buenos Aires, Argentina
.
Desbrow, C., Routledge, E. J., Brighty, G. C., Sumpter, J. P., Waldock, M.,
1998
.
Identification of estrogenic chemicals in STW effluent. 1. chemical fractionation and in vitro biological screening
.
J. Environ. Sci. Technol.
32
(
11
),
1549
-
1558
.
Desforges, J.P., Peachey, B.D., Sanderson, P.M., White, P.A., Blais, J.M,
2010
.
Plasma vitellogenin in male teleost fish from 43 rivers worldwide is correlated with upstream human population size
.
Environ Pollut.
158
(
10
):
3279
-
84
.
Du, B., Haddad, S. P., Luek, A., Scott, W. C., Casan, W., Saari, G. N., Kristofco, L. A., Connors, K., Rash, Ch., Rasmussen, J., Chambliss, C., Brooks, B. W.,
2014
.
Bioaccumulation and trophic dilution of human pharmaceuticals across trophic positions of an effluent-dependent wadeable stream
.
Philos. Trans. R. Soc. Lond., B, Biol. Sci.
369
(
1656
),
1
-
10
.
EPA US
,
2007
.
EPA Method: 1694, Pharmaceuticals and personal care products in water, soil, sediment and biosolids by HPLC/ M/M. EPA-821-R-08-002
(
2007
)
Escobar, J.,
2002
.
La contaminación de los ríos y sus efectos en las áreas costeras y el mar. (River pollution and its effects on coastal areas and the sea. In Spanish)
.
Comisión económica para América Latina y el Caribe (CEPAL) (Economic Commission for Latin America and the Caribbean)
,
Santiago de Chile, Chile
.
Estes, J., Duggins, D., Rathbun, G.,
1989
.
The ecology of extinctions in kelp forest communities
.
Conserv. Biol.
3
(
3
),
252
-
264
.
Falconer, I. R., Chapman, H. F., Moore, M. R., Ranmuthugala, G.,
2006
.
Endocrine-disrupting compounds: A review of their challenge to sustainable and safe water supply and water reuse
.
Environ. Toxicol.
21
(
2
),
181
-
191
.
Galvis, G., Mojica, J. I.,
2007
.
The Magdalena River freshwater fishes and fisheries
.
Aquat ecosyst health.
10
(
2
),
127
-
139
.
Gupta, P., Verma, S. K.,
2020
.
Impacts of herbicide pendimethalin on sex steroid level, plasma vitellogenin concentration and aromatase activity in teleost clarias batrachus (linnaeus)
.
Environ. Toxicol. Pharmacol.
75
(
103324
).
Harries, J. E., Runnalls, T., Hill, E., Harris, C. A., Maddix, S., Sumpter, J. P., Tyler, C. R.,
2000
.
Development of a reproductive performance test for endocrine disrupting chemicals using pair-breeding fathead minnows (pimephales promelas)
.
J. Environ. Sci. Technol.
34
(
14
),
3003
-
3011
.
Jones, H. S., Trollope, H. T., Hutchinson, T. H., Panter, G. H., Chipman, J. K.,
2012
.
Metabolism of ibuprofen in zebrafish larvae
.
Xenobiotica
42
(
11
),
1069
-
1075
.
Kime, D. E.,
1999
.
A strategy for assessing the effects of xenobiotics on fish reproduction
.
Sci. Total Environ
.
225
(
1-2
),
3
-
11
.
Klaminder, J., Jonsson, M., Fick, J., Sundelin, A., Brodin, T.,
2014
.
The conceptual imperfection of aquatic risk assessment tests: Highlighting the need for tests designed to detect therapeutic effects of pharmaceutical contaminants
.
Environ. Res. Lett.
9
(
8
),
1
-
7
.
Kolle, S. N., Ramirez, T., Kamp, H. G., Buesen, R., Flick, B., Strauss, V., van Ravenzwaay, B.,
2012
.
A testing strategy for the identification of mammalian, systemic endocrine disruptors with particular focus on steroids
.
Regul. Toxicol. Pharm.
63
(
2
),
259
-
278
.
Konwick, B. J., Garrison, A. W., Black, M. C., Avants, J. K., Fisk, A. T.,
2006
.
Bioaccumulation, biotransformation, and metabolite formation of fipronil and chiral legacy pesticides in rainbow trout
.
J. Environ. Sci. Technol.
40
(
9
),
2930
-
2936
.
Lubzens, E., Young, G., Bobe, J., Cerdà, J.,
2010
.
Oogenesis in teleosts: How fish eggs are formed
.
Gen. Comp. Endocrinol.
165
(
3
),
367
-
389
.
Mazur, C. S., Kenneke, J. F.,
2008
.
Cross-species comparison of conazole fungicide metabolites using rat and rainbow trout (onchorhynchus mykiss) hepatic microsomes and purified human CYP 3A4
.
J. Environ. Sci. Technol.
42
(
3
),
947
-
954
.
Mehinto, A. C., Hill, E. M., Tyler, C. R.,
2010
.
Uptake and biological effects of environmentally relevant concentrations of the nonsteroidal anti-inflammatory pharmaceutical diclofenac in rainbow trout (oncorhynchus mykiss)
.
J. Environ. Sci. Technol.
44
(
6
),
2176
-
2182
.
Mehinto, A. C., Jayasinghe, B. S., Vandervort, D. R., Denslow, N. D., Maruya, K. A.,
2016
.
Screening for endocrine activity in water using commercially-available in vitro transactivation bioassays
.
J. Vis. Exp.
(
118
).
Miao, X., Metcalfe, C. D.,
2003
.
Determination of carbamazepine and its metabolites in aqueous samples using liquid chromatography - electrospray tandem mass spectrometry
.
Anal. Chem.
75
(
15
),
3731
-
3738
.
Moeder, M., Schrader, S., Winkler, M., Popp, P.,
2000
.
Solid-phase microextraction-gas chromatography-mass spectrometry of biologically active substances in water samples
.
Journal of Chromatography A.
873
(
1
),
95
-
106
.
Mojica, J. I., Valderrama, M. y Barreto, C.
2012
.
Pseudoplatystoma magdaleniatum
. In: Mojica, J.I., Usma, J. S.; Álvarez-León, R. y Lasso, C. A. (Eds.),
2012
.
Libro rojo de peces dulceacuícolas de Colombia 2012. (Red Book of Freshwater Fishes of Colombia 2012. In Spanish)
, pp.
57
-
59
.
Instituto de Investigación de Recursos Biológicos Alexander von Humboldt, Instituto de Ciencias Naturales de la Universidad Nacional de Colombia, WWF Colombia y Universidad de Manizales Bogotá
,
D. C., Colombia
.
Montreuil, V., García A., Rodríguez R.
2001
.
Biología reproductiva de Prochilodus nigricans (boquichico), en la Amazonía peruana
.
Folia Amazónica
,
12
(
1-2
),
5
-
13
.
Oladejo, J., Olanrewaju Fatoba, O., Petrik, L.F.
2013
.
A Review of Pharmaceuticals and Endocrine-Disrupting Compounds: Sources, Effects, Removal, and Detections
.
Water Air and Soil Pollution
,
224
(
1770
):
1
-
29
Puckowski, A., Mioduszewska, K., Łukaszewicz, P., Borecka, M., Caban, M., Maszkowska, J., Stepnowski, P.,
2016
.
Bioaccumulation and analytics of pharmaceutical residues in the environment: A review
.
J. Pharm. and Biomed. Anal.
127
,
232
-
255
.
Qiang, L., Cheng, J., Yi, J., Rotchell, J. M., Zhu, X., Zhou, J.,
2016
.
Environmental concentration of carbamazepine accelerates fish embryonic development and disturbs larvae behavior
.
Ecotoxicology
,
25
(
7
),
1426
-
1437
.
Reinen, J., Suter, M. J. -., Vögeli, A. C., Fernandez, M. F., Kiviranta, H., Eggen, R. I. L., Vermeulen, N. P. E.,
2010
.
Endocrine disrupting chemicals-linking internal exposure to vitellogenin levels and ovotestis in abramis brama from dutch surface waters
.
Environ. Toxicol. Pharmacol.
30
(
3
),
209
-
223
.
Rougeot, C., Krim, A., Mandiki, S. N. M., Kestemont, P., Mélard, C.,
2007
.
Sex steroid dynamics during embryogenesis and sexual differentiation in eurasian perch, perca fluviatilis
.
Theriogenology
.
67
(
5
),
1046
-
1052
.
Saaristo, M., McLennan, A., Johnstone, C. P., Clarke, B.O., Wong, B. B.M.,
2017
.
Impacts of the antidepressant fluoxetine on the anti-predator behaviors of wild guppies (Poecilia rericulata)
.
Aquat. Toxicol.
183
,
38
-
45
.
Saborido-Rey, F.,
2008
.
Ecología de la reproducción y potencial reproductivo en las poblaciones de peces marinos
. Digital CSIC Ed. Disponible en: http://hdl.handle.net/10261/7260.
Sánchez, R.,
2012
.
Modelo de estrategias reproductivas en peces que forman agrupaciones de desove. (Tesis de Grado Doctor en Ciencias Marinas. (Model of reproductive strategies in fish that form spawning groups
. In Spanish Thesis. Doctor in Marine Sciences.
Instituto Politécnico Nacional. Centro Interdisciplinario de Ciencias Marinas
.
La Paz. BCS
.
Sánchez, W., Sremski, W., Piccini, B., Palluet, O., Maillot— Marechal, E., Betoulle, S., Jaffal, A., Ait— Aisa, S., Brion, F., Thybaud, E., Hinfray, N., Porcher, J. M.,
2011
.
Adverse effects in wild fish living downstream from pharmaceutical manufacture discharges
.
Environ. Int.
37
(
8
),
1342
1348
.
Santos, L. H. M. L. M., Araújo, A. N., Fachini, A., Pena, A., Delerue-Matos, C., Montenegro, M. C. B. S. M.,
2010
.
Ecotoxicological aspects related to the presence of pharmaceuticals in the aquatic environment
.
J. Hazard. Mater.
175
(
1-3
),
45
-
95
.
Scholz, S., Kordes, C., Hamann, J., Gutzeit, H. O.,
2004
.
Induction of vitellogenin in vivo and in vitro in the model teleost medaka (oryzias latipes): Comparison of gene expression and protein levels
.
Mar. Environ. Res.
57
(
3
),
235
-
244
.
Shioda, T., Wakabayashi, M.,
2000
.
Effect of certain chemicals on the reproduction of medaka (Oryzias latipes)
.
Chemosphere
,
40
,
239
243
.
Solé, M., De Alda, M. J. L., Castillo, M., Porte, C., Ladegaard-Pedersen, K., Barceló, D.,
2000
.
Estrogenicity determination in sewage treatment plants and surface waters from the catalonian area (NE spain)
.
J. Environ. Sci. Technol.
34
(
24
),
5076
-
5083
.
Solé, M., Raldua, D., Piferrer, F., Barceló, D. Porte, C., ,
2003
.
Long -term exposure effects in vitellogen in, sex hormones, and biotransformation enzymes in female carp in relation to a sewage treatment works
.
Ecotoxicol. Environ. Saf.
56
, (
3
),
373
-
380
.
Sumpter, J. P., Jobling, S.,
1995
.
Vitellogenesis as a biomarker for estrogenic contamination of the aquatic environment
.
Environ. Health Perspect.
103
(
SUPPL. 7
),
173
-
178
.
Valderrama, M., Zárate, M., Vera, G., Moreno, C., P. Caraballo, P., J. Martíne, J.,
1988
.
Determinación de la talla media de madurez y análisis de la problemática con referencia a las tallas medias de captura del bagre rayado Pseudoplatystoma fasciatum Linnaeus (Pisces: Pimelodidae) en la cuenca del río Magdalena, Colombia
. (Determination of the average size at maturity and analysis of the problem with reference to the average catch sizes of striped catfish Pseudoplatystoma fasciatum Linnaeus (Pisces: Pimelodidae) in the Magdalena river basin, Colombia. In Spanish).
Trianea
.
2
,
537
-
549
.
Valdés, M. E., Amé, M. V., Bistoni, M. D. L. A., Wunderlin, D. A.,
2014
.
Occurrence and bioaccumulation of pharmaceuticals in a fish species inhabiting the Suquía river basin (Córdoba, Argentina)
.
Sci. Total Environ.
472
,
389
-
396
.
Vernouillet, G., Eullaffroy, P., Lajeunesse, A., Blaise, C., Gagné, F., Juneau, P.,
2010
.
Toxic effects and bioaccumulation of carbamazepine evaluated by biomarkers measured in organisms of different trophic levels
.
Chemosphere
,
80
(
9
),
1062
-
1068
.
Zárate, M., J. Martinez, J., Caraballo, P.R.,
1988
.
Captura y esfuerzo pesquero en la cuenca del río Magdalena y su sistema de planos inundables durante la subienda 1987 y estado actual de sus pesquerías. Informe Técnico
. (Capture and fishing effort in the Magdalena river basin and its floodplain system during the shoal 1987 and current state of its fisheries. Technical report. In Spanish.) INDERENA, San Cristóbal (Bolívar)
Zárate, M., J. Martinez, J., Caraballo, P.R., Vera, G., Valderrama, M.,
1989
.
Evaluación de la captura y esfuerzo pesquero en la cuenca del río Magdalena y su sistema de planos inundables durante la subienda 1988. Informe Técnico
. (Evaluation of the catch and fishing effort in the Magdalena river basin and its floodplains system during the shoal 1988. Technical report. In Spanish). INDERENA, San Cristóbal (Bolívar). Zarate, 1989.
Zhang, Y., Geißen, S., Gal, C.,
2008
.
Carbamazepine and diclofenac: Removal in wastewater treatment plants and occurrence in water bodies
.
Chemosphere
,
73
(
8
),
1151
-
1161
.
Zhao, J., Furlong, E. T., Schoenfuss, H. L., Kolpin, D. W., Bird, K. L., Feifarek, D. J., Schwab, E.A.,Ying, G., ,
2017
.
Uptake and disposition of select pharmaceuticals by bluegill exposed at constant concentrations in a flow-through aquatic exposure system
.
J. Environ. Sci. Technol.
51
(
8
),
4434
-
4444
.