was observed and at 100 μg/L a decrease of 7.5%; likewise at these concentrations
(10 and 100 μg/L), there was a decrease in the larvae size and a reduction in the
general weight. Regarding bioconcentration, values of 2052.69 ng/g were determined. Naproxen can generate a decrease in the growth of zebrafish and affect early
life development remarkably [43].
Cyprinus carpio exposed to naproxen 10, 50, 100, and 200 μg/L showed a delay
in embryo hatching; a mortality of 24% was determined, and growth was delayed.
Some abnormalities were observed, and mainly pigmentation failure was observed;
at 6-day postfertilization, in addition to malformations, gill cells were affected,
alterations in the larval growth were generated, there was also a reduction in the
body weight in all treated groups, the enzymatic activity was evaluated, and glutathione reductase activity declined; likewise variations were observed in glutathione
transferase levels at 100 and 200 μg/L; finally the LOEC concentration was determined to be 10 μg/L [44].
The exposure of Danio rerio to naproxen at 0, 10, 20, 50, 75, 100, 125, 150,
175, 200, and 240 mg/L for 120 h induced a LC 50 of 115.2 mg/L; for embryos at
96 h, a LC 50 147.6 mg/L was obtained, and a decrease in the hatching rate of the
embryos was observed at 240 mg/L and also generated the greatest delay in
embryonic hatching. The heart rate was decreased as the pharmaceutical concentration increased, and it was significantly inhibited at concentrations of 100 and
125 mg/L. The most frequently observed abnormalities were pericardial edema,
yolk sac edema, and hemagglutination, weak pigmentation, hemorrhage, yolk condensation, and trunk abnormalities including without somites, tail not detached, axial
malformation, and tail twisting. The most frequent sublethal effect was pericardial
edema at a concentration of 20 mg/L; in addition, this malformation aggravated
according to the increase in naproxen concentration, and also exposure to this
pharmaceutical induced liver damage during the larval stage [45].
1.4 Ketoprofen
It is one of the first-line anti-inflammatory drugs for the treatment of several diseases,
and its consumption for human and veterinary use is high; its production in Taiwan
reached 7.9 kilotons in 2006 [46]. It has been detected in many bodies of water,
surface water, groundwater, wastewater, and drinking water and has also been
detected in solid atmospheres around the world [47].
Danio rerio embryos were exposed at 1, 10, and 100 μg/L of ketoprofen through
96 h; several malformations were observed in all concentrations tested, and the most
relevant ones were edema, spinal curvature, slow heartbeat, an elongation of the
heart, yolk sac edema, pericardial edema, and delayed hatching. After 48 h, a high
mortality rate was observed and a decrease in the heart rate at 10 and 100 μg/L,
whereas at 96 h, heart rate decreased significantly in comparison with the control
group. According to these results, it is possible that ketoprofen produces abnormalities in the pericardium that cause alterations in heart rate and blood flow [48].
Teratogenesis and Embryotoxicity Induced by Non-steroidal Anti-Inflammatory. . .
123
(10 and 100 μg/L), there was a decrease in the larvae size and a reduction in the
general weight. Regarding bioconcentration, values of 2052.69 ng/g were determined. Naproxen can generate a decrease in the growth of zebrafish and affect early
life development remarkably [43].
Cyprinus carpio exposed to naproxen 10, 50, 100, and 200 μg/L showed a delay
in embryo hatching; a mortality of 24% was determined, and growth was delayed.
Some abnormalities were observed, and mainly pigmentation failure was observed;
at 6-day postfertilization, in addition to malformations, gill cells were affected,
alterations in the larval growth were generated, there was also a reduction in the
body weight in all treated groups, the enzymatic activity was evaluated, and glutathione reductase activity declined; likewise variations were observed in glutathione
transferase levels at 100 and 200 μg/L; finally the LOEC concentration was determined to be 10 μg/L [44].
The exposure of Danio rerio to naproxen at 0, 10, 20, 50, 75, 100, 125, 150,
175, 200, and 240 mg/L for 120 h induced a LC 50 of 115.2 mg/L; for embryos at
96 h, a LC 50 147.6 mg/L was obtained, and a decrease in the hatching rate of the
embryos was observed at 240 mg/L and also generated the greatest delay in
embryonic hatching. The heart rate was decreased as the pharmaceutical concentration increased, and it was significantly inhibited at concentrations of 100 and
125 mg/L. The most frequently observed abnormalities were pericardial edema,
yolk sac edema, and hemagglutination, weak pigmentation, hemorrhage, yolk condensation, and trunk abnormalities including without somites, tail not detached, axial
malformation, and tail twisting. The most frequent sublethal effect was pericardial
edema at a concentration of 20 mg/L; in addition, this malformation aggravated
according to the increase in naproxen concentration, and also exposure to this
pharmaceutical induced liver damage during the larval stage [45].
1.4 Ketoprofen
It is one of the first-line anti-inflammatory drugs for the treatment of several diseases,
and its consumption for human and veterinary use is high; its production in Taiwan
reached 7.9 kilotons in 2006 [46]. It has been detected in many bodies of water,
surface water, groundwater, wastewater, and drinking water and has also been
detected in solid atmospheres around the world [47].
Danio rerio embryos were exposed at 1, 10, and 100 μg/L of ketoprofen through
96 h; several malformations were observed in all concentrations tested, and the most
relevant ones were edema, spinal curvature, slow heartbeat, an elongation of the
heart, yolk sac edema, pericardial edema, and delayed hatching. After 48 h, a high
mortality rate was observed and a decrease in the heart rate at 10 and 100 μg/L,
whereas at 96 h, heart rate decreased significantly in comparison with the control
group. According to these results, it is possible that ketoprofen produces abnormalities in the pericardium that cause alterations in heart rate and blood flow [48].
Teratogenesis and Embryotoxicity Induced by Non-steroidal Anti-Inflammatory. . .
123