at concentrations of 1,000 and 2,000 μg/L; a decrease in the hatching rate was
observed; however, the development was not affected, and no malformations were
observed, nor significant adverse effects in early life stages, nor substantial changes
were detected in stress proteins [33].
The evaluation 0.01, 0.05, 0.1, 0.5, 1 μg/L of diclofenac using Mytilus
galloprovincialis as a bioindicator, changes in the larval development were
observed, from the lowest concentration of barley (0.01 μg/L). Several
malformations were observed, as well as deformations of the dorsal margin line in
the shell of D-larvae; the LOAEC determined value was 0.01 μg/L. Diclofenac can
seriously disturb the development of mollusks in the larval state at concentrations as
low as 0.01 μg/L, without showing effects at higher concentrations. This research
shows that bivalves are sensitive to environmentally relevant concentrations of
diclofenac demonstrating the capacity of this pharmaceutical of generating irregularities in the formation of the shell [34].
Xenopus laevis embryos were exposed at diclofenac 1, 4, 16, 32, and 64 mg/L; the
frequency of malformations increased from 16 mg/L and higher concentrations; at
24 h of exposure, 100% mortality was generated in embryos exposed to 64 mg/L.
LC 50 of 30.32 mg/L and MC 50 of 12.25 mg/L were obtained, and a teratogenic index
of 2.64 was determined, demonstrating that diclofenac has teratogenic potential, and
as the degree of mortality increases, the degree of malformations increases as well.
The most commonly observed malformations were axis, gut, heart, head, and eye
abnormalities as well as blistering (edema); as the diclofenac concentration
increased, larval length decreased; during stage 36, malformations observed were
cardiac and intestinal. Effects on gene expression were generated; these failures
indicate that the damage caused by diclofenac may be related with some proteins; it
also generated neurological development failures [35]. The exposure of Xenopus
laevis and Lithobates catesbeianus to 1, 4, 8, 16, 32, and 62.5 mg/L diclofenac
resulted in a LC 50 for X. laevis of 12.11 mg/L and LC 50 9.56 mg/L for
L. catesbeianus; the highest concentration (62.5 mg/L, 100%) of mortality was
reached in both organisms; all concentrations generated a decrease in the larvae
size in both organisms; X. laevis was more sensitive than L. catesbeianus. The
teratogenic index for X. laevis was 3.5 and for L. catesbeianus was 4.2. The most
frequently observed malformations were axial malformations in the tail and notochord, edema, and hypopigmentation. Thus, this drug is a teratogenic agent for
Xenopus laevis and Lithobates catesbeianus [17].
1.2 Ibuprofen
It is the third over-the-counter anti-inflammatory drug with the highest consumption
worldwide, which is why it has been constantly detected in many bodies of water,
rivers, and wastewaters, and the concentrations in which it has been detected are in
the range of ng/L–μg/L [36, 37].
The exposure of adult organisms of Danio rerio to ibuprofen 1 μg/L induced
alterations in reproduction, decreased the number of spawned eggs, 10 μg/L
Teratogenesis and Embryotoxicity Induced by Non-steroidal Anti-Inflammatory. . .
121
observed; however, the development was not affected, and no malformations were
observed, nor significant adverse effects in early life stages, nor substantial changes
were detected in stress proteins [33].
The evaluation 0.01, 0.05, 0.1, 0.5, 1 μg/L of diclofenac using Mytilus
galloprovincialis as a bioindicator, changes in the larval development were
observed, from the lowest concentration of barley (0.01 μg/L). Several
malformations were observed, as well as deformations of the dorsal margin line in
the shell of D-larvae; the LOAEC determined value was 0.01 μg/L. Diclofenac can
seriously disturb the development of mollusks in the larval state at concentrations as
low as 0.01 μg/L, without showing effects at higher concentrations. This research
shows that bivalves are sensitive to environmentally relevant concentrations of
diclofenac demonstrating the capacity of this pharmaceutical of generating irregularities in the formation of the shell [34].
Xenopus laevis embryos were exposed at diclofenac 1, 4, 16, 32, and 64 mg/L; the
frequency of malformations increased from 16 mg/L and higher concentrations; at
24 h of exposure, 100% mortality was generated in embryos exposed to 64 mg/L.
LC 50 of 30.32 mg/L and MC 50 of 12.25 mg/L were obtained, and a teratogenic index
of 2.64 was determined, demonstrating that diclofenac has teratogenic potential, and
as the degree of mortality increases, the degree of malformations increases as well.
The most commonly observed malformations were axis, gut, heart, head, and eye
abnormalities as well as blistering (edema); as the diclofenac concentration
increased, larval length decreased; during stage 36, malformations observed were
cardiac and intestinal. Effects on gene expression were generated; these failures
indicate that the damage caused by diclofenac may be related with some proteins; it
also generated neurological development failures [35]. The exposure of Xenopus
laevis and Lithobates catesbeianus to 1, 4, 8, 16, 32, and 62.5 mg/L diclofenac
resulted in a LC 50 for X. laevis of 12.11 mg/L and LC 50 9.56 mg/L for
L. catesbeianus; the highest concentration (62.5 mg/L, 100%) of mortality was
reached in both organisms; all concentrations generated a decrease in the larvae
size in both organisms; X. laevis was more sensitive than L. catesbeianus. The
teratogenic index for X. laevis was 3.5 and for L. catesbeianus was 4.2. The most
frequently observed malformations were axial malformations in the tail and notochord, edema, and hypopigmentation. Thus, this drug is a teratogenic agent for
Xenopus laevis and Lithobates catesbeianus [17].
1.2 Ibuprofen
It is the third over-the-counter anti-inflammatory drug with the highest consumption
worldwide, which is why it has been constantly detected in many bodies of water,
rivers, and wastewaters, and the concentrations in which it has been detected are in
the range of ng/L–μg/L [36, 37].
The exposure of adult organisms of Danio rerio to ibuprofen 1 μg/L induced
alterations in reproduction, decreased the number of spawned eggs, 10 μg/L
Teratogenesis and Embryotoxicity Induced by Non-steroidal Anti-Inflammatory. . .
121