these effects can be subtle or severe and can be manifested during embryonic
development or subsequently throughout the life of the organisms. For the most
part, embryotoxicity and teratogenicity studies focus on the development of mammals; however, contaminants such as pharmaceuticals manage to reach the bodies of
water and come into contact with aquatic organisms; therefore, toxicity tests in early
development stages of aquatic organisms are important since these organisms have
its entire life cycle in aquatic environments and are frequently exposed to multiple
stressors; this kind of studies can be useful for the identification and prioritization of
development toxic substances [20].
Aquatic organisms are more sensitive during early stages of development; this
may be because organisms in early stages of development have highly permeable
membranes as well as different rates of absorption distribution and detoxification.
Immature detoxification mechanisms can increase sensitivity to toxic agents, due to
diverse physiological, morphological, and biochemical characteristics; since in the
early life stages these responses are underdeveloped or have not yet fully developed,
this contributes to a greater sensitivity compared to adult organisms [21].
Teratogens can affect morphogenesis, development, differentiation, and cell
death; generate failures in cell interactions and cell movement; and affect cellular
processes and different tissues; this can generate abnormalities and necrosis and can
cause birth defects [22]. The effects on the development occur due to different
mechanisms, depending on the teratogen agent will be the mechanism of action,
and there may be more than one of them involved in the generation of adverse
effects; there are some mechanisms described that can cause developmental alterations, some are disruptions in the central nervous system, modifications to DNA,
enzymatic inhibition, hormonal alterations, cell membranes disruption, proteins or
cellular organelles disturbances, and oxidative stress; Fig. 3 illustrates briefly how in
one way NSAIDs can cause alterations in development and therefore teratogenesis
[24, 25].
Since the toxicity of NSAIDs has been proven, special attention has been paid to
the study of the possible toxic effects that these can generate in early development, in
aquatic organisms; therefore some embryotoxic and teratogenic effects reported are
described below.
1.1 Diclofenac
Diclofenac is one of the most widely used non-steroidal anti-inflammatory pharmaceuticals worldwide [26] and has been frequently detected in surface waters and
effluents from wastewater treatment plants in concentrations in order of μg/L
[27]. Some adverse effects caused by diclofenac have been reported previously,
and herein are described some effects detected in early life stages of aquatic
organisms.
The exposure of two Argentina native amphibians Trachycephalus typhonius and
Physalaemus albonotatus to diclofenac at concentrations ranging from 125 to
4,000 μg/L for 96 h resulted in an LC 50 of 2,828.43 μg/L and 2,462.29 μg/L,
118
I. Pérez-Alvarez et al.
development or subsequently throughout the life of the organisms. For the most
part, embryotoxicity and teratogenicity studies focus on the development of mammals; however, contaminants such as pharmaceuticals manage to reach the bodies of
water and come into contact with aquatic organisms; therefore, toxicity tests in early
development stages of aquatic organisms are important since these organisms have
its entire life cycle in aquatic environments and are frequently exposed to multiple
stressors; this kind of studies can be useful for the identification and prioritization of
development toxic substances [20].
Aquatic organisms are more sensitive during early stages of development; this
may be because organisms in early stages of development have highly permeable
membranes as well as different rates of absorption distribution and detoxification.
Immature detoxification mechanisms can increase sensitivity to toxic agents, due to
diverse physiological, morphological, and biochemical characteristics; since in the
early life stages these responses are underdeveloped or have not yet fully developed,
this contributes to a greater sensitivity compared to adult organisms [21].
Teratogens can affect morphogenesis, development, differentiation, and cell
death; generate failures in cell interactions and cell movement; and affect cellular
processes and different tissues; this can generate abnormalities and necrosis and can
cause birth defects [22]. The effects on the development occur due to different
mechanisms, depending on the teratogen agent will be the mechanism of action,
and there may be more than one of them involved in the generation of adverse
effects; there are some mechanisms described that can cause developmental alterations, some are disruptions in the central nervous system, modifications to DNA,
enzymatic inhibition, hormonal alterations, cell membranes disruption, proteins or
cellular organelles disturbances, and oxidative stress; Fig. 3 illustrates briefly how in
one way NSAIDs can cause alterations in development and therefore teratogenesis
[24, 25].
Since the toxicity of NSAIDs has been proven, special attention has been paid to
the study of the possible toxic effects that these can generate in early development, in
aquatic organisms; therefore some embryotoxic and teratogenic effects reported are
described below.
1.1 Diclofenac
Diclofenac is one of the most widely used non-steroidal anti-inflammatory pharmaceuticals worldwide [26] and has been frequently detected in surface waters and
effluents from wastewater treatment plants in concentrations in order of μg/L
[27]. Some adverse effects caused by diclofenac have been reported previously,
and herein are described some effects detected in early life stages of aquatic
organisms.
The exposure of two Argentina native amphibians Trachycephalus typhonius and
Physalaemus albonotatus to diclofenac at concentrations ranging from 125 to
4,000 μg/L for 96 h resulted in an LC 50 of 2,828.43 μg/L and 2,462.29 μg/L,
118
I. Pérez-Alvarez et al.