alterations and with the triggering of antioxidant mechanisms. Despite the large
metabolic differences that occur among distinct aquatic species, generally paracetamol exposure results in oxidative stress or in adaptive responses aiming at
preventing the establishment of oxidative stress. Despite the common toxicological
and mechanistic basis, toxicity of paracetamol may be highly variable among
distinct species. According to the study by Nunes et al. [49], toxic effects measured
in terms of EC 50 values for different organisms yielded a remarkable variation.
According to this study, the most sensitive organism was Daphnia magna
(EC 50 ¼ 4.7 mg/L), followed by another crustacean species, namely, Daphnia
longispina (EC 50 ¼ 65.9 mg/L). The bacterial species Vibrio fischeri was also
sensitive to this drug, with a calculated EC 50 ¼ 92.2 mg/L. Algal species were
somewhat tolerant to this pharmaceutical since the EC 50 values calculated for
Raphidocelis subcapitata were of 317.4 mg/L, and for Cylindrospermopsis
raciborskii, of 192.9 mg/L. Aquatic plants were the least sensitive tested model
species, with EC 50 values of 429.9 mg/L for Lemna minor and exceeding 1,000 mg/
L for Lemna gibba.
The presence of paracetamol in the already determined levels is not life threatening for most aquatic organisms, as shown by Trombini et al. [50], after determining the toxic effects of this drug in terms of lethality of the copepod Tisbe battagliai.
This study demonstrated that concentrations that occur nowadays in the wild are not
high enough to cause mortality of this marine species. However, a similar assumption can be established for most anthropogenic compounds, since toxic effects are
likely to be reflected by subtle changes in the physiology of exposed organisms,
rather than resulting in mortality. Consequently, toxicity of drugs must be always
assessed by analyzing subindividual traits that are in close proximity with impacted
pathways, metabolic routes, or pharmacological receptors, whose activation/deactivation may occur as a consequence of the presence of a specific drug. In this sense, a
considerable number of studies have been published demonstrating that paracetamol
exposure can indeed result in significant changes in exposed species. These studies,
in general, report alterations in physiological, biochemical, and metabolic alterations
in key features of selected species.
1.3 Paracetamol Toxicity in Plants
Plant physiology seems to be altered in specific cases by paracetamol exposure, as a
consequence of its uptake and absorption [51] and metabolism [52]. However, this is
not the general rule. The study conducted by Rede et al. [53] assessed the acute
effects of paracetamol on several parameters (germination and growth) of Lactuca
sativa. Paracetamol alone was not capable of altering any of the analyzed parameters
(viz., percentage of seed germination, root elongation, shoot length, and leaf length),
in levels reaching 100 mg/L. These data show that the selected species was refractory
to the presence of this drug. The emergence time of maize (Zea mays L.) was not
affected by paracetamol acute exposure, as demonstrated by Hammad et al.
Ecotoxicological Effects of the Drug Paracetamol: A Critical Review of Past. . .
135
metabolic differences that occur among distinct aquatic species, generally paracetamol exposure results in oxidative stress or in adaptive responses aiming at
preventing the establishment of oxidative stress. Despite the common toxicological
and mechanistic basis, toxicity of paracetamol may be highly variable among
distinct species. According to the study by Nunes et al. [49], toxic effects measured
in terms of EC 50 values for different organisms yielded a remarkable variation.
According to this study, the most sensitive organism was Daphnia magna
(EC 50 ¼ 4.7 mg/L), followed by another crustacean species, namely, Daphnia
longispina (EC 50 ¼ 65.9 mg/L). The bacterial species Vibrio fischeri was also
sensitive to this drug, with a calculated EC 50 ¼ 92.2 mg/L. Algal species were
somewhat tolerant to this pharmaceutical since the EC 50 values calculated for
Raphidocelis subcapitata were of 317.4 mg/L, and for Cylindrospermopsis
raciborskii, of 192.9 mg/L. Aquatic plants were the least sensitive tested model
species, with EC 50 values of 429.9 mg/L for Lemna minor and exceeding 1,000 mg/
L for Lemna gibba.
The presence of paracetamol in the already determined levels is not life threatening for most aquatic organisms, as shown by Trombini et al. [50], after determining the toxic effects of this drug in terms of lethality of the copepod Tisbe battagliai.
This study demonstrated that concentrations that occur nowadays in the wild are not
high enough to cause mortality of this marine species. However, a similar assumption can be established for most anthropogenic compounds, since toxic effects are
likely to be reflected by subtle changes in the physiology of exposed organisms,
rather than resulting in mortality. Consequently, toxicity of drugs must be always
assessed by analyzing subindividual traits that are in close proximity with impacted
pathways, metabolic routes, or pharmacological receptors, whose activation/deactivation may occur as a consequence of the presence of a specific drug. In this sense, a
considerable number of studies have been published demonstrating that paracetamol
exposure can indeed result in significant changes in exposed species. These studies,
in general, report alterations in physiological, biochemical, and metabolic alterations
in key features of selected species.
1.3 Paracetamol Toxicity in Plants
Plant physiology seems to be altered in specific cases by paracetamol exposure, as a
consequence of its uptake and absorption [51] and metabolism [52]. However, this is
not the general rule. The study conducted by Rede et al. [53] assessed the acute
effects of paracetamol on several parameters (germination and growth) of Lactuca
sativa. Paracetamol alone was not capable of altering any of the analyzed parameters
(viz., percentage of seed germination, root elongation, shoot length, and leaf length),
in levels reaching 100 mg/L. These data show that the selected species was refractory
to the presence of this drug. The emergence time of maize (Zea mays L.) was not
affected by paracetamol acute exposure, as demonstrated by Hammad et al.
Ecotoxicological Effects of the Drug Paracetamol: A Critical Review of Past. . .
135