Complete Characterization of Degradation Byproducts of Olmesartan Acid, Degradation Pathway, and Ecotoxicity Assessment
Round 1
Reviewer 1 Report
The science is sound and the topic very relevant, as Sartan based compounds have been increasingly detected in the environment, and risk assessments have characterized them as potentially highly toxic. The main caveat of the manuscript at this point is the lack of information on exposure concentrations in the toxicity test - to try to understand the real risks in the environment and even to human health. It is generally accepted that any chemical compound in an excessively high concentration is toxic, so without this information (exposure concentration) to give context the manuscript falls short. I believe the authors can deal with this easily, and perhaps add a bit of information also on the discussion section - context of environmental concentrations - either wwtp or other systems.
Other minor comments:
Title - a bit repetitive, consider removing Elucidation of Their
Line 24 - evaluated on - evaluated in
line 26 - should indicate at which concentration range
Line 35 - repeats line 31, same sentence
Line 33 pollutants by definition don't include organisms - cyanobacteria- or naturally occurring compounds produced by organisms - mycotoxins - could you rephrase or remove these
Line 36 - Hence, there is a need to remove this new class of pollutants - which class of pollutants? you mentioned several in the previous sentence, please clarify
Line 42 -44 - not exactly true - there are EU level regulations for risk assessment requirements for e.g. pesticides, pharmaceuticals - need to rephrase
Line 45 - potentially toxic to microorganisms ... creating problems for the environment and humans. could you clarify? they are also potentially toxic to other organisms not just microorganisms
L55-56 - should mention that preliminary data already point to high environmental risk and toxicity of sartan based compounds detected in the aquatic environment (e.g. Fonseca 2021 doi: 10.1016/j.scitotenv.2021.147021; Mijangos 2018 https://doi.org/10.1016/j. watres.2018.09.033).
Line 56 CEs - is it ECs?
Line 69 - fig1 legend. remove already - also consider this figure in the Materials and methods section.
section 2.4. - and results and discussion- what were the concentrations used - this is relevant for environmental and human risk assessment - if concentrations well above those found in the environment, then risk would be low - toxicity needs to be in this context - so this information is key
Author Response
Dear reviewer,
I am pleased to submit the revised version of our manuscript entitled: "Complete Characterization of Degradation Byproducts of Olmesartan Acid, Elucidation of Their Degradation Pathway and Ecotoxicity Assessment" by G. Luongo et al., which I would like you consider for publication for the Special issue "Degradation and Transformation of Drugs and Organic Pollutants in Wastewater: Detection, Environmental Fate, and Remediation".
First of all, let me thank the referees for the gratifying comments and constructive criticisms. I have found referees’ remarks very punctilious and useful to improve the quality of the manuscript, and most of them have been taken into account during these revisions.
More in detail, replies:
Reviewer #1
Other minor comments:
The science is sound and the topic very relevant, as Sartan based compounds have been increasingly detected in the environment, and risk assessments have characterized them as potentially highly toxic. The main caveat of the manuscript at this point is the lack of information on exposure concentrations in the toxicity test - to try to understand the real risks in the environment and even to human health. It is generally accepted that any chemical compound in an excessively high concentration is toxic, so without this information (exposure concentration) to give context the manuscript falls short. I believe the authors can deal with this easily, and perhaps add a bit of information also on the discussion section - context of environmental concentrations - either wwtp or other systems.
Authors: as suggested, some information have also been added on the discussion section.
Other minor comments:
Title - a bit repetitive, consider removing Elucidation of Their
Line 24 - evaluated on - evaluated in
line 26 - should indicate at which concentration range
Line 35 - repeats line 31, same sentence
Line 33 pollutants by definition don't include organisms - cyanobacteria- or naturally occurring compounds produced by organisms - mycotoxins - could you rephrase or remove these
Line 36 - Hence, there is a need to remove this new class of pollutants - which class of pollutants? you mentioned several in the previous sentence, please clarify
Line 42 -44 - not exactly true - there are EU level regulations for risk assessment requirements for e.g. pesticides, pharmaceuticals - need to rephrase
Line 45 - potentially toxic to microorganisms ... creating problems for the environment and humans. could you clarify? they are also potentially toxic to other organisms not just microorganisms
L55-56 - should mention that preliminary data already point to high environmental risk and toxicity of sartan based compounds detected in the aquatic environment (e.g. Fonseca 2021 doi: 10.1016/j.scitotenv.2021.147021; Mijangos 2018 https://doi.org/10.1016/j. watres.2018.09.033).
Line 56 CEs - is it ECs?
Line 69 - fig1 legend. remove already - also consider this figure in the Materials and methods section.
section 2.4. - and results and discussion- what were the concentrations used - this is relevant for environmental and human risk assessment - if concentrations well above those found in the environment, then risk would be low - toxicity needs to be in this context - so this information is key
Authors: for all comments above we have been accepted by making the required corrections.
Reviewer 2 Report
Evaluation and specific comments
Authors present the results on the degradation of one pharmaceutical (olmesartan acid) belonging to the emerging pollutants. Six new degradation byproducts were identified, the degradation mechanism was proposed and ecotoxicity of parent compound and its degradation byproducts to bacteria and algae was assessed. The study are interesting, however, the manuscript needs improvements before considering to publish it. There is a lack of statistical evaluation of the ecotoxicity and almost no discussion in this paper.
Line 35: “there is a need to remove this new class of pollutants” – please specify here which pollutants you are referring to; in the previous sentence several groups of organic pollutants were listed
Lines 37-41: please rephrase this sentence: „Compared to organic pollutants, the concentration of these pollutants is much lower (on the order of ppm or ppb), and this characteristic has led to their classification as emerging contaminants (Emerging Contaminant (EC)), emerging organic contaminants (Emerging Organic Pollutants (EOP) or Persistent Organic Pollutants (POPs)” – the following needs clarification “compared to organic pollutants”? – to which one? Tested compound – olmesartan is organic compound. Please use the SI units e.g. mg/kg or mg/L, and decide are these pollutants “emerging organic contaminants” or “persistent organic pollutants”
Line 55: change “CEs” to “ECs”
Line 57: explain abbreviation “DDD”
Lines 69-79: please provide justification for this research, clearly formulate the objectives of this study and outline the importance for the environment
Line 93: please provide SI unit instead of ppm
Lines 122-125: this is the description of the results - transfer to chapter 3
Lines 255-267: please rephrase this paragraph – in its current form it is rather summary of methodological part than results and discussion
Line 269: please change “..degradation byproducts DP1-DP9” to “..degradation byproducts DP10-DP22”
Lines 288-301: the ecotoxicity data have to be statistically evaluated – method used for this evaluation (e.g. ANOVA) and significance level should be indicated in Figure 4.
Line 291: in DP22 stimulation was only observed in one test with R. subcapitata – please check and correct
Line 294: the inhibition growth rate of algae in DP16 exceed 70% - such toxicity was in the A. fischeri (not algae) test (Figure 4)
Lines 294-298: I disagree with the order of acute and chronic toxicity; according to results shown in Figure 4 the highest toxicity (the highest inhibition) in A. fischeri test (acute) was observed in DP16 and the lowest in DP14 (contrary to what the authors say). In the R. subcapitata test the highest inhibition was for DP10 and the lowest toxicity for DP22. Please carefully check the results in Figure 4 and correct this chapter.
Author Response
Dear Reviewr,
I am pleased to submit the revised version of our manuscript entitled: "Complete Characterization of Degradation Byproducts of Olmesartan Acid, Elucidation of Their Degradation Pathway and Ecotoxicity Assessment" by G. Luongo et al., which I would like you consider for publication for the Special issue "Degradation and Transformation of Drugs and Organic Pollutants in Wastewater: Detection, Environmental Fate, and Remediation".
First of all, let me thank the referees for the gratifying comments and constructive criticisms. I have found referees’ remarks very punctilious and useful to improve the quality of the manuscript, and most of them have been taken into account during these revisions.
More in detail, our replies:
Evaluation and specific comments
Authors present the results on the degradation of one pharmaceutical (olmesartan acid) belonging to the emerging pollutants. Six new degradation byproducts were identified, the degradation mechanism was proposed and ecotoxicity of parent compound and its degradation byproducts to bacteria and algae was assessed. The study are interesting, however, the manuscript needs improvements before considering to publish it. There is a lack of statistical evaluation of the ecotoxicity and almost no discussion in this paper.
Authors: as required, the ecotoxicity was discussed and statistical analysis was added.
Line 35: “there is a need to remove this new class of pollutants” – please specify here which pollutants you are referring to; in the previous sentence several groups of organic pollutants were listed
Lines 37-41: please rephrase this sentence: „Compared to organic pollutants, the concentration of these pollutants is much lower (on the order of ppm or ppb), and this characteristic has led to their classification as emerging contaminants (Emerging Contaminant (EC)), emerging organic contaminants (Emerging Organic Pollutants (EOP) or Persistent Organic Pollutants (POPs)” – the following needs clarification “compared to organic pollutants”? – to which one? Tested compound – olmesartan is organic compound. Please use the SI units e.g. mg/kg or mg/L, and decide are these pollutants “emerging organic contaminants” or “persistent organic pollutants”
Line 55: change “CEs” to “ECs”
Line 57: explain abbreviation “DDD”
Lines 69-79: please provide justification for this research, clearly formulate the objectives of this study and outline the importance for the environment
Line 93: please provide SI unit instead of ppm
Lines 122-125: this is the description of the results - transfer to chapter 3
Lines 255-267: please rephrase this paragraph – in its current form it is rather summary of methodological part than results and discussion
Line 269: please change “..degradation byproducts DP1-DP9” to “..degradation byproducts DP10-DP22”
Lines 288-301: the ecotoxicity data have to be statistically evaluated – method used for this evaluation (e.g. ANOVA) and significance level should be indicated in Figure 4
Line 291: in DP22 stimulation was only observed in one test with R. subcapitata – please check and correct
Line 294: the inhibition growth rate of algae in DP16 exceed 70% - such toxicity was in the A. fischeri (not algae) test (Figure 4)
Lines 294-298: I disagree with the order of acute and chronic toxicity; according to results shown in Figure 4 the highest toxicity (the highest inhibition) in A. fischeri test (acute) was observed in DP16 and the lowest in DP14 (contrary to what the authors say). In the R. subcapitata test the highest inhibition was for DP10 and the lowest toxicity for DP22. Please carefully check the results in Figure 4 and correct this chapter.
Authors: for all comments above we have been accepted by making the required corrections.
Round 2
Reviewer 2 Report
I reviewed this manuscript in the first round and had several comments, almost all my remarks were addressed. However, I still disagree with the description of ecotoxicity results. It is not consistent with results shown in Figure 4.
Firstly, from data given in Figure 4 it is obvious that in DP 16 the inhibition of A. fischeri luminescence exceed 70%, while in Lines 315-316 (version 2 of the manuscript) authors wrote “the inhibition of the growth rate of algae in DP16 exceeded 70%” – this is not true and have to be corrected before publishing.
Secondly, an order of acute toxicity should be as follows: DP14 < DP20 < DP21 < DP15 < DP22 < DP11 < DP10 < DP12 < DP18 < DP19 < DP13 < DP16 – in DP14 the inhibition (and hence toxicity) in A. fischeri was the lowest and in DP 16 – the highest.
Thirdly, an order of chronic toxicity should be: DP22 > DP20 > DP14 > DP13 > DP18 > DP15 > DP19 > DP12 > DP21 > DP11 > DP10 > DP16 – In the R. subcapitata test (chronic test) the highest inhibition was for DP10 and DP16 and the lowest toxicity for DP22.
Author Response
Dear Editor,
I am pleased to submit the revised version of our manuscript entitled: "Complete Characterization of Degradation Byproducts of Olmesartan Acid, Elucidation of Their Degradation Pathway and Ecotoxicity Assessment" by G. Luongo et al., which I would like you consider for publication for the Special issue "Degradation and Transformation of Drugs and Organic Pollutants in Wastewater: Detection, Environmental Fate, and Remediation".
I found the referee's remarks very punctilious and useful to improve the quality of the manuscript, and all have been taken into account during these revisions.
The corrections are highlighted in revision style (Revised applsci-1223996_with revisions.docx). We also attached a version of the final manuscript, where corrections are not highlighted (Revised applsci-1223996.docx).
best regards
Prof. Armando Zarrelli