Stability of the Macrocyclic Gd-DOTA Contrast Agent (DOTAREM) under Different Estuarine Environmental Conditions

Round 1

Reviewer 1 Report

The work is interesting and important because it complements the knowledge in the area of fate in the environment of compounds used in diagnostics as contrasts and based on complexes with Gd.

The experiment to obtain information on the persistence of such complexes in the environment was well planned.

The results are well and fairly presented.

The weaker point of the manuscript is the discussion of the results.

I suggest to reorganize the discussion:

1. remove information that is repeated from Introduction.

2. move to Introduction the information that should be in this chapter.

3. do not repeat in the Discution the information that should be in the Results and in the discussion itself avoid repeating the previously provided information.

4. I suggest to add:

- information that free Gd+3 is very toxic to living organisms, including humans (specify values...);

- discussion whether the results suggest that the presence of free Gd in the environment may reach concentrations dangerous for the environment/human;

- discussion whether the obtained results allow forecasting the impact on the environment in the long term;

Also, Conclusion is like Abstract, not Conclusion. I suggest re-editing the Conclusion.

Author Response

Please see the attachment

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments for author File: Comments.pdf

The flow of the writing is good but some terminologies are not well described. Also, there are some typos. 

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 3 Report

The authors studied the stability of Gadolinium-based contrast agents in wastewater. The work has merit for a possible publication, but it needs additional experiments and to re-write some parts. 

1) Please re-write the abstract and avoid redundant sentences like: "In this study, it was studied". 

2) The radiation experiments design can be improved. If evaporation is a problem, you can use a scale to quantify how much water was loss, and eventually correct the concentration. Also, the area of the plastic tank directly exposed to the light should be provided. i.e. the geometric shape of the container is important to reproduce the results.  I recommend to repeat that experiments (just 96 h) for the current paper (and not future work). 

3) Additionally, the authors do not mention why Gd3+ (free) is preferable in the nature instead of to the Gd-DOTA. 

Minor issues:

Figure 1) Algés is marked red on title's figure.  

Figure 3) and 4) Change Contolo to Control on the legend. 

Figure 4) where is the s36 data?

Table 6, exposure time is days? Don't you mean hours?

Why tables are green?  

Please review the English.  

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

please, check in all manuscript distance between digit and % [example line 242]

Author Response

The Authors are grateful for the comments and suggestions made by the reviewer, which allowed, once again, to improve the quality of the final manuscript.
All changes were made and are included in the revised version that is now being submitted.

Reviewer 2 Report

The comments have been addressed well form the authors. The manuscript looks good for publication.

Author Response

The Authors are grateful for the comments and suggestions made by the reviewer, which allowed, once again, to improve the quality of the final manuscript.

Reviewer 3 Report

The authors proceeded to the requested changes, and replied to all the questions. Although the radiation experiments deserved to be repeated, the authors justified why they could not repeat them. 

Minor:

Line 86, replace comma by dot Ktherm = 25,2–25,8

line 130: .. were left in plastic tanks on the  130 exterior (building’s roof).
Please add the dimensions of the tank (LxWxH) and the surface area exposed. 

The English is OK.

Author Response

The Authors are grateful for the comments and suggestions made by the reviewer, which allowed, once again, to improve the quality of the final manuscript.
All changes were made and are included in the revised version that is now being submitted.