How Pharmaceutical Residues Occur, Behave, and Affect the Soil Environment

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The present manuscript entitled “How Pharmaceutical Residues Occur, Behave, and Affect the Soil Environment" discusses pharmaceutical pollutants and their influence on the soil environment, which is an important issue in the current scenario. The study sounds interesting as the authors included comprehensive data about the source, behaviour, and fate of pharmaceutical residues in soils. I didn’t find any major flaws in this manuscript; however, a few points need to be addressed, as mentioned below:

1. Is there a specific reason for including the 2010-2024 publication period? Justify this in the text.

2. Why is the search string restricted to two keywords: pharmaceuticals and soils? The other keywords, such as pollutants, and wastewater treatment, could have been used in combination with pharmaceuticals, which might have generated more results.

3. The Introduction section can briefly discuss the background information regarding previous studies or comprehensive reviews conducted elsewhere in the world on the same topic.

4. What prompted the authors to initiate this study? It should be mentioned at the end of the introduction section.

5. The current study doesn’t specify whether the literature survey is restricted only to Europe or worldwide. The authors have primarily used European case studies as their reference material.

6. As far as bioremediation of pharmaceutically polluted sites is concerned, it would have been great if the authors could specifically mention/enlist plant species used.

 

 

Author Response

Comments to reviewer 1

Thanks for your kind and useful comments

 

The present manuscript entitled “How Pharmaceutical Residues Occur, Behave, and Affect the Soil Environment" discusses pharmaceutical pollutants and their influence on the soil environment, which is an important issue in the current scenario. The study sounds interesting as the authors included comprehensive data about the source, behaviour, and fate of pharmaceutical residues in soils. I didn’t find any major flaws in this manuscript; however, a few points need to be addressed, as mentioned below:

1. 
   Is there a specific reason for including the 2010-2024 publication period? Justify this in the text.

• This was due to the exponential growth of publications during this period (justified in the text).

2. 
   Why is the search string restricted to two keywords: pharmaceuticals and soils? The other keywords, such as pollutants, and wastewater treatment, could have been used in combination with pharmaceuticals, which might have generated more results.

• The search was restricted to pharmaceuticals and soils because the use of other keywords such as pollutants include many other compounds, mainly pesticides and the term wastewater treatment is mainly referred to the evolution of pollutants during water treatment. In any case, there are various references in the text to the behavior of pharmaceutical during wastewater treatment.
• As specified in Introduction, “A review of the literature obtained from the Web of Science™ (WoS), managed by Clarivate Analytics (Philadelphia, PA, USA), using the following search terms, “emerging pollutants” (title) OR “emerging contaminants” (title) AND “environment” (topic) AND “2010-2024” (year published), revealed more than 2,600 publications, with a clear trend of exponential growth over the last decades.

3. 
   The Introduction section can briefly discuss the background information regarding previous studies or comprehensive reviews conducted elsewhere in the world on the same topic.

• The introduction contains 55 references. In Section 3, there are many more references on the sources of pharmaceuticals in the environment, where various relevant reviews are included.

4. 
   What prompted the authors to initiate this study? It should be mentioned at the end of the introduction section.

• At the end of the introduction section, we mentioned “Although PhMs are generally present at low environmental concentrations, it remains uncertain whether their presence in terrestrial and aquatic environments may undesirably affect wildlife and humans. Therefore, to have a better knowledge of their impact on the environment and human health, information on their occurrence, behavior and fate in the environment must be studied in detail. Therefore, the occurrence, environmental fate and effects of PhMs on the soil are the focus of this review”.

5. 
   The current study doesn’t specify whether the literature survey is restricted only to Europe or worldwide. The authors have primarily used European case studies as their reference material.

• The study is not limited to Europe. Other worldwide studies are included in the text, although normative is mainly related to European directives.

6. 
   As far as bioremediation of pharmaceutically polluted sites is concerned, it would have been great if the authors could specifically mention/enlist plant species used.

• According to you, the following sentence has been included: For the removal of PhMs in soils, several plant species have been highlighted, such as Salix exigua (7α-ethynylestradiol), Helianthus annus (tetracycline and oxytetracycline), Softstem bulrush (caffeine, naproxen, diclofenac, carbamazepine and clofibric acid), Brassica nigra (aspirin and tetracycline), Typha latifolia, Phragmites, Iris germanica, Juncus effuses and Phragmites australis (ibuprofen), Lemna gibba (lomefloxacin, sulfamethoxazole, and chlortetracycline) or Glycine max (carbamazepine, diphenhydramine, fluoxetine, triclosan and triclocarban) among others [198].

 

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

The manuscript deals with a very current topic and has been well organized by the authors resulting in a linear reading. Only observation: I would advise the authors to standardize table 1 and table 2 regarding Log Kow (specify in table 1 what it corresponds to in the same way as in table 2) and water solubility (table 1 solubility (H2O) while in table 2 water solubility).

Author Response

Comments to reviewer 2

Thanks for your kind and useful comments

The manuscript deals with a very current topic and has been well organized by the authors resulting in a linear reading. Only observation: I would advise the authors to standardize table 1 and table 2 regarding Log Kow (specify in table 1 what it corresponds to in the same way as in table 2) and water solubility (table 1 solubility (H2O) while in table 2 water solubility).

• Following your suggestion, K_OW and water solubility have been standardized in both tables.

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

The authors, based on data from articles downloaded from the WoS database, developed a multi-faceted study on PhMs, their sources, behaviour and impact on the environment. Although the article is interesting and necessary in the face of the systematically increasing inflow of PhMs into the environment, it is very long and some sections (e.g. soil remediation) actually contain general information on the remediation of chemically polluted soils and not specific information regarding the remediation of soils containing PhMs. Generally I think that some sections (Adsorption/desorption, Biochemical degradation, Run-off, Impact of PhMs on the soil health) have too long introductory parts, which unnecessarily lengthen this already long article. I consider to shorten them to the minimum.

Detailed comments

Line 47 explain the abbreviations, please

Line 78-79 repetition from the abstract

Line 260 spelling mistake

Table 2 – explain abbreviations ex. GUS index

Conclusions:  shorten the first part of them, please

Comments on the Quality of English Language

Generally it is ok. I noticed only some spelling mistakes.

Author Response

Comments to reviewer 3

Thanks for your kind and useful comments

 

The authors, based on data from articles downloaded from the WoS database, developed a multi-faceted study on PhMs, their sources, behaviour and impact on the environment. Although the article is interesting and necessary in the face of the systematically increasing inflow of PhMs into the environment, it is very long and some sections (e.g. soil remediation) actually contain general information on the remediation of chemically polluted soils and not specific information regarding the remediation of soils containing PhMs. Generally I think that some sections (Adsorption/desorption, Biochemical degradation, Run-off, Impact of PhMs on the soil health) have too long introductory parts, which unnecessarily lengthen this already long article. I consider to shorten them to the minimum.

• Most of the specified techniques for soil remediation are valid for PhMs. According to your suggestion, Section 4 has been shortened, as far as possible, to maintain scientific rigor.

 

Detailed comments

Line 47 explain the abbreviations, please

• The text has been rewritten as follows: …. due to the development of analytical techniques, mainly gas (GC) and liquid (LC) chromatography coupled to mass spectrometry (MS) ……

Line 78-79 repetition from the abstract

• The sentence has been rewritten.

 

Line 260 spelling mistake

• Mistake has been corrected (an has been changed by a).

 

Table 2 – explain abbreviations ex. GUS index

• (Groundwater Ubiquity Score) has been included.

Conclusions:  shorten the first part of them, please

• The first paragraph has been shortened according to your suggestion.

 

 

Author Response File: Author Response.pdf

Reviewer 4 Report

Comments and Suggestions for Authors

The article raises a very important issue of contamination of the soil environment with pharmaceuticals. Such a review work is needed because many works on this topic have been published since the beginning of the 21st century. However, I believe that the work in its current form should not be published. It contains a lot of unnecessary information: Table 1, Table 3, chapter 6, fragment on volatile compounds, a lot of generalities and repetitions. At the same time, it does not contain necessary data presented in an orderly manner, e.g. a table of data on the occurrence of drugs, drug persistence in soil, Kd values, etc.

Pharmaceuticals are a very complex group of chemical compounds. The division into therapeutic classes (according to ATC) is not the same as the division into groups according to chemical structure. Therefore, statements such as "Even within the same therapeutic class, half lives can vary significantly (line 507)" do not make sense. Such generalities should be removed from the entire text.

Chapter 3 entitled “Sources of PhMs in the environment” should be tidied up. The authors should focus on the presence of PhMs in sewage sludge and soil environment and indicate general trends. They only gave examples of the presence of pharmaceuticals in different compartments including cultivated plants and their parts. In most European countries, the use of growth regulators in animal husbandry is banned.

There is a lot of text at the beginning of Section 4.2 on sorption, which was discussed in the previous chapter. As the authors pointed out, degradation was a complex process and depended on many factors. However, they did not indicate how or on which factors it depends. They also did not write that this process can lead to total or only partial degradation. Additionally, substances in the environment undergo transformations, not just degradation, e.g. hydroxylation, polymerization. This should be taken into account and the subsection titles corrected.

Table 3 gives complicated formulas, but without any indication of whether they have ever been used in the analysis of pharmaceuticals.

Paragraph 4.2.1 discusses photodegradation, but without explicitly stating that it can only occur on the soil surface. Even a thin layer of soil protects substances from UV radiation.

The concept of biochemical degradation introduced by the authors is misleading because the word "biochemical" is also associated with the action of organisms and not with both abiotic and biotic reactions.

Paragraph 4.3.2 should be deleted. Do the authors know of any pharmaceutical that is volatile? This also applies to mentions of the volatility of substances in other paragraphs (e.g. 4.3.5).

Chapter 4.3.4. deals with bioaccumulation very superficially and contains false statements. Bioaccumulation (in the authors' assumption - only in animals) does not depend only on Kow, but also, for example, on lipid content in organisms. Absorption is most often not through binding to receptors (line 700).

On the other hand, paragraph 4.3.5. is very extensive, but does the discussed absorption of substances by plants apply to PhMs? In line 744 the authors contradict their data presented in Table 1. The data on hydroponics is not a good example of drug uptake from soil (line 747).

In Chapter 5, in addition to general statements on soil health, data on the effects of PhMs on microorganisms are given. However, in addition to microorganisms, there are also other organisms in the soil (e.g. earthworms) and this effect should also be discussed.

Chapter 6 provides a very good discussion of remediation, particularly of soils. However, this issue is completely unrelated to pharmaceutical contamination. No soils have yet been identified that are contaminated with pharmaceuticals to such an extent that they require remediation. The entire chapter should be removed from this work.

The summary points out the fundamental role of "clays" and "humus" in the fate of PhMs in soil (line 1050). In the main text, this role is only mentioned.

Minor comments:

A list of abbreviations should be added to make the paper easier to read

The abbreviation PhMs has not been used so far.

Line 37, 51. microorganisms cannot be classified as compounds or substances

The list of citations should be made in accordance with the guideline for authors

Line 64. Active pharmaceutical ingredients should be instead of “drugs”

Line 81. The phrase "health effects" should not be used in the context of algae.

Line 178. illicit drugs are not pharmaceuticals! Opioids can be both drugs and illicit drugs. This should be clearly stated in the publication.

Why are these substances included in Table 1? What was the selection criterion?

Line 262. What do the Authors understand by the term: “immunize pathogenic microorganisms”?

Table 2. Should be: days instead of dias.

Line 416. Did you mean “pharmaceuticals”?

Line 648. Plants are also organisms and bioaccumulation can also occur in them.

General sentences should be removed, e.g. "Other studies have found similar results (line 774)".

Line 828. “persistent”?

Line 894. What do the terms: Cambisol, Chernozem, Arenozol mean?

Author Response

Comments to reviewer 4

Thanks for your kind and useful comments

The article raises a very important issue of contamination of the soil environment with pharmaceuticals. Such a review work is needed because many works on this topic have been published since the beginning of the 21st century. However, I believe that the work in its current form should not be published. It contains a lot of unnecessary information: Table 1, Table 3, chapter 6, fragment on volatile compounds, a lot of generalities and repetitions. At the same time, it does not contain necessary data presented in an orderly manner, e.g. a table of data on the occurrence of drugs, drug persistence in soil, Kd values, etc.

• We respect your opinion.

 

Pharmaceuticals are a very complex group of chemical compounds. The division into therapeutic classes (according to ATC) is not the same as the division into groups according to chemical structure. Therefore, statements such as "Even within the same therapeutic class, half lives can vary significantly (line 507)" do not make sense. Such generalities should be removed from the entire text.

• We agree with your comment on PhMs classification. The sentence has been deleted

 

Chapter 3 entitled “Sources of PhMs in the environment” should be tidied up. The authors should focus on the presence of PhMs in sewage sludge and soil environment and indicate general trends. They only gave examples of the presence of pharmaceuticals in different compartments including cultivated plants and their parts. In most European countries, the use of growth regulators in animal husbandry is banned.

• We honestly think that section 3 is well organized. PhMs are often found in significant concentrations in soils due to the continuous release of effluent and sludge from wastewater treatment plants (WWTPs), which is much faster than what they're capable of removing. Although they are generally present at low environmental concentrations, conventional wastewater treatment cannot successfully remove PhMs from influent streams and biosolids. In addition, soil application of animal manure can result in the pollution of soil, surface water, and groundwater with PhMs through surface runoff and leaching. It is true that growth regulators are banned in most European countries. However, they are used in other parts of the world.

 

There is a lot of text at the beginning of Section 4.2 on sorption, which was discussed in the previous chapter. As the authors pointed out, degradation was a complex process and depended on many factors. However, they did not indicate how or on which factors it depends. They also did not write that this process can lead to total or only partial degradation. Additionally, substances in the environment undergo transformations, not just degradation, e.g. hydroxylation, polymerization. This should be taken into account and the subsection titles corrected.

• This subsection has been shortened trying not to lose scientific rigor. We include now the following sentence at the beginning of the section: “Sorption is one of the key processes affecting the fate, mobility, migration and bioavailability of PhMs in the soil environment. It depends on several factors such as physico chemical properties of soil and PhMs, soil reaction, surface activity, temperature and moisture.
• At the end of Subsection 4.2, we say: “Due to the large number of PhMs with different properties currently in use, the number of metabolites or transformation products generated by dealkylation, dehalogenation, hydrolysis, oxidation, etc., is very high [133]. These new structures can be completely degraded by mineralization to CO2, H2O and mineral salts. Alternatively, they can be incorporated into the humic substances of the soil by polymerization. This leads to the formation of other highly stable substances. These nonextractable and chemically unidentifiable fractions, which remain in the humic fractions of the soil after extraction with solvents of different polarities, are known as soil-bound residues”.

 

Table 3 gives complicated formulas, but without any indication of whether they have ever been used in the analysis of pharmaceuticals.

• Previously to Table 3, we indicate: “Therefore, kinetic degradation experts from the European Commission-funded FOCUS group (Forum for the Coordination of Pesticide Fate Models and Their USe) proposed alternative equations for the degradation of soil organic pollutants [119], as summarized in Table 3.”

 

Paragraph 4.2.1 discusses photodegradation, but without explicitly stating that it can only occur on the soil surface. Even a thin layer of soil protects substances from UV radiation.

• Obviously, photodegradation occurs on the soil surface. If the compound is in lower layers, the process does not occur.

 

The concept of biochemical degradation introduced by the authors is misleading because the word "biochemical" is also associated with the action of organisms and not with both abiotic and biotic reactions.

This is true, but see our explanation in the first paragraph of Section 4.2.2.

• “In principle, chemical and biological degradation can be distinguished. However, in many cases, they are closely related, and it is not easy to establish the independence of the two processes. Chemical degradation involves oxidation, hydrolysis, and other reactions that occur in the soil as a function of pH, temperature, and moisture, while biodegradation can be defined as "the process by which soil microorganisms metabolically or enzymatically transform or modify the structure of PhMs present in the soil" [127] (Figure 7). To study both types of degradation (chemical and biological) separately, it is necessary to destroy soil microorganisms by appropriate irradiation or sterilization techniques. This would also require modification of other catalytic systems that have a significant impact on degradation. For this reason, the two types of degradation are often combined and treated as biochemical degradation.”

 

Paragraph 4.3.2 should be deleted. Do the authors know of any pharmaceutical that is volatile? This also applies to mentions of the volatility of substances in other paragraphs (e.g. 4.3.5).

All organic compounds are volatile to a greater or lesser extent depending on their vapor pressure and ambient temperature. Aniway, we say in Section 4.3.2.: A common pathway for the movement and disappearance of PhMs could be the volatilization of PhMs from the soil and their succeeding diffusion into the atmosphere. However, some studies indicate that the removal of PhMs by volatilization could be neglected due to their low Henry Law constants [135].

 

Chapter 4.3.4. deals with bioaccumulation very superficially and contains false statements. Bioaccumulation (in the authors' assumption - only in animals) does not depend only on Kow, but also, for example, on lipid content in organisms. Absorption is most often not through binding to receptors (line 700).

We difference bioaccumulation on soil organisms and plant uptake. We say: “To assess the likelihood of absorption and distribution of a PhM in a given organism, it is very useful to determine the partition coefficient (K_OW).” In addition, K_OW value is directly related to lipid content. We say: “The extent of the process depends on a number of factors, such as the type of crop, the physicochemical properties of the compound (molecular weight, vapor pressure, water solubility, and K_OW), environmental characteristics (soil type, temperature, water content, and agricultural practices), and plant characteristics (root development, shape and size of leaves, and lipid content) [151].

 

On the other hand, paragraph 4.3.5. is very extensive, but does the discussed absorption of substances by plants apply to PhMs? In line 744 the authors contradict their data presented in Table 1. The data on hydroponics is not a good example of drug uptake from soil (line 747).

• Section has been shortened according to you. The sentence “Most PhMs are ionizable and have low hydrophobicity” has been changed by “Many PhMs are ionizable and have low hydrophobicity”. We think that data on hydroponics complement the information provided in this section.

 

In Chapter 5, in addition to general statements on soil health, data on the effects of PhMs on microorganisms are given. However, in addition to microorganisms, there are also other organisms in the soil (e.g. earthworms) and this effect should also be discussed.

• We have included the following sentence: “In addition, the positive effect of macro-organisms such as earthworms and others must be considered [137]”.

 

Chapter 6 provides a very good discussion of remediation, particularly of soils. However, this issue is completely unrelated to pharmaceutical contamination. No soils have yet been identified that are contaminated with pharmaceuticals to such an extent that they require remediation. The entire chapter should be removed from this work.

• We respect your opinion, but we believe it is an appropriate addition to what has been discussed in the manuscript.

 

The summary points out the fundamental role of "clays" and "humus" in the fate of PhMs in soil (line 1050). In the main text, this role is only mentioned.

• The effect of inorganic and organic colloids in the fate of PhMs is commented in section 4

 

Minor comments:

 

A list of abbreviations should be added to make the paper easier to read

• If recommended by the Editor, we can include a list of abbreviations.

 

The abbreviation PhMs has not been used so far.

• This abbreviation has been proposed by us.

 

Line 37, 51. Microorganisms cannot be classified as compounds or substances

• Line 37: The sentence has been rewritten as follows: Recent studies have focused on the presence of a variety of identified anthropogenic compounds in addition to microorganisms in the environment …
• Line 51: We say: They are chemicals and/or microorganisms ….. We include and/or.

The list of citations should be made in accordance with the guideline for authors

• Reference list will be in accordance with the journal at the end of the process.

 

Line 64. Active pharmaceutical ingredients should be instead of “drugs”

• Drugs has been changed by active ingredients

 

Line 81. The phrase "health effects" should not be used in the context of algae.

• Health has been changed by adverse

 

Line 178. illicit drugs are not pharmaceuticals! Opioids can be both drugs and illicit drugs. This should be clearly stated in the publication.

• We are according to you

Why are these substances included in Table 1? What was the selection criterion?

• According to their presence in soil and water

 

Line 262. What do the Authors understand by the term: “immunize pathogenic microorganisms”?

• The sentence has been rewritten.

 

Table 2. Should be: days instead of dias.

• Sorry by mistake. It was modified.

 

Line 416. Did you mean “pharmaceuticals”?

• Newly, sorry by mistake. Pesticides has been changed by PhMs

 

Line 648. Plants are also organisms and bioaccumulation can also occur in them.

• - It has been distinguished between soil organisms and plants. Therefore, the sentence is now written as follows: “bioaccumulation by organisms and plant uptake (movement of PhMs into soil organisms and plants)”

 

General sentences should be removed, e.g. "Other studies have found similar results (line 774)".

• The sentence has been deleted according to your suggestion.

 

Line 828. “persistent”?

• Yes…… while carbamazepine was more persistent (55%-107%). It means that 55-107% of initial concentration was recovered.

 

Line 894. What do the terms: Cambisol, Chernozem, Arenozol mean?

• They are different soils according to Soil Taxonomy (soil classification).

 

Author Response File: Author Response.pdf

Round 2

Reviewer 4 Report

Comments and Suggestions for Authors

The manuscript has been revised sufficiently.