Additives in Processed Foods as a Potential Source of Endocrine-Disrupting Chemicals: A Review

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The review entitled "Additives in Processed Foods as a Potential Source of Endocrine Disrupting Chemicals (EDC): A Review" seems interesting. Although the review paper is an overview, it may be of interest to potential readers. However, as a review, the quality is poor; it is neither a systematic nor a comprehensive review. There is lack of cares noticed in the manuscript. Thus, the current version of the manuscript cannot be considered for publication. Please take care of some major issues as follows:

1. Abstract: It is written in a diluted way. It should have a hypothesis and clearly mentioned objectives, along with a short methodological touch.

2. In the introduction section: More relevant background information should be included. Need proper and updated citations. Please try to discuss the chemical and physical properties of several crucial EDCs (i.e., Phthalates, Bisphenol A, Yellow No.5, Red No.3, Artificial Sweeteners and Parabens) with chemical formula.  

A good review should clearly indicate the scope of the review, the criteria utilized to determine whether or not papers were to be included or excluded from the review, and a summary of previous review papers (thereby indicating whether or not, or to what extent, there is a gap and where or if a further review is required)

3. The Methodology section should discuss search strategy, exclusion and inclusion of articles and their criteria. However, the authors are requested to review their methodology section with cares. Why there is a reference in this section and “HM-induced toxicity” as search key word? It showed the evidence of lack of cares.

4. It would be better if the authors could add overall mechanistic figure that will show how EDCs impact the human health (from their review perspective). The figures 1 (table) and 4 should be redraw as it is directly collected from previous published materials. The quality of Figure 6 is not good enough for a journal article (very low resolution)

5. Please carefully review all the citations (style, consistency and updated) in the text and references. Number of references is also relatively low. Try to include more relevant and updated references.

Overall, it’s an important topic. However, it required a major revision before acceptance.

Comments on the Quality of English Language

None

Author Response

Comment 1: Abstract: It is written in a diluted way. It should have a hypothesis and clearly mentioned objectives, along with a short methodological touch. 

Response 1:  We thank the reviewer for pointing out this kind suggestion. We have revised as per the reviewer’s comments, the abstract has been rewritten and improved (the corrections highlighted in red) in the revised manuscript.

Comment 2: In the introduction section: More relevant background information should be included. Need proper and updated citations. Please try to discuss the chemical and physical properties of several crucial EDCs (i.e., Phthalates, Bisphenol A, Yellow No.5, Red No.3, Artificial Sweeteners and Parabens) with chemical formula. A good review should clearly indicate the scope of the review, the criteria utilized to determine whether or not papers were to be included or excluded from the review, and a summary of previous review papers (thereby indicating whether or not, or to what extent, there is a gap and where or if a further review is required).

Response 2: We thank and agree and have revised and updated as per the reviewer’s comments, we have included the relevant information in the introduction section. However, it is not possible to provide some information in the introduction section, so it is included in the relevant food additives section in the revised manuscript.

Comment 3: The Methodology section should discuss search strategy, exclusion and inclusion of articles and their criteria. However, the authors are requested to review their methodology section with cares. Why there is a reference in this section and “HM-induced toxicity” as search key word? It showed the evidence of lack of cares.

Response 3: We have incorporated the reviewer’s suggestions by making necessary changes in the methodology section. The revised manuscript now includes additional information and recent references.

Comment 4: It would be better if the authors could add overall mechanistic figure that will show how EDCs impact the human health (from their review perspective). The figures 1 (table) and 4 should be redraw as it is directly collected from previous published materials. The quality of Figure 6 is not good enough for a journal article (very low resolution)/

Response 4: As per the reviewer’s suggestion, we have provided the mechanism of each food additive, and how it disrupts the endocrine system. Also redrawn all the pictures in the revised manuscript.

Comment 5: Please carefully review all the citations (style, consistency and updated) in the text and references. Number of references is also relatively low. Try to include more relevant and updated references.

Response 5: As per the reviewer’s suggestion, we have changed the reference style with recent references, and improved the overall quality of the revised manuscript.

Author Response File: Author Response.docx

Reviewer 2 Report

Comments and Suggestions for Authors

The paper highlights the presence of EDCs such as phthalates, bisphenol A (BPA), and other additives in processed foods, which can lead to adverse health effects, including reproductive disorders, metabolic issues, and increased cancer risk. The paper emphasizes the need for further research to understand the mechanisms of EDCs, establish safe exposure levels, and develop alternative additives with reduced endocrine-disrupting properties. The paper is also ethically sound in its approach, as it aims to mitigate the harmful effects of EDCs on human health and future generations.

Comments for author File: Comments.pdf

Author Response

Comment 1: The abstract needs more revision, the authors must make clear the real motivation of the review. It is not clear in the abstract. Also, please provide a more detailed, step-by-step review abstract.

Response 1: We are extremely thankful for the kind suggestions and comments made. As per the reviewer’s comments, the abstract has been rewritten and improved (the corrections are highlighted in red).

Comment 2: Change the repeated keywords to different terms not included in the title

Response 2: As per the reviewer’s comments, we have changed the keywords and highlighted them in red

Comment 3: The article primarily presents information without providing a critical evaluation of the existing research. It should discuss controversies surrounding certain EDCs, limitations of studies, and potential biases in the literature.

Response 3: As per the reviewer’s suggestion, we have provided/encompassed the needed information with a critical evaluation

Comment 4: While the article provides a good overview, it oversimplifies some complex concepts, such as the role of gut microbiota in EDC effects or the variability in individual responses to EDCs.

Response 4: As per the reviewer’s suggestion, we have rewritten the concepts related to gut microbiota and how it interferes with endocrine and other metabolic process

Comment 5: The article mentions that "long-term exposure to these compounds, particularly at high levels, may increase the risk of endocrine-related disorders," but fails to adequately discuss the importance of dose-response relationships for EDC effects.

Response 5: As per the reviewer’s suggestion, we have discussed the long-term exposure of additives based on the available data

Comment 6: The review mentions regulatory agencies like the FDA and EFSA but doesn't provide a detailed analysis of current regulations surrounding EDCs in food additives.

Response 6: As per the reviewer’s suggestion, we have rewritten the details in the revised manuscript

Comment 7: The article briefly mentions the need for alternative additives but fails to explore promising options in more detail.

Response 7: As per the reviewer’s suggestion, we included the details of using the organic or plant-based additive to avoid health hazards in the revised manuscript

Comment 8: The article has a lot of good information, but the language needs a bit more polishing to achieve clarity and flow. By addressing these issues, the authors could make the article more engaging and accessible to a wider audience

Response 8: As per the reviewer’s suggestion, overall improvement in language has been carried out in the revised manuscript.

Comment 9: The figures should be replaced because most of them are not clear.

Response 9: As per the reviewer’s suggestion, we have redrawn the pictures and included them in the revised manuscript

Comment 10 : The authors must clearly explain the significance of dose-response relationships for understanding the risks of EDCs, acknowledging that effects may vary with exposure levels.

Response 10: As per the reviewer’s suggestion, we have included the available data in the revised manuscript

Comment 11: The review should provide a more detailed and critical analysis of current regulations, their effectiveness, and potential improvements.

Response 11: As per the reviewer’s suggestion, we have included the regulation details and potential possibility of improvement in the conclusion and recommendation section in the revised manuscript

Comment 12: The authors should present a more thorough exploration of alternative food additives that could reduce the need for EDCs, including their potential benefits and drawbacks.

Response 12: As per the reviewer’s suggestion, we have included the alternate additives and their benefits in the conclusion and recommendation section of the revised manuscript

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

The authors tried to address the reviews comments partially. The authors are requested to read the previous comments of the reviewers carefully and revise the manuscript accordingly. The methodology section needs significant improvement. Please discuss the criteria utilized to determine whether or not papers were to be included or excluded from the review.

-On Page 3, Figure 1, should be replaced with Table 1.

-On Page 4, Figure 2 legend needs more information and a precise discussion of the mechanism.

-Why is the figure “Mechanism of Perchlorate as EDC” absent in the revised manuscript? 

Comments on the Quality of English Language

 Minor editing of English language required

Author Response

You provided an insightful and thorough review. Your valuable comments have incredibly improved the manuscript, and we thank you.  

Comment 1: The methodology section needs significant improvement. Please discuss the criteria utilized to determine whether or not papers were to be included or excluded from the review.

Response 1: Thank you for making the suggestion/comment. We truly appreciate it. The revised manuscript incorporates the suggested corrections in the methodology section, which are indicated in blue.

Comment 2: On Page 3, Figure 1, should be replaced with Table 1

Response 1: Figure 1 has been replaced with Table 1

Comment 3: On Page 4, Figure 2 legend needs more information and a precise discussion of the mechanism.

Response 3: The Figure 2 legend has been modified and further the mechanism has been added in the revised manuscript.

Comment 4: Why is the figure “Mechanism of Perchlorate as EDC” absent in the revised manuscript?

Response 4: We sincerely thank you for your patience and understanding. During the revision process, we tried to shorten the manuscript by overlooking some food additives, based on their frequency in processed and packed food items. The use of perchlorate is comparatively minimal. Based on these reasons, we have removed the perchlorate section with its corresponding image in the revised manuscript.

Comment 5: Comments on the Quality of English Language -  Minor editing of English language required.

Response 5: In the revised manuscript, we have meticulously reviewed the document and enhanced the language as necessary.

Author Response File: Author Response.docx

Reviewer 2 Report

Comments and Suggestions for Authors

The authors have satisfactorily responded to all my questions and made the necessary changes to the manuscript. 

Author Response

Comment 1: The authors have satisfactorily responded to all my questions and made the necessary changes to the manuscript. 

Response 1: We appreciate your validation that our revised manuscript meets your comments satisfactorily. We are very grateful for your peer review of our manuscript, which has enhanced its quality.