Acute and Repeated Toxicological Study of Anti-Inflammatory Herbal Formula, Yeosinsan, in Rats

Round 1

Reviewer 1 Report

Herbal preparations are gaining interest in all kinds of medical applications. It is therefore of importance to study potential toxic effects. Here, the safety of yeosinsan, an anti-inflammatory herbal formulation, was studied in rats.

The first major concern for this study is that the authors report no conflict of interest, which is misleading as the yeosinsan was supplied by the company Cho-A Pharmaceutical Co. and one of the authors is an employee of this company. As this presents a possible conflict of interest, this should be clearly stated in the article.

Moreover, the presentation of the results in tables 1, 2 and 7 needs to be explained in more detail. For instance, it is stated that a number of animals was affected (tables 1 and 2), which is the same number as the total of examined animals. First, how were the animals affected and second, if all animals were affected how can the compound be safe? Also, what is meant by the "mean number of animal days with clinical signs". Again, what clinical signs and if the animals showed clinical signs for the whole observation period, how can it be safe? Furthermore, please check the sum of animals (unremarkable and with clinical signs) in table 7 as it does often not equal the total number of examined animals.

Author Response

As a corresponding author, I thanks the reviewer's constructive comments. I attached the response as a docx file. 

Author Response File: Author Response.docx

Reviewer 2 Report

Although there is an excellent description of the studies and description of the results, some comparisons with other similar treatments could be added?

What is new about Acute and repeated toxicology study of Yeosinsan anti-inflammatory formulation in this manuscript?

Comments for author File: Comments.docx

Author Response

As a corresponding author, I thanks the reviewer's critical and constructive comments. I attached the rebuttal as a docx file. 

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

Thank you for revising the manuscript, there are still some concerns not adequately addressed.

First, if an author is an employee of the company selling the product, this presents a serious conflict of interest and has to be mentioned as such.

Second, please have another look at table 7. If you use the first example given for the spleen at 1000 mg/(kg*d) it says that 10 animals were examined, that 5 were unremarkable and that total incidence finding was 3. Now 3 plus 5 equals 8 and that is not 10. What was with the other 2 animals?

Last but not least, it is recommended to state the examination periods in days in the acute oral (2.3) and chronic toxicity test (2.4).

Author Response

Dear Reviewer

I deeply appreciate to your prompt response and to have chance for second revision. The comments were very constructive to improve the manuscript. Here I attached the answer to second revision.

Author Response File: Author Response.docx