Do Synthetic Fragrances in Personal Care and Household Products Impact Indoor Air Quality and Pose Health Risks?

Round 1

Reviewer 1 Report

The paper is interesting and quite novel in its approach and topics faced. Given the global situation in terms of pollution and resources consumption, it could have an impact on the community, too. It has also the merit to see a burdensome global problem from a completely different perspective, which is the main topic of the article, itself.

However, my main concern regards the overall structure of the paper, which can be improved, together with the relative importance given to the different parts of it. For example, to the aims of the present article, Section 3-4, ideally being the "core" of the paper, should be expanded, with the citation of more papers and a more in-depth description, partially faced again in the Discussion.

As such, the Methodology, including search strategy, should be improved and possibly aligned to any related guidelines (e.g., the PRISMA guidelines).

Finally, a stronger take-home message for the reader is warmly welcome after such an important insight on the main topic of the paper.

Overall, English language and grammar could be improved, and typos should be checked throughout the manuscript.

Author Response

Response to reviewers and amendments

• I appreciate the reviewer's understanding of the topic and the recognition of the theme's importance;
• the manuscript was intended to be a critical opinion in the format of a short review, so the organization was maintained relatively simply, with examples giving a glimpse of the main issues;
• As described, the search for articles and studies followed the main guidelines of the PRISMA but was complemented with extra articles when a definition of a given field was required;
• In conclusion, a take-home message was included;
• The author re-checked the spelling and sentence coherence using an English Editor algorithm (Grammarly);

Author Response File: Author Response.pdf

Reviewer 2 Report

This article poses the question "Do Synthetic Fragrances in Personal Care and Household Products impact Indoor Air Quality and pose Health Risks?". The author presents this work as a review, aimed to address attention to the risks of odourant VOC's, particularly synthetic fragrances.

The article seems to hold the middle between a narrative review and an opinion article. 

Main concerns include:

(1) The review methodology is not provided

(2) It is not made clear if and how evidence was weighted 

(3) It is not made clear what the current article adds to existing literature. There have been various systematic reviews that are not referred to. 

(4) The introduction is way to broad as compared to the scope of the topic itself. Instead of text fragments such as 'population disparity (demographic, educational, financial ...)'  ' climate change.. global resources...' it seems more logical to pay attention to what is known on the topic the author aims to adress, and pay attention to what is NOT known that the paper aims to address.

Relevant references of existing reviews see e.g.:

 Liu et al (2022) Health effects of exposure to indoor volatile organic compounds from 1980 to 2017: A systematic review and meta-analysis. Indoor Air.

Halios et al 2022. Chemicals in European residences - Part I: A review of emissions, concentrations and health effects of volatile organic compounds (VOCs). Sci Total Environ 2022

Vardoulakis et al (2020) Indoor Exposure to Selected Air Pollutants in the Home Environment: A Systematic Review. IJERPH.

 

Paterson et al (2021). Indoor PM2.5, VOCs and asthma outcomes: A systematic review in adults and their home environments.

 

 

Author Response

Response to reviewers and amendments

• I appreciate the reviewer's understanding of the topic and the recognition of the theme's importance;
• This observation is correct: the manuscript was intended to be a critical opinion in the format of a short review, so the organization was maintained relatively simply with examples giving a glimpse of the main issues;
• This critical point #3 connected with point #4 was amended, and the suggested relevant references were presented for further readers' consultation;
• Overall, the article's structure was maintained considering the importance of population growth, energetic demands, and the production and utilization of chemicals and pharmaceuticals; All these topics are interconnected.

Author Response File: Author Response.pdf

Reviewer 3 Report

The current paper argues about the impact of fragrances on indoor air quality, but the discussion of indoor air quality is too brief. Section 4. Indoor air quality and fragrance VOCs should be extended. The authors showed just 2 references for experimental determinations. Adding more references and a table would be also good, showing the reference, type of products, setting/ experimental condition, concentration detected, and guidance level (e.g., whether the levels exceed the regulatory levels), etc.

Line 290: check the units for the following sentence, "several times higher (~ 35-180 mg/day) than the air (~ 30-160 ug/m3 )". Check other sections as well throughout the manuscript.

Author Response

Response to reviewers and amendments

• I appreciate the reviewer's understanding of the topic and the recognition of the theme's importance; the manuscript was intended to be a critical opinion in the format of a short review, so the organization was maintained relatively simply, with examples giving a glimpse of the main issues;
• Additional references were included in the revised version of the manuscript;
• The chemical and physical units of pollutants were checked through the text;

Author Response File: Author Response.pdf

Reviewer 4 Report

This is a paper with many interesting details. In my my opinion, it is not well structured. For example, the introduction is too long.

Comments in detail:

Title: Why are "impact" and "pose" written in lower cases?

Page 2, line 69: "benzophene few classes of hundreds of chemicals": I don't understand. Are there words missing?

Line 85: I'd write:  "due to, inter alia, emissions"

Line 88: "adverse health risks" is a pleonasm.

Line 97: "recent exciting review": I'd delete "exciting".

Page 3, line 100: "terpenes intrinsically are not harmful to human health": "terpenes in low concentrations might not be harmful" (see  Wolkoff)

Page 4, line 159: result PREDOMINANTLY from the perturbation of the endocrine-immune-neural axis

Line 176: E.G., dimethyl phthalate and diethyl phthalate

Line 185: aggression, and depression

Line 187: muskS, nitromuskS

Line 190: "the question is, what if these positive neuromodulatory effects observed in experimental models are sustained indoors for long periods of exposure?" I think you mean if these effects are still positive when there are long periods of exposure?

Line 195: benzYl  butyl

Page 5, line 208: I'd write "might not be a health risk"

Line 243: "extremely young children in development": you can delete "in development"

Line 253: "imply indoor air quality": "influence" would be better

Line 274: "more significant concentrations of VOCs": I'd write "much higher concentrations"

Line 290: "were several times higher (~ 35-180 mg/day) than the air (~ 30-160 µg/m3 )": Why do you compare emissions with immissions? I'd just report the numbers.

Page 7, line 350: ", they could have detrimental effects on human health": I'd write: "they can have".     

Author Response

Response to reviewers and amendments

• I appreciate the reviewer's understanding of the topic and the recognition of the theme's importance; the manuscript was intended to be a critical opinion in the format of a short review, so the organization was maintained relatively simply, with examples giving a glimpse of the main issues;
• The detailed comments and observations were taken into account, and the amendments appear in the revised version of the manuscript. Please, check the track changes

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

The paper was slightly improved and the fact it is presented as a Short Review can justify the main limitations previously acknowledged.

Author Response

Response to reviewers and amendments

• I appreciate the reviewer’s consideration and the recognition of the manuscript’s importance again;

Author Response File: Author Response.pdf

Reviewer 2 Report

Title:

The title mentions synthetic fragrances only, the paper pays attention to both natural and synthetic fragrances. Why does the title leave out the natural fragrances added to PCHP? Please check for consistency.

 

Abstract

Line 19: exposition -> exposure

Line 19: “ The negative impact of fragrance chemicals on human health includes cutaneous, respiratory, and systemic effects ( e.g., headaches, asthma attacks, breathing difficulties, cardiovascular and neurological problems) and distress in workplaces.”  -> formulate more carefully: Several previous studies suggest that exposure may increase risks for several health outcomes including e.g. [..].

Line 21: Similar remark for: “Pathologies related to synthetic perfumes are associated with the perturbation of the endocrine-immune-neural axis”  The sentence in its current form gives the impression that there is broad scientific consensus, and a large body of evidence that (all?) synthetic perfumes cause pathologies (perturbation of the endocrine-immune-neural axis”.
This is certainly not the case. Thus this sentence needs to be formulated more carefully. E.g.: “Previous research indicates/suggests/shows that synthetic perfumes may potentially cause perturbation of … ]

Mention also to make clear for the readers: What type of study is this (not a systematic review, but )

 

Introduction

[Comment 1]

Line 29-56: “In the middle of November 2022, the human population on Earth reached eight billion, and it is expected to continue growing, … particularly carbon emissions (carbon footprint), is increasing while the biocapacity is decreasing [9].”  It is clear that the transition to sustainability is important in view of population growth and planetary boundaries.. However this introduction needs to leave more space for stressing the importance of the specific topic of the paper:

Exposure in indoor air and potential health risks of synthetic fragrances in PCHP.
The commonly known broader context {line 29-56} needs to be shortened to max a few lines only and focus on:

- And why is this specific topic (of indoor exposure to natural and synthetic fragrances in PCHP) important?
- What does this paper aim to contribute?
- What is the current state of knowledge en what are the knowledge gaps?
- What does it add to existing knowledge?

[Comment 2]

please explain:

-          what precautionary measures are already taken to protect workers from health risks of exposure to fragrance-related (synthetic or natural) PCHD additions?

-          E.g. what regulations are there for the toxicity of these chemicals to be admitted to be added to products that are sold on the market?

-          What relevant limit values are applicable for indoor air?

-          To what extent do ventilation guidelines protect workers (by dilution of polluted indoor air with outdoor air?)

What are the limitations of these current regulations and exposure limits?

[Comment 3]

Line 57-71:” water and nutrients (food) are not the only requirements for human growth… pharmaceutical drug pollution … [..] ” Similar comment: also this needs to be shortened to 1 or max a few lines only, to make more space to pay more attention on the topic of this paper (exposure levels, mixture, and potential health effects of indoor air exposure to natural and synthetic fragrances in PCHP).

[Other points of attention]

Line 89: potential health risks.

Line 101: Please check: “However, terpenes intrinsically are not harmful to human health but are the secondary products of reaction with ozone and the hydroxyl radical that generate, for example, formaldehyde and ultrafine particles [21].”  

See for health effects of oxidized terpene mixtures e.g.:

-          Matura et al (2005). Selected oxidized fragrance terpenes are common contact allergens. Contact dermatitis, 52(6), 320-328.

Please note: although in its original form most terpenes are not very toxic, there are certainly some terpenes that are known to be toxic and may affect health, depending on exposure concentration.

See e.g.

-          Stewart et al (2000). The biochemistry and toxicity of atractyloside: a review.

-          Angus (2021). Chapter 4 - Terpene toxicity and oxidative stress. Toxicology

Oxidative Stress and Dietary Antioxidants.

Do you mean something alike: the chemical reaction between terpenes and ozone and the hydroxyl radical, generates secondary reaction products (e.g. oxidized terpenes, formaldehyde and ultrafine particles) that may cause adverse health effects?   

Line 114: Please include additional references

Tabel 1 may be strengthened by including more references.
Please discuss also: How consistent are the finding on potential health effects? On what chemicals is particularly a large body of evidence af adverse health effects of indoor exposure (or exposure in experimental settings in e.g. cell-models)?

Line 274: “ Intriguingly about the emission of limonene is that synthetic R-limonene was more repellent than natural R-limonene in vitro tests with a mosquito 275 assay model, while synthetic R-limonene and S-limonene displayed the same level of re- 276 pellency. These facts may affect indoor air quality.”  -> Please check the logic of this argumentation: Since synthetic limolene is more repellent than natural limolene to mosquito’s .. “these facts may affect indoor air quality”?  

High indoor emission levels of chemical pollutants in combination with low ventilation levels may affect indoor quality. But how does a difference in  mosquito repellency (synthetic vs natural limolene) affect indoor air concentrations?

 

Line 309: “ The most frequent VOCs found following terpenes were [..] formaldehyde”

What do you mean by “ following terpenes”  Do you mean: the most frequently found VOC’s that may be created as secondary reaction products from chemical reactions with terpenes in indoor air are..

 

Line 313-315: “in a ventilated controlled 50 m3 room, the concentrations of d-limonene […] emitted, were several times higher (~ 35-180 mg/day) than the air (~ 30-160 mg/m3 ) when the products were in use” Question: “ than the air” What do you want to explain here? That the emission rates under controlled laboratory conditions are higher than [..]

-          higher than what? higher than emissions in indoor air?

-          the sentence compares emission rates (mg/day) with concentration levels (ug/m3). That is not very logic to compare rates with concentrations?  

Line 316-318: “Glycol ethers are regulated toxic air contaminants, and terpenes can react with ozone to form secondary pollutants. In a systematic study, limonene and linalool were present as fragrance chemicals in 72% and 45% of the products analyzed.”  -> How many products and what type of products were analysed and for what? (e.g. chemical composition of the product? chemical composition of the emissions of the product to indoor air?)

“ These fragrance VOCs reached concentrations of 7 – 140 mg/m3 and 544 to 787 mg/m3 , respectively, from a range of 396 to 1013 mg/m3 of total terpenes during testing periods of 3 h in two different types of indoor environments” This statement is hard to interpret, and the concentration levels that are mentioned seem meaningless without knowing the context. E.g. nothing is known on the type of experiment. Was this a laboratory experiment under controlled conditions, or where the products put in a ‘ real life’ indoor environment, such as a workplace (e.g. an office). How much of the analyzed products was put (and how?) in what type of room. What was the size of the room? Was the room ventilated or not? Wat was the room temperature? Where representative use conditions simulated, or where high amounts of the product put in the room?

Line 328: please note: benzene might originate from outdoor sources e.g. traffic. But is it also used as a synthetic or natural fragrance in Personal Care or Household products? I find that hard to imagine.

Line 329-332: PLease check the logic of these sentences.

“Another systematic review by Vardoulakis and colleagues [60] reports the detrimental influence of several air pollutants on indoor air quality and human health.”

Please specify: “ several air pollutants” -> including natural of synthetic fragrances?

Air pollutants do not have “effects on the air quality”. The concentration levels of air pollutants can be high (either in in door and/or in outdoor air). High exposure levels may affect health.

Please check sentence: “ Multiple factors contribute to the decrease indoor air quality pollutants and are associated with adverse health effects, such as respiratory and cardiovascular illness, allergic symptoms, and cancers”  “ to the decrease indoor air quality pollutants” please check grammar. Reducing the concentration of toxic air pollutants in indoor air will decrease health risks (not increase)?     

Author Response

Response to reviewers and amendments

• The author thanks the anonymous reviewer for the observations and consideration.
• The author considered the observations and suggestions, and the text's modifications and changes appeared in red whenever applicable.
• A poi-by-point response is on the pdf form attached to this platform

Author Response File: Author Response.pdf

Reviewer 3 Report

The revision looks good to me.

Author Response

Response to reviewers and amendments

• I appreciate the reviewer’s consideration and recognition of the manuscript’s improvement.

Author Response File: Author Response.pdf

Reviewer 4 Report

Line 101: As mentioned before, it is not correct that "terpenes intrinsically are not harmful to human health". You cite Wolkoff and in his paper there are no such statements. Please rewrite this sentence, e.g. "terpenes IN LOW  CONCENTRATIONS"

Line 331: Should be "decrease of indoor quality"?

Line 338: I'd delete "occupational"

 

 

Author Response

Response to reviewers and amendments

• The author thanks the anonymous reviewer for the observations and consideration.
• The author considered the observations and suggestions, and the text's modifications and changes appear in red.

Author Response File: Author Response.pdf