A critical evaluation of the safety datasheets of graphene materials

Graphene, a single layer of carbon atoms, is a material that has held a leading position in material research owing to its excellent properties, allowing its use in innovative technologies. In spite of many advantages, the graphene’s potentially hazardous effect on the environment as well as human health constitutes a major drawback. Year after year, safety data sheets (SDS) constitute the main reference on a material’s potential hazards and the methods to prevent or address them if needed. However, SDS content has been heavily criticized due to incomplete, incorrect, or missing information and the cost required to produce and maintain it. The primary objective of this work is to introduce a stepwise process of knowledge management regarding SDSs, by identifying unexplored or neglected sections in a holistic approach. In this light, this work examines 37 graphene SDS, using modified Hodson’s criteria. The quality evaluation revealed that approximately 5% (2/37) of the datasheets were deemed reliable without restrictions (excellent), the majority 49% (18/37) were categorized as reliable with restrictions (good), while about reaching almost 46% (17/37) were deemed non-informative. It is noteworthy that approximately 73% of the SDS require major improvements; thus, the majority did not provide adequate data to be properly assessed. Section 15 could potentially trigger fundamental changes in the product status. The comprehensive evaluation of all 16 sections will enhance the capacity to conduct research mapping and formulate opinions on nanomaterials, thereby stimulating innovation.


Introduction
In the new global economy, appears to be a top priority on the global scientific and manufacturing agenda, promoted by many as the next industrial evolution [1,2]. There is a vast variety of available materials worldwide that are used in numerous applications throughout daily life [3]. Since its discovery in 2004, graphene has been deemed as one of the most impactful scientific and technological accomplishments [4]. Its monolayer of graphite (with carbon-to-carbon bond distance in the range of 0.14 nm) has been under the spotlight ever since [4][5][6]. Graphene exhibits improved physical properties compared to other alternatives, such as electron mobility and high thermal conductivity [7,8], high Young modulus levels [9], larger surface area [10], and improved electrical conductivity and optical transparency [11]. In view of the increased scientific interest, the potential applications of graphene have been heavily researched. Furthermore, both graphene and its derivatives have been evaluated for their capacity to manage pollution such as via gas adsorption [12].
Despite their successful applications, there is now extensive scientific literature regarding the necessity of nano-specific information with unique performance, such as graphene materials. Although their potential toxicity has been highlighted, there are few studies on their impact on human health [13]. Safety Data Sheets (SDS) are the main mechanism for communicating information regarding the safety and risks of chemicals [14]. They are relatively simple, brief documents (frequently less than 10 pages) that summarize critical identifiers about a specific substance [15]. There are currently numerous publications about SDSs, ranging on their definition [16], their indented audience [17], the manner they are used [18][19][20], and capturing the technical details in an easy-touse search engine. The research to date has tended to focus on the way SDSs can capture and communicate the nanomaterials' nature, replying to different guidelines like ISO TR 13,329, ECETOC TRA, and GHS implementations [18,[20][21][22][23][24][25][26] worldwide, reporting the important problem of missing "nano-specific" information, such as toxicity, physicochemical information, and precautionary measures. In Europe, the content of SDS is regulated by guidelines established under the Registration, Evaluation, Authorization and Restriction of Chemicals Regulation (REACH). REACH and the Classification Labeling and Packaging Regulation also incorporate the additional requirements provided by the United Nations, via the Globally Harmonized System for the Classification and Labeling of Chemicals (GHS), which offers a global standard about the mandatory data to include in a SDS [19]. The proposed guide suggests a 16-section format, where the exact hazards related to the material are mentioned in the second section of the SDS, while the material's physicochemical properties are recorded in Sect. 9 [27].
Despite the advancements made in community maturity, reduction of knowledge gaps, and establishment of safety protocols and controls in laboratories and workplaces, safety datasheets remain an unresolved issue. Three persistent issues have been identified.
The generation and upkeep of Safety Data Sheets and associated labels entail substantial expenses for all parties involved [14]. Despite the establishment of rigorous chemical risk assessment protocols over the course of three decades and the subsequent development of similar timelines for risk assessments in other fields [28], there remains a lack of standardized methods for companies to effectively manage Safety Data Sheets (SDSs). As a result, concerns persist regarding issues such as consistency and missing information, even after nearly four decades since the issuance of the Hazard Communication Standard [14]. There exists a notable disparity between the time required for risk assessment to adhere to REACH regulations, such as conducting chronic exposure studies for novel applications of nanomaterials, and the timeline for bringing these materials to market. Moreover, the associated costs of conducting such tests are also considerable [29].
Second, the costs of different SDS sections vary significantly due to the complexity of the information and the time required to obtain it (Fig. 1).
Almost two decades ago, discussions began on the fundamental issue of the cost of nanomaterials. According to Miller's report in 2005, research and development costs for nanoscience endeavors are very high, as are the resources needed to commercialize products [30]. Various studies in literature highlight the importance of cost. In 2007, Owen et al. underscored the importance of factoring in the cost burden of regulatory testing in health and safety regulations, as it serves as a critical determinant in prioritizing the risks associated with nanoparticles [31]. According to Choi et al., initial projections indicate that the process of developing and conducting quantitative risk assessments for nanomaterials and tested products could incur costs ranging from US$249 million to US$1.18 billion and could take anywhere from 24 to 53 years to complete [32].
Third, Anne DeMasi has noted that while risk information for particular chemicals does not change often, environmental and regulatory policies get updated much more frequently. Environmental and regulatory requirements are required for Sects. 12-15, but these sections are not mandatory according to the 2012 Hazard Communication Standard [14] (Fig. 1). The significance of environmental protection extends Page 3 of 21 99 Vol.: (0123456789) beyond technological and biochemical considerations, encompassing economic aspects as well. There exists a close interconnection between economic and environmental factors, as evidenced by these associations [33].
The reliability and accuracy of SDS assessments have been significantly compromised by the influence of the latter. In addition to the vast quantity and variety of nanomaterials, it is important to keep in mind that nanomaterials are highly heterogeneous in terms of their physicochemical properties, making their assessment a challenging task. The objective is thus to examine 47 MSDSs for graphene and graphenebased products, utilizing a scalable stepwise strategy. The resulting insights from this effort, particularly in unexplored sections, will be reflected upon. The scope of this study entails a quantitative evaluation of all sections, with the goal of obtaining a strategic management perspective by creating a holistic profile.

Methodology
The triangulation research approach was utilized in this study, employing a combination of qualitative and quantitative methods, as well as diverse data sources. To get past this challenge, a four-step procedure (Table 1) has been adopted, in order to create a dataset of "codified graphene and graphene-based SDS".

Filling the knowledge gaps
During the research clarification, the primary aim was to gain a clear understanding of the research objective that is both realistic and worthwhile to pursue. This was accomplished through an extensive literature review, which focused on identifying the factors that influence the objective and its potential success, particularly the relationship between them. An initial representation of the current state was recorded, along with the intended outcome, to clearly articulate the underlying assumptions for each description.
Collecting data and envisioning an improved scenario In STEP II, following the establishment of a clear research objective, a descriptive study was conducted to identify the Safety Data Sheets (SDS) for graphene. The first phase of the process required visiting the material vendors sites and looking up the SDS for graphene and graphene derivatives. More specifically, the selected vendors were chosen due to producing or re-selling graphene, graphene oxide (GO), or reduced GO (rGO). Each vendor offers the SDS as publicly available information that can be downloaded, while in some cases, they were procured after sending email requests to the vendor. Follow-up emails were sent after two weeks to ensure that the request would be addressed, when the initial request garnered no response. The reliability of each document was assessed depending on how accurate the provided information was, the amount of provided detail, and pre-existing understanding of a material's properties and behaviors. One SDS was taken into account per studied graphene-based nanomaterial by each vendor. This process resulted in an initial sample of 109 SDS, obtained from n = 90 vendors that will act as the basis for a more in-depth evaluation.

Designing SDS knowledge management
This was achieved through qualitative analysis of the obtained datasheets in order to identify the types of risks linked to the studied materials. The outcome underlined the need to study the SDSs in segments and further analyze them and evaluate their structure and what information is considered mandatory. Additional criteria such as regularity of updates to the SDS content were examined. When more than one version of a document was retrieved in the sample, the most recent one was selected for further evaluation, to ensure it contains the most up-to-date information. Furthermore, datasheets without a creation/revision date or when the revision took place more than four years ago were excluded from the sample. In addition, the language of all studied SDSs was English. After this screening process, 15 out of the 109 SDS were eliminated due to the absence of revision date. In effect, all the studied SDSs were created or revised after 2019. Lastly, one last exclusion criterion was the size of the particle of the substance. The final sample consisted of 37 SDS, obtained only from suppliers with compliance requirements in the EU, USA, UK, or Canada.

Classification of SDS
The fourth phase of the process was the evaluation of the SDSs using the Hodson et al. [20] method. More specifically, the SDS were evaluated based on the  [20] provided a ranking scheme appropriate for nanomaterial's SDS evaluation according to which the highest score a SDS can receive is 64, i.e., a maximum 4 per category, multiplied by the 16 categories, while the lowest is 32. Using this system, the calculated scores can be categorized as excellent (ranging between 56 and 64), good (ranging between 47 and 55), and required major improvement (scores between 32 and 46). The four questions of the Eastlake [18] approach, that the datasheets were evaluated on are: 1. Did the SDSs explicitly mention that the substance is in the nanoscale using a numerical system? 2. Did the SDSs mention any Occupational Exposure Limit for the larger versions of the material, and was there any information provided about the applicability of this limit to the nanosized form? 3. Did the SDSs reference particular toxicity-related data or information about the nanoscale version of the material and did it mention that the bulk versions may not have the same toxicities as the nanoscale forms? 4. Did the SDSs propose the use of PPE etc., in cases where exposure was possible?
Upon evaluating the datasheets using both methods, those that did not fail any or only one category were classified as "satisfactory." Datasheets with missing information in two categories were labeled as "in need of improvement." Lastly, if a datasheet failed in three or more categories, it was categorized as "in need of significant improvement." For the purposes of this work, the scoring information for each section, and then the total achieved for each datasheet are presented in Table 2. The datasheets were evaluated by the co-authors separately, and if there were any differences of opinion, an agreement was reached to assign the score.
Since this ranking model required to check whether toxicity data was provided and the Haz-Com standard mentions that there is no need for chemical testing, using just the Eastlake et al. system would not be sufficient for the assessment; thus, the Klimisch et al. approach received the most focus in this case.

Recommendations
Recommendations for the commercial status for the graphene products (investigational vs. semi-commercial) through Sect. 15 (b) Identification of the optimal MSDS were provided for decision making.

Results
A final sample of 37 SDSs for graphene-based nanomaterials were retrieved from producers and classified using the modified Hodson et al. method. The assessment results indicated that approximately 5% (2/37) of the datasheets were deemed reliable without restrictions (excellent), the majority 49% (18/37) were categorized as reliable with restrictions (good), while about reaching almost 46% (17/37) were deemed non-informative ( Table 3).
The datasheets that were revised between 2019 and 2020 were found to be 60% non-informative, 40% reliable with restrictions while those revised after 2021 were deemed approximately 36% noninformative, 55% reliable with restrictions, and 9% reliable without restrictions. None of the assessed SDSs managed to get a maximum score (64), as the highest reached was 57 points, due to missing specific toxicological and OEL data. The lowest score reached was 37, due to containing very generic statements such as to "follow general industrial hygiene practices," or that there is "no data available." Applying the second pillar of Hodson's evaluation system, the outcome for 2019-2022 was 38% in need of significant improvement, 32% in need of improvement, and 30% satisfactory. Figure 2 presents a breakdown of the SDSs according to reliability ranking, grouped per revision year. For the first group of SDSs, i.e., those created or revised during 2019-2020, the final ranking was 60% in need of significant improvement, 27% in need of improvement, and 13% satisfactory.
Safety data sheets that were created or revised over the last two years seem to score better when           examining Eastlake's criteria, since 28% of the studied datasheets were found as in need of significant improvement, 36% were in need of improvement, and 36% were deemed satisfactory. Figure 3 depicts the average total scores of the eleven sections of the studied SDSs, grouped per revision period. The lowest ranked sections were the 14th (transport information) and the 12th (ecological information), for all datasheets of our sample, while the best scores were achieved for Sect. 7 (handling and storage), 5 (firefighting measures), and 2 (hazard identification).
Upon further evaluation of the 37 datasheets, and using the Eastlake et al. approach, it was discovered that questions Q2 and Q1 had the fewest positive responses (27%), whereas Q4 had the most (97%) (Fig. 4). These findings suggest that even though information about protective measures were provided, the vast majority of the datasheets were lacking specific nanomaterial information. Technical specification sheets are becoming more popular, due to the need to document the physicochemical attributes particular to a material. From the datasheet sample, 41% were accompanied by a technical specification sheet, which is an important source of information regarding the material dimensions. Nevertheless, only 5 SDS out of 37 included size-related details, whereas 13 technical specification sheets supplementing them included the information. This resulted in an increase of the positive responses for the Eastlake et al. question 2 (state that material is in the nanoscale, numerically), moving from 14% (5/37) to 27% (10/37). None of the remaining details included in the technical specification sheets answered the model's questions.
The only notable difference when the technical specification sheet was included with the SDS was the information regarding the material size. This suggests that it might be mandatory to combine the details found on the datasheet with that on the TDS. A breakdown of the results for the Eastlake ranking system in terms of the inclusion of size data information via either the SDS or the TDS is presented in Table 4.
In order to know a material's status is to look at Sect. 15 (Fig. 5). In the United States, any chemical that is not listed on the Inventory is classified as a "new chemical substance." Moreover, apart from determining the "new" or "existing" status of a particular substance, the inventory also includes "flags" for existing chemical substances that are subject to manufacturing or usage restrictions. The US SDS for a specific material will change as the product moves from "newly prepared investigational materials" to a SNUR with consent order to a final SNUN (significant new use notification).
Only three percent refer that the material is not TSCA listed, which means the product is sold in small quantities to customers working in laboratory environments. The majority 84% do not include information. Fourteen percent have reached an intermediate degree of commercialization (TSCA listed) and for percental the SDS's there is a disclaimer.

Discussion
Although there were some missteps along the way, we are currently in the middle of a decade of discussions. Throughout this period, there have been numerous unfounded assumptions, underscoring the importance of conducting a comprehensive evaluation of Safety Data Sheets (SDS) to establish a sensible risk management approach. In order to chart a path forward, three key points have been identified: A notable aspect is the recent discovery that the exploration of chemicals is fundamentally driven by cost considerations, which may result in findings that contradict science-based risk assessments. The physical synthesis process for large-scale nanocomposite fabrication is laborious, involving extended reaction times and expensive equipment [35]. Furthermore, chemical methods utilized in the process often involve hazardous and toxic chemicals, posing risks to the environment [36]. The cost of determining the chemical composition is estimated to be high, as it requires digestion of the material and may necessitate expertise and time-consuming sample preparation [37].
Second, is the underemphasis given to Sect. 15 which can provide details on the product status. It is crucial to verify if a chemical is listed on the inventory before commencing the manufacture (including importation) of a chemical substance. Although positive effects have been reported in Table 3 (49% reliable with restrictions), limited data are available regarding information on inventory lists. For instance, 84% not mentioned US-TSCA list and 73% did not mention EU-SVHC list. This might be due to the fact that SDS preparers may not always have the necessary resources to obtain available information [14].
Third, these points invite us to reconsider the unchartered Sects. 12-15. These sections can provide valuable information regarding the status of the product. At practical level, this mean that none of the SDSs are graphene products that have reached an intermediate degree of commercialization (a SNUR in US parlance) and therefore have not generated more information pertinent to that product and useful to production workers.
The vast majority of the studied SDSs did not precisely indicate the possible risks in an informative manner. Upon evaluating the selected datasheets, 5% were deemed to be of excellent quality and accurately informed about the potential risks of graphene-based materials. There were 49% datasheets described as reliable with restrictions, meaning that they included some general statements about the required protection measures without offering any specific details or any indication that the nanoscale dimensions of the material might pose a risk. Lastly, 46% of SDSs were found to require major improvements at communicating possible risks.
Both vendors and end-users should be able to comprehend the related regulations and ensure they are properly following them. It should be mandatory for manufacturers to revise their datasheets and corresponding labels as more information becomes available about the materials and their behavior [14]. The compilation and maintenance of datasheets is Vol.: (0123456789) a significant expense [14], nevertheless, cannot be neglected. One of the positive outcomes is the verification that the majority of the datasheets offered advice about using protective equipment.
Kolchinski [38] delved on the problems related to incorrect or incomplete information on a safety datasheet. However, despite any quality control processes in effect, an error may happen during the publication of an SDS, which is a major concern and a potential safety hazard that should be taken into account.

Conclusions
This work proved that significant information is often omitted from SDSs. This assessment of graphene-based material SDS revealed that they are currently not yet fully reliable in terms of offering sufficient advice regarding the potential health and safety risks, and the appropriate handling and storage of nanoscale forms of the materials. It is concerning that based on our findings, multiple SDSs are considered to require major improvements; thus, the end users are not able to trust the information provided or interpret the limited information that might be included. The crux of the holistic evaluation approach is that all sections hold both economic and risk aspects. Section 15 can provide valuable information for material status (investigational vs. semi-commercial). The approach to form a holistic SDS profile provides an example with the promise of the field of knowledge. Moreover, one could realize that such an assessment will succeed by considering an SDS both from economic and safety side.