Nanotechnology Products in 2010: What You Need to Know Now About Warning, Labeling, and Instructions
January 21, 2010
Engineered nanomaterials are a diverse class of extremely small-scale materials formed by engineering at the molecular level. Recent toxicological studies have suggested that exposure to certain nanomaterials may cause harmful effects to humans and the environment. There has been much debate on the reliability and validity of these studies, and their relevance to actual exposures. Although such studies are on-going, uncertainty will remain regarding the ultimate safety of many types of nanomaterials and their applications for some time.
Using knowledge and experience in the latest in nanotechnology toxicology studies, as well as previous study in related topic areas, and the applicable products liability and workplace safety law and regulations, we assembled a panel of experienced professionals who addressed the following topics:
The existing uncertainties concerning nanomaterial product safety
The timeliness, development, content, and use of product warnings versus workplace warnings / instructions / labels in the nanotechnology industry
The ability of manufacturers, importers, distributors, and others to use such warnings and labeling to educate and inform consumers and employees on product and personal safety in connection with product manufacturing, product use and product disposal
This webinar targeted manufacturers, importers, distributors, sellers, product designers, plant managers, safety and risk managers, quality managers, insurers, underwriters, labor unions, government officials, government regulators and the consuming public, and addressed the timeliness, import, efficacy, use, and content of product warnings / instructions / labels in the nanotechnology industry. Many of the participants raised valuable questions during the Webinar. As time was limited, the speakers could not answer them all. Responses to the questions that the speakers did not get to are below.
Are there any useful rapid screening tests for nanomaterial toxicity?
Joyce Tsuji, Ph.D., DABT, FATS, Exponent: Many of the toxicity tests we have available now, particularly for the more novel products, are basically rapid tests because that is virtually all the data that are available so far. There has been quite a bit of research on developing tests for rapid screening of nanomaterial and other hazardous chemicals, so yes, this is an area of great interest, but unfortunately right now, I don't think there is a standard set of rapid screening tests that could accurately predict the toxicity even for the current variety of materials on the market. That being the case, I think you have to look at the weight of evidence of toxicology, epidemiology and other information available for your materials, some of which have been out for a while, or there have been historical exposures you can rely on. I think you have to be careful of rapid tests because often they are in-vitro tests on cells or tissues and that may not be reflective of whole animal exposures; however, but I think in the near future more refined tests will be developed.
What types of testing has been done on the safety of nanomaterials for products that are applied dermally, skin care products, cosmetics etc?
Joyce Tsuji, Ph.D., DABT, FATS, Exponent: Well there has been a lot of interest certainly in commonly used nanoscale materials such as micronized, titanium dioxide used in sunscreens, and there is probably ten years worth of research that is focused probably mostly on dermal penetration and whether they are absorbed systemically into the blood stream. A few related studies have also examined distribution within the body and potential effects after subcutaneous injections. Based on that literature, the record looks pretty good for those products not being of concern for dermal penetration, or if they do, their toxicity would be low. I should also mention that there are photo-toxicity studies that have been done. I think some of the European and Australian scientific committees have summarized that research as well as studies on potential dermal toxicity, genotoxicity and oral toxicity of some of the common materials in sunscreens. I think the other thing to keep in mind is that if new or different materials are developed, then those should be specifically investigated. A few studies, for example, have examined dermal penetration and toxicity of water-soluble fullerene derivatives used in cosmetics.
How often should you update and revise labels? The toxicological data on many nanomaterials is evolving, and how do you deal with situations where two valid studies come up with different health and safety results?
Steve Arndt, Ph.D., Exponent: I will address the beginning part of that question, I think Joyce can handle the second part. We always recommend that if you have a plan for design, development, and regular re-evaluation of your warnings, labels, workplace notices, process instructions, MSDS, worker notifications, and collateral safety materials, it should be independent of any data that you may gather. However, if new information is revealed that appears to be contradictory to your current safety information or reveals new hazards that had not been previously considered, you do need to evaluate that new information critically and possibly retain somebody who understands the studies and can evaluate the two of them scientifically. We look at warnings development as something that happens on a regular basis. Warnings evolution with new products and continually improving your product, is a regular situation for products and labeling and it should be no different than that when you revise products you can revise your labeling.
Joyce Tsuji, Ph.D., DABT, FATS, Exponent: I concur with Steve. A toxicologist will need to examine the nanomaterials and test conditions used in the two studies to examine why they are contradictory and whether they are applicable to your product and its uses. One also needs to evaluate these studies within the broader context of the weight of evidence from the scientific literature. For example, a recent study by Ryman-Rasmussen et al. (2006) reported dermal penetration of quantum dots through the outer layer to the living epidermal layer of porcine skin. Skin permeability in this study may have been increased by 24-hour exposure using a solution with high alkalinity. A later study by the same research group (Zhang et al. 2008) using a different shape of quantum dots with a solution with near neutral pH did not find such penetration. Another research group using quantum dots and human cadaver skin and mouse skin, likewise did not find such penetration, except for abraded skin (Kraeling et al. 2007; Gopee et al. 2009).
David Dahlstrom, C.I.H., Exponent: To add a perspective from the workplace, it is important to recognize the need to perform a job safety analysis whenever new materials, processes, work procedures, and job responsibilities and activity is modified. As we all recognize that such modifications will have an actual effect on the potential to increase or decrease the hazards associated with making such changes and the potential for unanticipated exposure to workers and the surrounding environment, a job safety analysis is integral. To effectively address the results of such an analysis, modifications to administrative (worker training, notification, health and safety programs) and engineering controls (ventilation, isolation, enclosure, etc.), worker and environmental protections may become necessary. Installation of effective work-area and employee protection notices, process line and materials labels and warnings become integral with efforts to ensure workplace safety and worker health.
How does personal protective equipment or PPE, protect workers from nano-size materials, is there a special coating needed on the worker's suits? If so, who approves it as effective protection? Lastly, has or will OSHA weigh in here?
David Dahlstrom, C.I.H., Exponent: In addressing the effectiveness of air filtering respirators for use in protection from the inhalation of ultrafine and nano-sized particulate matter, a substantial body of scientific evidence holds that airborne particles 0.3 micrometers (300 nm) in size are more likely to penetrate a porous material (i.e., filter material) than particles of other sizes. Particles larger than 0.3 um/300nm are blocked by fibers that compose the filter. Those smaller than 0.3 um/300 nm are stuck on and among the fibers through a process called "diffusional capture." Consequently, if a filtering media is tested and shown to effectively and efficiently capture particles 0.3 um in size, there is confidence that the filter would capture particles of any size. NIOSH and other scientific organizations have performed studies of particle penetration and retention within filtering media incorporated into various manufacturers' N95 and P100 respirators. As attested to within these studies and those performed by NIOSH in their respirator approval and certification process, NIOSH currently approves the use of either N95 or P100 filtering facepiece respirators for protection against nano-sized particulates. Of course, where there is any question of sufficient respiratory protection within the workplace, the use of supplied airline respirators is an appropriate alternative. Keep in mind, the respirator filter/cartridge selected must satisfy the ability to retain and cleanse the air of particulates as well as organic vapors, should such vapors also be present within a work area.
Regarding the use of other personal protective equipment, current recommendations for those who work in the manufacture of engineered nanomaterials are to wear appropriate PPE as a precautionary basis whenever a failure of a single control measure (i.e., an engineered control) could result in a significant risk of exposure to workers, researchers, or support personnel. To minimize the potential occurrence of such an incident, workplace protocols should be implemented designed to ensure that respective engineered controls are equipped with performance monitors (i.e., visual and audible alarms) that will notify users if equipment malfunctions.
The completion of an effective workplace/process hazard evaluation (as per the requirements set forth in 29 CFR 1910) designed to establish the appropriate selection and use of personal protective equipment (PPE) commensurate with the level of hazard is the first step in worker exposure protection. For most workplace purposes, the protective clothing regimen being recommended is that which is typically be required for a wet-chemistry laboratory and could include but not be limited to:
Closed-toed shoes made of a low permeability material. (Disposable over-the- shoe booties may be necessary to prevent tracking nanomaterials from the laboratory/workplace.) Long pants without cuffs
A long-sleeved shirt
Disposable coveralls or lab coats and hair covering
Wear approved polymer (e.g., nitrile rubber) gloves when handling engineered nanomaterials and particulates in liquids. Choose gloves elastomers based on their resistance degradation, penetration and permeation by both the nanomaterial and, if suspended in liquids, the liquid.
The use of face shields, chemical splash goggle, or other safety eyewear appropriate to the type and level of hazard is recommended. The worker should be provided eye protection, (e.g., approved (spectacle type) safety glasses with side shields (meeting basic impact resistance of ANSI Z87.1). As a precaution, do not consider face shields or safety glasses to provide sufficient protection against unbound, dry materials that could become airborne.
As a best practice, it is recommended the workers be provided disposable garments to wear in lieu of or over street clothing. For reasons discussed above regarding particle penetration, these disposable garments do not require a particular coating associated with them. This insight is based upon what is known now of the characteristics of the nanoparticle materials in common use today. However, disposable coveralls coated with saran are available and should be considered if mists, sprays or other forms of moisture in air to commingle with the nanomaterial manufacturing or use process. Part of the reason for this is, of course, that the particles are found to agglomerate rather readily within the workplace, and do not compromise/degrade or easily penetrate the fabric matrix of the disposable garment.
Regarding OSHA, as cited above, there are OSHA standards already in place covering the selection, use, and care of the various types of personal protective equipment. As many of these standards are "performance based" it is important for the employer to recognize that many of these protocols have been accepted as standards of practice by NIOSH, DOD, DOE, consensus approval organizations and industry specific groups.
Has or will OSHA weigh in here?
David Dahlstrom, C.I.H., Exponent: Yes, undoubtedly OSHA will become more active in workplace/worker monitoring and oversight. As was introduced during Bill's discussion earlier, the employer's responsibility to perform workplace hazards characterization and job safety analysis of new processes and modifications to existing workplace practices is a meaningful tool. Also, where the employer elects to supplement workplace hazard control with the use of personal protective equipment, the employer's compliance with the requirements specified in 29 CFR 1910 Parts 132-135 (among others) are enforceable by OSHA. However, as many of you may be aware, there is a great deal of flux occurring not only with EPA, FDA, DOD, and DOE as each of these agencies address occupational and consumer issues associated with nano-particles. We are witnessing efforts towards modifying such regulations as TSCA, the Toxic Substance Control Act, and FIFRA, the Federal Insecticide, Fungicide and Rodenticide Act to regulate the use of specific engineered nanomaterials incorporated into various products. Currently, there are efforts within OSHA to determine guidance to employers with regard to requirements under the hazard communication standard (29 CFR 1910.1200) as it may be applied to engineered nanomaterial use in the workplace.
A question for the group:
Is there presently a requirement for nanomanufacturers to be licensed and/or trained?
William S. Rogers, Jr., Esq., Day Pitney LLP: This is a broad question, and it will be dependent on state or local law. There is presently no federal licensing requirement for nanomaterial manufacturers. There has been at least one attempt in the last year to treat nanomaterials as within existing state hazardous substance safety, control and emergency response statutes, and would have required local filing of an emergency response plan and payment of a local licensure fee. That bill (AB 935), in California, was twice amended and appears not to have passed. The City of Berkeley California (Municipal Code Chapter 15, Section 12.040 et. seq.) required a written disclosure of nanomaterial manufacture or use be filed with the City, and issuance of required registrations and permits. If you have a specific state or local law question, we can research it for you.
David Dahlstrom, C.I.H., Exponent: With regard to employer requirements to train employees who work with nanomaterial producing processes, as we noted earlier, there is an implied duty of an employer's responsibility to properly train and inform their workers as to the safe practices, procedures, available control measures, and hazards related to materials used within the workplace.
One other aspect of regulatory focus on engineered nanomaterials that manufacturers should consider is the recent trend towards regulatory compliance with the Toxic Substance Control Act (TSCA) and the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). As was discussed during our presentation, EPA has proposed actions to require industry testing and reporting under the "Significant New Use Requirements" of TSCA for products containing specified carbon nanotubes. Under FIFRA, EPA is actively pursuing licensing requirements of products containing nano-silver where this nanomaterial is being incorporated as an anti-fungal agent. These are two examples of the regulatory trend towards requiring engineered nanomaterial manufacturer licensing to follow in the future.
Should decisions regarding labeling and contents therein be done with the oversight of counsel. Are such decisions protected by the attorney client privilege?
William S. Rogers, Jr., Esq., Day Pitney LLP: First, I think that for all the reasons that we have articulated today, the process of assessing, designing, creating, and drafting, any labeling and warnings, is a multi-faceted issue that requires input from counsel. I do believe that counsel should be involved in the overall process. However, whether you can completely shield the process from discovery by the attorney-client privilege or even by the application of the attorney work-product doctrine, becomes a little bit more of a complicated issue. If you do 100% of all facets of the work in creating labeling/warning using a team of expert people and counsel who are all employed by your company, there is a likelihood you can shield the process under the attorney-client privilege provided your counsel is serving your team in a legal capacity throughout the process and not in a managerial or non-legal business capacity. This is especially true if you are engaging in the process following some incident or known threat which has you anticipating any claims, litigation or a trial. The same is true if you use outside counsel in the same circumstances following some incident or known threat which has you anticipating any claims, litigation or a trial.
If you are undertaking these kinds of safety assessments as part of your company's ordinary course of business, even though inside or outside counsel may be involved in the process, to the extent that you are using any appropriate outside consultants (non-employees) from any required fields of expertise, it is unlikely that the attorney-client privilege is going to apply. The attorney-client privilege will not attach to the information because of the outside consultants in these circumstances. However, provided that either your inside or outside counsel engages the outside consultants as his agents for purposes of labeling/warning creation and is involved throughout the process, it is arguable that the work product doctrine should apply to these efforts and protect them from discovery in any future claims, litigation or a trial. There are no guaranties, and a final determination will depend on the facts and circumstances of each case. But again, I think the most important thing is to undertake these efforts and to document them well for the sake of managing your risk, and potentially for future defense. You may also need them for a thorough compliance program, so the fact that they cannot necessarily and conclusively be shielded from discovery, should not dissuade people from doing the right thing and doing it appropriately.
This is not oriented to end user products, but rather to industrial inputs. Are industrial users of various materials able to readily identify when the supply inputs they obtain contain nanomaterials? Does the nano aspect of an ingredient ever show up on a material safety data sheet or, a MSDS? Lastly, in the industrial context, do you see a trend in how producers of nanomaterials are communicating the nano aspects of their products to users?
Joyce Tsuji, Ph.D., DABT, FATS, Exponent: For the projects I have been involved in, in which a manufacturer is making a product that has a nanomaterial in it, often they are obtaining that material from a producer who is selling it for its functionality, because it is a nanoscale material. I have seen a trend for more information on the nanoscale ingredients on the product description that better characterize these materials beyond the chemical formula, including the range of particle sizes, because they usually are not one standard size. Very early MSDS for carbon had exposure limits for carbon graphite, which is now known to be inaccurate and insufficiently protective, so I think there have been a change and an increasing awareness to include more information specific to the nano ingredient. That being said, I have to say that nano-scale substances, or at least products containing materials with size distributions that may include some of the nano scale range, do exist in products and have existed for awhile, but have not been recognized as such. Consequently, compliance with emerging requirements to label or submit information on all nano scale ingredients may not be easy. Manufacturers will have difficulty complying if they don't know what their suppliers are giving them.
David Dahlstrom, C.I.H., Exponent: Given the limited toxicological data available for most engineered nanomaterials, the effective communication of risk associated with worker handling of these materials is difficult. As OSHA's Hazard Communication Standard require that chemical materials that have been designated as "Hazardous Chemicals" be identified as such on related Material Safety Data Sheets (MSDS), any engineered nanomaterials made of such designated hazardous chemical should be identified on the MSDS as such. Within my experience where a manufacturer is making a product containing an engineered nanomaterial, that manufacturer either creates or obtains a specific nanomaterial on the basis of a desired functionality from a producer/supplier who by selling it, acknowledges the "nano" nature of the material. The onus is upon the manufacturer to seek answers from their suppliers if there are questions regarding specific material characteristics to meet individual product specifications.
Although I am not aware of a universal approach within industry to identify the "nano aspect of an ingredient" on respective MSDSs. However, I refer those interested to the NIOSH/CDC Nanotechnology - Nanoparticle Information Library website. NIOSH has partnered with Oregon State University to maintain this site to provide a database of nanomaterial health and safety information with the intention of including postings of material safety data sheets (MSDS) for nanomaterials in its Nanoparticle Information Library (NIL). Recognizing the measures being taken by the USEPA in the application of TSCA, FIFRA, etc., as well as information based on emerging scientific studies, there is change afoot to include more information specific to the nano ingredient in the respective MSDS. That being said, nano-scale substances are currently found in products and are often not disclosed.
Currently we are observing a trend emerging (primarily within the EU) for the incorporation of language on product description labels to better characterize ingredients beyond the bulk chemical content and formula.
What types of testing has been done on safety of nano materials for products that are applied dermally (skin care products; etc.) if any? Should this be deleted as redundant? Can anyone tell us whether these two questions are connected to each other?
Is there any data to support the conclusion that there are no consumer hazards [from dermally applied products] - if not - is that the trigger for the need for some type of safety labeling?
Joyce Tsuji, Ph.D., DABT, FATS, Exponent: As noted in response to the previous question on toxicology studies on dermally applied nanomaterials, considerable data are becoming available regarding dermal penetration, phototoxicity, and dermal toxicity of the main relatively inert nanomaterials used in sunscreens. Whether a warning is appropriate will need to be assessed for the specific nanomaterial and product. As an example, given that some studies have noted dermal penetration when the skin is abraded or compromised, one possible warning may be to caution against applying the product to damaged skin. Other emulsifiers or emollients in the product, however, could also be irritating so the product may already have this label.
I should also mention that the nanoscale ingredients in some products are micelles or colloids made of existing substances in soaps and other products such as fatty esters and fatty acids from corn, grain, soybeans, potatoes, coconut, and palm. These micelles allow suspension of non-polar substances within an aqueous carrier. The toxicity of these substances in nanotechnology applications may be no different than their existing uses.
Is there any established standard for product warnings that is unique or particular to the medical field?
Joyce Tsuji, Ph.D., DABT, FATS, Exponent: Product warnings for the medical field (e.g., medical devices, pharmaceuticals) would be covered by FDA regulations. FDA has general guidance for labeling of drugs and medical devices which is usually based on clinical experience and toxicity studies and typically covers information on fundamental safety (e.g., adverse reactions) and effectiveness measures.
Regarding nanotechnology, FDA provides information on how products containing nanotechnology might be regulated by FDA in their responses to Frequently Asked Questions.
Specifically FDA notes:
Because FDA regulates products based on their statutory classification rather than the technology they employ, FDA's regulatory consideration of an application involving a nanotechnology product may not occur until well after the initial development of that nanotechnology.
Because FDA has limited regulatory authority over certain categories of products, the Agency may have limited authority over the use of nanotechnology related to those products. For example, there is no premarket approval of cosmetic products or their ingredients, with the exception of color additives.
Existing requirements may be adequate for most nanotechnology products that we will regulate. These products are in the same size-range as the cells and molecules with which FDA reviewers and scientists associate every day. In particular, every degradable medical device or injectable pharmaceutical generates particulates that pass through this size range during the processes of their absorption and elimination by the body. To date, FDA has no knowledge of reports of adverse reactions related to the "nano" size of reabsorbable drug or medical device products. If new risks are identified, arising from new materials or manufacturing techniques for example, new tests or other requirements may be needed.