NORA Manufacturing Sector Strategic Goals
HELD005 - Research Efforts in Support of the NIOSH Skin Notation ProjectStart Date: 10/1/2010
End Date: 9/30/2014
Principal Investigator (PI)Name: H.frederick frasch
Funded By: NIOSH
Primary Goal Addressed9.0
Secondary Goal Addressed
Attributed to Manufacturing
The purpose of the proposed research is to generate data and to provide expert opinion in support of the NIOSH Skin Notation effort. First, the project will provide data on chemicals of interest that will permit the appropriate assignment of skin notations, if justified. Existing data gaps will be filled through in vitro dermal penetration measurements, skin corrosivity measurements, and evaluation of the sensitization potential of a chemical (that is, its capacity to cause dermatitis). Additionally, the project will call upon the collective expertise of the skin research community to provide consensus opinion regarding several questions related to dermal risk assessment of chemicals. These questions have been raised through the process of assigning updated skin notations.
This project contributes primarily to the NIOSH Cross-Sector Program on Immune and Dermal Diseases.
Outputs of the project will be NIOSH Skin Notations. Research generated will be incorporated into the Skin Notation Profile, which is a brief but comprehensive assessment and rationale for assignment of the skin notation for a specific chemical.
Manuscripts describing research results will be published in peer review journals. Anticipated outcomes will be a broader acceptance and use of NIOSH skin notations by workers and industrial hygienists.
This purpose of this project is to address existing knowledge gaps that prohibit NIOSH from assigning appropriate Skin Notations to chemicals. By providing timely and focused data collection when insufficient data currently exists, the project will fill these data gaps. The project will perform several in vitro tests which will enable NIOSH to appropriately assign skin notations.
NIOSH skin notations are hazard warnings used worldwide to alert workers and employers to the health risks of skin exposures to chemicals in the workplace. A recent Current Intelligence Bulletin (#61, NIOSH 2009-147, “A Strategy for Assigning New NIOSH Skin Notations”) outlines the rationale behind the rationale and a new weight of evidence-based approach for assigning new NIOSH hazard-specific skin notations (SK). This new system entails the critical evaluation of existing data so that scientists may potentially assign multiple skin notations that distinguish between direct (SK: DIR), systemic (SK: SYS) and sensitizing (SK: SEN) effects of skin exposures to chemicals. In addition, specific hazards are addressed through the inclusion of subnotations; substances that are highly or extremely toxic and may be potentially lethal or life-threatening are designated with the systemic subnotation [SK: SYS (FATAL)], while potential irritants and corrosive chemicals are indicated by the direct effects subnotations [SK: DIR (IRR)] and [SK: DIR (COR)], respectively.
The following in vitro testing will be provided by the proposed core facility. All tests have been validated by international organizations. The skin notation addressed by each tests is listed.
1. Dermal penetration – SK: SYS; SK: SYS [FATAL]
Diffusion cell systems using excised human skin will assess dermal absorption and penetration potential for candidate compounds.
2. EPIDERM Skin Corrosivity Test – SK: DIR [(IRR); (COR)]
This in vitro test using reconstructed human epidermis will assess the irritation and corrosivity potential of a chemical.
3. Murine local lymph node assay (LLNA) and mouse ear swelling test – SK: SEN
The LLNA evaluates sensitization potential of a chemical by quantifying cell proliferation in the lymph nodes that drain the site of chemical application. In collaboration with Dr. Stacey Anderson (HELD), this assay may be performed for select chemicals.
The proposed facility will provide required data in a timely fashion in support of the development of skin notations. Candidate chemicals will be nominated through consultation with the Dermal Cross Sector Steering Committee. The Committee will undertake a thorough analysis of existing data and will evaluate data requirements related to the assignment of skin notations.
This testing will be ongoing throughout the duration of the project; there is no specific timeframe except for that of the project.
A second crucial component of the project will entail expert consensus-building among researchers in the skin permeation community. There are several areas related to the strategy for assigning new NIOSH skin notations that have been identified as requiring a more solid, science-based rationale. This project will address these areas by calling on the collective expertise of world-renowned specialists in the field with the goal of arriving at a consensus on how to proceed. Two areas have been identified thus far.
1. Percentage of applied dose that is absorbed
The current NIOSH strategy, stated in Current Intelligence Bulletin 61, states that “To differentiate between low and high dermal absorption, a 10% absorption rate has been selected as the critical cutoff value”. This value does not account for differences in experimental protocols (e.g., excess “applied dose”) or allow for consideration of highly volatile chemicals. These issues require further consideration, so that the seemingly arbitrary 10% cutoff level can be substantiated and qualified if necessary to account for experimental variables.
2. What constitutes a “substantial” penetration rate?
In the process of assigning skin notations, the question has arisen as to what constitutes a significant or substantial penetration rate. The answer must relate to some measure of acute or chronic toxicity, but how? This question can be addressed by experts to provide guidance on how skin notations can be assigned based on knowledge of the penetration rate and toxicological endpoints.
These components of the project will be addressed in years 2-4 of the project. For example, we will propose a 1-day meeting in conjunction with an international skin research meeting (Occupational and Environmental Exposures of Skin to Chemicals) to be held 06/11 through invitation to experts in the field to present these issues and gain consensus.
NIOSH estimates that workplace skin diseases account for 15-20% of all reported occupational diseases in the United States, with estimated total annual costs up to $ 1 billion. In addition, these statistics do not reflect the impact that skin exposures to chemicals have on the onset of systemic diseases, such as cancers, neurotoxcity, or reproductive toxicity. The Institute has long recognized the potential hazards associated with skin contact with chemicals in the workplace. For more than 20 years, the occupational safety and health community has relied on skin notations from NIOSH to warn workers about the health hazards of skin exposures to chemicals. NIOSH has recently embarked upon a far reaching effort to update and enhance the assignment of skin notations. This new system reflects the current state of scientific knowledge and involves critical evaluation of existing scientific data so that subject matter experts can assign multiple levels of skin notations that distinguish between systemic, direct and sensitizing effects of skin exposures to chemicals.
For some chemicals of interest, there is insufficient data upon which a reasoned decision can be made regarding the assignment of a skin notation. This project addresses these knowledge gaps by providing timely and focused data collection when insufficient data currently exists. The absence of quality data limits the ability to assign skin notations, which directly impacts NIOSH’s ability to protect workers life and health
The project will perform several in vitro tests which will enable NIOSH to appropriately assign skin notations. The proposed facility will provide required data in a timely fashion in support of the development of skin notations. In addition, the project will call upon the collective expertise of the skin penetration research community to arrive at consensus statements regarding several general questions that have been raised relating to NIOSH skin notation guidelines. This research will have immediate R2P impact and will advance NIOSH’s commitment to reducing workplace skin diseases. Clearly the proposed research is highly relevant to the mission of NIOSH to provide national and world leadership to prevent workplace illnesses and injuries.
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