The following speaker presentations are available to view/download:
Advanced Harmonization Techniques for Accurate Establishment of In Vitro-In Vivo Drug Permeation Relationships from Dermal Dosage Forms
Speaker: Audra Stinchcomb, University of Maryland
Description: Good correlation has been observed between pharmacokinetic (PK) human dermal absorption studies and in vitro permeation testing (IVPT). Due to the intrinsic variability associated with clinical PK evaluation, the prediction of in vivo exposure from in vitro absorption testing of topical semisolid and liquid dermal products has historically proven difficult. Since drug absorption from complex and unoccluded formulations/exposures can be significantly influenced by environmental factors such as temperature and humidity, maximal effort must be placed on the harmonization of experimental parameters between in vitro and in vivo clinic testing conditions to establish accurate in vitro/in vivo relationships (IVIVR). The goal of the studies was to investigate if increased control over experimental parameters would result in decreased inter-subject variability from common complex dermal formulations or exposure leading to acceptable IVIVR establishment. The low variability in the human PK data presents a proof-of-concept protocol design for testing of complex dermal formulations.
Approaches to Skin Notations NIOSH, ACGIH, and the MAK Commission
Speakers: Naomi Hudson, NIOSH; Jerry Kasting, University of Cincinnati; Michael Bader, MAK Commission; Michael DeLorme, ACGIH TLV Committee
Description: The National Institute for Occupational Safety and Health (NIOSH) Skin Notation Profiles evaluates skin exposures from chemicals known to absorb onto or through skin and result in systemic, direct, and sensitizing effects. To assign a skin notation, NIOSH reviews scientific and technical data that include the physicochemical properties, human exposures and health effects, data from in vivo toxicity testing, in vitro laboratory testing, and mathematical models. Additionally, about 40 % of all substances with an occupational exposure limit in Germany have been assigned an ‘H’ designation by the MAK Commission of the Deutsche Forschungsgemeinschaft (DFG). The designation indicates that the percutaneous absorption of a substance under typical workplace conditions can make a significant contribution to the systemic exposure of an employee, and hence increase the individual health risk associated with the substance. A designation with ‘H’ is warranted when the percutaneous uptake exceeds approximately 25 % or more of the tolerable quantity. Procedures for assigning skin notations are periodically revised. The panel will describe current procedures at NIOSH, ACGIH, and the MAK Commission, and entertain suggestions for updating and improving Skin Notation Profiles. The principles, results, and challenges of the skin notation assignment process will be illustrated by some recent examples.
Biological Monitoring: The Method of Choice for Dermal Risk Assessment?
Speaker: Kate Jones, HSE
Description: There are many challenges to dermal risk assessment, including a lack of information on percutaneous absorption for many chemicals, absence of a “gold standard” for surface and skin sampling techniques, limited interpretation for such methods, and uncertainties in models and in-vitro systems. Biological monitoring (human biomonitoring, HBM) offers the advantages of determining the actual systemic uptake of chemicals via all routes, including the skin. Although HBM does not exclusively assess skin uptake, it does provide a comprehensive measurement of the body burden arising from undertaking a particular job or task with all the exposure routes, control measures and behaviours taken into account. In many scenarios, skin contact will be the predominant route of exposure due to the nature of the task, the (low) volatility of the chemicals in use and/or the use of ventilation controls. The use of personal protective equipment (PPE), such as gloves and overalls, is often provided to prevent exposure to the skin but can actually exacerbate the issue if not considered properly and it is difficult to ensure the efficacy of PPE long-term. This presentation will provide examples of HBM in demonstrating the importance of skin uptake in the workplace, including the problems of relying on PPE. HBM provides a straightforward, practical means to demonstrate the problem of skin exposure even if the explanation of the problem requires additional techniques. Biological monitoring should therefore be the initial method of choice for dermal risk assessment.
Eww, I touched that! A Review of Measured Microbial Dermal Transfer Efficiencies with Guidance on Incorporation into Microbial Risk Assessments
Speaker: Heather Avens, Insight Exposure and Risk Sciences
Description: An important parameter in microbial risk assessment (MRA) is understanding how much virus or bacteria transfers to the skin from touching a contaminated surface. We present a review of existing dermal microbial transfer efficiencies, including guidance on how to select an appropriate value for use in a MRA. Based on our review of the available data, there is considerable variability in measured dermal transfer efficiencies, even among microbes of the same type. Thus, caution is necessary when selecting a transfer efficiency value to use in MRA. Though part of the variability is attributable to the nature of biological laboratory methods, many of the dermal transmission factors evaluated were found to impact transfer efficiency. For example, increased pressure, friction, and relative humidity have been reported to enhance microbial transfer. In contrast, factors that decrease viability, such as drying of the surface or increased time on the surface before contact, led to lower transfer efficiencies. Significant differences were also observed between different types of microbes and different surface materials. If no transfer efficiency data are available for the microbe of concern, data for a microbe with a similar physical structure and similar viability would be the most appropriate selection. To incorporate the variability inherent in the dermal transfer process, it is advisable to use a range of transfer efficiencies. Despite the variability in reported dermal transfer efficiencies, appropriate values can be selected for use in MRA models, through careful consideration of the key factors involved.
Importance of Standardization in Surface and Dermal Exposure Assessment
Speaker: Steven Verpaele, Nickel Institute
Description: There is growing interest in surface and dermal sampling and measurement of contaminants in workplace and other indoor settings. The Toxic Substances Control Act (TSCA) in North America and the registration, evaluation, authorization and restriction of chemicals (REACH) in Europe are driving legislations for introducing limits for various chemicals related to skin and surface exposure. In addition, ACGIH has established the Threshold Limit Value–Surface Limit (TLV–SL) as the concentration on workplace equipment and facility surfaces that is not likely to result in adverse effects following dermal exposure or incidental ingestion. Surface and dermal sampling are not currently a common practice, and apart from metals, metalloids and pesticides, there are few unambiguous measurement methods available. The development of consensus standards for sampling and measurement can help to overcome this shortcoming. This presentation will provide an overview of consensus standards that are available, under development, and proposed in different organizations (e.g., ISO, ASTM, and CEN).
Education, Intervention, and Control, Dermal Exposures in Additive Manufacturing
Speaker: Johan du Plessis, North-West University
Description: Additive manufacturing (AM) is a broad term for several types of processes that join materials to build objects from a computer-aided design file, often using layer-by-layer methodology. There are seven basic AM process categories, namely binder jetting (BJ), directed energy deposition (DED), material extrusion (ME), material jetting (MJ), powder bed fusion (PBF), sheet lamination (SL), and vat photopolymerization (VP). To date, most attention has been given to the inhalation exposure to particulates and gases emitted from these AM process categories. Very few dermal exposure studies have been published, even though risk assessments frequently identify potential dermal exposure to binders, powders (metals), resins, solvents, and ultraviolet radiation, and a few cases of allergic contact dermatitis associated with VP and MJ have already been reported. This presentation will provide an overview of potential dermal exposure in the different AM process categories, the current state of knowledge on AM dermal exposure, a justification for AM dermal exposure studies using proposed standardised/harmonised methods, and recommended control measures to limit and/or prevent dermal exposure.
Mattress Manufacturing - Bowtie Dermal Risk Assessment Model
Speaker: Georgi Popov, University of Central Missouri
Description: Polyurethane mattresses are popular and comfortable. However, the manufacturing of the mattresses involves toxic chemicals and creates skin exposure concerns. Mattress polyurethane is formed by mixing a polyol with Toluene diisocyanate (TDI) in the presence of suitable catalysts and additives. The purpose of this educational research project was to evaluate TDI exposures utilizing field methods and newly developed colorimetric wipe samplers (Direct-Read Wipes for Surface Chemical Detection). The project was initiated due to skin and respiratory irritation complaints. The authors performed dermal risk assessment using AIHA’s DRAM Tool and a Bowtie risk assessment methodology. The DRAM Tool is a very well-established skin risk assessment model. However, it allows for single substances or tasks to be assessed. The proposed Bowtie skin exposure risk assessment methodology allows for multiple substances additive effects evaluation. It is possible to estimate the skin exposure to mixtures using this methodology. The authors will present a real-world application of the newly proposed risk summation methodology.
Overview of Dermal Uptake Modeling Using AIHA’s IH SkinPerm Tool
Speaker: Josh Maskrey, Insight Exposure and Risk Sciences
Description: Dermal exposure and uptake modeling is a critical skill for practicing OEHS professionals. This presentation will provide attendees with a brief, practical overview of dermal exposure modeling approaches available in the AIHA’s IH SkinPerm modeling package, which is a free modeling tool. The session is intended to provide exposure and risk assessors with a working knowledge of the tool, the ability to explain the uptake modeling capabilities of the tool, and a basic overview of the theoretical basis of the tool. This session includes an overview of the four types of dermal uptake models available in IH SkinPerm including 1) instantaneous deposition, 2) deposition over time, 3) vapor absorption and 4) absorption from an aqueous solution. A practical treatment of the inputs and research required to effectively use the tool will be provided along with a brief explanation of the modeling theory used in the uptake models. The assumptions and limitations inherent to the modeling theory used in the tool will be explained. A use case involving dermal uptake of a semi-volatile chemical splashed on the skin will be used to provide an example of well-designed inputs and an explanation of the results panel in IH SkinPerm.
The Human Skin as a Route of Exposure to Biological Aerosols and the Role of Protective Clothing in Preventing Occupational Infectious Disease: Review of the Literature that forms the basis of Healthcare, Laboratory and Industrial Biosafety Practices
Speaker: Stephen R. Larson, Tufts University
Description: This presentation will review the existing scientific literature on the selection and use of protective clothing to prevent skin contact with clouds of aerosolized, airborne infectious agents. Standards, regulations and guidelines for the design, manufacture and use of protective clothing in the healthcare, laboratory and industrial environments will be summarized and evaluated. Clarification of the difference between the need to prevent skin contact with liquid splashes ,sprays and droplets and aerosols will be emphasized. Efforts to quantify the reduction of exposure through the use of suits ,gloves, headgear, respirators and other PPE will be discussed. The health risk of wearing street clothing in workplaces containing clouds of infectious agents will be presented.
What can we learn from novel consumer product dermal sampling methods and assessments?
Speaker: Renee Kalmes, Exponent
Description: Quantitatively characterizing dermal exposure from performing tasks involving handling or use of chemical-containing materials is challenging and complex, as many of the exposure assessment variables are scenario-specific. This session reviews some novel approaches being used to evaluate skin loading from contact with and use of phthalate and bisphenol A (BPA) containing materials. Phthalate and BPA skin loading data obtained from various exposure simulations methods (i.e., gloves, skin wipes) are presented, and comparisons with different sampling procedures are discussed. Calculation of the resultant dermal dose using the skin loading data and other exposure parameters is also reviewed. Although these methods are currently successfully being applied to assess skin loading from contact with consumer products, the utility of these approaches to evaluate dermal worker exposure in occupational settings is discussed.