A new approach to characterize dermal systemic exposure by use of chemicals' permeability coefficient (Kp) in finite dose – Application to some ingredients of nail polish by skin and nail exposure routes
Abstract
To evaluate systemic chemical exposure, the permeability coefficient can be used to estimate absorption. This parameter characterizes the transfer rate of a substance in a vehicle across a membrane. The biological membrane thickness is a factor of resistance to permeability. Thus, it seems interesting to take this parameter into consideration in the calculation of the absorption.
In this study, a calculation model of systemic exposure through the skin and the nail has been developed for finite dose conditions. It represents a new approach to systemic exposure assessment and is based on the following assumption: systemic exposure to a molecule is achieved when this substance has completely crossed the biological membranes. We used skin and nail thickness to integrate the permeability coefficient in the formula. The permeability coefficient, the membrane thicknesses and the contact time represent what is called the systemic absorption factor which can be incorporated in external exposure formulas. Presented in an exponential form, it can be used to determine the amount absorbed versus time and to assess the systemic exposure to an applied amount which is finite.
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Introduction
Chemical risk assessment is defined as a process to calculate or estimate the probability of an adverse health effect which occurs after humans are exposed to a substance. This process consists of three important steps: (i) hazard assessment (identification and characterization), (ii) exposure assessment (external or systemic) and (iii) risk characterization [1-3].
A cosmetic product is currently defined as "any substance or mixture intended to be placed in contact with the external parts of the human body (epidermis, hair system, nails, lips and external genital organs) or with the teeth and the mucous membranes of the oral cavity with a view exclusively or mainly to cleaning them, perfuming them, changing their appearance, protecting them, keeping them in good condition or correcting body odors" [4].
Some reference studies assess external exposure to cosmetic products [5-10]. However, a risk assessment to cosmetic products is currently not possible. It is necessary to know the ingredients and their concentrations in the finished product. Because regulations do not oblige industries to supply ingredient concentrations in the finished cosmetic product [4], and because there is limited data available in the literature [11, 12], it was necessary to be able to assess ingredient concentrations. A method was therefore developed to estimate ingredient concentrations from a standard composition of cosmetic products [13]. In this study, an exposure assessment to nail polish composition was performed by inhalation, oral and dermal (skin and nail) routes and was based on external nail polish exposure data carried out by Ficheux et al. [14]. According to the literature, these two studies have shown that the dermal route could not be considered as negligible in cosmetics exposure. However, the exposure assessment was performed by considering an absorption rate of 100% as recommended by the security agencies [15-17]. The skin and nails are very effective barriers against external substances and studies on chemical permeability often show a low passage of chemicals across these membranes. Justified as overly protective for the dermal route, such an external exposure assessment cannot be considered realistic in the risk assessment for the consumer; a systemic exposure assessment would be more appropriate.
Conclusion
In this study, a new calculation model of systemic exposure through the skin and the nail has been developed for finite dose conditions. It is based on a different approach to the models currently available in the literature: systemic exposure to a molecule is achieved when this substance has completely crossed the biological membrane which separates the internal environment from the external environment. Kp is directly used as transfer speed and not as a flux. We used skin and nail thickness to integrate Kp in the formula. The permeability coefficient, the membrane thicknesses and the contact time represent what is called the systemic absorption factor. Presented in an exponential form, it can be used to determine the amount absorbed versus time and to assess the systemic exposure to an applied amount which is finite.
In this study, six ingredients commonly found in the nail polish composition have been used as examples in the exposure assessment. The comparison of the results obtained with this model with results obtained from models of the RIVM and the US-EPA have shown that they are relatively close; moreover they are consistent with the theory in the application conditions. Like other models, assumptions and application criteria limit the accuracy of exposure estimation. However, the new equation structure reduces the number of parameters needed to assess systemic exposure and reduces uncertainties. Except for Kp, all of the “input data” can be integrated under distribution form. The use of probabilistic the Monte Carlo method enables us to consider all of these parameter variability’s, including the parameters that compose the absorption factor (l and t). Among other things, this method enables us to assess exposure by integrating inter-and intra-individual variability’s existing in the thickness of biological barriers and whose impact on the systemic exposure may be significant depending on the exposure time (contact time) and the transfer rate of the molecules (Kp).
As with the other models, the most significant uncertainties of the proposed model are associated with the use of Kp. Indeed, it involves many theoretical constraints that must be considered (i.e. transfer only by diffusion). However, this model can be easily adapted according to exposure conditions (more accurate and suitable Kp for substances and types of biological membranes etc.) and the desired accuracy (integration of additional parameters such as B, FA or evaporation).