Analysis of finite dose dermal absorption data: Implications for dermal exposure assessment

Frasch, H. Frederick; Dotson, G. Scott; Bunge, Annette L.; Chen, Chen Peng; Cherrie, John W.; Kasting, Gerald B.; Kissel, John C.; Sahmel, Jennifer; Semple, Sean; Wilkinson, Simon C.

doi:10.1038/jes.2013.23

Cited by 76 publications

(32 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, and generally speaking, the percent absorption is inversely related to mass coverage over a certain dose range. Therefore, the percent absorption that is presented for most compounds is a relative term that should be interpreted cautiously considering decreases in the efficiency of percutaneous absorption are expected as the applied dose is increased [25, 26]. A majority of the ZnPT doses used in the in vivo animal studies and in vitro human skin penetration studies far exceed clinically relevant deposition amounts.…”

Section: Introductionmentioning

confidence: 99%

Formulation and Artificial Sebum Effects on the Percutaneous Absorption of Zinc Pyrithione through Excised Human Skin

Rush

Nash

Smith

et al. 2019

Skin Pharmacol Physiol

View full text Add to dashboard Cite

Background: Zinc pyrithione (ZnPT) is deposited on the skin as a fine particulate and must reach microorganisms localized in the stratum corneum and hair follicles in molecular form to exert its broad-spectrum antimicrobial/antifungal activity. Dissolution of ZnPT particles followed by molecular speciation results in the organic portion, i.e. pyrithione, being more susceptible to skin penetration than the inorganic component, i.e. zinc, or the chelate itself, i.e. ZnPT. Objectives: To further test the hypothesis that ZnPT skin penetration is rate-limited by dissolution and molecular speciation, the effect of different formulations and artificial sebum on the in vitro percutaneous absorption of radiolabel associated with Zn[¹⁴C]PT was investigated. Method: In vitro penetration of [¹⁴C]PT into and through excised human skin was measured following application of Zn[¹⁴C]PT prepared as suspensions in distinct vehicles including water-based carboxymethylcellulose (CMC), diluted body wash comprised of surfactants, and castor oil, in the presence and absence of artificial sebum. Results: The steady-state flux and cumulative absorption of Zn[¹⁴C]PT increased 4- to 5-fold when deposited from a body wash or castor oil compared to a water-based CMC suspension. Tritiated water flux measured before and after treatment showed that neither the surfactant vehicle nor castor oil significantly altered barrier function versus water alone. An artificial sebum layer on the skin potentiated Zn[¹⁴C]PT and ³H₂O absorption when dosed from both aqueous formulations, but not from castor oil. Conclusion: These data are consistent with the hypothesis that ZnPT percutaneous absorption, as measured by [¹⁴C]PT kinetics, is controlled by particle dissolution and molecular speciation.

show abstract

Section: Introductionmentioning

confidence: 99%

Formulation and Artificial Sebum Effects on the Percutaneous Absorption of Zinc Pyrithione through Excised Human Skin

Rush

Nash

Smith

et al. 2019

Skin Pharmacol Physiol

View full text Add to dashboard Cite

show abstract

“…Kissel et al (2008) and Spalt et al (2009) point out that PADA was dependant on the amount of soil applied per unit area and that if multiple layers of soil are applied to the skin surface then the PADA decreases since the soil layers not touching the skin will supply less of the contaminant to the skin surface. This has been demonstrated or discussed in a number of studies (Kissel et al, 2008;Spalt et al, 2009;Frasch et al, 2014) as well as specifically for BaP in soils (Roy and Singh, 2001). Spalt et al (2009) provide an equation for loading a monolayer of soil (Equation 7).…”

Section: Soil Dosingmentioning

confidence: 71%

“…Dermal bioavailability review papers (n=18) appear in the literature from 2004 and cover the various aspects of dermal exposure assessment methods (Moody and Maibach, 2006;Van De Sandt et al, 2007;Frasch et al, 2014), compound group reviews (pesticides and organic flame retardants) (Tripp et al, 2007;Abdallah et al, 2015), metabolic pathways (Pannatier et al, 1978), contaminants in soil (Spalt et al,, 2009;Andersen et al, 2014), and in silico modelling (Moss et al,, 2002a;Cronin and Schultz, 2003;Degim, 2006;Anissimov et al,, 2013;Anissimov, 2014;Couto et al,, 2014 Whilst this review is primarily aimed at in vitro testing methodologies for dermal bioavailability it is important to give an overview of the in vivo approaches as these supply data from physiologically and metabolically intact systems and are considered the "gold standard", from which base in vitro tests can be developed and compared. In vivo studies are, however, associated with strong ethical issues and there is an increasing movement towards the reduction of the use of animal testing e.g.…”

Section: Dermal Bioavailability Literaturementioning

confidence: 99%

A review of the current state of the art of physiologically-based tests for measuring human dermal in vitro bioavailability of polycyclic aromatic hydrocarbons (PAH) in soil

Beriro

Cave

Wragg

et al. 2016

Journal of Hazardous Materials

View full text Add to dashboard Cite

Polycyclic Aromatic Hydrocarbons are classed as Persistent Organic Pollutants, a large group of compounds that share similar characteristics. They are lipophilic, resistant to degradation in the environment and harmful to human and environmental health. Soil has been identified as the primary reservoir for Polycyclic Aromatic Hydrocarbons in the United Kingdom. This study reviews the literature associated with, or is relevant to, the measurement and modelling of dermal absorption of Polycyclic Aromatic Hydrocarbons from soils. The literature illustrates the use of in vivo, in vitro and in silico methods from a wide variety of scientific disciplines including occupational and environmental exposure, medical, pharmaceutical and cosmetic research and associated mathematical modelling. The review identifies a number of practical shortcomings which must be addressed if they are to be applied to high throughput laboratory analysis of contaminated soils for human health risk assessment.

show abstract

“…This phenomenon has been explained in depth by Frasch et al [31]. For risk assessment purposes the amount absorbed is often expressed as a percentage.…”

Section: Resultsmentioning

confidence: 98%

In vitro Dermal Absorption of Hydroquinone: Protocol Validation and Applicability on Illegal Skin-Whitening Cosmetics

Desmedt

Ates²,

Courselle

et al. 2016

Skin Pharmacol Physiol

View full text Add to dashboard Cite

In Europe, hydroquinone is a forbidden cosmetic ingredient. It is, however, still abundantly used because of its effective skin-whitening properties. The question arises as to whether the quantities of hydroquinone used become systemically available and may cause damage to human health. Dermal absorption studies can provide this information. In the EU, dermal absorption has to be assessed in vitro since the Cosmetic Regulation 1223/2009/EC forbids the use of animals. To obtain human-relevant data, a Franz diffusion cell protocol was validated using human skin. The results obtained were comparable to those from a multicentre validation study. The protocol was applied to hydroquinone and the dermal absorption ranged between 31 and 44%, which is within the range of published in vivo human values. This shows that a well-validated in vitro dermal absorption study using human skin provides relevant human data. The validated protocol was used to determine the dermal absorption of illegal skin-whitening cosmetics containing hydroquinone. All samples gave high dermal absorption values, rendering them all unsafe for human health. These results add to our knowledge of illegal cosmetics on the EU market, namely that they exhibit a negative toxicological profile and are likely to induce health problems.

show abstract

Analysis of finite dose dermal absorption data: Implications for dermal exposure assessment

Cited by 76 publications

References 20 publications

Formulation and Artificial Sebum Effects on the Percutaneous Absorption of Zinc Pyrithione through Excised Human Skin

Formulation and Artificial Sebum Effects on the Percutaneous Absorption of Zinc Pyrithione through Excised Human Skin

A review of the current state of the art of physiologically-based tests for measuring human dermal in vitro bioavailability of polycyclic aromatic hydrocarbons (PAH) in soil

In vitro Dermal Absorption of Hydroquinone: Protocol Validation and Applicability on Illegal Skin-Whitening Cosmetics

Contact Info

Product

Resources

About