New in vitro dermal absorption database and the prediction of dermal absorption under finite conditions for risk assessment purposes

Buist, Harrie; Burgsteden, Johan A. van; Freidig, Andreas P.; Maas, Wilfred; Sandt, J.J.M. van de

doi:10.1016/j.yrtph.2010.02.008

Cited by 34 publications

(27 citation statements)

References 13 publications

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“…Caco-2 cell models) cannot capture the relevant complexity of the in vivo microenvironment as they lack a myriad of important signals, key regulators, and tissue phenotypes; cells growing in 3D tissue cultures have different cell surface receptor expression, proliferative capacity, extracellular matrix synthesis, cell density, and metabolic functions that resemble closely the original human tissue (Brohem et al, 2011). Consequently, validated protocols using 3D-HSE models have been approved by the OECD (Organisation for Economic Co-operation and Development) and ECVAM (European Centre for Validation of Alternative Methods) for testing skin irritation, phototoxicity and corrosion by xenobiotic chemicals (Ackermann et al, 2010;Buist et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of 3D-human skin equivalents for assessment of human dermal absorption of some brominated flame retardants

Abdallah

Pawar

Harrad

2015

Environment International

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Ethical and technical difficulties inherent to studies in human tissues are impeding assessment of the dermal bioavailability of brominated flame retardants (BFRs). This is further complicated by increasing restrictions on the use of animals in toxicity testing, and the uncertainties associated with extrapolating data from animal studies to humans due to inter-species variations. To overcome these difficulties, we evaluate 3D-human skin equivalents (3D-HSE) as a novel in vitro alternative to human and animal testing for assessment of dermal absorption of BFRs. The percutaneous penetration of hexabromocyclododecanes (HBCD) and tetrabromobisphenol-A (TBBP-A) through two commercially available 3D-HSE models was studied and compared to data obtained for human ex vivo skin according to a standard protocol. No statistically significant differences were observed between the results obtained using 3D-HSE and human ex vivo skin at two exposure levels. The absorbed dose was low (less than 7%) and was significantly correlated with log Kow of the tested BFR. Permeability coefficient values showed increasing dermal resistance to the penetration of γ-HBCD>β-HBCD>α-HBCD>TBBPA. The estimated long lag times (>30 min) suggests that frequent hand washing may reduce human exposure to HBCDs and TBBPA via dermal contact.

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Section: Introductionmentioning

confidence: 99%

Evaluation of 3D-human skin equivalents for assessment of human dermal absorption of some brominated flame retardants

Abdallah

Pawar

Harrad

2015

Environment International

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“…A simple model to predict dermal absorption under finite dose conditions was developed by Buist et al (2010). 109 In addition, Kasting and coworkers have developed a finite-dose model 110 that is implemented in a freely available web-based program (www.cdc.gov/niosh/topics/skin/finiteSkinPermCalc.html). A few studies have attempted to develop models for multicomponent mixtures (e.g., Ghafourian et al, 2010, 111 and Riviere and Brooks, 2011 112 ).…”

Section: In Silico Methodsmentioning

confidence: 99%

Review of the Availability ofIn VitroandIn SilicoMethods for Assessing Dermal Bioavailability

DumontCoralie

PrietoPilar

AsturiolDavid

et al. 2015

Applied In Vitro Toxicology

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The exposure of the skin to consumer products, drugs, and environmental chemicals can result in their penetrating the skin barrier and entering systemic circulation, potentially resulting in adverse effects in the skin and other organs. The assessment of dermal penetration and bioavailability (including penetration, metabolism, and entry into the systemic circulation) is therefore an important consideration in the risk assessment of chemicals. The skin is a heterogeneous organ with a multilayer structure. Based on its architecture and physiology, substances can penetrate through three major ways but can also be blocked in the different skin layers and in the skin appendages, which act as reservoir. In addition to that, as the skin is a metabolically competent organ, substances can undergo metabolism. After a brief description of the skin architecture, this review will focus on the skin penetration mechanisms and skin metabolic capacities. The skin absorption has traditionally been tested in vivo on animals. However, with the new legislation (i.e., Registration, Evaluation, Authorisation, and Restriction of Chemicals Regulation or Cosmetics Regulation), alternatives to animal testing have to be implemented. In a second part, this review will provide a description of the main in vitro and in silico or computational models available to study skin absorption and skin metabolism (i.e., ex vivo skin models, artificial membrane barriers, primary cells and cell lines, Quantitative Structure-Activity Relationship [QSAR], simulators for the prediction of skin metabolism).

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“…Unter Berücksichtigung der Daten zum applizierten Lösungsvolu-men (10 µl) sowie zur Resorptionsfläche (0,64 cm²) errechnen sich Fluxe von 23 µg/ cm² in acht Stunden bzw. 2,9 µg/cm² und Stunde (Buist et al 2010). Für Standardbedingungen (2000 cm² exponierte Hautfläche, eine Stunde Expositionsdauer) ergäbe sich hieraus eine Aufnahmemenge von 5,8 mg. Dabei ist zu berücksichtigen, dass die Konzentration der Testlösung etwa um ein 100-Faches über der Wasserlöslichkeit der Substanz (0,021 mg/ml) lag.…”

Section: Aufnahme Verteilung Ausscheidungunclassified

1‐Decanol [MAK Value Documentation in German language, 2017]

Hartwig

2017

The MAK‐Collection for Occupational Health and Safety

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The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has evaluated 1‐decanol [ 112‐30‐1 ] to derive a maximum concentration at the workplace (MAK value), considering all toxicity endpoints. Critical effects are irritation and the tumour‐promoting potential on the skin. Neither appropriate data in humans nor inhalation or oral studies of 1‐decanol with animals are available for derivation of a MAK value. An 8‐week feeding study in Wistar rats with the structurally related 1‐dodecanol resulted in a NOAEL of 100 mg/kg body weight and day. The same NOAEL is assumed for 1‐decanol. From this NOAEL, the concentration in workplace air was calculated according to the Commission's procedure to be 245 mg 1‐decanol/m 3 . However, as 1‐decanol is irritating and there are no studies of effects in the respiratory tract, a comparison with structurally‐related substances is indicated as well. The RD 50 values of 45 ml/m 3 and 50 ml/m 3 for 2‐ethylhexanol and 1‐octanol, respectively, are rather similar, which can also be assumed for 1‐decanol. Because of its similar irritating potency, the MAK value for 1‐decanol has been established at 10 ml/m 3 in analogy to 2‐ethylhexanol. As local effects are critical, the substance is assigned to Peak Limitation Category I. The excursion factor of 2 is set in analogy to 2‐ethylhexanol. From a synopsis of all data, 1‐decanol is classified in Pregnancy Risk Group C, despite the small difference between MAK value and NOAEC of 15 ml/m 3 for developmental toxicity. 1‐Decanol is not mutagenic in bacteria. There are no long‐term studies with 1‐decanol. Papillomas, squamous cell carcinomas and severe skin irritation occurred after 60‐week application to the skin of the mouse following initiation with 7,12‐dimethylbenz[a]anthracene. The maximum skin absorption of 10 mg is less than 25% of the systemically tolerable amount of 660 mg which is taken up by inhalation at the MAK value. There are no positive clinical findings of contact sensitization from 1‐decanol, nor are such effects expected from the structure and the comparison with homologous alcohols. Data for sensitization of the airways are not available.

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New in vitro dermal absorption database and the prediction of dermal absorption under finite conditions for risk assessment purposes

Cited by 34 publications

References 13 publications

Evaluation of 3D-human skin equivalents for assessment of human dermal absorption of some brominated flame retardants

Evaluation of 3D-human skin equivalents for assessment of human dermal absorption of some brominated flame retardants

Review of the Availability ofIn VitroandIn SilicoMethods for Assessing Dermal Bioavailability

1‐Decanol [MAK Value Documentation in German language, 2017]

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