OECD Guidelines

OECD Guideline 427: Skin Absorption: In Vivo Method (2004)
OECD Guideline 428: Skin Absorption: In Vitro Method (2004)
OECD Guidance Document No. 28 (2004)
OECD Guidance Notes on Dermal Absorption No.156 (2011)

European Commission

European Commission. Guidance Document on Dermal Absorption.
EFSA Guidance on Dermal Absorption (2012)

US Environmental Protection Agency

US Environmental Protection Agency, Office of Pesticides
Programs and Toxic Substances (OPPTS) Health Effects Test Guidelines, OPPTS 870.7600, Dermal Penetration (1998)

Japanese Ministry of Agriculture

Japanese Ministry of Agriculture Fisheries and Food
Test Data for Registration of Agricultural Chemicals, 12 Nohsan No 8147, Agricultural Production Bureau (November 24, 2000)

World Health Organization

WHO (World Health Organization) Dermal Absorption.
Environmental Health Criteria 235, International programme on chemical safety (IPCS) ISBN 92-4-157235 (2006)

In Vitro Diffusion Cell Methodology

Clowes H M, Scott R C and Heylings J R. Skin absorption: flow through or static diffusion cells. Toxicology In Vitro 8 827-830 1994.

Davies D J, Ward R J and Heylings J R. Multi-species assessment of electrical resistance as a skin integrity marker for in vitro percutaneous absorption studies. Toxicology In Vitro 18 351-358 2004.

Heylings J R, Davies D J, Correa M C, and McCarthy T J. Development of a compromised skin model in vitro using a tape stripping method.  The Toxicologist 132 205 2013.

Howes D, Guy R, Hadgraft J, Heylings J R, et al. Methods for assessing percutaneous absorption. Proceedings of the European Centre for the Validation of Alternative Methods (ECVAM). Alternative to Laboratory Animals 24 81-106 1996.

Trebilcock K L, Heylings J R and Wilks M F. In vitro tape stripping as a model for in vivo skin stripping. Toxicology In Vitro 8 665-667 1994.

Heylings J R, Davies D J and Burton R.  Dermal absorption of testosterone in human and pig skin in vitro.  Toxicology In Vitro 48 71-77 2018.

In Vitro Absorption and Skin Sensitisation

Dearman R J, Clowes H M, Cumberbatch M, Fielding I, Heylings J R, Hilton J and Kimber I. Influence of dibutyl phthalate on dermal sensitization to fluorescein isothiocyanate. Fundam Appl Toxicol 33 24-30 1996.

Heylings J R, Clowes H M, Cumberbatch M, Dearman R J, Fielding I, Hilton J and Kimber I. Sensitization to 2, 4-dinitrochlorobenzene: influence of vehicle on absorption and lymph node activation. Toxicology 109 57-65 1996.

Jewell C, Clowes, H M, Heylings J R, and Williams F M. Percutaneous absorption and metabolism of dinitrochlorobenzene in vitro. Archives of Toxicology 74 356-365 2000.

Formulation and Drug Delivery

Judd, A M, Heylings, J R, Wan, K-W, & Moss, GP (2012). PAMAM dendrimers as a skin permeation enhancer of chlorhexidine digluconate. Perspectives in Percutaneous Penetration 13, 58. (see Research Bibliography)

Judd A M, Scurr D J, Heylings J R, Wan K W, Moss G P. Distribution and visualisation of chlorhexidine within the skin using ToF-SIMS: A potential platform for the design of more efficacious skin antiseptic formulations. Pharmaceutical Research 30 1896-1905 2013.

Trottet L, Owen H, Holme P, Heylings J R, Collin I P, Breen A P, Siyad M N, Nandra R S, and Davis A F. Are all acyclovir cream formulations bioequivalent? International Journal of Pharmaceutics 304 63-71 2005

Dermal Absorption and Risk Assessment

Heylings J R and Esdaile D J. Dermal Absorption of Pesticides In: Dermal Absorption and Risk Assessment. Roberts M.S. and Walters K.A. 2nd Ed. Decker 2007.

Kleinhorn J, Bronaugh R, Bunge A L, Heylings J R et al. Dermal Absorption and Risk Assessment. WHO International Programme on Chemical Safety. Environmental Health Criteria 235 2006.

Purchase I F H, Heylings J R and Lewis R W. The development and strategic use of alternative tests in assessing the hazard of chemicals. Comments on Toxicology 5 271-300 1995.

In Vitro Compromised Skin Model

Davies D J, Heylings J R, McCarthy T J and Correa C M (2015). Development of an in vitro model for studying the penetration of chemicals through compromised skin.  Toxicology in Vitro 29(1) 176-181.   

Available on the TiV website as “open access”  http://dx.doi.org/10.1016/j.tiv.2014.09.012

Further Development of the In Vitro Compromised Skin Model

Davies D J, Heylings J R, Gayes H G, McCarthy T J and Mack M C (2017). Further development of an in vitro model for studying the penetration of chemicals through compromised skin. Toxicology in Vitro 38 101-107.

Available on the TiV website as “open access” http://dx.doi.org/10.1016/j.tiv.2016.10.004

Development of an In Vitro Compromised Skin Model and Effects on the Absorption of Caffeine and Aminophenol

THIS IS NOW A PUBLISHED ARTICLE 

PLEASE REFER TO OUR PUBLICATION SECTION OF THE WEBSITE

Jon R. Heylings, Diane J. Davies, Timothy J. McCarthy and M. Catherine Correa

Skin that has a compromised stratum corneum is likely to provide a less effective barrier to topically-applied chemicals when compared with normal skin. For example, skin that is impaired due to irritation, sensitisation or more chronic skin disease, such as psoriasis, is likely to be a less effective barrier to the entry of chemicals into the systemic circulation via the dermal route (Goon et al., 2004; Kim et al., 2006; Stamatas et al., 2011). The measurement of dermal absorption of chemicals for consumer products intended for application to the skin is an important part of risk assessment (OECD, 2004; SCCS, 2010). However, the in vitro models that assess the dermal penetration of topically applied products utilise intact skin. Since there is no standardised model for evaluating skin penetration in compromised skin barrier conditions, the use of additional safety factors is arbitrary. The purposeof this investigation was to explore whether the tape stripping procedure used to assess the distribution of chemicals in the skin could be adapted, in vitro, to mimic conditions where there is damage to the stratum corneum barrier.

PAMAM Dendrimers as a Skin Penetration Enhancer of Chlorhexidine Digluconate