In Vitro Dermal Toxicity Testing

Many acute toxicity tests have been or are being effectively replaced by in vitro human, animal and 3D tissue alternatives. This shift is particularly evident in skin irritation, skin corrosion and skin sensitization models, all of which are fully supported at Charles River.

For topically applied or exposed chemicals and drugs, assessment of the skin corrosion and skin irritation potential is a key element in their safety evaluations. Irritation and corrosion testing uses 3D human skin models (EpiDerm™ and EpiSkin®). In addition, an in chemico assay, Corrositex®, can be used to assign skin corrosion classifications. In silico models are also used to identify skin corrosion, irritation or sensitization potential.

Skin sensitization is a hypersensitivity reaction resulting from the interaction of a sensitizing agent with host proteins to form an immunogenic complex. Examples of sensitizers include para-phenylenediamine (PPD) in hair dyes and nickel in clothes or jewelry. When these small molecules (haptens) bind to proteins, they become immunogenic and activate the immune system, which causes localized inflammation at the site of sensitizing agent exposure.

There is now a regulatory requirement for REACH testing to utilize these alternative models in a tiered approach ahead of animal tests. Many of these tests are also applicable to screening prior to in vivo testing.

As part of our integrated toxicology testing strategy, there may be cases where the in vivo test should be performed rather than the in vitro test. For example, the in vivo test should be used when a classification cannot be assigned or where a regulatory authority specifically requires in vivo data. In European labs, in vitro tests and data collection must be performed prior to evaluating the need for or performing in vivo testing.

Outside Publications

Skin Sensitization Assays

  • DPRA (direct peptide reactivity assay)
  • KeratinoSens and LuSens
  • In silico (QSAR)
  • LLNA (local lymph node assay)
  • GPMT (guinea pig maximization test)
  • Buehler assay (contact sensitization)
  • DTH (delayed-type hypersensitization)
  • GARDskin® genome test

Skin Irritation Assays

  • SkinEthic EpiSkin® skin irritation (OECD 439)
  • Dermal acute nonrodent
  • Acute dermal rodent

Skin Corrosion Assays

  • SkinEthic EpiSkin® skin corrosion (OECD 431)
  • Corrositex® skin corrosion (OECD 435)
  • Acute dermal rodent


​In Vitro and Alternative Models for Regulatory Submission

Dr. Clive Roper and Dr. Lauren Black were honored to contribute to the American College of Toxicology’s ToxChats© podcast series. In the first chapter of this episode, they discuss the current landscape of in vitro and alternative models and share their thoughts about the future direction of the field. In the second chapter, Dr. Paul Brown, associate director of pharmacology and toxicology at CDER/FDA, discusses the acceptance of in vitro models for safety evaluations and the value of integrative toxicology. Listen Now