Little Pro on 2016-04-24

A sensitizer is an agent that can cause an allergic response in animals or humans. Like skin/eye irritation, sensitization also belongs to local effects. There are primarily two types of sensitization: skin sensitization and respiratory sensitization. In this summary, we will focus on skin sensitization.

If skin is exposed to a sensitizing chemical substance, allergic contact dermatitis or atopic dermatitis may be provoked. In vivo local lymph node assay in mouse (LLNA, OECD 429) is the most frequently used method to determine if a substance is sensitizing or not.

Sensitization: Local Lymph Node Assay (LLNA)

The basic principle underlying the Local Lymph Node Assay (LLNA) in mouse is that sensitizers induce a primary proliferation of lymphocytes in the auricular lymph nodes draining the site of chemical application. This proliferation is proportional to the dose applied and provides a measurement of sensitisation. A minimum of four animals is used per dose group, with a minimum of three concentrations of the test substance, plus a negative control group treated with the vehicle only, and a positive control, as appropriate. This study includes: measurements (weighing, DPM), and clinical daily observations. Results are expressed as the Stimulation Index (SI).

Dose Descriptor for Sensitization

Local lymph node assay (LLNA, OECD 429) sometimes can provide information on the dose response relationship. However, No Observed Adverse Effect Level (NOAEL) cannot be easily obtained due to study design. For sensitizers, the first approach should be the qualitative risk characterization based on potency categorization (strong/extreme/moderate sensitizers) and then defining the appropriate risk management measures (RMMs).

GHS Classification Criteria for Sensitization

Category 1 Skin Sensitization Category 1 Respiratory Sensitization

For substances and tested mixtures:

• If there is evidence in humans that the individual substance can induce sensitization by skin contact in a substantial number of persons, or where there are positive results from an appropriate animal test.

• If any individual skin sensitizer in the mixture has a concentration of: ≥ 1.0% Solid/Liquid/Gas

For substances and tested mixtures:

• If there is human evidence that the individual substance induces specific respiratory hypersensitivity, and/or Where there are positive results from an appropriate animal test.

• If any individual respiratory sensitizer in the mixture has a concentration of: ≥ 1.0% Solid/Liquid and ≥ 0.2% Gas

Testing Guidelines

It shall be noted that the LLNA should be used in preference to the guinea pig (TG 406) for both scientific and animal welfare reasons.


You have learned the definition of sensitization, local lymph node assay (LLNA), GHS classification criteria for skin sensitizers and respiratory sensitizers. 

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 Tags: Topics - CRAToxicology and Health Risk Assessment