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Skin and Eye Irritation

By Little Pro on 2016-04-24 Views:  Update:2017-01-18

Substances that cause adverse changes at the site of first contact (skin, eye, mucous membrane, respiratory tract etc) after a single exposure can be categorised as irritant or corrosive substances, depending on the reversibility of the effects observed. 

Skin corrosion is the production of irreversible damage to the skin. Skin irritation is the production of reversible changes (visible necrosis through the epidermis into the dermis) following the application of a test substance for up to 4 hours.

Serious eye damage is the production of tissue damage in the eye, or serious physical decay of vision, following the application of a test substance to the front outer surface of the eye, which is not fully reversible within 21 daysEye irritation is the production of changes in the eye following application of a test substance to the front outer surface of the eye, which is fully reversible within 21 days.

Both skin/eye irritation or corrosion belong to local effects.

Local Effect vs Systemic Effect

  • A local effect is an effect that is observed at the site of first contact, caused irrespective of whether a substance is systemically available. This mainly  includes skin/eye irritation/corrosion, skin or respiratory sensitization. 
  • A systemic effect is defined as an effect that is normally observed distant from the site of first contact, i.e., after having passed through a physiological barrier (mucous membrane of the gastrointestinal tract or of the respiratory tract, or the skin) and becomes systemically available. This includes acute toxicity, repeated dose toxicity, genotoxicity, reproductive toxicity and carcinogenicity. 

Dose Descriptor for Skin/Eye Irritation

No Observed Adverse Effect LeveL (NOAEL) cannot be obtained from skin/eye irritation tests due to study design. For skin/eye irritant, the first approach should be the qualitative risk characterization based on potency categorization (yes or no, corrosive, strong, mild) and then defining the appropriate risk management measures (RMMs).

GHS Classification Criteria for Skin Irritation/Corrosion

Category 1 Corrosive Category 2 Irritant Category 3 Mild Irritant

For substances and tested mixtures:

• Human experience showing irreversible damage to the skin;

• Structure/activity or structure property relationship to a substance or mixture already classified as corrosive;

• pH extremes of <=2 and >=11.5 including acid/alkali reserve capacity;

• Positive results in a valid and accepted in vitro skin corrosion test; or

• Animal experience or test data that indicate that the substance/mixture causes irreversible damage to the skin following exposure of up to 4 hours.

For mixtures where substances can be added:

• Classify as corrosive if the sum of the concentrations of corrosive substances in the mixture is ≥ 5% (for substances with additivity); or

For mixtures where substances cannot be added: ≥ 1%.

For substances and tested mixtures:

• Human experience or data showing reversible damage to the skin following exposure of up to 4 hours;

• Structure/activity or structure property relationship to a substance or mixture already classified as an irritant;

• Positive results in a valid and accepted in vitro skin irritation test; or

• Animal experience or test data that indicate that the substance/mixture causes reversible damage to the skin following exposure of up to 4 hours, mean value of ≥ 2.3 < 4.0 for erythema/eschar or for oedema, or inflammation that persists to the end of the observation period, in 2 of 3 tested animals.

For mixtures where substances can be added:

• The sum of concentrations of corrosive substances in the mixture is ≥ 1% but ≤ 5%;

• The sum of the concentrations of irritant substances is > 10%; or

• The sum of (10 × the concentrations of corrosive ingredients) + (the concentrations of irritant ingredients) is ≥ 10%;

or For mixtures where substances cannot be added: ≥ 3%..

For substances and tested mixtures:

• Animal experience or test data that indicates that the substance/mixture causes reversible damage to the skin following exposure of up to 4 hours, mean value of ≥ 1.5 < 2.3 for erythema/eschar in 2 of 3 tested animals.

For mixtures where substances can be added:

• The sum of the concentrations of irritant substances in the mixture is ≥ 1% but ≤ 10%;

For mixtures where substances cannot be added:

• The sum of the concentrations of mild irritant substances is ≥ 10%;

• The sum of (10 × the concentrations of corrosive substances) + (the concentrations of irritant substances) is ≥ 1% but ≤ 10%; or

• The sum of (10 × the concentrations of corrosive substances) + (the concentrations of irritant substances) + (the concentrations of mild irritant substances ) is ≥ 10%.

More info about additive hazards and non-additive hazards can be found here.

GHS Classification Criteria for Eye Irritation/Corrosion

Category 1 Corrosive Category 2A Irritant Category 2B Mild Irritant

For substances and tested mixtures

• Classification as corrosive to skin;

• Human experience or data showing damage to the eye which is not fully reversible within 21 days;

• Structure/activity or structure property relationship to a substance or mixture already classified as corrosive;

• pH extremes of < 2 and > 11.5 including buffering capacity;

• Positive results in a valid and accepted in vitro test to assess serious damage to eyes; or

• Animal experience or test data that the substance or mixture produces either

(1) in at least one animal, effects on the cornea, iris or conjunctiva that are not expected to reverse or have not reversed; or

(2) in at least 2 of 3 tested animals a positive response of corneal opacity ≥ 3 and/or iritis > 1.5.

For mixtures where substances can be added:

• Classify as Category 1 if the sum of the concentrations of substances classified as corrosive to the skin and/or eye Category 1 substances in the mixture is ≥ 3%;or

For mixtures where substances cannot be added: ≥ 1.

For substances and tested mixtures

• Classification as severe skin irritant;

• Human experience or data showing production of changes in the eye which are fully reversible within 21 days;

• Structure/activity or structure property relationship to a substance or mixture already classified as an eye irritant;

• Positive results in a valid and accepted in vitro eye irritation test; or

• Animal experience or test data that indicate that the substance/mixture produces a positive response in at least 2 of 3 tested animals of: corneal opacity ≥ 1, iritis ≥ 1, or conjunctival edema (chemosis) ≥ 2.

For mixtures where substances can be added:

• The sum of the concentrations of skin and/or eye Category 1 substances in the mixture is ≥ 1% but ≤ 3%; the sum of the concentrations of eye irritant substances is ≥ 10%; or

• The sum of (10 × the concentrations of skin and/or eye category 1 substances) + (the concentrations of eye irritants) is ≥ 10%;or

For mixtures where substances cannot be added:

• The sum of the concentrations of eye irritant ingredients is 3%.

For substances and tested mixtures;

• Human experience or data showing production of mild eye irritation;

• Animal experience or test data that indicate that the lesions are fully reversible within 7 days.

For mixtures where substances can be added:

• The sum of the concentrations of skin and/or eye Category 1 substances in the mixture is ≥ 1% but ≤ 3%;

• The sum of concentrations of eye irritant substances is ≥ 10%; or

• The sum of (10 × the concentrations of skin and/or eye category 1 substances) + (the concentrations of eye irritants) is ≥ 10%; or

For mixtures where substances cannot be added:

• The sum of the concentrations of eye irritant ingredients is ≥ 3%.

Skin and Eye Irritation Testing Guidelines

The classic skin and eye irritation test was the rabbit (Draize) test (OECD TG 404 and OECD TG 405). However, many in vitro methods have been validated and approved to avoid animal testing.

  • OECD TG 404 Acute Dermal Irritation / Corrosion (in vivo)
  • OECD TG 405 Acute Eye Irritation / Corrosion (in vivo)
  • OECD TG 430 In Vitro Skin Corrosion: Transcutaneous Electrical Resistance Test
  • OECD TG 431 In Vitro Skin Corrosion: Human Skin Model Test
  • OECD TG 432 In Vitro 3T3 NRU Phototoxicity
  • OECD TG 435 In Vitro Membrane Barrier Test Method for Skin Corrosion
  • OECD TG 437 In Vitro Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants
  • OECD TG 438 In Vitro Isolated Chicken Eye Test Method for Identifying Ocular Corrosives and Severe Irritants
  • OECD 439 In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method

Congratulations!

You have learned the definition of skin or eye irritation/corrosion, the difference between local effects and systemic effects, GHS classification criteria for skin and eye irritation, and typical in vitro and in vivo testing guidelines.

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 Tags: Topics - CRAToxicology and Health Risk Assessment

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