Activation of non-sensitizing or low-sensitizing fragrance substances into potent sensitizers: prehaptens and prohaptens

Ann-Therese Karlberg; Anna Borje; Jeanne Duus Johansen; Carola Liden; Suresh Rastogi; David Roberts; Wolfgang Uter; Ian R. White

doi:10.1111/cod.12127

Activation of non-sensitizing or low-sensitizing fragrance substances into potent sensitizers: prehaptens and prohaptens

Ann-Therese Karlberg^*, Anna Borje, Jeanne Duus Johansen, Carola Liden, Suresh Rastogi, David Roberts, Wolfgang Uter, Ian R. White

^*Corresponding author for this work

Research output: Contribution to journal › Literature review › peer-review

80 Citations (Scopus)

Abstract

Experimental and clinical studies have shown that fragrance substances can act as prehaptens or prohaptens. They form allergens that are more potent than the parent substance by activation outside or in the skin via abiotic (chemical and physical factors) and/or biotic activation, thus, increasing the risk of sensitization. In the present review a series of fragrance substances with well documented abiotic and/or biotic activation are given as indicative and illustrative examples of the general problem. Commonly used fragrance substances, also found in essential oils, autoxidize on contact with air, forming potent sensitizers that can be an important source for contact allergy to fragrances and fragranced products. Some of them can act as prohaptens and be activated in the skin as well. The experimental findings are confirmed in large clinical studies. When substances with structural alerts for acting as prohaptens and/or prehaptens are identified, the possibility of generating new potent allergens should be considered. Predictive testing should include activation steps. Further experimental and clinical research regarding activation of fragrance substances is needed to increase consumer safety.

Original language	English
Pages (from-to)	323-334
Number of pages	12
Journal	Contact Dermatitis
Volume	69
Issue number	6
DOIs	https://doi.org/10.1111/cod.12127
Publication status	Published - Dec 2013

Keywords

abiotic and biotic activation
autoxidation
directive 76
768
ECC
fragrance allergens
prehaptens
prohaptens
SCCS
scientific opinion
XENOBIOTIC METABOLISM CAPACITIES
IN-VITRO ALTERNATIVES
OXIDIZED D-LIMONENE
CONTACT ALLERGENS
SKIN SENSITIZATION
AIR EXPOSURE
LIQUID-CHROMATOGRAPHY
DERMATITIS PATIENTS
OXIDATION-PRODUCTS
MASS-SPECTROMETRY

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title = "Activation of non-sensitizing or low-sensitizing fragrance substances into potent sensitizers: prehaptens and prohaptens",

abstract = "Experimental and clinical studies have shown that fragrance substances can act as prehaptens or prohaptens. They form allergens that are more potent than the parent substance by activation outside or in the skin via abiotic (chemical and physical factors) and/or biotic activation, thus, increasing the risk of sensitization. In the present review a series of fragrance substances with well documented abiotic and/or biotic activation are given as indicative and illustrative examples of the general problem. Commonly used fragrance substances, also found in essential oils, autoxidize on contact with air, forming potent sensitizers that can be an important source for contact allergy to fragrances and fragranced products. Some of them can act as prohaptens and be activated in the skin as well. The experimental findings are confirmed in large clinical studies. When substances with structural alerts for acting as prohaptens and/or prehaptens are identified, the possibility of generating new potent allergens should be considered. Predictive testing should include activation steps. Further experimental and clinical research regarding activation of fragrance substances is needed to increase consumer safety.",

keywords = "abiotic and biotic activation, autoxidation, directive 76, 768, ECC, fragrance allergens, prehaptens, prohaptens, SCCS, scientific opinion, XENOBIOTIC METABOLISM CAPACITIES, IN-VITRO ALTERNATIVES, OXIDIZED D-LIMONENE, CONTACT ALLERGENS, SKIN SENSITIZATION, AIR EXPOSURE, LIQUID-CHROMATOGRAPHY, DERMATITIS PATIENTS, OXIDATION-PRODUCTS, MASS-SPECTROMETRY",

author = "Ann-Therese Karlberg and Anna Borje and Johansen, {Jeanne Duus} and Carola Liden and Suresh Rastogi and David Roberts and Wolfgang Uter and White, {Ian R.}",

year = "2013",

month = dec,

doi = "10.1111/cod.12127",

language = "English",

volume = "69",

pages = "323--334",

journal = "Contact Dermatitis",

issn = "0105-1873",

publisher = "Wiley-Blackwell",

number = "6",

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TY - JOUR

T1 - Activation of non-sensitizing or low-sensitizing fragrance substances into potent sensitizers

T2 - prehaptens and prohaptens

AU - Karlberg, Ann-Therese

AU - Borje, Anna

AU - Johansen, Jeanne Duus

AU - Liden, Carola

AU - Rastogi, Suresh

AU - Roberts, David

AU - Uter, Wolfgang

AU - White, Ian R.

PY - 2013/12

Y1 - 2013/12

N2 - Experimental and clinical studies have shown that fragrance substances can act as prehaptens or prohaptens. They form allergens that are more potent than the parent substance by activation outside or in the skin via abiotic (chemical and physical factors) and/or biotic activation, thus, increasing the risk of sensitization. In the present review a series of fragrance substances with well documented abiotic and/or biotic activation are given as indicative and illustrative examples of the general problem. Commonly used fragrance substances, also found in essential oils, autoxidize on contact with air, forming potent sensitizers that can be an important source for contact allergy to fragrances and fragranced products. Some of them can act as prohaptens and be activated in the skin as well. The experimental findings are confirmed in large clinical studies. When substances with structural alerts for acting as prohaptens and/or prehaptens are identified, the possibility of generating new potent allergens should be considered. Predictive testing should include activation steps. Further experimental and clinical research regarding activation of fragrance substances is needed to increase consumer safety.

AB - Experimental and clinical studies have shown that fragrance substances can act as prehaptens or prohaptens. They form allergens that are more potent than the parent substance by activation outside or in the skin via abiotic (chemical and physical factors) and/or biotic activation, thus, increasing the risk of sensitization. In the present review a series of fragrance substances with well documented abiotic and/or biotic activation are given as indicative and illustrative examples of the general problem. Commonly used fragrance substances, also found in essential oils, autoxidize on contact with air, forming potent sensitizers that can be an important source for contact allergy to fragrances and fragranced products. Some of them can act as prohaptens and be activated in the skin as well. The experimental findings are confirmed in large clinical studies. When substances with structural alerts for acting as prohaptens and/or prehaptens are identified, the possibility of generating new potent allergens should be considered. Predictive testing should include activation steps. Further experimental and clinical research regarding activation of fragrance substances is needed to increase consumer safety.

KW - abiotic and biotic activation

KW - autoxidation

KW - directive 76

KW - 768

KW - ECC

KW - fragrance allergens

KW - prehaptens

KW - prohaptens

KW - SCCS

KW - scientific opinion

KW - XENOBIOTIC METABOLISM CAPACITIES

KW - IN-VITRO ALTERNATIVES

KW - OXIDIZED D-LIMONENE

KW - CONTACT ALLERGENS

KW - SKIN SENSITIZATION

KW - AIR EXPOSURE

KW - LIQUID-CHROMATOGRAPHY

KW - DERMATITIS PATIENTS

KW - OXIDATION-PRODUCTS

KW - MASS-SPECTROMETRY

U2 - 10.1111/cod.12127

DO - 10.1111/cod.12127

M3 - Literature review

SN - 0105-1873

VL - 69

SP - 323

EP - 334

JO - Contact Dermatitis

JF - Contact Dermatitis

IS - 6

ER -

Activation of non-sensitizing or low-sensitizing fragrance substances into potent sensitizers: prehaptens and prohaptens

Abstract

Keywords

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