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Skin Reactions to Xenobiotics

Ola Bergendorff

Department of Occupational Dermatology

University Hospital

Malmö

Ola Bergendorff May 2017

This lecture has been prepared with help from

Associate Professors Malin Engfeldt and Cecilia Svedman

Department of Occupational Dermatology, University

Hospital, Malmö

Overview

1. Skin barrier

2. Chemical burn

3. Phototoxic reactions

4. Urticaria

5. Contact allergy

The skin barrier

The skin

Epidermis

0.1 mm

Skin blister

Epidermis

Dermis

Blister

Scarring permanent tattoo

Stratum

corneum

Tape strip

L M Milstone. Epidermal desquamation. Journal of Dermatological Science (2004) 36, 131-140

Psoriasis

4 days

Skin barrier

0.1 mm

Stratum

corneum

Keratinocyte

Melanocyte

Langerhans’ cell

Moghimi HR; Williams AC; Barry BW. A lamellar matrix model for stratum corneum intercellular lipids. 2. INTERNATIONAL

JOURNAL OF PHARMACEUTICS. 131 (2) 117-129. 1996

20 µm500 µm

Hadgraft J. Skin deep. Eur J Pharm Biopharm 2004: 58: 291-299

Lars Norlen, Karolinska Institute

How large particles will penetrate skin?

Rolland A, Wagner N, Chatelus A, Shroot B, Schaefer H. SITE-SPECIFIC DRUG-DELIVERY TO PILOSEBACEOUS

STRUCTURES USING POLYMERIC MICROSPHERES. Pharm Res 1993: 10: 1738-1744.

Nanoparticles < 0,1 µm

Chemical burns

Chemical burns due to Kathon CG- an allergenic preservative in paint

Chemical Treatment

Acids, bases Water

Hydrogen fluoride Calcium salt

Phenols Alcohol, PEG

Bromine, Iodine Thiosulfate

Chemical burn

Protect your skin!

• Wash your hands thoroughly after contamination

• Use moisturiser

• Use gloves but choose the right material

• Exchange gloves often

TOO MUCH WATER CONTACT WILL

DAMAGE YOUR SKIN BARRIER

Toxic (non-allergic)

photo reactions

Fytophotodermatitis

Photochemical DNA addition

Psoralen

Crosslinks in DNA

Fytophototoxic plants

Dictamnus albus

Burning bush /

Mose brinnande buske

Ruta graveolens

Rue / Vinruta

Citrus peel

Urticaria

UrticariaStinging nettle(Urtica dioica)

HistamineOla Bergendorff May 2017

Allergy towards rodents

Urticaria

Immunologic urticariaAllergy type 1

A fast antibody-mediated reaction to large molecules.

•Proteins from animal saliva, urine, dandruff.

•Pollen.

•House dust mites.

•Natural rubber latex

Occupational allergic asthma from small molecules that form

adducts with proteines in airway mucosa.

•Isocyanates in paints and polyurethane.

•Acid-anhydrides in polymer production.

•Acrylates in polymers. Dental technicians.

Skin prick test

Blood tests are also available for

most of the allergens.Ola Bergendorff May 2017

Contact allergy

Nickel Rubber additives

Allergic contact dermatitis

Contact allergens

• Metal salts: nickel, chromium, cobalt

• Electrophilic organic compounds, MW < 500

• 4000 known allergens

• Preservatives, fragrances, hair/textile-dyes, rubber

vulcanisers, plastic monomers, natural products,

pharmaceuticals

Contact allergens

Epicutaneous testings

”Patch test”

After a few days

”Reading” at day 3 and 7

Stefan R Ahlfors, Thesis 2008, dept of Dermatology LundOla Bergendorff May 2017

Metalsmetal ions

Nickel: 15-20% sensitive to Ni(II)

Jewellery is the main exposure

Coins, keys

Chromium: 4% sensitive to Chromium (VI)

Leather and cement main exposure

Legislation28 58.69

NiNickel

24 51.99

CrChromium

Directive 2003/53/EG reduction of Cr (VI) to insolubleCr (III) by addition of reducingagent. No more than 2 ppm Cr(IV) allowed. OCCUPATIONAL

Regulation (EU) 301/2014 content of Cr(IV) in leathermust not exceed 3 ppm.CONSUMER/OCCUPATIONAL

Annex XVII in 1907/2006 (REACH)In products intended to come intodirect and prolonged contact withthe skin the Ni release must not exceed 0.5 µg/cm2 per week after2 yrs of normal use.

Adopted in 1994, in force 2000.

CONSUMER

In contrast, 17% of the concreteworkers suffered from chromatedermatitis during construction of the tunnel between England and France.

Chromate allergyCement

During construction of the bridges over Öresund and Stora Bält no one ofthe builders suffered from chromateinduced dermatitis.

Irvine C et al. Cement dermatitis in underground workers during the construction ofthe Channel Tunnel, Occup Med 44:17-23

Fragrances

• 300-400 naturally

occuring substances

• More than 2500

synthetic fragrances

Limonene (citrus scent)

•Autoxidizes at 10 weeks: 40% limonene, 7% limonene OOH

•Allergenic oxidation products

•Hydroperoxides main allergens, also carvone, limonene oxideformed

0 10 20 30 40 50 60 70 80

Oxidation time (weeks)

Karlberg et al. Contact Dermatitis1997: 36: 201-206

Limonene (citrus scent)

•Autoxidizes at 10 weeks: 40% limonene, 7% limonene OOH

•Allergenic oxidation products

•Hydroperoxides main allergens, also carvone, limonene oxideformed

Allergenicity from air oxidation

Poison oak

Polymers

”Plastics”: Epoxy, acrylates, phenolic etcmonomers are allergens

”Rubber”: Additives are allergens

ACRYLATES

Exposure

Dental fillingsUV-curable paintArtificial nailsEye lash elongation

UV-curing nail gel

OligomerMethacrylate monomerPhotoinitiatorPigment

ACRYLATES

Oligomer

Methacrylatemonomer

Photoinitiator

Pigment

+ Pigments

Rubber

Rubber polymer

Polyisoprene. Isoprene monomers

Trans-isomer i gutta-percha.

Dental material: fillning of root canal.

100% cis-isomer i natural rubber.

95-99% cis-isomer i synthetic

polyisoprene

Palaquium guttaHevea brasiliensis

Natural rubber

VULCANIZATION

Rubber additives

Allergenic accelerators and antioxidants

Name Abbrev. Structure

Tetramethylthiuram monosulfide TMTM

Tetramethylthiuram disulfide TMTD

Tetraethylthiuram disulfide TETD

Dipentamethylenthiuram disulfide DPTD

Thiurams

Accelerators

Name Abbrev. Structure

2-Mercaptobenzotiazole MBT

2,2’-Dibenzotiazyl disulfide MBTS

2-(4-Morfolinylmercapto)

benzotiazoleMOR

N-Cyclohexyl-2-

benzotiazolsulfenamideCBS

Mercaptobenzothiazoles

NS N O

Acceleratorer

Soga F, Katoh N, Inoue T, Kishimoto S. Contact Dermatitis, 2008;58(2):116-117.

Preservatives

In water based products

Liquid soaps, shampoos, cosmetics, skin care products

Paint, metal working fluids

Isothiazolinones (MCI/MI)

Formaldehyde (formaldehyde releasers)

Preservatives

Bronopol

Quaternium 15

Imidazolidinylurea

Diazolidinylurea

DMDM hydantoin

Formaldehyde releasers

Bronopol

Quaternium 15

Imidazolidinylurea

Diazolidinylurea

DMDM hydantoin

Formaldehyde releasers

6 HCHO

Summary Chemical burn

• Can result in an allergy

• Important to wash thoroughly

• pH-indicator

Phenolics

HF (hydrogen fluoride)

Summary Phototoxic reaction

• Furocoumarin (psoralen) + UV

• DNA-damage

Wild plants

Cultivated plants

Citrus peel

Summary Urticaria

• Immunologic: type 1-allergy to macromolecules

• Antibody-mediated

• Skin Prick Test

• Immediate reaction

• Allergic asthma to small molecules in some cases

Summary Contact allergy

• Immunologic: type 4-allergy to small molecules

• Epicutaneous test (patch test)

• Delayed reaction

• T-cell-mediated

• Activation / air oxidation mechanisms

Photoallergy to NSAID and Sunscreens

Black henna tattooing

p-Phenylenediamine in

henna tattooing

Life-long allergy to:

Hair dyes

Textile dyes

Black rubber

Black henna

= Risk!

Brown-orange henna =

Minimal risk

skin reactions to xenobiotics - lunds universitet › education › phd courses › riskkursen ›...

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