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Observation
October 2006

Antimicrobial Allergy From Polyvinyl Chloride Gloves

Author Affiliations

Author Affiliations: Control of Hypersensitivity Diseases Team, Finnish Institute of Occupational Health, Helsinki (Drs Aalto-Korte, Alanko, and Jolanki), and Chemical Agents Team, Finnish Institute of Occupational Health, Turku (Ms Henriks-Eckerman), Finland.

Arch Dermatol. 2006;142(10):1326-1330. doi:10.1001/archderm.142.10.1326
Abstract

Background  Contact allergy to plastic gloves is rare. Benzisothiazolinone is a biocide that is mainly used in industrial settings. We first suspected delayed-type contact allergy to benzisothiazolinone from polyvinyl chloride (PVC) gloves in 2004. We looked through our medical records from 1991 to 2005 to find similar cases.

Observations  We found a total of 8 patients who are allergic to benzisothiazolinone and who had had exacerbations of their hand dermatitis while using PVC gloves. Patch testing revealed that 3 of them had weak allergic or doubtful reactions to the glove materials. Six of them had used Evercare Soft, Medi-Point, or Derma Grip PVC gloves, which in chemical analysis were shown to contain 9 to 32 ppm of benzisothiazolinone. Seven of the patients worked in dentistry or health care and 1 in farming. All of them had had hand dermatitis for many years.

Conclusions  To our knowledge, there have been no previous reports of contact allergy to antimicrobial agents in plastic gloves. Benzisothiazolinone is widely used as a biocide in the manufacture of disposable PVC gloves. Small amounts of benzisothiazolinone in the gloves may sensitize those who already have hand dermatitis. We recommend that all patients with hand dermatitis while using PVC gloves should be patch tested with benzisothiazolinone.

Allergic contact dermatitis from plastic gloves is rare compared with that from rubber gloves. Plastic gloves may be made from several types of polymers but most commonly are made from polyvinyl chloride (PVC). In past examinations of contact allergy to PVC gloves, the specific causative allergens have often remained unknown. Several cases of bisphenol A allergy1,2 and single cases caused by an organic pigment3 and adipic polyester4 have been reported, but to our knowledge, there are no previous case reports of allergic contact dermatitis from any antimicrobial substance in PVC gloves. Gloves made of PVC also contain phthalates that are potential allergens.

Benzisothiazolinone (1,2-benzisothiazolin-3-one [BIT]; Chemical Abstracts Service No. 2634-33-5) is an antimicrobial agent that is used in industry as a preservative in water-based solutions such as paints, lacquers, cutting fluids, printing inks, cleaning agents, polishes, fabric softeners, pigments, surfactants, binders, plasticizers, construction materials, curing agents, impregnating agents, antiadhesive agents, pesticides, adhesives, and glues.5,6 Occupational allergic contact dermatitis from handling the pure chemical or preservatives with a high concentration of BIT has been reported in industrial laboratory work710 and in the manufacture of paints,9,11,12 varnishes,9,13 plastic emulsions,7 paper,14 rubber,15 dyes,16 air fresheners,17 water softeners,18 and carpets.19 Other sources of sensitization include the use of metal-working fluids,2022 paints,23,24 putties, wallpaper paste,24,25 shoe glue,26 a releasing oil in the pottery industry,27 and gum arabic in lithographic printing.28 Allergic patch test reactions to BIT have also been found in 6 woodwork teachers,29 a plumber, and a silk-screen printer.25 Most of the reports consist of only a few cases.

We first suspected that 1 of our patients (patient 1 in the Table) had been sensitized to BIT by using PVC gloves in August 2004. Then, 3 other patients (patients 2-4) were seen for BIT contact allergy and hand dermatitis while using PVC gloves. We analyzed the gloves for BIT and looked through our medical records from January 1991 to September 2005 to find similar cases.

Table. 
Patients Allergic to BIT, Their Occupation, Patch Test Reactions, Exposure, and Diagnoses
Patients Allergic to BIT, Their Occupation, Patch Test Reactions, Exposure, and Diagnoses
METHODS

The Section of Dermatology at the Finnish Institute of Occupational Health (FIOH) is a special clinic for occupational skin diseases. We have just under 200 new patients each year, and they come from all parts of Finland.

We have included BIT in our oil and lubricant series since 1991, and in 1992 it was also added to our antimicrobial series. It was first tested at a 0.05% concentration in alcohol and since 1994 at the same concentration in petrolatum (Chemotechnique Diagnostics, Malmö, Sweden). Also, BIT 0.1% in petrolatum (Trolab; Hermal, Reinbeck, Germany) was included in a dental patch series that was used in a study of dental nurses in 1999.30

We analyzed our skin test files for reactions to BIT. We checked the clinical records of the patients with an allergic reaction (+, weak positive; ++, strong positive; and +++, extreme positive) for other skin test reactions, symptoms, exposure, and diagnosis. The skin tests of the 3 most recent cases of allergic reaction to BIT (patients 2-4) were not yet in the skin test files, but we nevertheless analyzed their medical records in the same way. (These patients were not yet in the file when analysis took place because the test results of a patient are not put into the file until the examination is complete and the report sent to the insurance company.)

Glove material was tested in 1 test chamber (Finn Chamber; Epitest Oy, Tuusula, Finland) with a drop of acetone and in another with a drop of water. We tested the acetone extract of the glove material made in an ultrasonic cleaning bath in 3 cases (patients 1, 3, and 4), and in 1 case (patient 1) we also tested the water and ethanol extracts.31

The concentrations of BIT in the suspected gloves (patients 1, 2, and 4) were analyzed by high-performance liquid chromatography with a UV detector at 230 nm. Mass spectrometry confirmed the detection. Accurately weighed slices taken from the palm or the back of a glove (100 and 200 mg, respectively) were extracted with 5 mL of a mixture of water and methanol (3:1) overnight at room temperature. The liquid chromatography column was a reversed-phase C18 column (Symmetry Shield; Waters Corp, Milford, Mass) (3.5-μm particles, 150 × 2 mm). The mobile phase was methanol and water (32:68) with 2mM of ammonium acetate, and the flow rate was 0.2 mL/min-1. The relative standard deviation of the repeatability of the analysis was about 25% for concentration levels corresponding to 20 to 200 ppm (wt/wt). The detection limit was about 2 ppm.

RESULTS
PATCH TEST REACTIONS TO BIT IN 2264 PATIENTS

From January 1991 to September 2005, BIT was tested on a total of 2264 patients, and 17 (0.75%) of them had an allergic reaction to it. We tested 163 patients with 0.05% BIT in alcohol (with 2 allergic reactions), 123 with 0.1% BIT in petrolatum (with no allergic reactions), 1963 with 0.05% BIT in petrolatum (with 15 allergic reactions), and 15 with both 0.1% and 0.05% BIT in petrolatum (with no allergic reactions). The reaction index32 for the current test substance, 0.05% (petrolatum), in 1978 patients was −0.34.

PATIENTS WITH ALLERGIC REACTION TO BIT

From 1991 to 2005 we had a total of 20 patients who had an allergic patch test reaction to BIT. Their patch test reactions to BIT and PVC gloves, occupations, exposure to BIT, and diagnoses are presented in the Table. Four of these 20 patients (patients 3, 10, 15, and 19) reacted to the mixture of 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one (CMI/MI) and 2 (patients 10 and 11) to 2-N-octyl-4-isothiazolin-3-one (OIT).

BIT CONCENTRATIONS IN PVC GLOVES (PATIENTS 1, 2, AND 4)

According to the analysis, the Evercare Soft (Selefatrade AB, Spånga, Sweden) PVC glove samples of patients 1 and 4 contained 20 and 22 ppm of BIT, respectively. The Derma Grip (Oriola Oy, Espoo, Finland) PVC glove samples of patients 2 and 4 contained 9 and 22 ppm of BIT, respectively. The Medi-Point (Insinööritoimisto Medi-Point Oy, Helsinki) PVC glove of patient 2 contained 31 ppm of BIT. (The Medi-Point glove of patient 3 was not analyzed because it was the same brand.) We also analyzed other gloves the patients had used, the Top Dent (Oriola Oy Hammashoito, Espoo) PVC glove of patient 2 and the Derma Grip nitrile glove of patient 4, but they did not contain BIT (concentrations were below the detection limit of 2 ppm). Patch tests with the Evercare Soft glove moistened with water and acetone were negative for allergic reaction in 5 control patients.

COMMENT

On patch testing, BIT is an irritant, and the test concentration has been gradually lowered since the 1980s from 1% to the present concentration of 0.05%.21,33 Although the possibility of false-positive reactions to BIT cannot be excluded in the present series of patients, it is also possible that some patients with irritant or doubtful reactions might truly have been sensitized to BIT. Among these patients was a dentist with a doubtful reaction to BIT who had used the BIT-containing Derma Grip gloves.

Despite the similarity in chemical structure, BIT is not considered to cross react with CMI/MI or OIT.3335 Concomitant reactions to these isothiazolinones were not common among our patients, which supports the idea of separate sensitization.

Occupational allergic contact dermatitis from BIT has been reported in a variety of industries using biocides with high BIT concentrations (>10%), and the relevance of the allergic reaction is usually clear in these cases. At the FIOH we have had 3 cases of occupational allergic contact dermatitis belonging to this category (patients 14, 16, and 18). In addition to these 3 cases, we have come across 1 case (patient 17) of occupational allergic contact dermatitis caused by BIT (1000 ppm) in a metal-working fluid; BIT is used in paints and putties at concentrations of 50 to 250 ppm.23 Our series included 1 patient (patient 12) who had possibly been sensitized to BIT when using water-based paints and another (patient 19) who had been handling metal-working fluids.

Among our patients there were 9 patients who were allergic to BIT and who had used PVC gloves at work daily. One of them (patient 9) had apparently not had dermatitis but rather dermographism, which explains why her symptoms arose from the use of various different gloves. Thus, we have had a total of 8 patients (patients 1-8) with BIT allergy and hand dermatitis in connection with PVC glove use. Six of them had used gloves that in the chemical analysis were shown to contain small amounts of BIT.

The question is whether the low BIT concentrations of 9 to 32 ppm in the gloves can sensitize or elicit contact allergy. Chemically, BIT is related to the extremely strong allergen CMI/MI, but it has been a somewhat weaker sensitizer in the local lymph node assay33,36 and in the human repeated insult patch test.33 Although the BIT concentrations in the PVC gloves were lower than those in the paints and putties, they were at the same level or a little higher than ordinary concentrations of CMI/MI in cosmetic products (3-15 ppm).37

In the present series of patients, the PVC glove material (or an ultrasonic bath extract from it) caused allergic reactions on patch testing in only 2 patients. One patient had doubtful reactions to the glove, and in 3 patients the BIT-containing glove was negative for allergic reaction in the patch test. In the 2 positive cases, the connection between BIT allergy and the PVC gloves is probable. However, the other patients' negative patch test results do not exclude sensitization from the glove. Similarly, CMI/MI–containing cosmetic products, although positive on repeated open application test, are often negative for reaction on patch testing.37 Also, BIT does not belong to the frequent sensitizers in dentistry38 or health care.39 We searched for other possible sources of BIT sensitization, but of all the products our patients had used, we found BIT only in the PVC gloves. In Finland, the use of BIT is forbidden as an antimicrobial agent in cosmetics,40 but in daily life consumers may have skin contact with BIT in fabric softeners, cleaning agents, and polishes.5

A common feature of patients 1 to 8 was a long history of hand dermatitis (of at least 5 years’ duration), and they had also been diagnosed with other types of hand dermatitis besides BIT contact allergy. Thus, sensitization to BIT in the gloves was probably not the primary event. The occlusive effect of the PVC gloves on their eczematous skin might have enhanced the percutaneous penetration of BIT so that they had become sensitized despite the low allergen concentration.

Most of our patients were able to continue their work after they changed to a different type of glove, usually to nitrile gloves. Only 1 patient (patient 6), a dental nurse with primary rubber glove allergy, had to change her job because the dermatitis reappeared with use of Derma Grip PVC gloves. At that time we were not aware that these PVC gloves contained BIT. This allergy may have quite serious consequences if it is not recognized.

Antimicrobial additive systems are increasingly used in plastic polymers, mainly in PVC plastics,41 and particularly in the medical and food industries.42 Products that are already on the market include domestic applications such as rubbish bins, kitchen utensils, tubing, air filters, containers, and mattresses. Medical antimicrobial products such as gloves, catheters, wound dressings, and bedding are also available.42 Antimicrobial agents are used in plastics to reduce microbe populations both within the material and at the surface.42 The organic antimicrobials used in plastics include 10′,10′-oxybisphenoxyarsine, OIT, dichloro-2-N-octyl-4-isothiazolin-3-one, tributyl tin, 2,4,4′-tricloro-2′-hydroxy diphenyl ether, zinc pyrithione, zinc omadine, N-butyl-1,2-benzisothiazolin-3-one, 3-iodo-2-propynyl butyl carbamate, and N-(tricholoromethylthio)phthalamide.41,43 The plasticizer can act as the carrier for the biocide (eg, 10′,10′-oxybisphenoxyarsine or OIT).42

The number of patients treated for allergic reaction to BIT in PVC gloves at our small clinic is alarming, although our patient material is strongly selected. The true extent of the problem remains to be settled in other clinics with larger patient populations. It is interesting that all 8 of these patients (patients 1-8) were investigated in 2001 or later, although we have tested BIT in almost every patient since 1992. Inquiries to several representatives of PVC glove sales representatives in Finland have uniformly revealed that BIT is a component in a biocide compound that has been widely used for at least 15 years as a slimicide in the manufacturing process of disposable PVC gloves. The market for these products has considerably increased over recent years.

At the FIOH, BIT is included in the antimicrobial series, which is tested on most of our patients, irrespective of their occupation. In the commercial patch test series, BIT is included in Chemotechnique Diagnostics' “Oils and Cooling Fluids” series and in Trolab's “Cutting Oils” and “Industrial Biocides” series. It is possible that BIT is not commonly tested on dental and health care personnel. We recommend that all patients with hand dermatitis while using PVC gloves should be patch tested with BIT.

In summary, to our knowledge, there are no previous reports of antimicrobial skin contact allergy deriving from PVC gloves. We described herein 8 patients with BIT allergy and hand dermatitis in connection with PVC glove use. In findings from chemical analysis, 3 brands of disposable PVC gloves contained small amounts of BIT, and 6 of the patients had used at least 1 of these brands. All of the patients had a long history of hand dermatitis. Small amounts of BIT in the glove seem to be able to sensitize persons who already have hand dermatitis. We recommend that BIT should be tested on all patients with hand dermatitis who use PVC gloves.

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Article Information

Correspondence: Kristiina Aalto-Korte, MD, PhD, Finnish Institute of Occupational Health, Control of Hypersensitivity Diseases Team, Topeliuksenkatu 41 a A, FIN-00250 Helsinki, Finland (kristiina.aalto-korte@ttl.fi).

Financial Disclosure: None reported.

Accepted for Publication: March 14, 2006.

Author Contributions:Study concept and design: Aalto-Korte, Alanko, and Jolanki. Acquisition of data: Aalto-Korte, Alanko, Henriks-Eckerman, and Jolanki. Analysis and interpretation of data: Aalto-Korte, Alanko, and Jolanki. Drafting of the manuscript: Aalto-Korte and Henriks-Eckerman. Critical revision of the manuscript for important intellectual content: Alanko and Jolanki.

References
1.
Aalto-Korte  KAlanko  KHenriks-Eckerman  MLEstlander  TJolanki  R Allergic contact dermatitis from bisphenol A in PVC gloves. Contact Dermatitis 2003;49202- 205
PubMedArticle
2.
Matthieu  LGodoi  AFLambert  JVan Grieken  R Occupational allergic contact dermatitis from bisphenol A in vinyl gloves. Contact Dermatitis 2003;49281- 283
PubMedArticle
3.
Kanerva  LJolanki  REstlander  T Organic pigment as a cause of plastic glove dermatitis. Contact Dermatitis 1985;1341- 43
PubMedArticle
4.
Sowa  JKobayashi  HTsuruta  DSugawara  KIshii  M Allergic contact dermatitis due to adipic polyester in vinyl chloride gloves. Contact Dermatitis 2005;53243- 244
PubMedArticle
5.
Nielsen  H Occupational exposure to isothiazolinones: a study based on a product register. Contact Dermatitis 1994;3118- 21
PubMedArticle
6.
Flyvholm  MA Preservatives in registered chemical products. Contact Dermatitis 2005;5327- 32
PubMedArticle
7.
Pedersen  NB Occupational allergy from 1,2-benzisothiazolin-3-one and other preservatives in plastic emulsions. Contact Dermatitis 1976;2340- 342
PubMedArticle
8.
Slovak  AJ Contact dermatitis due to benzisothiazolone in a works analytical team. Contact Dermatitis 1980;6187- 190
PubMedArticle
9.
Hardcastle  NJGawkrodger  DJ Occupational contact dermatitis to 1,2-benzisothiazolin-3-one and 5-chloro-2-methylisothiazolin-3-one/2-methylisothiazolin-3-one in paint manufacturers. Contact Dermatitis 2005;53115- 116
PubMedArticle
10.
Burden  ADO'Driscoll  JBPage  FCBeck  MH Contact hypersensitivity to a new isothiazolinone. Contact Dermatitis 1994;30179- 180
PubMedArticle
11.
Greig  DE Another isothiazolinone source. Contact Dermatitis 1991;25201- 202
PubMedArticle
12.
Sanz-Gallen  PPlanas  JMartinez  PGimenez-Arnau  JM Allergic contact dermatitis due to 1,2-benzisothiazolin-3-one in paint manufacture. Contact Dermatitis 1992;27271- 272
PubMedArticle
13.
Walker  SLYell  JABeck  MH Occupational allergic contact dermatitis caused by 1,2-benzisothiazolin-3-one in a varnish maker, followed by sensitization to benzalkonium chloride in Oilatum Plus bath additive. Contact Dermatitis 2004;50104- 105
PubMedArticle
14.
Cronin  E Contact Dermatitis.  Edinburgh, Scotland Churchill Livingstone1980;
15.
Foussereau  JBrandle  IBoujnah-Khouadja  A Allergic contact eczema caused by isothiazolin-3-one derivatives [in German]. Derm Beruf Umwelt 1984;32208- 211
PubMed
16.
Muhn  CSasseville  D Occupational allergic contact dermatitis from 1,2-benzisothiazolin-3-one without cross-sensitization to other isothiazolinones. Contact Dermatitis 2003;48230- 231
PubMedArticle
17.
Dias  MLamarao  PVale  T Occupational contact allergy to 1,2-benzisothiazolin-3-one in the manufacture of air fresheners. Contact Dermatitis 1992;27205- 207
PubMedArticle
18.
Cooper  SMShaw  S Occupational hand dermatitis due to 1,2-benzisothiazolin-3-one in the water-softener manufacturing industry. Contact Dermatitis 1999;40221
PubMedArticle
19.
Taran  JMDelaney  TA Allergic contact dermatitis to 1,2-benzisothiazolin-3-one in the carpet industry. Australas J Dermatol 1997;3842- 43
PubMedArticle
20.
Alomar  A Contact dermatitis from benzisothiazolone in cutting oils. Contact Dermatitis 1981;7155- 156
PubMedArticle
21.
Alomar  AConde-Salazar  LRomaguera  C Occupational dermatoses from cutting oils. Contact Dermatitis 1985;12129- 138
PubMedArticle
22.
Brown  R Concomitant sensitisation to additives in a coolant fluid. Contact Dermatitis 1979;5340- 341
PubMedArticle
23.
Fischer  TBohlin  SEdling  CRystedt  IWieslander  G Skin disease and contact sensitivity in house painters using water-based paints, glues and putties. Contact Dermatitis 1995;3239- 45
PubMedArticle
24.
Ezzelarab  M Occupational allergy caused by 1,2-benzisothiazolin-3-one in water-based paints and glues. Am J Contact Dermat 1994;5165- 167Article
25.
Damstra  RJvan Vlotten  WAvan Ginkel  CJ Allergic contact dermatitis from the preservative 1,2-benzisothiazolin-3-one (1,2-BIT; Proxel): a case report, its prevalence in those occupationally at risk and in the general dermatological population, and its relationship to allergy to its analogue Kathon CG. Contact Dermatitis 1992;27105- 109
PubMedArticle
26.
Ayadi  MMartin  P Pulpitis of the fingers from a shoe glue containing 1,2-benzisothiazolin-3-one (BIT). Contact Dermatitis 1999;40115- 116
PubMedArticle
27.
Roberts  DLMessenger  AGSummerly  R Occupational dermatitis due to 1,2-benzisothiazolin-3-one in the pottery industry. Contact Dermatitis 1981;7145- 147
PubMedArticle
28.
Freeman  S Allergic contact dermatitis due to 1,2-benzisothiazolin-3-one in gum arabic. Contact Dermatitis 1984;11146- 149
PubMedArticle
29.
Meding  BAhman  MKarlberg  AT Skin symptoms and contact allergy in woodwork teachers. Contact Dermatitis 1996;34185- 190
PubMedArticle
30.
Alanko  KSusitaival  PJolanki  RKanerva  L Occupational skin diseases among dental nurses. Contact Dermatitis 2004;5077- 82
PubMedArticle
31.
Bruze  MTrulsson  LBendsöe  N Patch testing with ultra-sonic bath extracts. Am J Contact Dermat 1992;3133- 137Article
32.
Brasch  JHenseler  T The reaction index: a parameter to assess the quality of patch test preparations. Contact Dermatitis 1992;27203- 204
PubMedArticle
33.
Basketter  DARodford  RKimber  ISmith  IWahlberg  JE Skin sensitization risk assessment: a comparative evaluation of 3 isothiazolinone biocides. Contact Dermatitis 1999;40150- 154
PubMedArticle
34.
Emmett  EANg  SKLevy  MAMoss  JNMorici  IJ The irritancy and allergenicity of 2-n-octyl-4-isothiazolin-3-one (Skane M-8), with recommendations for patch test concentration. Contact Dermatitis 1989;2021- 26
PubMedArticle
35.
Geier  JSchnuch  A No cross-sensitization between MCI/MI, benzisothiazolinone and octylisothiazolinone. Contact Dermatitis 1996;34148- 149
PubMedArticle
36.
Botham  PAHilton  JEvans  CDLees  DHall  TJ Assessment of the relative skin sensitizing potency of 3 biocides using the murine local lymph node assay. Contact Dermatitis 1991;25172- 177
PubMedArticle
37.
Tosti  A Prevalence and sources of Kathon CG sensitization in Italy. Contact Dermatitis 1988;18173- 174
PubMedArticle
38.
Rustemeyer  TFP Occupational contact dermatitis in dental personnel. Kanerva  LEPWahlberg  JEMaibach  HIeds.Handbook of Occupational Dermatology. Berlin, Germany Springer2000;
39.
Belsito  D Healthcare workers. Kanerva  LEPWahlberg  JEMaibach  HIeds.Handbook of Occupational Dermatology. Berlin, Germany Springer2000;
40.
 Kauppa-ja teollisuusministeriön asetus kosmeettisista valmisteista [Statute of cosmetic products given by the Ministry of Trade and Industry in Finland; statute in Finnish]. Suomen säädöskokoelma. 2005: 201-283. Statute No. 75 
41.
D'Arcy  N Antimicrobials in plastics: a global review. Plastics Additives Compounding 2001;312- 15Article
42.
Simmons  J Antimicrobial additive systems see increased use in polymers. Plastics Additives Compounding 2001;316- 18Article
43.
Markarian  J Antimicrobial plastics additives: trends and latest developments in North America. Plastics Additives Compounding 2002;418- 21Article
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