Allergies to rubber chemicals are one of the most common causes of
occupational contact dermatitis. Historically, chemical allergies have
been most prevalent in household and industrial gloves; however reactions to
the chemicals in surgical gloves or the chemicals that pass through them are
increasing.
In the 50s, the incidence of rubber allergies outside the manufacturing
industry was still relatively rare. The terms used to describe this industrial
form of "rubber eczema" seem curiously anecdotal. Rubber workers
discussed "rubber scabies" or "sypholatex chronica." In the past 2
years, studies in allergy centers worldwide have shown a 3 to 14
percent incidence frequency of allergic late-type reactions to chemicals (see Table 1).
Table 1
Incidence of sensitization to rubber chemicals |
| Authors |
Study Period |
Country |
Positive Patients |
Reaction |
Percent |
| Vincze et al. |
1979 |
Hungary |
369 |
52 |
14.1 |
| Nurse |
1976-1979 |
Australia |
486 |
50 |
10.2 |
| Gay |
1981-1984 |
France |
559 |
44 |
7.9 |
| Themido, Menezes Brandao |
1977-1982 |
Portugal |
4,565 |
313 |
6.8 |
| Cronin |
1965-1976 |
England |
19,204 |
1,184 |
6.2 |
Kammintausta
and Kalimo |
1980-1982 |
Finland |
3,3332 |
158 |
4.7 |
| Taylor et al. |
1977-1982 |
North America |
a) 9,571
(Thiuram Mix)
b) 9,567
(Mercap-to-Mix) |
a) 423
b) 261 |
a) 4.4
b) 2.7 |
Grubaka-Suchanck
et al. |
1980-1984 |
Poland |
1,240 |
51 |
4.1 |
| von Hintzenstern et al. |
1985-1990 |
Germany |
3,851 |
145 |
3.8 |
| Fuchs |
1984-1986 |
Germany |
2,771 |
748 |
5.3 |
| Fuchs |
1898-1991 |
Germany |
900 |
59 |
6.0 |
Chemical allergic reactions to gloves and other rubber products manifest
themselves primarily as late-type allergies (Type IV according to Coombs
and Gell). The clinical equivalent is allergic contact dermatitis (eczema),
distinguished from contact urticaria caused by natural latex proteins.
Pathogenetically speaking, both are immunological reactions, although in
this case the latter is either an immediate type reaction allergy mediated
by specific IgE-antibodies (Type I according to Coombs and Gell) or a
pseudo-allergic or anaphylactoid phenomenon,i.e., a non-immunological
reaction.
Contact dermatitis caused by rubber or its constituents can lead to patient
loss of occupation.
CLINICAL ASPECTS OF SENSITIZATION CAUSED
BY CHEMICALS USED IN RUBBER PRODUCTS
There are two types of rubber: domestic, used in the household or medical
field, and heavy duty black rubber for industrial use. In addition to gloves,
domestic rubber is used in a variety of consumer products where the
primary sensitizing substances, which mainly affect women, are the
thiurams, dithiocarbamates and the mercapto compounds. The
sensitizing substances in industrial rubber are comparably stronger and
affect mainly men. In this case, sensitization is predominantly
caused by the antioxidants of the PPD group such as IPPD, DPPD,
or CPPD. These can be found in a variety of products such as masks,
conveyer belts, rubber tires, inner tubes, hoses and rubber boots.
Other chemicals contained in heavy duty black rubber products are PBN,
DBNPD, mercapto compounds as well as DPG.
Cross reactions (group reactions), are allergic reactions to chemically-
related compounds containing the same molecular group. The paragroup
allergies are a well known example. Sensitization occurs through IPPD,
thus many other aromatic amino compounds substituted in paraposition
such as CPPD or DPPD also cannot be tolerated. Thiurams and
dithiocarbamates as well as mercapto compounds also show cross-
reactive responses.
GLOVES
Late-type allergic reactions to surgical or examination gloves typically
manifest themselves as eczema (contact dermatitis). Early stage, or mild
eczema, affects the fingertips and balls of the thumbs. A distinct
demarcation around the wrist where the cuff of the glove ends, and more
extensive evidence on the balls of the thumbs and/or back of the hands
are indications of a more serious reaction. Reactions outside the area of
contact often indicate extreme sensitization.
Of all rubber products, gloves most commonly cause allergic contact
dermatitis from chemicals in the products. The greatest allergenic
potential of rubber additives in surgical gloves is vulcanizers and
antioxidants. Due to their extensive use in the manufacturing process,
thiurams prove to be the predominant allergens, followed by the
dithiocarbamates and, to a lesser degree, the thiazoles, aldehydamines
and guanidines. Contact dermatitis is generally confirmed by patch
testing in which either individual substances or mixtures of various
vulcanizing agents are used.
The primary allergens to be considered are the thiurams disulfides and
monosulfides, followed by the dithiocarbamates and the mercapto and
sulfenamide group of thiazoles. Several studies have shown
mercaptobenzothiazole (MBT), also found in other products, to be the
most common rubber allergen of this group. It is also used as a
preservative in cooling agents, detergents and fungicides making them
possible causes of chemical allergic contact dermatitis.
Patch testing the above substances does more than show evidence of
chemical allergens. If the test substances show structural similarities,
they can demonstrate immunological cross-reactivity between, for
example, tetramethyl and tetraethylthiuram disulfide, between
tetraethylthiuram disulfide and zinc diethyldithiocarbamate or between
different thiazoles. Additional possible allergens which can cause
chemical allergic contact dermatitis are lanolin (used as a softener),
polyoxypropyleneglycole (a coagulant), and organic and inorganic
coloring pigments used in household gloves (e.g., orange 34).
Table 2
Positive Patch Test Reactions To The Thiuram-Mixer (TMTD) |
| Country |
Test Period |
% Positive |
Authors |
| England (London) |
1965-1976 |
2.3-5.4% |
Cronin (1980) |
| Finland |
1980-1982 |
2.2% |
Lammintausta et al. (1985) |
| North America |
1970-1982 |
3.6-5.2% |
Taylor (1986) |
| North America |
1984-1985 |
3.9% |
Stores et al. (1989) |
| Germany (Erlangen) (1991) |
1985-1990 |
2.5% |
von Hintzenstern et al. |
| Germany (Gottingen) |
1984-1986 |
2.2% |
Fuchs (1995) |
The risk of chemical allergic contact dermatitis from surgical gloves
may increase if ethylene oxide (ETO) gas sterilization is carried out after
packaging. This substance, the result of hydrogen chloride splitting off
from ethylenechlorhydrine is not only carcinogenic but also a potential
irritant and allergen.
Finally, there is a dyshidrotic form of chemical contact dermatitis
(caused by a water-soluble bacterial endotoxin contained in natural
latex) which does not fit the classic clinical picture of irritant or allergic
contact dermatitis.
Hand disinfectants containing alcohol, which are capable of destroying
gloves, phenols, PVP-iodine, aldehydes, phenylmercuriborate or
quarterneric ammonium compounds should also be considered
allergenic substances. Clinical manifestation of chemical allergic
reactions to gloves vary making clinical classification extremely
difficult. Abortive forms with individual eczemous foci on individual
fingertips or barely visible on the back of the hands can be problematic
to diagnose. In addition, dyshidrotic eczema does not immediately point
to chemical rubber allergy. A history of tolerance to gloves and other
rubber products (e.g., shoes or underwear) should be obtained from all
patients with eczema. If necessary, the relevant areas of contact should
be examined and patch tests used to confirm allergy.
Because epidemiological studies on chemical allergy do not exist, it is
my estimation, that such allergies have more often been suspected rather
than demonstrated. Patients with healthy skin occasionally complain of
itchiness under their gloves.
The occlusion effect can aggravate a preexisting skin disease due to the
irritants and allergens penetrating the horny layer of the skin. Itching can
also be caused by a natural latex contact urticaria or urticaria factitia
General Comments
The ideal glove is one which does not contain thiurams or
dithiocarbamates, but as essential components in the manufacturing
process, they cannot be avoided. Research should be undertaken to
develop a manufacturing process which either reduces the level of
accelerators or replaces them with less allergenic substances so that they
eliminate or reduce the allergy problems. From the point of view of
clinicians and users, it is difficult to assess the extent to which thiourea
might be suitable. Dithiocarbamates and thiazole derivatives are found
in synthetic rubber products recommended as alternatives to natural
rubber products (e.g., neoprene) and can, therefore, also be the cause of
chemical allergy.
Specifically developed "hypoallergenic" gloves are thought to be
particularly well tolerated. However, the term "hypoallergenic" is
misleading as it indicates to both users and clinicians that the gloves are
free of any substance likely to cause contact dermatitis. With very few
exceptions, and independent of genetic disposition, any substance which
occurs in rubber gloves can cause sensitization. A variety of factors
affect sensitization: length and method of exposure, concentration and
sensitizing nature of allergenic substances. Preexisting contact eczema
or irritative dermatitis can aggravate sensitization.
"Hypoallergenic" gloves should not be equated with "tolerated", "better
tolerated" or even "non-sensitizing." Such terms are often
misunderstood resulting in long-term diseases which could have been
avoided. "Hypoallergenic" gloves are also no alternative for latex protein
sensitive individuals as they may contain latex. In this case, certain
proteins may cause local contact urticaria leading to systemic reactions.
Lists of additives contained in rubber gloves are often incomplete and
have limited use. We recommend all additives be listed on packaging. In-
dependent laboratories can check the information utilizing gas and/or
liquid high-pressure-thin-layer chromatography.The goal must be to
eliminate all mistakes when recommending alternative surgical or
protective gloves and thus prevent the patient's loss of occupation.
Industry, the medical profession and regulatory authorities must
work together to solve the problem of allergens in gloves.
SOURCE TO SURGERY CHEMICAL ABBREVIATIONS
ANTIOXIDANTS PPD GROUP
IPPD N-Isopropyl-N phenyl-p-phenylenediamine
DPPD N, N-Diphenyl-p-phenylenediamine
CPPD N-phenyl-N-cyclohexyl-p-phenylenediamine
BLACK RUBBER CHEMICALS
PBN N-Phenyl-2-napthylamine
DBNPD N, N-di-B-Naphthyl4phenylenediamine
DM l, 3 Diphenylguanidine
Mercapto compounds
ZINC SALTS
ZDEC Zinc diethylditbiocarbamate
ZDMC Zinc dimethyldithiocarbamate
ZDBC Zinc dibutyldithiocarbamate
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