ARTICLE
Cyclohexylthiophtalimide is one of the less well-known rubber chemicals
in the rubber series of Trolab, Hermal Kurt Herrmann, Reinbeck/Hamburg,
Germany. It is a vulcanization retarder that is added in rubber processing
to prevent premature vulcanization, thus improving the safety of rubber
production [1-3].
Little data is available on allergic contact dermatitis caused by cyclohexylthiophthalimide
[2]. Therefore, we analyzed our data on allergic patch tests reactions
caused by CTP in our two departments in order to determine the frequency,
causes, and relevance of hypersensitivity to this rubber chemical.
Materials and methods
The material consists of the patch tests results for all patients who
had suffered from contact dermatitis to rubber products and who had been
tested with the rubber chemical series including cyclohexylthiophthalimide
in two departments of dermatology. At the Fournier Hospital in Nancy,
France, 141 such patients were patch tested over the last 5 years; at
the University Hospital KU Leuven, Belgium, 209 such patients were patch
tested between October 1990 and May 2000. All the patients had also been
patch tested with a European standard series and many also with other
allergens considered potentially relevant. In 8 patients reacting to CTP
(4 in Nancy and 4 in Leuven), the gloves that were not being tolerated
were also tested. One patient who reacted to CTP in Leuven was patch tested
with a rubber urinary probe. Two patients who reacted to CTP in Nancy
were patch tested with rubber from their pencil erasers, and 2 others
were patch tested with rubber from their shoes. In one case, the shoes
were subjected to chemical analysis.
Patch testing was performed on the back with a first reading of the
tests on Day 2 and a second reading on Day 3 or 4. The CTP (1% petrolatum,
as suggested by the ICDRG [4]) was obtained from Trolab, Hermal Kurt Herrman
(Reinbeck/Hamburg, Germany) manufactured from Monsanto's Santogard®
PVI. The patch test results were considered clearly positive when they
elicited at least erythema with infiltration (+ reaction).
Latex prick tests were performed in 9 cases reacting to CTP (3 in Nancy,
6 in Leuven), and latex RAST tests were performed in 2 cases in Leuven.
The clinical relevance was assessed in function of the patient history.
Results
The patch tests results with the rubber chemicals of the standard and
the rubber series are given in Table I. Eight (5.7%, 5 females,
3 males, mean age = 38 years) of the 141 patients in Nancy and 8 (3.8%,
3 female, 5 males, mean age = 37 years) of the 209 patients in Leuven
had clear positive patch test reactions to CTP. Furthermore, 6 patients
[4 (2.8%) in Nancy and 2 (1.0%) in Leuven] presented doubtful reactions
to CTP. Thirteen of the 22 patients with a positive or doubtful reaction
to CTP reacted only to CTP and not to other rubber chemicals, while the
other 9 patients concomitantly reacted to other rubber chemicals such
as thiuram, carbamate, or mercaptobenzothiazole derivatives. Three of
the 8 patients patch tested with their own protective gloves showed a
positive reaction. In those 3 cases, there was a concomitant reaction
to thiuram. The patient in Leuven patch tested with his urinary probe
showed a doubtful patch test reaction. The 2 patients in Nancy patch tested
with their pencil eraser showed a negative patch reaction, as did those
2 patients patch tested with their own shoes.
Chemical analysis of the shoes showed the presence of diphenylmethane-4,4-diisocyanate
(MDI) and phtalate. Cyclohexylthiophthalimide was absent. A patch test
performed with MDI was negative.
The latex prick tests performed in 9 cases and a latex RAST test performed
in 2 cases were all negative.
The occupation, location of the eczema, and rubber exposure of all patients
reacting to CTP with a clear positive reaction are given in Table II.
The table shows that the most common known rubber exposure of the patients
tested in Leuven (patients 1 to 6) was to protective gloves at work. One
patient with a strong reaction to CTP did not tolerate his wet suit during
surfing, while another patient with a strong reaction did not tolerate
his urinary probe. Two patients, of whom one with a doubtful allergic
reaction, had contact with rubber products at work. In Nancy, protective
gloves were also responsible for eczema in most of the cases (4 cases)
as reported in Table II. Shoes and elastic bands of underwear were
not well tolerated in 3 and 2 cases, respectively, and 2 patients developed
eczema by contact with their pencil erasers (Figs. 1 and 2).
Discussion
During rubber processing, it is necessary to prevent premature vulcanization.
This is achieved by the addition of vulcanization retarders, the most
common one being CTP [1-4]. It delays the onset of accelerated sulfur
vulcanization and is used particularly in the processing of solid rubber
products to prevent the rapid onset of curing [2, 3].
Few data are available on sensitization to CTP, and it is not listed
in the table of sensitizing rubber vulcanization agents in the technical
file of the Institut National de Recherche et de Sécurité
(INRS) published in 1993. In 1996, Kanerva [2] reported on the frequency
of positive patch tests to this rubber allergen. Of 310 patients, he found
11 who reacted positively to CTP, this being a frequency of 3.5%. We found
5.7% (8 out of 141 patients) in Nancy and 3.8% (8 out of 209 patients)
in Leuven. Kanerva [2] also reported that 30 (9.7%) of the 310 patients
had a doubtful positive reaction, in comparison with 4 (2.8%) of the 141
patients in Nancy and 2 (1.0%) of the 209 patients in Leuven. These doubtful
reactions could have been irritation.
The possible sources of exposure to CTP by the patients reported by
Kanerva [2] were protective gloves in 10 patients and a glassblower's
pipe in 1 case. In our series, the sensitization to CTP in most cases
was probably due to protective gloves, but contact allergy also seems
to have been due to exposure to shoes, the elastic band of underwear,
erasers or other rubber objects.
The difficulty of determining the relevance of positive patch test reactions
to CTP has already been mentioned by Kanerva [2]. Thus we have concentrated
particularly on determining the relevance of the positive reactions to
CTP, even with the chemical analysis (in Nancy) of shoes that were not
tolerated well.
As to why there should be such a high frequency of positive patch test
reactions to this little-known allergen, we suggest that its use may be
increasing in the rubber industry. Positive reactions to CTP might also
be due to sensitization to other molecules, which would indicate cross-sensitivity,
but we could not confirm this [2]. In both series, ours and that of Kanerva,
the patch tests were performed with the commercial product from Hermal-Trolab,
i.e. CTP diluted in petrolatum, the purity of which has been determined
to be 94-96%.
Article accepted on 17/4/01
CONCLUSION Cyclohexylthiophthalimide
is a little-known, but not rare, potential allergen in rubber products.
The life-time exposure of people to rubber is so extensive that it is very
difficult to identify the origin of rubber sensitization it may cause. The
determination of the relevance of positive tests remains difficult, particularly
because so little data are available on the components present in rubber
products. More cooperation with rubber manufacturers as well as chemical
analysis of rubber products is necessary if the relevance of positive patch
tests to cyclohexylthiophthalimide is to be determined.REFERENCES
1. Brandao FM. Rubber. In: Adams RM, ed. Occupational skin
disease. Philadelphia: W.B. Saunders Co, Harcourt Brace Jovanovich.
Inc., 1990: 469.
2. Kanerva L, Estlander T, Jolanki R. Allergic patch test reactions
caused by the rubber chemical cyclohexyl thiophthalimide. Contact Dermatitis
1996; 34: 23-6.
3. Kanerva L, Estlander T, Jolanki R. Letter to the Editor. The
chemical structure of the rubber chemical cyclohexyl thiophthalimide.
Contact Dermatitis 1996; 35: 319.
4. De Groot AC. Patch testing. The concentrations and vehicles
for 3,700 chemicals. Amsterdam: Elsevier, 1994: 85.
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