HDI oligomers, iminooxadiazindione

Sensitisation data (human)

Administrative data

Endpoint:

sensitisation data (humans)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: case report, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

No information

Author:

Aalto-Korte K et. al.

Year:

2010

Bibliographic source:

Contact Dermatitis, 63, 357-363

Materials and methods

Type of sensitisation studied:

skin

Study type:

case report

Principles of method if other than guideline:

Patch tests were performed according to the recommendations of the International Contact Dermatitis Research Group.

Test material

Test material information

Constituent 1

Reference substance name:

(6E)-3,5-bis(6-isocyanatohexyl)-6-[(6-isocyanatohexyl)imino]-1,3,5-oxadiazinane-2,4-dione

EC Number:

931-297-3

Molecular formula:

(C8H12N2O2)n

IUPAC Name:

(6E)-3,5-bis(6-isocyanatohexyl)-6-[(6-isocyanatohexyl)imino]-1,3,5-oxadiazinane-2,4-dione

Constituent 2

Reference substance name:

28182-81-2

Cas Number:

28182-81-2

IUPAC Name:

28182-81-2

Details on test material:

Hardeners from the workplace used in patch testings
Hardener B: according to the authors Hardener B was composed of 68.5 % aliphatic polyisocyanate (Desmodur N 3390 BA; Bayer AG), 12 % xylene, and 19.5 % propylene glycol methyl ether acetate.
Hardener C, D, E: according to the authors Hardener C, D, and E were composed of 25-50 %, 50-100 %, and 70-75 % polymeric HDI, respectively, of unknown type.
Hardener F: according to the authors Hardener F is a Desmodur N 3900-comparable Japanese product, > 99 % HDI homopolymer.

Desmodur products used in patch testings
Desmodur H, Desmodur N75 MPA/X, Desmodur N 3200, Desmodur N 3390 BA, Desmodur N 3300, and Desmodur N 3900.

Method

Type of population:

occupational

Subjects:

4 patients, coming from all over Finland, that are suspected of having an occupational skin disease after examination at the Finnish Institute of Occupational Health.

Clinical history:

Patient No 1: not relevant with regard to HDI oligomers, iminooxadiazindione type

Patient No 2: 53-year-old female office worker in a paint factory, not usually involved in the manufacture of paints. When she was carrying samples of three hardeners for industrial paints she accidentally spilled some of the substances on left forearm and thigh. After 1.5 weeks she developed dermatitis on the same areas.

Patient No 3: 38-year-old male painter with history of mild atopic dermatitis in wintertime. His main task in an aircraft repair workshop was the grinding of surfaces that had been painted with two-component paints. He developed new skin symptoms on his thighs and feet, and swelling on
his face while grinding. He had previously been involved in spray painting, but had not had skin symptoms at that time.

Patient No 4: 33-year-old female laboratory worker in a paint factory. She developed dermatitis on her face, the backs of the hands, and forearms, after working for 2 months. She left her job, and the dermatitis healed.

Controls:

with respect to patient No 1: not relevant with regard to HDI oligomers, iminooxadiazindione type
with respect to patient No 2: 9 control patients tested with 2 % Desmodur N 3200, and with 2 % and 1 % Hardener B, all in petrolatum.
with respect to patient No 3: no control patients reported
with respect to patient No 4: 20 control patients tested with Desmodur N 3900 (5 %, 1.65 % and 0.5 % in petrolatum)

Route of administration:

dermal

Details on study design:

Patch tests were performed using the Finn Chambers method (Epitest, Tuusula, Finland) and according to the recommendations of the International Contact Dermatitis Research Group. Readings were performed two or three times (on days 2, 3, and 4, or days 2, 3, and 6, or on days 2 and 5), depending on the day of the week when the test patches were applied. As vehicle petrolatum was used.

The first 2 patients were diagnosed by testing with their own polyurethane paint hardeners and the ingredients of the hardeners. In 2002, an aliphatic polyisocyanate of the isocyanurate type (Desmodur N 3300) was added to the isocyanate test series, and the last 2 patients were screened with this routine series.

Results and discussion

Results of examinations:

4 patients with skin sensitisation to lacquers, coatings, and spray paints based on HDI homopolymer were described. When patch-tested, all of the patients reacted not only to the specific type of HDI trimer to which they were exposed, but also to other types of HDI trimer. Due to the substance specification in the publication these cases are relevant for HDI oligomers, iminooxadiazindione type.

Any other information on results incl. tables

Patient No 1: not relevant with regard to HDI oligomers, isocyanurate type

Patient No 2: On patch testing, she reacted positively to one of the three hardeners (Hardener B). Hardener B was composed of 68.5 % aliphatic polyisocyanate (Desmodur N 3390 BA; Bayer AG), 12 % xylene, and 19.5 % propylene glycol methyl ether acetate. In the second patch test session, the patient was tested with the three ingredients of Hardener B, and reacted positively to Desmodur N 3390 BA. The main component in Desmodur N 3390 BA is an isocyanurate-type HDI trimer (90 %), and it also contained 10 % n-butylacetate. The patient was also positive with another isocyanurate-type product, Desmodur® N 3300, and with the biuret-type HDI trimer of patient no. 1, Desmodur N 3200. Nine control patients were negative with 2 % Desmodur N 3200, and with 2 % and 1 % Hardener B, all in pet.The patient had developed occupational allergic contact dermatitis in response to isocyanurate-type HDI trimer in Hardener B.

Patient No 3: On patch testing, he was positive with Desmodur N 3300 in the isocyanate series. In the second patch test session, the Desmodur N 3300 reactions were reproduced, and he also reacted to three different hardeners (Hardeners C, D, and E) from his work place, composed of polymeric HDI. He avoided the grinding work, and the symptoms did not reappear, but later he left the job. His diagnosis was occupational contact allergy to aliphatic polyisocyanate (HDI homopolymer) rather than allergic contact dermatitis, as it was not proven that the skin symptoms were caused by the contact allergy. He might have been sensitized earlier in the painting work, even though he had no symptoms while painting.

Patient No 4: On the first patch test session, she reacted to Desmodur N 3300 in the isocyanate series and was negative with monomeric HDI. She had prepared pilot batches of two-component paints, the hardeners of which contained HDI homopolymers. In the second patch test session, she reacted to two hardeners from her workplace, Desmodur N 3900 and a corresponding Japanese product (Hardener F). She also reacted to Desmodur N 3200 (the biuret-type HDI trimer of patient no. 1) and again to an isocyanurate-type HDI trimer, Desmodur N 3300. The latter gave positive reactions down to 0.005%. The cause of this case, Desmodur N 3900, was mainly composed of asymmetric HDI trimer. Twenty control patients were negative with Desmodur N 3900 (5%, 1.65% and 0.5% in pet.). The patient was diagnosed with occupational allergic contact dermatitis resulting from asymmetric HDI trimer in paint hardeners.

Cited from publication: "We describe 4 patients sensitized to products based on HDI homopolymers. The allergic reactions cannot be explained by sensitisation to HDI monomer, as none of the 4 patients reacted to HDI monomer. Furthermore, the concentration of the monomer in the products is very low."

"When patch-tested, all of the patients reacted not only to the specific type of trimer to which they were exposed, but also to other types of HDI trimer. Owing to structural similarity, there can be cross-allergy between the different types of trimer."