Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Additional information:

Studies in animals

Cited from SIAR for SIAM 18 (Paris, April 2004):

"In a guinea pig maximisation test according to OECD TG 406, sensitisation was observed in 18 of 20 animals 24 hrs after using a challenge concentration of 5 %. With a challenge concentration of 2.5 %, 7 of 20 animals were positive (Hüls AG, 1983a). The sensitising properties of 3-aminomethyl-3,5,5-trimethylcyclohexylamine were also observed in two other guinea pig maximisation tests (Inveresk, 1981; Thorgeirsson, 1978)."

Studies in humans

Cited from SIAR for SIAM 18 (Paris, April 2004):

"There are several publications describing 3-aminomethyl-3,5,5-trimethylcyclohexylamine related contact dermatitis: Three out of 15 workers manufacturing plastic tennis rackets developed allergic contact dermatitis when exposed concomitantly to 3-aminomethyl-3,5,5-trimethylcyclohexylamine and epoxy resin. Symptoms appeared 3 months, 6 weeks or 3 weeks after starting this work and disappeared completely within 3 weeks after moving to a different department. Patch tests were positive with 1, 2, or 5 % 3-aminomethyl-3,5,5-trimethylcyclohexylamine in both ethanol and olive oil. After the test it became obvious that the controls were also sensitised (Lachapelle, Tennstedt and Dumont- Fruytier, 1978). Two of the three workers positive for 3-aminomethyl-3,5,5-trimethylcyclohexylamine from the Lachapelle, Tennstedt and Dumont-Fruytier study (1978) and two additional ones who were also positive for 3-aminomethyl-3,5,5-trimethylcyclohexylamine, were patch tested 1 month later with isophorone diisocyanate (1 %). All four were positive, while five control volunteers were negative. This study may indicate a cross-sensitivity between 3-aminomethyl-3,5,5-trimethylcyclohexylamine and the corresponding diisocyanate, though its documentation is poor (Lachapelle and Lachapelle- Ketelaer, 1979). From 142 persons considered to have skin disorders from current occupational exposure to epoxy compounds, 135 had allergic contact dermatitis. 53 of those were patch tested for 3-aminomethyl- 3,5,5-trimethylcyclohexylamine, and three were positive towards this substance. Patch tests with 0.5 % 3-aminomethyl-3,5,5-trimethylcyclohexylamine were used, as this concentration was observed to induce neither irritation nor active sensitisation in the patch testing (Jolanki, 1991). A 38-year old bricklayer had prolonged skin contact with a work shoe contaminated with a 3- aminomethyl-3,5,5-trimethylcyclohexylamine containing two-component glue. The man developed a dermatitis on the chest, upper back, arms and legs and was tested positive for 3-aminomethyl- 3,5,5-trimethylcyclohexylamine (0.5%) 2 months after the generalised skin reaction had healed (Kelterer, Bauer and Elsner, 2000; short communication). A total of 137 employees of 10 companies preparing and using epoxy resins for coating, flooring, impregnating and repairing concrete, brick and wooden structures were examined. Positive patch tests were observed in 27 of the 137 employees, predominantly with epoxy resin (25 persons / 18.5 %), but also with 0.1 % 3-aminomethyl-3,5,5-trimethylcyclohexylamine (3 persons / 2.3 %). Positive correlation with the development of an allergy were observed with the frequency of exposure, the duration of employment and the permanent wearing of gloves (van Putten, Coenraads and Nater, 1984). 15 A 53-year-old male employed for laying impermeable floors had a very itchy, symmetrical, erythematous, edematous eruption of the face, which had begun during work. Repeatedly, it had healed within few weeks off work but recurred when returning to work. No working colleagues had similar problems, though in the past, a man had left the job following a similar history. From several patch tests with standard series and with his working materials, only 3-aminomethyl-3,5,5- trimethylcyclohexylamine was positive with erythema from 0.1 %, and erythema, oedema and vesicles from 1 % and 5 % after three days (Patussi et al., 1995). A 44-year old man working at a lamination machine, having had no previous skin problems except photosensitisation, after 2 years at the lamination machine observed eczema on the hands and wrists, as well as on the right upper arm. Enclosure of the process was improved. Four years later, his dermatitis worsened covering particularly typical sites of sun exposure. It healed during 2 weeks off work. In patch testing, positive reactions were observed for 3-aminomethyl-3,5,5- trimethylcyclohexylamine, the two glue components, plastic-laminated fiber cloth as such, perfume mix, and epoxy resin (Tarvainen et al., 1998). During January 1984 to May 1992, Tosti et al. (1993) patch tested 39 patients with occupational allergic contact dermatitis to epoxy resin system substances. Positive reactions for 3-aminomethyl- 3,5,5-trimethylcyclohexylamine were observed in 0/18 persons from electronics industry, 1/8 painters, 0/3 from fiberglass handling, 1/8 from gluing, 0/1 dental technicians, and 1/1 mechanics. The documentation of this study is not sufficient to allow a judgment on its validity. In a further poorly documented study, all persons from the contact dermatitis database at Waikato Hospital (Hamilton, NZ) with relevant and work related contact dermatitis to epoxy resin compounds, i.e. 16 males, average age 37 years (range 21-53 years), were subject to several patch tests. Among them, one reacted positive with 3-aminomethyl-3,5,5-trimethylcyclohexylamine (0.1 % in petrolatum) (Rademaker, 2000). Kanerva et al. (1999) studied the relative frequency of occupational contact dermatitis towards 53 sensitisers by patch testing all patients exposed to plastics and remitted to an occupational dermatology clinic during the years 1991 - 1996. 311 patients were tested using occlusive patches with 0.5 % 3-aminomethyl-3,5,5-trimethylcyclohexylamine in petrolatum for 48 hours followed by three readings, usually on days 2, 3, and 4-6. 3-Aminomethyl-3,5,5-trimethylcyclohexylamine was among the 26/53 substances which induced no allergic reaction, but it induced irritation in one case. Maximum frequencies were 5.1 % for sensitisation and 9.5 % for irritation."

Migrated from Short description of key information:
Cited from SIAR for SIAM 18 (Paris, April 2004):
"3-Aminomethyl-3,5,5-trimethylcyclohexylamine was found to induce dermal sensitisation when tested according to OECD TG 406 in guinea pigs. From a number of publications there is evidence that frequent occupational exposure to 3-aminomethyl-3,5,5-trimethylcyclohexylamine may lead to
the development of allergic contact dermatitis in humans."

Respiratory sensitisation

Endpoint conclusion
Additional information:

Studies in humans

Cited from SIAR for SIAM 18 (Paris, April 2004):

"A 44-year old man had a serious attack of bronchial obstruction after working with resins and hardeners, releasing fumes of a mixture of trimethyl-1,6-hexanediamine and 3-aminomethyl-3,5,5- trimethylcyclohexylamine. Eight hours after deliberate challenge with the hardener, a large increase of airway resistance was found. Seventy-two hours after challenge, eosinophilia in the bronchoalveolar fluid together with a decrease in peripheral eosinophils was seen. After cessation of contact with this hardener, no more acute episodes were seen, though maintenance treatment with a topical corticosteroid and a beta2-agonist remained necessary (Aleva et al., 1992).


Migrated from Short description of key information:
Cited from SIAR for SIAM 18 (Paris, 2004):
"Since there is only one publication on possible airway effects of 3-aminomethyl-3,5,5-trimethylcyclohexylamine (describing a single
human case) no definite conclusion can be drawn on respiratory sensitisation."

Justification for classification or non-classification

Because of outcome of the skin sensitisation studies the substance isophorone diamine is classified as R 43 (May cause sensitization by skin contact) according 67/548/EEC and Category 1, (H317: May cause an allergic skin reaction) according CLP regulation (1272/2008).