Registration Dossier

Administrative data

Description of key information

With regard to the skin irritation studies with rabbits and rats, 3-aminomethyl-3,5,5-trimethylcyclohexylamine (Isophorone diamine) is considered to be corrosive to the skin (IBR, 1977). Furthermore, regarding to the eye irritation study with a rabbit according to OECD 405, 3-aminomethyl-3,5,5-trimethylcyclohexylamine is considered to be corrosive to the eyes of rabbits (Hüls AG, 1983).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Summer of 1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
other: "Appraisal of the safety of chemicals in foods, drugs and cosmetics", by the staff of the Division of Pharmacology, FDA; scoring according to Draize (1959)
Principles of method if other than guideline:
Based on "Appraisal of the safety of chemicals in foods, drugs and cosmetics", FDA / Draize (1959)
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
- Age: adult
- Weight at study initiation: mean 2.5 kg
- Diet: ad libitum, Rabbit standard diet (Höing 222)
- Water: ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 1 °C
- Humidity (%): 50 - 60 %
- Photoperiod (hrs dark / hrs light): 12 hours light
Type of coverage:
occlusive
Preparation of test site:
other: shaved and scarified
Vehicle:
unchanged (no vehicle)
Controls:
other: 2 untreated skin areas per animal (both depilated, one scarified)
Amount / concentration applied:
Total volume applied: 2 x 0.5 ml / animal (undiluted)
- Occlusion:
Each 0.5 ml test substance on two plasters,
fixed to separate areas of the skin (both depilated, one scarified),
trunk wrapped in rubber sheet for 24 hours
Duration of treatment / exposure:
24 hour(s)
Removal of test substance: no
Observation period:
Postexposure period: 48 hours
Number of animals:
6
Details on study design:
- Examination time points: 24 hours = patch removal and 72 hours
- Scoring system: Draize scores, mean of two readings
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 hous; 72 hours
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 hours; 72 hours
Score:
> 0
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: The skin had become hard and leatherlike. Scoring was not possible.
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24 hours; 72 hours
Score:
> 4
Max. score:
8
Reversibility:
not reversible
Remarks on result:
other: The skin had become hard and leatherlike. Edema scoring was not possible.
Irritant / corrosive response data:
AVERAGE SCORE
- Erythema: 4.0
- Edema: The skin had become hard and leatherlike. Scoring was not possible.
REVERSIBILITY: Similar severity of effects was observed at both readings, i.e. there was no indication of reversibility within the observation period.
Other effects:
no other effects
Conclusions:
Isophorone diamine has to be considered to be corrosive to the skin of rabbits und the conditions and according to the results of the study.
Executive summary:

In this study with 6 adult rabbits 0.5 ml undiluted 3-aminomethyl-3,5,5-trimethylcyclohexylamine (Isophorone diamine) was applied to the shorn dorsal skin of the animals ( intact and scarified) and covered with gauze and adhesive tape for 24 hours. The results were assessed at patch removal (24h) and 48 hr later (72 h), the skin had become hard and leatherlike. Edema scoring was not possible. Similar severity of effects was observed at both readings, i.e. there was no indication of reversibility within the observation period. In the study Isophorone diamine is described to be a severe irritant according to the scoring system used. Thus, under the conditions and according to the results of this study isophorone diamine has to be considered to be corrosive to the skin of rabbits.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1983-11-24 - 1983-11-25
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
1981
Deviations:
no
GLP compliance:
no
Species:
rabbit
Strain:
other: Small white Russian
Details on test animals or tissues and environmental conditions:
- Sex: female
- Source: Dr. Karl Thomae, Biberach
- Weight at study initiation: 2.3 kg
- Sex: female
- Weight at study initiation: 2.8 kg
- Controls: untreated eye
- Housing: single housing
- Diet: ad libitum, special diet for rabbits, SSniff K4
- Water: ad libitum, tab water
- Acclimation period: 14 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.0 +/- 1 °C
- Humidity (%): 60 +/- 5 %
- Air changes (per hr): 15 times per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial light, 12 hours dark
Vehicle:
unchanged (no vehicle)
Controls:
other: Controls: right eye
Amount / concentration applied:
undiluted
Amount applied: 0.1 ml
Duration of treatment / exposure:
24 hour(s)
Observation period (in vivo):
Postexposure period: 24 hours
Number of animals or in vitro replicates:
1
Details on study design:
Comment: not rinsed
Irritation parameter:
overall irritation score
Basis:
animal #1
Time point:
other: 24 hours
Score:
110
Max. score:
110
Reversibility:
not reversible
Remarks on result:
other: Due to the strong corrosive effects of the test substance Isophorone diamine a scoring was not possible and therefore not reported (details see in section "Remarks on results including tables and figures")
Irritant / corrosive response data:
The undiluted substance produced serious injury almost immediately after application (corrosive effects, opalescence). 24 hours after treatment
conjunctiva showed necrosis. Due to the corrosive effect of the test material, only 1 animal was used and the experiment terminated after 24 hours.
Other effects:
no other effects

Due to the strong corrosive effects of the test substance Isophorone diamine a scoring was not possible and therefore not reported. The undiluted substance produced serious injury almost immediately after application (corrosive effects, opalescence). 24 hours after treatment conjunctiva showed necrosis. Due to the corrosive effect of the test material, only 1 animal was used and the experiment terminated after 24 hours.

Conclusions:
Isophorone diamine showed a strongly irritant and corrosive effect on the eye and on the mucosa of the rabbit under the conditions of the study.
Executive summary:

Isophorone diamine was investigated for irritant effects on the eye and associated mucous membranes of 1 female rabbit according to OECD TG 405 (1981). The test substance was applied in a single dose of 0.1 ml into the conjuntival sac of the animal. The undiluted substance produced serious injury almost immediately after application (corrosive effects, opalescence). 24 hours after treatment conjunctiva showed necrosis. Due to the corrosive effect of the test material, only 1 animal was used and the experiment terminated after 24 hours.The lesions were not reversible. Therefore, Isophorone diamine is considered to be corrosive.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

Studies in animals

A study was conducted with 6 adult rabbits and 0.5 ml undiluted 3-aminomethyl-3,5,5-trimethylcyclohexylamine (Isophorone diamine) was applied to the shorn dorsal skin of the animals (intact and scarified) and covered with gauze and adhesive tape for 24 hours (IBR, 1977). The results were assessed at patch removal (24 h) and 48 hours later (72 h), the skin had become hard and leather like. Edema scoring was not possible. Similar severity of effects was observed at both readings, i.e. there was no indication of reversibility within the observation period. In the study Isophorone diamine is described to be a severe irritant according to the scoring system used. Thus, under the conditions and according to the results of this study isophorone diamine has to be considered to be corrosive to the skin of rabbits.

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

"In a study with rabbits and rats, undiluted 3-aminomethyl-3,5,5-trimethylcyclohexylamine was massaged into the depilated back skin of the animals and covered with gauze and adhesive tape. Under these conditions (duration of the exposure not reported), 3-aminomethyl-3,5,5-trimethylcyclohexylamine penetrated the skin and caused swelling, irritation and inflammatory effects. Repeated application led to severe effects with formation of crusts and necroses. Effects were more pronounced with rabbits than with rats (Klimmer, 1965). Lack of documentation limits the value of the study, but the result is in reasonable agreement with the pKb of the substance (ca. 3.6; VEBA Chemie, 1975), with its classification as corrosive, and with observations in occupational medicine."

Eye irritation

Studies in animals

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

"In a study according to OECD TG 405 with rabbits (Small white Russian), undiluted 3-aminomethyl-3,5,5-trimethylcyclohexylamine produced serious injury (corrosive effects, opalescence) almost immediately after application. Twenty-four hours after application of the test substance, conjunctivae showed necrosis (Hüls AG, 1983b)."

Justification for classification or non-classification

Because of the results of the skin irritation studies the substance isophorone diamine is classified as Category 1B, (H314; Causes severe skin burns and eye damage) according CLP regulation (1272/2008). In an in vivo eye corrosion study according to OECD 405, the test substance was found to be severe corrosive to rabbits eyes and has to be classified as Eye damage Cat. 1 compound (H318; Causes serious eye damage).