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Description of key information

3 -Isocyanatomethyl-3,5,5 -trimethylcyclohexylisocyanate homopolymer, isocyanurate type (IPDI homopolymer) is not irritating to skin (LPT, 2005 ). In further studies, the test substance, tested approx. 70% in solvent (1-Methoxypropylacetate-2/Xylol (1:1)), is slightly irritating to eyes and to skin of rabbits (LPT, 2002; IBR, 1977), which do not meet criteria to be classified. The acute inhalation studies (see " Acute toxicity: inhalation") as well as the repeated dose study (see "Repeated dose toxicity: inhalation") do indicate that 3 -isocyanatomethyl-3,5,5 -trimethylcyclohexylisocyanate homopolymer, isocyanurate type (IPDI homopolymer) causes irritation of the respiratory tract.

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:
2005-09-27 - 2005-11-28
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study; GLP study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
(2002)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Directive 2004/73/EC, B.4
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
Himalayan
Details on test animals or test system and environmental conditions:
TEST ANIMALS: 
- Source: Laboratory of Pharmacology and Toxicology, Löhndorf (Germany)
- Sex: male
- Age: approx. 5-5.5 months at start of >= 20 days adaptation period
- Weight at study initiation: 2.3-2.4 kg
- Controls: untreated skin surrounding the application area

- storage conditions: at room temperature, in tightly closed container
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
yes, concurrent no treatment
Amount / concentration applied:
Concentration: 33.3 %
Duration of treatment / exposure:
4 hour(s)
Observation period:
Postexposure period: 72 hours (Because no effects have been observed the period of observation is not 14 days but 72 hours.)
Number of animals:
3 males
Details on study design:
ADMINISTRATION/EXPOSURE
- Preparation of test substance: fine grinding in mortar
- Area of exposure: dorsal area of trunk, shaved 24 hours in advance,  approx. 6 cm2
- Vehicle: aqua ad iniectabilia
- Concentration in vehicle: 500 mg test substance / ml vehicle
- Total volume applied: 1500 mg including vehicle = 500 mg test substance
- Occlusion: gauze patch held in place by semi-occlusive non-irritating  tape dressing
EXAMINATIONS
- Examination time points: 60 minutes, 24, 48, and 72 hours after patch  removal
- Scoring system: Draize (0-4 possible scores each for erythema/eschar  and for edema)
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 60 min, 24 hrs, 48 hrs, 72 hrs
Score:
0
Max. score:
8
Remarks on result:
other: none of the three rabbits showed any test item related changes; test substance: IPDI homopolymer, approx. 99.6%
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hrs
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24, 48 and 72 hrs
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 24, 48 and 72 hrs
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hrs
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24, 48 and 72 hrs
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 24, 48 and 72 hrs
Score:
0
Max. score:
4
Irritant / corrosive response data:
AVERAGE SCORE
- Erythema: 0
- Edema: 0
REVERSIBILITY: not applicable
Other effects:
Under the test conditions none of the three rabbits showed any test substance related changes.

Table: Acute dermal irritation/corrosion test (patch test) of test item in rabbits

0       no pathological findings

E       erythema and eschar formations

Oe      oedema

Findings of the skin Examination schedule     

Skin irritation scores        

animal no.
   

 1

E/Oe

 2

E/Oe

 3      

E/Oe

                   500 mg test item/patch/animal
erythema and eschar formations/oedema foramtion  before dosing

 0/0

  0/0

  0/0      
   time after removal of the patch (4 -hour exposure)  
   60 min   0/0    0/0

0/0
   24 hrs

   0/0

   0/0

0/0
   48 hrs

   0/0

   0/0

0/0
   72 hrs

   0/0

   0/0

0/0

Conclusions:
Under the present test conditions, none of the three rabbits exposed for 4 hours to 500 mg IPDI homopolymer per patch and animal
(semi-occlusive condition) showed any test item-related changes at the examination time-points 60 minutes, 24, 48 and 72 hours after patch
removal.
Executive summary:

The acute skin irritation properties of IPDI homopolymer were estimated according to OECD Guideline 404. A dose of 500 mg test item per animal was applied to the shaved, intact dorsal skin of 3 male rabbits under semi-occlusive conditions. After the 4 -hour exposure period the patch was removed and the resulting reactions were examined. The average scores at 60 min, 24, 48 and 72 hours after patch removal are as follows: erythema/eschar: 0, edema: 0. Therefore, IPDI homopolymer is not irritating to skin.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

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:
2002-03-09 - 2002-05-06
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study; GLP study without deviation
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
Himalayan
Details on test animals or tissues and environmental conditions:
TEST ANIMALS:
- Number of animals: 3 male rabbits
- Source: LPT, Löhndorf (Germany)
- Initial Age: approx. 3.5 months
- Weight at study initiation: 1.7 - 2.0 kg
- Diet: ssniff K-H
- Water: ad libitum
ENVIRONMENTAL CONDITIONS:
- Housing: seperately in cages
- Temperature: 20 °C +/- 3 °C
- Humidity: 55% +/- 15%
- Photoperiod (hrs dark/hrs light): 12 hours/day
Vehicle:
unchanged (no vehicle)
Controls:
other: identical animal, left eye
Amount / concentration applied:
undiluted
Amount applied: 0.1 ml/animal
Duration of treatment / exposure:
not rinsed; no removal of test substance
Observation period (in vivo):
- Ophthalmoscopic examination with a slit lamp: prior to the administration and 1, 24, 48 and 72 hours after administration; 24 hours after
administration, the eyes were treated additionally with fluorescein and examined.
- Scoring system: Draize
Number of animals or in vitro replicates:
3 male rabbits
Details on study design:
Based on most recent guidelines, the eye reactions are monitored until the changes observed have completely subsided, however not more than
21 days after application. Animals that do reveal any lesions anymore for 24 hours following the first 72 hours of observation are sacrificed.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: corneal opacity was observed in animal no.one 1 hour after instillation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
2
Remarks on result:
other: The iris was not effected after instillation of test substance.
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
2
Remarks on result:
other: The iris was not effected after instillation of test substance.
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
2
Remarks on result:
other: The iris was not effected after instillation of test substance.
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
3
Reversibility:
fully reversible
Remarks on result:
other: conjunctival redness was observed in all animals 1 hour after instillation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
3
Reversibility:
fully reversible
Remarks on result:
other: conjunctival redness was observed in all animals 1 hour after instillation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: conjunctival redness was observed in all animals 1 hour after instillation; in animal no. 3 until 24 hours after instillation.
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: conjunctival chemosis was observed in all animals 1 hour after instillation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: conjunctival chemosis was observed in all animals 1 hour after instillation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: conjunctival chemosis was observed in all animals 1 hour after instillation; test substance: IPDI homopolymer, 70 % solution in 1-Methoxypropylacetate-2/Xylol (1:1)
Irritant / corrosive response data:
AVERAGE SCORE
- Cornea: 0.11
- Iris: 0
- Conjunctivae (Redness): 0.11
- Conjunctivae (Chemosis): 0
Other effects:
There were no systemic intolerance reactions.
The fluorescein test performed 24 hours after instillation revealed corneal staining in animal no. 3 (1/4 of the surface).

no further remarks

Conclusions:
Under the conditions of this study IPDI homopolymer (approx. 70% in vehicle) showed only slightly eye irritating effects in rabbits, which do not meet
criteria according to EU Directive 67/548/EEC to be classified as "irritant to eyes".
Executive summary:

A study was performed to examine eye irritating effects of IPDI homopolymer according to OECD TG 405. An amount of 0.1 ml of the test substance (approx. 70% in solvent) was instilled into the conjunctival sac of the right eye of each of three male Himalayan rabbits, and the untreated left eye served as control. The eyes remained unrinsed and there was no removal of test substance. The eye reactions were monitored until the changes observed have completely subsided, however not for more than 21 days after application.

Under the present test conditions, IPDI homopolymer caused the following effects: Corneal opacity (grade 1) was observed in animal no. one 1 hour and in animal three 24 hours after instillation. The fluorescein test performed 24 hours after instillation revealed corneal staining in animal no. 3 (1/4 of the surface). Conjunctival redness (grade 1 and 2) was observed in all animals 1 hour after instillation, in animal no. 3 until 24 hours after instillation. Conjunctival chemosis (grade 1 and 2) was observed in all animals 1 hour after instillation. The iris was not effected after instillation of the test substance. There were no systemic intolerance reactions.

Therefore, under the conditions of this study IPDI homopolymer (approx. 70% in solvent) showed only slightly eye irritating effects in rabbits, which do not meet criteria according to EU Directive 67/548/EEC to be classified as "irritant to eyes".

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

3 -Isocyanatomethyl-3,5,5 -trimethylcyclohexylisocyanate homopolymer, isocyanurate type (IPDI homopolymer) is not irritating to skin of rabbits (OECD 404: LPT, 2005). In a second study, IPDI homopolymer, tested approx. 70% in solvent (1-Methoxypropylacetate-2/Xylol (1:1)), showed slightly skin irritating effects in rabbits (OECD 404: LPT, 2002), which do not meet the criteria to be classified as "irritating to skin".

The test substance (tested approx. 70 % in solvent, 1-Methoxypropylacetate-2/Xylol (1:1)) showed slightly eye irritating effects in rabbits (OECD 405: LPT, 2002; IBR, 1977), which also do not meet citeria to be classified as "irritating to eyes".

The repeated dose study (OECD 413: Ma-Hock et al, 2009) as well as the acute inhalation studies (OECD 403: Bayer AG, 1996; OECD 403: Pauluhn, 2003) indicate that 3 -isocyanatomethyl-3,5,5 -trimethylcyclohexylisocyanate homopolymer, isocyanurate type (IPDI homopolymer) causes irritation of the respiratory tract.


Justification for selection of skin irritation / corrosion endpoint:
The study with the highest test concentration (purity of the test item 99.6%) is selected.

Justification for selection of eye irritation endpoint:
The study conducted according to OECD 405 Guideline is selected.

Effects on respiratory irritation: irritating

Justification for classification or non-classification

According to criteria of EC Directive 67/548/EEC and EC Regulation 1272/2008 3 -isocyanatomethyl-3,5,5

-trimethylcyclohexylisocyanate homopolymer, isocyanurate type (IPDI homopolymer) is not irritating to skin and eyes.

Based on the assessment of two animals studies (acute and repeated inhalation) the test substance is a respiratory irritant.