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Administrative data

Description of key information

The study on skin irritation revealed, with regard to the irritation index (5.13 of max. 8.0), a “highly irritating” potential of the test substance.

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:
1984-09-25 to 1984-10-09
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
(1981)
Deviations:
no
GLP compliance:
no
Species:
rabbit
Strain:
other: Small white Russian
Details on test animals or test system and environmental conditions:
TEST ANIMALS: 
- Strain: Small white Russian, Chbb-SPF
- Sex: male and female
- Source: Dr. Karl Thomae GmbH, Biberach (Germany)
- Weight at study initiation: 2.2 - 2.6 kg
- Number of animals: 3 males, 3 females
Housing conditions:
- Room temperature: 20°C (+/- 1°C)
- Humidity: 60% (+/- 5%); light: 12 hours/day
- Air exchange: 15-fold/h
- Access to drinking water: ad libitum
- Diet: K4 diet for rabbits (Ssniff; Soest)
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
0.5 ml, undiluted
Duration of treatment / exposure:
4 hour(s)
Number of animals:
6
Details on study design:
ADMINISTRATION/EXPOSURE 
- Area of exposure: 6 cm2
- Total volume applied: 0.5 ml
- Occlusion: mull patch, polyethylene film, elastic dressing
- Removal of test substance: washing with deionized water
- Post exposure period: 3 weeks
EXAMINATIONS
- Scoring system: OECD; evaluation: VCI notes on safety data sheet and  Appendix VI of 79/831/EEC
- Examination time points: 1, 24, 48, 72 hours, 6, 8, 10, 14, and 21 days  after patch removal; evaluation based on readings 1-4
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 1, 24, 48, 72 h
Score:
5.13
Max. score:
8
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
2.67
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
2.44
Max. score:
4
Reversibility:
not reversible
Irritant / corrosive response data:
AVERAGE SCORE
- Erythema: 2.67
- Edema: 2.44
- irritation index: 5.13/8
REVERSIBILITY: Not reversible. Necrosis within 4 hours, not within 3  minutes. Eschars, incrustation, or scars by end of study in all animals.
Other effects:
no other effects

no further results

Conclusions:
Under the conditions of this study, the test item 2,2,4 -/2,4,4 -trimethylhexane-1,6 -diisocyanate showed severe damage on the skin
of male and female rabbits. All rabbits showed eschars, incrustation, or scars by end of  study.
Executive summary:

A study was performed to examine skin irritating effects of 2,2,4-/2,4,4-trimethylhexane-1,6-diisocyanate according to OECD TG 404 in rabbits. Undiluted test substance was applied in the study. In the study three rabbits per sex were exposed occlusively for four hours. Necrosis within 4 hours, not within 3  minutes was observed .  All rabbits showed eschars, incrustation, or scars by end of  study. The result was, with regard to the irritation index (5.13 of max. 8.0), described as “highly irritating”.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (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:
1984-09-25 to 1984-10-16
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study
Qualifier:
according to guideline
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:
TEST ANIMALS: 
- Strain: Small white Russian, Chbb-SPF
- Sex: male/female - Source: Dr. Karl Thomae GmbH, Biberach (Germany)
- Weight at study initiation: 2.3 - 2.5 kg
- Number of animals: 3 males, 3 females
- Controls: untreated eye
Housing conditions:
- Room temperature: 20°C (+/- 1°C)
- Humidity: 60% (+/- 5%); light: 12 hours/day
- Air exchange: 15-fold/h
- Access to drinking water: ad libitum
- Diet: K4 diet for rabbits (Ssniff; Soest)
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye
Amount / concentration applied:
undiluted
Amount applied: 0.1 ml
Duration of treatment / exposure:
not rinsed
Observation period (in vivo):
1, 24, 48, 72 hours, 6, 8, 10, 13, 15, 17,  and 21 days after treatment
Number of animals or in vitro replicates:
3 males, 3 females
Details on study design:
EXAMINATIONS
- Ophtalmoscopic examination: 1, 24, 48, 72 hours, 6, 8, 10, 13, 15, 17,  and 21 days after treatment
- Scoring system: Draize (1959); evaluation: VCI notes on safety data  sheet and Appendix VI of 79/831/EEC
- Tool used to assess score: sodium fluorescein / ophthalmic lamp /  visual inspections
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
1.22
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0.61
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
2.61
Max. score:
3
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
1.39
Max. score:
4
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
21 d
Score:
23.62
Max. score:
110
Irritant / corrosive response data:
AVERAGE SCORE
- Cornea: 1.22
- Iris: 0.61
- Conjunctivae (Redness): 2.61
- Conjunctivae (Chemosis): 1.39
- Overall irritation score: 23.62/110
REVERSIBILITY: Not reversible within 3 weeks. Eyelids were incrusted in 5  animals on days 15 and 17 and in 1 animal on day 21.
Other effects:
OTHER EFFECTS: Brightness reduced in eyes of 3 animals, redness in iris  of all animals (24 until maximum 72 hours), sticking and dryness in the  
eyes of the females (days 2-10), eyelids inelastic in all animals from  day 3 on and incrusted later, loss of hair in all animals by end of study

no further results

Conclusions:
Under the conditions of this study, the test item 2,2,4 -/2,4,4 -trimethylhexane-1,6 -diisocyanate showed severe damage on the eyes and mucosa
of male and female rabbits.y. The effects are not reversible within 3 weeks.
Executive summary:

The acute eye irritation properties of 2,2,4 -/2,4,4 -trimethylhexane-1,6 -diisocyanate were estimated in a Draize test according to OECD TG 405. An amount of 0.1 ml of the undiluted test substance was instilled into the left eye of three male and three female albino rabbits, and the untreated right eye served as control. The eye remained unrinsed and there was no removal of test substance. The undiluted substance produced reduced brightness in eyes of 3 animals, redness in iris of all animals (24 until maximum 72 hours), sticking and dryness in the eyes of the females (days 2 -10), eyelids inelastic in all animals from  day 3 on and incrusted later, loss of hair in all animals by end of study. The effects are not reversible within 3 weeks.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for selection of skin irritation / corrosion endpoint:
key study

Justification for selection of eye irritation endpoint:
key study

Effects on skin irritation/corrosion: highly irritating

Effects on eye irritation: slightly irritating

Justification for classification or non-classification

According to the criteria of EC Directive 67/548/EEC and EC Regulation 1272/2008 and subsequent regulations on classification, labelling and packaging of substances and mixtures and based on the results of the studies for 2,2,4(or 2,4,4)-trimethylhexane-1,6-diisocyanate, the test substance is classified for skin corrosion/irritation as category 1C, H314.


The classification "corrosive to skin" also implies corresponding effects on eyes. Therefore, no classification according this hazard class is necessary based on CLP regulation.