2H-Azepin-2-one, hexahydro-, polymer with 1,6-diisocyanatohexane

Endpoint summary

Description of key information

Hexamethylene diisocyanate, oligomeristion product, blocked with caprolactam is not irritating to skin (NOTOX, 2003).

The test substance is slightly irritating to eyes (NOTOX, 2003), which do not meet criteria according to EC Regulation 1272/2008 to be classified as "irritating to eyes".

With regard to local effects in the respiratory tract the substance is classified for repeated toxicity with STOT RE 1 (see chapter 'Repeated Dose Toxicity').

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:

weight of evidence

Study period:

2002-11-12 to 2002-11-15

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 92/69/EEC, B.4

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS: 
- Source: Charles River Deutschland (Germany)
- Sex: male
- Age: at least 6 weeks old
- Controls: untreated skin surrounding the application area
- Diet: ad libitum, Altromin special diet for rabbits
- Water: ad libitum, tap water
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 3 °C
- Humidity (%): 30 - 70 %
- Photoperiod (hrs dark / hrs light): 12 hours artificial light, 12 hours dark
- Air changes (per hr): 15 per hour

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.5 ml test substance, undiluted

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
- Area of exposure: dorsal area of trunk, shaved 24 hours in advance,  approx. 10 x 15 cm2
- Preparation of test substance: 0.5 ml undiluted
- Occlusion: metalline patch (2x3 cm) held in place by semi-occlusive non-irritating  tape dressing
- Duration: 4 h , after application was removed, skin was cleaned with water
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:

0.3

Max. score:

8

Reversibility:

fully reversible within: 48 h

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritant / corrosive response data:

AVERAGE SCORE
- Erythema: 0.30
- Edema: 0.30
REVERSIBILITY: fully reversible within 48 h

Other effects:

Under the test conditions the animals showed very slight erythema and very slight oedema in the treated skin-aeras. The skin irritation had resolved within 48 hours after exposure in all animals.

no other information

Conclusions:

Under the test conditions three male rabbits showed very slight erythema and very slight oedema in the treated skin-aeras after exposure to 2H-Azepin-2-one, hexahydro-, polymer with 1,6 diisocyanatohexane (90 % active ingredient in solvent). The skin irritation had resolved within 48 hours after exposure in all animals. Therefore, the test item is not irritating to skin.

Executive summary:

The acute skin irritation properties of 2H-Azepin-2-one, hexahydro-, polymer with 1,6 diisocyanatohexane were estimated according to OECD Guideline 404. A dose of 0.5 ml test item (90 % in solvent) 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. Observations were made 1, 24, 48 and 72 hours after exposure. The three male rabbits showed very slight erythema and very slight oedema in the treated skin-areas at 1 hour and 24 hours after exposure. The skin irritation had resolved within 48 hours in all animals. Sticky remnants of the test substance were present on the skin on day 1 and 2 and dry remnants were present on days 3 and 4. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occured.

Under the conditions of this study the test item 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:

weight of evidence

Study period:

2002-11-18 to 2002-11-25

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:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS: 
- Source: Charles River Deutschland (Germany)
- Sex: male
- Age: at least 6 weeks old
- Controls: untreated eye
- Diet: ad libitum, Altromin special diet for rabbits
- Water: ad libitum, tap water
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 3 °C
- Humidity (%): 30 - 70 %
- Photoperiod (hrs dark / hrs light): 12 hours artificial light, 12 hours dark
- Air changes (per hr): 15 per hour

Vehicle:

unchanged (no vehicle)

Controls:

other: identical animal, left eye

Amount / concentration applied:

0.1 ml undiluted test substance

Duration of treatment / exposure:

not rinsed; no removal of test substance

Observation period (in vivo):

1, 24, 48, 72 hours and 7 days after administration

Number of animals or in vitro replicates:

3 male rabbits

Details on study design:

- not rinsed
- Ophthalmoscopic examination with a slit lamp: prior to the administration and 1, 24, 48, 72 hours and 7 days after administration; 24 hours after
administration, the eyes were treated additionally with fluorescein and examined.
- Scoring system: Draize

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0.89

Max. score:

3

Reversibility:

fully reversible within: 7days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

AVERAGE SCORE
- Cornea: 0.0
- Iris: 0
- Conjunctivae (Redness): 0.89
- Conjunctivae (Chemosis): 0

Other effects:

Instillation of 0.1 ml test substance into one of each eye of three rabbits resulted in irritation of the conjunctivae, which was seen as redness, chemosis and discharge. The irritation had completely resolved within 72 hours in two animals and within 7 days in the other animal. No iridial irritation or corneal opacity was observed, and treatment of the eyes with 2% fuorescein, 24 hours after test substance instillation revealed no corneal epithelial damage in any of the animals. There was no evidence of ocular corrosion. Remnants of the test substance were presented on the outside of the eyelids of all animals from 1 to 72 hours after instillation. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

no further remarks

Conclusions:

Under the conditions of this study the test item 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 the test item according to OECD TG 405. An amount of 0.1 ml of

2H-Azepin-2-one, hexahydro-, polymer with 1,6 diisocyanatohexane (90 % in solvent) was instilled into the conjunctival sac of the right eye of each of three male rabbits, and the untreated left eye served as control. Observations were made 1, 24, 48, 72 hours and 7 days after instillation. The treatment resulted in irritation of the conjunctivae, which was seen as redness, chemosis and discharge. The irritation had completely resolved within 72 hours in two animals and within 7 days in the other animal. No iridial irritation or corneal opacity was observed, and treatment of the eyes with 2% fuorescein, 24 hours after test substance instillation revealed no corneal epithelial damage in any of the animals. There was no evidence of ocular corrosion. Remnants of the test substance were presented on the outside of the eyelids of all animals from 1 to 72 hours after instillation. There were no symptoms of systemic toxicity and no mortality occurred.

Therefore, under the conditions of this study the test item (90% active ingredient 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:

no adverse effect observed (not irritating)

Additional information

2H-Azepin-2-one, hexahydro-, polymer with 1,6 diisocyanatohexane is not irritating to skin (NOTOX, 2003). Although commercial products with 90 % and 72 % active ingredient in solvent were tested, it can be assumed that also 100 % active ingredient is not irritating to skin, as only very slightly skin irritating effects were observed, which could be interpreted as solvent driven. The test substance is slightly irritating to eyes (NOTOX, 2003), which do not meet criteria according to EC Regulation 1272/2008 to be classified as "irritating to eyes".

With regard to local effects in the respiratory tract the substance is classified for repeated toxicity with STOT RE 1 (see chapter 'Repeated Dose Toxicity').

Justification for selection of skin irritation / corrosion endpoint:
The study with the highest concentration of actual test substance in the tested formulation (90 % in solvent) is selected.

Justification for selection of eye irritation endpoint:
The study with the highest concentration of actual test substance in the tested formulation (90 % in solvent) is selected.

Justification for classification or non-classification

Based on the assessment of two animal studies (skin and eye irritating) and according to criteria of EC Regulation 1272/2008 2H-Azepin-2-one, hexahydro-, polymer with 1,6 diisocyanatohexane is not irritating to skin and eyes.

With regard to local effects in the respiratory tract the substance is classified for repeated toxicity with STOT RE 1.

Thus, according to EU Regulation 1272/2008 no classification for respiratory tract irritation is warranted.

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