Cyclohexane, 5-isocyanato-1-(isocyanatomethyl)-1,3,3-trimethyl-, homopolymer, 3,5-dimethyl-1H-pyrazole-blocked

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

March 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

(2002)

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

3-Isocyanatomethyl-3,5,5-trimethylcyclohexyl isocyanate, oligomers, reaction products with 3,5-dimethyl-1H-pyrazole

EC Number:

606-423-2

Cas Number:

200295-52-9

Molecular formula:

>= C51H78N12O6 (IPDI-Isocyanurate n=3, blocked with 3,5-dimethylpyrazole)

IUPAC Name:

3-Isocyanatomethyl-3,5,5-trimethylcyclohexyl isocyanate, oligomers, reaction products with 3,5-dimethyl-1H-pyrazole

Test material form:

solid: crystalline

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain: Albino rabbits Crl: KBL(NZW)BR
- Sex: female
- Source: Charles River, 88353 Kisslegg, Germany
- Age at study initiation: young adult animals
- Weight at study initiation: 2.6 - 2.7 kg
- Housing: individually in cage units Metall/Noryl by EBECO
- Diet and water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3
- Humidity (%): 50 +/- 25
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

other: unchanged (no vehicle), but moistened with corn oil to ensure good contact with the skin

Controls:

other: the contralateral skin area of the same animal, treated with 0.5 mL corn oil, was used as control

Amount / concentration applied:

0.5 g

Duration of treatment / exposure:

4 hours

Observation period:

Animals were monitored until changes had completely subsided, however, for not more than 14 days after application.

Number of animals:

3

Details on study design:

On the day before the test, the fur was shorn on the right and left side from the dorso-Iateral area of the trunk of each of the rabbits. Care was taken to avoid abrading the skin. Only animals with healthy and intact skin were used.
0.5 g of the pulverized test substance moistened with com oil (to ensure good contact with the skin) was applied to the skin of the animal under a gauze patch. 0.5 mL com oil was applied as control on the contra lateral skin area for the 4 hour treatment period. The treated skin area was approximately 2.5 cm by 2.5 cm in size. The patch was placed on the dorso-Iateral areas of the trunk of each animal and was held in place with non-irritating tape for the duration of the exposure period.

Due to a possible irritant potential of the test substance, in the first step only one animal was used and three test patches were applied successively to this animal, as described above. The first patch was removed after three minutes. As no serious skin reactions were observed, the second patch was applied and removed after one hour. At this stage the observations indicated that with respect to animal welfare the exposure can be allowed to extend to four hours, therefore the third patch was applied and removed after four hours and the responses were graded one hour later. The test was completed using two additional animals, exposed for four hours.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After 4 hours the exposed skin area was carefully washed with water.
- Time after start of exposure: After the exposure period (4 hours) the dressing and patch were removed.

OBSERVATION TIME POINTS
- 1, 24, 48 and 72 hours after patch removal. If no irritation indices were observed after 72 h, the study was finished. If dermal irritation was observed, animals were monitored usually on day 7 and 14 after patch removal until the changes had completely subsided, however for not more than 14 days after application.

SCORING SYSTEM: Draize

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Remarks:

(redness and eschar formation)

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

edema score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Other effects:

There were no relevant systemic intolerance reactions.

Applicant's summary and conclusion

Executive summary:

An acute skin irritation/corrosion test according to OECD TG 404 was conducted on 3 rabbits receiving each 0.5 g of the unchanged test substance on the previously shorn but healthy and intact skin. Corn oil was used to moisten the test substance in order to ensure a good contact with the skin. Due to a possible irritant potential of the test substance a stepwise approach was chosen. In the first step only one animal was used and three test patches were applied to this animal. After three minutes the first patch was removed and if no skin reactions were observed, the second patch was applied and removed after one hour. If at this stage the observations indicated that with respect to animal welfare the exposure can be extended to four hours, the third patch was applied and removed after four hours and the responses were graded one hour later. The test was then completed using two additional animals, each exposed for four hours. Skin irritation was scored and recorded approx. at 1, 24, 48 and 72 hours after patch removal. If no irritation indices were observed after 72 h, the study was finished. If dermal irritation was observed, animals were monitored usually on day 7 and 14 after patch removal until the changes had completely subsided, however for not more than 14 days after application.

As result a single application of 0.5 g test substance to the skin did not cause any changes (erythema and edema scores all zero after 24, 48, and 72 hours). No relevant systemic intolerance reactions were noted.