Reaction mass of 2-ethylhexyl (6-isocyanatohexyl)-carbamate and bis(2-ethylhexyl) 1,6-hexan-1,6-diylbiscarbamate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Feb-March 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

(1992)

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

2-ethylhexyl (6-isocyanatohexyl)-carbamate

EC Number:

247-735-5

EC Name:

2-ethylhexyl (6-isocyanatohexyl)-carbamate

Cas Number:

26488-60-8

Molecular formula:

C16H30N2O3

IUPAC Name:

6-Isocyanatohexylamino 3-ethylheptanoate

Constituent 2

Reference substance name:

Bis(2-ethylhexyl) 1,6-hexan-1,6-diylbiscarbamate

EC Number:

278-583-8

EC Name:

Bis(2-ethylhexyl) 1,6-hexan-1,6-diylbiscarbamate

Cas Number:

76977-79-2

Molecular formula:

C24H48N2O4

IUPAC Name:

6-(2-Ethylhexyloxycarbonylamino)hexylamino 3-ethylheptanoate

impurity 1

Reference substance name:

Hexamethylene diisocyanate

EC Number:

212-485-8

EC Name:

Hexamethylene diisocyanate

Cas Number:

822-06-0

Molecular formula:

C8H12N2O2

IUPAC Name:

1,6-diisocyanatohexane

Test material form:

liquid

Test animals

Species:

rabbit

Strain:

Himalayan

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Sex: male
- Source: LPT, 24601 Loehndorf/Post Wankendorf, Germany
- Age at study initiation: approx. 4.5 months
- Weight at study initiation: 2.1-2.5 kg
- Housing: singly
- Diet and water: ad libitum
- Acclimation period: at least 20 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3
- Humidity (%): 55 +/- 15
- 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:

unchanged (no vehicle)

Controls:

other: The surrounding untreated skin served as a control.

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

4 hour

Observation period:

up to 14 days

Number of animals:

3

Details on study design:

CONDUCT
Approx. 24 hours before the test, the fur was removed by shaving from the dorsal area of the trunk of the animals. Only animals with healthy intact skin were used.
- Area of exposure: approx. 6 cm²
- Type of wrap if used: The test substance was applied to the test site and then covered with a gauze patch, which was held in place with non-irritating tape for the duration of the exposure period.

EXAMINATIONS
After the 4-hour exposure period the patch was removed and the skin sites were evaluated. Scores were taken 60 min., 24, 48, and 72 hours and 4 to 11 days after patch removal. The skin reactions are monitored until the changes have completely subsided, however for not more than 14 days after substance application.

SCORING SYSTEM
Draize

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 11 days at the latest

Results 2

Irritation parameter:

edema score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Any other information on results incl. tables

Under the present test conditions all three rabbits exposed for 4 hours to 0.5 mL per patch and animal showed an erythema:
- animal no. one 24 hours to 4 days (grade 2) and 5 to 8 days (grade l) after patch removal,
- animal no. two 24 to 72 hours (grade 2) and 4 to 8 days (grade 1) after patch removal,
- animal no. three 24 hours to 9 days (grade 2) and 10 days (grade 1) after patch removal.

In addition, induration of the skin was noted in animal nos. one and three 72 hours to 4 days, in animal no. two 4 to 5 days after patch removal. Laceration of the skin was seen in animal nos. one and three 5 to 7 days, in animal no. two 6 and 7 days after patch removal. Peeling of the skin was observed in animal nos, one and two 8 and 9 days, in animal no. three 8 to 10 days after patch removal.

There were no systemic intolerance reactions.

Applicant's summary and conclusion

Executive summary:

For the assessment of skin irritation a study according to OECD TG 404 is available. In that study 0.5 mL of the unchanged test substance was applied semiocclusively for 4 hours to the shaved skin of three rabbits. Assessment of the test sites revealed no skin reactions one hour after patch removal, but erythema grade 2 in each of the three rabbits after 24, 48 and 72 hours. The erythema grades declined to score 0 after 11 days at the latest. Edema was not noted during the study. Induration, laceration and peeling of the skin was reported along with the erythema subsiding. All findings were resolved at Day 11 post application at the latest.