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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
16 February 2009 - 8 May 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
24 April 2002
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
Storage conditions: At room temperature

Test animals

Species:
rabbit
Strain:
other: Japanese white rabbits
Details on test animals and environmental conditions:
- Source: Japan Laboratory Animals, Inc.
- Age at study initiation: 17 or 18 weeks old
- Weight at study initiation: 3.02 - 3.74 kg
- Housing: Individually in aluminium cages with wire-mesh bottoms
- Diet: Free access to pelleted diet RC4 (Oriental Yeast Co., Ltd.,)
- Water: Free access to tap water.
- Acclimation period: 12 or 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 – 25
- Humidity (%): 40 - 57
- Air changes (per hr): 11 - 14
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 3 March 2009 to 7 March 2009

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
other: Adjacent areas of the clipped skin of each animal served as controls.
Amount / concentration applied:
TEST MATERIAL
- Volume applied: 0.5 mL
Duration of treatment / exposure:
Single application.
Observation period:
2 or 4 days.
Number of animals:
3 females.
Details on study design:
STUDY DESIGN
One animal was clipped to provide 4 regions for application of the test substance. 0.5 mL of the test item was applied for 3 minutes and observed after 1 hour. No corrosiveness was observed and 0.5 mL of the test item was applied for 1 hour to a new clean region. No corrosiveness were observed 1 hour after removal of the test item. Next, 0.5 mL of the test item was applied for 4 hours to a new clean region and observed for 24 hours. After 24 hours two new animals (animal 2 and 3) were clipped and 0.5 mL of the test item was applied to the skin for 4 hours.

TEST SITE
On the day of application the dorsal fur was clipped. 0.5 mL test substance was applied to a lint sheet of 2.5 x 2.5 cm. After application to the skin it was covered with tape.

REMOVAL OF TEST SUBSTANCE
The lint sheets on the application site were removed at specified timepoints, and exposed skin was wiped with absorbent cotton soaked with acetone (anhydrous).

OBSERVATIONS
- Toxicity: For the first animal, immediately after removal of test item and/or daily for all animals.
- Body Weight: At the day of administration and last day of observation.
- Necropsy: No necroscopy performed.
- Irritation and corrosiveness: The skin reactions for the first treated animal 1 were observed at 1, 24, 48 and 72 hours and on the 4th day after removal of the test substance. The second and third animals were only observed 1 hour and 24 hours after removal of test item before the experiment was terminated.

SCORING SYSTEM:
The irritation was assessed according to the numerical scoring system according to OECD 404.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Remarks:
(mean)
Basis:
animal #1
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
other: animal killed for humane reasons on day 4
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24 h
Score:
4
Max. score:
4
Reversibility:
other: animal killed for humane reasons on day 2.
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24 h
Score:
4
Max. score:
4
Reversibility:
other: animal killed for humane reasons on day 2.
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
other: animal killed for humane reasons on day 4.
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
other: animal killed for humane reasons on day 2.
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
other: animal killed for humane reasons on day 2
Irritant / corrosive response data:
No corrosiveness or dermal reactions were observed for skin that was 3 minutes or 1 hour exposed to the test article.

The skin of the first animal that was exposed to the test item showed severe erythema at 24 hours after removal of the test item. This changed to an eschar 72 hours after removal of the test item. On the 4th day it was concluded that the tissue damage was irreversible and thus the observation period was terminated for all animals.


Other effects:
All animals lost weight during the study period.
No other clinical signs were observed.

Applicant's summary and conclusion

Interpretation of results:
Category 1C (corrosive) based on GHS criteria
Conclusions:
A single semi-occlusive application of 1,4-Bis(isocyanatomethyl)cyclohexane to rabbit skin for four hours elicited skin corrosive effects after 4 days. Based on these results, 1,4-Bis(isocyanatomethyl)cyclohexane is classified as category 1C (corrosive) (H314) according to GHS and CLP criteria.
Executive summary:

In a skin irritation study with rabbits, performed according to OECD test guideline 404 and GLP principles, the irritation and corrosive effects of 1,4-bis(isocyanatomethyl)-cyclohexane were examined. 0.5 mL of the test item was applied to clipped skin of rabbits for 3 minutes, 1 hour or 4 hours. Observations took place 1 hour after application and over the next consecutive days. No corrosiveness or dermal reactions were observed for skin that was exposed for 3 minutes or 1 hour. Skin corrosion was observed after 4 days on skin that was exposed for 4 hours to the test item. Basd on this result 1,4 -Bis(isocyanatomethyl)cyclohexane is classified as category 1C (corrosive) (H314) according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments) and according to Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).