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

Endpoint summary

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:

Feb-March 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

(1992)

GLP compliance:

yes (incl. QA statement)

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

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

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

Irritation parameter:

edema score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

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.

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.

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:

key study

Study period:

March 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

(1987)

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

Himalayan

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Sex: male
- Source: LPT, 24601 Loehndorf/Post Wankendorf, Germany
- Age at study initiation: approx. 3.5 months
- Weight at study initiation: 1.8-2.4 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

Vehicle:

unchanged (no vehicle)

Controls:

other: The left eye, which remained untreated, served as a control

Amount / concentration applied:

0.1 mL

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

up to 21 days

Number of animals or in vitro replicates:

3

Details on study design:

CONDUCT
A dose of 0.1 mL test substance was administered into the conjunctival sac of the right eye of rabbits after gently pulling the lower lid away from the eyeball. The lid was then gently held together for about one second in order to prevent loss of test material.

EXAMINATIONS
The eyes were examined ophthalmoscopically with a slit lamp prior to the administration and also 1, 24, 48, and 72 hours after the administration. 24 hours after administration, the eyes were treated additionally with fluorescein and examined.

SCORING SYSTEM
Draize

Irritation parameter:

cornea opacity score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritation parameter:

chemosis score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Under the present test conditions, a single application of 0.1 mL per animal into the conjunctival sac of the right eye of three rabbits caused the following effects:
Conjunctival redness (grade 1) was observed in animal nos. one and two 1 hour after instillation.
The cornea and the iris were not affected by instillation of the test compound.

There were no systemic intolerance reactions.

Executive summary:

For the assessment of eye irritation a study according to OECD TG 405 is available. In this study 0.1 mL of the unchanged test substance was instilled in the conjunctival sac of the lower lid of each of three rabbits. Examination of the eyes revealed 1 hour after dosing conjunctiva (redness) score 1 in 2/3 animals. All changes were resolved 24 hours post application at the latest (all 24, 48 and 72 -hour scores zero).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

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.

For the assessment of eye irritation a study according to OECD TG 405 is available. In this study 0.1 mL of the unchanged test substance was instilled in the conjunctival sac of the lower lid of each of three rabbits. Examination of the eyes revealed 1 hour after dosing conjunctiva (redness) score 1 in 2/3 animals. All changes were resolved 24 hours post administration at the latest (all 24, 48 and 72 -hour scores zero).

The available studies with inhalation exposure reveal for the substance a respiratory irritant potential (OECD TG 403: The mortality patterns were typical of an irritation-related acute lung edema; OECD TG 412: Broncho-alveolar lavage (BAL) analysis and histopathology showed evidence of portal-of-entry related inflammatory processes in the respiratory tract). Especially the investigation of BAL after repeated inhalation exposure suggests a local irritant Mode of Action, e.g. by elevated percentages of inflammatory cells in BAL (lymphocytes and polymorphonuclear cells; see chapter repeated dose toxicity: inhalation). This is consistent with the reactive character of the isocyanate groups in the substance.

Justification for classification or non-classification

According to Regulation (EC) No. 1272/2008, Annex I, classification as skin irritant or eye damaging is not justified.

According to Regulation (EC) No. 1272/2008, Annex I, classification as STOT SE 3 for respiratory irritancy is justified (H335: May cause respiratory irritation).