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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2002-01-08 to 2002-01-23
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report date:
2002

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
17 July 1992
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
29 December 1992
Deviations:
no
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
Bis(2-ethylhexyl) carbonate
EC Number:
238-925-9
EC Name:
Bis(2-ethylhexyl) carbonate
Cas Number:
14858-73-2
Molecular formula:
C17H34O3
IUPAC Name:
bis(2-ethylhexyl) carbonate
Test material form:
other: liquid

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: no data
- Weight at study initiation: 3.41, 3.56 and 4.19 kg
- Housing: individual housing (100 x 45 x 40 cm, L x B x H) in a battery of cages, equipped with a paper roll disposal system
- Diet: ad libitum, standard laboratory rabbit diet Teklad Global Rabbit Diet (pelleted diet, batch no. H134) produced by Harlan Teklad, Shaw's farm, Blackthorn Bicester, Oxon, OX6 OTP, England
- Water: ad libitum, drinking water as for human consumption
- Acclimation period: about 6 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): 16
- Photoperiod: Artificial light was set to give a cycle of 12 hours light and 12 hours dark with light on at 7.00 a.m.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: Each animal served as its one control with adjacent area of untreated skin.
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 mL
- Concentration (if solution): undiluted
Duration of treatment / exposure:
4 h
Observation period:
8 days
Number of animals:
3
Details on study design:
PRE-EXPERIMENTAL PROCEDURE
The skin of the back of the animals was clipped 24 h before treatment and examined for potential lesions. Since the animals showed no evidence of abnormalities, it was allocated to the test.

ADMINISTRATION OF THE TEST ARTICLE
The test article was used as supplied by the sponsor. One of the animals (rabbit no. 1) was treated with 0.5 ml of the liquid test article, which was applied to the left side of the back, the untreated right side served as control. The test article was applied to a gauze patch and then applied to the skin. The closed patch exposure was effected by means of a semiocclusive bandage using Ypsiplast® (Holthaus Medical, Remscheid-Lüttringhausen), non-irritating tape Elastoplast® (Beiersdorf AG, Hamburg) and Stülpa® (P. Hartmann AG, Heidenheim-Brenz), which enveloped the whole of the animal's trunk. Exposure duration was 4 h. Since there were only a moderate response to the application of the test article, the further two animals were treated subsequently in the same manner.

SCORING SYSTEM: Draize scoring scheme as stipulated by OECD 404

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal: 1
Time point:
other: Mean 24, 48 and 72 h
Score:
2.33
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
erythema score
Basis:
animal: 2
Time point:
other: Mean 24, 48 and 72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: slight eschar formation recorded on day 4 and 5
Irritation parameter:
erythema score
Basis:
animal: 3
Time point:
other: Mean 24, 48 and 72 h
Score:
2.67
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
edema score
Basis:
animal: 1
Time point:
other: Mean 24, 48 and 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 4 days
Irritation parameter:
edema score
Basis:
animal: 2
Time point:
other: Mean 24, 48 and 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 6 days
Irritation parameter:
edema score
Basis:
animal: 3
Time point:
other: Mean 24, 48 and 72 h
Score:
1.67
Max. score:
4
Reversibility:
fully reversible within: 6 days
Irritant / corrosive response data:
CLINICAL SKIN OBSERVATIONS
- Slight to well-defined erythema was observed in all animals 1 h after patch removal following the 4-hour exposure and was still apparent, unchanging or increasing in degree, up to day 4 or 5 after exposure. The score 3 was observed in one animal 24 and 48 h and in one animal 72 h after exposure. Subsequently, a decreased degree of erythema was observed until the reversibility on days 7 and 8 after exposure.
Very slight to slight oedema was seen in the animals between 1 h and day 5 after exposure. Additionally, slight eschar formation was observed in one animal on days 4 and 5 after exposure.

REVERSIBILITY
- The observed findings were fully reversible within 8 days after patch removal.
Other effects:
TOXIC EFFECTS OTHER THAN SKIN IRRITATION
- No other toxic effects were observed.

Any other information on results incl. tables

Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Time point

Erythema

Max score 4

Edema

Max score 4

1 hour

1/2/1

0/1/0

24 hours

2/2/3

1/1/2

48 hours

2/2/3

1/1/2

72 hours

3/2/2

1/1/1

4 days

2/2#/2

0/1/1

5 days

1/2#/2

0/1/1

6 days

1/1/1

0/0/0

7 days

1/0/1

0/0/0

8 days

0/-/0

0/-/0

Average

24, 48, 72 hours

2.33/2/2.67

1/1/1.67

Reversibility*)

c/c/c

c/c/c

Time for reversion

8/7/8 days

4/6/6 days

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

# Slight eschar formation

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritant)
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008)
Conclusions:
Judgement is based on erythema/eschar and oedema calculated as the mean scores following grading at 24, 48 and 72 hours after removal of the test material, in consideration of reversibility.
The test substance is considered to be a skin irritant Category 2 according to CLP, EU GHS (Regulation (EC) No 1272/2008).
Executive summary:

In a primary dermal irritation study according to OECD Guideline 404, 17 July 1992 and EU Method B.4, 29 December 1992, three White New Zealand rabbits were semi-occlusive dermaly exposed to 0.5 mL of Bis(2-ethylhexyl) carbonate (approx. 100 % a.i.) for 4 hours. Animals then were observed for 8 days. Irritation was scored by the method of Draize as stipulated by OECD Guideline 404.

Slight to well-defined erythema was observed in all animals 1 h after patch removal following the 4-hour exposure and was still apparent, unchanging or increasing in degree, up to day 4 or 5 after exposure. The score 3 was observed in one animal 24 and 48 h and in one animal 72 h after exposure. Subsequently, a decreased degree of erythema was observed until the reversibility on days 7 and 8 after exposure. Very slight to slight oedema was seen in the animals between 1 h and day 5 after exposure. Additionally, slight eschar formation was observed in one animal on days 4 and 5 after exposure. The observed findings were fully reversible within 8 days after patch removal.

Mean values of skin reactions at 24, 48 and 72 h were ≥ 2.3 ≤ 4.0 for erythema/eschar in 2 of 3 animals.

The test substance Bis(2-ethylhexyl) carbonate is considered to be a skin irritant Category 2 according to CLP, EU GHS (Regulation (EC) No 1272/2008).