2,5,7,10-tetraoxaundecane

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

04.06.2012 – 11.06.2012

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2,5,7,10-tetraoxaundecane

EC Number:

224-631-8

EC Name:

2,5,7,10-tetraoxaundecane

Cas Number:

4431-83-8

Molecular formula:

C7H16O4

IUPAC Name:

2,5,7,10-tetraoxaundecane

Test material form:

other: liquid

Details on test material:

a/ information from sponsor
IUPAC name: 2,5,7,10-tetraoxaundecane
Molecular formula: C7H16O4
Molecular weight: 164.20
CAS No.: 4431-83-8
EC No.: 224-631-8
Batch No.: 1204051200
Purity: 99.966 % (w/w)
Impurities: 2-Methoxyethanol (0.0081 % (w/w)), Aldehyde (not found), Water (0.0161 % (w/w))
Storage: Store in supplied bottle in dark at the temperature below 25°C. Provide local exhaust or general room ventilation. Keep container closed when not in use. Keep away from heat.
Stability / Expiration date: 3 years / 05.04.2015
Safety precautions: Do not breathe gas, fumes, vapour and spray. Use respirator and goggles. In case of repeated or prolonged contact wear gloves.

b/ information from test facility
Appearance: Colourless liquid
pH: Approximately 6 (by contact of application form with universal indicator pH strip moistened with water, strip producer Lach-Ner, s.r.o. Neratovice)
Storage: During the study the test substance was stored in well closed original bottle in dark at the at the laboratory temperature.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Animals: Adults albino rabbits, strain New Zealand. Albino rabbit is the preferred species according to the guidelines
Source: breeding farm VELAZ s.r.o., Koleč u Kladna, Czech Republic, RČH CZ 21760152
Acclimatisation: 5 days
Total number: 3 animals
Sex: 3 females
Housing: individually in cages without bedding in conventional animal room
Diet: pelleted standard diet TM-MAK 1 for rabbits and guinea-pigs adlibitum (producer: Ing.Mrkvička Miroslav - Výroba krmných
směsí, Mlýn Kocanda, 252 42 Jesenice u Prahy)
Water: drinking tap water ad libitum (quality corresponding to Regulation No. 252/2004 Czech Coll. of Law)
Microclimatic conditions: room temperature 17 - 23°C, permanently monitored
Relative humidity: 30 – 70 %, permanently monitored
Light: 12-hour light/dark cycle
Identification of animals: code number on inner side of ear of animal, number of study on each cage
Health condition: certificate of good health condition – from breeding farm; no signs of diseases were observed at clinical check-in, in
acclimatization period and before the start of experiment.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
- Concentration (if solution): undiluted

Duration of treatment / exposure:

4-hour exposure

Observation period:

72 hours

Number of animals:

3

Details on study design:

Preparation of experimental animals
Approximately 24 hours before application the fur on the dorsal area of the trunk was removed by close clipping (area – 6 x 6 cm). Only adult animals with healthy intact skin were used.
After clipping the fur the animals were weighed.

Application of the test substance
The test substance in the dose of 0.5 ml was applied on intact skin and then it was covered by gauze patch, foil and cellulose cotton and held in place with non-irritating tape - Spofaplast.
At the end of each exposure period the patch was removed and remaining sample was washed with water.
In initial test three patches were applied sequentially to one animal (rabbit No. 16). The first patch was removed after three minutes. No serious skin reaction was observed, so the second patch was applied for one hour. The observations at this stage indicated that exposure can humanely be allowed to extend to four hours, so the third patch was applied for four hours.
After removing the patch, a response was graded. Because no corrosive or severe irritant effect was observed after a 4-hour exposure, the response was verified in confirmatory test using two additional animals, each with one patch for an exposure period of 4 hours.

Evaluation of skin reaction
Rabbits were examined for signs of erythema and oedema at 1, 24, 48 and 72 hours after patch removal. Dermal irritation was scored and recorded according to the grades given below:

Grading of skin reactions:
Erythema and Eschar Formation
0: No erythema
1: Very slight erythema (barely perceptible)
2: Well defined erythema
3: Moderate to severe erythema
4: Severe erythema (beet redness) to eschar formation preventing grading of erythema
Maximum possible 4

Oedema Formation
0: No oedema
1: Very slight oedema (barely perceptible)
2: Slight oedema (edges of area well defined by definite raising)
3: Moderate oedema (raised approximately 1 millimetre)
4: Severe oedema (raised more than 1 millimetre and extending beyond area of exposure)
Maximum possible 4

Clinical observation
Clinical observation of the animals was carried out before application and daily during the study.
In the end of observation period the animals were sacrificed by injection of veterinary preparation T61 (1 ml iv.).

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal: #16, 17 and 18

Time point:

other: 1 hour

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Results 2

Irritation parameter:

erythema score

Basis:

animal: #16, 17 and 18

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Results 3

Irritation parameter:

edema score

Basis:

animal: #16, 17 and 18

Time point:

other: 1 hour, 24, 48 and 72 hours

Score:

0

Max. score:

4

Irritant / corrosive response data:

Because during the initial test no irritating effect was observed, two additional animals (rabbits No. 17 and 18) were used to confirm the negative response. One patch was applied to each of 2 animals for an exposure period of 4 hours. Skin reaction was evaluated after patch removal after 1 hour, 24, 48 and 72 hours.

There was no evidence of a corrosive effect on the skin.
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.
No histopathology was performed.

Other effects:

Body weight varied from 2.70 kg prior applicaion to 2.80 kg at completion of the test for rabbit No. 16
Body weight varied from 2.50 kg prior applicaion to 2.70 kg at completion of the test for rabbit No. 17
Body weight varied from 2.70 kg prior applicaion to 2.60 kg at completion of the test for rabbit No. 18

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test substance, 2,5,7,10-TETRAOXAUNDECANE (TOU), was tested for acute dermal irritation/corrosion.
Three rabbits were exposed to 0.5 ml of test substance, applied onto clipped skin for 4 hours using a semi-occlusive dressing. Skin reactions were evaluated after patch removal and observations were made at the 1, 24, 48 and 72 hours after exposure.
Very slight erythema was observed at 1 hour after exposure in all rabbits. At 24, 48 and 72 hours after exposure no sign of erythema and oedema were recorded and no evidence of a corrosive effect or symptoms of irritation were observed on the skin in all animals.
No skin irritation was caused by 4-hour exposure of rabbits to 2,5,7,10-TETRAOXAUNDECANE (TOU).

Executive summary:

The test substance, 2,5,7,10-TETRAOXAUNDECANE (TOU), was tested in the study for acute dermal irritation/corrosion. Rabbits (New Zealand Albino breed) were used for the test. Test was performed according to Method B.4 - Acute Toxicity: Dermal Irritation/Corrosion, Council Regulation (EC) No.440/2008, published in O.J. L 142, 2008.

Three rabbits were exposed to 0.5 ml of test substance, applied onto clipped skin for 4 hours using a semi-occlusive dressing. Skin reactions were evaluated after patch removal and observations were made at 1, 24, 48 and 72 hours after exposure. At first the test substance was applied on the skin of one rabbit (test animal No. 16). Rabbit No. 16 was investigated 3 minutes, 1 hour and 4 hours after application of the test substance. Very slight erythema was observed on the skin at the 4 hours after application. In confirmatory test, two others rabbits (rabbit No. 17 and No. 18) were used with 4-hour exposition period. Very slight erythema was observed at 1 hour after exposure in all rabbits. At 24, 48 and 72 hours after exposure no sign of erythema and oedema were recorded and no evidence of a corrosive effect or symptoms of irritation were observed on the skin of all animals.

No skin irritation was caused by 4-hour exposure of rabbits to 2,5,7,10- TETRAOXAUNDECANE (TOU).