2,5,7,10-tetraoxaundecane

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:

04.06.2012 – 11.06.2012

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes

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.

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.).

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

Irritation parameter:

erythema score

Basis:

animal: #16, 17 and 18

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

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

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).

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:

From 2010-02-22 to 2010-02-22

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: breeding farm VELAZ s.r.o., Kolec u Kladna, Czech Republic, RCH CZ 21760152
- Age at study initiation: 4-5 months
- Weight at study initiation: 3.3-3.4 kg
- Housing: Conventional animal room – individually in metallic cages
- Diet (e.g. ad libitum): Standard pelleted diet TM-MAK 1 for rabbits and guinea pigs ad libidum (producer: Ing. Mrkvicka Miroslav – Vyroba krmnych smesi, Mlyn Kocanda, 252 42 Jesenice u Prahy)
- Water (e.g. ad libitum): Drinking tap water ad libitum (quality corresponding to the Regulation No.: 252/2004 Czech Coll. Of Law)
- Acclimation period: not specified

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3°C, permanently monitored
- Humidity (%): 30 – 70%, permanently monitored
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mM
- Concentration (if solution): not relevant

Duration of treatment / exposure:

Duration of exposure corresponds to duration of observation

Observation period (in vivo):

The eyes were examined at 1, 24, 48 and 72 hours after application, then once daily. After recording the observations at 24 hours, the eyes of rabbit were examined with the aid of fluorescinein and the ophthamoscopy. The grades of ocular reaction for single animal (observation of conjunctivae, cornea and iris) were recorded at each examination.

Number of animals or in vitro replicates:

3 males

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No
- Time after start of exposure: Not relevant

SCORING SYSTEM:
CORNEA
0 - No ulceration or opacity
1 - Scattered or diffuse areas of opacity; details of iris clearly visible
2 - Easily discernible translucent area;details of iris slightly obscured
3 – Nacrous area, no details of iris visible, size of pupil barely discernible
4 – Opaque cornea, iris not discernible through the opacy
Maximum possible: 4

IRIS
0 - Normal
1 – Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperemia ; or injection ; iris reactive to light (a sluggish reaction is considered to be an effect)
2 – Hemorrhage, gross destruction, or no reaction to light
Maximum possible: 2

CONJUNCTIVAE
0 - Redness (refers to palpebral and bulbar conjunctivae; excluding cornea and iris) normal
1 - Some blood vessels hyperarmic (injected)
2 - Diffuse, crimson color, individual vessels not easily discernible
3 - Diffuse beefy red
Maximum possible: 3

CHEMOSIS
0 - Normal no alterations
1 - Some swelling above normal
2 - Obvious swelling with partial eversion of lids
3- Swelling with lids about half closed
4 - Swelling with lids more than half closed
Maximum possible: 4

Irritation parameter:

cornea opacity score

Basis:

animal: #18, #17 and #16

Time point:

other: 1h, 24h, 48h and 72h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

iris score

Basis:

animal: #18, #17 and #16

Time point:

other: 1h, 24h, 48h and 72h

Score:

0

Max. score:

2

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal: #18

Time point:

other: 1h, 24h and 48h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72h

Irritation parameter:

conjunctivae score

Basis:

animal: #17 and #16

Time point:

other: 1h and 24h

Score:

2

Max. score:

3

Reversibility:

not fully reversible within: 72h

Irritation parameter:

conjunctivae score

Basis:

animal: #17 and #16

Time point:

other: 48h

Score:

1

Max. score:

3

Reversibility:

not fully reversible within: 72h

Irritation parameter:

chemosis score

Basis:

animal: #18, #17 and #16

Time point:

other: 1h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 48h

Irritation parameter:

chemosis score

Basis:

animal: #18, #17 and #16

Time point:

other: 24h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 48h

Irritant / corrosive response data:

Please refer to “Overall irritation/corrosion results”

Other effects:

Clinical observation and body weight are recorded under "Any other information on results incl. tables"

Clinical observation and body weight were recorded in the table below:

Rabbit No.	Clinical observation	Body weight (in kg)
		prior to application	at termination
18	No changes	3.30	3.40
17	No changes	3.40	3.50
16	No changes	3.30	3.40

No symptoms of systemic toxicity were observed in the animals during clinical observation in the test period and no mortality occurred.

Interpretation of results:

slightly irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Examination of eye irritation after single application demonstrated, that the test substance, 2,5,7,10-tetraoxaudecane (TOU), was slightly irritating for eye of rabbit, but all signs of irritation disappeared till 72h after exposure.

Executive summary:

The test substance, 2,5,7,10-tetraoxaudecane (TOU), was tested for the assessment of eye irritation/corrosion effects using albino rabbit (New Zealand Albino breed).

The test was performed according to the Method B.5 Acute Toxicity: Eye Irritation/Corrosion. Council Regulation (EC) No.440/2008, published in O.J. L 142, 2008.

The test was performed initially using one animal (No. 18). If the results of this test indicate the substance to be corrosive or a severe irritant to the eye, the response was confirmed using two additional animals (No. 17 and No. 16).

The following changes were observed on eye at 1 hour after application: conjunctivae - some blood vessels hyperaemic (injected); chemosis – obvious swelling with partial eversion of lids; lacrimation in one rabbit (No. 18) and conjunctivae conjunctivae – diffuse, crimson color, individual vessels not easily discernible; chemosis - obvious swelling with partial eversion of lids; lacrimation was observed in two rabbits (No. 17 and No. 16). Conjunctivae - some blood vessels hyperaemic (injected); chemosis – some swelling above normal; lacrimation was observed in all rabbits at 24h after application. Conjunctivae - some blood vessels hyperaemic (injected) was observed in all rabbits at the 48 hours after application. No signs of eye irritation were observed at 24 hours after application. No cinical signs of systemic intoxication were detected.

 

Examination of eye irritation after single application demonstrated, that the test substance, 2,5,7,10-tetraoxaudecane (TOU), was slightly irritating for eye of rabbit, but all signs of irritation disappeared till 72h after exposure.

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Justification for selection of skin irritation / corrosion endpoint:

Three tests was available for this endpoint:

- in vitro EPISKIN (corrosion) according to OECD TG 431,

- in vitro EPIDERM (irritation) according to OECD TG 439 and

- in vivo irritation according to OECD TG 404

The in vivo test was selected has the most relevant one.

Justification for selection of eye irritation endpoint:

This OECD TG 405 test was selected as the only one available.

Effects on eye irritation: slightly irritating

Justification for classification or non-classification

The test item was not classified for its skin and eye irritation tests performed according to OECD TG and GLP.