2,4,8,10-Tetraoxaspiro[5.5]undecane-3,9-diethanol, .beta.3,.beta.3,.beta.9,.beta.9-tetramethyl-

Endpoint summary

Description of key information

The test substance was assessed for irritancy potential to skin and to the eye according to OECD guideline 404 and OECD Guideline 405 respectively.  No corrosive effects were noted and a primary irritation index of 0.0 was observed in the skin and therefore was classified as non-irritant to the skin.  In the eye, the addition of the test material produced a very minimal initial irritation  which quickly resolved and was therefore classified as non-irritant to the eye.

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:

2006-05-23 to 2006-06-15

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Test was performed according to guideline.

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River France, Charlaronne, France.
- Age at study initiation: Twelve to twenty weeks old.
- Weight at study initiation: In the range of 2.0 to 3.5 kg.
- Housing: Animals were housed individually in suspended cages.
- Diet (e.g. ad libitum): Free access to Certified Rabbit Diet (5322), BCM IPS Ltd, London, UK) was allowed throughout the study.
- Water (e.g. ad libitum): Free access to mains drinking water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23 °C
- Humidity (%): 70 %
- Air changes (per hr): At least 15 changes per hour.
- Photoperiod (hrs dark / hrs light): Twelve hours continuous light and twelve hours darkness.

IN-LIFE DATES: From: Day 1 To: Day 1

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Remarks:

0.5 g material moistened with 0.5 mL distilled water

Controls:

no

Amount / concentration applied:

500 mg

Duration of treatment / exposure:

4 h

Observation period:

72 h

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: Dorsal/flank area.
- % coverage: Not specified
- Type of wrap if used: A cotton gauze patch secured in position with a strip of surgical adhesive tape. The trunk of each rabbit was wrapped in an elasticated corset.

REMOVAL OF TEST SUBSTANCE
- Washing: Residual test material removed by gentle swabbing with cotton wool soaked in distilled water.
- Time after start of exposure: Four hours after application.

SCORING SYSTEM: According to Draize, as follows:
Erythema and Eschar formation
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erytehma (beef redness) to eschar formation preventing grading of erythema. 4

Oedema formation
No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well-defined by definite raising) 2
Moderate oedema (raised approximately 1 mm) 3
Severe oedema (raised > 1mm and extending beyond the area of exposure) 4

Other skin reactions, if present, were also recorded.

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

24/48/72 h

Score:

0

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

24/48/72 h

Score:

0

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

24/48/72 h

Score:

0

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

24/48/72 h

Score:

0

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

24/48/72 h

Score:

0

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

24/48/72 h

Score:

0

Irritant / corrosive response data:

No evidence of skin irritation was noted during the study.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: other: Draize classification scheme

Conclusions:

The test material produced a primary irritation index of 0.0 and was classified as non-irritant to rabbit skin according to Draize classification system. No corrosive effects were noted.

Executive summary:

Introduction.

The study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method was designed to meet the requirements of the following:

·        OECD Guidelines for the Testing of Chemicals No. 404 “Acute Dermal Irritation/Corrosion” (adopted 24 April 2002)

·        Method B Acute Toxicity (Skin Irritation) of Commission Directive 2004/73/EC.

 

Results.

A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced no evidence of skin irritation.

 

Conclusion.

The test material produced a primary irritation index of 0.0 and was classified as non-irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

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:

2006-06-05 to 2006-06-09

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Test was performed according to guideline.

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd, Moston, Sandbach, Cheshire, UK.
- Age at study initiation: In the range of 12 to twenty weeks old.
- Weight at study initiation: In the range of 2.0 to 3.5 kg.
- Housing: The animals were individually housed in suspended cages.
- Diet (e.g. ad libitum): Free access to Certified Rabbit Diet (5322, BCM IPS Ltd, London, UK) was allowed throughout the study.
- Water (e.g. ad libitum): Free access to mains drinking water was allowed throughout the study.
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): At least 15 changes per hour
- Photoperiod (hrs dark / hrs light): Twelve hours continuous light and twelve hours darkness.

IN-LIFE DATES: From: Day 1 To: Day 3

Vehicle:

water

Controls:

other: The left eye of each animal remained untreated as a control.

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 mL (approximately 50 g)
- Concentration: Not applicable

VEHICLE
Not applicable

Duration of treatment / exposure:

Single application

Observation period (in vivo):

72 h, with assessment of ocular damage/irritation made at approximately 1, 24, 48 and 72 h.

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: No
- Time after start of exposure: Not applicable

SCORING SYSTEM: According to Draize.

TOOL USED TO ASSESS SCORE: Ophthalmoscope

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

24/48/72 h

Score:

0

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

24/48/72 h

Score:

0.3

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

24/48/72 h

Score:

0.67

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

24/48/72 h

Score:

0

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

24/48/72 h

Score:

0

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

24/48/72 h

Score:

0

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

24/48/72 h

Score:

0

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

24/48/72 h

Score:

0

Irritation parameter:

cornea opacity score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

24/48/72 h

Score:

0

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

24/48/72 h

Score:

0

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

24/48/72 h

Score:

0

Irritation parameter:

iris score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

24/48/72 h

Score:

0

Irritant / corrosive response data:

No corneal effects were noted during the study.
Iridial inflammation was noted in one eye treated one hour after treatment.
Minimal to moderate conjunctival irritation was noted in all eyes one hour after treatment with minimal conjunctival irritation noted in two treated eyes at the 24 h observation and persisted in one treated eye at the 48 h observation.
One treated eye appeared normal at the 24 h observation, one other treated eye appeared normal at the 48 h observation and the remaining eye appeared normal at the 72 h observation.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test substance was assessed for eye irritation according to OECD Guideline 405 and EU Method B5. Based on the results the test substance is not classified as an eye irritant.

Executive summary:

Introduction.

The study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. The method was designed to meet the requirements of the following:

OECD Guidelines for the Testing of Chemicals No. 405 “Acute Eye Irritation/Corrosion” (adopted 24 April 2002).

Method B5 Acute Toxicity (Eye Irritation) of Commission Directive 2004/73/EC.

 

Results.

A single application of the test material to the non-irrigated eye of three rabbits produced iridial inflammation and minimal to moderate conjunctival irritation. One treated eye appeared normal at the 24-h observation, one other treated eye appeared normal at the 48 h observation and the remaining treated eye appeared normal at the 72 h observation.

 

Conclusion.

Based on the results the test substance is not classified as an eye irritant.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

The study was performed to assess the irritancy potential of the test material following a single 4-hour, semi-occluded application to the intact rabbit skin. The study was performed according to OECD guideline 404 and Method B4 of Commission Directive 2004/73/EC. The application of the test material to the skin produced no evidence of skin irritation and there were no corrosive effects noted.

 

Eye irritation:

The study was performed to assess the irritancy potential of the test material following a single application to the rabbit eye. The study was performed according to OECD guideline 405 and Method B5 of Commission Directive 2004/73/EC. A single application to three rabbits produced iridial inflammation and minimal to moderate conjunctival irritation which was reversed in each case by 72 hours.

Justification for selection of skin irritation / corrosion endpoint:
The key study was performed to GLP according to OECD Guideline 404 in an appropriate test species.

Justification for selection of eye irritation endpoint:
The key study was performed to GLP according to OECD Guideline 405 in an appropriate test species.

Justification for classification or non-classification

Skin corrosion/irritation

The major criterion for a classification as an irritant is that at least two of three animals tested have a mean score of ≥ 2.3 - ≤ 4.0. The reversibility of skin lesions is also considered when evaluating irritant responses. When inflammation persists to the end of the observation period in two or more test animals, then a material may be considered as an irritant. As the in vivo test had a mean score of 0.0 the test item was classified as non-irritant to the skin.

 

Eye irritation

The classification system for substances involves a tired testing and evaluation scheme and a number of factors are considered in determining eye irritation or serious eye damage. pH extremes may produce serious eye damage and therefore the pH of the test substance is assessed before in vivo experiments are conducted. In this case, a 10 % w/w aqueous preparation of the test item gave a pH of 8.0, which is not within the parameters causing concern.

Testing conducted in vivo demonstrated minor effects over the initial 48 hours of testing. Where they occurred, these effects were fully resolved within 72 hours. 

Classification as an eye irritant is dependent on the severity and duration of the effects. If, when the substance is applied to the eye of an animal the substance produces corneal opacity of ≥ 1, and/or iritis ≥ 1, and/or conjunctival redness ≥ 2, and/or conjunctival oedema (chemosis) ≥ 2 in at least two of the three animals test then it is classified as irritating to eyes. This is calculated as the mean scores following grading at 24, 48 and 72 hours after installation of the test material. The mean scores following grading at 24, 48 and 72 hours did not meet the above requirements of classification as an eye irritant.