2,6-bis(4-ethylphenyl)perhydro-1,3,5,7-tetraoxanaphth-4-ylethane-1,2-diol

Endpoint summary

Description of key information

Skin irritation:

The skin irritation potential of the substance (EC 406-176-9) has been assessed by a study on substance itself and supported by reading across the results of studies conducted on two structurally similar analogue substances. It is proposed that these results can be used in the assessment of the target substance (EC 406-176-9).

Study on target substance (EC 406-176-9):

No dermal irritation was observed in 6 rabbits following a single application of test material for 4 hours.

Source Substance; 1,3:2,4-bis-O-(3,4-dimethylbenzylidene)-D-glucitol (EC-413 -110 -2):

A study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method used followed the recommendations of the OECD Guidelines for Testing of Chemicals No. 404 "Acute Dermal Irritation/Corrosion) and Method B4 of Commission Directive 92/69/EEC).

A single 4-hour, semi-occluded application of the test material to the intact skin of 3 rabbits produced very slight erythema. All treated skin sites appeared normal at the 24-hour observation.

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

The test material does not meet the criteria for classification as irritant or corrosive according to Regulation (EC) No. 1272/2008 (CLP).

Source Substance; 1-(2,6-bis(4-tolyl)-1,3-dioxano(5,4-d)-1,3-dioxan-4-yl)ethane-1,2-diol (EC 402-950-5):

The method used was designed to meet the requirements of OECD Guideline No. 404.

Test material, moistened with water, was applied for four hours under a semi-occlusive dressing to the clipped dorsal skin of three rabbits. Assessments for skin irritation were made 1, 24, 48 and 72 hours and 7 days after removal of the dressing.

No skin irritation was observed in any animal at any assessment.

Eye Irritation:

The eye irritation potential of the substance (EC 406-176-9) has been assessed by a study on substance itself and supported by reading across the results of studies conducted on two structurally similar analgoue substances. It is proposed that these results can be used in the assessment of the target substance (EC 406-176-9).

Study on target substance (EC 406-176-9):

No adverse effects were observed for the iris or corneal damage at any time point in any animal.

Minor conjuncitval irritation (redness) was observed in 4 animals and minor chemosis was observed in 1 animal. All eyes were normal after 1 day.

A single application of test material into the rabbit eye did not produce a positive response according to CLP criteria.

Source Substance; 1,3:2,4-bis-O-(3,4-dimethylbenzylidene)-D-glucitol (EC-413 -110 -2):

A study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. The method used followed that described in the OECD Guidelines for Testing of Chemicals No. 405 "Acute Eye Irritation/Corrosion" and Method B5 of Commission Directive 92/69/EEC.

A single application of the test material to the non-irrigated eye of three rabbits produced moderate conjunctival irritation. Treated eyes appeared normal at the 48 or 72-hour observations.

The test material produced a maximum group mean score of 8.7 and was classified as a mild irritant (class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

The test material did not produce positive criteria in any rabbit according to Regulation (EC) No. 1272/2008 (CLP).

Source Substance; 1-(2,6-bis(4-tolyl)-1,3-dioxano(5,4-d)-1,3-dioxan-4-yl)ethane-1,2-diol (EC 402-950-5):

The method used was designed to meet the requirements of OECD Guideline No. 405.

Gel All MD was instilled into the right eye of three rabbits. Assessments of eye irritation were made 1, 24, 48 and 72 hours and 7 days after installation.

One hour after instillation, well defined conjunctival redness was seen in two rabbits and slight redness in the third animal. Only slight conjunctival redness was seen after 24 hours in two animals. All eyes were normal within 48 hours. No chemosis, iridial irritation or cornea effects were observed.

The slight irritation (redness) was fully reversible and not sufficient for classification.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1987

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Qualifier:

according to guideline

Guideline:

EPA OTS 798.4470 (Acute Dermal Irritation)

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Remarks:

used to moisten application site

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

Duration of treatment / exposure:

4 hours

Observation period:

Four days

Number of animals:

6

Irritation parameter:

erythema score

Basis:

mean

Remarks:

6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: No effect at any time point

Irritation parameter:

edema score

Basis:

mean

Remarks:

6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: No effect at any time point

Irritant / corrosive response data:

There was no irritation response in any animals observed throughout the observation period.

Irritation endpoint	Mean Score	Maximum Value Observed	Maximum Duration of any Effect	Maximum value at the end the observation period
Erythema/eschar	0	0	-	0
Oedema	0	0	-	0

Interpretation of results:

GHS criteria not met

Conclusions:

No dermal irritation was observed in 6 rabbits following a single application of test material for 4 hours.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

29 September to 2 October 1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

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

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: David Percival Ltd, Moston, Sandbach, Cheshire, UK
- Age at study initiation: 12 to 16 weeks
- Weight at study initiation: 2.56 to 2.61 kg
- Housing: animals were housed individually in suspended metal cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 20 °C
- Humidity (%): 58 to 78 %
- Air changes (per hr): 15 per hour
- Photoperiod (hrs dark / hrs light): 12/ 12
- on 2 occasions the relative humidity was above the limit specified in the study protocol (70 %). This deviation was considered not to affect the purpose or integrity of the study.

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

other: moistened with water

Controls:

no

Amount / concentration applied:

0.5 g of the test material, moistened with 0.5 mL of distilled water

Duration of treatment / exposure:

4 h

Observation period:

72 h

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm cotton gauze patch secured with surgical adhesive tape
- Type of wrap if used: the trunk of each animal was wrapped in an elasticated corset (TUBIGRIP)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test material was removed by gentle swabbing with cotton wool soaked in distilled water
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize scheme

Irritation parameter:

erythema score

Basis:

mean

Remarks:

(Animal 2 - male)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: Score of 1 at 1 hour observation

Irritation parameter:

erythema score

Basis:

mean

Remarks:

(Animal 27 - male)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: No erythema/eschar observed at any observation

Irritation parameter:

erythema score

Basis:

mean

Remarks:

(Animal 167 - female)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: Score of 1 at 1 hour observation

Irritation parameter:

edema score

Basis:

mean

Remarks:

(Animal 2 - male)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: No edema observed at any observation

Irritation parameter:

edema score

Basis:

mean

Remarks:

(Animal 27 - male)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: No edema observed at any observation

Irritation parameter:

edema score

Basis:

mean

Remarks:

(Animal 167 - female)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: No edema observed at any observation

Irritant / corrosive response data:

The individual scores for erythemaleschar and oedema, are given in Table 1 (see attached background material)
Mean values required for EU labelling regulations are given in Table 2 (see attached background material).

Very slight erythema was noted in 2 treated skin sites 1 hour after patch removal. All treated skin sites appeared normal at the 24-hour observation.

Interpretation of results:

other: not irritating

Remarks:

Not classified as irritant according to CLP.

Conclusions:

The skin irritancy potential of the test material was assessed according to OECD guideline 404. The test material produced a primary irriation of 0.0 and was classified as a non-irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

The test material does not meet the criteria for classification as irritant or corrosive according to Regulation (EC) No. 1272/2008 (CLP).

Executive summary:

A study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method used followed the recommendations of the OECD Guidelines for Testing of Chemicals No. 404 "Acute Dermal Irritation/Corrosion) and Method B4 of Commission Directive 92/69/EEC).

A single 4-hour, semi-occluded application of the test material to the intact skin of 3 rabbits produced very slight erythema. All treated skin sites appeared normal at the 24-hour observation.

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

The test material does not meet the criteria for classification as irritant or corrosive according to Regulation (EC) No. 1272/2008 (CLP).

Reference 3

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1988-03-17 to 1988-03-24

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study was carried out to generally valid and internally-accepted guidelines and performed according to GLP.

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: Gorseside Rabbits, Northchurch, Berkhamstead, Hertfordshire
- Age at study initiation: 12 weeks
- Weight at study initiation: approx 2.0 kg
- Housing: Individually housed in grid-bottomed metal cages.
- Diet: SQC standard rabbit pellets produced by Special Diet Services, Witham, Essex, ad libitum (antibiotic free)
- Water: mains drinking water ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature: 17 to 20°C.
- Humidity: 44-77%.
- Air changes (per hr): No data
- Photoperiod: 12 hrs dark / 12 hrs light (fluorescent lighting)

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Remarks:

(distilled)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 g material mixed with 0.5 ml distilled water

VEHICLE
- distilled water

Duration of treatment / exposure:

4 hours

Observation period:

7 days (observations at 1 hr, 24 hr, 48 hr, 72 hr, 7 days)

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 2.5 cm × 2.5 cm
- Type of wrap if used: lint pad; held in place with 7.5 cm width elastic adhesive bandage

REMOVAL OF TEST SUBSTANCE
- Washing: With cotton wool soaked in water warmed to approx. 37 °C.
- Time after start of exposure: 4 hours

SCORING SYSTEM:
Animals were examined under a standard light source designed to comply with the requirements of BS 950 Part 1 (Artificial Daylight for the assessment of colour) and irritation allocated a numerical value based on the following:

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 slight eschar formation (injuries in depth)

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 1mm)
4 - Severe oedema (raised more than 1mm and extending beyond area of exposure)

Other signs of reaction to treatment such as systematic effects were recorded.

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal 769

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: No irritation at any observation

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal 773

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: No irritation at any observation

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal 774

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: No irritation at any observation

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal 769

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: No irritation at any observation

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal 773

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: No irritation at any observation

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal 774

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: No irritation at any observation

Irritant / corrosive response data:

No irritation or corrosion to any test animal was recorded at any time.

Other effects:

No other local or systemic effects.

Interpretation of results:

other: not irritating

Remarks:

Not classified as irritant according to CLP.

Conclusions:

No irritation was apparent in any animal during the course of the study. It is concluded that Gel All MD is not an irritant to rabbit skin.

Executive summary:

The purpose of the study was to assess the skin irritation potential of Gel All MD in rabbits.

The method used was designed to meet the requirements of OECD Guideline No. 404.

Gel All MD, moistened with water, was applied for four hours under a semi-occlusive dressing to the clipped dorsal skin of three rabbits. Assessments for skin irritation were made 1, 24, 48 and 72 hours and 7 days after removal of the dressing.

No skin irritation was observed in any animal at any assessment.

It was concluded that Gel All MD is not irritant to rabbit skin.

Reference 4

Endpoint:

skin irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
It is proposed that the structural similarity and properties of the target substance and the structural analogue (sources substance) are sufficiently close for there to be a reasonable expectation of similar effects.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Source chemical:
1-(2,6-bis(4-tolyl)-1,3-dioxano(5,4-d)-1,3-dioxan-4-yl)ethane-1,2-diol (EC 402-950-5, CAS 87826-41-3)

Taget chemical:
2,6-bis(4-ethylphenyl)perhydro-1,3,5,7-tetraoxanaphth-4-ylethane-1,2-diol (EC 406-176-9, CAS 79072-96-1)

3. ANALOGUE APPROACH JUSTIFICATION
Based on the structural similarity of the source substances and target substance, similarity of physic-chemical properties and similarity in experimental (eco)toxicological test data it is concluded that target substance and the structural analogue (source substance) are sufficiently close for there to be a reasonable expectation of similar effects, for the endpoints where results have been read-across.

4. DATA MATRIX
Please see 'Read-across justification to support the REACH registration of EC 406-176-9' document attached in section 13.

Reason / purpose for cross-reference:

read-across source

Amount / concentration applied:

VEHICLE
- distilled water

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal 769

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: No irritation at any observation

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal 773

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: No irritation at any observation

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal 774

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: No irritation at any observation

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal 769

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: No irritation at any observation

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal 773

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: No irritation at any observation

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal 774

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: No irritation at any observation

Irritant / corrosive response data:

No irritation or corrosion to any test animal was recorded at any time.

Other effects:

No other local or systemic effects.

Interpretation of results:

other: not irritating

Remarks:

Not classified as irritant according to CLP.

Conclusions:

No irritation was apparent in any animal during the course of the study. It is concluded that Gel All MD is not an irritant to rabbit skin.

Executive summary:

The purpose of the study was to assess the skin irritation potential of Gel All MD (EC 402-950-5) in rabbits.

The method used was designed to meet the requirements of OECD Guideline No. 404.

Gel All MD, moistened with water, was applied for four hours under a semi-occlusive dressing to the clipped dorsal skin of three rabbits. Assessments for skin irritation were made 1, 24, 48 and 72 hours and 7 days after removal of the dressing.

No skin irritation was observed in any animal at any assessment.

It was concluded that Gel All MD is not irritant to rabbit skin.

It is proposed that this result can be used in the assessment of the target substance (EC 406-176-9).

Reference 5

Endpoint:

skin irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
It is proposed that the structural similarity and properties of the target substance and the structural analogue (sources substance) are sufficiently close for there to be a reasonable expectation of similar effects.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Source chemical:
1,3:2,4-bis-O-(3,4-dimethylbenzylidene)-D-glucitol (EC 413-110-2, CAS 135861-56-2)

Taget chemical:
2,6-bis(4-ethylphenyl)perhydro-1,3,5,7-tetraoxanaphth-4-ylethane-1,2-diol (EC 406-176-9, CAS 79072-96-1)

3. ANALOGUE APPROACH JUSTIFICATION
Based on the structural similarity of the source substances and target substance, similarity of physic-chemical properties and similarity in experimental (eco)toxicological test data it is concluded that target substance and the structural analogue (source substance) are sufficiently close for there to be a reasonable expectation of similar effects, for the endpoints where results have been read-across.

4. DATA MATRIX
Please see 'Read-across justification to support the REACH registration of EC 406-176-9' document attached in section 13.

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

erythema score

Basis:

mean

Remarks:

(Animal 2 - male)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: Score of 1 at 1 hour observation

Irritation parameter:

erythema score

Basis:

mean

Remarks:

(Animal 27 - male)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: No erythema/eschar observed at any observation

Irritation parameter:

erythema score

Basis:

mean

Remarks:

(Animal 167 - female)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: Score of 1 at 1 hour observation

Irritation parameter:

edema score

Basis:

mean

Remarks:

(Animal 2 - male)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: No edema observed at any observation

Irritation parameter:

edema score

Basis:

mean

Remarks:

(Animal 27 - male)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: No edema observed at any observation

Irritation parameter:

edema score

Basis:

mean

Remarks:

(Animal 167 - female)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: No edema observed at any observation

Irritant / corrosive response data:

Very slight erythema was noted in 2 treated skin sites 1 hour after patch removal. All treated skin sites appeared normal at the 24-hour observation.

Interpretation of results:

other: not irritating

Remarks:

Not classified as irritant according to CLP.

Conclusions:

The skin irritancy potential of the test material was assessed according to OECD guideline 404. The test material produced a primary irriation of 0.0 and was classified as a non-irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

The test material does not meet the criteria for classification as irritant or corrosive according to Regulation (EC) No. 1272/2008 (CLP).

Executive summary:

A study was performed to assess the irritancy potential of the test material (EC 413-110-2) to the skin of the New Zealand White rabbit. The method used followed the recommendations of the OECD Guidelines for Testing of Chemicals No. 404 "Acute Dermal Irritation/Corrosion) and Method B4 of Commission Directive 92/69/EEC).

A single 4-hour, semi-occluded application of the test material to the intact skin of 3 rabbits produced very slight erythema. All treated skin sites appeared normal at the 24-hour observation.

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

The test material does not meet the criteria for classification as irritant or corrosive according to Regulation (EC) No. 1272/2008 (CLP).

It is proposed that this result can be used in the assessment of the target substance (EC 406-176-9).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1987

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Qualifier:

according to guideline

Guideline:

EPA OTS 798.4500 (Acute Eye Irritation)

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 30 mg

Duration of treatment / exposure:

Single application

Number of animals or in vitro replicates:

6

Irritation parameter:

iris score

Basis:

mean

Remarks:

6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: no effects at any time poiint

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects at any time point

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Remarks:

4 animals

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 24 hrs

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Remarks:

2 animals

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: no effects at any time point

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

1 animals

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 24 hrs

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

5 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects at any time point

Irritant / corrosive response data:

No adverse effects were observed for the iris or corneal damage at any time point in any animal.
Minor conjuncitval irritation (redness) was observed in 4 animals and resolved within 1 day.
Minor chemosis was observed in 1 animals and resolved within 1 day.

Endpoint	Mean score	Maximum value	Maximum duration of any effect	Maximum value at the end of observation period
Conjunctivae / redness	1 in 4 animals 0 in 2 animals	1 in 4 animals	1 day	0
Chemosis	1 in 1 animal 0 in 5 animals	1 in 1 animal	1 day	0
Cornea	0	0	-	0
Iris	0	0	-	0

Interpretation of results:

GHS criteria not met

Conclusions:

No adverse effects were observed for the iris or corneal damage at any time point in any animal.
Minor conjuncitval irritation (redness) was observed in 4 animals and minor chemosis was observed in 1 animal. All eyes were normal after 1 day.
A single application of test material into the rabbit eye did not produce a positive response according to CLP criteria.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

13 October 1997 to 19 October 1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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 (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: 12 to 16 weeks old
- Weight at study initiation: 2.54 to 2.75 kg
- Housing: animals were individually housed in suspended metal cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16- 19 °C
- Humidity (%): 55- 74 %
- Air changes (per hr): 15 changes per hr
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): volume 0.1 mL , which was found to weigh approximately 41 mg

Duration of treatment / exposure:

Single application

Observation period (in vivo):

72 h

Number of animals or in vitro replicates:

3

Details on study design:

One rabbit was initially treated. A volume of 0.1 mL of the test material was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about 1 s immediately after application, to prevent loss of the test material, and then released. The left eye remained untreated and was used for control purposes. Immediately after administration of the test material, an assessment of the initial pain reaction was made.

After consideration of the ocular responses produced in the first treated animal, 2 additional animals were treated.

Assessment of ocular damage/irritation was made approximately 1 h and 24, 48 and 72 h following treatment, according to the Draize scale for scoring ocular irritation.

Any other ocular effects were also noted. Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

all animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: No corneal effects at any observation in any animal

Irritation parameter:

iris score

Basis:

mean

Remarks:

all animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

other: No iridial effects at any observation in any animal

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Remarks:

(Animal 1 - male)

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Remarks:

(Animal 14 - male)

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Remarks:

(Animal 15 - male)

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

(Animal 1 - male)

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

(Animal 14 - male)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: Score of 1 at 1 hour observation

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

(Animal 15 - male)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: Score of 1 at 1 hour observation

Irritant / corrosive response data:

Individual and group mean scores for ocular irritation are given in Tables 1 and 2 (attached background material). The individual means scores are presented in Table 3 (attached background material).

Residual test material was noted around 1 treated eye at the 1-hour observation but did not prevent an evaluation of the ocular responses.

No corneal or iridial effects were noted during the study.

Moderate conjunctival irritation was noted in all treated eyes 1 h after treatment with minimal conjunctival irritation at the 24-hour observation. Minimal conjunctival persisted in 1 treated eye at the 48-hour observation.

Treated eyes appeared normal at the 48 or 72-hour observations.

Interpretation of results:

other: not irritating

Remarks:

Not classified as irritant according to CLP.

Conclusions:

The eye irritancy potential of the test material was assessed according to OECD guideline 405.

The test material produced a maximum group mean score of 8.7 and was classified as a mild irritant (class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

The test material did not produce postive criteria in any rabbit according to Regulation (EC) No. 1272/2008 (CLP).

Executive summary:

A study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. The method used followed that described in the OECD Guidelines for Testing of Chemicals No. 405 "Acute Eye Irritation/Corrosion" and Method B5 of Commission Directive 92/69/EEC.

A single application of the test material to the non-irrigated eye of three rabbits produced moderate conjunctival irritation. Treated eyes appeared normal at the 48 or 72-hour observations.

The test material produced a maximum group mean score of 8.7 and was classified as a mild irritant (class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

The test material did not produce positive criteria in any rabbit according to Regulation (EC) No. 1272/2008 (CLP).

Reference 3

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

21 March 1988 to 13 June 1988

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:

(adopted 24 February 1987)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Healthy female rabbits were obtained from Goreside Rabbits, Northchurch, Berkhamsted, Hereford
- Age at study initiation: At receipt the animals were 8 weeks of age, but left to acclimatise for at least 9 days.
- Weight at study initiation: See table.
- Housing: The rabbits were individually housed in grid-bottomed metal cages.
- Diet (e.g. ad libitum): A commercially available antibiotic free rabbit diet (SQC standard rabbit pellets produced by Special Diet Services, Witham, Essex), ad libitum.
- Water (e.g. ad libitum): Mains drinking water via an automatic nozzle, ad libitum.
- Acclimation period: At least 9 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 20°C
- Humidity (%): Relative humidity within the range 44 - 77%.
- Photoperiod (hrs dark / hrs light): Fluorescent lighting was controlled to give an artificial cycle of 12 hours light/12 hours dark per day.

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.1 mL of the supplied material (weighing approximately 30 mg)

Duration of treatment / exposure:

Single exposure with observation for 7 days

Observation period (in vivo):

One, 24, 48 and 72 hours and 7 days following instillation of the test material the animals eyes were examined macroscopically under a standard light source.

Number of animals or in vitro replicates:

3

Details on study design:

One restrained rabbit was dosed initially to assess the severity of any irritant response. As no marked irritation was seen a further two restrained animals were dosed, bringing the group size to three.

The test material was instilled into the right eye of each restrained animal by gently pulling away the lower lid from the eyeball to form a cup into which the test material was placed. The lids were then held shut for a few seconds. The treated eyes of the rabbits were not rinsed after dosing. The left eye was untreated and served as a control.

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

mean

Remarks:

(Animal No 781)

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

fully reversible within: 24 hours

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

mean

Remarks:

(Animal No 777)

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

mean

Remarks:

(Animal No 778)

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

(Animal No 781)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: No chemosis observed at any observation

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

(Animal No 777)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: No chemosis observed at any observation

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

(Animal No 778)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: No chemosis observed at any observation

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

(Animal No 781)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: No cornea effects observed at any observation

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

(Animal No 777)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: No cornea effects observed at any observation

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

(Animal No 778)

Time point:

other: mean of scores at 24, 48 and 72 h

Score:

0

Max. score:

4

Remarks on result:

other: No cornea effects observed at any observation

Irritation parameter:

iris score

Basis:

mean

Remarks:

(Animal No 781)

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

other: No iris effects observed at any observation

Irritation parameter:

iris score

Basis:

mean

Remarks:

(Animal No 777)

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

other: No iris effects observed at any observation

Irritation parameter:

iris score

Basis:

mean

Remarks:

(Animal No 778)

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

other: No iris effects observed at any observation

Irritant / corrosive response data:

One hour after instillation, well defined conjunctival redness was seen in two rabbits and slight redness in the third animal. Only slight conjunctival redness was seen after 24 hours in two animals. All eyes were normal within 48 hours.

Interpretation of results:

other: not irritating

Remarks:

Not classified as irritant according to CLP.

Conclusions:

Slight to moderate conjunctival irritancy (redness) was observed up to 24 hours post-installation.

Executive summary:

The purpose of the study was to assess the eye irritation potential of Gel All MD in rabbits.

The method used was designed to meet the requirements of OECD Guideline No. 405.

Gel All MD was instilled into the right eye of three rabbits. Assessments of eye irritation were made 1, 24, 48 and 72 hours and 7 days after installation.

One hour after instillation, well defined conjunctival redness was seen in two rabbits and slight redness in the third animal. Only slight conjunctival redness was seen after 24 hours in two animals. All eyes were normal within 48 hours. No chemosis, iridial irritation or cornea effects were observed.

The slight irritation (redness) was fully reversible and not sufficient for classification.

Reference 4

Endpoint:

eye irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
It is proposed that the structural similarity and properties of the target substance and the structural analogue (sources substance) are sufficiently close for there to be a reasonable expectation of similar effects.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Source chemical:
1,3:2,4-bis-O-(3,4-dimethylbenzylidene)-D-glucitol (EC 413-110-2, CAS 135861-56-2)

Taget chemical:
2,6-bis(4-ethylphenyl)perhydro-1,3,5,7-tetraoxanaphth-4-ylethane-1,2-diol (EC 406-176-9, CAS 79072-96-1)

3. ANALOGUE APPROACH JUSTIFICATION
Based on the structural similarity of the source substances and target substance, similarity of physic-chemical properties and similarity in experimental (eco)toxicological test data it is concluded that target substance and the structural analogue (source substance) are sufficiently close for there to be a reasonable expectation of similar effects, for the endpoints where results have been read-across.

4. DATA MATRIX
Please see 'Read-across justification to support the REACH registration of EC 406-176-9' document attached in section 13.

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

all animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: No corneal effects at any observation in any animal

Irritation parameter:

iris score

Basis:

mean

Remarks:

all animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

other: No iridial effects at any observation in any animal

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Remarks:

(Animal 1 - male)

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Remarks:

(Animal 14 - male)

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Remarks:

(Animal 15 - male)

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

(Animal 1 - male)

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

(Animal 14 - male)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: Score of 1 at 1 hour observation

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

(Animal 15 - male)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: Score of 1 at 1 hour observation

Irritant / corrosive response data:

Residual test material was noted around 1 treated eye at the 1-hour observation but did not prevent an evaluation of the ocular responses.

No corneal or iridial effects were noted during the study.

Moderate conjunctival irritation was noted in all treated eyes 1 h after treatment with minimal conjunctival irritation at the 24-hour observation. Minimal conjunctival persisted in 1 treated eye at the 48-hour observation.

Treated eyes appeared normal at the 48 or 72-hour observations.

Interpretation of results:

other: not irritating

Remarks:

Not classified as irritant according to CLP.

Conclusions:

The eye irritancy potential of the test material was assessed according to OECD guideline 405.

The test material produced a maximum group mean score of 8.7 and was classified as a mild irritant (class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

The test material did not produce postive criteria in any rabbit according to Regulation (EC) No. 1272/2008 (CLP).

Executive summary:

A study was performed to assess the irritancy potential of the test material (EC 413-110-2) to the eye of the New Zealand White rabbit. The method used followed that described in the OECD Guidelines for Testing of Chemicals No. 405 "Acute Eye Irritation/Corrosion" and Method B5 of Commission Directive 92/69/EEC.

A single application of the test material to the non-irrigated eye of three rabbits produced moderate conjunctival irritation. Treated eyes appeared normal at the 48 or 72-hour observations.

The test material produced a maximum group mean score of 8.7 and was classified as a mild irritant (class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

The test material did not produce positive criteria in any rabbit according to Regulation (EC) No. 1272/2008 (CLP).

Reference 5

Endpoint:

eye irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
It is proposed that the structural similarity and properties of the target substance and the structural analogue (sources substance) are sufficiently close for there to be a reasonable expectation of similar effects.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Source chemical:
1-(2,6-bis(4-tolyl)-1,3-dioxano(5,4-d)-1,3-dioxan-4-yl)ethane-1,2-diol (EC 402-950-5, CAS 87826-41-3)

Taget chemical:
2,6-bis(4-ethylphenyl)perhydro-1,3,5,7-tetraoxanaphth-4-ylethane-1,2-diol (EC 406-176-9, CAS 79072-96-1)

3. ANALOGUE APPROACH JUSTIFICATION
Based on the structural similarity of the source substances and target substance, similarity of physic-chemical properties and similarity in experimental (eco)toxicological test data it is concluded that target substance and the structural analogue (source substance) are sufficiently close for there to be a reasonable expectation of similar effects, for the endpoints where results have been read-across.

4. DATA MATRIX
Please see 'Read-across justification to support the REACH registration of EC 406-176-9' document attached in section 13,

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

mean

Remarks:

(Animal No 781)

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

fully reversible within: 24 hours

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

mean

Remarks:

(Animal No 777)

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

mean

Remarks:

(Animal No 778)

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

(Animal No 781)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: No chemosis observed at any observation

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

(Animal No 777)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: No chemosis observed at any observation

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

(Animal No 778)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: No chemosis observed at any observation

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

(Animal No 781)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: No cornea effects observed at any observation

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

(Animal No 777)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: No cornea effects observed at any observation

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

(Animal No 778)

Time point:

other: mean of scores at 24, 48 and 72 h

Score:

0

Max. score:

4

Remarks on result:

other: No cornea effects observed at any observation

Irritation parameter:

iris score

Basis:

mean

Remarks:

(Animal No 781)

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

other: No iris effects observed at any observation

Irritation parameter:

iris score

Basis:

mean

Remarks:

(Animal No 777)

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

other: No iris effects observed at any observation

Irritation parameter:

iris score

Basis:

mean

Remarks:

(Animal No 778)

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

other: No iris effects observed at any observation

Irritant / corrosive response data:

One hour after instillation, well defined conjunctival redness was seen in two rabbits and slight redness in the third animal. Only slight conjunctival redness was seen after 24 hours in two animals. All eyes were normal within 48 hours.

Interpretation of results:

other: not irritating

Remarks:

Not classified as irritant according to CLP.

Conclusions:

Slight to moderate conjunctival irritancy (redness) was observed up to 24 hours post-installation.

Executive summary:

The purpose of the study was to assess the eye irritation potential of Gel All MD (EC 402-950-5) in rabbits.

The method used was designed to meet the requirements of OECD Guideline No. 405.

Gel All MD was instilled into the right eye of three rabbits. Assessments of eye irritation were made 1, 24, 48 and 72 hours and 7 days after installation.

One hour after instillation, well defined conjunctival redness was seen in two rabbits and slight redness in the third animal. Only slight conjunctival redness was seen after 24 hours in two animals. All eyes were normal within 48 hours. No chemosis, iridial irritation or cornea effects were observed.

The slight irritation (redness) was fully reversible and not sufficient for classification.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the results of skin irritation studies, the substance is not an irritant to skin. The substance is therefore not classification according to EU CLP regulation as a corrosive or skin irritant.

Based on the result of an in-vivo eye irritation studies, the substance does not cause serious eye damage or irritation. The substance is therefore not classified according to EU CLP regulation as irritating to eyes.