Registration Dossier

Administrative data

Description of key information

The skin sensitisation 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).

OECD 406 study on target substance (EC 406-176-9):

The test material did not show any evidence of sensitisation in guinea pigs following induction and challenge at 2000 mg/kg bw.

0 of 20 animals (test and control groups) showed positive reactions for skin sensitization after challenge exposure.

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

A study was performed to assess the contact sensitisation potential of the test material (EC 413-110-2) in the albino guinea pig. The study was performed in compliance with the OECD Guidelines for Testing of Chemicals No. 406 "Skin Sensitisation" and Method B6 of Commission Directive 92/69/EEC.

Ten test and five control animals were used for the main study.

Based on the results of sighting tests, the concentrations of test material for the induction and challenge phases were selected as follows:

- lntradermal lnduction: 0.5 % w/v in arachis oil BP

- Topical lnduction: 25 % w/w in arachis oil BP

- Topical Challenge: 10 % and 5 % w/w in arachis oil BP

The test material produced a 0 % (0/10) sensitisation rate and was classified as a non-sensitiser to guinea pig skin.

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):

A modification of the Buehler method (OECD 406) was used to assess the skin sensitisation potential of technical Gel-All-MD (EC 402-950-5)

Following a preliminary study designed to determine the maximum non-irritant and minimum irritant concentrations, a 40% w/w concentration of the test material in 0.5% aqueous carboxymethyl cellulose was applied topically to the 10 animals within the test group, for a period of 6 hours. This procedure was repeated at weekly intervals for a period of three weeks. A further 10 animals forming the control group, remained untreated during this stage of the study.

After 14 days all animals were challenged using 40% and 20% w/w concentrations of the test material. Assessments of dermal reactions were made 24, 48 and 72 hours after the challenge application.

No evidence of any dermal reaction to treatment was seen after challenging with either 40 or 20% w/w concentrations of the test material.

It is concluded that technical Gel-All-MD did not induce delayed dermal hypersensitivity in the guinea pig.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1991
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
Buhler
GLP compliance:
not specified
Type of study:
Buehler test
Justification for non-LLNA method:
Available data provided by ECHA - study from 1991.
Species:
guinea pig
Strain:
other: Bor. DHPW (SPF)
Sex:
not specified
Route:
other: epicutaneous
Vehicle:
olive oil
Concentration / amount:
2000 mg/kg b.w in 1.0 ml olive oil applied
No.:
#1
Route:
other: epicutaneous
Vehicle:
olive oil
Concentration / amount:
2000 mg/kg b.w in 1.5 ml olive oil applied
No. of animals per dose:
20 in test group,
20 in negative control.
Details on study design:
RANGE FINDING TESTS: Maximum concentration not giving rise to irritating effects in the preliminary test: 2000 mg/lg

MAIN STUDY
A. INDUCTION EXPOSURE
Test group: 2000 mg/kg bw in 1.0 ml olive oil (Application: 1.0 ml olive oil)
Control group: Yes

B. CHALLENGE EXPOSURE
- No. of exposures :1
Test group: 2000 mg/kg bw in 1.5 ml olive oil (Application: 1.5 ml olive oil)
Control group: Yes

During inuduction exposure animals were observed for signs of irritation.

After challanged exposure animals were observed at 24 and 48 hrs for evidence of sensitization.
Positive control substance(s):
not specified
Positive control results:
Not specified
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
2000 mg/kg b.w
No. with + reactions:
0
Total no. in group:
20
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
2000 mg/kg b.w
No. with + reactions:
0
Total no. in group:
20
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
2000 mg/kg b.w
No. with + reactions:
0
Total no. in group:
20
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
2000 mg/kg b.w
No. with + reactions:
0
Total no. in group:
20

Signs of irritation during induction: None

Number of animals showing evidence of sensitization at challenge: None

Group

Challenge Concentration

Number of animals showing skin reactions after challenge

24 h

48 h

Test Group

2000 mg/kg

0/20

0/20

Control Group

 

0/20

0/20

Other Observations: No change in body weight was caused by the test substance.

Interpretation of results:
GHS criteria not met
Conclusions:
The test material did not show any evidence of sensitisation in guinea pigs following induction and challenge at 2000 mg/kg bw.
0 of 20 animals (test and control groups) showed positive reactions for skin sensitization after challenge exposure.
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
29 September 1997- 31 October 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The available guinea pig maximisation study was conducted in 1998 and is sufficient for assessment of skin sensitisation. Therefore, a LLNA study was not considered required.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Hall Limited, Burton-on-Trent, Staffodshire, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 311- 374 g
- Housing: animals were housed singly or in pairs in solid-floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19- 22 °C
- Humidity (%): 42- 62 %
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal and epicutaneous
Vehicle:
arachis oil
Concentration / amount:
SIGHTING TESTS
Intradermal induction: 0.1 %, 0.5 %, 1% and 5 % w/v
Topical Induction: 50 %, 25 %, 10 % and 5 % w/w

MAIN STUDY
Intradermal induction: 0.5 % w/v
Topical induction: 25 % w/w
Day(s)/duration:
48 hours (topical induction)
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
arachis oil
Concentration / amount:
Main study
Topical challange: 10 % and 5 % w/w
Day(s)/duration:
24 hours
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Sighting tests:
Intradermal induction: 4/ sex/ dose
Topical Induction: 2/ sex were treated with 4 preparations
Topical challange: 2/ sex were treated with 4 preparations

Main study: 10/ sex/ dose
Details on study design:
RANGE FINDING TESTS:
The concentrations of test material to be used at each stage of the main study were determined by 'sighting tests' in which groups of guinea pigs were treated with various concentrations of test material. The procedures were as follows:

-Selection of Concentration for lntradermal lnduction:
Four concentrations of test material were investigated (0.1 %, 0.5 %, 1 % and 5 % w/v in arachis oil BP). A total of 4 guinea pigs wereused, each guinea pig receiving four 0.1 mL injections of only 1 concentration of test material. The degree of erythema at the injection sites was assessed approximately 24, 48 and 72 h and 7 d after injection according to the Draize scale. The degree of oedema was not evaluated. Any evidence of systemic toxicity was also recorded. The highest concentration that caused only mild to moderate skin irritation, and which was well tolerated systemically, was selected for the intradermal induction stage of the main study.

-Selection of Concentration for Topical lnduction:
Two guinea pigs (intradermally injected with Freund's Complete Adjuvant 17 days earlier) were treated with 4 preparations of the test material (50 %, 25 %, 10 % and 5 % w/w in arachis oil BP). Applications were made to the clipped flanks under occlusive dressings for an exposure period of 48 h. The degree of erythema and oedema was evaluated approximately 1, 24 and 48 h after dressing removal. The highest concentration producing only mild to moderate dermal irritation was selected for the topical induction stage of the main study.

-Selection of Concentration for Topical Challenge:
Four preparations of the test material (25 %, 10 %, 5 % and 2 % w/w in arachis oil BP) were applied to the clipped flanks of 2 guinea pigs under occlusive dressings for an exposure period of 24 h. These guinea pigs did not form part of the main study but had been treated identically to the control animals of the main study, up to Day 14. The degree of erythema and oedema was evaluated approximately 1, 24 and 48 h after dressing removal. The highest non-irritant concentration of the test material and one lower concentration was selected for the topical challenge stage of the main study.

MAIN STUDY
- Test group: 1 group of 10 animals
- Control group: 1 group of 5 animals

A. INDUCTION EXPOSURE
- No. of exposures: 2; intradermal and topical
- Exposure period: 48 h (topical induction)
- Site: 40 mm x 20 mm on the shoulder region

Induction of test animals
- Shortly before treatment on Day 0 the hair was removed from an area approximately 40 mm x 60 mm on the shoulder region of each animal with veterinary clippers. A row of 3 injections (0.1 mL each) was made on each side of the mid-line. The injections were:
a) Freund's Complete Adjuvant plus distilled water in the ratio 1:1
b) a 0.5 % w/v formulation of the test material in arachis oil BP
c) a 0.5 % w/v formulation of the test material in a 1:1 preparation of Freund's Complete Adjuvant plus distilled water.
Approximately 24 and 48 hours after intradermal injection the degree of erythema at the test material injection sites (ie. Injection site b) was evaluated.
-One week later (Day 7), the same area on the shoulder region used previously for intradermal injections was clipped again and treated with a topical application of the test material formulation. A filter paper patch loaded with the test material formulation (25 % w/w in arachis oil BP) as a thick, even layer was applied to the prepared skin and held in place with a strip of surgical adhesive tape covered with an overlapping length of aluminium foil. The patch and foil were further secured with a strip of elastic adhesive wound in a double layer around the torso of each animal. This occlusive dressing was kept in place for 48 h.
- The degree of erythema and oedema was quantified 1 and 24 h following removal of the patches. Any other reactions were also recorded.

Induction of the control animals
-lntradermal injections were administered using an identical procedure to that used for the test animals, except that the injections were:
a) Freund's Complete Adjuvant plus distilled water in the ratio 1:1
b) arachis oil BP
C) a 50 % w/v formulation of arachis oil BP in Freund's Complete Adjuvant/distilled water 1:1
Approximately 24 and 48 hours after intradermal injection the degree of erythema at the vehicle injection sites was evaluated.
- The topical applications followed the same procedure as for the test animals except that the vehicle alone was applied to the filter paper. Skin reactions were quantified as for the test animals.

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 1
- Exposure period: 24 h
- Site: 20 mm x 20 mm
- Concentrations: 5 % and 10 % w/w in arachis oil BP
- Evaluation (hr after challenge): 24 and 48 h after challange dressing removal, the degree of erythema and oedema was quantified.
- Shortly before treatment on Day 21, an area of approximately 50 mm x 70 mm on both flanks of each animal, was clipped free of hair with veterinary clippers. A square filter paper patch loaded with a thick, even layer of test material at the maximum non-irritant concentration (10 % w/w in arachis oil BP) was applied to the shorn right flank of each animal and was held in place with a strip of surgical adhesive tape. To ensure that the maximum non-irritant concentration was used at challenge, the test material at a concentration of 5 % w/w in arachis oil BP was similarly applied to a skin site on the left shorn flank. The patches were occluded with an overlapping length of aluminium foil and secured with a strip of elastic adhesive bandage wound in a double layer around the torso of each animal.

After 24 h, the dressing was carefully cut using blunt-tipped scissors, removed and discarded. The challenge sites were swabbed with cotton wool soaked in diethyl ether to remove residual material. The position of the treatment sites was identified by using a black indelible marker-pen. Prior to the 24-h observation the flanks were clipped using veterinary clippers to remove regrown hair.
Positive control substance(s):
no
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None noted.
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 10 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None noted..
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
5 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None noted.
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 5 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None noted..
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None noted.
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 10 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None noted..
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
5 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None noted.
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 5 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None noted..
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
None noted.
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 10 %. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: None noted..
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
5 %
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
None noted.
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 5 %. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: None noted..
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
None noted.
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 10 %. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: None noted..
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
5 %
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
None noted.
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 5 %. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: None noted..

lntradermal and Topical Sighting Tests

Intradermal sighting test- summary of results. Vehicle: arachis oil BP

Animal identification

Time of observation

Concentration of test material (% w/v)

Grade of erythema at injection sites

Evidence of systemic toxicity

A

24 h

1

3

None

48 h

3-4N*

None

72 h

3-4N*

None

7 d

0

None

B

24 h

5

3-4N

None

48 h

4NE

None

72 h

4E

None

7 d

4E

None

C

24 h

0.1

1-2

None

48 h

2

None

72 h

2

None

7 d

1

None

D

24 h

0.5

1-2

None

48 h

2-3

None

72 h

2

None

7 d

1

None

E= eschar; N= green necrosis; N*= possible necrosis

Topical sighting test for induction application (48-h exposure)- individual skin reactions. Vehicle: arachis oil BP

Animal identification

Concentration of test material (% w/w)

Skin reaction (hours after removal of patches)

1

24

48

Er

Oe

Other

Er

Oe

Other

Er

Oe

Other

E

50*

2

2

-

2

0

-

1

0

-

25

2

2

-

2

0

-

1

0

D

10

1

0

-

0

0

-

0

0

-

5

1

0

-

0

0

-

0

0

-

F

50*

3

2

-

2

1

-

1

0

-

25

2

2

-

2

1

-

1

0

D

10

1

0

-

0

0

-

0

0

-

5

1

1

-

0

0

-

0

0

-

Er= erythema; Oe= oedema; -= no other reactions noted; D= desquamation; *= maximum attainable concentration suitable for topical application

Topical sighting test for challenge application (24-h exposure)- individual skin reactions. Vehicle: arachis oil BP

Animal identification

Concentration of test material (% w/w)

Skin reaction (hours after removal of patches)

1

24

48

Er

Oe

Other

Er

Oe

Other

Er

Oe

Other

G

25*

2

2

-

1

0

-

0

0

-

10

2

2

-

0

0

-

0

0

-

5

2

1

-

0

0

-

0

0

-

2

2

1

-

0

0

-

0

0

-

H

25*

2

2

-

1

1

-

0

0

-

10

2

1

-

0

0

-

0

0

-

5

1

1

-

0

0

-

0

0

-

2

1

1

-

0

0

-

0

0

-

Er= erythema; Oe= oedema; -= no other reactions noted; *= maximum attainable concentration suitable for topical application

Based on these results, the following concentrations were selected for the main study:

Intradermal induction: 0.5 % w/v in arachis oil BP

Topical induction: 25 % w/w in arachis oil BP

Topical challenge: 10 % and 5 % w/w in arachis oil BP

Main study

-Skin Reactions Observed After lntradermal lnduction:

Well-defined erythema was noted at the intradermal induction sites of all test group animals at the 24 and 48-hour observations. Very slight erythema was noted at the intradermal induction sites of all control group animals at the 24-h observation and in 4 control group animals at the 48-h observation.

-Skin Reactions Observed After Topical lnduction:

Very slight to well-defined erythema was noted at the induction sites of all test group animals at the 1-h observation with very slight erythema at the induction sites of 9 test group animals at the 24-h observation. Bleeding from the intradermal induction sites was noted in 5 test group animals at the 1-h observation. Residual test material was noted in all test group animals. Bleeding from the intradermal induction sites was noted in 1 control group animal at the 1-h observation. No signs of erythema or oedema were noted at the treatment sites of control group animals at the 1 and 24-h observations.

-Skin Reactions Observed After Topical Challenge:

No skin reactions were noted at the challenge sites of the test or control group animals at the 24 or 48-h observations.

-Bodyweight:

Bodyweight gains of guinea pigs in the test group, between Day 0 and Day 24, were comparable to those observed in the control group animals over the same period.

Interpretation of results:
GHS criteria not met
Conclusions:
The test material produced a 0 % (0/10) sensitisation rate and was classified as a non-sensitiser to guinea pig skin.
Executive summary:

A study was performed to assess the contact sensitisation potential of the test material in the albino guinea pig. The study was performed in compliance with the OECD Guidelines for Testing of Chemicals No. 406 "Skin Sensitisation" and Method B6 of Commission Directive 92/69/EEC.

Ten test and five control animals were used for the main study.

Based on the results of sighting tests, the concentrations of test material for the induction and challenge phases were selected as follows:

- lntradermal lnduction: 0.5 % w/v in arachis oil BP

- Topical lnduction: 25 % w/w in arachis oil BP

- Topical Challenge: 10 % and 5 % w/w in arachis oil BP

The test material produced a 0 % (0/10) sensitisation rate and was classified as a non-sensitiser to guinea pig skin.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
The study was conducted between March 1988 and April 1988
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Principles of method if other than guideline:
The test method is a modification of one of the accepted methods of test for skin sensitisation described in guideline No. 406 for the testing of chemicals, Organistaion for the Economic Cooperation and Development. The procedures that were used were those described by Buehler E.V., Arch, Dermatol. 91, 171-175, 1965.
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
The available guinea pig study was conducted in 1988 and is sufficient for assessment of skin sensitisation. Therefore, a LLNA study was not considered required.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: D. Hall, Darley Oaks, Burton-on-Trent, Staffordshire
- Age at study initiation: 4 to 11 weeks
- Weight at study initiation: Animals weighed between 357 and 433g
- Housing: Animals were housed in groups of 2 in grid-bottomed polypropylene cages and indentified within the cage by ear markings.
- Diet: A commercially available pelleted diet was provided with additional vitamin C - ad libitum
- Water: free access to tap water - ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 28 deg C
- Humidity (%): between 31 and 64%
- Air changes (per hr): not stated in report
- Photoperiod (hrs dark / hrs light): 12 hours light follwed by 12 hours of darkness

Route:
other: topical
Vehicle:
other: 0.5% w/v aqueous CMC
Concentration / amount:
Main study: A 40% concentration of the test material
Day(s)/duration:
Applied for a period of 6 hours, repeated at weekly intervals for a period of 3 weeks.
Adequacy of induction:
other: maximum non-irritant concentration
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: 0.5% w/v aqueous CMC
Concentration / amount:
40% and 20% concentration of the test material
Day(s)/duration:
6 hours
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
10
Details on study design:
RANGE FINDING TESTS:
On the day before dosing the flanks of four guinea pigs were clipped free of fur using a clipper. On the day of dosing four concentrations of the test material were prepared. These concentrations were 0.5, 5, 10 , 20 and 40% in aqueous carboxymethyl cellulose (CMC). 0.5g of each concentration was applied to a 20mm square of absorbent lint BPC which was in turn applied to a different skin site on the flank of each animal. These patches were then occluded for six hours using "Blenderm" occlusive tape and secured using an adhesive bandage. 24 and 48 hours after treatment commenced the treated sites were examined under a standard light source. Any response to the treatment was assessed.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 hours
- Test groups: ten female Dunkin Hartley rats
- Control group: yes
- Site: left shoulder
- Frequency of applications: Days 1, 8 and 15
- Concentrations:0.5 g of 40% w/w of test material in 0.5% w/v aqeous CMC

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: day 29
- Exposure period: 6 hours
- Test groups: ten female Dunkin Hartley rats
- Control group: yes
- Site: left and right flank
- Concentrations: 20% and 40% concentrations
- Evaluation (hr after challenge): 24, 48 and 72 hours after application of dressing
Challenge controls:
40% and 20% concentrations were also used in the challenge phase for control animals.
Positive control substance(s):
no
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
40%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 40%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
20%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 20%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
40%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 40%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
20%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 20%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
test group
Dose level:
40%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: other: 3rd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 40%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
test group
Dose level:
20%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: other: 3rd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 20%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
40%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 40%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
20%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 20%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
40%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 40%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
20%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 20%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
negative control
Dose level:
40%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: other: 3rd reading. . Hours after challenge: 72.0. Group: negative control. Dose level: 40%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
negative control
Dose level:
20%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: other: 3rd reading. . Hours after challenge: 72.0. Group: negative control. Dose level: 20%. No with. + reactions: 0.0. Total no. in groups: 10.0.

No evidence of dermal reaction to treatment was seen in any of the test or control animals challenged with 40% and 20% w/w concentrations of the test material in 0.5% w/v aqueous carboxymethyl cellulose.

Interpretation of results:
GHS criteria not met
Conclusions:
It is concluded that technical Gel-All-MD did not induce delayed dermal hypersensitivity in the guinea pig.
Executive summary:

A modification of the Buehler method (OECD 406) was used to assess the skin sensitisation potential of technical Gel-All-MD.

Following a preliminary study designed to determine the maximum non-irritant and minimum irritant concentrations, a 40% w/w concentration of the test material in 0.5% aqueous carboxymethyl cellulose was applied topically to the 10 animals within the test group, for a period of 6 hours. This procedure was repeated at weekly intervals for a period of three weeks. A further 10 animals forming the control group, remained untreated during this stage of the study.

After 14 days all animals were challenged using 40% and 20% w/w concentartions of the test material. Assessments of dermal reactions were made 24, 48 and 72 hours after the challenge application.

No evidence of any dermal reaction to treatment was seen after challenging with either 40 or 20% w/w concentrations of the test material.

It is concluded that technical Gel-All-MD did not induce delayed dermal hypersensitivity in the guinea pig.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
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:
read-across source
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None noted.
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 10 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None noted..
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
5 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None noted.
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 5 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None noted..
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None noted.
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 10 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None noted..
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
5 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None noted.
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 5 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None noted..
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
None noted.
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 10 %. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: None noted..
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
5 %
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
None noted.
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 5 %. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: None noted..
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
None noted.
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 10 %. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: None noted..
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
5 %
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
None noted.
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 5 %. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: None noted..

lntradermal and Topical Sighting Tests

Intradermal sighting test- summary of results. Vehicle: arachis oil BP

Animal identification

Time of observation

Concentration of test material (% w/v)

Grade of erythema at injection sites

Evidence of systemic toxicity

A

24 h

1

3

None

48 h

3-4N*

None

72 h

3-4N*

None

7 d

0

None

B

24 h

5

3-4N

None

48 h

4NE

None

72 h

4E

None

7 d

4E

None

C

24 h

0.1

1-2

None

48 h

2

None

72 h

2

None

7 d

1

None

D

24 h

0.5

1-2

None

48 h

2-3

None

72 h

2

None

7 d

1

None

E= eschar; N= green necrosis; N*= possible necrosis

Topical sighting test for induction application (48-h exposure)- individual skin reactions. Vehicle: arachis oil BP

Animal identification

Concentration of test material (% w/w)

Skin reaction (hours after removal of patches)

1

24

48

Er

Oe

Other

Er

Oe

Other

Er

Oe

Other

E

50*

2

2

-

2

0

-

1

0

-

25

2

2

-

2

0

-

1

0

D

10

1

0

-

0

0

-

0

0

-

5

1

0

-

0

0

-

0

0

-

F

50*

3

2

-

2

1

-

1

0

-

25

2

2

-

2

1

-

1

0

D

10

1

0

-

0

0

-

0

0

-

5

1

1

-

0

0

-

0

0

-

Er= erythema; Oe= oedema; -= no other reactions noted; D= desquamation; *= maximum attainable concentration suitable for topical application

Topical sighting test for challenge application (24-h exposure)- individual skin reactions. Vehicle: arachis oil BP

Animal identification

Concentration of test material (% w/w)

Skin reaction (hours after removal of patches)

1

24

48

Er

Oe

Other

Er

Oe

Other

Er

Oe

Other

G

25*

2

2

-

1

0

-

0

0

-

10

2

2

-

0

0

-

0

0

-

5

2

1

-

0

0

-

0

0

-

2

2

1

-

0

0

-

0

0

-

H

25*

2

2

-

1

1

-

0

0

-

10

2

1

-

0

0

-

0

0

-

5

1

1

-

0

0

-

0

0

-

2

1

1

-

0

0

-

0

0

-

Er= erythema; Oe= oedema; -= no other reactions noted; *= maximum attainable concentration suitable for topical application

Based on these results, the following concentrations were selected for the main study:

Intradermal induction: 0.5 % w/v in arachis oil BP

Topical induction: 25 % w/w in arachis oil BP

Topical challenge: 10 % and 5 % w/w in arachis oil BP

Main study

-Skin Reactions Observed After lntradermal lnduction:

Well-defined erythema was noted at the intradermal induction sites of all test group animals at the 24 and 48-hour observations. Very slight erythema was noted at the intradermal induction sites of all control group animals at the 24-h observation and in 4 control group animals at the 48-h observation.

-Skin Reactions Observed After Topical lnduction:

Very slight to well-defined erythema was noted at the induction sites of all test group animals at the 1-h observation with very slight erythema at the induction sites of 9 test group animals at the 24-h observation. Bleeding from the intradermal induction sites was noted in 5 test group animals at the 1-h observation. Residual test material was noted in all test group animals. Bleeding from the intradermal induction sites was noted in 1 control group animal at the 1-h observation. No signs of erythema or oedema were noted at the treatment sites of control group animals at the 1 and 24-h observations.

-Skin Reactions Observed After Topical Challenge:

No skin reactions were noted at the challenge sites of the test or control group animals at the 24 or 48-h observations.

-Bodyweight:

Bodyweight gains of guinea pigs in the test group, between Day 0 and Day 24, were comparable to those observed in the control group animals over the same period.

Interpretation of results:
GHS criteria not met
Conclusions:
The test material produced a 0 % (0/10) sensitisation rate and was classified as a non-sensitiser to guinea pig skin.
Executive summary:

A study was performed to assess the contact sensitisation potential of the test material (EC 413-110-2) in the albino guinea pig. The study was performed in compliance with the OECD Guidelines for Testing of Chemicals No. 406 "Skin Sensitisation" and Method B6 of Commission Directive 92/69/EEC.

Ten test and five control animals were used for the main study.

Based on the results of sighting tests, the concentrations of test material for the induction and challenge phases were selected as follows:

- lntradermal lnduction: 0.5 % w/v in arachis oil BP

- Topical lnduction: 25 % w/w in arachis oil BP

- Topical Challenge: 10 % and 5 % w/w in arachis oil BP

The test material produced a 0 % (0/10) sensitisation rate and was classified as a non-sensitiser to guinea pig skin.

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

Endpoint:
skin sensitisation: in vivo (non-LLNA)
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:
read-across source
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
40%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 40%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
20%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 20%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
40%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 40%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
20%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 20%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
test group
Dose level:
40%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: other: 3rd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 40%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
test group
Dose level:
20%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: other: 3rd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 20%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
40%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 40%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
20%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 20%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
40%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 40%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
20%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 20%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
negative control
Dose level:
40%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: other: 3rd reading. . Hours after challenge: 72.0. Group: negative control. Dose level: 40%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
negative control
Dose level:
20%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: other: 3rd reading. . Hours after challenge: 72.0. Group: negative control. Dose level: 20%. No with. + reactions: 0.0. Total no. in groups: 10.0.

No evidence of dermal reaction to treatment was seen in any of the test or control animals challenged with 40% and 20% w/w concentrations of the test material in 0.5% w/v aqueous carboxymethyl cellulose.

Interpretation of results:
GHS criteria not met
Conclusions:
It is concluded that technical Gel-All-MD did not induce delayed dermal hypersensitivity in the guinea pig.
Executive summary:

A modification of the Buehler method (OECD 406) was used to assess the skin sensitisation potential of technical Gel-All-MD (EC 402-950 -5).

Following a preliminary study designed to determine the maximum non-irritant and minimum irritant concentrations, a 40% w/w concentration of the test material in 0.5% aqueous carboxymethyl cellulose was applied topically to the 10 animals within the test group, for a period of 6 hours. This procedure was repeated at weekly intervals for a period of three weeks. A further 10 animals forming the control group, remained untreated during this stage of the study.

After 14 days all animals were challenged using 40% and 20% w/w concentartions of the test material. Assessments of dermal reactions were made 24, 48 and 72 hours after the challenge application.

No evidence of any dermal reaction to treatment was seen after challenging with either 40 or 20% w/w concentrations of the test material.

It is concluded that technical Gel-All-MD did not induce delayed dermal hypersensitivity in the guinea pig.

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 sensitising)

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The substance (EC 406-176-9), based on the results of skin sensitisation studies conducted and supported by two structurally similar substances, is not classified for skin sensitisation.