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Administrative data

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:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report date:
1988

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
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

Test material

Constituent 1
Chemical structure
Reference substance name:
1-(2,6-bis(4-tolyl)-1,3-dioxano(5,4-d)-1,3-dioxan-4-yl)ethane-1,2-diol
EC Number:
402-950-5
EC Name:
1-(2,6-bis(4-tolyl)-1,3-dioxano(5,4-d)-1,3-dioxan-4-yl)ethane-1,2-diol
Cas Number:
87826-41-3
Molecular formula:
C22 H26 O6
IUPAC Name:
(1R)-1-[(4R,4aR,8aS)-2,6-bis(4-methylphenyl)-hexahydro-[1,3]dioxino[5,4-d][1,3]dioxin-4-yl]ethane-1,2-diol
Details on test material:
Test material: technical Gel-All-MD
Batch number: 4140626
Appearance: White powder
arrival date: 19th February 1988
Storage: In a dark room at room temperature

In vivo test system

Test animals

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

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
CMC (carboxymethyl cellulose)
Concentration / amount:
Dose finding study: The following concentrations of test solution were prepared 0.5, 5, 10. 20 and 40% w/v

Main study: Based upon the results of the range finding study the following concentrations were used: A 40% concentration of the test material in 0.5% w/v aqueous CMC was chosen as the maximum non-irritant concentration for both the induction and challenge phases of the main study. A 20% w/w concentration was also used in the challenge phase
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
CMC (carboxymethyl cellulose)
Concentration / amount:
Dose finding study: The following concentrations of test solution were prepared 0.5, 5, 10. 20 and 40% w/v

Main study: Based upon the results of the range finding study the following concentrations were used: A 40% concentration of the test material in 0.5% w/v aqueous CMC was chosen as the maximum non-irritant concentration for both the induction and challenge phases of the main study. A 20% w/w concentration was also used in the challenge phase
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

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
40%
No. with + reactions:
0
Total no. in group:
10
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 chemical
Dose level:
20%
No. with + reactions:
0
Total no. in group:
10
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 chemical
Dose level:
40%
No. with + reactions:
0
Total no. in group:
10
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 chemical
Dose level:
20%
No. with + reactions:
0
Total no. in group:
10
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 chemical
Dose level:
40%
No. with + reactions:
0
Total no. in group:
10
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 chemical
Dose level:
20%
No. with + reactions:
0
Total no. in group:
10
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
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
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
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
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
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
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.

Any other information on results incl. tables

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.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
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.