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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:
1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD 406 guideline study performed according to GLP regulation

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report date:
1992

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test

Test material

Constituent 1
Chemical structure
Reference substance name:
Tris(oxiranylmethyl) benzene-1,2,4-tricarboxylate
EC Number:
230-638-7
EC Name:
Tris(oxiranylmethyl) benzene-1,2,4-tricarboxylate
Cas Number:
7237-83-4
Molecular formula:
C18H18O9
IUPAC Name:
1,2,4-tris[(oxiran-2-yl)methyl] benzene-1,2,4-tricarboxylate
Constituent 2
Reference substance name:
tris(oxiranylmethyl)benzene-1,2,3-tricarboxylate
IUPAC Name:
tris(oxiranylmethyl)benzene-1,2,3-tricarboxylate
Details on test material:
- Name of test material (as cited in study report): TKK 30009
- Trade name: LMB 5196
- Physical state: viscous liquid
- Analytical purity: > 75%
- Lot/batch No.: Z 2178
- Expiration date of the lot/batch: March 1995
- Storage condition of test material: room temperature

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Pirbright white strain (Tif: DHP)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ciba-Geigy Limited Animal Production 4332 Stein Switzerland
- Weight at study initiation: 324 to 416 g
- Housing: Individually in Macrolon type 3 cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 6 May 1992 to 10 May 1992


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 30 to 70
- Photoperiod (hrs dark / hrs light): 12 / 12


IN-LIFE DATES: From: May 11, 1992 To: June 12, 1992

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: Oleum arachidis and an adjuvant/saline mixture were used for the intradermal induction. Vaseline was used for the epidermal induction as well as for the challenge procedure.
Concentration / amount:
The substance at 1% in Oleum arachidis during the intradermal induction.
The undiluted substance (100%) was used during the epidermal induction.
The substance at 50% in vaseline was used during the challenge procedure.
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: Oleum arachidis and an adjuvant/saline mixture were used for the intradermal induction. Vaseline was used for the epidermal induction as well as for the challenge procedure.
Concentration / amount:
The substance at 1% in Oleum arachidis during the intradermal induction.
The undiluted substance (100%) was used during the epidermal induction.
The substance at 50% in vaseline was used during the challenge procedure.
No. of animals per dose:
10 control animals (5 males and 5 females)
20 test animals (10 males and 10 females)
Details on study design:
RANGE FINDING TESTS:
The substance at 1, 3 and 5% in Oleum arachidis was tested for the intradermal induction. Necrosis was noted at 3% and 5%. Therefore 1% was selected for the intradermal induction in the main study.
The substance at 1, 5, 10, 30, 70 and 100% in vaseline was tested for the epidermal induction. Erythema was noted at 70% and 100%. Therefore, 100% was selected for the epidermal induction and 50% was selected for the challenge procedure.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: one intradermal exposure and one epidermal exposure
- Exposure period: First induction week: intradermal induction
Second induction week: epidermal induction
- Test groups:
Intradermal Induction:
1) adjuvant / saline mixture 1:1 (v/v)
2) substance at 1% in Oleum arachidis (w/v)
3) substance at 1% in adjuvant/saline mixture (w/v)
Epidermal Induction:
The substance undiluted (100%)
- Control group:
The control animals were treated with adjuvant and vehicle during the induction period.
- Site: The intradermal induction was performed on the sahved neck of the guinea pigs. The epidermal induction was performed over the injection sites.
- Frequency of applications: One week after the intradermal induction injections the epidermal induction application was performed.
- Duration:
Three pairs of intradermal injections made simultaneously for the intradermal induction.
Colsed patch exposure for 48 hours for the epidermal induction.
- Concentrations:
0.1 mL of the substance at 1% for the intradermal induction
0.4 g of the substance undiluted (100%) for the epidermal induction

B. CHALLENGE EXPOSURE
- No. of exposures: single
- Day(s) of challenge: week 5
- Exposure period: 24 hours
- Test groups:
The animals were treated with the substance in vaseline (w/w) and the vehicle alone by occluded administration.
- Control group:
The animals were treated with the vehicle alone as well as with the maximum subirritant concentration of the substance
- Site: Flank
- Concentrations: 0.2 g of the substance at 50% in vaseline
- Evaluation (hr after challenge): 24 hours and 48 hours after removal of the dressings.


Positive control substance(s):
yes
Remarks:
Potassiumdichromate

Results and discussion

Positive control results:
Seven out of ten animals after 24 hours and six out of ten animals after 48 hours showed positive skin reactions after the challenge procedure with potassiumdichromate at 1% in vaseline, no skin effects were noted in the test animals when treated with the vehicle alone. No skin effects were noted in control group when treated with potassiumdichromate at 1% in vaseline or with the vehicle alone.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
vehicle
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: vehicle. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
vehicle
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: vehicle. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
50%
No. with + reactions:
1
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 50%. No with. + reactions: 1.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
50
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: 50. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
vehicle
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: vehicle. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
vehicle
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: vehicle. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
50%
No. with + reactions:
14
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50%. No with. + reactions: 14.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
50%
No. with + reactions:
20
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50%. No with. + reactions: 20.0. Total no. in groups: 20.0.

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information
Conclusions:
70% after 24 hours and 100% after 48 hours of the test animals were sensitised under the experimental conditions employed. The substance is considered to be an extreme skin sensitiser in albino guinea pigs.
Executive summary:

In order to assess the cutaneous allergenic potential of the substance, the Maximization-Test was performed in 30 (20 test and 10 control) males and females albino guinea pigs, in accordance with OECD Guideline No. 406 and the Directive 84/449/EEC, B.6.

The intradermal induction of sensitization in the test group was performed in the nuchal region with a 1% dilution of the test item in Oleum arachidis and in mixture of Freund's Complete Adjuvant (FCA) / physiological saline. The epidermal induction of sensitization was conducted for 48 hours under occlusion with the test item at 100 % one week after the intradermal induction. The animals of the control group were induced with the vehicle and Freund's Complete Adjuvant.

Two weeks after epidermal induction the control and test animals were challenged by epidermal application of the test item at 50 % in vaseline and vaseline alone under occlusive dressing.

Cutaneous reactions were evaluated at 24 and 48 hours after removal of the dressing. 14 out of t20 animals (70%) after 24 hours and all 20 animals (100%) after 48 hours showed positive skin reactions after the challenge procedure with the substance at 50% in vaseline, no skin effects were noted in the test animals when treated with the vehicle alone. Only one animal showed effects at the 24 -hour reading in the control group when treated with the substance at 50% in vaseline and no effects were noted when treated with vaseline alone. Based on the above mentioned findings the substance is considered to be a skin sensitiser.

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