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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:
1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Comparable to guideline study under GLP-like quality control with QAU statement provided. Replacement of the first intradermal injection by epicutaneous treatment due to insolubility of the test substance in stadard vehicles. No Purity of test substance available.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report date:
1985

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
(adopted 1981)
Deviations:
yes
Remarks:
due to the insolubility of the test substances in standard vehicles, the test substance was applied epicutaneously at the first induction treatment.
Principles of method if other than guideline:
The modification of the GPMT is not mentioned in the OECD guideline 406, but is scientifically based and published (Maurer Th and Hess R (1989) The maximization test for skin sensitization potential- updating the standard protocol and validation of a modified protocol. Fd. Chem. Toxic. (27) 12, 807-811)
GLP compliance:
no
Remarks:
but QAU statement included
Type of study:
guinea pig maximisation test

Test material

Constituent 1
Chemical structure
Reference substance name:
Calcium diethyl bis[[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methyl]phosphonate]
EC Number:
265-512-0
EC Name:
Calcium diethyl bis[[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methyl]phosphonate]
Cas Number:
65140-91-2
Molecular formula:
C17 H29 O4 P. 1/2Ca
IUPAC Name:
calcium diethyl bis[[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methyl]phosphonate]
Details on test material:
- Physical state: solid
- Storage condition of test material: room temperature
- Purity: commercial grade

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Pirbright-White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: ca. 10 weeks
- Weight at study initiation: 304-427 g
- Housing: single housing in Makrolon cages (Type 3)
- Diet: Standard guinea pig pellets, NAFAG No. 846, Gossau SG, supplemented with carrots, ad libitum
- Water: ad libitum
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21+/-2
- Humidity (%): 50+/-10
- Photoperiod: 12 hrs dark / 12 hrs light

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: vaseline
Concentration / amount:
First induction: 30% in vaseline (0.4 g per patch)
Second induction: 30% in vaseline (0.4 g per patch)
Challenge: 0.3% in vaseline (0.2 g per patch)
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: vaseline
Concentration / amount:
First induction: 30% in vaseline (0.4 g per patch)
Second induction: 30% in vaseline (0.4 g per patch)
Challenge: 0.3% in vaseline (0.2 g per patch)
No. of animals per dose:
10 males and 10 females
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: two
- Test groups: 0.1 ml of a freshly prepared adjuvant saline mixture was injected intracutaneously at 4 sites on the animal's neck. The test compound was applied on filter patches ( 2 x 4 cm) to the epidermis over the injection sites for 24 hours under an occlusive dressing. Dose of application: 30%, 0.4 g paste in vaseline. One week later the test compound was applied occlusively in the same way as during the first week on induction for 48 hours. Dose of application: 0.4 g paste in vaseline
- Control group: A control group was treated with adjuvant and the vehicle during the induction period.
- Concentrations: 30%
- Site: neck

B. CHALLENGE EXPOSURE
- No. of exposures: single exposure
- Day of challenge: 14 days after end of second induction period
- Exposure period: 24 h, epidermal, occlusive
- Test groups: After a rest period of 14 days the compound and the vehicle was applied on filter paper patches ( 2 x 2 cm) to the untreated contralateral flanks of the animals for 24 hours epidermal occlusively.
- Control group: treated with the vehicle as well as with the test compound to control the maximal subirritant concentration of the test compound in adjuvant treated animals.
- Site: contralateral flanks
- Concentrations: 0.3% (ca. 0.2 g per patch)
- Evaluation: 24 and 48 h after removing the dressing
Challenge controls:
A control group of 20 animals (10 m/10 f) was treated with adjuvant and the vehicle during the induction period. During the challenge period, the group was treated with the vehicle as well as with the test item to check the maximum subirritant concentration of the test article in adjuvant treated animals.
Positive control substance(s):
no

Results and discussion

Positive control results:
The sensitivity of the strain is checked every 6 months with p-phenylendiamine. No data were given in the test report.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0.3%
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: 0.3%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.3%
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: 0.3%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.3%
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: 0.3%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.3%
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: 0.3%. No with. + reactions: 0.0. Total no. in groups: 20.0.

Any other information on results incl. tables

The test substance at the concentration of 0.3% in vaseline, did neither induce edema nor erythema reactions after epidermal challenge application.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Based on the results of this study and under the test conditions chosen, the test substance is not considered to be a skin sensitizer.
Executive summary:

In a modified guinea pig maximization test, 10 male and 10 female animals were first induced and then challenged with the test article to investigate its sensitization potential. A modified procedure from the maximization test, as it is recommended in the OECD guidelines 1981 and in the EEC directive 79/831, was selected on account of its suitability for final formulations or for compounds which are not injectable on account of their insolubility in standard vehicles. Instead of an intradermal injection, the test substance was applied epicutaneously during induction. Induction was a two-stage operation: First, am mixture of adjuvant/saline was injected intracutaneously at four sites on the animals’ neck. The test compound (30% in vaseline) was applied to the epidermis over the injection sites for 24 hours under an occlusive dressing. One week later, the test compound was applied occlusively in the same way as during the first week on induction for 48 hours. After a rest period of 14 days the compound and the vehicle was applied on filter paper patches ( 2 x 2 cm) to the untreated contralateral flanks of the animals for 24 hours epidermal occlusively. Twenty four and 48 hours after removing the dressings the challenge reactions were graded according to the Draize scoring scale. A control group (10 m/10 f) was treated with adjuvant and the vehicle during the induction period. During the challenge period the group was treated with the vehicle as well as with the test compound to control the maximal subirritant concentration of the test compound in adjuvant treated animals. No animal of the test group was sensitized by the test substance, all skin reactions at 24 and 48 hour time points were scored 0. Therefore, under the experimental conditions of this study, the test material is non-sensitizing when topically applied to albino guinea pigs.

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