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Diss Factsheets

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP complaint guideline study, available as unpublished report, no restrictions, fully adequate for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report date:
1989

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test

Test material

Constituent 1
Chemical structure
Reference substance name:
4-(diethoxyphosphinyl)-2-methyl-2-butenoic acid ethyl ester
EC Number:
601-818-6
Cas Number:
122009-11-4
Molecular formula:
C11 H21 O5 P
IUPAC Name:
4-(diethoxyphosphinyl)-2-methyl-2-butenoic acid ethyl ester
Details on test material:
- Name of test material (as cited in study report): C-5-Ester-phosphonat tech.
- Substance No.: 88/876
- Physical state: liquid, yellowish
- Stability under test conditions: not limited
- Storage condition of test material: 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: Lippische Versuchstierzucht, Hagemann GmbH & Co. KG, Extertal, Germany.
- Age at study initiation: young adult animals
- Weight at study initiation: in the range between 233 and 262 g at the beginning of the study
- Housing: 5 animals per cage (Makrolon, type IV), Granulate Type 3/4 (staubfrei) bedding, SSNIFF
- Diet: Kliba 341.4 mm (Kaninchen-Meerscheinchen-Haltungsdiät); ad libitum. Supllied by Firma Klingentalmühle AG, CH-4303 Kaiseraugst Switzerland
- Water: tap water; ad libitum. The drinking water was supplemented with ascorbic acid, 0.2 g/L, twice per week
- Acclimation period: at least 8 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Air: fully air-conditioned rooms
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
olive oil
Remarks:
DAB 8
Concentration / amount:
- Intradermal induction: 5% in olive oil DAB 8 resp. in Freund's adjuvant/aqua dest. (1:1) resp. olive oil DAB 8
- Epicutaneous induction: 100% (unchanged)
- Challenge: 100% (unchanged)
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
olive oil
Remarks:
DAB 8
Concentration / amount:
- Intradermal induction: 5% in olive oil DAB 8 resp. in Freund's adjuvant/aqua dest. (1:1) resp. olive oil DAB 8
- Epicutaneous induction: 100% (unchanged)
- Challenge: 100% (unchanged)
No. of animals per dose:
- Control group: 10
- Test group: 20
Details on study design:
RANGE FINDING TESTS:
In a preliminary test, the highest non-irritating concentration of the test item was determined. The undiluted, liquid test substance was applied 2 times for 24 hours within a period of 96 hours to the flanks of 4 animals under occlusive conditions. Application sites were read at ca. 24 and 48 hours after beginning of application. The undiluted test substance was not irritating.

MAIN STUDY
A. INTRADERMAL INDUCTION EXPOSURE
- No. of exposures: 1 (on day 0)
- Test groups: A total of six intradermal injections in groups of two per animal was made. These injections were: A) front row: 2 injections each 0.1 mL Freund's adjuvant without test substance emulsified with water in ratio 1:1, B) middle row: 2 injections of each 0.1 mL test substance formulation, and C) back row: 2 injections of each 0.1 mL Freund's adjuvant/water 1:1 with test substance
- Control group: same as test groups, without test substance
- Site: animal shoulders
- Evaluation: 24 h after injections

B. EPICUTANEOUS INDUCTION EXPOSURE
- No. of exposures: 1
- Exposure period: about one week after intradermal induction (day 7)
- Test groups: 2 x 4 cm filter paper strips were applied to the skin of the shoulder under an occlusive dressing. In the case of liquids the filter paper strip was soaked in the unchanged test substance; thus, the animals were exposed to about 0.3 g of the test substance
- Control group: not treated, since the test substance was applied unchanged and thus no solvent was used
- Site: shoulder, same area as in the case of the previous intradermal application
- Frequency of applications: once
- Duration: 48 hours
- Evaluation: 48 h after the beginning of application

C. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: first challenge 14 days after epicutaneous application, second challenge one week later
- Exposure period: 24 hours
- Test/control groups: 1st challenge: treatment of the test group and of control group 1 with the test substance (control group 2 remained untreated); 2nd challenge: treatment of the test group and of control groups 1 and 2 with the test substance. 2 x 2 cm filter paper strips were applied to the skin of the flank under an occlusive dressing. The test filter paper strip was soaked in the test substance; thus the animals were exposed to about 0 .15 g of the test substance .
- Site: intact clipped flank
- Evaluation: about 24, 48 and 72 h after the beginning of application
Challenge controls:
1st challenge: treatment of the control group 1 with the test substance (control group 2 remained untreated);
2nd challenge: treatment of the test group and of control groups 1 and 2 with the test substance
Positive control substance(s):
no

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
48
Group:
other: negative control group 1
Dose level:
100% (unchanged)
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: other: negative control group 1. Dose level: 100% (unchanged). No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
other: negative control group 1
Dose level:
100% (unchanged)
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: other: negative control group 1. Dose level: 100% (unchanged). No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
other: negative control group 2
Dose level:
100% (unchanged)
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: other: negative control group 2. Dose level: 100% (unchanged). No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100% (unchanged)
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100% (unchanged). No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
100% (unchanged)
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 100% (unchanged). No with. + reactions: 0.0. Total no. in groups: 20.0.

Any other information on results incl. tables

INDUCTION:

After intradermal induction, distinct erythema and edema were observed at the injection sites of the control animals and the test animals at which only Freund's Adjuvant/water (1:1) was applied. Injection of test substance preparation in olive oil DAB 8 and in Freund's Adjuvant/water (1:1) caused necrotic skin changes in addition to distinct edema. The control animals injected with olive oil DAB 8 (vehicle) exhibited distinct erythema. After the epicutaneous induction, necrotic skin changes (caused by the intradermal induction) and distinct edema could be observed in the test animals. 

 

CHALLENGE AND RECHALLENGE: The epicutaneous challenges with the unchanged test substance did not cause any skin reactions either in the control animals or in the test animals.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Under the conditions of the test, the substance is not considered to be skin sensitizer.
Executive summary:

The substance was tested for its sensitizing effect on the skin of the Pirtbright-Hartley guinea pig, in a GLP complaint OECD 406 guideline study, based on the method of Magnusson and Klingman. 20 animals for the test group received six intradermal injections of 5% on day 0 and one epicutaneous application of the unchanged test substance on day 7. Two control groups (10 animals each) were treated similar but only with the vehicle. On day 21 all animals from the test group and animals from control group 1 were challenged epicutanously with the unchanged test substance. On day 28 day all animals (test group, control group 1 and control group 2) were challenged with the unchanged test substance. No skin effects were observed in either the test group or one of the control groups. It was therefore concluded that the substance is not a skin sensitizer.