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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Study period:
02 Dec 1991 - 03 Jan 1992
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP-guideline study with acceptable restrictions. No data on reliability check (positive control).

Data source

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

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
no data on reliabilty check (positive control)
GLP compliance:
yes
Type of study:
guinea pig maximisation test

Test material

Constituent 1
Reference substance name:
853947-59-8
Cas Number:
853947-59-8
IUPAC Name:
853947-59-8
Details on test material:
- Name of test material (as cited in study report): trade name
- Chemical denomination: 1,3-Butanediol diester of a mixture of 60% n-octanoic acid and 40% n-decanoic acid
- ID number: 3630/81 334
- Batch number: 12430
- Physical state: odourless oily liquid
- Analytical purity: Butanediol dioctanoate: 36.3 (% by area), butanediol octanoate decanoate: 46.3 (% by area), butanediol didecanoate: 15.1 (% by area)
- Expiration date of the lot/batch: 06/1993
- Storage condition of test material: In a closed container in a laboratory hood.
- pH: neutral
- Density (20 °C): 0.91 g/cm³

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Dunkin Hartley, Pirbright White Bor:DHPW [SPF]
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Age at study initiation: young adults
- Weight at study initiation: mean 425 g
- Housing: 5 animals of the same sex per cage in Makrolon IV cages.
- Diet: Ssniff G4 complete feed for guinea pigs (Ssniff Spezialfutter GmbH, Soest, Germany), ad libitum
- Water: drinking water (Gelsenwasser, Haltern, Germany), ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: maize germ oil MEH 56
Concentration / amount:
Preliminary test
Intradermal: 0.25, 0.5, 1.0, 2.5, 5.0 and 10%
Dermal: 2.5, 25, 50 and 100%

Main test
Induction: 10% (intradermal), 100% (dermal)
Challenge: 100%
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: maize germ oil MEH 56
Concentration / amount:
Preliminary test
Intradermal: 0.25, 0.5, 1.0, 2.5, 5.0 and 10%
Dermal: 2.5, 25, 50 and 100%

Main test
Induction: 10% (intradermal), 100% (dermal)
Challenge: 100%
No. of animals per dose:
Preliminary study
2 animals intradermal group, 4 animals dermal administration
Main study
10 (controls), 20 (in test group)
Details on study design:
RANGE FINDING TESTS:
Intracutaneous administration: The following concentrations of the test substance were each injected intracutaneously on the left flank (which had been shared 2-3 h before) of two animals to determine the intracutaneous tolerability (0.25, 0.5, 1, 2.5, 5 and 10% in maize germ oil MEH 56). The intracutaneous reaction was assessed 24 h after administration.
Dermal administration: About 2-3 h before dermal administration, the fur was removed mechanically from the left and right flanks. The patches were each impregnated with 0.15 mL of the appropriate formulation of test substance and applied to the sheared area. Each animal received 2 patches on each flank, the patches were covered with an occlusive plaster and fixed with a bandage for 24 h (left flank, front 2.5%, back 25%; right flank, front 50%, right flank, back 100%). The patches were removed after 24 h, and the dermal reaction was assessed immediately after removal and 48 h and 72 h after administration.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous, respectively)
- Exposure period: single injection (intradermal) and 48 h (epicutaneous)
- Test groups:
Intradermal (3 pairs of injections):
Injection 1: a 1:1 mixture (v/v) FCA/water
Injection 2: test substance in maize germ oil MEH 56
Injection 3: test substance in a 1:1 mixture (v/v) FCA/vehicle
Epicutaneous: test substance

- Control group 1:
Intradermal (3 pairs of injections):
Injection 1: a 1:1 mixture (v/v) FCA/water
Injection 2: maize germ oil MEH 56
Injection 3: a 1:1 mixture (v/v) FCA/vehicle
Epicutaneous: maize germ oil MEH 56

- Control group 2:
Intradermal (3 pairs of injections):
Injection 1: a 1:1 mixture (v/v) FCA/water
Injection 2: maize germ oil MEH 56
Injection 3: a 1:1 mixture (v/v) FCA/vehicle
Epicutaneous: maize germ oil MEH 56

- Site: shoulder region (intradermal + epicutaneous)
- Frequency of applications: every 7 days
- Duration: Day 0-7
- Concentrations: intradermal 10%, epicutaneous 100%

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: Day 21
- Exposure period: 24 h
- Test groups: test substance
- Control group I: test substance
- Control group II: vehicle control is employed only in the induction treatment; no challenge with vehicle
- Site: right flank
- Concentrations: 100%
- Evaluation (hr after challenge): 24, 48 and 72 h

OTHER: 2-3 h before the dermal treatment the right flank of the test animals and of control group I was sheared.
The highest concentration of test substance administered dermally in the preliminary test caused no irritation of the skin. In order to cause slight to moderate inflammation of the skin for the dermal induction, one day before the dermal administration (Day 6) all the test and control animals were sheared on the shoulder and treated with sodium dodecyl sulphate (10% in Vaseline).

Scoring scheme for dermal reactions: Draize scoring system
Challenge controls:
The control group is actually a challenge control.
Positive control substance(s):
not specified
Remarks:
The sensitivity of the test system was reported to be checked at regular intervals (no further information).

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
other: negative control group I
Dose level:
induction: 0%; challenge: 100%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: negative control group I. Dose level: induction: 0%; challenge: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
induction: 10%; challenge: 100%
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: induction: 10%; challenge: 100%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
other: negative control group I
Dose level:
induction: 0%; challenge: 100%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: negative control group I. Dose level: induction: 0%; challenge: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
induction: 10%; challenge: 100%
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: induction: 10%; challenge: 100%. No with. + reactions: 0.0. Total no. in groups: 20.0.

Any other information on results incl. tables

PRELIMINARY TEST

- Intracutaneous administration:

All test substance concentrations and the pure vehicle caused very slight erythema and well-defined oedema at the injection sites in both animals 24 h after the intradermal administration.

- Dermal administration:

None of the test substance concentrations (2.5, 25, 50 and 100%) caused dermal reactions 24, 48 and 72 h after administration, therefore the undiluted test substance was used for the dermal administration in the main test. Since the undiluted test substance had no irritant effect on the skin, pretreatment with sodium dodecyl sulphate (10% in Vaseline) was chosen to cause slight ot moderate inflammation of the skin in the dermal induction phase of the main test.

MAIN TEST

- Bodyweight changes and systemic effects:

No toxic effects were observed in the treated animals during the observation period.

 

- Intracutaneous and dermal induction:

1 h after intracutaneous injection of Freunds´s Adjuvant all the test and control animals showed severe erythema and severe oedema. After 24 h all the animals had severe erythema with deep damage and severe oedema. Injections of the test substance caused very slight to well-defined erythema and oedema in all the test animals 1 h and 24 h after administration. The injection sites treated only with maize germ oil MEH 56 showed very slight to well-defined erythema and oedema in all the control animals 1 h and 24 h after administration. The injection sites treated with the test substance in Freund´s Adjuvant showed very slight to moderate erythema and well-defined to moderately severe oedema in all test animals 1 h after administration. Severe erythema and severe oedema were observed in all animals after 24 h. Injection of FCA and the vehicle resulted in very slight to moderate erythema and well-defined to moderate oedema in all the control animals 1 h after administration. Severe erythema and severe oedema were observed 24 h later.

On Day 7 the shoulder region was distinctly reddened and swollen owing to the treatment with sodium dodecyl suphate the preceding day. After removal of the occlusive dressing, the skin showed schaling, and in some cases bleeding scratches, in all the test and control animals. 49 and 72 h after administration there was severe erythema with deep damage and severe oedema at the injection sites treated with FCA in all the test and control animals. There was well-defined erythema and oedema at the injection sites of the test substance and only with vehicle 49 h after administration. 24 h later, the skin showed scaling, reddening and swelling. There was severe erythema and severe oedema at the injection sites treated with 10% test substance in FCA 49 h after administration in 19/20 animals. 1/20 animals showed well-defined reddening and swelling. 9/20 animals also had deep damage. 72 h later, 19/20 animals had severe erythema with deep damage and severe oedema. One animal had moderate reddening and swelling. The sites of injection of FCA and the vehicle showed severe erythema and severe oedema in all control animals 49 h after administration. 10/20 animals showed deep damage at the injection sites. After 72 h all the animals had severe erythema with deep damage and severe oedema.

 

- Challenge treatments:

There were no signs of skin irritation in the administration area 48 and 72 h after administration either in the test animals or in the animals in control group I. 

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified