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Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
2-29 November 1994
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study was conducted according to the appropriate OECD test guideline and very largely in compliance with GLP. The study is a read accross from sodium citrate (CAS 68-04-2).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report Date:
1995

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Existing information

Test material

Reference
Name:
Unnamed
Type:
Constituent

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Himalayan Spotted (Ibm:GOHI)
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd, Wölferstrasse 4, 4414 Fűllinsdorf/Switzerland
- Age at study initiation: 5-7 wk
- Weight at study initiation: 311-452 g (start of acclimatization)
- Housing: 1/Makrolon type 3 cage, autoclaved standard softwood bedding
- Diet: standard diet ad libitum
- Water: drinking water ad libitum
- Acclimation period: 1 wk

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-23
- Humidity (%): 50-74 (OECD guideline recommends 30-70%)
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: From: 1994-11-02 To: 1994-11-29

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
Induction: intradermal injections 5% TS (with Freund's Complete Adjuvant in some cases); epicutaneous 10% SLS followed by 75% TS.
Challenge: 75, 50 & 25% TS.
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Induction: intradermal injections 5% TS (with Freund's Complete Adjuvant in some cases); epicutaneous 10% SLS followed by 75% TS.
Challenge: 75, 50 & 25% TS.
No. of animals per dose:
20 test animals, 10 vehicle controls, 2x10 positive controls
Details on study design:
RANGE FINDING TESTS:
Intradermal tests with 2 animals: 0.1 ml/site; 1, 3 and 5% TS in bidistilled water; evaluated at 24 h. 5% TS was selected
Epicutaneous tests with 4 animals: 2 cm x 2 cm saturated with 75, 50, 25 or 15% solutions of TS in bidistilled water, covered with aluminium foil, elastic plaster and impervious adhesive tape; 24-h contact; evaluation 24 h and 48 h after removal of dressing. 75% TS was selected for induction and challenge, and 50% and 25% were also selected for challenge.
The highest concentration tested, 75%, "was found to be the most qualified to assure an optimum technical application procedure" - it is not clear what this means

MAIN STUDY
A. INDUCTION EXPOSURE
intradermal injections (day 1)
- No. of exposures: 3 pairs of injections (0.1 ml/site)
- Test group: 1:1 Freund's Complete Adjuvant (FCA) and physiological saline; 5% TS in bidistilled water; 5% TS in 1:1 FCA: physiological saline
- Control group: 1:1 FCA and physiological saline; bidistilled water; 1:1 bidistilled water and 1:1 FCA: physiological saline
- Site: within a 4x6 cm clipped area

day 7: 6x8 cm area clipped. As no irritation had been observed in the pretest this area was pretreated with 10% sodium lauryl sulfate (SLS) in paraffinum per liquidum to provoke a mild inflammatory reaction.

epidermal applications (day 8, scapular area)
- No. of exposures: 1 (2x4 cm saturated filter paper)
- Exposure period: 48 h
- Test group: 2x4 filter paper saturated with 75% TS in bidistilled water, covered with aluminium foil, elastic plaster and impervious adhesive tape
- Control group: as for test group using bidistilled water
- evaluation at 24 and 48 h following removal of dressing

B. CHALLENGE EXPOSURE (day 22, flank)
Flanks shaved
- No. of exposures: 4 concentrations, each applied on saturated 2x2 cm filter paper
- Exposure period: 24 h
- Test groups: 75%, 50%, 25% and 0% TS in bidistilled water
- Control group: 75%, 50%, 25% and 0% TS in bidistilled water
- Site: left and right, caudal and cranial flanks
- Concentrations: 75%, 50%, 25% and 0% TS in bidistilled water
- Evaluation (hr after challenge): 24 h and 48 h

Challenge controls:
Naive controls: group of 10 males treated as described above.
Positive control substance(s):
yes
Remarks:
4-aminobenzoic acid ethyl ester (25 May to 27 June 1994); 2-mercaptobenzothiazol (25 May to 5 July 1994). Groups of 10 in each case.

Results and discussion

Positive control results:
Tests in the same strain of guinea pig using 4-aminobenzoic acid ethyl ester (25 May to 27 June 1994) and 2-mercaptobenzothiazol (25 May to 5 July 1994) (groups of 10 test and 4 or 5 controls; 25% in mineral oil in each case) found sensitization in 60% test animals and in none of the controls for both studies.

In vivo (non-LLNA)

Results
Reading:
other: readings at 24 and 48 h after challenge
Group:
test group
Dose level:
25, 50 and 75% TS
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No clinical signs or effect on body weight detected
Remarks on result:
other: Reading:

Any other information on results incl. tables

Table 1: Incidence of dermal response to challenge dosing

GROUP

MATERIAL

INTERVAL (AFTER 24 h CHALLENGE)

SKIN REACTIONS (NUMBERS OF ANIMALS)

NO. ANIMALS

SENSITIZATION INCIDENCE INDEX*

Test

TS (75%)

24 h

0

20

0/20=0%

48 h

0

20

TS (50%)

24 h

0

20

48 h

0

20

TS (25%)

24 h

0

20

48 h

0

20

Vehicle (bidistilled water)

24 h

0

20

0/20=0%

48 h

0

20

Positive control (2-mercaptobenzothiazol)

25% in vehicle

24 h

6

10

6/10=60%*

48 h

6

10

Vehicle (mineral oil)

24 h

0

10

0/10

48 h

0

10

Positive controls (4-aminobenzoic acid ethyl ester)

25% in vehicle

24 h

6

10

6/10=60%*

48 h

6

10

Vehicle (mineral oil)

24h

0

10

0/10=0%

48h

0

10

Negative (vehicle) control

TS (75%)

24 h

0

10

n/a

48 h

0

10

TS (50%)

24 h

0

10

48 h

0

10

TS (25%)

24 h

0

10

48 h

0

10

Vehicle (bidistilled water)

24 h

0

10

n/a

48 h

0

10

* A response of 30% or greater would indicate that a substance was a sensitizer

**The response of 60% in the positive controls confirms the sensitivity and reliability of the experimental technique

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
The result was a read accross from sodium citrate (CAS 68-04-2). A well conducted, well reported guinea-pig maximization test failed to identify any sensitizing potential in tests involving a 75% concentration of the test material.