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Toxicological information

Skin sensitisation

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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:
June-July 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study in compliance with OECD 406 under GLP without significant deviations

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
other: MAFF 59 NohSan No. 4200
Qualifier:
according to
Guideline:
EPA OPP 81-6 (Skin Sensitisation)
Qualifier:
according to
Guideline:
EPA OTS 798.4100 (Skin Sensitisation)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The study was done in 1995 before the LLNA became the required standard test method.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Contains more impurities than submission substance

Sponsor's identification : GBS-5
Label : Nervanaid GBS 5 PWD
Date received : 19 April 1995
Description : white powder
Storage conditions : room temperature

Composition according to Certificate of Analysis (see CoA in the report attached)
Glutamic acid - N,N -diacetic acid, tetrasodium salt 74.33%

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Hall Ltd., Burton-on-Trent, Staffordshire, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 318-398 g
- Housing:singly or in pairs in solid-floor polypoylene cages with woodflakes
- Diet (e.g. ad libitum): ad lib
- Water (e.g. ad libitum): ad lib
- Acclimation period: minimum of 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23
- Humidity (%): 44-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 12 June 1995 To: 13 July 1995

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
intradermal induction: 1% w/v in distilled water
topical induction: 50% w/w in distilled water
topical challenge: 50 and 25% w/w in distilled water
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
intradermal induction: 1% w/v in distilled water
topical induction: 50% w/w in distilled water
topical challenge: 50 and 25% w/w in distilled water
No. of animals per dose:
20 animals (test substance)
10 animals (control)
10 animals (positive control DNCB)
10 animals (vehicle control DNCB study)
Details on study design:
RANGE FINDING TESTS:

Intradermal induction: 2 animals, 1 animal 4 injections of 1% the other 4 injections of 5% w/v
topical induction: 2 animals (treated with FCA 7 days earlier), each animal 50, 25, 10, and 5% w/w
topical challenge: 2 animals, 50, 25, 10 and 5% w/w

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (day 0 and day 7)
- Exposure period: injection on day 0, topical application on day 7
- Test groups: 1
- Control group: 1
- Site: shoulder region (40x60 mm)
- Frequency of applications:3 injections in each animal (FCA:water, 1% w/v solution in water, 1% w/v emulsion in FCA:water 1:1)
- Duration: singe injections, topical application for 48 hours
- Concentrations: 0.1 ml 1% w/v (intradermal induction), 0.2-0.3 ml 50% w/w (topical induction)

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: day 21
- Exposure period: 24 hours
- Test groups: 1
- Control group: 1
- Site: flanks (50x70 mm)
- Concentrations: 0.1-0.2 ml 50 and 25% w/w
- Evaluation (hr after challenge): 24 and 48 hr:

Challenge controls:
Similar to test animals
Positive control substance(s):
yes
Remarks:
DNCB

Results and discussion

Positive control results:
The results of the positive control study were consistent with the known sensitising properties of DNCB.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
50% and 25% w/w
No. with + reactions:
0
Total no. in group:
19
Clinical observations:
no skin reactions noted
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50% and 25% w/w. No with. + reactions: 0.0. Total no. in groups: 19.0. Clinical observations: no skin reactions noted.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
50% and 25% w/w
No. with + reactions:
0
Total no. in group:
19
Clinical observations:
no skin reacions noted
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50% and 25% w/w. No with. + reactions: 0.0. Total no. in groups: 19.0. Clinical observations: no skin reacions noted.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
The test material produced a 0% (0/19) sensitisation rate and was classified as a non-sensitiser to guinea pigs.
Executive summary:

A study was performed to assess the contact sensitisation potential of the test material, GBS-5, in the albino guinea pig. Twenty test and ten control animals were used for the main study. Based on the results of sighting tests, the concentrations of test material for the induction and challenge phases were selected as follows:

lntradermal lnduction: 1% w/v in distilled water

Topical Induction: 50% w/w in distilled water

Topical Challenge: 50% and 25% w/w in distilled water.

A concurrent study, using groups of ten animals, was performed with the known contact sensitiser, 2,4 -dinitrochlorobenzene (DNCB). The concentrations used were as follows:

lntradermal lnduction: 0.1% w/v in arachis oil B.P.

Topical Induction: 0.75% w/v in absolute ethanol

Topical Challenge: 0.5% and 0.25% w/v in absolute ethanol.

The results are summarised as follows:

GBS-5: 0% animals showed positive skin responses

DNCB: 80% animals showed positive skin responses

The test material, GBS-5, was classified as a non-sensitiser to guinea pig skin. The test material was also classified as a non-sensitiser according to OECD-GHS classification. No symbol or risk phrases are required.

The results of the positive control study were consistent with the known sensitising properties of DNCB.