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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:
9 July 1985 - 2 August 1985
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was performed similar to OECD guidelines and under GLP.

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)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The default animal study for skin sensitisation in the ECHA Guidelines, is the Local Lymph Node Assay (LLNA) OECD429. However it is accepted in the OECD guideline for the LLNA that it has some limitations, as follows: “Despite the advantages of the LLNA over TG 406, it should be recognised that there are certain limitations that may necessitate the use of TG 406 (13) (e.g. false negative findings in the LLNA with certain metals, false positive findings with certain skin irritants [such as some surfactant type chemicals] (19) (20), or solubility of the test substance)”. For the amphoteric glycinate substances, there are available in-vivo skin sensitizing studies performed before the LLNA was recommended as a standard. As these studies are considered to be of high reliability rating and the results are considered relevant, it is not justified from an animal well-fare perspective to perform any additional skin sensitising studies. For this reason the available guinea pig studies are provided as key studies.

Test material

Constituent 1
Reference substance name:
Amines, N-C8-22-alkylpolytrimethylenepoly-, carboxymethyl derivs., sodium salts
EC Number:
307-458-3
EC Name:
Amines, N-C8-22-alkylpolytrimethylenepoly-, carboxymethyl derivs., sodium salts
Cas Number:
97659-53-5
Details on test material:
Appearance: clear amber liquid
Container: a screw capped plastic bottle
Identification: Ampholak 7TX

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: D. Hall, Darley Oaks, Burton-on-Trent , Staffordshire.
- Age at study initiation: young, not specified
- Weight at study initiation: 300-500g
- Housing: groups of five in grid bottomed polypropylene cages
- Diet (e.g. ad libitum): A commercially available pelleted diet with additional vitamin C (type TR2 supplied by Pilsbury's Limited of Birmingham) ad libitum.
- Water (e.g. ad libitum): Tap water containing 0.01% vitamin C were provided ad libitum
- Acclimation period: at least 3 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-24
- Humidity (%): 50-70
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: 9 July 1985 - 2 August 1985

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
Prior to each stage of the study the supplied test material was treated with a 50% aqueous solution of citric acid in order to adjust its pH to 6.6.

Induction:
Intradermal: 0.1ml
Epicutaneous: undiluted

Challenge:
Epicutaneous: undiluted and 50%
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Prior to each stage of the study the supplied test material was treated with a 50% aqueous solution of citric acid in order to adjust its pH to 6.6.

Induction:
Intradermal: 0.1ml
Epicutaneous: undiluted

Challenge:
Epicutaneous: undiluted and 50%
No. of animals per dose:
10
Details on study design:
RANGE FINDING TESTS: The procedures followed require that both the maximum non-irritating concentration of the test material be found and a concentration of the material that, although irritating , did not cause severe irritation to the skin (minimum irritant concentration). A dose-ranging study was carried out on four animals, weighing less than 650g, and previously treated with Freund's Complete Adjuvant by injection. This was necessary as the Adjuvant can also enhance irritation as well as sensitisation response in the animal, serial dilutions of the test material were made in distilled water to give concentrations of, 100%, 50%, 25% and 12.5%. An area 8cm x 5cm was clipped free of fur over the back and flanks of the four animals and four patches of Whatman No. 3 filter paper, 2mx2cm, each saturated with a different concentration of the test material placed onto the skin, two patches on each flank, Strips of 5m wide Blenderm surgical tape were placed over the patches - to act as occlusive barriers and the patches held i n place for twenty four hours by encircling the trunk of the animal with lengths of 5cm wide "Elastoplast" elastic adhesive bandage.' Twenty four and, forty eight hours a f t e r removing the patches and.dressings the animals were examined and skin reaction at the treated sites assessed under the same conditions and skin reaction at the treated sites assessed under the same conditions and using the Draize numerical scoring system. No skin reaction was seen in one of the four treated animals after 24 hours. Therefore 100% was chosen as the concetration for topical induction.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: Intradermal exposure: the test animals were treated with two injections each of 0.1ml Freund's Complete Adjuvant, two injections each of 0.1ml test material and two injections each of 0.1ml Freund's Complete Adjuvant mixed with an equal volume of the test material.The control animals were treated similarly by these animals were exposed to distilled water in stead of the test substance.
Epicutaneous exposure:
- Exposure period: on day 0 the animals were exposed intradermally and 7 days later the animals were exposed epicutaneously.
- Test groups: 10 animals
- Control group: 10 animals
- Site: Intradermal and epicutaneous exposure: the dorsal area between the shoulders.
- Frequency of applications: single applications
- Duration: the epicutaneous patches were kept in place for 48 hours.
- Concentrations:
Intradermal exposure: 0.1 ml testsubstance
Epicutaneous exposure: 100% concentration (shown to cause some irritancy in range finding study)

B. CHALLENGE EXPOSURE
- No. of exposures: single epicutaneous exposure
- Day(s) of challenge: 21 days after the start of the stuyd, 14 days after induction
- Exposure period: 24 hours
- Test groups: 10 animals
- Control group: 10 animals
- Site: flanks
- Concentrations: 50% and 100%
- Evaluation (hr after challenge): 24 and 48 hours after patch removal


OTHER:
Challenge controls:
The controls were treated similar to the test group but the test substance was replaced by water
Positive control substance(s):
not required

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
other: Challenge phase
Hours after challenge:
24
Group:
test chemical
Dose level:
100% test material (corresponds to 40% a.i)
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
Not described
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: Challenge phase
Hours after challenge:
48
Group:
test chemical
Dose level:
100% test material (corresponds to 40% a.i)
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
Not described
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: Challenge phase
Hours after challenge:
24
Group:
test chemical
Dose level:
50% test material (corresponds to 40% a.i)
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
Not described
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: Challenge phase
Hours after challenge:
48
Group:
test chemical
Dose level:
50% test material (corresponds to 40% a.i)
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
Not described
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: Challenge phase
Hours after challenge:
24
Group:
negative control
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
Not described
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: Challenge phase
Hours after challenge:
48
Group:
negative control
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
Not described
Remarks on result:
no indication of skin sensitisation

Any other information on results incl. tables

No reaction was observed in any of the animals exposed to the test substance or in the control group.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
On challenge with the test material, consisting of 40% active ingredient and 60% water, no visible response was exhibited by any animal in the test or control group when challenged with the undiluted test material and 50% aqueous concentration of the test material. From the results of this study there was no evidence to suggest that the active ingredient Sodium tallowamphopolycarboxyglycinate (Amines, N-[3-[(3-aminopro yl)amino]propyl]-N’-(C16-18 and C18-unsatd. alkyl)trimethylenedi-, N-(carboxymethyl) derivs., sodium salts with CAS no 2060541-47-9) acts as a sensitiser in the guinea pig.
Executive summary:

Accoring to methods similar to OECD 406 and under GLP ten guinea pigs were treated by intradermal injection in the shoulder region with the test material, Freund's Complete Adjuvant and a mixture of the test material and Freund's Complete Adjuvant. Seven days later this induction procedure was boosted by the topical application of the test material over the injection site. A second group of ten animals were similarly treated but distilled water was substituted for the test material. Two weeks after the induction phase all animals of both test and control groups were challenged with two concentrations of the test material applied topically to the flanks. On challenge with the test material no visible response was exhibited by any animal in the test or control group when challenged with the undiluted test material and 50% aqueous concentration of the test material. From the results of this study there was no evidence to suggest that the active ingredient of the test material, Sodium tallowamphopolycarboxyglycinate (Amines, N-[3-[(3-aminopro yl)amino]propyl]-N’-(C16-18 and C18-unsatd. alkyl)trimethylenedi-, N-(carboxymethyl) derivs., sodium salts with CAS no 2060541-47-9) acts as a sensitiser in the guinea pig.