N,N'-methylenedistearamide

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1994

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Remarks:

No clear description of methods, however a reference is made to the original GPMT procedure (Magnusson and Kligman, procedure similar to OECD TG 406)

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Multivariate QSAR analysis of a skin sensitization database.

Author:

Cronin MT, Basketter DA

Year:

1994

Bibliographic source:

SAR QSAR Environ Res. 1994;2(3):159-79.

Reference 2

Reference Type:

publication

Title:

The identification of contact allergens by animal assay. The guinea pig maximization test.

Author:

Magnusson B, Kligman AM.

Year:

1969

Bibliographic source:

J Invest Dermatol. 1969 Mar;52(3):268-76.

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

Test was performed according to Magnusson and Kligman (1969), which is also the basis for OECD TG 406

Principles of method if other than guideline:

No clear description of methods, however a reference is made to two well described standard procedure (Magnusson and Kligman, GPMT procedure similar to OECD TG 406; Goodwin and Johnson, SIAT test). All non-sensitizers were identified using the GPMT procedure.

MAGNUSSON AND KLIGMAN
Bibliographic source: J Invest Dermatol. 1969 Mar;52(3):268-76.
Name of the method: guinea pig maximization test (GPMT)
Principle of the method:
- Induction procedure: Injections are given intradermally with and without complete Freund's
Adjuvant (The final concentration of the allergen is 5% by weight provided that it can be well tolerated locally and generally) to Albino guinea pigs weighing 300-500 Grams. A row of 3 injections,
six in all, are made on each side as follows: (1) 0.1 ml of the adjuvant without the test agent, (2) 0.1 ml of test agent without adjuvant and (3) 0.1 ml of the test substance emulsified in complete adjuvant. One week later the test agent is applied topically over the injection site (The test agent in petrolatum is spread over a 2 x 4 cm patch of Whatman No. 3MM filter paper in a thick even layer or, if liquid, to saturation. The patch is covered by an overlapping impermeable, plastic adhesive tape. This in turn is firmly secured by elastic adhesive bandage (6.4 cm in width), wound around the torso of the animal. This dressing is left in place for 48 hours) .
- Challenge procedure: The animals are challenged by patch test two weeks later. The test agent is applied on a 2 x 2 cm piece of filter paper in the same fashion as for topical induction. The patch is sealed to the flank for 24 hours under a 4 cm strip.

GOODWIN AND JOHNSON
Bibliographic source: Curr Probl Dermatol. 1985;14:201-7.
Name of the method: Single injection adjuvant test (SIAT)
Principle of the method: the procedure involves a single injection of the test substance in Freund’s complete adjuvant followed 12 days later by challenge using a 6-hour occlude patch.

GLP compliance:

no

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Test was conducted before the LLNA method became a standard procedure for in vivo skin sensitisation

Test material

Test material information

Constituent 1

Reference substance name:

N,N'-methylenedistearamide

EC Number:

203-657-3

EC Name:

N,N'-methylenedistearamide

Cas Number:

109-23-9

Molecular formula:

C37H74N2O2

IUPAC Name:

N,N'-methylenedistearamide

Test material form:

solid

Specific details on test material used for the study:

- Name as cited in the report: methylene distearamide

In vivo test system

Test animals

Species:

guinea pig

Strain:

not specified

Sex:

not specified

Details on test animals and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 300-500 Grams (according to Magnusson and Kligman, 1969)

Study design: in vivo (non-LLNA)

Induction

Route:

intradermal and epicutaneous

Vehicle:

not specified

Challenge

Route:

epicutaneous, occlusive

Vehicle:

not specified

Concentration / amount:

Not specified

Day(s)/duration:

1 day

Details on study design:

METHODS AS DECRIBED IN MAGNUSSON AND KLIGMAN, 1969
- Induction procedure: Injections are given intradermally with and without complete Freund's Adjuvant (The final concentration of the allergen is 5% by weight provided that it can be well tolerated locally and generally) to Albino guinea pigs weighing 300-500 Grams. A row of 3 injections, six in all, are made on each side as follows: (1) 0.1 ml of the adjuvant without the test agent, (2) 0.1 ml of test agent without adjuvant and (3) 0.1 ml of the test substance emulsified in complete adjuvant. One week later the test agent is applied topically over the injection site (The test agent in petrolatum is spread over a 2 x 4 cm patch of Whatman No. 3MM filter paper in a thick even layer or, if liquid, to saturation. The patch is covered by an overlapping impermeable, plastic adhesive tape. This in turn is firmly secured by elastic adhesive bandage (6.4 cm in width), wound around the torso of the animal. This dressing is left in place for 48 hours) .
- Challenge procedure: The animals are challenged by patch test two weeks later. The test agent is applied on a 2 x 2 cm piece of filter paper in the same fashion as for topical induction. The patch is sealed to the flank for 24 hours under a 4 cm strip.

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Key result

Reading:

other: not specified

Group:

test chemical

Dose level:

not specified

Remarks on result:

no indication of skin sensitisation

Results 2

Reading:

other: not specified

Group:

negative control

Remarks on result:

not measured/tested

Results 3

Reading:

other: not specified

Group:

positive control

Remarks on result:

not measured/tested

Any other information on results incl. tables

From the scores obtained in the GPMT, chemicals may be classified qualitatively into one of four groups, i.e. non, weak, moderate or strong sensitisers. The substance under evaluation in this dossier was classified as non sensitiser.

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Conclusions:

In this study performed similar to OECD 406, the substance was considered to be non-sensitising.

Executive summary:

The sensitising potential of the test substance was assessed in a guinea pig maximisation test (GPMT test) performed similar to OECD 406. During the induction procedure the test animals were given a row of 3 injections on each side (six in total) as follows: (1) 0.1 ml of the adjuvant without the test agent, (2) 0.1 ml of test agent without adjuvant and (3) 0.1 ml of the test substance emulsified in complete adjuvant. One week later the test agent is applied topically over the injection site under occlusive conditions for 48 hours. The animals were challenged by patch test two weeks later. The test agent was applied on a 2 x 2 cm piece of filter paper in the same fashion as for topical induction. The patch was sealed to the flank for 24 hours under a 4 cm strip.

In this study, the substance was considered to be non-sensitising.