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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 from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
Not applicable
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: 2e: Meets generally accepted scientific standards, well-documented and acceptable for assessment
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Evaluation of skin sensitization and cross-reaction of nine alkyleneamines in the guinea pig maximization test.
Author:
Leung, H.W. and Auletta, C.S.
Year:
1997
Bibliographic source:
J Toxicol-Cut & Ocular Toxicol 16:189-195.

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
study examined sensitization capability of structurally similar amines
Principles of method if other than guideline:
Magnusson, B. and Kligman, A.M.: The identification of contact allergens by animal assay. The guinea pig maximization test. J. Invest. Dermatol. 52:268, 1969
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
At the time of registration adequate data for sensitisation where already available.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Test material was obtained from Union Carbide. No additional information available.

In vivo test system

Test animals

Species:
guinea pig
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
Dunkin Hartley Haz:(DH)fBR albino guinea pigs (5-7 weeks old, 278-444 gr) were obtained from HRP Inc. (Denver, PA).

Study design: in vivo (non-LLNA)

Induction
Route:
intradermal
Vehicle:
water
Concentration / amount:
5%
Day(s)/duration:
0
Adequacy of induction:
not specified
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
50%
Day(s)/duration:
on Day 14, 24 hour
Adequacy of challenge:
not specified
No. of animals per dose:
10/sex
Details on study design:
A range-finding study was conducted to select appropriate concentrations for the intradermal and epicutaneous procedures. Animals were inspected 24 and 48 hr after dosing for signs of necrosis and ulceration.

In the definitive sensitization test, groups of 10 male and 10 female guinea pigs each received 0.1 ml intradermal induction injections into 2 sites of the clipped shoulder skin as follows: 50% (v/v) Freund's complete adjuvant (FCA) water emulsion, the test material or vehicle, and the test material in FCA/water emulsion or FCA/water emulsion. Epicutaneous inductions were conducted 7 days later. The test material was applied to saturation ((0.2 ml) to a 2 x 4 cm filter paper, which was then placed on the test site and secured with tape. The patches were left in place for 48 hr, after which they were removed and the skin wiped free of any excess test material. Epicutaneous challenge was undertaken by applying 2 x 2 cm filter paper squares soaked in the appropriate concentration of the test material to a previously untreated site (right flank) 14 days after epicutaneous induction (i.e., 21 days from the start of the study). Patches were left in place for 24 hr, and the sites inspected for signs of irritation 24-48 hr after removal of the occlusive dressings.

Seven days after the challenge exposure(i.e., 28 days from the start of the study), the cross-challenge treatment was administered. Test materials were administered to the clipped skin in a similar manner as in the challenge phase but at previously untreated sites (left flank). Smaller patches (0.825 in2 adhesive bandages) were used in order to allow all of the test materials to fit on the test site. Materials were applied to saturation (0.03 ml per patch). Patches were left in place for 24 hr and the sites inspected for signs of irritation 24-48 hr after removal of the occlusive dressings.
Challenge controls:
Irritation control animals, five male and five female guinea pigs, received the same challenge procedures as in the definitive sensitization study, but did not have preceding intradermal and/or epicutaneous induction procedures. This allowed differentiation between primary skin irritation due to the test material, and those produced by a hypersensitivity reaction.

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
5% intradermal, 50% epicutaneous induction, 25% challenge
No. with + reactions:
5
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
10
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
Not included
No. with + reactions:
0
Total no. in group:
0

Any other information on results incl. tables

Based on the probe study, the maximum concentrations used were 5% for the intradermal induction, 50% for epicutaneous induction and 25% for epicutaneous challenge phases. 

In the definitive study, five of 20 guinea pigs had a positive response.
 

In the cross-reaction phase, animals induced with 50% demonstrated a greater response with diethylenetriamine (55%), hydroxyethylethylenediamine (75%), triethylenetetramine (45%) and piperazine (30%).
 Less of a response was observed in animals treated with ethylenediamine and tetraethylenepentamine (0 and 5% responded positive, respectively).

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information
Conclusions:
Positive in guinea pig maximization test.

Positive results were also obtained in a cross challenge with several structurally similar alkyleneamines.
Executive summary:

The dermal sensitization potential was examined in the Guinea Pig Maximization Assay with aminoethylpiperazine (AEP). Cross-reactivity was also examined with structurally similar ethyleneamines. In this assay, AEP was positive and was shown to produce positive results when cross challenged with several structurally similar alkyleneamines.