Registration Dossier

Diss Factsheets

Toxicological information

Skin sensitisation

Currently viewing:

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
22 May 2018 - 29 June 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
July 17th, 1992
Deviations:
yes
Remarks:
A relative humidity higher than 70% was registered. A temperature higher than 25°C was registered. As no effect was noted on the health of the animals, this deviation is considered as without impact on the conclusion of the study.
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
There are significant concerns raised in the toxicology literature regarding the suitability of the LLNA methodology for the assessment of surfactant substances. The literature recommends that in vivo testing of surfactants for sensitizing potential should be done using one of the available guinea pig test guidelines to insure the highest relevance of the results to humans ie either the Buehler or the GPMT. Generally the latter is considered to be the more rigorous of the two methods since it maximizes the conditions to provoke sensitization. Furthermore in this case the selection of this assay allows the results to be directly compared to the GPMT data on the analogue substances, as part of the discussion on read-across.

Test material

Constituent 1
Reference substance name:
9-Octadecenoic acid (Z)-, reaction products with diethylenetriamine, di-Me sulfate-quaternized
EC Number:
308-415-1
EC Name:
9-Octadecenoic acid (Z)-, reaction products with diethylenetriamine, di-Me sulfate-quaternized
Cas Number:
97953-16-7
IUPAC Name:
9-Octadecenoic acid (Z)-, reaction products with diethylenetriamine, di-Me sulfate-quaternized
Specific details on test material used for the study:
Batch No.: RL 55/17
Expiry date: 31 January 2019

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
5, 6, 7 or 8 weeks old at the beginning of the test.

Study design: in vivo (non-LLNA)

Induction
Route:
intradermal and epicutaneous
Vehicle:
physiological saline
Remarks:
Distilled water for topical applications.
Concentration / amount:
Intradermic injection at 0.025% and topical application at 10%
Adequacy of induction:
non-irritant substance, but skin pre-treated with 10% SDS
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
5% and diluted at 2.5% in distilled water
Day(s)/duration:
24 hours
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
GROUP 1 (negative control): 10 male guinea pigs.
GROUP 2 (treated): 20 male guinea pigs/dose.
Challenge controls:
Physiological saline and distilled water.
Positive control substance(s):
no

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Hours after challenge:
24
Group:
test chemical
Dose level:
5%
No. with + reactions:
8
Total no. in group:
20
Clinical observations:
Moderate erythema, discrete erythema and no cutaneous reaction was noted in 11, 6 and 3 animals, respectively, 24 hours after first induction. A scab and dryness of the skin was noted in 15 and 5 animals, respectively, after the second induction.
Remarks on result:
positive indication of skin sensitisation
Key result
Hours after challenge:
48
Group:
test chemical
Dose level:
5%
No. with + reactions:
7
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Key result
Hours after challenge:
72
Group:
test chemical
Dose level:
5%
No. with + reactions:
5
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Hours after challenge:
24
Group:
test chemical
Dose level:
2.5%
No. with + reactions:
8
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Key result
Hours after challenge:
48
Group:
test chemical
Dose level:
2.5%
No. with + reactions:
6
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Key result
Hours after challenge:
72
Group:
test chemical
Dose level:
2.5%
No. with + reactions:
4
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation

Applicant's summary and conclusion

Interpretation of results:
Category 1A (indication of significant skin sensitising potential) based on GHS criteria
Conclusions:
The substance produced positive skin sensitisation results and therefore has to be classified in category 1 (sub-category 1A) as a skin sensitizer.
Executive summary:

A Guinea Pig Maximisation Test was undertaken to evaluate the possible allergenic activity of the substance after intradermal and topical administration in guinea pigs. The induction phase (intradermic injection at 0.025% and topical application at 10%) was conducted with the substance to 20 Guinea pigs and a 10-day rest phase. The challenge phase conducted under occlusive dressing for 24 hours, consisted of a single topical application of the test item at 5% and diluted at 2.5% in distilled water. In the treated group (treatment dose of 5%), a discrete to intense erythema was noted in 40% (8/20), 35% (7/20) and 25% (5/20) of the animals, 24, 48 and 72 hours after the challenge phase, respectively. In the control group (associated with the treatment dose of 5%), no macroscopic cutaneous intolerance reactions were recorded after the challenge phase. In the treated group (treatment dose of 2.5%), a moderate to intense erythema was noted in 40% (8/20), 30% (6/20) and 20% (4/20) of the animals, 24, 48 and 72 hours after the challenge phase, respectively. In the control group (associated with the treatment dose of 2.5%, no macroscopic cutaneous intolerance reactions were recorded after the challenge phase. In conclusion, under these experimental conditions, the substance produced positive skin sensitisation results and therefore has to be classified in category 1 (sub-category 1A) as a skin sensitizer.