Registration Dossier

Administrative data

Description of key information

The read-across substance MPAAU is not classified as "sensitizer".

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 1995-05-24 till 1995-09-12
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Data from a reliable in vivo test conducted before the enforcement of Commission Regulation (EU) 640/2012 of 06 July 2012 amending, for the purpose of its adaptation to technical progress, Regulation (EC) No 440/2008 laying down test methods pursuant to Regulation (EC) No 1907/2006 of the European Parliament and of the Council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) are available.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Route:
intradermal
Vehicle:
other: water and Freund's Complete Adjuvant
Concentration / amount:
undiluted test substance
Day(s)/duration:
Day 3
Adequacy of induction:
highest technically applicable concentration used
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
undiluted test substance
Day(s)/duration:
Day 10
Adequacy of induction:
highest technically applicable concentration used
No.:
#1
Route:
epicutaneous, occlusive
Concentration / amount:
100 % , 50 %, and 25 % test item and the vehicle (0.05 ml)
Day(s)/duration:
Day 22
No.:
#2
Route:
epicutaneous, occlusive
Concentration / amount:
100 % , 50 %, and 25 % test item and the vehicle (0.05 ml)
Day(s)/duration:
Day 38
No. of animals per dose:
Preliminary study: 4 females
Experimental group: 10 females
Control group: 5 females
Details on study design:
Based on the results of the preliminary study, the test substance concentrations for the main study were selected to be the undiluted test substance for the intradermal and epidermal induction exposures.
Since no or negligible signs of irritation were observed to the concentration selected for the epidermal induction, it was decided to treat all animals with 10 % SDS approximately 24 hours before the epidermal induction.
The undiluted and a 50 % and 25 % concentration were selected for the challenge phase.
Positive control substance(s):
yes
Remarks:
alpha-Hexylcinnamicaldehyde techn. 85%
Positive control results:
The results of using alpha-Hexylcinnamicaldehyde (techn. 85 %) as positive control confirmed the skin sensitisation potential of alpha-Hexylcinnamicaldehyde and thereby the sensitivity and reliability of skin sensitisation study in guinea pig.
Reading:
other: Challenge
Hours after challenge:
48
Group:
test group
Dose level:
100, 50 and 25 %
No. with + reactions:
4
Total no. in group:
10
Clinical observations:
Skin reactions consisiting of grade 1, were observed in four experimental animals in response to the undiluted test substance only. No skin reactions were evident in the control animals.
Remarks on result:
other: first challenge
Reading:
rechallenge
Hours after challenge:
48
Group:
test group
Dose level:
all dose levels
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Reading:
other: challenge and rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
vehicle
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
no clinical signs
Reading:
other: challenge
Hours after challenge:
48
Group:
positive control
Dose level:
25, 10 and 5 %
No. with + reactions:
15
Total no. in group:
15
Remarks on result:
other: Skin reactions were observed in all the animals exposed to 25, 10 and 5 % exposure concentrations

Since the four animals, which showed skin reactions in the first challenge phase, showed no reactions in the second challenge to the same concentration, it was considered that these responses were non-specific signs of irritation and were not indicative of sensitisation. Therefore, it was concluded that no evidence was obtained that the test item had caused contact hypersensitivity in the guinea pig.

Interpretation of results:
GHS criteria not met
Conclusions:
MPAAU is not to be classified as "sensitizer".
Executive summary:

Assessment for Contact Hypersensitivity to MPAAU was carried out in a study conducted according to OECD Guideline 406 in the Albino Guinea Pig (Maximization Test) .

Test substance concentrations selected for the Main study were based on the results of a preliminary study. In the Main study, ten experimental animals were intradermally injected with and epidermally exposed to the undiluted test substance. Five control animals were similarly treated, but with omission of the test substance. Approximately 24 hours before the epidermal induction exposure all animals were treated with 10% SDS. Two weeks after the epidermal application all animals were challenged with a 100%, 50% and 25% test substance concentration and distilled water. A second challenge was performed one week later with the same test substance concentrations.

In the first challenge, skin reactions, consisting of grade 1, were observed in four experimental animals in response to the undiluted test substance only. No skin reactions were evident in the control animals. In the second challenge, no skin reactions were evident after the challenge exposure in the experimental and control animals.

Since the four animals, which showed skin reactions in the first challenge phase, showed no reactions in the second challenge to the same concentration, it was considered that these responses were non-specific signs of irritation and were not indicative of sensitisation. Therefore, it was concluded that no evidence was obtained that MPAAU had caused contact hypersensitivity in the guinea pig.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

The GLP study with the read-across substance MPAAU was conducted in female guinea pig according to TG 406 (Magnusson & Kligman Maximisation test). Alpha-Hexylcinnamicaldehyde tech. 85 % was used as positive control. Since the four animals, which showed skin reactions in the first challenge phase, showed no reactions in the second challenge to the same concentration, it was considered that these responses were non-specific signs of irritation and were not indicative of sensitisation. Therefore, it was concluded that no evidence was obtained that the test item had caused contact hypersensitivity in the guinea pig.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the above stated assessment of the skin sensitisation potential with read-across compound MPAAU, MPA does not need to be classified according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) or according to CLP (Regulation (EC) No 1272/2008 of the European Parliament and of the Council) as implementation of UN-GHS in the EU.