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Administrative data

Description of key information

not sensitising to skin (technical products: 50% MPAAU in water)

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

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:
other: Guideline study with GLP and without deviations.
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Existing guideline study data under GLP were considered to be sufficient for REACH registration.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Route:
intradermal
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100% v/v / 0.1 mL test chemical per site
Day(s)/duration:
Day 1 / single application
Adequacy of induction:
highest technically applicable concentration used
Route:
epicutaneous, semiocclusive
Concentration / amount:
100% v/v / 0.5 mL undiluted test substance
(treatment of all animals with 10% SDS approximately 24 hours before the epidermal induction, on Day 7)
Day(s)/duration:
Day 8 / 48 hours
Adequacy of induction:
highest technically applicable concentration used
No.:
#1
Route:
epicutaneous, semiocclusive
Vehicle:
water
Concentration / amount:
1st Challenge, Topical Application: 100% , 50%, and 25% test item and the vehicle (0.05 ml)
Day(s)/duration:
Day 22 / single application / 24 hours
Adequacy of challenge:
highest non-irritant concentration
No.:
#2
Route:
epicutaneous, semiocclusive
Vehicle:
water
Concentration / amount:
2nd Challenge, Topical Application: 100% , 50%, and 25% test item and the vehicle (0.05 ml)
Day(s)/duration:
Day 28 / 24 hours
Adequacy of challenge:
highest non-irritant concentration
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 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.
Key result
Reading:
other: Second challenge - Day 32 readings
Hours after challenge:
48
Group:
test chemical
Dose level:
2nd Challenge, Topical Application: 100% , 50%, and 25% test item and the vehicle (0.05 ml)
No. with + reactions:
0
Total no. in group:
9
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: Second challenge - Day 31 readings
Hours after challenge:
24
Group:
test chemical
Dose level:
2nd Challenge, Topical Application: 100% , 50%, and 25% test item and the vehicle (0.05 ml)
No. with + reactions:
0
Total no. in group:
9
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation
Reading:
other: First challenge - Day 24 readings
Hours after challenge:
24
Group:
test chemical
Dose level:
1st Challenge, Topical Application: 100% , 50%, and 25% test item and the vehicle (0.05 ml)
No. with + reactions:
3
Total no. in group:
9
Clinical observations:
skin reaction, grade 1
Remarks on result:
other: In the first challenge phase, 4 animals showed sporadic and inconsistent skin reactions. For confirmation, a 2nd challenge was performed one week later to the same concentrations.
Reading:
other: First challenge - Day 25 readings
Hours after challenge:
48
Group:
test chemical
Dose level:
1st Challenge, Topical Application: 100% , 50%, and 25% test item and the vehicle (0.05 ml)
No. with + reactions:
2
Total no. in group:
9
Clinical observations:
none
Remarks on result:
other: In the first challenge phase, 4 animals showed sporadic and inconsistent skin reactions. For confirmation, a 2nd challenge was performed one week later to the same concentrations.
Key result
Reading:
other: First challenge - Day 24 readings
Hours after challenge:
24
Group:
negative control
Dose level:
1st Challenge, Topical Application: 100% , 50%, and 25% test item and the vehicle (0.05 ml)
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: First challenge - Day 25 readings
Hours after challenge:
48
Group:
negative control
Dose level:
1st Challenge, Topical Application: 100% , 50%, and 25% test item and the vehicle (0.05 ml)
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
ALPHA-HEXYLCINNAMICALDEHYD (85%)
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
not reported
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
ALPHA-HEXYLCINNAMICALDEHYD (85%)
No. with + reactions:
8
Total no. in group:
10
Clinical observations:
not reported
Remarks on result:
positive indication of skin sensitisation

One experimental animal was found dead on day 16. No clinical signs were 


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:
The test item was assessed for skin sensitization using the Magnusson & Kligman Maximisation test (OECD 406). None of the animals showed skin reactions with the test item by the second challenge. These data clearly demonstrate that the test item has no sensitization potential.
Therefore, the test item is not to be classified as "sensitizer".
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 2003-10-22 till 2004-04-05
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study with GLP and without deviations.
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
1992
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The existing guideline study data under GLP were considered to be sufficient for REACH registration.
Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Route:
intradermal
Vehicle:
water
Concentration / amount:
5% test item v/v
Day(s)/duration:
Day 0/single application
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Concentration / amount:
100% test item (0.2 ml undiluted)
Day(s)/duration:
Day 7 / 48 hours
Adequacy of induction:
highest technically applicable concentration used
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: water and Freunds Complete Adjuvant
Concentration / amount:
100% test item (0.2 ml undiluted)
Day(s)/duration:
Day 21 / 24 hours
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
20 animals
Details on study design:
Three pairs of intradermal injections each of 0.1mL volume, were given in the scapular region, in such a way that each pair of injedction was sited contrlaterally to the median line of the animal.
Injection 1: a 1:1 mixture (v/v) Freund's Complete Adjuvant (FCA) with distilled water
Injection 2: 5 % test item in distilled water
Injection 3: 5 % test item in distilled water formulated in a mixture (v/v) FCA with distilled water.
Injection No 1 and 2 were administered close to each other on the scapular region while injection No 3 was administered towards the caudal part of the test area.

Criteria of the harmonised system for classification of chemicals (OECD, August 2001):
When an adjuvant type test method is used, a response at least of 30% of the animlas is considered as positive.
Challenge controls:
10 animals
Positive control substance(s):
yes
Remarks:
2-mercaptobenzothiazole
Positive control results:
The results of using 2-mercaptobenzothiazole as positive control confirmed the skin sensitisation potential of 2-mercaptobenzothiazole and thereby the sensitivity and reliability of skin sensitisation study in guinea pig.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.2 mL of undiluted test item
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No clinical signs related to treatment were observed.
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.2 mL of undiluted test item
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No clinical signs related to treatment were observed.
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0.2 mL of distilled water
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none observed
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.2 mL of distilled water
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none observed
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
2-Mercaptobenzothiazole
No. with + reactions:
12
Total no. in group:
20
Clinical observations:
12 GP showed skin response grade 1 and above (0,1,2,3)
Remarks on result:
positive indication of skin sensitisation
Remarks:
60% positive
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
2-Mercaptobenzthiazole
No. with + reactions:
7
Total no. in group:
20
Clinical observations:
7 GP showed skin response grade 1 and above (0,1,2,3)
Remarks on result:
positive indication of skin sensitisation
Remarks:
35% positive
Interpretation of results:
GHS criteria not met
Conclusions:
The test item was assessed for skin sensitization using the Magnusson & Kligman Maximisation test (OECD 406). Based on the results of an irritancy study, 5% concentration of FLAMMENTIN MSG in distilled water was selected for intradermal induction. 0.2 mL of undiluted technical MPAAU (FLAMMENTIN MSG) was selected for topical application during induction and challenge exposure.
The skin of the guinea pigs was observed at 24 and 48 hours after the end of the challenge exposure and the skin reactions were graded as per Magnusson and Kligman grading scale. None of the animals challenged with the test item exhibit positive skin response. No clinical signs related to treatment were observed during the study. 60% of the positive control animals exhibit positive responses at 24 hours and 35% of the positive control animals exhibit positive skin reactions at 48 hours. No systemic toxicity has been observed during the experimental period.
These data clearly demonstrate that the test item has no sensitization potential. Therefore, the test item is not to be classified for the endpoint.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Migrated from Short description of key information:
No positive reactions were observed in two Guinea pig maximisation tests with the substance.

Justification for selection of skin sensitisation endpoint:
No study selected because both GLP studies are with Klimisch score 1 and are negative.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:
Migrated from Short description of key information:
no data; not necessary.

Justification for classification or non-classification

According to the GHS criteria, listed in Annex I, the substance does not have to be classified as a hazardous substance regarding sensitisation.