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Description of key information

GPMT (Magnusson and Kligman), GLP not specified, reliability 2: not sensitizing


FCAT, GLP not specified, reliability 2: not sensitizing

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:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
1992
Deviations:
yes
Remarks:
No information regarding a reliability check of the test procedure; choice of the vehicle and justification for its usage not given; negative control data are not presented
Principles of method if other than guideline:
GPMT according to Magnusson and Kligman 1970
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The Guinea Pig Maximization Test (GPMT) has been carried out as an animal test to predict human sensitization for over a decade and is recommended by international test guidelines such as OECD. The available data do not justify conducting an additional LLNA due to animal welfare.
Specific details on test material used for the study:
- Source: Polyscience Inc., Warrington, USA
- Purity: > 99%
Species:
guinea pig
Strain:
other: Himalayan white spotted outbred strain
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Inst. for Biomedical Research, Füllinsdorf, CH
- Weight at study initiation: 350 - 450 g
- Housing: in pairs
- Diet (e.g. ad libitum): pellet diet containing vitamin C
Route:
intradermal
Vehicle:
peanut oil
Concentration / amount:
0.5 M/ 0.1 mL
Day(s)/duration:
day 0/ single injection
Adequacy of induction:
not specified
Route:
epicutaneous, occlusive
Vehicle:
other: 80 % ethanol
Concentration / amount:
1 M/ 1 mL
Day(s)/duration:
day 7-9
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: unclear: pet., peanut oil or Aramek
Concentration / amount:
highest non-irritant concentration and 2 lower concentrations (not further specified)/ 0.025 mL
Day(s)/duration:
day 21-22
Adequacy of challenge:
highest non-irritant concentration
No.:
#2
Route:
epicutaneous, open
Vehicle:
other: unclear: pet., peanut oil or Aramek
Concentration / amount:
highest non-irritant concentration and 2 lower concentrations (not further specified)/ 0.025 mL
Day(s)/duration:
day 35
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
10 (control 6)
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: up to 7 days
- Test groups: 3 pairs of intradermal injections (day 0): 1: FCA alone, 2: test material in vehicle, 3; test material in FCA; epicutaneous application (day 7)
- Control group: These animals received the same treatment without the test material
- Site: shoulder region, the injections with FCA and the test material in vehicle were close to each other and nearest to he head; the injection with FCA and the test material was caudally
- Frequency of applications: 3 injections, 1 epicutaneous application
- Duration: day 0- day 9
- Concentrations: 0.5 M (intradermal), 1 M (epicuateneous)

B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: day 21 and day 35
- Exposure period: 24 h (occlusive treatment)
- Test groups: epicutaneous application occlusive and open
- Control group: these animals received the same treatment; in addition the vehicle was tested alone
- Site: right flank (day 21), left flank (day 35)
- Concentrations: highest non-irritant concentration and two lower concentrations (not further specified)
- Evaluation (hr after challenge): 1st and 2nd challenge: 48 and 72 h

other: The maximum non-irritant concentration was determined in a pre-test. The used vehicle was Aramek (oleum arachidis/methylethylketone). Progressively dilutions of the test material were investigated after 24 and 48 h after single open application the clipped flank of 8 animals.
Challenge controls:
6 animals
Positive control substance(s):
no
Positive control results:
not included
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
highest non-irritant concentration and two lower concentrations
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no data
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
72
Group:
test chemical
Dose level:
highest non-irritant concentration and two lower concentrations
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no data
Remarks on result:
no indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
highest non-irritant concentration and two lower concentrations
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no data
Remarks on result:
no indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
72
Group:
test chemical
Dose level:
highest non-irritant concentration and two lower concentrations
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no data
Remarks on result:
no indication of skin sensitisation
Interpretation of results:
GHS criteria not met
Conclusions:
The test substance was not sensitizing under the conditions of the present study in guinea pigs.
Executive summary:

A publication is available which asesses the potential of the test substance to induce delayed contact hypersensitivity using the guinea pig maximization test (GPMT) based on the method of Magnusson and Kligman in a non-GLP conform study.


The concentrations of the test substance suitable for use in the main experiment were determined in a pretest. The minimum irritant concentration was determined in FCA pretreated animals. The maximum non-irritant concentration also was determined. The used vehicle in the pre-test was Aramek (oleum arachidis/methylethylketone). For the intradermal induction on day 0, 3 pairs of injections were set on the clipped shoulder region. One injection was with FCA alone, the second injection was the test material (0.5 M) in vehicle (peanut oil), the third injection was the test material (0.5 M) in FCA. On day 7, an epicutaneous induction with 1 M test material in the vehicle (80% ethanol) (the concentration giving a slight to moderate irritation) was performed on the same shoulder region. The challenge was performed on day 21 (epicutaneous, occlusive) and day 35 (epicutaneous, open) thereafter. The highest concentration tested was the maximum non-irritating concentration. In addition two lower concentrations and the vehicle were tested. The results were graded according to the classification of Magnusson & Kligman. Both challenges exhibited no positive reactions (0/10 animals).


Based on the results of this study it was concluded that t-butyl methacrylate does not have a sensitizing effect on the skin of the guinea pig in the Maximization Test under the test conditions chosen.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Principles of method if other than guideline:
The study was conducted according to the method described by Klecak (1977) and Klecak and Geleick (1977):
Klecak (1977), Dermatoxicology and Pharmacology. Eds, Marzulli F N, Maibach H I. New York: John Wiley & Sons.
Klecak and Geleick (1977), Journal of the Society of Cosmetic Chemists, 28: 53.

Freund's complete adjuvant test (FCAT): The guinea pigs were intradermally injected with 0.5 M of test substance in FCA and distilled water 5 times (day 0-9). On day 21 (challenge) and day 35 (rechallenge), the flank of the animals was treated epicutaneously in an open manner with different test substance concentrations including the highest non-irritant concentration and the skin reaction was observed 24 and 48 h after each application.
GLP compliance:
not specified
Type of study:
Freund's complete adjuvant test
Justification for non-LLNA method:
The Freund's complete adjuvant test has been carried out as an animal test to predict human sensitization. The reliable study data would not justify conducting an additional LLNA due to animal welfare.
Specific details on test material used for the study:
- Source: Polyscience Inc., Warrington, USA
- Purity: > 99%
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Olac Ltd., Bicester, GB
- Weight at study initiation: 350 - 450 g
- Housing: in pairs
- Diet (e.g. ad libitum): pellet diet containing vitamin C
Route:
intradermal
Vehicle:
other: Freund´s Complete Adjuvant and distilled water
Concentration / amount:
0.5 M/ 0.1 mL
Day(s)/duration:
days 0, 2, 4, 7, 9
Adequacy of induction:
not specified
No.:
#1
Route:
epicutaneous, open
Vehicle:
other: Freund´s Complete Adjuvant and distilled water
Concentration / amount:
highest non-irritant concentration and 2 lower concentrations (not further specified)/ 0.025 mL
Day(s)/duration:
day 21
Adequacy of challenge:
highest non-irritant concentration
No.:
#2
Route:
epicutaneous, open
Vehicle:
other: Freund´s Complete Adjuvant and distilled water
Concentration / amount:
highest non-irritant concentration and 2 lower concentrations (not further specified)/ 0.025 mL
Day(s)/duration:
day 35
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
8 (experimental group), 4-6 (control)
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 5 times 0.1 mL on day 0, 2, 4, 7 and 9

B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: day 21 and day 35
- Evaluation (hr after challenge): readings after 24 and 48 h

other: The maximum non-irritant concentration was determined in a pre-test. The used vehicle was Aramek (oleum arachidis/methylethylketone). Progressively dilutions of the test material were investigated after 24 and 48 h after single open application the clipped flank of 8 animals.
Challenge controls:
4-6 animals
Positive control substance(s):
no
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
highest non-irritant concentration and 2 lower concentrations (not further specified)/ 0.025 mL
No. with + reactions:
0
Total no. in group:
8
Clinical observations:
no data
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
highest non-irritant concentration and 2 lower concentrations (not further specified)/ 0.025 mL
No. with + reactions:
0
Total no. in group:
8
Clinical observations:
no data
Remarks on result:
no indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
highest non-irritant concentration and 2 lower concentrations (not further specified)/ 0.025 mL
No. with + reactions:
0
Total no. in group:
8
Clinical observations:
no data
Remarks on result:
no indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
highest non-irritant concentration and 2 lower concentrations (not further specified)/ 0.025 mL
No. with + reactions:
0
Total no. in group:
8
Clinical observations:
no data
Remarks on result:
no indication of skin sensitisation
Interpretation of results:
GHS criteria not met
Conclusions:
The test substance was not sensitizing under the conditions of the present study in guinea pigs.
Executive summary:

A publication is available which asesses the potential of the test substance to induce delayed contact hypersensitivity was assessed using the Freund's complete adjuvant test (FCAT), in a non-GLP study.


The concentrations of the test substance suitable for use in the main experiment were determined in a pretest. The minimum irritant concentration was determined in FCA pretreated animals. The maximum non-irritant concentration also was determined. The used vehicle in the pre-test was Aramek (oleum arachidis/methylethylketone). The guinea pigs were intradermally injected with 0.5 M of test substance in FCA and distilled water 5 times (day 0-9). On day 21 (challenge) and day 35 (rechallenge), the flank of the animals was treated epicutaneously in an open manner with different test substance concentrations including the highest non-irritant concentration and the skin reaction was observed 24 and 48 h after each application. The FCAT was carried out with 8 animals which showed no sensitising effects (0/8 animals) in the challenge and rechallenge.


 


Based on the results of this study it was concluded that the test material does not have a sensitizing effect on the skin of the guinea pig in the Maximization Test under the test conditions chosen.

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

A publication is available which asesses the potential of the test substance to induce delayed contact hypersensitivity using the guinea pig maximization test (GPMT) based on the method of Magnusson and Kligman and in the Freund's complete adjuvant test (FCAT), both in a non-GLP conform study with a reliability of 2 (van der Walle et al., 1982).


The concentrations of the test substance suitable for use in the main experiment were determined in a pretest. The minimum irritant concentration was determined in FCA pretreated animals. The maximum non-irritant concentration also was determined. The used vehicle in the pre-test was Aramek (oleum arachidis/methylethylketone). For the intradermal induction in the GPMT 3 pairs of injections were set on the clipped shoulder region on day 0. One injection was with FCA alone, the second injection was the test material (0.5 M) in vehicle (peanut oil), the third injection was the test material (0.5 M) in FCA. On day 7, an epicutaneous induction with 1 M test material in the vehicle (80% ethanol) (the concentration giving a slight to moderate irritation) was performed on the same shoulder region. The challenge was performed on day 21 (epicutaneous, occlusive) and day 35 (epicutaneous, open) thereafter. The highest concentration tested was the maximum non-irritating concentration. In addition two lower concentrations and the vehicle were tested. The results were graded according to the classification of Magnusson & Kligman. Both challenges exhibited no positive reactions (0/10 animals).


In the FACT, the guinea pigs were intradermally injected with 0.5 M of test substance in FCA and distilled water 5 times (day 0-9). On day 21 (challenge) and day 35 (rechallenge), the flank of the animals was treated epicutaneously in an open manner with different test substance concentrations including the highest non-irritant concentration and the skin reaction was observed 24 and 48 h after each application. The FCAT was carried out with 8 animals which showed no sensitising effects (0/8 animals) in the challenge and rechallenge.


Based on the results of the above mentioned studies it was concluded that the test substance does not have a sensitizing effect on the skin of the guinea pig under the test conditions chosen in both studies.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification