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Description of key information

In a GPMT (guinea pig maximisation test) 0 out of 20 animals showed a positive reaction.


 

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:
1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
EPA OTS 798.4100 (Skin Sensitisation)
Principles of method if other than guideline:
Tributyl phosphate (0.3 ml of a 10% mixture in mineral oil) was applied topically to the left shoulders (previously clipped free of hair) of 10 male and 10 female Hartley guinea pigs (test group). The test material mixture was left in contact with the skin for approximately 6 hours. The animals received 3 induction treatments one week apart. A concurrent positive control group of 10 animals (5 male and 5 female) was treated in a similar manner with DNCB (Dinitrochlorobenzene) (0.15%). An additional 10 animals (5 male and 5 female) were treated in a similar manner with mineral oil as a vehicle control group.
14 days after the third induction treatment, the animals were challenged with the test material mixture at a virgin skin site on the right shoulder. An additional 5 male and 5 female naive animals received 0.3 ml of the test material mixture (challenge control group). The positive control group was challenged with DNCB. The vehicle control group was challenged with mineral oil. Observations for skin reactions were recorded at 24 and 48 hours after each application. body weights were recorded at initiation and termination.
GLP compliance:
yes
Type of study:
open epicutaneous test
Justification for non-LLNA method:
The LLNA was not available at the time the study was conducted.
Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hazleton Research ANimals, Inc., Denver, Pennsylvania
- Housing: individually
- Weight at study initiation: 350 g to 470 g
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libtium


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 66 to 72°F
- Humidity (%): 17 to 63%
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12/12
- IN-LIFE DATES: December 1989 to 1990
Route:
epicutaneous, occlusive
Vehicle:
other: ethanol
Concentration / amount:
0.15% of positive control DNCB
Day(s)/duration:
6 hours; once weekly for 3 week
Route:
epicutaneous, occlusive
Vehicle:
other: mineral oil
Concentration / amount:
10 % of the test item
Day(s)/duration:
6 hours; once weekly for 3 weeks
Adequacy of induction:
other: highest non-irritating concentration
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: mineral oil
Concentration / amount:
10 %
Day(s)/duration:
6 hours
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
20 (10 male and 10 female guinea pigs) in the test item group; 10 animals in the positive control group, challenge control group and vehicle control group
Details on study design:
RANGE FINDING TESTS:
test on 2 animals; concentrations of 0.1, 1, 10 and 21% were tested; 10% was the highest non-irritating concentration

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6h
- Test groups: 10% test item
- Control group: vehicle only (mineral oil)

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 2
- Exposure period: 6 h
- Test groups: 10% test item
- Control group: 10% test item
Challenge controls:
yes
Positive control substance(s):
yes
Remarks:
1-chloro-2,4-dinitrobenzene (DNCB)
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
challenge control and vehicle control
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Remarks on result:
other: no indication of irritation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
challence control and vehicle control
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Remarks on result:
other: no indication of irritation
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.15% in acetone
No. with + reactions:
9
Total no. in group:
9
Clinical observations:
moderate to severe eryhtema and slight to moderate edema
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.15% in acetone
No. with + reactions:
9
Total no. in group:
9
Clinical observations:
moderate to severe eryhtema and slight to moderate edema
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.3 ml of a 10% solution
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.3 ml of a 10% solution
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation

All animals remained healthy throughout the study, except one female in the positive control group which was sacrificed on day 2 due to an apparent broken back.

Interpretation of results:
GHS criteria not met
Executive summary:

Tributyl phosphate (0.3 ml of a 10% mixture in mineral oil) was applied topically to the left shoulders (previously clipped free of hair) of 10 male and 10 female Hartley guinea pigs (test group). The test material mixture was left in contact with the skin for approximately 6 hours. The animals received 3 induction treatments one week apart. A concurrent positive control group of 10 animals (5 male and 5 female) was treated in a similar manner with DNCB (Dinitrochlorobenzene) (0.15%). An additional 10 animals (5 male and 5 female) were treated in a similar manner with mineral oil as a vehicle control group.
14 days after the third induction treatment, the animals were challenged with the test material mixture at a virgin skin site on the right shoulder. An additional 5 male and 5 female naive animals received 0.3 ml of the test material mixture (challenge control group). The positive control group was challenged with DNCB. The vehicle control group was challenged with mineral oil. Observations for skin reactions were recorded at 24 and 48 hours after each application. body weights were recorded at initiation and termination.
No irritation was noted on any animal in the test, challenge control or vehicle control groups during the study. animals in the positive control group showed no skin reactions after the first induction application. Mild to moderate erythema was noted after the second induction and mild to severe erythema, edema and eschar were noted after the third induction application. At challenge, all positive control animals exhibited severe reactions.
Under the conditions of this study, the test material is judged to be non-sensitizing when topically applied to Hartley guinea pigs.

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

Tributyl phosphate (0.3 ml of a 10% mixture in mineral oil) was applied topically to the left shoulders (previously clipped free of hair) of 10 male and 10 female Hartley guinea pigs (test group). The test material mixture was left in contact with the skin for approximately 6 hours. The animals received 3 induction treatments one week apart. A concurrent positive control group of 10 animals (5 male and 5 female) was treated in a similar manner with DNCB (Dinitrochlorobenzene) (0.15%). An additional 10 animals (5 male and 5 female) were treated in a similar manner with mineral oil as a vehicle control group.
14 days after the third induction treatment, the animals were challenged with the test material mixture at a virgin skin site on the right shoulder. An additional 5 male and 5 female naive animals received 0.3 ml of the test material mixture (challenge control group). The positive control group was challenged with DNCB. The vehicle control group was challenged with mineral oil. Observations for skin reactions were recorded at 24 and 48 hours after each application.


No irritation was noted on any animal in the test, challenge control or vehicle control groups during the study. Animals in the positive control group showed no skin reactions after the first induction application. Mild to moderate erythema was noted after the second induction and mild to severe erythema, edema and eschar were noted after the third induction application. At challenge, all positive control animals exhibited severe reactions.
Under the conditions of this study, the test material is judged to be non-sensitizing when topically applied to Hartley Guinea pigs.


 


A human patch test showed no sensitization in 53 volunteers exposed to 15 application of a < 5% solution of tributyl phosphate.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

In a GPMT the test material is juged to be non-sensitising when topically applied to hartley guinea pigs. Therefore a classification is not justified.