Triisobutyl phosphate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPP 81-6 (Skin Sensitisation)

GLP compliance:

yes

Type of study:

Buehler test

Justification for non-LLNA method:

study was conducted before implementation of LLNA

Test material

Test material information

Constituent 1

Reference substance name:

Triisobutyl phosphate

EC Number:

204-798-3

EC Name:

Triisobutyl phosphate

Cas Number:

126-71-6

Molecular formula:

C12H27O4P

IUPAC Name:

triisobutyl phosphate

Specific details on test material used for the study:

- Name of test material: Etingal
- Physical state: liquid, achromatic
- Lot/batch No.: MG-94-37
- Storage condition of test material: room temperature
- Substance number: 94/261

In vivo test system

Test animals

Species:

guinea pig

Strain:

other: Pirbright White, Dunkin Hartley Crl: (HA)BR (SPF)

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Charles River GmbH - Wiga, Sulzfeld, FRG
- Age at study initiation: Young adult animals
- Weight at study initiation: 313 - 388 g
- Housing: No. of animals per cage: 5. Type of cage: Makrolon, type IV. Bedding: Granulat Typ 3/4 (staubfrei); SSNIFF
- Diet (ad libitum): Kliba Labordiät 341 (Kaninchen- Meerschweinchen-Haltungsdiät)
- Water (ad libitum): tap water; about 2 g of ascorbic acid per 10 l water was added to the drinking water twice a week
- Acclimation period: 8 days before the beginning of the study in the laboratory for dermal toxicity

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24°C
- Humidity (%): 30 - 70% .
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12h light (6.00 a.m. - 6.00 p.m.) 12 h darkness (6.00 p.m. - 6.00 a.m.)

IN-LIFE DATES:
Not specified

Study design: in vivo (non-LLNA)

Induction

Route:

epicutaneous, occlusive

Vehicle:

other: olive oil

Concentration / amount:

75 % / 0.5 mL

Day(s)/duration:

3 times (once per week) for 6 hours, respectively

Challenge

Route:

epicutaneous, occlusive

Vehicle:

other: olive oil

Concentration / amount:

50 % / 0.5 mL

Day(s)/duration:

6 hours

No. of animals per dose:

Pretest: 4
Main test;
- control group: 10
- test group: 20

Details on study design:

2 x 2 cm gauze patches were applied to the skin of the flanks under an occlusive dressing (the bandage consists of rubberized linenpatches 4 x 4 cm
from Russka, test patch of Idealbinde 5 x 5 cm from Pfälzische Verbandstoff-Fabrik, and Fixomull® Stretch (adhesive fleece) from Beiersdorf AG). 0.5 mL of the test substance or test substance preparations were exposed to the animals.

RANGE FINDING TESTS:
Duration of exposure: 6 hours
Site of application: right and left flank
Application frequency: 2 times (one application per week) on the same application area
Number of test animals: 4 per test concentration
Readings: 24 and 48 h after the removal of the patch
Assessment of skin findings: according to Draize, J.H. (1959)

MAIN STUDY
A. INDUCTION EXPOSURE
- Exposure period: 6 hours
- Test groups: 20 animals
- Control group: 10 animals
- Site: anterior left flank
- Frequency of applications: 3 times (one application per week; days 0, 7 and 14) on the same application area
- Concentrations: 75%

B. CHALLENGE EXPOSURE
- Day(s) of challenge: 14 days after the third induction
- Exposure period: 6 hours
- Test groups: 20 animals
- Control group: 10 animals
- Site: Substance formulation: anterior right flank. Vehicle: posterior right flank
- Concentrations: 50%
- Evaluation (hr after challenge): 24 and 48 h after the removal of the patch

Challenge controls:

Treatment of the test group and of control group 1 with the test substance formulation. Additionally olive oil DAB 10 was applied as a vehicle. Control group 2 only received olive oil DAB 10.

Positive control substance(s):

yes

Remarks:

alpha-hexylcinnamaldehyde

Results and discussion

Positive control results:

The positive control showed that the test system was able to detect sensitizing compounds under laboratory conditions chosen.

In vivo (non-LLNA)

Results

Results 1

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

0.5 ml

No. with + reactions:

9

Total no. in group:

18

Clinical observations:

very slight erythema

Remarks on result:

other:

Results 2

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Results 3

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

undiluted

No. with + reactions:

4

Total no. in group:

20

Remarks on result:

positive indication of skin sensitisation

Remarks:

No concurrent positive control group. Separate studies were performed twice a year in the laboratory. The results of the latest study are reported.