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Administrative data

Description of key information

The skin irritation potential was examined GLP-compliant according to OECD Guideline 404 in rabbits. Examination of the eye irritation potential was conducted comparable to current Guidelines in rabbits. As a result of the respective studies, Triisobutyl phosphate is not irritating to the skin and eye of rabbits.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Specific details on test material used for the study:
- Name of test material: Tri-iso-butylphosphat
- Substance type: colorless to slightly yellowish liquid
- Composition of test material, percentage of components: 90% Tri-iso-butylphosphat, 10% n-propanol
- Stability under test conditions: unknown; excluded from statement of compliance
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: SAVO med. Versuchstierzuchten GmbH
- Age at study initiation: males-14 weeks, females-15 weeks
- Weight at study initiation: males 2.4-2.5 kg, females 2.5 kg
- Housing: Individually in stainlesss steel cages equipped with an automatic cleaning and drinking system
- Diet (e.g. ad libitum): Pellet standard Kliba 341, rabbit maintenance diet ad libitum.
- Water (e.g. ad libitum): Community tap water, ad libitum
- Acclimation period: four days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 (+/- 3)
- Humidity (%): 40-70%
- Air changes (per hr):10-15
- Photoperiod (hrs dark / hrs light): 12/12
- Music during light period

IN-LIFE DATES: From: 27/02/1990 To: 06/03/1990
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
7 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 6 cm2
- Area of coverage: 3 cm x 3 cm
- Type of wrap if used: surgical gauze covered with semi-occlusive dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): lukewarm tap water
- Time after start of exposure: 4 hours

SCORING SYSTEM:
Erythema and Eschar formation: 0 (no erythema)-4 (Severe erythema (beet redness) to slight escar formation (injuries in depth)
Edema formation: 0 (no edema)-4 (severe edema (raised more than 1 mm and extending beyonmd area of exposure)
Maximum cumulative score: -8
Irritation parameter:
erythema score
Basis:
animal: # 16
Remarks:
male
Time point:
24/48/72 h
Score:
0.33
Max. score:
1
Reversibility:
fully reversible within: 48 h
Irritation parameter:
erythema score
Basis:
animal: # 17
Remarks:
male
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal: # 18
Remarks:
female
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal: # 16
Remarks:
male
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
animal: # 17
Remarks:
male
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
animal: # 18
Remarks:
female
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritant / corrosive response data:
primary irritation score of 0.78 when applied to intact rabbit skin.
local signs (mean 1 hour to 7 days) consisted of grade 0.67 eythema and grade 0.00 edema. Reversible until day 7 of test.
No corrosive effect was evident on the skin

The bodyweight gain was similar for all rabbits

No clinical symptoms or morality during test period
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
according to
Guideline:
EPA OPP 81-4 (Acute Eye Irritation)
Qualifier:
according to
Guideline:
other: TSCA
Principles of method if other than guideline:
A single dose was introduced into the lower conjuctival sac of the right eye of Albino rabbits (4 males and 2 females).
GLP compliance:
yes
Specific details on test material used for the study:
- Name of test material: Tri-isobutylphosphate
- Physical state: clear liquid
- Analytical purity: 99.7%
- Lot/batch No.: NBP 983659
- Storage condition of test material: Room temperature
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Summit View Farm Hazleton, Pennsylvania
- Age at study initiation: at least 8 weeks old
- Weight at study initiation: not specified
- Housing: individually housed. Cages: suspended, stainless steel
- Diet (ad libitum): Lab Rabbit Chow HF (Purina # 5326)
- Water (ad libitum): automatic watering system. Municipal water supply
- Acclimation period: not specified

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15.6-21.1 °C
- Humidity (%): 30-70%
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark

IN-LIFE DATES: not specified
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
Single dose
Observation period (in vivo):
3 days
Number of animals or in vitro replicates:
4 males and 2 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: no washing
- Time after start of exposure: approximately 24 hours after application, the treated eyes were rinsed to remove any residual test material

SCORING SYSTEM:
At each interval, the treated and control eyes were examined and scored for ocular reactions according to the Draize scale

TOOL USED TO ASSESS SCORE:
Fluorescein dye was used to confirm presence or absence of corneal ulceration in treated eyes starting with the 24 hour observation and at each subsequent observation until there was no stain retention for two observations .
Remarks on result:
other: See remark in Irritant/corrosive response data
Irritant / corrosive response data:
Tri-isobutylphosphate produced mild to moderate, transient ocular irritation. Irritation consisted primarily of conjunctival irritation (redness, chemosis, discharge) with the most severe effects occuring at one hour. One animal exhibited iridial changes at one hour. No corneal changes were seen. Four of the six animals were free of ocular irritation within 24 hours after instillation of the test material; the remaining two animals were free of ocular irritation within 48 to 72 hours.
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

In the key study, Triisobutyl phosphate (0.5 mL) was applied to the skin of New Zealand White rabbits in a GLP-compliant OECD guideline 404 study for 4 hours (3 animals) under semi-occlusive conditions. Animals were observed after 1, 24, 48 and 72 hours and at day 7 after removal of the dressing (RCC, 1990). Under the conditions of this experiment, Triisobutyl phosphate was found to cause a primary irritation score of 0.78 when applied to intact rabbit skin. Local signs (mean 1 hour to 7 days) consisted of grade 0.67 erythema and grade 0.00 edema. They were reversible until day 7 of test. No corrosive effect had occurred on the skin at any measuring interval.

Due to the results described above, the test article (Triisobutyl phosphate) had to be classified as not irritant to the skin of rabbits.

Supportingly, Triisobutyl phosphate was tested in 13 rabbits (BASF, 1953). 50% Triisobutyl phosphate in oil gives mild irritation on the rabbits back, but stronger irritation on the ears; partly haemorhagic and necrotic inflammation symptoms. 20% Triisobutyl phosphate showes only minor irritation or only hints of irritation. Triisobutyl phosphate was also tested in 6 New Zealand White rabbits according to EPA OPP 81-5 (Bio/dynamics, Inc., 1989). A mean overall irritation score was calculated at 3.1. The signs were fully reversible within 11 days. Furthermore, Triisobutyl phosphate was tested in 2 guinea pigs (Eastman Kodak, 1986). No edema with dark mottled redness at the lower dose, and moderate edema with most of area light gray and brown with some dark red visible at the higher dose was observed. At time of discard, no hair had regrown on area.

 

Eye irritation

The eye irritation potential of Triisobutyl phosphate was tested in rabbits, without rinsing, using a procedure that complied with the main requirements of two protocols (EPA OPP 81-4 (Acute Eye Irritation) and TSCA) (Bio/Dymanics, 1988). Triisobutylphosphate (0.1 mL) was introduced into the lower conjunctival sac of the right eye of New Zealand White rabbits (4 males and 2 females).Approximately 24 hours after application, the treated eyes were rinsed to remove any residual test material.Fluorescein dye was used to confirm presence or absence of corneal ulceration in treated eyes starting with the 24 hour observation and at each subsequent observation until there was no stain retention for two observations.

Triisobutyl phosphate produced mild to moderate, transient ocular irritation. Irritation consisted primarily of conjunctival irritation (redness, chemosis, discharge) with the most severe effects occuring at one hour. One animal exhibited iridial changes at one hour. No corneal changes were seen. Four of the six animals were free of ocular irritation within 24 hours after instillation of the test material; the remaining two animals were free of ocular irritation within 48 to 72 hours.

Supportingly, Triisobutyl phosphate was tested in 13 rabbits (BASF, 1953). 20% Triisobutyl phosphate and 50% Triisobutyl phosphate in oil gives mild irritation on the mucous membrane of the rabbits eye.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. A GLP-compliant OECD 404 study is available for skin irritation. An animal study comparable to current guidelines is available for eye irritation. In both studies, the scores for the test item treated tissues were below the thresholds for classification as an irritant. As a result, the substance is not considered to be classified for skin or eye irritation under Regulation (EC) No. 1272/2008, as amended for the tenth time in Regulation (EC) No. 2017/776.