Bis(2,4-di-tert-butyl-6-methylphenyl)ethyl phosphate

Endpoint summary

Description of key information

Skin irritation (OECD 404 & GLP): not irritating (rabbit, in vivo) (CIBA-GEIGY Ltd., 924083, 1992)
Eye irritation (OECD 405 & GLP): not irritating (rabbit, in vivo) (CIBA-GEIGY Ltd., 924084, 1992) 

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

Study period:

1992-07-09 to 1992-08-04

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-Guideline study (OECD 404)

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted on May 1981

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr. K. Thomae GMBH, Chemisch-pharmazeutische Fabrik, D-7950 Biberach/Riss, Germany
- Weight at study initiation: 2250 to 2690g
- Housing: Individually in metal cages
- Diet: Standard rabbit pellet, ad libitum
- Water: Tap water, ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 +/-3°C
- Humidity: 30-70%
- Photoperiod: 12 hrs light cycle

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: the left flank of each treated rabbit served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 g of the test item

Duration of treatment / exposure:

4 hrs

Observation period:

The animals were checked daily for systemic symptoms and mortality. The skin reactions were evaluated 1, 24, 48, and 72 hours after removing the gauze patches according to the OECD scoring system.

Number of animals:

3 male rabbits

Details on study design:

TEST SITE
- Area of exposure: approx. 36 cm^2 on the flanks of the animals
- Type of wrap: the patches were loosely covered with an aluminum foil (approx. 36 cm^2) and held in place by an adhesive tape (Isoplast)

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 48, 72 hrs

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48, 72 hrs

Score:

0

Max. score:

4

Irritant / corrosive response data:

The test substance caused minimal erythema reactions in one animal. The reactions were observed only one hour after removing the bandages and reversed back to normal at the 24 hour time point.

Interpretation of results:

not irritating

Remarks:

Migrated information

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

Study period:

1992-07-27 to 1992-10-19

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-Guideline study (OECD Guideline 405)

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adpted on 12 May 1981

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Dr. K. Thomae GmbH, Chemisch-pharmazeutische Fabrik, D-7950 Biberach/Riss, Germany
- Weight at study initiation: 2340 to 2730g
- Housing: Individually in metal cages
- Diet: Standard rabbit pellet, ad libitum
- Water: Tap water, ad libitum
- Acclimation period: At least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature: 20 +/-3°C
- Humidity: 30-70%
- Photoperiod: 12 hrs light cycle

Vehicle:

unchanged (no vehicle)

Controls:

other: the right eye of each animal remained untreated and served as a control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.1mL (67 mg) of the test substance

Duration of treatment / exposure:

The eye was not rinsed after application.

Observation period (in vivo):

10 days

Number of animals or in vitro replicates:

3 male rabbits

Details on study design:

SCORING SYSTEM according to OECD 405 (1981):

CORNEA
Opacity: degree of density (area most dense taken for reading)
No ulceration or opacity 0
Scattered or diffuse areas of opacity (other than slight dulling of normal luster), details of iris clearly visible 1
Easily discernible translucent area, details of iris slightly obscured 2
Nacreous area, no details of iris visible, size of pupil barely discernible 3
Opaque cornea, iris not discernible through the opacity 4

IRIS
Normal 0
Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperemia, or injection, any of these or combination of any thereof, iris still reacting to light (sluggish reaction is positive) 1
No reaction to light, hemorrhage, gross destruction (any or all of these) 2

CONJUNCTIVAE
Redness (refers to most severe reading of palpebral and bulbar conjunctivae when compared with control eye)
Blood vessels normal 0
Some blood vessels definitely hyperemic (injected) 1
Diffuse, crimson color, individual vessels not easily discernible 2
Diffuse beefy red 3

CHEMOSIS: lids and/or nictitating membranes
No swelling 0
Any swelling above normal (including nictitating membranes) 1
Obvious swelling with partial eversion of lids 2
Swelling with lids about half-closed 3
Swelling with lids more than half-closed 4


TOOL USED TO ASSESS SCORE: hand-slit lamp

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 24, 48, 72 hrs

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hrs

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: 24, 48, 72 hrs

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

other: 24, 48, 72 hrs

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 24, 48, 72 hrs

Score:

0.7

Max. score:

2

Reversibility:

fully reversible within: 72 hrs

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: 24, 48, 72 hrs

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #3

Time point:

other: 24, 48, 72 hrs

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

other: 24, 48, 72 hrs

Score:

1.3

Max. score:

3

Reversibility:

fully reversible within: 10 days

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Time point:

other: 24, 48, 72 hrs

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 hrs

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #3

Time point:

other: 24, 48, 72 hrs

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 hrs

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 24, 48, 72 hrs

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hrs

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: 24, 48, 72 hrs

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: 24, 48, 72 hrs

Score:

0

Max. score:

4

Interpretation of results:

not irritating

Remarks:

Migrated information

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

The test article's potential to cause dermal irritation was assessed in a GLP-compliant study following OECD guideline 404 (CIBA-GEIGY Ltd., 924083, 1992). An amount of 0.5 g of the test substance was applied topically to the intact skin of 3 male rabbits for 4 hours under occlusive dressing. In one animal slight erythema reactions were observed one hour after removing of the dressing, reversible within 24 hours. All mean scores for erythema and edema at 24, 48 and 72 hours for all animals were zero and the substance was classified as not irritating to skin. This result was confirmed by another GLP-compliant in vivo study (CIBA-GEIGY Ltd., 914027, 1991) performed with one male rabbit. After application of the 0.5 g of test substance on the intact skin for 4 hours, no edema or erythema reactions could be observed at any give time during the course of this study. In conclusion, under the test conditions chosen, the test substance is not considered to be irritating to the skin.

 

Eye irritation

To assess the acute eye irritation potential of the test substance in vivo, a GLP-compliant study with three New Zealand white rabbits was performed according to OECD guideline 405 (CIBA-GEIGY Ltd., 924084, 1992). An amount of 0.1 ml (67 mg) of the test substance was applied into the conjunctival sac of the left eye and the ocular reactions were evaluated 1, 24, 48, and 72 hours after instillation. One animal displayed reactions to the cornea and iris and showed conjunctival redness and chemosis. The mean scores (24 - 72 hours) were 0.3 for cornea, 0.7 for iris, 1.3 for conjunctival redness and 0.3 for chemosis, all effects were reversible after 10 days. The other two animals showed only slight reactions to the conjunctivae, which had a mean score of 0.3 and were reversible after 48 hours. Because the mean values of the readings 24 to 72 hours after instillation are below the threshold of significance, the test article is considered to be not irritating. This result was confirmed by another GLP-compliant in vivo study (CIBA-GEIGY Ltd., 914026, 1991) performed with one male rabbit. In this study, after application of 0.1 ml (60 mg) of the test article into the conjunctival sac of the left eye, the animal showed only minimal redness of the conjunctiva, reversible within 48 hours. In conclusion, under the test conditions chosen and considering the present data, the test article induced minimal irritating reactions below the regulatory threshold and is therefore considered to be not irritating.

Respiratory Irritation

No data

Justification for selection of skin irritation / corrosion endpoint:
GLP-compliant guideline study

Justification for selection of eye irritation endpoint:
GLP-compliant guideline study

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available experimental test data is reliable and suitable for the purpose of classification under Directive 67/548/EEC. 

Based on the data, the test substance has not to be classified as skin or eye irritant.

 

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

The available experimental test data are reliable and suitable for the purpose of classification under Regulation (EC) No.1272/2008.

Based on the data, the test substance has not to be classified as skin or eye irritant.