Ethylenebis(oxyethylene) bis[3-(5-tert-butyl-4-hydroxy-m-tolyl)propionate]

Endpoint summary

Description of key information

The substance caused no signs of irritation on rabbit skin and in rabbit eyes.

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:

22.10.1979 to 12.11.1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

light/dark cycle, observation times, exposure time and the use of both intact and abraded skin.

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Ciba-Geigy Limited (Toxicology GU 2.1)
- Weight at study initiation: 2 to 3 kgs
- Housing: Individually in metal cages
- Diet: ad libitum standard rabbit food NAFAG No. 814
- Water: ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2°C
- Humidity (%): 55 +/- 10%
- Photoperiod (hrs dark / hrs light): 14 hrs dark/ 10 hrs light

Type of coverage:

occlusive

Preparation of test site:

other: Abraded and intact shaved

Vehicle:

other: Propylene glycol and saline (70:30)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Concentration (if solution): 50%
- amount: 0.5 g

Duration of treatment / exposure:

24 hours

Observation period:

7 days

Number of animals:

3 males and 3 females

Details on study design:

TEST SITE
- Area of exposure: 2.5 X 2.5 cm
- Type of wrap if used: impermeable material

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24 hours

SCORING SYSTEM:
Erythema and eschar formation
No erythema = 0
Very slight erythema (barely perceptible) = 1
Well defined erythema = 2
Moderate to severe erythema = 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth) = 4
Total possible erythema score = 4
Edema formation
No edema = 0
Very slight edema (barely perceptible) = 1
Slight edema (edges of area well defined bydefinite raising) = 2
Moderate edema (raised approximately 1 mm) = 3
Severe edema (raised more than 1 mm and extending beyond area of exposure) = 4
Total possible edema score = 4

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: for both intact and abraded skin

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: values for both intact and abraded skin

Irritant / corrosive response data:

No erythema or edema was observed on any of the test animals on abraded or intact skin.

Other effects:

None

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the present experiment the test article was found to cause no irritation when applied to intact and abraded rabbit skin.

Executive summary:

In a skin irritation study predating GLP the test substance was investigated for dermal effects in rabbits in a test similar to OECD testing guideline 404. An amount of 0.5 g test material was applied to the skin of 3 male and 3 female adult New Zealand White rabbits in an occlusive manner. The protocol differed by additional testing of abraded skin versus intact skin and a prolonged exposure time of 24h was used. Observation was terminated after 7 days which is acceptable as no indication of erythema or erythema was observed during the observation period. All scores for edema and erythema were zero at any time point. Based on the results of this study, the test article is considered to be not irritating to the rabbit skin.

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:

28.8.1979 to 12.11.1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

light/dark cycle; flushing of 3 of the rabbits' eyes after exposure.

Qualifier:

according to guideline

Guideline:

other: EPA 163.81-4 "Primary eye irritation study"

Deviations:

not specified

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Ciba-Geigy Limited
- Weight at study initiation: 2 to 3 kgs
- Housing: Individually in metal cages
- Diet: ad libitum standard rabbit food NAFAG No. 814
- Water: ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2°C
- Humidity (%): 55 +/- 10%
- Photoperiod (hrs dark / hrs light): 14 hrs dark/ 10 hrs light

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g

Duration of treatment / exposure:

In 3 of 6 rabbits the test substance was flushed with 10 mL of saline after 30 seconds of exposure, the other 3 rabbits did not have their eye flushed. The right eye of each rabbit served as the control.

Observation period (in vivo):

Observations were taken on day 1,2,3,4, and 7.

Number of animals or in vitro replicates:

6 animals

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Flushing with 10 mL of saline in 3 of the rabbits' eyes
- Time after start of exposure: Washing occurred 30 seconds after exposure


SCORING SYSTEM:
Score for eye irritation in rabbits (Table 1)
CORNEA:
A Opacity and degree of density (most dense eurea scored)
No opacity = 0
Scattered or diffuse area, details of iris clearly visible = 1
Easily discernible translucent areas, details of iris slightly obscured = 2
Opalescent areas, no detiails of iris visible, size of pupil barely discernible = 3
Opaque, iris invisible = 4
B Area of cornea involved
One quarter (or less) but not zero = 1
Greater than one quarter, but less than half = 2
Greater than half, but less than three quarters = 3
Greater than three quarters, up to whole area = 4
Calculation of Score: A X B X 5
Maximum possible score = 80
IRIS
A Values
Normal = 0
Folds above normal, congestion, swelling, circumcornea injection (any or all 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
Calculation of score: A X 5
Maximum possible score « 10

CONJUNCTIVAE:
A Redness (refers to palpebral and bulbar conjunctivae excluding cornea and iris)
Vessels normal = 0
Vessels definitely injected cibove normal = 1
More diffuse, deeper crimson red, individual vessels not easily discernible = 2
Diffuse beefy red = 3
B Chemosis
No swelling = 0
Any swelling eibove normal (Includes nictitating membrane) = 1
Obvious swelling with partial eversion of lids = 2
Swelling with lids about half closed = 3
Swelling with lids about half closed to completely closed = 4
C Discharge
No discharge = 0
Any amount different from normal (does not include small amounts observed in inner canthus of normal animals) = 1
Discharge with moistening of the lids and hairs just adjacent to lids = 2
Discharge with moistening of the lids and hairs, and considerable area around the eye = 3
Calculation of score: (A + B + C) X 2
Maximum possible score » 20

Calculation of the primary eye irritation index:
The mean reaction scores for cornea, iris and conjunctiva observed after 1, 2, 3, 4 and 7 days were summed up and the sum divided by 5. This procedure was carried out separately for unrinsed (A) and rinsed (B) eyes respectively.
Index
0 - 1 0 = Minimal
11 - 25 = Slight
26 - 55 = Moderate
56 - 84 = Marked
above 84 = Extreme
The ratio R = A : B indicates the effect of rinsing the eyes approximately 30 seconds after instillation of the compound.
If R is
<1 rinsing increased the effect of the compound
= 1 no effect
= 1.1 - 1.5 practically no effect
= 1.6 - 2 little but assessable effect
= 2.1 - 4 good effect
= 4.1 - 10 very good effect
>10 action of the compound practically abolished

TOOL USED TO ASSESS SCORE: hand-slit lamp

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

7 d

Score:

0

Max. score:

110

Remarks on result:

other: rinsed and unrinsed

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: rinsed and unrinsed

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

other: rinsed and unrinsed

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

other: rinsed and unrinsed

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: rinsed and unrinsed

Irritant / corrosive response data:

No irritation

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

Skin irritation

The substance was investigated for skin irritation in rabbits in a test similar to OECD testing guideline 404 predating GLP but with adequate reporting details. The protocol differed by additional testing of abraded skin versus intact skin and a prolonged exposure time of 24h was used. Observation was terminated after 7 days which is acceptable as no indication of erythema or erythema was observed during the observation period.

Eye irritation

The study on eye irritation followed the procedure of OECD testing guideline 405 predating GLP but with adequate reporting details. An additional number of animals for which the eyes were rinsed immediately after substance application. Observation was terminated after 7 days. No indication of effects on iris, cornea or conjunctivae was observed for rinsed or unrinsed eyes. No indication of systemic toxicity was recorded.

Justification for classification or non-classification

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

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for skin and eye irritation under Regulation (EC) No. 1272/2008.