2-hydroxy-1-(4-(4-(2-hydroxy-2-methylpropionyl)benzyl)phenyl)-2-methylpropan-1-one

Endpoint summary

Description of key information

Study conducted to recognised testing guidelines with GLP certification. 

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:

2002-10-08 to 2002-10-17

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

adopted 1992

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted 1992

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage Scientifique des Dombes; F-01400 Chatillon sur Chalaronne / France
- Age at study initiation: 10 weeks (male); 20 weeks (females)
- Weight at study initiation: male: 2173 g; female: 3018 g (mean)
- Housing: Individually in stainless steel cages
- Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum
- Water: Community tap water from Fullinsdorf, ad libitum.
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature: 17-23 °C
- Humidity: 30-70%
- Air changes: 10-15 air changes per hour
- Photoperiod: 12 hours light and 12 hours dark

IN-LIFE DATES: From: 08-Oct-2002 To: 17-Oct-2002

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
- Concentration (if solution): 0.5 g/0.1 mL

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

4 hours

Observation period:

72 hours (reading performed at 1, 24, 48 and 72 hours)

Number of animals:

3 (animals of both sexes were used)

Details on study design:

TEST SITE
- Area of exposure: 100 cm2 (10 cm x 10 cm)
- % coverage: no data
- Type of wrap if used:semi-occlusive dressing

REMOVAL OF TEST SUBSTANCE
- Washing: with lukewarm tap water to clean the application site
- Time after start of exposure: 4 hours

SCORING SYSTEM: the numerical scoring system listed in the EEC Commission Directive 92/69/EEC, July 31, 1992

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

male

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: no effects

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

female

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: no effects

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

female

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: no effects

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: no effects

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

male

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: no effects

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

female

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: no effects

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

female

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: no effects

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: no effects

Irritant / corrosive response data:

- Irritation:
The test item did not elicit any skin reactions at the application site of any animal at any of the observation times (all scores 0).
- Corrosion:
No corrosive effects were evident on the skin.

Other effects:

- Viability/mortality/clinical signs:
No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.
- Coloration:
No irreversible alterations of the treated skin were observed.
- Body weights:
The body weights of all rabbits were considered to be within the normal range of variability.

The test item is considered to be "not irritating" to rabbit skin.

Interpretation of results:

not irritating

Conclusions:

The test material was found to be not dermally irritating to the Rabbit under the conditions of the test.

Executive summary:

In this guideline (OECD 404) study conducted with GLP, the test material (EC 444-860-9) was induced mean erythema and edema scores of 0.0 in all test animals (rabbit) across the 24, 48, & 72 hour observation periods. The test material was exposed to the test animals (intact skin, 4 hours) under semi-occlusive conditions. The result of the test is not sufficient to meet the criteria for classification as a skin irritant under the criteria of the EU Classification, Labelling, and Packaging (CLP) regulation (1272/2008).

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:

2002-10-22 to 2001-10-31

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted 31 July 1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

1987

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Elevage Scientifique des Dombes F-01400 Chatillon sur Chalaronne / France
- Age at study initiation: 12 weeks (male); 21-22 weeks (females)
- Weight at study initiation: male (mean): 2563 g; female: 3058 g
- Housing: Individually in stainless steel cages
- Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum
- Water: Community tap water from Füllinsdorf, ad libitum.
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature: 17-23 °C
- Humidity: 30-70 %
- Air changes: 10-15 air changes per hour
- Photoperiod: 12 hours light and 12 hours dark

IN-LIFE DATES: From: 08-Oct-2002 To: 31-Oct-2002

Vehicle:

unchanged (no vehicle)

Controls:

other: The right eye remained untreated and served as the reference control.

Amount / concentration applied:

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

Duration of treatment / exposure:

single treatment; the treated eyes were not rinsed after instillation

Observation period (in vivo):

72 hours (readings performed at 1 h, 24, 48, 72 hours)

Number of animals or in vitro replicates:

3 rabbits

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treated eyes were not rinsed after instillation.


SCORING SYSTEM: The ocular reaction was assessed according to the numerical scoring system listed in the EEC Commission Directive 92/69/EEC, July 31, 1992

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

male

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: no effects

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

female

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: no effects

Irritation parameter:

cornea opacity score

Basis:

animal #3

Remarks:

female

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: no effects

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: no effects

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

male

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: no effects

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

female

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: no effects

Irritation parameter:

iris score

Basis:

animal #3

Remarks:

female

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: no effects

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: no effects

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

male

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: no effects

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

female

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: no effects

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

female

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: no effects

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: no effects

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Remarks:

male

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Remarks:

female

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #3

Remarks:

female

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

24/48/72 h

Score:

0.89

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Irritant / corrosive response data:

- Irritation:
Application of the test item to healthy rabbit conjunctivae resulted in a primary eye irritation score of 0.89. The mean score was calculated across 3 scoring times (24, 48 and 72 hours after instillation) for each animal for corneal opacity, iris, redness and chemosis of the conjunctivae, separately. The individual mean score for corneal opacity and iris was 0.00 for all three animals. The individual mean scores for the conjunctivae were 1.33, 0.33 and 1.00 for reddening and 0.00, 0.00 and 0.00 for chemosis, respectively.
No abnormal findings were observed in the iris of any animal at any of the measurement intervals.
A slight corneal opacity, affecting up to the whole area of the cornea, was observed in the treated eye of one animal at the 1-hour examination.
Slight to moderate reddening of the conjunctivae was observed in all animals from 1 to 24 hours after treatment and continued to be observed in two animals up to the 48-hour examination. Slight to obvious swelling of the conjunctivae was apparent in all animals 1 hour after treatment.
Assessment of the sclerae was not possible in one animal at the 1 -hour examination due to swelling of the conjunctivae. Scleral reddening, of various severity (mild to marked), was however subsequently observed in all animals up to 24 hours and in two animals up to 48 hours after treatment. Increased ocular discharge was observed in all animals 1 hour after treatment. Mucus was also present in the treated eye of one animal at the 24-hour examination. No abnormal findings were observed in the treated eye of any animal 72 hours after treatment, the end of the observation period for all animals.

Other effects:

-Viability/mortality and clinical signs:
No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.

- Coloration:
No staining of the treated eyes by the test item was observed. White remnants of the test item were observed in the eye or conjunctival sac of all animals 1 hour after treatment.

- Body weight:
The body weights of all rabbits were considered to be within the normal range of variability.

The test item is considered to be "not irritating" to the rabbit eye.

Interpretation of results:

not irritating

Conclusions:

The test material was found not to induce eye irritation in the Rabbit eye.

Executive summary:

In this guideline (OECD 405) study conducted with GLP certification, the test material (EC 444-860-9) did not induce any significant, irreversible irritation in the rabbit eye at 24/48/72 hours. The test material was exposed to the 3 rabbits with an 8 day observation period. Based upon the results of this study, the test material does not meet the criteria for classification as an eye irritant under the EU Classification, Labelling, and Packaging (CLP) regulation (1272/2008).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Method and observations

Two studies were performed to evaluate irritating potential of the test material to skin or eyes. In the first study, six rabbits (3/sex/dose) were each administered a single dermal dose of 0.5 g of the test substance. Semiocclusive application of the test material to intact rabbit skin for four hours did not cause any reaction on animals skin.

In a second study, three female rabbits were each administered a single ocular dose of 0.1 g of the test substance and observed for 72h after instillation. A single instillation of the test material into the eye of the rabbit elicited slight, transient redness of the conjunctiva which was fully reversible within 72h.

There are no data available about irritation to the respiratory system.

Discussion

Application of the test substance onto skin did not cause corrosion or irritation. Appllication into the conjunctival sac of the eye caused slight, transient conjuctival irritation which recoverd within 72h.

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. As a result the substance is not considered to be classified for irritation under Regulation (EC) No. 1272/2008.