REAKTIV OLIV F00-149

Endpoint summary

Description of key information

A skin irritation study in rabbits was performed according to OECD 404 and EU Method B.4 following GLP guidelines. An eye irritation study in rabbits was performed in one animal according to OECD 405 and EU Method B.5 following GLP guidelines. The test compound caused irreversible discolorations in the eye of the animal. This is not considered an adverse effect but substance specific staining.

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:

2001-12-03 to 2002-03-21

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland GmbH 88353 Kißlegg
- Weight at study initiation: 3.1 - 3.5 kg
- Housing: in fully air-conditioned rooms in separate cages arranged in a battery (room number 051).
- Diet (e.g. ad libitum): ssniff K-H (V2333), ad libitum and hay (approx. 15 g daily)
- Water (e.g. ad libitum): water from automatic water dispensers, ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3°C
- Humidity (%): 50 ± 20 %
- Photoperiod (hrs dark / hrs light): 12 hours light / dark cycle

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

no

Amount / concentration applied:

500 mg

Duration of treatment / exposure:

4 h

Observation period:

Examinations took place after 30 - 60 minutes, 24, 48 and 72 hours after removal of the patches.

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 25 cm²

REMOVAL OF TEST SUBSTANCE
- Washing (if done): test substance was carefully removed from the skin with warm tap water
- Time after start of exposure: following exposure period

SCORING SYSTEM: DRAIZE

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

other: overall at 24, 48 and 72 h

Score:

<= 0

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

other: overall at 24, 48 and 72 h

Score:

<= 0

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

other: overall at 24, 48 and 72 h

Score:

<= 0

Irritation parameter:

erythema score

Max. score:

0

Remarks on result:

other: Max. duration: d; Max. value at end of observation period: <= 0 (related to all animals)

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

other: overall at 24, 48 and 72 h

Score:

<= 0

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

other: overall at 24, 48 and 72 h

Score:

<= 0

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

other: overall at 24, 48 and 72 h

Score:

<= 0

Irritation parameter:

edema score

Max. score:

0

Remarks on result:

other: Max. duration: d; Max. value at end of observation period: <= 0 (related to all animals)

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Reactive Olive F00-0149 is not irritation to the skin based on results from a rabbit skin irritation test according to OECD 404.

Executive summary:

In a primary dermal irritation study, 3 rabbits weighing 3.1 -3.5 kg, were dermally exposed to 500 mg Reactive Olive F00-0149 in deionized water to 25 cm² dorsal region skin. Test sites were covered with a semi-occlusive dressing for 4 hours. Animals were then observed for 14 days.  Irritation was scored by the DRAIZE method.

In this study, Reactive Olive F00-0149 is not a dermal irritant.

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:

2002-01-14 to 2002-03-21

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP guideline study, only one animal tested

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland GmbH 88353 Kißlegg
- Weight at study initiation: 3.4 kg
- Housing: in fully air-conditioned rooms in separate cages arranged in a battery (room number 051).
- Diet (e.g. ad libitum): ssniff K-H (V2333), ad libitum and hay (approx. 15 g daily)
- Water (e.g. ad libitum): water from automatic water dispensers, ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3°C
- Humidity (%): 50 ± 20 %
- Photoperiod (hrs dark / hrs light): 12 hours light / dark cycle

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated right eye

Amount / concentration applied:

100 mg

Duration of treatment / exposure:

24h

Observation period (in vivo):

1, 24, 48 and 72 hours after administration of the test substance

Number of animals or in vitro replicates:

1

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): 24 hours after administration the treated eye was washed out thoroughly with isotonic saline at approx. 37 °C. The eye was also washed out at designated examination times at which discharge was observed or a corneal examination with fluorescein was performed.

SCORING SYSTEM:
-Cornea: opacity (0-4), affected area (0-4)
-Iris (0-2)
-Conjunctivae: redness (0-3,9), chemosis (0-4), discharge (0-3)

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

other: overall at 24, 48 and 72 h

Score:

<= 0.67

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Max. score:

2

Remarks on result:

other: Max. duration: 1 h; Max. value at end of observation period: 0 (related to all animals)

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

other: overall at 24, 48 and 72 h

Score:

<= 0.33

Irritation parameter:

chemosis score

Max. score:

2

Remarks on result:

other: Max. duration: 0 h; Max. value at end of observation period: 0 (related to all animals)

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

other: overall at 24, 48 and 72 h

Score:

<= 0

Irritation parameter:

cornea opacity score

Max. score:

0

Remarks on result:

other: Max. duration: h; Max. value at end of observation period: 0 (related to all animals)

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

other: overall at 24, 48 and 72 h

Score:

<= 0

Irritation parameter:

iris score

Max. score:

0

Remarks on result:

other: Max. duration: h; Max. value at end of observation period: 0 (related to all animals)

Irritant / corrosive response data:

Reversibility of any observed effect: Changes not fully reversible within 21 days

1 hour after the 72-hour injection a light redding of the conjunctiva was observed. 1 hour after the 24-hour injection

a light swelling occured. Clear green outflow. 2 days pa all signs of the swelling were disappeared.

Interpretation of results:

not irritating

Remarks:

Migrated information discolouration of the eye is considered a dye specific effect Criteria used for interpretation of results: expert judgment

Conclusions:

The applicant concluded that the persistent discolouration of the eye is a dye specific effect and does not require classification.

Executive summary:

In a primary eye irritation study, 100 mg of Reactive Olive F00 -0149 was instilled into the conjunctival sac of the left eye of 1 New Zealand White rabbit for 24 hours. The treated eye was washed out thoroughly with isotonic saline at approx. 37 °C after 24 hours. Additionally, the eye was washed out at designated examination times at which discharge was observed or a corneal examination with fluorescein was performed. The animal was then observed for 3 days. Irritation was scored by the method described by Draize.

From one hour up to one day after application the conjunctiva of the animal showed injected blood vessels up to a diffuse crimson red color and swelling with partial eversion of the lid. Additionally, there was presence of a clear substance colored (green) eye discharge. 2 days after application the irritations had disappeared. Nictitating membrane and conjunctiva were green discolored from day 2 up to the end of the study. Redness and chemois of the conjunctiva received a score of 0.67 and 0.33, respectively, while the corneal opacity and iris scores were 0.

In this study, Reactive Olive F00-0149 would be an eye irritant based on persistent discoloration. However, the applicant concluded that the persistent discolouration of the eye is a dye specific effect and does not require classification.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In a primary dermal irritation study, rabbits were dermally exposed to 500 mg Reaktiv Oliv F00-0149 in deionized water to 25 cm² dorsal region skin. Test sites were covered with a semi-occlusive dressing for 4 hours and then observed for 14 days.  Irritation scores for edema and erythema were both 0 indicating Reaktiv Oliv F00-0149 is not a dermal irritant.

In a primary eye irritation study, 100mg of Reaktiv Oliv F00 -0149 was instilled into the conjunctival sac of the left eye of one New Zealand White rabbit for 24 hours and observed for 3 days. The test compound caused irreversible discolorations in the eye of the animal. This is not considered an adverse effect but substance specific staining. Redness and chemois of the conjunctiva received a score of 0.67 and 0.33, respectively, while the corneal opacity and iris scores were 0.

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

Justification for selection of eye irritation endpoint:
GLP guideline study

Justification for classification or non-classification

No adverse effects have been reported in a primary dermal irritation study.

In a primary eye irritation study the test compound caused irreversible discolorations in the eye of the animal. This is not considered an adverse effect but substance specific staining.