AAA reaction product

Endpoint summary

Description of key information

AAA reaction product was found to be "not irritating " to rabbit skin and eye when evaluated in accordance to OECD testing guidelines. The studies were also performed in accordance to GLP, hence reliability scores of 1 was applied to these data. 

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:

2003-06-12 to 2003-09-18

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study performed in accordance to guideline with no deviations

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Principles of method if other than guideline:

NA

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: New Zealand White Rabbit, SPF
- Age at study initiation: 11 - 12 weeks (male), 9 - 10 weeks (females)
- Weight at study initiation: 1966 g (male), 2187 g (female), 2112 g (female)
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks and haysticks were provided.
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 28/03).
- Water (e.g. ad libitum): Community tap water from Füllinsdorf, ad libitum.
- Acclimation period: 2003-06-12 to 2003-06-16

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23 °C
- Humidity (%): 30-70 %
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): automatically controlled light cycle of 12 hours light and 12 hours dark. Music was played during the daytime light period.

IN-LIFE DATES: 2003-06-12 to 2003-06-20

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL (per animal)
- Concentration (if solution): NA

VEHICLE
- Amount(s) applied (volume or weight with unit): NA
- Concentration (if solution): NA
- Lot/batch no. (if required): NA
- Purity: NA

Duration of treatment / exposure:

4 h

Observation period:

The mean score was calculated across 3 scoring times (24, 48 and 72 hours after patch removal) for each animal for erythema/eschar grades and for oedema grades, separately.

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: Four days before treatment, one flank was clipped with an electric clipper, exposing an area of approximately 100 cm2 (10 cm x 10 cm). The skin of the animals was examined one day before treatment, and regrown fur of all animals was again clipped. Animals with overt signs of skin injury or marked irritation which may have interfered with the interpretation of the results were not used in the test.

- % coverage: 0.5 mL was applied to the exposed skin area covering 2 to 2.5 cm2.

- Type of wrap if used: A surgical gauze patch was applied onto the test item area. The patch was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The duration of treatment was 4 hours. Then the dressing was removed and the skin was flushed with lukewarm tap water to clean the application site so that any reactions (erythema) were clearly visible at that time.
- Time after start of exposure: 4 hours

SCORING SYSTEM: The skin reaction was assessed according to the numerical scoring system listed in the EEC Commission Directive 92/69/EEC, July 31, 1992 approximately 1, 24, 48 and 72 hours after the removal of the dressing, gauze patch and test item. Erythema/eschar grades and for oedema grades were recorded accordingly.

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

(mean score)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Max. score:

1

Reversibility:

fully reversible

Remarks on result:

other: Max. duration: 1h; Max. value at end of observation period: 0

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

(mean score)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Max. score:

1

Reversibility:

fully reversible

Remarks on result:

other: Max. score of 1 after 1h; Max. value at end of observation period: 0

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

(mean score)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Max. score:

1

Reversibility:

fully reversible

Remarks on result:

other: Max. score of 1 after 1h; Max. value at end of observation period: 0

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

(mean score)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

(mean score)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

(mean score)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Irritant / corrosive response data:

The application of AAA reaction product to the skin resulted in mild signs of irritation. These included erythema. These effects were reversible and were no longer evident 24 hours after treatment. AAA reaction product caused no staining of the treated skin. No corrosive effects were noted on the treated skin of any animal at any of the measuring intervals and no other clinical signs of AAA reaction product related effects were observed.

Other effects:

Very slight erythema was observed in all animal at the 1- hour reading.


No staining produced by the test item of the treated skin
was observed.


Neither alterations of the treated skin were observed nor
were corrosive effects evident on the skin.


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

Overall assessment of irritation scores in accordance to EEC grading systems

Erythema: Not irritating

Edema: Not irritating

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The primary skin irritation potential of AAA reaction product was evaluated according to OECD 404. Mild signs of irritation in terms of erythema was observed after 1 hour. These effects were reversible and were no longer evident 24 hours after treatment. AAA reaction was found to be "not irritating" to rabbit skin and is therefore not classified accordingly.

Executive summary:

The primary skin irritation potential of AAA reaction product was evaluated according to OECD 404. AAA reaction product was applied by topical semi-occlusive application of 0.5 mL to the intact left flank of each of three young adult New Zealand White rabbits. The duration of treatment was four hours. The scoring of skin reactions was performed 1, 24, 48 and 72 hours after removal of the dressing. The mean score was calculated across 3 scoring times (24, 48 and 72 hours after patch removal) for each animal for erythema/eschar grades and for oedema grades, separately.

The mean erythema/eschar score of the three animals was 0.00; 0.00 and 0.00, respectively and the mean oedema score was 0.00, 0.00 and 0.00, respectively. The application of AAA reaction product to the skin resulted in mild signs of irritation. These included erythema. These effects were reversible and were no longer evident 24 hours after treatment. No staining of the treated skin was seen. No corrosive effects were noted on the treated skin of any animal at any of the measuring intervals and no other clinical signs were observed. Based on these data, AAA reaction product is considered to be “not irritating” to rabbit skin and are therefore not classified accordingly.

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:

2003-07-01 to 2003-09-16

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study performed in accordance to guideline with no deviations

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Principles of method if other than guideline:

NA

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: New Zealand White Rabbit, SPF
- Age at study initiation: 10 - 11 weeks (male), 10 - 11 weeks (females)
- Weight at study initiation: 1966 g (male), 2187 g (female), 2112 g (female)
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks and haysticks were provided.
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 28/03).
- Water (e.g. ad libitum): Community tap water from Füllinsdorf, ad libitum.
- Acclimation period: 2003-06-12 to 2003-06-16

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23 °C
- Humidity (%): 30-70 %
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): utomatically controlled light cycle of 12 hours light and 12 hours dark. Music was played during the daytime light period.

IN-LIFE DATES: 2003-06-12 to 2003-06-20

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

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

VEHICLE
- Amount(s) applied (volume or weight with unit): NA
- Concentration (if solution): NA
- Lot/batch no. (if required): NA
- Purity: NA

Duration of treatment / exposure:

0.1 mL installed into the left conjuctival sac of the left eye of each of the animals. The right eye remained untreated and served as reference control.

Observation period (in vivo):

1, 24, 48, 72 hours and after 7days

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no
- Time after start of exposure: The test substance was not removed after installation

SCORING SYSTEM: The ocular reaction (corneal opacity, area, iris, conjunctivae (redness and chemosis) and schlera) was assessed according to the numerical scoring system listed in the EEC Commission Directive 92/69/EEC, July 31, 1992 approximately 1, 24, 48, 72 hours and 7 days after application.

TOOL USED TO ASSESS SCORE: Varta Cliptrix diagnostic-lamp (Roth Ag, Ch-4153 Reinach/Switzerland)

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #1

Remarks:

(mean score)

Time point:

other: overall at 24, 48 and 72 h

Score:

0.67

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #2

Remarks:

(mean score)

Time point:

other: overall at 24, 48 and 72 h

Score:

0.33

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #3

Remarks:

(mean score)

Time point:

other: overall at 24, 48 and 72 h

Score:

1

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Max. score:

1

Remarks on result:

other: Max. duration: 72 h; Max. value at end of observation period: 0 (related to all animals)

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

(mean score)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

(mean score)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

(mean score)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

(mean score)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

(mean score)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Irritation parameter:

cornea opacity score

Basis:

animal #3

Remarks:

(mean score)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

(mean score)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

(mean score)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Irritation parameter:

iris score

Basis:

animal #3

Remarks:

(mean score)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Irritant / corrosive response data:

The application of AAA reaction product to the eye resulted in slight swelling of the conjunctivae (chemosis) in 1 animal at the 1 hour reading. Slight reddening of the conjunctivae was observed in all animals at the 1- and 24-hour reading. Slight reddening was still evident in two animals 48 hours after treatment and persisted in on animal up to the 72-hour examination. Slight reddening of the schlerae was visible in one animal 1 hour after treatment. No ocular discharge was observed in any animal. No abnormal findings were observed in the treated eye of any animal 7 days after treatment, the end of the observation period for all animals. No staining or corrosion was observed.

Other effects:

The bodyweights of all rabbits were considered to be within the normal range of variability.


The bodyweights of all rabbits were considered to be within
the normal range of variability.

Overall assessment of irritation scores in accordance to EEC grading system

Corneal opacity: Not irritating

Iris: Not irritating

Conjunctivae - Redness: Not irritating

Conjunctivae - Chemosis: Not irritating

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The eye irritation potential of AAA reaction product to the rabbit eye was evaluated in accordance to OECD 405. AAA reaction product did not induce significant or irreversible damage to the rabbit eye and is therefore considered to be "not irritant" to the rabbit eye. No classification is applied.

Executive summary:

The primary eye irritation potential of AAA reaction product was evaluated in accordance to OECD 405. AAA reaction product was applied by installation of 0.1 mL into the left eye of each of 3 rabbits, the right eye serving as control. Scoring of irritation was performed after 1, 24, 48, 72 hours and after 7 days.

The individual mean scores for corneal opacity and iris were 0.00 for all 3 animals. The individual mean scores for conjuctivae were 0.67, 0.33 1.00 for reddening and for all 3 animals 0.00 for chemosis, respectively.

The instillation of AAA reaction product into the eye resulted in mild , early-onset and transient ocluar changes

No ocular discharge was observed in any animal. No abnormal findings were observed in the treated eye of any animal 7 days after treatment, the end of the observation period for all animals. No staining or corrosion was observed. Further, no other clinical signs were observed.

AAA reaction product did not induce significant or irreversible damage to the rabbit eye and is therefore considered to be "not irritant" to the rabbit eye. No classification is applied.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The skin irritation potential of AAA reaction product was evaluated according to OECD 404. Mild signs of irritation in terms of erythema was observed after 1 hour. These effects were reversible and were no longer evident 24 hours after treatment. AAA reaction was found to be "not irritating" to rabbit skin and is therefore not classified accordingly.

The eye irritation potential of AAA reaction product to the rabbit eye was evaluated in accordance to OECD 405. AAA reaction product did not induce significant or irreversible damage to the rabbit eye and is therefore considered to be "not irritating" to the rabbit eye. No classification is applied.

Justification for selection of skin irritation / corrosion endpoint:
Reliability score of 1.
GLP study performed in acordance to guideline with no deviations

Justification for selection of eye irritation endpoint:
Reliability score of 1.
GLP study performed in acordance to guideline with no deviations

Justification for classification or non-classification

Based on the available skin and eye toxicity data, AAA reaction product is not classified according to criteria in GHS/CLP regulation.