AAA reaction product

Skin irritation / corrosion

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

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)

Test material

Test material information

Constituent 1

Test material form:

liquid: viscous

Details on test material:

- Name of test material (as cited in study report): DEA/ACID ANHYDRIDE REACTION PRODUCT

- Physical state: highly viscous amber liquid

- Composition of test material, percentage of components:
Monomers: <17-35% (9-16% diethanolamine; 2-8% tetrahydrophthalic acid; 5-11% trimellitic acid; <0.1% tetrahydrophthalic anhydride; <0.8% trimellitic anhydride)
Dimers/trimers: <24-45%
Polymers: <10-25%
Not removable water: 5-15%

- Lot/batch No.: 200501.UN2810

- Expiration date of the lot/batch: september 2003

- Stability under test conditions: stable under storage condition

- Storage condition of test material: in the refrigerator in the original container away from direct sunlight

Test animals

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

Test system

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.

Results and discussion

In vivo

Results

Results 1

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

Results 2

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

Results 3

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

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

(mean score)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

(mean score)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Results 6

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.

Any other information on results incl. tables

Overall assessment of irritation scores in accordance to EEC grading systems

Erythema: Not irritating

Edema: Not irritating

Applicant's summary and conclusion

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.