AAA reaction product

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2003-05-17 to 2003-09-17

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 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Principles of method if other than guideline:

NA

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

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:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Rat, HanBrl: WIST (SPF)
- Age at study initiation: 8 - 9 weeks (male) and 11 - 12 weeks (female)
- Weight at study initiation: 246-257 g (male) and 187-196 g (female)
- Fasting period before study: No data
- Housing: During acclimatization in groups of five per sex in Makrolon type-4 cages with standard softwood bedding. Individually in Makrolon type 3 cages with standard softwood bedding during treatment and observation.
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet ad libitum.
- Water (e.g. ad libitum): Community tap water ad libitum
- Acclimation period: Under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/-3
- Humidity (%): 30-70 % (values above 70 % during cleaning process possible)
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours fluorescent light/ 12 hours dark, music during the light period.





IN-LIFE DATES: From: To:

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 10 % of the total body surface.
- % coverage: 10 % of the total body surface.
- Type of wrap if used: a patch covered with a semi-occlusive dressing.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the skin was flushed with lukewarm tap water and dried with disposable paper towels.
- Time after start of exposure: 24 hour

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2 g/kg bw
- Concentration (if solution): No
- Constant volume or concentration used: No
- For solids, paste formed: No

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

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

A total of 10 animals included in the study (5 male and 5 female).

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Daily during acclimatization and twice daily during days 1-15 (mortality/viability); On test days 1 (prior to administration), 8 and 15 (weighing)
- Necropsy of survivors performed: yes
- Other examinations performed: no

Statistics:

No statistical analysis was used.

Results and discussion

Preliminary study:

NA

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0

Clinical signs:

other: No systemic or local signs of toxicity were observed during the study period.

Gross pathology:

No macroscopic findings were observed at necropsy.

Other findings:

NA

Any other information on results incl. tables

NA

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The median lethal dose (LD50) of AAA reaction product following a single semi-occlusive dermal administration to rats of both sexes, was found to be greater than 2000 mg/kg bw.

Executive summary:

The acute dermal toxicity of AAA reaction product was evaluated in accordance to OECD 402. Five male and five female HanBrl: WIST (SPF) rats were treated with AAA reaction product at 2000 mg/kg by dermal application (undiluted). The application period was 24 hours. The animals were examined daily during the acclimatization period and mortality, body weight, viability and clinical signs were recorded. At termination. all animals were necropsied and examined macroscopically.

No deaths occurred during the study.Three female animals showed a loss of body weight (1.5 % to 4.7 %) during the first observation week and recovered from test day 8 to the end of the observation period. The body weight of the other animals was within the range commonly recorded for this strain and age. No macroscopic findings were observed at necropsy.

The median lethal dose (LD50) of AAA reaction product following a single semi-occlusive dermal administration to rats of both sexes, was found to be greater than 2000 mg/kg bw.