AAA reaction product

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2003-05-13 to 2003-09-15

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study performed in acordance 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 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

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:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Rat, HanBrl: WIST (SPF)
- Age at study initiation: 11 - 12 weeks
- Weight at study initiation: 246-257 g (male) and 187-196 g (female)
- Fasting period before study: No data
- Housing: In groups of three in Makrolon type-4 cages with wire mesh tops and standard softwood bedding
- 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.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Details on oral exposure:

VEHICLE
- Concentration in vehicle: AAA reaction product was diluted in vehicle (PEG 300) at a concentration of 0.2 g/mL.
- Amount of vehicle (if gavage): AAA reaction product was administered at a volume dosage of 10 mL/kg.
- Justification for choice of vehicle: PEG 300 was found to be a suitable vehicle. The vehicle was chosen after a non-GLP solubility trial which was performed before the study initiation date. This trial formulation is excluded from the GLP statement of compliance.
- Lot/batch no. (if required): 442989/1 54502013
- Purity: No information

MAXIMUM DOSE VOLUME APPLIED: AAA reaction product was administered at a volume dosage of 10 mL/kg.

DOSAGE PREPARATION (if unusual): NA

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Based on the expected low toxicity of AAA reaction product.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

Six female HanBrl: WIST (SPF) rats

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing:
Mortality / Viability: Daily during acclimatization and twice daily during days 1-15.
Body weights: on test days 1 (prior to administration), 8 and 15.
Clinical signs: Daily during acclimatization and at approximately 1, 2, 3 and 5 hours after administration on test day 1. Once daily during days 2-15.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight.

Statistics:

NA

Results and discussion

Preliminary study:

NA

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

Female: 2000 mg/kg bw; Number of animals: 6; Number of deaths: 0

Clinical signs:

other: Signs of toxicity related to dose levels: No clinical signs were observed during the course of the study.

Gross pathology:

Effects on organs: No macroscopic findings were recorded at necropsy.

Other findings:

- Organ weights: not examined
- Histopathology: not examined
- Potential target organs: NA
- Other observations: 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 acute toxicity of AAA reaction prodcut was evaluated in accordance to OECD 423. The median lethal dose (LD50) after single oral administration to female rats, observed over a period of 14 days was found to be greater than 2000 mg/kg body bw.

Executive summary:

The acute toxicity of AAA reaction prodcut was evaluated in accordance to OECD 423. Six female HanBrl: WIST (SPF) rats were treated with AAA reaction product by oral gavage administration at a dosage of 2000 mg/kg body weight.

All animals survived until the end of the study period. No clinical signs were observed during the course of the study. One animal showed a loss of body weight (2.3 %) and another animal did not gain body weight during the first observation week. Both animals recovered whereas a third animal lost body weight (0.6 %) between test day 8 and 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 recorded at necropsy.

The median lethal dose (LD50) after single oral administration to female rats, observed over a period of 14 days was found to be greater than 2000 mg/kg body bw.