AAA reaction product

Endpoint summary

Description of key information

The median lethal dose (LD50) was larger than 2000 mg/kg bw using oral and dermal application. 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

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

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.

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

Preliminary study:

NA

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

NA

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Reliability score of 1- GLP study performed in acordance to guideline with no deviations

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

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

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:

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.

Preliminary study:

NA

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

NA

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Reliability score of 1- GLP study performed in acordance to guideline with no deviations

Additional information

Annex VIII requirement for second exposure route is fulfilled as both an acute oral and an acute dermal toxicity study is availabe. No inhalation study available.

Justification for selection of acute toxicity – oral endpoint
Only acute toxicity study available using the oral route

Justification for selection of acute toxicity – dermal endpoint
Valid study. No other dermal acute toxicity study.

Justification for classification or non-classification

Based on the available acute oral and dermal toxicity data, AAA reaction product is not to be classified according to criteria in GHS/CLP regulation.