Registration Dossier

Administrative data

Description of key information

- Oral (rat): > 2000 mg/kg bw (f) (OECD 423)
- Dermal (rat): >2000 mg/kg bw (m+f) (OECD 402)

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP- and guideline compliant
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: 10 weeks
- Weight at study initiation: 176.7-179.3 g
- Fasting period before study: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum
- Housing:Makrolon cage, type III; Single housing
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period:5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 – 24°C
- Humidity (%): 20 – 80%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 h / 12 h

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2.08 mL

Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of
observation.Recording of clinical signs several times on the day of administration, and at least once daily thereafter each workday for the individual animals. A check for any dead or moribund animal was made at least once each workday.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
Calculations were performed using Microsoft Excel 2003 and checked with a calculator.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortality occurred.
Clinical signs:
No clinical signs were observed during clinical examination.
Body weight:
The mean body weight of the test groups increased throughout the study period within
the normal range.
Gross pathology:
There were no macroscopic pathological findings in the animals sacrificed at the end of
the observation period.
Other findings:
none
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study the median lethal dose of ASA after oral administration was found to be greater than 2000 mg/kg bw in rats.
Executive summary:

In an acute oral toxicity study performed according to the OECD 423 under GLP, 2000 mg/kg bw of the undiluted test-item was administered to two test groups of three fasted Wistar rats each by gavage. Because no mortality occurred in the six females administered 2000 mg/kg bw within the 14 day observation perid, the LD50 was estimated to be >2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP- and guideline compliant
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: male animals approx. 8 weeks, female animals approx. 12 weeks
- Weight at study initiation: male: 253.8 g (mean); female: 201,8 (mean)
- Housing: Makrolon cage, type III; Single housing
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 – 26°C
- Humidity (%): 20 – 80%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 h / 12 h


Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal and dorsolateral parts of the trunk
- % coverage: 10



REMOVAL OF TEST SUBSTANCE
- Washing (if done): Rinsing of the application site with warm water
- Time after start of exposure: 24h


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.08 ml/kg
- Concentration (if solution): 2000 mg/kg bw
- Constant volume or concentration used: yes
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 males, 5 females
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of
observation. Recording of clinical signs several times on the day of administration, and at least once daily thereafter each workday for the individual animals.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
Calculations were performed using Microsoft Excel 2003 and checked with a calculator.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortality occurred.
Clinical signs:
No systemic clinical signs were observed during clinical examination. Skin effects at the application site comprised erythema (grade 1 or 2), edema (grade 1), scaling and incrustations and were observed on study day 1 until study day 9 after application.
Body weight:
The mean body weight of the male animals increased within the normal range throughout the study period.
Mean body weight of the female animals decreased during the first post-exposure observation week, but increased during the second week within the normal range.
Gross pathology:
No macroscopic pathologic abnormalities were noted in the animals (5 males and 5
females) examined on the last day of observation.
Other findings:
none
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study the median lethal dose (LD50) of ASA after dermal application was found to be greater than 2000 mg/kg bw in male and female rats.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw

Additional information

Acute oral toxicity:

In an acute oral toxicity study performed according to the OECD 423 under GLP, 2000 mg/kg bw of the undiluted test-item was administered to two test groups of three fasted Wistar rats each by gavage. Because no mortality occurred in the six females administered 2000 mg/kg bw within the 14 day observation period, the LD50 was estimated to be >2000 mg/kg bw.

Acute dermal toxicity:

The LD50 was found >2000 mg/kg bw in a study on acute dermal toxicity performed in accordance with GLP and ORCD 402 with five male and five female Wistar rats. No No systemic clinical signs were noted and no mortality occurred during the 14 day observation period.


Justification for selection of acute toxicity – oral endpoint
Guideline study according to GLP

Justification for selection of acute toxicity – dermal endpoint
Guideline study according to GLP

Justification for classification or non-classification

There avaiable data are conclusive but not sufficient data for classification with regard to acute toxicity via oral or dermal route in accordance with Directive 67/548/EEC or the CLP Regulation (EC) No 1272/2008.