Registration Dossier

Administrative data

Description of key information

In the acute oral toxicity study, the LD50 was determined to be 1666 mg/kg bw for male/female.
Based on the criteria in the Regulation CE n.1272/2008, the tested substance needs to be classified as Acute Tox. Cat. 4.

No study available for dermal and inhalation toxicity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
other: experimental data on similar substance
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH
- Age at study initiation: 9-12 weeks
- Weight at study initiation: males: 195-265 g; females: 173-218 g
- Housing: 5 animals per Makrolon cage type III
- Diet (e.g. ad libitum): pellets of Kliba 343 ad libitum
- Water (e.g. ad libitum): tap water from Itingen, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 40 -70
- Air changes (per hr): 10/15
- Photoperiod (hrs dark / hrs light): 12 / 12

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
MAXIMUM DOSE: 20 ml at 5000 mg/kg bw (group 5)

RATIONALE FOR SELECTION OF DOSES:Oral administration has been proven to be an efficacious method to assess the test article absorption.


Doses:
Group 1: 10 ml at 750 mg/kg bw
Group 2: 10 ml at 1000 mg/kg bw
Group 3: 10 ml at 2000 mg/kg bw
Group 4: 20 ml at 3000 mg/kg bw
Group 5: 20 ml at 5000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of clinical observations: 4 times in day 1; daily during days 2-15
- Frequency of weighing: before application, after 8 days and after 15 days.
- Necropsy of survivors performed: yes, all animals
Statistics:
The LOGIT-Model (COX, Analysis of Binary Data, London 1977) was applied to estimate the toxicity value. Additionally, the 90, 95 and 99% confidence intervals for the toxicity for each sex the slope of the concentration response line were estimated.
Preliminary study:
N.A.
Sex:
male
Dose descriptor:
LD50
Effect level:
2 053 mg/kg bw
Based on:
test mat.
95% CL:
> 1 439 - < 4 878
Sex:
female
Dose descriptor:
LD50
Effect level:
1 336 mg/kg bw
Based on:
test mat.
95% CL:
> 934 - < 1 859
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 666 mg/kg bw
Based on:
test mat.
95% CL:
> 1 344 - < 2 147
Mortality:
Based on the values indicated in Appendix A1:
No mortality at 750 and 1000 mg/kg bw.
1 animal died at day 2 for 2000 mg/kg bw
5 animals died at day 2 for 3000 mg/kg bw
5 animals died at day 2 for 5000 mg/kg bw
Clinical signs:
The following symptoms were observed:
750 mg/kg bw: dyspnea
1000 mg/kg bw: sedation, dyspnea, curved body position, ruffled fur
2000 mg/kg bw: sedation, dyspnea, curved body position, ruffled fur, ataxis (females)
3000 mg/kg bw: sedation, dyspnea, curved body position, ruffled fur, ataxis
5000 mg/kg bw: sedation, dyspnea, curved body position, latero-abdominal position, ventral body position, ruffled fur, ataxis
Body weight:
No effects on the body weight were noted.
Gross pathology:
In killed rats, no pathologic changed were observed.
In dead animals some changes were observed (stomach and intestine descoloration, mottled lungs and discoloration, spleen and kidney discoloration.
Other findings:
N.A.
Interpretation of results:
other: Acute Toxicity Category 4
Conclusions:
In this acute oral toxicity study, the LD50 was determined to be 1666 mg/kg bw for male/female.
Executive summary:

In this acute oral toxicity study, the LD50 was determined to be 1666 mg/kg bw for male/female.
Based on the criteria in the Regulation CE n.1272/2008, the tested substance needs to be classified as Acute Tox. Cat. 4.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 666 mg/kg bw
Quality of whole database:
Good report

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

In the acute oral toxicity study, the LD50 was determined to be 1666 mg/kg bw for male/female.
Based on the criteria in the Regulation CE n.1272/2008, the tested substance needs to be classified as Acute Tox. Cat. 4, H302.