Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP Guideline study. According to ECHA guidance, a study with a read-across substance can have no reliability of higher than 2. The study itself is valid without restriction.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1986

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Batch #: Vers. 31-33
- Purity: pilot sample
- Storage: room temperature
- Physical state: liquid
- Expiry date: September 1991

Test animals

Species:
rat
Strain:
other: Tif: RAIf(SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Further description: F3-hybrid of RII 1/Tif x RII 2/Tif
- Source: Ciba-Geigy Ltd. Tierfarm, 4334 Sisseln, Switzerland
- Age at study initiation: 7-8 weeks
- Weight at study initiation: 173-195 (within ± 20% of mean value)
- Fasting period before study: overnight prior to dosing
- Housing: 5 per sex in Macrolon cage type 4 with standardized soft wood bedding (Societe Parisienne des sciures, Pantin).
- Diet: ad libitum; Rat food, NAFAG No. 890, NAFAG AG, Gossau, SG (Switzerland),
- Water: ad libitum
- Acclimation period: 6 days
- Rationale for choice: The rat has been selected for this test as being a standard species for the determination of an acute oral LD50

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 15
- Air changes (per hr): approx. 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: distilled water containing 0.5% carboxymethylcellulose and 0.1% polysorbate
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw
Doses:
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 observations: mortality; daily; a.m. and p.m. on working days, a.m. on weekend days, clinical signs of toxicity; daily
- Frequency of weighing: on days 1, 7, and 14
- Necropsy of survivors performed: yes
Statistics:
From the body weights, the group means and their standard deviations were calculated.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Remarks on result:
other: No deaths occurred
Mortality:
No deaths occurred
Clinical signs:
Dyspnea, exophthalmos, ruffled fur, and curved body position were seen, beginning as early as 1 hour post dosing and lasting up to 10 day. The animals were fully recovered within 11 days.
Body weight:
- males: day 1: 182 mg/kg bw, day 7: 247 mg/kg bw, day 14: 291 mg/kg bw
- females: day 1: 178 mg/kg bw, day 7: 208 mg/kg bw, day 14: 226 mg/kg bw
Gross pathology:
No deviations from normal morphology were found.

Applicant's summary and conclusion