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Acute Toxicity: oral

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acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 02 November 1995 to 29 April 1996
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study conducted according to OECD Guideline 401 without any deviation.
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Reference Type:
study report
Report date:

Materials and methods

Test guidelineopen allclose all
according to guideline
OECD Guideline 401 (Acute Oral Toxicity)
according to guideline
EU Method B.1 (Acute Toxicity (Oral))
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:

Test material

Constituent 1
Chemical structure
Reference substance name:
EC Number:
EC Name:
Cas Number:
Molecular formula:
Test material form:
other: solid
Details on test material:
- Name of test material (as cited in study report): G4375
- Physical state: whitish solid
- Analytical purity: 99% minimum
- Impurities (identity and concentrations): Methanol (<100 ppm) and Isopropanol (<100 ppm)
- Purity test date: certificate of analysis 20/10/1995
- Lot/batch No.: DEF/C 95003/B
- Expiration date of the lot/batch: No data
- Stability under test conditions: Stable under storage condition; Stable for 5 hours in Methylcellulose 4% + Tween 80R (determined in a subchronic 13-week oral toxicity study)
- Storage condition of test material: In the original container at room temperature away from direct sunlight.

Test animals

other: HanIbm: WIST (SPF)
Details on test animals or test system and environmental conditions:
- Source: BRL, Biological Research Laboratories, Ltd. Wölferstrasse 4, 4414 Füllinsdorf / Switzerland
- Age at study initiation: 8 weeks old for males; 10 weeks old for females
- Weight at study initiation: 239.9-257.6 g for males; 196.0-212.3 g for females
- Fasting period before study: yes, overnight prior to application (approximately 16h)
- Housing: Groups of five rats in Makrolon type-4 cages with autoclaved standard softwood bedding ("Lignoce1", Scill AG, CH-4132 Muttenz).
- Diet (e.g. ad libitum): Pelleted standar Kliba 343, Batch no. 66/95 rat maintenance diet ("Kliba", Klingentalmuehle AG, CH-4303 Kaiseraugst) available ad libitum (except for the overnight fasting period prior to application). Food was provided again approximately 3 hours after dosing.
- Water (e.g. ad libitum): Community tap water from Füllinsdorf, available ad libitum.
- Acclimation period: one week

- Temperature (°C): 20-23°C
- Humidity (%): 37-70 %
- Air changes (per hr): 10 to 15
- Photoperiod (hrs dark / hrs light): 12h dark/ 12h light

IN-LIFE DATES: From: 2 November 1995 To: 23 November 1995

Administration / exposure

Route of administration:
oral: gavage
other: methylcellulose 4% + Tween 80R 1%
Details on oral exposure:
- Concentration in vehicle: the test article was placed into a glass beaker on a tared Mettler PM 480 balance, and the vehicle (methylcellulose 4% + Tween 80R 1%) was added. A weight by volume dilution was prepared using a homogenizer (Ultra-Turrax, Janke & Kunkel, D-79219 Staufen). Homogeneity of the test article in the vehicle was maintained during treatment using a magnetic stirrer (Janke&Kunkel, D-79219 Staufen). The preparation was made shortly before dosing.
- Amount of vehicle (if gavage): 10 ml/kg bw
- Justification for choice of vehicle: no data
- Purity: no data
2000 mg/kg bw
No. of animals per sex per dose:
Control animals:
other: reference control
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality and viability were observed four times during test day 1 and daily during days 2-15, as well as clinical signs (changes in appearance and behaviour).
Body weights were measured on test day1 (pre-administration), 8 and 15.
- Necropsy of survivors performed: yes; at the end of the observation period all animal were anesthetized by intraperitoneal injection of NARCOREN (Rhone Merieux GmBH, D-88471 Laupheim) at a dose of at least 2.0 ml/kg bw (equivalent to at least 320 mg sodium pentobarbitone/kg bw) and sacrificed by exsanguination. The animals were examined macroscopically and all abnormalities recorded.

Results and discussion

Preliminary study:
Not applicable
Effect levels
Dose descriptor:
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
No unscheduled deaths occurred during the study.
Clinical signs:
other: No clinical signs of toxicity were observed during the observation period.
Gross pathology:
No organ abnormalities were observed at necropsy.
Other findings:

Any other information on results incl. tables


Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Criteria used for interpretation of results: EU
Under the test conditions, the oral LD50 of the test item, Silatrizole (encoded "G4375"), was higher than 2000 mg/kg in rats and no mortality occurred at this concentration. Therefore Silatrizole should not be classified for acute oral toxicity according to the Regulation (EC) N° 1272-2008 (CLP) and the Directive 67/548/EEC.
Executive summary:

In an acute oral toxicity study, performed according to the OECD guideline No. 401, and GLP-compliant, groups of (HanIbm: WIST (SPF)) male and female rats (5 animals/sex/dose) were given a single oral dose (by gavage) of 2000 mg/kg bw of Silatrizole (encoded "G4375") . Clinical signs, mortality and body weight gain were checked for a period of up to 14 days.


There were no deaths as a result of treatment with the test article. No clinical signs of toxicity were observed during the observation period. The body weight of the animals was within the normal range for rats of this strain and age, when compared to the body weights from reference control. No organ abnormalities were observed at necropsy.


Oral LD50 in rats (male and female) > 2000 mg/kg bw.


Under the test conditions, Silatrizole  is not classified for Acute oral toxicity according to the criteria of the CLP regulation (EC) N°1272/2008.


This study is considered as acceptable and satisfies the requirement for acute oral toxicity endpoint.