SILATRIZOLE

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 02 November 1995 to 29 April 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study conducted according to OECD Guideline 401 without any deviation.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

16-06-1994

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

422-940-4

EC Name:

-

Cas Number:

155633-54-8

Molecular formula:

C24H39N3O3Si3

IUPAC Name:

2-(2H-1,2,3-benzotriazol-2-yl)-4-methyl-6-[2-methyl-3-(2,2,4,6,6-pentamethyl-3,5-dioxa-2,4,6-trisilaheptan-4-yl)propyl]phenol

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

Species:

rat

Strain:

other: HanIbm: WIST (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- 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

ENVIRONMENTAL CONDITIONS
- 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

Vehicle:

other: methylcellulose 4% + Tween 80R 1%

Details on oral exposure:

VEHICLE
- 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

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

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.

Statistics:

None

Results and discussion

Preliminary study:

Not applicable

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

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:

None

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

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.