Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Aug - Sept 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report date:
2009

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Commission Regulation (EC) No 440/2008 of 30 May 2008 laying down test methods pursuant to Regulation (EC) No 1907/2006 of the European Parliament and of the Council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
ANIMALS
- Animals: Rat, RccHan: WIST(SPF)
- Number of Animals per Group: 3
- Total Number of Animals: 3 females and 3 males
- Age (when treated): 10 weeks (females), 9 weeks (males)
- Body Weight Range (when treated): 180.0 g - 199.8 g (females), 222.6 g - 226.1 g (males)
- Identification: Unique cage number and corresponding color-coded spots on the tail. The animals were marked at acclimatization start.
- Randomization: Selected by hand at time of delivery. No computer generated randomization program.
- Acclimatization: Under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.

HUSBANDRY
- Conditions: Standard Laboratory Conditions. Air-conditioned with 10-15 air changes per hour, and continuously monitored environment with ranges for room temperature 22 ± 3 °C and for relative humidity between 30-70% (values above 70% during cleaning process possible ), automatically controlled light cycle of 12 hours light and 12 hours dark, music during the daytime light period.
- Accommodation: In groups of three in Makrolon type-4 cages with wire mesh tops and standard softwood bedding ('Lignocel' J. Rettenmaier&Söhne GmbH&Co KG, 73494 Rosenberg I Germany, imported by Provimi Kliba AG, 4303 Kaiseraugst I Switzerland).
- Diet: Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 30109 (Provimi Kliba AG, 4303 Kaiseraugst I Switzerland) ad libitum (except for the ovemight fasting period prior to intubation and approximately 3-4 hours post dose). Results of analyses for contaminants are archived at Harlan Laboratories Ltd.
- Water: Community tap water from Fuellinsdorf ad libitum. Results of bacteriological, chemical and contaminant analyses are archived at Harlan Laboratories Ltd.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
The vehicle was chosen after a non-GLP solubility trial which was performed before the study initiation date. Since the test item was not soluble in water, solubility trials were performed in PEG 300 and corn oil. The test item was not soluble in PEG 300, but corn oil was found to be a suitable vehicle.

The animals received a single dose of the test item by oral gavage administration at 2000 mg/kg body weight after being fasted for approximately 18 to 19 hours (access to water was permitted). Food was provided again approximately 3 hours after dosing. The dosing volume was 10 mL/kg body weight.
Dosing started in three female animals at a dosage level of 2000 mg/kg. As this dose was well tolerated by the females, a group of three males was treated with 2000 mg/kg to assess possible gender differences concerning the acute oral toxicity of the test item.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
Two groups, each of three female or three male RccHan: WIST (SPF) rats, were treated with the test item by oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was formulated in corn oil at a concentration of 0.2 g/mL and administered at a dosing volume of 10 mL/kg.
The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs within the first 30 minutes and approximately 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15. Mortality/viability was recorded within the first 30 minutes and approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15. Body weights were recorded on day 1 (prior to administration) and on days 8 and 15. All animals were killed at the end of the observation period by carbon dioxide asphyxiation and discarded after macroscopic examinations were performed. No organs or tissues were retained.
Statistics:
No statistical analysis was used.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
All animals survived until the end of the observation period.
Clinical signs:
No clinical signs were observed during the course of the study in all three female animals.
Slightly ruffled fur was observed in two males following the treatment on day 1 only.
Body weight:
The body weight of the animals was within the range commonly recorded for this strain and age.
Gross pathology:
No macroscopic findings were recorded at necropsy.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The median lethal dose of Sa 190 after single oral administration to rats of both sexes, observed over a period of 14 days, is:
LD50 (rat): greater than 2000 mg/kg body weight.

Based upon the results of this study the following classifications are proposed:

• According to the Commission Directive 2001/59/EC of 06 August 2001 (Official Journal of the European Communities Nr. L 225/1, August 21,
2001), SAT 080004 does not have to be classified and labelled with respect to acute oral toxicity in the rat.

• According to the Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008, Sa 190 does not have to be classified and labelled with respect to acute oral toxicity in the rat.
Executive summary:

Two groups, each of three female or three male RccHan:WIST (SPF) rats, were treated with Sa 190 by oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was formulated in corn oil at a concentration of 0.2 g/mL and administered at a dosing volume of 10 mL/kg.

The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs within the first 30 minutes and approximately 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15. Mortality/viability was recorded within the first 30 minutes and approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15. Body weights were recorded on day 1 (prior to administration) and on days 8 and 15. All animals were necropsied and examined macroscopically.

All animals survived until the end of the observation period.

No clinical signs were observed during the course of the study in all three female animals. Slightly ruffled fur was observed in two males following the treatment on day 1 only.

The body weight of the animals was within the range commonly recorded for this strain and age.

No macroscopic findings were recorded at necropsy.

The median lethal dose of SAT 080004 after single oral administration to rats of both sexes, observed over a period of 14 days, is:

LD50 (rat): greater than 2000 mg/kg body weight

Based upon the results of this study the following classifications are proposed:

• According to the Commission Directive 2001/59/EC of 06 August 2001 (Official Journal of the European Communities Nr. L 225/1, August 21, 2001), Sa 190 does not have to be classified and labelled with respect to acute oral toxicity in the rat.

• According to the Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008, Sa 190does not have to be classified and labelled with respect to acute oral toxicity in the rat.