Registration Dossier

Diss Factsheets

Toxicological information

Acute Toxicity: oral

Currently viewing:

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
3 October 2006 - 13 December 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006

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:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: JMAFF guidelines (2000)
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Test material form:
solid: particulate/powder

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: ca. 10 weeks
- Weight at study initiation: 222 - 258 g (Day 1)
- Fasting period before study: yes (food was witheld overnight - for a maximumof 20 hours - prior to dosing until 3-4 hours after administration of the test material)
- Housing: animals were housed in groups of 3 in Macrolon cages furnished withy sterilised sawdust and paper as cage-enrichment.
- Diet: pelleted rodent diet, SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany (ad libitum)
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.8 - 23.0 °C
- Humidity (%): 41 - 91%
- Air changes (per hr): ca. 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Water (Milli-U)
Details on oral exposure:
The formulations were prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level.
Doses:
2000 mg/kg (10 mL/kg) bw
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
STUDY DESIGN
The toxicity of the test material was assessed by stepwise treatment of groups of 3 females. the first group was treated at a dose of 2000 mg/kg. Due to the absence of mortality, the second group of animals was also dosed at 2000 mg/kg.

OBSERVATIONS
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: mortality was observed twice daily. Body weights were recorded on day 1 (pre-administration), 8 and 15. Clinical signs were observed at periodic intervals on the day of dosing and once daily thereafter until day 15.
- Necropsy of survivors performed: yes (descriptions of all internal macroscopic abnormalities were recorded).

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
None of the animals died during the study.
Clinical signs:
other: No clinical signs were noted.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the study, the oral LD50 value of the test material in female Wistar rats was in excess of 2000 mg/kg bw, the highest permissible dose level tested.
Executive summary:

The acute oral toxicity of the test material was investigated in a study which was conducted under GLP conditions and in accordance with the standardised guidelines OECD 423, EU Method B.1 tris, EPA OPPTS 870.1100 and JMAFF guidelines, following the acute toxic class method.

During the study, the test material was administered by oral gavage to two subsequent groups of three female Wistar rats at 2000 mg/kg bw. All animals were subject to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice on day 15.

None of the animals died during the study and no clinical signs were noted. The mean body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain. Furthermore, no abnormalities were found at macroscopic post mortem

examination of the animals.

Therefore, under the conditions of the study, the oral LD50 value of the test material in female Wistar rats was in excess of 2000 mg/kg bw, the highest permissible dose level tested.