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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
12 Sep 2006 to 05 Oct 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD 423) performed in compliance with OECD GLP (1997)

Data source

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

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: OECD Guideline 423 "Acute Oral Toxicity - Acute Toxic Class Method" adopted 17 December 2001 and Directive 2004/73/EC, B.1 tris "Acute Oral Toxicity - Acute Toxic Class Method," April 29, 2004
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report: MTDID 8191
- Physical state: Yellowish Liquid
- Analytical purity: >98%
- Lot/batch no.: FC 03/167
- Expiration date of the lot/batch: 31 Jan 2007
- Storage condition of test material: At room temperature (range of 20 +/- 5 C), light protected
- Other: Stable under storage conditions

Test animals

Species:
rat
Strain:
other: HanRcc:WIST (SPF)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd, Laboratory Animal Services, Switzerland
- Age at study initiation: 11 weeks
- Weight at study initiation: 184.7 - 198.9 g
- Fasting period before study: 18-19 hours prior to treatment and 3 hours after treatment
- Housing: Housed in groups of three in Makrolon type-4 cages with wire mesh tops and standard softwood bedding
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet ad libitum
- Water (e.g. ad libitum): Community tap water ad libitum
- Acclimation period: 7 days; under laboratory conditions and after health examination
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 C
- Humidity (%): 30 - 70%
- Air changes (per hr): 10 - 15 per hour
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light
IN-LIFE DATES: Group 1: From: 19 Sep 2006 To: 03 Oct 2006; Group 2: From: 21 Sep 2006 To: 05 Oct 2006

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.2 g/mL
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: PEG300 was found to be an appropriate vehicle in a pre-study non-GLP solubility trial
- Lot/batch no. (if required): 1274877
- Purity:
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg
DOSAGE PREPARATION (if unusual):
CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Limit Dose
Doses:
2000 mg/kg
No. of animals per sex per dose:
6 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were performed at 0.5, 1, 2, 3, and 5 hours after dosing and then once daily for 14 days. Body weights were recorded weekly.
- Necropsy of survivors performed: Yes
- Other examinations performed: Gross pathology at termination

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
All animals survived.
Clinical signs:
Slightly ruffled fur was noted in three animals from 1 - 5 hours after dosing. All six animals were found in a hunched posture from either 2 - 5 or 2- 3 hours after dosing. There were no abnormal clinical signs in any animals on Day 2 or through the remainder of the study.
Body weight:
Animal body weights were 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:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
Based on the results of this study, the acute oral LD50 of MTDID 8191 is >2000 mg/kg in rats.
Executive summary:

OBJECTIVE: The acute oral toxicity potential of MTDID 8191 (lot FC 03/167) was tested in female Wistar rats.

METHODS: This test was compliant with Swiss GLP (2005) and OECD GLP (1997). The stability of the diluted test article and the acclimation of the animals were excluded from the GLP statement. This study was performed in accordance with Directive 2004/73/EC, B.1 "Acute Oral Toxicity-Acute Toxic Class Method” (2004) and OECD 423 "Acute Oral Toxicity – Acute Toxic Class Method" (2001). Two groups of fasted HanRcc:WIST (SPF) rats (three females/group) were treated with MTDID 8191 by oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was diluted in vehicle (PEG 300) at a concentration of 0.2 g/mL and administered at a dosing volume of 10 mL/kg. The test animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs at approximately 30 minutes, and 1, 2, 3 and 5 hours after dosing on day 1 and once daily during test days 2-15. Mortality/viability was recorded at approximately 30 minutes, 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 prior to administration on day 1 and on study days 8 and 15. All animals were necropsied and examined macroscopically at study termination.

RESULTS: All animals survived until the end of the study period. All six treated animals had clinical signs of toxicity (e.g., hunched posture, ruffled fur) on the day of dosing. No clinical signs were observed in any animal from day 2 through the end of the observation period. The body weights of the animals were within the range commonly recorded for the strain and age used in the study. No macroscopic findings were recorded at necropsy.

CONCLUSION: Based on the results of this study, the rat acute oral LD50 of MTDID 8191 is greater than 2000 mg/kg body weight.